We collated and synthesized information on 1,226 Elasmobranch species  globally from a wide range of sources. We obtained curated and standardized data from online databases, legal documents, press releases, and websites. All data were standardized according to the taxonomic nomenclature described in the Catalogue of Life. We grouped data into five categories: 1) biological information, 2) conservation status, 3) management opportunities, 4) use, and 5) inclusion in international conventions and treaties. For species biological information, we included migration, habitat, species characteristics such as length & body weight, their threat to humans, life-history trait data availability from FishBase, whether the species was listed on the Global Register of Migratory Species, the presence of occurrence data from the Global Biodiversity Information Facility (GBIF), information on genomics from GenBank, and species evolutionary distinctiveness scores. For conservation status, we recorded threat status from the International Union for Conservation of Nature Red List of Threatened Species™ and inclusion in the Alliance for Zero Extinction (AZE). For management opportunities, we identified species under human care in zoos and aquariums in the Species360 network, species under management in studbooks from the European Association of Zoos and Aquaria (EAZA), the American Association for Zoos and Aquariums (AZA), and the Zoo and Aquarium Association Australasia (ZAA), as well as data on recovery, management, and action plans at the class, family, and species levels. For use, we collated species-level data on international trade levels from the CITES  Trade Database, as used in aquaculture, as bait, and as gamefish, recording the purpose of the trade according to the IUCN Red List and the global catches reported to the FAO (Food and Agriculture Organization of the United Nations). Finally, we collated information from seven international conventions and treaties: CITES, UNCLOS (the United Nations Convention for the Law of the Sea), CMS , Shark MoU (the Memorandum of Understanding on the Conservation of Migratory Sharks), BERN , OSPAR (Protecting and conserving the North-East Atlantic and its resources), and the Barcelona Convention for the Protection of the Marine Environment and the Coastal Region of the Mediterranean. Our data are comparable across databases and will assist further research on in-situ and ex-situ population management for sharks and batoids. Our data can be of use to international policy makers, aquarium curators, management authorities, conservation practitioners, and scientists interested in prioritizing Elasmobranchs for conservation. We merged data from FishBase, the Global Register of Migratory Species (GROMS), the Global Biodiversity Information Facility (GBIF), the IUCN Red List, GenBank, the Vertebrate Genome Project (VGP), and evolutionary distinctiveness scores from the EDGE of Existence database We assessed sequence data from GenBank to identify the type of information available for each species in each of nine sequence types: 1) gene sequences (GEN), 2) genomic survey sequence (GSS), 3) nuclear marker (NM), 4) mitochondria (mtDNA), 5) pseudogene (PG), 6) RNA sequences (RNA), 7) whole genome sequence (WGS) or 8) other genetic sequences (Other). We found 736 species with records on any of the nine categories. In Supplementary File S1, we list for each species how many records were reported for each sequence type. For primary biodiversity data, we found 1,017 species of sharks and batoids with occurrence data on the GBIF website between 2000 and April 2020. In 1.2Conservation status was assessed with IUCN Red List extinction risk assessments and the Alliance for Zero Extinction (AZE) 1.3Data for ex-situ management include species holdings and total population size across aquariums in the Species360 network (ZIMS) and whether species are included in a captive breeding program by a regional association. Of the 1,226 species described in the Catalogue of Life, 159 were represented in ZIMS and 18 were managed in regional associations. Of these 18 species, five species were managed only by the European Association of Zoos and Aquaria (EAZA), five species were managed by both the EAZA and the American Association of Zoos and Aquariums (AZA), seven species were managed only by the AZA, and one species was managed by both the AZA and the Aquarium Association Australasia (ZAA).For in-situ management, we included information on conservation strategies from the IUCN Species Survival Commission (SSC) Shark Specialist Group (SSG) and recovery or action plans under the Australian or Canadian Government, which were the only countries with action plans that were found during the search, either at the family or species level. Additionally, we included national and regional plans both historically and in use from IPOA Sharks 1.4This category summarizes information available on the use of the species . We included information on international trade in Elasmobranchs between 2000 and 2018 at the species or genus level from the UNEP-WCMC (United Nations Environment Programme World Conservation Monitoring Centre), CITES Trade Database and global catches from the FAO from 2000 to 2017. The dataset in Supplementary File S1 includes CITES information on importing and exporting countries, the origin and source of the species of concern, the purpose of the transaction and quantities, and the terms the species was traded under. We also note the CITES Appendix under which each species is listed. In We also included data from the IUCN Red List indicating any purposes of trade for the focal species . From Fishbase we collated data on catch methods and if the species is used in aquariums, as bait, in aquaculture or as a gamefish.1.5We collated and standardized the information of seven legal instruments  protecting or managing Elasmobranchs. In Supplementary File S1, we include if the species is listed in the following international or regional conventions or treaties: CITES  both internationally and in the EU, UNCLOS (the United Nations Convention for the Law of the Sea), CMS , Shark MoU (the Memorandum of Understanding on the Conservation of Migratory Sharks), BERN , OSPAR (Protecting and conserving the North-East Atlantic and its resources), and the Barcelona Convention for the Protection of the Marine Environment and the Coastal Region of the Mediterranean.2taxize [To collate data across the 31 open-source repositories, databases, and documents, we standardized the Elasmobranch taxonomy using the Catalogue of Life taxize ,11, whichttp://www.marinespecies.org/aphia.php?p=match. We added the scientific name, the taxon status (if taxon is accepted or not according to WoRMS) and the internal taxon ID from WoRMS to the Supplementary File S1. We divided the data by taxonomic orders into sharks: Hexanchiformes, Squaliformes, Carcharhiniformes, Pristiophoriformes, Heterodontiformes, Lamniformes, Orectolobiformes, Squatiniformes and batoids: Rhinopristiformes, Rajiformes, Myliobatiformes, TorpediniformesFurthermore, we cross-referenced the species taxonomy from CoL with the taxonomy from the World Register of Marine Species (WoRMS) by using the WoRMS Taxon Match Tool available at 2.1List of Symbols and Abbreviations from Fishbase , the Fishbase System Glossary (https://www.fishbase.in/Glossary/Glossary.php?q=a&s=index) or the National Marine Sanctuaries: Fisheries Glossary - Voices of the Bay (https://sanctuaries.noaa.gov/education/voicesofthebay/glossary.html).We retrieved two types of data from FishBase, 1) we collected the data on biological traits available for the following variables: ecology, food, diet, predators, spawning, maturity, eggs, hatchlings, growth, mortality, length and weight, maximum size, genetics, or photo identification from the Fishbase Information Gaps webpage https://doi.org/10.15468/dl.59ncfb, Rajiformes: https://doi.org/10.15468/dl.un0pej, Torpediniformes: https://doi.org/10.15468/dl.5uuncg, Myliobatiformes: https://doi.org/10.15468/dl.8phc9c, Pristiophoriformes: https://doi.org/10.15468/dl.slawae, Hexaniformes: https://doi.org/10.15468/dl.obnvcs, Heterodontiformes: https://doi.org/10.15468/dl.kfr6u1, Lamniformes: https://doi.org/10.15468/dl.rwwqee, Squaliformes: https://doi.org/10.15468/dl.5yut6b, Carcharhiniformes: https://doi.org/10.15468/dl.54oesv, Orectolobiformes: https://doi.org/10.15468/dl.llxcxj, Squatiniformes: https://doi.org/10.15468/dl.kqmgn3). We indicate which species has been observed between 2000 and April 2020. Additionally, we filtered the data and counted the total number of observations for each species in the time period 2009 and 2019 for 1) All observation types and 2) only for human observations, machine observations and observations GBIF data were retrieved from GBIF's online database and each Elasmobranch order was downloaded separately (Rhinopristiformes: taxizehttps://vertebrategenomesproject.org/ways-to-help-1). We obtained Evolutionary Distinctiveness (ED) scores for each species from the EDGE of Existence webpage To retrieve genomic information from GenBank, we used the R package We gathered data on the species country distribution, generation length range, movement patterns, threats and stressors from the IUCN Red List Advanced Search version 2020-2 using the “country”, “threat” and ”all other fields” files.2.2We retrieved IUCN Red List assessments from the IUCN Red List of Threatened Species™ version 2020-1 from their website using the taxonomy function, selecting the 12 Elasmobranch orders. We downloaded information from the Alliance for Zero Extinction (AZE) data from the Global AZE map 2018 2.3We submitted a request for species holdings data to the Zoological Information Management System (ZIMS) managed by Species360. The species holdings files contain a list of species in Species360-member aquariums globally, the number of adult individuals alive at the time of data extraction and their sex (May 2019).We obtained the lists of species managed under a breeding program in a studbook from the websites of three regional associations: the European Association of Zoos and Aquaria (EAZA), the American Association of Zoos and Aquariums (AZA), and the Zoo and Aquarium Association Australasia (ZAA).EAZA reports two types of breeding programs: the European Endangered species Program (EEP) and the European Studbook (ESB). AZA reports on the Species Survival Plan (SSP) as a part of the Marine Fishes Taxon Advisory Group (TAG). ZAA reports on the Australasian Species Management Program (ASMP).We used the IUCN Species Survival Commission Shark Specialist Group's webpage to gather information on shark and batoid families with a conservation strategy. We