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The Volcán de Colima, one of the most active volcanoes in Mexico, has experienced several volcanic crises over the last century with the emplacement of voluminous block-and-ash flow deposits providing large volumes of loose material along the main ravines. During the rainy season, this material is easily eroded forming lahars. Over 40 events with variable magnitude (105-106 m3) have been detected each year. The largest events that cause damages to infrastructure are usually triggered during the hurricane season (from mid-August to October) when more than 250 mm of rain usually are accumulated over a few days. On 23 October 2015, Hurricane Patricia hit the Volcán de Colima. The hurricane was announced as having reached category 5 thereby representing the largest ever recorded hurricane event in Mexico. It rapidly weakened after landfall but followed a straight trajectory toward the volcano. Up to 400 mm of rain were recorded over 30 hours. The event was recorded at a monitoring station located in the middle reaches of the La Lumbre ravine on the SW flank of the volcano, which was equipped with a rain gauge, a geophone (10 Hz), and a video camera. A multi-pulse lahar started around 8 pm (GMT) and lasted for more than five hours. The seismic signal and the video images were analyzed to identify the timing of the main pulses, the sediment concentrations, and maximum flow peak discharge. Data show that the lahar was characterized by three main pulses, in the range of debris flows with maximum flow-depth of 8 m, interspersed by more dilute tails as hyperconcentrated flow, as also observed from the frequency contents of the seismic signal. A total volume of 2.5 × 106 m3 was estimated based on the strong correlation between the seismic amplitude and the flow discharge. The lahar destroyed one bridge and ~500 m of the interstate road leaving several villages cut off for a few days. Based on the flow magnitude, duration, and the associated damage, this event probably represents the largest one recorded over the last 20 years. The FLO-2D model was used to replicate the observed event to estimate the maximum inundation limits of lahars along the five principal ravines of the volcano, in an attempt to design a hazard map for catastrophic hurricane-induced events.

Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Laser welding of Al-Si-coated steels for hot stamping in automotive applications is problematic due to the mixing of the coating layers inside the molten pool that weakens the resulting weld seam. In this case, the most common welding procedure to overcome this issue consists in removing the Al-Si layer through laser ablation prior to the joining. This method continues to be the most widely used by major producers of tailor welded blanks, although in situ ablation of the Al-Si coating can be costly and time consuming. In this work, a novel approach consisting in joining as-received (i.e., not decoated) materials using a filler wire and an innovative variable energy distribution laser optics is introduced and tested on tailor welded blanks made of 22MnB5. Tensile tests of specimens obtained from a 33 full factorial design of experiment have shown an average value of ultimate tensile strength of 1523 MPa, which is much higher than the one usually observed in as-received welded then hot-stamped conditions and aligned with hot-stamped base material values. Hardness test results (494–543 HV0.5) were in the typical hot-stamped base material range of values as well, while SEM–EDS analyses detected no ferrite inclusions inside the fusion zone. Variations of the main process parameters have been considered on an iso-thickness and iso-material configuration, empirically demonstrating the stability and reliability of the proposed methodology as well as its suitability for production purposes.

This essay takes up two conceptual formations of great consequence to Herman Melville: “religion” and “literature.” Part of what binds them so tightly for Melville is a set of transformative upheavals in liberal culture that we have lately come to know by a different name: “secularism.” Melville helps us think secularism not as the extirpation of religion in modernity but as an ensemble of broadly disciplinary interventions, whose aim was both to exalt Protestant Christianity as the authorizing sign for planetary white dominion and to demote theology itself into a practice of gentle suasion, private consciousness-raising, influence. Moby-Dick is a novel shouting not into the void of a world abandoned by God—or not only—but into the empty space where the theocratic authority of the pulpit once was, where words fired by the titanic power of Godliness itself narrated, shaped, made history. In his fury and his despair, Melville maps out in cartographic detail the solidification of what would become “literature” as such as a by-product of secular discipline.

