bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normothermic Machine Perfusion for Declined Livers: A Strategy to Rescue Marginal Livers for Transplantation
Authors: Olumba Franklin C , Zhou Fangyu , Park Yikyung , Chapman William C ,   and the RESTORE Investigators Group
Published: February 2023

Background:
Organ waste is a major cause of the donor liver shortage. Roughly 67% of recovered organ donors have liver utilization annually. A new technology called Normothermic Machine Perfusion (NMP) offers a way to recover marginal and declined livers for transplant. We report interim results of the RESTORE trial (FDA-IDE trial, NCT04483102) that aims to transplant NMP-treated livers that would otherwise be discarded.

Study Design:
Declined livers were screened for NMP eligibility (e.g., DCD grafts with warm ischemic time <40 minutes, DBD grafts with cold ischemic time <8 hours). Livers meeting pre-NMP eligibility criteria received NMP using the OrganOx® metra device for minimum 4 hours. All NMP-treated livers meeting viability criteria were transplanted to consented recipients.

Results:
Over 22 months, 60 declined livers from three OPOs (40 DCD and 20 DBD donor livers) were offered, and 22 livers (10 DCD and 12 DBD livers) met the pre-NMP eligibility. After NMP, 16 of 22 livers passed viability testing and were transplanted into needy recipients (median MELD 8, range 6-24), resulting in 72.7% rescue rate (50% DCD, 91.7% DBD). The rate of early allograft dysfunction was 31.3% but there were no graft related deaths, primary non-function or instances of non-anastomotic biliary strictures.

Conclusion:
Interim results of the RESTORE trial suggest that a sizable number of declined livers can be reclaimed. They are safe for transplantation and can enable lower MELD patients at high risk of morbidity and mortality to receive lifesaving grafts while offering OPOs a way to allocate more livers and reduce organ waste.
Financial Toxicity in Emergency General Surgery: Novel Propensity-Matched Outcome Comparison
Authors: Parreco Joshua P , Avila Azalia , Pruett Rachel , Romero Dino C , Solomon Rachele , Buicko Jessica L , Rosenthal Andrew , Carrillo Eddy H 
Published: February 2023

Background:
Financial toxicity describes the harmful effect of individual treatment costs and fiscal burdens that have a compounding negative impact on outcomes in surgery. While this phenomenon has been widely studied in surgical oncology, the purpose of this study was to perform a novel exploration of the impact of financial toxicity in emergency general surgery (EGS) patients throughout the US.

Study Design:
The Nationwide Readmissions Database for January and February 2018 was queried for all EGS patients aged 18-65 years. One-to-one propensity matching was performed with and out risk for financial toxicity. The primary outcome was mortality, the secondary outcomes were venous thromboembolism (VTE), prolonged length of stay (LOS), and readmission within 30-days.

Results:
There were 24,154 EGS patients propensity matched. The mortality rate was 0.2% (n=39) and the rate of VTE was 0.5% (n=113). With financial toxicity there was no statistically significant difference for mortality (p=0.08) or VTE (p=0.30). The rate of prolonged LOS was 6.2% (n=824) and the risk was increased with financial toxicity (RR 1.24 [1.12-1.37] p<0.001). The readmission rate was 7.0% (n=926) and the risk with financial toxicity was increased (RR 1.21 [1.10-1.33] p<0.001). The mean count of comorbidities per patient per admission during readmission within 1 year with financial toxicity was 2.1 ± 1.9 versus 1.8 ± 1.7 without (p<0.001).

Conclusions:
Despite little difference in the rate of mortality or VTE, EGS patients at risk for financial toxicity have an increased risk of readmission and longer LOS. Fewer comorbidities were identified at index admission than during readmission in patients at risk for financial toxicity. Future studies aimed at reducing this compounding effect of financial toxicity and identifying missed comorbidities have the potential to improve EGS outcomes.
Machine Learning Models for Predicting the Outcomes of Surgical Treatment of Colorectal Liver Metastases
Authors: Moaven Omeed , Tavolara Thomas E , Valenzuela Cristian D , Cheung Tan to , Corvera Carlos U , Cha Charles H , Stauffer John A , Niazi Muhammad Khalid Khan , Gurcan Metin N , Shen Perry 
Published: February 2023

Background:
Surgical intervention remains the cornerstone of a multidisciplinary approach in the treatment of colorectal liver metastases (CLM). Nevertheless, patient outcomes vary greatly. While predictive tools can assist decision-making and patient counseling, decades of efforts have yet to result in generating a universally adopted tool in clinical practice.

