Patients requiring diagnostic testing for coronavirus disease 2019 (COVID-19) are routinely assessed by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) amplification of ...Sars-CoV-2 virus RNA extracted from oro/nasopharyngeal swabs. Despite the good specificity of the assays certified for SARS-CoV-2 molecular detection, and a theoretical sensitivity of few viral gene copies per reaction, a relatively high rate of false negatives continues to be reported. This is an important challenge in the management of patients on hospital admission and for correct monitoring of the infectivity after the acute phase. In the present report, we show that the use of digital PCR, a high sensitivity method to detect low amplicon numbers, allowed us to correctly detecting infection in swab material in a significant number of false negatives. We show that the implementation of digital PCR methods in the diagnostic assessment of COVID-19 could resolve, at least in part, this timely issue.
We present a phylogenetic analysis of spiders using a dataset of 932 spider species, representing 115 families (only the family Synaphridae is unrepresented), 700 known genera, and additional ...representatives of 26 unidentified or undescribed genera. Eleven genera of the orders Amblypygi, Palpigradi, Schizomida and Uropygi are included as outgroups. The dataset includes six markers from the mitochondrial (12S, 16S, COI) and nuclear (histone H3, 18S, 28S) genomes, and was analysed by multiple methods, including constrained analyses using a highly supported backbone tree from transcriptomic data. We recover most of the higher‐level structure of the spider tree with good support, including Mesothelae, Opisthothelae, Mygalomorphae and Araneomorphae. Several of our analyses recover Hypochilidae and Filistatidae as sister groups, as suggested by previous transcriptomic analyses. The Synspermiata are robustly supported, and the families Trogloraptoridae and Caponiidae are found as sister to the Dysderoidea. Our results support the Lost Tracheae clade, including Pholcidae, Tetrablemmidae, Diguetidae, Plectreuridae and the family Pacullidae (restored status) separate from Tetrablemmidae. The Scytodoidea include Ochyroceratidae along with Sicariidae, Scytodidae, Drymusidae and Periegopidae; our results are inconclusive about the separation of these last two families. We did not recover monophyletic Austrochiloidea and Leptonetidae, but our data suggest that both groups are more closely related to the Cylindrical Gland Spigot clade rather than to Synspermiata. Palpimanoidea is not recovered by our analyses, but also not strongly contradicted. We find support for Entelegynae and Oecobioidea (Oecobiidae plus Hersiliidae), and ambiguous placement of cribellate orb‐weavers, compatible with their non‐monophyly. Nicodamoidea (Nicodamidae plus Megadictynidae) and Araneoidea composition and relationships are consistent with recent analyses. We did not obtain resolution for the titanoecoids (Titanoecidae and Phyxelididae), but the Retrolateral Tibial Apophysis clade is well supported. Penestomidae, and probably Homalonychidae, are part of Zodarioidea, although the latter family was set apart by recent transcriptomic analyses. Our data support a large group that we call the marronoid clade (including the families Amaurobiidae, Desidae, Dictynidae, Hahniidae, Stiphidiidae, Agelenidae and Toxopidae). The circumscription of most marronoid families is redefined here. Amaurobiidae include the Amaurobiinae and provisionally Macrobuninae. We transfer Malenellinae (Malenella, from Anyphaenidae), Chummidae (Chumma) (new syn.) and Tasmarubriinae (Tasmarubrius, Tasmabrochus and Teeatta, from Amphinectidae) to Macrobuninae. Cybaeidae are redefined to include Calymmaria, Cryphoeca, Ethobuella and Willisius (transferred from Hahniidae), and Blabomma and Yorima (transferred from Dictynidae). Cycloctenidae are redefined to include Orepukia (transferred from Agelenidae) and Pakeha and Paravoca (transferred from Amaurobiidae). Desidae are redefined to include five subfamilies: Amphinectinae, with Amphinecta, Mamoea, Maniho, Paramamoea and Rangitata (transferred from Amphinectidae); Ischaleinae, with Bakala and Manjala (transferred from Amaurobiidae) and Ischalea (transferred from Stiphidiidae); Metaltellinae, with Austmusia, Buyina, Calacadia, Cunnawarra, Jalkaraburra, Keera, Magua, Metaltella, Penaoola and Quemusia; Porteriinae (new rank), with Baiami, Cambridgea, Corasoides and Nanocambridgea (transferred from Stiphidiidae); and Desinae, with Desis, and provisionally Poaka (transferred from Amaurobiidae) and Barahna (transferred from Stiphidiidae). Argyroneta is transferred from Cybaeidae to Dictynidae. Cicurina is transferred from Dictynidae to Hahniidae. The genera Neoramia (from Agelenidae) and Aorangia, Marplesia and Neolana (from Amphinectidae) are transferred to Stiphidiidae. The family Toxopidae (restored status) includes two subfamilies: Myroinae, with Gasparia, Gohia, Hulua, Neomyro, Myro, Ommatauxesis and Otagoa (transferred from Desidae); and Toxopinae, with Midgee and Jamara, formerly Midgeeinae, new syn. (transferred from Amaurobiidae) and Hapona, Laestrygones, Lamina, Toxops and Toxopsoides (transferred from Desidae). We obtain a monophyletic Oval Calamistrum clade and Dionycha; Sparassidae, however, are