bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer
Authors: Gao Huan , Tian Qi , Zhou Yan , Zhu Lizhe , Lu Yinliang , Ma Yingying , Feng Jinteng , Jiang Yina , Wang Bo
Published: June 2022

Background

Triple negative breast cancer (TNBC) is characterized by poor prognosis and a lack of effective therapeutic agents owing to the absence of biomarkers. A high abundance of tumor-infiltrating regulatory T cells (Tregs) was associated with worse prognosis in malignant disease. Exploring the association between Treg cell infiltration and TNBC will provide new insights for understanding TNBC immunosuppression and may pave the way for developing novel immune-based treatments.

Materials and Methods

Patients from TCGA were divided into Treg-high (Treg-H) and Treg-low (Treg-L) groups based on the abundance of Tregs according to CIBERSORT analysis. The association between expression level of Tregs and the clinical characteristics as well as prognosis of breast cancer were evaluated. Next, a Treg-related prognostic model was established after survival-dependent univariate Cox and LASSO regression analysis, companied with an external GEO cohort validation. Then, GO, KEGG and GSEA analyses were performed between the Treg-H and Treg-L groups. Masson and Sirius red/Fast Green staining were applied for ECM characterization. Accordingly, Jurkat T cells were encapsulated in 3D collagen to mimic the ECM microenvironment, and the expression levels of CD4, FOXP3 and CD25 were quantified according to immunofluorescence staining.

Results

The expression level of Tregs is significantly associated with the clinical characteristics of breast cancer patients, and a high level of Treg cell expression indicates a poor prognosis in TNBC. To further evaluate this, a Treg-related prognostic model was established that accurately predicted outcomes in both TCGA training and GEO validation cohorts of TNBC patients. Subsequently, ECM-associated signaling pathways were identified between the Treg-H and Treg-L groups, indicating the role of ECM in Treg infiltration. Since we found increasing collagen concentrations in TNBC patients with distant migration, we encapsulated Jurkat T cells within a 3D matrix with different collagen concentrations and observed that increasing collagen concentrations promoted the expression of Treg biomarkers, supporting the regulatory role of ECM in Treg infiltration.

Conclusion

Our results support the association between Treg expression and breast cancer progression as well as prognosis in the TNBC subtype. Moreover, increasing collagen density may promote Treg infiltration, and thus induce an immunosuppressed TME.
Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury
Authors: Wang Zhengjian , Li Fan , Liu Jin , Luo Yalan , Guo Haoya , Yang Qi , Xu Caiming , Ma Shurong , Chen Hailong
Published: June 2022

Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.
Predicting the Foraging Habitats of Sympatrically Breeding Gadfly Petrels in the South Pacific Ocean
Authors: Halpin Luke R. , Mott Rowan , Clay Thomas A. , Humphries Grant R. W. , Chatwin Trudy A. , Carlile Nicholas , Clarke Rohan H.
Published: June 2022

Gadfly petrels (genus Pterodroma) are one of the most threatened groups of birds. They are exceptionally well adapted to forage over enormous areas to maximize chances of encountering prey. Their wide-ranging travel, extensive use of oceanic habitats beyond national jurisdictions (the high seas), and limited information on their at-sea distributions and foraging ecology pose several management challenges. Here, we examined the foraging distributions and habitat preferences of three gadfly petrels that breed on Phillip Island (Norfolk Island Group), in the southwest Pacific Ocean, and tested the ability of species distribution models (SDMs) to predict important marine habitats. GPS loggers were deployed in 2018 and 2019 on chick-provisioning black-winged petrels (P. nigripennis) and white-necked petrels (P. cervicalis) and in 2020 on Kermadec petrels (P. neglecta), and hidden Markov models (HMMs) were used to estimate behavioral states across 387 foraging trips. SDMs were built using six algorithms and the predictive performance of models constructed using conventional random cross-validation (CV) was compared to those constructed with spatially independent CV. All three species demonstrated dual-foraging strategies with short trips closer to the colony and longer, presumably self-provisioning, trips with maximum distances from the colony of several thousand kilometers for black-winged and white-necked petrels. Foraging areas of each species were distinctly partitioned across the Tasman Sea during long trips, but there was high overlap during short trips. Black-winged and white-necked petrels exhibited area-restricted search foraging behavior throughout their foraging ranges which spanned almost the entire Tasman Sea and into the western Pacific, whereas the foraging range of Kermadec petrels was restricted closer to the colony. Approximately half of each species’ foraging range extended into the high seas. Response curves and variable importance between the two SDM CV approaches were similar, suggesting that model fitting was robust to the CV approach. However, evaluation using spatially independent CV indicated that generalizability of ensemble SDMs to new data ranged from poor to fair for all three species. This suggests that the maximal-area foraging strategy of gadfly petrels (whereby they search opportunistically for resources across expansive oceanic habitats) results in weak or wide associations with environmental features making predicting important habitats extremely challenging.
A Ranking of the Most Common Maternal COVID-19 Symptoms: A Systematic Review
Authors: Chao Melissa , Menon Carlo , Elgendi Mohamed
Published: June 2022

