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1.
Int J Spine Surg ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025527

RESUMO

BACKGROUND: This study aimed to clarify the quantitative threshold of intraoperative radiological parameters for suspecting posterior malposition of the oblique lumbar interbody fusion (OLIF) cage triggering contralateral radiculopathy. METHODS: We measured the sagittal center and axial rotation angle (ARA) of the cage using postoperative computed tomography (CT) in 130 patients (215 cages) who underwent OLIF. The location of the cage tip was determined from axial magnetic resonance imaging in selected cases based on CT simulations to assess whether the cage was in contact with the contralateral exiting nerve or whether the surgical instruments could contact the nerve during intradiscal maneuvers. RESULTS: The sagittal center of the cages was on average 41.5% from the anterior edge of the endplate (shown as AC/AP value: anterior end plate edge-cage center/anterior-posterior endplate edge ×100%), and posterior cage positioning ≥50% occurred in 14% of the cages. The ARA was -2.9°, and posterior oblique rotation of the cages ≥10° (ARA ≤ -10°) was observed in 13%. CT simulation showed that the cage tip could directly contact the contralateral nerve when the cage was placed deep in the posterior portion ≥50% of the AC/AP values with concomitant posterior axial rotation ≥10° (ARA ≤ -10°), or deep in an extremely rare portion ≥60% of the AC/AP values with posterior axial rotation ≥0° (ARA ≤ 0°). Six percent of the cages (13/215) were placed in these posterior oblique areas (potential contact area: PCA). Three cages in the PCA were in direct contact with the contralateral nerves, and 9 were placed deep just anterior to the nerves. Symptomatic contralateral radiculopathy occurred in 2 cages (2/13/215, 15.3%/0.9%). CONCLUSIONS: Two intraoperative radiological parameters (AC/AP and ARA) measurable during OLIF procedures may become practical indicators for suspecting cage malposition in PCA and may be available when determining whether to consider cage revision intraoperatively to a more ventral disc space or anteriorly from the opposite endplate edge.

2.
Transl Lung Cancer Res ; 13(6): 1420-1425, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38973944

RESUMO

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking. Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment. Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.

3.
Artigo em Chinês | MEDLINE | ID: mdl-38802310

RESUMO

Objective: To select chest CT image patterns for the diagnosis of pneumoconiosis and establish a method for determining the profusion of circular small shadows in chest CT. Methods: In April 2021, 66 cases of occupational pneumoconiosis patients with digital radiography (DR) chest radiographs and chest CT imaging data with circular small shadow as the main manifestations were selected as the study objects. 1.5 mm and 5 mm chest CT axial images, 1 mm and 5 mm chest CT coronal multi-plane recombination (MPR) images, and 5 mm chest CT coronal maximum intensity projection (MIP) images were used to observe the different characteristics of pneumoconiosis patients, and were compared and analyzed with DR chest radiographs to establish the experimental chest CT standards. The consistency of the profusion results between the experimental chest CT standards and GBZ 70-2015 Diagnosis of Occupational Pneumoconiosis was verified. Results: All the 66 objects were male, including 33 cases of stage Ⅰ pneumoconiosis, 17 cases of stage Ⅱ pneumoconiosis and 16 cases of stage Ⅲ pneumoconiosis. By observing five chest CT images of 66 objects, we found that chest CT images of different modes could clearly display and identify abnormal images such as small circular shadow, large shadow, small shadow aggregation, honeycomb glass shadow, flake glass shadow, uniform low-profusion glass shadow, mesh glass shadow, cable shadow, linear shadow, subpleural spinous shadow, subpleural nodules, various kinds of emphysema and lung texture distortion and fracture. Small shadow aggregation was usually accompanied by the appearance of large shadow. The vascular shadows in 5 mm CT images had good ductility, and small nodules were easy to distinguish. The coronal MIP image of 5 mm chest CT used edge enhancement technology, which was prone to small shadow fusion and fibrotic shadow fusion. The coronal MPR image of 5 mm chest CT was highly consistent with the DR chest radiographs in terms of the integrity of film reading. GBZ 70-2015 standard was used to compare the profusion of DR chest radiographs and 5 mm chest CT coronal MPR images of 66 objects, and the consistency test Kappa=0.64. GBZ 70-2015 standard and experimental chest CT standard were used to compare the profusion results of DR chest radiographs and 5 mm chest CT coronal MPR images of 66 objects, respectively, and the consistency test Kappa=0.80, with high consistency. Conclusion: 5 mm coronal MPR image is suitable for chest CT imaging in the diagnosis of pneumoconiosis. Following the selection path and method of GBZ 70-2015 profusion criterion, the established experimental chest CT standard in determining the profusion of small circular shadows in 5 mm coronal MPR images of chest CT with pneumoconiosis has a high consistency with GBZ 70-2015 standard.


