bluuebunny/crossref_metadata_2025 huggingface dataset:
An improved bioassay for the testing of entomopathogenic nematode virulence to the western corn rootworm (Diabrotica virgifera virgifera) (Coleoptera: Chrysomelidae): with focus on neonate insect assessments
Authors: Geisert Ryan W , Huynh Man P , Pereira Adriano E , Shapiro Ilan David I , Hibbard Bruce E
Published: April 2023

Bioassays involving newly hatched larval insects can be limited by the larvae’s feeding state. Assays attempting to monitor mortality effects can be negatively affected by starvation effects on the larvae. Neonate western corn rootworms have significant reductions in viability if not provided food within 24 h post hatch. The recent development of an improved artificial diet for western corn rootworm larvae provides a new bioassay type for evaluating entomopathogenic nematodes that also makes the testing arena easy to observe. Here, we evaluated four species of entomopathogenic nematodes including Heterorhabditis bacteriophora Poinar, Steinernema carpocapsae (Weiser), Steinernema diaprepesi Nguyen & Duncan, and Steinernema rarum (de Doucet) against neonate western corn rootworm, Diabrotica virgifera virgifera LeConte, in 96-well plate diet bioassays. Nematode inoculation levels were 0, 15, 30, 60, and 120 nematodes per larva. Percentage mortality increased for each species as the rate of inoculation increased. Overall, H. bacteriophora and S. carpocapsae caused the greatest amount of larval mortality. The diet-based bioassays were shown to be an effective method for nematode exposure to insect pests. The assays provided adequate moisture to keep nematode from desiccating while also allowing freedom of movement around the arenas. Both rootworm larvae and nematodes were contained within the assay arenas. The addition of nematodes did not cause any significant deterioration of the diet within the three-day period of testing. Overall, the diet bioassays worked well as a measure of entomopathogenic nematode virulence.
Plural and Quantified Protagonists in Free Indirect Discourse and Protagonist Projection
Authors: Abrusán Márta
Published: April 2023

In this paper I observe a number of new plural and (apparently) quantified examples of free indirect discourse (FID) and protagonist projection (PP). I analyse them within major current theoretical approaches, proposing extensions to these approaches where needed. In order to derive the wide range of readings observed with plural protagonists, I show how we can exploit existing mechanisms for the interpretation of plural anaphora and plural predication. The upshot is that the interpretation of plural examples of perspective shift relies on a remarkable concert of covert semantic and pragmatic operations.
Frequency of visits to Tomioka town and related factors among evacuees more than a decade after the Fukushima Daiichi Nuclear Power Plant accident
Authors: Matsunaga Hitomi , Xiao Xu , Hande Varsha , Orita Makiko , Kashiwazaki Yuya , Taira Yasuyuki , Takamura Noboru
Published: April 2023

This study aimed to clarify the frequency of visits (FOV) to Tomioka town, Japan, and related factors among evacuees more than a decade after the Fukushima Daiichi Nuclear Power Plant accident. A questionnaire survey was conducted on residents (age ≥ 18 years) who had residence cards in August 2021. Of the 2260 respondents, the FOV to Tomioka was as follows: 926 (41.0%) more than twice a year (Group 1 [G1]), 841 (37.2%) once a year (G2) and 493 (21.8%) no visits (G3). About 70% of the respondents who had decided not to return to Tomioka visited once a year or more. No significant differences in the FOV or radiation risk perception were found between groups. Multinomial logistic regression analysis using G3 as a reference revealed independent associations between living inside Fukushima in G1 (odds ratio [OR] = 5.4, 95% confidence interval [CI]: 4.1–7.3; P < 0.01) and G2 (OR = 2.3, 95% CI: 1.8–3.0, P < 0.01), undecided about returning in G1 (OR = 2.5, 95% CI: 1.9–3.3, P < 0.01), females in G1 (OR = 2.0, 95% CI: 1.6–2.6, P < 0.01) and motivation to learn more about tritiated water in G2 (OR = 1.8, 95% CI: 1.3–2.4, P < 0.01). Overall, 80% of the residents had visited Tomioka within a decade after the accident. These findings suggest the need to continue the effective dissemination of information about the effects of a nuclear accident and the subsequent decommissioning process to evacuees after evacuation orders have been lifted.
Management of epididymal leiomyosarcoma: literature narrative, case report and discussion on the use of simple epididymectomy or high radical orchiectomy
Authors: Tchienga Dimitri , Banayan Elliot , Arulin Micheal , Romulo Genato , Asarian Armand , Xiao Philip
Published: April 2023

Epididymal leiomyosarcomas are rare malignant tumors of smooth muscle origin. We present a case of a low-grade tumor with negative margins managed with a high-radical inguinal orchiectomy. Our review of the literature suggests that low-grade and localized tumors with negative margins can be managed with simple epididymectomy and imaging surveillance.
18O/17O abundance ratio towards a sample of massive star-forming regions with parallax distances
Authors: Ou Chao , Wang Junzhi , Zheng Siqi , Li Juan , Romano Donatella , Zhang Zhi-Yu
Published: April 2023

