bluuebunny/crossref_metadata_2025 huggingface dataset:
Sudden braking and turning with a two-field potential bump: primordial black hole formation
Authors: Fu Chengjie , Chen Chao
Published: May 2023

We investigate the amplification of curvature perturbations in a two-field inflation model
featuring a Gaussian potential bump. When the inflaton encounters a potential bump along the
inflationary trajectory, its rolling speed is generally reduced, potentially causing a violation
of the slow-roll condition. Consequently, the original decaying modes of comoving curvature
perturbations during the slow-roll phase start growing, and lead to enhanced small-scale density
perturbations which can produce amounts of primordial black holes (PBHs) and associated
scalar-induced gravitational waves. In addition, inflaton also undergoes sudden turnings at the
encounter of the Gaussian potential bump, which is insignificant to the overall curvature power
spectrum due to the short duration of these turns. Our paper offers a simple example of the
extension of a bump-like potential for PBH formation in a single-field inflation to a two-field
case, which helps alleviate the fine-tuning of initial conditions to some extent.
Possible relationship between initial conditions for inflation and past geodesic incompleteness of the inflationary spacetime
Authors: Kaganovich Alexander B.
Published: May 2023

According to the Borde-Guth-Vilenkin (BGV) theorem an expanding region of spacetime cannot
be extended to the past beyond some boundary ℬ. Therefore, the inflationary universe
must have had some kind of beginning. However, the BGW theorem says nothing about the boundary
conditions on ℬ, or even about its location. Here we present a single-scalar field
model of the Two-Measure Theory, where the non-Riemannian volume element Υ d
4
x is
present in the action. As a result of the model dynamics, an upper bound φ
0 of
admissible values of the scalar field φ appears, which sets the position of ℬ 
in the form of a spacelike hypersurface Υ(x) = 0 with a boundary condition:
 Υ → 0+ as φ → φ
0
-. A detailed study has
established that if the initial kinetic energy density ρ
kin
(in) prevails over initial
gradient energy density ρ
grad
(in) then there is an interval of initial values
 φ
in
(min) ≤ φ
in < φ
0, where ρ
kin
(in) and
 ρ
grad
(in) cannot exceed the potential energy density and hence the initial conditions
necessary for the onset of inflation are satisfied. It is shown that under almost all possible
left-handed boundary conditions on ℬ, that is where Υ → 0-, the
metric tensor in the Einstein frame has a jump discontinuity on ℬ, so the Christoffel
connection coefficients are not defined on the spacelike hypersurface Υ = 0. Thus, if
 φ
in
(min) ≤ φ
in < φ
0 and ρ
kin
(in) > ρ
grad
(in), then
there was an inflationary stage in the history of our Universe and the congruence of timelike
geodesics cannot be extended to the past beyond the hypersurface Υ = 0.
Numerical simulation of the nitrogen boil-off recondensation in hybrid cooling devices for HPGe detectors
Authors: Malgin V. , Vencels J.
Published: May 2023

This paper describes the results of a complex simulation of nitrogen boil-off recondensation in a hybrid cooling device for High Purity Germanium (HPGe) detectors. The OpenFOAM platform-based software was used. The proposed finite-volume axisymmetric 2D model combines cooling processes occurring in the considered three-phase medium, including a liquefier condenser (solid), nitrogen boil-off (gas) and the resulting condensate (liquid). At the beginning of the simulation condenser and gas temperatures are set above the condensation point while the end time is set such that the system reaches a quasi-steady state. For conical and hemispherical condensers, the energy consumption for the following processes occurring in the operating mode such as: condenser cooling; cooling of adjacent boil-off nitrogen vapors; their condensation; the gravity-driven flowing; condensate film subcooling and subsequent partial re-evaporation from its surface are compared. The visualizations of the temperature field of the finite-volume model and the velocity vectors of nitrogen vapors adjacent to the condenser are presented. The calculated integral mass recondensation rates were confirmed experimentally on a commercial hybrid cooling device, taking into account the actual equivalent characteristics of the liquefier on the Stirling cryocooler used.
Acetate regulates GAPDH acetylation and T helper 1 cell differentiation
Authors: Jing Xizhong , Lyu Junfang , Xiong Jianhua
Published: May 2023

The metabolite acetyl-CoA has emerged as a major signal transducer that can affect cell fate and function by influencing acetylation of key proteins. The mechanism by which acetyl-CoA regulates CD4+ T-cell fate determination remains poorly understood. Herein, it is reported that acetate modulates GAPDH acetylation and CD4+ T helper 1 cell differentiation by altering acetyl-CoA levels.
Increased bioavailability of diosmetin-7-glucoside-γ-cyclodextrin inclusion complex compared with diosmin in Sprague-Dawley rats
Authors: Moriwaki Masamitsu , Kito Kento , Nakagawa Ryo , Kapoor Mahendra P , Matsumiya Yoshiki , Fukuhara Tomohisa , Kobayashi Junya , Satomoto Kensuke , Yamagata Hiroshi , Kuroiwa Yuichi
Published: May 2023

Diosmin (DSN) is found mainly in citrus fruits, and has potent antioxidant effects. This study aimed to evaluate pharmacokinetics of diosmetin-7-glucoside-γ-cyclodextrin (DIOSG-CD) inclusion complex. The area under the curve values from AUC0-24 of DIOSG-CD, prepared by reacting DSN and naringinase with γ-CD, were approximately 800-fold higher than those of DSN following their administration in Sprague-Dawley rats.
Lichen planus-like rash in a patient with skin of colour
Authors: Jensen Mikkel B , Staun Pia W , Salim Saman , Svendsen Mathias T
Published: May 2023

