bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score*
Authors: Sikora Andrea , Ayyala Deepak , Rech Megan A. , Blackwell Sarah B. , Campbell Joshua , Caylor Meghan M. , Condeni Melanie Smith , DePriest Ashley , Dzierba Amy L. , Flannery Alexander H. , Hamilton Leslie A. , Heavner Mojdeh S. , Horng Michelle , Lam Joseph , Liang Edith , Montero Jennifer , Murphy David , Plewa-Rusiecki Angela M. , Sacco Alicia J. , Sacha Gretchen L. , Shah Poorvi , Smith Michael P. , Smith Zachary , Radosevich John J. , Vilella Antonia L. ,   for the MRC-ICU Investigator Team
Published: June 2022

OBJECTIVES:

Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population.

DESIGN:

This was a multicenter, observational cohort study.

SETTING:

Twenty-eight ICUs in the United States.

PATIENTS:

Adult ICU patients.

INTERVENTIONS:

Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively.

MEASUREMENTS AND MAIN RESULTS:

A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08–1.11; p < 0.01), ICU LOS (β coefficient, 0.41; 95% CI, 00.37–0.45; p < 0.01), total pharmacist interventions (β coefficient, 0.07; 95% CI, 0.04–0.09; p < 0.01), and a composite intensity score of pharmacist interventions (β coefficient, 0.19; 95% CI, 0.11–0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (β coefficient, 0.02; 0.00–0.04; p = 0.02) and reduced quantity (β coefficient, –0.03; 95% CI, –0.04 to –0.02; p < 0.01) and intensity of interventions (β coefficient, –0.05; 95% CI, –0.09 to –0.01).

CONCLUSIONS:

Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.
Coronavirus Disease 2019 and Heart Transplantation: Single-Center Experience and Review of the Literature
Authors: Greenberg Daniel , Li Bo , Okumura Kenji , Nabors Christopher , Dhand Abhay
Published: June 2022

Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020, and since then it has had a significant impact on healthcare including on solid organ transplantation. Based on age, immunosuppression, and prevalence of chronic comorbidities, heart transplant recipients are at high risk of adverse outcomes associated with COVID-19. In our center, 31 heart transplant recipients were diagnosed with COVID-19 from March 2020 to September 2021. They required: hospitalization (39%), intensive care (10%), and mechanical ventilation (6%) with overall short-term mortality of 3%. Early outpatient use of anti-SARS CoV-2 monoclonal antibodies in our heart transplant recipients was associated with a reduction in the risk of hospitalization, need for intensive care, and death related to COVID-19. In prior multicenter studies, completed in different geographic areas and pandemic timeframes, diverse rates of hospitalization (38–91%), mechanical ventilation (4–38%), and death (16–33%) have been reported. Progression of disease and adverse outcomes were most significantly associated with severity of lymphopenia, chronic comorbid conditions like older age, chronic allograft vasculopathy, increased body mass index, as well as intensity of baseline immune suppression. In this article, we also review the current roles and limitations of vaccination, anti-viral agents, and anti-severe acute respiratory syndrome coronavirus 2 monoclonal antibodies in the management of heart transplant recipients. Our single-center experience, considered together with other studies indicates a trend toward improved outcomes among heart transplant patients with COVID-19.
Safety and Acceptance of Acupuncture and Acupressure in Children, Adolescents, and Young Adults Undergoing Hematopoietic Stem Cell Transplant
Authors: Bettini Elizabeth , Idiokitas Risi , Mahmood Laila , Jacobs Shana , Steinhorn David
Published: June 2022

Background

Hematopoietic stem cell transplant (HSCT) is associated with significant morbidity and high symptom burden including mucositis pain, nausea, and vomiting. There is little documentation in the literature regarding acupuncture or acupressure for children undergoing HSCT.

Objective

The purpose of this study was to determine the safety and acceptance of acupuncture and acupressure in children undergoing HSCT in a large tertiary care children’s hospital.

Methods

This is a descriptive retrospective study that evaluated 80 admissions to the HSCT unit over a 24-month period. Every child admitted for HSCT was offered acupuncture or acupressure as part of their care.

Results

Of 80 patients, 46 were male patients (ages range, 0-32 years; mean, 8 years). Diagnoses include leukemia/lymphoma, sickle cell disease, aplastic anemia, neuroblastoma, and other metabolic, other solid tumor, or other hematologic disorders. Both allogenic and autologous were represented. Sixty-six patients (82.5%) agreed to treatment with acupuncture, acupressure, or both. There were no adverse effects or safety concerns noted. Symptoms addressed by acupuncture or acupressure included pain from mucositis, nausea, constipation, diarrhea, anxiety, insomnia, and general wellness or healing.

Conclusion

This study demonstrates that acupuncture and acupressure are well accepted by children and their families admitted for HSCT and are safe even when performed in the first 4 weeks following transplant when the patient is likely to have thrombocytopenia.

