Pub Date : 2023-06-01DOI: 10.1186/s40575-023-00129-w
Dan G O'Neill, Alison M Skipper, Kate Barrett, David B Church, Rowena M A Packer, Dave C Brodbelt
Background: The Boxer is a popular dog breed with a distinctive appearance. However, the breed has been linked with several health conditions, some of which have been associated with its moderately brachycephalic conformation and its white colouration. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Boxers in the UK in 2016.
Results: The study population of 336,865 dogs included 3,219 (0.96%) Boxers, of which 10.71% were recorded as white. The mean adult bodyweight was 30.43 kg (SD 5.73 kg). Annual disorder counts did not differ statistically between the sexes or between white and non-white Boxers. The most prevalent fine-level precision disorders were otitis externa (n = 230, 7.15%), epulis (188, 5.84%), corneal ulceration (161, 5.00%) and periodontal disease (149, 4.63%). Of the 34 most common fine-level disorders, none differed in prevalence between white and non-white dogs. The most prevalent disorder groups were skin disorder (n = 571, 17.74%), neoplasia (457, 14.20%) and ear disorder (335, 10.41%). White Boxers had higher prevalence than non-white Boxers for two disorder groups: dental disorder and brain disorder. The median longevity of 346 Boxers that died during the study was 10.46 years (IQR 9.00-11.98, range 2.76-18.00). Median longevity did not differ statistically between the sexes or between white and non-white Boxers. The most common grouped causes of death were death - unrecorded cause (n = 73, 21.10%), neoplasia (43, 12.43%) and brain disorder (33, 9.54%).
Conclusions: There was minimal evidence of substantial health differences between white and non-white Boxers. Among the four most common disorders recorded in Boxers, two were typically common across all types of dogs (otitis externa and periodontal disease) while two suggested strong predispositions for the Boxer breed (epulis and corneal ulceration), showing the value of eliciting breed-specific disorder patterns for insights for potential health reforms. The overall longevity of Boxer dogs was consistent with other breeds of similar body size.
{"title":"Demography, common disorders and mortality of Boxer dogs under primary veterinary care in the UK.","authors":"Dan G O'Neill, Alison M Skipper, Kate Barrett, David B Church, Rowena M A Packer, Dave C Brodbelt","doi":"10.1186/s40575-023-00129-w","DOIUrl":"https://doi.org/10.1186/s40575-023-00129-w","url":null,"abstract":"<p><strong>Background: </strong>The Boxer is a popular dog breed with a distinctive appearance. However, the breed has been linked with several health conditions, some of which have been associated with its moderately brachycephalic conformation and its white colouration. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Boxers in the UK in 2016.</p><p><strong>Results: </strong>The study population of 336,865 dogs included 3,219 (0.96%) Boxers, of which 10.71% were recorded as white. The mean adult bodyweight was 30.43 kg (SD 5.73 kg). Annual disorder counts did not differ statistically between the sexes or between white and non-white Boxers. The most prevalent fine-level precision disorders were otitis externa (n = 230, 7.15%), epulis (188, 5.84%), corneal ulceration (161, 5.00%) and periodontal disease (149, 4.63%). Of the 34 most common fine-level disorders, none differed in prevalence between white and non-white dogs. The most prevalent disorder groups were skin disorder (n = 571, 17.74%), neoplasia (457, 14.20%) and ear disorder (335, 10.41%). White Boxers had higher prevalence than non-white Boxers for two disorder groups: dental disorder and brain disorder. The median longevity of 346 Boxers that died during the study was 10.46 years (IQR 9.00-11.98, range 2.76-18.00). Median longevity did not differ statistically between the sexes or between white and non-white Boxers. The most common grouped causes of death were death - unrecorded cause (n = 73, 21.10%), neoplasia (43, 12.43%) and brain disorder (33, 9.54%).</p><p><strong>Conclusions: </strong>There was minimal evidence of substantial health differences between white and non-white Boxers. Among the four most common disorders recorded in Boxers, two were typically common across all types of dogs (otitis externa and periodontal disease) while two suggested strong predispositions for the Boxer breed (epulis and corneal ulceration), showing the value of eliciting breed-specific disorder patterns for insights for potential health reforms. The overall longevity of Boxer dogs was consistent with other breeds of similar body size.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"10 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9562862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-19DOI: 10.1186/s40575-023-00128-x
Karolina S Engdahl, Dave C Brodbelt, Carla Cameron, David B Church, Åke Hedhammar, Dan G O'Neill
Background: The English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS.
Results: English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25-8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12-17.35). The annual proportional birth rate was relatively stable between 2.97-3.51% from 2005-2016. The most common specific diagnoses were periodontal disease (n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31-22.62), otitis externa (n = 234, 10.09%, 95% CI: 8.87-11.32), obesity (n = 229, 9.88%, 95% CI: 8.66-11.09), anal sac impaction (n = 187, 8.07%, 95% CI: 6.96-9.18), diarrhoea (n = 113, 4.87%, 95% CI: 4.00-5.75), and aggression (n = 93, 4.01%, 95% CI: 3.21-4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) (P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) (P = 0.010). The median age at death was 11.44 years (IQR 9.46-13.47) and the most common grouped causes of death were neoplasia (n = 10, 9.26%, 95% CI: 3.79-14.73), mass-associated disorders (n = 9, 8.33%, 95% CI: 4.45-15.08), and collapse (n = 8, 7.41%, 95% CI: 3.80-13.94).
