bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consolidatory ablative stereotactic body radiation therapy after induction chemotherapy for unresectable pancreatic cancer: A single center experience
Authors: Lee Hye In , Kang Hyun-Cheol , Chie Eui Kyu 
Published: November 2022

Background and purposeConsolidatory radiotherapy in form of stereotactic body radiation therapy (SBRT) with an ablative dose following induction chemotherapy is emerging as a promising treatment scheme for unresectable pancreatic cancer. Outcomes of given treatment at a single center for contiguous patients with unresectable pancreatic cancer were evaluated to build the optimal treatment strategy.Materials and methodsIn this retrospective study, a total of 50 patients with unresectable pancreatic cancer who underwent induction chemotherapy and ablative dose SBRT were included. SBRT dose was 40–50 Gy in five fractions. Two strategies were adopted to adhere to the organs at risk (OAR) dose constraints: simultaneous integrated protection (SIP) technique and magnetic resonance (MR)-guided adaptive technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated from the start date of SBRT.ResultsThe median follow-up period for survivors was 21.1 months (range, 6.2–61.0 months). Eleven (22.0%) patients underwent resection after SBRT, which were all R0 resection. In patients with non-metastatic disease, the median OS was 26.5 months (range, 4.1–61.0 months), and the 1- and 3-year LPFS were 90.0% (95% confidence interval [CI], 72.0–96.7%) and 57.4% (95% CI, 31.7–76.4%), respectively. Patients with oligometastatic disease had inferior survival outcomes, but there was no survival difference among responders to induction chemotherapy. In the multivariable analysis, tumor size ≤4 cm, non-metastatic status, and good response to induction chemotherapy were associated with improved LPFS. In dosimetric analysis, GTV Dmin ≥50.5 Gy was the strongest prognosticator against local progression. Grade ≥3 adverse events occurred in two (4.0%) patients with non-adaptive RT, but none in patients with MR-guided adaptive RT.ConclusionAblative dose SBRT following induction chemotherapy is an effective strategy for selected patients with unresectable pancreatic cancer. The SIP technique and MR-guided adaptive RT were attributed to minimizing the risk of adverse events. Further studies are needed to identify the best candidates for consolidatory SBRT in unresectable pancreatic cancer.
Hypofractionated concurrent chemoradiotherapy related lymphopenia and its association with survival in locally advanced non-small cell lung cancer patients
Authors: Liu FangJie , Wu YingJia , Shao JianHui , Qiu Bo , Guo SuPing , Luo QiaoTing , Guo JinYu , Wang DaQuan , Chu Chu , Zhou Rui , Chen NaiBin , Ai XinLei , Liu Hui 
Published: November 2022

BackgroundTo evaluate longitudinal changes of concurrent chemoradiotherapy (CCRT) related lymphopenia and its association with survival in locally advanced non-small cell lung cancer (LA-NSCLC) patients.MethodsTotal lymphocyte count (TLC) at baseline, weekly intervals during CCRT and monthly intervals up to 12 months after CCRT were documented. The Common Terminology Criteria for Adverse Events version 5.0 was used to grade the severity of lymphopenia. Cox regression analysis was performed to evaluate the association between overall survival (OS) and CCRT related lymphopenia at different timepoints. Logistic regression model was used to determine the clinical factors associated with TLC level.Results381 LA-NSCLC patients treated with definitive CCRT without consolidation therapy (NCT02573506/NCT02577341) between 2011 to 2020 were analyzed. With a median follow-up of 45.8 months, the median OS was 41.0 months for all patients. Univariable analysis demonstrated that the 3 weeks during CCRT Grade (G) 4 lymphopenia (P=0.018), 2 months after CCRT G1-4 lymphopenia (P=0.004), 6 months after CCRT (6m-post-CCRT) G1-4 lymphopenia (P=0.001), and TLC nadir (P=0.020) were significantly associated with poorer OS. Multivariable analysis suggested that 6m-post-CCRT G1-4 lymphopenia (HR 2.614; P=0.041) were one of the independent predictors of OS. Further analysis inferred that radiation dose (OR: 1.328; P=0.005), GTV volume (OR: 1.004; P=0.036), and baseline TLC (OR: 0.288; P=0.001) were associated with 6m-post-CCRT lymphopenia.ConclusionThe persistent lymphopenia at 6 months after CCRT was an independent prognostic factor of OS in LA-NSCLC patients. Higher radiation dose, larger gross tumor volume and lower baseline TLC were significantly related to 6m-post-CCRT lymphopenia.
“Pain, Stress, and Emotions”: Uncontrolled trial of a single-session, telehealth, emotional awareness and expression therapy class for patients with chronic pain
Authors: Ziadni Maisa S. , Sturgeon John A. , Lumley Mark A. 
Published: November 2022

