bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of human respiratory viral RNA in wastewater-settled solids
Authors: Zhang Mengyang , Roldan-Hernandez Laura , Boehm Alexandria
Published: March 2024

Wastewater-based epidemiology has emerged as a valuable tool for monitoring respiratory viral diseases within communities by analyzing concentrations of viral nucleic-acids in wastewater. However, little is known about the fate of respiratory virus nucleic-acids in wastewater. Two important fate processes that may modulate their concentrations in wastewater as they move from household drains to the point of collection include sorption or partitioning to wastewater solids and degradation. This study investigated the decay kinetics of genomic nucleic-acids of seven human respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, human rhinovirus (HRV), and influenza A virus (IAV), as well as pepper mild mottle virus (PMMoV) in wastewater solids. Viruses (except for PMMoV) were spiked into wastewater solids and their concentrations were followed for 50 days at three different temperatures (4°C, 22°C, and 37°C). Viral genomic RNA decayed following first-order kinetics with decay rate constants
k
from 0 to 0.219 per day. Decay rate constants
k
were not different from 0 for all targets in solids incubated at 4°C;
k
values were largest at 37°C and at this temperature,
k
values were similar across nucleic-acid targets. Regardless of temperature, there was limited viral RNA decay, with an estimated 0% to 20% reduction, over the typical residence times of sewage in the piped systems between input and collection point (<1 day). The
k
values reported herein can be used directly in fate and transport models to inform the interpretation of measurements made during wastewater surveillance.

IMPORTANCE

Understanding whether or not the RNA targets quantified for wastewater-based epidemiology (WBE) efforts decay during transport between drains and the point of sample collection is critical for data interpretation. Here we show limited decay of viral RNA targets typically measured for respiratory disease WBE.
Structural insights into the Clp protein degradation machinery
Authors: Xu Xiaolong , Wang Yanhui , Huang Wei , Li Danyang , Deng Zixin , Long Feng
Published: March 2024

The Clp protease system is important for maintaining proteostasis in bacteria. It consists of ClpP serine proteases and an AAA+ Clp-ATPase such as ClpC1. The hexameric ATPase ClpC1 utilizes the energy of ATP binding and hydrolysis to engage, unfold, and translocate substrates into the proteolytic chamber of homo- or hetero-tetradecameric ClpP for degradation. The assembly between the hetero-tetradecameric ClpP1P2 chamber and the Clp-ATPases containing tandem ATPase domains from the same species has not been studied in depth. Here, we present cryo-EM structures of the substrate-bound ClpC1:shClpP1P2 from
Streptomyces hawaiiensis
, and shClpP1P2 in complex with ADEP1, a natural compound produced by
S. hawaiiensis
and known to cause over-activation and dysregulation of the ClpP proteolytic core chamber. Our structures provide detailed information on the shClpP1-shClpP2, shClpP2-ClpC1, and ADEP1-shClpP1/P2 interactions, reveal conformational transition of ClpC1 during the substrate translocation, and capture a rotational ATP hydrolysis mechanism likely dominated by the D1 ATPase activity of chaperones.

IMPORTANCE

The Clp-dependent proteolysis plays an important role in bacterial homeostasis and pathogenesis. The ClpP protease system is an effective drug target for antibacterial therapy.
Streptomyces hawaiiensis
can produce a class of potent acyldepsipeptide antibiotics such as ADEP1, which could affect the ClpP protease activity. Although
S. hawaiiensis
hosts one of the most intricate ClpP systems in nature, very little was known about its Clp protease mechanism and the impact of ADEP molecules on ClpP. The significance of our research is in dissecting the functional mechanism of the assembled Clp degradation machinery, as well as the interaction between ADEP1 and the ClpP proteolytic chamber, by solving high-resolution structures of the substrate-bound Clp system in
S. hawaiiensis
. The findings shed light on our understanding of the Clp-dependent proteolysis in bacteria, which will enhance the development of antimicrobial drugs targeting the Clp protease system, and help fighting against bacterial multidrug resistance.
Structural insight into
Escherichia coli
CsgA amyloid fibril assembly
Authors: Bu Fan , Dee Derek R. , Liu Bin
Published: March 2024