In this report, we describe a lichen planus-like eruption in a 30-year-old woman with dark skin and with HIV infection. The case of this patient adds to the existing body of literature on clinical presentations of skin findings in individuals with skin of colour, emphasizing the need for dermatologists to be vigilant and well-informed in their diagnostic approach in this patient population.
qSOFA Score is useful to predict in-hospital mortality and long-term outcomes in patients with acute coronary syndrome
Authors: Devesa Neto V , Correia J , Fiuza J , Santos L F
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Quick Sequential Organ Failure Assessment (qSOFA) is a bedside score widely used to identify patients at greater risk for a poor outcome outside the intensive care unit. Initially applied in patients with suspected infection, the score has recently emerged as a marker for poor prognosis or mortality across various patient groups.

Aim

To validate the qSOFA score as a predictor of in-hospital mortality and long-term outcomes in acute coronary syndrome (ACS) patients.

Methods

A retrospective analysis of 1296 patients admitted for ACS was performed. qSOFA score evaluates the presence of 3 variables: systolic blood pressure <120mmHg (1 point), respiratory rate ≥22 breaths per min (1 point), and Glasgow coma scale <15 (1 point). The score derived from these variables allowed the classification of patients into two risk categories: low risk (LR) (<2 points) and high risk (HR) (≥2 points). The Mann-Whitney U test was used for median comparison between groups. In addition, Kaplan-Meier survival plot was used to evaluate the predictive power of qSOFA score on in-hospital mortality and 12-month mortality (12MM).

Results

Mean age 69,1±13years; 70% were male. The mean time of hospitalization was 7,4±5days. 34% had a diagnosis of ST-elevation myocardial infarction (STEMI). Mean left ventricular ejection fraction (LVEF) was 56,4±14,6%. Global in-hospital mortality was 8%. qSOFA was calculated, and the population was divided into 2 groups: 78% had low risk (qSOFA <2) and 6% had high risk (qSOFA ≥2). HR group defined by qSOFA was significantly associated with in-hospital mortality (28% vs 8%; p<0,01, OR: 3,8 CI 95% 2,4;6,2). Kaplan-Meier survival analysis revealed that HR qSOFA was significantly associated with 12MM (p<0,01; 24% vs 7%; 260 vs 321 days until event, χ2 8,2). In logistic regression analysis, LVEF and diagnosis of STEMI did not increase the risk of a higher qSOFA score and in-hospital mortality (p=0,06 and p=0,94). HR group is significantly associated with left main coronary artery disease (12% vs 9%; p<0,01; OR 2,4; CI 95% 1,2;4,9) and in-hospital complications, including arrhythmia, mechanical complications, hemorrhagic events, acute kidney disease and hematological disorders (54% vs 28%; p<0,01; OR 3,0; CI 95% 1,9;4,6).

Conclusion

qSOFA score is associated with higher in-hospital mortality and 12 month-mortality in patients with ACS. Its use may identify patients with an increased risk of mortality, needing specialized care, and a close follow-up.
Temporal trends in Singapore for out-of-hospital cardiac arrest with an initial non-shockable rhythm
Authors: Lim S L , Chan S P , Shahidah N , Ng Q X , Ho A , Arulanandam S , Leong B , Ong M
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Medical Research Council Singapore

Background

Out-of-hospital cardiac arrest (OHCA) with an initial non-shockable rhythm is the predominant form of OHCA in adults, yet outcomes are dismal. We evaluated its 10-year trends in epidemiology and management in Singapore.

Methods

Using the national OHCA registry we studied the trends of 20,844 Emergency Medical Services (EMS)-attended adult OHCA from April 2010 to December 2019. Survival to hospital discharge was the primary outcome. Analyses of the trends and outcomes were performed with linear regression and logistic regression, respectively.

Results

Incidence rates of EMS-attended adult OHCAs increased during the study period, with increasing proportion of adult OHCA being non-shockable OHCA (Figure 1). Compared to shockable OHCA, non-shockable OHCAs were significantly older (median age 71 vs 61 years), had more comorbidities (median Charlson Comorbidity Index 4 vs 3), more likely unwitnessed (46% vs 25%) and residential arrests (77% vs 53%) (all p<0.001); non-shockable OHCAs had longer no-flow time (median 16 vs 13 minutes), and received less bystander cardiopulmonary resuscitation (CPR) (49% vs 61%) and in-hospital interventions (coronary revascularization 1% vs 18%, targeted temperature management (TTM) 3% vs 14%) (all p<0.001). Amongst non-shockable OHCA, age, comorbidities, residential arrests, no-flow time and time to patient increased during the study period, while presumed cardiac etiology decreased; bystander CPR, epinephrine use and TTM increased (all p<0.05) (Figure 2). Survival for non-shockable OHCA did not improve (1% in 2010 to 1.3% in 2019, p=0.107), unlike shockable OHCA (10% to 26%, p<0.001). The likelihood of survival for non-shockable OHCA increased with witnessed arrest (adjusted odds ratio (aOR) 2.281) and bystander CPR (aOR 3.569), but decreased with presumed cardiac etiology (aOR 0.553), epinephrine administration (aOR 0.646), time to patient (aOR 0.938) and comorbidity burden (aOR 0.897). Significant two-way interactions were observed for no-flow time and arrest location with bystander CPR. Cardiac revascularization improved the odds of survival in patients who survived to admission (aOR 2.63).

