Improved Glaucoma Medication Access Through Pharmacy Partnership: A Single Institution Experience.

Purpose: A major barrier to glaucoma medication adherence is the patient's out-of-pocket costs. At the University of Chicago Medical Center (UCMC), the institutional pharmacy piloted a program to query out-of-pocket costs for each patient's medication list based on their insurance coverage. This study aims to describe the impact of this collaboration between the glaucoma service and the outpatient pharmacy service. Methods: This study is a single institution, retrospective chart review of glaucoma patients with a formulary inquiry placed by a single glaucoma specialist between 4/1/2020 and 2/28/2022. Main outcome measures included medications before and after formulary inquiries, additional steps required to access the medications (ie, formulary exceptions, prior authorizations, tier exceptions), and out-of-pocket costs. Results: A total of 343 formulary inquiries, representing 568 individual medication inquiries, were conducted. Out of the 568 medication inquiries, only 78 could be filled for an affordable price without any additional steps. For 45 inquiries, additional steps were required for the medication to become covered at an affordable price. The remaining 445 inquires required additional steps with subsequent denial or prohibitive out-of-pocket costs. Conclusion: The UCMC workflow provided transparent out-of-pocket costs for patients to access glaucoma medications. This workflow may be cost-effective as it minimizes the burden on the overall system by reducing the number of patients who are unable to fill a prescription at the pharmacy due to issues with coverage or affordability. This model of physician-pharmacy collaboration can guide other institutions to implement similar workflows which directly mitigate costs and improve quality of care.

SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens.

BACKGROUND: Major depression and anxiety disorders are significant causes of disability and socioeconomic burden. Despite the prevalence and considerable impact of these affective disorders, their pathophysiology remains elusive. Thus, there is an urgent need to develop novel therapeutics for these conditions. We evaluated the role of SIRT1 in regulating dysfunctional processes of reward by using chronic social defeat stress to induce depression- and anxiety-like behaviors. Chronic social defeat stress induces physiological and behavioral changes that recapitulate depression-like symptomatology and alters gene expression programs in the nucleus accumbens, but cell type-specific changes in this critical structure remain largely unknown. METHODS: We examined transcriptional profiles of D1-expressing medium spiny neurons (MSNs) lacking deacetylase activity of SIRT1 by RNA sequencing in a cell type-specific manner using the RiboTag line of mice. We analyzed differentially expressed genes using gene ontology tools including SynGO and EnrichR and further demonstrated functional changes in D1-MSN-specific SIRT1 knockout (KO) mice using electrophysiological and behavioral measurements. RESULTS: RNA sequencing revealed altered transcriptional profiles of D1-MSNs lacking functional SIRT1 and showed specific changes in synaptic genes including glutamatergic and GABAergic (gamma-aminobutyric acidergic) receptors in D1-MSNs. These molecular changes may be associated with decreased excitatory and increased inhibitory neural activity in Sirt1 KO D1-MSNs, accompanied by morphological changes. Moreover, the D1-MSN-specific Sirt1 KO mice exhibited proresilient changes in anxiety- and depression-like behaviors. CONCLUSIONS: SIRT1 coordinates excitatory and inhibitory synaptic genes to regulate the GABAergic output tone of D1-MSNs. These findings reveal a novel signaling pathway that has potential for the development of innovative treatments for affective disorders.

Quantitative assessment of multiple pathogen exposure and immune dynamics at scale.

IMPORTANCE: Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.

The generation of genuine quadripartite Einstein-Podolsky-Rosen steering in an optical superlattice.

Einstein-Podolsky-Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing.

Transcriptomic analyses reveal proinflammatory activation of human brain microvascular endothelial cells by aging-associated peptide medin and reversal by nanoliposomes.