assumed that every species under a family with a conservation strategy would have higher in-situ conservation opportunities than those without one. We gathered data on if there is an active recovery plan in place for species and if the habitat lies partly or completely within a protected area from the IUCN Red List Advanced Search version 2020-2 and used the “all other fields” file.To find action plans at the species level, we used the search engine Google and the keywords: “action plan rays”, “recovery plan rays”, “management plan rays”, “recovery plan sharks”, “action plan sharks”, “management plan sharks”, “management plan Elasmobranchii”, and “action plan Elasmobranchii”. We did not include plans labelled as inactive. The list of species with a recovery, management, or action plan is available in Supplementary File S1. During the search, we found two databases with management plans and action plans at the country level . In 2.4Data on international trade was retrieved from the UNEP WCMC CITES Trade Database (2000–2018) for Elasmobranchii. We gathered the data from the FAO (2007–2017) on catches in Oceania, Africa, Asia, Europe, and the Americas for inland waters and marine areas. All marine species within the group “sharks, rays, and chimeras” were selected. Catches recorded at the order, the family, or the genus level were divided by the number of species within that taxon according to CoL, to get an overview of which species are possibly caught and at which quantities. We then estimated the total catch at the species level as the sum of catches recorded at the order, the family, the genus, and the species level for each species We included the data from the IUCN Red List Advanced Search version 2020-2 indicating the purpose of the trade with the particular species , and used the “usetrade” file. To gather data on describing if the species are used: i) in aquariums, ii) as bait, iii) in aquaculture, or iv) as a gamefish and catch methods, we retrieved data from Fishbase using the ‘rfishbase’ package from the open-source software R ,12.2.5We obtained names of all Elasmobranch species listed by seven international and regional conventions or treaties: CITES , UNCLOS (the United Nations Convention for the Law of the Sea), CMS , Shark MoU (the Memorandum of Understanding on the Conservation of Migratory Sharks), BERN , OSPAR (Protecting and conserving the North-East Atlantic and its resources), and the Barcelona Convention for the Protection of the Marine Environment and the Coastal Region of the Mediterranean.Information on each convention or treaty was obtained through online databases, legal documents, and official webpages . For CMSThe authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article.


Hepatocellular carcinoma (HCC) is a leading cause of cancer and cancer-related deaths in the world. Some of the risk factors for the development of HCC include Hepatitis B virus (HBV), Hepatitis C virus (HCV), chronic alcoholism, autoimmune hepatitis, among others. One manifestation of HCC includes tumor thrombus (TT) to the right atrium (RA), which occurs in 0.67-4.1% of patients with HCC. Our case focuses on a unique presentation of HCC with RA TT with initial symptoms of nausea and vomiting without signs of cardiac decompensation or hemodynamic instability. Although there is no definitive treatment for TT to the RA, there are a variety of proven avenues of management of HCC TT to the RA, especially pertaining to patients with adequate liver function.A 63-year old female with a past medical history of untreated HCV and alcohol abuse with no previously known liver disease or history of liver decompensation, presented with nausea, vomiting, and diarrhea. Initial labs revealed hypovolemic hyponatremia and transaminitis with negative ethanol levels. The model for end-stage liver disease (MELD-Na) score was calculated at 27, and she had a Child-Pugh class C score. Follow up labs were significant for elevated alpha-fetoprotein (AFP). Triple-phase CT of the liver revealed a large liver mass with extension into the RA with TT and necrosis of the liver. An echocardiogram revealed a RA mass versus thrombus. Throughout her hospitalization, she never admitted to cardiac symptoms, including shortness of breath, palpitations, or chest pain. No tachycardia was noted, and her blood pressure remained stable. She was not a candidate for surgery or chemotherapy. The patient declined any heroic measures, and palliative care was consulted for further management. She was transferred to hospice, where she died one week later. There are numerous etiologies and clinical presentations of HCC with TT to the RA. Its disease course is insidious and may not present as symptomatic until there is a sizable tumor burden. Therefore, treatment options for HCC with TT to the RA are reliant on HCC screening for at-risk populations, early diagnosis, and each individual patient’s baseline liver function. Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer in the world and the second leading cause of cancer-related deaths in the world . Common In this report, we focus on a rare manifestation of HCC, which is tumor thrombus (TT) to the right atrium (RA). This is most commonly due to liver cirrhosis, but can also be caused by inflammatory abdominal processes, such as pancreatitis, and occurs in 0.67-4.1% of patients with HCC ,4. NotabA 63-year old Caucasian female initially presented with persistent nausea and non-bloody, non-bilious vomiting for two weeks. She endorsed bloating and two episodes of non-bloody watery diarrhea. Her past medical history included untreated hepatitis C virus (HCV), hypertension, lung nodules, alcohol abuse, including a daily alcohol intake of one liter, and a history of intravenous drug use. She also had no previously known liver disease with no history of liver decompensation, including variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. On exam, the patient appeared jaundiced and was found to have a distended abdomen, moderate ascites, and a palpable lobulated liver with 2+ pitting edema on the bilateral lower extremities. No spider angiomas or jugular venous distension were appreciated. Initial labs revealed hypovolemic hyponatremia, aspartate aminotransferase (AST) of 93 U/L, international normalized ratio (INR) 1.4, albumin 3.2 g/dL, and a total bilirubin level of 4.4 mg/dL. A model for end-stage liver disease (MELD-Na) score was calculated at 27, and she had a Child-Pugh class C score. She had a hepatitis C virus (HCV) RNA level of 1075 IU/mL.An abdominal x-ray showed a non-obstructive bowel pattern. A computed tomography (CT) of the abdomen suggested a mass in the left lobe of the liver and was followed by an ultrasound (US) Figure , which rThe patient never presented with any cardiac symptoms during her stay at the hospital. Throughout her hospitalization, she denied shortness of breath, chest pain, or palpitations. No tachycardia was noted, and her blood pressure remained stable.She was seen by gastroenterology, hepatobiliary surgery, and oncology. All teams agreed that she was not a candidate for surgery or chemotherapy due to her advanced staging, thrombocytopenia, and coagulopathy. The patient was offered Sorafenib, which she declined, and palliative care was consulted for further management. She was transferred to hospice, where she died one week later.Review of cases of HCC tumor thrombus to the right atriumIn reviewing six other case reports of HCC with RA TT without intervention Table , our casThe other published case studies revealed various presentations of HCC with RA TT including cachexia, generalized edema, right upper quadrant pain and dyspnea secondary to Budd-Chiari syndrome, dyspnea secondary to pulmonary embolism, melena due to esophageal varices, and a combination of cachexia, abdominal distension, dyspnea and edema ,5-9. It Our patient also had the unique etiology of HCC with RA TT likely caused by HCV in conjunction with excessive alcohol consumption. Among the six cases we reviewed, two cases were due to HCV as seen in our patient, two cases were due to HBV, one case was due to autoimmune hepatitis, and one case was of unknown etiology ,5-9. PatSimilar to our patient, these cases received little to no intervention after the final diagnosis of their disease. One patient refused treatment, one patient started Sorafenib for two months with poor tolerance, and three of the patients received palliative care ,5-8. OneTumor thrombus in non-cirrhotic patientsPortal venous tumor thrombus (PVTT) can occur both in patients with cirrhosis and without cirrhosis. However, almost all cases of PVTT exist in patients with previous liver cirrhosis or at least one traditional risk factor for HCC . In non-Review of interventionsThere is no definitive treatment for HCC leading to tumor thrombus in the RA. In patients with good hepatic function and those who meet Child-Pugh class A criteria, studies have shown that surgical and non-surgical interventions can be successful. For minimal RA TT invasion, partial hepatectomies with thrombectomy, and total hepatic vascular exclusion (THVE) can be performed. This process involves reducing the liver to mobilize the TT downward from the RA into the IVC and clamping the IVC superior to the thrombus, followed by THVE and removal of the thrombus followed by partial hepatectomy . In situations with more invasive RA TT in which the thrombus cannot be mobilized into the IVC, THVE with cardiopulmonary bypass (CPB) has been studied to be effective. CPB utilizes an outside circuit that navigates venous blood to a reservoir, which is then oxygenated and pumped back into the body. In a study by Wakayama et al. studying surgical intervention in 13 patients with HCC with TT to the IVC and RA, five of the patients who underwent a curative resection experienced a recurrence with a total median survival of 15.3 months for patients with an IVC TT and 11.2 months in patients with an IVC TT extending to the RA . AnotherRadiation therapy has also been practiced in patients with HCC with TT to the RA. Although surgery has been proven to be superior in efficacy to radiation therapy, radiation therapy has shown to be overall better tolerated in patients and has moderate tumor response -15. TumoEvaluating liver function and cirrhosis severity when electing screening and treatment options for HCCIn considering treatment options, it is important to consider the patient’s liver function. One commonly used classification system in patients with liver disease is the MELD-Na score, which calculates a three-month mortality rate based on kidney function, bilirubin, INR, and sodium. Our patient had an initial MELD-Na score of 27, possibly contributed by untreated