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AbstractPurposeMethodResultConclusionTo discuss whether stuttering causality matters to clinicians during clinical practice, and how and why it might matter. Additionally, to provide early-career clinicians and students with entry-level assistance with this complex topic.The issue was discussed by two academics and two experienced speech-language pathologists in private practice. Written conversational turns in an exchange were limited to 100 words each. When that written dialogue was concluded, the moderator summarised the discussion.All participants agreed that the cause of stuttering does matter to speech-language pathologists during clinical practice.The following three key points emerged from the conversation. Firstly, no-one referred to a formally stated theory or model when explaining cause to clients. Instead, all in the conversation stayed on the solid ground of current facts about the cause of stuttering. Secondly, explaining the cause of stuttering can benefit clients and parents. It can support them and give them confidence and empowerment during clinical management and increase the credibility of a management plan. Finally, in essence, this topic relates to evidence-based practice, for which there are no fixed rules. Different clinicians may make different judgments about what is and what is not true, useful, and important. [ABSTRACT FROM AUTHOR]

Objectives. Infertility is a topic of great interest around the world because it affects many couples at young ages. It can be caused by genetic background, associated with pathologies and/or external factors. The purpose of our study was to identify the causes of infertility of women presented in our clinic with this pathology. Materials and Methods. This retrospective study was performed on women with primary or secondary infertility. The analyzed data were age, weight, hereditary and personal pathological history, medication, menstrual cycle characteristics, standard blood tests, ultrasound, hysterosalpingography and hysteroscopy. Results. The study included 204 women with average age 35 years. The main diagnosis was primary infertility in 68.63% and secondary infertility in 31.37% cases. One of the most common diagnosed findings in ultrasound were uterine fibroids with an incidence of 6.86%, the incidence being higher among women with primary infertility than in women with secondary infertility. Regarding endometrial polyps, 96.15% of cases were observed ultrasonographical and the incidence of endometrial polyps was higher among women with primary infertility than in women with secondary infertility. Conclusions. This study identified that infertility is a multifactorial pathology, which requires multidisciplinary addressability. Gynecological pathology (such as tubal pathologies, uterine malformations, uterine fibroids, endometriosis, endometrial polyps, etc.) was very common among these patients, finding and treating the condition being the main objective of the study.

Abstract Background PCOS is a serious endocrine-metabolic condition characterized by hyperandrogenemia, anovulation, or oligo-ovulation, and links to obesity, insulin resistance, and an elevated risk of type 2 diabetes mellitus. The pathophysiology of PCOS is thought to involve both environmental and genetic factors. PCOS etiology has been linked to genetic factors, with the CYP21 and CYP11A1 genes identified as possible candidate genes. Previous research has linked the rs13405728 polymorphism in the CYP21 gene and the rs4077582 polymorphism in the CYP11A1 gene to PCOS. However, more research is needed to confirm these connections in specific populations. The purpose of this study was to look at the role of single gene polymorphisms in PCOS, specifically the rs13405728 polymorphism in the CYP21 (LHCGR) gene and the rs4077582 polymorphism in the CYP11A1 gene. Blood was drawn from 150 PCOS patients and 150 age- and gender-matched healthy people. The phenol–chloroform procedure was used to extract DNA, and gel electrophoresis was used to quantify it. To analyze polymorphisms, researchers used polymerase chain reaction (PCR) with the allele-specific amplification refractory mutation system (ARMS-PCR) to amplify specific areas of DNA. ARMS-PCR was used to detect mutations in the CYP21 and CYP11A1 genes, followed by sequencing to examine the rs13405728 polymorphism and rs4077582 polymorphism, respectively, in 150 PCOS patients and 150 control people. ARMS-PCR polymorphism study of the CYP21 (LHCGR) and CYP11A1 genes indicated significant correlations. Results For the CYP21 gene, heterozygous (CT) carriers of the rs13405728 polymorphism had a fourfold greater incidence of PCOS (OR 4.10; CI 2.47–6.80; p = 0.0001), whereas homozygous mutant (TT) carriers had a significant connection with PCOS (OR 0.27; CI 0.16–0.45; p = 0.0001). These data imply that the CYP21 (LHCGR) gene polymorphism rs13405728 has a substantial impact on the development of polycystic ovarian syndrome. The data for the CYP11A1 gene show the SNP (rs4077582) heterozygous (CT) was associated with PCOS (OR 1.72; 95% CI 1.02–2.88; p = 0.0392). The identical SNP heterozygous (CT) raised the incidence of PCOS by up to onefold. The homozygous mutant SNP (TT) had no connection with illness onset (OR 1.377; 95% CI 0.85–2.2; p = 0.1855), while the mutant (TT) of the SNP nearly doubled the incidence of polycystic ovarian syndrome. The combined model of the same SNP (CT + TT) revealed a significant correlation with PCOS (OR 2.1905; 95% CI 1.355–3.53; p = 0.0014). The combination model (CT + TT) of the same SNP more than doubled the risk of polycystic ovarian syndrome. All the risk factors investigated had a substantial connection with PCOS. Conclusion In conclusion, this study supports the role of the CYP21 (LHCGR) and CYP11A1 gene polymorphism in PCOS. More studies are needed to investigate the functional significance of this polymorphism as well as its possible clinical impact on the diagnosis and treatment of PCOS.

