Miracle-dz/UniFAR-FTUs huggingface dataset:
Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus

Liver-generated plasma Apolipoprotein E (ApoE)-containing lipoproteins (LPs) (ApoE-LPs) play central roles in lipid transport and metabolism. Perturbations of ApoE can result in several metabolic disorders and ApoE genotypes have been associated with multiple diseases. ApoE is synthesized at the endoplasmic reticulum and transported to the Golgi apparatus for LP assembly; however, ApoE-LPs transport from there to the plasma membrane is largely unknown. Here, we established an integrative imaging approach based on a fully functional fluorescently tagged ApoE. We found that ApoE-LPs accumulate in CD63-positive endosomes of hepatocytes. In addition, we observed the co-egress of ApoE-LPs and extracellular vesicles (EVs) along the late endosomal trafficking route. Moreover, complexes of ApoE-LPs and CD63-positive EVs were found to be transmitted from cell to cell. Given the important role of ApoE in viral infections, we studied the hepatitis C virus (HCV) and found that the viral replicase protein NS5A is enriched in ApoE-containing intraluminal vesicles. Interaction between NS5A and ApoE is required for the efficient release of EVs containing viral RNA. These vesicles are transported along the endosomal ApoE egress pathway. Taken together, our data argue for endosomal egress and transmission of hepatic ApoE-LPs, a pathway that is hijacked by HCV. Given the more general role of EV-mediated cell-to-cell communication, these insights provide new starting points for research into the pathophysiology of ApoE-related metabolic and infection-related disorders. Author Summary The post-Golgi egress pathway of hepatocyte-derived ApoE-containing lipoproteins (ApoE-LPs) is largely unknown. By using integrative imaging analyses, we show that ApoE-LPs are enriched in CD63-positive endosomes suggesting that these endosomes might be a central hub for the storage of ApoE-LPs from which they are released into the circulation. In addition, we provide evidence for the co-egress of ApoE-LPs with extracellular vesicles (EVs) along the late endosomal route and their transfer from cell to cell. This pathway is hijacked by the hepatitis C virus that induces the production of ApoE-associated EVs containing viral RNA. Given the important role of ApoE in multiple metabolic, degenerative and infectious diseases, and the role of EVs in cell-to-cell communication, these results provide important information how perturbations of ApoE might contribute to various pathophysiologies.
Assessing the impacts of a transition to agroecology-based agricultural systems on smallholder farmers' livelihoods in Burkina Faso

During recent years, more and more studies have emphasized the importance of a transition to alternative agricultural systems through “an agroecological development paradigm based on the revitalization of small farms which emphasizes diversity, synergy, recycling and integration, and social processes that value community participation and empowerment”. While this debate is embedded in a context of global food systems, it is especially important in regard of the situation of African smallholders where “sustainable agriculture offers new opportunities, by emphasising the productive values of natural, social and human capital, all assets that Africa either has in abundance or that can be regenerated at low financial cost. ” According to the mentioned studies, agroecology and its field applied practices have the potential to meet the double challenge of high productivity and high sustainability and thus to improve livelihoods of smallholder farmers in developing countries.
Contamination of the marine environment by Antarctic research stations: Monitoring marine pollution at Casey station from 1997 to 2015

The contamination of the marine environment surrounding coastal Antarctic research stations remains insufficiently understood in terms of its extent, persistence, and characteristics. We investigated the presence of contaminants in marine sediments near Casey Station, located in the Windmill Islands of East Antarctica, during the period spanning from 1997 to 2015. Metals, hydrocarbons, PBDEs, PCBs, and nutrients were measured in sediments at anthropogenically disturbed sites, including the wastewater outfall, the wharf area, two former waste disposal sites, and various control locations. Sampling was carried out at three spatial scales: Locations, which were generally kilometres apart and formed the primary scale for comparison; Sites, which were 100 meters apart within each location; and Plots, which were 10 meters apart within each site. Consistently higher concentrations of most contaminants, and in some cases nutrients, were observed at disturbed locations. Some locations also exhibited an increase in contaminant concentrations over time. The spatial distribution of sediment properties (such as grain size and organic matter) and contaminants displayed intricate patterns of variation. Variation in grain size depended on the size category, with fine grains (e.g., <63 μm) showing the greatest variation at the Location scale, while coarse grains exhibited minimal variation at this scale. Contaminant levels demonstrated significant differences between Locations, accounting for approximately 55% of the overall variation for metals, while the variation within the 10-meter scale generally exceeded that within the 100-meter scale. Residual variation among replicate samples was also very high, demonstrating the need for adequate replication in studies of sediments and contaminants around stations. Some contaminants exceeded international guidelines for sediment quality, including metals, hydrocarbons, and PCBs. We conclude that Antarctic research stations such as Casey are likely to pose a moderate level of long-term ecological risk to local marine ecosystems through marine pollution. However, contamination is expected to be confined to areas in close proximity to the stations, although its extent and concentration are anticipated to increase with time. Raising awareness of the contamination risks associated with Antarctic stations and implementing monitoring programs for marine environments adjacent to these stations can contribute to informed decision-making and the improvement of environmental management practices in Antarctica.
A retrospective evaluation of the effect of oclacitinib (Apoquel) administration on development of surgical site infection following clean orthopedic stifle surgery