As the coronavirus disease 2019 (COVID-19) continues to devastate health systems worldwide, there is particular concern over the health and safety of one high-risk group, pregnant women, due to their altered immune systems. Since health workers regularly rely on symptoms to inform clinical treatment, it became critical to maintain a ranked list of COVID-19 symptoms specific to pregnant women. This systematic review investigated the prevalence of common COVID-19 symptoms in pregnant women and compared the ranked list of symptoms to articles of various sizes. Articles were included if they discussed pregnant women diagnosed with COVID-19 using polymerase chain reaction testing, and women present symptoms of COVID-19 and were published between December 1, 2019, and December 1, 2021; while articles were excluded if they did not report on pregnant women with COVID-19 displaying symptoms of COVID-19. Articles were identified on OVID MedLine and Embase in January of 2022. The risk of bias and quality appraisal was assessed using a nine-item modified Scottish Intercollegiate Guidelines Network checklist for case-control studies. The search results included 78 articles that described 41,513 pregnant women with 42 unique COVID-19 symptoms. When ranked, the most common symptoms were found to be cough (10,843 cases, 16.02%), fever (7,653 cases, 11.31%), myalgia (6,505 cases, 9.61%), headache (5,264 cases, 7.78%), and dyspnea (5,184 cases, 7.66%). When compared to other articles in the literature with sample sizes of n = 23,434, n = 8,207, and n = 651, the ranking largely aligned with those in other articles with large sample sizes and did not align with the results of articles with small sample sizes. The symptom ranking may be used to inform testing for COVID-19 in the clinic. Research is rapidly evolving with the ongoing nature of the pandemic, challenging the generalizability of the results.
A Comparison of Post-marketing Measures Imposed by Regulatory Agencies to Confirm the Tissue-Agnostic Approach
Authors: Mulder Jorn , van Stuijvenberg Odile C. , van Hennik Paula B. , Voest Emile E. , Pasmooij Anna M. G. , Stoyanova-Beninska Violeta , de Boer Anthonius
Published: June 2022

There are currently four anti-cancer medicinal products approved for a tissue-agnostic indication. This is an indication based on a common biological characteristic rather than the tissue of origin. To date, the regulatory experience with tissue-agnostic approvals is limited. Therefore, we compared decision-making aspects of the first tissue-agnostic approvals between the Food and Drug Administration (FDA), European Medicines Agency (EMA) and Pharmaceuticals and Medical Devices Agency (PMDA). Post-marketing measures (PMMs) related to the tissue-agnostic indication were of specific interest. The main data source was the publicly available review documents. The following data were collected: submission date, approval date, clinical trials and datasets, and PMMs. At the time of data collection, the FDA and PMDA approved pembrolizumab, larotrectinib, and entrectinib for a tissue-agnostic indication, while the EMA approved larotrectinib and entrectinib for a tissue-agnostic indication. There were differences in analysis sets (integrated vs. non-integrated), submission dates and requests for data updates between agencies. All agencies had outstanding issues that needed to be addressed in the post-market setting. For pembrolizumab, larotrectinib and entrectinib, the number of imposed PMMs varied between one and eight, with the FDA requesting the most PMMs compared to the other two agencies. All agencies requested at least one PMM per approval to address the remaining uncertainties related to the tissue-agnostic indication. The FDA and EMA requested data from ongoing and proposed trials, while the PMDA requested data from use-result surveys. Confirmation of benefit in the post-marketing setting is an important aspect of tissue-agnostic approvals, regardless of agency. Nonetheless, each approach to confirm benefit has its inherent limitations. Post-marketing data will be essential for the regulatory and clinical decisions-making of medicinal products with a tissue-agnostic indication.
Value of Contrast-Enhanced Ultrasound in the Ultrasound Classification of Cervical Tuberculous Lymphadenitis
Authors: Zhang Ying , Yu Tianzhuo , Su Dongming , Tang Wei , Yang Gaoyi
Published: June 2022

Purpose

The purpose of this study was to investigate the clinical value of contrast-enhanced ultrasound (CEUS) in the ultrasound (US) classification of cervical tuberculous lymphadenitis (CTL).

Materials and Methods

This retrospective study included 70 patients diagnosed with CTL. All patients underwent both conventional US and CEUS. Both methods were compared to determine their agreement with pathological CTL results.

Results

The results of conventional US classification were as follows: 18 patients (25.7%) were type I, 25 patients (35.7%) type II, 21 patients (30.0%) type III, and 6 patients (8.6%) type IV, respectively. The results of CEUS classification were as follows: 9 patients (12.9%) were type I, 33 patients (47.1%) type II, 22 patients (31.4%) type III, and 6 patients (8.6%) type IV. Conventional US classification and pathological results showed moderate agreement in terms of US classification results for CTL (Kappa = 0.693); the accuracy of conventional US classification was 78.6% (55/70), and the accuracy of types II and III were 71.0% (22/31) and 82.6% (19/23), respectively. CEUS classification and pathological results showed strong agreement (Kappa = 0.871); the accuracy of CEUS classification was 91.4% (64/70), and the accuracy of types II and III were 93.6% (29/31) and 87.0% (20/23), respectively.

