Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with immunotherapy in early-stage triple-negative breast cancer.

PURPOSE: This study aimed to assess safety and efficacy of a modified KEYNOTE 522 protocol, which incorporated pembrolizumab every 6 weeks, allowing for concomitant dose-dense (14 day) doxorubicin and cyclophosphamide (ddAC). By optimizing this dosing, the intention of this modified protocol was to improve pathologic complete response (pCR) rates in a population associated with a poorer prognosis. METHODS: This was a retrospective, single-center, cohort study. Patients were included if they had early stage, triple-negative breast cancer, and received at least one dose of AC. The entire cohort received neoadjuvant chemotherapy including weekly carboplatin and paclitaxel with pembrolizumab every 3 weeks for 12 weeks (4 cycles). The group then received either ddAC with pembrolizumab 400 mg every 6 weeks, or AC with pembrolizumab 200 mg every 3 weeks. The primary objective was pCR rate at time of surgery. RESULTS: This study assessed outcomes in 25 patients over 34 months. The pCR rate in the pembrolizumab, AC 3-week cohort was 64.3% versus 81.8% in the ddAC and 6-week pembrolizumab group. No pembrolizumab-associated grade 3-4 adverse events occurred in the either cohort. Despite seeing an increased incidence of grade 3-4 toxicities in the ddAC arm, this did not result in additional chemotherapy delays or dose reductions. CONCLUSION: This study demonstrated tolerability and a potential for favorable outcomes with this patient population, making this modified KEYNOTE 522 protocol a reasonable treatment approach. Larger, prospective studies are warranted to assess the feasibility of this dosing and true optimization of patient outcomes given the small sample size of this study.

Assessment of Embedded vs. Remote Pharmacist vs. Remote Student Pharmacist Outreach on Statin Prescribing.

BACKGROUND: The Statin Use in Persons with Diabetes (SUPD) measure is a Star measure by the Center for Medicare & Medicaid Services. The Duke Population Health Management Office (PHMO) has a team of pharmacists and pharmacy students who conduct targeted outreach to patients at risk of failing statin quality measures. Pharmacy services are embedded in select primary care clinics and other clinics are supported remotely. OBJECTIVE: The primary objective of this review is to compare the initiation rates of recommended statin prescriptions between embedded pharmacist vs remote pharmacist vs remote student pharmacist outreach groups, all of which have different levels of autonomy within pharmacy practice. The secondary objectives are to identify the barriers to the implementation of statin therapy and to assess the statin drugs and intensity of the statins prescribed. METHODS: A single-center, retrospective chart review was performed for SUPD patients with Medicare insurance. SUPD patients included patients 40-75 years of age, diagnosed with type 2 diabetes, and were not dispensed at least one statin medication of any intensity during the 6-month measurement period. The primary outcome was the initiation of recommended statin medications prescribed, or pended for the PCP to prescribe, for qualifying patients by embedded, remote, and remote student pharmacists. Secondary outcomes included the reasons for the non-implementation of statin recommendations, reasons statin therapy was not prescribed to patients contributing to the SUPD measure gap, and statin drug and dose prescribed for appropriateness. RESULTS: A total of 189 patients were included in the evaluation. In this study, 34.9% of the patients filled the prescribed or pended statin prescription and 83.3% of patients filled the prescribed or pended statin prescription at the recommended intensity according to the ACC/AHA guidelines, effectively closing the SUPD measure gap. The initiation rates of recommended statin prescriptions between the embedded pharmacist, remote pharmacist, and remote student pharmacist outreach were numerically different at 36.7%, 28.2%, and 36.7%, respectively, even though not statistically different (p=0.61). CONCLUSION: Remote student pharmacists' performance was equal to that of the embedded pharmacists when comparing the initiation rates of statin medications prescribed or pending the PCP's approval. The most common reason for non-implementation of statin therapy is that the statin was refused by the patient. Atorvastatin and rosuvastatin were the two most commonly prescribed statins.

MDT: semi-supervised medical image segmentation with mixup-decoupling training.

