bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ecotin‐like peptidase inhibitor of Trypanosoma cruzi prevents TMPRSS2‐PAR2‐TLR4 crosstalk downmodulating infection and inflammation
Authors: Costa Tatiana F. R. , Catta‐Preta Carolina M. C. , Goundry Amy , Carvalho Danielle B. , Rodrigues Nathalia S. , Vivarini Aislan C. , de Abreu Mayra Fonseca , Reis Flavia C. G. , Lima Ana Paula C. A. 
Published: March 2024

AbstractTrypanosoma cruzi is the causative agent of Chagas disease, a chronic pathology that affects the heart and/or digestive system. This parasite invades and multiplies in virtually all nucleated cells, using a variety of host cell receptors for infection. T. cruzi has a gene that encodes an ecotin‐like inhibitor of serine peptidases, ISP2. We generated ISP2‐null mutants (Δisp2) in T. cruzi Dm28c using CRISPR/Cas9. Epimastigotes of Δisp2 grew normally in vitro but were more susceptible to lysis by human serum compared to parental and ISP2 add‐back lines. Tissue culture trypomastigotes of Δisp2 were more infective to human muscle cells in vitro, which was reverted by the serine peptidase inhibitors aprotinin and camostat, suggesting that host cell epitheliasin/TMPRSS2 is the target of ISP2. Pretreatment of host cells with an antagonist to the protease‐activated receptor 2 (PAR2) or an inhibitor of Toll‐like receptor 4 (TLR4) selectively counteracted the increased cell invasion by Δisp2, but did not affect invasion by parental and add‐back lines. The same was observed following targeted gene silencing of PAR2, TLR4 or TMPRSS2 in host cells by siRNA. Furthermore, Δisp2 caused increased tissue edema in a BALB/c mouse footpad infection model after 3 h differently to that observed following infection with parental and add‐back lines. We propose that ISP2 contributes to protect T. cruzi from the anti‐microbial effects of human serum and to prevent triggering of PAR2 and TLR4 in host cells, resulting in the modulation of host cell invasion and contributing to decrease inflammation during acute infection.
Boarding in the emergency department: challenges and mitigation strategies
Authors: da Silva Ramos Fernando J. , Freitas Flavio G.R. , Machado Flavia R. 
Published: March 2024

Purpose of review
Herein, we conducted a review of the literature to better understand the issue of prolonged emergency department (ED) boarding by providing an overview of the current evidence on the available causes, consequences, and mitigation strategies.

Recent findings
Severely ill patients awaiting transfer to intensive care units (ICU) imposes additional burdens on the emergency care team from both a clinical and management perspective. The reasons for prolonged ED boarding are multifactorial. ED boarding compromises patients’ safety and outcomes, and is associated with increased team burnout and dissatisfaction. Mitigation strategies include the optimization of patients’ flow, the establishment of resuscitative care units, deployment of mobile critical care teams, and improvements in training. Staffing adjustments, changes in hospital operations, and quality improvement initiatives are required to improve this situation, while active bed management and implementation of capacity command centers may also help.

Summary
Considering the characteristics of healthcare systems, such as funding mechanisms, organizational structures, delivery models, access and quality of care, the challenge of ED boarding of critically ill patients requires a nuanced and adaptable approach. Solutions are complex but must involve the entirety of the hospital system, emergency department, staff adjustment, and education.
Artificial intelligence to advance acute and intensive care medicine
Authors: Biesheuvel Laurens A. , Dongelmans Dave A. , Elbers Paul W.G. 
Published: March 2024

Purpose of review
This review explores recent key advancements in artificial intelligence for acute and intensive care medicine. As artificial intelligence rapidly evolves, this review aims to elucidate its current applications, future possibilities, and the vital challenges that are associated with its integration into emergency medical dispatch, triage, medical consultation and ICUs.

Recent findings
The integration of artificial intelligence in emergency medical dispatch (EMD) facilitates swift and accurate assessment. In the emergency department (ED), artificial intelligence driven triage models leverage diverse patient data for improved outcome predictions, surpassing human performance in retrospective studies. Artificial intelligence can streamline medical documentation in the ED and enhances medical imaging interpretation. The introduction of large multimodal generative models showcases the future potential to process varied biomedical data for comprehensive decision support. In the ICU, artificial intelligence applications range from early warning systems to treatment suggestions.

