bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age and Anterior Basal Forebrain Volume Predict the Cholinergic Deficit in Patients with Mild Cognitive Impairment due to Alzheimer’s Disease
Authors: Richter Nils , David Lara-Sophia , Grothe Michel J. , Teipel Stefan , Dietlein Markus , Tittgemeyer Marc , Neumaier Bernd , Fink Gereon R. , Onur Oezguer A. , Kukolja Juraj 
Published: January 2022

Background: Early and severe neuronal loss in the cholinergic basal forebrain is observed in Alzheimer’s disease (AD). To date, cholinomimetics play a central role in the symptomatic treatment of AD dementia. Although basic research indicates that a cholinergic deficit is present in AD before dementia, the efficacy of cholinomimetics in mild cognitive impairment (MCI) remains controversial. Predictors of cholinergic impairment could guide individualized therapy. Objective: To investigate if the extent of the cholinergic deficit, measured using positron emission tomography (PET) and the tracer 11C-N-methyl-4-piperidyl acetate (MP4A), could be predicted from the volume of cholinergic basal forebrain nuclei in non-demented AD patients. Methods: Seventeen patients with a high likelihood of MCI due to AD and 18 age-matched cognitively healthy adults underwent MRI-scanning. Basal forebrain volume was assessed using voxel-based morphometry and a cytoarchitectonic atlas of cholinergic nuclei. Cortical acetylcholinesterase (AChE) activity was measured using MP4A-PET. Results: Cortical AChE activity and nucleus basalis of Meynert (Ch4 area) volume were significantly decreased in MCI. The extent of the cholinergic deficit varied considerably across patients. Greater volumes of anterior basal forebrain nuclei (Ch1/2 area) and younger age (Spearman’s rho (17)  = –0.596, 95% -CI [–0.905, –0.119] and 0.593, 95% -CI [0.092, 0.863])) were associated with a greater cholinergic deficit. Conclusion: Data suggest that less atrophy of the Ch1/2 area and younger age are associated with a more significant cholinergic deficit in MCI due to AD. Further investigations are warranted to determine if the individual response to cholinomimetics can be inferred from these measures.
Real-World Data of Anticoagulant Treatment in Non-valvular Atrial Fibrillation
Authors: Calderon Jose Miguel , Martinez Fernando , Diaz Javier , Fernandez Antonio , Sauri Inmaculada , Uso Ruth , Trillo Jose Luis , Vela Sara , Bea Carlos , Redon Josep , Forner Maria Jose 
Published: January 2022

AimsTo assess the impact of anticoagulant treatment on risk for stroke and all-cause mortality of patients with atrial fibrillation using real-world data (RWD).MethodsPatients with prevalent or incident atrial fibrillation were selected throughout a study period of 5 years. Stroke, transitory ischemic attack, hemorrhagic stroke, and all-cause mortality were identified in the claims of the electronic health records (EHRs). Subjects were classified according to the anticoagulant treatment in four groups: untreated, vitamin K antagonists (VKAs), New Oral Anticoagulants (NOACs), and antiplatelet (AP). Risk of events and protection with anticoagulant therapy were calculated by Cox proportional hazard models adjusted by potential confounders.ResultsFrom a total population of 3,799,884 patients older than 18,123,227 patients with incident or prevalent atrial fibrillation (AF) were identified (mean age 75.2 ± 11.5 years old; 51.9% women). In a follow-up average of 3.2 years, 17,113 patients suffered from an ischemic stroke and transitory ischemic attack (TIA), 780 hemorrhagic stroke, and 42,558 all-cause death (incidence of 46, 8, 2, and 120 per 1,000 patients/year, respectively). Among CHA2DS2, VASc Score equal or &gt;2, 11.7% of patients did not receive any anticoagulant therapy, and a large proportion of patients, 47%, shifted from one treatment to another. Although all kinds of anticoagulant treatments were significantly protective against the events and mortality, NOAC treatment offered significantly better protection compared to the other groups.ConclusionIn the real world, the use of anticoagulant treatments is far from guidelines recommendations and is characterized by variability in their use. NOACs offered better protection compared with VKAs.
Cardiovascular Phenotypes Profiling for L-Transposition of the Great Arteries and Prognosis Analysis
Authors: He Qiyu , Shen Huayan , Shao Xinyang , Chen Wen , Wu Yafeng , Liu Rui , Li Shoujun , Zhou Zhou 
Published: January 2022

