Selective Chemical Inhibition of PGC-1α Gluconeogenic Activity Ameliorates Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes. On the basis of potency and bioavailability, we selected a small molecule, SR-18292, that reduces blood glucose, strongly increases hepatic insulin sensitivity, and improves glucose homeostasis in dietary and genetic mouse models of T2D. These studies have important implications for understanding the regulatory mechanisms of glucose metabolism and treatment of T2D.

Inflammation Improves Glucose Homeostasis through IKKß-XBP1s Interaction.

It is widely believed that inflammation associated with obesity has an important role in the development of type 2 diabetes. IκB kinase beta (IKKß) is a crucial kinase that responds to inflammatory stimuli such as tumor necrosis factor α (TNF-α) by initiating a variety of intracellular signaling cascades and is considered to be a key element in the inflammation-mediated development of insulin resistance. We show here, contrary to expectation, that IKKß-mediated inflammation is a positive regulator of hepatic glucose homeostasis. IKKß phosphorylates the spliced form of X-Box Binding Protein 1 (XBP1s) and increases the activity of XBP1s. We have used three experimental approaches to enhance the IKKß activity in the liver of obese mice and observed increased XBP1s activity, reduced ER stress, and a significant improvement in insulin sensitivity and consequently in glucose homeostasis. Our results reveal a beneficial role of IKKß-mediated hepatic inflammation in glucose homeostasis.

Treatment of obesity with celastrol.

Despite all modern advances in medicine, an effective drug treatment of obesity has not been found yet. Discovery of leptin two decades ago created hopes for treatment of obesity. However, development of leptin resistance has been a big obstacle, mitigating a leptin-centric treatment of obesity. Here, by using in silico drug-screening methods, we discovered that Celastrol, a pentacyclic triterpene extracted from the roots of Tripterygium Wilfordi (thunder god vine) plant, is a powerful anti-obesity agent. Celastrol suppresses food intake, blocks reduction of energy expenditure, and leads to up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity, but it is ineffective in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mouse models. These results indicate that Celastrol is a leptin sensitizer and a promising agent for the pharmacological treatment of obesity.

Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis.

As in type 1 diabetes, the loss of pancreatic ß-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting ß-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exerciseinduced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.

Endoplasmic reticulum stress in pancreatic ß cells induces incretin desensitization and ß-cell dysfunction via ATF4-mediated PDE4D expression.

Pancreatic ß-cell dysfunction and eventual loss are key steps in the progression of type 2 diabetes (T2D). Endoplasmic reticulum (ER) stress responses, especially those mediated by the protein kinase RNA-like ER kinase and activating transcription factor 4 (PERK-ATF4) pathway, have been implicated in promoting these ß-cell pathologies. However, the exact molecular events surrounding the role of the PERK-ATF4 pathway in ß-cell dysfunction remain unknown. Here, we report our discovery that ATF4 promotes the expression of PDE4D, which disrupts ß-cell function via a downregulation of cAMP signaling. We found that ß-cell-specific transgenic expression of ATF4 led to early ß-cell dysfunction and loss, a phenotype that resembles accelerated T2D. Expression of ATF4, rather than C/EBP homologous protein (CHOP), promoted PDE4D expression, reduced cAMP signaling, and attenuated responses to incretins and elevated glucose. Furthermore, we found that ß-cells of leptin receptor-deficient diabetic (db/db) mice had elevated nuclear localization of ATF4 and PDE4D expression, accompanied by impaired ß-cell function. Accordingly, pharmacological inhibition of the ATF4 pathway attenuated PDE4D expression in the islets and promoted incretin-simulated glucose tolerance and insulin secretion in db/db mice. Finally, we found that inhibiting PDE4 activity with selective pharmacological inhibitors improved ß-cell function in both db/db mice and ß-cell-specific ATF4 transgenic mice. In summary, our results indicate that ER stress causes ß-cell failure via ATF4-mediated PDE4D production, suggesting the ATF4-PDE4D pathway could be a therapeutic target for protecting ß-cell function during the progression of T2D.NEW & NOTEWORTHY Endoplasmic reticulum stress has been implied to cause multiple ß-cell pathologies during the progression of type 2 diabetes (T2D). However, the precise molecular events underlying this remain unknown. Here, we discovered that elevated ATF4 activity, which was seen in T2D ß cells, attenuated ß-cell proliferation and impaired insulin secretion via PDE4D-mediated downregulation of cAMP signaling. Additionally, we demonstrated that pharmacological inhibition of the ATF4 pathway or PDE4D activity alleviated ß-cell dysfunction, suggesting its therapeutic usefulness against T2D.

