bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avenir® vs. AxiumTM Coils for the Treatment of Intracranial Aneurysms: Results of a Multicenter Randomized Controlled Trial With Short-Term Follow-Up
Authors: Li Wei , Ye Ming , Cimpoca Alexandru , Henkes Hans , Wang Honglei , Xu Xiang , Gu Yuxiang , Shi Huaizhang , Ji Hongming , Wang Feng , Zhao Yuanli , Guo Geng , Zhang Hongqi , Li Youxiang 
Published: January 2022

PurposeEndovascular coil occlusion is a successful and rapidly evolving strategy used to treat patients who present with intracranial aneurysms. This study aimed to compare the safety and efficacy of the Avenir® and AxiumTM passive mechanically detachable coil systems.MethodsA prospective, multicenter, randomized controlled study was carried out at ten medical centers from March 2018 to December 2019. A series of consecutive patients diagnosed with intracranial aneurysms were randomly assigned to undergo endovascular treatment with either the Avenir® or the AxiumTM mechanically detachable coil systems. The short-term outcomes from the two groups were compared with a focus on treatment efficacy and safety.ResultsA total of 162 and 161 patients were enrolled in the Avenir and Axium groups, respectively. The rate of successful coil detachment was 100% for the Avenir group and 99.38% for the Axium group. At the six-month follow-up visit, the overall aneurysm occlusion rate was 94.66% for the Avenir group and 96.95% for the Axium group (p &gt; 0.05). We observed no statistically significant differences in clinical condition (as per the modified Rankin Scale) or the degree of aneurysm occlusion (as determined by digital subtraction angiography [DSA] and Raymond-Roy Occlusion Classification). Surgical complications were reported in 27 subjects in the Avenir group and 22 in the Axium group (p &gt; 0.05). DSA performed at 6 months revealed complete aneurysm occlusion in 84 and 86% of patients in the Avenir and Axium groups, respectively.ConclusionWe observed no significant short-term differences with respect to efficacy or safety when using either Avenir® or AxiumTM coils for the treatment of intracranial aneurysms.
People With Parkinson’s Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles
Authors: Breu Maria-Sophie , Schneider Marlieke , Klemt Johannes , Cebi Idil , Gharabaghi Alireza , Weiss Daniel 
Published: January 2022

ObjectiveFreezing of gait is detrimental to patients with idiopathic Parkinson’s disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity.MethodsWe analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in ‘regular gait’ and during the ‘freezing’ episodes.ResultsIn stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing.ConclusionWe found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.
Evaluating the Diagnostic Value of a Combined Indicator of Vitamin B12 Status (cB12) Throughout Pregnancy
Authors: Dib Marie-Joe , Gumban-Marasigan Maria , Yoxall Rozzie , Andrew Toby , Harrington Dominic J. , Sobczyńska-Malefora Agata , Ahmadi Kourosh R. 
Published: January 2022

