Nonviral CRISPR/Cas9 mutagenesis for streamlined generation of mouse lung cancer models.

Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers. This approach allows the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specifically Rb1, Rbl1, Pten, and Trp53, which were chosen for their potential to cause lung tumors, namely small cell lung carcinoma (SCLC). Tumors with histologic and transcriptomic features of human SCLC emerged after intratracheal administration of CRISPR/polymer nanoparticles. These tumors carried loss-of-function mutations in all four tumor suppressor genes at the targeted positions. These findings were reproduced in two different pure genetic backgrounds. We provide a proof of principle for simplified modeling of lung tumorigenesis to facilitate functional testing of potential cancer-related genes.

Differential Laminar Activation Dissociates Encoding and Retrieval in the Human Medial and Lateral Entorhinal Cortex.

The hierarchically organized structures of the medial temporal lobe are critically important for episodic memory function. Accumulating evidence suggests dissociable information processing pathways are maintained throughout these structures including in the medial and lateral entorhinal cortex. Cortical layers provide an additional dimension of dissociation as the primary input to the hippocampus derives from layer 2 neurons in the entorhinal cortex, whereas the deeper layers primarily receive output from the hippocampus. Here, novel high-resolution T2-prepared functional MRI methods were successfully used to mitigate susceptibility artifacts typically affecting MRI signals in this region providing uniform sensitivity across the medial and lateral entorhinal cortex. During the performance of a memory task, healthy human subjects (age 25-33 years, mean age 28.2 ± 3.3 years, 4 female) showed differential functional activation in the superficial and deep layers of the entorhinal cortex associated with task-related encoding and retrieval conditions, respectively. The methods provided here offer an approach to probe layer-specific activation in normal cognition and conditions contributing to memory impairment.SIGNIFICANCE STATEMENT This study provides new evidence for differential neuronal activation in the superficial versus deep layers of the entorhinal cortex associated with encoding and retrieval memory processes, respectively, in cognitively normal adults. The study further shows that this dissociation can be observed in both the medial and the lateral entorhinal cortex. The study was achieved by using a novel functional MRI method allowing us to measure robust functional MRI signals in both the medial and lateral entorhinal cortex that was not possible in previous studies. The methodology established here in healthy human subjects lays a solid foundation for subsequent studies investigating layer-specific and region-specific changes in the entorhinal cortex associated with memory impairment in various conditions such as Alzheimer's disease.

On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).

PURPOSE: The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain. METHODS: Three sets of experiments were performed in three separate cohorts. (1) 3D iVASO MRI protocols were compared to single-slice iVASO, and the reproducibility of whole-brain 3D iVASO MRI was evaluated. (2) The effects from different vascular crushers in iVASO were assessed. (3) 3D iVASO MRI results were evaluated in arterial and venous blood vessels identified using ultrasmall-superparamagnetic-iron-oxides-enhanced MRI to validate its arterial origin. RESULTS: 3D iVASO scans showed signal-to-noise ratio (SNR) and CBVa measures consistent with single-slice iVASO with reasonable intrasubject reproducibility. Among the iVASO scans performed with different vascular crushers, the whole-brain 3D iVASO scan with a motion-sensitized-driven-equilibrium preparation with two binomial refocusing pulses and an effective TE of 50 ms showed the best suppression of macrovascular signals, with a relatively low specific absorption rate. When no vascular crusher was applied, the CBVa maps from 3D iVASO scans showed large CBVa values in arterial vessels but well-suppressed signals in venous vessels. CONCLUSION: A whole-brain 3D iVASO MRI scan was optimized for CBVa measurement in the human brain. When only microvascular signals are desired, a motion-sensitized-driven-equilibrium-based vascular crusher with binomial refocusing pulses can be applied in 3D iVASO.

What Are the Recurrence Rates, Complications, and Functional Outcomes After Multiportal Arthroscopic Synovectomy for Patients With Knee Diffuse-type Tenosynovial Giant-cell Tumors?