Implications for Practice

These findings suggest that there may be more therapies for patients undergoing HSCT to help with symptom control.
Effective amelioration of lucio phenomenon with adjuvant tofacitinib therapy in a patient with dual infection of M. leprae and M. lepromatosis : A case report from India.
Authors: Patel Nayankumar Harshadkumar , Padhiyar Jignaben Krunal , Patel Kathak Ashok , Patel Jahnvi Rakeshkumar , Lakum Megha Pratapabhai , Singh Itu
Published: June 2022

Introduction:  Lucio phenomenon (LP) is characteristic reaction pattern seen in patient of diffuse lepromatous leprosy(DLL). Dual infection of  M. leprae  and  M. lepromatosis  in case of DLL is confirmed from other endemic country but same is yet to be documented from India. Conventionally LP is treated with high dose of systemic glucocorticoid (GC) and anti-leprosy treatment (ALT). Here we are reporting an interesting case of leprosy lymphadenitis as initial presentation in case of LP and DLL due to dual infection with  M. leprae  and  M. lepromatosis  who responded favorably to tofacitinib as adjuvant to ALT and systemic GC therapy.  Case report:  A 24-year-old man presented with complaint of swelling over bilateral inguinal region, pus filled skin lesions with multiple ulcers, fever and joint pain. Post hospitalization investigations showed presence of anemia, leukocytosis and elevated acute and chronic inflammatory markers. Skin and lymph node biopsies were suggestive of LP and Leprosy lymphadenitis. Presence of  M.leprae  and  M. lepromatosis  was confirmed by PCR study of tissue. Despite of anti-leprosy treatment, oral GC and thalidomide therapy patient continue developing new lesions. Post one-month commencement of adjuvant tofacitinib, patient experienced excellent clinical improvement as healing of all existing lesions and cessation of new lesion of LP.  Conclusion:  Our case confirms the presence of dual infection with  M. leprae  and  lepromatosis  in India.  Lymph node involvement as initial presentation of DLL should be considered in endemic area. Tofacitinib can emerge as promising new adjuvant therapy for recalcitrant lepra reaction.
Catellatospora tritici sp. nov., a novel cellulase-producing actinobacterium isolated from rhizosphere soil of wheat (Triticum aestivum L.) and emended description of the genus Catellatospora
Authors: Yang Yanming , Qian Lulu , Lin Jiaying , Qi Cuiping , Zhao Tianxin , Wang Xiangjing , Zhao Junwei , Xiang Wensheng
Published: June 2022

A Gram-positive, cellulose-degrading actinobacterium, designed strain NEAU-YM18T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) sampled in Langfang, Hebei Province, PR China. The novel strain was characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed that strain NEAU-YM18T belonged to the genus

Catellatospora

. Cells of strain NEAU-YM18T were observed to contain meso- and 3-hydroxy-diaminopimelic acids as diagnostic cell-wall amino acids. The acyl type of the cell-wall muramic acid was glycolyl. The whole-cell hydrolysates were xylose, glucose and ribose. The phospholipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were iso-C15 : 0, iso-C16 : 0, C18 : 1
 ω9c and summed feature 5 (anteiso-C18 : 0/C18 : 2
 ω6,9c). The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The DNA G+C content was 71.1 %. The results of 16S rRNA gene sequence and phylogenetic analyses indicated that strain NEAU-YM18T was closely related to

Catellatospora chokoriensis

2-25(1)T (98.4 % 16S rRNA gene sequence similarity),

Catellatospora vulcania

NEAU-JM1T (98.3%) and

Catellatospora sichuanensis

H14505T (98.3 %) and formed a branch with

C. sichuanensis

H14505T. Furthermore, the whole genome phylogeny of strain NEAU-YM18T showed that the strain formed an independent clade. The digital DNA–DNA hybridization results between NEAU-YM18T and

C. chokoriensis

2-25(1)T,

C. vulcania

NEAU-JM1T and

C. sichuanensis

H14505T were 25.0, 24.7 and 24.7 %, respectively, and the whole-genome average nucleotide identity values between them were 81.5, 81.4 and 81.4 %, respectively. These genetic results and some phenotypic characteristics could distinguish strain NEAU-YM18T from its reference strains. In addition, genomic analysis confirmed that strain NEAU-YM18T had the potential to decompose cellulose and produce bioactive compounds. Therefore, strain NEAU-YM18T represents a novel species of the genus

Catellatospora

, for which the name Catellatospora tritici sp. nov. is proposed. The type strain is NEAU-YM18T (=CCTCC AA 2020040T=JCM 33977T).
Insights into plastic biodegradation: community composition and functional capabilities of the superworm (Zophobas morio) microbiome in styrofoam feeding trials
Authors: Sun Jiarui , Prabhu Apoorva , Aroney Samuel T. N. , Rinke Christian
Published: June 2022

