bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases – Final Results from the Phase III Randomized Controlled Trial SCANDIUM
Authors: Olofsson Bagge Roger , Nelson Axel , Shafazand Amir , All-Eriksson Charlotta , Cahlin Christian , Elander Nils , Gustavsson Anders , Helgadottir Hildur , Kiilgaard Jens Folke , Kinhult Sara , Ljuslinder Ingrid , Mattsson Jan , Rizell Magnus , Sternby Eilard Malin , Ullenhag Gustav J. , Nilsson Jonas A. , Ny Lars , Lindnér Per 
Published: February 2024

Objective:
To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases.

Summary Background Data:
Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS).

Methods:
In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months.

Results:
The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group.

Conclusions:
For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met.
Basiliximab Induction and Postoperative Steroid-free Immunosuppression With Tacrolimus in Pediatric Liver Transplantation: A Randomized Clinical Trial
Authors: Dong Chong , Song Zhuolun , Sun Chao , Wang Kai , Zhang Wei , Chen Jing , Zheng Weiping , Yang Yang , Wang Zhen , Han Chao , Jiao Lijun , Zhang Guofeng , Xie Enbo , Gao Wei , Shen Zhongyang 
Published: February 2024

Background.
Optimizing the immunosuppressive regimen is essential to improve the long-term outcomes of pediatric liver transplant recipients.

Methods.
We conducted a prospective, randomized, open-label study to compare the safety and efficacy of 2 treatment approaches during pediatric liver transplantation: tacrolimus monotherapy following basiliximab induction (the study group) and a dual regimen of tacrolimus plus steroids (the control group). A total of 150 patients were enrolled, with 75 patients allocated to each group.

Results.
In both groups, recipients achieved graft and recipient overall survival rates exceeding 93%, with no statistically significant differences between them. However, the study group exhibited a significantly lower incidence of acute cellular rejection (ACR), delayed occurrence of ACR, and an improved ACR-free survival rate at 2 y compared with the control group. Notably, the study group also showed a significant reduction in the incidence of de novo donor-specific antibodies at 3-mo and 2-y posttransplant. Furthermore, 6 mo after the transplant, the study group demonstrated significant improvements in weight-for-age Z score and height-for-age Z score. No notable differences were observed in postoperative complications or the incidence of liver fibrosis between the 2 groups.

Conclusions.
Basiliximab induction combine with tacrolimus (TAC) monotherapy is a safe and effective immunosuppressive regimen to reduce the episodes of ACR without influencing the development of liver fibrosis and graft and recipient survival rate after pediatric liver transplantation.
Localized Liver Injury During Normothermic Ex Situ Liver Perfusion Has No Impact on Short-term Liver Transplant Outcomes
Authors: Martin Jack L. , Rhodes Freya , Upponi Sara , Udeaja Yagazie , Swift Lisa , Fear Corina , Webster Rachel , Webb Gwilym James , Allison Michael , Paterson Anna , Gaurav Rohit , Butler Andrew J. , Watson Christopher J. E. 
Published: February 2024

Background.
Normothermic ex situ liver perfusion (NESLiP) has the potential to increase organ utilization. Radiological evidence of localized liver injury due to compression at the time of NESLiP, termed cradle compression, is a recognized phenomenon but is poorly characterized.

Methods.
A retrospective analysis of a prospectively collected database was performed of transplanted livers that underwent NESLiP and subsequently had a computed tomography performed within the first 14 d posttransplant. The primary study outcome was 1-y graft survival.

Results.
Seventy livers (63%) were included in the analysis. Radiological evidence of cradle compression was observed in 21 of 70 (30%). There was no difference in rate of cradle compression between donor after circulatory death and donated after brain death donors (P = 0.37) or with duration of NESLiP. Univariate analysis demonstrated younger (area under the receiver operating characteristic, 0.68; P = 0.008; 95% confidence interval [CI], 0.55-0.82) and heavier (area under the receiver operating characteristic, 0.80; P < 0.001; 95% CI, 0.69-0.91) livers to be at risk of cradle compression. Only liver weight was associated with cradle compression on multivariate analysis (odds ratio, 1.003; P = 0.005; 95% CI, 1.001-1.005). There was no difference in 1-y graft survival (16/17 [94.1%] versus 44/48 [91.6%]; odds ratio, 0.69; P = 0.75; 95% CI, 0.07-6.62).

