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Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis.We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems and were recapitulated in animal models of altered MYH10 activity. Variants were typically de novo missense changes with clustering observed in the motor domain. MYH10 knockout cells showed defects in primary ciliogenesis and reduced ciliary length with impaired Hedgehog signaling. MYH10 variant overexpression produced a dominant-negative effect on ciliary length.These data presented a novel genetic cause of isolated and syndromic neurodevelopmental disorders related to heterozygous variants in the MYH10 gene with implications for disrupted primary cilia length control and altered Hedgehog signaling in disease pathogenesis.

Este artículo contiene 18 páginas, 4 figuras., Good datasets of geo-referenced records of alien species are a prerequisite for assessing the spatio-temporal dynamics of biological invasions, their invasive potential, and the magnitude of their impacts. However, with the exception of first records on a country level or wider regions, observations of species presence tend to remain unpublished, buried in scattered repositories or in the personal databases of experts. Through an initiative to collect, harmonize and make such unpublished data for marine alien and cryptogenic species in the Mediterranean Sea available, a large dataset comprising 5376 records was created. It includes records of 239 alien or cryptogenic taxa (192 Animalia, 24 Plantae, 23 Chromista) from 19 countries surrounding the Mediterranean Sea. In terms of records, the most reported Phyla in descending order were Chordata, Mollusca, Chlorophyta, Arthropoda, and Rhodophyta. The most recorded species was Caulerpa cylindracea, followed by Siganus luridus, Magallana sp. (cf. gigas or angulata) and Pterois miles. The dataset includes records from 1972 to 2020, with the highest number of records observed in 2018. Among the records of the dataset, Dictyota acutiloba is a first record for the Mediterranean Sea. Nine first country records are also included: the alga Caulerpa taxifolia var. distichophylla, the cube boxfish Ostracion cubicus, and the cleaner shrimp Urocaridella pulchella from Israel; the sponge Paraleucilla magna from Libya and Slovenia; the lumpfish Cyclopterus lumpus from Cyprus; the bryozoan Celleporaria vermiformis and the polychaetes Prionospio depauperata and Notomastus aberans from Malta., The publication of this article is supported by the Open Access Publishing Fund of the International Association for Open Knowledge on Invasive Alien Species (INVASIVESNET; www.invasivesnet.org). Stelios Katsanevakis, Maria Sini and Konstantinos Tsirintanis were supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: HFRI-FM17-1597). Enalia Physis acknowledges Pantelis Patsalou for his support with field-logistics and links with fishers. Fiona Tomas would like to acknowledge funding from FECYT FCT- 14-9319 (¡OJO A LAS INVASORAS! BIODIVERSIDAD Y ESPECIES INVASORAS DEL MEDITERRÁNEO BALEAR). Vasilis Gerovasileiou, Thanos Dailianis and Maria Sini acknowledge the support by the MARISCA project (www.marisca.eu), co-funded (85%) by EEA GRANTS, 2009–2014, and the Public Investments Program (PIP) of the Hellenic Republic (15%). Razy Hoffman acknowledges funding by Yad-Hanadiv foundation, through the Israel Society of Ecology and Environmental Sciences and Israel Nature and Parks Authority (An integrated program for establishing biological baselines and monitoring protocols for marine reserves in the Israeli Mediterranean Sea). Argyro Zenetos and Paraskevi K. Karachle would like to thank the citizenscientists collaborating with the Ellenic Network on Aquatic Invasive Species (ELNAIS – elnais.hcmr.gr). Nikolaos Doumpas, Ioannis Giovos, Periklis Kleirou and Francesco Tiralongo would like to thank all the citizen-scientists that contributed with their shared records and data in the citizen-science project “Is it alien to you? Share it!!!” (https://www.facebook.com/ groups/104915386661854/). Data from Gyaros Island marine reserve were collected under the “GyarosMPA” project, funded by “MAVA Fondation pour la Nature”. Data