Summary
Despite promising academic strides, widespread artificial intelligence adoption in acute and critical care is hindered by ethical, legal, technical, organizational, and validation challenges. Despite these obstacles, artificial intelligence's potential to streamline clinical workflows is evident. When these barriers are overcome, future advancements in artificial intelligence have the potential to transform the landscape of patient care for acute and intensive care medicine.
Vonoprazan-amoxicillin dual therapy with different amoxicillin dosages for treatment-naive patients of Helicobacter pylori infection in China: a prospective, randomized controlled study
Authors: Liu Zhu , Sun Dongjie , Kou Luan , Jia Li , Hao Jiaorong , Zhou Jihai , Zheng Wenwen , Gao Fengyu , Chen Xin 
Published: March 2024

Background
The vonoprazan (VPZ)-amoxicillin (AMO) dual therapy (VA) demonstrates a satisfactory eradication rate for Helicobacter pylori (H. pylori). However, the optimal dosage of AMO in this regimen remains uncertain. The objective of this study is to investigate the efficacy of different doses of AMO in the VA regimen for first-line treatment of H. pylori infection.

Methods
A total of 192 treatment-naive H. pylori-infected patients were randomly assigned to one of three groups: low-dose VA (LD-VA: VPZ 20 mg b.i.d + AMO 750 mg t.i.d), moderate-dose VA (MD-VA:VPZ 20 mg b.i.d + AMO 1000 mg t.i.d), and high-dose VA (HD-VA: VPZ 20 mg b.i.d + AMO 1250 mg t.i.d). All groups received 14 days of treatment. The study evaluated and compared the eradication rates, adverse events (AEs), and patient compliance among the three groups.

Results
Eradication rates for LD-VA, MD-VA, and HD-VA were 76.6% (49/64), 79.7% (51/64), and 84.4% (54/64), respectively, as determined by intention-to-treat analysis; 90.6% (48/53), 94.3% (50/53), and 98.1% (53/54) according to per-protocol analysis; 89.1% (49/55), 94.4% (51/54), and 96.4% (54/56) with modified intention-to-treat analysis (all P > 0.05). Although not statistically significant, numerically higher eradication rates were observed with the higher dose AMO VA regimen. There were no statistically significant differences in the incidence of AEs and compliance among the three VA regimens.

Conclusion
Fourteen-day VA regimens with AMO doses exceeding 2 g/day demonstrated satisfactory eradication rates. HD-VA therapy is potentially the most effective regimen. Large-sample clinical trials are required to further validate these findings.
Association of Helicobacter pylori CagA seropositivity with gastric precancerous lesions: a systematic review and meta-analysis
Authors: Qiao Zengyun , Wang Enbo , Bao Boyang , Tan Xiaodong , Yuan Liu , Wang Dong 
Published: March 2024

The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CI = 2.25–3.32; P = 0.00; I2
= 60.4%), irrespective of H. pylori infection status. Within the H. pylori-infected cohort, the OR was 2.25 (95% CI = 1.99–2.56; P = 0.00; I2
= 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CI = 1.04–2.54; P = 0.038; I2
= 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.
Supportive Communication Between Emerging Adults With Cancer and Nurses During Diagnosis and Cancer Treatment
Authors: Kim Bora , Patterson Pandora , White Kate 
Published: March 2024

Background
Having a cancer diagnosis during early adulthood can be a significant challenge for an individual. Nurses’ supportive communication plays a vital role during the diagnosis and treatment period to lessen psychological distress and promote coping.

Objective
This exploratory study aimed to examine (1) the experiences of emerging adults with cancer (EAs) aged between 18 and 25 years in communicating with nurses during diagnosis and treatment and (2) nurses’ experiences of providing supportive communication with this patient group.

Methods
Semistructured interviews were conducted with EAs and nurses with experience caring for this patient group. Thematic analysis was conducted, guided by interpretive hermeneutic perspectives.

Results
Eight EA participants and 7 nurse participants participated in interviews. Five themes emerged: (1) having casual conversations with nurses helped EAs cope during cancer treatment and (2) helped EAs fulfill the need for social connectedness, (3) nurses as a different form of peer-like support, (4) nurses used themselves as a therapeutic tool to foster trust and emotional safety of EAs, and (5) nurses needed to maintain professional boundaries while being compassionate.

Conclusions
This study highlighted a rather underdocumented aspect of supportive communication: meeting psychosocial needs through casual, day-to-day conversations.

