bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of inflammatory markers for in-hospital mortality in intensive care patients with acute ischemic stroke: a retrospective observational study based on MIMIC-IV
Authors: Hu Xuyang , Liang Jiaru , Hao Wenjian , Zhou Jiaqi , Gao Yuling , Gong Xiaoyang , Liu Yong 
Published: June 2023

BackgroundAcute ischemic stroke (AIS) is a primary cause of death and disability worldwide. Four markers that can be readily determined from peripheral blood, namely, the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and total bilirubin, were measured in this study. We examined the relationship between the SII and in-hospital mortality after AIS and evaluated which of the above four indicators was most accurate for predicting in-hospital mortality after AIS.MethodsWe selected patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database who were aged &gt;18 years and who were diagnosed with AIS on admission. We collected the patients’ baseline characteristics, including various clinical and laboratory data. To investigate the relationship between the SII and in-hospital mortality in patients with AIS, we employed the generalized additive model (GAM). Differences in in-hospital mortality between the groups were summarized by the Kaplan–Meier survival analysis and the log-rank test. The receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of the four indicators (SII, NLR, PLR, and total bilirubin) for predicting in-hospital mortality in patients with AIS.ResultsThe study included 463 patients, and the in-hospital mortality rate was 12.31%. The GAM analysis showed a positive correlation between the SII and in-hospital mortality in patients with AIS, but the correlation was not linear. Unadjusted Cox regression identified a link between a high SII and an increased probability of in-hospital mortality. We also found that patients with an SII of &gt;1,232 (Q2 group) had a considerably higher chance of in-hospital mortality than those with a low SII (Q1 group). The Kaplan–Meier analysis demonstrated that patients with an elevated SII had a significantly lower chance of surviving their hospital stay than those with a low SII. According to the results of the ROC curve analysis, the in-hospital mortality of patients with AIS predicted by the SII had an area under the ROC curve of 0.65, which revealed that the SII had a better discriminative ability than the NLR, PLR, and total bilirubin.ConclusionThe in-hospital mortality of patients with AIS and the SII were positively correlated, but not linearly. A high SII was associated with a worse prognosis in patients with AIS. The SII had a modest level of discrimination for forecasting in-hospital mortality. The SII was slightly better than the NLR and significantly better than the PLR and total bilirubin for predicting in-hospital mortality in patients with AIS.
Cerebrolysin and repetitive transcranial magnetic stimulation (rTMS) in patients with traumatic brain injury: a three-arm randomized trial
Authors: Verisezan Rosu Olivia , Jemna Nicoleta , Hapca Elian , Benedek Irina , Vadan Iulia , Muresanu Ioana , Chira Diana , Radu Constantin , Cherecheş Răzvan , Strilciuc Stefan , Muresanu Dafin 
Published: June 2023

IntroductionTraumatic brain injury (TBI) is a major public health problem affecting millions worldwide. Despite significant advances in medical care, there are limited effective interventions for improving cognitive and functional outcomes in TBI patients.MethodsThis randomized controlled trial investigated the safety and efficacy of combining repetitive transcranial magnetic stimulation (rTMS) and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. Ninety-three patients with TBI were randomized to receive either Cerebrolysin and rTMS (CRB + rTMS), Cerebrolysin and sham stimulation (CRB + SHM), or placebo and sham stimulation (PLC + SHM). The primary outcome measures were the composite cognitive outcome scores at 3 and 6 months after TBI. Safety and tolerability were also assessed.ResultsThe study results demonstrated that the combined intervention of rTMS and Cerebrolysin was safe and well-tolerated by patients with TBI. Although no statistically significant differences were observed in the primary outcome measures, the descriptive trends in the study support existing literature on the efficacy and safety of rTMS and Cerebrolysin.DiscussionThe findings of this study suggest that rTMS and Cerebrolysin may be effective interventions for improving cognitive and functional outcomes in TBI patients. However, limitations of the study, such as the small sample size and exclusion of specific patient populations, should be considered when interpreting the results. This study provides preliminary evidence for the safety and potential efficacy of combining rTMS and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. The study highlights the importance of multidisciplinary approaches in TBI rehabilitation and the potential for combining neuropsychological measurements and interventions to optimize patient outcomes.ConclusionFurther research is needed to establish these findings’ generalizability and identify the optimal dosages and treatment protocols for rTMS and Cerebrolysin.
Combined optogenetic and electrical stimulation of the sciatic nerve for selective control of sensory fibers
Authors: Matarazzo Jerico V. , Ajay Elise A. , Payne Sophie C. , Trang Ella P. , Thompson Alex C. , Marroquin Jason B. , Wise Andrew K. , Fallon James B. , Richardson Rachael T. 
Published: June 2023