HCV, chronic alcoholism, and HCC. A MELD-Na score of 27 indicates an estimated three-month mortality rate of 19.6%. Any patient with a MELD-Na score greater than 10 should be referred to a hepatologist. Another common assessment of liver function is the Child-Pugh score, which assesses cirrhosis severity by creating a score based on total bilirubin, albumin, prothrombin time, INR, ascites, and degree of encephalopathy. Treatment for HCC with TT to the RA may be dependent on the class the patient falls in. All of the patients treated with surgical intervention in the previous studies had a Child-Pugh class A score ,14,17. PHCC screening guidelinesScreening and prevention of HCV in the USA should be a public health priority, as HCV continues to be the leading cause of HCC in the USA . ScreeniUltimately, this case highlights the differing etiologies and presentations for HCC with TT to the RA. Our patient’s unique presentation of nausea and vomiting as her primary symptom reveals how variable and insidious this disease can be. Our case report was limited due to lack of intervention and inability to evaluate the extent of metastasis to her regional lymph nodes and distant organs due to her rapid decompensation leading to death a few weeks after diagnosis. Strengths in this study include the evaluation of the extent of the tumor thrombus with CT and an echocardiogram. We were also able to find a possible etiology based on her past medical history and understand the extent of her declining liver function based on her risk factors and laboratory results. Our patient’s attributable risk factors to the development of her HCC with TT to the RA include alcohol abuse and HCV infection. Different screening options are available and involve a combination of imaging and serum markers to monitor for HCC. Few treatments are available in advanced HCC, but surgical intervention should be first-line. Based on our patient’s case and previously published presentations, we have seen that it is imperative for HCC with TT to the RA to be screened and diagnosed early for optimal treatment options. Assessing liver function is paramount in deciding the proper treatment course, and the number of treatment options available decreases in tandem with a decrease in liver function.


Haemaphysalis longicornis (H. longicornis), as well as the explanatory environmental variables, based on which, the potential geographic range of H. longicornis and risk areas for SFTS were mapped by applying two machine learning methods. Ten predictors were identified contributing to global distribution for H. longicornis with relative contribution ≥1%. Outside contemporary known distribution, we predict high receptivity to H. longicornis across two continents, including northeastern USA, New Zealand, parts of Australia, and several Pacific islands. Eight key drivers of SFTS cases occurrence were identified, including elevation, predicted probability of H. longicornis presence, two temperature-related factors, two precipitation-related factors, the richness of mammals and percentage coverage of water bodies. The globally model-predicted risk map of human SFTS occurrence was created and validated effective for discriminating the actual affected and unaffected areas  in three countries with reported cases outside China. The high-risk areas (probability ≥50%) were predicted mainly in east-central China, most parts of the Korean peninsula and southern Japan, and northern New Zealand. Our findings highlight areas where an intensive vigilance for potential SFTS spread or invasion events should be advocated, owing to their high receptibility to H. longicornis distribution.Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing spread. Currently SFTS transmission has expanded beyond Asian countries, however, with definitive global extents and risk patterns remained obscure. Here we established an exhaustive database that included globally reported locations of human SFTS cases and the competent vector,  Haemaphysalis longicornis (H. longicornis) ticks act as the main transmission vector [H. longicornis is native to East Asia and has established populations in the Australasian and Western Pacific Regions [H. longicornis, however lacking model-based prediction and not at international level, thus the spatiotemporal distribution pattern of the disease in the worldwide range warranted intense investigation.Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by a novel bunyavirus (SFTSV), with a wide clinical spectrum, ranging from mild febrile disease accompanied by thrombocytopenia and/or leukocytopenia to severe hemorrhagic fever, clinical encephalitis or multiple organ failure, with a case fatality rate (CFR) of 12‒50% ,4. Southn vector . H. long Regions . Very re Regions ,15. The  Regions ,17, togeH. longicornis was predicted based on data regarding the known locations of its occurrences by using the ecological niche (EN) modelling approach, which has been widely used in modelling species distribution when only presence data is available for prediction [In this study, we adopted a two-step strategy to predict the potential distribution of SFTS. For the first modelling step, the global distribution of ediction ,19. At sediction . This inH. longicornis, and a set of 56 explanatory variables at the county level in the world. Briefly, the report data of SFTS patients in China was extracted from the China Information System for Diseases Control and Prevention (CISDCP). The data on the SFTS patients in South Korea and Japan were obtained from the Korea Centers for Disease Control and Prevention (KCDC) (https://www.cdc.go.kr/) and the National Institute of Infectious Diseases (NIID) of Japan (https://www.niid.go.jp/), both supplemented by data in the published literature [H. longicornis was established that included data recording on survey sites and positive locations of H. longicornis in latitude and longitude, as well as the survey dates on record  (Supplementary Dataset S1) [H. longicornis [A comprehensive database was established by combining all SFTS case report, the recorded geographic distribution of terature . For eacaset S1) ,23–26. Taset S1) ,28. Eco-gicornis . The Glogicornis . Data ongicornis .H. longicornis was geo-referenced and linked to the digital world map according to its coordinates using Geographic Information System (GIS) technologies. Machine learning method with ecological niche (EN) model was applied at the 0.1° × 0.1°grid level to correlate the global observed locations of H. longicornis and 51 selected eco-geographical and climatic variables (Supplementary Table S1). The grid locations with the occurrence of H. longicornis were used in the model. Ten thousand grids were randomly selected from all grids without the presence of H. longicornis as control points for the model. The variables were first grouped according to the subject , and then multicollinearity was screened for each group and only one variable was chosen as the proxy of highly correlated variables (correlation coefficient ≥0.7) to be used for model-fitting (Supplementary Tables S2–S4). The variables whose contribution was less than 1% were removed from the ecological niche (EN) model (Supplementary Table S5). Ultimately, 10 variables were identified for the EN model after the variable selection, including elevation, three eco-climatic variables, three land cover types, population density, livestock density, and mammalian richness. In this study, the maximum entropy method (Maxent) was used [H. longicornis presence were mapped to display the potential habitat suitable for this vector tick around the world [Each occurrence record of was used ,19,36, aH. longicornis presence (Supplementary Table S1). We adopted the same variable selection method as the EN model, accounting for non-linear association and interactions between covariates , the variables whose contribution was less than 1% were eliminated to screen out the high-efficiency predictive variables (Supplementary Table S7). Finally, for each county, altogether 18 independent variables were considered in the model, which included 5 bioclimatic variables determined from 1950 to 2000, density of population, elevation, percentage coverages of land cover , the density of livestock, mammalian richness, predicted probability of H. longicornis presence which was extracted from the ecological niche model. A bootstrapping procedure was conducted for the BRT models to generate robust estimates of predicted probability, based on which the mean transmission risk of SFTS around the world was predicted (Supplementary Methods). The BRT models were also validated to be effective for discriminating the actual affected and unaffected areas by using the data in three SFTS-reporting countries outside China, i.e. Japan, South Korea and Vietnam.A boosted regression tree (BRT) approach was used to establish a multivariate empirical relationship between the probability of SFTS presence and the eco-geographic and environmental conditions at the county level  as had been widely used for assessing risk of infectious diseases ,37–39. TAs of 31 December 2018, a total of 13,259 SFTS patients were recorded, including 11,995, 396, and 866 cases who were respectively reported from China, Japan and South Korea, as well as 2 cases retrospectively identified in Vietnam. Of all SFTS cases, 1161 died, leading to an overall case fatality rate (CFR) of 8.76%, with the highest CFR observed in Japan . The age and gender pattern differed significantly among the three major affected countries, with patients in China having the lowest median age (62 years old), and highest female proportion (53.15%) . Over thH. longicornis on the global range  ≥1% to the established ENM model. Among which the precipitation of warmest quarter was the leading factor that contributed to the probability of H. longicornis presence, with the greatest RC of nearly 33%, followed by annual mean temperature, density of population, and density of livestock, with all their RCs exceeding 5% . To avoid overconfidence in the model, we also performed a sensitivity analysis by using sampling at the county level, namely the controls were set as the no-case-reporting-counties within 25 provinces that reported SFTS cases in China. The ROC and the AUC’s are similar to our current model that samples the whole country . The model-predicted risk probability of SFTS presence was further validated by using the reported data in three SFTS-affected countries, Japan, South Korea and Vietnam. The results showed effective for discriminating the actual affected and unaffected areas (P < 0.001), with a median predictive value of 0.74 (IQR: 0.54–0.86) for affected counties and 0.04 (IQR: 