Medin is a common vascular amyloidogenic peptide recently implicated in Alzheimer's disease (AD) and vascular dementia and its pathology remains unknown. We aim to identify changes in transcriptomic profiles and pathways in human brain microvascular endothelial cells (HBMVECs) exposed to medin, compare that to exposure to ß-amyloid (Aß) and evaluate protection by monosialoganglioside-containing nanoliposomes (NL). HBMVECs were exposed for 20 h to medin (5 µM) without or with Aß(1-42) (2 µM) or NL (300 µg/mL), and RNA-seq with signaling pathway analyses were performed. Separately, reverse transcription polymerase chain reaction of select identified genes was done in HBMVECs treated with medin (5 µM) without or with NFκB inhibitor RO106-9920 (10 µM) or NL (300 µg/mL). Medin caused upregulation of pro-inflammatory genes that was not aggravated by Aß42 co-treatment but reversed by NL. Pathway analysis on differentially expressed genes revealed multiple pro-inflammatory signaling pathways, such as the tumor necrosis factor (TNF) and the nuclear factor-κB (NFkB) signaling pathways, were affected specifically by medin treatment. RO106-9920 and NL reduced medin-induced pro-inflammatory activation. Medin induced endothelial cell pro-inflammatory signaling in part via NFκB that was reversed by NL. This could have potential implications in the pathogenesis and treatment of vascular aging, AD and vascular dementia.

[Prevalence of comorbid depression and anxiety and effect of psychological interventions among schistosomiasis patients in China: a meta-analysis].

OBJECTIVE: To investigate the prevalence of comorbid depression and anxiety and to evaluate the effect of psychological interventions among schistosomiasis patients in China, so as to provide insights into improvements of psychological health among schistosomiasis patients. METHODS: Publications pertaining to comorbid depression and anxiety and psychological interventions among Chinese schistosomiasis patients were retrieved in electronic databases, including CNKI, Wanfang Data, PubMed, Web of Science, and Embase. The prevalence of comorbidity, psychological interventions, and scores for the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) before and after psychological interventions among Chinese schistosomiasis patients were extracted. The prevalence of comorbid depression and anxiety was investigated among Chinese schistosomiasis patients using a meta-analysis, and the effect of psychological interventions for depression and anxiety was evaluated. RESULTS: A total of 231 publications were retrieved, and 14 publications that met the inclusion and exclusion criteria were included in the final analysis, including 2 English publications and 12 Chinese publications. Meta-analysis showed that the prevalence rates of comorbid depression and anxiety were 61% [95% confidential interval (CI): (48%, 72%)] and 64% [95% CI: (42%, 81%)] among Chinese schistosomiasis patients. Both the SDS [1.45 points, 95% CI: (1.30, 1.60) points] and SAS scores [2.21 points, 95% CI: (2.05, 2.38) points] reduced among Chinese schistosomiasis patients after psychological interventions than before psychological interventions, and the SDS [-0.47 points, 95% CI: (-6.90, -0.25) points] and SAS scores [-1.30 points, 95% CI: (-1.52, -1.09) points] reduced among Chinese schistosomiasis patients in the case group than in the control group. CONCLUSIONS: The comorbid anxiety and depression are common among Chinese schistosomiasis patients, and conventional psychological interventions facilitate the improvements of anxiety and depression among schistosomiasis patients.

[A prospective randomized controlled study of antibiotic bone cement in the treatment of diabetic foot ulcer].