Assuntos
Pneumoconiose , Radiografia Torácica , Tomografia Computadorizada por Raios X , Humanos , Pneumoconiose/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X/métodos , Radiografia Torácica/métodos , Pessoa de Meia-Idade , Processamento de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Idoso
4.
J Exp Anal Behav ; 122(1): 72-86, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38785258

RESUMO

Hyperbolic relations between independent and dependent variables are ubiquitous in the experimental analysis of behavior, mentioned in over 150 articles in the Journal of the Experimental Analysis of Behavior. There are two principal forms of hyperbolae: The first describes the relation between response rate and reinforcement rate on variable-interval schedules of reinforcement; it rises asymptotically toward a maximum. The second describes the relation between the current equivalent value of an incentive and its delay or (im)probability; it falls from a maximum toward an asymptote of 0. Where do these come from? What do their parameters mean? How are they related? This article answers the first two questions and addresses the last.


Assuntos
Esquema de Reforço , Reforço Psicológico , Animais , Humanos , Condicionamento Operante
6.
J Cardiothorac Surg ; 19(1): 213, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616246

RESUMO

BACKGROUND: Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) represents a rare malignancy characterized by its aggressive behavior and a notably high recurrence rate. Remarkably, there is currently no established standard treatment protocol for this condition. CASE DESCRIPTION: In this report, we present an intriguing case of pLCNEC diagnosed at clinical-stage IIB. This case involves a 64-year-old man with a smoking history spanning four decades. In our approach, we initiated a course of neoadjuvant chemotherapy in combination with pembrolizumab, administered for two cycles prior to surgical resection. This innovative treatment strategy resulted in a significant pathological response, culminating in a major pathological remission (MPR). As of the time of composing this report, the patient has been diligently monitored for 39 months post-surgery, exhibiting no indications of recurrence, and has demonstrated exceptional tolerance to the entire treatment regimen. CONCLUSIONS: We have first reported a clinically successful case of neoadjuvant combination chemotherapy with pembrolizumab in the treatment of pLCNEC. This case offers promising clinical insights and suggests that this therapeutic approach could be a viable option for managing pLCNEC.


Assuntos
Carcinoma Neuroendócrino , Neoplasias Pulmonares , Masculino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quimioterapia Combinada
7.
Sensors (Basel) ; 24(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38475236

RESUMO

The Multi-Point Relay (MPR) is one of the core technologies for Optimizing Link State Routing (OLSR) protocols, offering significant advantages in reducing network overhead, enhancing throughput, maintaining network scalability, and adaptability. However, due to the restriction that only MPR nodes can forward control messages in the network, the current evaluation criteria for selecting MPR nodes are relatively limited, making it challenging to flexibly choose MPR nodes based on current link states in dynamic networks. Therefore, the selection of MPR nodes is crucial in dynamic networks. To address issues such as unstable links, poor transmission accuracy, and lack of real-time performance caused by mobility in dynamic networks, we propose a comprehensive evaluation algorithm of MPR based on link-state awareness. This algorithm defines five state evaluation parameters from the perspectives of node mobility and load. Subsequently, we use the entropy weight method to determine weight coefficients and employing the method of Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for comprehensive evaluation to select MPR nodes. Finally, the Comprehensive Evaluation based on Link-state awareness of OLSR (CEL-OLSR) protocol is proposed, and simulated experiments are conducted using NS-3. The results indicate that, compared to PM-OLSR, ML-OLSR, LD-OLSR, and OLSR, CEL-OLSR significantly improves network performance in terms of packet delivery rate, average end-to-end delay, network throughput, and control overhead.