Background: PCOS is a serious endocrine-metabolic condition characterized by hyperandrogenemia, anovulation, or oligo-ovulation, and links to obesity, insulin resistance, and an elevated risk of type 2 diabetes mellitus. The pathophysiology of PCOS is thought to involve both environmental and genetic factors. PCOS etiology has been linked to genetic factors, with the CYP21 and CYP11A1 genes identified as possible candidate genes. Previous research has linked the rs13405728 polymorphism in the CYP21 gene and the rs4077582 polymorphism in the CYP11A1 gene to PCOS. However, more research is needed to confirm these connections in specific populations. The purpose of this study was to look at the role of single gene polymorphisms in PCOS, specifically the rs13405728 polymorphism in the CYP21 (LHCGR) gene and the rs4077582 polymorphism in the CYP11A1 gene. Blood was drawn from 150 PCOS patients and 150 age- and gender-matched healthy people. The phenol–chloroform procedure was used to extract DNA, and gel electrophoresis was used to quantify it. To analyze polymorphisms, researchers used polymerase chain reaction (PCR) with the allele-specific amplification refractory mutation system (ARMS-PCR) to amplify specific areas of DNA. ARMS-PCR was used to detect mutations in the CYP21 and CYP11A1 genes, followed by sequencing to examine the rs13405728 polymorphism and rs4077582 polymorphism, respectively, in 150 PCOS patients and 150 control people. ARMS-PCR polymorphism study of the CYP21 (LHCGR) and CYP11A1 genes indicated significant correlations. Results: For the CYP21 gene, heterozygous (CT) carriers of the rs13405728 polymorphism had a fourfold greater incidence of PCOS (OR 4.10; CI 2.47–6.80; p = 0.0001), whereas homozygous mutant (TT) carriers had a significant connection with PCOS (OR 0.27; CI 0.16–0.45; p = 0.0001). These data imply that the CYP21 (LHCGR) gene polymorphism rs13405728 has a substantial impact on the development of polycystic ovarian syndrome. The data for the CYP11A1 gene show the SNP (rs4077582) heterozygous (CT) was associated with PCOS (OR 1.72; 95% CI 1.02–2.88; p = 0.0392). The identical SNP heterozygous (CT) raised the incidence of PCOS by up to onefold. The homozygous mutant SNP (TT) had no connection with illness onset (OR 1.377; 95% CI 0.85–2.2; p = 0.1855), while the mutant (TT) of the SNP nearly doubled the incidence of polycystic ovarian syndrome. The combined model of the same SNP (CT + TT) revealed a significant correlation with PCOS (OR 2.1905; 95% CI 1.355–3.53; p = 0.0014). The combination model (CT + TT) of the same SNP more than doubled the risk of polycystic ovarian syndrome. All the risk factors investigated had a substantial connection with PCOS. Conclusion: In conclusion, this study supports the role of the CYP21 (LHCGR) and CYP11A1 gene polymorphism in PCOS. More studies are needed to investigate the functional significance of this polymorphism as well as its possible clinical impact on the diagnosis and treatment of PCOS. [ABSTRACT FROM AUTHOR]

Air pollution, particularly PM2.5, has long been a critical concern for the atmospheric environment. Accurately predicting daily PM2.5 concentrations is crucial for both environmental protection and public health. This study introduces a new hybrid model within the "Decomposition-Prediction-Integration" (DPI) framework, which combines variational modal decomposition (VMD), causal convolutional neural network (CNN), bidirectional long short-term memory (BiLSTM), and attention mechanism (AM), named as VCBA, for spatio-temporal fusion of multi-site data to forecast daily PM2.5 concentrations in a city. The approach involves integrating air quality data from the target site with data from neighboring sites, applying mathematical techniques for dimensionality reduction, decomposing PM2.5 concentration data using VMD, and utilizing Causal CNN and BiLSTM models with an attention mechanism to enhance performance. The final prediction results are obtained through linear aggregation. Experimental results demonstrate that the VCBA model performs exceptionally well in predicting daily PM2.5 concentrations at various stations in Taiyuan City, Shanxi Province, China. Evaluation metrics such as RMSE, MAE, and R2 are reported as 2.556, 1.998, and 0.973, respectively. Compared to traditional methods, this approach offers higher prediction accuracy and stronger spatio-temporal modeling capabilities, providing an effective solution for accurate PM2.5 daily concentration prediction. [ABSTRACT FROM AUTHOR]

Situated within the broad spectrum of neurodegenerative disorders, Alzheimer's disease (AD) is known for its complexity, heterogeneity, multiple genetic mutations, epigenetic and biochemical modifications, and irreversible progression from early stages characterized by deficits in the ability to encode and store new information to subsequent progressive cognitive, functional, and behavioral decline. The conducted study aimed to compile conclusive statistics, identify genetic factors, and correlate them with environmental ones, thus highlighting the importance of developing evaluation programs and early introduction of medication to decelerate the progression of neurodegenerative processes. The analytical, observational, retrospective study was conducted on an extended cohort of 2277 patients admitted with chronic neurological diseases to the Neurology Department of "Dr. Iacob Czihac" Clinical Military Emergency Hospital Iași from January 1, 2022, to December 31, 2023. Among these, 219 patients were diagnosed with AD at various stages. Forty-three cases exhibiting genetic predisposition (19.63%) were selected and thoroughly analyzed based on medical records. The study emphasizes the significant position of AD among chronic neurological diseases. Although the majority do not present hereditary antecedents (80.36%), predisposing conditions, environmental factors, stress, and the region of residence play fundamental roles in the disease's determinism. It is observed that individuals in the 60-70 age category (71.23%) from urban areas (63.01%), especially females (63.47%), have a higher probability of developing AD. Maternally transmitted AD prevalence was 58.13%, while paternally inherited AD accounted for 32.55%, with only 4 cases having antecedents on both lines (9.30%). Unequivocally characterized by a vast etiology, AD is a multifactorial disorder resulting from the bilateral interaction and continuous corroboration of genetic and environmental factors. [ABSTRACT FROM AUTHOR]

Objectives. Infertility is a topic of great interest around the world because it affects many couples at young ages. It can be caused by genetic background, associated with pathologies and/or external factors. The purpose of our study was to identify the causes of infertility of women presented in our clinic with this pathology. Materials and Methods. This retrospective study was performed on women with primary or secondary infertility. The analyzed data were age, weight, hereditary and personal pathological history, medication, menstrual cycle characteristics, standard blood tests, ultrasound, hysterosalpingography and hysteroscopy. Results. The study included 204 women with average age 35 years. The main diagnosis was primary infertility in 68.63% and secondary infertility in 31.37% cases. One of the most common diagnosed findings in ultrasound were uterine fibroids with an incidence of 6.86%, the incidence being higher among women with primary infertility than in women with secondary infertility. Regarding endometrial polyps, 96.15% of cases were observed ultrasonographical and the incidence of endometrial polyps was higher among women with primary infertility than in women with secondary infertility. Conclusions. This study identified that infertility is a multifactorial pathology, which requires multidisciplinary addressability. Gynecological pathology (such as tubal pathologies, uterine malformations, uterine fibroids, endometriosis, endometrial polyps, etc.) was very common among these patients, finding and treating the condition being the main objective of the study. [ABSTRACT FROM AUTHOR]

