bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prognostic Impact of Minimally Invasive Esophagectomy on Survival After Esophagectomy Following a Delayed Interval After Chemoradiotherapy
Authors: Markar Sheraz R. , Sgromo Bruno , Evans Richard , Griffiths Ewen A. , Alfieri Rita , Castoro Carlo , Gronnier Caroline , Gutschow Christian A. , Piessen Guillaume , Capovilla Giovanni , Grimminger Peter P. , Low Donald E. , Gossage James , Gisbertz Suzanne S. , Ruurda Jelle , van Hillegersberg Richard , D’journo Xavier Benoit , Phillips Alexander W. , Rosati Ricardo , Hanna George B. , Maynard Nick , Hofstetter Wayne , Ferri Lorenzo , Berge Henegouwen Mark I. , Owen Richard 
Published: June 2024

Objective:
To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT).

Background:
Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival.

Methods:
This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches.

Results:
A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate (P=0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14–2.5) and propensity-matched analysis (P=0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50 Gy dose groups (HR=1.9; 95% CI: 1.2–3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1–2.2).

Conclusions:
MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.
Effects of Cyclodextrin Curcumin Formulation on Ischemia-Reperfusion Injury in Porcine DCD Liver Transplantation
Authors: Meurisse Nicolas , Wylin Tine , Heedfeld Veerle , Fieuws Steffen , Ceulemans Laurens , Jochmans Ina , Pirenne Jacques , Monbaliu Diethard 
Published: June 2024

Background.
Curcumin is a pleiotropic antioxidant polyphenol, which has proven to be highly protective in various models of liver injury and inflammation. We hypothesized that adding a stable aqueous curcumin formulation which comprises a water-soluble cyclodextrin curcumin formulation (CDC) complex of the water-insoluble curcumin molecule (Novobion, Espoo, Finland) to preservation solution during liver procurement may reduce ischemia-reperfusion injury and improve graft function after liver transplantation using donation after circulatory death (DCD).

Methods.
In a preclinical pig model of DCD-liver transplantation, livers exposed to 15’ of warm ischemia were either modulated (N = 6) with a flush of preservation solution (histidine-tryptophan-ketoglutarate) containing CDC (60 µmol/L) through the vena porta and the aorta, or not (controls, N = 6) before 4 h of cold storage. Area under the curve of log serum aspartate aminotransferase, markers of graft function (lactate, glycemia, prothrombin time, and bile production), inflammation (tumor necrosis factor-alpha), and survival were monitored.

Results.
Area under the curve of log serum aspartate aminotransferase were similar between curcumin and control groups (22.12 [20.87–24.88] versus 25.08 [22.1–26.55]; P = 0.28). No difference in the liver function markers were observed between groups except a lower serum lactate level 3-h post-reperfusion in the curcumin group (3 [1.95–6.07] versus 8.2 [4.85–13.45] mmol/L; P = 0.05). Serum tumor necrosis factor-alpha levels were similar in each group. Recipient survival rates were found similar.

Conclusions.
CDC added to the preservation solution in DCD liver pig model did not improve ischemia-reperfusion injury severity, liver function, or survival. Further efforts are needed to explore this strategy, particularly with dynamic preservation, which finds its way into clinical practice.
The Cascade of Care in Management of Solid Organ Transplant Candidates With Latent Tuberculosis Infection
Authors: Chiu Chia-Yu , Mahmood Maryam , Brumble Lisa M. , Vikram Holenarasipur R. , Theel Elitza S. , Beam Elena 
Published: June 2024

Background.
Solid organ transplant (SOT) candidates should be screened and treated for latent tuberculosis infection (LTBI) to prevent tuberculosis (TB) reactivation after transplantation. We aimed to assess the steps from positive QuantiFERON (QFT) through LTBI treatment (cascade of care) in the SOT population.