The 18O/17O abundance ratio is, in principle, a powerful tool to estimate the relative contributions of massive stars and low- to intermediate-mass stars to the chemical enrichment of galaxies. We present 18O/17O ratios derived from simultaneous observations of C18O and C17O 1-0 towards 51 massive star-forming regions with the Institut de Radioastronomie Millimétrique (IRAM) 30 m telescope. Simultaneous observations of HC18O+ 1-0 and HC17O+ 1-0 with the Yebes 40m telescope towards five sources from this sample were also done to test the consistency of 18O/17O ratios derived from different isotopic pairs. From our improved measurements, resulting in smaller errors than previous work in the literature, we obtain a clear trend of increasing 18O/17O ratio with increasing Galactocentric distance (DGC), which provides a significant constraint on Galactic chemical evolution (GCE) models. Current GCE models have to be improved in order to explain the observed C18O/C17O 1-0 gradient.
Globular Cluster UVIT Legacy Survey (GlobULeS) – II. Evolutionary status of hot stars in M3 and M13
Authors: Kumar Ranjan , Pradhan Ananta C , Sahu Snehalata , Subramaniam Annapurni , Piridi Sonika , Cassisi Santi , Ojha Devendra K
Published: April 2023

We present a far-ultraviolet (FUV) study of hot stellar populations in the second parameter pair globular clusters (GCs) M3 and M13, as a part of the GC UVIT Legacy Survey programme (GlobULeS). We use observations made with F148W and F169M filters of the Ultraviolet Imaging Telescope (UVIT) onboard AstroSat along with ground-based data (UBVRI filters), Hubble Space Telescope(HST) GC catalogue, and Gaia EDR3 catalogue. Based on the FUV-optical colour–magnitude diagrams, we classify the sources into the horizontal branch (HB) stars, post-HB stars, and hot white dwarfs (WDs) in both the GCs. The comparison of synthetic and observed colours of the observed HB stars suggests that the mass-loss at the red giant branch and He spread in both clusters have a simultaneous effect on the different HB distributions detected in M3 and M13, such that HB stars of M13 require a larger spread in He (0.247–0.310) than those of M3 (Y = 0.252–0.266). The evolutionary status of HB stars, post-HB stars, and WDs are studied using SED fit parameters and theoretical evolutionary tracks on the H–R diagram. We found that the observed post-HB stars have evolved from zero-age HB (ZAHB) stars of the mass range of 0.48−0.55 M⊙ in M3 and M13. We detect 24 WD candidates in each cluster having ${\rm \log ({\it L}_{bol}/L_\odot)}$ in the range of −0.8 to +0.6 and ${\rm \log ({\it T}_{eff}/K)}$ in the range of 4.2–5.0. Placing the WDs on the H–R diagram and comparing them with models, it is found that M13 has a population of low-mass WDs, probably originating from binary evolution.
MaNGA galaxy properties – II. A detailed comparison of observed and simulated spiral galaxy scaling relations
Authors: Arora Nikhil , Courteau Stéphane , Stone Connor , Macciò Andrea V
Published: April 2023

We present a catalogue of dynamical properties for 2368 late-type galaxies from the MaNGA survey. The latter complements the catalogue of photometric properties for the same sample based on deep optical dark energy sky instrument legacy imaging survey (DESI) photometry processed with autoprof . Rotation curves (RCs), extracted by model-fitting H α velocity maps from the MaNGA Data Analysis Pipeline, extend out to 1.4 (1.9) Re for the primary (secondary) MaNGA samples, respectively. The RCs and ancillary MaNGA Pipe3D data products were used to construct various fundamental galaxy scaling relations that are also compared uniformly with similar relations from numerical investigation of a hundred astrophysical object (NIHAO) zoom-in simulations. Simulated NIHAO galaxies were found to broadly reproduce the observed MaNGA galaxy population for $\log (M_*/{\rm {\rm M}_{\odot })\, \gt\, 8.5}$. Some discrepancies remain, such as those pertaining to central stellar densities and the diversity of RCs due to strong feedback schemes. Also presented are spatially resolved scatters for the velocity-size-stellar mass (VRM*) structural relations using MaNGA and NIHAO samples. The scatter for these relations in the galaxian interiors is a consequence of the diversity of inner RC shapes, while scatter in the outskirts is dictated by the large range of stellar surface densities, which is itself driven by sporadic star formation. The detailed, spatially resolved scatter analysis highlights the complex interplay between local and global astrophysical processes and provides a strong constraint to numerical simulations.
Chandra X-ray measurement of gas-phase heavy element abundances in the central parsec of the galaxy
Authors: Hua Ziqian , Li Zhiyuan , Zhang Mengfei , Chen Zhuo , Morris Mark R
Published: April 2023

