Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer’s disease

Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic work-up of dementia in clinical practice and the design of clinical trials. Here, we created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm by evaluating cerebrospinal fluid (CSF) amyloid-{beta} (A{beta}) and tau biomarkers in 426 participants from BioFINDER-2, that represent the entire spectrum of AD. The model composition and main analyses were replicated in 222 participants from the Knight ADRC cohort. SuStaIn revealed in the two cohorts that the data was best explained by a single biomarker sequence (one subtype), and that five CSF biomarkers (ordered: A{beta}42/40, tau phosphorylation occupancies at the residues 217 and 205 [pT217/T217 and pT205/T205], microtubule-binding region of tau containing the residue 243 [MTBR-tau243], and total tau) were sufficient to create an accurate disease staging model. Increasing CSF stages (0-5) were associated with increased abnormality in other AD-related biomarkers, such as A{beta}- and tau-PET, and aligned with different phases of longitudinal biomarker changes consistent with current models of AD progression. Higher CSF stages at baseline were associated with higher hazard ratio of clinical decline. Our findings indicate that a common pathophysiologic molecular pathway develops across all AD patients, and that a single CSF collection is sufficient to reliably indicate the presence of both AD pathologies and the degree and stage of disease progression.
The Impact of Post-Acute Care on Depression and Anxiety in Stroke Patients: A Prospective Study to Explore the Mediating Effect of Cognitive Function

BACKGROUND: Cognitive function was significantly associated with post-stroke depression and anxiety in stroke patients. However, no studies have examined whether there is an interaction. this study purposed to investigate whether cognitive function mediates the effect of enrollment in post-acute care (PAC) programs on depression or anxiety in stroke patients and whether the indicators are moderated in the pathway. METHODS: This is a prospective observational cohort study. A group of patients who had received PAC for stroke at one of two medical centers (PAC group, n = 2,087) was compared with a group who had received standard care for stroke at one of four hospitals (three regional hospitals and one district hospital; non-PAC group, n = 1,591) in Taiwan from March, 2015, to March, 2022. The effects of PAC on cognitive function and depression and anxiety at baseline, 12th week, and 1st year after rehabilitation were investigated using structural equation modeling (SEM). The effect of each variable on the moderation of different pathways in the model was analyzed using AMOS 23.0, and The SPSS PROCESS macro also was used to perform mediation analysis. RESULTS: The PAC program had a mediating effect on cognition and depression at week 12 (a*b= -0.098, P<0.05) on cognition and anxiety at week 12 (a*b= -0.107, P<0.05), and the PAC program had a direct effect on depression and anxiety in the first year. It was found that acute lengths of stay had a significant moderation effect in the model (X*W[->]M=0.204, P=0.002), but the model lost its mediating effect when the moderation variable was added. CONCLUSIONS: Patients with stroke should receive post-acute care as soon as possible to improve their cognitive function after rehabilitation, to maximize the effectiveness of treatment for mental disorders, and to reduce the burden of the disease.
Cardiovascular Eligibility Criteria and Adverse Event Reporting in Cancer Therapy Trials of Combined Immune Checkpoint and VEGF Inhibitors: A Systematic Review

Background Combination therapy with immune checkpoint inhibitors (ICI) and vascular endothelial growth factor inhibitors (VEGFI) has improved cancer outcomes and are increasingly common treatment regimens. These drug classes are associated with cardiovascular toxicities when used alone but heterogeneity in trial design and reporting may limit knowledge of toxicities in people receiving these in combination. Our aims were to assess consistency and clarity in definitions and reporting of cardiovascular eligibility criteria, baseline characteristics and cardiovascular adverse events in ICI/VEGFI combination trials. Methods Systematic review of phase II-IV randomised controlled trials of ICI/VEGFI combination therapy for solid organ cancer. We assessed trial cardiovascular eligibility criteria and baseline cardiovascular characteristic reporting in trial publications. We also examined cardiovascular adverse events definitions and reporting criteria. Results Seventeen trials (10,313 participants; published 2018-2022) were included. There were multiple cardiovascular exclusion criteria in 15 trials. No primary trial publication reported baseline cardiovascular characteristics. Thirteen trials excluded people with prior heart failure, myocardial infarction, hypertension or stroke. There was heterogeneity in defining cardiovascular conditions. Grade 1-4 cardiovascular adverse events were reported when incidence was ? 5-25% in 15 trials. Nine trials applied a more sensitive threshold for reporting higher grade AEs (severity grade ? 3 or serious AE). Safety follow up was shorter than efficacy follow up. Incident hypertension was recorded in all trials but other cardiovascular events were not consistently reported. Myocardial infarction was only reported in four trials and heart failure was reported in three trials. No trial specifically noted the absence of events. Therefore, in trials that did not report CVAEs, it was unclear whether this was because CVAEs did not occur. AE reporting and classification were by the investigator without further adjudication in 16 trials and one trial had an independent CVAE adjudication committee. Conclusions In ICI/VEGFI combination trials, there is heterogeneity in cardiovascular exclusion criteria, reporting of baseline characteristics and lack of reporting of cardiovascular adverse events. This limits optimal understanding of the incidence and severity of events relating to these combinations. Better standardisation of these elements should be pursued.
Using Landweber iteration to quantify source conditions – a numerical study

