julilili42/papers huggingface dataset:
Impact of postoperative complications on clinical outcomes after gastrectomy for cancer: multicentre study
2025-03-28

Abstract Background To reduce the clinical and economic burden of complications after gastrectomy for gastric cancer, specific complications should be targeted to effectively allocate healthcare resources for quality improvement and preventive measures. The aim of this study was to assess the impact of complications on clinical outcomes. Methods This was a retrospective multicentre study of patients who underwent (sub)total gastrectomy for gastric or junctional adenocarcinoma at 43 centres in 16 countries between 2017 and 2021. Outcomes were escalation of care, reoperation, prolonged hospital stay (greater than the 75th percentile), readmission, and 30-day mortality. Adjusted relative risks and population attributable fractions were estimated for specific complication–outcome pairs. The population attributable fraction represents the percentage reduction in the frequency of an adverse outcome if a complication could be completely prevented in the population. Results In total, 7829 patients were included. Postoperative complications occurred in 1884 patients (24.1%). The most frequent complications were pulmonary complications (436 patients (5.6%)), anastomotic leakage (363 patients (4.6%)), and abdominal collection (301 patients (3.8%)). Anastomotic leakage, cardiac complications, and pulmonary complications had the greatest impact on 30-day mortality (population attributable fraction 26.6% (95% c.i. 14.5% to 38.6%), 18.7% (95% c.i. 9.4% to 28.0%), and 15.6% (95% c.i. 12.0% to 30.0%) respectively). Anastomotic leakage and pulmonary complications had the greatest impact on escalation of care (population attributable fraction 26.3% (95% c.i. 20.6% to 32.0%) and 18.4% (95% c.i. 11.7% to 25.2%) respectively), whereas anastomotic leakage and intra-abdominal bleeding had the greatest impact on reoperation (population attributable fraction 31.6% (95% c.i. 26.4% to 36.9%) and 8.5% (95% c.i. 5.5% to 11.5%) respectively). Most of the studied complications contributed to a prolonged hospital stay, whereas the contribution of complications to readmission did not exceed 15.9%. Subgroup analysis showed regional variation in the impact of complications. Conclusion Anastomotic leakage had the largest overall negative impact on clinical outcomes after gastrectomy for gastric adenocarcinoma. Reducing the incidence of anastomotic leakage and pulmonary complications would have the most impact on the burden of complications.
Cerebral autoregulation monitoring in neonates and infants after cardiac surgery with cardiopulmonary bypass - comparison of single ventricle and biventricular physiology
2025-03-28

Introduction Cardiopulmonary bypass surgery can lead to impaired cerebral autoregulation with the risk for ischemia, hemorrhage and delirium. In particular, infants with single ventricle physiology have altered hemodynamics with persistent veno-arterial shunting, cyanosis and diastolic run-off after surgery, which may have negative effects on cerebral autoregulation. Methods Cerebral autoregulation was prospectively monitored in 83 neonates and infants after open heart surgery with cardiopulmonary bypass after admission to the pediatric intensive care unit. Autoregulation indices were determined using near-infrared spectroscopy, correlating regional cortical oxygen saturation and local hemoglobin levels with invasive mean arterial pressure. Intact autoregulation was defined as cerebral oxygenation index (COx) &amp;lt; 0.4 and hemoglobin volume index (HVx) &amp;lt; 0.3. A subgroup analysis was performed between 55 infants after biventricular repair surgery and 15 infants after palliative surgery. Results The mean lower limit of autoregulation was 46 ± 6 mmHg (COx) and 46 ± 7 mmHg (HVx). The optimal mean arterial pressure according to cerebral autoregulation was 56 ± 8 mmHg (COx) and 55 ± 7 mmHg (HVx). The mean upper limit was 65 ± 9 mmHg (COx) and 65 ± 8 mmHg (HVx). Intact autoregulation occurred during 84 ± 8% (COx) and 77 ± 10% (HVx) of the monitored time. No significant differences were found in autoregulation parameters between single ventricle and biventricular groups. However, the single ventricle group had significantly lower arterial and cerebral oxygen saturation. Discussion A standardized blood pressure management may not be sufficient in children after cardiac surgery due to potentially impaired cerebral autoregulation. Therefore, cerebral autoregulation monitoring should be considered in this patient population.
Characterization of dengue patients in Vietnam: Clinical, virological, and IL-10 profiles during 2021– 2022 outbreaks
2025-03-28