Conclusions: Periodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS.
{"title":"Demography and disorders of English Cocker Spaniels under primary veterinary care in the UK.","authors":"Karolina S Engdahl, Dave C Brodbelt, Carla Cameron, David B Church, Åke Hedhammar, Dan G O'Neill","doi":"10.1186/s40575-023-00128-x","DOIUrl":"https://doi.org/10.1186/s40575-023-00128-x","url":null,"abstract":"<p><strong>Background: </strong>The English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS.</p><p><strong>Results: </strong>English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25-8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12-17.35). The annual proportional birth rate was relatively stable between 2.97-3.51% from 2005-2016. The most common specific diagnoses were periodontal disease (n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31-22.62), otitis externa (n = 234, 10.09%, 95% CI: 8.87-11.32), obesity (n = 229, 9.88%, 95% CI: 8.66-11.09), anal sac impaction (n = 187, 8.07%, 95% CI: 6.96-9.18), diarrhoea (n = 113, 4.87%, 95% CI: 4.00-5.75), and aggression (n = 93, 4.01%, 95% CI: 3.21-4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) (P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) (P = 0.010). The median age at death was 11.44 years (IQR 9.46-13.47) and the most common grouped causes of death were neoplasia (n = 10, 9.26%, 95% CI: 3.79-14.73), mass-associated disorders (n = 9, 8.33%, 95% CI: 4.45-15.08), and collapse (n = 8, 7.41%, 95% CI: 3.80-13.94).</p><p><strong>Conclusions: </strong>Periodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"10 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9549633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-28DOI: 10.1186/s40575-023-00127-y
Kim K L Bellamy, Frode Lingaas
Background: Cataract is considered an important health issue in Havanese, and studies indicate a breed predisposition. Possible consequences of cataracts include lens induced uveitis, reduced eyesight, and blindness in severe cases. Reducing the prevalence of cataracts could therefore improve health and welfare significantly. The most frequently diagnosed forms of cataract in Havanese are cortical- and anterior suture line cataract, but cases of posterior polar cataract are also regularly reported. Out of the three, posterior polar- and cortical cataracts are considered the most clinically relevant.
Results: We performed a genome wide association study that included 57 controls and 27 + 23 + 7 cases of cortical-, anterior suture line- and posterior polar cataract, respectively. An association analysis using a mixed linear model, revealed two SNPs on CFA20 (BICF2S23632983, p = 7.2e-09) and CFA21 (BICF2G630640490, p = 3.3e-09), that were significantly associated with posterior polar cataract, both of which are linked to relevant candidate genes. The results suggest that the two variants are linked to alleles with large effects on posterior polar cataract formation, possibly in a dominant fashion, and identifies regions that should be subject to further sequencing. Promising regions on CFA4 and CF30 were also identified in the association analysis of cortical cataract. The top SNPs on each chromosome, chr4_12164500 (p = 4.3e-06) and chr30_28836339 (p = 5.6e-06), are located within, or in immediate proximity to, potential cataract candidate genes. The study shows that age at examination is strongly associated with sensitivity of cataract screening. Havanese in Norway are on average 3.4 years old when eye examinations are performed: an age where most dogs that are genetically at risk have not yet developed clinically observable changes. Increasing the average age of breeding animals could increase accuracy of selection, leading to improved health.
Conclusions: The study identified two loci, on CFA20 and CFA21, that were significantly associated with posterior polar cataract in Havanese. SNPs that showed putative association with cortical cataracts, were observed on CFA4 and CFA30. All the top SNPs are located in close proximity to cataract candidate genes. The study also show that sensitivity of cataract screening is highly dependent on age at examination.