Elemental abundances are key to our understanding of star formation and evolution in the Galactic Centre. Previous work on this topic has been based on infrared (IR) observations, but X-ray observations have the potential of constraining the abundance of heavy elements, mainly through their K-shell emission lines. Using 5.7 Ms Chandra observations, we provide the first abundance measurement of Si, S, Ar, Ca, and Fe, in four prominent diffuse X-ray features located in the central parsec of the Galaxy, which are the manifestation of shock-heated hot gas. A two-temperature non-equilibrium ionization spectral model is employed to derive the abundances of these five elements. In this procedure, a degeneracy is introduced due to uncertainties in the composition of light elements, in particular, H, C, and N. Assuming that the hot gas is H-depleted but C- and N-enriched, as would be expected for a standard scenario in which the hot gas is dominated by Wolf–Rayet star winds, the spectral fit finds a generally subsolar abundance for the heavy elements. If, instead, the light elements had a solar-like abundance, the heavy elements have a fitted abundance of ∼1–2 solar. The α/Fe abundance ratio, on the other hand, is mostly supersolar and insensitive to the exact composition of the light elements. These results are robust against potential biases due to either a moderate spectral signal-to-noise ratio or the presence of non-thermal components. Implications of the measured abundances for the Galactic Centre environment are addressed.
Management of patients with inflammatory rheumatic diseases after treatment failure with a first tumour necrosis factor inhibitor: A narrative review
Authors: Caporali Roberto , Conti Fabrizio , Iannone Florenzo
Published: April 2023

The emergence of biologics with different modes of action (MoAs) and therapeutic targets has changed treatment patterns in patients with inflammatory rheumatic diseases. While tumour necrosis factor inhibitors (TNFis) are often utilized as the first biologic disease-modifying antirheumatic drug, some patients may not respond adequately (primary failure), fail to sustain response over time (secondary failure), or experience intolerable adverse events. Whether these patients would benefit more from cycling to a different TNFi or switching to a biologic with a different MoA is still unclear. We discuss here treatment outcomes of TNFi cycling versus MoA switching after treatment failure with a first TNFi in patients with inflammatory rheumatic diseases, focusing specifically on rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis. Treatment guidelines for these patients are ambiguous and, at times, contradictory in their recommendations. However, this is due to a lack of high-quality head-to-head data to definitively support cycling between TNFis after failure to a first-line TNFi over switching to a different MoA.
Follow the Money
Authors: Grotteria Marco
Published: April 2023

I study, both empirically and theoretically, the economic and financial consequences of corporate lobbying. Firms lobby politicians to increase their share of government contracts, but political competition creates firm-level risk, inflating their cost of capital and reducing their incentive to invest in research and development (R&D). I document an annual 6–8% return premium for stocks of high-lobbying firms, which compensates investors for political risk. An estimated model in which firms can lobby and innovate and investors are risk averse replicates key features of corporate lobbying in the U.S., including the well-established paradox that lobbying contributions are small relative to the policies at stake. The model predicts that if investors ceased seeking compensation for political risk, R&D investment would increase by 6% and the innovation rate by 0.4% points. The risk-premium costs of lobbying are quantitatively and economically important even if the resources “wasted” on lobbying are objectively small.
Antenatal care and adherence to intermittent preventive treatment for malaria during pregnancy with sulfadoxine-pyrimethamine in Gambia: an examination of Demographic and Health Survey data 2019–2020
Authors: Bash Claire E , McClintock Heather F
Published: April 2023

Background

Malaria during pregnancy is a major contributor to maternal and infant morbidity and mortality in Gambia. The World Health Organization recommends that women adhere to intermittent preventive treatment with sulfadoxine-pyrimethamine (SP-IPTp) provided through antenatal care (ANC) to prevent adverse outcomes. The aim of this study was to examine predictors of SP-IPTp adherence among women in Gambia.

Methods

Data analysis was conducted using the 2019–2020 Women's Health Survey from the Gambia Demographic and Health Survey dataset. χ2 tests and multivariate logistic regression were employed to assess the influence of ANC and sociodemographic characteristics on SP-IPTp adherence.

Results

Among 5381 women, less than half (47.3%) achieved adherence (three or more doses) to SP-IPTp. More than three-quarters (79.7%) attended four or more ANC visits. Women who attended four ANC visits were twice as likely to adhere to SP-IPTp than women who attended none to three ANC visits (adjusted odds ratio 2.042 [95% confidence interval 1.611 to 2.590]).

Conclusions

Attending four or more and earlier initiation of ANC visits may be related to improved SP-IPTp adherence. Additional research is needed to assess structural and healthcare system components that influence SP-IPTp adherence.
Abortion Access and Medically Complex Pregnancies Before and After Texas Senate Bill 8
Authors: Arey Whitney , Lerma Klaira , Carpenter Emma , Moayedi Ghazaleh , Harper Lorie , Beasley Anitra , Ogburn Tony , White Kari
Published: April 2023

OBJECTIVE:

To evaluate how Texas health care professionals who care for patients experiencing medically complex pregnancies navigate abortion restrictions.

METHODS:

We conducted qualitative in-depth interviews with health care professionals across Texas who cared for patients with life-limiting fetal diagnoses or who had existing or developed health conditions that adversely affected pregnancy. We conducted the first round of interviews March–June 2021 and the second round of interviews January–May 2022 after the implementation of Texas Senate Bill 8 (SB8), which prohibited most abortions after detection of embryonic cardiac activity. We used inductive and deductive qualitative analysis to identify themes and changes in practice after the implementation of SB8.

RESULTS:

We conducted a total of 50 interviews: 25 before implementation of SB8 and 25 after the law's implementation. We interviewed 21 maternal–fetal medicine specialists, 19 obstetrician–gynecologists, eight physicians whose primary practice is the provision of abortion care, and two genetic counselors. Participants reported presenting their patients with information about health risks and outcomes of continued pregnancy in each policy period; however, counseling on these options was curtailed after implementation of SB8. Even in cases in which a patient's health and, in some cases, life would be compromised, narrow criteria for abortions at hospitals limited care before implementation of SB8, and criteria often became more stringent after implementation of SB8. Administrative approval processes and referrals for abortion delayed care and endangered patients' health, which worsened after in-state options were eliminated after implementation of SB8. Participants noted that patients with more limited resources who were unable to travel out of state often had to continue pregnancies, further increasing their risk of morbidity.