Objective. In the field of medicine, semi-supervised segmentation algorithms hold crucial research significance while also facing substantial challenges, primarily due to the extreme scarcity of expert-level annotated medical image data. However, many existing semi-supervised methods still process labeled and unlabeled data in inconsistent ways, which can lead to knowledge learned from labeled data being discarded to some extent. This not only lacks a variety of perturbations to explore potential robust information in unlabeled data but also ignores the confirmation bias and class imbalance issues in pseudo-labeling methods.Approach. To solve these problems, this paper proposes a semi-supervised medical image segmentation method 'mixup-decoupling training (MDT)' that combines the idea of consistency and pseudo-labeling. Firstly, MDT introduces a new perturbation strategy 'mixup-decoupling' to fully regularize training data. It not only mixes labeled and unlabeled data at the data level but also performs decoupling operations between the output predictions of mixed target data and labeled data at the feature level to obtain strong version predictions of unlabeled data. Then it establishes a dual learning paradigm based on consistency and pseudo-labeling. Secondly, MDT employs a novel categorical entropy filtering approach to pick high-confidence pseudo-labels for unlabeled data, facilitating more refined supervision.Main results. This paper compares MDT with other advanced semi-supervised methods on 2D and 3D datasets separately. A large number of experimental results show that MDT achieves competitive segmentation performance and outperforms other state-of-the-art semi-supervised segmentation methods.Significance. This paper proposes a semi-supervised medical image segmentation method MDT, which greatly reduces the demand for manually labeled data and eases the difficulty of data annotation to a great extent. In addition, MDT not only outperforms many advanced semi-supervised image segmentation methods in quantitative and qualitative experimental results, but also provides a new and developable idea for semi-supervised learning and computer-aided diagnosis technology research.

Semi-supervised medical image segmentation via feature similarity and reliable-region enhancement.

Semantic segmentation is a crucial task in the field of computer vision, and medical image segmentation, as its downstream task, has made significant breakthroughs in recent years. However, the issue of requiring a large number of annotations in medical image segmentation has remained a major challenge. Semi-supervised semantic segmentation has provided a powerful approach to address the annotation problem. Nevertheless, existing semi-supervised semantic segmentation methods in medical images have drawbacks, such as insufficient exploitation of unlabeled data information and inefficient utilization of all pseudo-label information. We introduces a novel segmentation model, the Feature Similarity and Reliable-region Enhancement Network (FSRENet), to overcome these limitations. Firstly, this paper proposes a Feature Similarity Module (FSM), which combines the dense feature prediction ability of true labels for unlabeled images with segmentation features as additional constraints, utilizing the similarity relationship between dense features to constrain segmentation features, and thus fully exploiting the dense feature information of unlabeled data. Additionally, the Reliable-region Enhancement Module (REM) designs a high-confidence network structure by fusing two networks that can learn from each other, forming a triple-network structure. The high-confidence network generates reliable pseudo-labels that further constrain the predictions of the two networks, achieving the goal of enhancing the weight of reliable regions, reducing the noise interference of pseudo-labels, and efficiently utilizing all pseudo-label information. Experimental results on the ACDC and LA datasets demonstrate that the FSRENet model proposed in this paper excels in the task of semi-supervised semantic segmentation of medical images and outperforms the majority of existing methods. Our code is available at: https://github.com/gdghds0/FSRENet-master.

Effectiveness of Negative Pressure Wound Therapy of Diabetic Foot Ulcers Using Periplaneta Americana (Kangfuxin Liquid) Irrigation.

This study was to evaluate the efficacy of Periplaneta Americana (Kangfuxin Liquid) relative to normal saline when applied in negative-pressure wound therapy (NPWT) with instillation for facilitating diabetic foot ulcers (DFUs) healing. Eighty patients with Wagner grades 3 or 4 DFUs were enrolled in this retrospective study. Based on the treatment type, patients were equally assigned to either (i) an NPWT with Kangfuxin liquid instillation group (NPWT-K) or (ii) an NPWT with normal saline instillation group (NPWT-I). The primary study outcome was the wound healing rate and Kaplan-Meier survival estimate was used to examine the cumulative wound healing rate, while the secondary outcomes were the amputation rate, inpatient days, duration of antibiotic treatments, reinfection rate, new ulcer formation rate, readmission rate, and changes in the inflammatory markers (such as ESR, CRP, and PCT) and serum growth factors (including VEGF, EGF, and bFGF). The 12-week wound healing rate (31 of 40[77.5%] vs 22 of 40[55.0%], P = .033) and the cumulative wound healing rate was higher in the NPWT-K group than in the NPWT-I group (P = .004). The wound healing time was shorter in the NPWT-K group (55 days [95% CI 50-60]) than in the NPWT-K group (64 days [95% CI 59-69], P = .016). Patients who received NPWT-K had fewer inpatient days and duration of antibiotic treatment and faced lower reinfection and readmission rates (P < .05). After 1 week of treatment, the ESR, CRP, and PCT levels in the blood were lower in the NPWT-K group than in the NPWT-I group (P < .05), while the VEGF, EGF, and bFGF levels in the NPWT-K group were higher than those in the NPWT-I group (P < .001). The present study showed that NPWT with Kangfuxin liquid instillation was effective and showed significantly accelerated DFUs healing. Thus, Kangfuxin liquid is an effective instillation solution for use in the treatment of DFUs with NPWT.

