bluuebunny/crossref_metadata_2025_split huggingface dataset:
931. Host PFKFB3-dependent glycolytic reprogramming as a broad-spectrum antiviral strategy
Authors: Yuan Shuofeng , Ye Zi-Wei , Chu Hin 
Published: November 2023

Abstract

Background
The current therapeutic arsenal against viral infections remains poor, with limited spectrum of coverage and appears inadequate to face the emergence of pandemic and antiviral resistance. This study aims to develop a broad-spectrum antiviral strategy for rapid epidemic control and early treatment with better clinical outcome.

Methods
To investigate the in vivo change of glucose homeostasis under infectious circumstances, we carried out a time-course monitoring of blood glucose concentration in pdmH1N1-infected BALB/c mice and revealed that impairment of glucose tolerance and insulin sensitivity were caused when compared with the mock-infection control. To explore the change of gene expression file upon virus infection, we first plotted the pdmH1N1 virus replication kinetics in human primary bronchial/tracheal epithelial cells (hBTECs), followed by mRNA gene expression profiling of the key glycolytic enzymes at 0hpi, 6hpi and 24hpi, respectively. To discover potential enzymatic inhibitors/modulators of host glycolysis for antiviral treatment, we screened a small molecular compound library with 344 glycolysis compounds on pdmH1N1 infected hTBECs, followed by secondary validation to confirm the dose-dependent virus inhibition at non-toxic concentrations.

Results
Significant higher blood glucose level was detected in infected-mice with either glucose or insulin supplement, which suggested that host glucose metabolism, in particular the glycolysis homeostasis, were disrupted upon influenza virus infection. We also identified Glucose transporter 4 (GLUT4), enolase 2 (ENO2), monocarboxylate transporter 2 (MCT2), MCT4 and 6-phosphofructo-2-kinase (PFK2, also named PFKFB3) the most perturbed genes at 24hpi. KAN0438757, a potent and selective inhibitor of the metabolic kinase PFKFB3, was shown to be antiviral effective against both H1N1 and EV-A71 viruses in human primary cells. Moreover, Kan exhibited broad-spectrum antiviral activity in ZIKV-infected Huh7 cells and SARS-CoV-2 infected Caco-2 cells.
Metabolic profiling reveals significant perturbations of host glucose homeostasis after influenza A virus infection.

Conclusion
Host PFKFB3-dependent glycolysis pathway with broad-relevance to multiple virus replications, which might be a vulnerable host target for antiviral intervention.

Disclosures
All Authors: No reported disclosures
Long-lasting developmental effects in rat offspring after maternal exposure to acetamiprid in the drinking water during gestation
Authors: Longoni Victoria , Kandel Gambarte Paula Cristina , Rueda Lis , Fuchs Julio Silvio , Rovedatti María Gabriela , Wolansky Marcelo Javier 
Published: November 2023

Abstract
Neonicotinoids (NNTs) are a class of insecticides proposed to be safe for pest control in urban, suburban, and agricultural applications. However, little is known about their developmental effects after repeated low-dose exposures during gestation. Here, we tested a dose considered subthreshold for maternal toxicity in rats (6 mg/kg/day) by assessing several morphological, biochemical, and neurobehavioral features in preterm fetuses and developing pups after maternal administration of the NTT acetamiprid (ACP) dissolved in the drinking water during gestational days (GD) 2–19. The exploratory evaluation included monitoring maternal body weight gain, fetal viability, body weight and sex ratio, cephalic length, neonatal body weight and sex ratio, metabolic enzymes in the placenta, maternal blood and fetal liver, and anogenital distance and surface righting response during infancy. We also used the circling training test to study the integrity of the associative-spatial-motor response in adolescence. Results showed no consistent findings indicating maternal, reproductive or developmental toxicity. However, we found ACP effects on maternal body weight gain, placental butyrylcholinesterase activity, and neurobehavioral responses, suggestive of a mild toxic action. Thus, our study showed a trend for developmental susceptibility at a dose so far considered subtoxic. Although the ACP concentration in environmental samples of surface water and groundwater has been mostly reported to be much lower than that used in our study, our results suggest that the ACP point of departure used in current guidelines aimed to prevent developmental effects may need to be verified by complementary sensitive multiple-endpoint testing in the offspring.
Impact of Pretreatment Weight Loss on Radiotherapy Utilization and Clinical Outcomes in Non–Small Cell Lung Cancer
Authors: Alvarez Christian M. , Aliru Maureen , Gannavarapu Bhavani S. , Song Tidie , Gilmore Linda Anne , Olaechea Santiago , Gomez Daniel R. , Ahn Chul , Infante Rodney E. , Iyengar Puneeth 
Published: November 2023

Background:
Cancer cachexia is a syndrome of unintentional weight loss resulting in progressive functional impairment. Knowledge of radiation therapy utilization in patients with cancer cachexia is limited. We evaluated the use of curative and palliative-intent radiation for the management of patients with non–small cell lung cancer (NSCLC) with cachexia to determine whether tumor-directed therapy affected cachexia-associated outcomes.