not dionychans, but probably the sister group of those two clades. The composition of the Oval Calamistrum clade is confirmed (including Zoropsidae, Udubidae, Ctenidae, Oxyopidae, Senoculidae, Pisauridae, Trechaleidae, Lycosidae, Psechridae and Thomisidae), affirming previous findings on the uncertain relationships of the “ctenids” Ancylometes and Cupiennius, although a core group of Ctenidae are well supported. Our data were ambiguous as to the monophyly of Oxyopidae. In Dionycha, we found a first split of core Prodidomidae, excluding the Australian Molycriinae, which fall distantly from core prodidomids, among gnaphosoids. The rest of the dionychans form two main groups, Dionycha part A and part B. The former includes much of the Oblique Median Tapetum clade (Trochanteriidae, Gnaphosidae, Gallieniellidae, Phrurolithidae, Trachelidae, Gnaphosidae, Ammoxenidae, Lamponidae and the Molycriinae), and also Anyphaenidae and Clubionidae. Orthobula is transferred from Phrurolithidae to Trachelidae. Our data did not allow for complete resolution for the gnaphosoid families. Dionycha part B includes the families Salticidae, Eutichuridae, Miturgidae, Philodromidae, Viridasiidae, Selenopidae, Corinnidae and Xenoctenidae (new fam., including Xenoctenus, Paravulsor and Odo, transferred from Miturgidae, as well as Incasoctenus from Ctenidae). We confirm the inclusion of Zora (formerly Zoridae) within Miturgidae.
Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study ...was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy.
HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline–taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety.
A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89–1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74–1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22–0.50, P < 0.0001).
This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse.
EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.
Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been ...developed alongside this project and have allowed scientists to bypass the limitation of costs for whole‐genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan‐Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine‐learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning.
Since the publication of The Cancer Genome Atlas data in 2013, the advances in the sequencing techniques allowed us to study cancer through whole‐genome sequencing and multiomics approaches. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine learning approaches will be the next step towards personalized approaches for cancer medicine.
Abstract
Background
Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) ...emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. Whole-body autopsy studies of COVID-19 patients have been sparse.
Methods
To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy.
Results
COVID-19 caused multisystem pathology. Pulmonary and cardiovascular involvement were dominant pathological features. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without preexisting medical comorbidities.
Conclusions
SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities.
Autopsy findings in patients with COVID-19 showed deaths were due to cardiorespiratory failure, predominantly caused by acute lung injury, microvascular damage, and thrombosis. COVID-19 causes multisystem disease and significant pathology in most organs in patients with and without comorbidities.
A review of the content, structure, accuracy, and completeness of the Catalogue of Landslide OCcurrences in the Emilia-Romagna Region (CLOCkER) is presented. CLOCkER is a historical database, ...designed and developed for all types of landslides in the hilly-mountain area of the Emilia-Romagna section of the Northern Italian Apennines. Historical data have been gathered through a collection of numerous sources, including technical reports, historical archives, scientific literature, and newspapers. The information obtained, which has been evaluated to assess its temporal precision and spatial accuracy, has been recorded in a catalogue consisting of a Database Management System (DBMS) linked to a geographical information system (GIS) interface. The catalogue presently includes 14,416 records of documented landslide occurrences, dating from Middle Ages up to the present. The catalogue is associated with a landslide inventory, continuously updated by the Geological Survey of the Emilia-Romagna Region, where information on the shape, typology, and state of activity of more than 80,000 landslides is included. Our assessment of catalogue quality reveals a satisfactory spatial accuracy and a level of completeness comparable with the theoretical target proposed in the literature for complete inventories. Outputs indicate that CLOCkER can be a reference example useful for other regional historical landslide catalogues. Such reference datasets are useful for a wide range of landslide assessment purposes and can provide practical assistance for stakeholders involved in both scientific and technical fields, forming the basis for landslide temporal trend reconstruction that is essential for landslide hazard evaluation at different spatial-temporal scales. CLOCkER is open access, freely available online.
