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Background: Skin and soft-tissue infections (SSTIs) are common infectious syndromes in children. Overusing broad-spectrum antibiotics has contributed to rising antibiotic resistance, complicating treatment outcomes. To address this issue, antimicrobial stewardship programs (ASPs) have been implemented to optimize antibiotic use. This study evaluated the impact of a multifaceted ASP on antibiotic prescribing practices for SSTIs in a pediatric acute care setting over eight years. Methods: We conducted a quasi-experimental study at the Pediatric Acute Care Unit of the Padua University Hospital, including children admitted with SSTIs from October 2014 to September 2022, to evaluate the impact of a multifaceted ASP implemented in October 2015. The study was divided into three periods: pre-implementation (October 2014–September 2015), post-implementation (October 2015–March 2020), and COVID-19 (April 2020–August 2022). Data on antibiotic prescriptions and microbiological results were collected and analyzed. Results: The implementation of the ASP led to a significant reduction in the use of broad-spectrum antibiotics, particularly third-generation cephalosporins (from 40.4% to 9.8%) and glycopeptides (from 21.1% to 1.6%). There was a notable increase in the prescription of Access antibiotics, from 30% in the pre-implementation to over 60% in the post-implementation and 80% during COVID-19. No increase in the hospital length of stay was observed. Microbiological results showed no significant changes in bacterial profiles over time. Conclusions: The use of the ASP effectively improved antibiotic prescribing practices, reducing reliance on broad-spectrum antibiotics even during the COVID-19 pandemic. These findings highlight the value of ongoing stewardship efforts and suggest the need for similar programs in ambulatory settings to further address antibiotic resistance. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a serious threat to human and animal life on earth. Policies that are implemented to slow down or reverse AMR are termed antimicrobial stewardship programs (ASPs). The focus of this narrative review is to determine how ASPs policies can effectively change the way that antimicrobials are used. Specific search terms were used across three databases to generate an initial pool of papers. After careful review of all search results, 27 were selected and analyzed according to the type of study, themes, and discussion of AMR and ASPs. There was variety in the types of studies analyzed, however, there was a striking lack of research in veterinary medicine. Major themes of ASP success were discovered as follows: interprofessional collaboration, dedicated stakeholders, and importance of education. Several barriers to ASP success are discussed from staffing to facilities to information technology. Low to middle income countries (LMICs) have additional barriers to ASP implementation. ASPs can be effective methods at reducing antimicrobial usage and cost of treatment while improving patient care; however, current research on ASPs has shown little impact on AMR. [ABSTRACT FROM AUTHOR]

Objective: The objective was to review the pharmacology, efficacy, and safety of atezolizumab (Tecentriq) for the treatment of adult and pediatric patients aged 2 years and older with unresectable or metastatic alveolar soft part sarcoma (ASPS). Data Sources: A literature search was conducted using PubMed and MEDLINE databases, published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and May 31, 2023. Keywords included atezolizumab, Tecentriq, MPDL3280, immunotherapy, PD-L1, PD-1, pediatrics, sarcoma, and ASPS. Study selection and data extraction: All English-language studies involving atezolizumab for ASPS were included and discussed. Data synthesis: Atezolizumab is an anti-programmed death-ligand 1 (PD-L1) monoclonal antibody designed to block the interaction between PD-L1 and the programmed cell death protein 1 (PD-1) receptor. Atezolizumab was granted approval by the FDA specifically for ASPS based on a phase II clinical trial in adult and pediatric patients (n = 49), which reported an overall response rate of 24% and a durable response rate at 6 and 12 months of 67% and 42%, respectively. Common grade 3/4 adverse reactions include musculoskeletal pain (8%), followed by hypertension (6%), weight gain (6%), headache (4%), and dizziness (4%). Relevance to patient care and clinical practice in comparison with existing drugs: Advanced ASPS is a high-risk disease with limited treatment options. Atezolizumab appears to be a viable treatment option in ASPS demonstrating clinical efficacy and a manageable toxicity profile. Conclusions: With no other treatments that are FDA approved specifically for ASPS, and few demonstrating efficacy in the advanced setting, the approval of atezolizumab, including the first approval for pediatric patients, represents a landmark improvement to the therapeutic arsenal against this rare disease. [ABSTRACT FROM AUTHOR]

