bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Study Using Propensity Score Matching to Compare Long-term Survival Outcomes After Robotic-assisted, Laparoscopic, or Open Liver Resection for Patients With BCLC Stage 0-A Hepatocellular Carcinoma
Authors: Zhu Peng , Liao Wei , Zhang Wan-Guang , Chen Lin , Shu Chang , Zhang Zhi-Wei , Huang Zhi-Yong , Chen Yi-Fa , Lau Wan Yee , Zhang Bi-Xiang , Chen Xiao-Ping
Published: January 2022

Objective:

To compare the short- and long-term outcomes of robot-assisted (RALR), laparoscopic (LLR), or open liver resection (OLR) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC).

Summary Background Data:

Following the Balliol IDEAL classification, long-term oncological outcomes can be used to evaluate the value of minimally invasive techniques in the treatment of HCC, and to assess whether they should become a standard practice.

Methods:

Data from prospective cohorts of patients with BCLC stage 0-A HCC who underwent curative liver resection using OLR, LLR, or RALR at Tongji Hospital were reviewed. The short-term and long-term oncological outcomes of these 3 different surgical approaches after adequate follow-up were compared using propensity score matching to reduce selection bias.

Results:

Of 369 patients included in this study (71, RALR; 141, LLR; and 157, OLR), 56 patients in each of the 3 groups were chosen for further comparison, after propensity score matching. In the minimally invasive group (RALR+LLR), both the operative time and duration of Pringle’s maneuver were significantly longer than those in the OLR group; however, the length of hospital stay was significantly shorter. There were no significant differences in the other intraoperative parameters and the incidence of postoperative complications among the 3 groups. HCC recurrence in the minimally invasive group when compared with the OLR group was characterized by a significantly higher proportion of single lesion or early-stage HCC. However, there were no significant differences in the 5-year disease-free survival (63.8%, 54.4%, and 50.6%) or overall survival rates (80.8%, 78.6%, and 75.7%, respectively) among the 3 groups. Clinically significant portal hypertension was the only risk factor that negatively affected the 5-year disease-free survival rate. Multivariate Cox regression analysis showed that clinically significant portal hypertension, serum alpha-fetoprotein level (≥400 ng/mL), and Edmondson-Steiner grading (III+IV) were independent risk factors for poor long-term survival.

Conclusion:

Both robotic and laparoscopic hepatectomies were safe and effective for patients with BCLC stage 0-A HCC when compared with open hepatectomy.
Evaluating the complex association between Social Vulnerability Index and trauma mortality
Authors: Neiman Pooja U. , Flaherty Melanie M. , Salim Ali , Sangji Naveen F. , Ibrahim Andrew , Fan Zhaohui , Hemmila Mark R. , Scott John W.
Published: January 2022

INTRODUCTION

Social determinants of health are known to impact patient-level outcomes, but they are often difficult to measure. The Social Vulnerability Index was created by the Centers for Disease Control to identify vulnerable communities using population-based measures. However, the relationship between SVI and trauma outcomes is poorly understood.

METHODS

In this retrospective study, we merged SVI data with a statewide trauma registry and used three analytic models to evaluate the association between SVI quartile and inpatient trauma mortality: (1) an unadjusted model, (2) a claims-based model using only covariates available to claims datasets, and (3) a registry-based model incorporating robust clinical variables collected in accordance with the National Trauma Data Standard.

RESULTS

We identified 83,607 adult trauma admissions from January 1, 2017, to September 30, 2020. Higher SVI was associated with worse mortality in the unadjusted model (odds ratio, 1.72 [95% confidence interval, 1.30–2.29] for highest vs. lowest SVI quintile). A weaker association between SVI and mortality was identified after adjusting for covariates common to claims data. Finally, there was no significant association between SVI and inpatient mortality after adjusting for covariates common to robust trauma registries (adjusted odds ratio, 1.10 [95% confidence interval, 0.80–1.53] for highest vs. lowest SVI quintile). Higher SVI was also associated with a higher likelihood of presenting with penetrating injuries, a shock index of >0.9, any Abbreviated Injury Scale score of >5, or in need of a blood transfusion (p < 0.05 for all).

CONCLUSION

Patients living in communities with greater social vulnerability are more likely to die after trauma admission. However, after risk adjustment with robust clinical covariates, this association was no longer significant. Our findings suggest that the inequitable burden of trauma mortality is not driven by variation in quality of treatment, but rather in the lethality of injuries. As such, improving trauma survival among high-risk communities will require interventions and policies that target social and structural inequities upstream of trauma center admission.