Objective: To investigate the clinical effects and related mechanism of antibiotic bone cement in treating diabetic foot ulcer (DFU). Methods: A prospective randomized controlled study was conducted. From August 2020 to August 2022, 24 patients with DFU who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University. According to the block randomization, the patients were divided into 2 groups, with 12 patients in each group. In antibiotic bone cement group, there were 7 male and 5 female patients, aged (64±8) years, with the ulcer area of (41±21) cm2. In silver sulfadiazine group, there were 8 male and 4 female patients, aged (62±8) years, with the ulcer area of (38±19) cm2. Under the condition of ensuring the patency of at least one main inferior genicular artery in each patient, the continuous vacuum sealing drainage was performed for 3-5 days after thorough debridement. Thereafter, the wounds in antibiotic bone cement group were treated with gentamicin-laden bone cement, and the wounds in silver sulfadiazine group were treated with silver sulfadiazine cream for dressing change. After 3 weeks of dressing change, the wound was covered with split-thickness skin graft from the lateral thigh on the affected side. Before debridement and after 3 weeks of dressing change, the blood flow intensities of wound tissue and normal skin tissue in foot were measured using laser Doppler flowmeter, and then, the percentage of relative blood flow intensity of wound and the change rate of blood flow intensity were calculated. After 3 weeks of dressing change, the wound margin tissue was taken, the number of CD31-positive neovascular and the vascular morphology were observed and detected by immunohistochemical staining, the morphology of blood vessels surrounded by CD31 and α-smooth muscle actin (α-SMA) double-positive cells was observed by immunofluorescence staining, the cell proliferation activity was evaluated by immunofluorescence staining (denoted as the ratio of Ki67 positive cells), and the protein expression of vascular endothelial growth factor receptor 2 (VEGFR2) was detected by Western blotting. The skin graft survival was observed 3-5 days after skin grafting, and the wound healing time was recorded. Data were statistically analyzed with independent sample t test and Fisher's exact probability test. Results: The percentages of relative blood flow intensity of wounds of patients before debridement were similar between the two groups (P>0.05). After 3 weeks of dressing change, the percentage of relative blood flow intensity of wounds and the change rate of blood flow intensity of patients in antibiotic bone cement group were (44.7±2.0)% and (129±12)%, respectively, which were significantly higher than (28.3±1.2)% and (41±8)% in silver sulfadiazine group (with t values of 24.15 and 20.97, respectively, P<0.05). After 3 weeks of dressing change, compared with those in silver sulfadiazine group, the number of CD31-positive neovascular in the wound margin tissue of patients in antibiotic bone cement group was significantly increased (t=33.81, P<0.05) with larger diameter and more regular arrangement, the vascular wall continuity surrounded by CD31 and α-SMA double-positive cells was better, and the ratio of Ki67 positive cells and protein expression of VEGFR2 were significantly increased (with t values of 40.97 and 47.38, respectively, P<0.05). On post skin grafting day 3-5, all the patients in antibiotic bone cement group and 8 patients in silver sulfadiazine group had good skin graft survival, while 4 patients in silver sulfadiazine group showed spotted/patchy skin graft necrosis, which were cured after corresponding treatment. The wound healing time of patients in antibiotic bone cement group was (47.1±2.9) d, which was significantly shorter than (58.8±2.3) d in silver sulfadiazine group (t=10.86, P<0.05). Conclusions: Compared with silver sulfadiazine, clinical application of antibiotic bone cement for treating DFU has the characteristics of accelerating wound healing and better reconstruction of local blood flow, which may be closely related to the fact that antibiotic bone cement promoted the local angiogenesis effectively in the wound through enhancing the expression of VEGFR2.

[Effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint].

Objective: To investigate the effects of tibial second toe free flap bridged with blood flow and nerve in the treatment of severe flexion contracture of the proximal interphalangeal joint. Methods: A retrospective observational study was conducted. From March 2013 to October 2019, 9 patients with severe flexion contracture (type Ⅲ) of the proximal interphalangeal joint after trauma operation, conforming to the inclusion criteria, were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 4 females, aged from 17 to 62 years. After the contracture tissue affecting the extension of the proximal interphalangeal joint was cut off, and the scar tissue was resected, the size of the volar wound near the proximal interphalangeal joint in extended position was 2.0 cm×1.0 cm-2.5 cm×1.5 cm, with the length of proper digital artery and nerve defect being 1.0-1.5 cm. A free flap of the same size as the wound was cut from the tibial side of the second toe and transplanted to repair the wound, and the defective proper digital artery and nerve was repaired by bridging with the tibial proper plantar digital artery and nerve of about 1.5 cm in length. The full-thickness skin graft was taken from the proximal tibial side of the lower leg to repair the wound at flap donor site. The wound at skin graft donor site was sutured directly. The survival of flap and skin graft was observed after operation. The patients were followed up, and at the last follow-up, the recovery of the affected finger and the second toe, including the donor and recipient areas were observed, the two-point discrimination distances of the flap repaired site and the pulp of the affected finger were observed and measured at the same time, the blood flow patency of bridged vessel of the affected finger was examined by Allen test, and the function of the proximal interphalangeal joint of the affected finger was evaluated according to Chinese Medical Association's standard for the range of motion of proximal interphalangeal joint. Results: The flaps and skin grafts survived smoothly after operation. The follow-up after operation lasted for 5 to 22 months, with a mean of 10 months. At the last follow-up, the flap repaired site had good shape, good color and texture, with the two-point discrimination distance being 9-12 mm, and the two-point discrimination distance of the pulp of the affected finger was 6-10 mm; the Allen test results of the affected fingers were all negative (i.e., the bridged vessels had good blood flow patency), with no recurrence of flexion contracture, and the function of the proximal interphalangeal joint was evaluated as excellent; the skin graft area of the second toe was not ruptured but was a little pigmented, and the flexion and extension activities of toe were good. Conclusions: The tibial second toe free flap bridged with blood flow and nerve has reliable therapeutic effect in the treatment of severe flexion contracture of the proximal interphalangeal joint, and the color and texture of the flap repaired area are good. Bridging to repair the severely contracted proper digital artery and nerve is beneficial to improve the blood supply of the finger body and rebuild the sensation.