from Corsica coastline were mainly collected in the framework of the “Corsica Alien Network” initiated by “Office de l’Environnement de la Corse”. Carla Morri and Carlo Nike Bianchi received financial support from FFARB (funds for basic research activities) by the Italian Ministry of Education, University and Research. Ergün Taşkın has been supported by TÜBİTAK, Ankara, Turkey (Project Number: 114Y238). The Slovenian authors would like to acknowledge their financial support from the Slovenian Research Agency (research core funding No. P1-0237) and the Ministry of Agriculture, Forestry and Food of the Republic of Slovenia. Mehmet Fatih Huseyinoglu thanks University of Kyrenia’s Scientific Research Project numbered GRN-20191-004. Fabio Crocetta was funded by the COST (European Cooperation in Science and Technology) Action TD1209 Alien Challenge project. The FRI (HAO DEMETER) team is very grateful to the Marine Strategy Project for financial support. Records of NIS in Jbel Moussa, the National Park of Al Hoceima and Cap des Trois Fourches sites from Morocco were obtained during surveys conducted within the framework of the MedKeyHabitats and the MedMPAnet Projects implemented by UNEP/MAP-RAC/SPA in close collaboration with the Haut Commissariat aux Eaux et Forêts et à la Lutte Contre la Désertification (HCEFLCD) and financially supported by RAC/SPA, Tunisia and the MAVA Foundation, Switzerland (MedKeyHabitats Project) and the European Commission (EC), the Spanish Agency for International Cooperation to Development (AECID), and the French Global Environment Facility (MedMPAnet Project). Jamila Ben Souissi was partially funded by BiodivMex /Chantier MISTRALS. Konstantinos Tsiamis sampling records were retrieved during his post in the Hellenic Centre for Marine Research, which he would like to thank for. Periklis Kleitou and Demetris Kletou were supported by the LIFE financial instrument of the European Union – RELIONMED project [Grant Agreement LIFE16 NAT/ CY/000832]. Some of the data included in the dataset were obtained through the marine citizen science platform Observadores del Mar www.observadoresdelmar.es with the support of FECYT FCT-17-12469, LIFE IP Intemares and Fundació Marilles, and through the citizen science site of the Italian Marine Protected Area of “Regno di Nettuno” (islands of Ischia, Procida and Vivara): www.citizensciencerdn.org. Most data from Lebanon were retrieved from social media dedicated to citizen science (Facebook group: Sea Lebanon https://www.facebook.com/ groups/109615625861815/) or fishers and scuba divers WhatsApp groups). Jamila Rizgalla wishes to thank the administration of Regatta for granting a free pass to conduct field surveys and the security personnel for providing a safe environment. Anna Occhipinti-Ambrogi was supported by European Community’s Seventh Framework Program VECTORS (Vectors of Change in Oceans and Seas Marine Life, Impact on Economic Sectors). The long lasting collaboration with the ICES Working Group on Introductions and Transfer of Marine Organisms (WGITMO) has been a good forum where many information and ideas could be exchanged within some of the authors (Anna Occhipinti-Ambrogi, Argyro Zenetos, Agnese Marchini, and a wider community of scientists working on biological invasions). A. Rosso and R. Sanfilippo received grants from the Catania University Research Plan 2016/2018. Data from Kuriat island were collected under the “Kuriat project”, funded by “MAVA Fondation pour la Nature” executed by SPA/RAC in partnership with the Coastal Protection and Management Agency (APAL) and Notre Grand Bleu (NGB) NGO. The AIS/ERA (Environment and Resources Authority) Maltese data were obtained from the EU funded project EMFF 8.3.1 under the European Maritime and Fisheries Fund 2014–2020 with a total cost of €1.6 million in public eligible EMFF funds (75% EU 25% MT), managed by AIS/ERA (Environment and Resources Authority). The ultimate goals of this European Maritime and Fisheries Fund (EMFF 2014–2020) project are to devise a holistic approach towards marine monitoring and develop a comprehensive database of data collected about the Maltese waters., With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