LEVEL OF EVIDENCE

Prognostic / Epidemiologic, Level IV.
Life threat during assaultive trauma: Critical posttraumatic stress disorder risk factors for injured patients
Authors: Timmer-Murillo Sydney C. , Schramm Andrew , deRoon-Cassini Terri A.
Published: January 2022

BACKGROUND

Rates of posttraumatic stress disorder (PTSD) among injury survivors are higher relative to the general population, supporting the need to identify those most at risk for PTSD following injury given negative impact of PTSD on recovery. Perceived life threat and assaultive trauma are consistent risk factors for subsequent PTSD development, although less work has explored them in combination. The current study evaluated whether trauma type (assaultive vs. nonassaultive) and perceived life threat, together, led to greater PTSD symptoms 1 month and 6 months postinjury.

METHODS

Participants included adult injured trauma survivors admitted to a level 1 trauma center. While hospitalized, perceived life threat during trauma was assessed and mechanism of injury was collected via record review and was collapsed into two categories: assaultive and nonassaultive. The Clinician-Administered PTSD Scale (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) was administered at 1 month (N = 137) and 6 months (N = 220) after injury.

RESULTS

The four symptoms clusters of PTSD (intrusions, avoidance, hyperarousal, and negative mood/cognitions) were examined using four 2 (time) × 2 (life threat) × 2 (trauma type) mixed methods analyses of variance to assess differences based on risk factors and time. Results showed significant interaction effects of life threat, trauma type, and time for intrusive symptoms and avoidance symptoms. Individuals with life threat during assaultive traumas maintained heightened intrusive symptoms across time and increased avoidance at 6 months. On the other hand, participants with either life threat or assaultive traumas had decreased symptoms at 6 months.

CONCLUSION

Experiencing assaultive trauma and life threat led to greater symptoms of PTSD. Individuals with assaultive traumas who experienced life threat may represent a specific at-risk group following injury. Avoidance can protract functional impairment and impede access to care, negatively impacting recovery. This study highlights a need to assess for these peritrauma factors during hospitalization and supports early intervention targeting avoidance and intrusive symptoms in this group.

LEVEL OF EVIDENCE

Prognostic/Epidemiologic, Level IV.
Are burns a chronic condition? Examining patient reported outcomes up to 20 years after burn injury—A Burn Model System National Database investigation
Authors: Abouzeid Cailin A. , Wolfe Audrey E. , Ni Pengsheng , Carrougher Gretchen J. , Gibran Nicole S. , Hammond Flora M. , Holavanahalli Radha , McMullen Kara A. , Roaten Kimberly , Suman Oscar , Stewart Barclay T. , Wolf Steven , Zafonte Ross , Kazis Lewis E. , Ryan Colleen M. , Schneider Jeffrey C.
Published: January 2022

BACKGROUND

People living with burn injury often face long-term physical and psychological sequelae associated with their injuries. Few studies have examined the impacts of burn injuries on long-term health and function, life satisfaction, and community integration beyond 5 years postinjury. The purpose of this study was to examine these outcomes up to 20 years after burn injury.

METHODS

Data from the Burn Model System National Longitudinal Database (1993–2020) were analyzed. Patient-reported outcome measures were collected at discharge (preinjury status recall) and 5 years, 10 years, 15 years, and 20 years after injury. Outcomes examined were the SF-12/VR-12 Physical Component Summary and Mental Component Summary, Satisfaction with Life Scale, and Community Integration Questionnaire. Trajectories were developed using linear mixed models with repeated measures of outcome scores over time, controlling for demographic and clinical variables.

RESULTS

The study population included 421 adult burn survivors with a mean age of 42.4 years. Lower Physical Component Summary scores (worse health) were associated with longer length of hospital stay, older age at injury and greater time since injury. Similarly, lower Mental Component Summary scores were associated with longer length of hospital stay, female sex, and greater time since injury. Satisfaction with Life Scale scores decrease negatively over time. Lower Community Integration Questionnaire scores were associated with burn size and Hispanic/Latino ethnicity.

CONCLUSION

Burn survivors' physical and mental health and satisfaction with life worsened over time up to 20 years after injury. Results strongly suggest that future studies should focus on long-term follow-up where clinical interventions may be necessary.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Prehospital low titer group O whole blood is feasible and safe: Results of a prospective randomized pilot trial
Authors: Guyette Frank X. , Zenati Mazen , Triulzi Darrell J. , Yazer Mark H. , Skroczky Hunter , Early Barbara J. , Adams Peter W. , Brown Joshua B. , Alarcon Louis , Neal Matthew D. , Forsythe Raquel M. , Zuckerbraun Brian S. , Peitzman Andrew B. , Billiar Timothy R. , Sperry Jason L.
Published: January 2022

INTRODUCTION

Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remain limited.

METHODS

We performed a single-center, prospective, cluster randomized, prehospital through in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (systolic blood pressure ≤90 mm Hg and heart rate ≥108 beats per minute or systolic blood pressure ≤70 mm Hg for patients at risk of hemorrhage). Primary outcome was feasibility. Secondary outcomes included 28-day and 24-hour mortality, multiple organ failure, nosocomial infection, 24-hour transfusion requirements, and arrival coagulation parameters.