The aim of this study was to determine the effect of oclacitinib (Apoquel) on development of surgical site infections in canines following clean orthopedic stifle surgery. Medical records of dogs undergoing unilateral, clean orthopedic stifle procedures were retrospectively examined for development of post-operative surgical site infections. Data collected for statistical analysis included age, sex, body weight, current medications, anesthesia and surgery times, white blood cell count, and neutrophil count. Surgical site infections were identified in 8.7% (34/390) of stifle procedures– 8.0% (29/364) in dogs not treated with oclacitinib and 19.2% (5/26) in dogs treated with oclacitinib (p = 0.053). There was a significant difference in development of surgical site infection in dogs with longer anesthesia times (p = 0.003) and higher body weights (p = 0.037). Dogs being treated with oclacitinib at the time of clean, orthopedic stifle surgery did not have a significantly higher incidence of surgical site infections. However, client education regarding risk of infection and increased patient monitoring post-operatively are recommended, especially in patients with increased body weight or longer anesthetic times.
Development of betulinic acid as an agonist of Tgr5 receptor using a new in vitro assay

G-protein-coupled bile acid receptor 1, also known as TGR5 is known to be involved in glucose homeostasis. In animal models, treatment with a TGR5 agonist induces incretin secretion to reduce hyperglycemia. Betulinic acid, a triterpenoid present in the leaves of white birch, has been introduced as a selective TGR5 agonist. However, direct activation of TGR5 by betulinic acid has not yet been reported. Methods: Transfection of TGR5 into cultured Chinese hamster ovary (CHO-K1) cells was performed to establish the presence of TGR5. Additionally, TGR5-specific small interfering RNA was employed to silence TGR5 in cells (NCI-H716 cells) that secreted incretins. Uptake of glucose by CHO-K1 cells was evaluated using a ﬂuorescent indicator. Amounts of cyclic adenosine monophosphate and glucagon-like peptide were quantified using enzyme-linked immunosorbent assay kits. Results: Betulinic acid dose-dependently increases glucose uptake by CHO-K1 cells transfected with TGR5 only, which can be considered an alternative method instead of radioligand binding assay. Additionally, signals coupled to TGR5 activation are also increased by betulinic acid in cells transfected with TGR5. In NCI-H716 cells, which endogenously express TGR5, betulinic acid induces glucagon-like peptide secretion via increasing calcium levels. However, the actions of betulinic acid were markedly reduced in NCI-H716 cells that received TGR5-silencing treatment. Therefore, the present study demonstrates the activation of TGR5 by betulinic acid for the first time. Conclusion: Similar to the positive control lithocholic acid, which is the established agonist of TGR5, betulinic acid has been characterized as a useful agonist of TGR5 and can be used to activate TGR5 in the future.
The middle stone age at Klasies River, South Africa

OPSOMMING The Late Pleistocene, Middle Stone Age artefact sequence at the Klasies River main site, was studied to establish what information this held for inferences on the emergence of symbolic thought and communication. The approach adopted was to complement traditional typological analysis by a technological study of artefact production within the framework of the chafne opératoire. The results show that technology was aimed at producing preformed blanks. In the choice of materials, the technique and method of blank production and the retouch of blanks, arbitrary or stylistic choices were made. Changes in stylistic conventions can be documented through the sequence. Changing conventions in artefact production show that the lives of the people who made the artefacts were structured in a symbolic web. These results together with evidence from evolutionary biology, show that by at least 115 000 years ago, people were able to think and speak symbolically. This African archaeological evidence for the emergence of symbolism, a defining attribute of modem peoples, is much older than previously considered.
Systematic review and individual patient data meta-analysis of sex differences in depression and prognosis in persons with myocardial infarction: a MINDMAPS study Running head: Sex differences in depression post-MI

