bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C
Authors: Tse Chung Sang , Yang Ju Dong , Mousa Omar Y. , Nelson Kevin M. , Pungpapong Surakit , Keaveny Andrew , Aqel Bashar A. , Vargas Hugo , Dickson Rolland C. , Watt Kymberly , Gores Gregory J. , Roberts Lewis R. , Leise Michael D. 
Published: March 2021

Background:
Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC).

Methods:
We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models.

Results:
A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time.

Conclusions:
Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.
Impact of New UNOS Allocation Criteria on Heart Transplant Practices and Outcomes
Authors: Liu Jason , Yang Bin Q. , Itoh Akinobu , Masood Mohammed Faraz , Hartupee Justin C. , Schilling Joel D. 
Published: March 2021

Background.
In October 2018, a new heart allocation policy was implemented with intent of prioritizing the sickest patients and decreasing waitlist time. We examined the effects of the new policy on transplant practices and outcomes 1 year before and 1 year after the change.

Methods.
Transplant recipients from October 2017 to September 2019 at our institution were identified and divided into 2 cohorts, a preallocation and postallocation criteria change. Patient demographics, clinical data, and bridging strategy were assessed. Early outcomes including ischemic time, severe primary graft dysfunction, need for renal replacement therapy, and duration of hospital stay were investigated.

Results.
In the 12 months before the change, 38 patients were transplanted as compared to 33 patients in the 12 months after the change. The average wait-time to transplant decreased after the allocation change (49 versus 313 d, P = 0.02). Patients were more likely to be bridged with an intra-aortic balloon pump (45% versus 3%) and less likely to be supported with a durable left ventricular assist device (LVAD) after the change (24% versus 82%). There was an increase in total ischemic time after the change (177 versus 117 min, P ≤ 0.01). There were no significant differences in other early posttransplant outcomes.

Conclusions.
Implementation of the new allocation system for heart transplantation resulted in dramatic changes in the bridging strategy utilized at our institution. Temporary mechanical support usage increased following the change and the number of recipients supported with durable LVADs decreased. Early posttransplant outcomes appear similar.
Destination Transplant: Protocol for a Parallel-group Randomized Trial of an Educational Intervention to Increase Kidney Transplant Among Black People on the Transplant Waiting List
Authors: Weng Francis L. , Davis LaShara A. , Ohman-Strickland Pamela A. , Waterman Amy D. 
Published: March 2021

Background.
For most patients with kidney failure, living donor kidney transplant (LDKT) is their best treatment option. Compared with White people, Black people are more likely to have kidney failure but less likely to receive LDKTs. In this study, the investigators will test an educational intervention, Destination Transplant, designed to reduce this disparity, among Black people already listed for kidney transplant.

Methods.
The investigators will conduct a parallel group, 2-arm randomized clinical trial among 500 Black kidney transplant candidates. The main objective of this study is to test an educational and behavioral intervention that is designed to increase receipt of LDKT among transplant candidates (persons active on the deceased donor kidney transplant waiting list) who are Black. Candidates on the kidney transplant waiting list will be randomly assigned to 1 of 2 conditions: (1) a control group that will receive Usual Care, or (2) an Intervention group that will receive Destination Transplant, a 9-month intervention that includes an in-person group-based education session, postcards at monthly intervals, and a follow-up phone call from a transplant educator. At baseline and during 18 months of follow-up, demographic and clinical variables will be collected, as well as variables such as transplant derailers (factors that might be sources of delay, difficulty, or challenge to pursuing transplant), transplant knowledge, and health literacy, small steps taken to pursue LDKT, readiness for LDKT, decisional balance and self-efficacy LDKT, decisional conflict, family support, availability of potential living donors, and general health status.