8.
EFSA J ; 22(3): e8609, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435093

RESUMO

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Lietpak (EU register number RECYC319), which uses the EREMA MPR technology. The input material is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post-consumer PET containers, including no more than 5% PET from non-food consumer applications. The flakes are heated ■■■■■ under vacuum (step 2). Having examined the challenge test provided, the Panel concluded that this step 2, for which the challenge test was provided, is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of this step are temperature, pressure and residence time. It was demonstrated that this recycling process is able to ensure a level of migration of potential unknown contaminants into food below the conservatively modelled migration of 0.15 µg/kg food, derived from the exposure scenario for toddlers, when such recycled PET is used at up to 100%. Therefore, the Panel concluded that the recycled PET obtained from this process is not considered to be of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, except drinking water, for long-term storage at room temperature or below, with or without hot fill. Articles made of this recycled PET are not intended to be used in microwave or conventional ovens and such uses are not covered by this evaluation.

9.
Toxicol Mech Methods ; 34(5): 563-571, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38317456

RESUMO

BACKGROUND: In a previous study, diethylstilbestrol (DES) was shown to induce oocyte maturation in fish. In the present study, the interaction of DES on goldfish membrane progesterone receptor α (GmPRα) was investigated using a competitive binding assay with radiolabeled steroids. The results indicate that DES exerts its effects on membrane progesterone receptor alpha (mPRα) and induces oocyte maturation through nongenomic steroid mechanisms. This study provides empirical data that demonstrate the binding between DES and GmPRα. METHODS: Binding of DES to GmPRα was achieved by using radiolabeled DES and recombinant GmPRα expressed in culture cells or purified GmPRα proteins that coupled to graphene quantum dots (GQDs). Additionally, the competitive binding of fluorescently labeled progesterone to GmPRα-expressing cells was evaluated. RESULTS: Although significant nonspecific binding of radiolabeled DES to the cell membrane that expresses GmPRα has been observed, specific binding of DES to GmPRα has been successfully identified in the presence of digitonin. Furthermore, the specific binding of DES to GmPRα was confirmed by a binding assay using GQD-GmPRα. The radiolabeled DES was shown to bind to GQD-GmPRα. Additionally, the competition for the binding of fluorescently labeled progesterone to GmPRα-expressing cells was achieved with the DES. CONCLUSIONS: The results of the experiments revealed that DES binds to GmPRα. Thus, it can be concluded that DES induces goldfish oocyte maturation by binding to GmPRα.


Assuntos
Dietilestilbestrol , Proteínas de Peixes , Carpa Dourada , Receptores de Progesterona , Animais , Ligação Competitiva , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Dietilestilbestrol/toxicidade , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Carpa Dourada/metabolismo , Oócitos/metabolismo , Oócitos/efeitos dos fármacos , Progesterona/metabolismo , Ligação Proteica , Receptores de Progesterona/metabolismo
10.
Cell Oncol (Dordr) ; 47(3): 1005-1024, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38319500

RESUMO

PURPOSE: Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. METHODS: We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. RESULTS: Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. CONCLUSION: NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Prognóstico , Adulto , Resultado do Tratamento
11.
Front Bioeng Biotechnol ; 12: 1329209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318193

RESUMO

Myoelectric pattern recognition (MPR) has evolved into a sophisticated technology widely employed in controlling myoelectric interface (MI) devices like prosthetic and orthotic robots. Current MIs not only enable multi-degree-of-freedom control of prosthetic limbs but also demonstrate substantial potential in consumer electronics. However, the non-stationary random characteristics of myoelectric signals poses challenges, leading to performance degradation in practical scenarios such as electrode shifting and switching new users. Conventional MIs often necessitate meticulous calibration, imposing a significant burden on users. To address user frustration during the calibration process, researchers have focused on identifying MPR methods that alleviate this burden. This article categorizes common scenarios that incur calibration burdens as based on data distribution shift and based on dynamic data categories. Then further investigated and summarized the popular robust MPR algorithms used to reduce the user's calibration burden. We categorize these algorithms as based on data manipulate, feature manipulation and, model structure. And describes the scenarios to which each method is applicable and the conditions required for calibration. Finally, this review is concluded with the advantages of robust MPR and the remaining challenges and future opportunities.

