bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of home-based transcranial direct current stimulation in cognitive performance in fibromyalgia: A randomized, double-blind sham-controlled trial
Authors: Serrano Paul Vicuña , Zortea Maxciel , Alves Rael Lopes , Beltrán Gerardo , Bavaresco Cibely , Ramalho Leticia , Alves Camila Fernanda da Silveira , Medeiros Liciane , Sanches Paulo R. S. , Silva Danton P. , Lucena da Silva Torres Iraci , Fregni Felipe , Caumo Wolnei 
Published: November 2022

BackgroundTranscranial Direct Current Stimulation (tDCS) is a promising approach to improving fibromyalgia (FM) symptoms, including cognitive impairment. So, we evaluated the efficacy and safety of home-based tDCS in treating cognitive impairment. Besides, we explored if the severity of dysfunction of the Descendant Pain Modulation System (DPMS) predicts the tDCS effect and if its effect is linked to changes in neuroplasticity as measured by the brain-derived neurotrophic factor (BDNF).MethodsThis randomized, double-blind, parallel, sham-controlled clinical trial, single-center, included 36 women with FM, aged from 30 to 65 years old, assigned 2:1 to receive a-tDCS (n = 24) and s-tDCS (n = 12). The primary outcome was the Trail Making Test’s assessment of executive attention, divided attention, working memory (WM), and cognitive flexibility (TMT-B-A). The secondary outcomes were the Controlled Oral Word Association Test (COWAT), the WM by Digits subtest from the Wechsler Adult Intelligence Scale (WAIS-III), and quality of life. Twenty-minute daily sessions of home-based tDCS for 4 weeks (total of 20 sessions), 2 mA anodal-left (F3) and cathodal-right (F4) prefrontal stimulation with 35 cm2 carbon electrodes.ResultsGLM showed a main effect for treatment in the TMT-B-A [Wald χ2 = 6.176; Df = 1; P = 0.03]. The a-tDCS improved cognitive performance. The effect size estimated by Cohen’s d at treatment end in the TMT-B-A scores was large [–1.48, confidence interval (CI) 95% = –2.07 to–0.90]. Likewise, the a-tDCS effects compared to s-tDCS improved performance in the WM, verbal and phonemic fluency, and quality-of-life scale. The impact of a-tDCS on the cognitive tests was positively correlated with the reduction in serum BDNF from baseline to treatment end. Besides, the decrease in the serum BDNF was positively associated with improving the quality of life due to FM symptoms.ConclusionThese findings revealed that daily treatment with a home-based tDCS device over l-DLPFC compared to sham stimulation over 4 weeks improved the cognitive impairment in FM. The a-tDCS at home was well-tolerated, underlining its potential as an alternative treatment for cognitive dysfunction. Besides, the a-tDCS effect is related to the severity of DPMS dysfunction and changes in neuroplasticity state.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT03843203].
Short-term high-fat diet alters the mouse brain magnetic resonance imaging parameters consistently with neuroinflammation on males and metabolic rearrangements on females. A pre-clinical study with an optimized selection of linear mixed-effects models
Authors: Campillo Basilio Willem , Galguera David , Cerdan Sebastian , López-Larrubia Pilar , Lizarbe Blanca 
Published: November 2022

IntroductionHigh-fat diet (HFD) consumption is known to trigger an inflammatory response in the brain that prompts the dysregulation of energy balance, leads to insulin and leptin resistance, and ultimately obesity. Obesity, at the same, has been related to cerebral magnetic resonance imaging (MRI) alterations, but the onset of HFD-induced neuroinflammation, however, has been principally reported on male rodents and by ex vivo methods, with the effects on females and the origin of MRI changes remaining unassessed.MethodsWe characterized the onset and evolution of obesity on male and female mice during standard or HFD administration by physiological markers and multiparametric MRI on four cerebral regions involved in appetite regulation and energy homeostasis. We investigated the effects of diet, time under diet, brain region and sex by identifying their significant contributions to sequential linear mixed-effects models, and obtained their regional neurochemical profiles by high-resolution magic angle spinning spectroscopy.ResultsMale mice developed an obese phenotype paralleled by fast increases in magnetization transfer ratio values, while females delayed the obesity progress and showed no MRI-signs of cerebral inflammation, but larger metabolic rearrangements on the neurochemical profile.DiscussionOur study reveals early MRI-detectable changes compatible with the development of HFD-induced cerebral cytotoxic inflammation on males but suggest the existence of compensatory metabolic adaptations on females that preclude the corresponding detection of MRI alterations.
Nigral volumetric and microstructural measures in individuals with scans without evidence of dopaminergic deficit
Authors: Langley Jason , Hwang Kristy S. , Hu Xiaoping P. , Huddleston Daniel E. 
Published: November 2022