Plastics are inexpensive and widely used organic polymers, but their high durability hinders biodegradation. Polystyrene, including extruded polystyrene (also known as styrofoam), is among the most commonly produced plastics worldwide and is recalcitrant to microbial degradation. In this study, we assessed changes in the gut microbiome of superworms (Zophobas morio) reared on bran, polystyrene or under starvation conditions over a 3 weeks period. Superworms on all diets were able to complete their life cycle to pupae and imago, although superworms reared on polystyrene had minimal weight gains, resulting in lower pupation rates compared to bran reared worms. The change in microbial gut communities from baseline differed considerably between diet groups, with polystyrene and starvation groups characterized by a loss of microbial diversity and the presence of opportunistic pathogens. Inferred microbial functions enriched in the polystyrene group included transposon movements, membrane restructuring and adaptations to oxidative stress. We detected several encoded enzymes with reported polystyrene and styrene degradation abilities, supporting previous reports of polystyrene-degrading bacteria in the superworm gut. By recovering metagenome-assembled genomes (MAGs) we linked phylogeny and functions and identified genera including

Pseudomonas

,

Rhodococcus

and

Corynebacterium

that possess genes associated with polystyrene degradation. In conclusion, our results provide the first metagenomic insights into the metabolic pathways used by the gut microbiome of superworms to degrade polystyrene. Our results also confirm that superworms can survive on polystyrene feed, but this diet has considerable negative impacts on host gut microbiome diversity and health.
FtsZ at mid-cell is essential in Escherichia coli until the late stage of constriction
Authors: Corbin Goodman Lauren C. , Erickson Harold P.
Published: June 2022

There has been recent debate as to the source of constriction force during cell division. FtsZ can generate a constriction force on tubular membranes in vitro, suggesting it may generate the constriction force in vivo. However, another study showed that mutants of FtsZ did not affect the rate of constriction, whereas mutants of the PG assembly did, suggesting that PG assembly may push the constriction from the outside. Supporting this model, two groups found that cells that have initiated constriction can complete septation while the Z ring is poisoned with the FtsZ targeting antibiotic PC190723. PC19 arrests treadmilling but leaves FtsZ in place. We sought to determine if a fully assembled Z ring is necessary during constriction. To do this, we used a temperature-sensitive FtsZ mutant, FtsZ84. FtsZ84 supports cell division at 30 °C, but it disassembles from the Z ring within 1 min upon a temperature jump to 42 °C. Following the temperature jump we found that cells in early constriction stop constricting. Cells that had progressed to the later stage of division finished constriction without a Z ring. These results show that in

Escherichia coli

, an assembled Z ring is essential for constriction except in the final stage, contradicting the simplest interpretation of previous studies using PC19.
Social effects of rabies infection in male vampire bats (Desmodus rotundus)
Authors: Cárdenas Canales Elsa M. , Stockmaier Sebastian , Cronin Eleanor , Rocke Tonie , Osorio Jorge E. , Carter Gerald G.
Published: June 2022

Abstract (resumen en español, S1)

Rabies virus (RABV) transmitted by the common vampire bat (Desmodus rotundus) poses a threat to agricultural development and public health throughout the Neotropics. The ecology and evolution of rabies host-pathogen dynamics are influenced by two infection-induced behavioral changes. RABV-infected hosts often exhibit increased aggression which facilitates transmission, and rabies also leads to reduced activity and paralysis prior to death. Although several studies document rabies-induced behavioral changes in rodents and other dead-end hosts, surprisingly few studies have measured these changes in vampire bats, the key natural reservoir throughout Latin America. Here, we take advantage of an experiment designed to test the safety and efficacy of an oral rabies vaccine in captive male vampire bats to quantify for the first time how rabies affects allogrooming and aggressive behaviors in the vampire bat. Compared to non-rabid vampire bats, rabid individuals reduced their allogrooming prior to death, but we did not detect increases in aggression among bats. To put our results in context, we review what is known and what remains unclear about behavioral changes of rabid vampire bats.
Evaluation of sampling and concentration methods for Salmonella enterica serovar Typhi detection from wastewater
Authors: Zhou Nicolette A. , Ong Angelo Q.W. , Fagnant-Sperati Christine S. , Harrison Joanna Ciol , Kossik Alexandra L. , Beck Nicola K. , Shirai Jeffry H. , Burnor Elisabeth , Swanstrom Rachael , Demeke Bethel , Patel Suhani ,   Typhoid Environmental Surveillance Working Group, Meschke John Scott
Published: June 2022

Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of Typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens, and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with twelve variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on their ability to detect Salmonella Typhi and feasibility. Salmonella Typhi strains, Ty21a and Ty2, were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via qPCR. Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses including the Salmonella Typhi concentrations they are best suited for with a range of positive detections observed as low as 0.1-0.001 CFU Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned.
Application of neighborhood-scale wastewater-based epidemiology in low COVID-19 incidence situations
Authors: Oh Chamteut , Zhou Aijia , O’Brien Kate , Jamal Yusuf , Wennerdahl Hayden , Schmidt Arthur R , Shisler Joanna L. , Jutla Antarpreet , Schmidt Arthur R , Keefer Laura , Brown William M. , Nguyen Thanh H.
Published: June 2022