Conclusions.
This educational intervention aims to increase both readiness to pursue LDKT and actual receipt of LDKTs among Black and African American patients who are already on the kidney transplant waiting list. The aim of the intervention is to reduce racial disparities in access to LDKT.
Mucilaginibacter aquatilis sp. nov., Mucilaginibacter arboris sp. nov., and Mucilaginibacter ginkgonis sp. nov., novel bacteria isolated from freshwater and tree bark
Authors: Kang Heeyoung , Kim Haneul , Bae Seokhyeon , Joh Kiseong 
Published: March 2021

Three Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strains, designated as HME9299T, HMF7410T and HMF7856T, were isolated from freshwater and tree bark collected in Yong-in, Republic of Korea. Strains HME9299T, HMF7410T and HMF7856T exhibited the highest 16S rRNA gene sequence similarities of 97.2, 94.4 and 96.4 % to

Mucilaginibacter daejeonensis

Jip 10T,

Mucilaginibacter terrae

CCM 8645T and

Mucilaginibacter phyllosphaerae

PP-F2F-G21T, respectively. Among themselves, the values were 94.1–95.7 %. Phylogenetic analysis of the 16S rRNA gene sequences of the three isolates revealed that they belonged to the genus

Mucilaginibacter

within the family

Sphingobacteriaceae

. The predominant fatty acids of three strains were summed feature 3 (comprising C16 : 1
ω7c and/or C16 : 1
ω6c) and iso-C15 : 0. Strain HME9299T contained a relatively large amount of C16 : 1
ω5c. The predominant respiratory quinone was menaquinone-7. The genome sizes of strains HME9299T, HMF7410T and HMF7856T were 4.33, 4.16 and 3.68 Mbp, respectively, and their DNA G+C contents were 41.6, 38.4 and 43.9 mol%, respectively. Based on the results of the phenotypic, genotypic, chemotaxonomic and phylogenetic investigation, three novel species, Mucilaginibacter aquatilis sp. nov, Mucilaginibacter arboris sp. nov. and Mucilaginibacter ginkgonis sp. nov., are proposed. The type strains are HME9299T (=KCTC 42122T=DSM 29146T), HMF7410T (=KCTC 62464T=NBRC 113227T) and HMF7856T (=KCTC 72782T=NBRC 114275T), respectively.
Differential gene expression by RNA-Seq in Sigma-2 Receptor/TMEM97 knockout cells reveals its role in complement activation and SARS-CoV-2 viral uptake
Authors: Riad Aladdin , Aubert Yann , Zeng Chenbo , Graham Thomas J. A. , Petersson E. James , Capell Brian C. , Mach Robert H. 
Published: March 2021

ABSTRACTOur lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (sigma-2R/TMEM97) interacts with the low-density lipoprotein receptor (LDLR) and facilitates the enhanced uptake of various ligands including lipoproteins and intrinsically disordered proteins. TMEM97 has been recently been shown to interact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins, highlighting its potential involvement with viral entry into the cell. We hypothesized that sigma-2R/TMEM97 may play a role in facilitating viral uptake, and with the regulation of inflammatory and thrombotic pathways that are involved with viral infection. In this study, we identified the top differentially expressed genes upon the knockout of sigma-2R/TMEM97, and analyzed the genes involved with the inflammatory and thrombotic cascades, effects that are observed in patients infected with SARS-CoV-2. We found that the ablation of sigma-2R/TMEM97 resulted in an increase in Complement Component 4 Binding Protein (C4BP) proteins, at both the translational and transcriptional levels. We also showed that sigma-2R/TMEM97 interacts with the cellular receptor for SARS-CoV-2, the human angiotensin-converting enzyme 2 (ACE2) receptor, forming a protein complex, and that disruption of this complex results in the inhibition of viral uptake. The results of this study suggest that sigma-2R/TMEM97 may be a novel therapeutic target to inhibit SARS-CoV-2 viral uptake, as well as to decrease inflammatory and thrombotic effects through the modulation of the complement cascade.
The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus
Authors: Rathnasinghe Raveen , Jangra Sonia , Miorin Lisa , Schotsasert Michael , Yahnke Clifford , Garcίa-Sastre Adolfo 
Published: March 2021

AbstractGermicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit its use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) as well as the influenza A virus to 405nm, visible light in the absence of exogenous photosensitizers indicating a potential porphyrin-independent alternative mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are generally safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.
Understanding SARS-CoV-2 Infection and Dynamics with Long Term Wastewater based Epidemiological Surveillance
Authors: Tharak Athmakuri , Kopperi Harishankar , Hemalatha Manupati , Kiran Uday , Gokulan C. G. , Moharir Shivranjani , Mishra Rakesh K , Mohan S Venkata 
Published: March 2021