BACKGROUND: Diffuse-type tenosynovial giant-cell tumor (D-TGCT), formerly known as pigmented villonodular synovitis, is a rare, locally aggressive, invasive soft tissue tumor that primarily occurs in the knee. Surgical excision is the main treatment option, but there is a high recurrence rate. Arthroscopic surgical techniques are emphasized because they are less traumatic and offer faster postoperative recovery, but detailed reports on arthroscopic techniques and outcomes of D-TGCT in large cohorts are still lacking. QUESTIONS/PURPOSES: (1) What is the recurrence rate of knee D-TGCT after multiportal arthroscopic synovectomy? (2) What are the complications, knee ROM, pain score, and patient-reported outcomes for patients, and do they differ between patients with and without recurrence? (3) What factors are associated with recurrence after arthroscopic treatment in patients with D-TGCT? METHODS: In this single-center, retrospective study conducted between January 2010 and April 2021, we treated 295 patients with knee D-TGCTs. We considered patients undergoing initial surgical treatment with multiportal arthroscopic synovectomy as potentially eligible. Based on that, 27% (81 of 295) of patients were excluded because of recurrence after synovectomy performed at another institution. Of the 214 patients who met the inclusion criteria, 17% (36 of 214) were lost to follow-up, leaving 83% (178 of 214) of patients in the analysis. Twenty-eight percent (50 of 178) of patients were men and 72% (128 of 178) were women, with a median (range) age of 36 years (7 to 69). The median follow-up duration was 80 months (26 to 149). All patients underwent multiportal (anterior and posterior approaches) arthroscopic synovectomy, and all surgical protocols were determined by discussion among four surgeons after preoperative MRI. A combined open posterior incision was used for patients with lesions that invaded or surrounded the blood vessels and nerves or invaded the muscle space extraarticularly. Standard postoperative adjuvant radiotherapy was recommended for all patients with D-TGCT who had extraarticular and posterior compartment invasion; for patients with only anterior compartment invasion, radiotherapy was recommended for severe cases as assessed by the surgeons and radiologists based on preoperative MRI and intraoperative descriptions. Postoperative recurrence at 5 years was calculated using a Kaplan-Meier survivorship estimator. The WOMAC score (0 to 96, with higher scores representing a worse outcome; minimum clinically important difference [MCID] 8.5), the Lysholm knee score (0 to 100, with higher scores being better knee function; MCID 25.4), the VAS for pain (0 to 10, with higher scores representing more pain; MCID 2.46), and knee ROM were used to evaluate functional outcomes. Because we did not have preoperative patient-reported outcomes scores, we present data on the proportion of patients who achieved the patient-acceptable symptom state (PASS) for each of those outcome metrics, which were 14.6 of 96 points on the WOMAC, 52.5 of 100 points on the Lysholm, and 2.32 of 10 points on the VAS. RESULTS: The symptomatic or radiographically documented recurrence at 5 years was 12% (95% confidence interval [CI] 7% to 17%) using the Kaplan-Meier estimator, with a mean recurrence time of 33 ± 19 months. Of these, three were asymptomatic recurrences found during regular MRI reviews, and the remaining 19 underwent repeat surgery. There was one intraoperative complication (vascular injury) with no effect on postoperative limb function and eight patients with postoperative joint stiffness, seven of whom improved with prolonged rehabilitation and one with manipulation under anesthesia. No postradiotherapy complications were found. The proportion of patients who achieved the preestablished PASS was 99% (176 of 178) for the VAS pain score, 97% (173 of 178) for the WOMAC score, and 100% (178 of 178) for the Lysholm score. A lower percentage of patients with recurrence achieved the PASS for WOMAC score than patients without recurrence (86% [19] versus 99% [154], OR 0.08 [95% CI 0.01 to 0.52]; p = 0.01), whereas no difference was found in the percentage of VAS score (95% [21] versus 99% [155], OR 0.14 [95% CI 0.01 to 2.25]; p = 0.23) or Lysholm score (100% [22] versus 100% [156], OR 1 [95% CI 1 to 1]; p = 0.99). Moreover, patients in the recurrence group showed worse knee flexion (median 135° [100° to 135°] versus median 135° [80° to 135°]; difference of medians 0°; p = 0.03), worse WOMAC score (median 3.5 [0 to 19] versus median 1 [0 to 29]; difference of medians 2.5; p = 0.01), and higher VAS pain score (median 1 [0 to 4] versus median 0 [0 to 4]; difference of medians 1; p < 0.01) than those in the nonrecurrence group, although no differences reached the MCID. No factors were associated with D-TGCT recurrence, including the use of postoperative radiotherapy, surgical technique, and invasion extent. CONCLUSION: This single-center, large-cohort retrospective study confirmed that multiportal arthroscopic surgery can be used to treat knee D-TGCTs with a low recurrence rate, few complications, and satisfactory postoperative outcomes. Surgeons should conduct a thorough preoperative evaluation, meticulous arthroscopic synovectomy, and regular postoperative follow-up when treating patients with D-TGCT to reduce postoperative recurrence. Because the available evidence does not appear to fully support the use of postoperative adjuvant radiotherapy in all patients with D-TGCTs and our study design is inadequate to resolve this controversial issue, future studies should look for more appropriate indications for radiotherapy, such as planning based on a more precise classification of lesion invasion. LEVEL OF EVIDENCE: Level III, therapeutic study.