The discovery of functional amyloids in bacteria dates back several decades, and our understanding of the
Escherichia coli
curli biogenesis system has gradually expanded over time. However, due to its high aggregation propensity and intrinsically disordered nature, CsgA, the main structural component of curli fibrils, has eluded comprehensive structural characterization. Recent advancements in cryo-electron microscopy (cryo-EM) offer a promising tool to achieve high-resolution structural insights into
E. coli
CsgA fibrils. In this study, we outline an approach to addressing the colloidal instability challenges associated with CsgA, achieved through engineering and electrostatic repulsion. Then, we present the cryo-EM structure of CsgA fibrils at 3.62 Å resolution. This structure provides new insights into the cross-β structure of
E. coli
CsgA. Additionally, our study identifies two distinct spatial arrangements within several CsgA fibrils, a 2-CsgA-fibril pair and a 3-CsgA-fibril bundle, shedding light on the intricate hierarchy of the biofilm extracellular matrix and laying the foundation for precise manipulation of CsgA-derived biomaterials.

IMPORTANCE

The visualization of the architecture of
Escherichia coli
CsgA amyloid fibril has been a longstanding research question, for which a high-resolution structure is still unavailable. CsgA serves as a major subunit of curli, the primary component of the extracellular matrix generated by bacteria. The support provided by this extracellular matrix enables bacterial biofilms to resist antibiotic treatment, significantly impacting human health. CsgA has been identified in members of
Enterobacteriaceae
, with pathogenic
E. coli
being the most well-known model system. Our novel insights into the structure of
E. coli
CsgA protofilaments form the basis for drug design targeting diseases associated with biofilms. Additionally, CsgA is widely researched in biomaterials due to its self-assembly characteristics. The resolved spatial arrangements of CsgA amyloids revealed in our study will further enhance the precision design of functional biomaterials. Therefore, our study uniquely contributes to the understanding of CsgA amyloids for both microbiology and material science.
ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients
Authors: Song Yufeng , Myers Regan , Mehl Frances , Murphy Lila , Brooks Bailey , Wilson Jeffrey M. , Kadl Alexandra , Woodfolk Judith , Zeichner Steven L.
Published: March 2024

Many mechanisms responsible for COVID-19 pathogenesis are well-established, but COVID-19 includes features with unclear pathogenesis, such as autonomic dysregulation, coagulopathies, and high levels of inflammation. The receptor for the SARS-CoV-2 spike protein receptor-binding domain (RBD) is angiotensin-converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop antibodies that have a negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity—ACE2-like abzymes. To explore this hypothesis, we studied patients hospitalized with COVID-19 who had plasma samples available obtained about 7 days after admission. ACE2 is a metalloprotease that requires Zn
2+
for activity. However, we found that the plasma from some patients studied could specifically cleave a synthetic ACE2 peptide substrate, even though the plasma samples were collected using disodium EDTA anticoagulant. When we spiked plasma with synthetic ACE2, no ACE2 substrate cleavage activity was observed unless Zn
2+
was added or the plasma was diluted to decrease EDTA concentration. After processing samples by 100 kDa size exclusion columns and protein A/G adsorption, which depleted immunoglobulin by >99.99%, the plasma samples did not cleave the ACE2 substrate peptide. The data suggest that some patients with COVID-19 develop antibodies with abzyme-like activity capable of cleaving synthetic ACE2 substrate. Since abzymes can exhibit promiscuous substrate specificities compared to the enzyme whose active site image they resemble, and since proteolytic cascades regulate many physiologic processes, anti-RBD abzymes may contribute to some otherwise obscure COVID-19 pathogenesis.