Abstract Source conditions of the type x†∈ℛ⁢((A∗⁢A)μ){x^{\dagger}\in\mathcal{R}((A^{\ast}A)^{\mu})} are a standard assumption in the theory of inverse problems to show convergence rates of regularized solutions as the noise in the data goes to zero. Unfortunately, it is rarely possible to verify these conditions in practice, rendering data-independent parameter choice rules unfeasible. In this paper we show that such a source condition implies a Kurdyka–Łojasiewicz inequality with certain parameters depending on μ. While the converse implication is unclear from a theoretical point of view, we propose an algorithm which represents a first attempt that allows to approximate the value of μ numerically. It is based on combining the Landweber iteration with the Kurdyka–Łojasiewicz inequality. We conduct several numerical experiments to demonstrate the potential and limitations of the current method. We also show that the source condition implies a lower bound on the convergence rate which is of optimal order and observable without the knowledge of μ.
European research on information behaviour in the 21st century

This paper contributes to global knowledge of the study of information behaviour by offering a map of European research during the 21st century from quantitative and qualitative points of view. From a quantitative point of view, we detail the countries and institutions whose researchers have published results. From a qualitative point of view, we describe the researchers and areas of study at the main European research centres. The results show that there is no common research area, but rather isolated researchers or small leading research groups, generally from northern Europe, who worked in this area during the first years of the 21st century
Critique of Experimental Procedures Targeting Retinitis Pigmentosa

Retinitis Pigmentosa (RP) is a group of hereditary genetic disorders, all causing degradation of the retina through loss of rod photoreceptor cells, ultimately causing loss of vision and in many cases complete blindness. Despite the prevalence of Retinitis Pigmentosa disorders, safe and effective treatment methods have not yet been approved to stop or regain vision loss in patients diagnosed with RP. However, the ophthalmic field as a whole is working on several new technologies and procedures in order to both slow loss of vision as well as potentially regain lost sight. In this thesis, I describe the genetic causes and effects of retinitis pigmentosa, followed by an analysis of current experimental treatments. Possible treatments were screened based on the following criteria; potential release date, adverse effects, ability to treat children, convenience, and the exclusion of patients for each therapy. Finally, I lend to support my claim that stem cell therapy by mesenchymal stem cells through intravenous infusion appears to be the most effective and safest method of experimental treatments available today.
Co-culture with normal and senescent AC16 cardiomyocytes modulates fibrotic response in primary human ventricular fibroblasts

Transwell co-culture with human AC16 cardiomyocyte-like cells modifies the response of primary human ventricular fibroblasts to TGF-β stimulation. Fibrotic response markers including collagen I (COL1A1) and ɑ-smooth muscle actin (ACTA2) are amplified in the presence of AC16 cells, whereas others including periostin (POSTN) and fibronectin (FN1) are suppressed. Similar modulation is observed when the ventricular fibroblasts are co-cultured with AC16 cells under baseline and induced senescence conditions. Given that the response to TGF-β stimulation is commonly measured to study fibrotic signaling and drug treatments in vitro, the results here suggest that the effect of cellular crosstalk should be more broadly considered.
Thigh Length as the Most Consistent Anthropometric Parameter in Predicting the Size of Hamstring Tendon Autografts in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Cross-Sectional Study