Las transformaciones en el periodismo se han acelerado en las últimas décadas. Ha cambiado la forma de financiar la actividad, las formas de consumir información y las prácticas profesionales. Es en este contexto de hiperinformación y fake news donde surge la curación de contenidos periodísticos. El trabajo da inicio a la discusión de su inserción como contenido curricular. Por medio del paradigma hermenéutico, también llamado constructivista, se busca conceptualizar la curaduría de contenidos periodísticos con fines de su incorporación como contenido pedagógico en los planes de estudio de las carreras de periodismo. Se describe el origen de la curaduría hasta su llegada al oficio periodístico, se caracteriza la curación de contenidos periodísticos y se fundamenta la necesidad del estatus académico para proporcionar a los estudiantes competencias para la práctica profesional debido al contexto de infoxicación y desinformación vigente.

Background: Turner syndrome is a rare genetic condition in which a female is partly or completely missing an X chromosome. Signs and symptoms vary among those affected. In fetuses that survive at birth and without congenital malformations, the prognosis is usually positive, but it has high lethality in utero, especially in the first trimester of pregnancy. Methods: We report a case of monosomy X detected during a prenatal diagnosis for beta thalassemia on coelomic fluid (CF) at the VIII week of gestation. Beta globin gene analysis, whole genome amplification (WGA), quantitative fluorescent PCR and array comparative genomic hybridization (array-CGH) were performed on DNA extracted from CF. Results: A monoallelic pattern of all Short Tandem Repeats mapped on the X chromosome was found and array-CGH performed on WGA from a few fetal erythroblasts confirmed monosomy X. Conclusion: This report underlines the importance of an early prenatal diagnosis and the countless potentialities of array-CGH that could make definition of molecular karyotype possible from a few fetal cells, unlike conventional cytogenetic techniques that require a greater cellular content. This is the first report of a molecular karyotype obtained from two cells selected by micromanipulation of CF and defined at such an early gestational age.

Objective Ankle arthrodesis (AA) is often fixed using cannulated screws. The irritation from metalwork is a relatively common complication, but there is no consensus regarding the need to remove the screws on a systematic basis. The aim of this study was to determine (1) the proportion of screws removed after AA and (2) whether predictors of screw removal could be identified. Methods This PRISMA-compliant systematic review was part of a larger previous protocol registered on the PROSPERO platform. Multiple databases were searched including studies in which patients undergone AA using screws as exclusive fixation method were followed. Data were harvested regarding the cohort, the study design, the surgical technique, the nonunion and complication rate at the longest follow-up. Risk of bias was assessed using the modified Coleman Methodology Score (mCMS). Results Forty-four series of patients from thirty-eight studies (1990 ankles, 1934 patients) were selected. The average follow-up was 40.8 months (range 12–110). In all studies, hardware was removed due to symptoms reported by patients and related to the screws. The pooled proportion of removal of metalwork was 3% (95% CI 2–4). The pooled proportion of fusion was 96% (95%CI 95–98), while the pooled proportion of complications and reoperations (excluding the removal of metalwork) stood at 15% (95% CI 11–18) and 3% (95% CI 2–4), respectively. The mean mCMS (50.8 ± 8.1, range 35–66) revealed only an overall fair quality of studies. The univariate analysis and the multivariate model showed that the year of publication (R = − 0.004; p = 0.01) and the number of screws (R = 0.08; p = 0.01) were associated with the screw removal rate. Specifically, we found that over time the removal rate decreased by 0.4% per year and that the use of three screws instead of two reduced the risk of removal of metalwork by 8%. Conclusions In this review, removal of metalwork after ankle arthrodesis using cannulated screws was needed in 3% of cases at an average follow-up of 40.8 months. It was indicated only in case of symptoms related to soft tissue irritation from screws. The use of three screws was paradoxically related to a reduced risk of removal of screws as compared to two-screw constructs. Level of evidence Level IV, systematic review of Level IV.

In modern medicine, smart wireless connected devices are gaining an increasingly important role in aiding doctors' job of monitoring patients. More and more complex systems, with a high density of sensors capable of monitoring many biological signals, are arising. Merging the data offers a great opportunity for increasing the reliability of diagnosis. However, a huge problem is constituted by synchronization. Multi-board wireless-connected monitoring systems are a typical example of distributed systems and synchronization has always been a challenging issue. In this paper, we present a distributed full synchronized system for monitoring patients' health capable of heartbeat rate, oxygen saturation, gait and posture analysis, and muscle activity measurements. The time synchronization is guaranteed thanks to the Fractional Low-power Synchronization Algorithm (FLSA).