{"title":"Cataracts in Havanese: genome wide association study reveals two loci associated with posterior polar cataract.","authors":"Kim K L Bellamy, Frode Lingaas","doi":"10.1186/s40575-023-00127-y","DOIUrl":"https://doi.org/10.1186/s40575-023-00127-y","url":null,"abstract":"<p><strong>Background: </strong>Cataract is considered an important health issue in Havanese, and studies indicate a breed predisposition. Possible consequences of cataracts include lens induced uveitis, reduced eyesight, and blindness in severe cases. Reducing the prevalence of cataracts could therefore improve health and welfare significantly. The most frequently diagnosed forms of cataract in Havanese are cortical- and anterior suture line cataract, but cases of posterior polar cataract are also regularly reported. Out of the three, posterior polar- and cortical cataracts are considered the most clinically relevant.</p><p><strong>Results: </strong>We performed a genome wide association study that included 57 controls and 27 + 23 + 7 cases of cortical-, anterior suture line- and posterior polar cataract, respectively. An association analysis using a mixed linear model, revealed two SNPs on CFA20 (BICF2S23632983, p = 7.2e-09) and CFA21 (BICF2G630640490, p = 3.3e-09), that were significantly associated with posterior polar cataract, both of which are linked to relevant candidate genes. The results suggest that the two variants are linked to alleles with large effects on posterior polar cataract formation, possibly in a dominant fashion, and identifies regions that should be subject to further sequencing. Promising regions on CFA4 and CF30 were also identified in the association analysis of cortical cataract. The top SNPs on each chromosome, chr4_12164500 (p = 4.3e-06) and chr30_28836339 (p = 5.6e-06), are located within, or in immediate proximity to, potential cataract candidate genes. The study shows that age at examination is strongly associated with sensitivity of cataract screening. Havanese in Norway are on average 3.4 years old when eye examinations are performed: an age where most dogs that are genetically at risk have not yet developed clinically observable changes. Increasing the average age of breeding animals could increase accuracy of selection, leading to improved health.</p><p><strong>Conclusions: </strong>The study identified two loci, on CFA20 and CFA21, that were significantly associated with posterior polar cataract in Havanese. SNPs that showed putative association with cortical cataracts, were observed on CFA4 and CFA30. All the top SNPs are located in close proximity to cataract candidate genes. The study also show that sensitivity of cataract screening is highly dependent on age at examination.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"10 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-07DOI: 10.1186/s40575-023-00126-z
Brenda N Bonnett
{"title":"Brachycephalics: 'Once a problem is seen it cannot be unseen'.","authors":"Brenda N Bonnett","doi":"10.1186/s40575-023-00126-z","DOIUrl":"https://doi.org/10.1186/s40575-023-00126-z","url":null,"abstract":"","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"10 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2023-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-08DOI: 10.1186/s40575-023-00124-1
Megan N Dillon, Rachael Thomas, Timothy A Mousseau, Jennifer A Betz, Norman J Kleiman, Martha O Burford Reiskind, Matthew Breen
Background: Natural and anthropogenic disasters can have long-lasting impacts on the genetics and structure of impacted populations. The 1986 Chernobyl Nuclear Power Plant disaster led to extensive contamination of the local environment and the wildlife therein. Several ecological, environmental, and genetic studies reported various effects of this disaster on animal, insect, and plant species; however, little work has been done to investigate the genetics of the free-breeding dogs that occupy the Chernobyl Exclusion Zone (CEZ).
Results: We define the population genetic structure of two groups of dogs that reside within the CEZ, one around the reactor site itself and another living within Chernobyl City. We found little evidence of gene flow and a significant degree of genetic differentiation between the two populations dogs, suggesting that these are two distinct populations despite occupying areas located just 16 km apart. With an FST-based outlier analysis, we then performed a genome-wide scan for evidence of directional selection within the dog populations. We found 391 outlier loci associated with genomic regions influenced by directional selection, from which we identified 52 candidate genes.
Conclusions: Our genome scan highlighted outlier loci within or near genomic regions under directional selection, possibly in response to the multi-generational exposure faced. In defining the population structure and identifying candidate genes for these dog populations, we take steps towards understanding how these types of prolonged exposures have impacted these populations.
{"title":"Population dynamics and genome-wide selection scan for dogs in Chernobyl.","authors":"Megan N Dillon, Rachael Thomas, Timothy A Mousseau, Jennifer A Betz, Norman J Kleiman, Martha O Burford Reiskind, Matthew Breen","doi":"10.1186/s40575-023-00124-1","DOIUrl":"https://doi.org/10.1186/s40575-023-00124-1","url":null,"abstract":"<p><strong>Background: </strong>Natural and anthropogenic disasters can have long-lasting impacts on the genetics and structure of impacted populations. The 1986 Chernobyl Nuclear Power Plant disaster led to extensive contamination of the local environment and the wildlife therein. Several ecological, environmental, and genetic studies reported various effects of this disaster on animal, insect, and plant species; however, little work has been done to investigate the genetics of the free-breeding dogs that occupy the Chernobyl Exclusion Zone (CEZ).</p><p><strong>Results: </strong>We define the population genetic structure of two groups of dogs that reside within the CEZ, one around the reactor site itself and another living within Chernobyl City. We found little evidence of gene flow and a significant degree of genetic differentiation between the two populations dogs, suggesting that these are two distinct populations despite occupying areas located just 16 km apart. With an F<sub>ST</sub>-based outlier analysis, we then performed a genome-wide scan for evidence of directional selection within the dog populations. We found 391 outlier loci associated with genomic regions influenced by directional selection, from which we identified 52 candidate genes.</p><p><strong>Conclusions: </strong>Our genome scan highlighted outlier loci within or near genomic regions under directional selection, possibly in response to the multi-generational exposure faced. In defining the population structure and identifying candidate genes for these dog populations, we take steps towards understanding how these types of prolonged exposures have impacted these populations.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"10 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-08DOI: 10.1186/s40575-023-00125-0
Karin Westereng Handegård, Linn Mari Storengen, Dina Joergensen, Frode Lingaas
Background: Fear of firework noises and other loud, sudden noises (noise reactivity) is a significant problem for many dogs and may have a negative effect on both welfare and, in severe cases, the life expectancy of dogs. A wide range of behavior traits, including fear-related behaviors, have high heritability estimates in dogs. The aim of this study was to estimate genomic heritability for fear of fireworks and loud noises in dogs.