Salvage Latarjet may provide worse outcomes in terms of recurrent instability and returning to sports compared to primary Latarjet: a systematic review of comparative studies.

BACKGROUND: The Latarjet procedure (LP) is performed as a primary stabilization procedure (primary LP) and a salvage procedure when an earlier shoulder stabilization procedure has failed (salvage LP). However, whether primary LP or salvage LP provides better outcomes for anterior shoulder instability remains unknown. METHODS: Two independent reviewers performed the literature search based on the PRISMA guidelines. A comprehensive search of PubMed, Embase, web of science and Cochrane Library was performed from their inception date to December 4, 2023. Inclusion criteria mainly included the comparison of postoperative outcomes between primary and salvage LP, English language, and full text availability. Two reviewers independently examined the literature, collected data, and evaluated the methodological robustness of the included studies. The Methodological Index for Nonrandomized Studies was used to evaluate the quality of nonrandomized studies. Recurrent instability, complications, reoperations, return to sports, patient-reported outcomes, and range of motion were assessed. Statistical evaluations were conducted using Manager V.5.4.1 (The Cochrane Collaboration, Software Update, Oxford, UK). RESULTS: Twelve studies were included in the systematic review, with 940 shoulders undergoing primary LP and 631 shoulders undergoing salvage LP. Statistically significant differences in favor of primary LP were found in 2 of the 11 and 2 of 4 included studies in terms of recurrent instability and returning to the same sports (RTS) at preinjury level, respectively. In terms of the visual analog scale, subjective shoulder value and the Western Ontario Shoulder Instability Index, 2 of the 4, 1 of the 3 and 1 of the 3 included studies reported statistically significant differences in favor of primary LP. Differences were not noticed regarding complications, reoperations, the time to RTS, the Rowe score, the Athletic Shoulder Outcome Scoring System, and forward flexion. CONCLUSION: Current evidence suggests that compared with primary LP, salvage LP may provide inferior postoperative outcomes in terms of recurrent instability and the rate of RTS at preinjury level. Primary and salvage LP may yield comparable efficacy in terms of complications, reoperations, the rate of RTS, the time to RTS, pain, shoulder function, and range of motion. PROSPERO ID: CRD42023492027.

Virtual Reality-Based Training in Chronic Low Back Pain: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low back pain is one of the most prevalent pain conditions worldwide. Virtual reality-based training has been used for low back pain as a new treatment strategy. Present evidence indicated that the effectiveness of virtual reality-based training for people with chronic low back pain is inconclusive. OBJECTIVE: This study conducted a meta-analysis to evaluate the immediate- and short-term effects of virtual reality-based training on pain, pain-related fear, and disability in people with chronic low back pain. METHODS: We searched the PubMed, Embase, Web of Science, PEDro, CENTRAL, and CINAHL databases from inception until January 2024. Only randomized controlled trials assessing the effects of virtual reality-based training on individuals with chronic low back pain were selected. The outcomes were focused on pain, pain-related fear measured by the Tampa Scale of Kinesiophobia, and disability measured by the Oswestry Disability Index. The immediate term was defined as the immediate period after intervention, and the short term was defined as 3 to 6 months after intervention. The Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach were used to evaluate the quality of the methodology and evidence, respectively. RESULTS: In total, 20 randomized controlled trials involving 1059 patients were eligible for analysis. Virtual reality-based training showed significant improvements in pain (mean difference [MD] -1.43; 95% CI -1.86 to -1.00; I2=95%; P<.001), pain-related fear using the Tampa Scale of Kinesiophobia (MD -5.46; 95% CI -9.40 to 1.52; I2=90%; P=.007), and disability using the Oswestry Disability Index (MD -11.50; 95% CI -20.00 to -3.01; I2=95%; P=.008) in individuals with chronic low back pain immediately after interventions. However, there were no significant differences observed in pain (P=.16), pain-related fear (P=.10), and disability (P=.43) in the short term. CONCLUSIONS: These findings indicated that virtual reality-based training can be used effectively for individuals with chronic low back pain in the immediate term, especially to reduce pain, alleviate pain-related fear, and improve disability. However, the short-term benefits need more high-quality trials to be demonstrated. TRIAL REGISTRATION: PROSPERO CRD42021292633; http://tinyurl.com/25mydxpz.