12.
J Biol Chem ; 300(3): 105700, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307383

RESUMO

Selective retrograde transport from endosomes back to the trans-Golgi network (TGN) is important for maintaining protein homeostasis, recycling receptors, and returning molecules that were transported to the wrong compartments. Two important transmembrane proteins directed to this pathway are the Cation-Independent Mannose-6-phosphate receptor (CI-MPR) and the ATP7B copper transporter. Among CI-MPR functions is the delivery of acid hydrolases to lysosomes, while ATP7B facilitates the transport of cytosolic copper ions into organelles or the extracellular space. Precise subcellular localization of CI-MPR and ATP7B is essential for the proper functioning of these proteins. This study shows that both CI-MPR and ATP7B interact with a variant of the clathrin adaptor 1 (AP-1) complex that contains a specific isoform of the γ-adaptin subunit called γ2. Through synchronized anterograde trafficking and cell-surface uptake assays, we demonstrated that AP-1γ2 is dispensable for ATP7B and CI-MPR exit from the TGN while being critically required for ATP7B and CI-MPR retrieval from endosomes to the TGN. Moreover, AP-1γ2 depletion leads to the retention of endocytosed CI-MPR in endosomes enriched in retromer complex subunits. These data underscore the importance of AP-1γ2 as a key component in the sorting and trafficking machinery of CI-MPR and ATP7B, highlighting its essential role in the transport of proteins from endosomes.


Assuntos
Complexo 1 de Proteínas Adaptadoras , ATPases Transportadoras de Cobre , Endossomos , Transporte Proteico , Receptor IGF Tipo 2 , Rede trans-Golgi , Humanos , Endossomos/metabolismo , Células HeLa , Transporte Proteico/genética , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismo , Rede trans-Golgi/genética , Rede trans-Golgi/metabolismo , ATPases Transportadoras de Cobre/genética , ATPases Transportadoras de Cobre/metabolismo , Complexo 1 de Proteínas Adaptadoras/genética , Complexo 1 de Proteínas Adaptadoras/metabolismo , Subunidades gama do Complexo de Proteínas Adaptadoras/metabolismo
13.
Mod Pathol ; 37(1): 100353, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37844869

RESUMO

Neoadjuvant treatment of non-small cell lung cancer challenges the traditional processing of pathology specimens. Induction therapy before resection allows evaluation of the efficacy of neoadjuvant agents at the time of surgery. Many clinical trials use pathologic tumor response, measured as major pathologic response (MPR, ≤10% residual viable tumor [RVT]) or complete pathologic response (CPR, 0% RVT) as a surrogate of clinical efficacy. Consequently, accurate pathologic evaluation of RVT is crucial. However, pathologic assessment has not been uniform, which is particularly true for sampling of the primary tumor, which instead of the traditional processing, requires different tissue submission because the focus has shifted from tumor typing alone to RVT scoring. Using a simulation study, we analyzed the accuracy rates of %RVT, MPR, and CPR of 31 pretreated primary lung tumors using traditional grossing compared with the gold standard of submitting the entire residual primary tumor and identified the minimum number of tumor sections to be submitted to ensure the most accurate scoring of %RVT, MPR, and CPR. Accurate %RVT, MPR, and CPR calls were achieved in 52%, 87%, and 81% of cases, respectively, using the traditional grossing method. Accuracy rates of at least 90% for these parameters require either submission of all residual primary tumor or at least 20 tumor sections. Accurate %RVT, MPR, and CPR scores cannot be achieved with traditional tumor grossing. Submission of the entire primary tumor, up to a maximum of 20 sections, is required for the most accurate reads.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Pulmão/patologia , Resultado do Tratamento
14.
Oral Dis ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884358