Multifunctionality of Additively Manufactured Kelvin Foam for Electromagnetic Wave Absorption and Load Bearing.

Rationally engineered porous structures enable lightweight broadband electromagnetic (EM) wave absorbers for countering radar signals or mitigating EM interference between multiple components. However, the scalability of such structures has been hindered by their limited mechanical properties resulting from low density. Herein, an additively manufactured Kelvin foam-based EM wave absorber (KF-EMA) is reported that exhibits multifunctionality, namely EM wave absorption and light-weighted load-bearing structures with constant relative stiffness made possible using bending-dominated lattice structures. Based on tuning design parameters, such as the backbone structures and constituent materials, the proposed KF-EMA features a multilayered 3D-printed design with geometrically optimized KF structures made of carbon black-based backbone composites. The developed KF-EMA demonstrated an absorbance greater than 90% at frequencies ranging from 5.8 to 18 GHz (average EM wave absorption rates of 95.89% and maximum of 99.1% at 15.8 GHz), while the low-density structures of the absorber (≈200 kg m-3 ) still maintained a compression index between the stiffness and relative density (n = 2) under compression. The design strategy paves the way for using metamaterials as mechanically reinforced EM wave absorbers that enable multifunctionality by optimizing unit-cell parameters through a single and low-density structure.

Changes in the mean incidence and variance of orthopedic diseases before and during the COVID-19 pandemic in Korea: a retrospective study.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, the amount of moderate- to high-intensity physical activity significantly decreased. Therefore, the epidemiology of musculoskeletal diseases could possibly have changed. We assessed changes in the incidence of and variance in non-traumatic orthopedic diseases before and after the COVID-19 pandemic in Korea. METHODS: This study included data from the Korea National Health Insurance Service, which covers the entire Korean population (approximately 50 million), from January 2018 to June 2021. Using International Classification of Diseases, Tenth Revision codes, 12 common orthopedic diseases were evaluated, including cervical disc disorders, lumbar disc disorders, forward head posture, myofascial pain syndrome, carpal tunnel syndrome, tennis elbow, frozen shoulder, rheumatoid arthritis, gout, hip fracture, distal radius fracture, and spine fracture diseases. "Pre-COVID-19" was the period until February 2020, and "COVID-19 pandemic period" was the period starting March 2020. Differences in the mean incidence and variance of diseases before and during the COVID-19 pandemic were compared. RESULTS: In most cases, the incidence of orthopedic diseases decreased at the beginning of the pandemic and then increased thereafter. Among the 12 diseases, the incidence of three diseases showed a statistically significant change. The incidence of myofascial pain syndrome (P < 0.001) was lower during the COVID-19 pandemic than during the pre-COVID-19 period. The incidences of frozen shoulder (P < 0.001) and gout (P = 0.043) were higher during the COVID-19 pandemic than during the pre-COVID-19 period. However, no statistical difference in disease variations was observed between the two periods. CONCLUSIONS: The incidence of orthopedic diseases varied during the COVID-19 pandemic among the Korean population. Although the incidence of myofascial pain syndrome was lower, that of frozen shoulder and gout was higher during the COVID-19 pandemic than during the pre-COVID-19 period. No disease variations during the COVID-19 pandemic were found.

Latarjet procedure without capsular repair produces favorable clinical results and avoids limitation in external rotation.

PURPOSE: This study aimed at analyzing the range of motion (ROM) and other clinical outcomes in patients with > 20% glenoid bone loss who underwent the Latarjet procedure with or without anterior capsule repair. METHODS: This retrospective study included 47 patients with > 20% glenoid bone loss who underwent the classic Latarjet procedure from 2016 to 2021. Of these, 25 did not undergo capsular repair (no-capsular-repair group; group I) whereas 22 patients did (capsular-repair group; group II). The Rowe score, American Shoulder and Elbow Surgeons score, Visual Analogue Scale, ROM, recurrence, and complications were evaluated before and 3, 6, and 12 months after the surgery. A goniometer was used to measure the forward flexion and external rotation (arm adducted, 90° abducted) of both shoulders. The ROM deficit was measured as the difference from the contralateral healthy shoulder. RESULTS: The external rotation in arm adduction at 3 and 6 months after surgery showed significantly better results in group I than group II(p = 0.002 at 3 months; p = 0.005 at 6 months). The deficit in external rotation with arm adduction was also significantly lower in group I at 3 months (p = 0.001) and 6 months (p = 0.001) after surgery. However, external rotation with arm adduction at 12 months after surgery did not significantly differ between the groups. Moreover, the ROM in external rotation with 90° arm abduction was significantly better in group I than that in group II at 3, 6, and 12 months postoperatively (p = 0.002, p = 0.001, and p = 0.005, respectively). The deficit in external rotation with 90° arm abduction gradually decreased with time after surgery and differed significantly between the groups. However, the difference in deficit between the two groups at 12 months after surgery did not exceed the measurement error. All clinical scores significantly improved after surgery compared to before surgery; however, the improvement did not significantly differ between the two groups. CONCLUSION: The Latarjet procedure without capsular repair showed good laxity restoration and clinical results with less early postoperative external rotation limitation than that achieved by the same procedure with capsular repair. However, external rotation deficit at 1 year after surgery did not show a clinically relevant difference difference between the two groups. LEVEL OF EVIDENCE: Level III.