Methods.
We conducted a retrospective study of SOT recipients older than 18 y with a positive QFT during pretransplant evaluation at the Mayo Clinic from January 2010 to June 2023. We analyzed each cascade step to determine associated drop-out factors for LTBI management.

Results.
Of 629 patients who had positive QFT results, 587 (93%) were evaluated by an infectious disease (ID) specialist, 478 (76%) were recommended to start LTBI treatment, 473 (75%) initiated LTBI treatment, and 457 (73%) completed LTBI treatment. LTBI treatment was not recommended in 109 patients evaluated by infectious disease, most of whom had previously received either LTBI (n = 72) or TB (n = 14) treatment. LTBI treatment was initiated before or after transplantation for 45% and 55% of patients, respectively. Isoniazid monotherapy was the most common regimen (92%), and adverse events were rare (7%). Seven patients developed active TB infection posttransplantation under various circumstances (3 without LTBI treatment, 1 during LTBI treatment, and 3 after completing LTBI treatment).

Conclusions.
Our findings demonstrate the variability of LTBI management in SOT recipients with positive QFT. When recommended, most patients completed LTBI treatment successfully. Nonetheless, active TB was noted regardless of whether patients received LTBI treatment. This study highlights the importance of optimizing LTBI management in this population.
The Impact of Donor Body Mass Index on Safety and Outcomes in Living Donor Liver Transplantation: An Analysis of the National United States Database
Authors: Banker Amay , Cywes Claire , Muñoz Nicolas , Taj Raeda , Bittermann Therese , Abt Peter , Abu Gazala Samir 
Published: June 2024

Background.
The prevalence of obesity is rising in the general population. Donor obesity (body mass index ≥30 kg/m2) may potentially reduce the donor pool and impact outcomes in living donor liver transplantation (LDLT).

Methods.
We utilized the national transplant database to investigate the impact of donor obesity on donor and recipient outcomes. This was a retrospective cohort study of all LDLTs performed in the United States between January 2010 and June 2023. Outcomes of interest were analyzed by univariable and multivariable logistic regression. Patient and graft survival was evaluated using Kaplan-Meier and Cox proportional analysis.

Results.
Six hundred seventy-four donors with obesity and 3498 donors without obesity were analyzed. Donors with obesity had higher rates of readmission within 1 y of donation (15.9% versus 11.6%; P = 0.003). The risk of readmission was significantly different between 6 wk and 6 mo of donation (8.8% versus 5.9%; P = 0.036). Donor body mass index (odds ratio [OR], 1.460; 95% confidence interval [CI], 1.129-1.999; P = 0.004) and preoperative alkaline phosphatase levels (OR, 1.005; 95% CI, 1.000-1.011; P = 0.038) were independent predictors of donor readmission. High LDLT center volume was associated with reduced odds of donor readmission (OR, 0.509; 95% CI, 0.373-0.694; P < 0.001). Graft and recipient survival was comparable.

Conclusions.
Selection of living donors with obesity may be a potential avenue to increase the available donor pool without compromising recipient outcomes; however, they are at an increased risk for readmission between 6 wk and 6 mo of donation. The reason for readmission requires further study.
Unveiling the mechanisms of black phosphorus nanosheets-induced viable but non-culturable state inBacillus tropicus
Authors: Xiong Zhiqiang , Zhao Qing , Zhao Ming , Liu Liwei , Zeng Jin , Zhang Siyu , Deng Shuo , Liu Daxu , Zhang Xuejiao , Xing Baoshan 
Published: June 2024