Study Design:
An international collaborative database of CLM patients who underwent surgical therapy between 2000 and 2018 was used to select 1004 operations for this study. Two different machine learning methods were applied to construct two predictive models for recurrence and death, using 128 clinicopathologic variables: gradient-boosted trees (GBTs) and logistic regression with bootstrapping (LRB) – in a leave-one-out cross-validation.

Results:
Median survival after resection was 47.2 months, and disease-free survival was 19.0 months, with a median follow-up of 32.0 months in the cohort. Both models had good predictive power, with GBT demonstrating a superior performance in predicting overall survival (area under the receiver operating curve [AUC]: 0.773, 95%CI: 0.743-0.801 vs. LRB with AUC: 0.648, 95%CI: 0.614-0.682), and recurrence (AUC: 0.635, 95% CI: 0.599-0.669 vs. LRB with AUC: 0.570, 95%CI: 0.535-0.601). Similarly, better performances were observed predicting 3-year and 5-year survival, as well as 3-year and 5-year recurrence with GBT methods generating a higher AUC.

Conclusion:
Machine learning provides powerful tools to create predictive models of survival and recurrence after surgery for CLM. The effectiveness of both machine learning models varies, but on most occasions, GBT outperforms LRB. Prospective validation of these models lays the groundwork to adopt them in clinical practice.
Differences in Cognitive Adverse Effects and Seizure Parameters Between Thiopental and Propofol Anesthesia for Electroconvulsive Therapy
Authors: Kavakbasi Erhan , Stoelck Alexandra , Wagner Nana-Maria , Baune Bernhard T. 
Published: February 2023

Introduction
Electroconvulsive therapy (ECT) is a well-established treatment option in case of severe and treatment-resistant psychiatric conditions. In this retrospective study, we compared the 2 anesthetics propofol and thiopental in terms of seizure quality, cognitive adverse effects, and clinical outcome.

Methods
Data collection was performed retrospectively by a chart review, including patient files and medical records. A total of 64 patients (female = 60.9%) treated with ECT within the period of February 2019 to March 2020 were included. Of these, 35 (54.7%) received thiopental for ECT narcosis and 29 (45.3%) were treated with propofol.

Results
Six hundred sixteen ECT treatments (mean number per case, 9.6) were performed in total. The mean electroencephalogram seizure duration (38.3 vs 28.1 seconds, t = 3.534, degrees of freedom [df] = 62, P < 0.001) and motor seizure duration (21.5 vs 12.0, t = 4.336, df = 62, P < 0.001) as well as postictal suppression index and heart rate increase were significantly higher in the thiopental group. Mean stimulation energy needed per session was higher in the propofol group (88.6% vs 73.0%, Mann-Whitney U test, P = 0.042). The ECT series was more likely to be interrupted due to cognitive adverse effects in the thiopental group (P = 0.001, Pearson χ2 = 10.514, df = 1). Number of patients achieving remission was significantly higher in the thiopental group (31.4% vs 6.9%, P = 0.015, χ2 = 5.897, df = 1).

Conclusions
Thiopental led to better seizure duration and quality and was associated with a higher rate of remission. As a downside, thiopental was also associated with a greater risk of cognitive adverse effects.
RHINOORBITAL CEREBRAL MYCOSIS: A CASE SERIES OF NON-MUCORALES IN COVID PATIENTS
Authors: Patil Rajashri , Ajagunde Jyoti , KHAN SAMEENA , KANNURI SRIRAM , Gandham Nageswari , Mukhida Sahjid 
Published: February 2023

Introduction

Rhinocerebral mycoses are not only caused by Aspergillus spp. and Zygomycetes group but also can be associated with other rare species like Neurospora, Cladosporium, and Fusarium spp. post-COVID mucormycosis is caused by geriatric age group patients who have comorbidities like Diabetes Mellitus and/or Hypertension too. Clinical symptoms of COVID and Mucormycosis are a critical and relentless situation without a saving grace even with treatment.