Background: Skin and soft-tissue infections (SSTIs) are common infectious syndromes in children. Overusing broad-spectrum antibiotics has contributed to rising antibiotic resistance, complicating treatment outcomes. To address this issue, antimicrobial stewardship programs (ASPs) have been implemented to optimize antibiotic use. This study evaluated the impact of a multifaceted ASP on antibiotic prescribing practices for SSTIs in a pediatric acute care setting over eight years. Methods: We conducted a quasi-experimental study at the Pediatric Acute Care Unit of the Padua University Hospital, including children admitted with SSTIs from October 2014 to September 2022, to evaluate the impact of a multifaceted ASP implemented in October 2015. The study was divided into three periods: pre-implementation (October 2014–September 2015), post-implementation (October 2015–March 2020), and COVID-19 (April 2020–August 2022). Data on antibiotic prescriptions and microbiological results were collected and analyzed. Results: The implementation of the ASP led to a significant reduction in the use of broad-spectrum antibiotics, particularly third-generation cephalosporins (from 40.4% to 9.8%) and glycopeptides (from 21.1% to 1.6%). There was a notable increase in the prescription of Access antibiotics, from 30% in the pre-implementation to over 60% in the post-implementation and 80% during COVID-19. No increase in the hospital length of stay was observed. Microbiological results showed no significant changes in bacterial profiles over time. Conclusions: The use of the ASP effectively improved antibiotic prescribing practices, reducing reliance on broad-spectrum antibiotics even during the COVID-19 pandemic. These findings highlight the value of ongoing stewardship efforts and suggest the need for similar programs in ambulatory settings to further address antibiotic resistance.

This review emphasizes the significance of formulating control strategies for biological and advanced oxidation process (AOP)-based wastewater treatment systems. The aim is to guarantee that the effluent quality continuously aligns with environmental regulations while operating costs are minimized. It highlights the significance of understanding the dynamic behaviour of the process in developing effective control schemes. The most common process control strategies in wastewater treatment plants (WWTPs) are explained and listed. It is emphasized that the proper control scheme should be selected based on the process dynamic behaviour and control goal. This study further discusses the challenges associated with the control of wastewater treatment processes, including inadequacies in developed models, the limitations of most control strategies to the simulation stage, the imperative requirement for real-time data, and the financial and technical intricacies associated with implementing advanced controller hardware. It is discussed that the necessity of the availability of real-time data to achieve reliable control can be achieved by implementing proper, accurate hardware sensors in suitable locations of the process or by developing and implementing soft sensors. This study recommends further investigation on available actuators and the criteria for choosing the most appropriate one to achieve robust and reliable control in WWTPs, especially for biological and AOP-based treatment approaches. [ABSTRACT FROM AUTHOR]

This paper investigates the development of an intelligent system method to address completely locked-in-syndrome (CLIS) that is caused by some illnesses such as Amyotrophic Lateral Sclerosis (ALS) as the most predominant type of Motor Neuron Disease (MND). In the last stages of ALS and despite the limitations in body movements, patients however will have a fully functional brain and cognitive capabilities and able to feel pain but fail to communicate. This paper aims to address the CLIS problem by utilizing EEG signals that human brain generates when thinking about a specific feeling or imagination as a way to communicate. The aim is to develop a low-cost and affordable system for patients to use to communicate with carers and family members. In this paper, the novel implementation of the ASPS (Automated Sensor and Signal Processing Selection) approach for feature extraction of EEG is presented to select the most suitable Sensory Characteristic Features (SCFs) to detect human thoughts and imaginations. Artificial Neural Networks (ANN) are used to verify the results. The findings show that EEG signals are able to capture imagination information that can be used as a means of communication; and the ASPS approach allows the selection of the most important features for reliable communication. This paper explains the implementation and validation of ASPS approach in brain signal classification for bespoke arrangement. Hence, future work will present the results of relatively high number of volunteers, sensors and signal processing methods.

Introduction: In highly autonomous driving scenarios, it is critical to identify strategies to accelerate reaction times since drivers may take too long to take over control of the vehicle. Previous studies reported that an Acoustic Startling Pre-Stimulus (ASPS, i.e., a loud warning preceding an action) accelerated reaction times in simple ankle flexion exercises.Methods: In this study, we examined if an ASPS warning leads to shorter takeover reaction times in a sled-simulated evasive swerving maneuver. Twenty-eight participants (seven male adults, seven male teenagers, seven female adults, and seven female teenagers) were instructed to align a marker on the steering wheel with a marker on a lateral post as fast as they could as soon as the lateral sled perturbation (0.75 g) started. Four conditions were examined: with and without an ASPS (105 dB, played 250 ms before sled perturbation for 40 ms), and with and without a secondary task (i.e., texting). A catch trial (ASPS only) was used to minimize anticipation. Human kinematics were captured with an 8-camera 3D motion capture system.Results: Results showed that the drivers’ hands lifted towards the steering wheel more quickly with the ASPS (169 ± 55 ms) than without (194 ± 46 ms; p = 0.01), and that adult drivers touched the steering wheel quicker with the ASPS (435 ± 54 ms) than without (470 ± 33 ms; p = 0.01). Similar findings were not observed for the teen drivers. Additionally, female drivers were found to lift their hands towards the steering wheel faster than male drivers (166 ± 58 ms vs. 199 ± 36 ms; p = 0.009).Discussion: Our findings suggest that the ASPS may be beneficial to accelerate driver reaction times during the initiation of a correction maneuver, and that autonomous vehicle warnings may need to be tailored to the age and sex of the driver.

