bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of COPD systemic environment on the myogenic function of muscle precursor cells in vitro
Authors: Casadevall Carme , Sancho-Muñoz Antonio , Vicente Ignacio , Pascual-Guardia Sergi , Admetlló Mireia , Gea Joaquim 
Published: October 2022

AbstractBackground:Loss of muscle mass and function are well-recognized systemic manifestations of chronic obstructive pulmonary disease (COPD). Acute exacerbations, in turn, significantly contribute to upgrade these systemic comorbidities. Involvement of myogenic precursors in muscle mass maintenance and recovery is poorly understood. The aim of the present study was to investigate the effects of the vascular systemic environment from stable and exacerbated COPD patients on the myogenic behavior of human muscle precursor cells (MPC)in vitro.Methods:Serum from healthy controls and from stable and exacerbated COPD patients (before and after Methylprednisolone treatment) was used to stimulate human MPC cultures. Proliferation analysis was assessed through BrdU incorporation assays. MPC differentiation was examined through real-time RT-PCR, western blot and immunofluorescence analysis.Results:Stimulation of MPCs with serum obtained from stable COPD patients did not affect myogenic precursor cell function. The vascular systemic environment during an acute exacerbation exerted a mitotic effect on MPCs without altering myogenic differentiation outcome. After Methylprednisolone treatment of acute exacerbated COPD patients, however, the mitotic effect was further amplified, but it was followed by a deficient differentiation capacity. Moreover, these effects were prevented when cells were co-treated with the glucocorticoid receptor antagonist Mifepristone.Conclusion:Our findings suggest that MPC capacity is inherently preserved in COPD patients, but is compromised after systemic administration of MP. This finding strengthens the concept that glucocorticoid treatment over the long term can negatively impact myogenic stem cell fate decisions and interfere with muscle mass recovery.
Prognostic value of the modified systemic inflammation score in non-small-cell lung cancer with brain metastasis
Authors: Wang Feng , Chen Limin , Wang Zhao , Xu Qiuyan , Huang He , Wang Hairong , Li Xi , Yu Mingjie , Chen Jiangen , Lin Fuhua , Chen Zhenghe , Zhang Xiangheng , Yang Qunying , Mou Yonggao , Guo Chengcheng 
Published: October 2022

Abstract
Background
Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM.

Methods
A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan–Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort.

Results
The optimal cut-off value of the neutrophil–lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR < 4.71 and albumin ≥ 40 mg/l independently predicted improved survival. We combined the two inflammatory indexes (NLR and albumin level) to establish the modified systemic inflammation score (mSIS) which divides patients into low risk, medium risk or high-risk groups. The 1-year OS rates of three groups were 59.7%, 40.5% and 29.4%, respectively in the training cohort. The same result was verified in the validation cohort with the 1-year OS rates 69.7%, 47.0% and 7.7%, respectively. The mSIS exhibited better discrimination power than the American Joint Committee on Cancer’s (AJCC) 7th T + N staging system in the training cohort (Harrell’s concordance index (C-index): 0.744 vs 0.502, P < 0.05), and the discrimination was also superior to that of AJCC’s 7th T + N staging system in the validation cohort (C-index: 0.724 vs 0.527, P < 0.05). The 1-year and 2-year OS rates of the AUC also exhibited superior survival predictive ability to that of the AJCC’s 7th T + N staging system in NSCLC patients with BM.

Conclusion
The pretreatment mSIS may be an independent prognostic factor for OS in NSCLC patients with BM and warrants further research.
Thrombus-targeted nano-agents for NIR-II diagnostic fluorescence imaging-guided flap thromboembolism multi-model therapy
Authors: Cao Zichen , Zhang Xinyu , Wei Zheng , Song Chuanhui , Zou Huihui , Ran Jianchuan , Zhang Hongbo , Xie Diya , Han Shengwei , Wang Yufeng , Cai Yu , Han Wei 
Published: October 2022