IntroductionElectrical stimulation offers a drug-free alternative for the treatment of many neurological conditions, such as chronic pain. However, it is not easy to selectively activate afferent or efferent fibers of mixed nerves, nor their functional subtypes. Optogenetics overcomes these issues by controlling activity selectively in genetically modified fibers, however the reliability of responses to light are poor compared to electrical stimulation and the high intensities of light required present considerable translational challenges. In this study we employed a combined protocol of optical and electrical stimulation to the sciatic nerve in an optogenetic mouse model to allow for better selectivity, efficiency, and safety to overcome fundamental limitations of electrical-only and optical-only stimulation.MethodsThe sciatic nerve was surgically exposed in anesthetized mice (n = 12) expressing the ChR2-H134R opsin via the parvalbumin promoter. A custom-made peripheral nerve cuff electrode and a 452 nm laser-coupled optical fiber were used to elicit neural activity utilizing optical-only, electrical-only, or combined stimulation. Activation thresholds for the individual and combined responses were measured.ResultsOptically evoked responses had a conduction velocity of 34.3 m/s, consistent with ChR2-H134R expression in proprioceptive and low-threshold mechanoreceptor (Aα/Aβ) fibers which was also confirmed via immunohistochemical methods. Combined stimulation, utilizing a 1 ms near-threshold light pulse followed by an electrical pulse 0.5 ms later, approximately halved the electrical threshold for activation (p = 0.006, n = 5) and resulted in a 5.5 dB increase in the Aα/Aβ hybrid response amplitude compared to the electrical-only response at equivalent electrical levels (p = 0.003, n = 6). As a result, there was a 3.25 dB increase in the therapeutic stimulation window between the Aα/Aβ fiber and myogenic thresholds (p = 0.008, n = 4).DiscussionThe results demonstrate that light can be used to prime the optogenetically modified neural population to reside near threshold, thereby selectively reducing the electrical threshold for neural activation in these fibers. This reduces the amount of light needed for activation for increased safety and reduces potential off-target effects by only stimulating the fibers of interest. Since Aα/Aβ fibers are potential targets for neuromodulation in chronic pain conditions, these findings could be used to develop effective strategies to selectively manipulate pain transmission pathways in the periphery.
Outcomes in children with rheumatic diseases following COVID-19 vaccination and infection: data from a large two-center cohort study in Thailand
Authors: Lerkvaleekul Butsabong , Charuvanij Sirirat , Sukharomana Maynart , Pirojsakul Kwanchai , Kamolwatwong Malisa , Vilaiyuk Soamarat 
Published: June 2023