IMPORTANCE

We provide what we believe to be the first description of angiotensin-converting enzyme 2 (ACE2)-like enzymatic activity associated with immunoglobulin in COVID-19 patients. COVID-19 includes many puzzling clinical features that have unclear pathogenesis, including a hyperinflammatory state, abnormalities of the clotting cascade, and blood pressure instability. We hypothesized that some patients with COVID-19 patients may produce antibodies against SARS-CoV-2 with enzymatic activity, or abzymes, that target important proteolytic regulatory cascades. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein binds ACE2 on the surface of the future host cell. This means that the RBD has a negative molecular image of ACE2. We hypothesized that some antibodies produced against the RBD would have, in turn, a negative molecular image of the RBD sufficiently similar to ACE2 to have ACE2-like catalytic activity. In other words, some anti-RBD antibodies would be ACE2-like abzymes. Abzymes elicited by SARS-CoV-2 infection have the potential to affect host physiology.
Alternate typhoid toxin assembly evolved independently in the two
Salmonella
species
Authors: Chemello Antonio J. , Fowler Casey C.
Published: March 2024

AB
5
-type toxins are a diverse family of protein toxins composed of an enzymatic active (A) subunit and a pentameric delivery (B) subunit.
Salmonella enterica
serovar Typhi’s typhoid toxin features two A subunits, CdtB and PltA, in complex with the B subunit PltB. Recently, it was shown that
S
. Typhi encodes a horizontally acquired B subunit, PltC, that also assembles with PltA/CdtB to produce a second form of typhoid toxin.
S
. Typhi therefore produces two AB
5
toxins with the same A subunits but distinct B subunits, an evolutionary twist that is unique to typhoid toxin. Here, we show that, remarkably, the
Salmonella bongori
species independently evolved an analogous capacity to produce two typhoid toxins with distinct B subunits.
S. bongori
’s alternate B subunit, PltD, is evolutionarily distant from both PltB and PltC and outcompetes PltB to form the predominant toxin. We show that, surprisingly,
S. bongori
elicits similar levels of CdtB-mediated intoxication as
S
. Typhi during infection of cultured human epithelial cells. This toxicity is exclusively due to the PltB toxin, and strains lacking
pltD
produce increased amounts of PltB toxin and exhibit increased toxicity compared to the wild type, suggesting that the acquisition of the PltD subunit potentially made
S. bongori
less virulent toward humans. Collectively, this study unveils a striking example of convergent evolution that highlights the importance of the poorly understood “two-toxin” paradigm for typhoid toxin biology and, more broadly, illustrates how the flexibility of A-B interactions has fueled the evolutionary diversification and expansion of AB
5
-type toxins.

IMPORTANCE

Typhoid toxin is an important
Salmonella
Typhi virulence factor and an attractive target for therapeutic interventions to combat typhoid fever. The recent discovery of a second version of this toxin has substantial implications for understanding
S
. Typhi pathogenesis and combating typhoid fever. In this study, we discover that a remarkably similar two-toxin paradigm evolved independently in
Salmonella bongori
, which strongly suggests that this is a critical aspect of typhoid toxin biology. We observe significant parallels between how the two toxins assemble and their capacity to intoxicate host cells during infection in
S
. Typhi and
S. bongori
, which provides clues to the biological significance of this unusual toxin arrangement. More broadly, AB5 toxins with diverse activities and mechanisms are essential virulence factors for numerous important bacterial pathogens. This study illustrates the capacity for novel A-B interactions to evolve and thus provides insight into how such a diverse arsenal of toxins might have emerged.
Phylogenetic lineage dynamics of global parainfluenza virus type 3 post-COVID-19 pandemic
Authors: Lee Kihyun , Park Kuenyoul , Sung Heungsup , Kim Mi-Na
Published: March 2024

During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks of parainfluenza virus type 3 (PIV-3) decreased due to infection control measures. However, a post-pandemic resurgence of PIV-3 has recently been observed. Nonetheless, the role of viral genetic epidemiology, possibly influenced by a genetic bottleneck effect, remains unexplored. We investigated the phylogenetic structure of the publicly available PIV-3 whole-genome and hemagglutinin-neuraminidase (HN) gene sequences spanning the last 65 years, including the COVID-19 pandemic. Sequences were retrieved from the nucleotide database of the National Center for Biotechnology Information using the search term “Human respirovirus 3.” Sequence subsets covering all six genes of PIV-3 or the HN gene were designated as the whole-genome and HN surveillance data sets, respectively. Using these data sets, we constructed maximum-likelihood phylogenetic trees and performed a time-scaled analysis using a Bayesian SkyGrid coalescent prior. A total of 455 whole-genome and 1,139 HN gene sequences were extracted, revealing 10 and 11 distinct lineages, respectively, with >98% concurrence in lineage assignments. During the 2020 COVID-19 pandemic, only three single-lineage clusters were identified in Japan, Korea, and the USA. The inferred year of origin for PIV-3 was 1938 (1903–1963) for the whole-genome data set and 1955 (1930–1963) for the HN gene data set. Our study suggests that PIV-3 epidemics in the post-COVID era are likely influenced by a pandemic-driven bottleneck phenomenon and supports previous hypotheses suggesting s that PIV-3 originated during the early half of the 20th century.