Implications for Practice
Having casual conversations with nurses appeared to help EAs’ psychological coping during cancer treatment. These casual conversations, which on the surface seemed clinically insignificant, fulfilled their psychosocial needs. Considering the valuable interpersonal engagement that led to emotional benefits for EAs, communication training for cancer nurses needs to build their capacity to maintain both relational and emotional boundaries.
Is There a Current Role for Combination Chemotherapy or High-Dose Interleukin 2 in Melanoma?
Authors: Fishman Julie , Buchbinder Elizabeth I. 
Published: March 2024

Abstract
Immune checkpoint inhibition and targeted therapies have revolutionized the treatment of melanoma. However, chemotherapy and interleukin 2 (IL-2) therapy may still have a role in the later-line treatment of patients who do not have durable responses to other treatments. Chemotherapy can work transiently in patients whose disease has progressed on immune checkpoint inhibitors and for whom there are no appropriate targeted therapy options. High-dose IL-2 therapy can still be effective for a very small number of patients following progression on other therapies. In addition, modified IL-2 agents and IL-2 in combination with tumor-infiltrating lymphocyte therapy may play a role in future treatments for melanoma.
Updates in the Management of Uveal Melanoma
Authors: Barbi Mali , Carvajal Richard D. , Devoe Craig E. 
Published: March 2024

AbstractUveal melanoma (UM), arising from intraocular melanocytes, poses a complex clinical challenge with a substantial risk of distant metastasis, often to the liver. Molecular profiling, encompassing genetic, cytogenetic, gene expression, and immunological subsets, plays a pivotal role in determining prognoses. The evolving landscape includes promising systemic treatments, such as tebentafusp, a novel immune-modulating bispecific fusion protein, and targeted therapies. Combined regional and systemic approaches, including immune checkpoint inhibitors and innovative liver-directed therapy, are also under investigation. Although recent progress has improved outcomes, ongoing research aims to address the unique challenges of UM and develop effective therapies, particularly for HLA-A*02:01–negative patients who represent a significant unmet medical need. This review comprehensively discusses the molecular characteristics of UM, risk stratification methods, and the current and future spectrum of regional and systemic therapeutic modalities.
Impact of influenza and pneumococcal vaccines on HIV persistence and immune dynamics during suppressive antiretroviral therapy
Authors: Gianella Sara , Anderson Christy , Chaillon Antoine , Wells Alan , Porrachia Magali , Caballero Gemma , Meneses Milenka , Lonergan Joseph , Woodworth Brendon , Gaitan Noah C. , Rawlings Stephen A. , Muttera Leticia , Harkness Liliana , Little Susan J. , May Susanne , Smith Davey 
Published: March 2024

Objective:
We sought to determine if standard influenza and pneumococcal vaccines can be used to stimulate HIV reservoirs during antiretroviral therapy (ART).

Design:
A prospective, randomized, double-blinded, placebo-controlled, crossover trial of two clinically recommended vaccines (influenza and pneumococcal).

Methods:
Persons with HIV on ART (N = 54) were enrolled in the clinical trial. Blood was collected at baseline and days 2,4,7,14, and 30 postimmunizations. Levels of cellular HIV RNA and HIV DNA were measured by ddPCR. Expression of immunological markers on T cell subsets was measured by flow cytometry. Changes in unspliced cellular HIV RNA from baseline to day 7 postinjection between each vaccine and placebo was the primary outcome.

Results:
Forty-seven participants completed at least one cycle and there were no serious adverse events related to the intervention. We observed no significant differences in the change in cellular HIV RNA after either vaccine compared with placebo at any timepoint. In secondary analyses, we observed a transient increase in total HIV DNA levels after influenza vaccine, as well as increased T cell activation and exhaustion on CD4+ T cells after pneumococcal vaccine.