IntroductionVaccination against coronavirus disease 2019 (COVID-19) is effective in protecting patients from severe COVID-19 infection. Disease flare-up following immunization in children with rheumatic disorders may result in patient reluctance to receive the vaccine. Underlying rheumatic diseases or the use of immunosuppressive drugs may influence the outcomes of COVID-19 vaccination and infection. We aimed to describe outcomes in children with rheumatic diseases following COVID-19 immunization and infection.MethodsThis retrospective study was performed at two large academic centers in Thailand. During the COVID-19 pandemic, all patients were routinely queried about COVID-19-related conditions. We included patients with rheumatic diseases aged &lt;18 years who received at least one dose of a COVID-19 vaccine or had a history of COVID-19 infection with more than 6 months of recorded follow-up after the last vaccine dose or COVID-19 illness. Demographic information and data on clinical symptoms, disease activity, treatment, outcomes, and COVID-19 vaccination and infection were collected.ResultsA total of 479 patients were included. Most (229; 47.81%) patients had juvenile idiopathic arthritis, followed by connective tissue diseases (189; 39.46%), vasculitis syndromes (42; 8.76%), and other rheumatic diseases (19; 3.97%). Approximately 90% of patients received at least one dose of COVID-19 vaccination, and half of the patients had COVID-19 infection. Among patients, 10.72% and 3.27% developed a flare after COVID-19 vaccination and COVID-19 illness, respectively. Flare severity after COVID immunization and infection was mainly mild to moderate. The predictor of flare after COVID-19 vaccination was the use of prednisolone ≥10 mg/day before vaccination (hazard ratio: 2.04, 95% confidence interval: 1.05–3.97, p = 0.037). Inactive disease before receiving the COVID-19 vaccination was a predictor of inactive status after a flare (hazard ratio: 2.95, 95% confidence interval: 1.04–8.40; p = 0.043). Overall, 3.36% and 1.61% of patients experienced a new onset of rheumatic disease after receiving the COVID-19 vaccine and after COVID-19 infection, respectively.ConclusionThe COVID-19 vaccine is recommended for children with rheumatic disease, particularly those who are in stable condition. After COVID-19 vaccination, patients—especially those with active disease before vaccination or those receiving concurrent prednisolone doses of ≥10 mg/day—should be closely monitored.
Metformin alleviates lung-endothelial hyperpermeability by regulating cofilin-1/PP2AC pathway
Authors: Siddiqui M. Rizwan , Reddy Narsa M. , Faridi Hafeez M. , Shahid Mohd , Shanley Thomas P. 
Published: June 2023

Background: Microvascular endothelial hyperpermeability is an earliest pathological hallmark in Acute Lung Injury (ALI), which progressively leads to Acute Respiratory Distress Syndrome (ARDS). Recently, vascular protective and anti-inflammatory effect of metformin, irrespective of glycemic control, has garnered significant interest. However, the underlying molecular mechanism(s) of metformin’s barrier protective benefits in lung-endothelial cells (ECs) has not been clearly elucidated. Many vascular permeability-increasing agents weakened adherens junctions (AJ) integrity by inducing the reorganization of the actin cytoskeleton and stress fibers formation. Here, we hypothesized that metformin abrogated endothelial hyperpermeability and strengthen AJ integrity via inhibiting stress fibers formation through cofilin-1-PP2AC pathway.Methods: We pretreated human lung microvascular ECs (human-lung-ECs) with metformin and then challenged with thrombin. To investigate the vascular protective effects of metformin, we studied changes in ECs barrier function using electric cell-substrate impedance sensing, levels of actin stress fibers formation and inflammatory cytokines IL-1β and IL-6 expression. To explore the downstream mechanism, we studied the Ser3-phosphorylation-cofilin-1 levels in scramble and PP2AC-siRNA depleted ECs in response to thrombin with and without metformin pretreatment.Results: In-vitro analyses showed that metformin pretreatment attenuated thrombin-induced hyperpermeability, stress fibers formation, and the levels of inflammatory cytokines IL-6 and IL-β in human-lung-ECs. We found that metformin mitigated Ser3-phosphorylation mediated inhibition of cofilin-1 in response to thrombin. Furthermore, genetic deletion of PP2AC subunit significantly inhibited metformin efficacy to mitigate thrombin-induced Ser3-phosphorylation cofilin-1, AJ disruption and stress fibers formation. We further demonstrated that metformin increases PP2AC activity by upregulating PP2AC-Leu309 methylation in human-lung-ECs. We also found that the ectopic expression of PP2AC dampened thrombin-induced Ser3-phosphorylation-mediated inhibition of cofilin-1, stress fibers formation and endothelial hyperpermeability.Conclusion: Together, these data reveal the unprecedented endothelial cofilin-1/PP2AC signaling axis downstream of metformin in protecting against lung vascular endothelial injury and inflammation. Therefore, pharmacologically enhancing endothelial PP2AC activity may lead to the development of novel therapeutic approaches for prevention of deleterious effects of ALI on vascular ECs.
Effect of nitrogen application on enhancing high-temperature stress tolerance of tomato plants during the flowering and fruiting stage
Authors: Luo Jing , Yang Zaiqiang , Zhang Fengyin , Li Chunying 
Published: June 2023