Introduction: Autism Spectrum Disorder (ASD) is a complex and variable neurodevelopmental condition that affects how individuals perceive and interact with the world around them. Characterized by significant difficulties in social communication and the presence of restrictive and repetitive behaviors, ASD is a disorder that can influence all aspects of a person's life. Purpose: The purpose of this paper is to identify the influence that risk factors can have on the pathogenesis of autism spectrum disorder, through the description of a clinical case. Material and methods: We present the clinical case of a 7-year-old patient admitted to the Pediatric Psychiatry Department at the Clinic of Pediatric Neurology and Psychiatry in Timișoara, exhibiting clinical symptoms indicative of autism spectrum disorder. Results: Given the increasing frequency of this condition and its multiple implications on familial, social, educational, and professional aspects, this article will report on a clinical case diagnosed with autism spectrum disorder, highlighting the implications of risk factors. The patient underwent clinical and paraclinical investigations, psychiatric and psychological evaluations, and received specialized treatment, showing slow but favorable progress over time. Discussions: Understanding the risk factors associated with the pathogenesis of autism spectrum disorder is crucial for early diagnosis and intervention. Risk factors for ASD are diverse, encompassing both genetic and environmental components that impact the clinical presentation and long-term outcomes. Conclusions: Autism Spectrum Disorder (ASD) is a complex and multifactorial condition that requires a comprehensive understanding of the numerous risk factors involved in its pathogenesis. From genetic and hereditary components to prenatal, perinatal, environmental, and biological influences, each of these factors plays a crucial role in determining an individual's susceptibility to ASD. [ABSTRACT FROM AUTHOR]

Situated within the broad spectrum of neurodegenerative disorders, Alzheimer's disease (AD) is known for its complexity, heterogeneity, multiple genetic mutations, epigenetic and biochemical modifications, and irreversible progression from early stages characterized by deficits in the ability to encode and store new information to subsequent progressive cognitive, functional, behavioral decline. Objective: The conducted study aimed to compile conclusive statistics, identify genetic factors, and correlate them with environmental ones, thus highlighting the importance of developing evaluation programs and early introduction of medication in order to decelerate the progression of neurodegenerative processes. Materials and methods: The analytical, observational, retrospective study was conducted on an extended cohort of 2277 patients admitted with chronic neurological diseases to the Neurology Department of "Dr. Iacob Czihac" Clinical Military Emergency Hospital Iași from January 1, 2022 to December 31, 2023. Among these, 219 patients were diagnosed with AD at various stages. Forty-three cases exhibiting genetic predisposition (19.63%) were selected and thoroughly analyzed based on medical records. Results: The study emphasizes the significant position of AD among chronic neurological diseases. Although the majority do not present hereditary antecedents (80.36%), predisposing conditions, environmental factors, stress, and the region of residence play fundamental roles in the disease's determinism. It is observed that individuals in the 60-70 age category (71.23%) from urban areas (63.01%), especially females (63.47%), have a higher probability of developing AD. Maternally transmitted Alzheimer's prevalence was 58.13%, while paternally inherited AD accounted for 32.55%, with only 4 cases having antecedents on both lines (9.30%). Conclusion: Unequivocally characterized by a vast etiology, AD is a multifactorial disorder resulting from the bilateral interaction and continuous corroboration of genetic and environmental factors.

Abstract Introduction Preventing falls is a priority for aged care providers. Research to date has focused on fall prevention strategies in single settings (e.g., residential aged care (RAC) or community settings). However, some aged care providers deliver care, including fall prevention interventions, across RAC and community settings. We conducted an umbrella review to identify what type of fall prevention interventions had the greatest impact on falls outcomes in RAC and community settings. Methods Five databases were searched for systematic reviews of falls prevention randomised control trials in older adults living in the community or RAC. Data extracted included systematic review methods, population characteristics, intervention characteristics, setting details (RAC or community), and fall-related outcomes (falls, people who have had a fall, fall-related hospitalisations, and fall-related fractures). Review quality was appraised using the Assessment of Multiple Systematic Reviews-2 tool. Results One-hundred and six systematic reviews were included; 63 and 19 of these stratified results by community and RAC settings respectively, the remainder looked at both settings. The most common intervention types discussed in reviews included ‘exercise’ (61%, n = 65), ‘multifactorial’ (two or more intervention types delivered together) (26%, n = 28), and ‘vitamin D’ (18%, n = 19). In RAC and community settings, ‘exercise’ interventions demonstrated the most consistent reduction in falls and people who have had a fall compared to other intervention types. ‘Multifactorial’ interventions were also beneficial in both settings however demonstrated more consistent reduction in falls and people who fall in RAC settings compared to community settings. ‘Vitamin D’ interventions may be beneficial in community-dwelling populations but not in RAC settings. It was not possible to stratify fall-related hospitalisation and fall-related fracture outcomes by setting due to limited number of RAC-specific reviews (n = 3 and 0 respectively). Conclusion ‘Exercise’ interventions may be the most appropriate falls prevention intervention for older adults in RAC and community settings as it is beneficial for multiple fall-related outcomes (falls, fall-related fractures, and people who have had a fall). Augmenting ‘exercise’ interventions to become ‘multifactorial’ interventions may also improve the incidence of falls in both settings.

SUMMARY: The complexity of environmental conditions encountered by plants in the field, or in nature, is gradually increasing due to anthropogenic activities that promote global warming, climate change, and increased levels of pollutants. While in the past it seemed sufficient to study how plants acclimate to one or even two different stresses affecting them simultaneously, the complex conditions developing on our planet necessitate a new approach of studying stress in plants: Acclimation to multiple stress conditions occurring concurrently or consecutively (termed, multifactorial stress combination [MFSC]). In an initial study of the plant response to MFSC, conducted with Arabidopsis thaliana seedlings subjected to an MFSC of six different abiotic stresses, it was found that with the increase in the number and complexity of different stresses simultaneously impacting a plant, plant growth and survival declined, even if the effects of each stress involved in such MFSC on the plant was minimal or insignificant. In three recent studies, conducted with different crop plants, MFSC was found to have similar effects on a commercial rice cultivar, a maize hybrid, tomato, and soybean, causing significant reductions in growth, biomass, physiological parameters, and/or yield traits. As the environmental conditions on our planet are gradually worsening, as well as becoming more complex, addressing MFSC and its effects on agriculture and ecosystems worldwide becomes a high priority. In this review, we address the effects of MFSC on plants, crops, agriculture, and different ecosystems worldwide, and highlight potential avenues to enhance the resilience of crops to MFSC. [ABSTRACT FROM AUTHOR]