Methods:
Using an Institutional Tumor Registry, we evaluated all patients with stages of NSCLC treated at a tertiary care system from 2006 to 2013. We adopted the international consensus definition for cachexia, with staging designated by the registry and positron emission tomography. Radiotherapy delivery and intent were retrospectively assessed.

Results:
In total, 1330 patients with NSCLC were analyzed. Curative-intent radiotherapy was utilized equally between patients with cachexia and non-cachexia with stages I to III NSCLC. Conversely, significantly more patients with stage IV disease and cachexia received palliative radiotherapy versus those without (74% vs 63%, P = 0.006). Cachexia-associated survival was unchanged irrespective of tumor-directed radiation therapy with curative or palliative intent. In fact, pretreatment cachexia was associated with reduced survival for patients with stage III NSCLC receiving curative-intent radiotherapy (median survival = 23.9 vs 15.0 mo, P = 0.009). Finally, multivariate analysis identified pretreatment cachexia as an independent variable associated with worsened survival (hazard ratio = 1.31, CI: 1.14,1.52).

Conclusion:
Patients with advanced NSCLC with cachexia received more palliative-intent radiation than those without weight loss. Tumor-directed therapy in either a curative or palliative approach failed to alter cachexia patient survival across all stages of the disease. These findings offer critical information on the appropriate utilization of radiation in the management of patients with NSCLC with cachexia.
Quality Improvement Practices and Resources Targeting Firearm Injuries: A Survey of U.S. Pediatric Trauma Centers
Authors: Wurster Lee Ann , Herndon Michele , Seastrom David , Fritzeen Jennifer , Mitchell Kara , Schmid Moe , Rumsey Kelley 
Published: November 2023

BACKGROUND:
The increase in firearm injuries at U.S. pediatric trauma centers is a national public health crisis. This spike in penetrating trauma has challenged even the most mature pediatric trauma centers.

OBJECTIVE:
This project aims to identify U.S. pediatric trauma center best practices for the evaluation and resources dedicated to pediatric firearm injuries.

METHODS:
This study used an exploratory cross-sectional survey design using a study-specific questionnaire. An electronic survey was distributed to 159 verified U.S. pediatric trauma centers targeting patients younger than 15 years with firearm injuries from 2017 to 2021. Trauma approaches to injury prevention, advocacy, and common performance improvement events were surveyed. A follow-up survey provided a drill-down on the top three performance improvement events.

RESULTS:
A total 159 surveys were distributed, of which 63 (40%) submitted partial responses and 32 (20%) completed the initial survey in full. A 49% increase in pediatric firearm injuries occurred between 2019 and 2020. Eighty-six percent of the trauma centers identified at least one to two opportunities for improvement events related to firearm injuries, with most of these events requiring a tertiary level of review. The top three performance improvement events included the massive transfusion protocol/fluid resuscitation, emergency department procedures, and operating room resource availability.

CONCLUSIONS:
This study provides the first known examination of U.S. pediatric trauma center quality improvement efforts to address the crisis of pediatric firearm injuries. Our results indicate that most pediatric trauma centers are engaged in quality improvement and resource enhancement to combat firearm injuries.
Social Media and Website Use: The Experiences of Parents and Carers Accessing Care at the Oxford Craniofacial Unit
Authors: Kilcoyne Sarah , Overton Sarah , Brockbank Sally , Lloyd-White Samuel , Samuel Rosanna , Hotton Matthew , Cropper Jennifer , Thomas Gregory P.L. , Ching C. Rosanna , Johnson David 
Published: November 2023

Introduction:
Historically, medical professionals have been the providers of specialist information about rare medical conditions. Now, increasingly, patients and the public are using the internet to access and generate information about medical diagnoses. The global nature of the internet allows patients to connect across geographical borders, and to obtain and share information that would have been previously inaccessible to them. This research investigated the use of website and social media by parents of children with craniosynostosis.