Conclusion:
Clinically recommended vaccines were well tolerated but did not appear to stimulate the immune system strongly enough to elicit significantly noticeable HIV RNA transcription during ART.
Clinicaltrials.gov identifier: NCT02707692.
Fudan Zhongshan Plastic Surgery Forum
Authors: Qi Fazhi , Pan Yuyan 
Published: March 2024

Abstract
The Fudan Zhongshan Plastic Surgery Forum along with the National Continuing Education Course is authorized and supported by the Shanghai Medical Association for Plastic and Reconstructive Surgery and the Fudan University. The annual conference this year along with the course focusing on the “Advances and New Techniques in Plastic Surgery” is successfully held at Zhongshan Hospital affiliated with Fudan University, on August 26–27, 2023 in Shanghai, China.
MAN VERSUS MACHINE: PROVIDER DIRECTED VERSUS PRECISION AUTOMATED CRITICAL CARE MANAGEMENT IN A PORCINE MODEL OF DISTRIBUTIVE SHOCK
Authors: Sanin Gloria D. , Cambronero Gabriel E. , Wood Elizabeth C. , Patterson James W. , Lane Magan R. , Renaldo Antonio C. , Laingen Bonnie E. , Rahbar Elaheh , Adams Jason Y. , Johnson Austin , Neff Lucas P. , Williams Timothy K. 
Published: March 2024

ABSTRACTBackground:Critical care management of shock is a labor-intensive process. Precision Automated Critical Care Management (PACC-MAN) is an automated closed-loop system incorporating physiologic and hemodynamic inputs to deliver interventions while avoiding excessive fluid or vasopressor administration. To understand PACC-MAN efficacy, we compared PACC-MAN to provider-directed management (PDM). We hypothesized that PACC-MAN would achieve equivalent resuscitation outcomes to PDM while maintaining normotension with lower fluid and vasopressor requirements.Methods: Twelve swine underwent 30% controlled hemorrhage over 30 min, followed by 45 min of aortic occlusion to generate a vasoplegic shock state, transfusion to euvolemia, and randomization to PACC-MAN or PDM for 4.25 h. Primary outcomes were total crystalloid volume, vasopressor administration, total time spent at hypotension (mean arterial blood pressure <60 mm Hg), and total number of interventions.Results: Weight-based fluid volumes were similar between PACC-MAN and PDM; median and IQR are reported (73.1 mL/kg [59.0–78.7] vs. 87.1 mL/kg [79.4–91.8],P= 0.07). There was no statistical difference in cumulative norepinephrine (PACC-MAN: 33.4 μg/kg [27.1–44.6] vs. PDM: 7.5 [3.3–24.2] μg/kg,P= 0.09). The median percentage of time spent at hypotension was equivalent (PACC-MAN: 6.2% [3.6–7.4] and PDM: 3.1% [1.3–6.6],P= 0.23). Urine outputs were similar between PACC-MAN and PDM (14.0 mL/kg vs. 21.5 mL/kg,P =0.13).Conclusion: Automated resuscitation achieves equivalent resuscitation outcomes to direct human intervention in this shock model. This study provides the first translational experience with the PACC-MAN system versus PDM.
DIAMMONIUM GLYCYRRHIZINATE INHIBITED INFLAMMATORY RESPONSE AND MODULATED SERUM METABOLISM IN POLY(I:C)-INDUCED PNEUMONIA MODEL MICE
Authors: Meng Yan , Cai Xuanlin , Cong Shan , Sun Jiao , Du Wenjing , Cui Huantian , Luo Li , Ma Xiumin , Wang Li 
Published: March 2024

ABSTRACT
Currently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection of polyinosinic–polycytidylic acid (poly(I:C)) to induce pneumonia and were treated with DG. First, we evaluated the therapeutic potential of DG on poly(I:C)-induced pneumonia. Second, the anti-inflammatory and antioxidative activities and the impact of DG on the toll-like receptor 3 (TLR3) pathway were investigated. Third, the mechanism of DG was analyzed through untargeted metabolomics techniques. Our results revealed that DG intervention decreased permeability and reduced abnormal lung alterations in poly(I:C)-induced pneumonia model mice. DG intervention also downregulated cytokine levels in bronchoalveolar lavage fluid. Moreover, DG treatment inhibited the activation of TLR3 pathway. Furthermore, untargeted metabolomics analysis revealed that DG intervention could modulate serum metabolites involved in amino and nucleotide sugar metabolism, fructose and mannose metabolism, tyrosine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, our study showed that DG could ameliorate poly(I:C)-induced pneumonia by inactivating the TLR3 pathway and affecting amino and nucleotide sugar, fructose and mannose metabolism, as well as tryptophan, phenylalanine, and tyrosine biosynthesis.
UNVEILING THE CAUSAL ASSOCIATION BETWEEN NONINFECTIOUS RESPIRATORY DISORDERS AND SEPSIS THROUGH MENDELIAN RANDOMIZATION ANALYSIS
Authors: Liu Cheng , He Li , Zheng Xiangde 
Published: March 2024