AbstractIn oral and maxillofacial surgery, flap repair is essential to the quality of postoperative life. Still, thrombosis is fatal for the survival of the flaps. Besides, some postoperative thrombotic diseases, such as pulmonary embolism, also intimidate patients’ life. The traditional diagnostic methods are still limited by a large amount of hardware and suffer from inconvenience, delay, and subjectivity. Moreover, the treatments mainly rely upon thrombolytics, such as urokinase (UK) plasminogen activator, which may cause bleeding risk, especially intracerebral hemorrhage. Herein, a kind of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing a first near-infrared window (NIR-I) phototheranostic agent Y8 and urokinase plasminogen activator (UK) as the core, and modified with the fibrin-targeting peptide Gly–Pro–Arg–Pro–Pro (GPRPP) were developed for the flap and postoperative thromboembolism treatment (named GPRPP-Y8U@P). The conjugated molecule Y8 endows GPRPP-Y8U@P with the capacity of NIR-II imaging and excellent photothermal/photodynamic therapeutic effects. In vivo experiments demonstrated that GPRPP-Y8U@P could quickly locate thrombus by NIR-II fluorescence imaging, and semi-quantitative analysis of the embolized blood vessels' paraffin section verified its thrombolytic efficiency. Additionally, the urokinase trapped in the NPs would not result in nonspecific bleeding, tremendously improving physical security and curative effects with minimizing side effects. Overall, the advantages of GPRPP-Y8U@P, such as precise localization of the thrombus, thrombus ablation in the site, and mild side effects, demonstrated the attractiveness of this approach for effective clinical monitoring of thrombus therapy.
TPM1 mediates inflammation downstream of TREM2 via the PKA/CREB signaling pathway
Authors: Li Rong , Zhang Jing , Wang Qiong , Cheng Meng , Lin Bin 
Published: October 2022

Abstract
Background
Microglia, the innate immune cells in the central nervous system, play an essential role in brain homeostasis, neuroinflammation and brain infections. Dysregulated microglia, on the other hand, are associated with neurodegenerative diseases, yet the mechanisms underlying pro-inflammatory gene expression in microglia are incompletely understood.

Methods
We investigated the role of the actin-associated protein tropomyosin 1 (TPM1) in regulating pro-inflammatory phenotype of microglia in the retina by using a combination of cell culture, immunocytochemistry, Western blot, qPCR, TUNEL, RNA sequencing and electroretinogram analysis. TREM2−/− mice were used to investigate whether TPM1 regulated pro-inflammatory responses downstream of TREM2. To conditionally deplete microglia, we backcrossed CX3CR1CreER mice with Rosa26iDTR mice to generate CX3CR1CreER:Rosa26iDTR mice.

Results
We revealed a vital role for TPM1 in regulating pro-inflammatory phenotype of microglia. We found that TPM1 drove LPS-induced inflammation and neuronal death in the retina via the PKA/CREB pathway. TPM1 knockdown ameliorated LPS-induced inflammation in WT retinas yet exaggerated the inflammation in TREM2−/− retinas. RNA sequencing revealed that genes associated with M1 microglia and A1 astrocytes were significantly downregulated in LPS-treated WT retinas but upregulated in LPS-treated TREM2−/− retinas after TPM1 knockdown. Mechanistically, we demonstrated that CREB activated by TPM1 knockdown mediated anti-inflammatory genes in LPS-treated WT retinas but pro-inflammatory genes in LPS-treated TREM2−/− retinas, suggesting a novel role for TREM2 as a brake on TPM1-mediated inflammation. Furthermore, we identified that TPM1 regulated inflammation downstream of TREM2 and in a microglia-dependent manner.