The impact of the COVID-19 outbreak on activation of the massive transfusion protocol in the emergency department.

BACKGROUND AND OBJECTIVES: An outbreak of coronavirus disease 2019 (COVID-19) occurred in mid-May of 2021 in Taiwan. After 2 months of hard work, transmissions were successfully prevented and the number of newly confirmed COVID-19 cases fell remarkably. We evaluated the impact of this outbreak on the massive transfusion protocol (MTP) in the emergency department (ED) of a trauma centre. MATERIALS AND METHODS: We retrospectively compared the activation and efficacy of MTP before, during and after the outbreak by analysing the clinical data relevant to MTP activations. RESULTS: There was no remarkable change in the average number of MTP triggers per month during the outbreak. The interval from an MTP trigger to the first unit of blood transfused at bedside was significantly increased during the outbreak compared to that before the outbreak (22.4 min vs. 13.9 min, p < 0.001); while the 24-h survival rate decreased (57.1% vs. 71.1%, p = 0.938). There were no remarkable changes in blood unit return or wastage during the outbreak. CONCLUSION: The COVID-19 outbreak limitedly affected MTP activation and waste of blood products, but significantly increased the interval from an MTP trigger to the first unit of blood transfused at bedside.

Comparative DFT dual gas adsorption model of ZnO and Ag/ZnO with experimental applications as gas detection at ppb level.

By experimental and density functional theory calculations, the toxic gases (O3and NO2) sensing capability and mechanism of ZnO NRs and Ag/ZnO NRs have been comparatively studied in this work. Ag NPs arrays were employed for the growth of ZnO NRs. The experimental results show that when ZnO NRs are grown on Ag NPs, the response and adsorption rate towards the gases change significantly. The TDOS plot shows that the HOMO-LUMO gap changes after interaction with different oxidizing gases, and the peak intensity also decreases confirming the electron are transferred from ZnO to NO2and O3. The response to gases decreases and the adsorption reaction rate increases in Ag/ZnO NRs, as calculated by the Eyring-Polanyi equation, which is very similar to our experimental data. We also find that the absorption coefficient is different for O3and NO2. Finally, experimental response and theoretical results were compared and found to be in good agreement.

Health study of 11,800 workers under occupational noise in Xinjiang.

BACKGROUND: We investigated the health status of some workers exposed to occupational noise in Xinjiang, and explored the influencing factors of their health level. We aimed to determine the key protection groups of occupational noise hazards, which might provide the basis for the development of targeted noise prevention measures. METHODS: We used descriptive analysis to investigate a total of 11,800 participants who underwent occupational health examination in Xinjiang Occupational Disease Prevention Hospital. RESULTS: The hearing abnormality rate of noise exposure participants was 8.03%, which was higher in males than females (χ2 = 54.507, p < 0.05). The abnormal rate of high-frequency hearing threshold in Xinjiang minorities was lower than in Han nationality (χ2 = 11.780, p < 0.05), while the results of the electrocardiogram were reversed (χ2 = 9.128, p < 0.05). Differences in abnormal rates of blood pressure (χ2 = 149.734, p < 0.05), hearing (χ2 = 231.203, p < 0.05), and physical examination (χ2 = 360.609, p < 0.05) are statistically significant in different industries. The abnormal rates of blood pressure (χ2 = 67.416, p < 0.05) and hearing (χ2 = 49.535, p < 0.05) gradually decrease with the expansion of the enterprise scale. Logistic regression analysis showed that gender, nationality, age, enterprise size, and industry were closely related to pure tone audiometry examination abnormal rate. CONCLUSION: Workers of male, elder, in mine and small/medium enterprises should be the key populations to prevent occupational noise hazard. It is necessary to standardize occupational health management in enterprises, which helps to improve workers' self-protection awareness and quality of life.

Blood Lead, Systemic Inflammation, and Blood Pressure: Exploring Associations and Mediation Effects in Workers Exposed to Lead.