Strategic planning is critical in helping railways develop optimal programs for improving their business by making service more attractive and efficient. Preparing a strategic plan requires comparing multiple alternatives and options, each requiring time-consuming planning, evaluation, and analysis. To improve this process Jernbanedirektoratet, Norway’s Railway Directorate, began a research project to develop a state-of-the-art railway timetable generation tool that could be integrated into the agency’s existing timetable-planning process. The new tool, called Automatic Timetabler with Multiple Objectives, is designed to transform conceptual passenger and freight service requirements into working timetables, while ensuring robustness and minimizing time losses. It is designed to bridge the gap between less detailed (macroscopic) models used in timetable development and detailed (microscopic) traffic simulation models. More specifically, it is a mesoscopic model, simplifying some infrastructure elements while using more detailed representations of others (e.g., using specific track allocations in stations). In practice, the tool quickly provides planners with many feasible and good timetables using high-level timetable requirement data. This ability is very useful for strategic planning because it enables planners to quickly evaluate alternative timetable concepts. This paper describes the new timetable generator tool, its development, and the results of a case study application.

Socially Assistive Robots (SARs) are designed to support us in our daily life as a companion, and assistance but also to support the caregivers’ work. SARs should show personalized and human-like behavior to improve their acceptance and, consequently, their use. Additionally, they should be trustworthy by caregivers and professionals to be used as support for their work (e.g. objective assessment, decision support tools). In this context the aim of the paper is dual. Firstly, this paper aims to present and discuss the robot behavioral model based on sensing, perception, decision support, and interaction modules. The novel idea behind the proposed model is to extract and use the same multimodal features set for two purposes: (i) to profile the user, so to be used by the caregiver as a decision support tool for the assessment and monitoring of the patient; (ii) to fine-tune the human–robot interaction if they can be correlated to the social cues. Secondly, this paper aims to test in a real environment the proposed model using a SAR robot, namely ASTRO. Particularly, it measures the body posture, the gait cycle, and the handgrip strength during the walking support task. Those collected data were analyzed to assess the clinical profile and to fine-tune the physical interaction. Ten older people (65.2 ± 15.6 years) were enrolled for this study and were asked to walk with ASTRO at their normal speed for 10 m. The obtained results underline a good estimation (p

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants (CNVs) of the ARX locus found in patients presenting wide-ranging phenotypic variations including ID, speech delay, hypotonia and psychiatric abnormalities. We also report on a further novel Xp21.3 duplication detected in a male patient with moderate ID and carrying a fully duplicated copy of the ARX locus and the ultraconserved enhancers. As consequences of this rearrangement, the patient-derived lymphoblastoid cell line shows abnormal activity of the ARX-KDM5C-SYN1 regulatory axis. Moreover, the three-dimensional (3D) structure of the Arx locus, both in mouse embryonic stem cells and cortical neurons, provides new insight for the functional consequences of ARX duplications. Finally, by comparing the clinical features of the 16 CNVs affecting the ARX locus, we conclude that—depending on the involvement of tissue-specific enhancers—the ARX duplications are ID-associated risk CNVs with variable expressivity and penetrance.

Purpose Persistent nonsolid nodules (NSNs) usually exhibit an indolent course and may remain stable for several years; however, some NSNs grow quickly and require surgical excision. Therefore, identifying quantitative features capable of early discrimination between growing and nongrowing NSNs is becoming a crucial aspect of radiological analysis. The main purpose of this study was to evaluate the performance of an open-source software (ImageJ) to predict the future growth of NSNs detected in a Caucasian (Italian) population. Material and methods We retrospectively selected 60 NSNs with an axial diameter of 6–30 mm scanned with the same acquisition-reconstruction parameters and the same computed tomography (CT) scanner. Software-based analysis was performed on thin-section CT images using ImageJ. For each NSNs, several quantitative features were extracted from the baseline CT images. The relationships of NSN growth with quantitative CT features and other categorical variables were analyzed using univariate and multivariable logistic regression analyses. Results In multivariable analysis, only the skewness and linear mass density (LMD) were significantly associated with NSN growth, and the skewness was the strongest predictor of growth. In receiver operating characteristic curve analyses, the optimal cutoff values of skewness and LMD were 0.90 and 19.16 mg/mm, respectively. The two predictive models that included the skewness, with or without LMD, exhibited an excellent power for predicting NSN growth. Conclusion According to our results, NSNs with a skewness value > 0.90, specifically those with a LMD > 19.16 mg/mm, should require closer follow-up due to their higher growth potential, and higher risk of becoming an active cancer.