Case series

We are reporting 3 patients with COVID-19 infection, who during the course of the treatment, developed rhino-orbital-cerebral mycosis including oral cavity involvement. Rhinocerebral mycosis along with Oral cavity involvement was diagnosed by radiological investigations and preliminary screening for fungal infection (KOH mount) in all three cases. Empirical treatment was started but patients were not responding to treatment. All patients succumbed even after debridement and Maxillectomy type crucial surgical procedures. Onculture, rare species of fungi were isolated in all cases which were identified with the help of a reference laboratory. Neurospora is considered nonpathogenic to humans. Cladosporium is a dematiaceous fungus found in soil in all climates, associated with disseminated or cerebral infections; and Fusarium though considered a saprophytic colonizer of skin and respiratory mucosa along with other bacteria and common cause of mycotic keratitis worldwide.

Conclusion

Immune system modifications due to COVID-19 with/without other risk factors result in fungal co-infections proving to be fatal for the patients. It is vital to be aware that COVID-19 patients, particularly those who are critically ill, may acquire secondary fungal infections and early detection is critical.
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new genetic hits
Authors: Alemany Silvia , Soler Artigas María , Cabana Judit , Fakhreddine Dana Salim , Llonga Natalia , Vilar-Ribó Laura , Rodríguez-Urrutia Amanda , Palacio Judit , González-Castro Ana María , Lobo Beatriz , Alonso-Cotoner Carmen , Simrén Magnus , Santos Javier , Ramos-Quiroga Josep Antoni , Ribasés Marta 
Published: February 2023

ABSTRACTBackgroundIrritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them.MethodsWe quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date.ResultsIBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant hits for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety.ConclusionsThese findings provide evidence of the polygenic architecture of IBS, identify novel hits for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.
MUC17 mutations and methylation are associated with poor prognosis in adult-type diffuse glioma patients
Authors: Machado Gabriel Cardoso , Ferrer Valéria Pereira 
Published: February 2023

AbstractDiffuse gliomas are tumors that arise from glial or glial progenitor cells. They are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or oligodendroglioma IDH-mutant, and 1p/19q-codeleted, both slower-growing tumors, or glioblastoma (GBM), a more aggressive tumor. Despite advances in the diagnosis and treatment of gliomas, the median survival time after diagnosis of GBM remains low, approximately 15 months, with a 5-year overall survival rate of only 6.8%. Therefore, new biomarkers that could support the earlier diagnosis and prognosis of these tumors would be of great value. MUC17, a membrane-bound mucin, has been identified as a potential biomarker for several tumors. However, the role of this mucin in adult gliomas has not yet been explored. Here, we show for the first time, in a retrospective study and byin silicoanalysis that MUC17 is one of the relevant mutant genes in adult gliomas. Moreover, that an increase in MUC17 methylation correlates with an increase in glioma malignancy grade. Patients with MUC17 mutations had a poorer prognosis than their wild-type counterparts in both GBM and non-GBM glioma cohorts. We also analyzed mutational profiles that correlated strongly with poor survival. Therefore, in this study, we present a new potential biomarker for further investigation, especially for the prognosis of adult diffuse gliomas.
MNRR1 activation by nitazoxanide abrogates lipopolysaccharide-induced preterm birth in mice
Authors: Purandare Neeraja , Gomez-Lopez Nardhy , Arenas-Hernandez Marcia , Galaz Jose , Romero Roberto , Xi Yue , Fribley Andrew , Grossman Lawrence I. , Aras Siddhesh 
Published: February 2023