Conclusion

Singapore saw increasing incidence and interventions for non-shockable OHCA between 2010 and 2019 but limited gains in survival, partly explained by ageing population with increasing comorbidity burden. This contrasts with the improvement in survival for shockable OHCA over the same period. The interactions of location and no-flow time with bystander CPR highlight opportunities to improve pre-hospital care for residential and non-shockable OHCA.
Bridging glycoinformatics and cheminformatics: integration efforts between GlyCosmos and PubChem
Authors: Cheng Tiejun , Ono Tamiko , Shiota Masaaki , Yamada Issaku , Aoki-Kinoshita Kiyoko F , Bolton Evan E
Published: May 2023

The GlyCosmos Glycoscience Portal (https://glycosmos.org) and PubChem (https://pubchem.ncbi.nlm.nih.gov/) are major portals for glycoscience and chemistry, respectively. GlyCosmos is a portal for glycan-related repositories, including GlyTouCan, GlycoPOST, and UniCarb-DR, as well as for glycan-related data resources that have been integrated from a variety of ‘omics databases. Glycogenes, glycoproteins, lectins, pathways, and disease information related to glycans are accessible from GlyCosmos. PubChem, on the other hand, is a chemistry-based portal at the National Center for Biotechnology Information. PubChem provides information not only on chemicals, but also genes, proteins, pathways, as well as patents, bioassays, and more, from hundreds of data resources from around the world. In this work, these 2 portals have made substantial efforts to integrate their complementary data to allow users to cross between these 2 domains. In addition to glycan structures, key information, such as glycan-related genes, relevant diseases, glycoproteins, and pathways, was integrated and cross-linked with one another. The interfaces were designed to enable users to easily find, access, download, and reuse data of interest across these resources. Use cases are described illustrating and highlighting the type of content that can be investigated. In total, these integrations provide life science researchers improved awareness and enhanced access to glycan-related information.
Leveraging natural language processing to augment structured social determinants of health data in the electronic health record
Authors: Lybarger Kevin , Dobbins Nicholas J , Long Ritche , Singh Angad , Wedgeworth Patrick , Uzuner Özlem , Yetisgen Meliha
Published: May 2023

Objective

Social determinants of health (SDOH) impact health outcomes and are documented in the electronic health record (EHR) through structured data and unstructured clinical notes. However, clinical notes often contain more comprehensive SDOH information, detailing aspects such as status, severity, and temporality. This work has two primary objectives: (1) develop a natural language processing information extraction model to capture detailed SDOH information and (2) evaluate the information gain achieved by applying the SDOH extractor to clinical narratives and combining the extracted representations with existing structured data.

Materials and Methods

We developed a novel SDOH extractor using a deep learning entity and relation extraction architecture to characterize SDOH across various dimensions. In an EHR case study, we applied the SDOH extractor to a large clinical data set with 225 089 patients and 430 406 notes with social history sections and compared the extracted SDOH information with existing structured data.

Results

The SDOH extractor achieved 0.86 F1 on a withheld test set. In the EHR case study, we found extracted SDOH information complements existing structured data with 32% of homeless patients, 19% of current tobacco users, and 10% of drug users only having these health risk factors documented in the clinical narrative.

Conclusions

Utilizing EHR data to identify SDOH health risk factors and social needs may improve patient care and outcomes. Semantic representations of text-encoded SDOH information can augment existing structured data, and this more comprehensive SDOH representation can assist health systems in identifying and addressing these social needs.
Development and Validation of a Modified QuEChERS protocol Coupled to Liquid Chromatography–Tandem Mass Spectrometry for the Rapid and Accurate Determination of Acrylamide in Cereal-Based Baby Foods
Authors: Marzouk Abdelrahman M , Shendy Amr H , Aboelhassan AlaaEldean Fathy Ahmed , Gomaa Ahmed M , El-Shahat M F
Published: May 2023

Background

With the widespread consumption by children of cereal-based baby food, acrylamide contamination is a prevalent risk that may have carcinogenic consequences.

Objective

This study aims to develop and validate a modified QuEChERS protocol (quick, easy, cheap, effective, rugged, and safe) without solvent exchange, followed by rapid separation and accurate determination of acrylamide in cereal-based baby foods using reversed-phase (RP)-LC–MS/MS.

Methods

Samples were extracted using a modified QuEChERS protocol of the AOAC version and cleaned up with basic alumina. Separation was performed on a Phenomenex® Kinetex C18 column (100 Å × 3.5 µm × 4.6 mm × 150 mm) using a gradient elution program with a mobile phase of 10 mM ammonium formate–methanol. Determinations were conducted using electrospray ionization (ESI)-MS/MS in positive-ion mode.