[Establishment of the quality assessment system for pancreatic cancer surgery: from "single complication assessment" to "textbook outcome"].

With the development of neoadjuvant therapy and a multidisciplinary team, the treatment of pancreatic cancer has gradually expanded from "resection" to "cure"."Curative resection" as the core part of the integrated treatment model for patients, its quality directly determines the short-term outcome and affects the long-term prognosis. Previously, the "single complication assessment" model was used to measure the quality of pancreatic cancer surgery. However, the incidence of any specific complication cannot cover the entire surgical procedure, making it difficult to quantify and standardize the interpretation of the outcomes. Recently, the concept of textbook outcome, a comprehensive indicator, has gained popularity in surgical research. Textbook outcome includes multiple complication parameters and reflects optimal surgical outcomes in an "all or none" approach. Implementing a quality improvement program that focuses on textbook outcome will increase the overall standard of complex surgery, ultimately advancing the surgical care of pancreatic cancer in the future. In this article, the latest advances in relevant research are analyzed to provide a brief overview of the textbook outcome of pancreatic cancer.

Multidimensional quantitative phenotypic and molecular analysis reveals neomorphic behaviors of p53 missense mutants.

Mutations in the TP53 tumor suppressor gene occur in >80% of the triple-negative or basal-like breast cancer. To test whether neomorphic functions of specific TP53 missense mutations contribute to phenotypic heterogeneity, we characterized phenotypes of non-transformed MCF10A-derived cell lines expressing the ten most common missense mutant p53 proteins and observed a wide spectrum of phenotypic changes in cell survival, resistance to apoptosis and anoikis, cell migration, invasion and 3D mammosphere architecture. The p53 mutants R248W, R273C, R248Q, and Y220C are the most aggressive while G245S and Y234C are the least, which correlates with survival rates of basal-like breast cancer patients. Interestingly, a crucial amino acid difference at one position-R273C vs. R273H-has drastic changes on cellular phenotype. RNA-Seq and ChIP-Seq analyses show distinct DNA binding properties of different p53 mutants, yielding heterogeneous transcriptomics profiles, and MD simulation provided structural basis of differential DNA binding of different p53 mutants. Integrative statistical and machine-learning-based pathway analysis on gene expression profiles with phenotype vectors across the mutant cell lines identifies quantitative association of multiple pathways including the Hippo/YAP/TAZ pathway with phenotypic aggressiveness. Further, comparative analyses of large transcriptomics datasets on breast cancer cell lines and tumors suggest that dysregulation of the Hippo/YAP/TAZ pathway plays a key role in driving the cellular phenotypes towards basal-like in the presence of more aggressive p53 mutants. Overall, our study describes distinct gain-of-function impacts on protein functions, transcriptional profiles, and cellular behaviors of different p53 missense mutants, which contribute to clinical phenotypic heterogeneity of triple-negative breast tumors.

[Quality assessment indictors and benchmarks for pancreatic surgery].

Pancreatic surgery is the most complex type of abdominal surgery,with high technical requirements and long learning curve,and the quality of surgery is directly related to the prognosis of the patients. In recent years,more and more indicators have been used to evaluate the quality of pancreatic surgery,such as operation time,intraoperative blood loss,morbidity,mortality, prognosis and so on,and different evaluation systems have been established,including benchmarking,auditing,outcome evaluation based on risk factor adjustment and textbook outcomes. Among them,the benchmark is the most widely used to evaluate surgical quality and is expected to become the standard for comparison among peers. This article reviews existing quality evaluation indicators and benchmarks for pancreatic surgery and anticipates its future application prospects.

[Diagnosis and treatment of blunt high-grade pancreatic trauma].