Suture Button Could Result in More Functional Outcomes Improvement and Pain Relief Than Hook Plate Technique for Treating Acute Acromioclavicular Joint Dislocation: A Systematic Review of Comparative Studies.

PURPOSE: To systematically review the current evidence to compare the differences in outcomes of the suture button (SB) versus hook plate (HP) fixations for treating acute acromioclavicular joint dislocation (ACD). METHODS: Two independent reviewers performed the literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of the Embase, PubMed, and Cochrane Library databases was performed and Level I-IV evidence studies comparing the SB and HP procedures for acute ACD were included. Studies that met the following exclusion criteria were excluded: (1) letters, comments, case reports, reviews, animal studies, cadaveric studies, biomechanical studies, and study protocols; (2) incomplete data; and (3) repeated studies and data. The Newcastle-Ottawa Scale was used to evaluate the quality of nonrandomized studies. Constant score, visual analog scale (VAS) score, operation time, coracoclavicular distance (CCD), and complications were recorded and the mean differences of VAS and Constant were compared with preset minimal clinically important difference. RESULTS: Fourteen studies with 363 patients treated with SB procedures and 432 patients with the HP procedure were included. In terms of patient-reported outcomes, 5 of the 13 included studies reported significantly greater Constant score in SB group and most (4/5) used arthroscopic SB technique. Statistically significant differences in favor of SB were found in 3 of the 7 included studies in terms of VAS score whereas none of them reached the minimal clinically important difference. In terms of recurrent instability, no statistically significant difference was noted. All studies showed that the SB technique resulted in lower estimated blood loss. No difference was detected in CCD and complications. CONCLUSIONS: Based on the current body of evidence, it is suggested that employment of the SB technique may confer advantageous outcomes when compared to the HP technique in acute ACD patients. These potential benefits may include higher Constant scores, lower pain levels, and no discernible increases in operation time, CCD, or complication rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level II-IV studies.

Bone Marrow Stimulation Does Not Lead to Lower Retear Rates, Better Functional Outcomes, or Higher Complication Rates at Short-Term Follow-Up for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To determine the effect of bone marrow stimulation (BMS) on retear rates, functional outcomes, and complication rates in patients who underwent arthroscopic rotator cuff repair (RCR) through a meta-analysis of randomized controlled trials. METHODS: PubMed, EMBASE, Web of Science, and The Cochrane Library were searched on March 25, 2023. Two evaluators independently screened the literature, extracted data, and assessed the methodologic quality of the enrolled studies. Meta-analysis was conducted using RevMan software, version 5.4. RESULTS: A total of 7 randomized controlled trials with 638 patients were included. The evaluation of rotator cuff tendon integrity was conducted using distinct imaging modalities. Specifically, 259 patients underwent magnetic resonance imaging whereas 208 patients underwent ultrasound. Additionally, a subset of 95 patients underwent either of these modalities; however, the precise distribution between these 2 modalities was not explicitly delineated. Compared with RCR alone, RCR combined with BMS provided similar retear rates (P = .51, I2 = 46%), Constant-Murley scores (P = .14, I2 = 0%), American Shoulder and Elbow Surgeons (standardized shoulder assessment form) scores (P = .56, I2 = 0%), Western Ontario Rotator Cuff Index scores (P = .20, I2 = 0%), visual analog scale scores (P = .19, I2 = 0%), forward flexion (P = .18, I2 = 0%), external rotation (P = .62, I2 = 0%), severe complication rates (P = .56, I2 = 0%), and mild complication rates (P = .10, I2 = 0%). CONCLUSIONS: Compared with the outcomes observed after isolated arthroscopic RCR, arthroscopic RCR with BMS showed comparable results in terms of retear rate, functional outcomes, and incidence of complications. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

Lower Reoperation Rate and Superior Patient-reported Outcome Following Arthroscopic Rotator Cuff Repair with Concomitant Acromioplasty: An Updated Systematic Review of Randomized Controlled Trials.