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions. Published version

The recession of Alpine glaciers causes an increase in the extent of proglacial areas that leads to changes in the water and sediment balance morphodynamics and sediment transport. Although the processes occurring in proglacial areas are relevant not only from a scientific point of view but also for the purpose of climate change adaptation, there is a lack of studies on the continuous monitoring and multitemporal characterization of these areas. This work offers a multidisciplinary approach that merges the contributions of different scientific disciplines such as hydrology, geophysics, geomatics and water engineering to characterise the Rutor glacier and its proglacial area. We surveyed the glacier and its proglacial area since 2020 with both uncrewed (drone) and crewed aerial photogrammetric flights; we determined the bathymetry of the most downstream proglacial lake and the thickness of the sediments deposited on its bottom. Water depth at four different locations within the hydrographic network of the proglacial area and the bedload at the glacier snout were continuously monitored. The synergy of our approach enables the characterisation, monitoring and understanding of a set of complex and interconnected processes occurring in a proglacial area.

Results of two major projects funded by the European Union are taken into consideration: Fair4Health regarding the possibility of sharing clinical data in various environments applying FAIR principles and 1+Million Genome for the in-depth study of the human genome in Europe. Specifically, the Gaslini hospital plans to move on both areas joining the Hospital on FHIR initiative matured within the fair4health project and also collaborate with other Italian healthcare facilities through the implementation of a Proof of Concept (PoC) in the 1+MG. The aim of this short paper is to evaluate the applicability of some of the tools of the fair4health project to the Gaslini infrastructure to facilitate its participation in the PoC. One of the aims is also to prove the possibility of reuse the results of well-performed European funded projects to boost routine research in qualified healthcare facilities.

In mountain regions, debris flows are responsible for major damage to infrastructure and many casualties every year. Early Warning Systems (EWSs) based on sensor networks installed along the debris-flow channel have been implemented in some catchments around the world, including the Alps. Detecting the early phase of debris flows would allow expanding the lead time of an EWS compared to the monitoring of channelized flows upstream a vulnerable site. In this study, monitoring data gathered from 2019 to 2022 in the headwaters of the Gadria catchment, eastern Italian Alps, are analyzed. One active channel located at 2200 m a.s.l. was instrumented with a time-lapse video camera, a tipping-bucket rain gauge, and a 4.5-Hz vertical geophone. The dataset includes 5 debris-flow events that propagated from the monitored channel to the basin outlet and a large number of signals produced by other seismic sources (e.g., rockfalls, earthquakes, animals, wind). The peak amplitude, the duration and the frequency content of the seismic signals were analyzed with the support of video images to identify the different seismic sources. Results show that different seismic sources produce signals with different characteristics and that it is possible to discriminate the most intense channel processes by analyzing seismic data only. Adopting an approach similar to the rainfall thresholds, debris-flow and runoff events have been bounded by means of a power relationship between peak amplitude and signal duration. The next step of the research would be the development of an algorithm able to automatically classify the seismic sources and identify intense channel processes that can generate debris flows. A similar approach will be applied to the Blé catchment (Val Camonica, central Italian Alps) to study the triggering mechanisms and dynamics of debris flows and analyse whether the proposed approach is valid in other locations. The analysis of seismic data will be combined with the identification of triggering rainfall thresholds and the analysis of infrasound signals to develop reliable EWSs for debris flows.

