bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical Study and Clinical Application of Neuroendoscopic Transfarlateral Supracerebellar Infratentorial Approach
Authors: Yan Zhengcun , Zhang Hengzhu , Wang Xiaodong , Wei Min , Wang Xingdong , Wang Guangjie 
Published: October 2023

Background:
Tumors in the petroclival region have challenged neurosurgeons. However, neuroendoscopy has been increasingly applied internationally. This study simulated a pure neuroendoscopic transfarlateral supracerebellar infratentorial approach for petroclival tumor resection from the cadaveric head and discussed the advantages and safety of this approach.

Methods:
The anatomical structure for petroclival tumor resection was visualized using a pure neuroendoscopic transfarlateral supracerebellar infratentorial approach in 5 cadaveric heads. Ten cases with petroclival tumors were retrospectively analyzed and summarized between January 2020 and June 2021. All the cases had undergone surgery using a pure neuroendoscopic supracerebellar infratentorial approach.

Results:
The anatomical structure of the petroclival region was exposed using the pure neuroendoscopic supracerebellar infratentorial approach, and the partial anatomical structure of the middle skull base was further exposed by incision of the tentorium in the cadaveric head. Among the 10 cases, the tumors of 6 cases were totally removed, and those of 4 cases were subtotally removed; no cases of intracranial infection or death occurred after surgery.

Conclusion:
The neuroendoscopic transfarlateral supracerebellar infratentorial keyhole approach is a safe and effective surgical method to treat petroclival lesions and invasive middle cranial fossa lesions.
Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models
Authors: Sedki Mai , Kwong Allison , Bhargava Meera , Ahmed Aijaz , Daugherty Tami , Kwo Paul , Dronamraju Deepti , Kumari Radhika , Kim W. Ray , Esquivel Carlos , Melcher Marc , Bonham C. Andrew , Gallo Amy , Nelson Ashly , Norwood Amanda , Hussain Filza , Goel Aparna 
Published: October 2023

Background.
The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse.

Methods.
A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared.

Results.
Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%).

Conclusions.
AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.
A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation
Authors: Huang Howard J. , Schechtman Kenneth , Askar Medhat , Bernadt Cory , Mitter Brigitte , Dore Peter , Goodarzi Ahmad , Yau Simon , Youssef J. Georges , Witt Chad A. , Byers Derek E. , Vazquez-Guillamet Rodrigo , Halverson Laura , Nava Ruben , Puri Varun , Kreisel Daniel , Gelman Andrew E. , Hachem Ramsey R. 
Published: October 2023

Background.
Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.

Methods.
We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.

Results.
After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.

Conclusions.
We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.
Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage
Authors: Rao Jingyou , Xin Ruiqi , Macdonald Christian , Howard Matthew , Estevam Gabriella O. , Yee Sook Wah , Wang Mingsen , Fraser James S. , Coyote-Maestas Willow , Pimentel Harold 
Published: October 2023

AbstractDeep mutational scanning (DMS) enables functional insight into protein mutations with multiplexed measurements of thousands of genetic variants in a protein simultaneously. The small sample size of DMS renders classical statistical methods ineffective, for example, p-values cannot be correctly calibrated when treating variants independently. We proposeRosace, a Bayesian framework for analyzing growth-based deep mutational scanning data.Rosaceleverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. To benchmarkRosaceagainst existing methods, we developedRosette, a simulation framework that simulates the distributional properties of DMS. Further, we show thatRosaceis robust to the violation of model assumptions and is more powerful than existing tools underRosettesimulation and real data.
A female heterogametic ZW sex-determination system in Acariformes
Authors: Wulsch Svenja , Öztoprak Hüsna , Guiglielmoni Nadège , Jeffries Daniel L. , Bast Jens 
Published: October 2023

