bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver Transplantation as Definitive Treatment of Post-cholecystectomy Bile Duct Injury
Authors: Vilatobá Mario , Chávez-Villa Mariana , Figueroa-Méndez Rodrigo , Domínguez-Rosado Ismael , Cruz-Martínez Rodrigo , Leal-Villalpando Rafael P. , García-Juárez Ignacio , Mercado Miguel A. 
Published: October 2021

Objective:
To analyze the perioperative and long-term outcomes of patients undergoing LT due to BDI in a tertiary care center.

Background:
BDI is associated with significant morbidity and long-term impact on quality of life. LT represents the only possibility of a cure in patients with BDI who develop SBC.

Methods:
Retrospective cohort study from a prospective LT database. Between 2008 and 2019, patients with SBC due to BDI after cholecystectomy and requiring LT were identified. Perioperative and long-term outcomes were analyzed.

Results:
Among 354 LT, 12 patients underwent LT to treat post-cholecystectomy BDI and accounted for 3.4% of all LT. The median time from BDI to SBC diagnosis was 9.3 years (2.4–14). The mean time from SBC to inclusion on the waitlist was 2.4years (± 2.2). Postoperative complications occurred in 11 patients (91.6%); mainly infectious (9/12 patients, 75%), followed by renal complications (4/12 patients, 33.3%). Only 2 patients developed major complications, which were the patients who died, resulting in a 90-day mortality of 16.7%. After a mean follow-up of 40.3 months (± 42.2) survival at 1, 3, and 5 years was 83%.

Conclusions:
Although BDI is an unusual indication for LT worldwide, it accounted for 3.4% of all LT in our center. Although postoperative mortality remains high, LT is the only possibility of a cure, with acceptable long-term outcomes. Early referral to a tertiary care center is essential to avoid long-term complications of BDI, such as SBC.
Objective Activity Parameters Track Patient-specific Physical Recovery Trajectories After Surgery and Link With Individual Preoperative Immune States
Authors: Fallahzadeh Ramin , Verdonk Franck , Ganio Ed , Culos Anthony , Stanley Natalie , Maric Ivana , Chang Alan L. , Becker Martin , Phongpreecha Thanaphong , Xenochristou Maria , De Francesco Davide , Espinosa Camilo , Gao Xiaoxiao , Tsai Amy , Sultan Pervez , Tingle Martha , Amanatullah Derek F. , Huddleston James I. , Goodman Stuart B. , Gaudilliere Brice , Angst Martin S. , Aghaeepour Nima 
Published: October 2021

Objective:
The longitudinal assessment of physical function with high temporal resolution at a scalable and objective level in patients recovering from surgery is highly desirable to understand the biological and clinical factors that drive the clinical outcome. However, physical recovery from surgery itself remains poorly defined and the utility of wearable technologies to study recovery after surgery has not been established.

Background:
Prolonged postoperative recovery is often associated with long-lasting impairment of physical, mental, and social functions. Although phenotypical and clinical patient characteristics account for some variation of individual recovery trajectories, biological differences likely play a major role. Specifically, patient-specific immune states have been linked to prolonged physical impairment after surgery. However, current methods of quantifying physical recovery lack patient specificity and objectivity.

Methods:
Here, a combined high-fidelity accelerometry and state-of-the-art deep immune profiling approach was studied in patients undergoing major joint replacement surgery. The aim was to determine whether objective physical parameters derived from accelerometry data can accurately track patient-specific physical recovery profiles (suggestive of a ‘clock of postoperative recovery’), compare the performance of derived parameters with benchmark metrics including step count, and link individual recovery profiles with patients’ preoperative immune state.

Results:
The results of our models indicate that patient-specific temporal patterns of physical function can be derived with a precision superior to benchmark metrics. Notably, 6 distinct domains of physical function and sleep are identified to represent the objective temporal patterns: ‘‘activity capacity’’ and ‘‘moderate and overall activity (declined immediately after surgery); ‘‘sleep disruption and sedentary activity (increased after surgery); ‘‘overall sleep’’, ‘‘sleep onset’’, and ‘‘light activity’’ (no clear changes were observed after surgery). These patterns can be linked to individual patients preopera-tive immune state using cross-validated canonical-correlation analysis. Importantly, the pSTAT3 signal activity in monocytic myeloid-derived suppressor cells predicted a slower recovery.