PURPOSE: This study aims to systematically assess the postoperative outcomes in patients undergoing arthroscopic rotator cuff repairs with or without concomitant acromioplasty through a rigorous systematic review of randomized controlled trial s (RCTs). METHODS: This systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, aimed to identify RCTs comparing clinical outcomes of patients with full thickness rotator cuff tears undergoing arthroscopic rotator cuff repair with acromioplasty versus those without at a minimum of 12 months follow-up. Databases searched included PubMed, Web of Science, Embase, and the Cochrane Library. The risk of bias in the included studies was assessed using the revised Cochrane Risk of Bias 2 (RoB2). Meta-analysis was conducted for outcomes with at least three studies reporting, with pooled effect estimates calculated using either fixed-effect or random-effects models based on heterogeneity levels. Results were presented as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). For outcomes with fewer than three studies reporting, a Fisher exact test was conducted, with continuity correction applied if necessary. Primary outcomes include rates of retear and reoperation, while secondary outcomes included improvement in American Shoulder and Elbow Surgeons (ASES) score, range of motion (ROM), and complication rate. RESULTS: Five high-quality RCTs, with low bias risk, involving 409 patients, revealed demographics of 58.4% males, mean age 58.4 years, and acromion types: 12.2% type I, 70.7% type II, and 17.1% type III. Mean follow-up was 52.2 months. Retear (12.5% versus 16.1%, P = 0.536) and complication rates (OR, 3.11; 95% CI, 0.31-30.73; P=0.33) were comparable between the two groups. However, reoperation rate (5.3% versus 15.9%, P < 0.001) and improvement in ASES score (WMD, 3.99; 95% CI, 1.00-6.99; P=0.009) favored the acromioplasty group. Both groups showed significant improvements in ROM, but insufficient data prevented a comparison. CONCLUSIONS: Compared to arthroscopic rotator cuff repair alone, arthroscopic rotator cuff repair with acromioplasty demonstrated similar rates of retear and complications, but a significantly lower reoperation rate and superior improvement in ASES score. The available data were insufficient to draw a definitive conclusion regarding ROM. This conclusion is fragile due to a limited sample size.

3D Macrocyclic Structure Boosted Gene Delivery: Multi-Cyclic Poly(ß-Amino Ester)s from Step Growth Polymerization.

The topological structures of polymers play a critical role in determining their gene delivery efficiency. Exploring novel polymeric structures as gene delivery vectors is thus of great interest. In this work, a new generation of multi-cyclic poly(ß-amino ester)s (CPAEs) with unique topology structure was synthesized for the first time via step growth polymerization. Through controlling the occurrence stage of cyclization, three types of CPAEs with rings of different sizes and topologies were obtained. In vitro experiments demonstrated that the CPAEs with macro rings (MCPAEs) significantly boosted the transgene expression comparing to their branched counterparts. Moreover, the MCPAE vector with optimized terminal group efficiently delivered the CRISPR plasmid coding both Staphylococcus aureus Cas9 nuclease and dual guide sgRNAs for gene editing therapy.

Heterointerface and Tensile Strain Effects Synergistically Enhances Overall Water-Splitting in Ru/RuO2 Aerogels.

Designing robust electrocatalysts for water-splitting is essential for sustainable hydrogen generation, yet difficult to accomplish. In this study, a fast and facile two-step technique to synthesize Ru/RuO2 aerogels for catalyzing overall water-splitting under alkaline conditions is reported. Benefiting from the synergistic combination of high porosity, heterointerface, and tensile strain effects, the Ru/RuO2 aerogel exhibits low overpotential for oxygen evolution reaction (189 mV) and hydrogen evolution reaction (34 mV) at 10 mA cm-2 , surpassing RuO2 (338 mV) and Pt/C (53 mV), respectively. Notably, when the Ru/RuO2 aerogels are applied at the anode and cathode, the resultant water-splitting cell reflected a low potential of 1.47 V at 10 mA cm-2 , exceeding the commercial Pt/C||RuO2 standard (1.63 V). X-ray adsorption spectroscopy and theoretical studies demonstrate that the heterointerface of Ru/RuO2 optimizes charge redistribution, which reduces the energy barriers for hydrogen and oxygen intermediates, thereby enhancing oxygen and hydrogen evolution reaction kinetics.