AbstractSexual reproduction, while often associated with separate sexes, is an ancient and widespread feature of multicellular eukaryotes. While a diversity of sex-determination mechanisms exist, for many organisms, which of these mechanisms is used remains unknown. Exploring sex-determination mechanisms in Acariformes, among the oldest chelicerate clades, is intriguing due to its potential to unveil conserved sex-determination systems. This insight can have implications for understanding sex chromosome evolution and its broader impact on higher taxa.To identify the mechanism of sex determination in Acari, i.e., oribatid mites, we generated a high-quality chromosome-level genome assembly ofHermannia gibba(Koch, 1839) by combining PacBio HiFi and Hi-C sequencing. Coverage and allele-frequency analyses on pools of male and female individuals suggest a female-heterogametic ZW sex-determination system with little degeneration of the W chromosome. To date, this represents the only documented case of a ZW system in Acariformes. Further comparative studies in H.gibbawill reveal how old the ZW system is and whether it exhibits conservation or polymorphism.
A novel Bayesian model for assessing intratumor heterogeneity of tumor infiltrating leukocytes with multi-region gene expression sequencing
Authors: Yang Peng , Hubert Shawna M. , Futreal P. Andrew , Song Xingzhi , Zhang Jianhua , Lee J. Jack , Wistuba Ignacio , Yuan Ying , Zhang Jianjun , Li Ziyi 
Published: October 2023

AbstractIntratumor heterogeneity (ITH) of tumor-infiltrated leukocytes (TILs) is an important phenomenon of cancer biology with potentially profound clinical impacts. Multiregion gene expression sequencing data provide a promising opportunity that allows for explorations of TILs and their intratumor heterogeneity for each subject. Although several existing methods are available to infer the proportions of TILs, considerable methodological gaps exist for evaluating intratumor heterogeneity of TILs with multi-region gene expression data. Here, we develop ICeITH,immunecellestimation revealsintratumorheterogeneity, a Bayesian hierarchical model that borrows cell type profiles as prior knowledge to decompose mixed bulk data while accounting for the within-subject correlations among tumor samples. ICeITH quantifies intratumor heterogeneity by the variability of targeted cellular compositions. Through extensive simulation studies, we demonstrate that ICeITH is more accurate in measuring relative cellular abundance and evaluating intratumor heterogeneity compared with existing methods. We also assess the ability of ICeITH to stratify patients by their intratumor heterogeneity score and associate the estimations with the survival outcomes. Finally, we apply ICeITH to two multi-region gene expression datasets from lung cancer studies to classify patients into different risk groups according to the ITH estimations of targeted TILs that shape either pro- or anti-tumor processes. In conclusion, ICeITH is a useful tool to evaluate intratumor heterogeneity of TILs from multi-region gene expression data.
Bioactive coatings on 3D printed scaffolds for bone regeneration: Use of Laponite™ to deliver BMP-2 for bone tissue engineering – progression throughin vitro, chorioallantoic membrane assay and murine subcutaneous model validation
Authors: Marshall Karen. M. , Wojciechowski Jonathan P. , Echalier Cécile , Callens Sebastien J. P. , Yang Tao , Øvrebø Øystein , Jayawarna Vineetha , Kanczler Janos M. , Stevens Molly M. , Dawson Jonathan I. , Oreffo Richard O.C. 
Published: October 2023

AbstractFracture non-union occurs as a consequence of various factors, leading to the development of potentially substantial bone defects. Biomaterial-based approaches for bone regeneration aim to explore alternative strategies to repair non-healing fractures and critical-sized bone defects. Thus, rigorous assessment of the ability to translate biomaterials towards clinical use is vital. Growth factors induce an effect on cells to change their phenotype, behaviour and initiate signalling pathways, leading to an effect on matrix deposition and tissue formation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic growth factor, with a rapid clearance timein vivonecessitating clinical use of high doses, with potential deleterious side-effects. This work explored the potential for Laponite™ nanoclay coating of poly(caprolactone) trimethacrylate (PCL-TMA900) scaffolds to bind BMP-2 for enhanced osteoinduction.In vitroexperiments confirmed the cytocompatibility of the PCL-TMA900 scaffolds and effective osteogenic differentiation of C2C12 myoblast cells in response to the Laponite/BMP-2 coating. The chorioallantoic membrane (CAM) assay verified PCL-TMA900 scaffold material biocompatibility and ability to support angiogenesis. A murine subcutaneous implantation model assessed heterotopic bone formation in response to the Laponite/BMP-2 coating, when used immediately post-coating and after 24 hours of room temperature storage, to evaluate a delayed use manner. The Laponite/BMP-2 coated PCL-TMA900 scaffolds implanted showed consistent, significant bone formation over the study period compared to the uncoated PCL-TMA 900 scaffold and BMP-2 only coated control scaffoldsin vivo, indicating the ability of Laponite to bind the BMP-2 to the PCL-TMA900 scaffold. Bone formed peripherally around the Laponite/BMP-2 coated scaffold, with no aberrant bone formation observed. The Laponite/BMP-2 coating was found to retain its bioactivity after storage for 24 hours prior to usein vivo, however this was not to the same volume or reliability of bone formation as when used immediately post-coating. To take these studies forward, the Laponite/BMP-2 coating warrants examination in a critical-sized bone defect model to assess efficacy in an osseous site.
Multimodal fusion of brain signals for robust prediction of psychosis transition
Authors: Reinen Jenna M. , Polosecki Pablo , Castro Eduardo , Corcoran Cheryl M. , Cecchi Guillermo , Colibazzi Tiziano 
Published: October 2023