Results

Basic alumina yielded clean extracts, resulting in acceptable recovery percentages and a tolerable matrix effect (ME) <5%. This allowed extraction without a solvent exchange step. Efficient separation was achieved at a retention time (tR) of 3.39 ± 0.05 min employing an RP-C18 column with core-shell properties in a relatively short analysis run time of only 5 min. Trueness, precision, LOD, LOQ, linearity range, and R2 results were 92.5–104.6%, RSD ≤12.2%, 5 µg/kg, 20 µg/kg, 4.0–1000.0 µg/kg, and > 0.9999, respectively. The test method applicability was demonstrated by proficiency testing (PT) and 50 real samples of cereal-based baby foods. Most of the tested samples were in violation of acrylamide’s established European Union benchmark (40 µg/kg).

Conclusion

Acetate-buffered QuEChERS protocol in conjunction with optimized amounts of basic alumina was confirmed as an efficient extraction protocol for acrylamide from cereal-based baby foods resulting in optimal method performance. Successful selection of the RP-C18 column is key for selective separation for acrylamide in a relatively short analysis run time.

Highlights

The modified AOAC QuEChERS protocol with a dispersive solid phase extraction (d-SPE) of basic alumina assisted in reducing the ME to tolerable levels while maintaining acceptable method performance. The use of an RP-C18 column with core-shell properties enabled a rapid and accurate acrylamide determination.
A new form of corruption
Authors: Prince Michael of Liechtenstein H S H
Published: May 2023

For some years now, a new form of corruption has been rampant, having a negative influence on both the economy and citizens. This article examines how the decisions of the G20 relate to this and what impacts this new form of corruption has. It is necessary for fiduciaries to understand this development so that they can continue to fulfil their ancestral role which is to protect clients, their families, their businesses, assets and values.
Pathogenic and Saprophytic Growth Rates of Fusarium oxysporum f. sp. vasinfectum Interact to Affect Variation in Inoculum Density and Interannual Infection Risk
Authors: Davis Roy L. , Hayter Jensen T. , Marlino Margaret L. , Isakeit Thomas , Chappell Thomas M.
Published: May 2023

Fusarium wilt of cotton caused by the soilborne fungal pathogen Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4) is a contemporary epidemic affecting cotton production in Far West Texas. The spatial distribution of soilborne FOV4 can be heterogeneous at small scales, and the factors that lead to this heterogeneity require investigation. Hypothetical causes include dissemination of spores through soils and variable saprophytic growth of the fungus. In the field, FOV4 DNA was quantified from soil during and after the cotton-growing season, and though the average amounts of DNA were not different between these time points, the variances of DNA across space were significantly different. Variability was higher when pathogenic growth of the fungus was expected owing to the presence of live cotton plants and lower when saprophytic growth was expected after cropping. In sterile-environment growth chamber experiments, the abundance of organic matter influenced the fungal vegetative growth rate and maximum amount as measured through quantitative PCR and the timing of the fungus’ increasing its rate of spore production as measured through dilution plating. To investigate movement of spores in soils, spore mobility in experimental columns was quantified. Soil composition and organic matter abundance affected spore mobility, indicating that the timing of spore production relative to the availability of growth resources will affect the spatial spread of FOV4 and suggesting that soil properties affect the retention of conidia. The spatial spread of FOV4 through soil varies temporally and is affected by the shift between pathogenic and saprophytic growth modes of the fungus.
Computed Tomography Scan Versus Saline Load Test for Detection of Traumatic Shoulder Arthrotomy: A Cadaveric Study
Authors: Villacres Mori Benjamin , Lakra Akshay , Gheewala Rohan A. , Carroll Jeremy D. , Bibicheff Darrel , Smith Michael P. , Mulligan Michael T.
Published: May 2023

Objectives:

Traumatic shoulder arthrotomy (TSA) is a rare injury that is commonly detected through saline load test (SLT). There are no studies that have studied the ability of computed tomography (CT) scan to detect a TSA. The purpose of this study is to determine the ability of CT scan to detect a TSA and compare it with the SLT.

Methods:

Twelve cadaveric shoulders were included in the study. Before intervention, a CT scan was conducted to determine presence of intra-articular air. After confirmation that no air was present, an arthrotomy was made at the anterior or posterior portal site. A CT was obtained postarthrotomy to evaluate for intra-articular air. Each shoulder then underwent an SLT to assess the sensitivity of SLT and the volume needed for extravasation.

Results:

Twelve shoulders were included after a pre-intervention CT scan. Six shoulders received an arthrotomy through the anterior portal and six shoulders received an arthrotomy through the posterior portal. After the arthrotomy, air was visualized on CT scan in 11 of the 12 shoulders (92%). All 12 shoulders demonstrated extravasation during SLT. The mean volume of saline needed for extravasation was 29 mL with an SD of 10 and range of 18–50 mL.

Conclusions:

CT scan is a sensitive modality (sensitivity of 92%) for detection of TSA. In comparison, SLT is more sensitive (sensitivity of 100%) and outperforms CT scan for the diagnosis of TSA in a cadaveric model. Further research is needed to solidify the role that CT imaging has in the diagnosis of TSAs.
Opioid Use in Pediatric Patients After Common Orthopaedic Surgeries
Authors: Perkins Crystal A. , Murata Asahi , Kim Jason , Willimon Samuel Clifton
Published: May 2023

Background:

The use and misuse of opioid medications is an epidemic and public health emergency. There are currently no standard guidelines for treating perioperative pain in the pediatric population. The purpose of this study is to describe opioid use among pediatric patients after common orthopaedic surgeries.