The relative proportion of bedload and suspended sediment transport in rivers features very large variations both in space (within and among rivers) and in time (ordinary vs infrequent floods). However, the current knowledge about the temporal variability in bedload/suspended proportion is limited, as well as of its controlling factors (e.g., water runoff, sediment supply). The present work investigates the partitioning of sediment load into bedload and suspended fractions in the glacier-fed Sulden/Solda River (eastern Italian Alps, drainage area 130 km2), where a monitoring station for water and sediment transport has been operating since 2014.From 2014 to 2020 the station was equipped with one turbidimeter and 8 geophone plates for monitoring suspended sediment and bedload transport, respectively. Calibration curves for deriving suspended sediment concentrations were derived based on 474 water samples, whereas to convert the geophones signal to bedload mass a portable trap mounted on a crane was used (76 samples collected). Two meteorological stations located at about 2800 m and 1900 m a.s.l. recorded precipitation and air temperature within the catchment.A 10-minute interval dataset was established, including suspended load, bedload, water discharge, precipitation, and air temperature, measured from May to October 2014-2020 (2018 data had to be excluded for technical problems of the turbidimeter). Hourly intervals characterised by data gaps regarding geophone plates or turbidimeter were excluded from the analysis, and a total of 18,549 hourly data were analysed. The overall range of water discharge observed in the study period was 0.7 – 80.8 m3/s, but reliable suspended sediment data are available only up to about 40 m3/s (RI about 2 yr). The mean annual discharge of the Sulden River was 6.3 m3/s, while the mean discharge from May to October equalled 10.0 m3/s. Results show that suspended/bedload partitioning varied with water discharge and time of the year (month) in a complex way. On average, the relative contribution of suspended sediment transport was around 89% for Q20 m3/s. At the lower water discharges (Q10 m3/s), the percentage of sediments transported in suspension shows an opposite temporal trend, increasing from May (80%) to October (97%). Such a remarkable difference compared to lower discharges may be due to the strong increase in suspended sediment concentration at higher water discharges multiplied by larger water volumes carrying suspended transport through the entire flow depth, differently from bedload. Such complex dynamics is consistent with previous results in the Sulden River, where a low effective discharge for bedload – driven by the supply of coarse sediments during the glacier melt period – was observed for the same period analysed here.

Kaplan Meier survival analysis of mice using MDA-468 cells

Elevation of ALDH1A3 expression in BM tissues and cells

The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates; however, this has failed to positively affect the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial–mesenchymal transition (EMT) gene signature (mesenchymal markers, CD44 or Vimentin) were compared in tumors derived from BM, lung metastases (LM), or bone metastases (BoM) of patients as well as mice after injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small-molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment.

Primer sequences for qRT-PCR

Adhesion assay and migration assay using shALDH1A3 in MDA-468 cells

Physio-chemical and spectroscopic data of GA11 and MF7

IHC of BM and LM of human TNBC patients

Cell viability assay using ALDH1A3 inhibitors and ALDH1A3 expression in scRNA-seq data

Synthesis steps of MF-7 and GA11

Survival analysis of breast cancer patients

RNA sequence data in 373 EMT-representative genes

IHC for ALDH1A3 in a mouse BM tissues of MDA-468 cells

Glioma stem–like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1–ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural GSC subtype. shRNA-mediated attenuation of FOXD1 in MES GSC ablates their clonogenicity in vitro and in vivo. Mechanistically, FOXD1 regulates the transcriptional activity of ALDH1A3, an established functional marker for MES GSC. Indeed, the functional roles of FOXD1 and ALDH1A3 are likely evolutionally conserved, insofar as RNAi-mediated attenuation of their orthologous genes in Drosophila blocks formation of brain tumors engineered in that species. In clinical specimens of high-grade glioma, the levels of expression of both FOXD1 and ALDH1A3 are inversely correlated with patient prognosis. Finally, a novel small-molecule inhibitor of ALDH we developed, termed GA11, displays potent in vivo efficacy when administered systemically in a murine GSC-derived xenograft model of glioblastoma. Collectively, our findings define a FOXD1–ALDH1A3 pathway in controling the clonogenic and tumorigenic potential of MES GSC in glioblastoma tumors. Cancer Res; 76(24); 7219–30. ©2016 AACR.

Supplementary Table S1. Cohort demographics of 83, 84, 157, 1016, 28, 711 and 267 glioma spheres. Supplementary Table S2. STR analysis result of 83, 84, 157, 1016, 28, 711 and 267 glioma spheres. Supplementary Table S3. Physical chemical properties of GA11 and GA23, determined by BIOVIA Discovery Studio 4.5.