Pre-pretensioner (PPT) seatbelts have been found to be effective in controlling vehicle occupants' motion response to disturbances in optimally positioned occupants, but it is not clear how the PPT performs when the occupant is initially forward leaning. Previous work demonstrated that an acoustic startling pre-stimulus (ASPS) reduced trunk out-of-position in sled-simulated pre-crash maneuvers. Therefore, the aim of this study was to determine if coupling the PPT with the ASPS could reduce the needed magnitude and rate of belt tension of the PPT to reposition forward leaning occupants to their optimal position within the seatbelt. Sixteen belt-restrained adult human volunteers (8 males and 8 females) restrained by a 3-point seatbelt on a vehicle seat in a forward leaning posture on a sled simulating pre-crash braking (approx. 1 g of maximum acceleration and 0.3 s duration) were exposed to sled perturbations with three belt configurations (low and high force PPT and no PPT), and two warning conditions (ASPS and no-ASPS). Head and trunk positions were extracted from the 3D motion-capture data. Repeated measure ANOVAs were used to understand the effect of sex, PPT, ASPS, and repetition on head and trunk positions. A survival analysis was also performed to understand the probability of the occupants moving rearward in the different conditions. The probability of the head and trunk to move rearward from the initial position was greater with the PPT than without the PPT (p = 0.01) and with the high force level than the low force level (p = 0.01). The interaction effect of ASPS x PPT showed that with no PPT, there was a greater probability for the head to move rearward from the initial position with ASPS than without ASPS (p < 0.03). The trunk shows a similar trend to the head, but the ASPS vs no-ASPS differences were not statistically significant (p = 0.06). No sex differences were found. The PPT, particularly the high level, may be an effective countermeasure on its own to reduce trunk and head out-of-position in forward leaning postures in pre-crash scenarios. The ASPS reduced the occupants' head forward position when the PPT was not available. [ABSTRACT FROM AUTHOR]

Bader Alshamsan,1,2 Ahmad Badran,1,3 Aisha Alshibany,1 Fatma Maraiki,1 Mahmoud A Elshenawy,1,4 Tusneem Elhassan,1 Jean Paul Atallah1 1Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 2Department of Medicine, College of Medicine, Qassim University, Buraydah, Qassim, Saudi Arabia; 3Clinical Oncology Department, Ain Shams University Hospitals, Ain Shams, Cairo, Egypt; 4Clinical Oncology, Faculty of Medicine – Menoufia University, Shebeen El-Kom, Shibin el Kom, Menoufia Governorate, EgyptCorrespondence: Bader AlshamsanDivision of Medical Oncology, The Ottawa Hospital Cancer Centre, Box 920 General Campus, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, CanadaTel +1 6137377700 Ext. 73467Email bshmsan@qu.edu.saPurpose: Pazopanib has been approved for treating soft tissue sarcomas (STS) after chemotherapy. We aimed to evaluate the prognostic factors, clinical outcomes, and tolerability of pazopanib in patients with STS.Patients and Methods: Forty-five patients treated between June 2015 and August 2019 were reviewed. Clinical outcome was measured by assessing the disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors (version 1.1). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse effects were assessed using the Common Terminology Criteria for Adverse Events (version 5.0).Results: The median age of patients at diagnosis was 28 (interquartile range (IQR), 23– 45) years. Pazopanib was used as the second-line treatment in 46.7% and the subsequent line in 53.3% of patients. The overall DCR was 55.6%, and at 8 and 12 weeks, it was 52.3% and 35.5%, respectively; the median duration of response was 7 (IQR: 2– 18) months. Pazopanib-induced hypothyroidism was associated with DCR, with an odds ratio of 7 (95% confidence interval [95% CI: 1.7– 27.5], p< 0.01). The median PFS and OS were 4.1 (95% CI: 0.85– 7.42) and 12.4 months (95% CI: 6.5– 18.36), respectively. Hypothyroidism and response to pazopanib, better ECOG PS, histological subtypes desmoid tumor/aggressive fibromatosis (DT/AF), and alveolar soft part sarcoma (ASPS) were favorable prognostic factors for PFS. Hypothyroidism and response to pazopanib were significant favorable factors for OS. There was no statistical difference in the OS between patients using pazopanib as the second-line therapy and those using it as the subsequent-line therapy.Conclusion: Pazopanib is an effective treatment for STS. However, it showed variability in the clinical outcome in favor of ASPS and an outstanding response in the DF/AT subtype. Pazopanib-induced hypothyroidism is a good prognostic factor for disease control and is associated with prolonged PFS and OS.Keywords: STS, a tyrosine kinase inhibitor, pazopanib, DT/AF, UPS, LMS, ASPS, Saudi Arabia

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)—TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis. Herein, we report a rare case of primary ASPS of the cheek harbouring ASPSCR1 (exon 7)—TFE3 (exon 5) fusion gene in a 21 year-old woman. This tumour was a well-circumscribed, smooth, round mass that was clinically suspected as a benign tumour. However, histologically, it was observed that the polygonal tumour cells were arranged in solid and alveolar growth patterns. Post-operative examination of the whole body excluded the possibility of metastasis at other sites. Thus, careful immunohistochemical and genetic analyses, as well as whole-body examination, demonstrated that the tumour was a primary ASPS of the cheek. [ABSTRACT FROM AUTHOR]

