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Heart failure—either with reduced or preserved ejection fraction (HFrEF/HFpEF)—is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs. [ABSTRACT FROM AUTHOR]

In this review paper, we present the common etiology, presentation, diagnosis, and management of the following three common bunion formations: dorsal bunion, tailor's bunion, and hallux valgus (HV). Bunions are common pathologies that present to a variety of clinics, so it is important for providers to have a base understanding of these in order to provide the best care to patients. Many of these bunion formations have a variety of causes which allow providers to manage them before surgical intervention is required. The aim of this review paper is to bring attention and expanded insight on these common bunion presentations in order to minimize morbidity early on. The information provided in this review will allow both primary care and subspecialty physicians with the knowledge to accurately diagnose and optimally manage these bony deformities of the lower extremity. [ABSTRACT FROM AUTHOR]

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: PPHN is a common cause of neonatal respiratory failure and is still a serious condition and associated with high mortality. Objectives: To compare the demographic variables, clinical characteristics, and treatment outcomes in neonates with PHHN who underwent ECMO and survived compared to neonates with PHHN who underwent ECMO and died. Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of PPHN in neonates who underwent ECMO, published from January 1, 2010 to May 31, 2023, with English language restriction. Results: Of the 5689 papers that were identified, 134 articles were included in the systematic review. Studies involving 1814 neonates with PPHN who were placed on ECMO were analyzed (1218 survived and 594 died). Neonates in the PPHN group who died had lower proportion of normal spontaneous vaginal delivery (6.4% vs 1.8%; p value > 0.05) and lower Apgar scores at 1 min and 5 min [i.e., low Apgar score: 1.5% vs 0.5%, moderately abnormal Apgar score: 10.3% vs 1.2% and reassuring Apgar score: 4% vs 2.3%; p value = 0.039] compared to those who survived. Neonates who had PPHN and died had higher proportion of medical comorbidities such as omphalocele (0.7% vs 4.7%), systemic hypotension (1% vs 2.5%), infection with Herpes simplex virus (0.4% vs 2.2%) or Bordetella pertussis (0.7% vs 2%); p = 0.042. Neonates with PPHN in the death group were more likely to present due to congenital diaphragmatic hernia (25.5% vs 47.3%), neonatal respiratory distress syndrome (4.2% vs 13.5%), meconium aspiration syndrome (8% vs 12.1%), pneumonia (1.6% vs 8.4%), sepsis (1.5% vs 8.2%) and alveolar capillary dysplasia with misalignment of pulmonary veins (0.1% vs 4.4%); p = 0.019. Neonates with PPHN who died needed a longer median time of mechanical ventilation (15 days, IQR 10 to 27 vs. 10 days, IQR 7 to 28; p = 0.024) and ECMO use (9.2 days, IQR 3.9 to 13.5 vs. 6 days, IQR 3 to 12.5; p = 0.033), and a shorter median duration of hospital stay (23 days, IQR 12.5 to 46 vs. 58.5 days, IQR 28.2 to 60.7; p = 0.000) compared to the neonates with PPHN who survived. ECMO-related complications such as chylothorax (1% vs 2.7%), intracranial bleeding (1.2% vs 1.7%) and catheter-related infections (0% vs 0.3%) were more frequent in the group of neonates with PPHN who died (p = 0.031). Conclusion: ECMO in the neonates with PPHN who failed supportive cardiorespiratory care and conventional therapies has been successfully utilized with a neonatal survival rate of 67.1%. Mortality in neonates with PPHN who underwent ECMO was highest in cases born via the caesarean delivery mode or neonates who had lower Apgar scores at birth. Fatality rate in neonates with PPHN who underwent ECMO was the highest in patients with higher rate of specific medical comorbidities (omphalocele, systemic hypotension and infection with Herpes simplex virus or Bordetella pertussis) or cases who had PPHN due to higher rate of specific etiologies (congenital diaphragmatic hernia, neonatal respiratory distress syndrome and meconium aspiration syndrome). Neonates with PPHN who died may need a longer time of mechanical ventilation and ECMO use and a shorter duration of hospital stay; and may experience higher frequency of ECMO-related complications (chylothorax, intracranial bleeding and catheter-related infections) in comparison with the neonates with PPHN who survived. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a fatal lung disease affecting approximately 5 million people worldwide, with a 5-year survival rate of less than 50%. Currently, the only available treatments are palliative care and lung transplantation, as there is no curative drug for this condition. The disease involves the excessive synthesis of the extracellular matrix (ECM) due to alveolar epithelial cell damage, leading to scarring and stiffening of the lung tissue and ultimately causing respiratory failure. Although multiple factors contribute to the disease, the exact causes remain unclear. The mechanical properties of lung tissue, including elasticity, viscoelasticity, and surface tension, are not only affected by fibrosis but also contribute to its progression. This paper reviews the alteration in these mechanical properties as pulmonary fibrosis progresses and how cells in the lung, including alveolar epithelial cells, fibroblasts, and macrophages, respond to these changes, contributing to disease exacerbation. Furthermore, it highlights the importance of developing advanced in vitro models, based on hydrogels and 3D bioprinting, which can accurately replicate the mechanical and structural properties of fibrotic lungs and are conducive to studying the effects of mechanical stimuli on cellular responses. This review aims to summarize the current understanding of the interaction between the progression of pulmonary fibrosis and the alterations in mechanical properties, which could aid in the development of novel therapeutic strategies for the disease. [ABSTRACT FROM AUTHOR]

The International League Against Epilepsy ( ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century. [ABSTRACT FROM AUTHOR]

We investigated whether dried cerebrospinal fluid ( CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents ( GE)/μL (interquartile range 5.5 GE/μL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis ( n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples ( n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 104 GE/μL (1.2 × 105; 1 to 6.1 × 106 DNA GE/μL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies. [ABSTRACT FROM AUTHOR]

Sarcopenia is the age-associated loss of skeletal muscle mass and function. It is a major clinical problem for older people and research in understanding of pathogenesis, clinical consequences, management, and socioeconomic burden of this condition is growing exponentially. The causes of sarcopenia are multifactorial, including inflammation, insulin resistance, changing endocrine function, chronic diseases, nutritional deficiencies and low levels of physical activity. Operational definition of sarcopenia combines assessment of muscle mass, muscle strength and physical performance. The diagnosis of sarcopenia should be based on having a low appendicular fat free mass in combination with low handgrip strength or poor physical functioning. Imaging techniques used for estimating lean body mass are computed tomography, magnetic resonance imaging, bioelectrical impedance analysis and dual energy X-ray absorptiometry, the latter considered as the preferred method in research and clinical use. Pharmacological interventions have shown limited efficacy in counteracting the age-related skeletal muscle wasting. Recent evidence suggests physical activity and exercise, in particular resistance training, as effective intervention strategies to slow down sarcopenia. The Italian Society of Orthopaedics and Medicine (OrtoMed) provides this position paper to present the update on the role of exercise on sarcopenia in the elderly. [ABSTRACT FROM AUTHOR]