Methods:

Patients between 5 and 20 years of age undergoing one of 7 common orthopaedic surgeries between the years 2018 to 2020 were prospectively studied. Patients and their families completed a medication logbook to track all doses of pain medication and associated pain scores.

Results:

Three hundred forty-two patients completed the study, including 174 females and 168 males with a mean age of 14.0 years (range, 5 to 20 y). A total of 4351 tablets or liquid doses of the narcotic medication, 44% of the total prescribed, were consumed. Of the prescribed medication,56% remained unused. Nonsteroidal anti-inflammatory drug use was identified to be the only independent predictor of less narcotic use, with a mean of 5.1 tablets (P = 0.003) and 1.7 days (P < 0.01) less opioid consumed among these patients. Thirty-two (9.4%) patients consumed 100% of their prescriptions. Nonmedicinal methods of pain control, most commonly ice, were used by 77% of patients, and this was highly variable between procedures. Physicians were cited as a source of medication information by only 50% of patients, with high variability between procedures.

Conclusions:

Opioid medication use in children and adolescents after orthopaedic surgery is significantly less than the number of tablets prescribed, with 56% of the medication prescribed remaining unused in the postoperative period. Duration of narcotic use was longer than anticipated with a wide SD (4.7 d +/−3 d).

We recommend orthopaedic surgeons responsibly prescribe pain medications using evidence-based data or the results of their own experience monitoring medication consumption. In addition, and important in the setting of the “opioid epidemic,” physicians must counsel patients and families on postoperative pain expectations and appropriate medication use.

Level of Evidence:

Level IV, prospective case series.
Impact of Clonal Architecture on Clinical Course and Prognosis in Patients With Myeloproliferative Neoplasms
Authors: Luque Paz Damien , Bader Michael S. , Nienhold Ronny , Rai Shivam , Almeida Fonseca Tiago , Stetka Jan , Hao-Shen Hui , Mild-Schneider Gabriele , Passweg Jakob R. , Skoda Radek C.
Published: May 2023

Myeloproliferative neoplasms (MPNs) are caused by a somatic gain-of-function mutation in 1 of the 3 disease driver genes JAK2, MPL, or CALR. About half of the MPNs patients also carry additional somatic mutations that modify the clinical course. The order of acquisition of these gene mutations has been proposed to influence the phenotype and evolution of the disease. We studied 50 JAK2-V617F-positive MPN patients who carried at least 1 additional somatic mutation and determined the clonal architecture of their hematopoiesis by sequencing DNA from single-cell-derived colonies. In 22 of these patients, the same blood samples were also studied for comparison by Tapestri single-cell DNA sequencing (scDNAseq). The clonal architectures derived by the 2 methods showed good overall concordance. scDNAseq showed higher sensitivity for mutations with low variant allele fraction, but had more difficulties distinguishing between heterozygous and homozygous mutations. By unsupervised analysis of clonal architecture data from all 50 MPN patients, we defined 4 distinct clusters. Cluster 4, characterized by more complex subclonal structure correlated with reduced overall survival, independent of the MPN subtype, presence of high molecular risk mutations, or the age at diagnosis. Cluster 1 was characterized by additional mutations residing in clones separated from the JAK2-V617F clone. The correlation with overall survival improved when mutation in such separated clones were not counted. Our results show that scDNAseq can reliably decipher the clonal architecture and can be used to refine the molecular prognostic stratification that until now was primarily based on the clinical and laboratory parameters.
Orbital Dermoid Cysts in Monozygotic Twins
Authors: Gupta Akash , Terrell Jesse A. , Mudie Lucy I. , Shetlar Debra J. , Yen Michael T.
Published: May 2023

Two healthy 12-year-old monozygotic twin sisters presented with strikingly similar, painless orbital masses along their frontozygomatic suture line that had been slowly enlarging since birth. The masses were clinically consistent with orbital dermoid cysts and the patients underwent excision of their lesions, with the diagnosis confirmed by histological analysis. There are prior case reports of both nasal and ovarian dermoid cysts in twins, however, no prior case of orbital dermoid cysts in twins have been described. These dermoid cysts are generally thought to be a sporadic disorder of embryogenesis, yet the authors’ case suggests genetics may play a role in the underlying etiology of dermoid cysts.
Relationship of Ethinylestradiol/Drospirenone Prescription on Work Productivity and Activity Impairment Among Women With Menstruation-Related Symptoms
Authors: Ikeda Yumie , Egawa Miho , Ohsuga Takuma , Mandai Masaki , Takahashi Yoshimitsu , Nakayama Takeo
Published: May 2023

Objective

The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms.

Methods

Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline.

Results

A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%–26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%–24.7%) at 1 m and thereafter.

Conclusions

Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.
Current challenges and perspectives in lung cancer care during COVID-19 waves
Authors: Mariniello Domenica Francesca , Aronne Luigi , Vitale Maria , Schiattarella Angela , Pagliaro Raffaella , Komici Klara
Published: May 2023

Purpose of review

In the era of the SARS-Cov2 pandemic, the multidisciplinary care of patients with lung cancer is the main challenge for clinicians. The depiction of complex networking between SARS-CoV2 and cancer cells is crucial to understanding the downstream signalling pathways leading to more severe clinical behaviour of COVID-19 among lung cancer patients.

Recent findings

The immunosuppressive status caused by both blunted immune response and active anticancer treatments (e.g. radiotherapy, chemotherapy) affects also the response to vaccines. Furthermore, the COVID-19 pandemic has significantly influenced early detection, therapeutic management, and clinical research for patients with lung cancer.