Wastewater-based epidemiology (WBE), an emerging approach for community-wide COVID-19 surveillance, was primarily characterized at large sewersheds such as wastewater treatment plants serving a large population. Although informed public health measures can be better implemented for a small population, WBE for neighborhood-scale sewersheds is less studied and not fully understood. This study applied WBE to seven neighborhood-scale sewersheds (average population of 1,471) from January to November, 2021. Community testing data showed an average of 0.004% incidence rate in these sewersheds (97% of monitoring periods reported two or fewer daily infections). In 92% of sewage samples, SARS-CoV-2 N gene fragments were below the limit of quantification. We statistically determined 10-2.6 as the threshold of the SARS-CoV-2 N gene concentration normalized to pepper mild mottle virus (N/PMMOV) to alert high COVID-19 incidence rate in the studied sewershed. This threshold of N/PMMOV identified neighborhood-scale outbreaks (COVID-19 incidence rate higher than 0.2%) with 82% sensitivity and 51% specificity. Importantly, neighborhood-scale WBE can discern local outbreaks that would not otherwise be identified by city-scale WBE. Our findings suggest that neighborhood-scale WBE is an effective community-wide disease surveillance tool when COVID-19 incidence is maintained at a low level.

Graphical abstract
Structural mechanism of leaflet-specific phospholipid modulation of a pentameric ligand-gated ion channel
Authors: Petroff John T. , Deitzen Noah M. , Santiago-McRae Ezry , Deng Brett , Washington Maya S. , Chen Lawrence J. , Moreland K. Trent , Deng Zengqin , Rau Michael , Fitzpatrick James A. J. , Yuan Peng , Joseph Thomas T. , Hénin Jérôme , Brannigan Grace , Cheng Wayland W. L.
Published: June 2022

Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To elucidate the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open conformation. The structure shows a bound phospholipid in an outer leaflet site, and conformational changes in the phospholipid binding site unique to the open state. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the open state of a pLGIC by specific, state-dependent binding to this site.
Monitoring regional astrocyte diversity by cell-type specific proteomic labelingin vivo
Authors: Prabhakar Priyadharshini , Pielot Rainer , Landgraf Peter , Wissing Josef , Bayrhammer Anne , van Ham Marco , Gundelfinger Eckart D. , Jänsch Lothar , Dieterich Daniela C. , Müller Anke
Published: June 2022

Astrocytes exhibit regional heterogeneity in morphology, function and molecular composition to support and modulate neuronal function and signaling in a region-specific manner. To characterize regional heterogeneity of astrocytic proteomes of different brain regions we established an Aldh1l1- MetRSL274Gmouse line that allows cell-type specific labeling of newly synthesized proteinsin vivoand analyzed astrocytic proteins from four different brain regions by mass spectrometry. Identified proteins are specific for astrocytes and show a high overlap with proteins compiled in ‘AstroProt’, a newly established database for astrocytic proteins. Gene enrichment analysis reveals high overlap among brain regions, and only subtle changes in abundances of key astrocytic proteins for hippocampus, cortex and striatum. However, the cerebellar proteome stands out with proteins being associated with calcium signaling or bipolar disorder. Subregional differences of translation dynamics in single hippocampal astrocytes indicates distinct subregional heterogeneity and highlights the applicability of our toolbox to study dynamic astrocytic proteomesin vivo.
Trans-Driver: a deep learning approach for cancer driver gene discovery with multi-omics data
Authors: Yang Hai , Zhang Lei , Zhou Dan , Li Dongdong , Zhang Jing , Wang Zhe
Published: June 2022

Driver genes play a crucial role in the growth of cancer cells. Accurate identification of cancer driver genes is helping to strengthen the understanding of cancer pathogenesis and is conducive to the development of cancer treatment and drug-targe driver genes. However, due to the diversity and complexity of the multi-omics data, it is still challenging to identify cancer drivers.In this study, we propose Trans-Driver, a deep supervised learning method with a novel transformer network, which integrates multi-omics data to learn the differences and associations between different omics data for cancer drivers’ discovery. Compared with other state-of-the-art driver gene identification methods, Trans-Driver has achieved excellent performance on TCGA and CGC data Machine learning for multi-omics data integration in cancer. Among 20,000 protein-coding genes, Trans-Driver reported 185 candidate driver genes, of which 103 genes (about 55%) were included in the gold standard CGC data set. Finally, we analyzed the contribution of each feature to the identification of driver genes. We found that the integration of multi-omics data can improve the performance of our method compared with using only somatic mutation data. Through detailed analysis, we found that the candidate drivers are clinically meaningful, proving the practicability of Trans-Driver.

