Unusual Dzyaloshinskii-Moriya Interaction in Graphene/Fe3GeTe2 Van der Waals Heterostructure.

Dzyaloshinskii-Moriya interaction (DMI) is shown to induce a topologically protected chiral spin texture in magnetic/nonmagnetic heterostructures. In the context of van der Waals spintronic devices, graphene emerges as an excellent candidate material. However, due to its negligible spin-orbit interaction, inducing DMI to stabilize topological spins when coupled to 3d-ferromagnets remains challenging. Here, it is demonstrated that, despite these challenges, a sizeable Rashba-type spin splitting followed by significant DMI is induced in graphene/Fe3GeTe2. This is made possible due to an interfacial electric field driven by charge asymmetry together with the broken inversion symmetry of the heterostructure. These findings reveal that the enhanced DMI energy parameter, resulting from a large effective electron mass in Fe3GeTe2, remarkably contributes to stabilizing non-collinear spins below the Curie temperature, overcoming the magnetic anisotropy energy. These results are supported by the topological Hall effect, which coexists with the non-trivial breakdown of Fermi liquid behavior, confirming the interplay between spins and non-trivial topology. This work paves the way toward the design and control of interface-driven skyrmion-based devices.

Transcription factor ZmDof22 enhances drought tolerance by regulating stomatal movement and antioxidant enzymes activities in maize (Zea mays L.).

KEY MESSAGE: The Dof22 gene encoding a deoxyribonucleic acid binding with one finger in maize, which is associated with its drought tolerance. The identification of drought stress regulatory genes is essential for the genetic improvement of maize yield. Deoxyribonucleic acid binding with one finger (Dof), a plant-specific transcription factor family, is involved in signal transduction, morphogenesis, and environmental stress responses. In present study, by weighted correlation network analysis (WGCNA) and gene co-expression network analysis, 15 putative Dof genes were identified from maize that respond to drought and rewatering. A real-time fluorescence quantitative PCR showed that these 15 genes were strongly induced by drought and ABA treatment, and among them ZmDof22 was highly induced by drought and ABA treatment. Its expression level increased by nearly 200 times after drought stress and more than 50 times after ABA treatment. After the normal conditions were restored, the expression levels were nearly 100 times and 40 times of those before treatment, respectively. The Gal4-LexA/UAS system and transcriptional activation analysis indicate that ZmDof22 is a transcriptional activator regulating drought tolerance and recovery ability in maize. Further, overexpressed transgenic and mutant plants of ZmDof22 by CRISPR/Cas9, indicates that the ZmDof22, improves maize drought tolerance by promoting stomatal closure, reduces water loss, and enhances antioxidant enzyme activity by participating in the ABA pathways. Taken together, our findings laid a foundation for further functional studies of the ZmDof gene family and provided insights into the role of the ZmDof22 regulatory network in controlling drought tolerance and recovery ability of maize.

Lanthanide Metal-Organic Frameworks Exhibiting Fluoro-Bridged Extended Chains: Synthesis, Crystal Structures, and Magnetic Properties.

Two fluoro-bridged lanthanide-containing metal-organic frameworks (MOFs) were synthesized using 2,2'-bipyridine-4,4'-dicarboxylic acid (BPDC), a fluorinated modulator, and a lanthanide nitrate. The syntheses of MOFs containing Gd3+ or Tb3+ and a closely related MOF structure containing Ho3+, Gd3+, or Tb3+ are presented. The presence of the fluorinated metal chains in these MOFs is shown through single crystal X-ray diffraction, energy dispersion X-ray spectroscopy, 19F nuclear magnetic resonance, and X-ray photoelectron spectroscopy. Magnetic measurements reveal weak antiferromagnetic exchange between the Ln3+ ions mediated by fluoride anions along the zigzag ladder chains present in the crystal structures of these MOFs.

A bromide substituted 2D additive for stable and efficient perovskite photovoltaics.

In this article, a bromide substituted 2D layered perovskite having a repeated vertical orientation and coexisting with the bulk of a 3D perovskite is reported for the first time. This novel structure is obtained through controlled compositional engineering of the perovskite precursor solution. The photovoltaic performance of this novel 2D/3D perovskite was higher than that of 3D MAPbI3 and a maximum photoconversion efficiency (PCE) of 17.4% was achieved. The devices fabricated using this perovskite heterostructure were stable and retained their initial PCE up to 20 days when kept open in a laboratory environment with 40% relative humidity.