ALIEN: Assisted Learning Invasive Encroachment Neutralization for Secured Drone Transportation System.

Priority-based logistics and the polarization of drones in civil aviation will cause an extraordinary disturbance in the ecosystem of future airborne intelligent transportation networks. A dynamic invention needs dynamic sophistication for sustainability and security to prevent abusive use. Trustworthy and dependable designs can provide accurate risk assessment of autonomous aerial vehicles. Using deep neural networks and related technologies, this study proposes an artificial intelligence (AI) collaborative surveillance strategy for identifying, verifying, validating, and responding to malicious use of drones in a drone transportation network. The dataset for simulation consists of 3600 samples of 9 distinct conveyed objects and 7200 samples of the visioDECT dataset obtained from 6 different drone types flown under 3 different climatic circumstances (evening, cloudy, and sunny) at different locations, altitudes, and distance. The ALIEN model clearly demonstrates high rationality across all metrics, with an F1-score of 99.8%, efficiency with the lowest noise/error value of 0.037, throughput of 16.4 Gbps, latency of 0.021, and reliability of 99.9% better than other SOTA models, making it a suitable, proactive, and real-time avionic vehicular technology enabler for sustainable and secured DTS.

Expression and Role of Toll-like Receptors in Facial Nerve Regeneration after Facial Nerve Injury.

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1-13. Among these, TLR2-5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1-5, TLR8, and TLR10-13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.

Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.

AIM: To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like peptide-1 receptor (GLP-1R) agonists. METHODS: We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model. RESULTS: Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis. They also increased thermogenesis in brown adipose tissue, and lipolysis and ß-oxidation in white adipose tissue, with concomitant suppression of lipogenesis. Furthermore, both dual agonists activated the 5'-AMP-activated protein kinase signalling pathway and prevented palmitate-induced oxidative stress in skeletal muscle cells. CONCLUSION: Through their complementary dual agonism, sEx4-GCG(T) and sEx4-GCG(K) induce more marked weight loss and metabolic improvements than conventional agonists, and could be developed as novel therapeutic agents for the treatment of obesity and associated metabolic disorders in humans.

Safety and Diagnostic Yield of Radial Probe Endobronchial Ultrasound-Guided Biopsy for Peripheral Lung Lesions in Patients with Idiopathic Pulmonary Fibrosis: A Multicenter Cross-Sectional Study.

BACKGROUND: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) is widely used for diagnosis of peripheral lung lesions (PLLs). To date, there have been no reports regarding the clinical outcomes of RP-EBUS-TBLB for PLLs in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: This study was performed between October 2017 and December 2019 to identify the safety and diagnostic performance of RP-EBUS-TBLB in IPF patients. METHODS: Patients were divided into the usual interstitial pneumonia (UIP) group (n = 39, 4%), the probable UIP group (n = 12, 1%), and the noninterstitial lung disease (non-ILD) group (n = 903, 95%). RESULTS: The diagnostic yield was significantly lower in the UIP group than in the non-ILD group (62% vs. 76%; p = 0.042), but there were no significant differences between the UIP and probable UIP groups (62% vs. 83%; p = 0.293) or the probable UIP and non-ILD groups (83% vs. 76%; p = 0.741). Multivariate logistic analysis showed that the mean diameter of PLLs, positive bronchus sign on CT, and "within the lesion" status on EBUS were independently associated with success of the procedure. Especially, the presence of the UIP pattern on CT (OR, 0.385; 95% CI: 0.172-0.863; p = 0.020) was independently associated with failed diagnosis. Among patients with UIP, "within the lesion" status on EBUS (OR, 25.432; 95% CI: 2.321-278.666; p = 0.008) was shown to be a factor contributing to a successful diagnosis. Overall, there were no significant differences in complication rates among the 3 study groups. CONCLUSION: RP-EBUS-TBLB can be performed safely with an acceptable diagnostic yield, even in patients with IPF.