Supplement Fig. S1. Original film scan of western blots in indicated figures; Supplementary Fig. S2. FOXD1 is identified as a MES GSC-representative transcription factor, related to Figure 1.; Supplementary Fig. S3. Glycolysis assay by measuring relative lactic acid levels of MES83 glioma spheres transduced with shNT control or shFOXD1#1; Supplementary Fig. S4. FOXD1 transcriptionally regulates the expression of ALDH1A3 in MES83 GSCs, related to Figure 4.; Supplementary Fig. S5. RNA-interference mediated silencing of ALDH inhibits tumorigenicity of Drosophila eye neoplasia, related to Figure 5.; Supplementary Fig. S6. Analysis of Rembrandt database showing a higher expression of ALDH1A3 associated with poor prognosis in glioma patients, related to Figure 6.; Supplementary Fig. S7. ALDH inhibitor GA11 inhibits the tumorigenicity of MES83 glioma spheres, related to Figure 6.

Supplementary methods and materials

The “Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2) causes potentially fatal disease.The Covid-19 vaccine is the most effective weapon to reduce the virus spread. We describe a rare post-vaccine effect like Guillian Barré Syndrome. We reported a 66-years-old female patient with acute manifestations four weeks after vaccine administration.

Purpose Supraspinatus tendinosis (ST) refers to the intratendinous degeneration of the supraspinatus tendon. Platelet-Rich Plasma (PRP) is one of the possible conservative treatments for supraspinatus tendinosis. This prospective observational study aims to evaluate the efficacy and safety of a single ultrasound-guided PRP injection in the treatment of supraspinatus tendinosis and to assess its non-inferiority to the widely used shockwave therapy. Methods Seventy-two amateur athletes (35 male, mean age: 43.75 ± 10.82, range 21–58 years old) with ST were finally included in the study. All the patients underwent clinical evaluation at baseline, (T0) and at 1-month (T1), 3-month (T2) and 6-month (T3) follow-up using the following clinical scales: the Visual Analogue Scale for pain (VAS), Constant Score and the Disabilities of the Arm, Shoulder and Hand Score (DASH). A T0 and T3 ultrasound examination was also performed. The findings observed in the recruited patients were compared to the clinical results observed in a retrospective control group made up of 70 patients (32 male, mean age = 41.29 ± 13.85, range 20–65 years old) treated by extracorporeal shockwave therapy (ESWT). Results VAS, DASH and Constant scores significantly improved from T0 to T1; the improvement in clinical scores was kept until T3. No local nor systemic adverse events were observed. An improvement in the tendon structure was observed on ultrasound examination. PRP showed a non-statistical inferiority, in terms of efficacy and safety, compared to ESWT. Conclusion The PRP one-shot injection is a valid conservative treatment to reduce pain, and improve both quality of life and functional scores in patients with supraspinatus tendinosis. Furthermore, the PRP intratendinous one-shot injection showed a non-inferiority in terms of efficacy at the 6-month follow-up, compared to ESWT.

Spinal anesthesia is the best choice for caesarean delivery. This technique is characterized by a complete and predictable nerve block with a fast onset and few complications. Several intrathecal adjuvants are used in order to improve the quality and duration of anesthesia and reduce its side effects. Sixty-two patients who underwent caesarean delivery under spinal anesthesia were included in this medical records review. In this retrospective study, after adopting exclusion criteria, we assessed 24 patients who received Hyperbaric Bupivacaine 0.5% 10 mg and dexmedetomidine 10 μg (G1), and 28 patients who received an institutional standard treatment with Hyperbaric Bupivacaine 0.5% 10 mg and sufentanil 5 μg (G2). We evaluated the difference in terms of motor and sensory block, postoperative pain, and adverse effects during the first 24 h following delivery and neonatal outcome. Our study found that the sufentanil group had a significantly lower requirement for analgesia than the dexmedetomidine group. Postoperative pain, assessed with the VAS scale, was stronger in G1 than in G2 (4 ± 2 vs. 2 ± 1, p-value < 0.01). Differences between the two groups regarding the intraoperative degree of motor and sensory block, motor recovery time, and neonatal Apgar scores were not noticed. Pruritus and shivering were observed only in G2. Itching and shivering did not occur in the dexmedetomidine group. Postoperative analgesia was superior in the sufentanil group, but the incidence of side effects was higher. Adjuvant dexmedetomidine prevented postoperative shivering.

