Noticeable Symptoms Research Articles

A Comprehensive CNN Model for Age-Related Macular Degeneration Classification Using OCT: Integrating Inception Modules, SE Blocks, and ConvMixer

Background/Objectives: Age-related macular degeneration (AMD) is a significant cause of vision loss in older adults, often progressing without early noticeable symptoms. Deep learning (DL) models, particularly convolutional neural networks (CNNs), demonstrate potential in accurately diagnosing and classifying AMD using medical imaging technologies like optical coherence to-mography (OCT) scans. This study introduces a novel CNN-based DL method for AMD diagnosis, aiming to enhance computational efficiency and classification accuracy. Methods: The proposed method (PM) combines modified Inception modules, Depthwise Squeeze-and-Excitation Blocks, and ConvMixer architecture. Its effectiveness was evaluated on two datasets: a private dataset with 2316 images and the public Noor dataset. Key performance metrics, including accuracy, precision, recall, and F1 score, were calculated to assess the method’s diagnostic performance. Results: On the private dataset, the PM achieved outstanding performance: 97.98% accuracy, 97.95% precision, 97.77% recall, and 97.86% F1 score. When tested on the public Noor dataset, the method reached 100% across all evaluation metrics, outperforming existing DL approaches. Conclusions: These results highlight the promising role of AI-based systems in AMD diagnosis, of-fering advanced feature extraction capabilities that can potentially enable early detection and in-tervention, ultimately improving patient care and outcomes. While the proposed model demon-strates promising performance on the datasets tested, the study is limited by the size and diversity of the datasets. Future work will focus on external clinical validation to address these limita-tions.

Neuroanatomical heterogeneity drives divergent cognitive and motor trajectories in Parkinson's disease subtypes

IntroductionCognitive symptoms of Parkinson's disease (PD) may initially present subtly, often overshadowed by more noticeable motor symptoms. However, as PD progresses, predicting which individuals will experience significant cognitive decline becomes challenging due to variability, suggesting distinct PD subtypes with varying cognitive trajectories. This study aimed to identify early PD subtypes based on patterns of gray matter atrophy in brain regions associated with cognition and assess their distinct patterns of cognitive change over time. Recognizing PD primarily as a movement disorder, we also evaluated their motor symptoms. MethodsWe analyzed T1-weighted MRI data, cognitive, and motor scores from 114 de novo PD patients and 120 healthy controls. Multivariate gray matter volumetric distances (MGMV) across frontal, subcortical, parietal, temporal, and occipital regions were computed, and K-means clustering was used to identify PD subtypes. Subsequently, cognitive assessments were compared between subtypes at baseline and 48 months using linear mixed-effects models and reliable change indices. Motor-symptom changes were assessed using linear mixed-effects models. ResultsTwo PD subtypes were identified from baseline MRI. Subtype 1 showed significantly higher MGMV in frontal (p < 0.001) and subcortical (p < 0.001) regions, indicating atrophy. At 48 months, subtype 1 had poorer global cognitive performance than subtype 2 (p = 0.005) and faster progression of postural instability and gait disturbance (p = 0.04). ConclusionsPD subtypes identified early by distinct frontal and subcortical atrophy patterns exhibited divergent trajectories of cognitive decline and worsening motor symptoms over time, underscoring the neuroanatomical heterogeneity that drives clinical variability in PD.

Diagnosis of Bone Metastasis due to Medullary Thyroid Cancer With 99mTc‐ (V) DMSA SPECT Imaging

ABSTRACTGiven the limited availability of PET/CT scans, 99mTc‐(V) DMSA scintigraphy can be used to investigate possible metastases, especially in bone, in individuals with medullary thyroid cancer, even if there are no noticeable signs or symptoms of pain.

A case of double aneuploidy of Down and Klinefelter syndrome in an Indian infant: a detailed case report