Conclusions:
Accelerometry-based recovery trajectories are scalable and objective outcomes to study patient-specific factors that drive physical recovery.
Paradigms of frustration in superionic solid electrolytes
Authors: Wood Brandon C. , Varley Joel B. , Kweon Kyoung E. , Shea Patrick , Hall Alex T. , Grieder Andrew , Ward Michael , Aguirre Vincent P. , Rigling Dylan , Lopez Ventura Eduardo , Stancill Chimara , Adelstein Nicole 
Published: October 2021

Superionic solid electrolytes have widespread use in energy devices, but the fundamental motivations for fast ion conduction are often elusive. In this Perspective, we draw upon atomistic simulations of a wide range of superionic conductors to illustrate some ways frustration can lower diffusion cation barriers in solids. Based on our studies of halides, oxides, sulfides and hydroborates and a survey of published reports, we classify three types of frustration that create competition between different local atomic preferences, thereby flattening the diffusive energy landscape. These include chemical frustration, which derives from competing factors in the anion–cation interaction; structural frustration, which arises from lattice arrangements that induce site distortion or prevent cation ordering; and dynamical frustration, which is associated with temporary fluctuations in the energy landscape due to anion reorientation or cation reconfiguration. For each class of frustration, we provide detailed simulation analyses of various materials to show how ion mobility is facilitated, resulting in stabilizing factors that are both entropic and enthalpic in origin. We propose the use of these categories as a general construct for classifying frustration in superionic conductors and discuss implications for future development of suitable descriptors and improvement strategies.
This article is part of the Theo Murphy meeting issue ‘Understanding fast-ion conduction in solid electrolytes’.
Cellular and Antibody Immunity after COVID-19 Vaccination at >4-Month Follow Up in Immunocompetent and Immunocompromised Subjects
Authors: Sindhi Rakesh , Ashokkumar Chethan , Singh Vineeta , Spishock Brianna , Saunders Maggie , Mabasa Angelo , Sindhi Elizabeth , Sethi Pradeep , Reddy Ashok , Subramaniam Shankar , Nibhanupudy Bobby 
Published: October 2021

AbstractWe evaluated post-vaccination immunity after COVID-19 vaccination with serial changes in cellular and antibody responses to the spike protein S, its S2 component which is conserved between SARS-CoV-2 and human coronaviruses, and the S1 component, which is specific to SARS-CoV-2 and also contains its receptor binding domain (RBD). In 21 healthy immunocompetent subjects all of whom demonstrated circulating IgG antibodies 4 months after mRNA1273 or BNT162b vaccination, a) the strength of S-IgG was stable while RBD-IgG declined, b) S2-reactive B-cell frequencies increased progressively (p=0.002) c) S1-reactive CD8+T-cells and CD19+B-cells were undetectable after a transient increase, and d) monocytic and polymorphonuclear myeloid-derived suppressor cells (M-MDSC, PMN-MDSC) increased after the first vaccine dose. Compared with 4-month measurements from immunocompetent subjects, single samples from 20 vaccinated immunocompromised (IC) subjects revealed a) circulating S-IgG and RBD-IgG in 13 (65%) and 9 (45%) subjects, respectively, b) no differences in S2-reactive T- and B-cells, c) undetectable S1-reactive T- and B-cells, and d) fewer S-reactive CD8+T-cells and CD19+B-cells (p<0.05). Among 11 IC recipients who failed to make RBD-IgG, frequencies of PMN-MDSC were significantly higher (p<0.0004) compared with IC or immunocompetent subjects with RBD-IgG. COVID-19 vaccination induces stable antibodies to the spike protein and expands circulating B-cells reactive to the conserved spike protein sequence in immunocompetent subjects. MDSC which are known to suppress T- and B-cells, and which increase after vaccination, may limit post-vaccination responses especially among immunocompromised subjects. Antibody and cellular responses to SARS-CoV-2-specific spike antigenic sequences appear to be less durable.
Impact of the COVID-19 pandemic on mental healthcare consultations among children and adolescents in Norway: a nationwide registry study
Authors: Evensen Miriam , Hart Rannveig , Godøy Anna Aasen , Hauge Lars Johan , Lund Ingunn Olea , Knudsen Ann Kristin Skrindo , Grøtting Maja Weemes , Surén Pål , Reneflot Anne 
Published: October 2021