IMPORTANCE

Using publicly available parainfluenza virus type 3 (PIV-3) whole-genome sequences, we estimated that PIV-3 originated during the 1930s, consistent with previous hypotheses. Lineage typing and time-scaled phylogenetic analysis revealed that PIV-3 experienced a bottleneck phenomenon in Korea and the USA during the coronavirus disease 2019 pandemic. We identified the conservative hemagglutinin-neuraminidase gene as a viable alternative marker in long-term epidemiological studies of PIV-3 when whole-genome analysis is limited.
Cultivating efficiency: high-throughput growth analysis of anaerobic bacteria in compact microplate readers
Authors: Snoeyenbos-West Oona L. O. , Guerrero Christina R. , Valencia Makaela , Carini Paul
Published: March 2024

Anaerobic microbes play crucial roles in environmental processes, industry, and human health. Traditional methods for monitoring the growth of anaerobes, including plate counts or subsampling broth cultures for optical density measurements, are time and resource-intensive. The advent of microplate readers revolutionized bacterial growth studies by enabling high-throughput and real-time monitoring of microbial growth kinetics. Yet, their use in anaerobic microbiology has remained limited. Here, we present a workflow for using small-footprint microplate readers and the Growthcurver R package to analyze the kinetic growth metrics of anaerobic bacteria. We benchmarked the small-footprint Cerillo Stratus microplate reader against a BioTek Synergy HTX microplate reader in aerobic conditions using
Escherichia coli
DSM 28618 cultures. The growth rates and carrying capacities obtained from the two readers were statistically indistinguishable. However, the area under the logistic curve was significantly higher in cultures monitored by the Stratus reader. We used the Stratus to quantify the growth responses of anaerobically grown
E. coli
and
Clostridium bolteae
DSM 29485 to different doses of the toxin sodium arsenite. The growth of
E. coli
and
C. bolteae
was sensitive to arsenite doses of 1.3 µM and 0.4 µM, respectively. Complete inhibition of growth was achieved at 38 µM arsenite for
C. bolteae
and 338 µM in
E. coli
. These results show that the Stratus performs similarly to a leading brand of microplate reader and can be reliably used in anaerobic conditions. We discuss the advantages of the small format microplate readers and our experiences with the Stratus.

IMPORTANCE

We present a workflow that facilitates the production and analysis of growth curves for anaerobic microbes using small-footprint microplate readers and an R script. This workflow is a cost and space-effective solution to most high-throughput solutions for collecting growth data from anaerobic microbes. This technology can be used for applications where high throughput would advance discovery, including microbial isolation, bioprospecting, co-culturing, host-microbe interactions, and drug/toxin-microbial interactions.
Evaluation and model to achieve sex parity in cataract surgical coverage in Theni district, India
Authors: Gupta Sachin , Ravindran Ravilla D , Vardhan Ashok , Ravilla Thulasiraj D
Published: March 2024

Background/aims

To propose an approach to determine the target ratio of cataract surgical rates (CSRs) of female to male subpopulations to increase sex parity in cataract surgical coverage (CSC), based on the sex gap in cataract burden and incidence, and demonstrate its application to Theni district, India.

Methods

A population-based longitudinal study between January 2016 and April 2018. We recruited 24 327 participants using random cluster sampling. We conducted detailed eye examinations of 7087 participants aged ≥40 years (4098 females, 2989 males). We fit exponential models to the age-specific and sex-specific cataract burden and estimated annual incidence rates. We developed a spreadsheet-based planning tool to compute the target CSR ratio of female to male subpopulations.