Systematic review and individual patient data meta-analysis of sex differences in depression and prognosis in persons with myocardial infarction: A MINDMAPS study / Doyle, Frank; Mcgee, Hannah; Conroy, Ronán; Conradi, Henk Jan; Meijer, Anna; Steeds, Richard; Sato, Hiroshi; Stewart, Donna E. ; Parakh, Kapil; Carney, Robert; Freedland, Kenneth; Anselmino, Matteo; Pelletier, Roxanne; Bos, Elisabeth H. ; De Jonge, Peter. In: PSYCHOSOMATIC MEDICINE. ISSN 0033-3174. 77:4(2015), pp. 419-428. Original Citation: Systematic review and individual patient data meta-analysis of sex differences in depression and prognosis in persons with myocardial infarction: A MINDMAPS study
FISTULA-IN-ANO: A PROSPECTIVE AUDIT

Objective: Fistula-in-ano is a common condition that is characterized by intermittent pain and discharge. We present an audit of all patients seen with anal fistula at Prince Hashem Hospital during an eighteen month period. Methods: This audit includes all patients that underwent examination under anesthetic for fistula-in-ano from September 2006 to May 2008. Anatomic classification and operative procedures of all fistulae were recorded. Patients were followed-up for a mean period of 13 months and details of wound healing, fistula recurrence and function were gathered. Results: Forty three consecutive patients underwent examination under anesthesia for fistula. There were 36 males with a mean age of 32.2 years (range 17-65). Eight (18.6%) patients had superficial, 15 (34.9%) intersphincteric, 17 (39.5%) transphincteric, 3 (7%) suprasphincteric and none had extrasphincteric fistulae. Forty (93%) patients had fistulae of cryptoglandular (idiopathic) origin. Two (4.7%) patients had Crohn’s disease and one (2.3%) had low rectal malignancy. Thirty two (74.4%) patients underwent fistulotomy. One (2.3%) patient had advancement flap. Nine (21%) patients had loose seton in situ and one patient underwent abdominoperineal resection. Four (9.5%) patients had some degree of flatus incontinence, two (4.8%) had incontinence to liquid stool. Soiling was present in one patient. Conclusions: Fistula-in-ano is relatively a common condition in Jordan. Its variation in anatomical distribution should alert the surgeons for the variety of surgical options available for its treatment, especially the difficult and complex ones, that should be managed by a colorectal surgeon or general surgeon that has adequate experience in this field. Unusual causes like Crohn’s disease and malignancy should be kept in mind in complex, unhealed fistulae.
EEG Phase Can Be Predicted with Similar Accuracy across Cognitive States after Accounting for Power and Signal-to-Noise Ratio

Abstract EEG phase is increasingly used in cognitive neuroscience, brain–computer interfaces, and closed-loop stimulation devices. However, it is unknown how accurate EEG phase prediction is across cognitive states. We determined the EEG phase prediction accuracy of parieto-occipital alpha waves across rest and task states in 484 participants over 11 public datasets. We were able to track EEG phase accurately across various cognitive conditions and datasets, especially during periods of high instantaneous alpha power and signal-to-noise ratio (SNR). Although resting states generally have higher accuracies than task states, absolute accuracy differences were small, with most of these differences attributable to EEG power and SNR. These results suggest that experiments and technologies using EEG phase should focus more on minimizing external noise and waiting for periods of high power rather than inducing a particular cognitive state.
Optimized drug‐coated balloon angioplasty of the superficial femoral and proximal popliteal arteries using the Tack Endovascular System: Tack Optimized Balloon Angioplasty (TOBA) III 24‐month results in standard and long lesions

The Tack Endovascular System is a minimal‐metal dissection repair device that is purpose‐built to treat post‐percutaneous angioplasty (PTA) arterial dissections in patients with peripheral arterial disease (PAD). The Tack Optimized Balloon Angioplasty (TOBA) III trial evaluated the safety and effectiveness of the Tack Endovascular System in patients with superficial femoral artery (SFA) and/or proximal popliteal artery (PPA) dissection after PTA with a drug‐coated balloon (DCB). The objective of this study is to report the results in the standard‐ (SL) and long‐lesion (LL) cohorts through 24 months.
Evaluation of splenic infarction ratio and platelet increase ratio after partial splenic artery embolization