Thoracic Duct Visualization in Esophageal Resection: A Pilot Trial.

INTRODUCTION: Inadvertent thoracic duct injury is common during esophagectomy and may result in postoperative chylothorax. This study's objective was to investigate utility of patent blue injection as a modality for intraoperative thoracic duct visualization. METHODS: A prospective, single-arm, interventional study of patients undergoing minimally invasive esophagectomy was performed. Patients were injected with patent blue dye into both groins prior to thoracic stage of surgery and assessed for duct visualization. Control group was formed by propensity score matching using retrospectively collected data regarding patients who underwent esophagectomy. RESULTS: A total of 25 patients were included in analysis, compared to a control of 50 patients after matching. Thoracic duct was visualized in 60% of patients in the study group (15/25 patients). Significant differences were found between study and control groups (p < 0.05) with regards to median operative time (422 vs. 285 min, respectively), overall complications (16 vs. 34%, respectively), and median postoperative length of stay (13.5 vs. 10 days, respectively). There was a difference in rate of chyle leak between study and control groups; however, this was not significant (0 vs. 12%, respectively, p = 0.17). CONCLUSION: Patent blue injection represents a simple method for thoracic duct visualization during minimally invasive esophagectomy which may improve surgical outcomes.

The Impact of Surgeon Volume on Unicompartmental Knee Arthroplasty Survivorship: A Michigan Arthroplasty Registry Collaborative Quality Initiative Database Analysis.

BACKGROUND: The utilization of unicompartmental knee arthroplasty (UKA) has remained low when compared to total knee arthroplasty (TKA), possibly due to higher rates of revision and reoperation. This study aimed to quantify surgeon UKA case-volumes and measure the effect of surgeon volume on early revision. We hypothesized that surgeons who have high case volumes would have lower revision rates compared to medium- and low-volume surgeons. METHODS: Primary UKAs were performed between February 2012 and November 2021, and associated revisions were identified utilizing the Michigan Arthroplasty Registry Collaborative Quality Initiative. Surgeon information, including total cases and annual UKA volume, was collected. Case volume per year was stratified as High (≥ 35 cases per year), Medium (15 to 34 cases per year), and low (< 15 cases per year). RESULTS: There were a total of 15,542 UKAs performed. Of these, 701 (4.5%) were revised, and 412 (58.8%) revisions occurred within 2 years. Of the 287 surgeons who performed an UKA in the registry, 237 (82.6%) were low-volume surgeons, 36 (12.5%) were medium-volume, and 14 (4.9%) were high-volume. High-volume surgeons were more likely to operate on older patients (P < 0.01), Medicare patients (P < 0.01), and patients who had American Society of Anesthesiologists scores of III and IV (P < 0.01). High-volume surgeons had significantly lower 5-year revision rates compared to medium and low-volume surgeons (high: 4.3% (95% confidence interval: 3.7 to 4.9), medium: 5.2% (4.4 to 6.1), low: 7.2% (6.4 to 8.0); P < 0.001). In comparison, the 5-year revision rate for TKA in Michigan was 3.0% (95% confidence interval: 2.9 to 3.1). CONCLUSIONS: When UKAs were performed by high-volume surgeons in the state of Michigan, there was better survivorship when compared to low-and medium-volume surgeons. High-volume surgeons were more likely to perform UKA on older patients, Medicare patients, and patients who had American Society of Anesthesiologists scores of III and IV. The revision rate for the high-volume surgeons still exceeded the 5-year revision rate for TKA in Michigan.

Selenium-Priming mediated growth and yield improvement of turnip under saline conditions.