CONCLUSION:

Texas health care professionals' abilities to provide evidence-based abortion care to patients with medically complex pregnancies were constrained by institutional policies, and care options narrowed further after implementation of SB8. Abortion restrictions limit shared decision making, compromise patient care, and put pregnant people's health at risk.
Aided Cortical Auditory Evoked Potentials in Infants With Frequency-Specific Synthetic Speech Stimuli: Sensitivity, Repeatability, and Feasibility
Authors: Visram Anisa S. , Stone Michael A. , Purdy Suzanne C. , Bell Steven L. , Brooks Jo , Bruce Iain A. , Chesnaye Michael A. , Dillon Harvey , Harte James M. , Hudson Caroline L. , Laugesen Søren , Morgan Rhiannon E. , O’Driscoll Martin , Roberts Stephen A. , Roughley Amber J. , Simpson David , Munro Kevin J.
Published: April 2023

Objectives:

The cortical auditory evoked potential (CAEP) test is a candidate for supplementing clinical practice for infant hearing aid users and others who are not developmentally ready for behavioral testing. Sensitivity of the test for given sensation levels (SLs) has been reported to some degree, but further data are needed from large numbers of infants within the target age range, including repeat data where CAEPs were not detected initially. This study aims to assess sensitivity, repeatability, acceptability, and feasibility of CAEPs as a clinical measure of aided audibility in infants.

Design:

One hundred and three infant hearing aid users were recruited from 53 pediatric audiology centers across the UK. Infants underwent aided CAEP testing at age 3 to 7 months to a mid-frequency (MF) and (mid-)high-frequency (HF) synthetic speech stimulus. CAEP testing was repeated within 7 days. When developmentally ready (aged 7-21 months), the infants underwent aided behavioral hearing testing using the same stimuli, to estimate the decibel (dB) SL (i.e., level above threshold) of those stimuli when presented at the CAEP test sessions. Percentage of CAEP detections for different dB SLs are reported using an objective detection method (Hotellings T2). Acceptability was assessed using caregiver interviews and a questionnaire, and feasibility by recording test duration and completion rate.

Results:

The overall sensitivity for a single CAEP test when the stimuli were ≥0 dB SL (i.e., audible) was 70% for the MF stimulus and 54% for the HF stimulus. After repeat testing, this increased to 84% and 72%, respectively. For SL >10 dB, the respective MF and HF test sensitivities were 80% and 60% for a single test, increasing to 94% and 79% for the two tests combined. Clinical feasibility was demonstrated by an excellent >99% completion rate, and acceptable median test duration of 24 minutes, including preparation time. Caregivers reported overall positive experiences of the test.

Conclusions:

By addressing the clinical need to provide data in the target age group at different SLs, we have demonstrated that aided CAEP testing can supplement existing clinical practice when infants with hearing loss are not developmentally ready for traditional behavioral assessment. Repeat testing is valuable to increase test sensitivity. For clinical application, it is important to be aware of CAEP response variability in this age group.
Assessment of the Impact of Low-dose Ionizing Radiation Exposure on Health Care Workers: A Study of Methods Used from a Scoping Review
Authors: De Giorgi Andrea , Bongiovanni Andrea , De Sio Simone , Sernia Sabina , Adamo Giuseppe , La Torre Giuseppe
Published: April 2023

Healthcare workers may be exposed to ionizing radiation. Ionizing radiations are an important occupational risk factor for the potential damage they can cause to workers’ health. Actually, the attention is focused on diseases caused by damage to radiosensitive organs. The aim of our study is to evaluate the methods used for the assessment of the impact of exposure to low-dose ionizing radiation in a population of healthcare workers (HCWs). The electronic database PubMed was searched by title, abstract, and medical subheadings (MeSH) terms. The extracted data were arranged into tables by dividing bibliographic reference, exposure, and statistical analysis information. The quality assessment was performed with the use of the Newcastle-Ottawa Quality Assessment Scale. The search strategy involved retrieving 15 studies (eight cohorts and seven cross-sectional studies). The univariate tests have been performed in 14 studies (93.3%), and Chi-square and T-test were the most commonly used. Multivariate tests have been performed in 11 studies (73.3%), and the most commonly performed were Logistic and Poisson Regressions. The most rated organ was the thyroid gland (six studies). The annual cumulative effective dose was the most used method to assess the dose rate (seven studies). Due to the characteristics of pathologies involved, a retrospective cohort study with an adequate control group and use of the annual cumulative effective dose to account for exposure could be useful features to obtain the best possible evidence. All the elements were found rarely in studies considered. The need is highlighted for more in-depth studies to investigate this topic.
Take a Swipe at Actinide Bioavailability: Application of a New In Vitro Method
Authors: Griffiths N. M. , Moureau A. , Coudert S. , Huet F. , Defrance M. , Van der Meeren A.
Published: April 2023