Background: Functional somatic symptoms and disorders are common and complex phenomena involving both bodily and brain processes. They pose major challenges across medical specialties. These disorders are common and have significant impacts on patients' quality of life and healthcare costs.Main Body: We outline five problems pointing to the need for a new classification: (1) developments in understanding aetiological mechanisms; (2) the current division of disorders according to the treating specialist; (3) failure of current classifications to cover the variety of disorders and their severity (for example, patients with symptoms from multiple organs systems); (4) the need to find acceptable categories and labels for patients that promote therapeutic partnership; and (5) the need to develop clinical services and research for people with severe disorders. We propose 'functional somatic disorders' (FSD) as an umbrella term for various conditions characterised by persistent and troublesome physical symptoms. FSDs are diagnosed clinically, on the basis of characteristic symptom patterns. As with all diagnoses, a diagnosis of FSD should be made after considering other possible somatic and mental differential diagnoses. We propose that FSD should occupy a neutral space within disease classifications, favouring neither somatic disease aetiology, nor mental disorder. FSD should be subclassified as (a) multisystem, (b) single system, or (c) single symptom. While additional specifiers may be added to take account of psychological features or co-occurring diseases, neither of these is sufficient or necessary to make the diagnosis. We recommend that FSD criteria are written so as to harmonise with existing syndrome diagnoses. Where currently defined syndromes fall within the FSD spectrum - and also within organ system-specific chapters of a classification - they should be afforded dual parentage (for example, irritable bowel syndrome can belong to both gastrointestinal disorders and FSD).Conclusion: We propose a new classification, 'functional somatic disorder', which is neither purely somatic nor purely mental, but occupies a neutral space between these two historical poles. This classification reflects both emerging aetiological evidence of the complex interactions between brain and body and the need to resolve the historical split between somatic and mental disorders. [ABSTRACT FROM AUTHOR]

Studies on numerous species have demonstrated strikingly conserved mechanisms that determine the aging process, from yeasts to worms, flies, zebrafish, mice, and humans. The fruit fly Drosophila melanogaster is an excellent model organism for studying the biological basis of normal aging and etiology of age-related diseases. Since its inception in 1967, the Bloomington Drosophila Stock Center (BDSC) has grown into the largest collection of documented D. melanogaster strains (currently > 91,000). This paper aims to briefly review conserved mechanisms of aging and provides a guide to help users understand the organization of stock listings on the BDSC website and familiarize themselves with the search functions on BDSC and FlyBase, with an emphasis on using genes in conserved pathways as examples to find stocks for aging studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Eales' Disease, an ocular condition characterized by unknown pathophysiology, exhibits a higher prevalence among young males. Since the etiology of the disease remains unclear, a comprehensive exploration of clinical presentations and diagnostic approaches is undertaken to deepen insights into its current understanding. Furthermore, potential cofactors that may trigger Eales' Disease are reviewed, investigating the association between Eales' Disease and other ocular conditions such as diabetic retinopathy and glaucoma. Additionally, diverse therapeutic interventions across disease stages are examined to assess the efficacy and possibility of repurposing treatments from related conditions. Through this review, the aim is to extend and elucidate potential study areas to facilitate a comprehensive understanding of Eales' Disease and aid patients in preventing the disease or finding optimal treatment strategies. Eales' Disease is an idiopathic peripheral retinal vasculopathy first described by British ophthalmologist Henry Eales in 1880. Most prevalent in healthy young males, Eales' Disease often presents with symptoms of sudden blurry or decreased vision and floaters. Although no clear, standardized stage of the disease exists, it progresses through three overlapping phases—peripheral periphlebitis, ischemic capillary ischemia, and retinal neovascularization. The etiology of Eales' Disease is unknown and appears to be multifactorial, but post-TB hypersensitivity to tuberculoprotein and M. tuberculosis DNA is the most potential cause in the etiology of Eales' Disease. With a thorough examination of the clinical presentation and diagnosis of Eales' Disease—incorporating the latest clinical findings related to the condition—the investigation for Eales' Disease extends to explore recent potential connections with other ocular conditions or possible cofactors, such as glaucoma, uncontrolled diabetes, drug abuse, or inherited medical conditions. Moreover, focusing on critical insights into the treatment of Eales' Disease across its various stages of progression, the overarching goal of the paper is to refine and suggest possible future diagnostic and therapeutic strategies. Widening our understanding of pathophysiology and utilizing various treatment options for individual patients holds immense potential for advancing ocular medicine and optimizing patient care for people with this disease with unknown pathophysiology. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease. [ABSTRACT FROM AUTHOR]

Central precocious puberty (CPP) is a rare disease of poorly understood etiology. The cause is mostly idiopathic. However, congenital and acquired structural changes in the central nervous system are also involved. Prevalent organic changes in the central nervous system, especially among boys, prompt imaging assessment in each case of CPP. In addition, genetic and environmental factors have been reported. Safe and effective treatment is available. The time of treatment implementation is crucial to the successful outcome. Proper diagnosis and treatment make it possible to avoid a number of complications of untreated CPP. There are only a few studies analyzing the prevalence and risk factors for the disease. The aim of this paper is to discuss the current causes of CPP with particular consideration of neurological aspects. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor–1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets. [ABSTRACT FROM AUTHOR]

In Romania, 7.9% in men and 3.8% in women of the general population have used cannabis at least once in their lives. The purpose of this paper is to highlight and evaluate aspects regarding the etiology and epidemiology of lethal cases caused by intoxications using case studies provided by the Sibiu Forensic Medicine Service. The case showcases a period of 10 years (2010-2019), documented within the archives of the service, where personal data of the deceased, as well as causal aspects of the death, are recorded. The present paper includes 169 cases in which the intoxication had a lethal result, registered at the Sibiu Forensic Medicine Service between 2010-2019. Out of the total deaths in the same period (3,355), deaths from intoxication represent a percentage of 5.04%, and of the total violent deaths a percentage of 8.68%. Prevention is the most effective method of combating intoxication. [ABSTRACT FROM AUTHOR]