RESULTS

Between November 2018 and October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent-to-treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p < 0.01) and a lower incidence of abnormal thromboelastographic measurements. No transfusion reactions during the prehospital or in-hospital phase of care were documented.

CONCLUSION

Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with protocol adjustment and would allow the effects of prehospital LTOWB on survival and other pertinent clinical outcomes to be appropriately characterized.

LEVEL OF EVIDENCE

Therapeutic/Care Management, Level II.
Agromyces agglutinans sp. nov., isolated from saline lake sediment
Authors: Yi Bing-fang , Xia Ting-ting , Niu Ming-ming , Zhao Zi-yu , Su Qing-yang , Ming Hong , Nie Guo-xing
Published: January 2022

A novel actinobacterium, designated strain CFH 90414T, was isolated from sediment sampled at a saline lake in Yuncheng, Shanxi, PR China. The taxonomic position of the strain was investigated by using a polyphasic approach. Cells of strain CFH 90414T were Gram-reaction-positive, aerobic and non-motile. Growth occured at 4−40 °C, pH 5.0−9.0 and in the presence of up to 0–3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CFH 90414T was a member of the genus

Agromyces

. The 16S rRNA gene sequence similarity analysis indicated that strain CFH 90414T was most closely related to

Agromyces italicus

JCM 14320T (98.07 %) and

Agromyces lapidis

JCM 14321T (97.18 %). The whole genome of CFH 90414T was 3.64 Mb, and showed a G+C content of 71.5 mol%. The average nucleotide identity (ANI) values and digital DNA–DNA hybridization (dDDH) values between CFH 90414T and the other species of the genus

Agromyces

were found to be low (ANI <78.99 % and dDDH <22.9 %). The whole-cell sugars were rhamnose, mannose, ribose, glucose and galactose. The isolate contained l-2,4-diaminobutyric acid, d-alanine, d-glutamic acid and glycine in the cell-wall peptidoglycan. The predominant menaquinone was MK-12. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol and an unidentiﬁed glycolipid. On the basis of phenotypic, genotypic and phylogenetic data, strain CFH 90414T is considered to represent a novel species of the genus

Agromyces

, for which the name Agromyces agglutinans sp. nov. is proposed. The type strain is CFH 90414T (=DSM 105966T=KCTC 49062T).
Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes
Authors: Lund David , Kieffer Nicolas , Parras-Moltó Marcos , Ebmeyer Stefan , Berglund Fanny , Johnning Anna , Larsson D. G. Joakim , Kristiansson Erik
Published: January 2022

Macrolides are broad-spectrum antibiotics used to treat a range of infections. Resistance to macrolides is often conferred by mobile resistance genes encoding Erm methyltransferases or Mph phosphotransferases. New erm and mph genes keep being discovered in clinical settings but their origins remain unknown, as is the type of macrolide resistance genes that will appear in the future. In this study, we used optimized hidden Markov models to characterize the macrolide resistome. Over 16 terabases of genomic and metagenomic data, representing a large taxonomic diversity (11 030 species) and diverse environments (1944 metagenomic samples), were searched for the presence of erm and mph genes. From this data, we predicted 28 340 macrolide resistance genes encoding 2892 unique protein sequences, which were clustered into 663 gene families (<70 % amino acid identity), of which 619 (94 %) were previously uncharacterized. This included six new resistance gene families, which were located on mobile genetic elements in pathogens. The function of ten predicted new resistance genes were experimentally validated in

Escherichia coli

using a growth assay. Among the ten tested genes, seven conferred increased resistance to erythromycin, with five genes additionally conferring increased resistance to azithromycin, showing that our models can be used to predict new functional resistance genes. Our analysis also showed that macrolide resistance genes have diverse origins and have transferred horizontally over large phylogenetic distances into human pathogens. This study expands the known macrolide resistome more than ten-fold, provides insights into its evolution, and demonstrates how computational screening can identify new resistance genes before they become a significant clinical problem.
A single amino acid exchange converts FocA into a unidirectional efflux channel for formate
Authors: Kammel Michelle , Trebbin Oliver , Pinske Constanze , Sawers R. Gary
Published: January 2022

During mixed-acid fermentation,

Escherichia coli

initially translocates formate out of the cell, but re-imports it at lower pH. This is performed by FocA, the archetype of the formate-nitrite transporter (FNT) family of pentameric anion channels. Each protomer of FocA has a hydrophobic pore through which formate/formic acid is bidirectionally translocated. It is not understood how the direction of formate/formic acid passage through FocA is controlled by pH. A conserved histidine residue (H209) is located within the translocation pore, suggesting that protonation/deprotonation might be linked to the direction of formate translocation. Using a formate-responsive lacZ-based reporter system we monitored changes in formate levels in vivo when H209 in FocA was exchanged for either of the non-protonatable amino acids asparagine or glutamine, which occur naturally in some FNTs. These FocA variants (with N or Q) functioned as highly efficient formate efflux channels and the bacteria could neither accumulate formate nor produce hydrogen gas. Therefore, the data in this study suggest that this central histidine residue within the FocA pore is required for pH-dependent formate uptake into