BackgroundInadequate provision of vitamin B12 during pregnancy is associated with a number of adverse maternal and fetal outcomes. We set out to (1) suggest pregnancy-specific reference ranges for a range of biomarkers of vitamin B12; (2) assess the temporal behaviors of these markers over the course of pregnancy; and (3) test whether any biomarkers, including the genetic marker HIBCH rs291466 strongly associated with MMA measured early in pregnancy could reliably and significantly predict future B12 status within a healthy UK population of pregnant women.Materials and MethodsWe used existing biobank samples from the placebo arm of the UK Selenium in PRegnancy Intervention (SPRINT) study, to generate biochemical data for serum folate, B12, holotranscobalamin (HoloTC), total homocysteine (tHcy), and MMA, calculate cB12, and genotyped the polymorphism rs291466 in gene HIBCH on a total of n=114 women across trimesters 1–3 of their pregnancy. We performed a series of exploratory cross-sectional and longitudinal analyses to investigate levels at each trimester, suggest references ranges, evaluate changes and correlations between the B12 biomarkers, and assess the predictive capabilities of each biomarker from 12-weeks to 35-weeks of gestation.ResultsSignificant changes in all vitamin B12 biomarker values were observed over the three trimesters (P &lt; 0.05). Our study shows that cB12 values were largely constant and stable throughout trimester 1 (T1) and T2 (i.e., up to week 20), but declined significantly in T3 (−66% | P &lt; 0.001). Yet, cB12 generally remained within the normal boundaries. We identified pregnancy and trimester-specific reference ranges for each biomarker at each trimester, notably for total serum B12. This marker fell below the recommended cut-offs in 1/3 of the cohort at the third trimester, contrasting other markers (mostly normal). Our multivariate analyses indicated that none of the biomarkers could reliably and accurately predict any other biomarkers than themselves later in pregnancy. Yet, HoloTC seems to be a promising predictor within the limitations of our cohort, constituted of B12-replete individuals. Most notably, cB12 did not significantly predict itself between trimesters. Finally, we show that the HIBCH variant has little predictive power for MMA or cB12 as it does not explain the significant increase in MMA concentrations nor the decline of cB12 throughout pregnancy.ConclusionTrimester-specific reference ranges for biomarkers of vitamin B12 in normal pregnancy are suggested. However, these biomarkers have limited predictive value in identifying mothers at elevated risk of vitamin B12 insufficiency/deficiency during pregnancy.
Efficacy of Probiotics in Children and Adolescents With Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Andrade Paula Danielle Santa Maria Albuquerque de , Maria e Silva Jorgete , Carregaro Vanessa , Sacramento Laís Amorim , Roberti Luciana Rodrigues , Aragon Davi Casale , Carmona Fabio , Roxo-Junior Pérsio 
Published: January 2022

ObjectiveTo evaluate the clinical efficacy of a mixture of probiotics (Lactobacillus and Bifidobacterium) in children and adolescents with atopic dermatitis (AD) and the effects on sensitization, inflammation, and immunological tolerance.MethodsIn this double-blind, randomized, placebo-controlled clinical trial, we enrolled 60 patients aged between 6 months and 19 years with mild, moderate, or severe AD, according to the criteria proposed by Hanifin and Rajka. Patients were stratified to receive one gram per day of probiotics or placebo for 6 months. The primary outcome was a decrease in SCORing Atopic Dermatitis (SCORAD). Secondary outcomes were to assess the role of probiotics on the use of topical and oral medicines (standard treatment), serum IgE levels, skin prick test (SPT), and tolerogenic and inflammatory cytokines. Background therapy was maintained.ResultsForty patients completed the study (24 probiotics, 16 placebo). After treatment for six months, the clinical response was significantly better in the probiotics group; the SCORAD decreased [mean difference (MD) 27.69 percentage points; 95% confidence interval (CI), 2.44–52.94], even after adjustment for co-variables (MD 32.33 percentage points; 95%CI, 5.52–59.13), especially from the third month of treatment on. The reduction of the SCORAD in probiotic group persisted for three more months after the treatment had been discontinued, even after adjustment for co-variables (MD 14.24 percentage points; 95%CI, 0.78–27.70). Patients in the probiotics group required topical immunosuppressant less frequently at 6 and 9 months. No significant changes were found for IgE levels, SPT and cytokines.ConclusionsChildren and adolescents with AD presented a significant clinical response after 6 months with a mixture of probiotics (Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus paracasei, and Bifidobacterium lactis. However, this clinical benefit is related to treatment duration. Probiotics should be considered as an adjuvant treatment for AD.
Development and Validation of a Radiomics Nomogram for Predicting Clinically Significant Prostate Cancer in PI-RADS 3 Lesions
Authors: Li Tianping , Sun Linna , Li Qinghe , Luo Xunrong , Luo Mingfang , Xie Haizhu , Wang Peiyuan 
Published: January 2022

