bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral blood monocytes as a therapeutic target for marrow stromal cells in stroke patients
Authors: Satani Nikunj , Parsha Kaushik , Davis Courtney , Gee Adrian , Olson Scott D. , Aronowski Jaroslaw , Savitz Sean I. 
Published: October 2022

BackgroundSystemic administration of marrow stromal cells (MSCs) leads to the release of a broad range of factors mediating recovery in rodent stroke models. The release of these factors could depend on the various cell types within the peripheral blood as they contact systemically administered MSCs. In this study, we assessed the immunomodulatory interactions of MSCs with peripheral blood derived monocytes (Mϕ) collected from acute stroke patients.MethodsPeripheral blood from stroke patients was collected at 5–7 days (N = 5) after symptom onset and from age-matched healthy controls (N = 5) using mononuclear cell preparation (CPT) tubes. After processing, plasma and other cellular fractions were removed, and Mϕ were isolated from the mononuclear fraction using CD14 microbeads. Mϕ were then either cultured alone or co-cultured with MSCs in a trans-well cell-culture system. Secretomes were analyzed after 24 h of co-cultures using a MAGPIX reader.ResultsOur results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5–7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1β, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients.ConclusionThe systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke.
Association between the LACE+ index and unplanned 30-day hospital readmissions in hospitalized patients with stroke
Authors: Jun-O'Connell Adalia H. , Grigoriciuc Eliza , Silver Brian , Kobayashi Kimiyoshi J. , Osgood Marcey , Moonis Majaz , Henninger Nils 
Published: October 2022

BackgroundThe LACE+ index is used to predict unplanned 30-day hospital readmissions, but its utility to predict 30-day readmission in hospitalized patients with stroke is unknown.MethodsWe retrospectively analyzed 1,657 consecutive patients presenting with ischemic or hemorrhagic strokes, included in an institutional stroke registry between January 2018 and August 2020. The primary outcome of interest was unplanned 30-day readmission for any reason after index hospitalization for stroke. The 30-day readmission risk was categorized by LACE+ index to high risk (≥78), medium-to-high risk (59–77), medium risk (29–58), and low risk (≤ 28). Kaplan-Meier analysis, Log rank test, and multivariable Cox regression analysis (with backward elimination) were used to determine whether the LACE+ score was an independent predictor for 30-day unplanned readmission.ResultsThe overall 30-day unplanned readmission rate was 11.7% (194/1,657). The median LACE+ score was higher in the 30-day readmission group compared to subjects that had no unplanned 30-day readmission [74 (IQR 67–79) vs. 70 (IQR 62–75); p &lt; 0.001]. On Kaplan-Meier analysis, the high-risk group had the shortest 30-day readmission free survival time as compared to medium and medium-to-high risk groups (p &lt; 0.01, each; statistically significant). On fully adjusted multivariable Cox-regression, the highest LACE+ risk category was independently associated with the unplanned 30-day readmission risk (per point: HR 1.67 95%CI 1.23–2.26, p = 0.001).ConclusionSubjects in the high LACE+ index category had a significantly greater unplanned 30-day readmission risk after stroke as compared to lower LACE+ risk groups. This supports the validity of the LACE+ scoring system for predicting unplanned readmission in subjects with stroke. Future studies are warranted to determine whether LACE+ score-based risk stratification can be used to devise early interventions to mitigate the risk for unplanned readmission.
Efficacy of miRNA-modified mesenchymal stem cell extracellular vesicles in spinal cord injury: A systematic review of the literature and network meta-analysis
Authors: Yang Zhelun , Rao Jian , Liang Zeyan , Xu Xiongjie , Lin Fabin , Lin Yike , Wang Chunhua , Chen Chunmei 
Published: October 2022