This study was conducted to investigate the effects of nitrogen application on growth, photosynthetic performance, nitrogen metabolism activities, and fruit quality of tomato plants under high-temperature (HT) stress. Three levels of daily minimum/daily maximum temperature were adopted during the flowering and fruiting stage, namely control (CK; 18°C/28°C), sub-high temperature (SHT; 25°C/35°C), and high-temperature (HT; 30°C/40°C) stress. The levels of nitrogen (urea, 46% N) were set as 0 (N1), 125 (N2), 187.5 (N3), 250 (N4), and 312.5 (N5) kg hm2, respectively, and the duration lasted for 5 days (short-term). HT stress inhibited the growth, yield, and fruit quality of tomato plants. Interestingly, short-term SHT stress improved growth and yield via higher photosynthetic efficiency and nitrogen metabolism whereas fruit quality was reduced. Appropriate nitrogen application can enhance the high-temperature stress tolerance of tomato plants. The maximum net photosynthetic rate (PNmax), stomatal conductance (gs), stomatal limit value (LS), water-use efficiency (WUE), nitrate reductase (NR), glutamine synthetase (GS), soluble protein, and free amino acids were the highest in N3, N3, and N2, respectively, for CK, SHT, and HT stress, whereas carbon dioxide concentration (Ci), was the lowest. In addition, maximum SPAD value, plant morphology, yield, Vitamin C, soluble sugar, lycopene, and soluble solids occurred at N3-N4, N3-N4, and N2-N3, respectively, for CK, SHT, and HT stress. Based on the principal component analysis and comprehensive evaluation, we found that the optimum nitrogen application for tomato growth, yield, and fruit quality was 230.23 kg hm2 (N3-N4), 230.02 kg hm2 (N3-N4), and 115.32 kg hm2 (N2), respectively, at CK, SHT, and HT stress. Results revealed that the high yield and good fruit quality of tomato plants at high temperatures can be maintained by higher photosynthesis, nitrogen efficiency, and nutrients with moderate nitrogen.
Trauma-Informed Care on mental health wards: the impact of Power Threat Meaning Framework Team Formulation and Psychological Stabilisation on self-harm and restrictive interventions
Authors: Nikopaschos Faye , Burrell Gail , Clark Jordan , Salgueiro Ana 
Published: June 2023

AimThe aim of this evaluation was to assess the impact of introducing a model of Trauma-Informed Care (TIC), comprising weekly Power Threat Meaning Framework (PTMF) Team Formulation and weekly Psychological Stabilisation staff training, to a National Health Service (NHS) adult acute inpatient mental health unit over a four-year period.MethodA retrospective service evaluation design was employed to assess for differences in the number of incidents of self-harm, seclusion and restraint in the four-year period following the introduction of TIC, when compared to the year prior.ResultsSignificant reductions were demonstrated in the monthly number of incidents of self-harm (p &lt; 0.01; r = 0.42), seclusion (p &lt; 0.05; r = 0.30) and restraint (p &lt; 0.05; d = 0.55) following the introduction of TIC.ConclusionFindings suggest that PTMF Team Formulation and Psychological Stabilisation training can contribute to significant reductions in self-harm and restrictive interventions (seclusion and restraint) on adult mental health wards. Qualitative interviews with staff and service users from the unit will support a better understanding of the mechanisms of this change. Further research, employing a randomised control trial design, could increase the validity and generalisability of findings. However, the ethical implications of withholding potentially beneficial practices from a control group would need to be considered.
Psychological and functional outcomes following a randomized controlled trial of surf and hike therapy for U.S. service members
Authors: Walter Kristen H. , Otis Nicholas P. , Miggantz Erin L. , Ray Travis N. , Glassman Lisa H. , Beltran Jessica L. , Kobayashi Elliott Kim T. , Michalewicz-Kragh Betty 
Published: June 2023