Filter swipe tests are used for routine analyses of actinides in nuclear industrial, research, and weapon facilities as well as following accidental release. Actinide physicochemical properties will determine in part bioavailability and internal contamination levels. The aim of this work was to develop and validate a new approach to predict actinide bioavailability recovered by filter swipe tests. As proof of concept and to simulate a routine or an accidental situation, filter swipes were obtained from a nuclear research facility glove box. A recently-developed biomimetic assay for prediction of actinide bioavailability was adapted for bioavailability measurements using material obtained from these filter swipes. In addition, the efficacy of the clinically-used chelator, diethylenetriamine pentaacetate (Ca-DTPA), to enhance transportability was determined. This report shows that it is possible to evaluate physicochemical properties and to predict bioavailability of filter swipe-associated actinides.
Demographic Features and Laboratory Parameters Among Hospitalized Vaccinated Patients With COVID-19 in Istanbul, Turkey
Authors: Yagci Ayşegul Karahasan , Alci Gamze , Guncu Mehmet Mucahit , Yilmaz Omer Bugrahan , Tekin Eranalp , Cakir Safa Emre , Cebe Burak , Ozturk Cem , Sirikci Onder
Published: April 2023

Background

The number of COVID-19 cases has been decreasing recently, and the restrictions are waived in many countries. The data about vaccine efficacy are essential to be prepared for the future even if the pandemic ends and the disease becomes endemic.

Aims

The aim of this study was to define demographic and laboratory data for disease severity among vaccinated COVID-19 cases who were hospitalized.

Study Design

This is a retrospective cohort study.

Methods

SARS-CoV-2 polymerase chain reaction–positive patients who were fully vaccinated (2 doses of vaccines and 3 doses of vaccines) and had been hospitalized at least 15 days after the last vaccine dose were enrolled in this study. Patients' data including laboratory parameters were retrieved, and descriptive statistics and comparison of variables were calculated.

Results

Between September 1, 2021, and February 28, 2022, 685 patients (mean age, 67.84 years; 50.8% female) were hospitalized. Inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac) had been administered to 467 of the patients (68.4%), BNT162b2 mRNA vaccine (Pfizer-Pfizer-BioNTech) had been administered to 107 of the patients (15.6%), and to 111 of the patients (16%), a combination of 2 vaccines had been administered. At least 1 comorbidity was present in 160 participants (23%) and more than 4 comorbidities in 46 patients (6.6%). The most common comorbidity was hypertension (349, 50.2%). The presence of comorbidities was significantly higher in patients having 3 doses of vaccine. Increased ferritin levels were determined in 56.4% of the patients, increased D-dimer levels in 69.9% of the patients, increased C-reactive protein levels in 79.7% of the patients, and increased procalcitonin levels in 61.5% of the patients. A total of 36.4% of the patients had decreased lymphocyte counts, 20% had low lymphocyte/monocyte ratio, and 22% had decreased neutrophil/lymphocyte ratio. The only parameter that was significantly higher in patients having 3 vaccine doses was procalcitonin. Mean duration of hospitalization was 9.68 ± 7.29 days. In the CoronaVac and Pfizer-BioNTech groups, 68.5% and 21.4%, respectively, of the patients were older than 65 years. Seventeen (3.6%) patients in the CoronaVac group, 6 (5.4%) patients in the combination group, and 3 (2.8%) patients in Pfizer-BioNTech group had been admitted to the intensive care unit. Mortality rate was 0.3% (2 of 685 patients).

Conclusions

The incidence of severe COVID-19 disease among fully vaccinated patients is low even in the presence of comorbidities, older age, and presence of abnormal laboratory parameters, regardless of the vaccine type.
Extended pelvic lymph node dissection in muscle invasive bladder cancer
Authors: Katims Andrew B. , Bochner Bernard H.
Published: April 2023

Purpose of review

Bilateral pelvic lymph node dissection (PLND) at the time of radical cystectomy (RC) provides important staging information and oncologic benefit in patients with bladder cancer. The optimal extent of the PLND remains controversial. Our aim is to highlight nodal mapping studies and the data that guides optimization of both staging and oncologic outcomes. We then review contemporary randomized trials studying the extent of PLND.

Recent findings

A recent randomized trial (RCT) powered for a 15% improvement in recurrence-free survival (RFS) of extended (e) over limited (l)PLND was completed but failed to identify this large difference in outcome. Concerns over study design limit the ability to interpret the oncologic results. Importantly, ePLND minimally changed surgical morbidity. An ongoing, similar RCT (SWOG S1011) powered to detect a 10% difference in RFS has completed accrual, but no published outcomes are available.

RC and ePLND can provide cure in 33% of LN positive bladder cancer patients. Current data support a 5% improvement in RFS if ePLND is routinely used in MIBC patients. Two randomized trials powered to identify much larger (15 and 10%) improvements in RFS are unlikely to identify such an ambitious benefit by extending the PLND.
Effect of the olive leaf extract in chronic spinal cord injury model: an experimental research
Authors: Nasution Iqbal P.A. , Ibrahim Sabri , Riawan Wibi
Published: April 2023

Introduction:

Posttraumatic myelopathy is defined as a spinal cord injury (SCI) that results in varying degrees of motor and sensory deficits. The degree of ‘secondary damage,’ which is caused by a variety of cellular, molecular, and biochemical cascades is linked to the outcome of SCI. According to research, the beneficial effects of oleuropein and its derivatives have been linked to radical scavenging/antioxidant actions and anti-inflammatory effects.

