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Despite the introduction of targeted vaccines and screening protocols, locally advanced cervical cancer represents a median proportion of 37% among all cervical carcinomas. Compared to early stages, it presents significantly lower cure rates, with a 5-year disease-free survival rate of 68% and a 5-year overall survival rate of 74%. According to current guidelines, definitive radiotherapy with concomitant chemotherapy represents the gold standard for locally advanced cervical cancer treatment. However, a significant number of patients relapse and die from metastatic disease. The aim of this narrative review is to examine the recent advancements in treating locally advanced cervical cancer, exploring new frontiers in therapeutic approaches. The PubMed database and clinical trial registries were searched to identify relevant articles published on locally advanced cervical cancer treatment up to March 2024, mainly focusing on papers published in the last decade. Abstracts presented at major international congresses that bring relevant evidence were included. Progress achieved in refining radiotherapy techniques, recent evidence regarding neoadjuvant treatment preceding surgery or concurrent chemoradiotherapy, and key findings concerning adjuvant treatment are thoroughly explored. Furthermore, a comprehensive review of prominent phase II and phase III trials examining the integration of immune checkpoint inhibitors is conducted, analyzing the various contexts in which they are applied. In light of the new evidence that has emerged in recent years and is discussed in this article, the appropriate selection of the most suitable therapeutic approach for each patient remains a complex but crucial issue. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3–5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. Results: Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. Conclusions: The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions. [ABSTRACT FROM AUTHOR]

The Letter to the Galatians is a polemical correspondence about the course of gospel mission that is at stake in the view of the apostle Paul. When Paul represents his own contacts with the Jerusalem church, he defends "our freedom which we have in Christ Jesus" (Gal 2:4). In his aim to focus on the unity of all in Christ, Paul even goes at lengths to state that there is no difference between slave and free (Gal 3:28), while polemically associating both a former state of unbelievers (Gal 4:8) and the emphasis by missionary opponents on circumcision and the covenant of the law (Gal 4:12–31) with bondage and slavery. Yet, what did freedom (ἐλευθερία, Gal 2:4) and its opposite, slavery (δουλεία, Gal 4:24, 5:1), exactly mean in the ancient world in which Paul and his readers lived and communicated? Jews, Greeks, and Romans did not necessarily mean the same by these terms, nor did freedom necessarily mean exactly the same as modern conceptions of the term. This paper aims to contextualize Paul's imagery with a view to biblical traditions, early Jewish notions of freedom, and Graeco-Roman registers of discourse, taking into account historical, literary, linguistic, and rhetorical-critical contexts of interpretation and revisiting the language of freedom and slavery with a view to insights from linguistic anthropology. The paper then revisits the Pauline position of "freedom in Christ" in relation to previous hypotheses of Paul's gospel mission. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Increasing farmers' income has always been the core task of China's land reform. In 2017, a nationwide pilot project on the use of collective construction land for the construction of rental housing was launched. This study employed the synthetic difference-in-differences method to examine whether the reform contributed to the growth of farmers' property income. It was found that, compared with non-pilot areas, the property income of farmers in the pilot reform of collective construction land rental housing has increased by about 0.4334% on average, and this conclusion is still valid after a series of robustness tests. The role of the reform in promoting farmers' property income is more evident in Western China, Southern China and non-major grain-producing areas. By revealing the impact of the reform on farmers' property income, this paper enriches the literature related to the field of farmers' income increase and provides a policy reference for narrowing the urban–rural gap and achieving the development of rural revitalization and common prosperity. [ABSTRACT FROM AUTHOR]

In emergency response and disaster rescue, unmanned aerial vehicles (UAVs) onboard thermal infrared (TIR) sensors are an essential means of acquiring ground information in the nighttime working environment. To enable field personnel to make better decisions based on TIR video streams returned from a UAV, the geographic information enhancement of TIR video streams is required. At present, it is difficult for low-cost UAVs to carry high-precision attitude sensors and thus obtain high-precision camera attitude information to meet the enhanced processing requirements of UAV TIR video streams. To this end, this paper proposes an improved Kalman filter algorithm to improve the geographic registration (geo-registration) accuracy by fusing the positioning and heading data from the dual-antenna real-time kinematic global positioning system (RTK-GPS) with onboard internal measurement unit (IMU) data. This method can yield high-precision position and attitude data in real time based on low-cost UAV hardware, based on which high-precision geo-registration results can be obtained. The computational complexity can be reduced compared with video stream feature tracking algorithms. Furthermore, the problem of unstable matching due to the low resolution and texture level of TIR video streams can be avoided. The experimental results prove that the proposed method can reduce the registration error by 66.15%, and significantly improve the geo-registration accuracy of UAV TIR video streams. Thus, it can strongly support the popularization and practicality of the application of augmented reality (AR) technology to low-cost UAV platforms. [ABSTRACT FROM AUTHOR]