Methods:
A cross-sectional survey-based design was employed. Participants were parents of children with craniosynostosis attending multidisciplinary craniofacial clinics within the Oxford Craniofacial Unit. A questionnaire was administered which assessed social media and website use adapted from the questionnaire created by Khouri and colleagues (2016) and Huggons and colleagues (2019). The surveys were administered over an 18-month period (November 2020 to May 2022).

Results:
The final sample comprised 82 parents [70 mothers; 10 fathers; 1 sister/carer and 1 parent (mother/father unspecified)]. The children were aged 11 months—16 years of age (average age 6 y and 3 mo). Children had a variety of diagnoses: 31 sagittal, 19 metopic, 14 syndromic craniosynostosis, 8 unicoronal, 6 multisuture, 3 bicoronal, and 1 unilambdoid.
Results showed that 93% (n=76/82) of parents used the internet to find out more about craniosynostosis, with 72% (n=59/82) of parents specifically using social media to find out more about craniosynostosis. The social media platforms used included: Facebook 64% (n=53/82), Instagram 24% (n=20/82), Blogs 12% (n=10/82), Twitter 4% (n= 4/82), Tik Tok 2% (n=2/82), and Snapchat 0.01% (n=1/82).
Parents reported that Facebook was the most helpful source of information about craniosynostosis (52%; n=43/82). Parents indicated the key timepoints they used social media included: when their child received a diagnosis (70%; n=58/82), before their child’s surgery (34%; n=28/82), before their first craniofacial clinic appointment (83%; n=25/30), and when child was older (17%; n=14/84). Forty percent (n=33/82) of parents said that a diagnosis of craniosynostosis made no difference to their social media use, whereas 34% (n=28/82) of parents used social media more, and 20% (n=16/82) used it less.

Conclusion:
Results highlight that parents use social media and other websites to access information relating to craniosynostosis. Future research should examine whether parental use of social media changes across their child’s lifespan and evaluate the quality of this information.
MALAT1 DEREPRESSES MIR-433-3P–MEDIATED RPTOR SUPPRESSION TO IMPAIR AUTOPHAGY AND DRIVE PYROPTOSIS IN ENDOTOXEMIA
Authors: Wu Kun , Yu Xiangyou , Wang Yi , Li Xiang , An Yuanyuan , Zhao Zuyi , Ma Long 
Published: November 2023

ABSTRACT

Objective: Autophagy elevation in endotoxemia plays a protective role by negatively regulating the pyroptosis of vascular endothelial cells, but the molecular mechanisms are still poorly understood. The present study aimed to identify the mechanism underlying autophagy and pyroptosis in endotoxemia. Methods: Bioinformatics analysis and whole-gene transcriptome sequencing prediction were used to identify the endotoxemia-related lncRNA-miRNA-mRNA axis of interest. Human umbilical vein endothelial cells (HUVECs) were activated by lipopolysaccharide (LPS) to mimic the inflammatory environment encountered in endotoxemia. Autophagy and pyroptosis of LPS-treated HUVECs were assessed in response to the knockdown of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1)/miR-433-3p (miRNA-433-3p)/RPTOR (regulatory-associated protein of mTOR). The binding affinity of MALAT1, miR-433-3p, and RPTOR was detected by RNA pull-down and luciferase activity assays. The endothelial cell-specific RPTOR knockout mice were developed and rendered septic using LPS induction to verify the role of RPTOR in autophagy, pyroptosis, and inflammatory response in vivo. Results: The in vitro experiments indicated that LPS could stimulate HUVECs to highly express RPTOR, and its knockdown enhanced cellular autophagy and restricted pyroptosis to curb inflammatory responses. Mechanically, MALAT1 is competitively bound to miR-433-3p to release RPTOR expression, thereby promoting pyroptosis and aggravating endotoxemia. In vivo experiments further confirmed that the knockdown of RPTOR activated autophagy and curtailed pyroptosis in septic mice. Conclusion: MALAT1 is highly expressed in endotoxemia. MALAT1 promotes RPTOR expression by competitively absorbing miR-433-3p, inhibits LPS-activated HUVEC cell autophagy, promotes cell death, enhances LPS-induced inflammatory activation of vascular endothelial cells, and ultimately promotes the progression of endotoxemia.
IN VITRO EVALUATION OF A NOVEL AUTOMATIC INTRAOPERATIVE BLOOD LOSS MONITOR
Authors: Bai Jiangtao , Jin Qi , Zheng Qihui , Zhang LuYang , Guo Ting , Wang Guilin , Wang Zhiping 
Published: November 2023