Author summary

Many methods have been developed to identify cancer driver genes. However, most of these methods use single-omics data for cancer driver gene identification. Multi-omics-based methods for cancer driver gene identification are rare. Trans-Driver uses deep learning to process multi-omics data and learn the relationships between multi-omics data for cancer driver gene prediction. We have predicted 185 candidate cancer driver genes out of among 20,000 protein-coding genes. Also, we performed cancer driver gene prediction on 33 cancer types, and we identified the cancer driver genes corresponding to each cancer type. And, we observed that the predicted cancer driver genes were shown to have a role in cancer progression in recent studies. Our proposed method for cancer driver gene identification using multi-omics data has improved performance compared to using mutation data alone.
Redefining and subtyping of major depression based on brain functional connectivity signatures with high generalization: an ensemble hybrid framework
Authors: Zheng Kaizhong , Lu Hongbing , Wu Yuxia , Wang Huaning , Hu Dewen ,   the DIRECT consortium, Chen Badong , Li Baojuan
Published: June 2022

Current clinical diagnosis of major depression is solely based on subjective symptoms and signs rather than the underlying biological mechanisms, which has hindered the improvement in treatment effectiveness and outcomes. Redefining and subtyping major depressive disorder (MDD) based on neural circuits has been an emerging consensus. Here, we proposed a novel ensemble hybrid deep-learning framework based on graph neural network for redefining and subtyping of MDD with the brain’s “fingerprinting”, i.e. nuanced functional connectivity profiles. A graph neural network (GNN) based supervised model was first employed to discriminate MDD patients from healthy controls. The graph embedding features obtained from the supervised classifier was then employed for subtyping of MDD with an unsupervised clustering by fast search and find of density peaks (CFDP) approach. The generalization accuracy and reproducibility of the proposed framework were further validated with one of the largest resting-state fMRI data set for MDD which included 2428 participants recruited from 25 independent sites. Our classifier showed a high generalization of 75% for leave-one-site-out cross validation. In addition, we obtained three biologically homogenous MDD subtypes characterized by impairments in subcortical-limbic, DMN-FPN, VN-SMN circuits, respectively. Notably, we demonstrated that subtyping of MDD according to graph embedding features showed high robustness and reproducibility across different sites. The proposed framework is not only essential for redefining and subtyping of MDD, but also paves the way towards precision medicine of mental disorders.
Root architecture plasticity in response to endoparasitic cyst nematodes is mediated by damage signaling
Authors: Guarneri Nina , Willig Jaap-Jan , Sterken Mark G. , Zhou Wenkun , Hasan M. Shamim , Grundler Florian M. W. , Willemsen Viola , Goverse Aska , Smant Geert , Lozano-Torres Jose L.
Published: June 2022

Plant root architecture plasticity in response to biotic stresses has not been thoroughly investigated. Infection by the endoparasitic cyst nematodes induces root architectural changes that involve the formation of secondary roots at infection sites. However, the molecular mechanisms regulating secondary root formation in response to cyst nematode infection remain largely unknown.

We first assessed whether secondary roots form in a nematode-density dependent manner by challenging wild type Arabidopsis plants with increasing numbers of cyst nematodes (Heterodera schachtii). Next, by using jasmonate-related reporter lines and knock-out mutants, we tested if tissue damage by nematodes triggers secondary root formation. Finally, we verified whether damage-induced secondary root formation depends on local auxin biosynthesis at nematode infection sites.

Intracellular host invasion by H. schachtii triggers a transient local increase in jasmonates, which activates the expression of ERF109 in a COI1-dependent manner. Knock-out mutations in COI1 and ERF109 disrupt the nematode-density dependent increase of secondary roots observed in wildtype plants. Furthermore, ERF109 regulates secondary root formation upon H. schachtii infection via local auxin biosynthesis.

Host invasion by H. schachtii triggers secondary root formation via the damage-induced jasmonate-dependent ERF109 pathway. This points at a novel mechanism underlying plant root plasticity in response to biotic stress.
Imagining and reading actions: towards similar motor representations
Authors: Dupont W , Papaxanthis C , Madden-Lombardi C , Lebon F
Published: June 2022

While action language and motor imagery both engage the motor system, determining whether these two processes indeed share the same motor representations would contribute to better understanding their underlying mechanisms. We conducted two experiments probing the mutual influence of these two processes. In Exp.1, hand-action verbs were presented subliminally, and participants (n=36) selected the verb they thought they perceived from two alternatives. When congruent actions were imagined prior to this task, accuracy significantly increased, i.e. participants were better able to “see” the subliminal verbs. In Exp.2, participants (n=19) imagined hand flexion or extension, while corticospinal excitability was measured via transcranial magnetic stimulation. Corticospinal excitability was modulated by action verbs subliminally presented prior to imagery. Specifically, the typical increase observed during imagery was suppressed after presentation of incongruent action verbs. This mutual influence of action language and motor imagery, both at behavioral and neurophysiological levels, suggests overlapping motor representations.
A Tomato Genome From The Italian Renaissance Provides Insights Into Columbian and Pre-Columbian Exchange Links And Domestication
Authors: Vos Rutger , van Andel Tinde , Gravendeel Barbara , Kakakiou Vasia , Michels Ewout , Schijlen Elio , Stefanaki Anastasia
Published: June 2022