Alveolar soft-part sarcoma (ASPS) is an extremely rare malignancy characterized by the unbalanced translocation der(17)t(X;17)(p11;q25). This translocation generates a fusion protein, ASPL-TFE3, that drives pathogenesis through aberrant transcriptional activity. Although considerable progress has been made in identifying ASPS therapeutic vulnerabilities (e.g., MET inhibitors), basic research efforts are hampered by the lack of appropriate in vitro reagents with which to study the disease. In this report, previously unmined microarray data for the ASPS cell line, ASPS-1, was analyzed relative to the NCI sarcoma cell line panel. These data were combined with meta-analysis of pre-existing ASPS patient microarray and RNA-seq data to derive a platform-independent ASPS transcriptome. Results demonstrated that ASPS-1, in the context of the NCI sarcoma cell panel, had some similarities to normal mesenchymal cells and connective tissue sarcomas. The cell line was characterized by high relative expression of transcripts such as CRYAB, MT1G, GCSAML, and SV2B. Notably, ASPS-1 lacked mRNA expression of myogenesis-related factors MYF5, MYF6, MYOD1, MYOG, PAX3, and PAX7. Furthermore, ASPS-1 had a predicted mRNA surfaceome resembling an undifferentiated mesenchymal stromal cell through expression of GPNMB, CD9 (TSPAN29), CD26 (DPP4), CD49C (ITGA3), CD54 (ICAM1), CD63 (TSPAN30), CD68 (SCARD1), CD130 (IL6ST), CD146 (MCAM), CD147 (BSG), CD151 (SFA-1), CD166 (ALCAM), CD222 (IGF2R), CD230 (PRP), CD236 (GPC), CD243 (ABCB1), and CD325 (CDHN). Subsequent re-analysis of ASPS patient data generated a consensus expression profile with considerable overlap between studies. In common with ASPS-1, elevated expression was noted for CTSK, DPP4, GPNMB, INHBE, LOXL4, PSG9, SLC20A1, STS, SULT1C2, SV2B, and UPP1. Transcripts over-expressed only in ASPS patient samples included ABCB5, CYP17A1, HIF1A, MDK, P4HB, PRL, and PSAP. These observations are consistent with that expected for a mesenchymal progenitor cell with adipogenic, osteogenic, or chondrogenic potential. In summary, the consensus data generated in this study highlight the unique and highly conserved nature of the ASPS transcriptome. Although the ability of the ASPL-TFE3 fusion to perturb mRNA expression must be acknowledged, the prevailing ASPS transcriptome resembles that of a mesenchymal stromal progenitor.

fusion protein, ASPL-TFE3, that drives pathogenesis through aberrant transcriptional activity. Although considerable progress has been made in identifying ASPS therapeutic vulnerabilities (e.g., MET inhibitors), basic research efforts are hampered by the lack of appropriate in vitro reagents with which to study the disease. In this report, previously unmined microarray data for the ASPS cell line, ASPS-1, was analyzed relative to the NCI sarcoma cell line panel. These data were combined with meta- analysis of pre-existing ASPS patient microarray and RNA-seq data to derive a platform- independent ASPS transcriptome. Results demonstrated that ASPS-1, in the context of the NCI sarcoma cell panel, had some similarities to normal mesenchymal cells and connective tissue sarcomas. The cell line was characterized by high relative expression of transcripts such as CRYAB, MT1G, GCSAML, and SV2B. Notably, ASPS-1 lacked mRNA expression of myogenesis-related factors MYF5, MYF6, MYOD1, MYOG, PAX3, and PAX7. Furthermore, ASPS-1 had a predicted mRNA surfaceome resembling an undifferentiated mesenchymal stromal cell through expression of GPNMB, CD9 (TSPAN29), CD26 (DPP4), CD49C (ITGA3), CD54 (ICAM1), CD63 (TSPAN30), CD68 (SCARD1), CD130 (IL6ST ), CD146 (MCAM), CD147 (BSG), CD151 (SFA-1), CD166 (ALCAM), CD222 (IGF2R), CD230 (PRP), CD236 (GPC), CD243 (ABCB1), and CD325 (CDHN). Subsequent re-analysis of ASPS patient data generated a consensus expression profile with considerable overlap between studies. In common with ASPS-1, elevated expression was noted for CTSK, DPP4, GPNMB, INHBE, LOXL4, PSG9, SLC20A1, STS, SULT1C2, SV2B, and UPP1. Transcripts over-expressed only in ASPS patient samples included ABCB5, CYP17A1, HIF1A,MDK, P4HB, PRL, and PSAP. These observations are consistent with that expected for a mesenchymal progenitor cell with adipogenic, osteogenic, or chondrogenic potential. In summary, the consensus data generated in this study highlight the unique and highly conserved nature of the ASPS transcriptome. Although the ability of the ASPL-TFE3 fusion to perturb mRNA expression must be acknowledged, the prevailing ASPS transcriptome resembles that of a mesenchymal stromal progenitor. [ABSTRACT FROM AUTHOR]

