Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct immune surveillance in primary biliary cholangitis and primary sclerosing cholangitis is linked with discrete cholangiocarcinoma risk

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are 2 major liver autoimmune diseases. PBC is common in women and primarily affects intrahepatic small bile duct epithelial cells, known as cholangiocytes. In contrast, PSC is dominant in men and primarily affects medium and big intrahepatic and extrahepatic bile duct epithelial cells. Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes, and its incidence is increasing worldwide in both men and women. Numerous retrospective and clinical studies have suggested that PBC patients rarely develop CCA compared to PSC patients. CCA is accountable for the higher deaths in PSC patients due to ineffective therapies and our inability to diagnose the disease at an early stage. Therefore, it is paramount to understand the differences in immune surveillance mechanisms that render PBC patients more resistant while PSC patients are susceptible to CCA development. Here, we review several potential mechanisms contributing to differences in the susceptibility to CCA in PBC versus PSC patients.
Skeletal and dental maxillary morphological characteristics in patients with impacted canines: systematic review and meta-analysis

Abstract Background There are a few hypotheses for the origin of palatally impacted canines (PIC). Nevertheless, the results of different studies are controversial. Objective Considering the evidence available in the literature to determine the skeletal and dentoalveolar dimensions in patients with PIC using cone beam computed tomography (CBCT). Search methods This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement. The literature search with no publication date restriction in five databases and hand searching was performed until April 2023. Data collection and analysis Data assessing the skeletal and dentoalveolar characteristics of subjects with PIC evaluated with CBCT was extracted, and the studies’ quality was evaluated with the Newcastle-Ottawa Scale (NOS). Skeletal and dentoalveolar characteristics of subjects with PIC were compared with non-impacted subjects or non-impacted sides. MedCalc software was used to perform the meta-analysis. Statistical heterogeneity was assessed using the chi-square and I-square tests. Results The initial database search identified a total of 1153 studies. After applying the selection criteria, nine articles were included in the systematic review and meta-analysis. According to the NOS, all included articles were graded as “Good” quality. The meta-analysis showed a non-significant difference in measuring dentoalveolar height, alveolar first molar width, and basal lateral width. Controversial results were observed when evaluating both basal and alveolar first premolar widths. A significant difference was found when assessing anterior alveolar crest height and basal maxillary width. Conclusions Studies demonstrated the reduction of both dentoalveolar and skeletal maxillary parameters of the patients with PIC. The meta-analysis indicated that PIC correlates to both vertical and transverse skeletal dimensions of the maxilla. However, the results remain controversial. The findings should be interpreted with caution due to different study designs and unbalanced groups in the included studies; therefore, further research is needed for more reliable conclusions. Registration This systematic review and meta-analysis were registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42022362124)
Donor-derived infections in solid organ transplant recipients

Purpose of review The potential for transmission of donor-derived infections (DDIs) is impossible to eliminate, but a thoughtful and systematic approach to donor evaluation can mitigate the risk. Prevention is a key issue and clinicians must maintain a high index of suspicion and remain vigilant in staying up to date on emerging infections. COVID-19 and Monkeypox have represented a new challenge for infectious disease screening and recommendations have been evolving, as knowledge in the field has grown. Additional considerations for pretransplant deceased donor screening include testing for neglected and endemic infectious diseases such as strongyloidiasis and HTLV 1/2. Molecular diagnostic tests have improved awareness on pathogenicity of mollicutes and fungi in the setting of DDIs. The aim of this review is to provide an update on the most recent literature on DDI with a special focus on these emerging hot topics. Recent findings Donor screening for uncommon pathogens must be guided by knowledge of changing epidemiology of infectious disease and availability of new diagnostic methods. Summary Appropriate screening, early recognition, timely reporting, close monitoring, and appropriate management are essential to help reducing the risk of emerging DDIs.
The cardiac preparticipation sports evaluation

Purpose of review Sudden cardiac death (SCD) is the leading cause of death in young athletes during sports participation. Preparticipation cardiovascular screening aims to identify those at an increased risk of SCD. This review aims to provide a background of SCD in young athletes, to discuss the various screening recommendations of major medical societies, and to review recent evidence and current practice. Recent findings Numerous studies have evaluated various preparticipation screening practices, particularly regarding the inclusion of ECG as part of an initial evaluation to identify conditions with an increased risk of SCD. Some analyses have shown ECG inclusion to provide increased screening sensitivity and specificity, though others have shown no benefit when compared with evaluation with history and physical examination alone. Furthermore, in countries for which more extensive screening protocols have been employed, postimplementation statistics have not shown a significant decrease in SCD. Summary SCD in young athletes primarily results from underlying cardiac disease. Various preparticipation screening recommendations exist globally, with the common goal of decreasing the rates of SCD by identifying youth at risk during sports participation. Current guidelines in the United States support universal preparticipation evaluation using history and physical examination, with cardiology referral if abnormalities are identified.
Aspirin and nonaspirin nonsteroidal antiinflammatory drug use and occurrence of colorectal adenoma in Black American women