ABSTRACTThe COVID-19 pandemic and its associated restrictions may have affected children and adolescent’s mental health adversely. We cast light on this question using primary and specialist consultations data for the entire population of children 6-19 years in Norway (N=908 272). Our outcomes are the monthly likelihood of having a consultation or hospitalization related to mental health problems and common mental health diagnoses. We compared a pandemic (2019-2021) to a pre-pandemic (2017-2019) cohort using event study and difference-in-difference designs that separate the shock of the pandemic from linear period trends and seasonal variation. We found temporary reductions in all mental health consultations during lockdown in spring 2020. In fall 2020 and winter 2021, consultation volumes in primary care increased, stabilizing at a higher level in 2021. Consultations in specialist care increased from spring 2021. Our findings could suggest a worsening of mental health among adolescents.
Interaction studies of risk proteins in human induced neurons reveal convergent biology and novel mechanisms underlying autism spectrum disorders
Authors: Pintacuda Greta , Hsu Yu-Han H. , Tsafou Kalliopi , Li Ka Wan , Martín Jacqueline M. , Riseman Jackson , Biagini Julia C. , Ching Joshua K.T. , Gonzalez-Lozano Miguel A. , Egri Shawn B. , Jaffe Jake , Smit August B. , Fornelos Nadine , Eggan Kevin C. , Lage Kasper 
Published: October 2021

AbstractSequencing studies of autism spectrum disorders (ASDs) have identified numerous risk genes with enriched expression in the human brain, but it is still unclear how these genes converge into cell type-specific networks and how their encoded proteins mechanistically contribute to ASDs. To address this question, we performed brain cell type-specific interaction proteomics to build a protein-protein interaction network for 13 ASD risk genes in human excitatory neurons derived from iPS cells. The network contains many (>90%) interactions not reported in the literature and is enriched for transcriptionally perturbed genes observed in layer 2/3 cortical neurons of ASD patients, indicating that it can be explored for ASD-relevant biological discovery. We leveraged the network dataset to show that the brain-specific isoform of ANK2 is important for its interactions with synaptic proteins and characterized a PTEN-AKAP8L interaction that influences neuronal growth through the mTOR pathway. The IGF2BP1-3 complex emerges as a point of convergence in the network, and we showed that this complex is involved in a transcriptional circuit concentrating both common and rare variant risk of ASDs. Finally, we found the network itself enriched for ASD rare variant risk, indicating that it can complement genetic datasets for prioritizing additional risk genes. Our findings establish brain cell type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in ASDs and illustrate how both individual and convergent interactions lead to biological insights into the disease.
Virulence constrains transmission even in the absence of a genetic trade-off
Authors: Godinho Diogo P. , Rodrigues Leonor R. , Lefevre Sophie , Delteil Laurane , Mira André F. , Fragata Inês R. , Magalhães Sara , Duncan Alison B. 
Published: October 2021