RESUMO

OBJECTIVES: We investigated the association between statin compliance and the risk of dementia among patients with chronic periodontitis. METHODS: Chronic periodontitis patients were extracted from the National Health Insurance Service-Health Screening Cohort Database, covering the period from 2002 to 2019. A total of 22,089 subjects were included in the study and divided into three groups based on their compliance with statin administration. The Cox proportional hazard model was utilized to calculate hazard ratios and 95% confidence intervals for analyzing the risk of dementia. RESULTS: In the restricted cubic spline of the multivariable-adjusted model, the hazard ratio for dementia decreased prominently with a higher medication possession ratio. The hazard ratios and 95% confidence intervals in the multivariable-adjusted model for dementia risk in the middle and high medication possession ratio groups, compared to the low medication possession ratio group, were confirmed as 0.70 (0.57-0.87) and 0.57 (0.45-0.72), respectively. In the subgroup analysis, a significant association between dementia and good statin medication possession ratio was found in both severe periodontitis and mild periodontitis cases. CONCLUSIONS: Our findings suggest that a group of patients with chronic periodontitis who maintain good statin compliance are associated with a reduced risk of dementia.

16.
J Exp Anal Behav ; 120(3): 289-319, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37706228

RESUMO

The three principles of reinforcement are (1) events such as incentives and reinforcers increase the activity of an organism; (2) that activity is bounded by competition from other responses; and (3) animals approach incentives and their signs, guided by their temporal and physical conditions, together called the "contingencies of reinforcement." Mathematical models of each of these principles comprised mathematical principles of reinforcement (MPR; Killeen, 1994). Over the ensuing decades, MPR was extended to new experimental contexts. This article reviews the basic theory and its extensions to satiation, warm-up, extinction, sign tracking, pausing, and sequential control in progressive-ratio and multiple schedules. In the latter cases, a single equation balancing target and competing responses governs behavioral contrast and behavioral momentum. Momentum is intrinsic in the fundamental equations, as behavior unspools more slowly from highly aroused responses conditioned by higher rates of incitement than it does from responses from leaner contexts. Habits are responses that have accrued substantial behavioral momentum. Operant responses, being predictors of reinforcement, are approached by making them: The sight and feel of a paw on a lever is approached by placing paw on lever, as attempted for any sign of reinforcement. Behavior in concurrent schedules is governed by approach to momentarily richer patches (melioration). Applications of MPR in behavioral pharmacology and delay discounting are noted.


Assuntos
Condicionamento Operante , Reforço Psicológico , Animais , Esquema de Reforço , Motivação , Modelos Teóricos
17.
J Thorac Oncol ; 18(10): 1290-1302, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37702631

RESUMO

INTRODUCTION: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria. METHODS: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion. RESULTS: Unanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76-0.92) and 0.86 (95% CI: 0.79-0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96-1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89-0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma. CONCLUSIONS: Our study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante/métodos , Reprodutibilidade dos Testes , Carcinoma Pulmonar de Células não Pequenas/patologia , Pulmão/patologia
18.
Steroids ; 199: 109295, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37558174

RESUMO

Substantial progress has been made in our understanding of the nongenomic actions, ligand binding, intracellular signaling pathways, and functions of membrane progesterone receptors (mPRs) in reproductive and nonreproductive tissues since their discovery 20 years ago. The five mPRs are members of the progestin adipoQ receptor (PAQR) family which also includes adiponectin receptors (AdipoRs). However, unlike AdipoRs, the 3-D structures of mPRs are unknown, and their structural characteristics remain poorly understood. The mechanisms regulating mPR functions and their trafficking to the cell surface have received little attention and have not been systematically reviewed. This paper summarizes some structural aspects of mPRs, including the ligand binding pocket of mPRα recently derived from homology modeling with AdipoRs, and the proposed topology of mPRs from the preponderance of positively charged amino acid residues in their intracellular domains. The mechanisms of trafficking membrane receptors to the cell surface are discussed, including the amino acid motifs involved with their export to the cell surface, the roles of adaptor proteins, and post-translational glycosylation and palmitoylation modifications that promote cell surface expression and retention. Evidence for similar mechanisms regulating the expression and functions of mPRs on the cell surface is discussed, including the identification of potential export motifs on mPRα required for its trafficking to the cell membrane. Collectively, these results have identified several potential mechanisms regulating the expression and functions of mPRs on the cell membrane for further investigation.