Salt toxicity is one of the foremost environmental stresses that declines nutrient uptake, photosynthetic activity and growth of plants resulting in a decrease in crop yield and quality. Seed priming has become an emergent strategy to alleviate abiotic stress and improve plant growth. During the current study, turnip seed priming with sodium selenite (Na2SeO3) was investigated for its ability to mitigate salt stress. Turnip (Brassica rapa L. var. Purple Top White Globe) seeds primed with 75, 100, and 125 µML-1 of Se were subjected to 200 mM salt stress under field conditions. Findings of the current field research demonstrated that salt toxicity declined seed germination, chlorophyll content, and gas exchange characteristics of B. rapa seedling. Whereas, Se-primed seeds showed higher germination rate and plant growth which may be attributed to the decreased level of hydrogen peroxide (H2O2) and malondialdehyde (MDA) decreased synthesis of proline (36%) and besides increased total chlorophyll (46%) in applied turnip plants. Higher expression levels of genes encoding antioxidative activities (CAT, POD, SO,D and APX) mitigated oxidative stress induced by the salt toxicity. Additionally, Se treatment decreased Na+ content and enhanced K+ content resulting in elevated K+/Na+ ratio in the treated plants. The in-silico assessment revealed the interactive superiority of Se with antioxidant enzymes including CAT, POD, SOD, and APX as compared to sodium chloride (NaCl). Computational study of enzymes-Se and enzymes-NaCl molecules also revealed the stress ameliorative potential of Se through the presence of more Ramachandran-favored regions (94%) and higher docking affinities of Se (-6.3). The in-silico studies through molecular docking of Na2SeO3, NaCl, and ROS synthesizing enzymes (receptors) including cytochrome P450 (CYP), lipoxygenase (LOX), and xanthine oxidase (XO), also confirmed the salt stress ameliorative potential of Se in B. rapa. The increased Ca, P, Mg, and Zn nutrients uptake nutrients uptake in 100 µML-1 Se primed seedlings helped to adjust the stomatal conductivity (35%) intercellular CO2 concentration (32%), and photosynthetic activity (41%) resulting in enhancement of the yield attributes. More number of seeds per plant (6%), increased turnip weight (115 gm) root length (17.24 cm), root diameter (12 cm) as well as turnip yield increased by (9%tons ha-1) were recorded for 100 µML-1 Se treatment under salinity stress. Findings of the current research judiciously advocate the potential of Se seed priming for salt stress alleviation and growth improvement in B. rapa.

According to our best of knowledge, it is the first time that seed primed with Selenium have been evaluated regarding NaCl stress mitigation in turnip. Salinity toxicity negatively affected physiochemical activities and growth of B.rapa.Seed priming with Selenium (Na₂SeO₃) mitigated salinity stress.Selenium (Se) enhanced nutrition, photosynthetic and antioxidant activity of applied plants.Selenium treated plants exhibited improved growth and reduced salinity content.

Evaluating the Impact of Pre-Configured Uplink Resources in Narrowband IoT.

Deploying Cellular Internet of Things (CIoT) devices in urban and remote areas faces significant energy efficiency challenges. This is especially true for Narrowband IoT (NB-IoT) devices, which are expected to function on a single charge for up to 10 years while transmitting small amounts of data daily. The 3rd Generation Partnership Project (3GPP) has introduced energy-saving mechanisms in Releases 13 to 16, including Early Data Transmission (EDT) and Preconfigured Uplink Resources (PURs). These mechanisms extend battery life and reduce latency by enabling data transmission without an active Radio Resource Control (RRC) connection or Random Access Procedure (RAP). This paper examines these mechanisms using the LENA-NB simulator in the ns-3 environment, which is a comprehensive framework for studying various aspects of NB-IoT. The LENA-NB has been extended with PURs, and our analysis shows that PURs significantly enhance battery life and latency efficiency, particularly in high-density environments. Compared to the default RAP method, PURs reduce energy consumption by more than 2.5 times and increases battery life by 1.6 times. Additionally, PURs achieve latency reductions of 2.5-3.5 times. The improvements with PURs are most notable for packets up to 125 bytes. Our findings highlight PURs' potential to enable more efficient and effective CIoT deployments across various scenarios. This study represents a detailed analysis of latency and energy consumption in a simulated environment, advancing the understanding of PURs' benefits.

Pulsed-Mode Metalorganic Vapor-Phase Epitaxy of GaN on Graphene-Coated c-Sapphire for Freestanding GaN Thin Films.

We report the growth of high-quality GaN epitaxial thin films on graphene-coated c-sapphire substrates using pulsed-mode metalorganic vapor-phase epitaxy, together with the fabrication of freestanding GaN films by simple mechanical exfoliation for transferable light-emitting diodes (LEDs). High-quality GaN films grown on the graphene-coated sapphire substrates were easily lifted off by using thermal release tape and transferred onto foreign substrates. Furthermore, we revealed that the pulsed operation of ammonia flow during GaN growth was a critical factor for the fabrication of high-quality freestanding GaN films. These films, exhibiting excellent single crystallinity, were utilized to fabricate transferable GaN LEDs by heteroepitaxially growing InxGa1-xN/GaN multiple quantum wells and a p-GaN layer on the GaN films, showing their potential application in advanced optoelectronic devices.