SARS-CoV-2 infection does undoubtedly represent a challenge for care of patients with lung cancer. Since symptoms of infection may overlap with underlying condition, diagnosis must be reached and treatment should start as soon as possible. Although any cancer treatment should be procrastinated as long as infection is not cured, every choice must be pondered on individual basis, according to clinical conditions. Underdiagnosis should be avoided, and both surgical and medical treatment must be tailored to each patient. Therapeutic scenario standardization represents a major challenge for clinicians and researchers.
Exploration of the inhibitory effect of Cassia fistula on quorum sensing mediated virulence factor production and biofilm activity in Pseudomonas aeruginosa: an in vivo study in model organism Caenorhabditis elegans
Authors: Peerzada Zoya , Shah Mayank D. , Kharkar Prashant S. , Desai Krutika B.
Published: May 2023

Introduction. Resistance to antibiotics is leading to challenges in the treatment of microbial diseases. One amongst the various approaches to control these pathogens is quorum sensing (QS), which is used to rectify resistance issues. Blocking the bacterial QS circuit is the most reliable anti-virulence therapy to control pathogenicity-associated genes.

Pseudomonas aeruginosa

is a contagious bacterium that proliferates in the host by using signalling molecules like acyl-homoserine lactones; these molecules generate and disseminate toxins and virulence factors for increasing host infection.

Hypothesis. The herb Cassia fistula is known to have antimicrobial, antidiabetic, anti-inflammatory, antitumor medicinal properties amongst others. We hypothesize that its crude extracts will inhibit the QS circuit of

Pseudomonas aeruginosa

(P. aeruginosa).

Aim. The research work was aimed at evaluating anti-quorum sensing and anti-biofilm activity of various crude extracts from Cassia fistula against

P. aeruginosa

.

Methodology. Various extraction methods and solvents were availed for maximum separation, and the extracts were screened for anti-quorum sensing activity. The most potent Fruit Ethyl acetate (FEE) extract at non-inhibitory concentrations was found to interrupt both short-chain (RhlI/R) and long-chain (LasI/R) QS circuits and other virulence factors (P<0.05) such as elastase, protease, rhamnolipids and pyocyanin levels in

P. aeruginosa

. Biofilm inhibitory properties of FEE were demonstrated using atomic force microscopy, scanning electron microscope and confocal laser microscope. Caenorhabditis elegans infection model (Paralytic assay) was developed to determine the protective role of FEE by reducing the pathogenicity of

P. aeruginosa

.

Results. The study results suggest that hot crude FEE extract interfered in the QS circuit, leading to comprehensive debilitation of QS-controlled virulence factors. The extract reduced virulence factor production in

P. aeruginosa

at 4 mg ml-1 concentration whilst paradoxically promoting biofilm formation. Possibly, higher sugar content in the extract promoted clump formation of biofilm architecture by increasing exopolysaccharide production. Moreover, in vivo analysis of bacterial pathogenesis on Caenorhabditis elegans reveals a drastic increase in survival rates in FEE treated worms compared to untreated control.

Conclusions. FEE showed promising QS inhibitory activity against

P. aeruginosa

. In the future, additional purification of crude FEE is required to remove carbohydrates, and pure isolated phytochemicals from FEE could be used as therapeutic agents to control QS-mediated infections in

P. aeruginosa

.
Sporadic type VI secretion in seventh pandemic Vibrio cholerae
Authors: Proutière Alexis , Drebes Dörr Natália C. , Bader Loriane , Stutzmann Sandrine , Metzger Lisa C. , Isaac Sandrine , Chiaruttini Nicolas , Blokesch Melanie
Published: May 2023

Vibrio cholerae

is a pathogen that causes disease in millions of people every year by colonizing the small intestine and then secreting the potent cholera toxin. How the pathogen overcomes the colonization barrier created by the host’s natural microbiota is, however, still not well understood. In this context, the type VI secretion system (T6SS) has gained considerable attention given its ability to mediate interbacterial killing. Interestingly, and in contrast to non-pandemic or environmental

V. cholerae

isolates, strains that are causing the ongoing cholera pandemic (7PET clade) are considered T6SS-silent under laboratory conditions. Since this idea was recently challenged, we performed a comparative in vitro study on T6SS activity using diverse strains or regulatory mutants. We show that modest T6SS activity is detectable in most of the tested strains under interbacterial competition conditions. The system’s activity was also observed through immunodetection of the T6SS tube protein Hcp in culture supernatants, a phenotype that can be masked by the strains’ haemagglutinin/protease. We further investigated the low T6SS activity within the bacterial populations by imaging 7PET

V. cholerae

at the single-cell level. The micrographs showed the production of the machinery in only a small fraction of cells within the population. This sporadic T6SS production was higher at 30 °C than at 37 °C and occurred independently of the known regulators TfoX and TfoY but was dependent on the VxrAB two-component system. Overall, our work provides new insight into the heterogeneity of T6SS production in populations of 7PET

V. cholerae

strains in vitro and provides a possible explanation of the system’s low activity in bulk measurements.
COVID AMP: An Open Access Dataset of COVID-19 Response Policies
Authors: Katz Rebecca , Toole Kate , Robertson Hailey , Case Alaina , Kerr Justin , Robinson-Marshall Siobhan , Schermerhorn Jordan , Orsborn Sarah , Van Maele Michael , Zimmerman Ryan , Stevens Tess ,   COVID AMP Coding Team, Phelan Alexandra , Carlson Colin , Graeden Ellie
Published: May 2023