BackgroundA variation in the number of chromosomes can lead to chromosomal disorders. These chromosomal aberrations might be related to autosomes or sex chromosomes. The most common chromosomal aberrations that are sex-linked and autosomal are Klinefelter syndrome and Down syndrome, respectively. However, the worldwide occurrence of double chromosomal aneuploidy in a single individual is relatively exceptional event and random meiotic nondisjunction events result in double aneuploidy, which causes trisomy of two distinct chromosomes. The clinical manifestations vary depending on whether aneuploidy is dominant or an amalgam of both. Moreover, double aneuploidy including autosome and sex chromosome is not often documented. In this paper, we document a case of Down–Klinefelter double aneuploidy syndrome in an Indian infant hospitalized to the neonatal care unit.Case presentationA full-term 9-month-old male infant born to a 36-year-old female with classical clinical signs of Down syndrome like epicanthus, a depressed nasal bridge, a flat face, small ears, an open mouth, thick lower lip vermilion, a protruding tongue, and a short neck was referred for cytogenetic examination, revealing a rare karyotype of 48, XXY, + 21.ConclusionDown–Klinefelter syndrome is a rare chromosomal anomaly with unique characteristics, often displaying only Down syndrome-like traits at birth. Early diagnosis can be challenging due to the lack of noticeable symptoms until puberty. Early cytogenetic investigation can detect double aneuploidy, improving the affected person's quality of life and educating family members about potential medical and psychosocial difficulties.

Spontaneous Rupture of Splenic Artery Aneurysm: A Case Report and Review of the Literature

Introduction: Splenic artery aneurysms are uncommon and typically asymptomatic. However, they pose a high risk of mortality if they rupture. Case Report: This case report describes the occurrence of a spontaneous rupture of a splenic artery aneurysm in a 55-year-old man with no known previous diseases, no trauma history, and no risk factors for developing an aneurysm who applied to the emergency department with abdominal pain. The diagnosis was determined with an urgent abdominal computed tomography angiography scan. The patient received urgent surgical intervention consisting of splenectomy and excision of the splenic artery aneurysm. Conclusion: The rupture of a spontaneous splenic artery aneurysm is a rare and fatal disease that necessitates urgent diagnosis and treatment. Spontaneous splenic artery aneurysm usually develops without any noticeable symptoms and is frequently discovered by chance. In the event of a rupture, it can lead to abrupt abdominal pain and hypovolemic shock and the mortality rate is high. Ultrasound, Computed Tomography, Magnetic Resonance Imaging, and abdominal aortic arteriography are the methods of imaging that are used to diagnose splenic artery aneurysms. The key elements in patient management include prompt resuscitation, diagnostic imaging, surgical consultation, and subsequently performing a laparotomy. In our case, the diagnosis was determined using emergency contrast-enhanced Computed Tomography and was treated with open surgery, specifically splenectomy and excision of the splenic artery aneurysm.

"There is a lot of shame that comes with this": A qualitative study of patient experiences of isolation, embarrassment, and stigma associated with overactive bladder.

Beyond causing physical discomfort, overactive bladder (OAB) is distressing to patients across a variety of psychosocial domains. In this qualitative component of a larger mixed methods study, we explore patients' lived experience with OAB to understand how this condition impacts individuals on a personal and social level, as well as their experiences interacting with the health care system. A total of 20 patients and 12 physicians completed a questionnaire and semi-structured interview. The interview guide, developed in an iterative fashion by the authors, included questions about treatment decision making as well as experiences living with or treating OAB; this manuscript focuses on the questions probing lived experiences and interactions between patients and physicians. The interviews were recorded, transcribed and inductively coded and analyzed according to the principles of interpretive description to develop themes. Analysis of patient and physician interviews yielded five key themes: isolation due to OAB diagnosis, social stigma associated with noticeable OAB symptoms, embarrassment from interactions with the health care system, feeling invalidated and dismissed by physicians, and OAB patients as a "vulnerable" population with "desperation" for cure. OAB causes patients marked distress beyond their physical symptoms; it causes feelings of isolation from friends and family and makes them feel embarrassed to discuss their condition with loved ones and physicians alike. Efforts to destigmatize OAB, validate patient experiences, and improve access to OAB care may help diminish the psychosocial burden of OAB.

Detached pyloric gland adenoma of gallbladder: A case report and review of literature.

Vigilant intraoperative inspection is crucial during gallbladder surgery to detect any abnormal tissue including the rare pyloric gland adenomas, which can be easily missed. Thorough examination and removal of unusual lymph nodes or thickened tissues are essential to prevent the risk of malignant transformation and ensure comprehensive patient care. Pyloric gland adenomas are uncommon tumors that can be discovered in various organs such as the stomach, gallbladder, and pancreas. Typically lacking noticeable symptoms, these tumors are categorized into subtypes, with the pyloric variant being the most frequent. The term "intracholecystic papillary-tubular neoplasms (ICPN)" is used to emphasize growth patterns and associated risks. In a discussed case, a detached pyloric gland adenoma was identified incidentally during a cholecystectomy procedure. A 58-year-old obese male presented with upper abdominal pain, nausea, and vomiting. He was diagnosed with early cholecystitis caused by gallstones. Subsequently, during a laparoscopic cholecystectomy, a detached adenoma was discovered. Vigilant screening is crucial, as the identification of gallbladder pyloric gland adenomas is a rare occurrence that might be missed during gallbladder surgery. Any unusual lymph nodes or thickened tissues found in association with the gallbladder ought to be carefully removed, as they could potentially indicate detached gallbladder adenomas with a significant risk of becoming malignant. Failing to consider this possibility may subject the patient to prolonged risks if not meticulously examined.

