Programmed death-ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma of HIV-infected and non-infected patients.

Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus-positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease.

Beta-HCG secretion by a pulmonary pleomorphic carcinoma: A case report.

Ectopic secretion of beta-subunit of human chorionic gonadotropin (ß-HCG) in pulmonary pleomorphic carcinoma is remarkably rare. Such unusual ectopic hormone production by lung cancer may be initially misinterpreted as extragonadal choriocarcinoma or germ cell tumor. We report a 56-year-old postmenopausal female, smoker, who presented a 5-month history of progressive dyspnea, dry paroxysmal cough, and significant weight loss. She was referred by a local hospital with the preliminary diagnosis of gestational trophoblastic neoplasia due to a rapidly growing thoracic tumor with persistently elevated serum ß-HCG. Computed tomography of the chest showed a lung mass in the right upper lobe associated with homolateral pleural effusion. Positron emission tomography showed pathological 2-[18F]FDG uptake at the mass lesion. Biopsies were performed. Histological examination described pleomorphic carcinoma with positive immunostaining for ß-HCG. The serum levels of ß-HCG were also elevated indicating ectopic secretion. The patient had rapid clinical deterioration and deceased before chemotherapy initiation. Only a few cases of paraneoplastic ß-HCG secretion have been reported in the literature. Previous studies suggested that the ability to secrete ß-hCG in tumors may correlate to some extent to chemoresistance; thus, it might be useful as a prognosis marker.

Solitary fibrous tumor of the pleura: A giant finding, a benign entity?

Solitary fibrous tumor of the pleura (SFTP) is a rare tumor. The prognosis is relatively good, but up to 20% of the cases are malignant. We presented a case of a large mass of the thorax, showing malignant poor prognosis features. A 73-year-old male, former smoker, presented with a history of dry cough. Chest CT revealed a left bronchopulmonary mass (11 cm × 14 cm) extending from the costal pleura to the left hilum. Histopathologic examination of the transbronchial lung biopsy was consistent with SFTP. A left pneumonectomy was performed due to invasive nature of the lesion. According to features associated to poor prognosis (lung tumor ≥ 10 cm, hipercellularity, abundant intratumor blood vessels and areas of necrosis), and in spite of proliferation index (Ki67+) <1%, the case was discussed in a multidisciplinary meeting, and was assumed to be malignant. At the present time, the patient is his fifth month after surgery, in tight follow up. This case highlights a rare SFTP presenting bad prognosis features, that although completely resected should have long-term follow-up due to the high risk of recurrence.

Detection of HIV mRNA in routine liquid-based cytology specimens of HIV-infected women.

OBJECTIVE: Human immunodeficiency virus-infected women have a high incidence of HPV infection, and HIV and HPV coinfection is associated with high incidence of cervical intraepithelial lesions and cervical cancer. This study investigated the ability to detect HIV mRNA in routine screening cervical liquid-based cytology (LBC) samples and its correlation with HPV coinfection and cervical intraepithelial lesions. METHODS: Liquid-based cytology samples from 80 HIV-infected women under combined antiretroviral therapy (cART) were studied for detection of HIV and HPV mRNA using Aptima® tests and for cytology diagnosis according to the 2014 Bethesda System for Reporting Cervical Cytology. Peripheral blood (PB) HIV mRNAs were assessed by real-time polymerase chain reaction (RT-PCR). Statistical analysis used Fisher's exact or Chi-square test to compare frequencies among groups and the Mann-Whitney U test to compare continuous variables. RESULTS: Human immunodeficiency virus mRNA was present in 21.3% of routine LBC samples in HIV-infected women, 12.5% of which had no detectable PB viral load. Among 10 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL), 50% had detectable HIV viral load. The occurrence of HSIL vs low-grade intraepithelial lesion/negative intraepithelial lesion or malignancy in LBC samples was significantly higher in women with detectable HIV viral load (P = .029). CONCLUSIONS: Human immunodeficiency virus mRNA was present in routine LBC samples in HIV-positive women under cART. Detection of HIV viral load in LBC is significantly associated with cervical HSIL. This suggests the relevance of HIV mRNA viral load assessment in routine LBC, to evaluate patients' infectious potential and monitor efficacy of the cART scheme.

CD4+ and CD8+ cell populations in HIV-positive women with cervical squamous intra-epithelial lesions and squamous cell carcinoma.

INTRODUCTION: This study aimed to analyse cervical lymphocytic populations in HIV+ and HIV- patients and correlate different cervical lesions with HIV viral load and presence of high-risk HPV types. MATERIAL AND METHODS: A total of 132 histological specimens from 40 HIV+ and 72 HIV- patients were evaluated for CD4+ and CD8+ T cell distribution, presence of high-risk HPV types, peripheral blood HIV viral load and CD4+/CD8+ ratio. RESULTS: High-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) from HIV+ patients had lower CD4+ T cell scores compared with HIV- patients. In all lesion groups, HIV+ patients presented higher epithelial and stromal CD8+ T cell scores. HIV viral load was more often detectable in patients with SCC than in those with low-grade squamous intraepithelial lesion (LSIL) (p = 0.0409). HSIL HIV+ patients had lower circulating CD4+ T cell counts (p = 0.0434) and CD4+/CD8+ ratio (p = 0.0378) compared with LSIL HIV+ patients. High-risk HPV types other than 16 and 18/45 were more prevalent in the HIV+ group. DISCUSSION: These results support an imbalance between cervical CD4+ and CD8+ T lymphocytes of HIV+ patients with SIL and SCC, with increased CD8+ infiltrate density with lesion severity, even in patients with immune system recovery under cART.