Systematic Analysis of the BrHAT Gene Family and Physiological Characteristics of Brassica rapa L. Treated with Histone Acetylase and Deacetylase Inhibitors under Low Temperature.

Brassica rapa L. is an important overwintering oilseed crop in Northwest China. Histone acetyltransferases (HATs) play an important role in epigenetic regulation, as well as the regulation of plant growth, development, and responses to abiotic stresses. To clarify the role of histone acetylation in the low-temperature response of B. rapa L., we identified 29 HAT genes in B. rapa L. using bioinformatics tools. We also conducted a comprehensive analysis of the physicochemical properties, gene structure, chromosomal localization, conserved structural domains and motifs, cis-acting regulatory elements, and evolutionary relationships of these genes. Using transcriptome data, we analyzed the expression patterns of BrHAT family members and predicted interactions between proteins; the results indicated that BrHATs play an important role in the low-temperature response of B. rapa L. HAT inhibitor (curcumin; CUR) and histone deacetylase inhibitor (Trichostatin A; TSA) were applied to four B. rapa L. varieties varying in cold resistance under the same low-temperature conditions, and changes in the physiological indexes of these four varieties were analyzed. The inhibitor treatment attenuated the effect of low temperature on seed germination, and curcumin treatment was most effective, indicating that the germination period was primarily regulated by histone acetylase. Both inhibitor treatments increased the activity of protective enzymes and the content of osmoregulatory substances in plants, suggesting that histone acetylation and deacetylation play a significant role in the response of B. rapa L. to low-temperature stress. The qRT-PCR analyses showed that the expression patterns of BrHATs were altered under different inhibitor treatments and low-temperature stress; meanwhile, we found three significantly differentially expressed genes. In sum, the process of histone acetylation is involved in the cold response and the BrHATs gene plays a role in the cold stress response.

Chemical Composition of Essential Oils from Natural Populations of Artemisia scoparia Collected at Different Altitudes: Antibacterial, Mosquito Repellent, and Larvicidal Effects.

The current study aimed to evaluate the presence of chemical variations in essential oils (EOs) extracted from Artemisia scoparia growing at different altitudes and to reveal their antibacterial, mosquito larvicidal, and repellent activity. The gas chromatographic-mass spectrometric analysis of A. scoparia EOs revealed that the major compounds were capillene (9.6-31.8%), methyleugenol (0.2-26.6%), ß-myrcene (1.9-21.4%), γ-terpinene (1.5-19.4%), trans-ß-caryophyllene (0.8-12.4%), and eugenol (0.1-9.1%). The EO of A. scoparia collected from the city of Attock at low elevation was the most active against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa bacteria (minimum inhibitory concentration of 156-1250 µg/mL) and showed the best mosquito larvicidal activity (LC50, 55.3 mg/L). The EOs of A. scoparia collected from the high-altitude areas of Abbottabad and Swat were the most repellent for females of Ae. aegypti and exhibited repellency for 120 min and 165 min, respectively. The results of the study reveal that different climatic conditions and altitudes have significant effects on the chemical compositions and the biological activity of essential oils extracted from the same species.

Chemical Composition, Repellent, and Oviposition Deterrent Potential of Wild Plant Essential Oils against Three Mosquito Species.

In this study, the chemical composition, repellent, and oviposition deterrent effects of five plant essential oils (EOs) extracted from Lantana camara (Verbenaceae), Schinus terebinthifolia (Anacardiaceae), Callistemon viminalis (Myrtaceae), Helichrysum odoratissimum (Asteraceae), and Hyptis suaveolens (Lamiaceae) were evaluated against Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus. When tested at 33.3 µg/cm2, L. camara, S. terebinthifolia, C. viminalis, and H. odoratissimum were effective repellents against Ae. aegypti (89%, 91%, 90%, and 51% repellency, respectively), but they were less repellent against An. gambiae (66%, 86%, 59%, and 49% repellency, respectively). Interestingly, L. camara, S. terebinthifolia, C. viminalis, and H. odoratissimum exhibited 100% repellency against Cx. quinquefasciatus at 33.3 µg/cm2. In time-span bioassays performed at 333 µg/cm2, the EO of L. camara exhibited 100% repellence against Ae. aegypti and An. gambiae for up to 15 min and against Cx. quinquefasciatus for 75 min. The oviposition bioassays revealed that L. camara exhibited the highest activity, showing 85%, 59%, and 89% oviposition deterrence against Ae. aegypti, An. gambiae, and Cx. quinquefasciatus, respectively. The major compounds of L. camara, S. terebinthifolia, and C. viminalis were trans-ß-caryophyllene (16.7%), α-pinene (15.5%), and 1,8-cineole (38.1%), respectively. In conclusion, the L. camara and S. terebinthifolia EOs have the potential to be natural mosquito repellents.