Background The pathogenesis of dengue is attributed to a complex interaction between the dengue virus (DENV) and the host immune system. The aim of this study is to investigate the clinical, virological, and Interleukin-10 (IL-10) profiles of dengue patients in Vietnam from two consecutive outbreaks in 2021 and 2022. Methods A total of n=306 dengue patients were examined, who were clinically stratified according to dengue without warning signs (DF; n=178), dengue with warning signs (DWS; n=115) and severe dengue (SD; n=13). Patients were screened for dengue, Zika and chikungunya viruses. DENV were subjected to serotype specific real-time RT-PCR. Interleukin-10 (IL-10) levels were measured by ELISA, and IL-10 promoter variants (-1082G/A; -819C/T; -592C/A) were genotyped by direct Sanger sequencing to determine a possible association with susceptibility to dengue and disease severity. Results No chikungunya or Zika viruses were detected. Patients were infected by one of the three different DENV serotypes (DENV-1, -2, -4). Plasma IL-10 levels were significantly elevated in patients (DF vs. DWS, p=0.004; DF vs. SD, p=0.001; DWS vs. SD, p=0.015). While the IL-10 allele -819C contributed to an increased risk of dengue (OR = 1.5, 95% CI = 1.1-2.0, p=0.04), genotype -1082GA showed a protective role against the disease (OR = 0.45, 95% CI = 0.27-0.72, p=0.009), and allele -1082G showed a protective role against DWS (OR = 0.44, 95% CI = 0.22-0.81, p=0.049). Also, the IL-10 GTA (-1082G/-819T/-592A) haplotype was observed to confer protection (OR = 0.31, 95% CI = 0.14-0.67, p&lt; 0.003). Conclusion While DENV-1 and DENV-2 were the predominant serotypes in circulation, plasma IL-10 levels and IL-10 promoter variants were also significantly associated with dengue and its severity.
Application of curcuminoids in inflammatory, neurodegenerative and aging conditions - Pharmacological potential and bioengineering approaches to improve efficiency
2025-03-29

Curcumin, a natural compound found in turmeric, has shown promise in treating brain-related diseases and conditions associated with aging. Curcumin has shown multiple anti-inflammatory and brain-protective effects, but its clinical use is limited by challenges like poor absorption, specificity and delivery to the right tissues. A range of contemporary approaches at the intersection with bioengineering and systems biology are being explored to address these challenges. Data from preclinical and human studies highlight various neuroprotective actions of curcumin, including the inhibition of neuroinflammation, modulation of critical cellular signaling pathways, promotion of neurogenesis, and regulation of dopamine levels. However, curcumin's multifaceted effects - such as its impact on microRNAs and senescence markers - suggest novel therapeutic targets in neurodegeneration. Tetrahydrocurcumin, a primary metabolite of curcumin, also shows potential due to its presence in circulation and its anti-inflammatory properties, although further research is needed to elucidate its neuroprotective mechanisms. Recent advancements in delivery systems, particularly brain-targeting nanocarriers like polymersomes, micelles, and liposomes, have shown promise in enhancing curcumin's bioavailability and therapeutic efficacy in animal models. Furthermore, the exploration of drug-laden scaffolds and dermal delivery may extend the pharmacological applications of curcumin. Studies reviewed here indicate that engineered dermal formulations and devices could serve as viable alternatives for neuroprotective treatments and to manage skin or musculoskeletal inflammation. This work highlights the need for carefully designed, long-term studies to better understand how curcumin and its bioactive metabolites work, their safety, and their effectiveness.
Outcomes of Patients With Extramedullary Disease in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma From the Pooled LocoMMotion and MoMMent Studies
2025-03-30

These results demonstrate the urgent need for more effective novel therapies for patients with EMD and highlight the need to use clear definitions of EMD and EMD response criteria for clinical trials.
Heterozygous RAB3A variants cause cerebellar ataxia by a partial loss-of-function mechanism
2025-03-30