Results: A genomic heritability estimate was performed based on genome-wide SNPs from standard poodles with records of fear of fireworks and noise reactivity. The study was based on questionnaires answered by owners, who also volunteered to return a cheek swab from their dog for DNA analyses. SNP-based heritability was estimated to be 0.28 for firework fear and 0.16 for noise reactivity. We also identified an interesting region on chromosome 17 that was weakly associated with both traits.
Conclusions: We have estimated low to medium genomic heritabilities for fear of fireworks and noise reactivity in standard poodles. We have also identified an interesting region on chromosome 17, which harbors genes that have been shown to be involved in different psychiatric traits with anxiety components in humans. The region was associated with both traits; however, the association was weak and need further verification from other studies.
{"title":"Genomic analysis of firework fear and noise reactivity in standard poodles.","authors":"Karin Westereng Handegård, Linn Mari Storengen, Dina Joergensen, Frode Lingaas","doi":"10.1186/s40575-023-00125-0","DOIUrl":"https://doi.org/10.1186/s40575-023-00125-0","url":null,"abstract":"<p><strong>Background: </strong>Fear of firework noises and other loud, sudden noises (noise reactivity) is a significant problem for many dogs and may have a negative effect on both welfare and, in severe cases, the life expectancy of dogs. A wide range of behavior traits, including fear-related behaviors, have high heritability estimates in dogs. The aim of this study was to estimate genomic heritability for fear of fireworks and loud noises in dogs.</p><p><strong>Results: </strong>A genomic heritability estimate was performed based on genome-wide SNPs from standard poodles with records of fear of fireworks and noise reactivity. The study was based on questionnaires answered by owners, who also volunteered to return a cheek swab from their dog for DNA analyses. SNP-based heritability was estimated to be 0.28 for firework fear and 0.16 for noise reactivity. We also identified an interesting region on chromosome 17 that was weakly associated with both traits.</p><p><strong>Conclusions: </strong>We have estimated low to medium genomic heritabilities for fear of fireworks and noise reactivity in standard poodles. We have also identified an interesting region on chromosome 17, which harbors genes that have been shown to be involved in different psychiatric traits with anxiety components in humans. The region was associated with both traits; however, the association was weak and need further verification from other studies.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"10 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9092595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-10DOI: 10.1186/s40575-022-00123-8
Dan G O'Neill, Janine Su Pheng Khoo, Dave C Brodbelt, David B Church, Camilla Pegram, Rebecca F Geddes
Background: Hypothyroidism is a commonly diagnosed endocrinopathy in dogs. This study aimed to investigate the frequency and risk factors for diagnosis of hypothyroidism in UK primary-care practice. Dogs diagnosed with hypothyroidism were identified by searching electronic patient records of primary-care practices participating in VetCompass. A cohort study design estimated one-year (2016) period prevalence and incidence risk for hypothyroidism. Multivariable binary logistic regression models were used to evaluate associations between demographic risk factors and hypothyroidism.
Results: From 905,553 dogs, 2,105 dogs were recorded with diagnosed hypothyroidism in 2016; 359 incident and 1,746 pre-existing, giving an annual prevalence of 0.23% (95% CI 0.22-0.24) and annual incidence risk of 0.04% (95% CI 0.04-0.04). Multivariable logistic regression identified 24 predisposed and nine protected breeds. Standard Doberman pinscher (odds ratio [OR] = 17.02, 95% CI 12.8-22.64), Tibetan terrier (11.25, 95% CI 8.27-15.32) and boxer (10.44, 95% CI 8.66-12.58) breeds showed high predisposition. Pug (OR 0.29, 95% CI 0.09-0.89), Yorkshire terrier (OR 0.38, 95% CI 0.24-0.59), Shih-tzu (OR 0.38, 95% CI 0.23-0.64) and Jack Russell terrier (OR 0.40, 95% CI 0.29-0.54) were the most protected breeds. Overall, being a purebred dog, being insured, having bodyweight above the breed-sex mean, increasing age, being neutered and rising adult bodyweight also showed increased odds being a dog living with a diagnosis of hypothyroidism.
Conclusions: Several strong breed predispositions for diagnosis of hypothyroidism were identified that can assist with disorder prioritisation in ongoing efforts to improve breed health. Other risk factors were also identified that can assist veterinary surgeons during clinical work-up of suspected cases. Identification of novel evidence for protected breeds provides useful information for research into genetic mechanisms.