Concurrent measurement of perfusion parameters related to small blood vessels and cerebrospinal fluid circulation in the human brain using dynamic dual-spin-echo perfusion MRI.

Accumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic susceptibility contrast (DSC) MRI for blood vessels and DSC MRI-in-the-cerebrospinal fluid (CSF) (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan offers advantages such as a halved scan time and contrast dosage. This study attempts to develop one such approach by optimizing a dual-echo turbo-spin-echo sequence, termed "dynamic dual-spin-echo perfusion (DDSEP) MRI". Bloch simulations were performed to optimize the dual-echo sequence for the measurement of gadolinium (Gd)-induced blood and CSF signal changes using a short and a long echo time, respectively. The proposed method furnishes a T1-dominant contrast in CSF and a T2-dominant contrast in blood. MRI experiments were performed in healthy subjects to evaluate the dual-echo approach by comparing it with existing separate methods. Based on simulations, the short and long echo time were chosen around the time when blood signals show maximum difference between post- and pre-Gd scans, and the time when blood signals are completely suppressed, respectively. The proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than from lymphatic vessels after intravenous Gd injection. In conclusion, Gd-induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. The temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd injection was confirmed using the proposed approach in the same human subjects. Results from this proof-of-concept study will be used to further optimize DDSEP MRI in subsequent studies.

Accelerated Scheme to Predict Ring-Opening Polymerization Enthalpy: Simulation-Experimental Data Fusion and Multitask Machine Learning.

Ring-opening enthalpy (ΔHROP) is a fundamental thermodynamic quantity controlling the polymerization and depolymerization of an important class of recyclable polymers, namely, those created from ring-opening polymerization (ROP). Highly accurate first-principles-based computational methods to compute ΔHROP are computationally too demanding to efficiently guide the design of depolymerizable polymers. In this work, we develop a generalizable machine-learning model that was trained on experimental measurements and reliably computed simulation results of ΔHROP (the latter provides a pathway to systematically increase the chemical diversity of the data). Predictions of ΔHROP using this machine-learning model require essentially no time while the prediction accuracy is about ∼8 kJ/mol, approaching the well-known chemical accuracy. We hope that this effort will contribute to the future development of new depolymerizable polymers.

Optimization on structure and operation parameters of biofilter for decentralized sewage treatment.

Aiming for treating decentralized domestic wastewater in rural China, this study evaluates the effects of ceramsite size and structure, and water recirculation parameters, upon the performance of recirculating biofilter (RBF). RBF shows stable capability of chemical oxygen demand (COD) remediation and ammonia nitrification. In addition, the microbial flora and structures of the various layers in the system are analyzed via high-throughput sequencing in order to study the microbial diversity. The results indicate that while the ceramic particle size has no significant influence on the COD remediation capacity, the ceramics with smaller particle sizes exhibit better ammonia nitrogen (NH4+-N) removal ability, with a first-order linear relationship between the influent ammonia nitrogen load and the effluent NH4+-N concentration in RBF (R2 > 0.64). An increased hydraulic load and intermittent operation are shown to deteriorate the water quality with respect to NH4+-N, while an increased recirculation ratio increases the removal rate of NH4+-N from the effluent. Further, the water distribution time has a stronger effect upon the NH4+-N concentration in the effluent than does the recirculation ratio. Moreover, the microbial structure of the multi-layer recirculating trickle biofilter varies significantly during the process. The results indicate that a high recirculation ratio, long water distribution time, and multi-layer structure will be beneficial for improving the pollutant treatment capacity of RBF.

Enhancement of Growth and Synthesis of Extracellular Enzymes of Morchella sextelata Induced by Co-culturing with Trichoderma.

Trichoderma is a genus of common filamentous fungi that display a various range of lifestyles and interactions with other fungi. The interaction of Trichoderma with Morchella sextelata was explored in this study. Trichoderma sp. T-002 was isolated from a wild fruiting body of Morchella sextelata M-001 and identified as a closely related species of Trichoderma songyi based on morphological chracteristics and phylogenetic analysis of translation elongation factor1-alpha and inter transcribed spacer of rDNA. Further, we focussed on the influence of dry mycelia of T-002 on the growth and synthesis of extracellular enzymes of M-001. Among different treatments, M-001 showed the highest growth of mycelia with an optimal supplement of 0.33 g/100 mL of T-002. Activities of extracellular enzymes of M-001 were enhanced significantly by the optimal supplement treatment. Overall, T-002, a unique Trichoderma species, had a positive effect on mycelial growth and synthesis of extracellular enzymes of M-001.

