bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between hemoglobin level and cognitive profile in old adults: A cross‐sectional survey
Authors: Yang Yaqi , Liu Shuai , Gan Jinghuan , Zhu Han , Du Xiaoshan , Chen Zhichao , Ma Lingyun , Meng Qingbo , Yang Fan , Chen Hui , Ji Yong 
Published: August 2022

AbstractObjectiveIn the present study, the association between Hemoglobin (HGB) level and cognitive profile was investigated and whether it affected the dementia risk in older adults.MethodsA cross‐sectional population‐based survey that included 3519 individuals ≥65 years of age was conducted in 2019. Basic demographic characteristics were collected. The neuropsychological assessments and blood tests were administered to evaluate cognition and HGB level. Generalized additive models were used to analyze the non‐linear association between HGB levels and cognitive function. Logistics regression models were utilized to analyze the associations between HGB level and dementia risk.ResultsOverall, 459 (12.7%) participants were diagnosed with dementia and there were more females (54.7%) than males (45.3%). The number of subjects with anemia (3%) or hyperhemoglobinemia (5.2%) was higher than participants with normal HGB level. A visual representation of the relationship between HGB level and Mini‐Mental State Examination (MMSE) score showed an inverted U‐curve, which is more evident in female. Logistics regression models showed that anemia (odds ratio, OR = 1.826, 95% confidence interval, CI: 1.166–2.860, p < 0.01), but not hyperhemoglobinemia, significantly increased the risk of dementia. These trends were not the same for males and females. An abnormal HGB level had greater effects in females, resulting in higher risk of dementia for females with anemia or hyperhemoglobinemia than subjects with normal HGB level including males.ConclusionBoth low and high HGB levels can lead to cognitive decline in the incidence of dementia, indicating an inverted U‐shaped curve association may exist between HGB level and global cognitive profile.
Adeno‐associated virus serotype 2 capsid variants for improved liver‐directed gene therapy
Authors: Meumann Nadja , Cabanes‐Creus Marti , Ertelt Moritz , Navarro Renina Gale , Lucifora Julie , Yuan Qinggong , Nien‐Huber Karin , Abdelrahman Ahmed , Vu Xuan‐Khang , Zhang Liang , Franke Ann‐Christin , Schmithals Christian , Piiper Albrecht , Vogt Annabelle , Gonzalez‐Carmona Maria , Frueh Jochen T. , Ullrich Evelyn , Meuleman Philip , Talbot Steven R. , Odenthal Margarete , Ott Michael , Seifried Erhard , Schoeder Clara T. , Schwäble Joachim , Lisowski Leszek , Büning Hildegard 
Published: August 2022

Background and Aims:
Current liver‐directed gene therapies look for adeno‐associated virus (AAV) vectors with improved efficacy. With this background, capsid engineering is explored. Whereas shuffled capsid library screenings have resulted in potent liver targeting variants with one first vector in human clinical trials, modifying natural serotypes by peptide insertion has so far been less successful. Here, we now report on two capsid variants, MLIV.K and MLIV.A, both derived from a high‐throughput in vivo AAV peptide display selection screen in mice.

Approach and Results:
The variants transduce primary murine and human hepatocytes at comparable efficiencies, a valuable feature in clinical development, and show significantly improved liver transduction efficacy, thereby allowing a dose reduction, and outperform parental AAV2 and AAV8 in targeting human hepatocytes in humanized mice. The natural heparan sulfate proteoglycan binding ability is markedly reduced, a feature that correlates with improved hepatocyte transduction. A further property that might contribute to the improved transduction efficacy is the lower capsid melting temperature. Peptide insertion also caused a moderate change in sensitivity to human sera containing anti‐AAV2 neutralizing antibodies, revealing the impact of epitopes located at the basis of the AAV capsid protrusions.