IntroductionStriatal dopamine transporter (DAT) imaging using 123I-ioflupane single photon positron emitted computed tomography (SPECT) (DaTScan, GE) identifies 5−20% of newly diagnosed Parkinson’s disease (PD) subjects enrolling in clinical studies to have scans without evidence of dopaminergic deficit (SWEDD). These individuals meet diagnostic criteria for PD, but do not clinically progress as expected, and they are not believed to have neurodegenerative Parkinsonism. Inclusion of SWEDD participants in PD biomarker studies or therapeutic trials may therefore cause them to fail. DaTScan can identify SWEDD individuals, but it is expensive and not widely available; an alternative imaging approach is needed. Here, we evaluate the use of neuromelanin-sensitive, iron-sensitive, and diffusion contrasts in substantia nigra pars compacta (SNpc) to differentiate SWEDD from PD individuals.MethodsNeuromelanin-sensitive, iron-sensitive, and diffusion imaging data for SWEDD, PD, and control subjects were downloaded from the Parkinson’s progression markers initiative (PPMI) database. SNpc volume, SNpc iron (R2), and SNpc free water (FW) were measured for each participant.ResultsSignificantly smaller SNpc volume was seen in PD as compared to SWEDD (P &lt; 10–3) and control (P &lt; 10–3) subjects. SNpc FW was elevated in the PD group relative to controls (P = 0.017). No group difference was observed in SNpc R2.ConclusionIn conclusion, nigral volume and FW in the SWEDD group were similar to that of controls, while a reduction in nigral volume and increased FW were observed in the PD group relative to SWEDD and control participants. These results suggest that these MRI measures should be explored as a cost-effective alternative to DaTScan for evaluation of the nigrostriatal system.
Higher blood cotinine level is associated with worse cognitive functioning in non-smoking older adults
Authors: Fu Zhenmei , Qi Guiye , Qu Zhe , Lin Xuechun , Xu Li , Shen Biyu , Dong Fanghong , Ge Song 
Published: November 2022

IntroductionSecondhand smoke (SHS) is common in older adults; however, its cognitive effect is unclear. We aimed to examine the association between serum cotinine level and cognitive functioning among non-smoking older adults.Materials and methodsA total of 2,703 older adults aged 60 and above from the National Health and Nutrition Examination (NHANES) Survey 2011–2014 were included. Serum cotinine level was analyzed in the laboratory. A level ≤10 ng/ml and a response of “no” to the question “Do you currently smoke?” were used to select non-smokers. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer’s disease Word Learning subtest (CERAD-WL) immediate and delayed recall tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariable linear regression models were constructed to examine the association between serum cotinine level quartile and test-specific and global cognition z scores adjusting for age, race/ethnicity, education, depressive symptoms, body mass index, alcohol use, smoking history, prevalent coronary heart disease (CHD), stroke, and systolic blood pressure.ResultsAbout half of the participants (mean age 70.5 years) were female (53.6%), non-Hispanic White (48.3%), and completed some college and above (50.2%). Multivariate linear regressions with a reference group being those in the 1st quantile (lowest) showed that participants in the 4th quartile (highest) of serum cotinine level had lower immediate recall [β = −0.16, 95% confidence interval (CI) = −0.29, −0.03], AFT (β = −0.19, 95% CI = −0.33, −0.05), DSST (β = −0.27, 95% CI = −0.39, −0.15), and global cognition (β = −0.26, 95% CI = −0.39, −0.14) z scores. Participants in the 3rd quartile had lower immediate recall (β = −0.16, 95% CI = −0.30, −0.02) and global cognition (β = −0.16, 95% CI = −0.29, −0.02) z scores. Participants in the 2nd quartile had lower delayed recall z scores (β = −0.16, 95% CI = −0.29, −0.02).ConclusionHigher serum cotinine level was associated with worse cognitive functioning in non-smoking older adults. Prevention and reduction of SHS in older adults may help protect their cognitive functioning.
Clinical use and adjustment of ultrasound elastography for breast lesions followed WFUMB guidelines and recommendations in the real world
Authors: Tang Lei , Wang Yuqun , Chen Pingping , Chen Man , Jiang Lixin 
Published: November 2022