This is a first-in-human phase I study investigating the safety and efficacy of toripalimab, a humanized monoclonal antibody against the programmed cell death-1 (PD-1) receptor, in Chinese patients with advanced or recurrent malignant tumor refractory to standard treatment. During dose escalation, patients received a single-dose intravenous infusion of toripalimab for 56 days followed by multidose infusions every two weeks. The planned dosing groups were 1, 3 and 10 mg/kg. During dose expansion, patients received toripalimab every two weeks. Clinical response was evaluated by investigators every 6 weeks. Thirty-three patients were enrolled, including 12 patients with alveolar soft part sarcoma (ASPS), seven with non–small-cell lung cancer and 11 with lymphoma. Patients were heavily pretreated with a median of 3 prior lines of systemic treatments. Toripalimab was well tolerated without dose-limiting toxicity. All patients experienced treatment-related adverse events. Grade 3 and above treatment-related adverse events occurred in six (18.2%) patients. Among 22 solid tumors, the objective response rate (ORR) was 22.7% per RECIST v1.1. The ORR was 90.9% in 11 lymphoma patients per IWG 2007. The median duration of response was 21.5 months. The median progression-free survival was 5.7 months for solid tumors and 8.3 months for lymphomas. The median OS was not reached for all patients and the lymphoma subgroups. The median OS was 34.7 months for patients with ASPS. Toripalimab was well tolerated up to 10 mg/kg Q2W without dose-limiting toxicity and showed promising and durable antitumour activities in patients with ASPS and lymphoma, who were heavily pretreated. ClinicalTrials.gov Identifier: NCT02836834. • First-in-human Phase I study of toripalimab in patients with advanced malignant tumor. • Toripalimab was well tolerated up to 10mg/kg Q2W without DLT. • 25.0% (3/12) ORR and 91.7% (11/12) DCR in alveolar soft part sarcoma patients. • 90.9% (10/11) ORR and 90.9% (10/11) DCR in lymphoma patients. • Median DOR 21.5 months for all responding patients. [ABSTRACT FROM AUTHOR]

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Apatinib has been proved effective in the treatment of advanced gastric cancer. Traditional Chinese medicine is often considered as adjuvants which could increase the effects and counteract the side effects of chemotherapy. The present study aims to explore the antitumor effects of Astragalus polysaccharide (AsPs) in combination with Apatinib in gastric cancer AGS cells. Our results demonstrated that the expression of VEGFR-2 was observed in human gastric cancer line AGS. Both Apatinib and AsPs could significantly inhibit the proliferation of AGS cells in a dose-dependent manner and Apatinib in combination with AsPs showed enhanced inhibitory effects on cell proliferation, migration and invasion compared with Apatinib monotherapy. Moreover, there was a remarkable increase in apoptosis following Apatinib treatment which could be enhanced by the addition of AsPs. Western blotting showed that the combination of Apatinib and AsPs could inhibit the expression of phosphorylated AKT (p-AKT) and MMP-9 expression. In addition, both Apatinib alone and Apatinib in combination with AsPs induced celluar autophagy which could be attenuated by the autophagy inhibitor 3-MA. The suppression of autophagy leaded to further apoptosis induction and cell proliferation suppression. In conclusion, the current study showed AsPs enhanced antitumor effects of Apatinib on AGS cells by the mechanism which includes inhibition of AKT signaling pathway. Apatinib-induced autophagy could be attenuated by 3-MA, which subsequently increased the apoptosis rate. On the basis of our study, the combination of Apatinib and AsPs could be considered as a potential candidate in the gastric cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS. Patients and methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250mg bd. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The primary end point was the objective response rate (ORR) according to local investigator. Secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate, overall survival (OS) and safety. Results: Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and assessable. Among 40 MET+patients, 1 achieved a confirmed partial response (PR) that lasted 215 days and 35 had stable disease (SD) as best response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI 22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET- patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI 0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in MET- cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI 12.8% to 96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and fatigue [19/48 (39.6%)]. Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+patients. [ABSTRACT FROM AUTHOR]

The province of Ain Defla, located in the northern - Center region of Algeria, extends on an area of 4544,28 km². The objective of our article is to model sustainable development and propose a scenario of sustainable management of natural resources. In this context, this research builds on a reflection involving indicators and indices of sustainable development. Our analysis is conducted in four phases: 1) collection of necessary data, 2) calculation of indices and indicators, 3) Aggregation of indicators and 4) modeling by the grid amoeba. The modeling of the forty (40) socio-economic and environmental indicators makes complexity of the ecosystem problems understandable and intelligible. The diagnosis of the current situation has led us to propose the assumptions and scenarios in order to reduce some of the indicators and to increase other.