Aim: This bibliometric analysis aims to evaluate the characteristics and impact of the top 100 cited articles published under the title of diabetes mellitus. Metods: We performed to define the most cited articles in diabetes research by using the Web of Science. The papers were analyzed in terms of their year of publication, journal of publication, authors, impact factor (IF), total citations number, the average number of citations per year, studies topic, and type. Results: The number of citations ranged from 1519 to 17.298. They were published from 1987 to 2018. The most cited articles were published in the New England Journal of Medicine (n = 26), followed by Diabetes Care (n = 17) and Lancet (n = 9). The original scientific paper was the most popular article type (46%), followed by review article (36%). The generality studies' subject was about treatment (n = 22), followed by pathogenesis (n = 19), etiology and risk factors (n = 16), diagnosis, screening, classification (n = 15), epidemiology (n = 11), prevention (n = 11) and complications (n = 6). There was a correlation between the average number of citations per year (ACpY) and IF (p = < 0.010, r = 0.259), citations and ACpY (p = < 0.001, r = 0.646), citations and time (p = 0.008, r = 0.266). Conclusion: This study showed that original scientific papers were the most-cited and more articles were published in influential journals. Articles on diabetes treatment and pathogenesis were popular topics. Future interventions should focus on the management and prevention of diabetes. [ABSTRACT FROM AUTHOR]

Background: The concept of control has long been suggested as a central factor in eating disorder (ED) aetiology. The concept is now so mainstream that it risks being used in a potentially reductionist, stigmatising or otherwise harmful manner. In this paper, we explore and discuss our positions on the use of control-related terminology for EDs. Methods: The authors of this auto-ethnographic position paper include academic researchers, individuals with lived experience and clinicians (not mutually exclusive). In sharing our experiences and observations, we aim to raise awareness of the wider impacts that control framing can have on ED perceptions, treatment, recovery and individuals' lived experience. Results: We argue that although control can play a role in some ED experiences, an overemphasis upon this factor to the exclusion of other conceptualisations is not beneficial. Conclusions: To mitigate against pathologisation of an individual, it is important to challenge a discourse that can lead to EDs being perceived as something 'wrong' with the individual, rather than a consequence of life events or other environmental influences. We identify priorities for the future for researchers, clinicians, policy makers and the wider public. Plain English summary: Control has often been described as a central factor within Eating Disorders (EDs). Whilst control can play a role in ED experiences, we argue that overemphasis upon this factor can result in other important factors being overlooked. For many individuals, EDs are the consequence of life events and/or other environmental influences. With this in mind, discourse which overemphasises control (e.g., rather than coping) can inaccurately portray EDs as something 'wrong' with the individual. It is important to challenge this discourse to encourage more appropriate perceptions of EDs. In turn, this could improve understanding and treatment of EDs, reduce stigma, and promote recovery. [ABSTRACT FROM AUTHOR]

A previous version was presented as an oral paper at the Annual National Conference of The Indian Psychiatric Society (ANCIPS), Ranchi, India, 2018. ABSTRACT Intracranial space-occupying lesions (ICSOLs) like hematomas, neoplasms, granulomas, or brain abscesses can present with diverse neuropsychiatric manifestations. Subtle cognitive deficits, anxiety, affective symptoms--especially depression, personality changes, and psychosis, most commonly hallucinations, have been associated with organic etiology. Catatonia has seen a paradigmatic shift in its etiological basis and space-occupying lesion is a rare yet important cause to be investigated for, as it poses a challenge in terms of searching for early clinical indicators of cerebral pathology and difference in treatment outcome due to etiology. Here we present a case of catatonia due to ICSOL in a patient of affective disorder with a history of recurrent catatonic episodes, highlighting the importance of approaching each catatonic presentation as a syndrome with diverse possible etiology. [ABSTRACT FROM AUTHOR]

Ferroptosis, an emerging paradigm of programmed cellular necrosis posited in recent years, manifests across a spectrum of maladies with profound implications for human well-being. Numerous investigations substantiate that modulating ferroptosis, whether through inhibition or augmentation, plays a pivotal role in the etiology and control of numerous age-related afflictions, encompassing neurological, circulatory, respiratory, and other disorders. This paper not only summarizes the regulatory mechanisms of ferroptosis, but also discusses the impact of ferroptosis on the biological processes of aging and its role in age-related diseases. Furthermore, it scrutinizes recent therapeutic strides in addressing aging-related conditions through the modulation of ferroptosis. The paper consolidates the existing knowledge on potential applications of ferroptosis-related pharmacotherapies and envisages the translational prospects of ferroptosis-targeted interventions in clinical paradigms. [Display omitted] [ABSTRACT FROM AUTHOR]

Goose astrovirus (GAstV) is a small, non-encapsulated virus, whose genome consists of a single-stranded, positive-stranded RNA molecule with a genome length of 7.1-7.3 kb. GAstV is a new member of the genus avian astrovirus in the family Astroviridae, which can be classified into two genetic subgroups (GAstV-1, GAstV-2) based on genetic homology and genetic distance, which are not yet involved in official classification. GAstV infection can lead to diarrhea, growth inhibition, and clinical signs dominated by joint urate deposition and visceral urate deposition in geese, and it is considered to be the main etiological agent causing gout in geese. There is a lack of commercialized vaccines or therapeutic drugs against GAstV, relying mainly on biosecurity measures for prevention and control. China's researchers first detected and isolated the GAstV strain in gouty geese flocks in Shandong Province in 2017. GAstV spreads quickly and radiates widely, with related cases reported in Guangdong, Fujian, and Anhui in the same year, resulting in up to 1.2 billion yuan to 1.5 billion yuan in economic losses. The incidence of GAstV can be up to 80%, and the mortality rate can be up to 50%. GAstV can lead to immunosuppression in geese, and they are susceptible to infection with other pathogens in the course of feeding, resulting in more severe clinical symptoms and increasing the difficulty of pathogen prevention and control. GAstV not only infects its natural host, geese, but also has the ability to cross the species barrier, causing diarrhea, growth inhibition, and triggering urate deposition in internal organs or joints in chickens and ducks. This suggests that GAstV may have the potential for human-animal transmission, and subsequent studies should strengthen the epidemiological monitoring of GAstV and pay close attention to the changes in its transmission characteristics. At present, scholars have made certain research progress in the pathogen detection of GAstV, and have established various technical methods that can efficiently and accurately detect GAstV. However, the research on the pathogenic mechanism of GAstV has not yet been in-depth, the research on vaccine preparation is relatively weak, and there is no uniform and effective in vitro culture method for GAstV, which has seriously hindered the pace of basic research on the pathogen. In order to better understand the impact of GAstV on goose farming industry in China, this paper reviews four aspects of GAstV, namely, pathogenesis, epidemiology, host immune response, and the association between GAstV and gout, which will provide a reference for the follow-up research and scientific control of GAstV. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a complex autoimmune disease with an unknown aetiology. However, rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) play a significant role in initiating and perpetuating destructive joint inflammation by expressing immuno-modulating cytokines, adhesion molecules, and matrix remodelling enzymes. In addition, RA-FLS are primary drivers of inflammation, displaying high proliferative rates and an apoptosis-resistant phenotype. Thus, RA-FLS-directed therapies could become a complementary approach to immune-directed therapies by predicting the optimal conditions that would favour RA-FLS apoptosis, limit inflammation, slow the proliferation rate and minimise bone erosion and cartilage destruction. In this paper, we present a large-scale Boolean model for RA-FLS that consists of five submodels focusing on apoptosis, cell proliferation, matrix degradation, bone erosion and inflammation. The five-phenotype-specific submodels can be simulated independently or as a global model. In silico simulations and perturbations reproduced the expected biological behaviour of the system under defined initial conditions and input values. The model was then used to mimic the effect of mono or combined therapeutic treatments and predict novel targets and drug candidates through drug repurposing analysis. [ABSTRACT FROM AUTHOR]