E. coli

cells. We also address why H209 is evolutionarily conserved and provide a physiological rationale for the natural occurrence of N/Q variants of FNT channels.
Impact of a native hemiparasitic plant on invasive and native hosts in the field
Authors: Cirocco Robert M. , Watling Jennifer R. , Facelli José M.
Published: January 2022

There is increasing evidence that native parasitic plants are showing potential as biocontrols for plant invasions which are a major global threat to biodiversity. However, for this potential to be realised, the range of invasive hosts that can be controlled needs to be identified while also evaluating any potential off-target effects the parasite may pose. To address this, we investigated the impact of the Australian native shoot hemiparasitic plant,Cassytha pubescenson the major invasive speciesRubus anglocandicansand two native shrubs,Acacia pycnanthaandBursaria spinosain naturally occurring populations in southern Australia. We measured foliar predawn and midday quantum yield, electron transport rate (ETR), stomatal conductance (gs), carbon isotope composition and foliar nitrogen concentration [N] of uninfected and infected plants and, apart from gs, also forC. pubescens. Infection significantly decreased predawn and midday quantum yield, ETR and gsof invasiveR. anglocandicans. In contrast, infection had no effect on predawn and midday quantum yield, ETR or carbon isotope composition of the native hosts. However,C. pubescenshad a significant negative effect on native host gs, and a positive effect on host [N]. Parasite stem [N] was significantly higher when infectingA. pycnanthathanB. spinosa. These results strengthen evidence for native parasitic plants having greater impact on invasive hosts while having mild off-target effects on native hosts and thus, show potential to mitigate plant invasions and help protect biodiversity.
Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate
Authors: Li Li-Hsin , Liesenborghs Laurens , Wang Lanjiao , Lox Marleen , Yakass Michael Bright , Jansen Sander , Rosales Rosas Ana Lucia , Zhang Xin , Thibaut Hendrik Jan , Teuwen Dirk , Neyts Johan , Delang Leen , Dallmeier Kai
Published: January 2022

New platforms are urgently needed for the design of novel prophylactic vaccines and advanced immune therapies. Live-attenuated yellow fever vaccine YF17D serves as vector for several licensed vaccines and platform for novel vaccine candidates. Based on YF17D, we developed YF-S0 as exceptionally potent COVID-19 vaccine candidate. However, use of such live RNA virus vaccines raises safety concerns, i.e., adverse events linked to original YF17D (yellow fever vaccine-associated neurotropic; YEL-AND, and viscerotropic disease; YEL-AVD). In this study, we investigated the biodistribution and shedding of YF-S0 in hamsters. Likewise, we introduced hamsters deficient in STAT2 signaling as new preclinical model of YEL-AND/AVD. Compared to parental YF17D, YF-S0 showed an improved safety with limited dissemination to brain and visceral tissues, absent or low viremia, and no shedding of infectious virus. Considering yellow fever virus is transmitted by Aedes mosquitoes, any inadvertent exposure to the live recombinant vector via mosquito bites is to be excluded. The transmission risk of YF-S0 was hence evaluated in comparison to readily transmitting YFV-Asibi strain and non-transmitting YF17D vaccine, with no evidence for productive infection of vector mosquitoes. The overall favorable safety profile of YF-S0 is expected to translate to other novel vaccines that are based on the same YF17D platform.
Dynamic observation of2H labeled compounds in the human brain with1H versus2H magnetic resonance spectroscopy at 9.4T
Authors: Ruhm Loreen , Ziegs Theresia , Wright Andrew Martin , Mathy Claudius Sebastian , Murali-Manohar Saipavitra , Dorst Johanna , Avdievich Nikolai , Henning Anke
Published: January 2022

