bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-induced P4HA1 overexpression promotes post-ischemic angiogenesis by enhancing endothelial glycolysis through downregulating FBP1
Authors: Xu Yating , Xia Di , Huang Kai , Liang Minglu 
Published: January 2024

Abstract
Background
Angiogenesis is essential for tissue repair in ischemic diseases, relying on glycolysis as its primary energy source. Prolyl 4-hydroxylase subunit alpha 1 (P4HA1), the catalytic subunit of collagen prolyl 4-hydroxylase, is a glycolysis-related gene in cancers. However, its role in glycolysis-induced angiogenesis remains unclear.

Methods
P4HA1 expression was modulated using adenoviruses. Endothelial angiogenesis was evaluated through 5-ethynyl-2′-deoxyuridine incorporation, transwell migration, and tube formation assays in vitro. In vivo experiments measured blood flow and capillary density in the hindlimb ischemia (HLI) model. Glycolytic stress assays, glucose uptake, lactate production, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were employed to assess glycolytic capacity. Transcriptome sequencing, validated by western blotting and RT-PCR, was utilized to determine underlying mechanisms.

Results
P4HA1 was upregulated in endothelial cells under hypoxia and in the HLI model. P4HA1 overexpression promoted angiogenesis in vitro and in vivo, while its knockdown had the opposite effect. P4HA1 overexpression reduced cellular α-ketoglutarate (α-KG) levels by consuming α-KG during collagen hydroxylation. Downregulation of α-KG reduced the protein level of a DNA dioxygenase, ten–eleven translocation 2 (TET2), and its recruitment to the fructose-1,6-biphosphatase (FBP1) promoter, resulting in decreased FBP1 expression. The decrease in FBP1 enhanced glycolytic metabolism, thereby promoting endothelial angiogenesis.

Conclusions
Hypoxia-induced endothelial P4HA1 overexpression enhanced angiogenesis by promoting glycolytic metabolism reprogramming through the P4HA1/α-KG/TET2/FBP1 pathway. The study’s findings underscore the significance of P4HA1 in post-ischemic angiogenesis, suggesting its therapeutic potential for post-ischemic tissue repair.
Comparative study of locking neutralization plate construct versus tension band wiring with a cannulated screw for patella fractures: experimental and finite element analysis
Authors: Kim Sunjung , Mungalpara Nirav , Wangikar Rohan , Tarabichi Majd , Karam Joseph , Bedi Asheesh , Koh Jason , Amirouche Farid 
Published: January 2024

AbstractTransverse patella fractures, accounting for approximately 1% of Orthopedic injuries, pose intricate challenges due to their vital role in knee mechanics. This study aimed to compare the biomechanical performance of a construct, integrating cannulated screws and an anterior locking neutralization plate, with the conventional tension band wiring technique for treating these fractures. Experimental testing and Finite Element Analysis were employed to evaluate the constructs and gain profound insights into their mechanical behavior. Sixteen cadaveric knees were prepared, and transverse patella fractures were induced at the midpoints using a saw. The plate construct and tension band wire fixation were randomly assigned to the specimens. A cyclic test evaluated the implants' durability and stability, simulating knee movement during extension and flexion. Tensile testing assessed the implants' maximum failure force after cyclic testing, while Finite Element Analysis provided detailed insights into stress distribution and deformation patterns. Statistical analysis was exclusively performed for the experimental data. Results showed the plate enhanced stability with significantly lower deformation (0.09 ± 0.12 mm) compared to wire fixation (0.77 ± 0.54 mm) after 500 cycles (p = 0.004). In tensile testing, the construct also demonstrated higher failure resistance (1359 ± 21.53 N) than wire fixation (780.1 ± 22.62N) (p = 0.007). Finite Element Analysis highlighted distinct stress patterns, validating the construct's superiority. This research presents a promising treatment approach for transverse patella fractures with potential clinical impact and future research prospects. This study presents a promising advancement in addressing the intricate challenges of transverse patella fractures, with implications for refining clinical practice. The construct's improved stability and resistance to failure offer potential benefits in postoperative management and patient outcomes.
Structure-primed embedding on the transcription factor manifold enables transparent model architectures for gene regulatory network and latent activity inference
Authors: Tjärnberg Andreas , Beheler-Amass Maggie , Jackson Christopher A. , Christiaen Lionel A. , Gresham David , Bonneau Richard 
Published: January 2024