The clinical data of 20 patients with blunt high-grade pancreatic trauma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of Changhai Hospital Affiliated to Naval Military Medical University from December 2003 to February 2022 were retrospectively analyzed. There were 15 males and 5 females with a median age of 39 years (range: 14-54 years). The degree of pancreatic injury was graded according to the American Association for the Surgery of Trauma (AAST) scale, including 10 cases of grade Ⅲ (50%), 8 cases of grade Ⅳ (40%), and 2 cases of grade Ⅴ (10%). Then, the strategy of diagnosis and treatment for blunt high-grade pancreatic trauma was summarized. The diagnostic rate of CT was 78.9%. Finally, 17 cases (85%) were cured and 3 cases (15%) died. Among the 10 patients with grade Ⅲ pancreatic injury, 7 cases received distal pancreatectomy and splenectomy, 1 case received distal pancreatectomy with spleen preserved, 1 case received pancreatic duct stent placement under endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous catheter drainage (PCD), and 1 case received only PCD. Among 8 cases of grade Ⅳ, 3 cases underwent Roux-en-Y pancreaticojejunostomy, 1 case received distal pancreatectomy and splenectomy, 1 case underwent distal pancreatectomy with spleen preserved, 2 cases received necrotic tissue removal+external drainage of pancreatic duct+abdominal drainage, and 1 case received exploratory laparotomy and gauze packing hemostasis. For 2 cases of grade Ⅴ, 1 underwent pylorus preserving pancreaticoduodenectomy, and the other case underwent pancreaticoduodenectomy combined with right hemicolectomy and splenectomy. Therefore, the treatment of blunt high-grade pancreatic trauma should follow the individualized treatment strategy, pay attention to the control of bleeding, extensive external drainage, appropriate debridement and resection and rational application of damage control surgery, select appropriate patients for conservative treatment, and ultimately benefit the patient.

Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules.

BACKGROUND: CT screening can detect lung cancer early but suffers a high false-positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan. METHODS: We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific antimicrobial antibodies. RESULTS: Analyzing fourth quartile ORs, we found more antibodies with higher prevalence in the three BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-Helicobacter pylori antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤20 pack-years) compared with heavy smokers (>20 pack-years), in BNC with nodule size >1 cm than in those with ≤1 cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC versus SMC and ADC versus BNC with area under the ROC curve (AUC) of 0.88 and 0.80, respectively. CONCLUSIONS: Antimicrobial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development. IMPACT: Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.

Clinical analysis of prophylactic para-aortic intensity-modulated radiation in cervical cancer.

AIM: This study aimed to compare the survival and toxicity of patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIIC cervical cancer without common iliac node metastasis treated with extended-field intensity-modulated radiotherapy (EF-IMRT) or pelvic IMRT (P-IMRT). MATERIALS AND METHODS: Thirty-one patients treated with EF-IMRT and 37 patients who underwent P-IMRT were analysed retrospectively. Both groups were treated with high-dose-rate 192Ir two-dimensional brachytherapy and concurrent chemotherapy. The chi-square test and Kaplan-Meier method were used to compare toxicity and survival between the two groups. RESULTS: The median follow-up time of EF-IMRT group and P-IMRT group was 22 and 30 months, respectively. The 3-year overall survival (OS), progression-free survival (PFS), and para-aortic lymph node metastasis-free survival (PAMFS) in the EF-IMRT group and P-IMRT group were 87% versus 74.6%, 83.6% versus 61.7%, and 96% versus 80.5%, respectively. Treatment regimens, tumour size, and radiation time were independent prognostic factors of OS and PFS. Treatment regimens, tumour size, and total equivalent dose in 2 Gy/f (EQD2) of point A were independent prognostic factors of PAMFS. Five patients in the EF-IMRT group and 14 patients in P-IMET group experienced treatment failure. The cumulative incidence of grade 3 and 4 acute leukopenia in the EF-IMRT group was 51.6%, in comparison with 27.03% in the pelvic group. No difference was found in thrombocytopenia between two groups. CONCLUSIONS: Patients with FIGO 2009 stage IB1-IIIC cervical cancer without common iliac node metastases may be benefit from EF-IMRT. Notably, EF-IMRT exhibits increased toxicity incidence; however, this remains within an acceptable range.

Generation of chimeric antigen receptor macrophages from human pluripotent stem cells to target glioblastoma.