Conclusions:
In conclusion, MLIV.K and MLIV.A are AAV peptide display variants selected in immunocompetent mice with improved hepatocyte tropism and transduction efficiency. Because these features are maintained across species, MLIV variants provide remarkable potential for translation of therapeutic approaches from mice to men.
Ecological interface design and emergent users: Designing for small‐scale trucking ecology in India
Authors: Kant Vivek , Karthikeyan Varun V. , Sharma Nishant 
Published: August 2022

AbstractEffective on‐road safety requires proper maintenance of vehicles. In the trucking sector in India, there is a need for supporting predictive maintenance to decrease downtime and improve safety. Improving maintenance in this sector involves certain challenges. First, most trucks are owned by small‐scale fleet owners (trucks < 5). Second, maintenance is often handled by small‐scale mechanic workshops. The fault diagnosis is very often limited to recognition by the driver and later reassessed by the mechanic by relying on the feel or the sound of the vehicle. Third, a majority of stakeholders in this sector—drivers, mechanics, and owners—have low levels of education. Despite these challenges, with the increase in the rate of digitalization, in the future, it will be easier to monitor the health of the parts of a truck. In addition, there is a developing trend of mobile phone and internet penetration in India that has leapfrogged a majority of Indians into becoming “emergent users” of information technology. Therefore, this article shows that sociotechnical approaches such as ecological interface design can be used to develop mobile interfaces for supporting predictive maintenance through health and usage monitoring of trucks for small‐scale fleet owners in India. To develop the interface, a field study was conducted at several sites in the state of Tamil Nadu, India. The insights were used to develop scenarios and the abstraction hierarchy, which were later used creatively to develop the interface design for emergent users.
Ibrutinib combined with low‐dose histone deacetylases inhibitor chidamide synergistically enhances the anti‐tumor effect in B‐cell lymphoma
Authors: Yu Hui , Mi Lan , Zhang Weimin , Ye Yingying , Li Miaomiao , Hu Dingyao , Cao Jiaowu , Wang Dedao , Wang Xiaogan , Ding Ning , Song Yuqin , Zhu Jun 
Published: August 2022

AbstractAberrant activity of histone deacetylases (HDACs) is frequently detected in B‐cell lymphomas, which indicated the therapeutic implications of HDAC inhibitors for B‐cell malignancies. We have discovered that lymphoma cells treated with HDAC inhibitor presented with activation of Bruton tyrosine kinase (BTK) which played an important role in the development of B‐cell malignancies. Therefore, our study intended to explore whether the addition of ibrutinib (BTK inhibitor) to chidamide (HDAC inhibitor) could generate combined anti‐tumor effects in B‐cell lymphomas. Using cell viability assay, cell cycle and apoptosis kit, we demonstrated an evident synergistic action of ibrutinib and chidamide in inhibiting tumor cell proliferation and motility. Consistent with in vitro data, the synergistic anti‐tumor effects were also observed in multiple tumor‐bearing mice models. By performing RNA‐seq and flow cytometry of tumor tissue, the enhancement of anti‐tumor immunity was observed with the co‐treatment of chidamide and ibrutinib. Together, these mechanistic insights indicated that simultaneously targeting BTK and HDAC could be a promising clinical therapy for B‐cell lymphomas.
Normal but skewed?
Authors: Amengual Dante , Bei Xinyue , Sentana Enrique 
Published: August 2022

SummaryWe propose a multivariate normality test against skew normal distributions using higher‐order log‐likelihood derivatives, which is asymptotically equivalent to the likelihood ratio but only requires estimation under the null. Numerically, it is the supremum of the univariate skewness coefficient test over all linear combinations of the variables. We can simulate its exact finite sample distribution for any multivariate dimension and sample size. Our Monte Carlo exercises confirm its power advantages over alternative approaches. Finally, we apply it to the joint distribution of US city sizes in two consecutive censuses finding that non‐normality is very clearly seen in their growth rates.
Development of an acellular nerve cap xenograft for neuroma prevention
Authors: Faust Anne E. , Soletti Lorenzo , Cwalina Nicole A. , Miller Andrew D. , Wood Matthew D. , Mahan Mark A. , Cheetham Jonathan , Brown Bryan N. 
Published: August 2022