The metabolic pathway of [6,6’-2H2]-labeled glucose was investigated with two different techniques. The first technique used direct detection of deuterium applying Deuterium Metabolic Imaging (DMI). The second technique used the indirect detection of deuterium with proton MR spectroscopy (MRS) called Quantitative Exchanged-label Turnover (QELT) MRS. For the first time, time-resolved data was acquired for both techniques in the same healthy human subjects and directly compared. The time-curves were used in a kinetic model to estimate rates of the metabolic pathway of glucose. Two different kinetic models were compared. One included only DMI data, the second one combined DMI and QELT. For the first model, a tricarboxylic acid (TCA) cycle rate of 0.69 ± 0.10 μmol·min-1·g-1was determined. For the second model, the estimated TCA cycle rate was 0.68 ± 0.12 μmol·min-1·g-1. In addition, the rate of glutamine synthesis from glutamate could be estimated with model 2 (0.51 ± 0.15 μmol·min-1·g-1). The sensitivity of both methods was evaluated and compared to alternative techniques.
PSGL-1 directs early TCR signaling to repress metabolism and promote T cell exhaustion by modulating the TCF-1/TOX axis in CD8+ T cells
Authors: Hope Jennifer L. , Otero Dennis C. , Bae Eun-Ah , Stairiker Christopher J. , Palete Ashley B. , Faso Hannah A. , Henriquez Monique L. , Seo Hyungseok , Lei Xue , Wang Eric S. , Tinoco Roberto , Campos Alexandre Rosa , Yin Jun , Adams Peter D. , Rao Anjana , Bradley Linda M.
Published: January 2022

Summary/Abstract

We previously identified the adhesion molecule PSGL-1 as a T cell intrinsic immune checkpoint regulator of T cell exhaustion. Here we show that the ability of PSGL-1 to restrain TCR sginaling correlates with decreased expression of the Zap70 inhibitor Ubash3b (Sts-1) in PSGL-1-deficient T cells. PSGL-1-deficency in T cells supports antitumor responses to a PD-1 blockade resistant melanoma wherein tumor-specific CD8+ T cells sustain an enhanced metabolic state, with an elevated metabolic gene signature that promotes increased glycolysis and glucose uptake to support effector functions. In models of chronic virus infection and cancer, this outcome was associated with CD8+ T cell stemness, as PSGL-1 deficient CD8+ T cells displayed increased TCF-1 and decreased TOX expression, a phenotype shown to be crucial for responsiveness to checkpoint inhibition. Further, we demonstrate that PSGL-1 signaling promotes development of exhaustion in human CD8+ T cells. Finally, pharmacologic blockade of PSGL-1 was sufficient to curtail T cell exhaustion and enhance functionality both with melanoma tumors and chronic LCMV infection, demonstrating that PSGL-1 represents a therapeutic target for immunotherapy for PD-1/PD-L1 resistant tumors.
Phenotypic and genotypic characterization of Listeria monocytogenes in clinical ruminant cases in Korea
Authors: Kim Jongho , Kim Jong Wan , Kim Ha-Young
Published: January 2022

Listeria monocytogenes is a foodborne human and veterinary pathogen. This study aimed to determine the phenotypic and genotypic characteristics of L. monocytogenes isolates from clinical cases of Korean ruminants. We collected 24 L. monocytogenes isolates from clinical cases with caprine neurological symptoms and bovine abortion. The most prevalent serotypes were 4b (IVb), 1/2a (IIa; IIc), and 1/2b (IIb). All isolates, including two found in humans, formed three genetically diverse pulsed-field gel electrophoresis clusters according to serotype, lineage, and sequence type. The most prevalent sequence type was ST1, followed by ST365 and ST91. L. monocytogenes isolates from ruminant listeriosis were resistant to oxacillin and ceftriaxone. These clinical ruminant isolates showed diverse lineage, serotype (serogroup), and sequence type characteristics. Considering that the atypical sequence types exhibited clinical manifestations and histopathological lesions, further study is needed to elucidate the pathogenicity of genetically diverse ruminant L. monocytogenes isolates. Furthermore, continuous monitoring of antimicrobial resistance is required to prevent the emergence of L. monocytogenes strains resistant to common antimicrobials.
Dysregulation of stress-induced translational control by Porphyromonas gingivalis in host cells
Authors: Knowles Alex A , Campbell Susan G , Cross Neil A , Stafford Prachi
Published: January 2022

Periodontitis, a chronic inflammatory gum disease, is caused in part by the periodontopathogen Porphyromonas gingivalis. Infection triggers activation of host inflammatory responses which induce stresses such as oxidative stress. Under such conditions, cells can activate the Integrated Stress Response (ISR), a signalling cascade which functions to determine cellular fate, by either downregulating protein synthesis and initiating a stress-response gene expression program, or if stress cannot be overcome, initiating programmed cell death. Recent studies have implicated the ISR signalling in both host antimicrobial defences and within the pathomechanism of certain microbes.

In this study, we investigated how P. gingivalis infection alters translation attenuation during oxidative stress-induced activation of the ISR pathway in oral epithelial cells. P. gingivalis infection alone did not result in ISR activation. In contrast, infection coupled with stress led to differential stress granule formation and composition, along with dysregulation of the microtubule network. Infection also heightened stress-induced translational repression, a response which could not be rescued by ISRIB, a potent ISR inhibitor. Heightened translational repression during stress was observed with both P. gingivalis conditioned media and outer membrane vesicles, implicating the role of a secretory factor, probably proteases known as gingipains, in this exacerbated translational repression. The effects of gingipain inhibitors and gingipains-deficient P. gingivalis mutants further confirmed these pathogen-specific proteases as the effector.