Abstract
Background
Modeling of gene regulatory networks (GRNs) is limited due to a lack of direct measurements of genome-wide transcription factor activity (TFA) making it difficult to separate covariance and regulatory interactions. Inference of regulatory interactions and TFA requires aggregation of complementary evidence. Estimating TFA explicitly is problematic as it disconnects GRN inference and TFA estimation and is unable to account for, for example, contextual transcription factor-transcription factor interactions, and other higher order features. Deep-learning offers a potential solution, as it can model complex interactions and higher-order latent features, although does not provide interpretable models and latent features.

Results
We propose a novel autoencoder-based framework, StrUcture Primed Inference of Regulation using latent Factor ACTivity (SupirFactor) for modeling, and a metric, explained relative variance (ERV), for interpretation of GRNs. We evaluate SupirFactor with ERV in a wide set of contexts. Compared to current state-of-the-art GRN inference methods, SupirFactor performs favorably. We evaluate latent feature activity as an estimate of TFA and biological function in S. cerevisiae as well as in peripheral blood mononuclear cells (PBMC).

Conclusion
Here we present a framework for structure-primed inference and interpretation of GRNs, SupirFactor, demonstrating interpretability using ERV in multiple biological and experimental settings. SupirFactor enables TFA estimation and pathway analysis using latent factor activity, demonstrated here on two large-scale single-cell datasets, modeling S. cerevisiae and PBMC. We find that the SupirFactor model facilitates biological analysis acquiring novel functional and regulatory insight.
Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock
Authors: Blixt Patrik Johansson , Nguyen Maxime , Cholley Bernard , Hammarskjöld Fredrik , Toiron Alois , Bouhemad Belaid , Lee Shaun , De Geer Lina , Andersson Henrik , Aneq Meriam Åström , Engvall Jan , Chew Michelle S. 
Published: January 2024

Abstract
Background
Left ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock.

Methods
A total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis.

Results
LVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality.

Conclusions
MAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear.
Trial registration NCT01747187 and NCT04695119.
Robotic spleen-preserving distal pancreatectomy using the first domestic surgical robot platform (the hinotori™ Surgical Robot System): a case report
Authors: Tomihara Kazuki , Ide Takao , Ito Kotaro , Tanaka Tomokazu , Noshiro Hirokazu 
Published: January 2024

Abstract
Background
Robotic pancreatectomy has been performed worldwide mainly using the da Vinci® Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Recently, because of the death of some patents related to the da Vinci® system, new surgical robot systems have been introduced that are characterized by unique technical refinements. In Japan, the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan) was approved for use in gastroenterological surgery in October 2022. Since then, we have attempted complicated procedures using this robot. In this report, we report our first experience performing spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein using this first Japanese domestic surgical robot.

Case presentation
The patient was a 58-year-old woman with a mass in the pancreatic tail identified during medical screening. Further examinations resulted in a diagnosis of a pancreatic neuroendocrine tumor. The patient consented to surgical resection, and we planned robotic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein, using the hinotori™. Five trocars, including one port for the assistant surgeon, were placed in the upper abdomen. The operating unit was rolled in from the patient’s right side. The pivot position was set for each robotic arm, and this setting was specific to the hinotori™. The cockpit surgeon performed all surgical procedures, excluding port placement and pancreatic transection. There were no unrecoverable device errors during the operation. The operation time was 531 min, and blood loss was 192 ml. The postoperative course was uneventful. We were able to safely perform this highly complicated surgery for a pancreatic tumor using the first Japanese domestic surgical robot platform.

Conclusions
The first Japanese domestic surgical robot platform, hinotori™, has different features from those of the da Vinci® and performed sufficiently as a surgical robot system in highly advanced pancreatic surgery.
A novel missense mutation (FGG c.1168G > T) in the gamma chain of fibrinogen causing congenital hypodysfibrinogenemia with bleeding phenotype
Authors: Xu Nuo , Zheng Liping , Dai Zhehao , Zhu Jun , Xie Peng , Yang Shun , Chen Fei 
Published: January 2024

Abstract
Background
Fibrinogen plays pivotal roles in multiple biological processes. Genetic mutation of the fibrinogen coding genes can result in congenital fibrinogen disorders (CFDs). We identified a novel heterozygous missense mutation, FGG c.1168G > T (NCBI NM_000509.6), and conducted expression studies and functional analyses to explore the influence on fibrinogen synthesis, secretion, and polymerization.