Abstract RAB3A encodes a small GTP-binding protein that is abundant in brain synaptic vesicles and crucial for the release of neurotransmitters and synaptic plasticity. Here, we identified RAB3A as a candidate gene for autosomal dominant cerebellar ataxia by two independent approaches: linkage in a large dominant ataxia family and, in parallel, an untargeted computational genetic association approach, analysing the 100 000 Genomes Project datasets. To validate the role of RAB3A in ataxia, we next screened large rare disease databases for rare heterozygous RAB3A variants in probands with ataxia features. In total, we identified 18 individuals from 10 unrelated families all sharing a cerebellar ataxia phenotype. Notably, 9 of the 10 families carried a recurrent variant in RAB3A, p.Arg83Trp, including one de novo occurrence. In addition, our screening revealed three families with a neurodevelopmental phenotype and three unique RAB3A variants, which were either de novo or loss-of-function variants. In line with the different RAB3A variant types, protein domains and predicted functional consequences, a comprehensive set of complementary methods was used to characterize the identified variants functionally. As expected, GTPase-activating protein (GAP)-dependent GTP hydrolysis was reduced for those two missense variants located in the GAP-binding domain of RAB3A (Arg83Trp and Tyr91Cys). In a Drosophila Rab3 loss-of-function model, these two missense variants also failed to rescue a synaptic phenotype. Overexpression of Rab3 variants in Drosophila wild-type background did not cause an obvious phenotype, making a dominant negative effect of these variants unlikely. Lastly, exploring interactors of RAB3A variants by using co-immunoprecipitation and mass spectrometry showed differential changes in variant-specific interactions with known RAB3A key regulatory and effector proteins. In sum, our results establish RAB3A as a neurological disease gene. It represents an autosomal dominant gene for cerebellar ataxia with different variants associated with disease, including the frequent reoccurring variant p.Arg83Trp. Our study sheds light on the variant-specific interactome of RAB3A. Finally, we suggest an association of RAB3A with a neurodevelopmental phenotype, as reported for variants in several RAB3A interaction partners and as seen in Rab3A-deficent mice, although this possible association warrants further investigation by future studies.
Refractory autoimmune heparin-induced thrombocytopenia following cardiac surgery
2025-03-30

Autoimmune heparin-induced thrombocytopenia (aHIT) is a severe subtype of heparin-induced thrombocytopenia characterized by persistent thrombocytopenia and prothrombotic condition, even though anticoagulation with heparin has been discontinued. Here, we report on a patient with a previous history of aHIT where reexposure to heparin during cardiac surgery resulted in recurrent aHIT with pulmonary embolism. Alternative anticoagulants, as well as high-dose intravenous immunoglobulin, were ineffective, and only multiple cycles of therapeutic plasma exchange restored platelet counts and prevented further thrombosis progression. The therapy was guided by an ex vivo model of antiplatelet factor 4 (PF4)-mediated thrombosis that showed accurate performance in predicting the clinical outcome. Most importantly, the ability to induce thrombus formation was mainly caused by anti-PF4 (heparin-independent) antibodies. Our paper provides the first description of recurrent aHIT with translational evidence that pathogenic heparin-independent anti-PF4 antibodies can be specifically targeted by therapeutic plasma exchange, emphasizing the clinical use in refractory cases of aHIT.
Limitations of the molybdenum blue method for phosphate quantification in the presence of organophosphonates
2025-03-31