Featured Application: In this paper, we propose a lightweight key-value store for managing various types of data, which are generated from Big data applications, in a very simple form. The proposed technique can be used in any environments where Windows operating systems are running, which encompass from client environments (e.g., Windows 10) to server environments (e.g., Windows Server 2016), with the minimum effort for the installation. For the other environments without Windows operating systems, we can easily migrate data to the other any environments that support existing key-value stores by using the ETL (Extract-Transform-Load) method proposed by this paper. In this paper, we propose a method to construct a lightweight key-value store based on the Windows native features. The main idea is providing a thin wrapper for the key-value store on top of a built-in storage in Windows, called Windows registry. First, we define a mapping of the components in the key-value store onto the components in the Windows registry. Then, we present a hash-based multi-level registry index so as to distribute the key-value data balanced and to efficiently access them. Third, we implement basic operations of the key-value store (i.e., Get, Put, and Delete) by manipulating the Windows registry using the Windows native APIs. We call the proposed key-value store WR-Store. Finally, we propose an efficient ETL (Extract-Transform-Load) method to migrate data stored in WR-Store into any other environments that support existing key-value stores. Because the performance of the Windows registry has not been studied much, we perform the empirical study to understand the characteristics of WR-Store, and then, tune the performance of WR-Store to find the best parameter setting. Through extensive experiments using synthetic and real data sets, we show that the performance of WR-Store is comparable to or even better than the state-of-the-art systems (i.e., RocksDB, BerkeleyDB, and LevelDB). Especially, we show the scalability of WR-Store. That is, WR-Store becomes much more efficient than the other key-value stores as the size of data set increases. In addition, we show that the performance of WR-Store is maintained even in the case of intensive registry workloads where 1000 processes accessing to the registry actively are concurrently running. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of treatments such as surgery and hormonal therapy, women with endometriosis often endure chronic problems. This review aims to evaluate the effectiveness and safety of neuropelveology. Methods: In a systematic review with a meta-analysis, we searched three electronic databases: MEDLINE (PubMed), Scopus, Embase, and Web of Science (WOS). The search was conducted in January 2024 with no date or language restrictions using a carefully curated set of keywords. We conducted a comprehensive review, including all observational and clinical trials reporting data on neuropelveology approaches in the management of endometriosis, irrespective of geographical location. The studies included in our review were required to be published in peer-reviewed journals and be available in any language, with at least an abstract in English. The data of all included studies were summarized in excel (version 19) and were analyzed by Comprehensive Meta-analysis v3.3 (Biostat) and STATA (version 17). A multilevel meta-analysis was performed on studies with two arms (intervention and control) to evaluate the efficacy of neuropelveology in managing women with endometriosis. Results: After screening 476 records, 30 studies, published from 1952 to 2021, were included in this review, each employing various methodologies. The studies were divided into the following three categories: (a) efficacy of neurectomy or nerve resection (n = 20), (b) efficacy of neurolysis (nerve blocks) (n = 4), and (c) efficacy of neuromodulation (n = 6) in the management of endometriosis. Among the studies evaluating the efficacy of neurectomy or nerve resection, 10 studies (with 18 group comparisons) were included in the random-effects meta-analysis. Treatment success (not occurrence of pain) was higher with neurectomy vs. controls (RR = 0.497, 95% CI = 0.236 to 1.04, p = 0.06 (for experimental studies) and RR = 0.248, 95% CI = 0.14 to 0.43, p < 0.001 (for observational studies)), representing a 50% and 75.2% risk reduction in the recurrence of pain in experimental and observational studies, respectively. Similarly, neurolysis, particularly superior hypogastric plexus blocks and uterine nerve ethanol neurolysis, demonstrated encouraging outcomes in pain reduction and an improved quality of life for women with endometriosis. The efficacy of neuromodulation in managing endometriosis symptoms appears promising but requires further investigation. Conclusions: In conclusion, neuropelveology approaches, such as neurectomy, neurolysis, and neuromodulation, offer significant potential for pain reduction in endometriosis patients, albeit with risks of complications and high recurrence rates, necessitating careful patient selection and long-term monitoring. [ABSTRACT FROM AUTHOR]

Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to prevent it. Downregulating the mitogen-activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL, but the molecular targets and the mechanism of protection are not fully understood. Here, we tested specifically the role of the kinases ERK1/2 in noise otoprotection using a newly developed, highly specific ERK1/2 inhibitor, tizaterkib, in preclinical animal models. Tizaterkib is currently being tested in phase 1 clinical trials for cancer treatment and has high oral bioavailability and low predicted systemic toxicity in mice and humans. In this study, we performed dose–response measurements of tizaterkib's efficacy against permanent NIHL in adult FVB/NJ mice, and its minimum effective dose (0.5 mg/kg/bw), therapeutic index (>50), and window of opportunity (<48 h) were determined. The drug, administered orally twice daily for 3 days, 24 h after 2 h of 100 dB or 106 dB SPL noise exposure, at a dose equivalent to what is prescribed currently for humans in clinical trials, conferred an average protection of 20–25 dB SPL in both female and male mice. The drug shielded mice from the noise-induced synaptic damage which occurs following loud noise exposure. Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases' inhibition could be a promising strategy for the treatment of NIHL. [ABSTRACT FROM AUTHOR]

Background: Oral mucositis is a common and distressing side effect of head and neck oncology treatment. Photobiomodulation therapy can be utilized to prevent and treat oral mucositis. Its impact on salivary cytokines has yet to be thoroughly investigated. This is the first systematic review aiming to evaluate the effect of photobiomodulation on salivary cytokines in patients undergoing anticancer treatment. Methods: Numerous data resources, from the Web of Science, Embase, ScienceDirect, PubMed, Cochrane Library, and Scopus were sought. Articles published up until February 2024 were included if they met the following inclusion criteria: clinical trials reporting the effect on salivary cytokines in patients undergoing anticancer therapy. The methodological quality was assessed using several appraisal tools. Results: Four studies were deemed eligible for inclusion. All the studies were conducted in Brazil and used an InGaAlP diode laser with a wavelength of 660 nm. The included studies had a relatively low risk of bias. The head and neck cancer patients' salivary cytokines that were assessed by the studies, along with photobiomodulation therapy, included IL-12p70, TNF-α, IL-6, IL-8, IL-10, CXCL8, and IL-1β. The results varied among the studies. Conclusions: Our results show that photobiomodulation demonstrated positive results for reducing the severity of OM in all the included studies. Among the examined salivary cytokines, IL-6 is the most relevant cytokine for oral mucositis development and severity. A variation in the cytokine levels between the studies was noted due to differences in the type of anticancer treatment and saliva sampling. [ABSTRACT FROM AUTHOR]