Biological fish can always sense the state of water flow and regulate the angle of attack in time, so as to maintain the highest movement efficiency during periodic flapping. The biological adjustment of the caudal fin's angle of attack (AoA) depends on the contraction/relaxation of the tail muscles, accompanying the variation in tail stiffness. During an interaction with external fluid, it helps to maintain the optimal angle of attack during movement, to improve the propulsion performance. Inspired by this, this paper proposes a tail joint motion control scheme based on AoA feedback for the high-speed swimming of bionic dolphins. Firstly, the kinematic characteristics of the designed robot dolphin are analyzed, and the hardware basis is clarified. Second, aiming at the deficiency of the tail motor, which cannot effectively cooperate with the waist joint motor during high-frequency movement, a compensation model for the friction force and latex skin-restoring force is designed, and a joint angle control algorithm based on fuzzy inference is proposed to realize the tracking of the desired joint angle for the tail joint in torque mode. In addition, a tail joint closed-loop control scheme based on angle of attack feedback is proposed to improve the motion performance. Finally, experiments verify the effectiveness of the proposed motion control scheme. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the percentage of posterior circulation arterial ischaemic stroke (PCAIS) caused by craniovertebral junction (CVJ) anomalies and describe their clinical course. Children admitted to a tertiary care paediatric hospital with PCAIS between July 2017 and December 2020 were assessed retrospectively for disease aetiology. We reviewed the clinical, radiological, and surgical details of children with evidence of CVJ anomalies. Fourteen (24.1%) of 58 children admitted with arterial ischaemic stroke had posterior circulation involvement. The mean age of patients presenting with posterior circulation stroke was 6 years 6 months (range 3 months–15 years), 11 were male. Six of 14 cases with PCAIS were due to CVJ anomaly, their ages ranged from 4 months to 15 years (two age ranges were noted, 4 months–4 years and 11–15 years), four were male. Two children had atlantoaxial dislocation with basilar invagination, two had Bow Hunter syndrome with Chiari malformation type 1 (one with completed stroke), one had Chiari malformation type 1 alone, and one presented with Farber disease with proatlas segmentation anomaly in CVJ. The time lag to stroke and CVJ diagnosis ranged from 2 weeks to 24 months. A dynamic angiogram was required to evaluate biomechanical changes on scans with inconclusive findings on standard stroke imaging. CVJ anomalies are an important treatable cause of paediatric posterior circulation stroke. Cervical spine x‐ray in flexion and extension should be done in all patients with posterior circulation stroke beyond the acute period. In cryptogenic aetiology, provocative angiography with guarded neck rotation should be considered to evaluate possible dynamic vertebral artery compression. What this paper adds: Craniovertebral junction anomalies are an important cause of posterior circulation stroke in children.Evidence of flat occiput, short neck, and short stature in children with posterior circulation stroke should be assessed.Dynamic imaging helps identify dynamic vertebral artery compression. [ABSTRACT FROM AUTHOR]

Glaucoma is a series of linked optic diseases resulting in progressive vision loss and total blindness due to the acquired loss of retinal ganglion cells. This harm to the optic nerve results in visual impairment and, ultimately, total blindness if left untreated. Primary open-angle glaucoma (POAG) is the most frequent variety within the large family of glaucoma. It is a multifaceted and heterogeneous condition with several environmental and genetic variables aiding in its etiology. By 2040, there will be 111.8 million glaucoma patients globally, with Asia and Africa accounting for the vast majority. The goal of this review is to elaborate on the role of genes (nuclear and mitochondrial) as well as their variants in the pathogenesis of POAG. PubMed and Google Scholar databases were searched online for papers until September 2022. Prevalence and inheritance patterns vary significantly across different ethnic and geographic populations. Numerous causative genetic loci may exist; however, only a few have been recognized and characterized. Further investigation into the genetic etiology of POAG is expected to uncover novel and intriguing causal genes, allowing for a more precise pathogenesis pattern of the disease. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around the age of 20–30 years. Still, in recent years, MS has been increasingly recognized among the pediatric population, being characterized by several peculiar features compared to adult-onset disease. Unfortunately, the etiology and disease mechanisms are poorly understood, rendering the already limited MS treatment options with uncertain efficacy and safety in pediatric patients. Thus, this review aims to shed some light on the progress in MS therapeutic strategies specifically addressed to children and adolescents. In this regard, the present paper briefly discusses the etiology, risk factors, comorbidities, and diagnosis possibilities for pediatric-onset MS (POMS), further moving to a detailed presentation of current treatment strategies, recent clinical trials, and emerging alternatives. Particularly, promising care solutions are indicated, including new treatment formulations, stem cell therapies, and cognitive training methods. [ABSTRACT FROM AUTHOR]