AbstractPsychosis symptoms are often evident before diagnosis, suggesting the underlying biology of high-risk status may predict later disease outcomes. However, a single predictor remains unknown, indicating a need for algorithms that integrate complex information. Here, to identify risk and psychosis conversion, we implemented multiple kernel learning (MKL), a multimodal machine learning approach allowing patterns from each modality to inform each other. Baseline multimodal scans (n=74, 11 converters) included structural, resting-state functional imaging, and diffusion-weighted data. Multimodal MKL outperformed unimodal models (AUC=0.73 vs. 0.66 in predicting conversion). Moreover, patterns learned by MKL were robust to training set variations, suggesting it can identify cross-modality redundancies and synergies to stabilize the predictive pattern. We identified many predictors consistent with the literature, including frontal cortices, cingulate, thalamus, and striatum. This highlights the advantage of methods that leverage the complex pathophysiology of psychosis.
Decomposing the effects of α-tACS on brain oscillations and aperiodic 1/f activity
Authors: Kasten Florian H. , Lattmann René , Strüber Daniel , Herrmann Christoph S. 
Published: October 2023

AbstractBackgroundAftereffects of transcranial alternating current stimulation (tACS) are usually analyzed with a focus on the individual frequency band, thereby neglecting broadband spectral components. Recently, it was shown that the broadband spectrum, which exhibits a 1/f-like characteristic, is functionally relevant.Objective/HypothesisThe goal of this study was a spectral parameterization of brain activity into oscillatory alpha activity and aperiodic 1/f components before and after tACS and sham stimulation. It was expected that the broadband spectrum will not be differentially influenced by 20-min of tACS at individual α-frequency (IAF) in comparison to sham. Additionally, it was expected that the tACS aftereffect on the α-band can still be observed, even when controlling for 1/f activity differences.MethodsWe performed a re-analysis of a recently published resting-state tACS-magnetoencephalography (MEG) data set. Parameterization of the frequency spectrum was computed with the fitting-oscillations-and-one-over-F (FOOOF) algorithm. The intercept as well as the slope parameter of the aperiodic 1/f fit was extracted. Data was analyzed in sensor space with a focus on magnetometers. Comparison of changes in α-band power and 1/f activity was performed with non-parametric cluster-based random permutation tests.ResultsThe tACS aftereffect survived the 1/f-correction. The previously observed natural rise in alpha oscillations over time independent of experimental conditions could not be replicated. However, differences in aperiodic parameters over time were observed. Especially, the intercept parameter increased from pre to post stimulation to a similar degree in both conditions.ConclusionIt is imperative to correct for the aperiodic 1/f spectral component when analyzing aftereffects of brain stimulation on brain oscillations.
PCMD: A Multilevel Comparison Database of Intra- and Cross-species Metabolic Profiling in 530 Plant Species
Authors: Hu Yue , Ruan Yao , Zhao Xin-Le , Jiang Feng , Zhu Qiang , Zhang Qing-Ye , Yang Qing-Yong 
Published: October 2023