Conclusions
We demonstrate that TPM1 mediates inflammation downstream of TREM2 via the PKA/CREB signaling pathway. Our findings suggest that TPM1 could be a potential target for therapeutic intervention in brain diseases.
Beyond steps per day: other measures of real-world walking after stroke related to cardiovascular risk
Authors: Miller Allison , Collier Zachary , Reisman Darcy S. 
Published: October 2022

AbstractBackgroundSignificant variability exists in how real-world walking has been measured in prior studies in individuals with stroke and it is unknown which measures are most important for cardiovascular risk. It is also unknown whether real-world monitoring is more informative than laboratory-based measures of walking capacity in the context of cardiovascular risk. The purpose of this study was to determine a subset of real-world walking activity measures most strongly associated with systolic blood pressure (SBP), a measure of cardiovascular risk, in people with stroke and if these measures are associated with SBP after accounting for laboratory-based measures of walking capacity.MethodsThis was a cross-sectional analysis of 276 individuals with chronic (≥ 6 months) stroke. Participants wore an activity monitor for ≥ 3 days. Measures of activity volume, activity frequency, activity intensity, and sedentary behavior were calculated. Best subset selection and lasso regression were used to determine which activity measures were most strongly associated with systolic blood pressure. Sequential linear regression was used to determine if these activity measures were associated with systolic blood pressure after accounting for walking capacity (6-Minute Walk Test).ResultsAverage bout cadence (i.e., the average steps/minute across all bouts of walking) and the number of long (≥ 30 min) sedentary bouts were most strongly associated with systolic blood pressure. After accounting for covariates (ΔR2 = 0.089, p < 0.001) and walking capacity (ΔR2 = 0.002, p = 0.48), these activity measures were significantly associated with systolic blood pressure (ΔR2 = 0.027, p = 0.02). Higher systolic blood pressure was associated with older age (β = 0.219, p < 0.001), male gender (β = − 0.121, p = 0.046), black race (β = 0.165, p = 0.008), and a slower average bout cadence (β = − 0.159, p = 0.022).ConclusionsMeasures of activity intensity and sedentary behavior may be superior to commonly used measures, such as steps/day, when the outcome of interest is cardiovascular risk. The relationship between walking activity and cardiovascular risk cannot be inferred through laboratory-based assessments of walking capacity.
The impact of a targeted education package on the knowledge, attitudes, and utilisation of patient reported outcome measures amongst chiropractors in Australia
Authors: Clohesy Natalie , Schneiders Anthony , Barbery Gaery , Obst Steven 
Published: October 2022

Abstract
Background
Patient Reported Outcome Measures (PROMs) have been shown to be valid and reliable indicators of health status and treatment outcomes, however, the current knowledge, understanding, and utilisation of PROMs within the Australian Chiropractic profession is limited. This study used the New World Kirkpatrick Model (NWKM) to evaluate whether an online PROM education package could improve knowledge, confidence, attitude, and utilisation of PROMs by chiropractors in Australia.

Methods
A longitudinal cohort interventional study of chiropractors in Australia. The recruitment phase and data collection period occurred from November 2020 – May 2021. Participants completed three online surveys two weeks before, four weeks after, and 12 weeks after receiving an online education package that included ten evidence-based region-specific modules on PROMs. Survey questions were grouped into five subthemes for analysis according to the NWKM levels: (1) Reaction; (2) Learning - knowledge; (3) Learning – confidence; (4) Behaviour – attitude; (5) and Behaviour - utilisation).

Results
Of the 116 participants that enrolled in the study, 43 completed all three survey and were included in the analysis. There was very positive reaction to the education package with mean response scores (1–5 Likert scale) for the reaction questions ranging from 3.75 to 4.43. There was a small, but significant, increase in knowledge (out of 32) at four weeks (24.3 ± 6.1) and 12 weeks after receiving the education package (27.2 ± 5.5), compared to baseline (27.4 ± 5.1). There was no effect of the intervention on clinician confidence or attitude towards PROMs. Utilisation of function- and pain-related PROMs did not change after the intervention. There was a small and significant (p < 0.05) increase in utilisation of health-related PROMs 12 weeks after the intervention.