Results

Among those aged ≥40 years, cataract burden was 21.4% for females and 17.5% for males (p<0.05). CSC was 73.9% for females versus 78.6% for males (p<0.05), with an effective CSC of 52.6% for females versus 57.6% for males (p<0.05). Treating only incident cataracts each year requires a target CSR ratio of female to male subpopulations of 1.30, while addressing in addition 10% of the coverage backlog for females and 5% for males requires a target CSR ratio of 1.48.

Conclusions

The female population in Theni district, as in many low-income and middle-income countries, bears a higher cataract burden and lower CSC. To enhance sex parity in coverage, both the higher number of annual incident cataracts and the larger backlog in females will need to be addressed.
Using drones to measure the status of cavity-nesting raptors
Authors: Bird David M. , Petalas Christina , Pace Paul , Elliott Kyle H.
Published: March 2024

Many wildlife species, including hole-nesting raptors, occupy cavities that are challenging or unsafe for observers to examine. We conducted field tests using an inexpensive, off-the-shelf camera attached to an affordable commercial drone to assess the reproductive success of American kestrels ( Falco sparverius), a small, cavity-nesting raptor. Specifically, we developed a system that consisted of (1) a wireless mini camera transmitting images to an observer’s phone and (2) a Mini-Mavic 2 drone controlled through direct line-of-sight piloting. Following successful preliminary flights involving chicken eggs and other inanimate objects, we field-tested the system in two kestrel nest boxes in the wild. The system accurately recorded the contents of all nest boxes during the trials, provided the wind speed remained below approximately 2.5 m/s (5 knots). However, wind speeds at this level were observed only 40% of the days in our study area during kestrel breeding, which limited the surveying opportunities. Our system offers a promising method for surveying wildlife inhabiting inaccessible cavities.
Cosmology of f(Q) gravity in non-flat Universe
Authors: Shabani Hamid , De Avik , Loo Tee-How , Saridakis Emmanuel N.
Published: March 2024

We investigate the cosmological implications of f(Q) gravity, which is a modified theory of gravity based on non-metricity, in non-flat geometry. We perform a detailed dynamical-system analysis keeping the f(Q) function completely arbitrary. As we show, the cosmological scenario admits a dark-matter dominated point, as well as a dark-energy dominated de Sitter solution which can attract the Universe at late times. However, the main result of the present work is that there are additional critical points which exist solely due to curvature. In particular, we find that there are curvature-dominated accelerating points which are unstable and thus can describe the inflationary epoch. Additionally, there is a point in which the dark-matter and dark-energy density parameters are both between zero and one, and thus it can alleviate the coincidence problem. Finally, there is a saddle point which is completely dominated by curvature. In order to provide a specific example, we apply our general analysis to the power-law case, showing that we can obtain the thermal history of the Universe, in which the curvature density parameter may exhibit a peak at intermediate times. These features, alongside possible indications that non-zero curvature could alleviate the cosmological tensions, may serve as advantages for f(Q) gravity in non-flat geometry.
A Population Initialization Method Based on Similarity and Mutual Information in Evolutionary Algorithm for Bi-Objective Feature Selection
Authors: Cai Xu , Xue Yu
Published: March 2024

Feature selection (FS) is an important data pre-processing technique in classification. It aims to remove redundant and irrelevant features from the data, which reduces the dimensionality of data and improves the performance of the classifier. Thus, FS is a bi-objective optimization problem, and evolutionary algorithms (EAs) have been proven to be effective in solving bi-objective FS problems. EA is a population-based metaheuristic algorithm, and the quality of the initial population is an important factor affecting the performance of EA. An improper initial population may negatively affect the convergence speed of the EA and even make the algorithm fall into the local optimum. In this article, we propose a similarity and mutual information-based initialization method, named SMII, to improve the quality of the initial population. This method determines the distribution of initial solutions based on similarity and shields features with high correlation to the selected features according to mutual information. In the experiment, we embed SMII, the latest four initialization methods, and a traditional random initialization method into NSGA-II and compared their performance on 15 public datasets. The experimental results show that SMII performs best on most datasets and can effectively improve the performance of the algorithm. Moreover, we compare the performance of two other EAs before and after embedding SMII on 15 datasets, and the results further prove that the proposed method can effectively improve the search capability of the EA for FS.
A Rapid and Easy Procedure of Enzyme Biosensor based on Nitrogen-Doped Graphene for Detection of Methyl Parathion in CHM
Authors: Sun Bolu , Yu Shixing , Ma Quhuan , Shi Hongxia , Dang Qiaoning , Liu Yuhong , Hu Jiali , Bao Liangrong , Yang Lin , Shi Xiaofeng
Published: March 2024