AbstractComparative metabolomics plays a crucial role in understanding gene function, exploring metabolite evolution, and improving crop genetic breeding. However, a systematic platform for comparing intra- and cross-species metabolites is currently lacking. In this study, we present the plant comparative metabolome database (PCMD;http://yanglab.hzau.edu.cn/PCMD), a comprehensive multi-level comparison database encompassing intra- and cross-species metabolic profiling in 530 plants. Remarkably, PCMD offers a multi-level platform for comparative metabolite analysis, allowing for the examination of metabolite characteristics across species at various levels including species, metabolites, pathways, and biological taxonomy. In addition, PCMD standardizes metabolite numbering, establishing a uniform system based on existing metabolite-related databases. The database also provides a range of user-friendly online tools, such as Species-comparison, Metabolites-enrichment, and ID conversion, enabling users to perform comparisons and enrichment analyses of metabolites across different species. PCMD stands out as the most comprehensive and species-rich comparative plant metabolomics database currently available, as demonstrated by two case studies that highlight its ability to supplement phylogenetic similarity mining among species through phylogenetic trees and offer new insights into the diversity and species-specificity of metabolites.
ZNF865 Regulates Senescence and Cell Cycle for Applications to Cell Engineering and Gene Therapy
Authors: Levis Hunter , Lewis Christian , Stockham Elise , Weston Jacob , Lawal Ameerah , Lawrence Brandon , Gullbrand Sarah E. , Bowles Robby D. 
Published: October 2023

AbstractZinc finger (ZNF) proteins represent the largest group of regulatory proteins within eukaryotic genomes. However, despite their broad regulatory function, the majority of ZNF protein function remains unknown. Recently, we discovered ZNF865, which has no in-depth publications and has not been functionally characterized. Utilizing CRISPR-guided gene modulation, we show that ZNF865 regulates key cellular and molecular processes associated with healthy cell function by primarily regulating cellular senescence, cell cycle progression, and protein processing. As a result, regulating this gene acts as a primary titratable regulator of cell activity, and we demonstrate the potential of targeted ZNF865 regulation as a tool to control senescence and protein production in multiple clinically relevant cell types for cell engineering/tissue engineering/gene therapy applications. We demonstrate its ability to rescue human senescent cell populations, boost T-cell activity, and dramatically deposit more cartilaginous tissue in a whole organ tissue-engineered intervertebral disc. Overall, we present novel biology and regulatory mechanisms of senescence and cell cycle that were previously unknown and display the power of CRISPR-cell engineering to enhance cell engineering strategies treating disease.
X-chromosome inactivation in human iPSCs provides insight into escape-regulated gene expression
Authors: Topa Hande , Benoit-Pilven Clara , Tukiainen Taru , Pietiläinen Olli 
Published: October 2023

AbstractEpigenetic variation in the X chromosome inactivation (XCI) of human induced pluripotent stem cells (hiPSCs) can impact their ability to accurately model biological sex biases. However, the gene-wise landscape of escape from XCI remains unresolved in female hiPSCs. To characterize the patterns of escape from inactivation, we performed a systematic survey of allele specific expression (ASE) in 165 female hiPSC lines. The analysis revealed that the escape from XCI was non-random and affected primarily genes that escape also in human tissues. However, individual genes and cell lines varied in the frequency and degree of escape. The escape increased gradually after modest decrease ofXISTin cultures, whose loss is commonly used to mark lines with eroded XCI. We identified three clusters of female lines at different stages of XCI. The increased degree of escape from XCI amplified female-biased expression and reduced male-female differences in genes with male-biased expression in the X chromosome. In autosomes, the increased escape modified genuine sex differences in a dose-dependent way suggesting that escape from XCI directly regulated autosomal gene expression. The variation in escape was sufficient to compensate for a dominant loss of function effect in several disease genes. The study presents a comprehensive view of escape from XCI in hiPSCs and emphasizes the need to monitor the XCI status at gene level for disease modeling. It further suggests that the uncommon and variable escape in hiPSCs can provide insight into X chromosome’s role in regulating gene expression and sex differences in humans.
Assessing the impact of 20th century internal migrations on the genetic structure of Estonia
Authors: Kuznetsov Ivan A. ,   Estonian Biobank Research Team, Metspalu Mait , Vainik Uku , Pagani Luca , Montinaro Francesco , Pankratov Vasili 
Published: October 2023

AbstractSpatial genetic structure observed in many human populations is in large part attributed to past demographic events and isolation by distance. However, how intensifying migration affects this structure remains understudied. Here we harness a sample of more than 180 thousand individuals to explore the genetic correlates and consequences of contemporary migrations in Estonia. While we show that migration smoothens the genome-wide genetic structure, it intensifies inter-regional differences in polygenic scores (PGS) for certain traits, derived both from population as well as within-sibship studies. The strongest effect is observed for educational attainment which is consistent with previous observations in the UK and suggests this to be a general pattern. We explore those regional differences in PGS in terms of the driving forces behind them and from a temporal perspective, and suggest urbanisation as a major driver for this pattern in Estonia from at least the first half of the 20th century.