Materials and Methods:

This study was divided into six groups: control negative (sham-operated) group, control positive 1 and 2 (early chronic and chronic), treatment groups 1, 2, and 3 (prophylactic, concomitant, and late). Olive leaf extract (OLE) given dose was 350 mg/kg body weight. Blood was taken from the left corotic artery before the animals were terminated, seromarker assessment, enzyme-linked immunosorbent assay of IL-6, TNF-α, brain-derived neurotrophic factor (BDNF), and assessment of functional motoric outcome before the animal was terminated.

Results:

Chronic spinal cord compression increased serum levels of IL-6, TNF-α, and decreased serum level of BDNF. OLE 350 mg/kg body weight decreased serum levels of IL-6, TNF-α and increased functional motoric outcome, especially in prophylactic and concomitant therapy.

Discussion:

These findings indicate that OLE may be effective in protecting chronic SCI model.

Conclusion:

Oleuropein has a potential effect to reduce the IL-6 and TNF-α in rabbit model of SCI, and the BDNF value risen after the administration of Oleuropein.
Antiviral activity of salt-coated materials against SARS-CoV-2.
Authors: Coleman Christopher Michael , Wang Belinda , Wang Yixin , Tapia-Brito Emannuel , Chen Ziwei , Riffat James , Riffat Saffa , Tarlinton Rachael , Ghaemmaghami Amir
Published: April 2023

The SARS-CoV-2 pandemic demonstrated the importance of human coronaviruses and the need to develop materials to prevent the spread of emergent viruses. Here we describe that simple salt coating on a range of surfaces can degrade SARS-CoV-2.
Thermococcus argininiproducens sp. nov., an arginine biosynthesis archaeal species isolated from the Central Indian Ocean ridge
Authors: Park Yeong-Jun , Lim Jae Kyu , Kim Yun Jae , Yang Sung-Hyun , Lee Hyun Sook , Kang Sung Gyun , Lee Jung-Hyun , Yang Youngik , Kwon Kae Kyoung
Published: April 2023

A strictly anaerobic hyperthermophilic archaeon, designated strain IOH2T, was isolated from a deep-sea hydrothermal vent (Onnuri vent field) area on the Central Indian Ocean Ridge. Strain IOH2T showed high 16S rRNA gene sequence similarity to

Thermococcus sibiricus

MM 739T (99.42 %),

Thermococcus alcaliphilus

DSM 10322T (99.28 %),

Thermococcus aegaeus

P5T (99.21 %),

Thermococcus litoralis

DSM 5473T (99.13 %), ‘Thermococcus bergensis’ T7324T (99.13 %),

Thermococcus aggregans

TYT (98.92 %) and

Thermococcus prieurii

Bio-pl-0405IT2T (98.01 %), with all other strains showing lower than 98 % similarity. The average nucleotide identity and in silico DNA–DNA hybridization values were highest between strain IOH2T and

T. sibiricus

MM 739T (79.33 and 15.00 %, respectively); these values are much lower than the species delineation cut-offs. Cells of strain IOH2T were coccoid, 1.0–1.2 µm in diameter and had no flagella. Growth ranges were 60–85 °C (optimum at 80 °C), pH 4.5–8.5 (optimum at pH 6.3) and 2.0–6.0 % (optimum at 4.0 %) NaCl. Growth of strain IOH2T was enhanced by starch, glucose, maltodextrin and pyruvate as a carbon source, and elemental sulphur as an electron acceptor. Through genome analysis of strain IOH2T, arginine biosynthesis related genes were predicted, and growth of strain IOH2T without arginine was confirmed. The genome of strain IOH2T was assembled as a circular chromosome of 1 946 249 bp and predicted 2096 genes. The DNA G+C content was 39.44 mol%. Based on the results of physiological and phylogenetic analyses, Thermococcus argininiproducens sp. nov. is proposed with type strain IOH2T (=MCCC 4K00089T=KCTC 25190T).
DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation
Authors: Mullen Nicholas J. , Shukla Surendra K. , Thakur Ravi , Kollala Sai Sundeep , Wang Dezhen , Chaika Nina , Santana Juan F. , Miklavcic William R. , LaBreck Drew A. , Mallareddy Jayapal Reddy , Price David H. , Natarajan Amarnath , Mehla Kamiya , Sykes David B. , Hollingsworth Michael A. , Singh Pankaj K.
Published: April 2023