ObjectivesCongenitally corrected transposition of the great arteries (ccTGA) is a rare and complex congenital heart disease with the characteristics of double discordance. Enormous co-existed anomalies are the culprit of prognosis evaluation and clinical decision. We aim at delineating a novel ccTGA clustering modality under human phenotype ontology (HPO) instruction and elucidating the relationship between phenotypes and prognosis in patients with ccTGA.MethodsA retrospective review of 270 patients diagnosed with ccTGA in Fuwai hospital from 2009 to 2020 and cross-sectional follow-up were performed. HPO-instructed clustering method was administered in ccTGA risk stratification. Kaplan-Meier survival, Landmark analysis, and cox regression analysis were used to investigate the difference of outcomes among clusters.ResultsThe median follow-up time was 4.29 (2.07–7.37) years. A total of three distinct phenotypic clusters were obtained after HPO-instructed clustering with 21 in cluster 1, 136 in cluster 2, and 113 in cluster 3. Landmark analysis revealed significantly worse mid-term outcomes in all-cause mortality (p = 0.021) and composite endpoints (p = 0.004) of cluster 3 in comparison with cluster 1 and cluster 2. Multivariate analysis indicated that pulmonary arterial hypertension (PAH), atrioventricular septal defect (AVSD), and arrhythmia were risk factors for composite endpoints. Moreover, the surgical treatment was significantly different among the three groups (p &lt; 0.001) and surgical strategies had different effects on the prognosis of the different phenotypic clusters.ConclusionsHuman phenotype ontology-instructed clustering can be a potentially powerful tool for phenotypic risk stratification in patients with complex congenital heart diseases, which may improve prognosis prediction and clinical decision.
Chromosome-Scale Genome of Masked Palm Civet (Paguma larvata) Shows Genomic Signatures of Its Biological Characteristics and Evolution
Authors: Lan Tianming , Fang Dongming , Li Haimeng , Sahu Sunil Kumar , Wang Qing , Yuan Hao , Zhu Yixin , Yang Zipeng , Zhang Le , Yang Shangchen , Lu Haorong , Han Lei , Zhang Shaofang , Yu Jieyao , Mahmmod Yasser S. , Xu Yanchun , Hua Yan , He Fengping , Yuan Ziguo , Liu Huan 
Published: January 2022

The masked palm civet (Paguma larvata) is a small carnivore with distinct biological characteristics, that likes an omnivorous diet and also serves as a vector of pathogens. Although this species is not an endangered animal, its population is reportedly declining. Since the severe acute respiratory syndrome (SARS) epidemic in 2003, the public has been particularly concerned about this species. Here, we present the first genome of the P. larvata, comprising 22 chromosomes assembled using single-tube long fragment read (stLFR) and Hi-C technologies. The genome length is 2.41 Gb with a scaffold N50 of 105.6 Mb. We identified the 107.13 Mb X chromosome and one 1.34 Mb Y-linked scaffold and validated them by resequencing 45 P. larvata individuals. We predicted 18,340 protein-coding genes, among which 18,333 genes were functionally annotated. Interestingly, several biological pathways related to immune defenses were found to be significantly expanded. Also, more than 40% of the enriched pathways on the positively selected genes (PSGs) were identified to be closely related to immunity and survival. These enriched gene families were inferred to be essential for the P. larvata for defense against the pathogens. However, we did not find a direct genomic basis for its adaptation to omnivorous diet despite multiple attempts of comparative genomic analysis. In addition, we evaluated the susceptibility of the P. larvata to the SARS-CoV-2 by screening the RNA expression of the ACE2 and TMPRSS2/TMPRSS4 genes in 16 organs. Finally, we explored the genome-wide heterozygosity and compared it with other animals to evaluate the population status of this species. Taken together, this chromosome-scale genome of the P. larvata provides a necessary resource and insights for understanding the genetic basis of its biological characteristics, evolution, and disease transmission control.
Two-Dimensional Hexagonal Boron Nitride Nanosheets as Lateral Heat Spreader With High Thermal Conductivity
Authors: Kong Xiangdong , Li Linhong , Li Maohua , Xia Juncheng , Wang Yandong , Wei Xianzhe , Xiong Shaoyang , Gong Ping , Pan Zhongbin , Wu Xinfeng , Cai Tao , Nishimura Kazuhito , Lin Cheng-Te , Jiang Nan , Yu Jinhong 
Published: January 2022