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self‐identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow‐up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78‐0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66‐0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55‐0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.
Effect of atmospheric pressure changes on the development of pulmonary embolism: a retrospective analysis of 8 years of data

BACKGROUND: Pulmonary embolism (PE) is a condition with high mortality, and determining its etiology is as important as its treatment. There are limited studies in the literature examining the effect of atmospheric pressure (AP) change on PE. OBJECTIVES: Analyze the effect of AP level and the change in AP level on the development of PE according to year, season and months. DESIGN: Retrospective SETTING: Department of tertiary care center PATIENTS AND METHODS: Patients with diagnosed or presumed PE who were followed up in the Erzurum Atatürk University Medicine Chest Diseases Clinic between 2012 and 2020 (8 years) were retrospectively screened for inclusion in the study by examining hospital records. Daily AP values were obtained electronically through official correspondence with the Erzurum Regional Meteorological Directorate. Patients diagnosed with PE were recorded using the hospital database and anamnesis forms. The dates of admission to hospital were recorded. Risk factors leading to the development of PE were identified using the records. MAIN OUTCOME MEASURES: Relationship between AP values and the incidence of PE. SAMPLE SIZE: 592 RESULTS: APmin, APmax, and APmean were significantly lower on days with PE cases compared to days without PE cases (P<.001 for all). ΔAPmin, ΔAPmax, and ΔAPmean values were all negative on days with PE, but only the difference in ΔAPmin was significant (P=.04). CONCLUSIONS: This study showed that lower AP values were significantly associated with the incidence of PE. In particular, a drop in APmin compared to the previous day seemed to be most associated with PE development. LIMITATIONS: Retrospective design and only applicable to region. CONFLICT OF INTEREST: None.
ATP modulates the activity of the voltage‐gated proton channel through direct binding interaction

ATP is an important molecule implicated in diverse biochemical processes, including the modulation of ion channel and transporter activity. The voltage‐gated proton channel (Hv1) controls proton flow through the transmembrane pathway in response to membrane potential, and various molecules regulate its activity. Although it is believed that ATP is not essential for Hv1 activity, a report has indicated that cytosolic ATP may modulate Hv1. However, the detailed molecular mechanism underlying the effect of ATP on Hv1 is unknown, and whether ATP is involved in the physiological regulation of Hv1 activity remains unclear. Here, we report that cytosolic ATP is required to maintain Hv1 activity. To gain insight into the underlying mechanism, we analysed the effects of ATP on the mouse Hv1 channel (mHv1) using electrophysiological and microscale thermophoresis (MST) methods. Intracellular ATP accelerated the activation kinetics of mHv1, thereby increasing the amplitude of the proton current within the physiological concentration range. The increase in proton current was reproduced with a non‐hydrolysable ATP analogue, indicating that ATP directly influences Hv1 activity without an enzymatic reaction. The direct molecular interaction between the purified mHv1 protein and ATP was analysed and demonstrated through MST. In addition, ATP facilitation was observed for the endogenous proton current flowing through Hv1 in the physiological concentration range of ATP. These results suggest that ATP influences Hv1 activity via direct molecular interactions and is required for the physiological function of Hv1.
Highly reproducible and cost-effective one-pot organoid differentiation using a novel platform based on PF-127 triggered spheroid assembly

Organoid technology offers sophisticated in vitro human models for basic research and drug development. However, low batch-to-batch reproducibility and high cost due to laborious procedures and materials prevent organoid culture standardization for automation and high-throughput applications. Here, using a novel platform based on the findings that Pluronic F-127 (PF-127) could trigger highly uniform spheroid assembly through a mechanism different from plate coating, we develop a one-pot organoid differentiation strategy. Using our strategy, we successfully generate cortical, nephron, hepatic, and lung organoids with improved reproducibility compared to previous methods while reducing the original costs by 80%–95%. In addition, we adapt our platform to microfluidic chips allowing automated culture. We showcase that our platform can be applied to tissue-specific screening, such as drug toxicity and transfection reagents testing. Finally, we generate NEAT1 knockout tissue-specific organoids and show NEAT1 modulates multiple signaling pathways fine-tuning the differentiation of nephron and hepatic organoids and suppresses immune responses in cortical organoids. In summary, our strategy provides a powerful platform for advancing organoid research and studying human development and diseases.
Elderly migration and population redistribution : a comparative study