Exploring Machine Learning-Based Fault Monitoring for Polymer-Based Additive Manufacturing: Challenges and Opportunities.

Three-dimensional printing, often known as additive manufacturing (AM), is a groundbreaking technique that enables rapid prototyping. Monitoring AM delivers benefits, as monitoring print quality can prevent waste and excess material costs. Machine learning is often applied to automating fault detection processes, especially in AM. This paper explores recent research on machine learning-based mechanical fault monitoring systems in fused deposition modeling (FDM). Specifically, various machine learning-based algorithms are applied to measurements extracted from different parts of a 3D printer to diagnose and identify faults. The studies often use mechanical-based fault analysis from data gathered from sensors that measure attitude, acoustic emission, acceleration, and vibration signals. This survey examines what has been achieved and opens up new opportunities for further research in underexplored areas such as SLM-based mechanical fault monitoring.

Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic ß-Cell Dysfunction and Senescence in Type 2 Diabetes.

An increased life span and accompanying nutritional affluency have led to a rapid increase in diseases associated with aging, such as obesity and type 2 diabetes, imposing a tremendous economic and health burden on society. Pancreatic ß-cells are crucial for controlling glucose homeostasis by properly producing and secreting the glucose-lowering hormone insulin, and the dysfunction of ß-cells determines the outcomes for both type 1 and type 2 diabetes. As the native structure of insulin is formed within the endoplasmic reticulum (ER), ER homeostasis should be appropriately maintained to allow for the proper metabolic homeostasis and functioning of ß-cells. Recent studies have found that cellular senescence is critically linked with cellular stresses, including ER stress, oxidative stress, and mitochondrial stress. These studies implied that ß-cell senescence is caused by ER stress and other cellular stresses and contributes to ß-cells' dysfunction and the impairment of glucose homeostasis. This review documents and discusses the current understanding of cellular senescence, ß-cell function, ER stress, its associated signaling mechanism (unfolded protein response), and the effect of ER stress on ß-cell senescence and dysfunction.

The Common Cellular Events in the Neurodegenerative Diseases and the Associated Role of Endoplasmic Reticulum Stress.

Neurodegenerative diseases are inseparably linked with aging and increase as life expectancy extends. There are common dysfunctions in various cellular events shared among neurogenerative diseases, such as calcium dyshomeostasis, neuroinflammation, and age-associated decline in the autophagy-lysosome system. However, most of all, the prominent pathological feature of neurodegenerative diseases is the toxic buildup of misfolded protein aggregates and inclusion bodies accompanied by an impairment in proteostasis. Recent studies have suggested a close association between endoplasmic reticulum (ER) stress and neurodegenerative pathology in cellular and animal models as well as in human patients. The contribution of mutant or misfolded protein-triggered ER stress and its associated signaling events, such as unfolded protein response (UPR), to the pathophysiology of various neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease, amyotrophic lateral sclerosis, and prion disease, is described here. Impaired UPR action is commonly attributed to exacerbated ER stress, pathogenic protein aggregate accumulation, and deteriorating neurodegenerative pathologies. Thus, activating certain UPR components has been shown to alleviate ER stress and its associated neurodegeneration. However, uncontrolled activation of some UPR factors has also been demonstrated to worsen neurodegenerative phenotypes, suggesting that detailed molecular mechanisms around ER stress and its related neurodegenerations should be understood to develop effective therapeutics against aging-associated neurological syndromes. We also discuss current therapeutic endeavors, such as the development of small molecules that selectively target individual UPR components and address ER stress in general.

Therapeutic Potential of Human Fetal Mesenchymal Stem Cells in Musculoskeletal Disorders: A Narrative Review.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta.

The Roles of NOD-like Receptors in Innate Immunity in Otitis Media.

Acute otitis media (AOM) can persist or lead to various complications in individuals in which the innate immune system is impaired. In this context, impaired expression of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor (PRR), is involved in the etiology of OM in humans and animals, affecting its development, severity, chronicity, recurrence, and associated complications. To assess this relationship, we reviewed literature reports relating NLR expression patterns with the pathophysiology and clinical features of OM in the larger context of impaired innate immunity. We summarized the results of published studies on the expression of NLRs in animals and humans in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. NLRs were expressed mainly in association with bacterial infection in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. In addition, expression of NLRs was affected by the presence or absence of bacteria, fluid characteristics, disease recurrence, tissue type, and repeated surgery. Various factors of the innate immune system are involved in the pathogenesis of OM in the middle ear. NLRs are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. Impaired NLR expression induced the development, chronicity and recurrence of OM and exacerbated associated complications, indicating that NLRs have important roles in the pathogenesis of OM.

