bluuebunny/crossref_metadata_2025_split huggingface dataset:
Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract
Authors: DeFilipp Zachariah , Damania Ashish V. , Kim Haesook T. , Chang Chia-Chi , El-Jawahri Areej , McAfee Steven L. , Bottoms AJ S. , Toncheva Vesselina , Smith Melissa M. , Dolaher Maria , Perry Lindsey , White Meghan , Diana Brittany , Connolly Sheila , Dey Bimalangshu R. , Frigault Matthew J. , Newcomb Richard A. , O’Donnell Paul V. , Spitzer Thomas R. , Mansour Michael K. , Weber Daniela , Ajami Nadim J. , Hohmann Elizabeth , Jenq Robert R. , Chen Yi-Bin 
Published: March 2024

Abstract
Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary end point, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at day 28 was 70%. Initial clinical response was observed within 1 week for all responders, and clinical responses were durable without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased after FMT. Although recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT04139577.
Evaluation of the high-energy flood of mid-July 2021 as a morphologic driver in the anthropogenically developed Ahr Valley, Germany, in interaction with infrastructures
Authors: Wolf Stefanie , Stark Nina , Holste Ina , Lehmkuhl Frank , Römer Wolfgang , Burghardt Lisa , Schüttrumpf Holger 
Published: March 2024

Abstract
Background
This study explores morphologic changes in the Ahr River, Germany, caused by the high-energy flood in mid-July 2021. This study aims to assess the flood's significance as a morphological driver using the Lateral Mobility Index (LMI), as well as the impact of infrastructure on morphodynamics in terms of the formation of mud deposits and stagnant water pools, considering three focus areas of about 1 to 5 km river length. The three focus areas cover differences in the valley morphology as well as near natural and anthropogenically affected sections.

Results
The LMI is derived from orthophotos from 1998 to 2022, and based on the surface area of the old and the new channel. It describes the sum of new and abandoned channel area in relation to the previous channel area. For the 2021 high-energy event, an increased LMI suggests an increasing change in river course and morphology. Post-flood, the LMI in focus areas 1 (furthest upstream, LMI of 1.5) and 3 (at the Rhine confluence, LMI of 3.2) surpasses the historic LMI by a factor of about 3. Focus area 3 exhibits the highest activity, while focus area 2 (LMI between 0.25 and 0.70) the lowest. The area of mud deposits and stagnant water pools increased immediately after the flood, especially in focus area 3. Over the following months, initial post-flood mud deposits not only washed away but also rebuilt to some degree later on.

Conclusions
The LMI enabled to quantitatively identify a rare and significant morphological disruption in the Ahr River’s lateral development in three focus areas, and thus, serves as additional proof that the flood of mid-July 2021 was a high-energy event impacting the local river geomorphology. Infrastructure impacted the formation of mud deposits and stagnant water zones during and after the flood, with additional influence from factors such as driftwood and valley width. The data suggested a phase of resuspension of sediments after the flood, likely due to cleanup and ad hoc river management, highlighting the need for continued river monitoring.
Placement of bronchial occluder outside the tracheal tube in a patient combined with airway compression undergoing mediastinal tumors resection: a case report
Authors: Zhou Yihu , Jiang Yueyi , Ding Yuyan , Gu Lianbing , Tan Jing 
Published: March 2024

Abstract
Background
Mediastinal tumors pose a challenging respiratory and circulatory management during anesthesia procedures, there is a risk of circulatory collapse or complete airway obstruction, which in severe cases can lead to cardiac arrest. We reported a case of anesthetic management using a bronchial blocker placed outside the tracheal tube. In this case report, the patient’s trachea was so severely compressed that the airway was extremely narrow, only 4 mm at its narrowest point. By reporting the anesthetic management of this patient, we intend to provide an unusual approach for airway management.

Case presentation
A 52-year-old male patient was admitted to the hospital due to cough and expectoration for one year. Additionally, the patient experienced chest tightness and asthma after physical activity. The enhanced computed tomography revealed there existed an irregular soft tissue mass in the right upper mediastinum, which significantly compressed the trachea and esophagus. The results of the mediastinal puncture pathology showed the presence of mesenchymal tumors. According to the results above, the patient was diagnosed with a mediastinal tumor and scheduled to undergo tumor resection under general anesthesia. We used a bronchial occluder outside the tracheal tube for general anesthesia. After surgery, the patient received thorough treatment and was subsequently discharged from the hospital.