Abstract

The history of the tomato’s interactions with humans spans both a pre-Columbian period of millennia of cultivation and domestication in South and Central America as well as the plant’s rise to becoming one of the world’s major cash crops following the arrival of Europeans in the Neotropics and the subsequent Columbian Exchange. In the process, the influence of successive regimes of artificial selection gave rise to an entangled species complex comprised of a wild ancestor and numerous cultivars exhibiting a great diversity of fruit phenotypes (often sorted in ‘cherry’ and big types). Here, we provide a snapshot into these dynamics by presenting the ancient nuclear and plastid genomes of one of the oldest tomatoes still in existence: the almost half a millennium old En Tibi specimen from the Italian Renaissance. By placing the genome skimming data obtained from this specimen within the phylogenomic context of wild relatives and Neotropical tomato cultivars and land races, we are able to show that the most likely geographic origins of the specimen’s immediate ancestors, i.e. whence the exchange of this particular lineage originated, are around the Gulf of Mexico. We also show that this specimen was less inbred than present-day tomatoes, shedding light on the genomic signatures of historical domestication processes. Probing deeper into the ancestry that shaped extant genetic diversity within the complex, we reconstruct multiple ancestral populations with diffuse but distinct signatures in cherry and big tomatoes. The geographic structure of these ancestries within the nearest wild relative of tomatoes and the differential extent to which these ancestries are represented in domesticates points to early cultivation and human-assisted dispersal of tomatoes originating from the northern extreme of the natural range of the species. Our findings illustrate the inferences that can be drawn from ancient DNA extracted from herbarium specimens and historic plant collections. At the same time, we stress that our findings draw on multiple disciplines including ethnobotanical and historical research and on the (agri)cultural contributions of a variety of world cultures.
Minimal frustration underlies the usefulness of incomplete and inexact regulatory network models in biology
Authors: Tripathi Shubham , Kessler David A. , Levine Herbert
Published: June 2022

Regulatory networks as large and complex as those implicated in cell-fate choice are expected to exhibit intricate, very high-dimensional dynamics. Cell-fate choice, however, is a macroscopically simple process. Additionally, regulatory network models are almost always incomplete and / or inexact, and do not incorporate all the regulators and interactions that may be involved in cellfate regulation. In spite of these issues, regulatory network models have proven to be incredibly effective tools for understanding cell-fate choice across contexts and for making useful predictions. Here, we show that minimal frustration—a feature of biological networks across contexts but not of random networks—can compel simple, low-dimensional steady-state behavior even in large and complex networks. Moreover, the steady-state behavior of minimally frustrated networks can be recapitulated by simpler networks such as those lacking many of the nodes and edges, and those that treat multiple regulators as one. The present study provides a theoretical explanation for the success of network models in biology and for the challenges in network inference.
HBs-S antigen-dependent enhancement of HBV infection
Authors: Sanada Takahiro , Yoshida Osamu , Hiasa Yoichi , Kohara Michinori
Published: June 2022

Background Aims

In natural infections with hepatitis B virus (HBV), large amounts of hepatitis B surface-small antigen (HBs-S) subviral particles (SVPs), which do not contain viral nucleocapsid, are secreted into the blood. The function of excess amounts of SVPs remains largely unknown. In this study, we analyzed the function of HBs-S in HBV infection.

Methods

The effect of HBs-S in HBV infection was evaluated in a human hepatoma cell line, in primary human hepatocytes, and in chimeric mice with humanized livers. To analyze the involvement of glycosaminoglycan, HBs-S attachment to cells in the presence of heparin was evaluated by enzyme-linked immunosorbent assay (ELISA), and the enhancement of viral attachment was evaluated by measurement of viral DNA. Additionally, the interaction between HBs-S and viral particles was analyzed by immunoprecipitation.

Results

Attachment of the HBV DNA to cells inoculated with the combination of virus and HBs-S was significantly higher than that to cells inoculated with HBV only. Pretreatment of the cells with HBs-S also increased viral DNA levels significantly compared to that in untreated cells. In contrast, HBs-L did not enhance the viral attachment. Enhancement of viral attachment was associated with the attachment of HBs-S to the cells via heparan sulfate. HBs-S also interacted with the viral particle. Furthermore, in chimeric mice with humanized livers, HBs-S enhanced HBV infection.