The connection between the festival of Pesaḥ-Maṣṣot and the Israelites' exodus from Egypt is a cornerstone of Jewish identity and religious practice which has its roots in the festival calendars of the Pentateuch (Exod. 12–13; Exod. 23; Lev. 23; Deut. 16). However, a closer investigation shows that the texts in question differ considerably both with respect to the characteristics of the festival and its etiological connection with the exodus. The present paper focuses particularly on the complex, and in parts contradictory, festival ordinances in Exod. 12:1–13:16 and argues that the present form of the passage results from a multi-step process of supplementation and revision. In this process, the once separate festivals of Pesaḥ and Maṣṣot were gradually merged to a single celebration which, in turn, led to various adjustments of their etiological connection to the events of the exodus. [ABSTRACT FROM AUTHOR]

The aetiology of foetal presentation in cattle is still unresolved. The hind legs are the main source of propulsive movement in cattle, which provides changes in foetal presentation. The assumption is that in the absence of hind leg movements of the foetus, as in the case of the congenital malformation, Perosomus elumbis, the incidence of the anterior and posterior presentation will be the same. The Scopus database, the world wide web (www), and the list of article references were searched using the keyword, Perosomus elumbis. Manuscripts with data about the foetal presentation were included and 21 cases in 16 articles were identified. There were 11 cases of anterior presentation and 10 of posterior presentation. The Chi-square test didn't show a statistically significant difference between the incidence of anterior and posterior presentation. This finding supports the assumption that the posterior presentation is the result of the random occupying of the intrauterine space with the same probability of anterior and posterior presentation. To confirm or exclude at random the occupant of the intrauterine space with the same probability for anterior and posterior presentation as a general mechanism for posterior presentation in cattle foetuses, it is necessary to determine the incidence of foetal presentation at birth in various veterinary entities accompanied by an increased incidence of posterior presentation. The aim of the paper was to investigate the incidence of posterior and anterior presentation in Perosomus elumbis. [ABSTRACT FROM AUTHOR]

This paper presents and responds to On the Heels of Ignorance, a sociological study which identifies five fundamental epistemological paradigm changes in American psychiatry in the service of its survival and details several tactics that have been employed to facilitate these professional reinventions. Issues raised in this presentation include the relationship between psychiatry, society and the state, and the nature and significance of psychiatric expertise. The dynamic of these relationships and the complexities of the required expertise create their own challenges for the advancement and professional accountability of the specialty. The conclusion suggests some future imperatives. [ABSTRACT FROM AUTHOR]

Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the most promising and evidence-based hypothesis is the development of sarcoidosis as an autoimmune disease, provoked by various adjuvants in genetic predisposed individuals. This concept fits into the structure of the autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) that was proposed in 2011 by Professor Shoenfeld Y. In this paper, the authors reveal the presence of major and minor ASIA criteria for sarcoidosis, propose a new concept of the course of sarcoidosis within the framework of ASIA, and point out the difficulties in creating a model of the disease and the selection of therapy. It is obvious that the data obtained not only bring us closer to understanding the nature of sarcoidosis, but also potentiate new studies confirming this hypothesis by obtaining a model of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Gender Incongruence refers to the discordance between biological sex and gender identity. Although it is possible to find literature reviews about the etiology of Gender Incongruence, almost all of these correspond to non-systematic narrative reviews, so they do not make explicit the methodology used in the collection and analysis of sources, even less its levels of evidence. In order to remedy this, we will conduct a scoping review to answer the question: what are the factors associated with gender incongruence and what level of evidence is there for each factor in the scientific literature? Methods and analysis: We will conduct a scoping review according to the methodology specified in the JBI Manual for Evidence Synthesis (Chapter 11) and the PRISMA extension for scoping reviews (PRISMA-ScR). Four databases will be reviewed to identify papers that match our search criteria, followed by a screening of titles and abstracts, the complete reading of those articles that have not been excluded, and the coding of these using the data extraction instrument developed for this research (see S1 Appendix). Data extracted will be analyzed in terms of frequency counts of factors, types of factors and levels of evidence for each factor. Results will be presented in tabular or diagrammatic forms supported by a narrative summary. Findings: The present review will help to map the factors associated with incongruence between biological sex and gender identity, specifying their levels of evidence. This evidence-based knowledge will be useful for clinicians evaluating gender incongruence, especially given that international guidelines recommend careful assessment of factors that may interfere with the clarity of gender identity development and decision making. [ABSTRACT FROM AUTHOR]

The periodontal disease etiology has been a demesne of scrupulous research, with a myriad of bacterial phylotypes inhabiting the periodontal pockets. The aim of our study was to assess the frequency of Filifactor alocis in type 2 diabetes mellitus (DM) subjects having a healthy periodontium (DH) or chronic periodontitis (DCP) and its correlation with clinical parameters and red complex bacteria. Polymerase chain reaction was carried out for the detection of F. alocis and red complex bacteria from subgingival plaque samples. The data were analyzed using Fisher's Exact Test and Pearson's chi-square test. A p value < 0.05 was considered statistically significant. F. alocis was detected at considerably higher levels in DCP (p < 0.05). F. alocis presence was also positively correlated with T. forsythia detection and the clinical parameters PD and CAL (p < 0.05). Subjects with good glycemic control showed a considerably lower detection of F. alocis as compared to fair- and poor-glycemic-control subjects. This is the first paper reporting the co-occurrence of F. alocis and T. forsythia in diabetic subjects with chronic periodontitis. These findings show that F. alocis can play an important role in establishing synergistic collaborations with other pathogenic oral microorganisms and speeding up the course of periodontal disease in diabetics. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a widespread condition when the blood's force on the artery walls is extremely high to develop adverse health effects. This paper aimed to jointly model the longitudinal change of blood pressures (systolic and diastolic) and time to the first remission of hypertensive outpatients receiving treatment. Methods: A retrospective study design was used to collect appropriate data on longitudinal changes in blood pressure and time-to-event from the medical charts of 301 hypertensive outpatients under follow-up at Felege Hiwot referral hospital, Ethiopia. The data exploration was done using summary statistics measures, individual profile plots, Kaplan-Meier plots, and log-rank tests. To get wide-ranging information about the progression, joint multivariate models were employed. Results: A total of 301 hypertensive patients who take treatment was taken from Felege Hiwot referral hospital recorded between Sep. 2018 to Feb. 2021. Of this 153 (50.8%) were male, and 124 (49.2%) were residents from rural areas. About 83(27.6%), 58 (19.3%), 82 (27.2%), and 25 (8.3%) have a history of diabetes mellitus, cardiovascular disease, stroke, and HIV respectively. The median time of hypertensive patients to have first remission time was 11 months. The hazard of the patient's first remission time for males was 0.63 times less likely than the hazard for females. The time to attain the first remission for patients who had a history of diabetes mellitus was 46% lower than for those who had no history of diabetes mellitus. Conclusion: Blood pressure dynamics significantly affect the time to the first remission of hypertensive outpatients receiving treatment. The patients who had a good follow-up, lower BUN, lower serum calcium, lower serum sodium, lower hemoglobin, and take the treatment enalapril showed an opportunity in decreasing their blood pressure. This compels patients to experience the first remission early. Besides, age, patient's history of diabetes, patient's history of cardiovascular disease, and treatment type were the joint determinant factors for the longitudinal change of BP and the first remission time. The Bayesian joint model approach provides specific dynamic predictions, wide-ranging information about the disease transitions, and better knowledge of disease etiology. [ABSTRACT FROM AUTHOR]