Gingipains are known to degrade the mammalian target of rapamycin (mTOR) and these studies implicate the gingipain-mTOR axis as the effector of host translational dysregulation during stress.
Circuit-seq: Circular reconstruction of cut in vitro transposed plasmids using Nanopore sequencing
Authors: Emiliani Francesco E. , Hsu Ian , McKenna Aaron
Published: January 2022

Recombinant DNA is a fundamental tool in biotechnology and medicine. Validation of the resulting plasmid sequence is a critical and time-consuming step, which has been dominated for the last 35 years by Sanger sequencing. As plasmid sequences grow more complex with new DNA synthesis and cloning techniques, we need new approaches that address the corresponding validation challenges at scale. Here we prototype a high-throughput plasmid sequencing approach using DNA transposition and Oxford Nanopore sequencing. Our method, Circuit-seq, creates robust, full-length, and accurate plasmid assemblies without prior knowledge of the underlying sequence for approximately $1.50 per plasmid. We demonstrate the power of Circuit-seq across a wide range of plasmid sizes and complexities, generating accurate and contiguous plasmid maps. We then leverage our long read-data to characterize epigenetic marks and estimate plasmid contamination levels. Circuit-seq scales to large numbers of samples at a lower cost than commercial Sanger sequencing, accelerating a key step in synthetic biology, with low startup costs make it practical for individual laboratories.
Genome-wide analysis ofSchistosoma mansonireveals population structure and praziquantel drug selection pressure within Ugandan hot-spot communities
Authors: Vianney Tushabe John , Berger Duncan J. , Doyle Stephen R. , Sankaranarayanan Geetha , Serubanja Joel , Nakawungu Prossy Kabuubi , Besigye Fred , Sanya Richard E. , Holroyd Nancy , Allan Fiona , Webb Emily L. , Elliott Alison M. , Berriman Matt , Cotton James A.
Published: January 2022

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.

Author summary

Schistosomiasis is caused by parasitic helminths of the genusSchistosoma.Schistosoma mansoniis the primary cause of intestinal schistosomiasis, a devastating and widespread parasitic infection that causes morbidity, death and socio-economic impact on endemic communities across the world and especially sub-Saharan Africa. Using whole-genome sequencing, we were able to elucidate the parasite population within Lake Victoria island fishing communities in Uganda which are among the major hotspots for schistosomiasis. We further assessed genetic markers that might be linked to recent observations concerning reduced susceptibility to praziquantel, the major drug used in the treatment of this disease. Whole-genome data on the population genetics ofS. mansoniin an African setting will provide a strong basis for future functional genomics or transcriptomic studies that will be key to identifying drug targets, improving existing drugs or developing new therapeutic interventions.
Machine Learning for the Identification of Viral Attachment Machinery from Respiratory Virus Sequences
Authors: Demidkin Stepan , Shwarts Maïa , Chakravarty Arijit , Joseph-McCarthy Diane
Published: January 2022

At the outset of an emergent viral respiratory pandemic, sequence data is among the first molecular information available. As viral attachment machinery is a key target for therapeutic and prophylactic interventions, rapid identification of viral “spike” proteins from sequence can significantly accelerate the development of medical countermeasures. For five families of respiratory viruses, covering the vast majority of airborne and droplet-transmitted diseases, host cell entry is mediated by the binding of viral surface glycoproteins that interact with a host cell receptor. In this report it is shown that sequence data for an unknown virus belonging to one of the five families above provides sufficient information to identify the protein(s) responsible for viral attachment and to permit an assignment of viral family. Random forest models that take as input a set of respiratory viral sequences can classify the protein as “spike” vs. non-spike based on predicted secondary structure elements alone (with 97.8 % correctly classified) or in combination with N-glycosylation related features (with 98.1 % correctly classified). In addition, a Random Forest model developed using the same dataset and only secondary structural elements was able to predict the respiratory virus family of each protein sequence correctly 89.0 % of the time. Models were validated through 10-fold cross-validation as well as bootstrapping. Surprisingly, we showed that secondary structural element and N-glycosylation features were sufficient for model generation. The ability to rapidly identify viral attachment machinery directly from sequence data holds the potential to accelerate the design of medical countermeasures for future pandemics.
Inhibitory IL-10-producing CD4+ T cells develop in a T-bet-dependent manner and facilitate cytomegalovirus persistence via coexpression of arginase-1
Authors: Clement Mathew , Ladell Kristin , Miners Kelly L. , Marsden Morgan , Chapman Lucy , Figueras Anna Cardus , Scott Jake , Andrews Robert , Clare Simon , Kriukova Valeriia V. , Lupyr Ksenia R. , Britanova Olga V. , Withers David R. , Jones Simon A. , Chudakov Dmitriy M. , Price David A. , Humphreys Ian R.
Published: January 2022