Evaluating iodine deficiency and goiter in hilly areas of District Poonch Azad Jammu Kashmir.

Background & Objectives: Iodine deficiency is considered as a global challenge, even after decades of efforts to solve the issue. Our objective was to assess the iodine deficiency status and associated prevalence of goiter in population groups (school-age children and women) from rural areas of District Poonch, and to assess the determinants of iodine deficiency in the area. Methods: Cross-sectional study was conducted in District Poonch Azad Jammu and Kashmir from 25 April 2022 to 30 June 2023. A total of 150 goiter patients from different villages of the District Poonch was included. Their urinary iodine concentration and goiter prevalence was assessed. Using palpation techniques, a trained and experienced public health officer assessed the presence of goiters based on WHO/ UNICEF/ICCIDD criteria. Descriptive statistics were computed for continuous variables and presented in frequency and percentage, based on the distributional characteristics of the data. chi-square was used to check association between socio-demographic factors and goiter. It was a HEC Project No.: 20-16988/NRPU/R&D/HEC/2021. Results: Iodine status and associated goiter prevalence was high and 59.3% of them were severely iodine deficient. Within the district, the highest severe iodine deficiency was observed in 81.1% goiter patients of the Rawalakot subdivision, Hajira and Abbaspur subdivisions. Regarding goiter status 40% of the patients were classified with palpable-visible goiter and 56% were characterized with visible but nodular goiter. Conclusion: Study showed that there was a severe iodine deficiency and associated goiter prevalence in the area. Policymakers should take actions for future to overcome iodine deficiency in future.

Binary and ternary complex formation and characterization of artemisinin with sulfobutyl ether ß-cyclodextrin and oleic acid.

Drug-resistant malaria is a global risk to the modern world. Artremisinin (ART) is one of the drugs of choice against drug-resistant (malaria) which is practically insoluble in water. The objective of our study was to improve the solubility of artemisinin (ART) via development of binary complexes of ART with sulfobutylether ß-cyclodextrins (SBE7 ß-CD), sulfobutylether ß-cyclodextrins (SBE7 ß-CD) and oleic acid (ternary complexes). These are prepared in various drugs to excipients ratios by physical mixing (PM) and solvent evaporation (SE) methods. Characterizations were achieved by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and attenuated total reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy. The aqueous-solubility in binary complexes was 12-folds enhanced than ternary complexes. Dissolution of binary and ternary complexes of artemisinin in simulated gastric fluid (pH 1.6) was found highest and 35 times higher for ternary SECx. The crystallinity of artemisinin was decreased in physical mixtures (PMs) while SECx exhibited displaced angles. The attenuated-intensity of SECx showed least peak numbers with more displaced-angles. SEM images of PMs and SECx showed reduced particle size in binary and ternary systems as compared to pure drug-particles. ATR-FTIR spectra of binary and ternary complexes revealed bonding interactions among artemisinin, SBE7 ß-CD and oleic acid.

Pyroptosis, ferroptosis, and autophagy cross-talk in glioblastoma opens up new avenues for glioblastoma treatment.

Glioma is a common primary tumor of the central nervous system (CNS), with glioblastoma multiforme (GBM) being the most malignant, aggressive, and drug resistant. Most drugs are designed to induce cancer cell death, either directly or indirectly, but malignant tumor cells can always evade death and continue to proliferate, resulting in a poor prognosis for patients. This reflects our limited understanding of the complex regulatory network that cancer cells utilize to avoid death. In addition to classical apoptosis, pyroptosis, ferroptosis, and autophagy are recognized as key cell death modalities that play significant roles in tumor progression. Various inducers or inhibitors have been discovered to target the related molecules in these pathways, and some of them have already been translated into clinical treatment. In this review, we summarized recent advances in the molecular mechanisms of inducing or inhibiting pyroptosis, ferroptosis, or autophagy in GBM, which are important for treatment or drug tolerance. We also discussed their links with apoptosis to better understand the mutual regulatory network among different cell death processes. Video Abstract.