Obesity or Adiposity is a worldwide common health problem that is related with an augmented risk of a number of medical conditions, morbidity and mortality. This mini review recapitulates the epidemiology, Etiology, associated comorbidities, biomarkers and available pharmacotherapy of obesity. The epidemiology of obesity is increasing in low-, middle- and high-income countries, with sociodemographic, behavioural, and genetic factors all playing a role. Comorbidities include hypertension, diabetes mellitus, stroke, coronary artery disease, and melanoma. Biomarkers associated with obesity include anthropometric markers, biochemical markers, hormonal markers, molecular biomarkers. Obesity related Oxidative stress is also discussed in this paper as per current findings from various clinical and preclinical data available up to January 2023. Treatment approaches range from lifestyle changes to pharmacotherapy and surgery. The available pharmacotherapy is either connected with precarious ill effects or overpriced, therefore, alternative therapies for obesity attenuation are required. Article under discussion provides an insight into oxidative stress attenuation, gene therapy via biomarkers regulation for combating obesity. Prevention strategies should include multidimensional approaches tailored to each nation [ABSTRACT FROM AUTHOR]

The paper focuses on the problem of scrupulosity in the context of cognitive-behavioural therapy. The disorder has long aroused the curiosity of both psychologists and theologians. Advances in clinical psychology have directed the attention of researchers and therapists to the aetiology and nosological classification of this psychological/moral phenomenon. For many years, the variety of psychological approaches and the ambiguities of treatment strategies have aroused controversy, with treatment outcomes considered only negligible, resulting in scepticism among patients. The change was brought about by the conceptualisation of the disorder in the cognitive-behavioural paradigm. This paper briefly discusses the evolution of therapeutic models and techniques used in patients diagnosed with scrupulosity. Reference was made to the epidemiology of the phenomenon in the context of its place in the group of obsessive-compulsive disorders. The changes in the conceptualisation of problems experienced by scrupulous individuals are also presented, taking into account the cognitive-behavioural models of an obsessive-compulsive disorder, the subtype of which is nowadays scrupulosity, most often cited in psychological-medical literature. The cognitive-behavioural model of the disorder, which is not widely discussed in Polish literature, and its implications for clinical practice, as well as modifications in the standard protocol for treating patients diagnosed with obsessivecompulsive disorder, introduced to adjust for the needs of patients presenting with the moral-religious aspect of the disease, are also discussed. The aim of the article is also to promote knowledge about scrupulosity among therapists, priests and scientists, thereby inspiring creative work and improvement of the quality of everyday functioning of patients [ABSTRACT FROM AUTHOR]

An unbiased, widely accepted estimate of the rate of occurrence of new cases of autism over time would facilitate progress in understanding the causes of autism. The same may also apply to other disorders. While incidence is a widely used measure of occurrence, birth prevalence—the proportion of each birth year cohort with the disorder—is the appropriate measure for disorders and diseases of early childhood. Studies of autism epidemiology commonly speculate that estimates showing strong increases in rate of autism cases result from an increase in diagnosis rates rather than a true increase in cases. Unfortunately, current methods are not sufficient to provide a definitive resolution to this controversy. Prominent experts have written that it is virtually impossible to solve. This paper presents a novel method, time-to-event birth prevalence estimation (TTEPE), to provide accurate estimates of birth prevalence properly adjusted for changing diagnostic factors. It addresses the shortcomings of prior methods. TTEPE is based on well-known time-to-event (survival) analysis techniques. A discrete survival process models the rates of incident diagnoses by birth year and age. Diagnostic factors drive the probability of diagnosis as a function of the year of diagnosis. TTEPE models changes in diagnostic criteria, which can modify the effective birth prevalence when new criteria take effect. TTEPE incorporates the development of diagnosable symptoms with age. General-purpose optimization software estimates all parameters, forming a non-linear regression. The paper specifies all assumptions underlying the analysis and explores potential deviations from assumptions and optional additional analyses. A simulation study shows that TTEPE produces accurate parameter estimates, including trends in both birth prevalence and the probability of diagnosis in the presence of sampling effects from finite populations. TTEPE provides high power to resolve small differences in parameter values by utilizing all available data points. [ABSTRACT FROM AUTHOR]

Motivation: Exploring the potential long noncoding RNA (lncRNA)-disease associations (LDAs) plays a critical role for understanding disease etiology and pathogenesis. Given the high cost of biological experiments, developing a computational method is a practical necessity to effectively accelerate experimental screening process of candidate LDAs. However, under the high sparsity of LDA dataset, many computational models hardly exploit enough knowledge to learn comprehensive patterns of node representations. Moreover, although the metapath-based GNN has been recently introduced into LDA prediction, it discards intermediate nodes along the meta-path and results in information loss. Results: This paper presents a new multi-view contrastive heterogeneous graph attention network (GAT) for lncRNA-disease association prediction, MCHNLDA for brevity. Specifically, MCHNLDA firstly leverages rich biological data sources of lncRNA, gene and disease to construct two-view graphs, feature structural graph of feature schema view and lncRNA-gene-disease heterogeneous graph of network topology view. Then, we design a cross-contrastive learning task to collaboratively guide graph embeddings of the two views without relying on any labels. In this way, we can pull closer the nodes of similar features and network topology, and push other nodes away. Furthermore, we propose a heterogeneous contextual GAT, where long short-term memory network is incorporated into attention mechanism to effectively capture sequential structure information along the meta-path. Extensive experimental comparisons against several state-of-the-art methods show the effectiveness of proposed framework.The code and data of proposed framework is freely available at  https://github.com/zhaoxs686/MCHNLDA. [ABSTRACT FROM AUTHOR]