As the COVID-19 pandemic unfolded in the spring of 2020, governments around the world began to implement policies to mitigate and manage the outbreak. Significant research efforts were deployed to track and analyse these policies in real-time to better inform the response. While much of the policy analysis focused narrowly on social distancing measures designed to slow the spread of disease, here, we present a dataset focused on capturing the breadth of policy types implemented by jurisdictions globally across the whole-of-government. COVID Analysis and Mapping of Policies (COVID AMP) includes nearly 50,000 policy measures from 150 countries, 124 intermediate areas, and 235 local areas between January 2020 and June 2022. With up to 40 structured and unstructured characteristics encoded per policy, as well as the original source and policy text, this dataset provides a uniquely broad capture of the governance strategies for pandemic response, serving as a critical data source for future work in legal epidemiology and political science.
Astrocytic Foxo1 regulates hippocampal spinogenesis and synaptic plasticity to enhance fear memory
Authors: Viana João Filipe , Guerra-Gomes Sónia , Abreu Daniela Sofia , Machado João Luís , Barsanti Sara , Gonçalves Mariana , Martín-Monteagudo Cristina , Sardinha Vanessa Morais , Marques Nascimento Diana Sofia , Tavares Gabriela , Irmler Martin , Beckers Johannes , Korostynski Michal , Sousa Nuno , Navarrete Marta , Teixeira-Castro Andreia , Pinto Luísa , Oliveira João Filipe
Published: May 2023

Astrocytes are active players in brain circuits, sensing and responding to neuronal activity, impacting behavior production. Activation of astrocytes triggers intracellular calcium elevations displaying complex spatiotemporal properties. Intracellular calcium activity is thought to underlie synaptic transmission, metabolism, and brain homeostasis modulation. However, the calcium-dependent signaling pathways involved in these processes are poorly understood, representing a critical knowledge gap in this field. To reveal calcium-dependent signaling pathways involved in circuit structure and function, we performed a multi-level analysis of the inositol 1,4,5-triphosphate receptor type 2 knockout (IP3R2 KO) mouse model which lacks somatic calcium elevations specifically in astrocytes. We focused on the hippocampus, a brain region responsible for cognitive function and emotional behaviors.

The transcriptomic analysis of hippocampal tissue revealed that the lack of astrocytic somatic calcium causes the differential expression of hundreds of genes. Among these, 76 genes are regulated by the astrocyte-specific Foxo1 transcription factor. This transcription factor is over-expressed in the hippocampal astrocytes of this mouse model and regulates the expression of genes involved in spinogenesis and synaptic coverage. A detailed morphological analysis of hippocampal pyramidal neurons revealed dendrites with a shift to a more immature spine profile. This spine profile shift may underlie previously described a reduction of long-term depression and performance in fear memory tasks observed in this mouse model. Indeed, we confirmed that these mice lacking astrocytic somatic calcium display an enhancement of long-term fear memory. To verify a causal relationship between these structural, synaptic, and behavioral observations, we used a viral approach to induce the over-expression of Foxo1 in hippocampal astrocytes in naïve C57BL/6J mice. This viral-driven over-expression of Foxo1 in astrocytes of thestratum radiatumreplicated the shift to an immature spine profile in dendrites of pyramidal neurons crossing the territory of these astrocytes and led to a reduction of long-term depression in the same region. Finally, this manipulation was sufficient to enhance long-term fear memory.

The detailed characterization of the mouse model lacking astrocytic somatic calcium revealed that astrocytes modulate hippocampal circuit structure and function through Foxo1 signaling to enhance fear memory.
Phages overcome bacterial immunity via diverse anti-defense proteins
Authors: Yirmiya Erez , Leavitt Azita , Lu Allen , Avraham Carmel , Osterman Ilya , Garb Jeremy , Antine Sadie P. , Mooney Sarah E. , Hobbs Sam J. , Kranzusch Philip J. , Amitai Gil , Sorek Rotem
Published: May 2023

It was recently shown that bacteria employ, apart from CRISPR-Cas and restriction systems, a considerable diversity of phage resistance systems, but it is largely unknown how phages cope with this multilayered bacterial immunity. Here, we analyzed groups of closely relatedBacillusphages that showed differential sensitivity to bacterial defense systems, and identified multiple families of anti-defense proteins that inhibit the Gabija, Thoeris, and Hachiman systems. We show that these proteins efficiently cancel the defensive activity when co-expressed with the respective defense system or introduced into phage genomes. Homologs of these anti-defense proteins are found in hundreds of phages that infect taxonomically diverse bacterial species. We show that an anti-Gabija protein, denoted Gad1, blocks the ability of the Gabija defense complex to cleave phage-derived DNA. Our data further reveal an anti-Thoeris protein, denoted Tad2, which is a “sponge” that sequesters the immune signaling molecules produced by Thoeris TIR-domain proteins in response to phage. Our results demonstrate that phages encode an arsenal of anti-defense proteins that can disable a variety of bacterial defense mechanisms.
Sulfur oxidation and reduction are coupled to nitrogen fixation in the roots of a salt marsh foundation plant species
Authors: Rolando J.L. , Kolton M. , Song T. , Liu Y. , Pinamang P. , Conrad R. , Morris J.T. , Konstantinidis K.T. , Kostka J.E.
Published: May 2023