PurposeTo develop and validate a radiomics nomogram for the prediction of clinically significant prostate cancer (CsPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) category 3 lesions.MethodsWe retrospectively enrolled 306 patients within PI-RADS 3 lesion from January 2015 to July 2020 in institution 1; the enrolled patients were randomly divided into the training group (n = 199) and test group (n = 107). Radiomics features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) imaging, and dynamic contrast-enhanced (DCE) imaging. Synthetic minority oversampling technique (SMOTE) was used to address the class imbalance. The ANOVA and least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection and radiomics signature building. Then, a radiomics score (Rad-score) was acquired. Combined with serum prostate-specific antigen density (PSAD) level, a multivariate logistic regression analysis was used to construct a radiomics nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate radiomics signature and nomogram. The radiomics nomogram calibration and clinical usefulness were estimated through calibration curve and decision curve analysis (DCA). External validation was assessed, and the independent validation cohort contained 65 patients within PI-RADS 3 lesion from January 2020 to July 2021 in institution 2.ResultsA total of 75 (24.5%) and 16 (24.6%) patients had CsPCa in institution 1 and 2, respectively. The radiomics signature with SMOTE augmentation method had a higher area under the ROC curve (AUC) [0.840 (95% CI, 0.776–0.904)] than that without SMOTE method [0.730 (95% CI, 0.624–0.836), p = 0.08] in the test group and significantly increased in the external validation group [0.834 (95% CI, 0.709–0.959) vs. 0.718 (95% CI, 0.562–0.874), p = 0.017]. The radiomics nomogram showed good discrimination and calibration, with an AUC of 0.939 (95% CI, 0.913–0.965), 0.884 (95% CI, 0.831–0.937), and 0.907 (95% CI, 0.814–1) in the training, test, and external validation groups, respectively. The DCA demonstrated the clinical usefulness of radiomics nomogram.ConclusionThe radiomics nomogram that incorporates the MRI-based radiomics signature and PSAD can be conveniently used to individually predict CsPCa in patients within PI-RADS 3 lesion.
Stereotactic Body Radiotherapy Immunological Planning—A Review With a Proposed Theoretical Model
Authors: Swamy Kumara 
Published: January 2022

In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward an “immunological radiation plan”, i.e., radiation scheduling with abscopal effect as a vital endpoint as well. The literature review of part A enumerates the advantages of the intermediate dose of SBRT 6–10 Gy per fraction, appropriate use of dose painting, proper timing with immunotherapy, and the potential of immunoadjuvants to maximize cell kill in the irradiated lesions, found to have improved the abscopal effects. Part B summarizes part A, primarily the findings of animal trials, forming the basis of the tenets of the proposed model given in part C to realize the true abscopal potential of the SBRT tumor cell kill of the index lesions. Part C proposes a theoretical model highlighting tumor vasculature integrity as the central theme for converting “abscopal effect by chance” to “abscopal effect by design” using a harmonized combinatorial approach. The proposed model principally deals with the use of SBRT in strategizing increased cell kill in irradiated index tumors along with immunomodulators as a basis for improving the consistency of the abscopal effect. Included is the possible role of integrating immunotherapy just after SBRT, “cyclical” antiangiogenics, and immunoadjuvants/immune metabolites as abscopal effect enhancers of SBRT tumor cell kill. The proposed model suggests convergence research in adopting existing numerous SBRT abscopal enhancing strategies around the central point of sustained vascular integrity to develop decisive clinical trial protocols in the future.
Pevonedistat Suppresses Pancreatic Cancer Growth via Inactivation of the Neddylation Pathway
Authors: Xu Junfeng , Li Zheng , Zhuo Qifeng , Ye Zeng , Fan Guixiong , Gao Heli , Ji Shunrong , Yu Xianjun , Xu Xiaowu , Liu Wensheng , Xu Wenyan 
Published: January 2022