Immune Modulation by Epstein-Barr Virus Lytic Cycle: Relevance and Implication in Oncogenesis.

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV's lytic phase contribution to oncogenesis.

Approaches to Early Parkinson's Disease Subtyping.

Parkinson's disease (PD) unfolds with pathological processes and neurodegeneration well before the emergence of noticeable motor symptoms, providing a window for early identification. The extended prodromal phase allows the use of risk stratification measures and prodromal markers to pinpoint individuals likely to develop PD. Importantly, a growing body of evidence emphasizes the heterogeneity within prodromal and clinically diagnosed PD. The disease likely comprises distinct subtypes exhibiting diverse clinical manifestations, pathophysiological mechanisms, and patterns of α-synuclein progression in the central and peripheral nervous systems. There is a pressing need to refine the definition and early identification of these prodromal subtypes. This requires a comprehensive strategy that integrates genetic, pathological, imaging, and multi-omics markers, alongside careful observation of subtle motor and non-motor symptoms. Such multi-dimensional classification of early PD subtypes will improve our understanding of underlying disease pathophysiology, improve predictions of clinical endpoints, progression trajectory and medication response, contribute to drug discovery and personalized medicine by identifying subtype-specific disease mechanisms, and facilitate drug trials by reducing confounding effects of heterogeneity. Here we explore different subtyping methodologies in prodromal and clinical PD, focusing on clinical, imaging, genetic and molecular subtyping approaches. We also emphasize the need for refined, theoretical a priori disease models. These will be prerequisite to understanding the biological underpinnings of biological subtypes, which have been defined by large scale data-driven approaches and multi-omics fingerprints.

Prevalence And Severity Of High Blood Pressure In Morocco

Background: Hypertension, also known as high blood pressure (HBP), is a chronic medical condition characterized by persistently elevated blood pressure in the arteries. Although it may not always exhibit noticeable symptoms, hypertension can lead to serious long-term health complications, including an increased risk for coronary artery disease, stroke, heart failure, atrial fibrillation, peripheral vascular disease, vision loss, chronic kidney disease, and dementia. The objective of this study is to determine the prevalence and severity of hypertension among patients in Rabat, Morocco. Methods: This is a retrospective descriptive study that included all patients diagnosed with hypertension at the Military Hospital Mohammed V of Rabat (Morocco), during the period between 2004 and 2018. A standardized questionnaire was completed for each patient. Prior to data collection, patients were informed about the objectives of the study, and measures were taken to protect their confidentiality and anonymity. The study parameters included age, gender, time elapsed since hypertension diagnosis, and hypertension severity. Results: A total of 10,929 individuals were included in the study, with half being male. The mean age of the patients was 71 ± 17 years. The age group most affected was those aged 65 years or older, representing 62% of all groups. Of the hypertensive cases, 70% were classified as moderate hypertension. Furthermore, hypertension significantly increased with age (p˂0.001). Conclusion: Adopting positive lifestyle changes and adhering to prescribed medications are key strategies that can effectively lower blood pressure and reduce the risks of severe health complications commonly associated with hypertension. Examples of effective lifestyle changes include weight loss, regular physical exercise, reduced salt and alcohol consumption, and a healthy diet. Medications for managing hypertension may also be necessary in some cases.

Asymptomatic pediatric presentation of S-adenosylhomocysteine hydrolase deficiency.

