bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular outcomes in subjects with pre-diabetes: a large cohort study from China
Authors: Liu Shuo-Lin , Feng Bao-Yu , Song Qi-Rui , Zhang Ying-Mei , Wu Shuo-Ling , Cai Jun 
Published: September 2022

Abstract
Background
This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels.

Methods
A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction.

Results
Over a median of 12.53 (8.95–13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15–1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21–1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38–1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001).

Conclusions
Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.
A case of Vp4 hepatocellular carcinoma with tumor thrombosis extending into the confluence of the splenic/portal vein achieved a good prognosis with emergent hepatectomy and postoperative adjuvant therapy with lenvatinib
Authors: Kato Hiroyuki , Asano Yukio , Ito Masahiro , Arakawa Satoshi , Shimura Masahiro , Koike Daisuke , Ochi Takayuki , Yasuoka Hironobu , Kawai Toki , Higashiguchi Takahiko , Tani Hiroki , Kunimura Yoshiki , Kondo Yuka , Nagata Hidetoshi , Sato Harunobu , Horiguchi Akihiko 
Published: September 2022

AbstractIn this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.
Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population
Authors: Gan Caiyan , Zhang Yinmei , Liang Fei , Guo Xuemin , Zhong Zhixiong 
Published: September 2022

AbstractBackgroundHuman apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4.APOEpolymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type ofAPOEpolymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role ofAPOEpolymorphisms on the tumor with or without CVD in southern China.MethodsA total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls.APOEpolymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis.ResultsThe present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (allP< 0.05). The frequency ofAPOEε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P< 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P= 0.037, adjustedOR= 1.92, 95%CI1.04–3.55) and tumor + CVD patients group (P= 0.012, adjustedOR= 2.53, 95%CI1.22–5.23).ConclusionsIndividuals carrying ε4 are at a higher risk of tumor with or without CVD, andAPOEpolymorphisms affect the serum lipid profiles.
Metabonomics profile analysis in inflammation-induced preterm birth and the potential role of metabolites in regulating premature cervical ripening
Authors: Yan Yan , Gu Zhuorong , Li Baihe , Guo Xirong , Zhang Zhongxiao , Zhang Runjie , Bian Zheng , Qiu Jin 
Published: September 2022

Abstract
Background
Preterm birth (PTB) is the primary cause of infant morbidity and mortality. Moreover, previous studies have established that PTB is related to premature cervical ripening. However, the underlying mechanism remains to be elucidated. This study sought to identify differentially expressed metabolites and investigate their potential biological functions in PTB.

Methods
Pregnant C57BL/6 J mice were treated with either LPS or normal saline and cervical alterations before labor were detected by staining. Metabolic profiles in the plasma of PTB and control mice were examined through non-targeted metabonomics analyses, quantitative polymerase chain reaction and immunofluorescence staining were performed on human cervical smooth cells.

Results
The study demonstrated that the mRNA and protein levels of α-SMA, SM-22, and calponin in cervical smooth muscle cells of PTB mice were lower while OR was higher at both mRNA and protein levels compared to the CTL group. A total of 181 differentially expressed metabolites were analyzed, among them, 96 were upregulated, while 85 were downregulated in the PTB group. Differentially expressed metabolites may play a role in STAT3, RhoA, mTOR, TGF-β, and NK-κB signaling pathways. Furthermore, when treated with taurine, the levels of α-SMA and SM-22 in human cervical smooth muscle cells were elevated, whereas that of connexin-43 was decreased.

Conclusion
Our study highlighted the changes of metabolites in the peripheral blood changed prior to PTB and revealed that these differentially expressed metabolites might participate in the development of premature cervical ripening. Taurine was identified as an important metabolite may modulate human cervical smooth muscle cells. Our study provided new insights into the mechanism underlying premature cervical ripening in PTB.
Risk of root damage after using lateral cephalogram and intraoral scan for guided insertion of palatal miniscrews
Authors: Nienkemper Manuel , Ludwig Björn 
Published: September 2022

