bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized controlled trial of the influence of yoga for women with symptoms of post-traumatic stress disorder
Authors: Yi Lei , Lian Yunling , Ma Ning , Duan Ni 
Published: April 2022

Abstract
Background
Survivors in motor vehicle accident (MVA) may have posttraumatic stress disorder (PTSD). Yoga is a complementary approach for PTSD therapy.

Methods
This randomized controlled trial explored whether yoga intervention has effects on reducing the symptoms of PTSD in women survived in MVA. Participants (n = 94) were recruited and randomized into control group or yoga group. Participants attended 6 45-minuite yoga sessions in 12 weeks. Depression Anxiety Stress Scales (DASS) and Impact of Events Scale-Revised (IES-R) were used to assess psychological distress.

Results
Post-intervention IES-R total score of yoga group was significantly lower than that of control group (p = 0.01). At both post-intervention and 3-months post intervention, the DASS-21 total scores of yoga group were both significantly lower than those of control group (p = 0.043, p = 0.024). Yoga group showed lower anxiety and depression level compared to control group at both post-intervention (p = 0.033, p < 0.001) and post-follow-up (p = 0.004, p = 0.035). Yoga group had lower levels of intrusion and avoidance compared to control group after intervention (p = 0.002, p < 0.001).

Conclusion
Results illustrate that yoga intervention may alleviate anxiety and depression and improve the symptoms of PTSD in women with PTSD following MVA.
Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma
Authors: Guida Michele , Bartolomeo Nicola , Quaresmini Davide , Quaglino Pietro , Madonna Gabriele , Pigozzo Jacopo , Di Giacomo Anna Maria , Minisini Alessandro Marco , Tucci Marco , Spagnolo Francesco , Occelli Marcella , Ridolfi Laura , Queirolo Paola , De Risi Ivana , Valente Monica , Sciacovelli Angela Monica , Chiarion Sileni Vanna , Ascierto Paolo Antonio , Stigliano Lucia , Strippoli Sabino 
Published: April 2022

AbstractBackgroundTo evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response toimmune checkpoint inhibitors (ICI) in metastatic melanoma (MM).MethodsWe performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve.ResultsAt baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months).ConclusionsBaseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.
Ruxolitinib suppresses liver fibrosis progression and accelerates fibrosis reversal via selectively targeting Janus kinase 1/2
Authors: Song Zhenghui , Liu Xinhui , Zhang Wan , Luo Yue , Xiao Hua , Liu Yun , Dai Guanqi , Hong Jian , Li Aimin 
Published: April 2022

Abstract
Background
JAK1 and JAK2 have been implicated in fibrosis and cancer as a fibroblast-related marker; however, their role in liver fibrosis has not been elucidated. Here, we aim to determine the effect and underlying mechanism of JAK1/2 inhibition on liver fibrosis and hepatic stellate cells (HSCs) and further explore the therapeutic efficacy of Ruxolitinib, a JAK1/2 selective inhibitor, on preventing and reversing liver fibrosis in mice.

Methods
Immunohistochemistry staining of JAK1 and JAK2 were performed on liver tissue in mice with hepatic fibrosis and human liver tissue microarray of liver cirrhosis and liver cancer. LX-2 cells treated with specific siRNA of JAK1 and JAK2 were used to analysis activation, proliferation and migration of HSCs regulated by JAK1/2. The effects of Ruxolitinib (JAK1/2 inhibitor) on liver fibrosis were studied in LX-2 cells and two progressive and reversible fibrosis animal models (carbon tetrachloride (CCl4), Thioacetamide (TAA)).

Results
We found that JAK1/2 expression was positively correlated with the progression of HCC in humans and the levels of liver fibrosis in mice. Silencing of JAK1/2 down-regulated their downstream signaling and inhibited proliferation, migration, and activation of HSCs in vitro, while Ruxolitinib had similar effects on HSCs. Importantly, Ruxolitinib significantly attenuated fibrosis progression, improved cell damage, and accelerated fibrosis reversal in the liver of mice treated with CCl4 or TAA.