AbstractWastewater-based epidemiology (WBE) of SARS-CoV-2 emerged as an advantageous method to study the infection dynamics at substantial population level. A temporal glimpse at sewage viral genome helps as diagnostic tool to understand the viral spread at community level. In this study, for the long-term epidemiological surveillance, we monitored the SARS-CoV-2 genetic material in domestic sewage by adopting the longitudinal sampling to represent a selected community (∼1.8 lakhs population which occupies 1.79% of the total population of Hyderabad city) to understand the dynamics of infection. Dynamics and spread of COVID-19 outbreak within the selected community were achieved by studying the longitudinal sampling for a specific period of time. WBE also promotes clinical scrutiny along with disease detection and management, in contrast to an advance warning signal to anticipate outbreaks.
Novel MOG analogues to explore the MCT2 pharmacophore, α-ketoglutarate biology and cellular effects ofN-oxalylglycine
Authors: Fets Louise , Bevan Natalie , M. Nunes Patrícia , Campos Sebastien , dos Santos Mariana Silva , Sherriff Emma , MacRae James I. , House David , Anastasiou Dimitrios 
Published: March 2021

ABSTRACTα-ketoglutarate (αKG) is a central metabolic node with a broad influence on cellular physiology. The αKG analogueN-oxalylglycine (NOG) and its membrane-permeable pro-drug derivative dimethyl-oxalylglycine (DMOG) have been extensively used as tools to study prolyl hydroxylases (PHDs) and other αKG-dependent processes. In cell culture media, DMOG is rapidly converted to MOG, which enters cells through monocarboxylate transporter MCT2, leading to intracellular NOG concentrations that are sufficiently high to inhibit glutaminolysis enzymes and cause cytotoxicity. Therefore, the degree of (D)MOG instability together with MCT2 expression levels determine the intracellular targets NOG engages with and, ultimately, its effects on cell viability. Here we designed and characterised a series of MOG analogues with the aims of improving stability and exploring the functional requirements for interaction with MCT2, a relatively understudied member of the SLC16 family. We report MOG analogues that maintain ability to enter cells via MCT2, and identify compounds that do not inhibit glutaminolysis or cause cytotoxicity but can still inhibit PHDs. We use these analogues to show that glutaminolysis-induced activation of mTORC1 can be uncoupled from PHD activity. Therefore, these new compounds can help deconvolute cellular effects that result from the polypharmacological action of NOG.
Vtc5 is localized to the vacuole membrane by the conserved AP-3 complex to regulate polyphosphate synthesis in budding yeast
Authors: Bentley-DeSousa Amanda , Downey Michael 
Published: March 2021

ABSTRACTPolyphosphates (polyP) are energy-rich polymers of inorganic phosphates assembled into chains ranging from 3-1000s of residues in length. They are thought to exist in all cells on earth and play roles in an eclectic mix of functions ranging from phosphate homeostasis to cell signaling, infection control, and blood clotting. In the budding yeastSaccharomyces cerevisiae, polyP chains are synthesized by the vacuole-bound VTC complex, which synthesizes polyP while simultaneously translocating it into the vacuole lumen where it is stored at high concentrations. VTC’s activity is promoted by an accessory subunit called Vtc5. In this work, we find that the conserved AP-3 complex is required for proper Vtc5 localization to the vacuole membrane. In human cells, previous work has demonstrated that mutation of AP-3 subunits gives rise to Hermansky-Pudlak Syndrome, a rare disease with molecular phenotypes that include decreased polyP accumulation in platelet dense granules. In yeast AP-3 mutants, we find that Vtc5 is rerouted to the vacuole lumen by the ESCRT complex, where it is degraded by the vacuolar protease Pep4. Cells lacking functional AP-3 have decreased levels of polyP, demonstrating that membrane localization of Vtc5 is required for its VTC stimulatory activityin vivo. Our work provides insight into the molecular trafficking of a critical regulator of polyP metabolism in yeast. We speculate that AP-3 may also be responsible for the delivery of polyP regulatory proteins to platelet dense granules in higher eukaryotes.HIGHLIGHTSVtc5 localization to the vacuole membrane depends on the AP-3 complexThe ESCRT pathway brings mislocalized Vtc5 to the vacuole lumen where it is degradedDecreased polyP levels in AP-3 mutants are explained by Vtc5 mislocalizationDeletion ofDOA4restores wild-type localization of Vtc5 without restoring polyP levels
One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening
Authors: Urdaniz Irene Francino , Steiner Paul J. , Kirby Monica B. , Zhao Fangzhu , Haas Cyrus M. , Barman Shawn , Rhodes Emily R. , Peng Linghang , Sprenger Kayla G. , Jardine Joseph G. , Whitehead Timothy A. 
Published: March 2021