Pleural Sarcoidosis and Occult Lymphatic Anthracosis: An Unusual Symptomatic Association.

Sarcoidosis is a chronic multisystemic inflammatory disease of unknown aetiology. Virtually any organ or system can be involved, resulting in a wide range of clinical presentation. Pleural sarcoidosis is rare. Pleural effusion can only be attributed to pleural sarcoidosis in the presence of pleural non-caseating epithelioid granulomas and after excluding other granulomatous diseases. Anthracosis is a pneumoconiosis associated with thoracic adenopathies and bronchial disease, and it is usually asymptomatic. The authors present a case of a middle-aged man hospitalized due to cough, right-sided pleuritic chest pain and trepopnoea. LEARNING POINTS: To pursue a systematic and exhaustive investigation of pleuraleffusion until a definitive diagnosis is established.To recognize atypical presentations of sarcoidosis with a high degree of suspicion whenever the initial investigation is inconclusive.

Effects of trust-based decision making in disrupted supply chains.

The United States has experienced prolonged severe shortages of vital medications over the past two decades. The causes underlying the severity and prolongation of these shortages are complex, in part due to the complexity of the underlying supply chain networks, which involve supplier-buyer interactions across multiple entities with competitive and cooperative goals. This leads to interesting challenges in maintaining consistent interactions and trust among the entities. Furthermore, disruptions in supply chains influence trust by inducing over-reactive behaviors across the network, thereby impacting the ability to consistently meet the resulting fluctuating demand. To explore these issues, we model a pharmaceutical supply chain with boundedly rational artificial decision makers capable of reasoning about the motivations and behaviors of others. We use multiagent simulations where each agent represents a key decision maker in a pharmaceutical supply chain. The agents possess a Theory-of-Mind capability to reason about the beliefs, and past and future behaviors of other agents, which allows them to assess other agents' trustworthiness. Further, each agent has beliefs about others' perceptions of its own trustworthiness that, in turn, impact its behavior. Our experiments reveal several counter-intuitive results showing how small, local disruptions can have cascading global consequences that persist over time. For example, a buyer, to protect itself from disruptions, may dynamically shift to ordering from suppliers with a higher perceived trustworthiness, while the supplier may prefer buyers with more stable ordering behavior. This asymmetry can put the trust-sensitive buyer at a disadvantage during shortages. Further, we demonstrate how the timing and scale of disruptions interact with a buyer's sensitivity to trustworthiness. This interaction can engender different behaviors and impact the overall supply chain performance, either prolonging and exacerbating even small local disruptions, or mitigating a disruption's effects. Additionally, we discuss the implications of these results for supply chain operations.

Mantle cell lymphoma of the cecum.

The authors have read with great interest the recently published article "Colon lymphomas: an analysis of our experience over the last 23 years" by Martín Domínguez V et al., a single center retrospective review of 29 patients diagnosed with colon lymphoma. The present report describes a case of mantle cell lymphoma (MCL) of the cecum that aims to improve the knowledge regarding this unusual clinical and endoscopic entity.

Project INSIDE: towards autonomous semi-unstructured human-robot social interaction in autism therapy.

This paper describes the INSIDE system, a networked robot system designed to allow the use of mobile robots as active players in the therapy of children with autism spectrum disorders (ASD). While a significant volume of work has explored the impact of robots in ASD therapy, most such work comprises remotely operated robots and/or well-structured interaction dynamics. In contrast, the INSIDE system allows for complex, semi-unstructured interaction in ASD therapy while featuring a fully autonomous robot. In this paper we describe the hardware and software infrastructure that supports such rich form of interaction, as well as the design methodology that guided the development of the INSIDE system. We also present some results on the use of our system both in pilot and in a long-term study comprising multiple therapy sessions with children at Hospital Garcia de Orta, in Portugal, highlighting the robustness and autonomy of the system as a whole.

A comunicação dos treinadores de futebol de equipes infanto-juvenis amadores e profissionais durante a competição / The coach's communication with scholastic and adult teams during soccer matches

No futebol, a comunicação durante a competição é a forma que o treinador utiliza para transmitir informação com o objetivo de otimizar o rendimento dos jogadores. Pretendemos caracterizar e comparar os comportamentos de instrução dos treinadores de times de jogadores infanto-juvenis e adultos. Foram filmados dez treinadores (cinco de equipes infanto-juvenis e cinco de equipes de adultos) em dezenove jogos. O sistema de observação para recolha de dados relativos ao comportamento de instrução foi o SAIC. Os resultados obtidos demonstram a existência de diferenças entre os treinadores de equipes infanto-juvenis e de adultos no que diz respeito à instrução, à atenção e ao comportamento motor reativo.

During soccer competitions, coaches communicate with the players to address information that should optimize performance of the players. Our purpose is to characterize and compare the coach behaviors during instruction to adults and scholastic teams. Ten coaches (five from scholastic soccer teams and five from adult teams) were videotaped during nineteen games. The observation system used for data collection of instruction behaviors was the SAIC. The results indicate the existence of differences between coaches from scholastic soccer teams and five from adult teams with regard to instruction, attention and reactive motor behavior.