AbstractNeuroma formation following limb amputation is a prevalent and debilitating condition that can deeply affect quality of life and productivity. Several approaches exist to prevent or treat neuromas; however, no approach is either consistently reliable or surgically facile, with high rates of neuroma occurrence and/or recurrence. The present study describes the development and testing of a xenogeneic nerve cap graft made from decellularized porcine nerve. The grafts were tested in vitro for cellular removal, cytotoxicity, mechanical properties, and morphological characteristics. The grafts were then tested in rat sciatic nerve gap reconstruction and nerve amputation models for 8 weeks. Gross morphology, electrophysiology, and histopathology assessments were performed to determine the ability of the grafts to limit pathologic nerve regrowth. In vitro testing showed well decellularized and demyelinated nerve cap graft structures without any cytotoxicity from residual reagents. The grafts had a proximal socket for the proximal nerve stump and longitudinally oriented internal pores. Mechanical and surgical handling properties suggested suitability for implantation as a nerve graft. Following 8 weeks in vivo, the grafts were well integrated with the proximal and distal nerve segments without evidence of fibrotic adhesions to the surrounding tissues or bulbous outgrowth of the nerve. Electrophysiology revealed absence of nerve conduction within the remodeled nerve cap grafts and significant downstream muscle atrophy. Histologic evaluation showed well organized but limited axonal regrowth within the grafts without fibrous overgrowth or neuromatous hypercellularity. These results provide proof of concept for a novel xenograft‐based approach to neuroma prevention.
Collagen membrane from bovine pericardium for treatment of long bone defect
Authors: Yamanaka Jéssica S. , Oliveira Ana Clara , Bastos Ana Raquel , Fernandes Emanuel M. , Reis Rui L. , Correlo Vitor M. , Shimano Antônio Carlos 
Published: August 2022

AbstractThe treatment of bone regeneration failures has been constantly improved with the study of new biomaterials. Techgraft® is a collagen membrane derived from bovine pericardium, which has been shown to have biocompatibility and effectiveness in tissue repair. However, its use in orthopedics has not yet been evaluated. Therefore, the purpose of this study was to characterize a bovine pericardium collagen membrane and evaluate the effects of its use in the regeneration of a bone defect in rat tibia. Scanning electron microscopy, atomic force microscopy, weight lost and water uptake tests, and mechanical test were performed. Afterwards, the membrane was tested in an experimental study, using 12 male Sprague Dawley rats. A bone defect was surgically made in tibiae of animals, which were assigned to two groups (n = 6): bone defect treated with collagen membrane (TG) and bone defect without treatment (CONT). Then, tibiae were submitted to micro‐CT. The membranes preserved their natural collagen characteristics, presenting great strength, high water absorption, hydrophilicity, and almost complete dissolution in 30 days. In the experimental study, the membrane enhanced the growth of bone tissue in contact with its surface. A higher bone volume and trabeculae number and less trabecular space was observed in bone defects of the membrane group compared to the control group at 21 days. In conclusion, the Techgraft membrane seems to have favorable characteristics for treatment of long bone repair.
C5aR2 receptor: The genomic twin of the flamboyant C5aR1
Authors: Das Aurosikha , Gupta Pulkit K. , Rana Soumendra 
Published: August 2022

AbstractThe complement fragment C5a is one of the most potent proinflammatory glycoproteins liberated by the activation of the biochemical cascade of the complement system. C5a is established to interact with a set of genomically related transmembrane receptors, like C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2) with comparable affinity. The C5aR1 is a classical G‐protein‐coupled receptor (GPCR), whereas C5aR2 is a nonclassical GPCR that tailors immune cell activity potentially through β‐arrestins rather than G‐proteins. Currently, the exact function of the C5aR2 is actively debated in the context of C5aR1, even though both C5aR1 and C5aR2 are coexpressed on myriads of tissues. The functional relevance of C5aR2 appears to be context‐dependent compared to the C5aR1, which has received enormous attention for its role in both acute and chronic inflammatory diseases. In addition, the structure of C5aR2 and its interaction specificity toward C5a is not structurally elucidated in the literature so far. The current study has attempted to close the gap by generating highly refined model structures of C5aR2, respectively in free (inactive), complexed to C‐terminal peptide of C5a (meta‐active) and the C5a (active), embedded to a model palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine bilayer. The computational modeling and the 1.5‐μs molecular dynamics data presented in the current study are expected to further enrich the understanding of C5a–C5aR2 interaction compared to C5a–C5aR1, which will surely help in elaborating the currently debated biological function of C5aR2 better in the foreseeable future.
Test–retest stability, convergent validity, and sensitivity to change for the Goal‐Based Outcome tool for adolescents: Analysis of data from a randomized controlled trial
Authors: Duncan Charlie , Cooper Mick , Saxon David 
Published: August 2022