背景:甲状腺功能减退症是犬类常见的内分泌疾病。本研究旨在调查英国初级保健实践中甲状腺功能减退症的诊断频率和危险因素。通过检索参与VetCompass的初级保健实践的电子病历来确定诊断为甲状腺功能减退的狗。一项队列研究设计估计了一年(2016年)期间甲状腺功能减退的患病率和发病率风险。采用多变量二元logistic回归模型评价人口统计学危险因素与甲状腺功能减退之间的关系。结果:2016年在905553只犬中,有2105只犬被诊断为甲状腺功能减退;359例发病和1746例既往病史,年患病率为0.23% (95% CI 0.22-0.24),年发病风险为0.04% (95% CI 0.04-0.04)。多变量logistic回归鉴定出24个易感品种和9个受保护品种。标准杜宾犬(比值比[OR] = 17.02, 95% CI 12.8 ~ 22.64)、藏獒(比值比11.25,95% CI 8.27 ~ 15.32)和拳师犬(比值比10.44,95% CI 8.66 ~ 12.58)的易感性较高。巴哥犬(OR 0.29, 95% CI 0.09-0.89)、约克夏犬(OR 0.38, 95% CI 0.24-0.59)、西施犬(OR 0.38, 95% CI 0.23-0.64)和杰克罗素犬(OR 0.40, 95% CI 0.29-0.54)是最受保护的品种。总的来说,纯种狗、有保险、体重高于纯种狗的平均体重、年龄的增长、被阉割以及成年后体重的增加,都显示出患甲状腺功能减退症的几率增加。结论:几个强大的品种倾向诊断甲状腺功能减退症被确定,可以帮助疾病优先级在正在进行的努力,以改善品种健康。还确定了其他风险因素,这些因素可以帮助兽医对疑似病例进行临床检查。鉴定受保护品种的新证据为遗传机制的研究提供了有用的信息。
{"title":"Frequency, breed predispositions and other demographic risk factors for diagnosis of hypothyroidism in dogs under primary veterinary care in the UK.","authors":"Dan G O'Neill, Janine Su Pheng Khoo, Dave C Brodbelt, David B Church, Camilla Pegram, Rebecca F Geddes","doi":"10.1186/s40575-022-00123-8","DOIUrl":"https://doi.org/10.1186/s40575-022-00123-8","url":null,"abstract":"<p><strong>Background: </strong>Hypothyroidism is a commonly diagnosed endocrinopathy in dogs. This study aimed to investigate the frequency and risk factors for diagnosis of hypothyroidism in UK primary-care practice. Dogs diagnosed with hypothyroidism were identified by searching electronic patient records of primary-care practices participating in VetCompass. A cohort study design estimated one-year (2016) period prevalence and incidence risk for hypothyroidism. Multivariable binary logistic regression models were used to evaluate associations between demographic risk factors and hypothyroidism.</p><p><strong>Results: </strong>From 905,553 dogs, 2,105 dogs were recorded with diagnosed hypothyroidism in 2016; 359 incident and 1,746 pre-existing, giving an annual prevalence of 0.23% (95% CI 0.22-0.24) and annual incidence risk of 0.04% (95% CI 0.04-0.04). Multivariable logistic regression identified 24 predisposed and nine protected breeds. Standard Doberman pinscher (odds ratio [OR] = 17.02, 95% CI 12.8-22.64), Tibetan terrier (11.25, 95% CI 8.27-15.32) and boxer (10.44, 95% CI 8.66-12.58) breeds showed high predisposition. Pug (OR 0.29, 95% CI 0.09-0.89), Yorkshire terrier (OR 0.38, 95% CI 0.24-0.59), Shih-tzu (OR 0.38, 95% CI 0.23-0.64) and Jack Russell terrier (OR 0.40, 95% CI 0.29-0.54) were the most protected breeds. Overall, being a purebred dog, being insured, having bodyweight above the breed-sex mean, increasing age, being neutered and rising adult bodyweight also showed increased odds being a dog living with a diagnosis of hypothyroidism.</p><p><strong>Conclusions: </strong>Several strong breed predispositions for diagnosis of hypothyroidism were identified that can assist with disorder prioritisation in ongoing efforts to improve breed health. Other risk factors were also identified that can assist veterinary surgeons during clinical work-up of suspected cases. Identification of novel evidence for protected breeds provides useful information for research into genetic mechanisms.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":" ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33498542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-15DOI: 10.1186/s40575-022-00122-9
Kristofer R Luethcke, Lauren A Trepanier, Ashleigh N Tindle, Julia D Labadie
Lymphoma is the second most common cancer affecting Golden Retrievers and is hypothesized to arise through a complex interaction of genetic and environmental factors. The aim of this nested case-control study was to investigate the association between potential environmental pollutant sources and lymphoma risk among Golden Retrievers participating in the Golden Retriever Lifetime Study. Forty-nine Golden Retrievers with non-cutaneous lymphoma and 98 Golden Retrievers without a history of cancer matched by age, sex and neuter status were selected from the Golden Retriever Lifetime Study cohort. Geographic proximity between each dog's primary residence and nine potential sources of environmental pollution was determined. In addition, the average annual ozone and airborne fine particulate matter levels for each dog's county of residence and owner-reported secondhand smoke exposure were evaluated. Environmental pollution sources of interest included chemical plants, municipal dumps, manufacturing plants, incineration plants, railroad embankment tracks, landfills, coal plants, high-voltage transmission lines, and nuclear power plants. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each exposure of interest. Subgroup analyses were conducted to evaluate whether associations differed among 1) dogs with multicentric lymphoma, 2) dogs with B-cell lymphoma, and 3) dogs with T-cell lymphoma. No variables reached statistical significance when evaluating all cases together. However, cumulative exposure burden (household proximity to 3 or more pollution sources) approached significance within the multicentric lymphoma subgroup (OR = 2.60, 95%CI 0.99-6.86, p-value = 0.053). Patterns emerged among B- and T-cell subgroups, but none reached statistical significance. Ongoing research is warranted to discern if different environmental mechanisms may be driving B- and T-cell lymphoma immunophenotypes, consistent with previously reported regional differences in subtype prevalence.