ObjectiveThis study aimed to explore the value of strain elastography (SE) and shear wave elastography (SWE) following the World Federation of Ultrasound in Medicine and Biology (WFUMB) guidelines and recommendations in the real world in distinguishing benign and malignant breast lesions and reducing biopsy of BI-RADS (Breast Imaging Reporting and Data System) 4a lesions.MethodsThis prospective study included 274 breast lesions. The elastography score (ES) by the Tsukuba score, the strain ratio (SR) for SE, and Emax for SWE of the lesion(A) and the regions(A’) included the lesion and the margin (0.5-5 mm) surrounding the lesion were measured. The sensitivity, specificity, and AUC were calculated and compared by the cutoff values recommended by WFUMB guidelines.ResultsWhen scores of 1 to 3 were classified as probably benign by WFUMB recommendation, the ES was significantly higher in malignant lesions compared to benign lesions (p &lt; 0.05) in all lesions. For the cohort by size &gt;20 mm, the sensitivity was 100%, and the specificity was 45.5%. ES had the highest AUC: 0.79(95% CI 0.72-0.86) with a sensitivity of 96.2%, and a specificity of 61.8% for the cohort by size ≤20 mm. For the Emax-A’-S2.5mm, when the high stiffness would be considered with Emax above 80 kPa in SWE, the malignant lesions were diagnosed with a sensitivity of 95.8%, a specificity of 43.3% for all lesions, a sensitivity of 88.5% for lesions with size ≤20 mm, and sensitivity of 100.0% for lesions with size &gt;20 mm. In 84 lesions of BI-RADS category 4a, if category 4a lesions with ES of 1-3 points or Emax-A’-S2.5 less than 80 kPa could be downgraded to category 3, 52 (61.9%) lesions could be no biopsy, including two malignancies. If category 4a lesions with ES of 1-3 points and Emax-A’-S2.5 less than 80kPa could be downgraded to category 3, 23 (27.4%) lesions could be no biopsy, with no malignancy.ConclusionsThe elastography score for SE and Emax-A’ for SWE after our modification were beneficial in the diagnosis of breast cancer. The combination of SWE and SE could effectively reduce the biopsy rate of BI-RADS category 4a lesions.
Safety and efficacy of radiotherapy combined with lenvatinib plus PD-1 inhibitors as neo-adjuvant therapy in hepatocellular carcinoma with portal vein thrombus: protocol of an open-label, single-arm, prospective, multi-center phase I trial
Authors: Li Guangxin , Shu Bin , Zheng Zhuozhao , Yin Hongfang , Zhang Chen , Xiao Ying , Yang Yanmei , Yan Zhe , Zhang Xiaofei , Yang Shizhong , Li Gong , Dong Jiahong 
Published: November 2022

BackgroundSurgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported.MethodsThis open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS).DiscussionThis trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT.Clinical trial registrationhttps://clinicaltrials.gov/, identifier (NCT05225116).
Associations between disrupted functional brain network topology and cognitive impairment in patients with rectal cancer during chemotherapy
Authors: Guo Yesong , Liu Siwen , Yan Fei , Yin Na , Ni Jie , Li Chenchen , Pan Xuan , Ma Rong , Wu Jianzhong , Li Shengwei , Li Xiaoyou 
Published: November 2022