AbstractObjective(s)To examine the psychometric properties of the idiographic Goal‐Based Outcome (GBO) tool for young people: test–retest stability, convergent validity, and sensitivity to an intervention.MethodsThis measure validation study used data from a randomized controlled trial of school‐based humanistic counseling. We used multilevel analyses to assess test–retest stability, convergent validity of the GBO tool against nomothetic measures of mental wellbeing, and sensitivity to an intervention.ResultsThe GBO tool showed acceptable stability over a 6–24 week period; moderate convergent validity with nomothetic measures of mental well‐being, self‐esteem, and depression; and greater sensitivity to an intervention than a measure of psychological distress.ConclusionsThe GBO tool shows evidence of having acceptable psychometric properties and is suitable for monitoring change on individual goals. It may also have the capacity to function as a population‐level indicator of outcomes in conjunction with the use of other measures of mental health and wellbeing.
Joint developmental trajectories and correlates of internalizing and externalizing problems among Chinese adolescents
Authors: Wang Shuo , Shi Xuliang , Wang Zhen , Li Zihan , Wang Anqi , Hu Xinhui , Li Zhipeng 
Published: August 2022

AbstractBackgroundInternalizing and externalizing problems are the most prevalent health problems among adolescents. However, few studies have examined co‐occurring internalizing and externalizing problems from a longitudinal perspective.MethodsA total of 1051 seventh‐grade students from two junior high schools were recruited at baseline. Among them, 932 valid participants were reassessed 1 year and 2 years later. Data were analyzed using parallel‐process latent class growth analysis and multinominal logistic regression.ResultsFour joint trajectories of internalizing and externalizing problems were identified. Compared with the low‐risk group, adolescents in the moderate and chronic co‐occurring group had lower resilience, higher levels of insecure attachment, family conflicts, and academic pressure. Adolescents in the pure internalizing group had higher levels of family conflicts and academic pressure compared with the low‐risk group.ConclusionsCo‐occurrence of symptoms is very high in adolescents. More individualized intervention programs should be provided to these specific groups.
Drug Combination Modeling: Methods and Applications in Drug Development
Authors: Pearson Rachael A. , Wicha Sebastian G. , Okour Malek 
Published: August 2022

AbstractCombination therapies have become increasingly researched and used in the treatment and management of complex diseases due to their ability to increase the chances for better efficacy and decreased toxicity. To evaluate drug combinations in drug development, pharmacokinetic and pharmacodynamic interactions between drugs in combination can be quantified using mathematical models; however, it can be difficult to deduce which models to use and how to use them to aid in clinical trial simulations to simulate the effect of a drug combination. This review paper aims to provide an overview of the various methods used to evaluate combination drug interaction for use in clinical trial development and a practical guideline on how combination modeling can be used in the settings of clinical trials.
Graphs of low average degree without independent transversals
Authors: Groenland Carla , Kaiser Tomáš , Treffers Oscar , Wales Matthew 
Published: August 2022

AbstractAn independent transversal of a graph with a vertex partition is an independent set of intersecting each block of in a single vertex. Wanless and Wood proved that if each block of has size at least and the average degree of vertices in each block is at most , then an independent transversal of exists. We present a construction showing that this result is optimal: for any and sufficiently large , there is a forest with a vertex partition into parts of size at least such that the average degree of vertices in each block is at most , and there is no independent transversal. This unexpectedly shows that methods related to entropy compression such as the Rosenfeld–Wanless–Wood scheme or the Local Cut Lemma are tight for this problem. Further constructions are given for variants of the problem, including the hypergraph version.
Planar Legendrian Θ ${\rm{\Theta }}$‐graphs
Authors: Lambert‐Cole Peter , O'Donnol Danielle 
Published: August 2022

AbstractWe classify topologically trivial Legendrian ‐graphs in and identify the complete family of nondestabilizable Legendrian realizations in this topological class. In contrast to all known results for Legendrian knots, this is an infinite family of graphs. We also show that any planar graph that contains a subdivision of a ‐graph or as a subgraph will have an infinite number of distinct, topologically trivial nondestabilizable Legendrian embeddings. Additionally, we introduce two moves, vertex stabilization and vertex twist, that change the Legendrian type within a smooth isotopy class.
Preoperative Diagnosis of Dual‐Phenotype Hepatocellular Carcinoma Using Enhanced MRI Radiomics Models
Authors: Wu Qian , Yu Yi‐xing , Zhang Tao , Zhu Wen‐jing , Fan Yan‐fen , Wang Xi‐ming , Hu Chun‐hong 
Published: August 2022