ObjectivesTrauma- and emotion-focused chronic pain interventions, particularly Emotional Awareness and Expression Therapy (EAET), show much promise for reducing pain and improving functioning. We developed a novel, single-session, telehealth-delivered EAET class (“Pain, Stress, and Emotions”; PSE) and tested it on adults with chronic pain of mixed etiology.MethodsAfter an initial developmental phase, we conducted an uncontrolled trial, providing PSE to 74 individuals with chronic pain (63.5% female; 64.9% White; 60.8% with pain duration &gt;5 years) in four class administrations. Participants completed self-report measures (primary outcomes: pain intensity and pain interference) at baseline and multiple follow-ups to 12 weeks. Linear mixed-models examined changes over time, and effect sizes were calculated on change from baseline to 4-week (primary endpoint) and 12-week follow-ups. The trial was registered with clinicaltrials.gov (NCT05014126)ResultsParticipants reported high satisfaction with the PSE class. Pain intensity showed a significant, medium reduction across time (p &lt; .001; d = 0.60 at 4 weeks); one-quarter of participants had clinically meaningful pain reduction (≥30%). Pain interference had a large reduction (p &lt; .001; d = 0.74). There were significant but smaller improvements in most secondary outcomes (ds = 0.15 to 0.55; ps &lt; .01). Effects were generally maintained or increased at 12-week follow-up. Higher education and baseline ambivalence over emotional expression predicted greater pain reductions.ConclusionsPeople taking this EAET class had reduced pain severity and interference and improvements in other pain-related outcomes. The single-session, telehealth class holds promise as an easily delivered, efficient, and potentially impactful intervention for some patients with chronic pain, although controlled trials are needed.
Seasonal variation of ambulatory blood pressure in Chinese hypertensive adolescents
Authors: Zhou Yi , Zhao Lin , Meng Xu , Cai Qiu-Jing , Zhao Xiao-Lei , Zhou Xian-Liang , Hu Ai-Hua 
Published: November 2022

BackgroundBlood pressure (BP) exhibits seasonal variation with lower levels at higher temperatures and vice versa. This phenomenon affects both sexes and all age groups. So far, only a few research studies have investigated this condition in adolescents and none of them were based on hypertensive population or ever applied ambulatory blood pressure monitor (ABPM). Therefore, we carried out the first study that used ABPM to record seasonal variation of blood pressure in hypertensive adolescents.MethodsFrom March 2018 to February 2019, 649 ABPMs from hypertensive adolescents between 13 and 17 years who were referred to wear an ABPM device in Beijing and Baoding were extracted. Seasonal change in ambulatory BP value, dipping status, and prevalence of different BP phenotypes were analyzed and compared.ResultsMean age of participants was 14.9 ± 1.5 years and 65.8% of them were boys. Of the participants, 75.3% met the criteria of overweight or obesity. From summer to winter, average 24-hour, day-time, and night-time BP showed significant rise, which was 9.8/2.8, 9.8/3.0, and 10.9/3.4 mmHg, respectively. This seasonal effect on BP was not dependent on the obesity degree. In addition, higher prevalence of nondippers and risers existed in winter while white coat hypertension was more frequent in warmer seasons.ConclusionHypertensive adolescents showed evident seasonal change in their ABPM results, which was featured by elevated BP level and more frequent abnormal dipping patterns in winter. On the contrary, higher prevalence of white coat hypertension was found in warmer seasons. Physicians should take seasonal variation into consideration when managing adolescent hypertension.
Tactile stimulation in very preterm infants and their needs of non-invasive respiratory support
Authors: Kaufmann Maxi , Seipolt Barbara , Rüdiger Mario , Mense Lars 
Published: November 2022

AimDespite the lack of evidence, current resuscitation guidelines recommend tactile stimulation in apneic infants within the first minutes of life. The aim was to investigate whether timing, duration or intensity of tactile stimulation influences the extent of non-invasive respiratory support in extremely preterm infants during neonatal resuscitation.MethodsIn an observational study, we analyzed 47 video recordings and physiological parameters during postnatal transition in preterm infants below 320/7 weeks of gestational age. Infants were divided into three groups according to the intensity of respiratory support.ResultsAll infants were stimulated at least once during neonatal resuscitation regardless of their respiratory support. Only 51% got stimulated within the first minute. Rubbing the feet was the preferred stimulation method and was followed by rubbing or touching the chest. Almost all very preterm infants were exposed to stimulation and manipulation most of the time within their first 15 min of life. Tactile stimulation lasted significantly longer but stimulation at multiple body areas started later in infants receiving prolonged non-invasive respiratory support.ConclusionThis observational study demonstrated that stimulation of very preterm infants is a commonly used and easy applicable method to stimulate spontaneous breathing during neonatal resuscitation. The concomitant physical stimulation of different body parts and therefore larger surface areas might be beneficial.
Identification of a novel oxidative stress-related prognostic model in lung adenocarcinoma
Authors: Zhu Yifan , Tang Quanying , Cao Weibo , Zhou Ning , Jin Xin , Song Zuoqing , Zu Lingling , Xu Song 
Published: November 2022