We empirically examine whether feedback traders are active in the Bitcoin and the extent to which their presence is affected by a series of noise-related factors (sentiment; volume; liquidity) at three different frequencies (hourly; daily; weekly) for the April 2013–July 2019 period based on Bitstamp data. Our findings suggest that positive feedback trading grows stronger for higher (hourly; daily) frequencies, with its presence manifesting itself mainly during periods of high/improving sentiment and high/rising volume/liquidity. Additional tests reveal that the significance of hourly feedback trading is identified during hours corresponding to the trading hours of major European/North American markets. Overall, our results confirm extant literature evidence on the prevalence of noise trading in cryptocurrencies, while further showcasing that the factors motivating feedback trading in other asset classes (equities; ETFs; futures) exhibit similar effects over the presence of feedback traders in the cryptocurrency market.

We observed an increased frequency of massive perivillous fibrin deposition (MPFD) during the second coronavirus disease 2019 (COVID-19) pandemic wave dominated by the Alpha variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MPFD associated with 100% reverse transcription polymerase chain reaction (RT-PCR) positivity for SARS-CoV-2 and detection by immunohistochemistry. The Alpha variant was identified in all placentas with MPFD that could be sequenced.

The mucopolysaccharidoses (MPS) are a group of rare genetic disorders characterized by progressive multisystem disease. We sought to identify the perceptions and support needs of siblings, who often have lifelong relationships and assume important roles for their brothers and sisters with MPS. We designed an online survey to ask siblings about their experiences through a series of Likert statements and open-ended questions. A mixed methods approach was used to analyze the results. We analyzed eligible responses from 97 participants, ages 18.1-61.2 years, who have brothers and sisters with MPS I, II, III, IV, and VI. Participants reported serving as caregivers for their siblings with MPS, at all ages. While over 62% of siblings often felt sad because they have a brother or sister with MPS, over 90% of siblings reported that they like their brothers and sisters and expressed feelings of pride. Siblings wanted information about MPS, guidance for caregiving activities, genetic counseling, and opportunities to connect with other siblings. Families and professionals should acknowledge the unique experiences and needs of siblings, include siblings in medical conversations and care plans when appropriate, and connect siblings to resources for informational and emotional support.

In order to increase their catches, longliners targeting sharks in the Gulf of Gabes, Tunisia, have increased the number of hooks per basket and have included new bait types instead of mackerel (Scomber scombrus). This paper reports the effects of these changes on catch composition, catch rates, size distribution, life‐stage captures, and mortality at haulback. Data from 48 and 96 longline sets, carried out during the shark fishing seasons of 2007 and 2008, with two hooks per basket, and 2016 and 2017, with five hooks per basket, respectively, were examined to assess the effect of gear change. Moreover, the effects of bait types were inspected based on 33 fishing sets using whole mackerel, 19 using salema (Sarpa salpa) halves, and 27 using pieces of stingray (Dasyatis spp.), sampled during 2016 and 2017. The species composition indicated that longliners expand the vertical distribution of their hooks to operate from the surface to the bottom. The catches with both longline designs were dominated by sandbar shark (Carcharhinus plumbeus). Despite gear changes, the catch rate of C. plumbeus decreased by 42.21%, suggesting population decline. The size composition indicated a shift towards larger specimens, mainly adult females, which could jeopardize the shark population. Moreover, the mortality of the main species at haulback seems to be affected by the design of the longline. The bait used, mainly pieces of stingray, significantly increased the catch rate of sandbar shark, which suggests a greater attractiveness of the new bait; however, fish size and mortality rates at haulback were unchanged in response to bait variation. The fishery operates in shark nursery grounds, which exposes these fish (principally C. plumbeus) to considerable exploitation pressure. The new fishing practices intensified the pressure and thus the risk of a rapid depletion of populations. To preserve the shark species in the area, the use of new gear and attractive bait should be banned.