Conclusions

We demonstrated that HBs-S enhances viral attachment in vitro and viral infection in vivo. HBs-S interacted with heparan sulfate on the cellular surface, and this interaction contributed to the enhancement of viral attachment. These data indicate that HBs-S enhances the viral infection, and may contribute to the high transmissibility of HBV.
Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the emergence of acute hepatitis of unknown origin
Authors: Wollants Elke , Keyaerts Els , Cuypers Lize , Bloemen Mandy , Thijssen Marijn , Ombelet Sien , Raymenants Joren , Beuselinck Kurt , Laenen Lies , Budts Lore , Pussig Bram , Lagrou Katrien , Van Ranst Marc , André Emmanuel
Published: June 2022

The recent surge of hepatitis of unknown origin in children is hypothesized to be caused by adenovirus 41 and/or SARS-CoV-2 infections. A relatively high proportion of patients testing positive for these viruses concomitantly with the development of acute hepatitis supports this hypothesis. To formally incriminate these viral infections as causative agents of hepatitis, both a plausible physiopathological pathway and supporting epidemiological dynamics in the community need demonstration. In this study, we measured the level of circulation of adenovirus 40/41 and SARS-CoV-2 in the general population of the city of Leuven in Belgium using wastewater monitoring between December 2020 and May 2022 and indoor air sampling in day care centers between November 2021 and May 2022. We also retrospectively analyzed medical records of 12.672 children attending a tertiary hospital draining the same region between January 2019 and April 2022. Our results demonstrate a recent but modest increase in hepatitis of unknown origin concomitant with a surge of circulating adenovirus 41 and SARS-CoV-2 in the general population, including in children under 5.
The landscape of secondary malignancies in cancer survivors and the susceptibility to hereditary multiple cancer syndrome: a Korean nationwide population-based study
Authors: Choi Yoon Young , Lee Myeongjee , Kim Eun Hwa , Lee Jae Eun , Jung Inkyung , Cheong Jae-Ho
Published: June 2022

Background

Cancer survivors and secondary malignancy risk have increased following early diagnosis and advanced cancer treatments; however, secondary malignancy risk in cancer survivors and possibility of genetic susceptibility among young individuals with multiple cancers have scarcely been evaluated. We evaluated the risk of secondary malignancies in cancer survivors by primary cancer type, and the combination of cancer types frequently observed in young patients with multiple cancers.

Methods and Findings

Patients diagnosed with cancer, from Korea Health Insurance Review and Assessment database, between January 2009 and December 2010, were followed-up until December 2019. Cancer survivors and those with secondary cancers were defined as having lived >5 years without developing other cancers; and being newly diagnosed with cancer at another site, respectively. To identify possible hereditary multiple cancer syndrome (HMCS), combinations of multiple cancers frequently observed in young individuals compared to older adults were evaluated. Of the 371,181 patients in 3,008,274 person-years of follow-up, 266,241 were cancer survivors; of these 7,348 had secondary cancers (2.76%; 2,759.9 persons/100,000 population), higher than primary cancer risk in general population. The common primary cancer types were those mainly observed as secondary cancer in cancer survivors. Contrarily, higher-risk cancers among those with secondary cancers compared to those in the general population varied by sex and primary cancer type, suggesting the need for tailored cancer screening for cancer survivors. Combinations of well-known hereditary cancer syndrome-related cancer types were mainly observed in younger compared to older patients with multiple cancers, which could be HMCS, including cancer combinations those may be caused by a novel cancer predisposition gene.

Conclusions

Cancer survivors harbor high and distinctive secondary cancer risk than the general population, necessitating tailored cancer screening in survivors. Genetic screening should be considered for young patients with multiple cancers to validate genetic predisposition.
Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial
Authors: Yoshikata Remi , Yamaguchi Michiko , Mase Yuri , Tatsuyuki Ayano , Myint Khin Z. , Ohta Hiroaki
Published: June 2022

Objective

As estrogen level decreases with aging, the vaginal mucosa gets thinner, and collagen amount decreases. In addition, the population of Lactobacillus in the vagina declines, increasing the risk of atrophic vaginitis, bacterial vaginosis, and genitourinary symptoms in the postmenopausal women. In this study, we evaluated the effects of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women.

Methods

This was a pilot randomized controlled trial in 35 premenopausal and 35 postmenopausal healthy women. For 4 weeks, treatment 1 group (14 premenopausal and 16 postmenopausal women) used the Lactobacillus-containing feminine soap and cream, and treatment 2 group (15 premenopausal and 14 postmenopausal women) used Lactobacillus-containing feminine gel in addition to soap and cream. The remaining 6 premenopausal and 5 postmenopausal women served as controls without using any products. We then compared the changes in the vaginal microbiota, genitourinary symptoms, and other related biomarkers after completion of treatment.