A highly thermally conductive heat spreader for applications in electronic devices is becoming increasingly demanding, and therefore the removal of excess heat requires an efficient heat dissipating device. Boron nitride nanosheets (BNNSs) were prepared as thermally conductive fillers using hexagonal boron nitride (h-BN) powder as raw material by a water exfoliation method. A composite film was prepared by vacuum filtration using cellulose nanofibers (CNFs) as the substrate with an in-plane thermal conductivity (TC) of 82.4 W m−1 K−1, thermal conductivity enhancement increasing by 9,486% compared to pure cellulose film. Thus, CNF/BNNS composite films are promising as effective thermal interface materials (TIMs) in electronic devices and electronic component applications.
Velvet Antler Peptides Reduce Scarring via Inhibiting the TGF-β Signaling Pathway During Wound Healing
Authors: Zhang Guokun , Wang Dongxu , Ren Jing , Sun Hongmei , Li Jiping , Wang Shengnan , Shi Liyan , Wang Zhen , Yao Mengjie , Zhao Haiping , Li Chunyi 
Published: January 2022

AimScar formation generally occurs in cutaneous wound healing in mammals, mainly caused by myofibroblast aggregations, and currently with few effective treatment options. However, the pedicle wound (about 10 cm in diameter) of the deer can initiate regenerative healing, which has been found to be achieved via paracrine factors from the internal tissues of antlers.MethodsEnzymatically digested velvet antler peptides (EVAP) were prepared along with other types of antler extracts as the controls. The effects of EVAP on healing of full-thickness skin wounds were evaluated using rats in vivo, and on myofibroblast transdifferentiation tested using transforming growth factor-β1 (TGF-β1)-induced human dermal fibroblasts in vitro.ResultsEVAP significantly accelerated the wound healing rate, reduced scar formation, and improved the healing quality, including promoted angiogenesis, increased number of skin appendages (hair follicles and sebaceous glands) and improved the distribution pattern of collagen fibers (basket-wave like) in the healed tissue. Moreover, EVAP significantly down-regulated the expression levels of genes pro- scar formation (Col1a2 and TGF-β1), and up-regulated the expression levels of genes anti-scar formation (Col3a1 and TGF-β3), and suppressed the excessive transdifferentiation of myofibroblasts and the formation of collagen I in vivo and in vitro. Furthermore, we found these effects were highly likely achieved by inhibiting the TGF-β signaling pathway, evidenced by decreased expression levels of the related genes, including TGF-β1, Smad2, p-Smad2, α-SMA, and collagen I.ConclusionsEVAP may be a promising candidate to be developed as a clinic drug for regenerative wound healing.
Dual-Task nTMS Mapping to Visualize the Cortico-Subcortical Language Network and Capture Postoperative Outcome—A Patient Series in Neurosurgery
Authors: Ohlerth Ann-Katrin , Bastiaanse Roelien , Nickels Lyndsey , Neu Beate , Zhang Wei , Ille Sebastian , Sollmann Nico , Krieg Sandro M. 
Published: January 2022