Rates of perceived fatigue, anxiety, depression, sleepiness and mitochondrial disease severity were assessed prospectively in 2017-2018 using established validated questionnaires in 48 adult patients with genetically confirmed primary mitochondrial disease. Fatigue was found to be very common among patients with primary mitochondrial disease, with 34 to 48 (71-100%) patients reporting fatigue depending on the measure used, and the severity of fatigue correlating with the severity of disease. Moderate-to-severe depression (10/48; 20.8%) anxiety (28/48; 58.3%) and sleep problems (16/48; 33.3%) were frequent in our patients with fatigue and these conditions were even more prevalent in those with severe fatigue. In conclusion, perceived fatigue was common in patients with primary mitochondrial disease and appeared to correlate with disease severity. Depression, anxiety and sleep disorders were more common in the cohort than those with other chronic diseases but with rates similar to that seen in multiple sclerosis. The severity of perceived fatigue correlated with an increased risk of these comorbid conditions. The Fatigue Severity Scale may more selectively measure non-anxiety/sleep-related fatigue in primary mitochondrial disease and additional testing is planned.

A retrospective survey assessed the gynecologic, obstetric and fertility history of 103 women with mitochondrial disease (MD)/dysfunction (Md) aged 16 to 75 who had previously been pregnant. Most participants (34%) had a mitochondrial myopathy and there were 248 combined pregnancies with live deliveries (average 3.6 pregnancies/woman). In general, pregnancy in those with MD/Md appears to exacerbate some constitutional and neurological symptoms and may be more frequently associated with common obstetric complications, but this did not appear to result in worse pregnancy outcomes. Most women carried their pregnancy to term, but their neonates tended to have more congenital anomalies than expected.

Primary genetic mitochondrial diseases are often difficult to diagnose, and the term ‘possible’ mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. In instances when a genetic diagnosis cannot be confirmed, a diagnosis of ‘possible’ mitochondrial disease may result in harm to patients and their families, creating anxiety, delaying appropriate diagnosis and leading to inappropriate management or care. A categorisation of ‘diagnosis uncertain’, together with a specific description of the metabolic or genetic abnormalities identified, is preferred when a mitochondrial disease cannot be genetically confirmed.

We consider the numerical approximation of a semilinear fractional order evolution equation involving a Caputo derivative in time of order $\alpha\in (0, 1)$. Assuming a Lipschitz continuous nonlin...

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Relation extraction in biomedical texts intends to uncover interactive features about concepts from these texts. This paper focuses on the extraction of relations between diseases and treatments. For this purpose, an approach combining association rules mining, and a statistical method, TFIDF is proposed. We suggest an extension of Apriori, the most popular algorithm used in association rules mining. The novel algorithm Apriori-TFID generates all frequent item sets. Nonetheless, pruning the infrequent item sets is performed according to the support, and the TFIDF weight. The algorithm is implemented and integrated on the platform Weka. The evaluations show, that the algorithm Apriori-TFID outperforms the ancient Apriori algorithm.

Since December 2019, a new coronavirus disease (COVID-19) was detected in Wuhan, China, spread all over the world. Many research papers have been published to study this disease and help humans to overcome this pandemic. Here, we highlighted the prediction process of COVID-19 based on a combination between wrapper feature selected (FS) algorithm and four different classifiers, namely Convolutional Neural Network (CNN), decision trees (C4.5), nearest neighbors (kNN) and, Naive Bayes (NB). A real dataset has been used in this paper generated by Hospital Israelita Albert Einstein at Sao Paulo, Brazil. The obtained results show an excellent performance of BGA with CNN compared to other methods with accuracy 76%