Results

Vaginal pH and pathogenic flora were reduced in both treatment groups compared to control group. It was more significant in the treatment 2 group of postmenopausal women. Genitourinary symptoms significantly improved in 60% of premenopausal women in treatment 1 group and 81.3% of postmenopausal women in treatment 2 group, compared to control group (0%). Overactive bladder symptom scores were significantly improved after using the products in the postmenopausal women suspected of having overactive bladder.

Conclusion

The use of Lactobacillus-containing feminine products was associated with improved vaginal ecosystem and urogenital health compared to control group, especially in those women using feminine gel.
Intraoperative Plasma Proteomic Changes in Cardiac Surgery: In Search of Biomarkers of Post-operative Delirium
Authors: Wiredu Kwame , O’Connor Sean , Monteith Erika , Brauer Brooke , Kettenbach Arminja N. , Frost Hildreth R. , Shaefi Shahzad , Gerber Scott A.
Published: June 2022

Purpose

Delirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse hospital outcomes, longer hospital stays and higher overall cost of care. Moreover, the nature of delirium following cardiac surgery with cardiopulmonary bypass (CPB) remains unclear, the underlying pathobiology is poorly understood, status quo diagnostic methods are subjective, and diagnostic biomarkers are currently lacking.

Objective

To identify diagnostic biomarkers of delirium and for insights into possible neuronal pathomechanisms.

Experimental design

Comparative proteomic analyses were performed on plasma samples from a nested matched cohort of patients who underwent cardiac surgery on CPB. A targeted proteomics strategy was used for validation in an independent set of samples. Biomarkers were assessed for biological functions and diagnostic accuracy.

Results

47% of subjects demonstrated delirium. Of 3803 total proteins identified and quantified from patient plasma samples by multiplexed quantitative proteomics, 16 were identified as signatures of exposure to CPB, and 11 biomarkers distinguished delirium cases from non-cases (AuROC = 93%). Notable among these biomarkers are C-reactive protein, serum amyloid A-1 and cathepsin-B.

Conclusions and clinical relevance

The interplay of systemic and central inflammatory markers shed new light on delirium pathogenesis. This work suggests that accurate identification of cases may be achievable using a panel of biomarkers.

Statement of Clinical Relevance

The acute implication of delirium is well-documented, yet the true extent of the consequences beyond the immediate post-operative period has yet to be fully known. Despite its impact on the geriatric population, delirium remains underdiagnosed. Correctly identifying cases remain a challenge in clinical practice: the arbitrary and subjective nature of current diagnostic tools, such as the confusion assessment method, underscores the urgent need for diagnostic biomarkers. The clinical usefulness of delirium biomarkers extent beyond the objective identification of cases. Delirium biomarkers will also be useful for risk stratification, long-term follow-up of patients and may offer insights into possible etiologies that underpin the condition. In this report, we found systemic markers of inflammation with well-established association with delirium, as well as new biomarkers that shed new light on the condition. Although validation in a larger cohort is the necessary next step, our efforts lay the groundwork for future studies and highlight new frontiers in delirium research yet to be explored.
Fecal bile acid profiles predict recurrence in patients with primary Clostridioides difficile infection
Authors: Mullish Benjamin H. , Martinez-Gili Laura , Chekmeneva Elena , Correia Gonçalo D. S. , Lewis Matthew R. , Der Sluis Verena Horneffer-Van , McDonald Julie A. K. , Pechlivanis Alexandros , Walters Julian R. F. , McClure Emma L , Marchesi Julian R. , Allegretti Jessica R.
Published: June 2022

1.

Background

Factors that influence recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools to predict recurrence are lacking. Perturbations in microbial-derived bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis.

Aims

To define stool bile acid profiles and microbial bile-metabolising functionality in primary CDI patients, and explore signatures predicting recurrence.

Methods

Weekly stool samples were collected from primary CDI patients from the last day of anti-CDI therapy until recurrence, or through eight weeks post-completion otherwise. Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to profile bile acids, and bacterial bile salt hydrolase (BSH) activity was measured to determine primary BA deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in recurrers versus non-recurrers, and assess fecal bile acids as predictive markers for recurrence.

Results

Twenty (36%) out of 56 patients (median age 57, 64% male) recurred, with 80% of recurrence occurring within the first nine days post-antibiotic treatment. Principal component analysis (PCA) of stool bile acid profiles demonstrated clustering of samples by recurrence status and post-treatment time point. Longitudinal fecal bile acid trajectories in non-recurrers showed a recovery of secondary bile acids and their derivatives in non-recurring patients that was not observed in recurrers. BSH activity increased over time amongst patients who did not relapse (β= 0.056; likelihood ratio test p=0.018). A joint longitudinal-survival model identified five stool bile acids with AUROC > 0.73 for prediction of recurrence within nine days post-CDI treatment.

Conclusions

Gut bile acid metabolism dynamics differ in primary CDI patients between those who develop recurrence versus those who do not. Individual bile acids show promise in primary CDI patients as potential novel biomarkers to predict CDI recurrence.