Conclusion
Despite modest improvements in knowledge, which were retained 12 weeks after the educational package was provided, there was no evidence that participant confidence, attitude, or utilisation of PROMs changed because of the intervention. While the respondents’ have positive attitudes and beliefs regarding PROMs use, further education surrounding the clinical translation process into clinical practice is required. Caution is advised when interpreting these findings due to the low participant response and completion rate with the potential for selection bias and the inability to generalise the results.
Black girls and referrals: racial and gender disparities in self-reported referral to substance use disorder assessment among justice-involved children
Authors: Johnson Micah E. , Lloyd Shawnta L. , Bristol Skye C. , Elliott Amy L. , Cottler Linda B. 
Published: October 2022

Abstract
Background
There is a higher prevalence of substance use disorder (SUD) among justice-involved children (JIC). It is critical to ensure that JIC who report current use are referred for SUD assessment and potentially life-saving treatment services. Prior research suggests that certain minoritized groups may be less likely to have ever been referred for screening, and research on intersectionality suggests that these disparities may be exacerbated for racially minoritized females.

Methods
Multivariate logistic regression and interaction effects were employed to analyze longitudinal data from the Florida Department of Juvenile Justice on 12,128 JIC who reported SU in the past 6 months. The main and interaction effects of race and gender on the odds of having a history of reporting a referral to SUD assessment were tested. The primary outcome variable was a self-reported measure of a youth’s history of being referred to service. The control variables included substance type, household income, current SU problems, history of mental health problems, number of misdemeanors, risk to recidivate, and age at first offense.

Results
There were no significant differences in the likelihood of having a history of reporting being referred to SUD assessment between White females, White males, and Latinx females. However, Black females (AOR = 0.62), Latinx males (AOR = 0.71), and Black males (AOR = 0.65) were significantly less likely to self-report having a history of being referred than White males. Black females were 34% likely to report a history of being referred as White males and females.

Conclusion
In this sample, Black females who use substances were substantially less likely to self-report being referred to SUD screening. According to officials, FLDJJ has solid process to ensure referrals are made. Therefore, the results are likely to be due to external factors and alternative explanations. Community leaders and stakeholders may consider culturally relevant and gender-sensitive programs to expand access to services for minoritized adolescents in their communities, schools, and other institutions.
Measuring results of humanitarian action: adapting public health indicators to different contexts
Authors: Altare Chiara , Weiss William , Ramadan Marwa , Tappis Hannah , Spiegel Paul B. 
Published: October 2022

AbstractHumanitarian crises represent a significant public health risk factor for affected populations exacerbating mortality, morbidity, disabilities, and reducing access to and quality of health care. Reliable and timely information on the health status of and services provided to crisis-affected populations is crucial to establish public health priorities, mobilize funds, and monitor the performance of humanitarian action. Numerous efforts have contributed to standardizing and presenting timely public health information in humanitarian settings over the last two decades. While the prominence of process and output (rather than outcome and impact) indicators in monitoring frameworks leads to adequate information on resources and activities, health outcomes are rarely measured due to the challenges of measuring them using gold-standard methods that are difficult to implement in humanitarian settings.We argue that challenges in collecting the gold-standard performance measures should not be a rationale for neglecting outcome measures for critical health and nutrition programs in humanitarian emergencies. Alternative indicators or measurement methods that are robust, practical, and feasible in varying contexts should be used in the interim while acknowledging limitations or interpretation constraints. In this paper, we draw from existing literature, expert judgment, and operational experience to propose an approach to adapt public health indicators for measuring performance of the humanitarian response across varied contexts.Contexts were defined in terms of parameters that capture two of the main constraints affecting the capacity to obtain performance information in humanitarian settings: (i) access to population or health facilities; and (ii) availability of resources for measurement. Consequently, 2 × 2 tables depict four possible scenarios: (A) a situation with accessible populations and with available resources; (B) a situation with available resources but limited access to affected populations; (C) a situation with accessible populations and limited resources; and (D) a situation with both limited access and limited resources.Methods and data sources can vary from large population-based surveys, rapid assessments of populations or health facilities, routine health management information systems, or data from sentinel sites in the community or among facilities. Adapting indicators and methods to specific contexts of humanitarian settings increases the potential for measuring the performance of humanitarian programs beyond inputs and outputs by assessing health outcomes, and consequently improving program impact, reducing morbidity and mortality, and improving the quality of lives amongst persons affected by humanitarian emergencies.
PARP1-MGMT complex underpins pathway crosstalk in O6-methylguanine repair
Authors: Cropper Jodie D. , Alimbetov Dauren S. , Brown Kevin T. G. , Likhotvorik Rostislav I. , Robles Andrew J. , Guerra James T. , He Boxue , Chen Yidong , Kwon Youngho , Kurmasheva Raushan T. 
Published: October 2022