Extracting the relations between medical concepts is very valuable in the medical domain. Scientists need to extract relevant information and semantic relations between medical concepts, including protein and protein, gene and protein, drug and drug, and drug and disease. These relations can be extracted from biomedical literature available on various databases. This study examines the extraction of semantic relations that can occur between diseases and drugs. Findings will help specialists make good decisions when administering a medication to a patient and will allow them to continuously be up to date in their field. The objective of this work is to identify different features related to drugs and diseases from medical texts by applying Natural Language Processing (NLP) techniques and UMLS ontology. The Support Vector Machine classifier uses these features to extract valuable semantic relationships among text entities. The contributing factor of this research is the combination of the strength of a suggested NLP technique, which takes advantage of UMLS ontology and enables the extraction of correct and adequate features (frequency features, lexical features, morphological features, syntactic features, and semantic features), and Support Vector Machines with polynomial kernel function. These features are manipulated to pinpoint the relations between drug and disease. The proposed approach was evaluated using a standard corpus extracted from MEDLINE. The finding considerably improves the performance and outperforms similar works, especially the f-score for the most important relation “cure,” which is equal to 98.19%. The accuracy percentage is better than those in all the existing works for all the relations.

Summary Background Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. Methods We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov , NCT02782741 . We report results of the 49-week primary analysis period. Findings Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI −0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). Interpretation We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. Funding Sanofi Genzyme.

The paper presents a recommendation model for developing new smart city and smart health projects. The objective is to provide recommendations to citizens about smart city and smart health startups to improve entrepreneurship and leadership. These recommendations may lead to the country’s advancement and the improvement of national income and reduce unemployment. This work focuses on designing and implementing an approach for processing and analyzing tweets inclosing data related to smart city and smart health startups and providing recommended projects as well as their required skills and competencies. This approach is based on tweets mining through a machine learning method, the Word2Vec algorithm, combined with a recommendation technique conducted via an ontology-based method. This approach allows discovering the relevant startup projects in the context of smart cities and makes links to the needed skills and competencies of users. A system was implemented to validate this approach. The attained performance metrics related to precision, recall, and F-measure are, respectively, 95%, 66%, and 79%, showing that the results are very encouraging.

Simple Summary Retinoblastoma, a childhood cancer of the eye, is thought to be caused by inactivating mutations of both copies of the RB1 gene. The majority of RB1 mutations can be detected by clinical screening. However, retinoblastoma cases exist where mutations in RB1 have not been detected. We used whole-genome sequencing to investigate the landscape of mutations in a cohort of sporadic retinoblastomas, including cases where mutations in both copies of RB1 had not been previously identified. We looked for mutations in cancer driver genes and revealed a wide variety of structural rearrangements disrupting RB1. In addition, we investigated mutation burden and specific mutation patterns (mutational signatures), uncovering a treatment-related mutational signature in a tumour exposed to chemotherapy. The power of whole-genome sequencing to identify RB1 mutations of all mutation types can have significant relevance to the clinical management of retinoblastoma patients and genetic counselling of their families. Abstract The development of retinoblastoma is thought to require pathological genetic changes in both alleles of the RB1 gene. However, cases exist where RB1 mutations are undetectable, suggesting alternative pathways to malignancy. We used whole-genome sequencing (WGS) and transcriptomics to investigate the landscape of sporadic retinoblastomas derived from twenty patients, sought RB1 and other driver mutations and investigated mutational signatures. At least one RB1 mutation was identified in all retinoblastomas, including new mutations in addition to those previously identified by clinical screening. Ten tumours carried structural rearrangements involving RB1 ranging from relatively simple to extremely complex rearrangement patterns, including a chromothripsis-like pattern in one tumour. Bilateral tumours obtained from one patient harboured conserved germline but divergent somatic RB1 mutations, indicating independent evolution. Mutational signature analysis showed predominance of signatures associated with cell division, an absence of ultraviolet-related DNA damage and a profound platinum-related mutational signature in a chemotherapy-exposed tumour. Most RB1 mutations are identifiable by clinical screening. However, the increased resolution and ability to detect otherwise elusive rearrangements by WGS have important repercussions on clinical management and advice on recurrence risks.