In both the Geospatial (Geo) and Building Information Modelling (BIM) domains, it is widely acknowledged that the integration of geo-data and BIM-data is beneficial and a crucial step towards solving the multi-disciplinary challenges of our built environment. The result of this integration—broadly termed GeoBIM—has the potential to be particularly beneficial in the context of the construction of large infrastructure projects, which could make use of data relating to the larger spatial extents typically handled in geographical information systems (GIS) as well as the detailed models generated by BIM. To date, GeoBIM integration has mainly been explored for buildings, in a 3D context and for small projects. This paper demonstrates the results of the next level of integration, exploring the addition of the fourth dimension by linking project schedule information to create 4D GeoBIM, examining interoperability challenges and benefits in the context of a number of use cases relating to the enabling works for a major commercial infrastructure project. The integrating power of location and time—knowing where and when data relate to—allows us to explore data interoperability challenges relating to linking real world construction data, created using commercial software, with other data sources; we are then able to demonstrate the benefits of 4D GeoBIM in the context of three decision making scenarios: examining the potential for prioritisation of noise mitigation interventions by identifying apartments closest to the noisiest construction process; development of a 4D location-enabled risk register allowing, for example, work to continue underground if a risk is specific to the top of a building; ensuring construction safety by using 3D buffering to ensure that the required distances between moving construction equipment and surrounding infrastructure are not breached. Additionally, once integrated, we are able to 'democratize' the data—make it accessible beyond the BIM and GIS expert group—by embedding it into a 3D/4D open source Web GIS tool. [ABSTRACT FROM AUTHOR]

(1) Background: This systematic review and meta-analysis aims to evaluate the impact of a low glycemic index (LGI) and low glycemic load (LGL) diet on children with overweight and obesity, analyzing any changes in anthropometric, cardiometabolic, and glucometabolic parameters. (2) Methods: Three electronic databases (PubMed, Scopus, CENTRAL), as well as clinical trial registries and reference lists of the included studies, were searched for eligible randomized control trials (RCTs). Two independent reviewers performed the screening of the studies, data extraction, and risk of bias assessment. Mean difference (MD) and 95% confidence intervals (CI) using a random effects model were calculated for each outcome. (3) Results: Eleven RCTs (n = 634) examining the effect of LGI diet versus control were identified. The synthesized data provided from the RCTs indicate no difference between intervention and control groups regarding primary outcomes (body weight (MD: −0.14; 95% CI −1.93 to 1.64, 5 trials), body mass index (BMI) (MD: −0.31; 95% CI −0.85 to 0.23, 6 trials), BMI z-score (MD: −0.03; 95% CI −0.09 to 0.02, 5 trials), and waist circumference (MD: −0.52; 95% CI −2.35 to 1.31, 5 trials)) and other measures of cardiometabolic and glucometabolic parameters. The majority of trials were classified as "some concerns". (4) Conclusions: LGI and LGL diets do not seem to be associated with changes in adiposity, cardiometabolic or glucometabolic markers in children with overweight or obesity. Further research comparing the LGI diet to a high glycemic index diet, with proper methodological standards, is required to clarify the benefits of a LGI diet in this population. [ABSTRACT FROM AUTHOR]

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6–12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11–52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival. [ABSTRACT FROM AUTHOR]

Background: Somatostatin analogues (SSAs) are the cornerstone of treatment for carcinoid syndrome (CS)-related symptoms. The aim of this systematic review and meta-analysis is to evaluate the percentage of patients achieving partial (PR) or complete response (CR) with the use of long-acting SSAs in patients with CS. Methods: A systematic electronic literature search was conducted in PubMed, Cochrane, and Scopus to identify eligible studies. Any clinical trials reporting data on the efficacy of SSAs to alleviate symptoms in adult patients were considered as potentially eligible. Results: A total of 17 studies reported extractable outcomes (PR/CR) for quantitative synthesis. The pooled percentage of patients with PR/CR for diarrhea was estimated to be 0.67 (95% confidence interval (CI): 0.52–0.79, I2 = 83%). Subgroup analyses of specific drugs provided no evidence of a differential response. With regards to flushing, the pooled percentage of patients with PR/CR was estimated to be 0.68 (95% CI: 0.52–0.81, I2 = 86%). Similarly, no evidence of a significant differential response in flushing control was documented. Conclusions: We estimate there is a 67–68% overall reduction in symptoms of CS associated with SSA treatment. However, significant heterogeneity was detected, possibly revealing differences in the disease course, in management and in outcome definition. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) paradigm has revolutionized several industries (e.g., manufacturing, health, transport, education, among others) by allowing objects to connect to the Internet and, thus, enabling a variety of novel applications. In this sense, IoT devices have become an essential component of smart cities, allowing many novel and useful services, but, at the same time, bringing numerous cybersecurity threats. The paper at hand proposes BlockSIEM, a blockchain-based and distributed Security Information and Event Management (SIEM) solution framework for the protection of the aforementioned smart city services. The proposed SIEM relies on blockchain technology to securely store and access security events. Such security events are generated by IoT sentinels that are in charge of shielding groups of IoT devices. The IoT sentinels may be deployed in smart city scenarios, such as smart hospitals, smart transport systems, smart airports, among others, ensuring a satisfactory level of protection. The blockchain guarantees the non-repudiation and traceability of the registry of security events due to its features. To demonstrate the feasibility of the proposed approach, our proposal is implemented using Ethereum and validated through different use cases and experiments. [ABSTRACT FROM AUTHOR]