Assuntos
Progesterona , Receptores de Progesterona , Membrana Celular/metabolismo , Ligantes , Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Transdução de Sinais
19.
Artigo em Inglês | MEDLINE | ID: mdl-37492275

RESUMO

Tomosynthesis acquires projections over a limited angular range, resulting in anisotropic sampling in the Fourier domain. The volume of the sampled space is therefore spatially dependent; different Fourier components are sampled for the same object, depending upon where the object is located relative to the system origin. A next-generation tomosynthesis (NGT) system was developed at the University of Pennsylvania to increase the spatial isotropy in DBT, by incorporating additional system motions. In this work, we investigate the spatial dependency of image quality in tomosynthesis and compare conventional and NGT tomosynthesis in terms of multiplanar reconstruction (MPR). Two test objects, a high-frequency star pattern and a low-frequency octagon phantom, were placed throughout the detector field of view at various obliquities to analyze the anisotropic nature of tomosynthesis. Reconstructions of the star pattern were analyzed both qualitatively and quantitatively using the Fourier distortion metric (FSD). Reconstructions of the octagon phantom were analyzed qualitatively. In a separate experiment, a container filled with water and acrylic beads of various diameters were imaged at various locations to simulate low-contrast objects mimicking breast tissue. We show that the spatial dependency of MPR is unique to the tilt angle, orientation, and frequency of the input. The NGT geometry benefitted the visualization of objects by reducing the out-of-plane artifacts in MPR.

20.
J Oncol Pharm Pract ; 29(8): 1921-1927, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37350157

RESUMO

PURPOSE: To evaluate the impact that a pharmacist-managed oral anticancer clinic has on patient adherence to oral anticancer therapy in regard to medication adherence and adherence to lab monitoring. METHODS: A retrospective chart review was completed for patients prescribed abiraterone, enzalutamide, or ibrutinib within the study time period. The primary outcome was assessing medication adherence by comparing the medication possession ratio (MPR) before (Phase 1) and after (Phase 2) initiation of the pharmacist-led oral anticancer therapy clinic. The secondary outcome was assessing lab monitoring adherence by patients and providers in Phase 1 and Phase 2. This will be done by assessing whether labs were ordered at the appropriate time frame by oncology providers, as well as whether or not the patient came and got these labs drawn. This study will also examine outcomes related to the pharmacist-led oral anticancer therapy clinic (phase 2) for descriptive purposes. RESULTS: A total of 189 charts were analyzed with 134 excluded and 55 included (25 patients in phase 1 and 30 patients in phase 2). Independent sample t-test analyses revealed a statistically significant increase (t(30.57) = -1.99; p = 0.027) in the MPR ratio between phase 1 (mean = 0.98, SD = 0.13) compared to phase 2 (mean = 1.04, SD = 0.08). For patient adherence to lab monitoring, there was a statistically significant improvement between phase 1 and phase 2 for patients on abiraterone (21.9% vs 67%; t(25) = -5.73; p < 0.001) and enzalutamide (35.7% vs. 90.5%; t(8) = -3.26; p = 0.006). However, for patients on ibrutinib, there was a slight decline in lab monitoring adherence between phase 1 and phase 2 but this effect was not statistically significant (56.2% vs. 51%; t(17) = 0.58; p = 0.283). Similar results were shown for provider adherence to lab monitoring. Descriptive outcomes showed that the pharmacist had, on average, 6.7 encounters per patient with the majority being phone and face-to-face appointments. CONCLUSIONS: Data from this study demonstrated that a pharmacist-led oral anticancer clinic can improve MPR ratios and patient adherence to oral anticancer medication regimens. In addition, patient and provider lab monitoring adherence was improved for abiraterone and enzalutamide. Improvement in patient and provider lab monitoring adherence for ibrutinib was not shown, possibly due to the impact of the COVID-19 pandemic, relatively small sample size, and retrospective nature of this study. The results of this study support that overall, a pharmacist-led oral anticancer clinic can significantly improve patient outcomes, which aligns with previous smaller studies that have shown similar benefits.


Assuntos
Antineoplásicos , Farmacêuticos , Humanos , Estudos Retrospectivos , Pandemias , Antineoplásicos/efeitos adversos , Adesão à Medicação
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