ABSTRACT

Background: The association between sepsis and noninfectious respiratory diseases is well-documented, yet the specific causal link between the two remains unclear. In order to explore this relationship further, we employed a Mendelian randomization (MR) analysis utilizing data from the UK Biobank and FinnGen Biobank. Methods: We analyzed the summary statistics of a genome-wide association study summary statistics for chronic obstructive pulmonary disease (COPD), asthma, pulmonary embolism (PE), idiopathic pulmonary fibrosis (IPF), obstructive sleep apnea (OSA), lung cancer, sepsis, and sepsis-related mortality. We employed the inverse-variance weighted (IVW) method and four additional MR methods. Heterogeneity and horizontal pleiotropy were assessed using the Cochrane’s Q test, MR-Egger intercept, and MR-PRESSO test. A sensitivity analysis was also performed. Results: MR analysis showed associations between COPD and lung cancer with increased sepsis risk (odds ratio (OR)IVW 1.138, P = 0.006; (OR)IVW 1.123, P = 0.031; respectively) and sepsis mortality ((OR)IVW 1.350, P = 0.022; (OR)IVW 1.312, P = 0.022; respectively). Asthma exhibited a potential protective effect against sepsis mortality ((OR)IVW = 0.300, P = 0.039), while PE demonstrated a risk effect ((OR)IVW = 1.148, P = 0.032). No causal association was observed between asthma, PE, and sepsis (P > 0.05). IPF and OSA were not significantly associated with sepsis or sepsis-related mortality (P > 0.05). Heterogeneity and horizontal pleiotropy were not evident for asthma or lung cancer (P > 0.05). However, horizontal pleiotropy was suggested for COPD by the MR-Egger regression (P < 0.05), but not by the MR-PRESSO test (P > 0.05). IPF and OSA were not significantly associated with sepsis or sepsis-related mortality (P > 0.05). Conclusion: Our MR analysis offers new insights into potential links between noninfectious respiratory diseases and the risk of sepsis. However, additional investigation into the underlying mechanisms and clinical studies are necessary to confirm these findings.
SIRT3 MEDIATES THE CARDIOPROTECTIVE EFFECT OF THERAPEUTIC HYPOTHERMIA AFTER CARDIAC ARREST AND RESUSCITATION BY RESTORING AUTOPHAGIC FLUX VIA THE PI3K/AKT/MTOR PATHWAY
Authors: Wang Hui , Wang Wenwen , Xue Zhiwei , Gong Huiping 
Published: March 2024

ABSTRACTBackground: Postresuscitation cardiac dysfunction is a significant contributor to early death following cardiopulmonary resuscitation (CPR). Therapeutic hypothermia (TH) mitigates myocardial dysfunction due to cardiac arrest (CA); however, the underlying mechanism remains unclear. Sirtuin 3 (Sirt3) was found to affect autophagic activity in recent research, motivating us to investigate its role in the cardioprotective effects of TH in the treatment of CA.Methods: Sprague-Dawley rats were used to establish an in vivo CA/CPR model and treated with a selective Sirt3 inhibitor or vehicle. Survival rate, myocardial function, autophagic flux, and Sirt3 expression and activity were evaluated. H9C2 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injuryin vitro. The cells were transfected with Sirt3-siRNA and treated with the autophagy inhibitor chloroquine or the PI3K inhibitor LY294002, and cell viability and autophagic flux were assessed.Results: Rats exhibited decreased survival and impaired cardiac function after CA/CPR, which were alleviated by TH. Mechanistically, TH restored Sirt3 expression and autophagic flux, which were impaired by CA/CPR. Sirt3 inactivation diminished the capacity of TH to restore autophagic flux and partially abolished the improvements in myocardial function and survival. Anin vitrostudy further showed that TH-induced restoration of disrupted autophagic flux by OGD/R was attenuated by pretreatment with Sirt3-siRNA, and this attenuation was partially rescued by the inhibition of PI3K/Akt/mTOR signaling cascades.Conclusions: Sirt3 mediates the cardioprotective effect of TH by restoring autophagic flux via the PI3K/Akt/mTOR pathway. These findings suggest the potential of Sirt3 as a therapeutic target for CA.