The province of Ain Defla, located in the northern - Center region of Algeria, extends on an area of 4544,28 km2. The objective of our article is to model sustainable development and propose a scenario of sustainable management of natural resources. In this context, this research builds on a reflection involving indicators and indices of sustainable development. Our analysis is conducted in four phases: 1) collection of necessary data, 2) calculation of indices and indicators, 3) Aggregation of indicators and 4) modeling by the grid amoeba. The modeling of the forty (40) socio-economic and environmental indicators makes complexity of the ecosystem problems understandable and intelligible. The diagnosis of the current situation has led us to propose the assumptions and scenarios in order to reduce some of the indicators and to increase other. [ABSTRACT FROM AUTHOR]

Background: Alveolar soft part sarcoma (ASPS) is a rare entity of soft tissue malignancies with uncommon spinal involvements. Surgical management should be the best choice of cure. Methods: Five patients with spinal ASPS were interviewed retrospectively, where data was collected. The relevant literatures were also systematically examined. Thereafter, patient and surgical data were obtained and pooled for prognostic analysis. Results: A total of five patients with eight surgeries were reviewed retrospectively, and three patients previously reported were also included. All patients were surgically treated, where five of them underwent additional adjuvant therapies such as chemotherapy, radiotherapy, and targeted therapy in order to manage their local and/or systematic diseases. One patient was lost in follow-up. For the remaining seven patients, the mean follow-up period was 19.7 ± 8. 8 months, two succumbed to disease while five were alive at the time of the study. Conclusions: Surgical management is shown to be the most important and the most effective treatment strategy for spinal ASPS, whereas adjuvant therapies made little impact. The prognostic factors for spinal ASPS are primary or metastatic lesions, neurological status, disease progression, systematic conditions, and resection approaches. [ABSTRACT FROM AUTHOR]

The selection of most sensitive sensors and signal processing methods is essential process for the design of condition monitoring and intelligent fault diagnosis and prognostic systems. Normally, sensory data includes high level of noise and irrelevant or redundant information which makes the selection of the most sensitive sensor and signal processing method a difficult task. This paper introduces a new application of the Automated Sensor and Signal Processing Approach (ASPS), for the design of condition monitoring systems for developing an effective monitoring system for gearbox fault diagnosis. The approach is based on using Taguchi’s orthogonal arrays, combined with automated selection of sensory characteristic features, to provide economically effective and optimal selection of sensors and signal processing methods with reduced experimental work. Multi-sensory signals such as acoustic emission, vibration, speed and torque are collected from the gearbox test rig under different health and operating conditions. Time and frequency domain signal processing methods are utilised to assess the suggested approach. The experiments investigate a single stage gearbox system with three level of damage in a helical gear to evaluate the proposed approach. Two different classification models are employed using neural networks to evaluate the methodology. The results have shown that the suggested approach can be applied to the design of condition monitoring systems of gearbox monitoring without the need for implementing pattern recognition tools during the design phase; where the pattern recognition can be implemented as part of decision making for diagnostics. The suggested system has a wide range of applications including industrial machinery as well as wind turbines for renewable energy applications. [ABSTRACT FROM AUTHOR]

Alveolar Soft Part Sarcoma (ASPS) is a very rare type of soft tissue sarcoma. Its cell of origin is unclear. It usually presents in the second to fourth decade of life. The most common reported sites of ASPS are the lower extremities, the head and the neck. Because of the rarity of this disease, there is no standard treatment plan. Surgical excision with negative margins is considered as the treatment of choice. We are reporting a rare presentation of ASPS as a male breast lump.

Alveolar soft part sarcoma (ASPS) is a rare, malignant mesenchymal tumor of distinctive clinical, morphologic, ultrastructural, and cytogenetical characteristics. It typically arises in the extremities of adolescents and young adults, but has also been documented in a number of unusual sites, thus causing diagnostic confusions both clinically and morphologically. The molecular signature of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in the fusion of TFE3 transcription factor gene at Xp11.2 with ASPL at 17q25. Recent studies have shown that the ASPL-TFE3 fusion transcript can be identified by reverse-transcriptase polymerase chain reaction analysis and TFE3 gene rearragement can be detected using a dual-color, break apart fluorescence in situ hybridization assay in paraffin-embedded tissue, and the resultant fusion protein can be detected immunohistochemically with antibody directed to the carboxy terminal portion of TFE3. Herein, we report a unique case of ASPS presenting as an asymptomatic mass in the lung of a 48 year-old woman without evidence of a primary soft tissue tumor elsewhere at the time of initial diagnosis. To the best of our knowledge, this is the third report of such cases appearing in the English language literature to date. We emphasize the differential diagnoses engendered by ASPS including a series of tumors involving the lung that have nested and alveolar growth patterns, and both clear and eosinophilic cytoplasm, and demonstrate the utility of molecular genetic analysis for TFE3 rearrangement and immunohistochemistry for TFE3 antigen expression for arriving at accurate diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Alveolar soft part sarcoma (ASPS) commonly arises in the soft tissue of the lower extremities. Primary bone involvement is rare. Methods/Results: We report a 23-year-old male who presented with pathologic fracture of the clavicle, and diagnosis of clavicular ASPS. Workup demonstrated a lumbar meningeal mass, also involving the vertebral bodies. Conclusions: Few cases of primary bone ASPS have been identified. Most common primary bone involvement includes the fibula, ilium and tibia. Likewise, meningeal involvement is quite rare. In summary, primary bone ASPS is rare and may involve the clavicle. Meningeal involvement is likewise rare, and presumably represents metastatic spread. [ABSTRACT FROM AUTHOR]