AbstractBackgroundGuided insertion of palatal miniscrews using a lateral cephalogram instead of cone beam computed tomography (CBCT) significantly reduces the radiation level for the patient. Till now no data are available on the risk of hitting the incisors in this regard, which is one of the worst clinical complications when inserting a paramedian miniscrew. Hence, this study aims to investigate the distance between the mini-implant and the roots of the central and lateral incisors.MethodsLateral cephalogram, an intraoral scan, and CBCT of 20 patients were superimposed. After a miniscrew (1.7 × 8 mm) placement based on intraoral scan and lateral cephalogram, the CBCT was used as control for the distance between the miniscrews and the roots of the incisors.ResultsThe mean value of the shortest distance between the miniscrew and roots of the incisors in the lateral cephalogram was 4.74 ± 1.67 mm. The distance between both miniscrews and the central incisors measured in the CBCT was 5.03 ± 2.22 mm and 5.26 ± 2.21 mm and between the two miniscrews and the lateral incisors was 4.93 ± 1.91 mm and 5.21 ± 2.64 mm. No significant differences between the distances in the CBCT and the lateral cephalogram could be observed. In one case, the CBCT control revealed the penetration of two palatally displaced canines after insertion based on intraoral scan and lateral cephalogram.ConclusionsThe use of an intraoral scan and a lateral cephalogram for guided paramedian insertion of palatal miniscrews can prevent incisor root damage. This may reduce the radiation since no CBCT seems necessary. The current investigation focuses on the anterior paramedian area of the palate. Outside that region and in complex cases with displaced teeth in the palatal area, a CBCT might be indicated.
Recruitment interventions for trials involving adults lacking capacity to consent: methodological and ethical considerations for designing Studies Within a Trial (SWATs)
Authors: Shepherd Victoria , Wood Fiona , Gillies Katie , O’Connell Abby , Martin Adam , Hood Kerenza 
Published: September 2022

Abstract
Background
The number of interventions to improve recruitment and retention of participants in trials is rising, with a corresponding growth in randomised Studies Within Trials (SWATs) to evaluate their (cost-)effectiveness. Despite recognised challenges in conducting trials involving adults who lack capacity to consent, until now, no individual-level recruitment interventions have focused on this population. Following the development of a decision aid for family members making non-emergency trial participation decisions on behalf of people with impaired capacity, we have designed a SWAT to evaluate the decision aid in a number of host trials (CONSULT). Unlike in recruitment SWATs to date, the CONSULT intervention is aimed at a ‘proxy’ decision-maker (a family member) who is not a participant in the host trial and does not receive the trial intervention. This commentary explores the methodological and ethical considerations encountered when designing such SWATs, using the CONSULT SWAT as a case example. Potential solutions to address these issues are also presented.

Discussion
We encountered practical issues around informed consent, data collection, and follow-up which involves linking the intervention receiver (the proxy) with recruitment and retention data from the host trial, as well as issues around randomisation level, resource use, and maintaining the integrity of the host trial. Unless addressed, methodological uncertainty about differential recruitment and heterogeneity between trial populations could potentially limit the scope for drawing robust inferences and harmonising data from different SWAT host trials. Proxy consent is itself ethically complex, and so when conducting a SWAT which aims to disrupt and enhance proxy consent decisions, there are additional ethical issues to be considered.

Conclusions
Designing a SWAT to evaluate a recruitment intervention for non-emergency trials with adults lacking capacity to consent has raised a number of methodological and ethical considerations. Explicating these challenges, and some potential ways to address them, creates a starting point for discussions about conducting these potentially more challenging SWATs. Increasing the evidence base for the conduct of trials involving adults lacking capacity to consent is intended to improve both the ability to conduct these trials and their quality, and so help build research capacity for this under-served population.
Transcriptional dynamics of transposable elements in the type I IFN response in Myotis lucifugus cells
Authors: Pasquesi Giulia Irene Maria , Kelly Conor J. , Ordonez Andrea D. , Chuong Edward B. 
Published: September 2022

Abstract
Background
Bats are a major reservoir of zoonotic viruses, and there has been growing interest in characterizing bat-specific features of innate immunity and inflammation. Recent studies have revealed bat-specific adaptations affecting interferon (IFN) signaling and IFN-stimulated genes (ISGs), but we still have a limited understanding of the genetic mechanisms that have shaped the evolution of bat immunity. Here we investigated the transcriptional and epigenetic dynamics of transposable elements (TEs) during the type I IFN response in little brown bat (Myotis lucifugus) primary embryonic fibroblast cells, using RNA-seq and CUT&RUN.