This collection of studies by various authors is the product of a 1991 conference held in Colorado concerning elderly migration. The studies focus on the migration of those aged 60 and over in Western developed countries. The book "examines the factors that govern why the elderly decide to migrate how the migration processes operate and the impact the arrival and departure of an age-specific group has on the population at large. The study is cast in a comparative framework that points out the similarities and contrasts between North America Europe and Japan. " The contributions are organized into four parts which deal with motivation and causes the proximity of children and living arrangements elderly metropolitan redistribution patterns and three case studies concerning Japan the United Kingdom and the United States. (EXCERPT)
Weakest link or strongest node? Prospects for inland port development in transnational European corridors

In a context of increasing global freight transportation and transnational corridor development, inland ports are becoming more important in enhancing hinterland accessibility of deep-sea ports. At the same time, however, when considering the ‘weakest link’ principle, the increasing reliance on inland hubs can also pose a threat to efficient transnational corridor development, especially in relation to adjacent urban regions. Port literature pays limited but growing attention to the conflicting port and urban functions in inland ports. The aim of this paper is therefore to reflect on the findings of a cross-national comparison of governance strategies for inland port development in four different countries along the CEF Rhine-Alpine Corridor (Rotterdam-Genoa). Our findings reflect the difficult position of inland ports within a densely populated corridor. On the one hand, sufficient capacity is needed to prevent the occurrence of bottlenecks, which could threaten flows on other parts of the corridor. On the other hand, increasing port capacity should be aligned with policy measures on the level of the urban region, to avoid the overlapping of port and urban functions, which could lead to conflicts with respect to land-use, economic development and quality of life. This poses challenges in terms of port governance. We observe that cases in which the port and urban administrations open up the policy process to other private stakeholders and the public, common governance strategies for inland port development are more likely to occur.
Changes in diet and supplement use in dogs with cancer

Abstract Background Many dog owners alter their dog's nutritional regimen after a diagnosis of cancer. There are limited data as to specific changes made and reasons behind these changes. Hypothesis/Objectives To collect updated and detailed data on changes made by owners to their dog's diet and supplements after a cancer diagnosis. Animals Responses were collected from a survey of dog owners who brought their dogs to the UC Davis Veterinary Medical Teaching Hospital's Oncology Service for the first time after a cancer diagnosis. Dogs with recurrence or presenting for a second type of cancer were excluded. Methods Eligible owners were surveyed between December 2020 and March 2022. The survey contained 62 questions regarding diet, supplement use, and treats, and how these were altered after a cancer diagnosis. Responses were matched to medical record data. Results One hundred twenty‐eight surveys were retained for analysis, including 120 respondents that completed the survey. In response to a cancer diagnosis, 54.8% (95% CI; 45.7%‐63.8%) of owners altered diets or supplements or both. The most common informational resource for dog diets was veterinarians (53.9%). Usage of home‐prepared foods significantly increased after a cancer diagnosis (P = .03). There was no significant difference in commercial diet usage before or after a diagnosis (P = .25). Joint support products were the most common supplements given both before (37.4%) and after (35.0%) diagnosis. Conclusions and Clinical Importance Many dog owners alter their dog's nutritional intake after a cancer diagnosis. These owners should be provided information relating to commonly observed alterations, including home‐prepared foods and supplements.
Endocytosis of red blood cell extracellular vesicles by macrophages leads to cytoplasmic heme release and prevents foam cell formation in atherosclerosis

Abstract Extracellular vesicles (EVs) can be produced from red blood cells (RBCs) on a large scale and used to deliver therapeutic payloads efficiently. However, not much is known about the native biological properties of RBCEVs. Here, we demonstrate that RBCEVs are primarily taken up by macrophages and monocytes. This uptake is an active process, mediated mainly by endocytosis. Incubation of CD14+ monocytes with RBCEVs induces their differentiation into macrophages with an Mheme‐like phenotype, characterized by upregulation of heme oxygenase‐1 (HO‐1) and the ATP‐binding cassette transporter ABCG1. Moreover, macrophages that take up RBCEVs exhibit a reduction in surface CD86 and decreased secretion of TNF‐α under inflammatory stimulation. The upregulation of HO‐1 is attributed to heme derived from haemoglobin in RBCEVs. Heme is released from internalized RBCEVs in late endosomes and lysosomes via the heme transporter, HRG1. Consequently, RBCEVs exhibit the ability to attenuate foam cell formation from oxidized low‐density lipoproteins (oxLDL)‐treated macrophages in vitro and reduce atherosclerotic lesions in ApoE knockout mice on a high‐fat diet. In summary, our study reveals the uptake mechanism of RBCEVs and their delivery of heme to macrophages, suggesting the potential application of RBCEVs in the treatment of atherosclerosis.
Digital Image Analysis and Use-Wear Accrual as a Function of Raw Material: An Example from Northwestern New Mexico