This paper investigates the social, demographic, and economic factors determining differences between forest identification based on remote sensing techniques and land registry. The Database of Topographic Objects and Sentinel-2 satellite imagery data from 2018 were used to train a forest detection supervised machine learning model. Results aggregated to communes (NUTS-5 units) were compared to data from land registry delivered in Local Data Bank by Statistics Poland. The differences identified between above mentioned sources were defined as errors of land registry. Then, geographically weighted regression was applied to explain spatially varying impact of investigated errors' determinants: Urbanization processes, civic society development, education, land ownership, and culture and quality of spatial planning. The research area covers the entirety of Poland. It was confirmed that in less developed areas, local development policy stimulating urbanization processes does not respect land use planning principles, including the accuracy of land registry. A high education level of the society leads to protective measures before the further increase of the investigated forest cover's overestimation of the land registry in substantially urbanized areas. Finally, higher coverage by valid local spatial development plans stimulate protection against forest classification errors in the land registry. [ABSTRACT FROM AUTHOR]

A USB mass storage device yields a lot of artifacts when connected to a system. These artifacts are persistent in nature and are retained even after the system has been shut down and the information they contain may assist in carrying out forensic analysis on a suspect system. In this paper, we demonstrate how Windows Event Viewer can be used to find forensic artifacts in a suspect system for investigative purposes. We also discuss the potential that Windows registry holds to identify USB devices' information that have been connected to the system, to corroborate our findings from Windows Event Viewer. Finally, we use the Windows 10 file system to extract log details that contain the setup information of a USB device that was connected to the system the very first time, and obtain the necessary identifiers and time stamp details. [ABSTRACT FROM AUTHOR]

Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic literature search was performed in four databases. Randomized clinical trials reporting on patients with chronic wounds treated with platelet-rich plasma (PRP) were included, comparing PRP with conventional ulcer therapy. We pooled the data using the random effects model. Our primary outcome was the change in wound size. Results: Our systematic search provided 2688 articles, and we identified 48 eligible studies after the selection and citation search. Thirty-three study groups of 29 RCTs with a total of 2198 wounds showed that the odds for complete closure were significantly higher in the PRP group than in the control group (OR = 5.32; CI: 3.37; 8.40; I2 = 58%). Conclusions: PRP is a safe and effective modality to enhance wound healing. By implementing it in clinical practice, platelet-rich plasma could become a widely used, valuable tool as it could not only improve patients' quality of life but also decrease the healthcare burden of wound management. [ABSTRACT FROM AUTHOR]

The aim of this systematic review was to summarise the comparative evidence on the risk of contrast-associated acute kidney injury (CA-AKI) with CO2 or iodinated contrast medium (ICM) for peripheral vascular interventions. We searched Ovid MEDLINE, Cochrane Library, Embase, Epistemonikos, PubMed-similar-articles, clinical trial registries, journal websites, and reference lists up to February 2022. We included studies comparing the risk of CA-AKI in patients who received CO2 or ICM for peripheral angiography with or without endovascular intervention. Two reviewers screened the references and assessed the risk of bias of the included studies. We extracted data on study population, interventions and outcomes. For the risk of CA-AKI as our primary outcome of interest, we calculated risk ratios (RRs) with a 95% confidence interval (CI) and performed random-effects meta-analyses. We identified three RCTs and five cohort studies that fully met our eligibility criteria. Based on a random-effects meta-analysis, the risk of CA-AKI was lower with CO2 compared to ICM (8.6% vs. 15.2%; RR, 0.59; 95% CI 0.33–1.04). Only limited results from a few studies were available on procedure and fluoroscopy time, radiation dose and CO2-related adverse events. The evidence suggests that the use of CO2 for peripheral vascular interventions reduces the risk of CA-AKI compared to ICM. However, due to the relevant residual risk of CA-AKI with the use of CO2, other AKI risk factors must be considered in patients undergoing peripheral vascular interventions. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal cancer is best addressed by a multimodal treatment approach, including cytoreductive surgery, systemic immunochemotherapy, and intraperitoneal chemotherapy (HIPEC, PIPAC). The present Swiss Peritoneal Cancer Group comprehensive treatment algorithms offer consensus guidance for interdisciplinary care of patients with peritoneal cancer from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include straight complete surgical resection, multimodal neoadjuvant treatment, HIPEC and PIPAC, and referral to palliative care. These state-of-the-art algorithms have been endorsed by all Swiss clinicians routinely involved in the multimodal care of patients with peritoneal cancer of gastrointestinal origin. Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients. [ABSTRACT FROM AUTHOR]