{"title":"Environmental exposures and lymphoma risk: a nested case-control study using the Golden Retriever Lifetime Study cohort.","authors":"Kristofer R Luethcke, Lauren A Trepanier, Ashleigh N Tindle, Julia D Labadie","doi":"10.1186/s40575-022-00122-9","DOIUrl":"https://doi.org/10.1186/s40575-022-00122-9","url":null,"abstract":"<p><p>Lymphoma is the second most common cancer affecting Golden Retrievers and is hypothesized to arise through a complex interaction of genetic and environmental factors. The aim of this nested case-control study was to investigate the association between potential environmental pollutant sources and lymphoma risk among Golden Retrievers participating in the Golden Retriever Lifetime Study. Forty-nine Golden Retrievers with non-cutaneous lymphoma and 98 Golden Retrievers without a history of cancer matched by age, sex and neuter status were selected from the Golden Retriever Lifetime Study cohort. Geographic proximity between each dog's primary residence and nine potential sources of environmental pollution was determined. In addition, the average annual ozone and airborne fine particulate matter levels for each dog's county of residence and owner-reported secondhand smoke exposure were evaluated. Environmental pollution sources of interest included chemical plants, municipal dumps, manufacturing plants, incineration plants, railroad embankment tracks, landfills, coal plants, high-voltage transmission lines, and nuclear power plants. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each exposure of interest. Subgroup analyses were conducted to evaluate whether associations differed among 1) dogs with multicentric lymphoma, 2) dogs with B-cell lymphoma, and 3) dogs with T-cell lymphoma. No variables reached statistical significance when evaluating all cases together. However, cumulative exposure burden (household proximity to 3 or more pollution sources) approached significance within the multicentric lymphoma subgroup (OR = 2.60, 95%CI 0.99-6.86, p-value = 0.053). Patterns emerged among B- and T-cell subgroups, but none reached statistical significance. Ongoing research is warranted to discern if different environmental mechanisms may be driving B- and T-cell lymphoma immunophenotypes, consistent with previously reported regional differences in subtype prevalence.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":" ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40595451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-15DOI: 10.1186/s40575-022-00118-5
Dan G O'Neill, Alison Skipper, Rowena M A Packer, Caitriona Lacey, Dave C Brodbelt, David B Church, Camilla Pegram
Background: The English Bulldog has risen sharply in popularity over the past decade but its distinctive and extreme conformation is linked to several serious health conditions. Using multivariable analysis of anonymised veterinary clinical data from the VetCompass Programme, this study compared the odds of common disorders between English Bulldogs and all remaining dogs in the UK during 2016.
Results: From 905,544 dogs under veterinary care during 2016, the analysis included a random sample of 2,662 English Bulldogs and 22,039 dogs that are not English Bulldogs. English Bulldogs had 2.04 times the odds of diagnosis with ≥ 1 disorder than dogs that are not English Bulldogs (95% confidence interval [CI] 1.85 to 2.25). At a specific-level of diagnostic precision, English Bulldogs had increased odds of 24/43 (55.8%) disorders. These included: skin fold dermatitis (odds ratio [OR] 38.12; 95% CI 26.86 to 54.10), prolapsed nictitating membrane gland (OR 26.79; 95% CI 18.61 to 38.58) and mandibular prognathism (OR 24.32; 95% CI 13.59 to 43.53). Conversely, English Bulldogs had significantly reduced odds of 6/43 (14.0%) disorders. These included: retained deciduous tooth (OR 0.02; 95% CI 0.01 to 0.17), lipoma (OR 0.06; 95% CI 0.01 to 0.40) and periodontal disease (OR 0.23; 95% CI 0.18 to 0.30). At a grouped-level of diagnostic precision, English Bulldogs had significantly increased odds of 17/34 (50.0%) disorders. These included: congenital disorder (OR 7.55; 95% CI 5.29 to 10.76), tail disorder (OR 6.01; 95% CI 3.91 to 9.24) and lower respiratory tract disorder (OR 5.50; 95% CI 4.11 to 7.35). Conversely, English Bulldogs had significantly reduced odds of 3/34 (8.8%) disorders. These were: dental disorder (OR 0.25; 95% CI 0.20 to 0.31), spinal cord disorder (OR 0.31; 95% CI 0.14 to 0.71) and appetite disorder (OR 0.43; 95% CI 0.20 to 0.91).