Methyl parathion (MP), an organophosphorus pesticide that is frequently used to control pests during the planting process of Chinese herbal medicine (CHM), has been used without sufficient control, leading to excessive residues on the surface of CHM, which has a serious impact on the quality and safety of CHM and their preparations. Consequently, it is crucial to carefully control MP during the cultivation, processing, and manufacture of CHM. Based on this, nitrogen-doped graphene (N-Gr) with a high conductivity and chitosan (CS) with good stability were used to modify the glassy carbon electrode (GCE). Subsequently, the prussian blue (PB) with catalytic activity and gold nanoparticles (AuNPs) with excellent biocompatibility were deposited by the electrodeposition method to form the AuNPs/PB/CS@N-Gr/GCE. Then, the acetylcholinesterase (AChE) was effectively immobilized on the electrode surface by covalent bonding between AuNPs and AChE through gold-sulfhydryl bonds. Finally, a rapid and easy procedure of enzyme biosensor (AChE/AuNPs/PB/CS@N-Gr/GCE) for sensitive detection of MP pesticide residues was fabricated. Herein, PB catalyzes the redox reaction of thiocholine, which is produced when acetylthiocholine iodide (ATCHI) undergoes efficient hydrolysis catalyzed by AChE. This process effectively promoted electron transfer, amplifying the sensor’s response signal. After the experimental conditions are optimized, the limit of detection (LOD) for MP is found to be 9.47 × 10−5
μg ml−1. Exhibits a good linear relationship within the concentration range of 1 × 10−3
μg ml−1 ∼ 1 × 101
μg ml−1. Significantly, the fabricated enzyme biosensor excels in swiftly and sensitively detecting trace amounts of MP in real examples. Furthermore, it exhibits robust stability and reproducibility. The excellent performance of this enzyme biosensor not only offers a rapid and easy way to identify and find minute amounts of trace MP pesticide residues in CHM, but also serves as a technical guide for the creation of new, portable, and on-site pesticide residue detection technology for law enforcement.
Understanding the Corrosion Behaviour of Steel Under Alternate Oil/Water Wetting with Different Oil Viscosities
Authors: Ma W. L. , Wang H. X. , Neville A. , Hua Y.
Published: March 2024

The corrosion behaviour of steel under alternate wetting conditions with various oil viscosities was investigated by an “alternate wetting cell,” combined with electrochemistry measurements, contact angle measurements, and molecular dynamics simulation. Under static conditions, corrosion was mitigated more efficiently with an increase of viscosity, because a large static friction force between high-viscosity oil and the steel surface prolongs the oil film lifetime and oil wetting time. Under dynamic conditions, the effect of oil viscosity on the corrosion and wetting behaviour of carbon steel was not dominated in comparison to that of the static conditions.
Effect of TiO2 Abutment Coatings on Peri‐Implant Soft Tissue Behavior: A Systematic Review of In Vivo Studies
Authors: Areid Nagat , Abushahba Faleh , Riivari Sini , Närhi Timo
Published: March 2024