Even in the era of information "prosperity" in the form of databases and registries that compile a wealth of data, information about ASD and ADHD remains scattered and disconnected. These data systems are powerful tools that can inform decision-making and policy creation, as well as advancing and disseminating knowledge. Here, we review three types of data systems (patient registries, clinical trial registries and genetic databases) that are concerned with ASD or ADHD and discuss their features, advantages and limitations. We noticed the lack of ethnic diversity in the data, as the majority of their content is curated from European and (to a lesser extent) Asian populations. Acutely aware of this knowledge gap, we introduce here the framework of the Neurodevelopmental Disorders Database (NDDB). This registry was designed to serve as a model for the national repository for collecting data from Saudi Arabia on neurodevelopmental disorders, particularly ASD and ADHD, across diverse domains. [ABSTRACT FROM AUTHOR]

In this work, we propose a versatile, low-cost, and tunable electronic device to generate realistic electrocardiogram (ECG) waveforms, capable of simulating ECG of patients within a wide range of possibilities. A visual analysis of the clinical ECG register provides the cardiologist with vital physiological information to determine the patient's heart condition. Because of its clinical significance, there is a strong interest in algorithms and medical ECG measuring devices that acquire, preserve, and process ECG recordings with high fidelity. Bearing this in mind, the proposed electronic device is based on four different mathematical models describing macroscopic heartbeat dynamics with ordinary differential equations. Firstly, we produce full 12-lead ECG profiles by implementing a model comprising a network of heterogeneous oscillators. Then, we implement a discretized reaction–diffusion model in our electronic device to reproduce ECG waveforms from various rhythm disorders. Finally, in order to show the versatility and capabilities of our system, we include two additional models, a ring of three coupled oscillators and a model based on a quasiperiodic motion, which can reproduce a wide range of pathological conditions. With this, the proposed device can reproduce around thirty-two cardiac rhythms with the possibility of exploring different parameter values to simulate new arrhythmias with the same hardware. Our system, which is a hybrid analog–digital circuit, generates realistic ECG signals through digital-to-analog converters whose amplitudes and waveforms are controlled through an interactive and friendly graphic interface. Our ECG patient simulator arises as a promising platform for assessing the performance of electrocardiograph equipment and ECG signal processing software in clinical trials. Additionally the produced 12-lead profiles can be tested in patient monitoring systems. [ABSTRACT FROM AUTHOR]

Objective: To systematically review literature enabling the comparison of the efficacy of pharmaceutical treatments for tinea pedis in adults. Design: Systematic review of randomised controlled trials (RCTs) with mycological cure as the primary outcome. Secondary outcomes did include the clinical assessment of resolving infection or symptoms, duration of treatment, adverse events, adherence, and recurrence. Eligibility Criteria: Study participants suffering from only tinea pedis that were treated with a pharmaceutical treatment. The study must have been conducted using an RCT study design and recording age of the participant > 16 years of age. Results: A total of seven studies met the inclusion criteria, involving 1042 participants. The likelihood of resolution in study participants treated with terbinafine was RR 3.9 (95% CI: 2.0–7.8) times those with a placebo. Similarly, the allylamine butenafine was effective by RR 5.3 (95% CI: 1.4–19.6) compared to a placebo. Butenafine was similarly efficacious to terbinafine RR 1.3 (95% CI: 0.4–4.4). Terbinafine was marginally more efficacious than itraconazole, RR 1.3 (95% CI: 1.1–1.5). Summary/Conclusion: Topical terbinafine and butenafine treatments of tinea pedis were more efficacious than placebo. Tableted terbinafine and itraconazole administered orally were efficacious in the drug treatment of tinea pedis fungal infection. We are concerned about how few studies were available that reported the baseline characteristics for each treatment arm and that did not suffer greater than 20% loss to follow-up. We would like to see improved reporting of clinical trials in academic literature. Registration name: Treatment's for athlete's foot—systematic review with meta-analysis [CRD42020162078]. [ABSTRACT FROM AUTHOR]

Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2–30.3); diclofenac 3% 2.9 (1.9–4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6–13.5); fluorouracil 4% 30.3 (9.1–144.7); fluorouracil 5% 35.0 (10.2–164.4); imiquimod 3.75% 8.5 (3.5–22.4); imiquimod 5% 17.9 (9.1–36.6); ingenol mebutate 0.015% 12.5 (8.1–19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9–52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0–21.9); tirbanibulin 1% 11.1 (6.2–20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm2 treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe. [ABSTRACT FROM AUTHOR]

Colorectal cancer is ranked third and fourth in terms of mortality and cancer incidence in the world. While advances in treatment strategies have provided cancer patients with longer survival, potentially harmful second primary cancers can occur. Therefore, second primary colorectal cancer analysis is an important issue with regard to clinical management. In this study, a novel predictive scheme was developed for predicting the risk factors associated with second colorectal cancer in patients with colorectal cancer by integrating five machine learning classification techniques, including support vector machine, random forest, multivariate adaptive regression splines, extreme learning machine, and extreme gradient boosting. A total of 4287 patients in the datasets provided by three hospital tumor registries were used. Our empirical results revealed that this proposed predictive scheme provided promising classification results and the identification of important risk factors for predicting second colorectal cancer based on accuracy, sensitivity, specificity, and area under the curve metrics. Collectively, our clinical findings suggested that the most important risk factors were the combined stage, age at diagnosis, BMI, surgical margins of the primary site, tumor size, sex, regional lymph nodes positive, grade/differentiation, primary site, and drinking behavior. Accordingly, these risk factors should be monitored for the early detection of second primary tumors in order to improve treatment and intervention strategies. [ABSTRACT FROM AUTHOR]