Results
We found multiple bat-specific TEs that undergo both locus-specific and family-level transcriptional induction in response to IFN. Our transcriptome reassembly identified multiple ISGs that have acquired novel exons from bat-specific TEs, including NLRC5, SLNF5 and a previously unannotated isoform of the IFITM2 gene. We also identified examples of TE-derived regulatory elements, but did not find strong evidence supporting genome-wide epigenetic activation of TEs in response to IFN.

Conclusion
Collectively, our study uncovers numerous TE-derived transcripts, proteins, and alternative isoforms that are induced by IFN in Myotis lucifugus cells, highlighting candidate loci that may contribute to bat-specific immune function.
Neural correlates of episodic memory in adults with Down syndrome and Alzheimer’s disease
Authors: Benejam Bessy , Aranha Mateus Rozalem , Videla Laura , Padilla Concepción , Valldeneu Silvia , Fernández Susana , Altuna Miren , Carmona-Iragui Maria , Barroeta Isabel , Iulita Maria Florencia , Montal Víctor , Pegueroles Jordi , Bejanin Alexandre , Giménez Sandra , González-Ortiz Sofía , Videla Sebastián , Bartrés-Faz David , Alcolea Daniel , Blesa Rafael , Lleó Alberto , Fortea Juan 
Published: September 2022

Abstract
Background
Adults with Down syndrome are at an ultra-high risk of developing early-onset Alzheimer’s disease. Episodic memory deficits are one of the earliest signs of the disease, but their association with regional brain atrophy in the population with Down syndrome has not been explored. We aimed to investigate the neuroanatomical correlates of episodic memory in adults with Down syndrome and symptomatic Alzheimer’s disease.

Methods
Single-center, cross-sectional study. A total of 139 adults with Down syndrome (85 asymptomatic and 54 with symptomatic Alzheimer’s disease) were included in the study (mean age 43.6 ± 10.9 years, 46% female). Episodic memory was assessed using the modified Cued Recall Test. Immediate (trial 1 free immediate recall, trial 3 free immediate recall, total free immediate recall score, and total immediate score) and delayed scores (free delayed recall score and total delayed score) were examined. Cortical thickness from magnetic resonance imaging was determined with surface-based morphometry using the FreeSurfer 6.0 software package. The clusters of reduced cortical thickness were compared between symptomatic and asymptomatic participants to create a cortical atrophy map. Then, the correlation between cortical thickness and the modified Cued Recall Test subscores were separately assessed in symptomatic and asymptomatic subjects, controlling for age, sex, and severity of intellectual disability.

Results
Compared with asymptomatic participants, those with symptomatic Alzheimer’s disease showed a pattern of cortical atrophy in posterior parieto-temporo-occipital cortices. In symptomatic subjects, trial 1 immediate free recall significantly correlated with cortical atrophy in lateral prefrontal regions. Trial 3 free immediate recall and total free immediate recall were associated with the most widespread cortical atrophy. Total immediate score was related to posterior cortical atrophy, including lateral parietal and temporal cortex, posterior cingulate cortex, precuneus, and medial temporal lobe areas. Delayed memory scores were associated with cortical atrophy in temporoparietal and medial temporal lobe regions. No significant relationships were observed between episodic memory measures and cortical atrophy in asymptomatic subjects.

Conclusions
Different episodic memory measures were associated with cortical atrophy in specific brain regions in adults with Down syndrome and Alzheimer’s disease. These results overlap with those described in sporadic Alzheimer’s disease and further support the similarities between Down syndrome-associated Alzheimer’s disease and that in the general population.
Longitudinal change in ATN biomarkers in cognitively normal individuals
Authors: Ebenau Jarith L. , Visser Denise , Kroeze Lior A. , van Leeuwenstijn Mardou S. S. A. , van Harten Argonde C. , Windhorst Albert D. , Golla Sandeep V. S. , Boellaard Ronald , Scheltens Philip , Barkhof Frederik , van Berckel Bart N. M. , van der Flier Wiesje M. 
Published: September 2022

Abstract
Background
Biomarkers for amyloid, tau, and neurodegeneration (ATN) have predictive value for clinical progression, but it is not clear how individuals move through these stages. We examined changes in ATN profiles over time, and investigated determinants of change in A status, in a sample of cognitively normal individuals presenting with subjective cognitive decline (SCD).