Abstract Organophosphonates (OPs) are widely used as chelating agents in domestic and industrial applications. While regarded as hardly biodegradable, OPs can undergo abiotic transformation with phosphate (PO 4 3− ) as a main transformation product. As some OPs are suspected precursors of glyphosate in surface waters, their environmental fate is of current interest. Due to analytical challenges posed by quantification of individual OPs, monitoring PO 4 3− formation is a widely used proxy to monitor OP transformations. The molybdenum blue (MB) method, employing UV/Vis spectroscopy, is frequently used for PO 4 3− quantification due to its sensitivity and operational simplicity. However, while interference of certain inorganic ions is well-documented, the effects of OPs on the accuracy of the MB method remain unexplored. This study investigated the effects of six OPs, namely N -(phosphonomethyl)glycine (glyphosate), 1-hydroxyethylidene(1,1-diphosphonic acid) (HEDP), iminodi(methylene phosphonate) (IDMP), aminotris(methylene phosphonate) (ATMP), ethylenediaminetetra(methylene phosphonate) (EDTMP), and diethylenetriaminepenta(methylene phosphonate) (DTPMP). Spectral analysis of pure PO 4 3− standards using the MB method exhibits two characteristic absorption maxima (λ max ) at 710 and 880 nm. In the presence of OPs, a new λ max appears around 760 nm. This is accompanied by an increase in absorbance values at both 710 and 880 nm, leading to significant over-quantification of PO 4 3− concentrations. Among the evaluated OPs, DTPMP exhibits the most substantial interference (PO 4 3− over-quantification by up to 240%), while glyphosate causes minimal interference (≤ 20%). The effects are most pronounced at OPs:PO 4 3− ratios ≥1. A case study simulating DTPMP transformation confirms PO 4 3− over-quantification of up to 350%, revealing limitations of the MB method. Therefore, careful data evaluation and complementary analytical techniques for accurate PO 4 3− measurements are indispensable in OP transformation research. Graphical abstract
AhR activation mitigates graft-versus-host disease of the central nervous system by reducing microglial NF-κB signaling
2025-03-31

Abstract Acute graft-versus-host disease (GVHD) that occurs after allogeneic hematopoietic cell transplantation (allo-HCT) can affect the central nervous system (CNS). Most patients who have undergone allo-HCT receive antibiotic treatment, which alters the microbiome and essential microbiome-derived metabolites. We investigated the impact of microbiome modifications on CNS GVHD and therapeutic strategies to overcome the microbiome-derived metabolite depletion. Antibiotic treatment of mice undergoing allo-HCT increased microglia numbers in the brain, indicating increased inflammation. In addition, microglial morphology shifted toward a highly branched phenotype. Consistent with a proinflammatory phenotype, the microglia exhibited increased NF-κB and Src activity. Antibiotic treatment caused the depletion of the bacteria-derived aryl hydrocarbon receptor (AhR) ligand indole-3-acetate in the brain. Conversely, treatment of the primary microglia with the AhR ligand 6-formylindolo(3,2-b)carbazole (FICZ) reduced NF-κB activity and phagocytic potential. Microglia expansion and morphological changes were reversed by AhR ligand FICZ treatment. Moreover, the AhR ligand indole-3-acetate was also reduced in the CNS of patients who developed acute GVHD concomitant with increased microglial NF-κB expression. In summary, we demonstrated that antibiotic treatment and a subsequent decrease of AhR ligands resulted in increased microglial activation in CNS GVHD. FICZ treatment hampered CNS inflammation by inhibiting NF-κB activity, thereby providing a metabolic modifier to interfere with pathogenic microglia signaling and CNS GVHD in vivo.
Culture is critical in driving orangutan diet development past individual potentials
2025-03-31

<title>Abstract</title> Humans accumulate extensive repertoires of culturally-transmitted information, reaching breadths exceeding any individual’s innovation capacity (culturally-dependent repertoires). It is unclear whether other animals require social learning to acquire adult-like breadths of information in the wild, including by key developmental milestones, or if animals are capable of constructing their knowledge repertoires primarily through independent exploration. We investigated whether social learning mediates orangutans' diet-repertoire development, by translating an extensive dataset describing wild orangutans’ behavior into an empirically-validated experimental simulation. Diets only reliably developed to adult-like breadths when simulated immatures benefitted from multiple forms of social learning. Moreover, social learning was required for diets to reach adult-like breadths by the maximum age immatures become independent from their mothers. Social learning is therefore integral for the timing and outcomes of orangutans’ broad-scale diet learning, demonstrating that culture can profoundly influence other animals’ development. We discuss prospective avenues for researching cultural-repertoire-building in hominids and other species.
Turning Trash into Treasure: Silicon Carbide Nanoparticles from Coal Gangue and High-Carbon Waste Materials
2025-03-31