0.03–0.05) for unaffected counties.The predictive map for occurrence of SFTS was created, demonstrating the highest-risk areas located in the east-central China, in most parts of the Korean peninsula and southern Japan, additionally at the coastal areas in northern and limited region in the southern New Zealand . The recH. longicornis, and its quick spread in the United State demonstrated the possibility of the disease to be global rather than regional [H. longicornis across two continents, including northeastern USA, New Zealand, parts of Australia, and several Pacific islands . Our prediction map  have attracted much attention because of their increasing incidence. In addition to SFTSV and HRTV which had severely threatened human health, other novel TBPV continued to be identified and isolated from ticks, such as Guertu virus (GTV) from e, China , and Hune, China . In addinfection ,54. The H. longicornis), the infection rate of SFTSV in H. longicornis and animal hosts, which would inevitably result in a bias in the risk evaluation. All these limitations called for a further systematic epidemiological study that fully consider the complex interaction between SFTSV, the competent transmission tick species, their hosts, and the habitat environment after obtaining a continuous and evenly sampling and detection of SFTSV by field researches. Still, this study represented the first mapping of the potential-risk areas of SFTS occurrence at the global level. The high resolution risk maps provided an evidence base to prioritize areas for targeting risk zones, where public health authorities should be most vigilant for potential spread or importation events, and advocate intensive surveillance on H. longicornis population and the situation of SFTSV infection.Limitations of this study are needed to be recognized that are relevant to the interpretation of the results. First, because of the inaccuracies in human case report data, especially in the low-risk region, the lack of valid diagnosis methods and low vigilance to the disease of the local public health were responsible for the underestimation of the human cases, which might lead to the misclassification of the regions with or without risk of SFTS occurrence. Second, some potential determinants of the human SFTSV infections were not included in our BRT model due to the lacking of data. This included but not limited to density of the main vector tick (


Safflower injection (SFI), a popular Chinese patent drug, is commonly used to treat acute coronary syndromes (ACSs) in China. The research seeks to scientifically estimate the clinical efficacy of SFI for ACS patients.  Eight electronic databases were retrieved for eligible research from the founding date to September 8, 2020. Odds ratio (OR) was adopted to assess the total effective rate, ECG improvement, and adverse reaction, and mean difference (MD) was used for assessing the hemorheology indexes as well as the LVEF. P < 0.00001), ECG improvement , and LVEF . Moreover, SFI combined with conventional treatment significantly decreased hemorheology indexes including BV , HCT , FIB , and PAR . However, no notable contrast was observed to link the experimental and the control team for PV  and adverse reactions .  Sixteen randomized controlled trials involving 1620 sufferers with ACS were incorporated. The outcomes showed that, in comparison to conventional medication alone, SFI combined with conventional treatment remarkably enhanced the total effective rate (OR = 3.66, 95% CI ,  Despite the limitations that existed in this meta-analysis, the outcomes demonstrated that SFI and conventional combined medication is an effective and relatively safe therapy for ACS sufferers. Acute coronary syndrome (ACS) is a category of clinical syndromes resulting from acute myocardial ischemia. These syndromes include ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina pectoris . The maiβ-blockers, nitrates, calcium channel restrictors, and angiotensin-converting enzyme inhibitors [The treatment of ACS mainly includes medication, surgery, and intervention operation . Among thibitors . Howeverhibitors . TherefoCarthami flos by water extraction and alcohol precipitation [Safflower injection (SFI) is a popular Chinese patent drug that has been authorized by the China Food and Drug Administration. It is prepared from pitation . The majpitation . Howeverpitation . SFI haspitation .Along with the development of integration of traditional Chinese and Western medicine, SFI combined with conventional treatment (Western medicines) was increasingly prescribed for treating ACS over the past decades, and some studies showed that it might bring beneficial effects to the patients . HoweverThe PRISMA statement was used to form a basis for the meta-analysis . RandomiAfter consulting with several cardiologists, the inclusion criteria were formulated as follows: subjects were confirmed to suffer from ACS according to the cardiovascular disease examination method formulated by the Chinese Medical Society (CMA) as well as the American Heart Association (AHA) with randomized controlled trials (RCTs) , 18; allThis was formulated as follows: reviews, case report, animal experiments, editorials, and unrelated clinical studies; research studies were found not to be RCTs or diagnosis standards were unclear; studies containing patients diagnosed with stable angina; the interference of ACS sufferers was not accordant; and for the studies with information replication, the subsequent publications were considered as data fraud and were then denied once the authors were unreachable.Details on relevant studies which include author names, issuance year, sample capacity, intervening measures, and outcomes were generalized. In accordance to the Cochrane Handbook for Systematic Reviews of Interventions, quality evaluation of the incorporated research studies was separately carried out by the researchers (Qiang Lu and Qian Li) using the risk of bias table from Review Manager 5.3 . From thI2 statistic was employed to evaluate the level of heterogeneity. A fixed-effect model was employed to process data with low heterogeneity (P > 0.1 and I2 < 50%), and data having high heterogeneity (P < 0.1 or I2 > 50%) were assessed by a random-effect model [Review Manager 5.3 (Cochrane Collaboration) was employed to process the extracted data from the relevant studies . Resultict model . The risOne hundred and fifty-three possible data from Chinese databases were selected in the initial analysis, and similar data were not recovered from English databases. Eighty-five replicated articles were removed as a result of overlapping of the database scope. A sum of 68 studies was acquired for title or abstract check up, and 27 research studies were eliminated due to irrelevant subjects. Forty-one articles were put aside to examine complete information.In the inspection of complete information, 25 pieces of research were excluded as a result of the following: 7 studies were single-arm designs, diagnosis in 6 researches was unclear, 9 studies brought up unsuitable interferences, and 3 trials severally presented similar records with another publication. In the end, there were sixteen pieces of study used for this meta-analysis .Due to SFI-based treatments being mainly used in Chinese Medicine or Integrative Medicine, 16 relevant studies consisting of 1620 sufferers were documented in Chinese databases from 2003 to 2020. The experimental team had 832 patients, while the control team had 788 patients. The total number of males (59.1%) is higher than that of females in the included studies, and the mean age of all the patients was approximately 60.9, ranging from 37 to 83. All the adopted trials were RCTs with a contrast between the SFI and conventional combined treatment and single conventional treatment, and there were some similarities and differences in the conventional treatments. The dosage of SFI was between 15 to 40 mL/day by intravenous drip, and most researchers documented the span of drug administration to be 2 weeks. An absolute dissimilarity was not seen evident between the two groups from fundamental data .The methodological quality of the selected research studies was judged by the Cochrane risk of bias assessment and presented universally low. All the included studies were parallelly designed –36. ElevP < 0.00001). No statistically notable heterogeneity  was detected among studies individually . There was no statistically notable heterogeneity  in the meta-analysis ; therefore, a random-effect model was employed to perform a meta-analysis which indicated that SFI and conventional combined administration notably lessened BV   .P < 0.00001, I2 = 95%) among individual studies, and a meta-analysis employing a random-effect model manifested no difference linking the PV in the experimental and control teams   .P < 0.00001). There was no notable heterogeneity detected in the research studies   .P=0.04, I2 = 60%). A random-effect meta-analysis was undertaken to indicate that the combination of SFI and conventional medication notably lowered FIB concentration in blood plasma   .P=0.56, I2 = 0%) among the researches, so a fixed-effect model meta-analysis was conducted. The pooled OR indicated the SFI-conventional combined medication notably decreased PAR in contrast to the conventional medication alone   .P=0.45, I2 = 0%). An OR with 95% CI was used to show the contrast link of LVEF in the experimental and control teams . It indicated that SFI could notably extend LVEF for ACS patients  was detected in the researches, so a random-effect model was employed to carry out this meta-analysis. The merged OR with 95% CI indicated no difference in the occurrence of adverse reactions linked the experimental and control teams  (One  of the i P=0.50) .A funnel plot was used to estimate the publication bias. There were 14 and 6 pieces of research severally brought into the funnel plots of total effective rate and ECG improvement. As indicated in Cardiovascular disease (CVD) is caused by multiple risk factors such as development standards of life, lifestyle switches, aging of the population, and the gradually changing environment . The morCarthami flos  is a Chinese traditional medicine, which has been applied in the clinic since the Han Dynasty. Its main function is activating blood to promote menstruation and eliminating stasis to stop the pain [Carthami flos in 1973 and has been widely used for more than 40 years [Over the years, Chinese medics have been seeking for more effective treatments for ACS. TCM has been used to treat coronary heart disease (including ACS) for more than 2000 years. The curative efficacy of Chinese medicines in dealing with ACS is clear and more