AbstractThe virulence-transmission trade-off predicts that parasite fitness peaks at intermediate virulence. However, whether this relationship is driven by the environment or genetically determined and if it depends on transmission opportunities remains unclear. We tackled these issues using inbred lines of the macro-parasitic spider-miteTetranychus urticae. When transmission was not possible during the infection period, we observed a hump-shaped relationship between virulence and parasite fitness, as predicted by theory. This was environmentally driven, as no genetic correlation between traits was detected. However, when transmission to uninfected hosts occurred during the infection period, virulence was positively, environmentally and genetically correlated with parasite fitness. Therefore, the virulence-transmission trade-off depends on within-host dynamics and on the timing of transmission, rather than on a genetic correlation. This fundamental correlation may thus be easier to manipulate than previously thought.
Loss-of-function ROX1 mutations suppress the fluconazole susceptibility of upc2AΔ mutation in Candida glabrata, implicating additional positive regulators of ergosterol biosynthesis
Authors: Ollinger Tomye L. , Vu Bao , Murante Daniel , Parker Josie E. , Simonicova Lucia , Doorley Laura , Stamnes Mark A. , Kelly Steven L. , Rogers P. David , Moye-Rowley W. Scott , Krysan Damian J. 
Published: October 2021

AbstractTwo of the major classes of antifungal drugs in clinical use target ergosterol biosynthesis. Despite its importance, our understanding of the transcriptional regulation of ergosterol biosynthesis genes in pathogenic fungi is essentially limited to the role of hypoxia and sterol-stress induced transcription factors such as Upc2 and Upc2A as well as homologs of Sterol Response Element Binding (SREB) factors. To identify additional regulators of ergosterol biosynthesis in Candida glabrata, an important human fungal pathogen with reduced susceptibility to ergosterol biosynthesis inhibitors relative to other Candida spp., we used a serial passaging strategy to isolate suppressors of the fluconazole hypersusceptibility of a upc2AΔ deletion mutant. This led to the identification of loss of function mutants in two genes: ROX1, the homolog of a hypoxia gene transcriptional suppressor in Saccharomyces cerevisiae, and CST6, a transcription factor that is involved in the regulation of carbon dioxide response in C. glabrata. Here, we describe a detailed analysis of the genetic interaction of ROX1 and UPC2A. In the presence of fluconazole, loss of Rox1 function restores ERG11 expression to the upc2AΔ mutant and inhibits the expression of ERG3 and ERG6, leading to increased levels or ergosterol and decreased levels of the toxic sterol, 14α methyl-ergosta-8,24(28)-dien-3β, 6α-diol, relative to upc2AΔ. Our observations establish that Rox1 is a negative regulator of ERG gene biosynthesis and indicate that a least one additional positive transcriptional regulator of ERG gene biosynthesis must be present in C. glabrata.ImportanceCandida glabrata is one of the most important human fungal pathogens and has reduced susceptibility to azole class inhibitors of ergosterol biosynthesis. Although ergosterol is the target of two of the three classes of antifungal drugs, relatively little is known about the regulation of this critical cellular pathway. Sterols are both essential components of the eukaryotic plasma membrane and potential toxins; therefore, sterol homeostasis is critical for cell function. Here, we identified two new negative regulators of C. glabrata of ergosterol (ERG) biosynthesis gene expression. Our results also indicate that in addition to Upc2A, the only known activator of ERG genes, additional positive regulators of this pathway must exist.s
Integrating de novo and inherited variants in over 42,607 autism cases identifies mutations in new moderate risk genes
Authors: Zhou Xueya , Feliciano Pamela , Wang Tianyun , Astrovskaya Irina , Shu Chang , Hall Jacob B. , Obiajulu Joseph U. , Wright Jessica , Murali Shwetha , Xu Simon Xuming , Brueggeman Leo , Thomas Taylor R. , Marchenko Olena , Fleisch Christopher , Barns Sarah D. , Snyder LeeAnne Green , Han Bing , Chang Timothy S. , Turner Tychele N. , Harvey William , Nishida Andrew , O’Roak Brian J. , Geschwind Daniel H. ,   The SPARK Consortium, Michaelson Jacob J. , Volfovsky Natalia , Eichler Evan E. , Shen Yufeng , Chung Wendy K. 
Published: October 2021