Talonavicular-cuneiform arthrodesis for the treatment of Müller-Weiss: mid-term results of 15 cases after 5 years.

BACKGROUND: There is no gold standard for the operative treatment of patients with Müller-Weiss disease (MWD). This study reports the mid-term follow-up results for at least 5 years following talonavicular-cuneiform (TNC) arthrodesis for Müller-Weiss disease. METHODS: A total of 15 patients undergoing TNC arthrodesis for MWD were retrospectively reviewed between January 2015 and August 2017. Two senior doctors assessed the radiographic results twice at each visit (preoperative, three months after the operation, and final follow-up). The clinical results and complications from preoperative and final follow-up were recorded. RESULTS: The mean follow up period was 74.0 (range 64 to 90) months. The calcaneal pitch angle, lateral Meary's angle, anteroposterior (AP) Meary's angle, AP talocalcaneal angle, and talonavicular coverage were significantly different before and three months after the operation (p < 0.05). There was no significant difference between the radiographic results of three months after the operation and the final follow-up (p > 0.05). The radiological measurements of the two senior doctors were calculated and found to be moderate to strong (ICC:0.899-0.995). The AOFAS, VAS, and SF-12 scores significantly improved at the last follow-up compared to those before the operation (p < 0.05). Two patients experienced early complications, four had late complications, and one underwent a second operation of midfoot fusion with calcaneal osteotomy. CONCLUSION: This research confirms that using TNC arthrodesis for the treatment of MWD can substantially improve the clinical and radiographic results. These results were maintained until mid-term follow-up.

Platelet-Rich Plasma Injection Can Be a Viable Alternative to Corticosteroid Injection for Conservative Treatment of Rotator Cuff Disease: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To explore whether platelet-rich plasma (PRP) injection can be a viable alternative to corticosteroid (CS) injection for conservative treatment of rotator cuff disease. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, EMBASE, The Cochrane Library, and Web of Science were searched from January 1, 1990, to March 20, 2022, for English-language randomized controlled trials that compared PRP and CS injections for patients with rotator cuff disease. Two evaluators independently screened the literature, extracted data, and assessed the level of evidence and methodologic quality of the enrolled studies. The meta-analysis was conducted using RevMan software (version 5.3.3). RESULTS: Thirteen nonsurgical randomized controlled trials with 725 patients were included. Compared with CS, PRP provided statistically worse short-term (<2 months) changes in American Shoulder and Elbow Surgeons (ASES) assessment scores, Simple Shoulder Test scores, and Disabilities of the Arm, Shoulder and Hand questionnaire scores but provided better medium-term (2-6 months) changes in Disabilities of the Arm, Shoulder and Hand scores, as well as long-term (≥6 months) changes in Constant-Murley scores, ASES scores, and Simple Shoulder Test scores. No statistically significant differences regarding pain reduction were found between the 2 groups. PRP injections led to worse short-term changes in forward flexion and internal rotation but better medium-term changes in forward flexion and external rotation. PRP showed significantly lower rates of post-injection failure (requests for subsequent injections or surgical intervention prior to 12 months) than CS. No outcome reached the minimal clinically important difference. After sensitivity analyses excluding studies with substantial clinical and/or methodologic heterogeneity, PRP showed better medium-term changes in ASES scores and visual analog scale scores and long-term changes in visual analog scale scores that reached the minimal clinically important difference. CONCLUSIONS: Without the drawbacks of CS injection, PRP injection is not worse than CS injection in terms of pain relief and function recovery at any time point during follow-up. PRP injection may reduce rates of subsequent injection or surgery, and it might provide better improvements in pain and function in the medium to long term. PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease. LEVEL OF EVIDENCE: Meta-analysis of Level I and II studies.

A Combined Surgical Approach for Recurrent Patellar Dislocation in Adolescents with Patella Alta and Increased Tibial Tuberosity-Trochlear Groove Distance: Improved Clinical Outcomes but Decreased Posterior Tibial Slopes in Skeletally Immature Patients at Minimum Four-Year Follow-up.