AbstractThe release of black phosphorus (BP) nanosheets has raised concerns regarding potential ecological risks. Previous studies have confirmed their toxicity to bacteria, but discrepancies were observed between results obtained from the growth curve and colony forming unit (CFU) methods, indicating the possibility of bacterial cells entering a viable but non-culturable (VBNC) state induced by BP nanosheets. To accurately assess the risks, it is crucial to understand the underlying mechanisms. In this study, we investigated the effect of BP nanosheets onBacillus tropicus, a gram-positive bacterium, using transcriptome sequencing and biological assays. Our findings revealed that BP nanosheets caused minimal cell death but predominately induced the VBNC state in most cells. At the transcriptional level, we observed significant down-regulation of pathways associated with cellular metabolism and respiratory chain in response to BP nanosheet treatment. Bacterial cells in the VBNC state exhibited depressed respiration to maintain basal cellular activity. Additionally, the reduced cellular respiration and metabolic activity were associated with a decrease in antibiotic susceptibility of the bacteria. These results provide new insights into the antibacterial mechanisms of BP nanosheets and emphasize the necessity of employing appropriate approaches, beyond the traditional CFU method, to assess the bacterial toxicity of nanomaterials.Environmental implicationBacteria play a crucial role as indicators in ecological risk assessment. Although numerous studies have highlighted the exceptional antibacterial properties of black phosphorus (BP) nanosheets, the unique viable but non-culturable (VBNC) state of bacteria is often overlooked when evaluating the ecological risks of nanomaterial, including BP nanosheets. In our study, we found that BP nanosheets can induceBacillus tropicusinto a VBNC state by suppressing cellular metabolism- and respiratory chain-related pathways, shedding light on their ecological risk assessment implications. This finding underscores the importance of utilizing appropriate approaches in evaluating the bacterial toxicity of nanomaterials.
Hair follicle-resident progenitor cells are a major cellular contributor to heterotopic subcutaneous ossifications in a mouse model of Albright hereditary osteodystrophy
Authors: McMullan Patrick , Maye Peter , Root Sierra H. , Yang Qingfen , Edie Sarah , Rowe David , Kalajzic Ivo , Germain-Lee Emily L. 
Published: June 2024

AbstractHeterotopic ossifications (HOs) are the pathologic process by which bone inappropriately forms outside of the skeletal system. Despite HOs being a persistent clinical problem in the general population, there are no definitive strategies for their prevention and treatment due to a limited understanding of the cellular and molecular mechanisms contributing to lesion development. One disease in which the development of heterotopic subcutaneous ossifications (SCOs) leads to morbidity is Albright hereditary osteodystrophy (AHO). AHO is caused by heterozygous inactivation ofGNAS, the gene that encodes the α-stimulatory subunit (Gαs) of G proteins. Previously, we had shown using our laboratory’s AHO mouse model that SCOs develop around hair follicles (HFs). Here we show that SCO formation occurs due to inappropriate expansion and differentiation of HF-resident stem cells into osteoblasts. We also show in AHO patients and mice thatSecreted Frizzled Related Protein 2(SFRP2)expression is upregulated in regions of SCO formation and that elimination ofSfrp2in male AHO mice exacerbates SCO development. These studies provide key insights into the cellular and molecular mechanisms contributing to SCO development and have implications for potential therapeutic modalities not only for AHO patients but also for patients suffering from HOs with other etiologies.
Next Generation Aging Clock: A Novel Approach to Decoding Human Aging Through Over 3000 Cellular Pathways
Authors: Xiong Jianghui 
Published: June 2024

AbstractThis paper introduces ‘Next Generation Aging Clock Models,’ a new approach aimed at improving disease prediction by defining aging clocks for specific cellular components or pathways, rather than giving a single value for the entire human body. The methodology consists of two stages: a pre-training stage that creates 3,028 generic pathway aging models by integrating genome-wide DNA methylation data with gene ontology and pathway databases, and a fine-tuning stage that produces 30,280 disease-specific pathway aging models using DNA methylation profiles from 3,263 samples across 10 age-related diseases. Our findings show the model’s predictive power for various diseases. For example, the aging index of blood vessel endothelial cell migration can predict Atherosclerosis with an odds ratio of 80. Alzheimer’s disease can be predicted by the aging index of response to DNA damage stimulus, Major Depressive Disorder by the organization of the mitochondrion, breast cancer by DNA repair, and the severity of COVID-19 by neutrophil degranulation, with an odds ratio of 8.5. Additionally, a global analysis revealed that aging-related diseases can be categorized into nucleus aging (such as Alzheimer’s disease) and cytoplasm aging (such as Parkinson’s disease). This model provides a comprehensive view of aging from the organelle to the organ level using just a blood or saliva sample. This innovative approach is expected to be a valuable tool for research into aging-related diseases and for personalized aging interventions.
Effects of low-dose monacolin K on the circulating proteome in individuals with suboptimal cholesterolaemia: A randomised clinical trial
Authors: Cicero Arrigo F.G. , Uboldi Patrizia , Beretta Giangiacomo , Fogacci Federica , Grandi Elisa , Svecla Monika , Norata Giuseppe Danilo 
Published: June 2024