Inhibitory CD4+ T cells have been linked with suboptimal immune responses against cancer and pathogen chronicity, but the mechanisms that underpin the development of such regulatory networks in vivo have remained obscure. To address this knowledge gap, we performed a comprehensive functional, phenotypic, and transcriptomic analysis of IL-10-producing CD4+ T cells induced by chronic infection with murine cytomegalovirus (MCMV). We identified these cells as clonally expanded and highly differentiated TH1-like cells that developed at sites of viral persistence in a T-bet-dependent manner and coexpressed arginase-1 (Arg1), which promotes the catalytic breakdown of L-arginine. Mice lacking Arg1-expressing CD4+ T cells exhibited more robust antiviral immunity and were better able to control MCMV. Conditional deletion of T-bet in the CD4+ lineage suppressed the development of these inhibitory cells and also enabled better immune control of MCMV. Collectively, these data elucidated the ontogeny of IL-10-producing CD4+ T cells and revealed a previously unappreciated mechanism of immune regulation, whereby viral persistence was facilitated by the coexpression of Arg1.
Bistable nerve conduction
Authors: Zhang Zhaoyang , Qu Zhilin
Published: January 2022

The essence of the nerve system is to transmit information from and to different parts of the body in response to environmental changes. Here we show that a bistable conduction behavior can occur in the nerve system, which exhibits stimulus-dependent fast and slow conduction waves. The bistable behavior is caused by a positive feedback loop of the wavefront upstroke speed, mediated by the sodium channel inactivation properties, which is further potentiated by the calcium current. This provides a mechanism for the slow and fast conduction in the same nerve system observed experimentally. We show that the bistable conduction behavior is robust with respect to the experimentally determined activation thresholds of the known sodium and calcium channel families. The theoretical insights provide a generic mechanism for stimulus-dependent fast and slow conduction in the nerve system, which is applicable to conduction in other electrically excitable tissue, such as cardiac muscles.
Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine
Authors: Wu Yangtao , Wang Shaojuan , Zhang Yali , Yuan Lunzhi , Zheng Qingbing , Wei Min , Shi Yang , Wang Zikang , Ma Jian , Wang Kai , Nie Meifeng , Xiao Jin , Huang Zehong , Chen Peiwen , Guo Huilin , Lan Miaolin , Xu Jingjing , Hou Wangheng , Hong Yunda , Chen Dabing , Sun Hui , Xiong Hualong , Zhou Ming , Liu Che , Guo Wenjie , Guo Huiyu , Gao Jiahua , Li Zhixiong , Zhang Haitao , Wang Xinrui , Li Shaowei , Cheng Tong , Zhao Qinjian , Chen Yixin , Wu Ting , Zhang Tianying , Zhang Jun , Cao Hua , Zhu Huachen , Yuan Quan , Guan Yi , Xia Ningshao
Published: January 2022

The widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron; and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.
Inhibitory CCK+ basket synapse defects in mouse models of dystroglycanopathy
Authors: Jahncke Jennifer N. , Miller Daniel S. , Krush Milana , Schnell Eric , Wright Kevin M.
Published: January 2022

Dystroglycan (Dag1) is a transmembrane glycoprotein that links the extracellular matrix to the actin cytoskeleton. Mutations inDag1or the genes required for its glycosylation result in dystroglycanopathy, a type of congenital muscular dystrophy characterized by a wide range of phenotypes including muscle weakness, brain defects, and cognitive impairment. We investigated interneuron (IN) development, synaptic function, and associated seizure susceptibility in multiple mouse models that reflect the wide phenotypic range of dystroglycanopathy neuropathology. Mice that model severe dystroglycanopathy due to forebrain deletion ofDag1orPomt2, which is required for Dystroglycan glycosylation, show significant impairment of CCK+/CB1R+IN development. CCK+/CB1R+IN axons failed to properly target the somatodendritic compartment of pyramidal neurons in the hippocampus, resulting in synaptic defects and increased seizure susceptibility. Mice lacking the intracellular domain of Dystroglycan have milder defects in CCK+/CB1R+IN axon targeting, but exhibit dramatic changes in inhibitory synaptic function, indicating a critical postsynaptic role of this domain. In contrast, CCK+/CB1R+IN synaptic function and seizure susceptibility was normal in mice that model mild dystroglycanopathy due to partially reduced Dystroglycan glycosylation. Collectively, these data show that inhibitory synaptic defects and elevated seizure susceptibility are hallmarks of severe dystroglycanopathy, and show that Dystroglycan plays an important role in organizing functional inhibitory synapse assembly.
Nutrient and salt depletion synergistically boosts glucose metabolism in individual bacteria
Authors: Glover Georgina , Voliotis Margaritis , Łapińska Urszula , Invergo Brandon M. , Soanes Darren , O’Neill Paul , Moore Karen , Nikolic Nela , Petrov Peter G. , Milner David S. , Roy Sumita , Heesom Kate , Richards Thomas A. , Tsaneva-Atanasova Krasimira , Pagliara Stefano
Published: January 2022