Conclusions.
This is the first study assessing the impact of cradle compression on outcome. We have identified increased donor liver weight and younger age as risk factors for the development of this phenomenon. Increasing utilization of NESLiP will result in the increased incidence of cradle compression but the apparent absence of long-term sequelae is reassuring. Routine postoperative axial imaging may be warranted.
Outcomes and Management of Re-Establishing Bariatric Patients
Authors: Medhati Pourya , Saleh Omnia S , Nimeri Abdelrahman , Apovian Caroline , Thompson Christopher , Jirapinyo Pichamol , Sheu Eric G , Tavakkoli Ali 
Published: February 2024

BACKGROUND:
Lifelong follow-up after metabolic and bariatric surgery (MBS) is necessary to monitor for patient outcomes and nutritional status. However, many patients do not routinely follow-up with their MBS team. We studied what prompted MBS patients to seek bariatric care after being lost to follow-up and the subsequent treatments they received.

STUDY DESIGN:
A retrospective cohort study of patients after MBS who had discontinued regular MBS follow-up but represented to the MBS clinic between July 2018 and December 2022 to re-establish care. Patients with a history of a sleeve gastrectomy (SG), Roux-En-Y gastric bypass (RYGB), and adjustable gastric banding (AGB) were included.

RESULTS:
We identified 400 patients (83.5% women, mean age 50.3 ± 12.2 years at the time of re-establishment of bariatric care), of whom 177 (44.3%) had RYGB, 154 (38.5%) had SG, and 69 (17.2%) had AGB. Overall, recurrent weight gain was the most common reason for presentation for all three procedures (81.2% in SG, 62.7% in RYGB, and 65.2% in AGB; p < 0.001). Patients who underwent SG were more likely to undergo a revision MBS compared with patients who underwent RYGB (16.9% vs 5.8%, p < 0.001), whereas patients who underwent RYGB were more likely to undergo an endoscopic intervention than patients who underwent SG (17.5% vs 7.8%, p < 0.001). The response to antiobesity medication agents, specifically glucagon-like peptide-1 receptor agonists drugs, was better in patients who underwent RYGB, than that in patients who underwent SG.

CONCLUSIONS:
This study highlights recurrent weight gain as the most common reason for patients after MBS seeking to re-establish care with the MBS team. SG had a higher rate of revision MBS than RYGB, whereas endoscopic interventions were performed more frequently in the RYGB group. Antiobesity medication agents, especially glucagon-like peptide-1 receptor agonists drugs, were more effective in patients who underwent RYGB.
Evaluating the Safety and Efficacy of Topical Insulin for Ocular Disease: A Systematic Review
Authors: de Oliveira Andrade Luís Jesuino , Matos de Oliveira Gabriela Correia , Santos França Caroline , Matos de Oliveira Luís 
Published: February 2024

ABSTRACTIntroductionOcular surface disorders are prevalent, impacting millions worldwide and causing significant morbidity. Conventional treatments often fall short in addressing refractory cases. Topical insulin has emerged as a potential therapeutic option.ObjectiveThis systematic review aimed to evaluate the safety and efficacy of topical insulin for ocular diseases.MethodsWe conducted a systematic review in major databases including the PubMed, MEDLINE, and EMBASE for studies published from (1976 Jan - 2024 Feb) investigating topical insulin for ocular conditions. Studies were screened and selected based on predefined inclusion/exclusion criteria. Data on safety and efficacy were extracted and analyzed.ResultsTen studies (1 case-control, 3 randomized prospective, 3 retrospective, and 3 double-blind designs) met the inclusion criteria. Studies explored various indications, including neurotrophic corneal ulcers, persistent epithelial defects, recurrent epithelial erosions, dry eye disease, and postoperative corneal wound healing in diabetic patients. Overall, findings suggested promising outcomes with topical insulin: promoting healing of refractory neurotrophic corneal ulcers, accelerating reepithelialization in persistent epithelial defects, reducing recurrence of recurrent epithelial erosions, improving symptoms and reducing corneal staining in dry eye disease, enhancing postoperative corneal epithelial wound healing in diabetic patients. Adverse events were minimal and primarily reported as transient stinging or discomfort.ConclusionThis review provides encouraging evidence for the therapeutic potential of topical insulin in diverse ocular diseases. While methodological limitations exist, particularly in non-randomized studies, the current body of literature suggests topical insulin may offer a safe and effective treatment option for patients with refractory corneal disorders.
Mitigating Stress: Exploring how our feet change shape with size
Authors: Treherne Paige , Lee Erin CS , Rainbow Michael J , Kelly Luke A 
Published: February 2024

AbstractIf human skeletal shape increases proportionally with size (isometric scaling) this can produce exponential increases in joint contact stresses. However, if skeletal shape changes as a function of size (allometric scaling) this can mitigate increases in joint contact stress by changing the surface area to volume ratio. Here we explored whether human foot bones scale with allometry and, if so, to identify the shape features that are associated with bone size. Computed tomography scans of the two largest foot bones (talus, calcaneus) were obtained from 36 healthy individuals. We implemented a scaling analysis for each joint surface area and bone. We performed a Procrustes ANOVA to establish the shape features associated with bone size. In line with our hypothesis, articular surfaces on the talus and the posterior facet of the calcaneus all scaled with positive allometry. Interestingly, the calcaneus scaled with negative allometry, appearing more cube-like with increasing size. This may be important for mitigation of internal bone stresses with increasing skeletal size. Our findings suggest distinct, but varied scaling strategies within the foot. This may reflect the requirement to maintain healthy joint contact and internal bone stresses with increasing size.
STCC: consensus clustering enhances spatial domain detection for spatial transcriptomics data
Authors: Hu Congcong , Wei Nana , Yang Jiyuan , Wu Hua-Jun , Zheng Xiaoqi 
Published: February 2024