Conclusions
JAK1/2 regulates the function of HSCs and plays an essential role in liver fibrosis and HCC development. Its inhibitor, Ruxolitinib, may be an effective drug for preventing and treating liver fibrosis.
Associated predictors of functional impairment among adolescents with ADHD—a cross-sectional study
Authors: Meyer Jenny , Alaie Iman , Ramklint Mia , Isaksson Johan 
Published: April 2022

Abstract
Background
Attention-deficit/hyperactivity disorder (ADHD) in adolescence is associated with functional impairment in several domains of life. To enable development of interventions that more effectively target functional impairment in this age group, the associations between clinical characteristics and impairment need to be clarified. The aim of this study was to investigate the associations between ADHD and functional impairment, if they varied by sex, and the potential impact of comorbid psychiatric symptoms on the associations.

Methods
This was a cross-sectional study including adolescents with ADHD (n = 164) and a reference group of adolescents without ADHD (n = 106). Self-ratings and parental ratings of functional impairment in different life domains were used as outcomes in all analyses. Differences between groups were investigated with comparative analyses. General linear models (GLMs) were used to explore associations between ADHD symptoms and functional impairment in adolescents with ADHD, while adjusting for of comorbid symptoms, sex, and medication.

Results
Adolescents with ADHD displayed higher levels of functional impairment than peers without ADHD, and girls with ADHD rated higher impairment than their male counterparts. The combined ADHD presentation was associated with the highest levels of self-reported impairment, while parental ratings indicated comparable levels of overall impairment across presentations. In the adjusted GLMs, symptoms of inattention were strongly associated with self- and parent-rated impairment in school, but symptoms of hyperactivity/impulsivity were not, whereas symptoms of both inattention and hyperactivity/impulsivity were modestly associated with self-rated impairment with friends. Further, both emotional and conduct problems were associated with impairment in daily life.

Conclusions
Our results suggest that attention difficulties, in particular, seem to impair academic functioning in adolescents with ADHD, and interventions targeting such difficulties are warranted. In addition, comorbid symptoms need to be assessed and treated, and self-reports of functioning should be included in research and clinical practice involving adolescents.
Frequency of BRCA1 and BRCA2 mutations in ovarian cancer patients in South-East Poland
Authors: Jasiewicz Andrzej , Rudnicka Helena , Kluźniak Wojciech , Gronwald Wojciech , Kluz Tomasz , Cybulski Cezary , Jakubowska Anna , Lubiński Jan , Gronwald Jacek 
Published: April 2022

Abstract
Background
Mutations in BRCA1 and BRCA2 genes are well-established risk factors of breast and ovarian cancer. In our former study, we observed that approximately 6% of unselected ovarian cancer patients in the region of Podkarpacie (South-East Poland) carry BRCA1 causative founder variants, which is significantly lower than in other regions of Poland. Therefore, it is deeply justified to do research based on the sequencing of whole BRCA1 and BRCA2 genes.

Methods
We examined 158 consecutive unselected cases of ovarian cancer patients from the region of Podkarpacie. We performed BRCA1 and BRCA2 genes Next-Generation Sequencing study in all cases.

Results
Altogether, in 18 of 158 (11.4%) ovarian cancer patients with BRCA1 or BRCA2 pathogenic mutations were found. BRCA1 pathogenic variants were detected in 11 of the 158 (7.0%) ovarian cancer cases. 10 of 11 (91%) detected BRCA1 mutations were founder mutations, detectable with the standard test used in Poland. BRCA2 pathogenic variants were found in 7 of the 158 (4.4%) cases. No BRCA2 pathogenic variants were founder mutations. The median age of patients at the diagnosis of the 18 hereditary ovarian cancers was 57.5 years.

Conclusions
The frequency of BRCA1 or BRCA2 gene mutation carriers among patients with ovarian cancer from the Podkarpacie region is comparable to other regions of Poland. However, a significantly higher percentage of BRCA2 gene mutations was observed, that were not detectable with a standard test for detection of founder mutations. Diagnostics based only on testing the BRCA1/2 Polish founder mutations is characterized by relatively low sensitivity in the case of ovarian cancer patients from South-East Poland and should be supplemented by NGS study, in particular of the BRCA2 gene.
Breast cancer metastasis to brain results in recruitment and activation of microglia through annexin-A1/formyl peptide receptor signaling
Authors: Foo Sok Lin , Sachaphibulkij Karishma , Lee Corinne L. Y. , Yap Gracemary L. R. , Cui Jianzhou , Arumugam Thiruma , Lim Lina H. K. 
Published: April 2022

Abstract
Background
Despite advancements in therapies, brain metastasis in patients with triple negative subtype of breast cancer remains a therapeutic challenge. Activated microglia are often observed in close proximity to, or within, malignant tumor masses, suggesting a critical role that microglia play in brain tumor progression. Annexin-A1 (ANXA1), a glucocorticoid-regulated protein with immune-regulatory properties, has been implicated in the growth and metastasis of many cancers. Its role in breast cancer-microglia signaling crosstalk is not known.