BackgroundAlthough some previous studies have indicated that extracellular vesicles (EVs) secreted from miRNA-modified mesenchymal stem cells (MSCs) may be more effective as compared with control EVs in the treatment of rats with spinal cord injuries (SCI), the efficacy of this treatment modality remains controversial.ObjectivesThe current study comprehensively evaluated the efficacy of different administered doses of EVs, including miRNA-overexpressing MSCs-derived EVs, among SCI rats. The efficacy of EVs' treatment was evaluated in different SCI models to provide evidence for preclinical trials.MethodsWe extensively searched the following databases to identify relevant studies: PubMed, Embase, Scopus, The Cochrane Library, and Web of Science (from inception to July 20, 2022). Two trained investigators independently screened literature, extracted the data, and evaluated literature quality.ResultsThirteen studies were included in this network meta-analysis. The results demonstrated that miRNA-overexpressing MSCs-derived EVs (100 and 200 μg of total protein of EVs) significantly improved hind limb motor function in rats at early stages of SCI (i.e., at 3 days after injury) as compared with EVs (100 and 200 μg of total protein of EVs, respectively). However, in the middle and late stages (14 and 28 days), there were no statistically significant differences between EVs with 200 μg dosages and miRNA-loaded EVs with 100 μg dosages. In the late stages (28 days), there were no statistically significant differences between EVs with 100 μg dosages and miRNA-loaded EVs with 200 μg dosages. We found that miRNA-overexpressing MSCs-derived EVs significantly improved motor function among early-stage SCI rats in a compression and contusion model (3 days) as compared with MSCs-derived EVs and miRNA-overexpressing MSCs-derived EVs likewise significantly improved motor function among SCI rats in a contusion model at middle and late stages (14 and 28 days).ConclusionOur results suggest that miRNA-overexpressing MSCs-derived EVs (200 μg of total protein of EVs) may be the best choice for the effective treatment of SCI, and miRNA-overexpressing MSCs-derived EVs may likewise be the best choice for treating contusions. However, there are some risks of bias in our included studies, and the mechanisms underlying the efficacy of EVs remain unclear.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282051, identifier: CRD42021282051.
Swallowing function after acute ischemic stroke: Development and validation of a novel clinical prognostic model
Authors: Zhang Peiliang , Zhang Wenbo , Shi Wujie , Weng Jianbin , Zhang Zhongyuan , Lin Chao , Wang Ning , Shen Zhipeng , Chen Zhi-Lin 
Published: October 2022

BackgroundPredicting the duration of dysphagia after acute ischemic stroke (AIS) is important for clinical treatment decisions.ObjectiveThe purpose of this study is to assess the swallowing function of AIS patients and to develop and validate a prognostic model for the need for nasogastric tube (NGT) in these patients.Materials and methodsWe included 554 AIS patients during 2018–2019 as the development group and had 186 AIS patients as the external validation group. The primary end point of the study was the retention of NGT in patients 1 week after admission (Functional Oral Intake Scale ≤ 4). Swallowing function and stroke-associated pneumonia (SAP) at 1 month post-onset were also the objectives of this study. The volume-viscosity swallow test (V-VST) was used to assess the patient’s impaired swallowing function. The Predictive model was built by logistic regression.ResultsOverall, a total of 104 patients required indwelling NGT at 1 week of AIS onset in development group. The final prognostic model includes 5 variables: age (OR: 1.085, 95%CI: 1.049–1.123), neutrophil-to-lymphocyte ratio (NLR) (OR: 1.332, 95%CI: 1.090–1.626), NIHSS (OR: 1.092, 95%CI: 1.025–1.164), history of drinking (OR: 2.532, 95%CI: 1.452–4.417) and stroke location (Subtentorial vs. Supratentorial, OR: 1.954, 95%CI: 1.088–3.509). The prediction model had an AUC of 0.810, while the external validation group was 0.794.ConclusionIn stroke patients, it is very important to decide early whether to indwell a NGT. The nomogram will support decision making for NGT insertion and help these patients recover from their condition.
The prognostic nutritional index, an independent predictor of overall survival for newly diagnosed follicular lymphoma in China
Authors: Ge Jingjing , Lei Yaxin , Wen Qing , Zhang Yue , Kong Xiaoshuang , Wang Wenhua , Qian Siyu , Hou Huting , Wang ZeYuan , Wu Shaoxuan , Dong Meng , Ding Mengjie , Wu Xiaolong , Feng Xiaoyan , Zhu Linan , Zhang Mingzhi , Chen Qingjiang , Zhang Xudong 
Published: October 2022