Chronic kidney disease (CKD) represents a public health problem because it is characterized by several comorbidities, including uremic sarcopenia (US), and a poor quality of life. Currently, there ...are no standardized treatments available to counteract the onset of US but only some possible therapeutic approaches to slow its progression. The aim of this pilot study is to collect descriptive data in order to design a clinical trial based on the power analysis and simple size. The purpose of this pilot study was to evaluate the possible beneficial action induced by the functional anti-inflammatory and antioxidant bars in combination with the adapted physical activity (APA), on the onset and progression of US and other related-CKD comorbidities. We enrolled 21 CKD patients under conservative therapy, divided into four groups: (A) the physical exercise program (PEP), three times a week, in combination with the daily consumption of the two functional bars group; (B) the PEP group; (C) the daily consumption of the two functional bars group; (D) the control group. The duration of the study protocol was 12 weeks. We observed an improvement trend of body composition, blood pressure levels, lipid metabolism, and functional test in A and B groups. These preliminary data would seem to confirm the effectiveness of APA and to demonstrate the additive role of the natural bioactive compound's assumption in countering US and other CKD comorbidities.
The identification of individual or clusters of predictive genetic alterations might help in defining the outcome of cancer treatment, allowing for the stratification of patients into distinct ...cohorts for selective therapeutic protocols. Neuroblastoma (NB) is the most common extracranial childhood tumour, clinically defined in five distinct stages (1-4 & 4S), where stages 3-4 define chemotherapy-resistant, highly aggressive disease phases. NB is a model for geneticists and molecular biologists to classify genetic abnormalities and identify causative disease genes. Despite highly intensive basic research, improvements on clinical outcome have been predominantly observed for less aggressive cancers, that is stages 1,2 and 4S. Therefore, stages 3-4 NB are still complicated at the therapeutic level and require more intense fundamental research. Using neuroblastoma as a model system, here we herein outline how cancer prediction studies can help at steering preclinical and clinical research toward the identification and exploitation of specific genetic landscape. This might result in maximising the therapeutic success and minimizing harmful effects in cancer patients.
Image-guided thermal ablations are increasingly applied in the treatment of renal cancers, under the guidance of ultrasound (US) or computed tomography (CT). Sometimes, multiple ablations are needed. ...The aim of the present study was to evaluate the long-term results in patients with renal mass treated with radiofrequency ablation (RFA) with both US and CT, with a focus on the multiple ablations rate. 149 patients (median age 67 years) underwent RFA from January 2008 to June 2015. Median tumor diameter was 25 mm (IQR 17-32 mm). Median follow-up was 54 months (IQR 44-68). 27 (18.1%) patients received multiple successful ablations, due to incomplete ablation (10 patients), local tumor progression (8 patients), distant tumor progression (4 patients) or multiple tumor foci (5 patients), with a primary and secondary technical efficacy of 100%. Complications occurred in 13 (8.7%) patients (6 grade A, 5 grade C, 2 grade D). 24 patients died during follow-up, all for causes unrelated to renal cancer. In conclusion, thermal ablations with the guidance of US and CT are safe and effective in the treatment of renal tumors in the long-term period, with a low rate of patients requiring multiple treatments over the course of their disease.
Liquid biopsies and cancer omics Amelio, Ivano; Bertolo, Riccardo; Bove, Pierluigi ...
Cell death discovery,
11/2020, Volume:
6, Issue:
1
Journal Article
Peer reviewed
Open access
The development of the sequencing technologies allowed the generation of huge amounts of molecular data from a single cancer specimen, allowing the clinical oncology to enter the era of the precision ...medicine. This massive amount of data is highlighting new details on cancer pathogenesis but still relies on tissue biopsies, which are unable to capture the dynamic nature of cancer through its evolution. This assumption led to the exploration of non-tissue sources of tumoral material opening the field of liquid biopsies. Blood, together with body fluids such as urines, or stool, from cancer patients, are analyzed applying the techniques used for the generation of omics data. With blood, this approach would allow to take into account tumor heterogeneity (since the circulating components such as CTCs, ctDNA, or ECVs derive from each cancer clone) in a time dependent manner, resulting in a somehow "real-time" understanding of cancer evolution. Liquid biopsies are beginning nowdays to be applied in many cancer contexts and are at the basis of many clinical trials in oncology.
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