Methods
We included 92 individuals with SCD from the SCIENCe project with [18F]florbetapir PET (A) available at two time points (65 ± 8y, 42% female, MMSE 29 ± 1, follow-up 2.5 ± 0.7y). We additionally used [18F]flortaucipir PET for T and medial temporal atrophy score on MRI for N. Thirty-nine individuals had complete biomarker data at baseline and follow-up, enabling the construction of ATN profiles at two time points. All underwent extensive neuropsychological assessments (follow-up time 4.9 ± 2.8y, median number of visits n = 4). We investigated changes in biomarker status and ATN profiles over time. We assessed which factors predisposed for a change from A− to A+ using logistic regression. We additionally used linear mixed models to assess change from A− to A+, compared to the group that remained A− at follow-up, as predictor for cognitive decline.

Results
At baseline, 62% had normal AD biomarkers (A−T−N− n = 24), 5% had non-AD pathologic change (A−T−N+ n = 2,) and 33% fell within the Alzheimer’s continuum (A+T−N− n = 9, A+T+N− n = 3, A+T+N+ n = 1). Seventeen subjects (44%) changed to another ATN profile over time. Only 6/17 followed the Alzheimer’s disease sequence of A → T → N, while 11/17 followed a different order (e.g., reverted back to negative biomarker status). APOE ε4 carriership inferred an increased risk of changing from A− to A+ (OR 5.2 (95% CI 1.2–22.8)). Individuals who changed from A− to A+, showed subtly steeper decline on Stroop I (β − 0.03 (SE 0.01)) and Stroop III (− 0.03 (0.01)), compared to individuals who remained A−.

Conclusion
We observed considerable variability in the order of ATN biomarkers becoming abnormal. Individuals who became A+ at follow-up showed subtle decline on tests for attention and executive functioning, confirming clinical relevance of amyloid positivity.
Emerging roles of mesenchymal stem cell therapy in patients with critical limb ischemia
Authors: Shirbaghaee Zeinab , Hassani Mohammad , Heidari Keshel Saeed , Soleimani Masoud 
Published: September 2022

AbstractCritical limb ischemia (CLI), the terminal stage of peripheral arterial disease (PAD), is characterized by an extremely high risk of amputation and vascular issues, resulting in severe morbidity and mortality. In patients with severe limb ischemia with no alternative therapy options, such as endovascular angioplasty or bypass surgery, therapeutic angiogenesis utilizing cell-based therapies is vital for increasing blood flow to ischemic regions. Mesenchymal stem cells (MSCs) are currently considered one of the most encouraging cells as a regenerative alternative for the surgical treatment of CLI, including restoring tissue function and repairing ischemic tissue via immunomodulation and angiogenesis. The regenerative treatments for limb ischemia based on MSC therapy are still considered experimental. Despite recent advances in preclinical and clinical research studies, it is not recommended for regular clinical use. In this study, we review the immunomodulatory features of MSC besides the current understanding of different sources of MSC in the angiogenic treatment of CLI subjects and their potential applications as therapeutic agents. Specifically, this paper concentrates on the most current clinical application issues, and several recommendations are provided to improve the efficacy of cell therapy for CLI patients.
Rise of the human-mouse chimeric brain models
Authors: Jiang Peng , Alam Mahabub Maraj 
Published: September 2022

AbstractHuman-mouse chimeras offer advantages for studying the pathophysiology of human cells in vivo. Chimeric mouse brains have been created by engrafting human fetal tissue- or pluripotent stem cell-derived progenitor cells into the neonatal mouse brain. This provides new opportunities to understand human brain development and neurological disorders.
A sensor selection approach to maneuvering target tracking based on trajectory function of time
Authors: Liu Changyi , Di Kuangyu , Li Tiancheng , Elvira Victor 
Published: September 2022

AbstractIn this paper, we propose a computationally efficient sensor selection approach for maneuvering target tracking using a sensor network with communication bandwidth constraints, given limited prior information on the target maneuvering models. We formulate the stochastic sensor selection problem as a linear programming problem which consists of two easily implementable steps. First, the Cramér–Rao lower bound corresponding to the sensor subset is derived as the objective function of the proposed sensor selection method based on a partially observable Markov decision process. Second, the target trajectory is modeled by a function of time to enable online target tracking which is free of the conventional, a priori Markov modeling of the target dynamics. We demonstrate the effectiveness of our method through several numerical examples.