ObjectiveThe prognostic nutritional index (PNI) is an important prognostic factor for survival outcomes in various hematological malignancies. The current study focused on exploring the predictive value of the PNI in newly diagnosed follicular lymphoma (FL) in China.Materials and methodsThe clinical indicators and follow-up data of 176 patients who received chemotherapy or immunotherapy combined with chemotherapy with FL in our hospital from January 2016 to March 2022 were retrospectively analyzed. Cox proportional hazard model was used for univariate and multivariate analyses. Kaplan–Meier curves were used to calculate survival rates and draw survival curves. The log-rank test was applied to compare differences between groups.ResultsThe optimal cut-off value of PNI was 44.3. All patients were divided into a high PNI group (&gt;44.3) and a low PNI group (≤44.3). The low PNI group had a low CR rate and a high risk of death, with a tendency toward POD24, and Both OS and PFS were worse than those in the high PNI group. PNI was able to predict OS and PFS in FL patients and was the only independent predictor of OS (P = 0.014 HR 5.024; 95%CI 1.388∼18.178) in multivariate analysis. PNI could re-stratify patients into groups of high FLIPI score, high FLIPI2 score, no POD24, and rituximab combined with chemotherapy. Moreover, integrating PNI into the FLIPI and FLIPI2 models improved the area under the curve (AUC) for more accurate survival prediction and prognosis.ConclusionPNI is a significant prognostic indicator for newly diagnosed FL in China that can early identify patients with poor prognosis and guide clinical treatment decisions.
Cost and effectiveness of microwave ablation versus video-assisted thoracoscopic surgical resection for ground-glass nodule lung adenocarcinoma
Authors: Han Xiaoying , Wei Zhigang , Zhao Zhenxing , Yang Xia , Ye Xin 
Published: October 2022

PurposeTo retrospectively evaluate the cost and effectiveness in consecutive patients with ground-glass nodules (GGNs) treated with video-assisted thoracoscopic surgery (VATS; i.e., wedge resection or segmentectomy) or microwave ablation (MWA).Materials and methodsFrom May 2017 to April 2019, 204 patients who met our study inclusion criteria were treated with VATS (n = 103) and MWA (n = 101). We calculated the rate of 3-year overall survival (OS), local progression-free survival (LPFS), and cancer−specific survival (CSS), as well as the cost during hospitalization and the length of hospital stay.ResultsThe rates of 3-year OS, LPFS, and CSS were 100%, 98.9%, and 100%, respectively, in the VATS group and 100%, 100% (p = 0.423), and 100%, respectively, in the MWA group. The median cost of VATS vs. MWA was RMB 54,314.36 vs. RMB 21,464.98 (p &lt; 0.001). The length of hospital stay in the VATS vs. MWA group was 10.0 vs. 6.0 d (p &lt; 0.001).ConclusionsMWA had similar rates of 3-year OS, LPFS, and CSS for patients with GGNs and a dramatically lower cost and shorter hospital stay compared with VATS. Based on efficacy and cost, MWA provides an alternative treatment option for patients with GGNs.
Inhibition of induced-hepatic cancer in vivo through IQGAP1-shRNA gene therapy and modulation of TRAIL-induced apoptosis pathway
Authors: Zoheir Khairy M. A. , Abd-Rabou Ahmed A. , Darwish Ahmed M. , Abdelhafez Mohamed A. , Mahrous Karima F. 
Published: October 2022