A Bayesian Approach to Predict Football Matches with Changed Home Advantage in Spectator-Free Matches after the COVID-19 Break.

Since the coronavirus disease 2019 (COVID-19) pandemic, most professional sports events have been held without spectators. It is generally believed that home teams deprived of enthusiastic support from their home fans experience reduced benefits of playing on their home fields, thus becoming less likely to win. This study attempts to confirm if this belief is true in four major European football leagues through statistical analysis. This study proposes a Bayesian hierarchical Poisson model to estimate parameters reflecting the home advantage and the change in such advantage. These parameters are used to improve the performance of machine-learning-based prediction models for football matches played after the COVID-19 break. The study describes the statistical analysis on the impact of the COVID-19 pandemic on football match results in terms of the expected score and goal difference. It also shows that estimated parameters from the proposed model reflect the changed home advantage. Finally, the study verifies that these parameters, when included as additional features, enhance the performance of various football match prediction models. The home advantage in European football matches has changed because of the behind-closed-doors policy implemented due to the COVID-19 pandemic. Using parameters reflecting the pandemic's impact, it is possible to predict more precise results of spectator-free matches after the COVID-19 break.

Exposure to opposing views on social media can increase political polarization.

There is mounting concern that social media sites contribute to political polarization by creating "echo chambers" that insulate people from opposing views about current events. We surveyed a large sample of Democrats and Republicans who visit Twitter at least three times each week about a range of social policy issues. One week later, we randomly assigned respondents to a treatment condition in which they were offered financial incentives to follow a Twitter bot for 1 month that exposed them to messages from those with opposing political ideologies (e.g., elected officials, opinion leaders, media organizations, and nonprofit groups). Respondents were resurveyed at the end of the month to measure the effect of this treatment, and at regular intervals throughout the study period to monitor treatment compliance. We find that Republicans who followed a liberal Twitter bot became substantially more conservative posttreatment. Democrats exhibited slight increases in liberal attitudes after following a conservative Twitter bot, although these effects are not statistically significant. Notwithstanding important limitations of our study, these findings have significant implications for the interdisciplinary literature on political polarization and the emerging field of computational social science.

The Hybrid Latissimus Dorsi Flap in Immediate Breast Reconstruction: A Comparative Study With the Abdominal-Based Flap.

PURPOSE: The implant-enhanced latissimus dorsi (LD) flap, or a hybrid LD flap, is widely used in certain indications, even though abdominal-based flaps are now considered the gold standard of autologous breast reconstruction. However, few articles distinguish the hybrid LD flap from traditional LD flaps, and not many articles have compared the surgical outcomes, with the abdominal-based flap procedure, especially in the area of immediate breast reconstruction. In addition, it is often overlooked that the reported esthetic comparisons are based on different populations and contralateral balancing procedures (CBPs). Thus, this study aimed to review the reconstruction outcomes and to compare the variable-matched esthetic outcomes between 2 groups. METHODS: A retrospective review of patients who underwent immediate breast reconstruction with either a hybrid LD flap or an abdominal-based free flap and had completed at least 2 years of follow-up visits was carried out. The patient demographics, oncologic data, breast parameters, and postoperative outcomes were compared across the entire patient group. The body mass index (BMI)- and CBP-matched cohort was randomly selected and assessed using the Aesthetic Outcome parameter of the Aesthetic Item Scale. RESULT: Thirty-eight hybrid LD flap and 51 abdominal-based free flap procedures were included. The hybrid LD group showed a shorter operation time (330 ± 260 minutes vs 550 ± 480 minutes, respectively; P < 0.01), and fewer patients in the hybrid LD group underwent additional revision surgeries (7 [18.4%] vs 20 [39.2%], respectively; P < 0.01). Other complication rates were not significantly different between groups. A BMI- and CBP-matched esthetic analysis revealed that the hybrid LD group showed superior results in symmetry (Mann-Whitney U test, P = 0.047). CONCLUSIONS: The LD flap in combination with an implant remains a viable option in immediate breast reconstruction and had a similar complication profile while having a shorter operative time compared with the abdominal-based autologous breast reconstruction procedure. If properly used in certain populations, hybrid LD flaps may offer superior results regarding symmetry over the abdominal-based flap procedure.