S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive inborn error of metabolism affecting methylation by disrupting the methionine cycle. Its clinical spectrum spans from severe perinatal encephalomyopathy and liver failure to asymptomatic course in patients with isolated hypermethioninemia. We present two new cases of S-adenosylhomocysteine hydrolase deficiency from Pakistani origin clinically asymptomatic at presentation. Both siblings showed mild chronic liver failure and elevation of creatine kinase. The older patient presented at 6 years of age with isolated verbal processing difficulty and mild diffuse leukodystrophy, reversible 12 months after introduction of methionine dietary restriction. The patient showed subtle atrophy in the muscle MRI at the age of 7 years. S-adenosylhomocysteine hydrolase deficiency was confirmed with homozygous missense variant c.146G>A (p.Arg49His) in the AHCY gene, a genotype previously reported in Pakistani patients with mild presentation. Dietary methionine restriction decreased plasma methionine but not plasma S-adenosylhomocysteine and S-adenosylmethionine. This work expands the mild spectrum of S-adenosylhomocysteine hydrolase deficiency with no noticeable clinical symptoms in children, highlighting a specific hotspot variant from South Asia. This mild form of the disease is likely underdiagnosed and raises the question of therapeutic management to prevent long-term complications documented in the literature, such as hepatocellular carcinoma and myopathy in early adulthood.

Characterizing the adult zebrafish model of Parkinson's disease: a systematic review of dynamic changes in behavior and physiology post-MPTP administration.

Adult zebrafish are increasingly used in Parkinson's disease (PD) research due to their well-characterized dopaminergic system. Among the toxin-based models, the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely utilized to induce parkinsonism in adult zebrafish. Therefore, this review presents an overview of the procedures and the dynamic changes in behavior and physiology observed in the adult zebrafish PD model following a single intraperitoneal injection of MPTP. A systematic literature search in the PubMed and Google Scholar databases was conducted to identify relevant articles. Of the 165 articles identified, 9 were included in this review. These chosen articles are original works published before March 2024, all of which utilized adult zebrafish induced with MPTP as the model for PD. Other articles were excluded based on factors such as limited relevance, utilization of zebrafish embryos or larvae instead of adults, and variations in MPTP deliveries. Studies indicated that the ideal model entails the utilization of mixed gender zebrafish aged between 4 and 6 months from the wild-type strain. The acceptable MPTP doses ranges between 20 μg/g (lowest) and 225 μg/g (highest) and doses above 292 μg/g are lethal. Furthermore, noticeable parkinsonian symptoms appear 1 day after administration and persist for more than 1 week. Mitochondrial dysfunction precedes dopaminergic neurodegeneration within this experimental regime. A single administration of MPTP effectively induces PD in adult zebrafish. This study aids in crafting the adult zebrafish PD model, outlining the progressive behavioral and physiological changes ensuing from MPTP administration.

Causal Relationships between Gut Microbiotas, Blood Metabolites, and Neuroendocrine Tumors: A Mediated Mendelian Randomization Study

Plain Language SummaryNeuroendocrine tumors (NETs) are a rare type of cancer that can develop in different parts of the body, including the intestines, lungs, and pancreas. These tumors are often hard to detect early because they may not cause noticeable symptoms until they have spread to other parts of the body. This study aimed to better understand how certain bacteria in the gut, known as the gut microbiota, and the substances they produce, called metabolites, might influence the development of NETs. To investigate this, we used a method called Mendelian randomization, which helps to identify cause-and-effect relationships by analyzing genetic data. We looked at genetic information from large groups of people to see if there is a link between specific gut bacteria and the risk of developing NETs. We also explored whether certain metabolites produced by these bacteria might play a role in this process. Our findings suggest that some types of gut bacteria and their metabolites may either increase or decrease the risk of NETs, depending on the specific bacteria and metabolites involved. For example, some bacteria were found to protect against certain types of NETs, while others were linked to a higher risk. This research provides new insights into how gut bacteria and their products might contribute to the development of NETs and highlights potential areas for future studies aimed at preventing or treating these tumors.

Hypertension: a PCN Clinical Pharmacist‐led intervention

Cardiovascular disease (CVD) remains the second most common cause of death in England, after dementia and Alzheimer disease, causing a quarter of all deaths. Hypertension is the largest single known risk factor for CVD; however, as the condition rarely has noticeable symptoms, an estimated 4.2 million people in England are walking around with undiagnosed hypertension. This article presents how one primary care network (PCN), Nottingham West, is working in new ways to make a difference to the health of their local population about hypertension.

The genetic analysis of eight families with hemophilia B in Mongolia: Identification of two novel mutation.