Methods
The importance of microglia proliferation and activation in breast cancer to brain metastasis was evaluated in MMTV-Wnt1 spontaneous mammary tumor mice and BALBc mice injected with 4T1 murine breast cancer cells into the carotid artery using flow cytometry. 4T1 induced-proliferation and migration of primary microglia and BV2 microglia cells were evaluated using 2D and coculture transwell assays. The requirement of ANXA1 in these functions was examined using a Crispr/Cas9 deletion mutant of ANXA1 in 4T1 breast cancer cells as well as BV2 microglia. Small molecule inhibition of the ANXA1 receptor FPR1 and FPR2 were also examined. The signaling pathways involved in these interactions were assessed using western blotting. The association between lymph node positive recurrence-free patient survival and distant metastasis-free patient survival and ANXA1 and FPR1 and FPR2 expression was examined using TCGA datasets.

Results
Microglia activation is observed prior to brain metastasis in MMTV-Wnt1 mice with primary and secondary metastasis in the periphery. Metastatic 4T1 mammary cancer cells secrete ANXA1 to promote microglial migration, which in turn, enhances tumor cell migration. Silencing of ANXA1 in 4T1 cells by Crispr/Cas9 deletion, or using inhibitors of FPR1 or FPR2 inhibits microglia migration and leads to reduced activation of STAT3. Finally, elevated ANXA1, FPR1 and FPR2 is significantly associated with poor outcome in lymph node positive patients, particularly, for distant metastasis free patient survival.

Conclusions
The present study uncovered a network encompassing autocrine/paracrine ANXA1 signaling between metastatic mammary cancer cells and microglia that drives microglial recruitment and activation. Inhibition of ANXA1 and/or its receptor may be therapeutically rewarding in the treatment of breast cancer and secondary metastasis to the brain.
TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation
Authors: Tolić Anja , Ravichandran Mirunalini , Rajić Jovana , Đorđević Marija , Đorđević Miloš , Dinić Svetlana , Grdović Nevena , Jovanović Jelena Arambašić , Mihailović Mirjana , Nestorović Nataša , Jurkowski Tomasz P. , Uskoković Aleksandra S. , Vidaković Melita S. 
Published: April 2022

Abstract
Background
Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA—the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP–TET interplay.

Results
Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo.

Conclusions
According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.
Serum IGF-1 in patients with rheumatoid arthritis: correlation with disease activity
Authors: Lee Hanna , Suh Young Sun , Lee Sang-Il , Cheon Yun-Hong , Kim Mingyo , Noh Hae Sook , Kim Hyun-Ok 
Published: April 2022

AbstractObjectiveInsulin-like growth factor (IGF)-1 participates in modulating immunity and inflammation. Its bioactivity is controlled by six IGF-binding proteins (IGFBP-1 to IGFBP-6). In particular, the IGFBP-3 level is reportedly linked to the disease activity of rheumatoid arthritis (RA), consistent with our previous study. Therefore, the present study aimed to reproduce the previous results.ResultsThe serum IGFBP-3 level was not significantly different among the three groups according to disease activity based on the DAS28-ESR/CRP (p > 0.05) but was significantly different between the low- and high-disease-activity groups based on the DAS28-CRP (p = 0.036). Meanwhile, the interleukin-6 (IL-6) level moderately correlated with DAS28-CRP (Spearman’s rho = 0.583,p < 0.001).
Reimagining peer review as an expert elicitation process
Authors: Marcoci Alexandru , Vercammen Ans , Bush Martin , Hamilton Daniel G. , Hanea Anca , Hemming Victoria , Wintle Bonnie C. , Burgman Mark , Fidler Fiona 
Published: April 2022

AbstractJournal peer review regulates the flow of ideas through an academic discipline and thus has the power to shape what a research community knows, actively investigates, and recommends to policymakers and the wider public. We might assume that editors can identify the ‘best’ experts and rely on them for peer review. But decades of research on both expert decision-making and peer review suggests they cannot. In the absence of a clear criterion for demarcating reliable, insightful, and accurate expert assessors of research quality, the best safeguard against unwanted biases and uneven power distributions is to introduce greater transparency and structure into the process. This paper argues that peer review would therefore benefit from applying a series of evidence-based recommendations from the empirical literature on structured expert elicitation. We highlight individual and group characteristics that contribute to higher quality judgements, and elements of elicitation protocols that reduce bias, promote constructive discussion, and enable opinions to be objectively and transparently aggregated.
What’s the cut-point?: a systematic investigation of tau PET thresholding methods
Authors: Weigand Alexandra J. , Maass Anne , Eglit Graham L. , Bondi Mark W. 
Published: April 2022

Abstract
Background
Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer’s disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity.