Alveolar soft part sarcoma (ASPS) is a distinct type of soft tissue sarcoma holding a specific ASPL-TFE3 fusion transcript. Curative therapy is based on surgical removal, whereas lately, antiangiogenic targeted therapy regimens have proven effective. In ASPS, analysis of small series additionally display mTOR (mammalian target of rapamycin) pathway activity, thus making mTOR a possible additive target in ASPS, because it is in other tumor entities. Therefore, we systematically evaluated mTOR pathway activity in a large series of ASPS in comparison with soft tissue sarcomas of other differentiation (non-ASPS). Upstream and downstream factors of mTOR signaling and ancillary targets were analyzed in 103 cases (22 ASPS, 81 non-ASPS) by immunohistochemistry mostly using phospho-specific antibodies. TFE3 (transcription factor for immunoglobulin heavy-chain enhancer 3) translocation status was determined by FISH and RT-PCR. All ASPS were positive in TFE3 break-apart FISH and exhibited specific fusion products when RNA was available (type 1: 9x, type 2: 11x), whereas TFE3-immunoreactive non-ASPS did not. In ASPS, TFE3-, cMET-, pAKT T308- (all P < .0001), pp70S6K- (P = .002), and p4EBP1 (P = .087) expression levels were elevated, whereas pAKT S473 was decreased (P < .0001). In addition, ASPS exhibited higher TFE3-, cMET-, pAKT T308-, and pp70S6K- expression levels compared with TFE3-immunopositive non-ASPS sarcomas (all P < .001). We demonstrate elevated mTOR complex 1 (mTORC1) activity in ASPS independent of mTOR complex 2 (mTORC2) activation. mTORC1 activity seems to be related to the existence of ASPL-TFE3 fusion transcripts because TFE3-immunoreactive non-ASPS without ASPL-TFE3 fusion transcripts exhibit significantly lower mTORC1 activation status. Small molecule-based targeting of mTOR might therefore represent a potential mechanism in ASPS alone or in combination with contemporary upstream approaches. [ABSTRACT FROM AUTHOR]

Laboratory-reproduced and bred asps were experimentally infected with Contracaecum rudolphii larvae, either directly or with previously infected copepods. In the fish exposed to larval infection, the intensity and prevalence of infection were noticeably higher than in the group exposed to copepods. The course of larvae development was similar in both groups. In the larvae measuring ca. 1000 μm in length, the gastrointestinal tract with a developed ventriculus, ventricular appendix and intestinal caecum was clearly visible. The mouth was surrounded by three lips. Over the 10-week experimental period, slightly-coiled larvae surrounded with a thin theca but no encysted larvae were found in the fish exposed to larvae. On the other hand, spirally-stranded and encysted larvae were observed after the 7th week in the fish exposed to infected copepods. The results demonstrated that in the experimentally infected asps, the intensity and prevalence of infection as well as the location of the larvae in a fish depended on the type of invasive material applied. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to confirm sunitinib activity in alveolar soft part sarcoma (ASPS) and to report on new insights into the molecular bases thereof.Patients and methods: From July 2007, nine patients with progressive metastatic ASPS received sunitinib 37.5 mg/day, within a named use program. Cryopreserved material was available for five naive patients, among whom three received sunitinib. Immunofluorescence (IF)/confocal microscopy, biochemical, and molecular/cytogenetic analyses were carried out, complemented by antiproliferative and activation assays in a short-term culture derived from one case.Results: All patients were eligible for response. Best RECIST response was partial response in five cases, stable disease in three, and progression in one. The median progression-free survival was 17 months. Positron emission tomography results were consistent. Two cases of interval progressions were recorded. Antiproliferative assays and biochemistry on short-term culture showed that sunitinib is able to markedly impair ASPS cells growth and switch-off PDGFRB. IF/confocal microscopy demonstrated coexpression and physical association between PDGFRB/vascular endothelial growth factor receptor 2 (VEGFR2) and RET/VEGFR2 in ASPS cells, which was validated by biochemistry. PDGFRB, RET, and MET ligand-dependent activation was confirmed.Conclusions: We confirm the clinical efficacy of sunitinib in ASPS, mediated by PDGFRB, VEGFR2, and RET, which are all expressed in tumor cells. A direct antitumor effect was shown in a short-term cell culture. [ABSTRACT FROM AUTHOR]