Insight into crustacean cathepsins: Structure-evolutionary relationships and functional roles in physiological processes.

Cathepsins belong to a group of proteins that are present in both prokaryotic and eukaryotic organisms and have an extremely high degree of evolutionary conservation. These proteins are functionally active in extracellular environments as soluble enzymatic proteins or attached to plasma membrane receptors. In addition, they occur in cellular secretory vesicles, mitochondria, the cytosol, and within the nuclei of eukaryotic cells. Cathepsins are classified into various groups based on their sequence variations, leading to their structural and functional diversification. The molecular understanding of the physiology of crustaceans has shown that proteases, including cathepsins, are expressed ubiquitously. They also contain one of the central regulatory systems for crustacean reproduction, growth, and immune responses. This review focuses on various aspects of the crustaceans cathepsins and emphasizes their biological roles in different physiological processes such as reproduction, growth, development, and immune responses. We also describe the bioactivity of crustaceans cathepsins. Because of the vital biological roles that cathepsins play as cellular proteases in physiological processes, they have been proposed as potential novel targets for the development of management strategies for the aquaculture industries.

Synthesis of Fluoro-Bridged Ho3+ and Gd3+ 1,3,5-Tris(4-carboxyphenyl)benzene Metal-Organic Frameworks from Perfluoroalkyl Substances.

A new fluoro-bridged rare-earth (RE) metal-organic framework consisting of 15-connected nonanuclear and 9-connected trinuclear clusters {[RE9-(µ3-F)14(H2O)6][RE3(µ3-F)(H2O)3](HCO2)3-(BTB)6}·(solvent)x 2 (RE = Ho3+ and Gd3+) was synthesized through the transformation of a dimeric complex formulated as bis(2,2'-bipyridine)tetrakis(µ-2-fluorobenzoato-O,O')-bis(2-fluorobenzoato)diRE(III) 1 with the bridging linker 1,3,5-tris(4-carboxyphenyl)benzene (H3BTB). The rare-earth metal ions Ho3+ and Gd3+ were also found to remove fluorine from other organo-fluorine compounds such as perfluorohexanoic acid (PFHxA) and perfluorooctanoic acid (PFOA), resulting in the new fluoro-bridged RE-MOFs.

Bcl6 drives stem-like memory macrophages differentiation to foster tumor progression.

Cancer development is a long-lasting process during which macrophages play a pivotal role. However, how macrophages maintain their cellular identity, persistence, expanding and pro-tumor property during malignant progression remains elusive. Inspired by the recent report of the activation of stem cell-like self-renewal mechanism in mature macrophages, we postulate that intra-tumoral macrophages might be trained to assume stem-like properties and memory-like activity favoring cancer development. Herein we demonstrated that tumor infiltrating macrophages rapidly converted into the CD11b+F4/80+Ly6C-Bcl6+ phenotype, and adopted stem cell-like properties involving expression of stemness-related genes, long-term persistence and self-renewing. Importantly, Bcl6+ macrophages stably maintained cell identity, gene signature, metabolic profile, and pro-tumor property even after long-term culture in tumor-free medium, which were hence termed stem cell-like memory macrophages (SMMs). Mechanistically, we showed that transcriptional factor Bcl6 co-opted the demethylase Tet2 and the deacetylase SIRT1 to confer the epigenetic imprinting and mitochondrial metabolic traits to SMMs, bolstering the stability and longevity of trained immunity in tumor-associated macrophages (TAMs). Furthermore, tumor-derived redHMGB1 was identified as the priming signal, which, through TLR4 and mTOR/AKT pathway, induced Bcl6-driven program underpinning SMMs generation. Collectively, our study uncovers a distinct macrophage population with a hybrid of stem cell and memory cell properties, and unveils a regulatory mechanism that integrates transcriptional, epigenetic and metabolic pathways to promote long-lasting pro-tumor immunity.

Blood Flow Restriction Therapy for 2 Weeks Prior to Anterior Cruciate Ligament Reconstruction Did Not Impact Quadriceps Strength Compared to Standard Therapy.