Conclusions: These results suggest that the health of English Bulldogs is substantially lower than dogs that are not English Bulldogs and that many predispositions in the breed are driven by the extreme conformation of these dogs. Consequently, immediate redefinition of the breed towards a moderate conformation is strongly advocated to avoid the UK joining the growing list of countries where breeding of English Bulldogs is banned.
背景:在过去的十年里,英国斗牛犬的受欢迎程度急剧上升,但它独特而极端的体型与几种严重的健康状况有关。通过对VetCompass项目匿名兽医临床数据的多变量分析,本研究比较了2016年英国斗牛犬和英国所有其他狗之间常见疾病的几率。结果:从2016年接受兽医护理的905,544只狗中,分析包括随机抽样的2662只英国斗牛犬和22039只非英国斗牛犬。英国斗牛犬诊断为≥1障碍的几率是非英国斗牛犬的2.04倍(95%可信区间[CI] 1.85 ~ 2.25)。在特定的诊断精度水平上,英国斗牛犬患疾病的几率增加了24/43(55.8%)。包括:皮肤褶皱性皮炎(优势比[OR] 38.12;95% CI 26.86 ~ 54.10),脱垂的隐膜腺(OR 26.79;95% CI 18.61 ~ 38.58)和下颌前突(OR 24.32;95% CI 13.59 ~ 43.53)。相反,英国斗牛犬患6/43(14.0%)疾病的几率显著降低。这些包括:保留乳牙(OR 0.02;95% CI 0.01 ~ 0.17),脂肪瘤(OR 0.06;95% CI 0.01 ~ 0.40)和牙周病(OR 0.23;95% CI 0.18 ~ 0.30)。在诊断精度的分组水平上,英国斗牛犬患疾病的几率显著增加17/34(50.0%)。这些包括:先天性疾病(OR 7.55;95% CI 5.29 ~ 10.76),尾部紊乱(OR 6.01;95% CI 3.91 ~ 9.24)和下呼吸道疾病(OR 5.50;95% CI 4.11 ~ 7.35)。相反,英国斗牛犬的3/34(8.8%)疾病几率显著降低。这些是:牙齿紊乱(OR 0.25;95% CI 0.20 - 0.31),脊髓障碍(OR 0.31;95% CI 0.14 ~ 0.71)和食欲障碍(OR 0.43;95% CI 0.20 ~ 0.91)。结论:这些结果表明,英国斗牛犬的健康状况明显低于非英国斗牛犬,并且该品种的许多易感性是由这些犬的极端构象驱动的。因此,为了避免英国加入越来越多的禁止繁殖英国斗牛犬的国家,强烈主张立即对品种进行重新定义,以达到适度的一致性。
{"title":"English Bulldogs in the UK: a VetCompass study of their disorder predispositions and protections.","authors":"Dan G O'Neill, Alison Skipper, Rowena M A Packer, Caitriona Lacey, Dave C Brodbelt, David B Church, Camilla Pegram","doi":"10.1186/s40575-022-00118-5","DOIUrl":"https://doi.org/10.1186/s40575-022-00118-5","url":null,"abstract":"<p><strong>Background: </strong>The English Bulldog has risen sharply in popularity over the past decade but its distinctive and extreme conformation is linked to several serious health conditions. Using multivariable analysis of anonymised veterinary clinical data from the VetCompass Programme, this study compared the odds of common disorders between English Bulldogs and all remaining dogs in the UK during 2016.</p><p><strong>Results: </strong>From 905,544 dogs under veterinary care during 2016, the analysis included a random sample of 2,662 English Bulldogs and 22,039 dogs that are not English Bulldogs. English Bulldogs had 2.04 times the odds of diagnosis with ≥ 1 disorder than dogs that are not English Bulldogs (95% confidence interval [CI] 1.85 to 2.25). At a specific-level of diagnostic precision, English Bulldogs had increased odds of 24/43 (55.8%) disorders. These included: skin fold dermatitis (odds ratio [OR] 38.12; 95% CI 26.86 to 54.10), prolapsed nictitating membrane gland (OR 26.79; 95% CI 18.61 to 38.58) and mandibular prognathism (OR 24.32; 95% CI 13.59 to 43.53). Conversely, English Bulldogs had significantly reduced odds of 6/43 (14.0%) disorders. These included: retained deciduous tooth (OR 0.02; 95% CI 0.01 to 0.17), lipoma (OR 0.06; 95% CI 0.01 to 0.40) and periodontal disease (OR 0.23; 95% CI 0.18 to 0.30). At a grouped-level of diagnostic precision, English Bulldogs had significantly increased odds of 17/34 (50.0%) disorders. These included: congenital disorder (OR 7.55; 95% CI 5.29 to 10.76), tail disorder (OR 6.01; 95% CI 3.91 to 9.24) and lower respiratory tract disorder (OR 5.50; 95% CI 4.11 to 7.35). Conversely, English Bulldogs had significantly reduced odds of 3/34 (8.8%) disorders. These were: dental disorder (OR 0.25; 95% CI 0.20 to 0.31), spinal cord disorder (OR 0.31; 95% CI 0.14 to 0.71) and appetite disorder (OR 0.43; 95% CI 0.20 to 0.91).</p><p><strong>Conclusions: </strong>These results suggest that the health of English Bulldogs is substantially lower than dogs that are not English Bulldogs and that many predispositions in the breed are driven by the extreme conformation of these dogs. Consequently, immediate redefinition of the breed towards a moderate conformation is strongly advocated to avoid the UK joining the growing list of countries where breeding of English Bulldogs is banned.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"9 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10785169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-24DOI: 10.1186/s40575-022-00121-w
N K Ringstad, F Lingaas, S I Thoresen
Background: Diabetes mellitus (DM) and hypothyroidism are common canine endocrinopathies. Both canine DM and primary hypothyroidism are assumed to originate from autoimmune destruction of the respective endocrine glands and have been associated with the major histocompatibility complex (MHC) gene region. This study aims to investigate breed distributions for DM and hypothyroidism in the Norwegian canine population by calculating odds ratios (OR) from two different comparator groups.