BackgroundThe neddylation pathway is aberrantly overactivated in multiple human cancers and has been indicated as an effective target for anticancer therapy in clinical trials. We aimed to study whether the neddylation pathway is upregulated in pancreatic cancer and whether pevonedistat, a first-in-class anticancer agent specifically targeting this pathway, will suppress cancer tumorigenesis and progression.MethodsWe evaluated the expression pattern of neddylation pathway components in 179 pancreatic adenocarcinoma (PAAD) compared with 171 normal tissues from The Cancer Genome Atlas (TCGA) dataset and further assessed PAAD patient prognosis with high neddylation pathway expression via Gene Expression Profiling Interactive Analysis (GEPIA). We then analyzed malignant cancer phenotypes both in vitro and in vivo, as well as intrinsic molecular mechanisms upon pevonedistat treatment.ResultsWe found that the neddylation pathway was hyperactivated in pancreatic cancer. Patients with high neddylation pathway expression exhibited worse prognoses. Pevonedistat significantly inhibited the cancer cell cycle, cell growth, and proliferation; increased cell apoptosis; and decreased cancer cell xenografts in a mouse model. Mechanistically, pevonedistat treatment and the siRNA knockdown neddylation pathway were able to remarkably induce the accumulation of Wee1, p27, and p21. Further mechanistic studies revealed that pevonedistat mainly impaired the ubiquitination level and delayed the protein degradation of Wee1, p27, and p21.ConclusionsOur results showed that pevonedistat targeted the overexpression of the neddylation pathway in pancreatic cancer to induce cell growth suppression by inducing the accumulation of the cell cycle regulators Wee1, p27, and p21, which provides sound evidence for the clinical trial of pevonedistat for pancreatic cancer therapy.
Diagnostic Accuracy of Infection Markers to Diagnose Infections in Neonates and Children Receiving Extracorporeal Membrane Oxygenation
Authors: Doo Irene , Staub Lukas P. , Mattke Adrian , Haisz Emma , Seidler Anna Lene , Alphonso Nelson , Schlapbach Luregn J. 
Published: January 2022

BackgroundInfections represent one of the most common complications in patients managed on Extracorporeal Membrane Oxygenation (ECMO) and are associated with poorer outcomes. Clinical signs of infection in patients on ECMO are non-specific. We assessed the diagnostic accuracy of Procalcitonin (PCT), C-reactive protein (CRP) and White cell count (WCC) to diagnose infection on ECMO.MethodsRetrospective single center observational study including neonates and children &lt;18 years treated with ECMO in 2015 and 2016. Daily data on PCT, CRP and WCC were assessed in relation to microbiologically confirmed, and clinically suspected infection on ECMO using operating characteristics (ROC) curves.ResultsSixty-five ECMO runs in 58 patients were assessed. CRP had the best accuracy with an area under the ROC curve (AUC) of 0.79 (95%-CI 0.66–0.92) to diagnose confirmed infection and an AUC of 0.72 (0.61–0.84) to diagnose confirmed and suspected infection. Abnormal WCC performed slightly worse with an AUC of 0.70 (0.59–0.81) for confirmed and AUC of 0.66 (0.57–0.75) for confirmed and suspected infections. PCT was non-discriminatory.ConclusionThe diagnosis of infections acquired during ECMO remains challenging. Larger prospective studies are needed that also include novel infection markers to improve recognition of infection in patients on ECMO.
Three-Carbon Linked Dihydroartemisinin-Isatin Hybrids: Design, Synthesis and Their Antiproliferative Anticancer Activity
Authors: Dong Min , Zheng Guili , Gao Feng , Li Min , Zhong Chen 
Published: January 2022

Fifteen dihydroartemisinin-isatin hybrids (5a-e and 6a-j) linked with three-carbon were designed, synthesized. The antiproliferative activity against lung cancer cell lines including drug-sensitive A549, doxorubicin-resistant A549 (A549/DOX) and cisplatin-resistant A549 (A549/DDP) lung cancer cell lines was tested. The cytotocivity towards normal lung epithelial BEAS-2B cell line was also investigated. From the structure-activity relationship (SAR), it was found that hydrogen bond donors (especially hydroxime and thiosemicarbazide) at C-3 position and electron-withdrawing groups (fluoro and chloro) at C-5 position of isatin moiety were beneficial for the activity. A significant part of them (half maximal inhibitory concentration/IC50: 5.72–55.52 μM) demonstrated considerable antiproliferative activity, and the activity was superior to that of dihydroartemisinin (IC50: 69.42–88.03 μM) and artemisinin (IC50: &gt;100 μM). In particular, two hybrids 6a, e (IC50: 5.72–9.84 μM) were not inferior to doxorubicin (IC50: 4.06 μM) and cisplatin (IC50: 9.38 μM) against drug-sensitive A549 cells and were more potent than doxorubicin (IC50: 54.32 and 15.10 μM) and cisplatin (IC50: 19.74 and 66.89 μM) against multidrug-resistant A549/DOX and A549/DDP lung cancer cell lines. In addition, hybrids 6a, e (IC50: &gt;100 μM) showed no toxicity towards BEAS-2B cells, proving their excellent selectivity profile. Furthermore, hybrid 6a also possessed good stability in mouse and human microsomes, as well as excellent pharmacokinetic properties. Accordingly, hybrid 6a could serve as a promising anti-lung cancer chemotherapeutic candidate for further preclinical evaluations.
Born Under COVID-19 Pandemic Conditions: Infant Regulatory Problems and Maternal Mental Health at 7 Months Postpartum
Authors: Perez Anna , Göbel Ariane , Stuhrmann Lydia Yao , Schepanski Steven , Singer Dominique , Bindt Carola , Mudra Susanne 
Published: January 2022