ABSTRACTThe potential emergence of SARS-CoV-2 Spike (S) escape mutants is a threat to reduce the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutations landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site. We identified escape mutants for five nAbs, including three from the public germline class VH3-53 elicited by natural COVID-19 infection. Escape mutations predominantly mapped to the periphery of the ACE2 recognition site on the RBD with K417, D420, Y421, F486, and Q493 as notable hotspots. We provide libraries, methods, and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2.One Sentence SummaryWe present a facile method to identify antibody escape mutants on SARS-CoV-2 S RBD.
An ecological basis for dual genetic code expansion in marine deltaproteobacteria
Authors: Kivenson Veronika , Paul Blair G. , Valentine David L. 
Published: March 2021

AbstractMarine benthic environments may be shaped by anthropogenic and other localized events, leading to changes in microbial community composition evident decades after a disturbance. Marine sediments in particular harbor exceptional taxonomic diversity and can shed light on distinctive evolutionary strategies. Genetic code expansion may increase the structural and functional diversity of proteins in cells, by repurposing stop codons to encode noncanonical amino acids: pyrrolysine (Pyl) and selenocysteine (Sec). Here, we show that the genomes of abundant Deltaproteobacteria from the sediments of a deep-ocean chemical waste dump site, have undergone genetic code expansion. Pyl and Sec in these organisms appear to augment trimethylamine (TMA) and one-carbon metabolism, representing key drivers of their ecology. The inferred metabolism of these sulfate-reducing bacteria places them in competition with methylotrophic methanogens for TMA, a contention further supported by earlier isotope tracer studies and reanalysis of metatranscriptomic studies. A survey of genomic data further reveals a broad geographic distribution of a niche group of similarly specialized Deltaproteobacteria including at sulfidic sites in the Atlantic Ocean, Gulf of Mexico, Guayamas Basin, and North Sea, as well as in terrestrial and estuarine environments. These findings reveal an important biogeochemical role for specialized Deltaproteobacteria at the interface of the carbon, nitrogen and sulfur cycles, with their niche adaptation and ecological success seemingly enabled by genetic code expansion.
Using fecal immunochemical tubes for the analysis of the gut microbiome has the potential to improve colorectal cancer screening
Authors: Krigul Kertu Liis , Aasmets Oliver , Lüll Kreete , Org Tõnis , Org Elin 
Published: March 2021

ABSTRACTBackgroundColorectal cancer (CRC) is an important and challenging public health problem which successful treatment depends on the early detection of the disease. Recently, colorectal cancer specific microbiome signatures have been proposed as an additional marker for CRC detection. A desirable aim would be the possibility to analyze microbiome from the fecal samples collected during CRC screening programs into FIT tubes for fecal occult blood testing.MethodsWe investigated the impact of the Fecal Immunohistochemical Test (FIT) and stabilization buffer on the microbial community structure in stool samples from 30 volunteers and compared their communities to fresh-frozen samples highlighting also the previously published cancer-specific communities. Altogether 214 samples were analyzed including positive and negative controls using 16S rRNA gene sequencing.ResultsThe variation between individuals is greater than the differences introduced by collection strategy. The vast majority of the genera are stable for up to 7 days. None of the changes observed between fresh frozen samples and FIT tubes are related to previously shown colorectal-cancer specific bacteria.ConclusionsOverall, our results show that FIT tubes can be used for profiling the gut microbiota in colorectal cancer screening programs as the community is similar to fresh frozen samples and stable at least for 7 days.ImpactSample material from FIT tubes could be used in addition to fecal immunochemical tests for future investigations into the role of gut microbiota in colorectal cancer screening programs circumventing the need to collect additional samples and possibly improving the sensitivity of FIT.