Conclusion

In combined with conventional US, CEUS could provide more information on blood flow enhancement patterns and identify the area of lymph node necrosis in CTL. This could contribute to a more accurate US classification of CTL.
Immunotherapy and the Spectrum of Kidney Disease: Should We Individualize the Treatment?
Authors: Bermejo Sheila , Bolufer Mónica , Riveiro-Barciela Mar , Soler Maria José
Published: June 2022

The new targeted cancer therapies including immune checkpoint inhibitors (ICIs) have been demonstrated to improve the survival of oncological patients, even in cases of metastatic cancer. In the past 5 years, several studies have revealed that ICI can produce several immune-mediated toxicities involving different organs, such as the skin, the gastrointestinal tract, the liver, and, of course, the kidney. The most frequent lesion of immunotoxicity in the kidney is acute interstitial nephritis (AIN), although other nephropathies have also been described as a consequence of the use of ICI, such as glomerulonephritis and acute thrombotic microangiopathy, among others. In addition, kidney rejection has also been reported in kidney transplant patients treated with ICI. Normally randomized clinical trials with ICI exclude patients with end-stage kidney disease, namely, patients undergoing dialysis and kidney transplant patients. Several important questions need to be addressed in relation to immunotherapy and patients with kidney disease: (a) when to start corticosteroid therapy in a patient with suspected acute kidney injury (AKI) related to ICI, (b) the moment of nephrologist referral and kidney biopsy indication, (c) management of ICI in patients undergoing dialysis, and (d) the effect of ICI in kidney transplantation, immunosuppressive personalized treatment, and risk of allograft rejection in kidney transplant patients. The objective of this review was to summarize the recently published literature on a wide spectrum of kidney disease patients with cancer and ICI. This review will address three main important groups of individuals with kidney disease and cancer immunotherapy, AKI associated with ICI, patients undergoing dialysis, and kidney transplant recipients. We believe that the information provided in this review will enlighten the personalized ICI treatment in individuals with a broader spectrum of kidney diseases.
Acupuncture Regulates Symptoms of Parkinson’s Disease via Brain Neural Activity and Functional Connectivity in Mice
Authors: Oh Ju-Young , Lee Ye-Seul , Hwang Tae-Yeon , Cho Seong-Jin , Jang Jae-Hwan , Ryu Yeonhee , Park Hi-Joon
Published: June 2022

Parkinson’s disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.
Screening Method for Assessment of Work Ability for Patients Suffering From Mental Fatigue
Authors: Johansson Birgitta
Published: June 2022

Pathological mental fatigue adversely affects endurance in the performance of tasks over time, with negative impact on work ability. There are currently no methods for objectively assessing work ability for patients suffering from mental fatigue. In this study, work ability in relation to mental fatigue as a screening method was evaluated, using the Work Ability Index (WAI) and Mental Fatigue Scale (MFS). Included participants represented three patient groups commonly affected by mental fatigue; acquired brain injury (n = 49, traumatic brain injury, stroke), burn-out syndrome (55) and hypothyroidism (50). The results showed a significant correlation between WAI and MFS (r = –0.754) and status in the workplace (WAI r = 0.722, MFS r = –0.443) for all groups. The WAI and MFS were significant predictors for status in the workplace (p < 0.001) and explained 53% of the variance. This screening method can help health care professionals to identify people who are mentally fatigued with a reduced ability to work or return to work after illness, and who are in need of in-depth investigation. It is important to initiate treatment early with the aim of promoting a sustainable working life and general well-being of the individual.
Neuroimmunology of CNS HIV Infection: A Narrative Review
Authors: Meyer Ana-Claire , Njamnshi Alfred Kongnyu , Gisslen Magnus , Price Richard W.
Published: June 2022

This short review provides an overview of the interactions of human immunodeficiency virus type 1 (HIV), immune and inflammatory reactions, and CNS injury over the course of infection. Systemic infection is the overall driver of disease and serves as the “platform” for eventual CNS injury, setting the level of immune dysfunction and providing both the HIV seeding and immune-inflammatory responses to the CNS. These systemic processes determine the timing of and vulnerability to HIV-related neuronal injury which occurs in a separate “compartment” with features that parallel their systemic counterparts but also evolve independently. Direct CNS HIV infection, along with opportunistic infections, can have profound neurological consequences for the infected individual. HIV-related CNS morbidities are of worldwide importance but are enhanced by the particular epidemiological, socioeconomic and environmental factors that heighten the impact of HIV infection in Africa.
Neuroimaging Markers of Chronic Eye Diseases and Their Application Values
Authors: Yu Chen-Yu , Huang Rong , Li Shi-Qi , Shao Yi
Published: June 2022