This study aimed to conduct molecular diagnostics among individuals with hemophilia B (HB) and carriers of hemophilia in Mongolia. Eight patients (six severe, two mild) with HB and their 12 female relatives were enrolled from eight families. Sanger sequence was performed for mutation identification. The questionnaire survey was conducted to evaluate carrier symptoms in female relatives. Two families had a history of HB. A total of five different variants (c.223C > T; c.344A > G; c.464G > C; c.187_188del; and c.1314_1314delA) were identified in six patients with severe HB. Of these, two (c.187_188del and c.1314_1314delA) were novel. No variant in the entire F9 was found in two patients with mild HB. Nonsense c.223C > T (p.Arg75*) mutation was detected in two unrelated patients. Carrier testing identified five mothers as carriers, while one younger sister was a non-carrier. The carrier status of six female relatives of the two mild patients remained undetermined. By questionnaire survey, only one of the five genetically identified carriers displayed noticeable symptoms of being a carrier. The novel variants c.187_188del and c.1314_1314delA can cause severe hemophilia B. This study did not observe a significant association between symptoms and carrier status in the five carriers.

Resistance of Sesame (&amp;lt;i&amp;gt;Sesamum indicum L&amp;lt;/i&amp;gt;.) Genotypes Against Bacterial Blight (&amp;lt;i&amp;gt;Xanthomonas campestris pv. sesami&amp;lt;/i&amp;gt;) in Benishangul Gumuz Region, Northwestern Ethiopia

Bacterial blight poses a significant threat to sesame production in Ethiopia, especially in regions with high rainfall. It causes yield reduction and affects seed quality by inducing premature leaf defoliation. To address these challenges, evaluating existing germplasm for disease resistance is crucial. This study assessed various sesame genotypes for resistance to bacterial blight and their performance in seed yield and seed yield related traits. Seventeen genotypes were evaluated in a randomized complete block design at Kamashi research sub-station. Resistance evaluations were conducted every 14 days from emergence up to 72 days, along with recording seed yield and related agronomic and morphological traits. The mean area under the disease progress curve (AUDPC) varied from 673.86 to 825.01, indicating differing susceptibility levels to disease advancement. Approximately 46.67% of the tested genotypes exhibited lower AUDPC compared to Benishangul-1, a variety specifically developed for its adaptability and resistance for bacterial blight-prone regions. Initially, at 14 and 28 days after emergence (DAE), no noticeable bacterial blight symptoms were observed across the genotypes. However, at 42, 56, and 72 DAE, the average severity index steadily rose to 16.92%, 20.78%, and 27.71%, respectively. This transition from immunity to moderate susceptibility underscores the dynamic nature of disease progression and the significant challenge posed by bacterial blight in later sesame growth stages. Notably, significant differences (P&amp;lt;0.05) were noted in days to 50% flowering, days to 90% maturity, plant height to the first branch, overall plant height, length of the capsule-bearing zone, and seed yield. This comprehensive evaluation offers valuable insights into the genetic diversity to improve crop performance and yield potential.

Preparation of hydrogel from the hydroalcoholic root extract of Premna integrifolia L. and its mediated green synthesis of silver nanoparticles for wound healing efficacy

The current investigation concentrated on the fabrication of silver nanoparticles through the root of Premna integrifolia L. The antibacterial and wound healing effects of their silver nanoparticles-hydrogel and root extract-hydrogel were evaluated. The hydroalcoholic root extract of P. integrifolia was enriched with crocetin, ferulic acid, oleanolic acid, oleic acid, syringic acid, and vanillin. The silver nanoparticles were biosynthesized through secondary metabolite-enriched hydroalcoholic root extract (5 %) when mixed with 1 mM AgNO3 and kept under sunlight for 10 minutes. They showed an optimum surface plasmon resonance (SPR) at 447 nm. The aldehyde, phenol, and primary amine groups of the extract reduce silver cations into nanoparticles. The nanoparticles band gap of 2.06 eV showed their semi-conductance behavior. The nanoparticles were spherical, uniformly distributed, and stable. The nanoparticles had a good roughness profile and 57.55 % elemental silver. The silver nanoparticles-hydrogel (10 %) showed an efficient 11±0.11 nm zone of inhibition of S. aureus in comparison to the root extract-hydrogel (10 %), i.e., 9±0.15 nm. The nanoparticles-hydrogel and the root extract-hydrogel did not show noticeable symptoms of acute dermal toxicity. The nanoparticles-hydrogel (10 %) and the root extract-hydrogel (10 %) healed 99.9 % and 97.3 % of the S. aureus- infected wound, respectively. The nanoparticle-hydrogel efficiently induced re-epithelialization in the dermis of S. aureus-infected wound compared to the extract-hydrogel. The nanoparticle-hydrogel enhanced the rate of wound closure.