To reduce solid waste production and enable the synergistic conversion of solid waste into high-value-added products, we introduce a novel, sustainable, and ecofriendly method. We fabricate nanofiber and nanosheet silicon carbides (SiC) through a carbothermal reduction process. Here, the calcined coal gangue, converted from coal gangue, serves as the silicon source. The carbon sources are the carbonized waste tire residue from waste tires and the pre-treated kerosene co-refining residue. The difference in carbon source results in the alteration of the morphology of the SiC obtained. By optimizing the reaction temperature, time, and mass ratio, the purity of the as-made SiC products with nanofiber-like and nanosheet-like shapes can reach 98%. Based on the influence of synthetic conditions and the results calculated from the change in the Gibbs free energy of the reactions, two mechanisms for SiC formation are proposed, namely the reaction of intermediate SiO with CO to form SiC-nuclei-driven nanofibrous SiC and the SiO-deposited carbon surface to fabricate nuclei-induced polymorphic SiC (dominant nanosheets). This work provides a constructive strategy for preparing nanostructured SiC, thereby achieving “turning trash into treasure” and broadening the sustainable utilization and development of solid wastes.
GGA2-depletion in beta cells by Enteroviruses causes Golgi acidification, premature activation of cathepsins and alters the MHC class I immunopeptidome
2025-03-31

Abstract Enteroviruses (EVs), such as Coxsackievirus B5 (CVB5), are linked to pancreatic beta cell autoimmunity in type 1 diabetes (T1D). CVB5 infection of beta cells blocks their cap-dependent translation but spares cap-independent translation of insulin secretory granule (SG) cargoes, including major T1D autoantigens. Despite this, insulin SG stores are depleted. We show that CVB5 protease 2A rapidly depletes Golgi-associated sorting factor GGA2 in beta cells due to its short half-life. Immunostaining of pancreas sections from recent-onset T1D donors confirmed reduced GGA2 in beta cells expressing EV capsid protein VP1. Both GGA2 depletion and CVB5 2A expression impair SG biogenesis at the TGN without affecting MHC class I trafficking. They also disrupt the sorting of vacuolar ATPase and cathepsins, leading to TGN acidification and premature lysosomal hydrolase activation, which typically generate peptides presented in HLA-II alleles. Notably, the unique immunopeptidome of EV-infected, GGA2-depleted ECN90 beta-like cells is mainly presented via HLA-B alleles with an average isoelectric point (pI) of ∼5, compared to a pI of ∼7 of the prevailing HLA-I A allele immunopeptidome of non-infected cells. We propose that delayed sorting at the acidified TGN promotes cathepsin-mediated processing of in-transit secretory proteins, including SG cargoes, thereby generating novel peptides that may replace HLA class I antigens due to the acidic environment. This novel cross-presentation mechanism could have implications for T1D pathogenesis and antigen presentation in general.
Designing Chatbots to Treat Depression in Youth: Qualitative Study
2025-03-31

Abstract Background Depression is a severe and prevalent mental disorder among youth that requires professional care; however, various barriers hinder access to effective treatments. Chatbots, one of the latest innovations in the research on digital mental health interventions, have shown potential in addressing these barriers. However, most studies on how to design chatbots to treat depression have focused on adult populations or prevention in the general population. Objective This study aimed to investigate the problems faced by youth with depression and their adaptive coping strategies, as well as attitudes, expectations, and design preferences for chatbots designed to treat depression. Methods We conducted a qualitative study, consisting of a semistructured interview and a concurrent think-aloud session, in which participants interacted with a chatbot prototype with 14 youth with a current or remitted depressive episode. Results The participants reported a wide range of problems beyond core depressive symptoms, such as interpersonal challenges, concerns about school and the future, and problems with human therapists. Adaptive coping strategies varied, with most seeking social support or engaging in pleasant activities. Attitudes toward chatbots for depression treatment were predominantly positive, with participants expressing less anxiety about using a chatbot than about seeing a human therapist. Participants showed diverse and partially contradictory design preferences, which included diverse dialogue topics, such as discussing daily life, acute problems, and therapeutic exercises, as well as various preferences for personality, language use, and personalization of the chatbot. Conclusions Our study provides a comprehensive foundation for designing chatbots that meet the unique needs and design preferences of youth with depression. These findings can inform the design of engaging and effective chatbots tailored to this vulnerable population.
Amygdalar lesions may impair emotion recognition in patients with temporal lobe epilepsy: Results from a pilot study
2025-03-31

In the present study, only TLE patients with amygdalar pathology showed deficits in visual and auditory emotion recognition. These results provide preliminary evidence for the importance of intact amygdalae in TLE for basic emotion processing in both modalities. The findings need to be confirmed in studies with larger samples.