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

During the COVID-19 emergency, most domiciliary social services were suspended to avoid the risk of contagion, leaving older people at a greater risk of social isolation. Assistive technology has the potential to support the work of social professionals in promoting social inclusion and assistance of the older people. In this context, this paper aims to investigate the expectations of social operators toward assistive technology before and during the COVID-19 emergency. It also explores how the said emergency could guide us to implement social services in the future, including a discussion on the barriers to the adoption of assistive technologies. A total of 72 social professionals participated in this study comprising of three phases: two online questionnaires and one semi structured interview. In the first two phases, the two online questionnaires were administered before and during the COVID-19 emergency to 62 social professionals. In the third phase, 10 social workers were interviewed to discuss the results of the previous questionnaires to gain an in-depth understanding. The results highlight that the COVID-19 emergency is responsible for an increased perceived need of services involving telepresence, proposing a hybrid paradigm of assistance with both remote and in-presence assistance. Furthermore, the identified barriers to technology adoption are lack of organizational structure and ready-to-use technology. As for the facilitators for the technology adoption, social workers suggested investing in education and training of social professionals to reduce skepticism towards the usefulness of technology. The social professionals involved in this study highlight a generally positive view of technology in supporting their work. Finally, the lessons learned is also presented as a guideline for researchers in this field. Supplementary Information The online version contains supplementary material available at 10.1007/s12008-021-00836-3.

This essay argues that configurations of what we have been calling “method” will not save the humanities from the compounding disasters of austerity, and that pretending this is not so makes for an especially airless kind of criticism. It tracks the insalubrious persistence of a critical grammar across the terrain of method polemicizing. “Method Wars,” it argues, have bequeathed to us nothing so much as an intricate machinery for metabolizing variance in approach as antagonism, the better to produce differing inflections of the fairly standard practice of “reading” as innovations of “method” that, through the rupturing force of their departures, might rescue the declining humanities. But the decimation of the humanities is, paradigmatically, a problem of structural disinvestment proper to the Long Downturn—a problem, that is, of political–economic conditions. Whatever their virtues or liabilities, our methods do not remake those conditions, though pretending that they might imparts a doomed glamour to our conceptual labors. Doing without that pretense, the essay contends, enables a larger purchase on the invigoratingly synthesizing critical projects that have flourished across the discipline—projects that are of more use to us in their fractious noncoincidence than their polemical overcoming. “Financialization” is Giovanni Arrighi’s term for what happens to capitalist systems in the long last moments of their lurch toward collapse. “Method wars,” a friend recently suggested, “are the financialization of academic literary criticism.”

Regression testing is a practice that ensures a System Under Test (SUT) still works as expected after changes have been implemented. The simplest approach for regression testing is Retest-all, which consists of re-executing the entire Test Suite (TS) on the changed version of the SUT. Retest-all could be expensive in case a SUT and its TS grow in size and, if resources are insufficient, its application could be impracticable. A Test Suite Reduction (TSR) approach aims to overcome these issues by reducing the size of TSs, while preserving their fault-detection capability. In this paper, we introduce and validate an approach for TSR based on a multi-objective evolutionary algorithm, namely, Non-dominated Sorting Genetic Algorithm II (NSGA-II). This approach seeks to reduce TSs by maximizing both statement coverage and diversity of test cases of the reduced TSs, while minimizing the size of the reduced TSs. We named this approach Genetic Algorithm for teSt SuitE Reduction (GASSER). To assess GASSER, we conducted an experiment on 19 versions of four software systems from a public dataset—i.e. Software-artifact Infrastructure Repository (SIR). We compared GASSER with nine baseline approaches. The comparison was based on the size of the reduced TSs and their fault-detection capability. The most important take-away result is that GASSER, as compared with the baseline approaches, reduces more the size of the TSs with a non-significant effect on their fault-detection capability. The results of our empirical assessment suggest that the application of multi-objective evolutionary algorithms and, in particular, NSGA-II might represent a viable means to deal with TSR.