BackgroundPerioperative assessment of language function in brain tumor patients commonly relies on administration of object naming during stimulation mapping. Ample research, however, points to the benefit of adding verb tasks to the testing paradigm in order to delineate and preserve postoperative language function more comprehensively. This research uses a case series approach to explore the feasibility and added value of a dual-task protocol that includes both a noun task (object naming) and a verb task (action naming) in perioperative delineation of language functions.Materials and MethodsSeven neurosurgical cases underwent perioperative language assessment with both object and action naming. This entailed preoperative baseline testing, preoperative stimulation mapping with navigated Transcranial Magnetic Stimulation (nTMS) with subsequent white matter visualization, intraoperative mapping with Direct Electrical Stimulation (DES) in 4 cases, and postoperative imaging and examination of language change.ResultsWe observed a divergent pattern of language organization and decline between cases who showed lesions close to the delineated language network and hence underwent DES mapping, and those that did not. The latter displayed no new impairment postoperatively consistent with an unharmed network for the neural circuits of both object and action naming. For the cases who underwent DES, on the other hand, a higher sensitivity was found for action naming over object naming. Firstly, action naming preferentially predicted the overall language state compared to aphasia batteries. Secondly, it more accurately predicted intraoperative positive language areas as revealed by DES. Thirdly, double dissociations between postoperatively unimpaired object naming and impaired action naming and vice versa indicate segregated skills and neural representation for noun versus verb processing, especially in the ventral stream. Overlaying postoperative imaging with object and action naming networks revealed that dual-task nTMS mapping can explain the drop in performance in those cases where the network appeared in proximity to the resection cavity.ConclusionUsing a dual-task protocol for visualization of cortical and subcortical language areas through nTMS mapping proved to be able to capture network-to-deficit relations in our case series. Ultimately, adding action naming to clinical nTMS and DES mapping may help prevent postoperative deficits of this seemingly segregated skill.
Management of Spinal Bone Metastases With Radiofrequency Ablation, Vertebral Reinforcement and Transpedicular Fixation: A Retrospective Single-Center Case Series
Authors: Giammalva Giuseppe Roberto , Costanzo Roberta , Paolini Federica , Benigno Umberto Emanuele , Porzio Massimiliano , Brunasso Lara , Basile Luigi , Gulì Carlo , Pino Maria Angela , Gerardi Rosa Maria , Messina Domenico , Umana Giuseppe Emmanuele , Palmisciano Paolo , Scalia Gianluca , Graziano Francesca , Visocchi Massimiliano , Iacopino Domenico Gerardo , Maugeri Rosario 
Published: January 2022

Spine is a frequent site of bone metastases, with a 8.5 months median survival time after diagnosis. In most cases treatment is only palliative. Several advanced techniques can ensure a better Quality of Life (QoL) and increase life expectancy. Radiofrequency ablation (RFA) uses alternating current to produce local heating and necrosis of the spinal lesion, preserving the healthy bone. RFA is supported by vertebral reinforcement through kyphoplasty and vertebroplasty in order to stabilize the fracture with polymethylmethacrylate (PMMA) injection, restoring vertebral body height and reducing the weakness of healthy bone. The aim of this study is to demonstrate the efficacy and advantages of RFA plus vertebral reinforcement through PMMA vertebroplasty and fixation in patients affected by bone spinal metastases. We retrospectively analyzed 54 patients with thoraco-lumbar metastatic vertebral fractures admitted to our Unit between January 2014 and June 2020. Each patient underwent RFA followed by PMMA vertebroplasty and transpedicle fixation. We evaluated pain relief through the Visual Analogue Scale (VAS) Score and PMMA vertebral filling based on the mean Saliou filling score. Analysis of variance (ANOVA) was used to test pain relief with statistical significance for p&lt;0.05. A total of 54 patients (median age 63,44 years; range 34-86 years), with a total of 63 infiltrated vertebrae, were treated with RFA, PMMA vertebroplasty and transpedicular screw fixation; average operative time was 60.4 min (range 51–72). The preoperative average VAS score decreased significantly from 7.81 to 2.50 (p &lt; 0.05) after 12 months. Based on Saliou filling score, filling was satisfactory (12–18) in 20 vertebrae (31,7%), mediocre (6–11) in 33 vertebrae (52,4%), inadequate (0–5) in 10 vertebrae (15,9%). A consistent PMMA filling of vertebral bodies was successfully achieved with significant pain relief. Concomitant RFA, PMMA vertebroplasty and pedicle screw fixation represent a safe and effective technique for the management of spinal metastases, improving clinical outcome and pain control.
Liver Transplantation for Intrahepatic Cholangiocarcinoma: What Are New Insights and What Should We Follow?
Authors: Sun Dawei , Lv Guoyue , Dong Jiahong 
Published: January 2022