Pyrimidine nucleotide biosynthesis is a druggable metabolic dependency of cancer cells, and chemotherapy agents targeting pyrimidine metabolism are the backbone of treatment for many cancers. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine biosynthesis pathway that can be targeted by clinically approved inhibitors. However, despite robust preclinical anticancer efficacy, DHODH inhibitors have shown limited single-agent activity in phase 1 and 2 clinical trials. Therefore, novel combination therapy strategies are necessary to realize the potential of these drugs. To search for therapeutic vulnerabilities induced by DHODH inhibition, we examined gene expression changes in cancer cells treated with the potent and selective DHODH inhibitor brequinar (BQ). This revealed that BQ treatment causes upregulation of antigen presentation pathway genes and cell surface MHC class I expression. Mechanistic studies showed that this effect is 1) strictly dependent on pyrimidine nucleotide depletion, 2) independent of canonical antigen presentation pathway transcriptional regulators, and 3) mediated by RNA polymerase II elongation control by positive transcription elongation factor B (P-TEFb). Furthermore, BQ showed impressive single-agent efficacy in the immunocompetent B16F10 melanoma model, and combination treatment with BQ and dual immune checkpoint blockade (anti-CTLA-4 plus anti-PD-1) significantly prolonged mouse survival compared to either therapy alone. Our results have important implications for the clinical development of DHODH inhibitors and provide a rationale for combination therapy with BQ and immune checkpoint blockade.
Algal symbioses with fire corals demonstrate host genotype specificity and niche adaptation at subspecies resolution
Authors: Dubé Caroline E , Hume Benjamin CC , Boissin Emilie , Mercière Alexandre , Bourmaud Chloé A-F , Ziegler Maren , Voolstra Christian R
Published: April 2023

Corals share an intimate relationship with photosynthetic dinoflagellates that contribute to the biology of the emerging metaorganism. While many coral-algal associations exhibit high host fidelity, the extent of this specificity under environmental change remains to be fully understood and is a prerequisite to forecasting the adaptive potential of this obligate symbiosis. Here, we disentangled the contribution of host genotype and environment on governing coral-algae associations by working at subspecies resolution. We used fine-scale genotyping of algal symbionts from 198 fire coral colonies (Milleporacf.platyphylla)that map to ten distinct sexually produced clonal host genotypes across three environmentally distinct reef habitats. Based on microalgal ITS2 genotyping, we show that algal-host specificity extends down to the Symbiodiniaceae subspecies level in a natural reef environment. Closely relatedSymbiodinium(A7)-dominated algal assemblages almost perfectly mapped to fire coral host genotype. Furthermore, identification of host genotype- and habitat-specificSymbiodiniumalga suggest the presence of algal phenotypic diversity even at this taxonomic resolution (i.e., withinSymbiodiniumA7), which may aid environmental niche adaptation of the metaorganism. Our results suggest that the here-identifiedMillepora-Symbiodiniumassociations are co-evolved to match their prevailing environment. Thus, despite the presence of rarer host generalistCladocopiumalgae, scope for environmentally induced modification of the cnidarian-algal association is likely constrained by host genotype.
Effects of VCD-induced ovarian failure on single muscle fiber contractility in a mouse model of menopause
Authors: Mashouri Parastoo , Saboune Jinan , Glen Pyle W. , Power Geoffrey A.
Published: April 2023

Objective

Menopause is associated with impairments in muscle contractile function. The temporal and mechanistic basis of this dysfunction are not known. Using a mouse model of menopause we identified how gradual ovarian failure affects single muscle fiber contractility.

Study design

Mice were injected with VCD over 15 days and ovarian failure developed over 120 days. Mice were then sacrificed and slow-type soleus (SOL) and fast-type extensor digitorum longus (EDL) muscles were dissected and chemically permeabilized for mechanical testing.

Main outcome measures

Muscle fiber contractility was assessed via: force, rate of force redevelopment, instantaneous stiffness, and calcium sensitivity across three relative force levels (pCa10,pCa50,pCa90).

Results

Peak force and cross-sectional area (CSA) of the SOL were ∼33% and ∼24% greater in the VCD group as compared with controls (P<0.05), respectively, with no differences in force produced by the EDL fibers across groups (P>0.05). Upon normalizing force to CSA there were no differences across groups (P>0.05). Rate of force development was ∼33% faster for SOL in the VCD group compared to control. Ca2+sensitivity did not differ between groups for either muscle at pCa50(P>0.05). In the VCD group, Ca2+sensitivity was higher for EDL, but lower for SOL at pCa10and pCa90(P<0.05), respectively.

Conclusions

In our mouse model of menopause, alterations to muscle contractility were much less evident as compared with ovariectomized models. This divergence across models highlights the importance of better approximating the natural trajectory of menopause during and after the transitional phase of ovarian failure on neuromuscular function.
Characterization of mitotic phenotypes associated with a MYC synthetic lethal compound
Authors: Shi Qiong , Liu Xuemei , Kalashova Julia , Yang Chenglu , Li Hongmei , Long Yan , Zhang Ting , Zhang Shenqiu , Lv Gang , Huang Jian , Liu Hong , Zhang Jing , Allen Thaddeus D. , Yang Dun
Published: April 2023

Therapeutic targeting of MYC directly has proven difficult, but several means to target MYC indirectly using a synthetic lethal drug approach have been proposed. Synthetic lethal approaches for MYC have sought to take advantage of vulnerabilities MYC imposes related to either metabolic reprogramming, apoptotic signaling or the cycling of cancer cells. Here, we describe in detail the cell division phenotypes induced by a MYC synthetic lethal compound, dimethylfasudil (diMF). DiMF is a known ROCK inhibitor, but structurally related ROCK inhibitors are not synthetic lethal with MYC, so the activity of diMF is not related to blockade of this family of kinases. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe-induced death and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as CENP-F, failed to localize at the metaphase plate, confirming a deficit in centromere assembly. This, presumably, contributed to the development of segregation anomalies in diMF-treated cells. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the centralspindlin complex and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death phenotypes induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.
Inter-user comparison for quantification of superparamagnetic iron oxides with magnetic particle imaging across two institutions highlights a need for standardized approaches
Authors: Good Hayden J. , Sehl Olivia C. , Gevaert Julia J. , Yu Bo , Berih Maryam A. , Montero Sebastian A. , Rinaldi-Ramos Carlos M. , Foster Paula J.
Published: April 2023

Purpose

Magnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions.