AbstractDNA lesions induced by alkylating agents are repaired by two canonical mechanisms, base excision repair dependent on poly(ADP) ribose polymerase 1 (PARP1) and the other mediated by O6-methylguanine (O6meG)-DNA methyltransferase (MGMT) in a single-step catalysis of alkyl-group removal. O6meG is the most cytotoxic and mutagenic lesion among the methyl adducts induced by alkylating agents. Although it can accomplish the dealkylation reaction all by itself as a single protein without associating with other repair proteins, evidence is accumulating that MGMT can form complexes with repair proteins and is highly regulated by a variety of post-translational modifications, such as phosphorylation, ubiquitination, and others. Here, we show that PARP1 and MGMT proteins interact directly in a non-catalytic manner, that MGMT is subject to PARylation by PARP1 after DNA damage, and that the O6meG repair is enhanced upon MGMT PARylation. We provide the first evidence for the direct DNA-independent PARP1-MGMT interaction. Further, PARP1 and MGMT proteins also interact via PARylation of MGMT leading to formation of a novel DNA damage inducible PARP1-MGMT protein complex. This catalytic interaction activates O6meG repair underpinning the functional crosstalk between base excision and MGMT-mediated DNA repair mechanisms. Furthermore, clinically relevant ‘chronic’ temozolomide exposure induced PARylation of MGMT and increased binding of PARP1 and MGMT to chromatin in cells. Thus, we provide the first mechanistic description of physical interaction between PARP1 and MGMT and their functional cooperation through PARylation for activation of O6meG repair. Hence, the PARP1-MGMT protein complex could be targeted for the development of advanced and more effective cancer therapeutics, particularly for cancers sensitive to PARP1 and MGMT inhibition.
The molecular and functional characterization of ferritins in the hard tick Hyalomma rufipes
Authors: Gao Zhihua , Zheng Peijing , Wang Kuang , Ji Xin , Shi Yanqing , Song Xuecheng , Liu Jingze , Yu Zhijun , Yang Xiaolong 
Published: October 2022

Abstract
Background
The protein ferritin, which plays an important role in the maintenance of iron homeostasis, is indispensable for iron detoxification, resistance to oxidative stress and innate immunity. Ticks, which are obligate blood-sucking ectoparasites, have to deal with a large amount of iron when they take a blood meal.

Methods
Sequence analysis was undertaken using bioinformatics. A recombinant (r) expression vector, rferritin, was constructed for a prokaryotic expression system. A quantitative polymerase chain reaction platform was used to detect the spatial and temporal expression patterns of target genes and their responses to a low temperature environment. Knockdown of the ferritin genes through RNA interference was used to analyze their effects on physiological parameters of ticks.

Results
Two ferritin genes, HrFer1 and HrFer2, were cloned from the tick Hyalomma rufipes. Their open reading frames are 519 base pairs (bp) and 573 bp in length, and number of coding amino acids 170 and 190, respectively. The phylogenetic tree showed that HrFer1 and HrFer2 have a close evolutionary relationship with the H subunit of ferritin. In vitro experiments showed that rHrFer1 and rHrFer2 had concentration-dependent iron chelating activity. The relative expression of the two ferritin genes was higher in the ovary and midgut of H. rufipes. RNA interference results demonstrated that HrFer1 and HrFer2 expression had a significant effect on engorged body weight, number of eggs laid, and mortality of H. rufipes, and that HrFer2 also had a significant effect on feeding duration. Furthermore, the relative expression of ferritin decreased significantly in a low temperature environment, suggesting that HrFer1 and HrFer2 play a regulatory role in the cold stress response of H. rufipes.

Conclusions
The results of the present study improve our understanding of the involvement of ferritins in tick blood-feeding.

Graphical Abstract