ABSTRACT

Introduction: Accurate and real-time monitoring of surgical blood loss is essential for ensuring intraoperative safety. However, there is currently no standard way to assess the amount of blood lost in patients during surgery. This study aims to evaluate the accuracy and precision of a new automatic intraoperative blood loss monitor, which can measure both free blood volume and blood content in sponges in real time. Methods: The monitor uses an integrated photoelectric probe to gauge hemoglobin levels in both free blood and blood taken from surgical sponges. These data, combined with initial hemoglobin levels, are processed using specific calculations to determine blood volume. We created 127 diverse free blood samples and 160 blood-containing sponge samples by using fresh pig blood and physiological saline. The monitor then measured these samples. We subsequently compared its measurements with actual values acquired through physical measurements, detecting both agreement and measurement errors. Repeated measurements were performed to calculate the coefficient of variation, thereby evaluating the monitor’s precision. Results: The estimated blood loss percentage error of the monitor was 5.2% for free blood, −5.7% for small sponge, −6.3% for medium sponge, and −6.6% for large sponge. The coefficient of variation of free blood with different hemoglobin concentrations measured by the monitor was less than 10%. Bland-Altman analysis showed that the limits of agreement between the monitor and the reference method were all within the acceptable clinical range. Conclusion: The new automatic intraoperative blood loss monitor is an accurate and reliable device for monitoring both free blood and surgical sponge blood, and shows high performance under various clinical simulation conditions.
Evidence for Beneficial use of the Compensatory Reserve Measurement (CRM) in Guiding Intraoperative Resuscitation: A Prospective Cohort Study of Orthotopic Liver Transplant Recipients
Authors: Ciaraglia Angelo , Osta Eri , Wang Hanzhang , Cigarroa Francisco , Thomas Elizabeth , Fritze Danielle , Nicholson Susannah , Eastridge Brian , Convertino Victor A. 
Published: November 2023

Abstract

Introduction
The Compensatory Reserve Measurement (CRM) is a continuous non-invasive monitoring technology that provides an assessment of the integrated capacity of all physiological mechanisms associated with responses to a hypovolemic stressor such as hemorrhagic shock. No prior studies have analyzed its use for intraoperative resuscitation guidance.

Methods
A prospective observational study was conducted of 23 patients undergoing orthotopic liver transplant (OLT). Chart review was performed to identify timing of various intraoperative events. Data were compared based on predefined thresholds for existence of hemorrhagic shock: CRM below 40% (CRM40), systolic blood pressure below 90 mmHg (SBP90), and heart rate above 100 bpm (HR100). Regression analysis was performed for predicting resuscitation events and non-linear XGBoost models were used to compare CRM to standard vital sign measures.

Results
Events where CRM dropped below 40% were 2.25 times more likely to lead to an intervention, while HR100 and SBP90 were not associated with intraoperative interventions. XGBoost prediction models showed superior discriminatory capacity of CRM alone compared to the model with SBP and HR and no difference when all three were combined (CRM + HR + SBP). All XGBoost models outperformed equivalent linear regression models.

Conclusions
Theses results demonstrate that CRM can provide an adjunctive clinical tool that can augment early and accurate of hemodynamic compromise and promote goal-directed resuscitation in the perioperative setting.
TREATMENT OF COMATOSE SURVIVORS OF IN-HOSPITAL CARDIAC ARREST WITH EXTENDED ENDOVASCULAR COOLING METHOD FOR 72 H: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Jiang Lijun , Bian Yuan , Liu Weikang , Zheng Wen , Zheng Jiaqi , Li Chuanbao , Lv Ruijuan , Pan Yuhui , Zheng Zhaolei , Wang Mingjie , Sang Shaowei , Pan Chang , Wang Chunyi , Liu Rugang , Cheng Kai , Zhang Jianbo , Ma Jingjing , Chen Yuguo , Xu Feng 
Published: November 2023