IntroductionExercise-based interventions have established benefits for the treatment of depression and other psychological outcomes; however, limited data exist evaluating psychological, social, and functional outcomes for exercise outdoors.MethodsThe current study sought to expand knowledge about the breadth of effects following outdoor exercise interventions by using data from a randomized control trial comparing Surf and Hike Therapy among 96 U.S. active duty service members with major depressive disorder (MDD). Assessments examining psychological symptoms and functioning were completed before and after the 6-week programs, and 3 months following program completion. Participants also completed assessments before and after each exercise session. Multilevel modeling was used to determine whether psychological and functional outcomes (anxiety, positive and negative affect, resilience, pain, and physical and social functioning) improved for service members receiving Surf or Hike Therapy, and whether improvements differed by intervention.ResultsStudy findings showed improved anxiety (p &lt; 0.001), negative affect (p &lt; 0.001), psychological resilience (p = 0.013), and social functioning (p &lt; 0.001) following program participation, with no differences by intervention. Positive affect, pain, and physical functioning did not significantly improve after the program. Within sessions, positive affect (p &lt; 0.001) and pain (p = 0.036) changed, and to a greater extent for those in the Surf Therapy condition.ConclusionStudy results suggest that both Surf Therapy and Hike Therapy can improve psychological symptoms and social functioning impairments that commonly co-occur among service members with MDD, but Surf Therapy may provide enhanced immediate effects on positive affect and pain.Clinical trial registrationClinicalTrials.gov, NCT03302611.
The association between ambient temperature and antimicrobial resistance of Klebsiella pneumoniae in China: a difference-in-differences analysis
Authors: Zeng Yingchao , Li Weibin , Zhao Manzhi , Li Jia , Liu Xu , Shi Lin , Yang Xinyi , Xia Haohai , Yang Shifang , Yang Lianping 
Published: June 2023

IntroductionAntimicrobial resistance (AMR) of Klebsiella pneumoniae (K. pneumoniae) poses a significant global public health threat and is responsible for a high prevalence of infections and mortality. However, knowledge about how ambient temperature influences the AMR of K. pneumoniae is limited in the context of global warming.MethodsAMR data of 31 Chinese provinces was collected from the China Antimicrobial Resistance Surveillance System (CARSS) between 2014 and 2020. Socioeconomic and meteorological data were collected from the China Statistical Yearbook during the same period. A modified difference-in-differences (DID) approach was applied to estimate the association between ambient temperature and third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) and carbapenem-resistant K. pneumoniae (CRKP). Furthermore, moderating effects of socioeconomic factors were also evaluated.ResultsEvery 1°C increase in annual average temperature was associated with a 4.7% (relative risk (RR):1.047, 95% confidence intervals (CI): 1.031–1.082) increase in the detection rate of 3GCRKP, and a 10.7% (RR:1.107, 95% CI: 1.011–1.211) increase in the detection rate of CRKP. The relationships between ambient temperature and 3GCRKP and CRKP were found to be moderated by socioeconomic status (GDP per capita, income per capita, and consumption per capita; the interaction p-values &lt;0.05), where higher economic status was found to strengthen the effects of temperature on the detection rate of 3GCRKP and weaken the effects on the detection rate of CRKP.DiscussionAmbient temperature was found to be positively associated with AMR of K. pneumoniae, and this association was moderated by socioeconomic status. Policymakers should consider the impact of global warming and high temperatures on the spread of 3GCRKP and CRKP when developing strategies for the containment of AMR.