Background Individual variability in the length and thickness of hamstring tendon autografts is a serious drawback in using these tendons for anterior cruciate ligament reconstruction (ACLR). In this study, we aimed to determine the correlation between the anthropometric parameters and the size of hamstring tendon autografts. Methods In a cross-sectional study, 52 male ACLR candidates were included. The length of semitendinosus and gracilis tendons and the diameter of single, doubled, and quadrupled tendons were measured. A graft sizing block device with an incremental size change of 0.5 mm (range 4.5-12) was used to measure the tendon graft diameter. The evaluated anthropometric parameters included age, gender, height, weight, BMI, thigh length and diameter, calf length, thigh-to-calf ratio, wrist diameter, and ankle diameter. A Pearson's or Spearman's correlation coefficient test was used for evaluating the correlation of anthropometric factors with graft characteristics. Results The mean age of the patients was 27.1 ± 6.4 years. The semitendinosus length was significantly correlated with the patient's height (r = 0.373, P = 0.007), thigh length (r = 0.364, P = 0.009), and calf length (r = 0.340, P = 0.015). The gracilis length was significantly correlated with thigh length (r = 0.278, P = 0.049). The mean quadruple diameter was 8.56 ± 1.15 mm (range 6.5-11). The quadruple diameter was significantly correlated with the thigh length (r = 0.283, P = 0.044). No other significant correlation was found between the tendons’ size and evaluated anthropometric parameters. Conclusion Thigh length was correlated with the semitendinosus length, gracilis length, and quadruple diameter. Therefore, it could be regarded as the most consistent and promising anthropometric factor in the prediction of hamstring autograft size.
Advancing Artificial Intelligence for Clinical Knowledge Retrieval: A Case Study Using ChatGPT-4 and Link Retrieval Plug-In to Analyze Diabetic Ketoacidosis Guidelines

Introduction This case study aimed to enhance the traceability and retrieval accuracy of ChatGPT-4 in medical text by employing a step-by-step systematic approach. The focus was on retrieving clinical answers from three international guidelines on diabetic ketoacidosis (DKA). Methods A systematic methodology was developed to guide the retrieval process. One question was asked per guideline to ensure accuracy and maintain referencing. ChatGPT-4 was utilized to retrieve answers, and the 'Link Reader' plug-in was integrated to facilitate direct access to webpages containing the guidelines. Subsequently, ChatGPT-4 was employed to compile answers while providing citations to the sources. This process was iterated 30 times per question to ensure consistency. In this report, we present our observations regarding the retrieval accuracy, consistency of responses, and the challenges encountered during the process. Results Integrating ChatGPT-4 with the 'Link Reader' plug-in demonstrated notable traceability and retrieval accuracy benefits. The AI model successfully provided relevant and accurate clinical answers based on the analyzed guidelines. Despite occasional challenges with webpage access and minor memory drift, the overall performance of the integrated system was promising. The compilation of the answers was also impressive and held significant promise for further trials. Conclusion The findings of this case study contribute to the utilization of AI text-generation models as valuable tools for medical professionals and researchers. The systematic approach employed in this case study and the integration of the 'Link Reader' plug-in offer a framework for automating medical text synthesis, asking one question at a time before compilation from different sources, which has led to improving AI models' traceability and retrieval accuracy. Further advancements and refinement of AI models and integration with other software utilities hold promise for enhancing the utility and applicability of AI-generated recommendations in medicine and scientific academia. These advancements have the potential to drive significant improvements in everyday medical practice.
Local weather affects body condition of three North American songbird species on the Texas Coast

Abstract Body condition is a frequently used physiological indicator of avian health and can be affected by an array of environmental variables. Although a number of studies have investigated the specific effects of individual weather variables on body condition in birds, few have analyzed the effects of both temperature and precipitation within the context of an extreme weather event such as hurricanes. In this study, we examined the relationship between breeding‐season body condition and daily maximum temperature, daily minimum temperature, and monthly total precipitation for three passerine bird species at the Welder Wildlife Refuge near Rockport, Texas. We also evaluated yearly changes in body condition over a 12‐year period for northern cardinals (Cardinalis cardinalis), painted buntings (Passerina ciris), and white‐eyed vireos (Vireo griseus), focusing on the extreme precipitation event of Hurricane Harvey, which caused heavy localized flooding. We found that body condition declined with average daily minimum and maximum temperatures, while precipitation had varied, species‐specific effects in the three species analyzed. Our results also suggest that northern cardinals experienced a notable reduction in average body condition in the 2 years following Hurricane Harvey. Taken together, we conclude that short‐term precipitation and temperature drivers can be important correlates of body condition in songbirds and that severe weather events may reduce body condition in some bird species.
BPA interferes with granulosa cell development and oocyte meiosis in mouse preantral follicles