IntroductionCognitive impairment has been identified in patients with non-central nervous system cancer received chemotherapy. Chemotherapy-induced changes in the brain are considered as the possible causes of the cognitive deficits of patients. This study aimed to explore chemotherapy-related functional brain changes and cognitive impairment in rectal cancer (RC) patients who had just finished chemotherapy treatment.MethodsIn this study, RC patients after chemotherapy (on the day patients received the last dose of chemotherapy) (n=30) and matched healthy controls (HCs) (n=30) underwent cognitive assessments, structural magnetic resonance imaging (MRI) and resting-state functional MRI. The functional brain networks were constructed by thresholding the partial correlation matrices of 90 brain regions in the Anatomical Automatic Labeling template and the topologic properties were evaluated by graph theory analysis. Moreover, correlations between altered topological measures and scores of cognitive scales were explored in the patient group.ResultsCompared with HCs, RC patients had lower scores of cognitive scales. The functional brain network had preserved small-world topological features but with a tendency towards higher path length in the whole network. In addition, patients had decreased nodal global efficiency (Eglo(i)) in the left superior frontal gyrus (dorsolateral), superior frontal gyrus (orbital part), inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part) and right inferior frontal gyrus (triangular part). Moreover, values of Eglo(i) in the superior and inferior frontal gyrus were positively associated with cognitive function in the patient group.ConclusionThese results suggested that cognitive impairment was associated with disruptions of the topological organization in functional brain networks of RC patients who had just finished chemotherapy, which provided new insights into the pathophysiology underlying acute effects of chemotherapy on cognitive function.
Neoadjuvant therapy in pancreatic neuroendocrine neoplasms: A systematic review and meta-analysis
Authors: Li Yongzheng , Fan Zhiyao , Zhang Feifei , Yang Jian , Shi Ming , Liu Shujie , Meng Yufan , Zhan Hanxiang 
Published: November 2022

Background and ObjectivesNeoadjuvant therapy plays an increasingly important role in pancreatic neuroendocrine neoplasms (pNENs), but the systematic evaluation of its efficacy is still lacking. The purpose of this study is to explore the role of neoadjuvant therapy in pNENs.MethodsWe systematically reviewed the literatures published online until October 1, 2021. Meta-analysis was conducted to generate proportion with 95% confidence intervals (95% CI) for tumor response, resection rate, R0 resection rate and survival time.ResultsNine studies with 468 patients were involved in the systematic review. None of these patients met complete response (CR). Furthermore, 43.6% (95% CI [18.1, 69.0]) patients were expected to achieve partial response (PR), 51.3% (95% CI [27.9, 78.3]) to stable disease (SD), and 4.3% (95% CI [0.7, 7.9]) to progressive disease (PD). The estimate resection rate and R0 resection rate after neoadjuvant therapy were 68.2% (95% CI [44.5, 91.9]) and 60.2% (95% CI [53.5, 66.9]), respectively. There was no significant difference in resection rate between different chemotherapy regimens (41.67% vs 33.93%, P=0.453), as well as R0 resection rate (62.50% vs 68.30%, P=0.605). In terms of objective response rate (ORR), there was no significant difference between CAPTEM and FAS (41.67% vs 33.93%, P=0.453), while PRRT showed a higher ORR compared with chemotherapy, although there was also no statistical difference (49.06% vs 36.96%, P=0.154).ConclusionNeoadjuvant therapies could reduce the tumor size and stage of some borderline resectable or unresectable pNENs, and give some patients the chance of radical resection. However, according to the current data, the best treatment regimen for pNENs neoadjuvant therapy is still unknown.
Suicide risk among female breast cancer survivors: A population–based study
Authors: Shi Jian , Yang Yongping , Guo Yu , Ren Wu 
Published: November 2022