Methods
Coagulation tests were performed on the patients to detect the fibrinogen concentration. Whole-exome sequencing (WES) and Sanger sequencing were employed to detect the novel mutation. Recombinant fibrinogen-producing Chinese hamster ovary (CHO) cell lines were built to examine the recombinant fibrinogen synthesis and secretion by western blotting and enzyme-linked immunosorbent assay (ELISA). The functional analysis of fibrinogen was performed by thrombin-catalyzed fibrin polymerization assay. In silico molecular analyses were carried out to elucidate the potential molecular mechanisms.

Results
The clinical manifestations, medical history, and laboratory tests indicated the diagnosis of hypodysfibrinogenemia with bleeding phenotype in two patients. The WES and Sanger sequencing revealed that they shared the same heterozygous missense mutation, FGG c.1168G > T. In the expression studies and functional analysis, the missense mutation impaired the recombinant fibrinogen's synthesis, secretion, and polymerization. Furthermore, the in silico analyses indicated novel mutation led to the hydrogen bond substitution.

Conclusion
The study highlighted that the novel heterozygous missense mutation, FGG c.1168G > T, would change the protein secondary structure, impair the “A: a” interaction, and consequently deteriorate the fibrinogen synthesis, secretion, and polymerization.
Resistance to biotic and abiotic stress in potato: the origin of the genes and corresponding molecular markers
Authors: Islam Saiful , Li Jiana , Rahman Mohammad Ataur , Xie Fangru , Song Botao , Nie Bihua 
Published: January 2024

AbstractThe integration of molecular markers in the realm of potato genetics has opened new avenues for accelerating genotype analysis and developing improved varieties. Many markers linked to important features have been discovered so far and are consistently distributed across 12 chromosomes (× = 12) of potato. Notably, the genes allied to disease resistance stand out as significant and prevalent. Molecular markers associated with these genes have revolutionized selection processes, making them faster and more effective. Besides, advanced technologies such as kompetitive allele-specific PCR, high-resolution melting assay, SNP-array, genotyping by sequencing, and genome-wide association study, are emphasizing the use of those molecular markers with greater accuracy to detect R genes aligning with the phenotypes. This review discusses advances in potato breeding for resistance against common stresses, focusing on progress made through molecular marker-assisted selection.
Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors
Authors: Sotelo-Rodríguez Carolina , Vallejo-Ardila Dora , Ruiz-Patiño Alejandro , Chamorro Diego F. , Rodríguez July , Moreno-Pérez Darwin A. , Carranza Hernán , Otero Jorge , Vargas Carlos , Archila Pilar , Rojas Leonardo , Zuluaga Jairo , Rubio Cladelis , Ordóñez-Reyes Camila , Garcia-Robledo Juan Esteban , Mejía Sergio , Jaller Elvira , Arrieta Oscar , Cardona Andrés F. 
Published: January 2024

PURPOSE Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia. METHODS Demographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care. RESULTS A total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non–small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively. CONCLUSION Using an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.
Cellular Mass Response to Therapy Correlates With Clinical Response for a Range of Malignancies
Authors: Stevens Mark M. , Kimmerling Robert J. , Olcum Selim , Vacha Madeleine , LaBella Rachel , Minnah Anthony , Katsis Katelin , Fujii Juanita , Shaheen Zayna , Sundaresan Srividya , Criscitiello Joseph , Niesvizky Ruben , Raje Noopur , Branagan Andrew , Krishnan Amrita , Jagannath Sundar , Parekh Samir , Sperling Adam S. , Rosenbaum Cara A. , Munshi Nikhil , Luskin Marlise R. , Tamrazi Anobel , Reid Clifford A. 
Published: January 2024