Methods: Results from canine serum samples submitted from 2001 to 2018 to the Veterinary Clinical Pathology Laboratory (VCPL) at the Faculty of Veterinary Medicine, Norwegian University of Life Sciences for analysis of fructosamine and thyroid hormones in serum were used as cases in a retrospective bivariate analysis of canine breeds. The ORs were calculated as a measure of risk for the included breeds, where all the submitted blood samples to the VCPL and dogs registered in the Norwegian Kennel Club (NKK), the national organization for dog owners, were used as two comparator groups.
Results: Significant differences in disease prevalence between breeds were discovered using both comparator groups. Australian terrier, Swedish lapphund, Samoyed, and Schipperke were at highest risk for DM. German Shepherd, Golden retriever, German pointing dog, and Collie presented as the breeds with lowest risk for DM. For hypothyroidism, Schnauzer, Eurasier, Dunker, and English setter were at highest risk for developing the disease. The breeds at lowest risk of developing hypothyroidism were Rottweiler, Dachshund, German shepherd, and Border collie. The results from the different comparator groups gave different ORs and ranks, but the breeds with highest and lowest odds showed the same susceptibility using both comparators.
Conclusions: These findings support that there are breeds more and less prone to develop DM and hypothyroidism. A strong genetic predisposition involved in the aetiology of these two diseases is therefore likely. Interestingly, there also appeared to be an inverse relationship of odds for the two diseases for some of the breeds since some breeds that had a high OR for DM or hypothyroidism had a lower OR for the other disease. This indicates that there may be different risk alleles/haplotypes for the two diseases. The possible aetiological relationship between canine DM and hypothyroidism should be further investigated.
{"title":"Breed distributions for diabetes mellitus and hypothyroidism in Norwegian dogs.","authors":"N K Ringstad, F Lingaas, S I Thoresen","doi":"10.1186/s40575-022-00121-w","DOIUrl":"https://doi.org/10.1186/s40575-022-00121-w","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) and hypothyroidism are common canine endocrinopathies. Both canine DM and primary hypothyroidism are assumed to originate from autoimmune destruction of the respective endocrine glands and have been associated with the major histocompatibility complex (MHC) gene region. This study aims to investigate breed distributions for DM and hypothyroidism in the Norwegian canine population by calculating odds ratios (OR) from two different comparator groups.</p><p><strong>Methods: </strong>Results from canine serum samples submitted from 2001 to 2018 to the Veterinary Clinical Pathology Laboratory (VCPL) at the Faculty of Veterinary Medicine, Norwegian University of Life Sciences for analysis of fructosamine and thyroid hormones in serum were used as cases in a retrospective bivariate analysis of canine breeds. The ORs were calculated as a measure of risk for the included breeds, where all the submitted blood samples to the VCPL and dogs registered in the Norwegian Kennel Club (NKK), the national organization for dog owners, were used as two comparator groups.</p><p><strong>Results: </strong>Significant differences in disease prevalence between breeds were discovered using both comparator groups. Australian terrier, Swedish lapphund, Samoyed, and Schipperke were at highest risk for DM. German Shepherd, Golden retriever, German pointing dog, and Collie presented as the breeds with lowest risk for DM. For hypothyroidism, Schnauzer, Eurasier, Dunker, and English setter were at highest risk for developing the disease. The breeds at lowest risk of developing hypothyroidism were Rottweiler, Dachshund, German shepherd, and Border collie. The results from the different comparator groups gave different ORs and ranks, but the breeds with highest and lowest odds showed the same susceptibility using both comparators.</p><p><strong>Conclusions: </strong>These findings support that there are breeds more and less prone to develop DM and hypothyroidism. A strong genetic predisposition involved in the aetiology of these two diseases is therefore likely. Interestingly, there also appeared to be an inverse relationship of odds for the two diseases for some of the breeds since some breeds that had a high OR for DM or hypothyroidism had a lower OR for the other disease. This indicates that there may be different risk alleles/haplotypes for the two diseases. The possible aetiological relationship between canine DM and hypothyroidism should be further investigated.</p>","PeriodicalId":72519,"journal":{"name":"Canine medicine and genetics","volume":"9 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}