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Background Multifactorial fall prevention trials providing interventions based on individual risk factors have variable success in aged care facilities. To determine configurations of trial features that reduce falls, intervention component analysis (ICA) and qualitative comparative analysis (QCA) were undertaken. Methods Randomised controlled trials (RCTs) from a Cochrane Collaboration review (Cameron, 2018) with meta-analysis data, plus trials identified in a systematic search update to December 2021 were included. Meta-analyses were updated. A theory developed through ICA of English publications of trialist's perspectives was assessed through QCA and a subgroup meta-analysis. Results Pooled effectiveness of multifactorial interventions indicated a falls rate ratio of 0.85 (95% confidence interval, CI, 0.65–1.10; I 2 = 85%; 11 trials). All tested interventions targeted both environmental and personal risk factors by including assessment of environmental hazards, a medical or medication review and exercise intervention. ICA emphasised the importance of co-design involving facility staff and managers and tailored intervention delivery to resident's intrinsic factors for successful outcomes. QCA of facility engagement plus tailored delivery was consistent with greater reduction in falls, supported by high consistency (0.91) and coverage (0.85). An associated subgroup meta-analysis demonstrated strong falls reduction without heterogeneity (rate ratio 0.61, 95%CI 0.54–0.69, I 2 = 0%; 7 trials). Conclusion Multifactorial falls prevention interventions should engage aged care staff and managers to implement strategies which include tailored intervention delivery according to each resident's intrinsic factors. Such approaches are consistently associated with a successful reduction in falls, as demonstrated by QCA and subgroup meta-analyses. Co-design approaches may also enhance intervention success. [ABSTRACT FROM AUTHOR]

Dongna Hui,1,2 Fang Zhang,3 Yuanyue Lu,4 Huiqiang Hao,3 Shuangshuang Tian,3 Xiuzhao Fan,3 Yanqin Liu,3 Xiaoshuang Zhou,2 Rongshan Li1,2 1Institute of Biomedical Sciences, Shanxi University, Taiyuan, People’s Republic of China; 2Department of Nephrology, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China; 3Kidney Disease Data Center, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China; 4Department of Nephrology, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Xiaoshuang Zhou, Department of Nephrology, Shanxi Provincial People’s Hospital, No. 29 Shuangta Street, Yingze District, Taiyuan, Shanxi, 030012, People’s Republic of China, Tel +86 13485318729, Email zhouxiaoshuang@sxmu.edu.cn Rongshan Li, Institute of Biomedical Sciences, Shanxi University, No. 92 Wucheng Road, Xiaodian District, Taiyuan, Shanxi, 030006, People’s Republic of China, Tel +86-0351-4960486, Email rongshanli@126.comPurpose: In-depth investigations of risk factors for the identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) are rare. We aimed to investigate the risk factors for developing DKD from multiple types of clinical data and conduct a comprehensive risk assessment for individuals with diabetes.Methods: We carried out a case-control study, enrolling 958 patients to identify the risk factors for developing DKD in T2DM patients from a database established from inpatient electronic medical records. Multivariable logistic regression was applied to develop a prediction model and the performance of the model was evaluated using the area under the curve (AUC) and calibration curve. A multifactorial risk score system was established according to the Framingham Study risk score.Results: DKD accounted for 34.03% of eligible patients in total. Twelve risk factors were selected in the final prediction model, including age, duration of diabetes, duration of hypertension, fasting blood glucose, fasting C-peptide, insulin use, systolic blood pressure, low-density lipoprotein, γ-glutamyl transpeptidase, platelet, uric acid, and thyroid stimulating hormone; and one protective factor, serum albumin. The prediction model showed an AUC of 0.862 (95% Confidence Interval (CI) 0.834– 0.890) with an accuracy of 81.5% in the derivation dataset and an AUC of 0.876 (95% CI 0.825– 0.928) in the validation dataset. The calibration curves were excellent and the estimated probability of DKD was more than 80% when the cumulative score for risk factors reached 17 points.Conclusion: Newly recognized risk factors were applied to assess the development of DKD in T2DM patients and the established risk score system was a reliable and feasible tool for assisting clinicians to identify patients at high risk of DKD.Keywords: diabetic kidney disease, multifactorial, prediction model, risk factors, type 2 diabetes

Introduction: In Alzheimer's disease (AD), cognitive decline is driven by various interlinking causal factors. Systems thinking could help elucidate this multicausality and identify opportune intervention targets. Methods: We developed a system dynamics model (SDM) of sporadic AD with 33 factors and 148 causal links calibrated with empirical data from two studies. We tested the SDM's validity by ranking intervention outcomes on 15 modifiable risk factors to two sets of 44 and 9 validation statements based on meta‐analyses of observational data and randomized controlled trials, respectively. Results: The SDM answered 77% and 78% of the validation statements correctly. Sleep quality and depressive symptoms yielded the largest effects on cognitive decline with which they were connected through strong reinforcing feedback loops, including via phosphorylated tau burden. Discussion: SDMs can be constructed and validated to simulate interventions and gain insight into the relative contribution of mechanistic pathways. [ABSTRACT FROM AUTHOR]

Populations face a suite of anthropogenic stressors acting simultaneously, which can combine additively or interact to have complex effects on population persistence. Yet we still know relatively little about the mechanisms underlying population-level responses to multifactorial combinations of stressors because multiple stressor impacts across organisms' life cycles have not been systematically considered in population models. Specifically, different anthropogenic stressors can have variable effects across an organism's life cycle, resulting in non-intuitive results for long-term population persistence. For example, synergistic or antagonistic interactions might exacerbate or alleviate the effects of stressors on population dynamics, and different life-history stages or vital rates might contribute unequally to long-term population growth rates. Demographic modelling provides a framework to incorporate individual vital rate responses to multiple stressors into estimates of population growth, which will allow us to make more informed predictions about population-level responses to novel combinations of anthropogenic change. Without integrating stressors' interactive effects across the entire life cycle on population persistence, we may over- or underestimate threats to biodiversity and risk missing conservation management actions that could reduce species' vulnerability to stress. [ABSTRACT FROM AUTHOR]