Abstract The influence of raw material properties on rates of use-related wear accrual has often been acknowledged, but rarely assessed quantitatively. This paper offers such quantification regarding three varieties of chert and one of silicified wood exploited during the occupation of the Late Archaic FA2–13 site in northwestern New Mexico. The results show significant differences between rates of wear accrual among these four materials. Therefore, caution is necessary when making assertions regarding tool function and use intensity on the basis of wear extent alone. This study also has implications for assessing use-related reduction of both short- and long-term use implements.
Clearance phagocytosis by the retinal pigment epithelial during photoreceptor outer segment renewal: Molecular mechanisms and relation to retinal inflammation

Mammalian photoreceptor outer segment renewal is a highly coordinated process that hinges on timed cell signaling between photoreceptor neurons and the adjacent retinal pigment epithelial (RPE). It is a strictly rhythmic, synchronized process that underlies in part circadian regulation. We highlight findings from recently developed methods that quantify distinct phases of outer segment renewal in retinal tissue. At light onset, outer segments expose the conserved “eat‐me” signal phosphatidylserine exclusively at their distal, most aged tip. A coordinated two‐receptor efferocytosis process follows, in which ligands bridge outer segment phosphatidylserine with the RPE receptors αvβ5 integrin, inducing cytosolic signaling toward Rac1 and focal adhesion kinase/MERTK, and with MERTK directly, additionally inhibiting RhoA/ROCK and thus enabling F‐actin dynamics favoring outer segment fragment engulfment. Photoreceptors and RPE persist for life with each RPE cell in the eye servicing dozens of overlying photoreceptors. Thus, RPE cells phagocytose more often and process more material than any other cell type. Mutant mice with impaired outer segment renewal largely retain functional photoreceptors and retinal integrity. However, when anti‐inflammatory signaling in the RPE via MERTK or the related TYRO3 is lacking, catastrophic inflammation leads to immune cell infiltration that swiftly destroys the retina causing blindness.
Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus

Besides its established impact on bone and mineral metabolism, it was suggested that fibroblast growth factor 23 (FGF23) might play an important role in the pathogenesis of type 2 diabetes. The impact of FGF23 on gestational diabetes mellitus (GDM), however, is not well understood. iFGF23 ELISAs measure the intact FGF23 molecule, whereas cFGF23 assays measure intact FGF23 as well as degradation products of FGF23.
Quantitative reverse transcription PCR to determine the inactivation of Human Rotavirus by chlorine Authors’ names:

Human rotaviruses (HRVs) are the major cause of acute diarrhea in infants and young children. Here, a real-time reverse transcription polymerase chain reaction assay targeting the rotaviral VP4 gene (VP4-RT-qPCR) was established to evaluate the inactivation of HRV upon chlorine disinfection, based on a previous report that
Domain-Specific Cognitive Impairment Reflects Prefrontal Dysfunction in Aged Common Marmosets

Abstract Age-related cognitive impairment is not expressed uniformly across cognitive domains. Cognitive functions that rely on brain areas that undergo substantial neuroanatomical changes with age often show age-related impairment, whereas those that rely on brain areas with minimal age-related change typically do not. The common marmoset has grown in popularity as a model for neuroscience research, but robust cognitive phenotyping, particularly as a function of age and across multiple cognitive domains, is lacking. This presents a major limitation for the development and evaluation of the marmoset as a model of cognitive aging and leaves open the question of whether they exhibit age-related cognitive impairment that is restricted to some cognitive domains, as in humans. In this study, we characterized stimulus–reward association learning and cognitive flexibility in young adults to geriatric marmosets using a Simple Discrimination task and a Serial Reversal task, respectively. We found that aged marmosets show transient impairment in learning-to-learn but have conserved ability to form stimulus–reward associations. Furthermore, aged marmosets have impaired cognitive flexibility driven by susceptibility to proactive interference. As these impairments are in domains critically dependent on the prefrontal cortex, our findings support prefrontal cortical dysfunction as a prominent feature of neurocognitive aging. This work positions the marmoset as a key model for understanding the neural underpinnings of cognitive aging.