AbstractRed yeast rice (RYR) is a traditional Chinese product obtained by fermenting rice with the yeastMonascus purpureusand contains monacolin K, which is chemically identical to lovastatin, a drug with cholesterol-lowering activity. The European Food Safety Authority (EFSA) has evaluated the safety and efficacy of RYR supplements for managing cholesterol levels. In 2018, EFSA published a scientific opinion on the use of monacolin K from RYR in food supplements, concluding that monacolins from RYR may raise significant safety concerns at a use level of 10 mg/ day. Following that, the European Commission declared in 2022 that RYR products must contain less than 3 mg of monacolins for daily consumption. The aim of this work was to perform a comprehensive profiling of plasma markers of muscle and liver dysfunction by extensive untargeted plasma proteomics in healthy volunteers with suboptimal cholesterolaemia who were randomly assigned to receive a dietary supplement containing RYR (total monacolin <3 mg) or placebo for one month.No changes in classical markers of liver (AST, ALT) or muscle (CPK) function were detected in the plasma samples of patients treated with the supplement compared to placebo. Interestingly, the analysis of circulating proteins marking an early acute response in the liver, such as serum amyloid A4, orosomucoid 2, haptoglobin-related protein, prothrombin, α-1-antitrypsin, α-2-HS- glycoprotein, serum amyloid P (APCS), orosomucoid 1, c-reactive protein (CRP) and α-2- macroglobulin confirmed an overlapping profile in the two groups. Similarly, the analysis of ryanodine receptor 1, titin, dystrophin and myosin 7 again showed a similar profile in the two groups. These data indicate that a low dose of monacolin K (<3 mg/day) in subjects with suboptimal cholesterolaemia does not increase levels of markers of liver and skeletal muscle function in plasma, excluding a deleterious effect of monacolin K on these tissues.
Electrical signaling and coordinated behavior in the closest relative of animals
Authors: Colgren Jeffrey , Burkhardt Pawel 
Published: June 2024

AbstractThe transition between simple to complex multicellularity involves large degrees of division of labor and specialization of cell types. In animals, complex sensory motor systems are primarily built around the fundamental cell types of muscles and neurons, though the evolutionary origin of these cells, and their integration, remains unclear. Here, in order to investigate sensory-behavior coupling in the closest relatives of animals, we established a line of the choanoflagellate,Salpingoeca rosetta, which stably expresses the calcium indicator RGECO1. Using this, we identify a novel cellular behavior associated with electrical signaling, in which ciliary arrest is coupled with apical-basal contraction of the cell. This behavior, and the associated calcium transients, are synchronized in the multicellular state and result in coordinated ciliary arrest and colony wide contraction, suggesting information is spread amongst the cells. Our work reveals fundamental insights into how choanoflagellates sense and respond to their environment and offer a new perspective into the integration of cellular and organism wide behavior in the closest protistan relatives of animals.
Reconstructing Biological Molecules with Help from Video Gamers
Authors: Petrides Andreas C. , Joosten Robbie P. , Players Foldit , Khatib Firas , Horowitz Scott 
Published: June 2024