AbstractThe rapid advance of spatially resolved transcriptomics technologies has yielded substantial spatial transcriptomics data. Deriving biological insights from these data poses non-trivial computational and analysis challenges, of which the most fundamental step is spatial domain detection (or spatial clustering). Although a number of tools for spatial domain detection have been proposed in recent years, their performance varies across datasets and experimental platforms. It is thus an important task to take full advantage of different tools to get a more accurate and stable result through consensus strategy. In this work, we developed STCC, a novel consensus clustering framework for spatial transcriptomics data that aggregates outcomes from state-of-the-art tools using a variety of consensus strategies, including Onehot-based, Average-based, Hypergraph-based and wNMF-based methods. Comprehensive assessments on simulated and real data from distinct experimental platforms show that consensus clustering significantly improves clustering accuracy over individual methods under varied input parameters. For normal tissue samples exhibiting clear layered structure, consensus clustering by integrating multiple baseline methods leads to improved results. Conversely, when analyzing tumor samples that display scattered cell type distribution patterns, integration of a single baseline method yields satisfactory performance. For consensus strategies, Average-based and Hypergraph-based approaches demonstrated optimal precision and stability. Overall, STCC provides a scalable and practical solution for spatial domain detection in spatial transcriptomic data, laying a solid foundation for future research and applications in spatial transcriptomics.
Blind individuals’ enhanced ability to sense their own heartbeat is related to the thickness of their occipital cortex
Authors: Stroh Anna-Lena , Radziun Dominika , Korczyk Maksymilian , Crucianelli Laura , Henrik Ehrsson H. , Szwed Marcin 
Published: February 2024

AbstractBlindness is associated with heightened sensory abilities, such as improved hearing and tactile acuity. Moreover, recent evidence suggests that blind individuals are better than sighted individuals at perceiving their own heartbeat, suggesting enhanced interoceptive accuracy. Structural changes in the occipital cortex have been hypothesized as the basis of these behavioral enhancements. Indeed, several studies have shown that congenitally blind individuals have increased cortical thickness within occipital areas compared to sighted individuals, but how these structural differences relate to behavioral enhancements is unclear. This study investigated the relationship between cardiac interoceptive accuracy and cortical thickness in 23 congenitally blind individuals and 23 matched sighted controls. Our results show a significant positive correlation between performance in a heartbeat counting task and cortical thickness only in the blind group, indicating a connection between structural changes in occipital areas and blind individuals’ better ability to perceive heartbeats.
Long-access heroin self-administration induces region specific reduction of grey matter volume and microglia reactivity in the rat
Authors: Cannella Nazzareno , Tambalo Stefano , Lunerti Veronica , Scuppa Giulia , de Vivo Luisa , Abdulmalek Sarah , Kinen Analia , Mackle James , Kuhn Brittany , Solberg Woods Leah C. , Chung Dongjun , Kalivas Peter , Soverchia Laura , Ubaldi Massimo , Hardiman Gary , Bifone Angelo , Ciccocioppo Roberto 
Published: February 2024

ABSTRACTIn opioid use disorder (OUD) patients, a decrease in brain grey matter volume (GMV) has been reported. It is unclear whether this is the consequence of prolonged exposure to opioids or is a predisposing causal factor in OUD development. To investigate this, we conducted a structural MRI longitudinal study in NIH Heterogeneous Stock rats exposed to heroin self-administration and age-matched naïve controls housed in the same controlled environment. Structural MRI scans were acquired before (MRI1) and after (MRI2) a prolonged period of long access heroin self-administration resulting in escalation of drug intake. Heroin intake resulted in reduced GMV in various cortical and sub-cortical brain regions. In drug-naïve controls no difference was found between MRI1and MRI2. Notably, the degree of GMV reduction in the medial prefrontal cortex (mPFC) and the insula positively correlated with the amount of heroin consumed and the escalation of heroin use. In a preliminary gene expression analysis, we identified a number of transcripts linked to immune response and neuroinflammation. This prompted us to hypothesize a link between changes in microglia homeostasis and loss of GMV. For this reason, we analyzed the number and morphology of microglial cells in the mPFC and insula. The number of neurons and their morphology was also evaluated. The primary motor cortex, where no GMV change was observed, was used as negative control. We found no differences in the number of neurons and microglia cells following heroin. However, in the same regions where reduced GMV was detected, we observed a shift towards a rounder shape and size reduction in microglia, suggestive of their homeostatic change towards a reactive state. Altogether these findings suggest that escalation of heroin intake correlates with loss of GMV in specific brain regions and that this phenomenon is linked to changes in microglial morphology.
Heterogeneity and evolution of DNA mutation rates in microsatellite stable colorectal cancer
Authors: Grassi Elena , Vurchio Valentina , Cresswell George D. , Catalano Irene , Lupo Barbara , Sassi Francesco , Galimi Francesco , Borgato Sofia , Ferri Martina , Viviani Marco , Pompei Simone , Urgese Gianvito , Chen Bingjie , Zanella Eugenia R. , Cottino Francesca , Bardelli Alberto , Cosentino Lagomarsino Marco , Sottoriva Andrea , Trusolino Livio , Bertotti Andrea 
Published: February 2024