PURPOSE: To evaluate the efficacy of a 2-week home-based blood flow restriction (BFR) prehabiliation program on quadriceps strength and patient-reported outcomes prior to anterior cruciate ligament (ACL) reconstruction. METHODS: Patients presenting with an ACL tear were randomized into two groups, BFR and control, at their initial clinic visit. Quadriceps strength was measured using a handheld dynamometer in order to calculate peak force, average force, and time to peak force during seated leg extension at the initial clinic visit and repeated on the day of surgery. All patients were provided education on standardized exercises to be performed 5 days per week for 2 weeks between the initial clinic visit and date of surgery. The BFR group was instructed to perform these exercises with a pneumatic cuff set to 80% of limb occlusion pressure placed over the proximal thigh. Patient-Reported Outcome Measurement System Physical Function (PROMIS-PF), knee range of motion, and quadriceps circumference were gathered at the initial clinic visit and day of surgery, and patients were monitored for adverse effects. RESULTS: A total 45 patients met inclusion criteria and elected to participate. There were 23 patients randomized to the BFR group and 22 patients randomized into the control group. No significant differences were noted between the BFR and control groups in any demographic characteristics (48% vs 64% male [P = .271] and average age 26.5 ± 12.0 vs 27.0 ± 11.0 [P = .879] in BFR and control, respectively). During the initial clinic visit, there were no significant differences in quadriceps circumference, peak quadriceps force generation, time to peak force, average force, pain, and PROMIS scales (P > .05 for all). Following completion of a 2-week home prehabilitation protocol, all patients indeterminant of cohort demonstrated decreased strength loss in the operative leg compared to the nonoperative leg (P < .05 for both) However, there were no significant differences in any strength or outcome measures between the BFR and control groups (P > .05 for all). There were no complications experienced in either group, and both were compliant with the home-based prehabilitation program. CONCLUSIONS: A 2-week standardized prehabilitation protocol preceding ACL reconstruction resulted in a significant improvement in personal quadriceps peak force measurements, both with and without the use of BFR. No difference in quadriceps circumference, strength, or patient reported outcomes were found between the BFR and the control group. The home-based BFR prehabiliation protocol was found to be feasible, accessible, and well tolerated by patients. LEVEL OF EVIDENCE: Level II, randomized controlled trial with small effect size.

Machine Learning Model Identifies Preoperative Opioid Use, Male Sex, and Elevated Body Mass Index as Predictive Factors for Prolonged Opioid Consumption Following Arthroscopic Meniscal Surgery.

PURPOSE: To develop a predictive machine learning model to identify prognostic factors for continued opioid prescriptions after arthroscopic meniscus surgery. METHODS: Patients undergoing arthroscopic meniscal surgery, such as meniscus debridement, repair, or revision at a single institution from 2013 to 2017 were retrospectively followed up to 1 year postoperatively. Procedural details were recorded, including concomitant procedures, primary versus revision, and whether a partial debridement or a repair was performed. Intraoperative arthritis severity was measured using the Outerbridge Classification. The number of opioid prescriptions in each month was recorded. Primary analysis used was the multivariate Cox-Regression model. We then created a naïve Bayesian model, a machine learning classifier that uses Bayes' theorem with an assumption of independence between variables. RESULTS: A total of 581 patients were reviewed. Postoperative opioid refills occurred in 98 patients (16.9%). Multivariate logistic modeling was used; independent risk factors for opioid refills included male sex, larger body mass index, and chronic preoperative opioid use, while meniscus resection demonstrated decreased likelihood of refills. Concomitant procedures, revision procedures, and presence of arthritis graded by the Outerbridge classification were not significant predictors of postoperative opioid refills. The naïve Bayesian model for extended postoperative opioid use demonstrated good fit with our cohort with an area under the curve of 0.79, sensitivity of 94.5%, positive predictive value (PPV) of 83%, and a detection rate of 78.2%. The two most important features in the model were preoperative opioid use and male sex. CONCLUSION: After arthroscopic meniscus surgery, preoperative opioid consumption and male sex were the most significant predictors for sustained opioid use beyond 1 month postoperatively. Intraoperative arthritis was not an independent risk factor for continued refills. A machine learning algorithm performed with high accuracy, although with a high false positive rate, to function as a screening tool to identify patients filling additional narcotic prescriptions after surgery. LEVEL OF EVIDENCE: III, retrospective comparative study.