AbstractFoldit is a citizen science video game in which players tackle a variety of complex biochemistry puzzles. Here, we describe a new series of puzzles in which Foldit players improve the accuracy of the public repository of experimental protein structure models, the Protein Data Bank (PDB). Analyzing the results of these puzzles showed that the Foldit players were able to considerably improve the deposited structures and thus, in most cases, improved the output of the automated PDB-REDO refinement pipeline. These improved structures are now being hosted at PDB-REDO. These efforts highlight the continued need for the engagement of the lay population in science.
Inflammatory markers in pregnancy – surprisingly stable. Mapping trajectories and drivers in four large cohorts
Authors: Gigase Frederieke A.J. , Suleri Anna , Isaevska Elena , Rommel Anna-Sophie , Boekhorst Myrthe G.B.M. , Dmitrichenko Olga , El Marroun Hanan , Steegers Eric A.P. , Hillegers Manon H.J. , Muetzel Ryan L. , Lieb Whitney , Cecil Charlotte A.M. , Pop Victor , Breen Michael , Bergink Veerle , de Witte Lot D. 
Published: June 2024

AbstractAdaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers are the mainstay. The design and interpretation of human biomarker studies require additional insights in the trajectories and drivers of peripheral immune markers. The current study mapped maternal inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17A, IL-23, interferon-γ) during pregnancy and investigated the impact of demographic, environmental and genetic drivers on maternal inflammatory marker levels in four multi-ethnic and socio-economically diverse population-based cohorts with more than 12,000 pregnant participants. Additionally, pregnancy inflammatory markers were compared to pre-pregnancy levels. Cytokines showed a high correlation with each other, but not with CRP. Inflammatory marker levels showed high variability between individuals, yet high concordance within an individual over time during and pre-pregnancy. Pre-pregnancy body mass index (BMI) explained more than 9.6% of the variance in CRP, but less than 1% of the variance in cytokines. The polygenic score of CRP was the best predictor of variance in CRP (>14.1%). Gestational age and previously identified inflammation drivers, including tobacco use and parity, explained less than 1% of variance in both cytokines and CRP. Our findings corroborate differential underlying regulatory mechanisms of CRP and cytokines and are suggestive of an individual inflammatory marker baseline which is, in part, genetically driven. While prior research has mainly focused on immune marker changes throughout pregnancy, our study suggests that this field could benefit from a focus on intra-individual factors, including metabolic and genetic components.
The BMP2 prodomain promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers in vivo
Authors: Chauhan Pooja , Xue Yongqiang , Fisher Allison L. , Kim Hyung-Seok , Babitt Jodie L. , Christian Jan L. 
Published: June 2024

AbstractBone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage assays, which revealed that BMP2 is sequentially cleaved by furin at two sites, initially at a site upstream of the mature ligand, and then at a site adjacent to the ligand domain, while BMP6 is cleaved at a single furin motif. Cleavage of both sites of BMP2 is required to generate fully active BMP2 homodimers when expressed inXenopusembryos or liver endothelial cells, and fully active BMP2/6 heterodimers inXenopus. We analyzed BMP activity inXenopusembryos expressing chimeric proteins consisting of the BMP2 prodomain and BMP6 ligand domain, or vice versa. We show that the prodomain of BMP2 is necessary and sufficient to generate active BMP6 homodimers and BMP2/6 heterodimers, whereas the BMP6 prodomain cannot generate active BMP2 homodimers or BMP2/6 heterodimers. We examined BMP2 and BMP6 homodimeric and heterodimeric ligands generated from native and chimeric precursor proteins expressed inXenopusembryos. Whereas native BMP6 is not cleaved when expressed alone, it is cleaved to generate BMP2/6 heterodimers when co-expressed with BMP2. Furthermore, BMP2-6 chimeras are cleaved to generate BMP6 homodimers. Our findings reveal an important role for the BMP2 prodomain in dimerization and proteolytic activation of BMP6.