Despite studies on the etiology of Kawasaki disease (KD) ongoing for half a century since its discovery, its cause has not yet been clearly identified. Although the clinical, epidemiological, and pathophysiological characteristics of KD are presumed to be closely related to infectious diseases, studies of various pathogens to identify its etiology have been actively conducted. To date, bacteria, fungi, and viruses have been investigated to determine the relationship between KD and infection, among which viruses have attracted the most attention. In particular, during the coronavirus disease 2019 pandemic, there were many reports in Europe of a sharp increase in cases of Kawasaki-like disease (KLD), while conflicting reports that the prevalence of KD decreased due to thorough "social distancing" or "wearing mask" in Asian countries drew more attention regarding the association between KD and viral infection. Therefore, the differential diagnosis of KD from KLD with these similar spectra has become a very important issue; simultaneously, research to solve questions about the association between KD and viral infections, including sudden acute respiratory syndrome coronavirus 2, is drawing attention again. Moreover, a new concept has emerged that immune responses occurring in patients with KD can be caused by the pathogen itself as well as host cells damaged by infection. This paper summarizes the research trends into KD etiology and related pathophysiology, especially its association with viral infections, and present future research tasks to increase our understanding of KD. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of the study were to describe the burden, etiology, and fatality rates of heart failure in Nigerian children. Methods: We searched PubMed database, Google scholar, TRIP database, EMBASE, African Index Medicus, and reference lists of selected articles for studies on burden, etiology, and fatality rates of heart failure in children in Nigeria published from 1977 to 2016. Two researchers reviewed the papers independently. Ten studies were selected that included 14,921 children and 1353 with heart failure. Results: The overall prevalence of heart failure using all the studies reviewed was 8.3% (95% CI: 4.9–12.6). The prevalence was 13.4% (95% CI: 10.9–16.3) in studies that excluded neonates and 4.5% (95% CI: 2.8–6.5) in studies that included neonates. The most common causes of heart failure were severe anemia (38.9%, 95% CI: 30.0–49.4), respiratory tract infections (32.4%, 95% CI: 25.5–39.7), congenital heart disease (8.4%, 95% CI: 6.8–10.2), and sepsis (7.6%, 95% CI: 3.0–14.0). The overall fatality rate was 16.0% (95% CI: 9.0 – 24.6) and was higher in studies that include neonates. Conclusion: Heart failure is common in children hospitalized in Nigeria. Its etiology is largely from non-cardiac conditions associated with severe hypoxia and mortality rates are high in children in Nigeria. [ABSTRACT FROM AUTHOR]

Protein self-assembly into fibrils and oligomers plays a key role in the etiology of degenerative diseases. Several pathways for this self-assembly process have been described and shown to result in different types and ratios of final assemblies, therewith defining the effective physiological response. Known factors that influence assembly pathways are chemical conditions and the presence or lack of agitation. However, in natural and industrial systems, proteins are exposed to a sequence of different and often complex mass transfers. In this paper, we compare the effect of two fundamentally different mass transfer processes on the fibrilization process. Aggregation-prone solutions of hen egg white lysozyme were subjected to predominantly non-advective mass transfer by employing centrifugation and to advective mass transport represented by orbital shaking. In both cases, fibrilization was triggered, while in quiescent only oligomers were formed. The fibrils obtained by shaking compared to fibrils obtained through centrifugation were shorter, thicker, and more rigid. They had rod-like protofibrils as building blocks and a significantly higher β-sheet content was observed. In contrast, fibrils from centrifugation were more flexible and braided. They consisted of intertwined filaments and had low β-sheet content at the expense of random coil. To the best of our knowledge, this is the first evidence of a fibrilization pathway selectivity, with the fibrilization route determined by the mass transfer and mixing configuration (shaking versus centrifugation). This selectivity can be potentially employed for directed protein fibrilization. [ABSTRACT FROM AUTHOR]

The pathogenesis of vitiligo remains unclear. In this review, we comprehensively describe the role of damage associated molecular patterns (DAMPs) during vitiligo pathogenesis. Published papers on vitiligo, oxidative stress and DAMPs were collected and reviewed via database searching on PubMed, MEDLINE and Embase, etc. Oxidative stress may be an important inducer of vitiligo. At high oxidative stress levels, damage-associated molecular patterns (DAMPs) are released from keratinocytes or melanocytes in the skin and induce downstream immune responses during vitiligo. Treatment regimens targeting DAMPs can effectively improve disease severity. DAMPs play key roles in initiating host defenses against danger signals, deteriorating the condition of vitiligo. DAMP levels in serum and skin may be used as biomarkers to indicate vitiligo activity and prognosis. Targeted therapies, incorporating HMGB1, Hsp70, and IL-15 could significantly improve disease etiology. Thus, novel strategies could be identified for vitiligo treatment by targeting DAMPs. [ABSTRACT FROM AUTHOR]

Epigenetic modifications offer compelling evidence of the environmental etiology of complex diseases. Social and biographical conditions, as well as material exposures, all modulate our biology with consequences for risk predispositions and health conditions. Elucidating these complex biosocial loops is one of the main challenges animating epigenetics. Yet, research on the development of epigenetic biomarkers often pulls in a direction that departs from a view of biological determinants of health embedded in their social and material environment. Taking the example of the epigenetics of cardiovascular diseases, this paper illustrates how common understandings of epigenetic biomarkers strongly lean toward considering them as mere targets for molecular intervention, rather than as correlates of a complex biological and social patterning of disease. This reductionism about biosocial dynamics of disease, we argue, hampers the pursuit of the goals epigenetics has given itself (in cardiology and beyond). If epigenetic mechanisms point to the deep socio-environmental embeddedness of our health, we conclude, future designs and methods of this research may require an improved methodological consideration of a biosocial perspective. [ABSTRACT FROM AUTHOR]