Procedures

Six users (3 from each institute) imaged a known amount of Vivotrax+ (10 μg Fe), diluted in a small (10 μL) or large (500 μL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users x triplicate samples x 2 sample volumes x 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax+ quantification, and ROI selection was compared across users, within and across institutions.

Results

MPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax+. Overall quantification yielded measurements that were within ± 20% from ground truth, however SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples.

Conclusions

This study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental set up, image acquisition parameters, and ROI selection analysis.
How Connecting the Legs with a Spring Improves Human Running Economy
Authors: Stingel Jon P. , Hicks Jennifer L. , Uhlrich Scott D. , Delp Scott L.
Published: April 2023

Connecting the legs with a spring attached to the shoelaces reduces the energy cost of running, but how the spring reduces the energy burden of individual muscles remains unknown. We generated muscle-driven simulations of seven individuals running with and without the spring to discern whether savings occurred during the stance phase or the swing phase, and to identify which muscles contributed to energy savings. We computed differences in muscle-level energy consumption, muscle activations, and changes in muscle-fiber velocity and force between running with and without the spring. Across participants, running with the spring reduced the measured rate of energy expenditure by 0.9 W/kg (8.3%). Simulations predicted a 1.4 W/kg (12.0%) reduction in the average rate of energy expenditure and correctly identified that the spring reduced rates of energy expenditure for all participants. Simulations showed most of the savings occurred during stance (1.5 W/kg), though the rate of energy expenditure was also reduced during swing (0.3 W/kg). The energetic savings were distributed across the quadriceps, hip flexor, hip abductor, hamstring, hip adductor, and hip extensor muscle groups, whereas no changes in the rate of energy expenditure were observed in the plantarflexor or dorsiflexor muscles. Energetic savings were facilitated by reductions in the rate of mechanical work performed by muscles and their estimated rate of heat production. The simulations provide insight into muscle-level changes that occur when utilizing an assistive device and the mechanisms by which a spring connecting the legs improves running economy.
Meta-analysis of gene activity (MAGA) contributions and correlation with gene expression, through GAGAM
Authors: Martini Lorenzo , Bardini Roberta , Savino Alessandro , Di Carlo Stefano
Published: April 2023

It is well-known how sequencing technologies propelled cellular biology research in the latest years, giving an incredible insight into the basic mechanisms of cells. Single-cell RNA sequencing is at the front in this field, with Single-cell ATAC sequencing supporting it and becoming more popular. In this regard, multi-modal technologies play a crucial role, allowing the possibility to perform the mentioned sequencing modalities simultaneously on the same cells. Yet, there still needs to be a clear and dedicated way to analyze this multi-modal data. One of the current methods is to calculate the Gene Activity Matrix, which summarizes the accessibility of the genes at the genomic level, to have a more direct link with the transcriptomic data. However, this concept is not well-defined, and it is unclear how various accessible regions impact the expression of the genes. Therefore, this work presents a meta-analysis of the Gene Activity matrix based on the Genomic-Annotated Gene Activity Matrix model, aiming to investigate the different influences of its contributions on the activity and their correlation with the expression. This allows having a better grasp on how the different functional regions of the genome affect not only the activity but also the expression of the genes.
Aberrant centrosome biogenesis disrupts nephron progenitor cell renewal and fate resulting in fibrocystic kidney disease
Authors: Cheng Tao , Agwu Chidera , Shim Kyuhwan , Wang Baolin , Jain Sanjay , Mahjoub Moe R.
Published: April 2023

Mutations that disrupt centrosome structure or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, it remains unclear how mutations in proteins essential for centrosome biogenesis impact embryonic kidney development. Here, we examined the consequences of conditional deletion of a ciliopathy gene,Cep120, in the two nephron progenitor niches of the embryonic kidney.Cep120loss led to reduced abundance of both metanephric mesenchyme and ureteric bud progenitor populations. This was due to a combination of delayed mitosis, increased apoptosis, and premature differentiation of progenitor cells. These defects resulted in dysplastic kidneys at birth, which rapidly formed cysts, displayed increased interstitial fibrosis, and decline in filtration function. RNA sequencing of embryonic and postnatal kidneys from Cep120-null mice identified changes in pathways essential for branching morphogenesis, cystogenesis and fibrosis. Our study defines the cellular and developmental defects caused by centrosome dysfunction during kidney development, and identifies new therapeutic targets for renal centrosomopathies.

Graphical Abstract

Highlights

Defective centrosome biogenesis in nephron progenitors causes:

Reduced abundance of metanephric mesenchyme and premature differentiation into tubular structures

Abnormal branching morphogenesis leading to reduced nephron endowment and smaller kidneys

Changes in cell-autonomous and paracrine signaling that drive cystogenesis and fibrosis

Unique cellular and developmental defects when compared to Pkd1 knockout models