Conclusion
In patients with severe airway compression from a mediastinal tumor airway compression, positioning a bronchial occluder externally to the tracheal tube is an effective method of airway management. However, we still need more clinical practice to help the process become more standardized.
Assessing the research landscape and clinical utility of large language models: a scoping review
Authors: Park Ye-Jean , Pillai Abhinav , Deng Jiawen , Guo Eddie , Gupta Mehul , Paget Mike , Naugler Christopher 
Published: March 2024

Abstract
Importance
Large language models (LLMs) like OpenAI’s ChatGPT are powerful generative systems that rapidly synthesize natural language responses. Research on LLMs has revealed their potential and pitfalls, especially in clinical settings. However, the evolving landscape of LLM research in medicine has left several gaps regarding their evaluation, application, and evidence base.

Objective
This scoping review aims to (1) summarize current research evidence on the accuracy and efficacy of LLMs in medical applications, (2) discuss the ethical, legal, logistical, and socioeconomic implications of LLM use in clinical settings, (3) explore barriers and facilitators to LLM implementation in healthcare, (4) propose a standardized evaluation framework for assessing LLMs’ clinical utility, and (5) identify evidence gaps and propose future research directions for LLMs in clinical applications.

Evidence review
We screened 4,036 records from MEDLINE, EMBASE, CINAHL, medRxiv, bioRxiv, and arXiv from January 2023 (inception of the search) to June 26, 2023 for English-language papers and analyzed findings from 55 worldwide studies. Quality of evidence was reported based on the Oxford Centre for Evidence-based Medicine recommendations.

Findings
Our results demonstrate that LLMs show promise in compiling patient notes, assisting patients in navigating the healthcare system, and to some extent, supporting clinical decision-making when combined with human oversight. However, their utilization is limited by biases in training data that may harm patients, the generation of inaccurate but convincing information, and ethical, legal, socioeconomic, and privacy concerns. We also identified a lack of standardized methods for evaluating LLMs’ effectiveness and feasibility.

Conclusions and relevance
This review thus highlights potential future directions and questions to address these limitations and to further explore LLMs’ potential in enhancing healthcare delivery.
Investigating the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles in atherosclerosis treatment
Authors: Yang Rongfeng , Lin Fengxia , Wang Wenlin , Dai Gang , Ke Xiao , Wu Guifu 
Published: March 2024

Abstract
Background
Carthamus tinctorius L., a traditional herbal medicine used for atherosclerosis (AS), lacks a clear understanding of its therapeutic mechanisms. This study aimed to investigate the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles (CDNVs) in AS treatment.

Methods
CDNVs were isolated and characterized using improved isolation methods. Transmission electron microscopy, nanoparticle tracking analysis, and protein analysis confirmed their morphology, size, and protein composition. Small RNA sequencing was performed to identify the miRNA profile of CDNVs, and bioinformatics analysis was used to determine their potential biological roles. In vivo biodistribution and toxicity studies were conducted in mice to assess the stability and safety of orally administered CDNVs. The anti-atherosclerotic effects of CDNVs were evaluated in ApoE-/- mice through plaque burden analysis. The protective effects of CDNVs on ox-LDL-treated endothelial cells were assessed through proliferation, apoptosis, reactive oxygen species activation, and monocyte adhesion assays. miRNA and mRNA sequencing of CDNV-treated endothelial cells were performed to explore their regulatory effects and potential target genes.

Results
CDNVs were successfully isolated and purified from Carthamus tinctorius L. tissue lysates. They exhibited a saucer-shaped or cup-shaped morphology, with an average particle size of 142.6 ± 0.7 nm, and expressed EV markers CD63 and TSG101. CDNVs contained proteins, small RNAs, and metabolites, including the therapeutic compound HSYA. Small RNA sequencing identified 95 miRNAs, with 10 common miRNAs accounting for 72.63% of the total miRNAs. These miRNAs targeted genes involved in cell adhesion, apoptosis, and cell proliferation, suggesting their relevance in cardiovascular disease. Orally administered CDNVs were stable in the gastrointestinal tract, absorbed into the bloodstream, and accumulated in the liver, lungs, heart, and aorta. They significantly reduced the burden of atherosclerotic plaques in ApoE-/- mice and exhibited superior effects compared to HSYA. In vitro studies demonstrated that CDNVs were taken up by HUVECs, promoted proliferation, attenuated ox-LDL-induced apoptosis and ROS activation, and reduced monocyte adhesion. CDNV treatment resulted in significant changes in miRNA and mRNA expression profiles of HUVECs, with enrichment in inflammation-related genes. CXCL12 was identified as a potential direct target of miR166a-3p.