Objective The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter the blood, remove old blood cells, and fight infection. Partial splenic artery embolization (PSE) is widely used to treat pancytopenia and portal hypertension. The efficacy of PSE for improving thrombocytopenia has been well demonstrated. In this study, we evaluated the splenic infarction ratio and platelet increase ratio after PSE. Methods Forty-five consecutive patients underwent PSE from January 2014 to August 2022. We retrospectively evaluated the splenic infarction volume and ratio after PSE and analyzed the relationship between the splenic infarction ratio and platelet increase ratio after PSE. Results The platelet increase ratio was correlated with the splenic infarction ratio after PSE. The cutoff value for the splenic infarction ratio with a two-fold platelet increase was 63.0%. Conclusion We suggest performance of PSE in patients with a splenic infarction ratio of 63% to double the expected platelet count.
Assessment of financial screening and navigation capabilities at National Cancer Institute community oncology clinics

Abstract Background Cancer-related financial hardship is a side effect of cancer diagnosis and treatment, and affects both patients and caregivers. Although many oncology clinics have increased financial navigation services, few have resources to proactively provide financial counseling and assistance to families affected by cancer before financial hardship occurs. As part of an ongoing randomized study testing a proactive financial navigation intervention, S1912CD, among sites of the National Cancer Institute Community Oncology Research Program (NCORP), we conducted a baseline survey to learn more about existing financial resources available to patients and caregivers. Methods The NCORP sites participating in the S1912CD study completed a required 10-question survey about their available financial resources and an optional 5-question survey that focused on financial screening and navigation workflow and challenges prior to starting recruitment. The proportion of NCORP sites offering financial navigation services was calculated and responses to the optional survey were reviewed to determine current screening and navigation practices and identify any challenges. Results Most sites (96%) reported offering financial navigation for cancer patients. Sites primarily identified patients needing financial assistance through social work evaluations (78%) or distress screening tools (76%). Sites revealed challenges in addressing financial needs at the outset and through diagnosis, including lack of proactive screening and referral to financial navigation services as well as staffing challenges. Conclusions Although most participating NCORP sites offer some form of financial assistance, the survey data enabled identification of gaps and challenges in providing services. Utilizing community partners to deliver comprehensive financial navigation guidance to cancer patients and caregivers may help meet needs while reducing site burden.
Reducing Vision-Answer Biases for Multiple-Choice VQA

Multiple-choice visual question answering (VQA) is a challenging task due to the requirement of thorough multimodal understanding and complicated inter-modality relationship reasoning. To solve the challenge, previous approaches usually resort to different multimodal interaction modules. Despite their effectiveness, we find that existing methods may exploit a new discovered bias (vision-answer bias) to make answer prediction, leading to suboptimal VQA performances and poor generalization. To solve the issues, we propose a Causality-based Multimodal Interaction Enhancement (CMIE) method, which is model-agnostic and can be seamlessly incorporated into a wide range of VQA approaches in a plug-and-play manner. Specifically, our CMIE contains two key components: a causal intervention module and a counterfactual interaction learning module. The former devotes to removing the spurious correlation between the visual content and the answer caused by the vision-answer bias, and the latter helps capture discriminative inter-modality relationships by directly supervising multimodal interaction training via an interactive loss. Extensive experimental results on three public benchmarks and one reorganized dataset show that the proposed method can significantly improve seven representative VQA models, demonstrating the effectiveness and generalizability of the CMIE.
Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1 (HIF-1 ) accumulation via redox-dependent mechanisms

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Semimechanistic pharmacokinetic–pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy

Tripegfilgrastim is a long‐acting granulocyte colony‐stimulating factor (G‐CSF) that has been used to prevent chemotherapy‐induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)–pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed‐dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK‐PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics‐mediated drug disposition model assuming quasi‐equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G‐CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim‐G‐CSF receptor complex (Kd) and apparent volume of distribution (Vd/F). Patients treated with chemotherapy had a higher Vd/F and 62% lower Kd than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G‐CSF receptor‐mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G‐CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10–20, 21–30, 31–44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight‐based treatment with 100 μg/kg.