In recent years, the impact of various chronic eye diseases on quality of life has become increasingly apparent. Therefore, it is particularly important to control the progress of chronic diseases at an early stage. Many studies have used neuroimaging methods to explore the effects of chronic eye diseases on the brain, and to identify changes in brain function that may act as markers for early diagnosis and treatment. This article reviews the clinical application of different techniques of functional magnetic resonance imaging in chronic eye diseases.
Pre-stroke Disability and Long-Term Functional Limitations in Stroke Survivors: Findings From More of 12 Years of Follow-Up Across Three International Surveys of Aging
Authors: Gil-Salcedo Andres , Dugravot Aline , Fayosse Aurore , Landré Benjamin , Jacob Louis , Bloomberg Mikaela , Sabia Séverine , Schnitzler Alexis
Published: June 2022

Background

Almost 50% of the post-stroke disabled population already have a premorbid disability before stroke. These patients may be offered a different care pathway in the acute and subacute phase than those without pre-morbid disability. Therefore, the aim of this study was to assess the association of the severity of premorbid disability with change of limitations in basic and instrumental activities of daily living (ADL/IADL) 1 year after stroke and over the following decade.

Methods

Among 3,432 participants from HRS, SHARE and ELSA cohorts with a first stroke, ADL/IADL limitations were measured at 1–2 years prior to stroke, at 1 year post-stroke, and during the chronic phase. Modified Ranking Scale (P-mRS) was used to categorize the participants by level of premorbid disability (1–2 years pre-stroke). Change in ADL/IADL limitations by P-mRS level (0–1, 2–3, and 4–5) was assessed using a piecewise linear mixed model with a breakpoint set at 1 year post-stroke, stratified by median age groups.

Results

Increase in ADL limitations at 1 year post-stroke was less pronounced in P-mRS ≥2 (p < 0.005). After years of relative stability, limitations of ADL increased for all P-mRS levels (p = 0.003). In those aged ≥75 years at stroke event, the increase was similar irrespective of P-mRS (p = 0.090). There were no significant differences in IADL trajectories between P-mRS levels (p ≥ 0.127).

Conclusion

These results suggest similar trajectories of functional limitations between P-mRS levels up to 9 years post-stroke, highlighting the possible benefit of including patients with pre-morbid disability to certain treatments during the acute phase.
Acute-Onset Visual Impairment in Wilson's Disease: A Case Report and Literature Review
Authors: Zheng Zi-Wei , Xu Meng-Hui , Sun Chuan-Bin , Wu Zhi-Ying , Dong Yi
Published: June 2022

Objective

We reported the case of a patient with Wilson's disease (WD) with acute-onset visual impairment and summarized previously reported cases to make physicians aware of the complicated clinical expressions of WD and improve diagnosis efficiency.

Methods

The patient was recruited from the Second Affiliated Hospital of Zhejiang University School of Medicine. Clinical data, including cranial images, laboratory tests, and ophthalmic findings were obtained. The PubMed database was searched for published cases of WD with visual impairment.

Results

We reported a 22-year-old male who presented with hand tremor, personality change, and acute-onset binocular vision blurring. WD was considered to be closely correlated with neuropsychiatric and ocular involvements. After low-copper diet and regular copper-chelation therapy, the related symptoms improved compared to before. Six WD cases of optic neuropathy have been reported, including ours. The patients usually had neurological and/or hepatic symptoms for a period without any treatment. All the reported cases manifested as acute episodes of visual changes, and the ocular manifestations improved after copper-chelation treatment.

Conclusions

Excess copper accumulation may be a rare cause of visual impairment in patients with WD. While the etiology behind patients' acute-onset visual impairment remained uncertain, the possibility of WD should be considered through neuropsychiatric and hepatic symptoms, corneal K-F rings, decreased serum ceruloplasmin, and low likelihood or exclusion of other causes. Clinicians need to recognize this rare manifestation and give appropriate treatment to avoid misdiagnosis and unnecessary overtreatment.
Transcranial Direct Current Stimulation Over Motor Areas Improves Reaction Time in Parkinson's Disease
Authors: Sadler Christin M. , Kami Aline Tiemi , Nantel Julie , Lommen Jonathan , Carlsen Anthony N.
Published: June 2022

Background

Transcranial direct current stimulation (tDCS) has been shown to modulate cortical motor excitability and improve bradykinesia symptoms in Parkinson's disease. It is unclear how targeting different cortical motor areas with tDCS may differentially influence upper limb function for individuals diagnosed with PD.

Objective

This study investigated whether anodal tDCS applied separately to the primary motor cortex and the supplementary motor area would improve upper limb function for individuals with Parkinson's disease. In addition, a startling acoustic stimulus was used to differentiate between the effect of stimulation on motor preparatory and initiation processes associated with upper limb movements.

Methods

Eleven participants with idiopathic Parkinson's disease performed two upper limb simple reaction time tasks, involving elbow extension or a button press before and after either anodal tDCS or sham tDCS was applied over the primary motor cortex or supplementary motor area. A loud, startling stimulus was presented on a selection of trials to involuntarily trigger the prepared action.