The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.
Environmental cell for in situ X-ray synchrotron micro-CT imaging with simultaneous acoustic measurements
Authors: Drobchik Arkady N. , Nikitin Viktor V. , Fokin Mikhail I. , Dugarov Geser A. , Shevchenko Pavel D. , Deriy Alex L. , Manakov Andrey Yu. , Kuper Konstantin E. , Duchkov Anton A.
Published: January 2022

Synchrotron radiation provides the necessary spatial and temporal resolution for non-invasive operando studies of dynamic processes under complex environmental conditions. Here a new environmental cell for simultaneous in situ dynamic X-ray imaging and measuring acoustic properties of geological samples is presented. The primary purpose of this cell is to study gas-hydrate formation in porous geo-materials and its influence on their acoustic properties. The cell is designed for cylindrical samples of 9 mm in diameter, confining and pore pressures up to 12 MPa, and temperatures from −20°C to room temperature. The cell is portable and can be easily assembled and operated at different X-ray sources. This cell enables a wide range of experiments studying physical/chemical processes in the Earth subsurface that change the mechanical properties of rocks (geochemical reactions, phase transitions, etc.).
FOX-7 high-energy-density material: thermal expansion and phase transitions revisited
Authors: McMonagle Charles J. , Michalchuk Adam A. L. , Chernyshov Dmitry
Published: January 2022

Variable-temperature single-crystal diffraction experiments treated with the Gandolfi method reveal the detailed temperature evolution of the unit-cell dimensions, structural transformations and the phase co-existence of the energetic material FOX-7. Two first-order phase transitions are observed accompanied by abrupt changes in volume and unit-cell dimensions. The thermal expansion is found to be linear for all three phases, albeit highly anisotropic. Moreover, the experimental thermal expansion coefficients differ from those predicted from literature atomistic simulations.
Systematic fuzzy Navier–Stokes equations for aerospace vehicles
Authors: Chen ZY , Meng Yahui , Wang Ruei-Yuan , Chen Timothy
Published: January 2022

Purpose

To prove the effectiveness of the proposed design method, this study aims to propose the Fisher equation and temperature cooling fins that control high-speed aerospace vehicles.

Design/methodology/approach

A new approach whereby the control of aerospace vehicles can be achieved by fuzzy controller and appropriate Navier–Stokes equations in this article. The design of the controller based on models of Navier–Stokes equations simplified complex mathematical simulations and approximations.

Findings

If the fuzzy controller cannot stabilize the system, the Navier–Stokes fuzzy function is injected into the system as a controller tool, and the system is asymptotically stabilized by adjusting the fuzzy parameters.

Originality/value

The simulation results show that if the tuning frequency is high enough, the fuzzy controller and fuzzy observer can create chaotic movements by adjusting the dither amplitude appropriately. The demonstration of the Fisher equation and the temperature-cooled fin control problem for high-speed aerospace vehicles has displayed the benefits of combining fuzzy control with the Navier–Stokes equation.
Branding through visitors: how cultural differences affect brand co-creation in independent hotels in Iran
Authors: Ranjbaran Alireza , Shabankareh Mohammadjavad , Nazarian Alireza , Seyyedamiri Nader
Published: January 2022

Purpose

In most countries, independent hotels are a major contributor to both national economy and the hospitality sector, but to the best of the authors’ knowledge, there is a lack of any study on brand co-creation (BCC) in independent hotels. This study aims to examine the interrelationship of moral judgement (MJ), self–brand connection, customer–brand engagement (CBE), electronic word-of-mouth (eWOM) and how BCC occurs in independent hotels and contrasts visitors’ perspectives between two different Global Leadership and Organizational Behavior Effectiveness clusters in independent hotels. Furthermore, this study also examines the moderating impact of privacy concern (PC) on the relationship between eWOM and brand co-creation.

Design/methodology/approach

Data were collected from two groups of tourists, Iranian (290) and European (224), who visited and stayed in independent hotels in some major cities in Iran. The structural equation modelling using AMOS 22 was adopted to test the hypotheses.

Findings

The study’s findings revealed that there are significant differences between two culturally different travellers in terms of selected variables, suggesting that MJ is a main antecedent of CBE, which leads to eWOM among Iranian travellers, which consequently leads to BCC. Moreover, the study’s data indicates that European travellers show a high level of PCs while staying in independent hotels in Iran, which prevents them from sharing and getting engaged in the social media, which could delay the BCC process especially in international level.

Originality/value

This study contributes to literature by providing new insights on the differences in the concept of brand co-creation between two culturally different groups in the context of independent hotels, which require special attention of independent hotel managers.