Background: Oxidative stress (OxS) participates in a variety of biological processes, and is considered to be related to the occurrence and progression of many tumors; however, the potential diagnostic value of OxS in lung cancer remains unclear.Methods: The clinicopathological and transcriptome data for lung adenocarcinoma (LUAD) were collected from TCGA and GEO database. LASSO regression was used to construct a prognostic risk model. The prognostic significance of the OxS-related genes was explored using a Kaplan-Meier plotter database. The prediction performance of the risk model was shown in both the TCGA and GSE68465 cohorts. The qRT-PCR was performed to explore the expression of genes. CCK-8, Edu and transwell assays were conducted to analyze the role of CAT on cell proliferation migration and invasion in lung cancer. Immune infiltration was evaluated by CIBERSORT and mutational landscape was displayed in the TCGA database. Moreover, the relationship between risk score with drug sensitivity was investigated by pRRophetic.Results: We identified a prognosis related risk model based on a four OxS gene signature in LUAD, including CYP2D6, FM O 3, CAT, and GAPDH. The survival analysis and ROC curve indicated good predictive power of the model in both the TCGA and GEO cohorts. LUAD patients in the high-risk group had a shorter OS compared to the low-risk group. QRT-PCR result showed that the expression of four genes was consistent with previous analysis in cell lines. Moreover, overexpression of CAT could decrease the proliferation, invasion and migration of lung cancer cells. The Cox regression analysis showed that the risk score could be used as an independent prognostic factor for OS. LUAD patients in the high-risk score group exhibited a higher tumor mutation burden and risk score were closely related to tumor associated immune cell infiltration, as well as the expression of immune checkpoint molecules. Both the high- and low-risk groups have significant differences in sensitivity to some common chemotherapy drugs, such as Paclitaxel, Docetaxel, and Vinblastine, which may contribute to clinical treatment decisions.Conclusion: We established a robust OxS-related prognostic model, which may contribute to individualized immunotherapeutic strategies in LUAD.
CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response
Authors: Li Nan , Wu Jing-Jing , Qi Meng , Wang Zi-Ying , Zhang Sheng-Nan , Li Xiu-Qin , Chen Ting-Ting , Wang Mei-Fang , Zhang Ling-Ling , Wei Wei , Sun Wu-Yi 
Published: November 2022

Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6′-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model in vivo. CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4+, activated CD8+ T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.
Low-dose naloxone for prophylaxis of sufentanil-induced choking and postoperative nausea and vomiting
Authors: Qian Yiling , Huang Zhifei , Wang Guilong , Han Jinghong , Zhou Difei , Ding Hailei , Zhang Xin 
Published: November 2022

Sufentanil, a potent opioid, serves as the first option for perioperative analgesia owing to its analgesic effect, long duration and stable hemodynamics, whereas its side effects frequently blunt its application. The intravenous (IV) injection of sufentanil during anesthesia induction has high incidence of choking or bucking reaction, which is defined as sufentanil-induced cough (SIC). Moreover, postoperative nausea and vomiting (PONV) is a common and stressful complication, which is also related to the usage of opioid. High incidence of PONV is reported in the patients with SIC. Hence, we sought to determine whether naloxone, an opioid antagonist, at low dose would decrease the incidences of SIC and PONV. 216 female patients undergoing gynecological laparoscopic operation (&lt;2 h) under general anesthesia were recruited in this study, and randomly assigned into two groups: Group N (patients receiving naloxone and Group C (patients receiving vehicle). Sufentanil (0.5 μg/kg within 5 s) was given in anesthesia induction, and low-dose naloxone (1.25 μg/kg) or identical vehicle was initially injected 5 min prior to induction, with the incidence and severity of SIC estimated. Subsequently, naloxone or vehicle was continuously infused at the rate of 0.5 μg/kg/h in the initiation of operation until the end of the operation, and the transverse abdominal fascia block (TAP) was performed for postoperative analgesia. The PONV profiles such as incidence and the severity, grading, and the frequencies of antiemetic usage within 24 h were evaluated, with VAS scores and remedial measures for analgesia during the first 24 h postoperatively were recorded. Our results revealed that one bolus of low-dose naloxone prior to the induction significantly mitigated the incidence of SIC, and intraoperative continuous infusion of low-dose naloxone reduced the incidence and the severity of PONV, so that the postoperative VAS scores and further remedial analgesia were not altered. These results not only provide clinical solutions for prophylaxis of SIC and PONV, but also suggests that opioids may act as a key role in both SIC and PONV, whereas opioid antagonist may hit two tasks with one stone. Moreover, further investigations are required to address the underlying mechanism of SIC and PONV.Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2200064865].
Buprenorphine exposure levels to optimize treatment outcomes in opioid use disorder
Authors: Laffont Celine M. , Ngaimisi Eliford , Gopalakrishnan Mathangi , Ivaturi Vijay , Young Malcolm , Greenwald Mark K. , Heidbreder Christian 
Published: November 2022