Symbiotic root microbiota are crucial for plant growth as they assist their hosts in nutrient acquisition. In the roots of coastal marine plants, heterotrophic activity in the rhizosphere by sulfate-reducing microorganisms has been linked to nitrogen fixation. In this study, we recovered 239 high-quality metagenome-assembled genomes (MAGs) from a salt marsh dominated by the foundation plantSpartina alterniflora, including diazotrophic sulfate-reducing and sulfur-oxidizing bacteria thriving in the root compartment. Here we show for the first time that highly-abundant sulfur-oxidizing bacteria in the roots of a coastal macrophyte encode and highly express genes for nitrogen fixation (nifHDK). Further, we leveraged aS. alterniflorabiomass gradient to gain a mechanistic understanding on how root-microbe interactions respond to abiotic stress from anoxia and elevated sulfide concentration. We observed that the roots of the stressedS. alternifloraphenotype exhibited the highest rates of nitrogen fixation and expression levels of both the oxidative and reductive forms of the dissimilatory sulfite reductase gene (dsrAB). Approximately 25% and 15% of all sulfur-oxidizing dsrA and nitrogen-fixing nifK transcripts, respectively, were associated with novel MAGs of theCandidatusThiodiazotropha genus in the roots of the stressedS. alternifloraphenotype. We conclude that the rapid cycling of sulfur in the dynamicS. alternifloraroot zone is coupled to nitrogen fixation during both reductive and oxidative sulfur reactions, and that theS. alterniflora–Ca.Thiodiazotropha symbiosis is an adaptive response to anoxic and sulfidic sediment conditions, whereby the plants benefit from reduced sulfide toxicity and potential nitrogen acquisition.
Photosynthetic living fibers fabrication from algal-bacterial consortia with controlled spatial distribution
Authors: Sun Zitong , Di Zhengao , Zhang Yang , Wen Huilin , Zhang Shaobin , Zhang Zhiqian , Zhang Jing , Yu Ziyi
Published: May 2023

Living materials that combine active cells and synthetic matrix materials have become a promising research field in recent years. While multicellular systems present exclusive benefits in developing living materials over single-cell systems, creating artificial multicellular systems can be challenging due to the difficulty in controlling the multicellular assemblies and the complexity of cell-to-cell interactions. Here, we propose a co-culture platform capable of isolating and controlling the spatial distribution of algal-bacterial consortia, which can be used to construct photosynthetic living fibers. Through coaxial extrusion-based 3D printing, hydrogel fibers containing bacteria or algae can be deposited into designated structures and further processed into materials with precise geometries. In addition, the photosynthetic living fibers demonstrate a significant synergistic catalytic effect resulting from the immobilization of both bacteria and algae, which effectively optimize sewage treatment for bioremediation purposes. The integration of microbial consortia and 3D printing gives functional living materials that have promising applications in biocatalysis, biosensing, and biomedicine. Our approach provides an optimized solution for constructing efficient multicellular systems and opens a new avenue for the development of advanced materials.
High carbohydrate to protein ratio promotes changes in intestinal microbiota and host metabolism in rainbow trout (Oncorhynchus mykiss) fed plant-based diet
Authors: Defaix Raphaël , Lokesh Jep , Ghislain Mylène , Bechec Mickael Le , Marchand Michaël , Véron Vincent , Surget Anne , Biasutti Sandra , Terrier Frederic , Pigot Thierry , Panserat Stéphane , Ricaud Karine
Published: May 2023

To ensure the sustainability of aquaculture, it is necessary to change the “menu” of carnivorous fish such as rainbow trout from a fish-based diet to one with plant-based ingredients. However, there is a major problem with the growth performance decrease of fish fed with a 100% plant-based diet due to the reduction in feed intake and feed efficiency. For the first time, we incorporated high levels of digestible carbohydrates (high-starch diet) in a 100% plant-based diet during a 12-week feeding trial in order to improve protein utilization for growth (protein sparing effect) and reduce nitrogen waste.

We measured the changes in the intestinal microbiota, Short-Chain Fatty Acid (SCFA) levels and metabolic responses in liver. Dietary carbohydrates had a strong effect on alpha and beta diversity and abundance of 12 genera, includingRalstoniaandBacillusin digesta associated microbiota whereas mucosa associated microbiota was less affected. The change in microbial diversity might be linked to the change observed in SCFA production. High levels ofMycoplasmawere observed in the intestinal mucosa. Overall, hepatic gene expression was significantly altered by the CHO/protein ratio. Up-regulation of genes involved in glucose metabolism (gcka,gckb,g6pcb2a), down-regulation of genes involved in lipid metabolism (hadh,acox3,srebp2a, andcyp51a) were associated with higher enzymatic activities (such as glucokinase or pyruvate kinase) and higher glycogen levels in the liver, suggesting adequate adaptation to diet. Interestingly, strong correlations were observed between abundances of certain bacterial OTUs and gene expression in the liver.

The inclusion of digestible carbohydrates in combination with a 100% plant-based diet, could be a promising way to improve and reduce the use of plant proteins in rainbow trout. In addition, the relationship between intestinal microbiota and host metabolism needs further investigation to better understand fish nutrition.