Bisphenol A (BPA) is an established environmental endocrine disruptor and can interfere with the development of female germ cells. However, the underlying mechanisms are still unclear. We investigated the effects of BPA on granulosa cell development and meiosis of oocytes using in vitro culture system of mouse preantral follicles. Preantral follicles from D14 mouse ovary were treated with 10 μg/mL BPA in vitro for 11 days. The adherent area of follicles was measured. On D11, cumulus cell expansion was observed. The meiosis recovery rate was calculated. Western blot detected P53, proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), and cyclin B1. ELISA measured estrogen and progesterone levels. Immunofluorescence detected Cx37 on oocyte membrane. Gap junction communication was assessed. We found that BPA significantly promoted the expressions of PCNA and ERα in granulosa cells and the secretion of estrogen and progesterone by granulosa cells on D10 and significantly increased the attachment area of the follicles on D8 and D10. However, it reduced the expansion of cumulus cells, Cx37 expression, and the gap junction communication between cumulus cells and oocytes on D11. BPA promoted the recovery of oocytes from meiosis, interrupted the expression of cyclin B1 protein in arrested germinal vesicle breakdown (GVBD) oocytes, and reduced the in vitro maturation rate of oocytes. These GVBD oocytes were live without apoptosis or death. Conclusively, BPA disturbs the development of granulosa cells and the meiosis progression of oocytes by decreasing gap junction communication between oocytes and the granulosa cells as well as regulating cyclin B1 expression in GVBD oocytes.
Clinical predictors of polyps recurring in patients with chronic rhinosinusitis and nasal polyps: a systematic review and meta-analysis.

INTRODUCTION Silent sinus syndrome (SSS) is a rare disorder of the maxillary sinus, which may present with orbital symptoms. Most reports of silent sinus syndrome are limited to small series or case reports. This systematic review comprehensively characterizes the various clinical presentations, management, treatment, and outcomes in patients with SSS. METHODS A systematic literature search of the PubMed, Cochrane, Web of Science, and Scopus databases. Inclusion criteria were studies describing the presentation, management, or treatment of SSS or chronic maxillary atelectasis. RESULTS One hundred fifty-three articles were included in the final review (n=558 patients). Mean age at diagnosis was 38.8 ± 14.1 years, with a relatively even distribution among sexes. Enophthalmos and/or hypoglobus were the most frequent symptoms, along with diplopia, headache, or facial pressure/pain. Most patients (87%) underwent functional endoscopic sinus surgery (FESS), and 23.5% received orbital floor reconstruction. Post-treatment, patients had significant reductions in enophthalmos and hypoglobus. Most patients (83.2%) achieved partial or total resolution of clinical symptoms. CONCLUSIONS SSS has a variable clinical presentation, with enophthalmos and hypoglobus being most common. FESS with or without orbital reconstruction are effective treatments to address the underlying pathology and structural deficits.
Oscillometry in severe asthma: the state of the art and future perspectives

ABSTRACT Introduction Approximately 3–10% of people with asthma have severe asthma (SA). Patients with SA have greater impairment in daily life and much higher costs. Even if asthma affects the entire bronchial tree, small airways have been recognized as the major site of airflow limitation. There are several tools for studying small airway dysfunction (SAD), but certainly the most interesting is oscillometry. Despite several studies, the clinical usefulness of oscillometry in asthma is still in question. This paper aims to provide evidence supporting the use of oscillometry to improve the management of SA in clinical practice. Areas covered In the ATLANTIS study, SAD was strongly evident across all severity. Various tools are available for evaluation of SAD, and certainly an integrated use of these can provide complete and detailed information. However, the most suitable method is oscillometry, implemented for clinical routine by using either small pressure impulses or small pressure sinusoidal waves. Expert opinion Oscillometry, despite its different technological implementations is the best tool for determining the impact of SAD on asthma and its control. Oscillometry will also be increasingly useful for choosing the appropriate drug, and there is ample room for a more widespread diffusion in clinical practice.
Recurrent allopolyploidizations diversify ecophysiological traits in marsh orchids (Dactylorhiza majalis s.l.)

Whole‐genome duplication has shaped the evolution of angiosperms and other organisms, and is important for many crops. Structural reorganization of chromosomes and repatterning of gene expression are frequently observed in allopolyploids, with physiological and ecological consequences. Recurrent origins from different parental populations are widespread among polyploids, resulting in an array of lineages that provide excellent models to uncover mechanisms of adaptation to divergent environments in early phases of polyploid evolution. We integrate here transcriptomic and ecophysiological comparative studies to show that sibling allopolyploid marsh orchid species (Dactylorhiza, Orchidaceae) occur in different habitats (low nutrient fens vs. meadows with mesic soils) and are characterized by a complex suite of intertwined, pronounced ecophysiological differences between them. We uncover distinct features in leaf elemental chemistry, light‐harvesting, photoprotection, nutrient transport and stomata activity of the two sibling allopolyploids, which appear to match their specific ecologies, in particular soil chemistry differences at their native sites. We argue that the phenotypic divergence between the sibling allopolyploids has a clear genetic basis, generating ecological barriers that maintain distinct, independent lineages, despite pervasive interspecific gene flow. This suggests that recurrent origins of polyploids bring about a long‐term potential to trigger and maintain functional and ecological diversity in marsh orchids and other groups.