Geo-sensor is the term used for the deployment of a wireless sensor network (WSN) in a real environment, which can be a hideous task due to many influential variables in a given environment. The spatial context of a sensor in a smart environment can be of huge significance and can also play an important role in improving the smart services provision. In this work, we propose a DIY geo-sensor framework and data composition toolbox for the deployment of sensors data in smart IoT environments along with geographical context. A geo-sensor framework is deployed, which enables the registration of multiple geo-sensor networks by providing multiple geo-sensor platforms. The framework's logic is based on the combination of a geo-sensor service registry, geo-sensor composition toolbox, and geo-sensor platforms. A geo-sensor platform provides the content to the toolbox, enabling relaxed real-time geo-sensor data management. Our proposed work is two-fold. Firstly, we propose the design details for the geo-sensor framework and composition toolbox. The proposed design for the geo-sensor framework aims to provide a DIY platform for multiple geo-sensor networks and services deployment, giving access to multiple users resulting in reuse of resources and reduction in deployment costs by avoiding duplicate deployments. Secondly, we implement the proposed design based on RESTful web services and SOAP web services. Performance comparison analysis is then performed among the two web services to find the best suited implementation for given scenarios. The results of the performance analysis prove that RESTful web services are the better choice for ease of implementation, access, and light-weightiness. [ABSTRACT FROM AUTHOR]

Approximately 270 species of mushrooms have been reported as potentially useful for human health. However, few mushrooms have been studied for bioactive compounds that can be helpful in treating various diseases. Like other natural regimens, the mushroom treatment appears safe, as could be expected from their long culinary and medicinal use. This review aims to provide a critical discussion on clinical trial evidence for mushrooms to treat patients with diverse types of cancer. In addition, the review also highlights the identified bioactive compounds and corresponding mechanisms of action among the explored mushrooms. Furthermore, it also discusses mushrooms with anticancer properties, demonstrated either in vitro and/or in vivo models, which have never been tested in clinical studies. Several mushrooms have been tested in phase I or II clinical trials, mostly for treating breast cancer (18.6%), followed by colorectal (14%) and prostate cancer (11.6%). The majority of clinical studies were carried out with just 3 species: Lentinula edodes (22.2%), Coriolus versicolor, and Ganoderma lucidum (both 13.9%); followed by two other species: Agaricus bisporus and Grifola frondosa (both 11.1%). Most in vitro cell studies use breast cancer cell lines (43.9%), followed by lung (14%) and colorectal cancer cell lines (13.1%), while most in vivo animal studies are performed in mice tumor models (58.7%). Although 32 species of mushrooms at least show some promise for the treatment of cancer, only 11 species have been tested clinically thus far. Moreover, most clinical studies have investigated fewer numbers of patients, and have been limited to phase III or IV. Therefore, despite the promising preclinical and clinical data publication, more solid scientific efforts are required to clarify the therapeutic value of mushrooms in oncology. [ABSTRACT FROM AUTHOR]

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medline PubMed Advanced Search Builder, Scopus, Web Of Science and Google Scholar were searched (until 1 January 2021). Inclusion criteria were pregnant women with COVID-19 (or SARS-CoV-2 infection), in whom convalescent plasma (or hyperimmune plasma) was used as treatment. We searched clinical trial registries (censored 5 January 2021) for eligible studies under way. After elimination of duplications, the initial search yielded 79 potentially relevant records, of which 67 were subsequently excluded. The 12 remaining records were case reports involving 12 pregnancies. Six of the mothers were reported to be well, two were reported to have preeclampsia, and in one case each the maternal outcome was described as survival, clinical improvement, discharged with oxygen and rehabilitation. With regard to the neonates, two were declared to be well, four had transient morbidity, two were critically ill and one died; normal ongoing pregnancies, but no post-delivery information, were reported for the remaining three cases. Clinical trials under way or planned to investigate the use of convalescent plasma for COVID-19 during pregnancy are lacking. This is the first systematic review of the literature regarding the treatment of COVID-19 in pregnancy. The published literature data seem to indicate that convalescent plasma administered to pregnant women with severe COVID-19 provides benefits for both the mother and the fetus. The quality of the available studies is, however, very limited since they are all case reports and thus suffer from relevant reporting bias. [ABSTRACT FROM AUTHOR]

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392). [ABSTRACT FROM AUTHOR]

Close connections between depression and type 2 diabetes (T2DM) have been suggested by many epidemiological and experimental studies. Disturbances in insulin sensitivity due to the disruption of various molecular pathways cause insulin resistance, which underpins many metabolic disorders, including diabetes, as well as depression. Several anti-hyperglycemic agents have demonstrated antidepressant properties in clinical trials, probably due to their action on brain targets based on the shared pathophysiology of depression and T2DM. In this article, we review reports of clinical trials examining the antidepressant effect of these medications, including insulin, metformin, glucagon like peptide-1 receptor agonists (GLP-1RA), and peroxisome proliferator-activated receptor (PPAR)-γ agonists, and briefly consider possible molecular mechanisms underlying the associations between amelioration of insulin resistance and improvement of depressive symptoms. In doing so, we intend to suggest an integrative perspective for understanding the pathophysiology of depression. [ABSTRACT FROM AUTHOR]

Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited. Methods: This randomized control trial—ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID ISRCTN15312724—was aimed at comparing the effect of a tele-assisted and in-person intervention based on a behavioral intervention protocol for families with children affected by ASDs. Forty-two parents with children with autism (30 months to 10 years old) were randomly assigned to 12 sessions of an applied behavioral analysis (ABA) intervention implemented in an individual and group setting, either with or without the inclusion of tele-assistance. Pre- and postintervention assessments were conducted using the Home Situation Questionnaire (HSQ-ASD) and the Parental Stress Index (PSI/SF). Results: Substantial improvements in the perception and management of children's behavior by parents, as well as in the influence of a reduction in parent stress levels on said children's behavior through the use of a tele-assisted intervention, were obtained. Conclusions: This randomized controlled trial demonstrates the evidence-based potential for telehealth to improve treatment of ASDs. [ABSTRACT FROM AUTHOR]

Peri-implantitis is a biofilm-related disease whose characteristics are peri-implant tissues inflammation and bone resorption. Some clinical trials report beneficial effects after implantoplasty, namely the surgical smoothening of the implant surface, but there is a lack of data about the development of the bacterial biofilm on those smoothened surfaces. The aim of this study is to evaluate how implantoplasty influences biofilm formation. Three implants with moderately rough surfaces (control) and three implants treated with implantoplasty (test) were set on a tray reproducing the supra- and sub-gingival environment. One volunteer wore this tray for five days. Every 24 h, plaque coverage was measured and, at the end of the period of observartion, the implant surfaces were analyzed using scanning electron microscopy and confocal laser scanning microscopy. The proportion of implant surface covered with plaque was 65% (SD = 7.07) of the control implants and 16% (SD = 0) of the test implants. Untreated surfaces showed mature, complex biofilm structures with wide morphological diversity, and treated surfaces did not show the formation of mature biofilm structures. This study supports the efficacy of implantoplasty in reducing plaque adhesion and influencing biofilm formation. These results can be considered a preliminary proof of concept, but they may encourage further studies about the effects of implantoplasty on biofilm formation. [ABSTRACT FROM AUTHOR]

Circulating miRNA species are promising symptom markers for various diseases, including cardiovascular disease. However, studies regarding their role in the treatment process are limited, especially concerning cerebral infarction. This study aimed to extract miRNA markers to investigate whether they reflect both onset and treatment process of cerebral infarction. A total of 22 patients (P-group) and 22 control subjects (C-group) were examined for their whole-blood miRNA profiles using DNA GeneChip™ miRNA 4.0 Array, with six patients examined after treatment (T-group). A total of 64 miRNAs were found to be differentially expressed between the C- and P-groups. Out of 64 miRNAs, the expression levels of two miRNAs correlated with hypertension. A total of 155 miRNAs were differentially expressed between the P- and T-groups. Five common miRNAs were found among the 64 and 155 miRNAs identified. Importantly, these common miRNAs were inversely regulated in each comparison (e.g., C < P > T), including miR-505-5p, which was previously reported to be upregulated in aortic stenosis patients. Our previous study using rat cerebral infarction models detected the downregulation of an apoptosis repressor, WDR26, which was repressed by one of the five miRNAs. Our results provide novel information regarding the miRNA-based diagnosis of cerebral infarction in humans. In particular, the five common miRNAs could be useful makers for the onset and the treatment process. Trial registration: This study was registered in the UMIN Clinical Trials Registry (UMIN000038321). [ABSTRACT FROM AUTHOR]

We examined the national mine waste registries from seven European countries, created to fulfil the requirements of the "Mine Waste Directive" (2006/21/EC), for their potential use as an initial source of information for the valorisation of specific mine waste deposits for their resource recovery. A set of parameters for mine waste valorisation was defined and divided into three groups: the "basic", the "metal-centric" and the "material-centric" group. The "basic" group of 19 parameters considers properties of the mine waste deposit, including the location, history, homogeneity and quantity, among others, while the other two groups relate to the two desired material recovery types. The "metal-centric" group of parameters contains the six parameters needed to preliminarily assess the potential to valorise mine waste for metal extraction, while the "material-centric" group contains the nine parameters needed to consider the use of mine waste for the production of different construction materials. National mine waste registries from Slovenia, France, Spain, Italy, UK, Hungary and Portugal were reviewed to determine whether they contain information about each of the parameters. In line with the objectives of the Mine Waste Directive, the national mine waste registries were developed to reduce or prevent environmental damage, and not to enable resource recovery from mine waste. The registries contain most of the information for the parameters in the "basic" group, less information for the parameters in the "metal-centric" group and almost no information to define the parameters in the "material-centric" group. The conclusion is that national mine waste registries could serve only as an initial source of information, and more detailed information must be obtained from other sources. This misses an opportunity to see these sites as a resource, and not only as a potential source of pollution, given the urgent need to find alternative stocks of metals within the EU (European Union). [ABSTRACT FROM AUTHOR]