Background: Glioblastoma (GBM) is an aggressive brain tumor giving a poor prognosis with the current treatment options. The advent of chimeric antigen receptor (CAR) T-cell therapy revolutionized the field of immunotherapy and has provided a new set of therapeutic options for refractory blood cancers. In an effort to apply this therapeutic approach to solid tumors, various immune cell types and CAR constructs are being studied. Notably, macrophages have recently emerged as potential candidates for targeting solid tumors, attributed to their inherent tumor-infiltrating capacity and abundant presence in the tumor microenvironment. Materials and methods: In this study, we developed a chemically defined differentiation protocol to generate macrophages from human pluripotent stem cells (hPSCs). A GBM-specific CAR was genetically incorporated into hPSCs to generate CAR hPSC-derived macrophages. Results: The CAR hPSC-derived macrophages exhibited potent anticancer activity against GBM cells in vitro. Conclusion: Our findings demonstrate the feasibility of generating functional CAR-macrophages from hPSCs for adoptive immunotherapy, thereby opening new avenues for the treatment of solid tumors, particularly GBM.

[Mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence].

Objective: To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence. Methods: After excluding individuals with missing educational levels and cancer information at baseline, 446 772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer. Results: During a median follow-up of 7.13 years, 1 994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer (HR=0.88, 95%CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self-report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95%CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with ß coefficients (95%CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score (ß=0.042, 95%CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95%CI: 31.802%-51.659%) and 1.784% (95%CI: 0.405%-3.713%), respectively. Conclusion: Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.

Quantum enhancement of a single quantum battery by repeated interactions with large spins.

A generalized collision model is developed to investigate coherent charging a single quantum battery by repeated interactions with many-atom large spins, where collective atom operators are adopted and the battery is modeled by a uniform energy ladder. For an initially empty battery, we derive analytical results of the average number of excitations and hence the charging power in the short-time limit. Our analytical results show that a faster charging and an increased amount of the power in the coherent protocol uniquely arise from the phase coherence of the atoms. Finally, we show that the charging power defined by the so-called ergotropy almost follows our analytical result, due to a nearly pure state of the battery in the short-time limit.

First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

[Comparative study of the effects between second toe tibial dorsal artery flap and second toe tibial plantar proper artery flap in repairing finger skin and soft tissue defects].

Objective: To compare the effects between second toe tibial dorsal artery flap (2-TDAF) and second toe tibial plantar proper artery flap (2-TPPAF) in repairing finger skin and soft tissue defects. Methods: A retrospective cohort study was conducted. From January 2019 to June 2020, 27 patients with skin and soft tissue defects at the fingertips with area of 1.5 cm×1.2 cm-2.6 cm×1.8 cm after debridement who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 21 males and 6 females, aged 19-59 (37±10) years. According to flap repair methods used in the defective fingers, the patients were divided into 2-TDAF group (12 cases) and 2-TPPAF group (15 cases). The area of 2-TDAF ranged from 1.5 cm×1.2 cm to 2.5 cm×1.6 cm, and the area of 2-TPPAF ranged from 1.7 cm×1.3 cm to 2.6 cm×1.8 cm. Full-thickness skin grafts from the medial side of the ipsilateral leg were grafted to the wounds in donor sites, and the wounds in donor sites of skin grafts were directly sutured. Flap arterial diameter, flap excision time, flap survival situation of patients in 2 weeks after operation, and follow-up time were recorded. At the last follow-up, the two-point discrimination distance of flap graft site, total action motion (TAM) of the finger joints, and wound healing of the flap donor site were recorded; the Vancouver scar scale (VSS) was used to score the scar in donor area of the second toe and the recipient area of fingers; the appearance and self-satisfaction subscales of the Michigan hand outcomes questionnaire (MHQ) were used to evaluate the affected finger. Data were statistically analyzed with independent sample t test or Fisher's exact probability test. Results: The flap artery diameter of patients in 2-TDAF group was 0.35-0.80 (0.56±0.14) mm and the flap cutting time was (14.0±2.7) min, which were significantly shorter than 0.80-1.35 (1.02±0.16) mm and (19.7±3.4) min in 2-TPPAF group (with t values of 7.81 and 4.79, respectively, P<0.01). The flaps of patients in the 2 groups in recipient areas survived well in 2 weeks after operation, and the wounds in donor areas of flaps of patients in the 2 groups healed well at the last follow-up. There was no statistically significant difference in the postoperative follow-up time, and two-point discrimination distance of flap graft site, TAM of the finger joints, VSS score of scar in the second toe donor site and the finger recipient site, and the appearance and self-satisfaction of MHQ scores of the affected finger at the last follow-up (P>0.05). Conclusions: Compared with 2-TPPAF, 2-TDAF has a shallower anatomical layer and shorter time for surgical flap removal, which can preserve the proper arteries and nerves at the base of the toes and reduce the damage to the donor site.