Conclusion
CDNVs isolated from Carthamus tinctorius L. tissue lysates represent a promising oral therapeutic option for cardiovascular diseases. The delivery of miRNAs by CDNVs regulates inflammation-related genes, including CXCL12, in HUVECs, suggesting their potential role in modulating endothelial inflammation. These findings provide valuable insights into the therapeutic potential of CDNVs and their miRNAs in cardiovascular disease.
Transient but not chronic hyperglycemia accelerates ocular glymphatic transport
Authors: Delle Christine , Wang Xiaowei , Giannetto Michael , Newbold Evan , Peng Weiguo , Gomolka Ryszard Stefan , Ladrón-de-Guevara Antonio , Cankar Neža , Schiøler Nielsen Elise , Kjaerby Celia , Weikop Pia , Mori Yuki , Nedergaard Maiken 
Published: March 2024

AbstractGlymphatic transport is vital for the physiological homeostasis of the retina and optic nerve. Pathological alterations of ocular glymphatic fluid transport and enlarged perivascular spaces have been described in glaucomatous mice. It remains to be established how diabetic retinopathy, which impairs vision in about 50% of diabetes patients, impacts ocular glymphatic fluid transport. Here, we examined ocular glymphatic transport in chronic hyperglycemic diabetic mice as well as in healthy mice experiencing a daily transient increase in blood glucose. Mice suffering from severe diabetes for two and four months, induced by streptozotocin, exhibited no alterations in ocular glymphatic fluid transport in the optic nerve compared to age-matched, non-diabetic controls. In contrast, transient increases in blood glucose induced by repeated daily glucose injections in healthy, awake, non-diabetic mice accelerated antero- and retrograde ocular glymphatic transport. Structural analysis showed enlarged perivascular spaces in the optic nerves of glucose-treated mice, which were absent in diabetic mice. Thus, transient repeated hyperglycemic events, but not constant hyperglycemia, ultimately enlarge perivascular spaces in the murine optic nerve. These findings indicate that fluid transport in the mouse eye is vulnerable to fluctuating glycemic levels rather than constant hyperglycemia, suggesting that poor glycemic control drives glymphatic malfunction and perivascular enlargement in the optic nerve.
Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment
Authors: Isaiah Simon , Loots Du Toit , van Furth A. Marceline Tutu , Davoren Elmarie , van Elsland Sabine , Solomons Regan , van der Kuip Martijn , Mason Shayne 
Published: March 2024

AbstractBackgroundThe pathogenesis of tuberculous meningitis (TBM) involves infection byMycobacterium tuberculosisin the meninges and brain. However, recent studies have shown that the immune response and inflammatory processes triggered by TBM can have significant effects on gut microbiota. Disruptions in the gut microbiome have been linked to various systemic consequences, including altered immunity and metabolic dysregulation. Inflammation caused by TBM, antibiotic treatment, and changes in host immunity can all influence the composition of gut microbes. This complex relationship between TBM and the gut microbiome is of great importance in clinical settings. To gain a deeper understanding of the intricate interactions between TBM and the gut microbiome, we report innovative insights into the development of the disease in response to treatment. Ultimately, this could lead to improved outcomes, management strategies and quality of life for individuals affected by TBM.MethodWe used a targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) approach to investigate metabolites associated with gut metabolism in paediatric participants by analysing the urine samples collected from a control group (n = 40), and an experimental group (n = 35) with confirmed TBM, which were subdivided into TBM stage 1 (n = 8), stage 2 (n = 11) and stage 3 (n = 16).FindingsOur metabolomics investigation showed that, of the 78 initially selected compounds of microbiome origin, eight unique urinary metabolites were identified: 2-methylbutyrlglycine, 3-hydroxypropionic acid, 3-methylcrotonylglycine, 4-hydroxyhippuric acid, 5-hydroxyindoleacetic acid, 5-hydroxyhexanoic acid, isobutyrylglycine, and phenylacetylglutamine as urinary markers of dysbiosis in TBM.ConclusionThese results – which are supported by previous urinary studies of tuberculosis – highlight the importance of gut metabolism and of identifying corresponding microbial metabolites as novel points for the foundation of improved management of TBM patients.
Cryopreserved cGMP-compliant human pluripotent stem cell-derived hepatic progenitors rescue mice from acute liver failure through rapid paracrine effects on liver cells
Authors: Gantier Malika , Rispal Raphaël , Fourrier Angélique , Ménoret Séverine , Delbos Frédéric , Anegon Ignacio , Nguyen Tuan Huy 
Published: March 2024

Abstract
Background
Liver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation. Considering their unique expansion capabilities and their potency to be driven toward a chosen cell fate, pluripotent stem cells are extensively studied as an unlimited cell source of hepatocytes for cell therapy. It has been previously shown that freshly prepared hepatocyte-like cells can cure mice from acute and chronic liver failure and restore liver function.