The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal gynecological cancer, and despite years of research, with the exception of a BRCA mutation driving the use of PARP inhibitors, no new prognostic/predictive biomarkers are clinically available. Improvement in biomarker selection and validation may derive from the systematic inclusion of translational analyses into the design of clinical trials. In the era of personalized medicine, the prospective centralized collection of high-quality biological material, expert pathological revision, and association to well-controlled clinical data are important or even essential added values to clinical trials. Here, we present the academic experience of the MITO (Multicenter Italian Trial in Ovarian Cancer) group, including gynecologists, pathologists, oncologists, biostatisticians, and translational researchers, whose effort is dedicated to the care and basic/translational research of gynecologic cancer. In our ten years of experience, we have been able to collect and process, for translational analyses, formalin-fixed, paraffin-embedded blocks from more than one thousand ovarian cancer patients. Standard operating procedures for collection, shipping, and processing were developed and made available to MITO researchers through the coordinating center's web-based platform. Clinical data were collected through dedicated electronic case report forms hosted in a web-based electronic platform and stored in a central database at the trial's coordinating center, which performed all the analyses related to the proposed translational researches. During this time, we improved our strategies of block management from retrospective to prospective collection, up to the design of a prospective collection with a quality check for sample eligibility before patients' accrual. The final aim of our work is to share our experience by suggesting a guideline for the process of centralized collection, revision processing, and storing of formalin-fixed, paraffin-embedded blocks for translational purposes. [ABSTRACT FROM AUTHOR]

Photobiomodulation (PBM) might be an effective treatment for Parkinson's disease (PD) in human patients. PBM of the brain uses red or near infrared light delivered from a laser or an LED at relatively low power densities, onto the head (or other body parts) to stimulate the brain and prevent degeneration of neurons. PD is a progressive neurodegenerative disease involving the loss of dopamine-producing neurons in the substantia nigra deep within the brain. PD is a movement disorder that also shows various other symptoms affecting the brain and other organs. Treatment involves dopamine replacement therapy or electrical deep brain stimulation. The present systematic review covers reports describing the use of PBM to treat laboratory animal models of PD, in an attempt to draw conclusions about the best choice of parameters and irradiation techniques. There have already been clinical trials of PBM reported in patients, and more are expected in the coming years. PBM is particularly attractive as it is a non-pharmacological treatment, without any major adverse effects (and very few minor ones). [ABSTRACT FROM AUTHOR]

The amount of data collected and managed in (bio)medicine is ever-increasing. Thus, there is a need to rapidly and efficiently collect, analyze, and characterize all this information. Artificial intelligence (AI), with an emphasis on deep learning, holds great promise in this area and is already being successfully applied to basic research, diagnosis, drug discovery, and clinical trials. Rare diseases (RDs), which are severely underrepresented in basic and clinical research, can particularly benefit from AI technologies. Of the more than 7000 RDs described worldwide, only 5% have a treatment. The ability of AI technologies to integrate and analyze data from different sources (e.g., multi-omics, patient registries, and so on) can be used to overcome RDs' challenges (e.g., low diagnostic rates, reduced number of patients, geographical dispersion, and so on). Ultimately, RDs' AI-mediated knowledge could significantly boost therapy development. Presently, there are AI approaches being used in RDs and this review aims to collect and summarize these advances. A section dedicated to congenital disorders of glycosylation (CDG), a particular group of orphan RDs that can serve as a potential study model for other common diseases and RDs, has also been included. [ABSTRACT FROM AUTHOR]

Background: To improve outcomes for patients who present to hospital with suspected sepsis, it is necessary to accurately identify those at high risk of adverse outcomes as early and swiftly as possible. To assess the prognostic accuracy of shock index (heart rate divided by systolic blood pressure) and its modifications in patients with sepsis or community-acquired pneumonia. Methods: An electronic search of MEDLINE, EMBASE, Allie and Complementary Medicine Database (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Open Grey, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (WHO ITRP) was conducted from conception to 26th March 2019. Eligible studies were required to assess the prognostic accuracy of shock index or its modifications for outcomes of death or requirement for organ support either in sepsis or pneumonia. The methodological appraisal was carried out using the Downs and Black checklist. Evidence was synthesised using a narrative approach due to heterogeneity. Results: Of 759 records screened, 15 studies (8697 patients) were included in this review. Shock index ≥ 1 at time of hospital presentation was a moderately accurate predictor of mortality in patients with sepsis or community-acquired pneumonia, with high specificity and low sensitivity. Only one study reported outcomes related to organ support. Conclusions: Elevated shock index at time of hospital presentation predicts mortality in sepsis with high specificity. Shock index may offer benefits over existing sepsis scoring systems due to its simplicity. [ABSTRACT FROM AUTHOR]

(1) Despite many years of research, melanoma still remains a big challenge for modern medicine. The purpose of this article is to review publicly available clinical trials to find trends regarding the number of trials, their location, and interventions including the most frequently studied drugs and their combinations. (2) We surveyed clinical trials registered in the International Clinical Trials Registry Platform (ICTRP), one of the largest databases on clinical trials. The search was performed on 30 November 2018 using the term "melanoma". Data have been supplemented with the information obtained from publicly available data repositories including PubMed, World Health Organization, National Cancer Institute, Centers for Disease Control and Prevention, European Cancer Information System, and many others to bring the historical context of this study. (3) Among the total of 2563 clinical trials included in the analysis, most have been registered in the USA (1487), which is 58% of the total. The most commonly studied drug in clinical trials was ipilimumab, described as applied intervention in 251 trials. (4) An increase in the number of melanoma clinical trials using immunomodulating monoclonal antibody therapies, small molecule-targeted therapies (inhibitors of BRAF, MEK, CDK4/6), and combination therapies is recognized. This illustrates the tendency towards precision medicine. [ABSTRACT FROM AUTHOR]

Aim: The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. Methods: An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. Results: A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). Conclusions: To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation. [ABSTRACT FROM AUTHOR]