Results

Anodal tDCS led to improved premotor reaction time in both tasks, but this was moderated by reaction time in pre-tDCS testing, such that individuals with slower pre-tDCS reaction time showed the greatest reaction time improvements. Startle-trial reaction time was not modified following tDCS, suggesting that the stimulation primarily modulated response initiation processes.

Conclusion

Anodal tDCS improved response initiation speed, but only in slower reacting individuals with PD. However, no differences attributable to tDCS were observed in clinical measures of bradykinesia or kinematic variables, suggesting that reaction time may represent a more sensitive measure of some components of bradykinesia.
Effects of Flavonoid Supplementation on Nanomaterial-Induced Toxicity: A Meta-Analysis of Preclinical Animal Studies
Authors: Xie Dongli , Hu Jianchen , Wu Tong , Xu Wei , Meng Qingyang , Cao Kangli , Luo Xiaogang
Published: June 2022

Background

Nanomaterials, widely applied in various fields, are reported to have toxic effects on human beings; thus, preventive or therapeutic measures are urgently needed. Given the anti-inflammatory and antioxidant activities, supplementation with flavonoids that are abundant in the human diet has been suggested as a potential strategy to protect against nanomaterial-induced toxicities. However, the beneficial effects of flavonoids remain inconclusive. In the present study, we performed a meta-analysis to comprehensively explore the roles and mechanisms of flavonoids for animals intoxicated with nanomaterials.

Methods

A systematic literature search in PubMed, EMBASE, and Cochrane Library databases was performed up to April 2022. STATA 15.0 software was used for meta-analyses.

Results

A total of 26 studies were identified. The results showed that flavonoid supplementation could significantly increase the levels of antioxidative enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione-S-transferase), reduce the production of oxidative agents (malonaldehyde) and pro-inflammatory mediators (tumor necrosis factor-α, interleukin-6, IL-1β, C-reactive protein, immunoglobulin G, nitric oxide, vascular endothelial growth factor, and myeloperoxidase), and alleviate cell apoptosis (manifested by decreases in the mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2), DNA damage (reductions in tail length and tail DNA%), and nanomaterial-induced injuries of the liver (reduced alanine aminotransferase and aspartate aminotransferase activities), kidney (reduced urea, blood urea nitrogen, creatinine, and uric acid concentration), testis (increased testosterone, sperm motility, 17β-hydroxysteroid dehydrogenase type, and reduced sperm abnormalities), and brain (enhanced acetylcholinesterase activities). Most of the results were not changed by subgroup analyses.

Conclusion

Our findings suggest that appropriate supplementation of flavonoids may be effective to prevent the occupational detriments resulting from nanomaterial exposure.
Numerical Investigation on Spray Characteristics With Upstream Flow Pulsation of a Pintle Injector
Authors: Xie Yuan , Nie Wansheng , Gao Yuchao , Tong Yiheng
Published: June 2022

The volume of fluid (VOF) model and the adaptive mesh refinement (AMR) method are used to study the spray characteristics of a gas–liquid pintle injector and the effects of mass flow pulsation of liquid on it. A pintle injector is a thrust adjusting device that changes the injection area using movable parts. Pressure pulsation in the supply pipeline is simulated by periodically changing the mass flow rate of the inlet. Spray characteristics with constant and pulsating upstream flows are compared with each other. The effect of frequency and amplitude of upstream liquid flow pulsation on the spray performance was studied. The results reveal that holding the mass flow rate of the upstream liquid flow constant, under the impact of gas flow, the liquid block, the liquid filament, and a large number of small droplets are peeled off from the liquid film. The film breakup position stays relatively fixed, and the spray has a conical shape. However, when the upstream liquid flow is pulsating, the film breakup position changes periodically, and the spray has a “Christmas tree”-shape. The pulsation frequency has little effect on the spray angle. But it strongly determines the droplet size and the spatial distribution of the spray. In addition, the pulsation amplitude can enhance the phenomenon of “Christmas tree.” With the increase in pulsation amplitude, the liquid film at the outlet of the pintle injector appears with a periodic phenomenon of “contraction–expansion.”
Development and Validation of a Nomogram for Predicting the Risk of Bell's Stage II/III Necrotizing Enterocolitis in Neonates Compared to Bell's Stage I
Authors: Song Shuting , Zhang Jian , Zhao Yuwei , Dai Liying
Published: June 2022

Background

Patients with Bell's Stage II/III necrotizing enterocolitis (NEC) may have more severe presentations, higher rates of death, and more long-term complications than those with Bell's Stage I NEC, so the purpose of this article was to construct a nomogram model to distinguish Bell's stage II/III NEC early from Bell's Stage I NEC, which is critical in the clinical management of NEC.

Patients and Methods

A total of 730 NEC newborns diagnosed from January 2015 to January 2021 were retrospectively studied. They were randomly divided into training and validation groups at the ratio of 7:3. A nomogram model for predicting NEC was developed based on all the independent risk factors by multivariate regression analysis. The model's performance was mainly evaluated through three aspects: the area under the curve (AUC) to verify discrimination, the Hosmer–Lemeshow test and calibration curve to validate the consistency, and decision curve analysis (DCA) to determine the clinical effectiveness.