Methods
First, a literature search was conducted in PubMed to identify studies of AD and related clinical phenotypes that used the Flortaucipir (AV-1451) tau PET tracer to derive a binary cut-point for tau positivity. Of 540 articles screened and 47 full-texts reviewed, 23 cohort studies met inclusion criteria with a total of 6536 participants. Second, we derived and compared tau PET cut-points in a 2 × 2 × 2 design that systematically varied region (temporal meta-ROI and entorhinal cortex), analytic method (receiver operating characteristics and 2 standard deviations above comparison group), and criterion/comparison variable (amyloid-beta negative cognitively unimpaired or cognitively unimpaired only) using a sample of 453 older adults from the Alzheimer’s Disease Neuroimaging Initiative.

Results
For the systematic review, notable variability in sample characteristics, preprocessing methods, region of interest, and analytic approach were observed, which were accompanied by discrepancy in proposed tau PET cut points. The empirical follow-up indicated the cut-point derived based on 2 standard deviations above a either comparison group in either ROI best differentiated tau positive and negative groups on cerebrospinal fluid phosphorylated tau, Mini-Mental State Examination score, and delayed memory performance.

Conclusions
Given the impact of discrepant thresholds on tau positivity rates, biomarker staging, and eligibility for future clinical treatment trials, recommendations are offered to select cut-point derivations based on the unique goals and priorities of different studies.
Emotional prosody recognition is impaired in Alzheimer’s disease
Authors: Amlerova Jana , Laczó Jan , Nedelska Zuzana , Laczó Martina , Vyhnálek Martin , Zhang Bing , Sheardova Kateřina , Angelucci Francesco , Andel Ross , Hort Jakub 
Published: April 2022

Abstract
Background
The ability to understand emotions is often disturbed in patients with cognitive impairments. Right temporal lobe structures play a crucial role in emotional processing, especially the amygdala, temporal pole (TP), superior temporal sulcus (STS), and anterior cingulate (AC). Those regions are affected in early stages of Alzheimer´s disease (AD). The aim of our study was to evaluate emotional prosody recognition (EPR) in participants with amnestic mild cognitive impairment (aMCI) due to AD, AD dementia patients, and cognitively healthy controls and to measure volumes or thickness of the brain structures involved in this process. In addition, we correlated EPR score to cognitive impairment as measured by MMSE. The receiver operating characteristic (ROC) analysis was used to assess the ability of EPR tests to differentiate the control group from the aMCI and dementia groups.

Methods
Eighty-nine participants from the Czech Brain Aging Study: 43 aMCI due to AD, 36 AD dementia, and 23 controls, underwent Prosody Emotional Recognition Test. This experimental test included the playback of 25 sentences with neutral meaning each recorded with different emotional prosody (happiness, sadness, fear, disgust, anger). Volume of the amygdala and thickness of the TP, STS, and rostral and caudal parts of AC (RAC and CAC) were measured using FreeSurfer algorithm software. ANCOVA was used to evaluate EPR score differences. ROC analysis was used to assess the ability of EPR test to differentiate the control group from the aMCI and dementia groups. The Pearson’s correlation coefficients were calculated to explore relationships between EPR scores, structural brain measures, and MMSE.

Results
EPR was lower in the dementia and aMCI groups compared with controls. EPR total score had high sensitivity in distinguishing between not only controls and patients, but also controls and aMCI, controls and dementia, and aMCI and dementia. EPR decreased with disease severity as it correlated with MMSE. There was a significant positive correlation of EPR and thickness of the right TP, STS, and bilateral RAC.

Conclusions
EPR is impaired in AD dementia and aMCI due to AD. These data suggest that the broad range of AD symptoms may include specific deficits in the emotional sphere which further complicate the patient’s quality of life.