The benefits of the newer antidiabetic agents available for managing type 2 diabetes mellitus (T2DM) remain indisputable, but many patients will require insulin therapy in the disease course. Given the limited access to newer antidiabetic agents, insulin remains a standard treatment modality in T2DM in South Africa. Early, multifactorial intervention remains ideal, but glucose, blood pressure and cholesterol values remain above target in many countries. Barriers to achieving glucose control in South Africa include the healthcare provider's being unfamiliar with the practicalities of insulin administration, initiation and titration. This article highlights these gaps and offers pragmatic solutions to overcome them. [ABSTRACT FROM AUTHOR]

The benefits of the newer antidiabetic agents available for managing type 2 diabetes mellitus (T2DM) remain indisputable, but many patients will require insulin therapy in the disease course. Given the limited access to newer antidiabetic agents, insulin remains a standard treatment modality in T2DM in South Africa. Early, multifactorial intervention remains ideal, but glucose, blood pressure and cholesterol values remain above target in many countries. Barriers to achieving glucose control in South Africa include the healthcare provider’s being unfamiliar with the practicalities of insulin administration, initiation and titration. This article highlights these gaps and offers pragmatic solutions to overcome them.

The aim of study is to re-evaluate the risk-benefits of intensive glycemic control in the context of multi-factorial intervention in adults with T2D. We searched Ovid MEDLINE, Embase, Cochrane, and CINHAL for randomized control trials comparing standard glucose targets to intensive glucose targets with pre-specified HbA1clevels. Subgroup analysis was also performed to account for the inclusion of glucose only versus multi-factorial intervention trials. Results are reported as risk ratio (RR) and 95% confidence interval (CI). Fifty-seven publications including 19 trials were included. Compared to conventional glycemic control, intensive glycemic control decreased the risk of non-fatal myocardial infarction (0.8, 0.7-0.91), macroalbuminuria (0.72, 0.5-–0.87), microalbuminuria (0.67, 0.52–0.85), major amputation (0.6, 0.38–0.96), retinopathy (0.75 ,0.63–0.9), and nephropathy (0.78, 0.63–0.97). The risk of hypoglycemia increased with intensive glycemic control than conventional treatment (2.04, 1.34–3.1). No reduction in all-cause or cardiovascular mortality was observed. However, in the context of multifactorial intervention, intensive glucose control was associated with a significant reduction in all-cause mortality (0.74, 0.57–0.95). Targeting HbA1c levels should be individualized based on the clinical status, balancing risks and benefits and potential risk for developing these complications among people with T2D. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is a debilitating condition characterized by abnormal movement or posture, beginning early in development. Early family and twin studies and more recent genomic investigations clearly demonstrate that genetic factors of major effect contribute to the etiology of CP. Most copy number variants and small alterations of nucleotide sequence that cause CP arise as a result of de novo mutations, so studies that estimate heritability on basis of recurrence frequency within families substantially underestimate genetic contributions to the etiology. At least 4% of patients with typical CP have disease-causing CNVs, and at least 14% have disease-causing single nucleotide variants or indels. The rate of pathogenic genomic lesions is probably more than twice as high among patients who have atypical CP, i.e., neuromotor dysfunction with additional neurodevelopmental abnormalities or malformations, or with MRI findings and medical history that are not characteristic of a perinatal insult. Mutations of many different genetic loci can produce a CP-like phenotype. The importance of genetic variants of minor effect and of epigenetic modifications in producing a multifactorial predisposition to CP is less clear. Recognizing the specific cause of CP in an affected individual is essential to providing optimal clinical management. An etiological diagnosis provides families an "enhanced compass" that improves overall well-being, facilitates access to educational and social services, permits accurate genetic counseling, and, for a subset of patients such as those with underlying inherited metabolic disorders, may make precision therapy that targets the pathophysiology available. Trio exome sequencing with assessment of copy number or trio genome sequencing with bioinformatics analysis for single nucleotide variants, indels, and copy number variants is clinically indicated in the initial workup of CP patients, especially those with additional malformations or neurodevelopmental abnormalities. • Clinical features suggestive of cerebral palsy are caused by copy number variants in ≥4% of patients single nucleotide variants or indels in ≥14%. • Disease-causing genomic lesions are ≥2 times as frequent in CP patients with additional malformations or neurodevelopmental abnormalities. • Aberrations of many different genetic loci can produce a CP-like phenotype. • Recognizing the cause of CP in an affected patient is essential to providing optimal clinical management, including precision therapy. • Genome-wide (exome or genome) sequencing is indicated in the initial work-up of patients with CP. [ABSTRACT FROM AUTHOR]

The success rate in medical practice will probably never reach 100%. Success rates depend on many factors. Defining the success rate is both a technical and a philosophical issue. In opposition to the concept of success, medical failure should also be discussed. Its causality is multifactorial and extremely complex. Its actual rate and its real impact are unknown. In medical practice, failure depends not only on the human factor but also on the medical system and has at its center a very important variable—the patient. To combat errors, capturing, tracking, and analyzing them at an institutional level are important. Barriers such as the fear of consequences or a specific work climate or culture can affect this process. Although important data regarding medical errors and their consequences can be extracted by analyzing patient outcomes or using quality indicators, patient stories (clinical cases) seem to have the greatest impact on our subconscious as medical doctors and nurses and these may generate the corresponding and necessary reactions. Every clinical case has its own story. In this study, three different cases are presented to illustrate how human error, the limits of the system, and the particularities of the patient's condition (severity of the disease), alone or in combination, may lead to tragic outcomes There is a need to talk openly and in a balanced way about failure, regardless of its cause, to look at things as they are, without hiding the inconvenient truth. The common goal is not to find culprits but to find solutions and create a culture of safety. [ABSTRACT FROM AUTHOR]