DNA interaction of selected tetrahydropyrimidine and its effects against CCl4-induced hepatotoxicity in vivo: Part II.

Tetrahydropyrimidine (compound A = methyl 4-[4'-(heptyloxy)-3'-methoxyphenyl]-1,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate) was chosen for in vivo studies after exhibiting noteworthy in vitro activity against the K562 and MDA-MB-231 cell lines, with IC50 values of 9.20 ± 0.14 µM and 12.76 ± 1.93 µM, respectively. According to experimental (fluorescence titration, viscosity, and differential scanning calorimetry) results, A interacts with DNA via the minor groove. In vivo, acute oral toxicity studies in Wistar albino rats proved no noticeable symptoms of either toxicity or death during the follow-up period. Genotoxic and antigenotoxic studies at three different concentrations of A (5, 10, and 20 mg/kg of body weight) in Wistar albino rats showed that the dose of 5 mg/kg body weight did not cause DNA damage and had a remarkable DNA protective activity against CCl4-induced DNA damage, with a percentage reduction of 78.7%. It is also important to note that, under the investigated concentrations of A, liver damage is not observed. Considering all experimental outcomes realized under various in vivo investigations (acute oral toxicity, genotoxicity, antigenotoxicity, and biochemical tests), compound A could be a promising candidate for further clinical testing.

The Multicenter STudy On a Precise algorithm for diagnosis of heart failure with preserved ejection fraction, STOP-HFPEF study: study protocol and design.

This study aims to develop a new heart failure with preserved ejection fraction (HFpEF) diagnostic algorithm tailored to Asian populations, addressing limitations of current diagnostic models. Existing HFpEF diagnostic algorithms primarily target patients with dyspnea and metabolic comorbidities, such as obesity, which are more prevalent in Western populations. However, in Asian countries, HFpEF cases are less frequently associated with obesity, leading to less prominent dyspnea and more noticeable symptoms such as fatigue. By incorporating exercise stress echocardiography and focusing on early-stage HFpEF, particularly in patients with symptoms beyond dyspnea, we seek to enable early diagnosis and intervention, ultimately extending healthy life expectancy and improving quality of life. The STOP-HFPEF (The Multicenter STudy On a Precise algorithm for diagnosis of Heart Failure with Preserved Ejection Fraction) study is a multicenter prospective observational investigation in Japan. Certified by the Japanese Society of Echocardiography, the study includes participants aged 20 and older who undergo exercise stress echocardiography. The primary goal is to develop a scoring model for diagnosing HFpEF in heart-failure stages A, B, and C. Secondary outcomes will assess the clinical utility of the new diagnostic score by comparing heart-failure incidence, cardiovascular events, and mortality rates.Study registration: Registered at the UMIN registry (UMIN000054565) on 1 July 2024.

Comparative Analysis of Intralesional Immunotherapy and Conventional Treatments for Non-Genital Warts: A Systematic Review and Network Meta-Analysis.

Warts, benign skin growths caused by various human papillomavirus strains, are categorized as genital and non-genital. Non-genital warts often lack noticeable symptoms but can lead to psychological distress due to factors like embarrassment. Traditional treatments, including physical and chemical methods, show limitations, prompting the exploration of novel approaches like intralesional immunotherapy. The clinical challenge lies in selecting the most effective modality. In our study, we used the network meta-analysis (NMA) as a statistical tool to explore the most effective intralesional immunotherapy interventions. Comprehensive searches of Web of Science, PubMed, Cochrane, and Scopus databases were conducted until December 2023. Eligible studies were analyzed for outcomes presented as risk ratios (RRs) with 95% confidence intervals (CI). Treatments were ranked using the P-score in an NMA performed with R software. We included 68 RCTs in our study. For complete response, needling showed a significant difference compared to Candida albicans antigen (RR= 0.13, 95% CI [0.02; 0.99]) and Mw (RR= 0.12, 95% CI [0.02; 0.94]). In overall response, both bleomycin and furosemide with digoxin were significant compared to autoimplantation (RR= 0.46, 95% CI [0.24; 0.88]) and (RR= 0.40, 95% CI [0.18; 0.91]) respectively. Similarly, both were significant compared to cryotherapy (RR= 0.45, 95% CI [0.27; 0.76]) and (RR= 0.40, 95% CI [0.19; 0.82]) respectively. This NMA indicates needling, furosemide with digoxin, and PBP antigen stimulants as effective for non-genital warts, surpassing traditional treatments in complete and overall response. Direct comparisons in future research are warranted to confirm their superiority.