The severity of the ongoing opioid crisis, recently exacerbated by the COVID-19 pandemic, emphasizes the importance for individuals suffering from opioid use disorder (OUD) to have access to and receive efficacious, evidence-based treatments. Optimal treatment of OUD should aim at blocking the effects of illicit opioids while controlling opioid craving and withdrawal to facilitate abstinence from opioid use and promote recovery. The present work analyses the relationship between buprenorphine plasma exposure and clinical efficacy in participants with moderate to severe OUD using data from two clinical studies (39 and 504 participants). Leveraging data from placebo-controlled measures assessing opioid blockade, craving, withdrawal and abstinence, we found that buprenorphine plasma concentrations sustained at 2–3 ng/ml (corresponding to ≥70% brain mu-opioid receptor occupancy) optimized treatment outcomes in the majority of participants, while some individuals (e.g., injecting opioid users) needed higher concentrations. Our work also included non-linear mixed effects modeling and survival analysis, which identified a number of demographic, genetic and social factors modulating treatment response and retention. Altogether, these findings provide key information on buprenorphine plasma levels that optimize clinical outcomes and increase the likelihood of individual treatment success. NLM identifiers: NCT02044094, NCT02357901.
Systematic review of efficacy, safety and pharmacokinetics of intravenous and intraventricular vancomycin for central nervous system infections
Authors: Liu Shu-Ping , Xiao Jing , Liu Ya-Li , Wu Yue-E , Qi Hui , Wang Zhuang-Zhuang , Shen A-Dong , Liu Gang , Zhao Wei 
Published: November 2022

Objective: The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not been confirmed by human studies. This study systematically reviewed the literatures on vancomycin in patients with meningitis, ventriculitis, and CNS device-associated infections, to assess efficacy, safety, and pharmacokinetics to better serve as a practical reference.Methods: Medline, Embase, and Cochrane Library were searched using terms vancomycin, Glycopeptides, meningitis, and central nervous system infections. Data were extracted including characteristics of participants, causative organism(s), administration, dosage, etc., The clinical response, microbiological response, adverse events and pharmacokinetic parameters were analyzed.Results: Nineteen articles were included. Indications for vancomycin included meningitis, ventriculitis, and intracranial device infections. No serious adverse effects of intravenous (IV) and intraventricular (IVT) vancomycin have been reported. Dosages of IV and IVT vancomycin ranged from 1000–3000 mg/day and 2–20 mg/day. Duration of IV and IVT vancomycin therapy most commonly ranged from 3–27 days and 2–21 days. Therapeutic drug monitoring was conducted in 14 studies. Vancomycin levels in CSF in patients using IV and IVT vancomycin were varied widely from 0.06 to 22.3 mg/L and 2.5–292.9 mg/L. No clear relationships were found between vancomycin CSF levels and efficacy or toxicity.Conclusion: Using vancomycin to treat CNS infections appears effective and safe based on current evidence. However, the optimal regimens are still unclear. Higher quality clinical trials are required to explore the vancomycin disposition within CNS.
Identification of potential extracellular signal-regulated protein kinase 2 inhibitors based on multiple virtual screening strategies
Authors: Yang Ruoqi , Zhao Guiping , Zhang Lili , Xia Yu , Yu Huijuan , Yan Bin , Cheng Bin 
Published: November 2022

The integration of multiple virtual screening strategies facilitates the balance of computational efficiency and prediction accuracy. In this study, we constructed an efficient and reliable “multi-stage virtual screening-in vitro biological validation” system to identify potential inhibitors targeting extracellular signal-regulated protein kinase 2 (ERK2). Firstly, we rapidly obtained 10 candidate ERK2 inhibitors with desirable pharmacokinetic characteristics from thousands of named natural products in ZINC database based on machine learning classification models and ADME/T prediction. The structure-based molecular docking approach was then used to obtain four further hits with lower binding free energy compared to the positive control molecule Magnolipin. Subsequently, the two compounds were purchased for in vitro biological validation considering commercial availability and economic cost, and the results showed that Dodoviscin A exhibited acceptable inhibitory activity on ERK2 (IC50 = 10.79 μm). Finally, the mechanism of action and binding stability of this natural product inhibitor were investigated by binding mode analysis and molecular dynamics simulation.