BackgroundLiver cancer is the deadliest malignancy among common tumors. It is the top cause of cancer-related deaths in Egypt, and it is characterized by increasing occurrence among the population. The objective of this study was to determine the outcome of pre-treatment of IQGAP1-shRNA on induced mouse hepatocellular carcinoma model and evaluate the potency of this IQGAP1-shRNA plasmid to recover hepatic cancer as a new tool of cancer therapy. Therefore, we will use RNA interference (RNAi) technology to silence IQGAP1 oncogene to completely recover the chemically induced models for hepatic cancer by designing short RNAi specific for IQGAP1 gene in HCC cells in vivo and construct new vectors suitable for this purpose. We assigned mice into three groups: the first negative control group (NC) was injected with saline, the second control group was injected with shRNA (shNC), the third positive control group was injected with diethylnitrosamine (DENAA), and the fourth group was treated with the IQGAP1-shRNA prior to its exposure to DENA.ResultsOur results revealed that the treated group with IQGAP1-shRNA with DENA developed very few cases of hepatic cancer when compared with the positive control group. The positive control group exhibited significant increases in the liver function level as well as a decrease in serum albumin levels when compared to both the treated and the negative control groups. The altered levels of the serum α-fetoprotein as well as of the tumor necrosis factor-alpha, and interleukin-4 in DENA-treated mice were significantly ameliorated by IQGAP1-shRNA administration. Flow cytometer analyses have indicated that the silencing of IQGAP1 cannot significantly modulate DENA-induced apoptosis in the circulating blood cells. Moreover, the elevated mRNA expression levels of IQGAP1, IQGAP3, KRas, HRas, interleukin-8, nuclear factor kappa B, caspase-3, caspase-9 and Bcl-2, were significantly decreased by the IQGAP1-shRNA treatment. However, the IQGAP2, DR4, DR5, p53 and BAX genes were found to be significantly up-regulated post-therapy. In agreement with these findings, IQGAP1-shRNA was able to modulate the DENA-induced histological changes in the mice liver which were represented by severe necrosis and hydropic degenerative changes.ConclusionOur study revealed that IQGAP1-shRNA was able to preserve hepatocyte integrity and the liver histological architecture through the regulation of the expression of IQGAPs, Ras, TRAILs and IL-8 receptors, as well as of pro-apoptotic and anti-apoptotic genes. Therefore, the silencing of IQGAP1 could be part of a promising therapeutic strategy against hepatic cancer.
Therapeutic hypothermia for encephalopathic newborns with congenital heart defect: A cross-sectional survey on current practices and opinions in Germany
Authors: Boos Vinzenz , Berger Felix 
Published: October 2022

BackgroundTherapeutic hypothermia (TH) reduces neonatal mortality and long-term neurodevelopmental impairment in infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) caused by perinatal asphyxia. There is an increasing trend to apply TH in other indications and populations, such as infants with mild HIE or neonates with congenital heart defects (CHD), even though there is little evidence to support or refute this.ObjectiveThe aim of this survey was to analyze practice variations with respect to TH use in neonates with CHD and to assess expert opinions on this topic across tertiary neonatal departments in Germany.Methods/DesignA web-based survey was sent to all tertiary neonatal departments in Germany. The questionnaire contained 32 multiple-choice questions. The survey inquired current practices on TH in newborns with CHD and expert opinions on various clinical scenarios.Main resultsA total 80 (51.3%) neonatal departments partially completed the survey, and 69 (44.2%) respondents filled out the whole questionnaire. All 80 (100.0%) departments perform TH. TH is offered by 76 (95.0%) respondents to encephalopathic newborns with simple CHD. In infants with critical/complex CHD, TH is offered after perinatal asphyxial HIE and in newborns with encephalopathy after severe acidosis associated with cardiac complications by 25 (31.3%), or 17 (22.1%) respondents, respectively, whereas a clear majority of centers reject TH in these infants. Unclear effects of TH on any ongoing prostaglandin therapy (57.6 and 52.3%, respectively), an increased risk for adverse reactions during TH (51.6 and 52.3%, respectively) and lack of evidence (33.3 and 53.8%, respectively) are the most frequently cited reasons for not performing TH in these infants. The majority of experts from neonatal departments providing comprehensive care for neonates with severe CHD support the initiation of TH in encephalopathic neonates.DiscussionThe considerable heterogeneity in the use of TH in neonates with CHD emphasizes the need for further research to optimize treatment strategies for these patients.
Skeletal muscle deficits are associated with worse exercise performance in pediatric pulmonary hypertension
Authors: Avitabile Catherine M. , McBride Michael G. , Harris Matthew A. , Whitehead Kevin K. , Fogel Mark A. , Paridon Stephen M. , Zemel Babette S. 
Published: October 2022