potent than some Western drugs, and Chinese medicines have less toxicity and fewer side effects. Thus, use of the Chinese medicines on ACS is also as important. Together with the improvement of contemporary pharmacy techniques, all kinds of medicinal preparations for treating patients of ACS that based on classical prescriptions of Chinese medicines have been greatly developed . Carthamthe pain . SFI was40 years . It has 40 years . HoweverThe pathogenesis of ACS mainly involves the atherosclerotic plaque rupture, platelet aggregation, and thrombosis, in which plaque rupture is the dominant initiating event . It was P < 0.00001). Hemorheology indexes, such as BV, PV, HCT, FIB, and PAR, were employed to investigate the flow and deformation of blood in ACS patients. In comparison to single conventional therapy, SFI-conventional combination therapy was linked to notably lower BV, HCT, FIB, and PAR (P < 0.05). This showed that SFI improved the antithrombotic and anticoagulation actions. LVEF was employed to evaluate the cardiac function of ACS sufferers. Compared to single conventional therapy, SFI-conventional combination therapy was linked with a notably higher LVEF (P < 0.00001). There was, however, no contrast in the adverse reactions linking the experimental and control teams (P=0.5). Because SFI did not reduce the incidence of adverse reactions caused by Western medicines, a temporary conclusion could be reached only that SFI is almost safe.This meta-analysis is the first research conducted to assess the safety and efficacy of SFI for curing ACS systematically. Total effective rate and ECG improvement were used to evaluate the efficacy of SFI for ACS. In comparison to single conventional therapy, SFI-conventional combination therapy was linked with a notably higher total effective rate and ECG improvement (Extensive searching and stern procedures were applied to select trials and look into the medical efficacy and safety linked with SFI administration. However, many possible restrictions were present in the meta-analysis and need to be contemplated. Firstly, despite adoption of a comprehensive searching strategy to lessen the publication bias as far as possible, there was still a certain level of selective bias which this meta-analysis only narrowed down to Chinese and English databases, and no mention of studies written in different languages was made. Secondly, all relevant studies were conducted in China, and the majority of the patients were Chinese. However, population diversity is important when doing such a study for one to get better convincing and well-grounded results. Thirdly, the majority of the relevant studies exhibited relatively low methodological quality. Eleven of the 16 researches employed “randomization,” whereas no mention of the particular procedure used was made. Furthermore, all the relevant studies did not indicate allocation concealment and blindness. Fourthly, we did not get more details of the studies from the authors through telephone and electronic mail. Fifthly, there was a statistically notable heterogeneity found in the indexes of hemorheology including BV, PV, and FIB. It is rather hard to investigate the heterogeneity in the results of continuous variables. We cannot conduct a subgroup analyses for the few studies giving hemorheology indexes and also did not find the origins of the heterogeneity after carrying out sensitivity analyses. It can be inferred that the heterogeneity resulted from two or more factors, which include sex, age, and period of therapy. Finally, treatment safety is important to come up with other treatments. However, there were only two of the 16 studies which informed adverse reactions. In light of the restraints that existed in the meta-analysis, high-quality and large-scale RCTs, with a fine design and methodology, are required to study the efficacy and safety of SFI for ACS in time to come.The therapy of ACS has become a global challenge. The combination of Chinese patent drug SFI and conventional medication may bring advantageous effects to improve blood rheology and cardiac function of sufferers with ACS. Thus, it is recommended to consider SFI in the conventional treatment of ACS. It is worthy of paying attention to the limitations in the meta-analysis. Furthermore, the therapeutic effect and safety of SFI as an adjunctive therapy for ACS still requires methodologically strict studies to prove.


Encephalitis caused by Epstein-Barr virus infection is uncommon, but most patients have a good outcome after symptomatic treatment. The infiltration of mononuclear cells in blood vessels and necrosis resulting from the immune response to Epstein-Barr virus infection in a very small number of patients seem to be the main cause of death. We describe a fatal case of Epstein-Barr virus encephalitis diagnosed by next-generation sequencing in an immune-competent adult but progressed to brainstem hemorrhage. Epstein-Barr virus (EBV) encephalitis is a rare type of viral encephalitis that is associated with hematopoietic stem cell transplantation , 2, soliIn adults, there are no reports of brainstem hemorrhage caused by EBV encephalitis before. Here, we describe the first fatal case of EBV encephalitis diagnosed by next-generation sequencing (NGS) in an immune-competent adult and soon progressed to brainstem hemorrhage.A 59-year-old man developed dizziness and fever  6 days ago without obvious causes and was not given any treatment. He developed several seizures 1 day ago and was brought to the emergency department (ED) of our hospital by his family, as shown in the timeline in 2O, and CSF was colorless and not turbid. Analysis of CSF showed a red blood cell count of 12×106/L and a mononuclear cell count of 28×106/L (75% lymphocytes and 25% monocytes)  Table 1.Cryptococcus neoformans antigen assay), virus assay in the blood , autoantibodies , and tumor markers . The EBV DNA detected with primers targeting BamHI-W was 1,300 copies/ml in blood, anti-EBV capsid antigen IgM was negative, and anti-EBV capsid antigen IgG was positive blood. The patient’s CRP levels were normal, and PCT levels were below 0.5 ng/ml.The patient was transferred from the ED to the infection department, and cerebral tuberculosis was suspected. Over the next three days, he was administered anti-tuberculosis treatment, moxifloxacin for anti-infection treatment, and mannitol three times a day to reduce intracranial pressure. Additionally, autoimmune encephalitis was suspected, and the patient was intravenously administered 10 mg dexamethasone. A series of blood tests conducted over the next three days revealed negative results for the T-spot test, cytomegalovirus DNA, bacteria assay , fungal assay , a decrease of protein content to 1.010 g/L, and normal glucose and Cl- levels.On the fourth day of hospitalization, the patient was still unconscious. Lumbar puncture was performed again under normal opening pressure. Additionally, pathogen detection in the CSF was performed by NGS. The NGS detection method was the same as we described before . The meaOn the fifth day of hospitalization, circulatory failure and a decrease in oxygen saturation were observed, and the patient was transferred to the intensive care unit (ICU) with a GCS score of E1V1M3. After transfer to the ICU, tracheal intubation was performed. The NGS results showed that the CSF was positive for the EBV Figure 3After the patient was stable, a head CT examination was performed that revealed a massive hemorrhage in the brainstem that could not be surgically removed Figure 2In this study, we describe a rare case of an immune-competent patient with EBV encephalitis in whom the intracranial pressure continued to increase progressively despite mannitol treatment. The case was complicated by brainstem hemorrhage in a short time, and the patient eventually died. In this case, cancer, other pathogen infections, autoimmune encephalitis, and other conditions were ruled out, and NGS showed that the CSF was positive for EBV DNA. Therefore, EBV encephalitis was diagnosed.- levels were normal which was also observed in this case. EBV encephalitis has no typical symptoms, and the results of CSF examination are similar to those for cerebral tuberculosis  and Zhejiang Provincial Natural Science Foundation of China (grant #LQ19H190001 to XZ). The funders had no role in the decision to publish or prepare the manuscript. We thank Dr. Xia Jin from IngeniGen XunMinKang Biotechnology Inc. for her work on NGS data processing and analysis in this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Attempts to classify the mobility levels of people with stroke (PWS) for a tailored exercise program in community settings have been few. We developed and evaluated a classified and tailored community-based (CTC) exercise program according to the mobility level of PWS. Forty-two PWS were classified into the Supine and Sitting, Sitting and Standing, and Standing and Gait groups, based on a newly developed classification model and participated in a group-based CTC exercise program for 1 h/day twice/week for 10 weeks. The health outcome measures were blood pressure, lipid profile, glucose control, body composition, ventilatory capacity, and physical and psychological function. The rate of agreement on classification results among the physiotherapists was analysed. For all participants, significant improvements were noted in the blood pressure, lipid profile, body composition, ventilatory capacity, and physical and psychological function. The lower mobility groups showed significant improvements in a greater number of health outcomes than the higher mobility group. The physiotherapists’ agreement regarding the classification results was 91.16 ± 5.14%, verifying the model’s possible high relevance to the community. The effective improvement in participant health implied that the CTC exercise program was well tailored to the participants’ mobility levels, particularly the lower mobility groups. People with stroke (PWS) comprise the third highest number of hospital visits and annual average medical expenses among disabled populations in South Korea . The medStroke recurrence is influenced by a number of metabolic risk factors, including hypertension, impaired glucose control, dyslipidaemia, obesity, and low cardiorespiratory fitness ,4. ExercHowever, the effective community-based exercise programs for PWS in previous studies mostly targeted people who were able to walk independently ,12,13,14In developing a CTC exercise for PWS, prior evidence is not available for either community or clinical settings. In the clinical setting, there are personnel resources with highly specialised knowledge required to perform various clinical and physical