Methods
Human PSC-derived immature hepatic progenitors (GStemHep) were generated using a new protocol with current good manufacturing practice compliant conditions from PSC amplification and hepatic differentiation to cell cryopreservation. The therapeutic potential of these cryopreserved cells was assessed in two clinically relevant models of acute liver failure, and the mode of action was studied by several analytical methods, including unbiased proteomic analyses.

Results
GStemHep cells present an immature hepatic phenotype (alpha-fetoprotein positive, albumin negative), secrete hepatocyte growth factor and do not express major histocompatibility complex. A single dose of thawed GStemHep rescue mice from sudden death caused by acetaminophen and thioacetamide-induced acute liver failure, both in immunodeficient and immunocompetent animals in the absence of immunosuppression. Therapeutic biological effects were observed as soon as 3 h post-cell transplantation with a reduction in serum transaminases and in liver necrosis. The swiftness of the therapeutic effect suggests a paracrine mechanism of action of GStemHep leading to a rapid reduction of inflammation as well as a rapid cytoprotective effect with as a result a proteome reprograming of the host hepatocytes. The mode of action of GStemHep relie on the alleviation of inhibitory factors of liver regeneration, an increase in proliferation-promoting factors and a decrease in liver inflammation.

Conclusions
We generated cryopreserved and current good manufacturing practice-compliant human pluripotent stem cell-derived immature hepatic progenitors that were highly effective in treating acute liver failure through rapid paracrine effects reprogramming endogenous hepatocytes. This is also the first report highlighting that human allogeneic cells could be used as cryopreserved cells and in the absence of immunosuppression for human PSC-based regenerative medicine for acute liver failure.
Systematic analysis, aggregation and visualisation of interaction fingerprints for molecular dynamics simulation data
Authors: Jaeger-Honz Sabrina , Klein Karsten , Schreiber Falk 
Published: March 2024

AbstractComputational methods such as molecular docking or molecular dynamics (MD) simulations have been developed to simulate and explore the interactions between biomolecules. However, the interactions obtained using these methods are difficult to analyse and evaluate. Interaction fingerprints (IFPs) have been proposed to derive interactions from static 3D coordinates and transform them into 1D bit vectors. More recently, the concept has been applied to derive IFPs from MD simulations, which adds a layer of complexity by adding the temporal motion and dynamics of a system. As a result, many IFPs are obtained from one MD simulation, resulting in a large number of individual IFPs that are difficult to analyse compared to IFPs derived from static 3D structures. Scientific contribution: We introduce a new method to systematically aggregate IFPs derived from MD simulation data. In addition, we propose visualisations to effectively analyse and compare IFPs derived from MD simulation data to account for the temporal evolution of interactions and to compare IFPs across different MD simulations. This has been implemented as a freely available Python library and can therefore be easily adopted by other researchers and to different MD simulation datasets.
A global analysis of the introduction pathways and characteristics associated with non-native fish species introduction, establishment, and impacts
Authors: Bernery Camille , Bellard Céline , Courchamp Franck , Brosse Sébastien , Leroy Boris 
Published: March 2024

Abstract
Background
The invasion success of introduced freshwater fishes is influenced by many factors, including ecological, species, and socioeconomic characteristics. Most studies that document the importance of these characteristics are conducted at local scales and/or focus on a single step of the invasion process. In this study, we aim to determine the species characteristics, ecological characteristics, and socioeconomic characteristics of non-native freshwater fish invasions. Our assessment was done at the global scale and considers all three steps of the invasion (i.e., introduction, establishment, and impact). For this purpose, we applied generalized linear models to 20 variables collected for 307 non-native species and modeled them as a function of ecological characteristics (i.e., environmental features), species traits (i.e., functional and morphological), and socioeconomic characteristics (i.e., human use and introduction pathways). We considered the number of countries in which each species was introduced, established, or had ecological impacts as a proxy of invasion step success. We also explored the specifics of species introduced through the aquaculture and the ornamental fish trade pathways.

Results
We found that non-native freshwater fishes with broad diets, high parental care, and multiple introduction pathways are the most widely introduced and established worldwide. The number of countries with impacts reported was best explained by the type of introduction pathway (i.e., aquaculture or fisheries). Moreover, among non-native species introduced through aquaculture, those belonging to Cypriniformes and having broad diets were the most widely introduced and established species. In contrast, the species introduced through the ornamental fish trade pathway belonged to various taxonomic orders but were mainly native to tropical regions.

Conclusions
Considering several types of factors is important when analyzing the invasion success of freshwater fish and disentangling the different invasion steps. These findings have strong implications for anticipating the profile of species with a high potential to invade many countries.