Public stigma and prejudice toward people with psychiatric conditions is highly prevalent and damaging. Explanations for the origins of mental illness can influence attitudes toward people with these conditions. To date, studies exploring the effects of explanations for the origins of mental illness have focused on genetic or environmental explanations, and the impact of evidence-based multifactorial explanations for psychiatric illness on public attitudes remains unknown. Participants were recruited through Amazon Mechanical Turk to watch a 4-min video about the "mental illness jar model"-an evidence-based analogy that explains the complex interactions between genes and environment in the development of mental illness. Participants provided demographic information and completed questions regarding knowledge about the causes of mental illness, and the Prejudice towards People with Mental Illness (PPMI) scale both before and after watching the video. A total of 106 eligible participants completed the study. Watching the video had no significant effect on participants' knowledge about the causes of mental illness (p = 0.06), but there was a significant decrease in prejudicial attitudes toward mental illness (p = 0.0003), the effect size was small (-0.15). The use of this brief video (available at cogastudy.org) is a promising tool to decrease prejudicial attitudes toward mental illness that warrants further study., (© 2024 The Author(s). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Most large-scale genetic studies of autism have focused on the discovery of genes by proving an enrichment of de novo mutations (DNMs) in autism probands or characterizing polygenic risk based on the association of common variants. We present evidence in support of an oligogenic model where two or more ultrarare mutations of more modest effect are preferentially transmitted to children with autism. Such private gene-disruptive mutations are enriched in families where there are multiple affected individuals, emerged two or three generations ago, and map to genes not previously associated with autism. Although no single gene has reached statistical significance, this class of variation should be considered along with genetic and nongenetic factors to better explain the etiology of this complex trait. De novo mutation (DNM) and common genetic variation analyses support a role for variants of large effect as well as polygenic risk contributing to the genetic architecture of autism. However, the majority of autism-associated genes remain unknown and most families do not receive a gene-based diagnosis following genetic analyses. An analysis of ultrarare private mutations that are unique to a family shows that autism probands are significantly enriched for gene-disruptive mutations compared with unaffected siblings. These private inherited mutations are estimated to have arisen two or three generations ago, are more likely to be found in individuals with a family history of autism, and map to genes generally more tolerant to mutation than DNM events enriched in similar functional networks. The transmission of private inherited mutations in autism families supports an oligogenic model of disease where mutations in different genes of moderate effect transmit and accumulate leading to autism development. Larger sample sizes are required to identify genes associated with private gene-disruptive mutations. A multifactorial model including monogenic, oligogenic, and polygenic components along with nongenetic factors will advance our understanding of the development of the disorder. [ABSTRACT FROM AUTHOR]

Copyright of Cultura, Ciencia y Deporte is the property of Cultura, Ciencia y Deporte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objectives: Altered mental status (AMS) is a challenging diagnosis in elderly patients and has a wide range of etiologies. The aim of this study was to know the clinical and etiological profile in the elderly, so that physicians will be better aware of AMS backgrounds and reducing morbidity and mortality rates among the patients. Materials and Methods: This was a prospective observational study conducted at the emergency department (ED) and medical intensive care unit (MICU) of a tertiary care hospital in South India from November 1, 2019, to October 31, 2020. Patients aged 65 years and older who presented to the ED and MICU with AMS were included in this study. They were evaluated clinically and necessary investigations were done to know the etiologies. Results: Among 100 elderly patients, 64% belonged to young old (age group of 65–74 years), 30% belonged to old (age group of 75–84 years), and 6% belonged to oldest old (>85 years). Sixty‑one percent were male and 39% were female. The most common cause for AMS in elderly was primary neurological cause (40%, cerebrovascular accident was most common cause). The other causes were metabolic encephalopathy (29%, hyponatremia being most common) followed by multifactorial causes (24%). Infections and hypertensive encephalopathy were noted in 6% and 1% respectively. The common comorbidities found were hypertension (71%) and type 2 diabetes mellitus (50%), and 28% had diabetes mellitus and hypertension, whereas 25% had multiple comorbidities. Conclusion: The elderly patients who present with AMS must be screened for the above etiologies. This study helps the physicians to have an idea regarding common causes of AMS in elderly patients at presentation, hence appropriate management approach thus helps in reducing morbidity and mortality. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a reproductive disorder with multiple etiologies, mainly characterized by the excess production of androgens. It is equally contributed to by genes and environment. The CYP11A1 gene is imperative for steroidogenesis, so any dysregulation or mutation in this gene can lead to PCOS pathogenesis. Therefore, nucleotide diversity in this gene can be helpful in spotting the likelihood of developing PCOS. The present study was initiated to investigate the effect of single nucleotide polymorphisms in human CYP11A1 gene on different attributes of encoded mutated proteins, i.e., sub-cellular localization, ontology, half-life, isoelectric point, instability index, aliphatic index, extinction coefficient, 3-D and 2-D structures, and transmembrane topology. For this purpose, initially coding sequence (CDS) and single nucleotide polymorphisms (SNPs) were retrieved for the desired gene from Ensembl followed by translation of CDS using EXPASY tool. The protein sequence obtained was subjected to different tools including CELLO2GO, ProtParam, PHYRE2, I-Mutant, SIFT, and PolyPhen. It was found that out of seventy-eight SNPs analyzed in this project, seventeen mutations, i.e., rs750026801 in exon 1, rs776056840, rs779154292 and rs1217014229 in exon 2, rs549043326 in exon 3, rs755186597 in exon 4, rs1224774813, rs757299093 and rs1555425667 in exon 5, rs1454328072 in exon 7, rs762412759 and rs755975808 in exon 8, and rs754610565, rs779413653, rs765916701, rs1368450780, and rs747901197 in exon 9 considerably altered the structure, sub-cellular localization, and physicochemical characteristics of mutated proteins. Among the fifty-nine missense SNPs documented in present study, fifty-five and fifty-three were found to be deleterious according to SIFT and PolyPhen tools, respectively. Forty-nine missense mutations were analyzed to have a decreasing effect on the stability of mutant proteins. Hence, these genetic variants can serve as potential biomarkers in human females for determining the probability of being predisposed to PCOS. [ABSTRACT FROM AUTHOR]

Background: Cleft lip with or without cleft palate (CL/P) is a facial growth ‘disorder that occurs during gestation and has multifactorial causes owing to both genetic and environmental factors. Several factors can increase the likelihood of CL/P, and one of them is family history. Differences in results obtained from studies conducted across several countries concerning family history as a risk factor for CL/P suggest there is no consensus on how the condition is inherited. Purpose: This study aims to review the literature on the role of family history as a risk factor contributing to the incidence of non-syndromic CL/P (NSCL/P). Review: This review discusses the etiology of CL/P and the risk factors influencing the incidence of CL/P. The review also examines the criteria for inheriting multifactorial disorders to calculate the risks involved should there be a recurrence of the condition based on family history. Conclusion: CL/P is a type of multifactorial disorder with unclear etiology. Therefore, it is important to investigate the risk factors stemming from family history (which play an important role) related to the recurrence risk. Additionally, there should be focus on increasing genetic education and offering counselling to parents and pregnant women.