Results

Predictors included in the prediction model were gestational age (GA), birth weight (BW), asphyxia, septicemia, hypoglycemia, and patent ductus arteriosus (PDA). This nomogram model containing the above-mentioned six risk factors had good discrimination ability in both groups, and the AUCs were 0.853 (95% CI, 0.82–0.89) and 0.846 (95% CI, 0.79–0.90), respectively. The calibration curve and DCA confirmed that the nomogram had good consistency and clinical usefulness.

Conclusions

This individual prediction nomogram based on GA, BW, asphyxia, septicemia, hypoglycemia, and PDA served as a useful tool to risk-stratify patients with NEC, and can help neonatologists early distinguish Bell's stage II/III NEC early from Bell's Stage I NEC.
A Statewide Collaboration to Deliver and Evaluate a Pediatric Critical Care Simulation Curriculum for Emergency Medical Services
Authors: Farrell Caitlin , Dorney Kate , Mathews Bonnie , Boyle Tehnaz , Kitchen Anthony , Doyle Jeff , Monuteaux Michael C. , Li Joyce , Walsh Barbara , Nagler Joshua , Chung Sarita
Published: June 2022

Objective

Care of the critically ill child is a rare but stressful event for emergency medical services (EMS) providers. Simulation training can improve resuscitation care and prehospital outcomes but limited access to experts, simulation equipment, and cost have limited adoption by EMS systems. Our objective was to form a statewide collaboration to develop, deliver, and evaluate a pediatric critical care simulation curriculum for EMS providers.

Methods

We describe a statewide collaboration between five academic centers to develop a simulation curriculum and deliver it to EMS providers. Cases were developed by the collaborating PEM faculty, reviewed by EMS regional directors, and based on previously published EMS curricula, a statewide needs assessment, and updated state EMS protocols. The simulation curriculum was comprised of 3 scenarios requiring recognition and acute management of critically ill infants and children. The curriculum was implemented through 5 separate education sessions, led by a faculty lead at each site, over a 6 month time period. We evaluated curriculum effectiveness with a prospective, interventional, single-arm educational study using pre-post assessment design to assess the impact on EMS provider knowledge and confidence. To assess the intervention effect on knowledge scores while accounting for nested data, we estimated a mixed effects generalized regression model with random effects for region and participant. We assessed for knowledge retention and self-reported practice change at 6 months post-curriculum. Qualitative analysis of participants' written responses immediately following the curriculum and at 6 month follow-up was performed using the framework method.

Results

Overall, 78 emergency medical technicians (EMTs) and 109 paramedics participated in the curriculum over five separate sessions. Most participants were male (69%) and paramedics (58%). One third had over 15 years of clinical experience. In the regression analysis, mean pediatric knowledge scores increased by 9.8% (95% CI: 7.2%, 12.4%). Most (93% [95% CI: 87.2%, 96.5%]) participants reported improved confidence caring for pediatric patients. Though follow-up responses were limited, participants who completed follow up surveys reported they had used skills acquired during the curriculum in clinical practice.

Conclusion

Through statewide collaboration, we delivered a pediatric critical care simulation curriculum for EMS providers that impacted participant knowledge and confidence caring for pediatric patients. Follow-up data suggest that knowledge and skills obtained as part of the curriculum was translated into practice. This strategy could be used in future efforts to integrate simulation into EMS practice.
Multidisciplinary Approach for Adult Patients With Childhood-Onset Chronic Disease Focusing on Promoting Pediatric to Adult Healthcare Transition Interventions: An Updated Systematic Review
Authors: Wakimizu Rie , Sasaki Keita , Yoshimoto Mitsuki , Miyazaki Akari , Saito Yumiko
Published: June 2022

Introduction

Owing to improved prognosis, the number of adult patients with childhood-onset chronic disease (APCCD) has increased. In this systematic review, we evaluated a multidisciplinary approach toward APCCD, focusing on promoting pediatric to adult healthcare transition interventions and their effects.

Methods

We reviewed literature comparing the effects of pediatric to adult healthcare transition interventions in children and adolescents with childhood-onset chronic disease, using PubMed, MEDLINE, and CINAHL, from 2010 to 2021 (keywords: “transition,” “children,” “intervention,” “healthcare,” etc.). The inclusion criteria were as follows: (i) original studies, (ii) studies on pediatric to adult healthcare transition interventions in children with chronic disease, (iii) patients including “adolescents” aged 12 and older receiving intervention, and (iv) studies that included the four elements of the PICO model: Patient/ Problem, Intervention, Comparison and Outcome model.

Results

After evaluating 678 studies, 16 were selected, comprising topics such as “individual education programs” (n = 6), “group meetings” (n = 6), “active learning using information and communications technology” (n = 2), and “transition clinics” (n = 2). The effects obtained varied, depending on the contents and methods of the intervention. Additionally, there was no evidence of adverse outcomes from these interventions.