With the development of research on the complex aetiology of many diseases, computational drug repositioning methodology has proven to be a shortcut to costly and inefficient traditional methods. Therefore, developing more promising computational methods is indispensable for finding new candidate diseases to treat with existing drugs. In this paper, a model integrating a new variant of message passing neural network and a novel-gated fusion mechanism called GLGMPNN is proposed for drug–disease association prediction. First, a light-gated message passing neural network (LGMPNN), including message passing, aggregation and updating, is proposed to separately extract multiple pieces of information from the similarity networks and the association network. Then, a gated fusion mechanism consisting of a forget gate and an output gate is applied to integrate the multiple pieces of information to extent. The forget gate calculated by the multiple embeddings is built to integrate the association information into the similarity information. Furthermore, the final node representations are controlled by the output gate, which fuses the topology information of the networks and the initial similarity information. Finally, a bilinear decoder is adopted to reconstruct an adjacency matrix for drug–disease associations. Evaluated by 10-fold cross-validations, GLGMPNN achieves excellent performance compared with the current models. The following studies show that our model can effectively discover novel drug–disease associations. [ABSTRACT FROM AUTHOR]

The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment. [ABSTRACT FROM AUTHOR]

Which papers have provided the most interesting recent advances in tuberculosis research? Which new discoveries in pathogenesis, epidemiology, drug discovery or vaccine development have been the most important or are likely to have the highest impact to the field? [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) is increasingly employed as a technique to assess the causation of a risk factor on an outcome using observational data. The two-stage least-squares (2SLS) procedure is commonly used to examine the causation using genetic variants as the instrument variables. The validity of 2SLS relies on a representative sample randomly selected from a study cohort or a population for genome-wide association study (GWAS), which is not always true in practice. For example, the extreme phenotype sequencing (EPS) design is widely used to investigate genetic determinants of an outcome in GWAS as it bears many advantages such as efficiency, low sequencing or genotyping cost, and large power in detecting the involvement of rare genetic variants in disease etiology. In this paper, we develop a novel, versatile, and efficient approach, namely MR analysis under Extreme or random Phenotype Sampling (MREPS), for one-sample MR analysis based on samples drawn through either the random sampling design or the nonrandom EPS design. In simulations, MREPS provides unbiased estimates for causal effects, correct type I errors for causal effect testing. Furthermore, it is robust under different study designs and has high power. These results demonstrate the superiority of MREPS over the widely used standard 2SLS approach. We applied MREPS to assess and highlight the causal effect of total fetal hemoglobin on anemia risk in patients with sickle cell anemia using two independent cohort studies. A user-friendly Shiny app web interface was implemented for professionals to easily explore the MREPS. [ABSTRACT FROM AUTHOR]

Aim. The paper represents a review of the current state of knowledge regarding lenticulostriate vasculopathy (LSV) in premature and term neonates. Material and method. There are reviewed the definition, the history of this diagnosis, the epidemiology, the anatomy of the vessels the etiology and the methods of diagnosis. Results. LSV is defined as the bright hyperechoic blood vessels in the region of the thalamus and basal ganglia. It was first described in 1960. The incidence is 0.3-2% of live births. The etiology is infectious (congenital rubella, cytomegalovirus, toxoplasma, or other chronic intrauterine infections), hypoxic-ischemic, and in many cases idiopathic (without a clear cause). The diagnosis is mainly done by ultrasonography – the are also proposed classification systems based on the number of vessels affected and/or the echogenicity of the vessels involved. Conclusion. LSV represents a pathology recognized for a long time, in the past, it was considered mainly associated with chronic intrauterine infections, at present, it is more and more seen as a consequence of perinatal hypoxic events. Further large follow-up studies are needed in order to better characterize the etiology and prognosis of this pathologic condition. [ABSTRACT FROM AUTHOR]

Oral ulcers affect oral and systemic health and have high prevalence in the population. There are significant individual differences in the etiology and extent of the disease among patients. In the treatment of oral ulcers, nanofiber films can control the drug-release rate and enable long-term local administration. Compared to other drug-delivery methods, nanofiber films avoid the disadvantages of frequent administration and certain side effects. Electrospinning is a simple and effective method for preparing nanofiber films. Currently, electrospinning technology has made significant breakthroughs in energy-saving and large-scale production. This paper summarizes the polymers that enable oral mucosal adhesion and the active pharmaceutical ingredients used for oral ulcers. Moreover, the therapeutic effects of currently available electrospun nanofiber films on oral ulcers in animal experiments and clinical trials are investigated. In addition, solvent casting and cross-linking methods can be used in conjunction with electrospinning techniques. Based on the literature, more administration systems with different polymers and loading components can be inspired. These administration systems are expected to have synergistic effects and achieve better therapeutic effects. This not only provides new possibilities for drug-loaded nanofibers but also brings new hope for the treatment of oral ulcers. [ABSTRACT FROM AUTHOR]

In this work, we explore data‐driven techniques for the fast and early diagnosis concerning the etiological origin of meningitis, more specifically with regard to differentiating between viral and bacterial meningitis. We study how machine learning can be used to predict meningitis aetiology once a patient has been diagnosed with this disease. We have a dataset of 26,228 patients described by 19 attributes, mainly about the patient's observable symptoms and the early results of the cerebrospinal fluid analysis. Using this dataset, we have explored several techniques of dataset sampling, feature selection and classification models based both on ensemble methods and on simple techniques (mainly, decision trees). Experiments with 27 classification models (19 of them involving ensemble methods) have been conducted for this paper. Our main finding is that the combination of ensemble methods with decision trees leads to the best meningitis aetiology classifiers. The best performance indicator values (precision, recall and f‐measure of 89% and an AUC value of 95%) have been achieved by the synergy between bagging and NBTrees. Nonetheless, our results also suggest that the combination of ensemble methods with certain decision tree clearly improves the performance of diagnosis in comparison with those obtained with only the corresponding decision tree. [ABSTRACT FROM AUTHOR]

Introduction: Aetiology of psoriasis is complex with risk factors involving both environmental triggers and genetic background. Although the best characterized genetic risk factor for psoriasis is HLA-C*06 allele, a number of other variants were associated with the disease. Aim: In the current paper we have conducted a confirmation study for SNPs located in 9 gene regions in a casecontrol analysis of 507 psoriatic patients and 396 controls from the Polish population. Material and methods: Subsequently the impact of genetic variants on response to topical and NB-UVB therapy (reduction in the Psoriasis Area and Severity Index) was analysed. Results: Significant differences in genotype and/or allelic frequency were observed for the following SNPs: rs33980500 (TRAF3IP2), rs582757 (TNFAIP3I), rs12188300 (IL12B), rs28998802 (NOS2), and rs2233278 (TNIP1). None of the genetic factors was associated with treatment outcome. Conclusions: Although the genetic variants have an impact on the disease risk, they are unlikely to be useful in personalization of topical therapy. [ABSTRACT FROM AUTHOR]