BackgroundDual‐phenotype hepatocellular carcinoma (DPHCC) is highly aggressive and difficult to distinguish from hepatocellular carcinoma (HCC).PurposeTo develop and validate clinical and radiomics models based on contrast‐enhanced MRI for the preoperative diagnosis of DPHCC.Study typeRetrospective.PopulationA total of 87 patients with DPHCC and 92 patients with non‐DPHCC randomly divided into a training cohort (n = 125: 64 non‐DPHCC; 61 DPHCC) and a validation cohort (n = 54: 28 non‐DPHCC; 26 DPHCC).Field Strength/SequenceA 3.0 T; dynamic contrast‐enhanced MRI with time‐resolved T1‐weighted imaging sequence.AssessmentIn the clinical model, the maximum tumor diameter and hepatitis B virus (HBV) were independent risk factors of DPHCC. In the radiomics model, a total of 1781 radiomics features were extracted from tumor volumes of interest (VOIs) in the arterial phase (AP) and portal venous phase (PP) images. For feature reduction and selection, Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were used. Clinical, AP, PP, and combined radiomics models were established using machine learning algorithms (support vector machine [SVM], logistic regression [LR], and logistic regression‐least absolute shrinkage and selection operator [LR‐LASSO]) and their discriminatory efficacy assessed and compared.Statistical TestsThe independent sample t test, Mann–Whitney U test, Chi‐square test, regression analysis, receiver operating characteristic curve (ROC) analysis, Pearson correlation analysis, the Delong test. A P value < 0.05 was considered statistically significant.ResultsIn the validation cohort, the combined radiomics model (area under the curve [AUC] = 0.908, 95% confidence interval [CI]: 0.831–0.985) showed the highest diagnostic performance. The AUCs of the PP (AUC = 0.879, 95% CI: 0.779–0.979) and combined radiomics models were significantly higher than that of clinical model (AUC = 0.685, 95% CI: 0.526–0.844). There were no significant differences in AUC between AP or PP radiomics model and combined radiomics model (P = 0.286, 0.180 and 0.543).ConclusionMRI radiomics models may be useful for discriminating DPHCC from non‐DPHCC before surgery.Evidence Level4Technical EfficacyStage 2
Combined liver transplantation and sleeve gastrectomy: Report of a brief‐interval staged approach
Authors: Tariq Nabil , Saharia Ashish , Nwokedi Ugoeze , Hobeika Mark J. , Mobley Constance M. , Hsu David , Potter Lucy M. , Moore Linda W. , Elaileh Ahmed , Sherman Vadim , Ghobrial R. Mark 
Published: August 2022

Pretransplantation bariatric surgery in patients with high Model for End‐Stage Liver Disease (MELD) score is fraught with risks. Bariatric surgery after liver transplantation (LT) may be complicated by surgical adhesions but could have advantages if performed at the time of transplantation. We investigated a method of brief‐interval staging combining LT and sleeve gastrectomy (SG). LT recipients with a body mass index (BMI) > 40 kg/m2 received an SG during the same hospitalization as the LT (LT/SG), at the same time as a planned brief‐interval return to the operating room for biliary anastomosis. Differences in intraoperative attributes of the LT (Stage 1) versus SG (Stage 2) procedures were analyzed using Wilcoxon signed‐rank test with significance p < 0.05 and compared with patients with obesity having a two‐stage LT without SG. A total of 14 cases {median MELD score 33 (interquartile range [IQR], 18–40)} were compared with 28 controls; 60% were critically ill prior to surgery with mechanical ventilation, vasopressors, or continuous renal replacement therapy. Median interval between procedures was 16.1 (IQR, 12.5–22.7) hours for cases and 12.2 (IQR, 11.1–16.6) hours for controls, p = 0.27. Median BMI at LT/SG was 47.0 (IQR, 41.7–51.3) kg/m2 versus 38.1 (IQR, 35.7–39.8) kg/m2 for controls, p < 0.001. At 1 year, median excess body weight loss was 74.0% (IQR, 46.2%–78.7%) in cases and 15.8% (IQR, −5.4% to 62.6%) in controls, p = 0.13; total weight loss was 38.1% (IQR, 23.9–42.9) in cases versus 7.7% (IQR, −2.4% to 27.6%) for controls, p = 0.03. Graft survival at 1 year was 92.9% for cases and 89.3% for controls with similar early postoperative outcomes. This proof‐of‐concept study revealed that a brief‐interval SG during LT is feasible in patients with high MELD and resulted in sustained weight loss at 1 year with similar graft survival. Further studies are needed to determine an optimal strategy.