Conclusions

Pediatric to adult healthcare transition interventions provide systematic support for the transition, patient independence, and social participation; thus, they should be adopted based on their expected effects.
An Opioid-Sparing Strategy for Laparoscopic Sleeve Gastrectomy: A Retrospective Matched Case-Controlled Study in China
Authors: Ma Yuanyuan , Zhou Di , Fan Yu , Ge Shengjin
Published: June 2022

Background: Opioid-sparing anesthesia may enhance postoperative recovery by reducing opioid-related side effects. The present study was to evaluate the effect of an opioid-sparing strategy in bariatric surgery.

Methods: This study was conducted as a retrospective matched case-controlled (1:1) study. A total of 44 patients receiving either an opioid-based approach (OBA group) or an opioid-sparing strategy (OSA group) who under laparoscopic sleeve gastrectomy were included between May 2017 and October 2020. The primary outcome was the postoperative hospital length of stay (PLOS). Secondary outcomes were the hospital costs, operative opioid consumption, time to recovery, postoperative pain score at rest and rescue antiemetic administered in the PACU.

Results: The clinical demographic and operative data in both groups were comparable. There were no significant differences between the two groups in the PLOS (OSA vs. OBA: 6.18 ± 0.23 days vs. 6.73 ± 0.39 days, p = 0.24). Compared to the OBA group, opioid consumption in the OSA group was significantly decreased (48.79 ± 4.85 OMEs vs. 10.57 ± 0.77 OMEs, p < 0.001). There were no significant differences in the hospital costs, time to recovery, and rescue antiemetic administered, the incidence of intravenous opioids and vasopressor use in the PACU.

Conclusion: The opioid-sparing anesthesia for laparoscopic sleeve gastrectomy was feasible but did not decrease the PLOS.
Exploring Ganweikang Tablet as a Candidate Drug for NAFLD Through Network Pharmacology Analysis and Experimental Validation
Authors: Ma Chuanrui , Wang Xinyu , Zhang Jing , Zhao Yun , Hua Yunqing , Zhang Chao , Zheng Guobin , Yang Guangyan , Guan Jianli , Li Huahuan , Li Meng , Kang Lin , Xiang Jiaqing , Fan Guanwei , Yang Shu
Published: June 2022

Nonalcoholic fatty liver disease (NAFLD) is defined as liver disease in which more than 5% of hepatocytes are steatotic with little or no alcohol consumption. NAFLD includes benign nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Importantly, NASH is an advanced progression of NAFL and is characterized by steatosis, hepatocyte ballooning, lobular inflammation, and fibrosis. However, to date, no drugs specifically targeting NAFLD have been approved by the FDA. Therefore, a new drug or strategy for NAFLD treatment is necessary. However, the pathogenesis of NAFLD is complex and no single-target drugs have achieved the desired results. Noticeably, traditional Chinese medicine formulations are a complex system with multiple components, multiple targets, and synergistic effects between components. The Ganweikang tablet is a compound formula based on traditional Chinese medicine theory and clinical experience. In this study, network pharmacology analysis indicates Ganweikang tablet as a candidate for NAFLD treatment. Furthermore, we evaluated the therapeutic effects of Ganweikang tablet on the NAFL and NASH and tried to clarify the underlying molecular mechanisms in animal models and cell experiments. As expected, Ganweikang tablet was found to improve NAFL and NASH by modulating inflammation, apoptosis, and fatty acid oxidation by inhibiting NFκB, caspase-8, and activating PPARα, which not only indicates that Ganweikang tablet as a drug candidate but also provides a theoretical basis of Ganweikang tablet for the treatment of NAFL and NASH.
Phosphatase and Tensin Homology Deleted on Chromosome 10 Inhibitors Promote Neural Stem Cell Proliferation and Differentiation
Authors: Liu Xiaojiang , Cui Yiqiu , Li Jun , Guan Cheng , Cai Shu , Ding Jinrong , Shen Jianhong , Guan Yixiang
Published: June 2022

Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor gene. Its encoded protein has phosphatase and lipid phosphatase activities, which regulate the growth, differentiation, migration, and apoptosis of cells. The catalytic activity of PTEN is crucial for controlling cell growth under physiological and pathological conditions. It not only affects the survival and proliferation of tumor cells, but also inhibits a variety of cell regeneration processes. The use of PTEN inhibitors is being explored as a potentially beneficial therapeutic intervention for the repair of injuries to the central nervous system. PTEN influences the proliferation and differentiation of NSCs by regulating the expression and phosphorylation of downstream molecular protein kinase B (Akt) and the mammalian target of rapamycin (mTOR). However, the role of PTEN inhibitors in the Akt/mTOR signaling pathway in NSC proliferation and differentiation is unclear. Dipotassium bisperoxo (picolinoto) oxovanadate (V) [bpv(pic)] is a biologically active vanadium compound that blocks PTEN dephosphorylation and suppresses its activity, and has been used as a PTEN lipid phosphatase inhibitor. Here, bpv(pic) intervention was found to significantly increase the number of rat NSCs, as determined by bromodeoxyuridine staining and the cell counting kit-8, and to increase the percentage of neurons undergoing differentiation, as shown by immunofluorescence staining. Bpv(pic) intervention also significantly increased PTEN and mTOR expression, as shown by real-time PCR analysis and western blotting. In conclusion, PTEN inhibitor bpv(pic) promotes the proliferation and differentiation of NSCs into neurons.
Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction by Inhibiting TLR4-NOX1/ROS Signaling Pathway in Caco-2 Cells
Authors: Xia Fan , Li Yuxin , Deng Lijun , Ren Ruxia , Ge Bingchen , Liao Ziqiong , Xiang Shijian , Zhou Benjie
Published: June 2022