Alveolar Soft Part Sarcoma is one of the less commonly diagnosed soft tissue sarcoma subtypes, an infrequent subtype within the already rare category of human malignancy of sarcoma. In this article we will summarize the histopathological features, natural history and distinct molecular and biological features that have become increasingly appreciated with newer technologies and precision oncology. We will discuss the contemporary management of this disease as well as emerging treatment options. [ABSTRACT FROM AUTHOR]

Alveolar Soft Part Sarcoma (ASPS) is a very rare type of soft tissue sarcoma. Its cell of origin is unclear. It usually presents in the second to fourth decade of life. The most common reported sites of ASPS are the lower extremities, the head and the neck. Because of the rarity of this disease, there is no standard treatment plan. Surgical excision with negative margins is considered as the treatment of choice. We are reporting a rare presentation of ASPS as a male breast lump. [ABSTRACT FROM AUTHOR]

Alveolar soft?part sarcoma (ASPS) is a rare, distinctive sarcoma, typically occurring in young patients. The disease runs a relatively indolent clinical course, wherein the prognosis is poor and is often characterised by late metastases. Since its formal description by Christopherson et al at Memorial Sloan Kettering Cancer Center, New York, USA, ASPS has been the subject of considerable interest for pathologists and clinicians, owing to its unique microscopic features, uncertain line of differentiation and unpredictable clinical behaviour. In the past several years, our understanding of the genetic events underlying the pathogenesis of ASPS has greatly increased. It is usually seen in young patients of < 30 years of age though there is an age range of 0- 74 years. Most of the patients are young females. It usually occurs in extremities specially thigh, buttock, oral cavity, pharynx including tongue, mediastinum, sometimes from pulmonary vein, stomach, retroperitoneum, uterus, vagina, and orbit. The most common site of the tumor is lower extremities in adults[8], representing about 60% of ASPS cases. It is a very vascular tumour and bruit is usually present. Local recurrence rate is 20-33% and the tumor is known to have late recurrences. Incidence of metastasis is 66% & the most common metastatic sites are Lung, Bone, Central Nervous System and Liver. Despite the occurrence of metastases in up to 79% of patients, 5-year overall survival rates range from 45 to 88%. Here we present a case of a 20 year old girl, with thigh swelling since 1 year, with associated symptom of shortness of breath. Clinically, she had a diffuse swelling over the lateral aspect of left thigh, 14cms below the Anterior superior iliac spine and 40 cms in circumference. Swelling was firm, non mobile, fixed, smooth surface and non tender. Inguinal lymphadenopathy was present on both sides, measuring approx 1x1 cm. Investigative evaluation showed a Soft tissue Space Occupying Lesion in Lateral compartment of thigh involving the vastii on Contrast Mangnetic Resonance Imaging. An X-ray and a Computed, Tomography scan of the chest showed multiple nodular opacities in both lungs, pointing to a metastatic disease. A biopsy of the swelling was carried showed tumor cells arranged in nesting and organoid pattern. The cellular nests were separated by sinusoidal vascular channels lined by flattened epithelium. The nuclei were vesicular with prominent nucleoli and no mitotic figures were seen. Based on the above stated findings, a diagnosis of Alveolar Soft Part Sarcoma was made. On Immunohistochemistry, tissue showed PAS positivity with non immunoreactive score for CKc, Vimentin, S100, Desmin and myogenic stains, thus, confirming the diagnosis. Following the above immunohistochemical confirmation, post literature search & after Expert discussion and consultation, plan was made to keep the patient on surveillance and close follow up. As this is a rare presentation, there are no standard guidelines for the management of this subset of Sarcoma cases. Surgical management has some role but no role of chemotherapy has been documented and most of the cases were kept on surveillance. We report this case of ASPS with Pulmonary mets, continued on surveillance management. [ABSTRACT FROM AUTHOR]

Objectives: We reviewed the clinical characteristics and outcomes of patients treated for alveolar soft part sarcoma (ASPS) and analyzed the effect of surgery for patients presenting with and without metastatic disease (DM)., Methods: The SEER Registry was queried for patients with ASPS from 1973-2012. The Kaplan-Meier estimate and Cox proportional hazards were used to analyze survival outcomes and risk variables., Results: Among 251 patients, 43% had DM and 67% locoregional disease (LR) on presentation. The 5-year overall survival (OS) for all patients was 56% (82% and 27% for LR and DM, respectively). Multivariate analysis identified older age (hazard ratio [HR] = 1.03 per year, P < 0.001), tumor size >10 cm (HR = 2.76, P = 0.013), DM at diagnosis (HR = 3.79, P < 0.001), and truncal primary site (HR = 1.63, P = 0.035) as independent factors predicting worse OS. For LR patients, surgery plus radiotherapy (RT) resulted in better OS compared to surgery alone P = 0.014. For DM patients, primary site surgery significantly improved survival (P < 0.001)., Conclusion: ASPS presents with high metastasis rate but has a relatively indolent clinical course and a favorable prognosis with prolonged survival. Aggressive treatment using adjuvant RT with surgery is indicated in patients with LR disease and surgery is indicated in patients presenting with DM. J. Surg. Oncol. 2016;113:581-586. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)