AbstractIntra-amniotic inflammation leading to preterm birth is one of the leading causes of neonatal morbidity and mortality. We recently found that the mitochondrial levels of MNRR1 (Mitochondrial Nuclear Retrograde, Regulator 1; also called CHCHD2, AAG10, or PARK22), an important bi-organellar regulator of cellular function, are reduced in the context of inflammation and that both genetic and pharmacological increase in MNRR1 levels can counter the inflammatory profile. We show here that nitazoxanide, a clinically-approved drug, is an activator of MNRR1 and prevents preterm birth in a well-characterized murine model caused by intra-amniotic lipopolysaccharide (LPS) injection.HighlightsNitazoxanide exerts anti-inflammatory functions via activation of MNRR1.Oral administration of nitazoxanide prevents preterm birth in mouse model of intra-intraamniotic LPS-induced inflammation.
The omnitig framework can improve genome assembly contiguity in practice
Authors: Schmidt Sebastian , Toivonen Santeri , Medvedev Paul , Tomescu Alexandru I. 
Published: February 2023

AbstractDespite the long history of genome assembly research, there remains a large gap between the theoretical and practical work. There is practical software with little theoretical underpinning of accuracy on one hand and theoretical algorithms which have not been adopted in practice on the other. In this paper we attempt to bridge the gap between theory and practice by showing how the theoretical safe-and-complete framework can be integrated into existing assemblers in order to improve contiguity. The optimal algorithm in this framework, called the omnitig algorithm, has not been used in practice due to its complexity and its lack of robustness to real data. Instead, we pursue a simplified notion of omnitigs, giving an efficient algorithm to compute them and demonstrating their safety under certain conditions. We modify two assemblers (wtdbg2 and Flye) by replacing their unitig algorithm with the simple omnitig algorithm. We test our modifications using real HiFi data from the Drosophilia melanogaster and the Caenorhabditis elegans genome. Our modified algorithms lead to a substantial improvement in alignment-based contiguity, with negligible computational costs and either no or a small increase in the number of misassemblies.
Skin microbiome attributes associate with biophysical skin aging
Authors: Zhou Wei , Fleming Elizabeth , Legendre Guylaine , Roux Lauriane , Latreille Julie , Gendronneau Gaëlle , Forestier Sandra , Oh Julia 
Published: February 2023

AbstractTwo major arms of skin aging are changes in the skin’s biophysical conditions and alterations in the skin microbiome. This work partitioned both arms to study their interaction in detail. Leveraging the resolution provided by shotgun metagenomics, we explored how skin microbial species, strains, and gene content interact with the biophysical traits of the skin during aging. With a dataset well-controlled for confounding factors, we found that skin biophysical traits, especially the collagen diffusion coefficient, are associated with the composition and the functional potential of the skin microbiome, including the abundance of bacterial strains found in nosocomial infections and the abundance of antibiotic resistance genes. Our findings reveal important associations between skin biophysical features and aging-related changes in the skin microbiome and generate testable hypotheses for the mechanisms of such associations.
Plasma and Liver Lipids are Differentially Regulated After Cannabinoid Treatments in Male and Female Mice
Authors: Johnson Clare T , Bosquez-Berger Taryn , Bentz Hannah R , de Abreu Gabriel H Dias , Mackie Ken , Lu Hui-Chen , Bradshaw Heather B 
Published: February 2023