AbstractDespite the known heritable nature of autism spectrum disorder (ASD), studies have primarily identified risk genes with de novo variants (DNVs). To capture the full spectrum of ASD genetic risk, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases recruited online by SPARK. In the first stage, we analyzed 19,843 cases with one or both biological parents and found that known ASD or neurodevelopmental disorder (NDD) risk genes explain nearly 70% of the genetic burden conferred by DNVs. In contrast, less than 20% of genetic risk conferred by rare inherited loss-of-function (LoF) variants are explained by known ASD/NDD genes. We selected 404 genes based on the first stage of analysis and performed a meta-analysis with an additional 22,764 cases and 236,000 population controls. We identified 60 genes with exome-wide significance (p < 2.5e-6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1, and HNRNPUL2). The association of NAV3 with ASD risk is entirely driven by rare inherited LoFs variants, with an average relative risk of 4, consistent with moderate effect. ASD individuals with LoF variants in the four moderate risk genes (NAV3, ITSN1, SCAF1, and HNRNPUL2, n = 95) have less cognitive impairment compared to 129 ASD individuals with LoF variants in well-established, highly penetrant ASD risk genes (CHD8, SCN2A, ADNP, FOXP1, SHANK3) (59% vs. 88%, p= 1.9e-06). These findings will guide future gene discovery efforts and suggest that much larger numbers of ASD cases and controls are needed to identify additional genes that confer moderate risk of ASD through rare, inherited variants.
Neandertal introgression dissects the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes
Authors: Dannemann Michael , Milaneschi Yuri , Yermakovich Danat , Stiglbauer Victoria , Friese Manuel A. , Otte Christian , Penninx Brenda W.J.H. , Kelso Janet , Gold Stefan M. 
Published: October 2021

AbstractBackgroundAdvances have recently been made in identifying the genetic basis of psychiatric and neurological disorders, however, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm.MethodsWe compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions as a proxy for disease, and related non-disease phenotypes in the UK biobank (UKBB), the NESDA cohort and the Biobank Japan.ResultsWhile no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumptions. Several of these associations were also observed in NESDA and the Biobank Japan, suggesting their evolutionary relevance across different ancestry backgrounds. Intriguingly, in some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide.ConclusionsOur data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute pathology in modern humans, possibly due to changes in lifestyle and maladaptation.
Prospective predictors of risk and resilience trajectories during the early stages of the COVID-19 pandemic: a longitudinal study
Authors: Shilton Tal , Mancini Anthony D , Perlstein Samantha , Didomenico Grace E , Visoki Elina , Greenberg David M , Brown Lily A , Gur Raquel E , Waller Rebecca , Barzilay Ran 
Published: October 2021

AbstractBackgroundThe COVID-19 pandemic is a rapidly evolving stressor with significant mental health consequences. We aimed to delineate distinct anxiety-response trajectories during the early stages of the pandemic and to identify baseline risk and resilience factors as predictors of anxiety responses.MethodsUsing a crowdsourcing website, we enrolled 1,362 participants, primarily from the United States (n = 1064) and Israel (n = 222) over three time-points from April-September 2020. We used latent growth mixture modeling to identify anxiety trajectories over time. Group comparison and multivariate regression models were used to examine demographic and risk and resilience factors associated with class membership.ResultsA four-class model provided the best fit. The resilient trajectory (stable low anxiety) was the most common (n = 961, 75.08%), followed by chronic anxiety (n = 149, 11.64%), recovery (n = 96, 7.50%) and delayed anxiety (n = 74, 5.78%). While COVID-19 stressors did not differ between trajectories, resilient participants were more likely to be older, living with another person and to report higher income, more education, fewer COVID-19 worries, better sleep quality, and more dispositional resilience factors at baseline. Multivariate analyses suggested that baseline emotion regulation capabilities and low conflictual relationships uniquely distinguished participants in distinct trajectories.ConclusionsConsistent with prior resilience research following major adversities, a majority of individuals showed stable low levels of low anxiety in response to the COVID-19 pandemic. Knowledge about dispositional resilience factors may prospectively inform mental health trajectories early in the course of ongoing adversity.