BackgroundThe SARS-COVID-19 pandemic and its associated disease control restrictions have in multiple ways affected families with young children, who may be especially vulnerable to mental health problems. Studies report an increase in perinatal parental distress as well as symptoms of anxiety or depression in children during the pandemic. Currently, little is known about the impact of the pandemic on infants and their development. Infant regulatory problems (RPs) have been identified as early indicators of child socio-emotional development, strongly associated with maternal mental health and the early parent–infant interaction. Our study investigates whether early parenthood under COVID-19 is associated with more maternal depressive symptoms and with a perception of their infants as having more RPs regarding crying/fussing, sleeping, or eating, compared to mothers assessed before the pandemic.MethodsAs part of a longitudinal study, 65 women who had given birth during the first nationwide disease control restrictions in Northern Germany, were surveyed at 7 months postpartum and compared to 97 women assessed before the pandemic. RPs and on maternal depressive symptoms were assessed by maternal report. Number of previous children, infant negative emotionality, and perceived social support were assessed as control variables.ResultsCompared to the control cohort, infants born during the COVID-19 pandemic and those of mothers with higher depressive symptoms were perceived as having more sleeping and crying, but not more eating problems. Regression-based analyses showed no additional moderating effect of parenthood under COVID-19 on the association of depressive symptoms with RPs. Infant negative emotionality was positively, and number of previous children was negatively associated with RPs.LimitationsDue to the small sample size and cross-sectional assessment, the possibility for more complex multivariate analysis was limited. The use of parent-report questionnaires to assess infant RPs can support but not replace clinical diagnosis.ConclusionsThe pandemic conditions affecting everyday life may have a long-term influence on impaired infant self- and maternal co-regulation and on maternal mental health. This should be addressed in peripartum and pediatric care. Qualitative and longitudinal studies focusing on long-term parental and infant outcomes under ongoing pandemic conditions are encouraged.
Cortical Inhibition and Plasticity in Major Depressive Disorder
Authors: Castricum Jesminne , Birkenhager Tom K. , Kushner Steven A. , Elgersma Ype , Tulen Joke H. M. 
Published: January 2022

BackgroundMajor depressive disorder (MDD) is a severe psychiatric disorder that is associated with various cognitive impairments, including learning and memory deficits. As synaptic plasticity is considered an important mechanism underlying learning and memory, deficits in cortical plasticity might play a role in the pathophysiology of patients with MDD. We used Transcranial Magnetic Stimulation (TMS) to assess inhibitory neurotransmission and cortical plasticity in the motor cortex of MDD patients and controls.MethodsWe measured the cortical silent period (CSP) and short interval cortical inhibition (SICI), as well as intermittent theta-burst stimulation (iTBS), in 9 drug-free MDD inpatients and 18 controls.ResultsThe overall response to the CSP, SICI, and iTBS paradigms was not significantly different between the patient and control groups. iTBS induction resulted in significant potentiation after 20 mins in the control group (t(17) = −2.8, p = 0.01), whereas no potentiation was observed in patients.ConclusionsPotentiation of MEP amplitudes was not observed within the MDD group. No evidence was found for medium-to-large effect size differences in CSP and SICI measures in severely depressed drug-free patients, suggesting that reduced cortical inhibition is unlikely to be a robust correlate of the pathophysiological mechanism in MDD. However, these findings should be interpreted with caution due to the high inter-subject variability and the small sample size.SignificanceThese findings advance our understanding of neurophysiological functioning in drug-free severely depressed inpatients.