Intrahepatic cholangiocarcinoma (iCCA) is a complex malignancy carrying poor prognosis. Liver transplantation (LT) was historically contraindicated for iCCA, due to poor outcomes after LT. However, an increasing number of studies have challenged this premise, because LT alone or combined with neoadjuvant chemotherapy has achieved relatively satisfactory transplant outcomes in well selected iCCA cases. This current review based on existing clinical researches, evinced that LT might serve as a viable option in iCCA cases as follows: ① unresectable tumor restricted to 2 cm, along with context of chronic liver diseases; and ② unresectable tumor locally advanced within the liver (without extrahepatic metastasis or vascular invasion) but responses to tumor down-staging treatments (namely, systemic neoadjuvant therapy and/or locoregional therapy). On the contrary, it is recommended as contraindications in iCCA cases as follows: ① patients with tumor progression while waiting for a transplant (increase of diameter, macrovascular invasion, new nodules, escalation of carbohydrate antigen 19-9, or extrahepatic spread); ② patients with iCCA recurrence. Conclusively, tumor burden, tumor biology, and response to down-staging strategies should be taken into consideration before LT. Whereas, the concept of “locally advanced stage” remains to be defined in the future, especially the optimized combination of “maximum size of largest lesion”, “number of lesions”, with/without “tumor differentiation”, just like the Milan criteria which is widely used for hepatocellular carcinoma. Given the scarcity of donor organ, and also the debate about LT in iCCA, accurate consensus about LT for iCCA patients is still urgently warranted.
Simplifying Diagnosis of Fetal Alcohol Syndrome Using Machine Learning Methods
Authors: Blanck-Lubarsch Moritz , Dirksen Dieter , Feldmann Reinhold , Bormann Eike , Hohoff Ariane 
Published: January 2022

IntroductionThe fetal alcohol spectrum disorder (FASD) is a complex and heterogeneous disorder, caused by gestational exposure to alcohol. Patients with fetal alcohol syndrome (FAS—most severe form of FASD) show abnormal facial features. The aim of our study was to use 3D- metric facial data of patients with FAS and identify machine learning methods, which could improve and objectify the diagnostic process.Material and MethodsFacial 3D scans of 30 children with FAS and 30 controls were analyzed. Skeletal, facial, dental and orthodontic parameters as collected in previous studies were used to evaluate their value for machine learning based diagnosis. Three machine learning methods, decision trees, support vector machine and k-nearest neighbors were tested with respect to their accuracy and clinical practicability.ResultsAll three of the above machine learning methods showed a high accuracy of 89.5%. The three predictors with the highest scores were: Midfacial length, palpebral fissure length of the right eye and nose breadth at sulcus nasi.ConclusionsWith the parameters right palpebral fissure length, midfacial length and nose breadth at sulcus nasi, machine learning was an efficient method for the objective and reliable detection of patients with FAS within our patient group. Of the three tested methods, decision trees would be the most helpful and easiest to apply method for everyday clinical and private practice.
Association Between Vitamin D Level and Neonatal Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis
Authors: Zang Rina , Zhang Yayu , Zhang Hanshuo , Zhang Xueyi , Lv Yuening , Li Dan 
Published: January 2022

BackgroundIn recent years, vitamin D in the occurrence of lung diseases has gradually become a hot topic. Although the role of vitamin D in normal lung development has been confirmed, the correlation between vitamin D level and neonatal respiratory distress syndrome (NRDS) is not clear.ObjectiveTo evaluate the association between vitamin D level and NRDS.MethodsWe performed a comprehensive search of the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI). Literature screening and quality assessment were performed according to inclusion and exclusion criteria. The Newcastle–Ottawa Scale was used to assess the methodological components of each study, and Stata 15.1 software to perform the Meta-analysis.ResultsA total of nine case-control studies were included, with 653 infants with NRDS and 501 infants without NRDS. The Meta-analysis showed no heterogeneity across all studies(I2=0.0%, P=0.583). The fixed-effect model showed that 25 hydroxy vitamin D level of children in the NRDS group was significantly lower than that of the non-NRDS group(SMD = −0.51, 95%CI: −0.63 to −0.39, p ≤ 0.05).ConclusionThis systematic review and meta-analysis study suggests that vitamin D deficiency is very likely to be a high-risk factor of NRDS, and reasonable vitamin D supplementation during pregnancy and after birth is of great significance.