ABSTRACT

Aims: Targeted temperature management is recommended for at least 24 h in comatose survivors of in-hospital cardiac arrest (IHCA) after the return of spontaneous circulation; however, whether an extension for 72 h leads to better neurological outcomes is uncertain. Methods: We included data from the Qilu Hospital of Shandong University between July 20, 2019, and June 30, 2022. Unconscious patients who had return of spontaneous circulation lasting >20 consecutive min and received endovascular cooling (72 h) or normothermia treatment were compared in terms of survival-to-discharge and favorable neurological survival. Propensity score matching was used to formulate balanced 1:3 matched patients. Results: In total, 2,084 patients were included. Sixteen patients received extended endovascular cooling and 48 matched controls received normothermia therapy. Compared with the normothermia group, patients who received prolonged endovascular cooling had a higher survival-to-discharge rate. However, good neurological outcomes did not differ significantly. Before matching, Cox regression analysis, using mortality as the event, showed that extended endovascular cooling independently affected the survival of IHCA patients. Conclusions: Among comatose patients who had been resuscitated from IHCA, the use of endovascular cooling for 72 h might confer a benefit on survival-to-discharge.
Adenosine influences Foxp3 expression of Tregs via the A2aR/CREB pathway in a mouse model of sepsis
Authors: Zhang Teng , Fu Wei , Liu Dongjie , He Yuxin , Wang Jianyao , Ma Tao 
Published: November 2023

Abstract
The adenosine concentration and forkhead box protein (Foxp3) expression in T regulatory cells (Tregs) are increased during sepsis. However, the mechanism by which adenosine induces Foxp3 expression is incompletely understood. A cecal ligation and puncture (CLP) model was constructed using C57BL/J mice. The plasma adenosine concentration and Foxp3 expression in splenic Tregs were increased consistently for 15 days after sepsis onset. Analysis of the mean fluorescence intensity of Foxp3 and adenosine concentration in the same mice revealed a linear correlation. In the CLP model, adenosine 2a receptor (A2aR) blockade inhibited Foxp3 expression in Tregs. In vitro activation of A2aR promoted Foxp3 expression in Tregs and facilitated secretion of extracellular vesicles. Transcriptome sequencing revealed that A2aR blockade led to changes in cyclic adenosine monophosphate response element-binding protein (CREB) transcription in Tregs in our sepsis model. Use of adenosine or A2aR agonists promoted CREB expression, CREB phosphorylation at S133, Treg expression of Foxp3, and enhanced inhibition of proliferation of cluster of differentiation (CD)4+ lymphocytes. A2aR blockade or inhibition of CREB expression inhibited Foxp3 expression in Tregs. In the CLP model, use of CREB inhibitors could inhibit Foxp3 expression and reduce the bacterial load. In summary, adenosine in sepsis promotes CREB phosphorylation via A2aR which, in turn, upregulates Foxp3 expression in Tregs.
Distinguishing Convulsive Syncope From Seizure Induced by Repetitive Transcranial Magnetic Stimulation
Authors: Mukhtar Fahad , Feuer Elyssa , Beynel Lysianne , Jones Eudora , Regenold William T. , Lisanby Sarah H. 
Published: November 2023

Abstract
Repetitive transcranial magnetic stimulation (rTMS) is Food and Drug Administration cleared for clinical use in treatment-resistant depression and a growing list of other disorders. The clinical uptake of rTMS has been facilitated by its relatively benign adverse-effect profile compared with other treatment modalities. Seizure is a rare but serious adverse event that has been reported with rTMS, when dosage exceeds safety guidelines or in individuals at increased risk for seizure. Fortunately, most rTMS-induced seizures are typically transient, with no adverse sequelae, but they may lead to treatment discontinuation. Seizure is not the only cause of loss of conscious and abnormal movements induced by rTMS. Convulsive syncope, a more common adverse event that involves loss of consciousness associated with myoclonic movements, can be difficult to differentiate from an rTMS-induced seizure. We report the case of a 52-year-old man with no known seizure risk factors, enrolled in an institutional review board–approved research study who developed what appeared to be a convulsive syncopal episode lasting 10 to 15 seconds during day 2 of a 30-day rTMS protocol (10 Hz, 120% of motor threshold, 4-second pulse train, 26-second intertrain interval, 3000 pulses per session), with no adverse sequelae. The patient's history, screening, physical examination, pertinent laboratory, neurology consult, electroencephalogram, and imaging findings are discussed. This case demonstrates that distinguishing between convulsive syncope and rTMS-induced seizure can be a diagnostic challenge. Clinicians and researchers delivering rTMS should be familiar with the risk factors for rTMS-induced seizures and rTMS-induced convulsive syncope, to screen for predisposing factors and to manage these rare adverse events if they occur.