AbstractCannabinoids (CBs) have sex-dependent behavioral and physiological effects and modulate lipids across the body. To understand how some of these sex differences may be due to differences how both phyto- and endocannabinoids are regulated in the liver and plasma, male and female CD1 mice were administered 10 mg/kgi.p. of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), or THC+CBD then core blood and liver tissue were collected after 2 hours. Lipids were extracted from both liver and plasma, and samples were screened via HPLC/MS/MS for Δ9-tetrahydrocannabinol (THC), metabolites 11-OH-THC and 11-COOH-THC, cannabidiol (CBD), metabolites 7-OH-CBD and 7-COOH-CBD, ~70 endolipids including the endocannabinoids,N-arachidonoyl ethanolamine (Anandamide; AEA) and 2-sn-arachidonoyl glycerol (2-AG). Structural analogs to AEA (e.g. lipoamino acids, lipoamines) and 2-acyl glycerols) as well as free fatty acids and prostaglandins were also evaluated. Results show that at 2 hours post injection levels of CBs demonstrate key differences between males and females in both plasma and liver, and that these differences vary when co-administered as opposed to administered alone. Illustrating a link between liver and plasma, directionality of CB differences are similar between the two tissue types as a function of both sex and CB treatment. By contrast, endolipids had very different profiles as a function of sex, CB administration, and tissue type. Importantly, there are baseline differences between male and female mice in endocannabinoids and related lipids, which likely impact how CB administration modulates these endolipids. These data illustrate the complexity of outcomes of CB treatment between males and females on circulating CBs and endolipids and highlight the need to consider these factors when evaluating efficacy of CB drug treatments or usage.
Characterizing transcriptomic responses to sediment stress across location and morphology in reef-building corals
Authors: Ashey Jill , McKelvie Hailey , Freeman John D. , Shpilker Polina , Zane Lauren H. , Becker-Polinski Danielle M. , Cowen Lenore , Richmond Robert H. , Paul Valérie , Seneca Francois , Putnam Hollie M. 
Published: February 2023

AbstractAnthropogenic activities increase sediment suspended in the water column and deposition on reefs can be largely dependent on colony morphology. Massive and plating corals have a high capacity to trap sediments, and active removal mechanisms can be energetically costly. Branching corals trap less sediment, but are more susceptible to light limitation caused by suspended sediment. Despite deleterious effects of sediments on corals, few studies have examined the molecular response of corals with different morphological characteristics to sediment stress. To address this knowledge gap, this study assessed the transcriptomic responses of branching and massive corals in Florida and Hawai□i to varying levels of sediment exposure. Gene expression analysis revealed a molecular responsiveness to sediments across species and sites. Differentially Gene Expression (DEG) followed by Gene Ontology (GO) enrichment analysis identified that branching corals had the largest transcriptomic response to sediments, in developmental processes and metabolism, while significantly enriched GO terms were highly variable between massive corals, despite similar morphologies. Comparison of DEGs within orthogroups revealed that while all corals had DEGs in response to sediment, there was not a concerted gene set response by morphology or location. These findings illuminate the species specificity and genetic basis underlying coral susceptibility to sediments.
BZINB model-based pathway analysis and module identification facilitates integration of microbiome and metabolome data
Authors: Lin Bridget , Cho Hunyong , Liu Chuwen , Roach Jeff , Ribeiro Apoena Aguiar , Divaris Kimon , Wu Di 
Published: February 2023

AbstractIntegration of multi-omics data is a challenging but necessary step to advance our understanding of the biology underlying human health and disease processes. To date, investigations seeking to integrate multi-omics (e.g., microbiome and metabolome) employ simple correlation-based network analyses; however, these methods are not always well-suited for microbiome analyses because they do not accommodate the excess zeros typically present in these data. In this paper, we introduce a bivariate zero-inflated negative binomial (BZINB) model-based network and module analysis method that addresses this limitation and improves microbiome-metabolome correlation-based model fitting by accommodating excess zeros. We use real and simulated data based on a multi-omics study of childhood oral health (ZOE 2.0; investigating early childhood dental disease, ECC) and find that the accuracy of the BZINB model-based correlation method is superior compared to Spearman’s rank and Pearson correlations in terms of approximating the underlying relationships between microbial taxa and metabolites. The new method, BZINB-iMMPath facilitates the construction of metabolite-species and species-species correlation networks using BZINB and identifies modules of (i.e., correlated) species by combining BZINB and similarity-based clustering. Perturbations in correlation networks and modules can be efficiently tested between groups (i.e., healthy and diseased study participants). Upon application of the new method in the ZOE 2.0 study microbiome-metabolome data, we identify that several biologically-relevant correlations of ECC-associated microbial taxa with carbohydrate metabolites differ between healthy and dental caries-affected participants. In sum, we find that the BZINB model is a useful alternative to Spearman or Pearson correlations for estimating the underlying correlation of zero-inflated bivariate count data and thus is suitable for integrative analyses of multi-omics data such as those encountered in microbiome and metabolome studies.