BackgroundSkeletal muscle deficits are associated with worse exercise performance in adults with pulmonary hypertension (PH) but the impact is poorly understood in pediatric PH.ObjectiveTo study muscle deficits, physical inactivity, and performance on cardiopulmonary exercise test (CPET) and exercise cardiac magnetic resonance (eCMR) in pediatric PH.MethodsYouth 8–18 years participated in a prospective, cross-sectional study including densitometry (DXA) for measurement of leg lean mass Z-score (LLMZ), handheld dynamometer with generation of dominant and non-dominant handgrip Z-scores, Physical Activity Questionnaire (PAQ), CPET, and optional eCMR. CPET parameters were expressed relative to published reference values. CMR protocol included ventricular volumes and indexed systemic flow at rest and just after supine ergometer exercise. Relationships between LLMZ, PAQ score, and exercise performance were assessed by Pearson correlation and multiple linear regression.ResultsThere were 25 participants (13.7 ± 2.8 years, 56% female, 64% PH Group 1, 60% functional class I); 12 (48%) performed both CPET and eCMR. Mean LLMZ (–0.96 ± 1.14) was associated with PAQ score (r = 50, p = 0.01) and with peak oxygen consumption (VO2) (r = 0.74, p = &lt; 0.001), VO2 at anaerobic threshold (r = 0.65, p &lt; 0.001), and peak work rate (r = 0.64, p &lt; 0.01). Higher handgrip Z-scores were associated with better CPET and eCMR performance. On regression analysis, LLMZ and PAQ score were positively associated with peak VO2, while handgrip Z-score and PAQ score were positively associated with peak work rate.ConclusionMuscle mass and strength are positively associated with exercise performance in pediatric PH. Future studies should determine the effect of rehabilitation programs on muscle properties and exercise performance.
Gastrointestinal bleeding after endoscopic mucosal resection in a case of Peutz–Jeghers syndrome with hypofibrinogenemia: A case report
Authors: Kakiuchi Toshihiko , Takedomi Hironobu , Akutagawa Takashi , Tsuruoka Nanae , Sakata Yasuhisa , Matsuo Muneaki 
Published: October 2022

BackgroudPeutz–Jegers syndrome (PJS) is an autosomal dominant hereditary disorder characterized by hamartomatous polyposis of the entire gastrointestinal tract. Fibrinogen (Fbg) is synthesized by the liver, and hypofibrinogenemia is often asymptomatic and manifests with bleeding after trauma or invasive surgical procedures. Here, we present a case of a pediatric patient with PJS and hypofibrinogenemia who manifested with gastrointestinal bleeding after endoscopic mucosal resection (EMR) of small intestinal polyps.Case PresentationAn 11-year-old boy with PJS was referred to our hospital. Since his mother was diagnosed with PJS, with black pigments being observed on his lips, mouth, and limbs, he underwent upper and lower gastrointestinal endoscopy at the age of 8 years at a previous hospital. EMR for duodenal polyp was performed, and the pathological findings were consistent with hamartoma. His Fbg level was 117 mg/dl at the time, with no post-bleeding being detected after EMR. The small intestine was not assessed at the prior facility and was left neglected for three years. At our hospital, small intestine fluoroscopy was performed and revealed a polyp in the jejunum, and abdominal computed tomography showed two polyps and intussusception. On double-balloon enteroscopy, the resected polyps were hamartoma with diameters of 20 and 30 mm. The patient’s Fbg level was 107 mg/dl. The day after EMR, he had melena and black stools. He was diagnosed with post-EMR bleeding and started to stop eating, and hemostatic agents were given. His hemoglobin level dropped to 9.2 g/dl the next day. Genetic testing for congenital Fbg deficiency revealed a heterozygous pathogenic variant in fibrinogen gamma chain Exon 10. Therefore, he was diagnosed with concurrent hypofibrinogenemia and PJS.ConclusionTo the best of our knowledge, this is the first reported case with concurrent PJS and hypofibrinogenemia. In patients with PJS, hypofibrinogenemia should be considered as one of the risk factors of postoperative bleeding during polypectomy, and appropriate prophylactic measures should be taken.