AbstractDNA sequence mutability in tumors with chromosomal instability is conventionally believed to remain uniform, constant, and low, based on the assumption that further mutational accrual in a context of marked aneuploidy is evolutionarily disadvantageous. However, this concept lacks robust experimental verification. We adapted the principles of mutation accumulation experiments, traditionally performed in lower organisms, to clonal populations of patient-derived tumoroids and empirically measured the spontaneous rates of accumulation of new DNA sequence variations in seven chromosomally unstable, microsatellite stable colorectal cancers (CRCs) and one microsatellite unstable CRC. Our findings revealed heterogeneous mutation rates (MRs) across different tumors, with variations in magnitude within microsatellite stable tumors as prominent as those distinguishing them from microsatellite unstable tumors. Moreover, comparative assessment of microsatellite stable primary tumors and matched synchronous metastases consistently documented a pattern of MR intensification during tumor progression. Therefore, wide-range diversity and progression-associated evolvability of DNA sequence mutational instability emerge as unforeseen hallmarks of microsatellite stable CRC, complementing karyotype alterations as selectable traits to increase genetic variation.One sentence summaryTumors with chromosomal instability accrue DNA sequence mutations at highly variable rates, which increase during metastatic progression.
Stable sequential dynamics in prefrontal cortex represents subjective estimation of time
Authors: Li Yiting , Yin Wenqu , Wang Xin , Li Jiawen , Zhou Shanglin , Ma Chaolin , Yuan Peng , Li Baoming 
Published: February 2024

AbstractTime estimation is an essential prerequisite underlying various cognitive functions. Previous studies identified “sequential firing” and “activity ramps” as the primary neuron activity patterns in the medial frontal cortex (mPFC) that could convey information regarding time. However, the relationship between these patterns and the timing behavior has not been fully understood. In this study, we utilizedin vivocalcium imaging of mPFC in rats performing a timing task. We observed cells that showed selective activation at trial start, end, or during the timing interval. By aligning long-term time-lapse datasets, we discovered that sequential patterns of time coding were stable over weeks, while cells coding for trial start or end showed constant dynamism. Furthermore, with a novel behavior design that allowed the animal to determine individual trial interval, we were able to demonstrate that real-time adjustment in the sequence procession speed closely tracked the trial-to-trial interval variations. And errors in the rats’ timing behavior can be primarily attributed to the premature ending of the time sequence. Together, our data suggest that sequential activity maybe a stable neural substrate thatrepresentstime under physiological conditions.Furthermore, our results imply the existence of a unique cell type in the mPFC that participates in the time-related sequences. Future characterization of this cell type could provide important insights in the neural mechanism of timing and related cognitive functions.
Causal inference with observational data and unobserved confounding variables
Authors: Byrnes Jarrett E. K. , Dee Laura E. 
Published: February 2024

AbstractExperiments have long been the gold standard for causal inference in Ecology. Observational data has been primarily used to validate experimental results or to find patterns that inspire experiments – not for causal inference. As ecology tackles progressively larger problems, we are moving beyond the scales at which randomized controlled experiments are feasible. Using observational data for causal inference raises the problem of confounding variables, those affecting both a causal variable and response of interest. Unmeasured confounders lead to statistical bias, creating spurious correlations and masking true causal relationships. To combat this Omitted Variable Bias, other disciplines have developed rigorous approaches for causal inference from observational data addressing the problems of confounders. We show how Ecologists can harness some of these methods: identifying confounders via causal diagrams, using nested sampling designs, and statistical designs that address omitted variable bias for causal inference. Using a motivating example of warming effects on intertidal snails, we show how current methods in Ecology (e.g., mixed models) produce incorrect inferences, and how methods presented here outperform them, reducing bias and increasing statistical power. Our goal is to enable the widespread use of observational data as tool for causal inference for the next generation of Ecological studies.