Relationships of lead exposure with blood pressure and blood lead with inflammation have been previously established yet, but the conclusions are still controversial. The objective of our study was to investigate the role of systemic inflammation in the relationships between blood lead concentration and blood pressure. We quantified the levels of blood lead and white blood cell count in 505 lead-exposed workers with 842 observations. Associations between blood lead, white blood cell count, and blood pressure were evaluated by using linear mixed models. We further performed mediation analysis to investigate the role of white blood cell count in the associations between blood lead concentration and blood pressure. We observed that each 1% increase of blood lead levels was significantly positively associated with a 0.9%, 1.7%, and 1.1% increases in systolic blood pressure, white blood cell count, and blood platelet count, respectively. Also, we found that the levels of white blood cell count were positively correlated with diastolic blood pressure and systolic blood pressure in a dose-response manner. Mediation analysis showed that the levels of white blood cell significantly mediated the associations between concentration of blood lead and systolic blood pressure. Collectively, our findings suggest that blood lead was positively associated with systolic blood pressure and that systemic inflammation might play a key role in this association.

How intestinal bacteria can promote HIV replication.

Since the 1950s, researchers have gradually realized that the body's bacteria help fight infection by crowding out potential pathogens. In the past decades, scientists have even begun to see our microbiota as thick­and­thin allies. However, the influence of gut bacteria on HIV is largely unknown. Our review likely sheds light on the previously indistinct role of commensal microbiota in retroviral pathogenesis. The delicate yet critical balance between this enormous bacterial population and the gastrointestinal tract is gradually destroyed along with HIV incursion. The leakage into the systemic circulation of bacterial and byproducts such as lipopolysaccharide directly stimulates the innate immune system through toll­like receptors. As a result, toll­like receptor­4 activation provokes production of interleukin­10, which mediates immunological tolerance. Therefore, a solid deduction is that intestinal microbes may be involved in triggering of replication and transmission of HIV, just like other retroviruses.

[Effect of pH value and fluoride ions on corrosion resistance of pure Ti and Ni-Cr-Ti alloy in artificial saliva].

OBJECTIVE: To investigate the effect of pH value and fluoride ions on the corrosion resistance of pure Ti and Ni-Cr-Ti alloy in the artificial saliva. METHODS: Electrochemical technique was used to measure the electric potential of corrosion (Ecorr), current density of corrosion (Icorr) and polarization resistance (Rp) of pure titanium and Ti-Ni-Cr alloy in the artificial saliva with different pH value and fluoride concentrations. After electrochemical analysis, microstructure and phase diffraction were examined by FSEM. RESULTS: With the lower pH value, the Ecorr and Icorr of pure titanium and Ti-Ni-Cr alloy increased, the Rp decreased, there was a significant difference (P<0.05). The Ecorr and Icorr increased markedly, the Rp significantly reduced in the artificial saliva containing 0.2% NaF (P<0.01). FSEM showed that pure titanium and Ti-Ni-Cr alloy surface corrosion, pure titanium in the artificial saliva containing 0.2% NaF was most serious. CONCLUSION: Lower pH value decreases the corrosion resistance of pure titanium and Ti-Ni-Cr alloy and the artificial saliva containing fluoride ions decreases the corrosion resistance of pure titanium.

Dexamethasone treatment improves sarcoplasmic reticulum function and contractile performance in aged myocardium.

Corticosteroids are thought to be involved in the maintenance of normal myocardial function by mechanisms incompletely understood. This study investigated the potential therapeutic benefit of the synthetic glucocorticoid, dexamethasone, in reversing age-associated deterioration in cardiac contractile performance and Ca2+ sequestration function of the sarcoplasmic reticulum. Dexamethasone was administered to senescent (26-28-month old), male Fischer 344 rats at a rate of 4 microg/h for 5 days via subcutaneously implanted osmotic mini pumps. Control rats received vehicle solution in similar manner. Contractile performance was assessed in Langendorff-perfused, electrically paced hearts from control and dexamethasone-treated rats. The results obtained showed that dexamethasone-treatment of aged rats resulted in significant improvement in myocardial contractile performance as evidenced by (i) increase (approximately 30-60%) in developed peak tension at a wide range of beating frequencies (2-6 Hz), (ii) unaltered time to peak tension, and (iii) decrease (approximately 8-15%) in time to half-relaxation. Also, SR isolated from dexamethasone-treated rats displayed approximately 2-fold higher rates of ATP-energized Ca2+ uptake compared to SR from control rats. The deficits in contractile performance of the senescent heart (prolonged contraction duration and diminished contractile force) are reversible through a glucocorticoid-mediated improvement in SR Ca2+ pump function.