examinations and provide tailored interventions on a one-to-one basis, while in community settings, health professionals with varied work experience have insufficient time to perform examinations of and provide interventions to individuals due to uncontrolled conditions such as manpower or budgetary shortages. The knowledge translation method might be useful for solving the problem of the gap between prior evidence and the real world, which is a dynamic and iterative process of moving knowledge into action that includes the synthesis, dissemination, exchange, and ethically sound application of knowledge to provide more effective health services and strengthen the health care system . Graham The purpose of this study was to develop and evaluate a CTC exercise program according to the mobility levels of PWS using the knowledge to action framework. In the evaluation, first, the effectiveness of the program on health outcomes was analysed; second, the rate of agreement among the physiotherapists regarding the classification results was analysed; and third, the physiotherapists’ experience and perceived supplemental points of the CTC exercise program implementation were explored.We established community-academic partnerships with eight community physiotherapists in the community health centres of three different districts of Seoul, i.e., Jung-gu, Dongjak-gu, and Jongno-gu, to enhance the relevance of the research results in the community context. We built an equitable collaboration while developing and evaluating a CTC exercise program. Three physiotherapists were female. The physiotherapists were aged 30–48 years, with a clinical experience of 5–20 years.The research team advertised information about the study on a message board at the community health centre for 1 month to recruit PWS. A total of 50 volunteers were assessed for eligibility; of them, eight were excluded from the study for the following reasons: ineligible according to the inclusion criteria (n = 5) and too busy to participate (n = 3), leaving 42 enrolled participants. PWS were included if they had experienced a stroke ≥1 year prior and were not already engaging in regular exercise . They were excluded if they were unable to communicate sufficiently to participate in the assessment and intervention phases  , presentAll phases of the study were based on the knowledge to action framework  Table 1Table 1. In the first regular meeting, the researchers and physiotherapists identified the problems related to implementing an exercise program for the PWS in a community health centre. The following two problems were identified: (1) difficulty in implementing a tailored exercise program due to a lack of a standardised method or criteria for judging participant mobility level and (2) tendency for the exercise program to have a limited ability to target PWS roughly judged as those who could walk independently because they were easy to control in groups to minimise the risk of falls.Literature review. In previous studies, community-based exercise programs for PWS consisted of some combination of postural control, stretching, muscle strength and resistance exercises, and aerobic endurance and mostly targeted PWS who were able to walk independently with or without an assistive device ,12,13,14Expert consultation. For uncovered knowledge through literature review, we were consulted three times by professors and practitioners in the fields of sports and physiotherapy. To determine participant mobility level, sub-categories of the mobility chapter of the International Classification of Functioning, Disability, and Health framework , such asDevelopment of a classification model. Given the combination of available prior evidence, expert consultation, and field experience of physiotherapists, we designed a classification model according to the mobility level . The criDevelopment of a tailored exercise program. The exercise program for the Standing and Gait group was adapted from the previously suggested community-based exercise program for PWS ,11,13, wThe physiotherapists identified several contextual barriers to knowledge use in the community, including: (1) shortage of time and manpower to provide personalised one-to-one exercise training and (2) insufficient knowledge and lack of experience on the part of the physiotherapists to provide a tailored exercise program for PWS with low mobility.To address the first identified problem, a CTC exercise program was planned that was to be administered groups of PWS with the same mobility level by an instructing physiotherapist and one or two assistant physiotherapists. The group-based CTC exercise program was conducted for 1 h/day twice/week for 10 weeks at the community health centre. In addition, an exercise manual detailing the exercise motions and an exercise diary book, including individual goal setting, pre-intervention test results, and a daily exercise log, were provided to participants to encourage them to perform the exercises at home during the intervention period. Before starting each exercise session, the physiotherapists briefly assessed whether the participants had performed the exercises at home and if they were encountering obstacles. At the end of every exercise session, the physiotherapists selected some motions in the exercise manual tailored to each participant’s mobility level and assigned them as homework for the week. To address the second identified problem, after the CTC exercise program was designed, three workshops were held for the physiotherapists with the specialised experts to promote co-learning and standardisation of the CTC exercise program delivery according to mobility level and review any precautions requiring attention.The health outcomes were evaluated before and after the intervention. After the intervention period, the rate of agreement among the physiotherapists regarding the classification results was analysed to validate the ability of the developed classification model to appropriately reflect the participants’ mobility levels. The physiotherapists’ experience and perceived supplemental points during the implementation of the CTC exercise program’s implementation were gathered from physiotherapist intervention logs at every session.The participants’ baseline characteristics  were obtained. Cognitive status was based on the Mini-Mental State Examination score . SeveritFor health outcomes, the following metabolic risk factors and physical and psychological function were measured.Resting blood pressure. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded using a semiautomated sphygmomanometer after a 10-min seated rest .Lipid profile and glucose control. After an overnight fast, blood was collected from each participant and total cholesterol , high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and haemoglobin A1c (HbA1c) levels were measured ,26.Body composition. Body mass index and waist circumference were measured ,28.Ventilatory capacity. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio were assessed .Physical function. MAS item 4 score  , upper extremity portion of the Fugl–Meyer Assessment (UE-FMA)  , the ModPsychological function. The Patient Health Questionnaire (PHQ)-9  .Each physiotherapist determined whether the classification results appropriately reflected the participants’ mobility levels. For the decision rule, “Complete” was adopted , which wThe physiotherapists briefly recorded their experience and perceived supplement points during CTC exercise program implementation in the field notes at every exercise session.Health outcomes were analysed all participants and each group using SPSS 21.0.b . The normality of the distribution was assessed using the Kolmogorov–Smirnov test. For all participants, the paired t-test was performed to compare all of the pre- and post-intervention values except MBI, MAS item 4, and FMA, which were analysed using the Wilcoxon signed-rank test because they were non-normally distributed. For each group, the Wilcoxon signed-rank test was performed to compare all of the pre- and post-intervention values. A summative content analysis was performed to evaluate the physiotherapists’ responses by counting and comparing keywords in the text with the purpose of understanding the contextual meaning of the sentence . Two resForty-two participants completed all of the assessments. The mean participant age was 64.79 ± 10.54 years; 54.76% of the participants were female. The mean duration since stroke was 9.54 ± 5.79 years. Stroke severity varied from grade 1 to grade 6. At baseline, the largest number of participants was assigned to the Sitting and Standing group (45.24%), followed by the Supine and Sitting (35.71%) and Standing and Gait (19.05%) groups. The participants’ characteristics are shown in For all participants, significant improvements were noted in blood pressure, lipid profile, body composition, ventilatory capacity, and physical and psychological function . The lowp = 0.028) and DBP (p < 0.001). For the Supine and Sitting group, significant increases in DBP (p = 0.007) were observed. For the Sitting and Standing group, significant increases in SBP (p = 0.014) and DBP (p = 0.002) were seen. For the Standing and Gait group, significant increases in DBP (p = 0.017) were observed.Blood pressure. For all participants, significant increases were noted in SBP (p = 0.013) and LDL-C (p < 0.001) were observed. For the Supine and Sitting group, significant increases in Total-C (p = 0.005) and LDL-C (p = 0.004) were noted. For the Sitting and Standing group, significant increases in LDL-C (p = 0.022) were seen.Lipid profile and glucose control. For all participants, significant increases in Total-C (p = 0.011) were noted.Body composition. For all participants, significant increases in waist circumference (p = 0.005) and FVC (p = 0.018) were seen. For the Sitting and Standing group, significant increases in FVC (p = 0.045) were observed. For the Standing and Gait group, significant increases in FEV (p = 0.025) were noted.Ventilatory capacity. For all participants, significant increases in FEV (p < 0.001), MBI (p = 0.009), 30-sec chair-to-stand test (p = 0.001), and 8-foot up-and-go test (p = 0.011) results were seen. For the Supine and Sitting groups, significant increases in MAS item 4 (p = 0.041), UE-FMA (p = 0.004), and MBI (p = 0.003) were observed. For the Sitting and Standing group, significant increases in the UE-FMA (p = 0.019), 30-sec chair-to-stand test (p = 0.006), and 8-foot up-and-go test (p = 0.005) results were noted.Physical function. For the total participants, significant increases in the UE-FMA (p = 0.001) score were seen. For the Supine and Sitting group, significant increases in the PHQ-9 (p = 0.006) score were observed.Psychological function. For all participants, significant increases in the PHQ-9  classification, (2) group-based intervention, (3) tailored exercise program, and (4) self-exercise at home.The majority of the physiotherapists agreed with the classification results: five physiotherapists reported that some participants who were assigned to the lower mobility groups could actually stand or perform gait to some degree; however, they were at risk of falling and injury due to decreased balance ability. Thus, the physiotherapists agreed that the classification results were appropriate, particularly in terms of self-exercise at home; two physiotherapists recognised that participating in an exercise class of a similar mobility level seemed to increase the participants’ confidence, while they often felt shy when they exercised on a one-to-one basis with a physiotherapist or with PWS of different mobility levels. Besides, four physiotherapists recommended that before the classification was applied, it would be necessary to persuade the participants to accept the result since most of them hoped to be assigned to the high mobility group and were very disappointed when they were assigned to a lower mobility group.The majority of the physiotherapists recommended that the exercise classes for the PWS with different mobility levels be offered separately because those in the lower mobility group required more help due to their greater risk of falling; however, if this was impossible due to a lack of space or time, the patients should at least be grouped by ability level. They also suggested that one physiotherapist could instruct four or five participants of the same level at a time. If a greater number of participants required treatment, one or more assistant physiotherapists should be involved to prevent an accident. The physiotherapists also suggested that participants be addressed by name to correct their poor posture since they experienced that this approach highly motivated them to engage in the exercise.The majority of the physiotherapists reported that recreational programs such as balloon badminton and volleyball were favoured by participants and that various creative rules applied to recreational program were helpful to draw their continued interest, such as matches between two teams or hitting only a ball the colour that was called by the physiotherapist. Besides, two physiotherapists suggested increasing the difficulty of the motions and developing additional exercises for the high mobility group.The physiotherapists recognised that tailored guidance for self-exercise at home was necessary, as evidenced by the participants’ positive reactions to the provided exercise manual and diary log and recommended that the self-exercise motions should consist of supine and sitting positions to prevent falling accidents at home. Some of the physiotherapists suggested that the contents of the self-exercise program be provided in video format via a mobile application to help the participants follow the motions.This study is one of the first to develop and evaluate a CTC exercise program tailored to the mobility level of PWS. The participants were classified into three groups accordingly and participated in the group-based exercise program tailored to their mobility level. The classification model and tailored exercise program were developed using the knowledge to action framework, which consisted of several phases to move knowledge into action. As a result, the participants showed significant improvements in metabolic risk factors as well as physical and psychological function. The majority of the physiotherapists agreed with the classification results.Significant improvements in metabolic risk factors were observed. This is noteworthy since stroke recurrence was influenced by modifiable metabolic risk factors ,4. HowevFor physical function, significant improvements in mobility, upper extremity function, and ability to perform activities of daily living were observed. Tests for assessing mobility  were adopted as recommended by experts due to the ease of performing them in community settings and the ability to assess PWS with various mobility levels, while many previous studies adopted the Berg Balance Scale ,11, 5- oFor physical function, the Supine and Sitting group showed improvements in basic physical function, while the Sitting and Standing group improvements in lower limb strength and dynamic balance, implying that the exercise programs for the lower mobility groups targeted their mobility levels well. In contrast, the Standing and Gait group showed no significant improvement in physical function, possibly since it included the smallest number of participants among the three groups or the program failed to target the participants’ mobility levels well. The physiotherapists reported via field notes that increases in the difficulty of the motions and the development of additional exercise contents would be necessary for the high mobility group. For the Standing and Gait group, it is worthy referring to Olafsdottir and colleagues’ recent report about the feasibility of ActivABLES to promote home-based exercise and physical activity of community-dwelling stroke survivors, which consisted of six interactive tangible tools . The physiotherapists presented their opinions based on their experiences and perceived supplemental points. For example, most of them agreed with the classification results. In particular, the physiotherapists’ judgments considered that the participants conducted self-exercise themselves at home without supervision, a consideration of ours in the mobility level determination criteria. Regarding the group-based intervention, the physiotherapists suggested that one physiotherapist could instruct up to five participants at a time. In some previous studies, one class included up to six or nine participants with a single physiotherapist and/or one or two assistant physiotherapists ,13. GiveIn the current study, the knowledge to action framework enabled us to identify and solve problems in the community setting and develop a CTC exercise program with high relevance by establishing community–academic partnerships. Further, the physiotherapists obtained local knowledge based on their experiences by evaluating this CTC exercise program. Importantly, this local knowledge would promote their empowerment, enabling them to sustain health services that consider the local context even after study completion.This study has several limitations. First, it lacked a control group, which limits its power. Thus, future large-scale randomised trials are needed to definitely conclude the effectiveness of this CTC exercise program. Second, the intervention was limited to 10 weeks. Therefore, a long-term study accompanied by follow-up tests is recommended to verify the longer-term effect of the program on health outcomes. Third, it was conducted using a small sample size, in particular in the Standing and Gait group, limiting the generalizability of the result of current study.The group-based CTC exercise program effectively improved the health outcomes of PWS, such as metabolic risk factors and physical and psychological function. Further, the majority of the community physiotherapists agreed that the classification results reflected the mobility levels of the PWS using this newly developed classification model, accompanied by positive experiences during CTC exercise program implementation. These results imply that the classification model and a CTC exercise program tailored to the mobility level of each study group would be effective and feasible in the community setting.


The Food Disgust Scale (FDS) was recently developed and validated in Swiss adult population. This study aims to: (1) validate the FDS for the first time in a Spanish-speaking Mexican population, (2) correlate food disgust sensitivity with picky eating measures, and (3) explore the association between food disgust sensitivity and body mass index (BMI).A Spanish version of the FDS (FDS-Sp) and its short version (FDS-Sp short) were tested with confirmatory factor analysis (CFA) in order to test the original item/factor structure. Bivariate correlations were performed to determine the association between FDS-Sp/FDS-Sp short scores and picky eating. Lastly, hierarchical linear regression analysis was carried out to determine the relationship between food disgust sensitivity and BMI.The factor structure of the FDS was replicated and acceptable internal consistency values were observed for FDS-Sp subscales (α varied between 0.781 and 0.955). Moreover, FDS-Sp subscales and FDS-Sp short were correlated with picky eating. Higher score in VEGI subscale of the FDS-Sp was a significant predictor for higher BMI, explaining 4% of the variance.FDS-Sp is a useful, reliable and robust psychometric instrument to measure the sensitivity to unpleasant food situations in a Mexican adult Spanish-speaking population. A relationship between food disgust sensitivity and picky eating, selective eating behaviors and neophobia in Mexicans was confirmed. BMI is multifactorial and only one subscale of FDS-Sp is a significant predictor for BMI status. These results are helpful to continue exploring food disgust in diverse populations. Disgust is one of the basic human emotions that shoot up quickly as a reflex response to protect us from a potentially toxic/infectious exposure. Disgust mainly relays on sensory inputs from smell and/or taste, but also it is possible to trigger it by visual and vestibular stimulation . ParticuPredation and food intake tend to follow stable patterns, since exposure to new unfamiliar food sources represents a potential health threat. This leads individuals to reject unfamiliar and new foods to an innate food neophobia as an adaptive survival mechanism . UsuallyOn the other hand, non-spoiled food that is unfamiliar may provoke aversion and avoidance to a wide variety of commonly accepted foods; what is known as picky eating . Often tBoth, picky eating and food neophobia are correlated with food disgust sensitivity . ConsequHaving a varied diet increases the likelihood of greater nutrient intake. In contrast, people with extreme picky eating behaviors who meet criteria for ARFID can even suffer from nutritional deficiencies . It is sInterestingly, Differences among individuals may be due by habituation to normalize some food cultural practices, cognition (risk perception vs. innocuity) and protective mechanisms acquired ontogenetically by individual experiences  . Also, sRecently, the Food Disgust Scale (FDS) was developed to specifically measure sensitivity to food related situations that may threaten health . This ps®, Twitter® and WhatsApp®) during February 21 to March 4, 2018. Recruitment was voluntary, and no monetary incentives were given to the participants. Although no location was registered, it is assumed that most of the volunteers are urban residents of the metropolitan area of Mexico City.Volunteers were Mexican adults recruited through social media . Based on Additional data were also self-reported such as sex, age, educational level, weight and height.