In this work, we provide a mechanistic understanding of the degradation of perovskite solar cells in operation by focusing on methylammonium lead triiodide (CH 3 NH 3 PbI 3 or MAPbI 3) and tracking the evolution of electronic defects via photo-induced current transient spectroscopy (PICTS). Moreover, we also record the degradation of its photovaltaic characteristics over time under various electric load and temperature conditions. Using PICTS, we found that bands of trap states, initially highly localized deep within the band gap of the perovskite, widened over the exposure period. This effect was exacerbated with increasing temperature. Further, using the design of experiment methodology for this multifactorial study, we found that two interaction factors (temperature× load & temperature× time) were significant in the degradation of the perovskite cells, validating the importance of our holistic approach. Through these observations, we establish a mechanistic link between deep-level traps and photovoltaic characteristics. [Display omitted] • Deep-level traps in degrading perovskites were measured via PICTS. • Band of trap states widen in degrading perovskites. • Fill factor tracks well with the trap activation energy. • These measurements can inform the quality of the fabrication process. [ABSTRACT FROM AUTHOR]

The study aim was to identify the effects of the rearing management applied throughout the heifers' life on the carcass (e.g., conformation, marbling, fat) and meat (color, texture, and sensory profiles) properties. From the individual data of 171 heifers from 25 commercial farms, a typology of four rearing managements was established from 50 rearing factors. The managements had an effect on the conformation, the color (fat and muscle), and the rhomboideus grain meat, for the carcass, and the lightness, the atypical flavor, and the overall acceptability for the longissimus (LM) meat. The carcass traits compared to the meat were more sensitive to a change of rearing management. Our results confirmed that it was possible to target the same carcass or meat quality from different managements. Moreover, according to the aims of the targeted carcass and LM meat quality, management 3 could be an interesting trade-off to jointly manage the quality of both products. For example, the carcasses that were produced had a high conformation, smooth meat grain and the LM meat was more liked. This management was intermediate compared to the other rearing managements and had a long fattening period with a diet mainly based on conserved grass and a high concentrate quantity. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Age-related decline in physical capacity can lead to frailty, associated with an increased vulnerability to adverse health outcomes and greater healthcare utilization. In an aging population, effective strategies to prevent physical decline and frailty, and preserve independence are needed. Prevention programs for vulnerable community-dwelling older adults are, however, often not yet established and implemented in routine practice. Research on the feasibility, implementation, and (cost-)effectiveness of multifactorial, interdisciplinary intervention programs that take advantage of available services of healthcare providers is also limited. The main aim of this study is to evaluate the effectiveness of such an intervention program (PromeTheus) to prevent functional and mobility decline for more participation in community-dwelling (pre-)frail older adults.Methods: The study is designed as a three-center, randomized controlled trial with a 12-month intervention period. Four hundred community-dwelling (pre-)frail (Clinical Frailty Scale score 4-6) older adults (≥70 years) will be randomized in a 1:1 ratio to the intervention group (IG) or the control group (CG). The IG will receive the PromeTheus program consisting of obligatory home-based physical exercises (Weight-bearing Exercise for Better Balance) accompanied by physiotherapists and facultative counseling services (person-environment-fit, coping with everyday life, nutrition, group-based activities) delivered via existing healthcare structures (e.g., social workers, nutritionists). The CG will receive usual care and a one-time counseling session on recommendations for physical activity and nutrition. Primary outcomes assessed at months 6 and 12 are the function component of the Late-Life Function and Disability Instrument and the University of Alabama at Birmingham Life-Space Assessment. Secondary outcomes are disability, physical capacity and activity, frailty, nutritional status, falls, fear of falling, health status, and psychosocial components. Process and economic evaluations are also conducted. Primary statistical analyses will be based on the intention-to-treat principle.Discussion: Compared to usual care, the PromeTheus program is expected to result in higher function and mobility, greater independence and lower need for care, and more participation. As the PromeTheus program draws on existing German healthcare structures, its large-scale translation and delivery will be feasible, if evidence of (cost-)effectiveness and successful implementation can be demonstrated.Trial Registration: German Clinical Trials Register, . Registered on March 11, 2021. [ABSTRACT FROM AUTHOR]

Kidney stone disease is one of the most common urologic disorders worldwide. The incidence of kidney stones disease is increasing all over the world. It is a multifactorial disease accompanied by various factors. The dietary factor is one of the most important risk factors for the formation and recurrence of kidney stone disease. Formation and recurrence of kidney stone disease can be prevented by modifying our day to day dietary habits. Fewer intakes of animal protein, higher intake of fluid, higher intake of fruits, and higher intake of green leafy vegetables, which contain a low amount of oxalate, can prevent the formation of kidney stones and recurrence of kidney stones. From this review, it may be presumed that the higher prevalence rate of kidney stone disease in northeast India may be the dietary factors accompanied by environmental and climatic conditions of the region.

Electric power dispatch issue mainly consists of two optimization tasks: active and reactive power dispatches, each of which is a non-linear multi-objective optimization problem with a series of constraints. Traditional evolutionary algorithms are focused on single-task optimization for active or reactive power dispatch and they are not able to deal with several (single- or multi-objective) optimization tasks simultaneously. In this paper, to solve this problem, a multitasking electric power dispatch approach is proposed by introducing the multi-objective multifactorial optimization (MO-MFO) algorithm and integrating it with the characteristics of power system. The approach exhibits the great potential to be developed as a cloud-computing solver or platform for future large-scale smart grid applications involving different market entities because of its implicit parallel computation mechanism. The multitasking approach is thoroughly tested and benchmarked with IEEE-30-bus and IEEE-118-bus standard systems and exhibits generally better performances as compared to previously proposed Pareto heuristic approaches for electric power dispatch.