PURPOSE: (1) To report the clinical and radiological outcomes of a surgical technique combining anatomic medial patellofemoral ligament reconstruction and tibia tuberosity transfer in adolescents with patella alta and elevated tibial tuberosity-trochlear groove (TT-TG) distance in the treatment of recurrent patellar dislocation (RPD); and (2) To investigate the potential risks of growth arrest or developmental deformities associated with this combined technique. METHODS: Medical records of patients who underwent the combined surgery from 2015 to 2019 were reviewed. This study included adolescents aged between 14 and 18 years with a Caton-Deschamps index (CDI) > 1.30 and TT-TG distance > 20 mm, with a minimum follow-up of 4 years. Radiological examinations including lateral views and full-length posteroanterior standing radiographs were investigated to assess patella height by CDI, posterior tibial slope (PTS) angle, side-to-side difference (SSD) in bone length, and lower extremity alignment by hip-knee-ankle (HKA) angle; computed tomography scans and magnetic resonance imaging (MRI) profiles were investigated to evaluate TT-TG distance and staging of growth plate closure. Other evaluations included preoperative and postoperative physical examination, Kujala score, and Tegner activity score. The patients were stratified into 3 subgroups according to an MRI-based staging system of the growth plate closure, and each outcome was analyzed. A cohort-specific minimal clinically important difference (MCID) estimation was performed using standard error of measurement. RESULTS: The average age at the time of surgery was 16.1 years (range, 14.1-17.8). The average follow-up was 5.6 years (range, 4.0-7.6). No recurrent dislocation occurred, and no clinically significant deformity or axis deviation was encountered. Postoperative patellar height by CDI was 1.00 ± 0.11 (range, 0.81-1.15). No significant differences were found in the preoperative and postoperative HKA angle or SSD in femur/tibia length among all subgroups. A significantly decreased PTS angle was found in patients with open growth plates, from 10.2° ± 1.7° before surgery to 8.1° ± 1.0° after surgery (P = .015). The Kujala score and Tegner score both significantly improved, from 65.5 ± 13.9 before surgery to 90.4 ± 7.2 after surgery in the Kujala score (P < .001) and from 4.0 ± 1.1 before surgery to 4.7 ± 1.3 after surgery in the Tegner score (P < .001). Of the whole cohort, 63.1%, 100%, 47.1%, and 94.1% of patients achieved the MCID for PTS angle, CDI, Tegner score, and Kujala score, respectively. CONCLUSION: This combined technique is safe and effective in treating RPD in skeletally mature adolescents with concurrent patella alta (CDI > 1.30) and TT-TG distance > 20 mm, permitting patients to have improved knee function and low complication rates. Nonetheless, patients with open growth plates demonstrated a decrease in PTS, which might predispose the knee to recurvatum and osteoarthritis in the long term. LEVEL OF EVIDENCE: Level IV, controlled case series.

Silver-Based Surface Plasmon Sensors: Fabrication and Applications.

A series of novel phenomena such as optical nonlinear enhancement effect, transmission enhancement, orientation effect, high sensitivity to refractive index, negative refraction and dynamic regulation of low threshold can be generated by the control of surface plasmon (SP) with metal micro-nano structure and metal/material composite structure. The application of SP in nano-photonics, super-resolution imaging, energy, sensor detection, life science, and other fields shows an important prospect. Silver nanoparticles are one of the commonly used metal materials for SP because of their high sensitivity to refractive index change, convenient synthesis, and high controllable degree of shape and size. In this review, the basic concept, fabrication, and applications of silver-based surface plasmon sensors are summarized.

Modelling Development in Radical (Co)Polymerization of Multivinyl Monomers.

Radical polymerization (RP) of multivinyl monomers (MVMs) provides a facile solution for manipulating polymer topology and has received increasing attention due to their industrial and academic significance. Continuous efforts have been made to understand their mechanism, which is the key to regulating materials structure. Modelling techniques have become a powerful tool that can provide detailed information on polymerization kinetics which is inaccessible by experiments. Many publications have reported the combination of experiments and modelling for free radical polymerization (FRP) and reversible-deactivation radical polymerizations (RDRP) of MVMs. Herein, a minireview is presented for the most important modelling techniques and their applications in FRP/RDRP of MVMs. This review hopes to illustrate that the combination of modelling and wet experiments can be a great asset to polymer researchers and inspire new thinking for the future MVMs experiment optimization and product design.