® Docs platform  was performed for each subscale. In the original study, an exploratory factor analysis yielded an eight-factor model, and each subscale corresponds to each of the eight factors. In this study, the same eight-factor model was assumed with the version of 32 items , and it p < 0.01.Bivariate Pearson correlations were calculated between the mean score of each FDS-Sp subscale and the raw score of each of the SFQ items. Partial correlation analysis corrected by age and sex was calculated additionally. Statistically significance was set at R2 to test for significant change in outcomes’ explained variance. A p-value < 0.01 was set for determination of statistical significance.A hierarchical linear regression analyses was performed in two steps. The first one included mean score of each of the eight factors  and FDS-Sp short mean score as predictive variables for BMI. For the second step, sex and age were added since these variables have been reported to have a significant effect on food disgust. Both models were compared using ΔRRID:BDSC_7008)  .n [%] = 778 [67.7%]). Data exploration identified that some BMI values were extreme, which could indicate error in the size/weight report, or some pathological condition that would place them with extreme obesity or low weight. Based on BMI distribution, outliers were detected by the “identify unusual cases algorithm” implemented in SPSS. Sixty subjects were excluded: 36 “underweight” (BMI Min–max: 14.69–18.56), 24 “obesity II, III” (BMI Min–max = 36.98–59.44). The final sample consisted of 1,149 persons. For the internal consistency analysis and the confirmatory factor analysis, the sample was randomly divided into two parts in order to have a sample size similar to that used in the original validation of the scale.Recruitment yielded 1,328 volunteers. In order to have a comparable sample with the FDS original study by 2 = 1020.434, p < 0.001, df = 436). Short version of FDS-Sp reached an internal consistency value of α = 0.677. The CFA for the short version yielded the following goodness-of-fit indices: CFI = 0.827, NFI = 0.803, RMSEA = 0.095, χ2 = 125.761, p < 0.001, df = 20. Given the value of modification index between the measurement errors of items MEAT1 and FISH4, and also between FRUIT4 and VEGI1, it is inferred that these pairs of items are highly correlated. The CFA for the short version adding co-variables showed better goodness-of-fit indices: CFI = 0.951, NFI = 0.925, RMSEA = 0.053, χ2 = 47.903, p < 0.001, df = 18. The factor models of the 32-item version and the one-factor model of the short version are shown in n = 586; FDS-Sp reached acceptable internal consistency values for each of the eight subscales . The CFA for the eight-factor model had acceptable goodness-of-fit indexes in the standardized solution  differences between Swiss and Mexican populations in the subscales of HYG, FRUIT, FISH, VEGI, and LCON, with the Mexican population having the higher scores in all those subscales, except in FISH . Also, for FDS-Sp short, difference was statistically significant . Additionally, we found a weak positive correlations with age  and negative correlations with age were found   .Correlations between the mean score of each FDS-Sp subscale and SFQ1 (“Are you a picky eater?”) were positive and statistically significant, as well, almost all for FDS-Sp mean score and SFQ2 (“Do you have strong likes with regard to food?”) . CorrelaF  = 5.39, p < 0.01), with a R2 of 0.036. In the second model, also a significant regression equation was found , with R2 of 0.090, being significantly higher than the first model . Also, in the first model, the variables MEAT, FRUIT, and VEGI predicted 4% of the variance in BMI. Higher scores on the subscales of MEAT and FRUIT predicted lower BMI, while higher scores on the subscale of VEGI predicted higher BMI. Adding age and sex in the second model, the variance explained increased to 9%. However, except for the VEGI subscale, none of the other subscales of the FDS-Sp were significant predictors of BMI anymore when simultaneously including sex and age in the model. Thus, there is a tendency for the more disgust sensitivity for vegetable related cues, the higher the BMI might be.Hierarchical linear regression was calculated to predict BMI based on each factor of FDS-Sp in the first model. Age and sex were added in the second model . In the The FDS-Sp eight-factor model replicates in adult Mexican population with similar values as in the original FDS version developed with Swiss adults: both internal consistency values and goodness-of-fit indexes for the 8-factor model and short version are acceptable and similar to those originally reported . The parSmall, but statistically significant differences were found in the mean values of some FDS subscales between populations, with Mexicans reporting higher scores in VEGI, FRUIT  and LCON . Given the Mexican sample has more proportion of women, we analyze separately the subsamples of men and women, and differences remained. One might speculate that the lower FDS scores of the Swiss population may be related to social and cultural aspects. For instance, it is possible that there is greater societal confidence toward food quality control and sanitary regulation in Switzerland in comparison to Mexico. The Mexican population may feel that some foods are not safe because, compared to Switzerland, there is a higher rate of infectious gastrointestinal diseases and foodborne illnesses. In this regard, epidemiological data shows higher vulnerability to gastrointestinal infections in Latin American than in European countries . BesidesInterestingly, the only subscale in which Mexicans on average obtained lower FDS scores than Swiss and which Mexicans considered least disgusting was the FISH subscale. This might indicate that Mexican adults seem more tolerant to disgusting situations related to fish consumption. According to statistics of Food and Agriculture Organization (FAO), the annual per capita consumption of fish meal in 2013 in Switzerland was 17.78 kg, whereas in Mexico was 10.46 kg . RegardlIn the Mexican sample, we found differences between sexes for each subscale and in the short version, with women obtaining higher scores. In the study of The SFQ was used as an external criterion of disgust construct validity. It has been suggested that picky eating is an encompassing construct, and that only some picky eaters have high sensitivity to the disgusting situations that arise in the FDS. Food disgust and picky eating can be taken as constructs that seem to share similar underlying psychological drivers, and therefore, they may have convergent validity. The positive correlation between all FDS-Sp subscales and SFQ1 yielded the expected result: the greater the pickiness, the larger sensitivity to disgusting situations related to food. The SFQ2 item measures how selective a person is when eating, then, it is likely that people who score high on SFQ2 have little variety in the foods in their diet. High disgust sensitivity is associated with more restrictive eating behavior, and in fact, picky eaters often describe themselves as unhealthy eaters . Poor hyConclusively, initially we hypothesized that there might be a positive correlation between BMI and food disgust. This question arose from studies that show association between picky eating and BMI in adolescents  and the Finally, we identified the following limitations in our study: it would be relevant to have the validity of the total scale score in order to make correlations with the other constructs. For now, we only perform the analyzes with the scores of each of the eight subscales, which correspond to the eight factors. Another limitations are that: (a) the data was collected via Internet; (b) the sample characteristics were self-reported, so we cannot confirm age, sex, weight and height; (c) 67.7% of our sample were females, which can be a bias, since it has been shown the sensitivity of disgust to food differs between sexes. Also, we assume that most of the participants are from a Mexico City metropolitan area, but we don’t design any item to assess urban vs. rural category. Finally, it would have been interesting to know the socioeconomic income variable, as it is likely that this variable also has an influence on the sensitivity to disgust, as has been reported before .Our findings document FDS as a useful psychometric instrument to measure the sensitivity to unpleasant situations related to food in a Mexican adult population. The food disgust construct, measured by FDS, mainly stands beside the language, cultural, and culinary differences. Thus, we argue that the FDS can be also extrapolated to other societies; however, further replications in other geographical and cultural contexts would increase its validity and reliability. Furthermore, as the comparison between Mexico and Switzerland showed differences in food disgust sensitivity, we encourage further exploration of the construct in other countries-cultures. We confirmed that there are food disgust differences between sexes, and it correlates with age. Also, we conclude that food disgust and picky eating are convergent concepts. Finally, the VEGI subscale was modestly predictive of BMI. Our results are helpful to continue exploring food disgust in diverse cultures.http://hdl.handle.net/20.500.12222/244).The datasets for this study can be found in the XOGI Institutional Repository of the Metropolitan Autonomous University (UAM), Campus Lerma  . The patients/participants provided their written informed consent to participate in this study.LG-G coordinated the data collection along with CR-R, wrote the manuscript, and conducted the statistical analyses. CH and MS developed the original FDS and performed a critical review of the final version of the manuscript. GF, RG-A and SV advised the methodology and performed the critical review of the final version of the manuscript. GP-L conceptualized and coordinated the study as senior author, performed critical review of all versions of the manuscript, and managed international cooperation. All authors contributed to the final version of the manuscript and have approved the current version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.