BackgroundBreast cancer is the most common cancer type for females and has the highest relative number of suicide cases among female-specific cancers. This study aimed to demonstrate suicide rates and changing trends and to identify risk factors for suicide among female breast cancer survivors.MethodsData were derived from the surveillance, epidemiology, and end results database for women diagnosed with breast cancer from 2000 to 2017. Mortality rate and standardized mortality ratios (SMRs) were calculated to describe the incidence rate and trend of suicide among female breast cancer survivors. Gray’s test and cumulative incidence function (CIF) curves were used to assess difference of cumulative suicide incidence in subgroups. Multivariate Fine-Gray competing risk model was used to identify risk factors for individual survivors and nomogram model was used to estimate the probability of suicide.ResultThere were 414 suicide cases among 638,547 female breast cancer survivors observed for 5,079,194 person-years, and the suicide rate and SMRs gradually increased with the year of diagnosis. Female breast cancer survivors had a higher risk of suicide than the general population (SMR = 1.19; 95% CI (1.08–1.31)). Based on the result of Fine-Gray competing risk models, age group (50-70 vs &lt;50: HR=0.65, 95% CI:0.52-0.80; &gt;70 vs &lt;50: HR=0.22, 95% CI:0.15-0.32), race/ethnicity (black vs white: HR= 0.20, 95% CI: 0.11-0.36; other race vs white: HR= 0.67, 95% CI: 0.46-0.97), marital status (separated vs married: HR= 1.50, 95% CI: 1.16-1.94; single vs married: HR= 1.70, 95% CI: 1.31-2.20), stage (distant vs regional: HR= 0.30, 95% CI: 0.14-0.63), radiotherapy (Yes vs No/Unknown: HR= 0.62, 95% CI: 0.49-0.77), and molecular subtypes (HER-2 vs Luminal B (HR= 2.53, 95% CI: 1.10-5.82), TNBC vs Luminal B (HR= 2.11, 95% CI: 1.01-4.42)) were independent predictors of suicide among female breast cancer patients. A nomogram was constructed to predict the suicide probability for individual survivors with a C-index of 0.62 (95%CI: 0.59-0.66).ConclusionFemale breast cancer survivors with younger age (less than 50 years old), white race, unmarried status, regional stage, HER-2 or TNBC subtype, and no radiotherapy performed were more likely to commit suicide. The clinicians and family members should pay more attention to patients with high risk factors of suicide to decrease the mortality rate.
Synergy of Losartan and chemotherapy for patients with cholangiocarcinoma: A propensity score-matched analysis
Authors: Li Qing , Chang Zhenyu , Wang Tianyi , Liu Bing , Wang Ximin , Ge Xin-Yu , Yang Tao , Liu Qu , Wang Wei 
Published: November 2022

BackgroundCholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelial cells that no obvious clinical symptoms and specific clinical manifestations are shown in the early stage of CCA.MethodsPropensity score matching (PSM) is a quasi-experimental method in which this study used. Patients were enrolled from Department of General surgery, First Affiliated Hospital of Jinzhou Medical University from March 1, 2010, to December 30, 2019. Totally 170 patients with CCA were enrolled in this study.ResultsWe performed a 1:2 PSM study and found that patients with losartan group showed both comparable median OS (overall survival) and TTR (time to recurrence) to those in the patients without losartan group before PSM. However, after matching, patients with losartan group showed favorable median OS and TTR than those in the patients without losartan group. Then we performed Cox proportional hazards models and found that patients with losartan was an independent factor after multivariable analysis for patients with CCA. Furtherly, we sequenced serial cfDNA were performed in 10 patients with losartan and 9 patients without losartan who received adjuvant chemotherapy after tumor resection. These results showed that the treatment of losartan was related with tumor microenvironment and could be potentially useful to combine the immunotherapy for patients with CCA.ConclusionIn conclusion, this study demonstrated that the treatment of losartan could increase the efficacy of adjuvant chemotherapy and identified as an independent survival predictor for patients with CCA. Moreover, losartan could be potentially useful to combine the immunotherapy for patients with CCA.