Alisol B 23-Acetate (AB23A) is a naturally occurring triterpenoid, which can be indicated in the rhizome of medicinal and dietary plants from Alisma species. Previous studies have demonstrated that AB23A could inhibit intestinal permeability by regulating tight junction (TJ)-related proteins. Even so, the AB23A protective mechanism against intestinal barrier dysfunction remains poorly understood. This investigation seeks to evaluate the AB23A protective effects on intestinal barrier dysfunction and determine the mechanisms for restoring intestinal barrier dysfunction in LPS-stimulated Caco-2 monolayers. According to our findings, AB23A attenuated the inflammation by reducing pro-inflammatory cytokines production like IL-6, TNF-α, IL-1β, and prevented the paracellular permeability by inhibiting the disruption of TJ in LPS-induced Caco-2 monolayers after treated with LPS. AB23A also inhibited LPS-induced TLR4, NOX1 overexpression and subsequent ROS generation in Caco-2 monolayers. Transfected with NOX1-specific shRNA diminished the up-regulating AB23A effect on ZO-1 and occludin expression. Moreover, transfected with shRNA of TLR4 not only enhanced ZO-1 and occludin expression but attenuated NOX1 expression and ROS generation. Therefore, AB23A ameliorates LPS-induced intestinal barrier dysfunction by inhibiting TLR4-NOX1/ROS signaling pathway in Caco-2 monolayers, suggesting that AB23A may have positive impact on maintaining the intestinal barrier’s integrity.
The Role of Pharmacological Treatment in the Chemoreflex Modulation
Authors: Langner-Hetmańczuk Anna , Tubek Stanisław , Niewiński Piotr , Ponikowski Piotr
Published: June 2022

From a physiological point of view, peripheral chemoreceptors (PCh) are the main sensors of hypoxia in mammals and are responsible for adaptation to hypoxic conditions. Their stimulation causes hyperventilation—to increase oxygen uptake and increases sympathetic output in order to counteract hypoxia-induced vasodilatation and redistribute the oxygenated blood to critical organs. While this reaction promotes survival in acute settings it may be devastating when long-lasting. The permanent overfunctionality of PCh is one of the etiologic factors and is responsible for the progression of sympathetically-mediated diseases. Thus, the deactivation of PCh has been proposed as a treatment method for these disorders. We review here physiological background and current knowledge regarding the influence of widely prescribed medications on PCh acute and tonic activities.
Efficacy of Shexiang Tongxin Dropping Pills in a Swine Model of Coronary Slow Flow
Authors: Bai Yupeng , Zhang Mingjing , Peng Sheng , Wang Yuting , Gu Ye , Fang Qianqian , Hu Liqun
Published: June 2022

Objective: Preliminary clinical studies have confirmed that Shexiang Tongxin dropping pills (STDPs) could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow, but the underlying mechanism is not fully unclear. We aimed to investigate the impact of STDP in a swine model of coronary slow flow (SF) and related mechanisms.

Methods: SF was induced by coronary injection of 40μm microspheres, and pigs were randomly divided into the SF group and SF plus STDP group. Pigs in the STDP group received sublingual STDP for 10 min, followed by 1 g STDP oral administration daily for 6 days. Coronary angiography was performed, the TIMI frame count (TFC) was determined, and hemodynamic measurements were performed before, at 30 min, and 7 days post-SF. Serum levels of total NO, NOS, ET-1, C-TNI, and BNP were measured. Myocardial expressions of TNF and IL-6, eNOS, VEGF, CD31, and α-SMA were analyzed by immunohistochemistry and Western blotting.

Results: Compared to the SF group, LVEF and TFC were significantly improved at 7 days post-SF in the STDP group. The serum ET-1 level was significantly reduced at 7 days, and NO and NOS levels were significantly higher in the STDP group. Seven days post-SF, myocardial TNF and IL-6 expressions were significantly downregulated, while the expressions of eNOS and VEGF, CD31, and ɑ-SMA were significantly upregulated in the STDP group.

Conclusion: Our results showed that STDP improved cardiac function and coronary flow, possibly through reducing inflammatory responses and upregulating myocardial eNOS and VEGF, CD31, and the ɑ-SMA expression.