A multifactorial experimental research on erosion-corrosion behavior of liquid–solid swirling flow in pipeline was carried out by a circulating loop system in combination with a variety of test methods. The analysis of statistical significance reveals that the variation of erosion-corrosion rate is explained by three main effects (velocity, sand size, and sand concentration) and two interactions (velocity/sand size and sand size/sand concentration). An empirical linear regression equation with a R2 value of 0.9043 was established to describe the correlation of erosion-corrosion rate with the test parameters and their interactions. It is concluded by microstructural examination of the working electrode surface that under the condition of liquid–solid swirling flow, cutting and corrosion pits are the primary forms of surface damage. The comparative analysis of erosion-corrosion between swirling flow and non-swirling flow shows that the net effect of swirling flow on erosion-corrosion varies with sand size. The corrosion product analysis by EDS and XPS show the presence of Fe2O3 and CaCO3 under swirling flow and non-swirling flow conditions. Furthermore, the element content analysis of EDS and XPS showed that compared with the non-swirling flow, the oxygen content on the electrode surface under the swirling flow condition increased by 42.42% and 35.06%, respectively.

La maternité précoce est classée comme un problème de santé publique majeur par l'Organisation mondiale de la santé. À Haïti, en dépit de l'instauration de nombreux programmes de planification familiale par les pouvoirs publics, la fécondité précoce demeure relativement élevée. Ainsi, au regard de la persistance de ce phénomène et de ses conséquences tant sur la jeune fille que sur son enfant, cet article a pour objectifs d'identifier et de hiérarchiser les facteurs sous-jacents de la fécondité précoce à Haïti. Afin de parvenir aux objectifs fixés dans le cadre de cet article, nous avons mobilisé les données de la dernière Enquête Démographique et de Santé réalisée à Haïti en 2017. L'analyse des données a consisté à la réalisation de tris à plats, de tris croisés et à l'estimation d'un modèle de régression logistique. Nous observons que la religion, le niveau d'instruction, l'âge à la première relation sexuelle, l'âge à la première union et le nombre idéal d'enfants sont les facteurs qui influencent la maternité au moment de l'adolescence. Et parmi ces facteurs, on constate que l'âge à la première union et l'âge à la première relation sexuelle sont ceux qui contribuent le plus à l'explication de ce phénomène. Étant donné que la maternité à l'adolescence à Haïti est un phénomène multifactoriel, la prévention exige l'application de stratégies multidimensionnelles par les pouvoirs publics. The World Health Organization classifies adolescent motherhood as a significant public health problem. In Haiti, despite the government's effort to establish family planning programs, fertility among adolescents remains relatively high. Considering the persistence of this phenomenon as well as associated consequences for young girls and their children, this paper aims to identify the underlying factors of early fertility in Haiti. We analyzed data from the 2017 Haiti Demographic and Health Survey. Our analysis focused on women of reproductive age (15–49 years) who had their first birth before the age of 20 years. We conducted a descriptive analysis and estimated a logistic regression model to analyze the association of socioeconomic factors with adolescent fertility. We observed that religion, education level, age at first sexual intercourse, age at first union and ideal number of children significantly influenced adolescent motherhood in Haiti. Further, we found that age at first union and age at first sexual intercourse had the most significant effect on the phenomenon. Given that adolescent motherhood is a multifactorial phenomenon in Haiti, prevention is essential and requires policymakers' multidimensional strategies. [ABSTRACT FROM AUTHOR]

Background: Although falls are common, costly, and often preventable, emergency department (ED)‐initiated fall screening and prevention efforts are rare. The Geriatric Emergency Medicine Applied Research Falls core (GEAR‐Falls) was created to identify existing research gaps and to prioritize future fall research foci. Methods: GEAR's 49 transdisciplinary stakeholders included patients, geriatricians, ED physicians, epidemiologists, health services researchers, and nursing scientists. We derived relevant clinical fall ED questions and summarized the applicable research evidence, adhering to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Scoping Reviews. The highest‐priority research foci were identified at the GEAR Consensus Conference. Results: We identified two clinical questions for our review (1) fall prevention interventions (32 studies) and (2) risk stratification and falls care plan (19 studies). For (1) 21 of 32 (66%) of interventions were a falls risk screening assessment and 15 of 21 (71%) of these were combined with an exercise program or physical therapy. For (2) 11 fall screening tools were identified, but none were feasible and sufficiently accurate for ED patients. For both questions, the most frequently reported study outcome was recurrent falls, but various process and patient/clinician‐centered outcomes were used. Outcome ascertainment relied on self‐reported falls in 18 of 32 (56%) studies for (1) and nine of 19 (47%) studies for (2). Conclusion: Harmonizing definitions, research methods, and outcomes is needed for direct comparison of studies. The need to identify ED‐appropriate fall risk assessment tools and role of emergency medical services (EMS) personnel persists. Multifactorial interventions, especially involving exercise, are more efficacious in reducing recurrent falls, but more studies are needed to compare appropriate bundle combinations. GEAR prioritizes five research priorities: (1) EMS role in improving fall‐related outcomes, (2) identifying optimal ED fall assessment tools, (3) clarifying patient‐prioritized fall interventions and outcomes, (4) standardizing uniform fall ascertainment and measured outcomes, and (5) exploring ideal intervention components. [ABSTRACT FROM AUTHOR]

Multigene panel testing has led to an increase in the number of variants of uncertain significance identified in the TP53 gene, associated with Li‐Fraumeni syndrome. We previously developed a quantitative model for predicting the pathogenicity of P53 missense variants based on the combination of calibrated bioinformatic information and somatic to germline ratio. Here, we extended this quantitative model for the classification of P53 predicted missense variants by adding new pieces of evidence (personal and family history parameters, loss‐of‐function results, population allele frequency, healthy individual status by age 60, and breast tumor pathology). We also annotated which missense variants might have an effect on splicing based on bioinformatic predictions. This updated model plus annotation led to the classification of 805 variants into a clinically relevant class, which correlated well with existing ClinVar classifications, and resolved a large number of conflicting and uncertain classifications. We propose this model as a reliable approach to TP53 germline variant classification and emphasize its use in contributing to optimize TP53‐specific ACMG/AMP guidelines. [ABSTRACT FROM AUTHOR]