PURPOSE Cancer patients with advanced-stage disease have poor prognosis, typically having limited options for efficacious treatment, and genomics-based therapy guidance continues to benefit only a fraction of patients. Next-generation ex vivo approaches, such as cell mass-based response testing (MRT), offer an alternative precision medicine approach for a broader population of patients with cancer, but validation of clinical feasibility and potential impact remain necessary. MATERIALS AND METHODS We evaluated the clinical feasibility and accuracy of using live-cell MRT to predict patient drug sensitivity. Using a unified measurement workflow with a 48-hour result turnaround time, samples were subjected to MRT after treatment with a panel of drugs in vitro. After completion of therapeutic course, clinical response data were correlated with MRT-based predictions of outcome. Specimens were collected from 104 patients with solid (n = 69) and hematologic (n = 35) malignancies, using tissue formats including needle biopsies, malignant fluids, bone marrow aspirates, and blood samples. Of the 81 (78%) specimens qualified for MRT, 41 (51%) patients receiving physician-selected therapies had treatments matched to MRT. RESULTS MRT demonstrated high concordance with clinical responses with an odds ratio (OR) of 14.80 ( P = .0003 [95% CI, 2.83 to 102.9]). This performance held for both solid and hematologic malignances with ORs of 20.67 ( P = .0128 [95% CI, 1.45 to 1,375.57]) and 8.20 ( P = .045 [95% CI, 0.77 to 133.56]), respectively. Overall, these results had a predictive accuracy of 80% ( P = .0026 [95% CI, 65 to 91]). CONCLUSION MRT showed highly significant correlation with clinical response to therapy. Routine clinical use is technically feasible and broadly applicable to a wide range of samples and malignancy types, supporting the need for future validation studies.
Detection of Copy-Number Variation in Circulating Cell-Free DNA in Patients With Uveal Melanoma
Authors: Sato Takuto , Montazeri Kamaneh , Gragoudas Evangelos S. , Lane Anne Marie , Aronow Mary Beth , Cohen Justine V. , Boland Genevieve M. , Banks Eric , Kachulis Christopher , Fleharty Mark , Cibulskis Carrie , Lawless Aleigha , Adalsteinsson Viktor A. , Sullivan Ryan J. , Kim Ivana K. 
Published: January 2024

PURPOSE Somatic chromosomal alterations, particularly monosomy 3 and 8q gains, have been associated with metastatic risk in uveal melanoma (UM). Whole genome-scale evaluation of detectable alterations in cell-free DNA (cfDNA) in UM could provide valuable prognostic information. Our pilot study evaluates the correlation between genomic information using ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA in UM and associated clinical outcomes. MATERIALS AND METHODS ULP-WGS of cfDNA was performed on 29 plasma samples from 16 patients, 14 metastatic UM (mUM) and two non-metastatic, including pre- and post-treatment mUM samples from 10 patients treated with immunotherapy and one with liver-directed therapy. We estimated tumor fraction (TFx) and detected copy-number alterations (CNAs) using ichorCNA. Presence of 8q amplification was further analyzed using the likelihood ratio test (LRT). RESULTS Eleven patients with mUM (17 samples) of 14 had detectable circulating tumor DNA (ctDNA). 8q gain was detected in all 17, whereas monosomy 3 was detectable in 10 of 17 samples. TFx generally correlated with disease status, showing an increase at the time of disease progression (PD). 8q gain detection sensitivity appeared greater with the LRT than with ichorCNA at lower TFxs. The only patient with mUM with partial response on treatment had a high pretreatment TFx and undetectable on-treatment ctDNA, correlating with her profound response and durable survival. CONCLUSION ctDNA can be detected in mUM using ULP-WGS, and the TFx correlates with DS. 8q gain was consistently detectable in mUM, in line with previous studies indicating 8q gains early in primary UM and higher amplification with PD. Our work suggests that detection of CNAs by ULP-WGS, particularly focusing on 8q gain, could be a valuable blood biomarker to monitor PD in UM.
Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion
Authors: Dehne Sarah , Riede Carlo , Feisst Manuel , Klotz Rosa , Etheredge Melanie , Hölle Tobias , Merle Uta , Mehrabi Arianeb , Michalski Christoph W. , Büchler Markus W. , Weigand Markus A. , Larmann Jan 
Published: January 2024

BACKGROUND:
Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss.

METHODS:
We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model.

RESULTS:
Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600–5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, −0.020 [−0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [−0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [−0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903–1.365], P = .321).

CONCLUSIONS:
Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.