Establishing a proper soft tissue adhesion around the implant abutment is essential to prevent microbial invasion, inhibit epithelial downgrowth, and obtain an optimal healing process. This systematic review aims to evaluate the real potential of TiO2 coating on the behavior of peri‐implant soft tissue health and maintenance. A specific aim was to evaluate clinically and histologically the effect of TiO2 abutment coating on epithelial and connective tissue attachment. Electronic database searches were conducted from 1990 to 2023 in MEDLINE/PubMed and the Web of Science databases. In total, 15 out of 485 publications were included. Eight studies involved humans, and seven were animal studies. Exposure time ranges from 2 days to 5 years. The peri‐implant soft tissue evaluations included clinical assessment (plaque index (PI), peri‐implant probing pocket depth (PPD), and bleeding on probing (BoP)), histological as well as histomorphometric analysis. The Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies was used to evaluate the overall quality of the studies included in the review. The results showed some variation but remained within acceptable limits. Within the limitations of this systematic review, the present findings suggest that TiO2 coatings seem to influence soft tissue healing. TiO2‐coated abutments with a roughness value between 0.2 and 0.5 μm enhance soft tissue health. Sol‐gel‐derived TiO2 coatings induced better soft tissue attachment than noncoated machined abutment surfaces. The anodized titanium abutments demonstrate comparable clinical and histological outcomes to conventional machined abutments. However, there was variation among the included studies concerning TiO2 coating characteristics and the measured outcomes used to evaluate the soft tissue response, and therefore, quantitative analysis was not feasible. Long‐term in vivo studies with standardized soft tissue analysis and coating surface parameters are necessary before a definitive conclusion can be drawn. OSF Registration No.: 10.17605/OSF.IO/E5RQV.
Xevinapant Combined with Pembrolizumab in Patients with Advanced, Pretreated, Colorectal and Pancreatic Cancer: Results of the Phase Ib/II CATRIPCA Trial
Authors: Voisin Allison , Terret Catherine , Schiffler Camille , Bidaux Anne-Sophie , Vanacker Hélène , Perrin-Niquet Marlène , Barbery Maud , Vinceneux Armelle , Eberst Lauriane , Stéphan Pierre , Garin Gwenaële , Spaggiari Dany , Pérol David , Grinberg-Bleyer Yenkel , Cassier Philippe A.
Published: March 2024

Purpose:

Xevinapant is an orally available inhibitor of apoptosis proteins (IAP) inhibitor. Preclinical data suggest that IAP antagonism may synergize with immune checkpoint blockers by modulating the NFκB pathway in immune cells.

Patients and Methods:

Adult patients with non–high microsatellite instability advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer were enrolled in this phase Ib/II study and received pembrolizumab 200 mg every 3 weeks intravenously, and ascending doses of oral xevinapant (100, 150, and 200 mg daily for 14 days on/7 days off). Dose escalation followed a 3+3 design with a 21-day dose-limiting toxicity (DLT) evaluation period. Following the determination of the recommended phase II dose (RP2D), 14 patients with PDAC and 14 patients with colorectal cancer were enrolled in expansion cohorts to assess preliminary efficacy.

Results:

Forty-one patients (26 males) with a median age of 64 years were enrolled: 13 in the dose escalation and 28 in the two expansion cohorts. No DLT was observed during dose escalation. The RP2D was identified as xevinapant 200 mg/day + pembrolizumab 200 mg every 3 weeks. The most common adverse events (AE) were fatigue (37%), gastrointestinal AE (decreased appetite in 37%, nausea in 24%, stomatitis in 12%, and diarrhea and vomiting in 10% each), and cutaneous AE (pruritus, dry skin, and rash seen in 20%, 15%, and 15% of patients, respectively). The best overall response according to RECIST1.1 was partial response (confirmed) in 1 (3%), stable disease in 4 (10%), and progressive disease in 35 (88%).

Conclusions:

Xevinapant combined with pembrolizumab was well tolerated with no unexpected AEs. However, antitumor activity was low.
Autophagy Induced by Low Shear Stress Leads to Endothelial Glycocalyx Disruption
Authors: Lin Lina , Gao Wei , Feng Linya , Wang Chundong , Yang Ruiqi , Wang Weijian , Wu Qiaolin
Published: March 2024

Introduction: Previous studies have confirmed that low shear stress (LSS) induces glycocalyx disruption, leading to endothelial dysfunction. However, the role of autophagy in LSS-induced glycocalyx disruption and relevant mechanism are not clear. In this study, we hypothesized that LSS may promote autophagy, disrupting the endothelium glycocalyx. Methods: Human umbilical vein endothelial cells were subjected to physiological shear stress and LSS treatments, followed by the application of autophagy inducers and inhibitors. Additionally, cells were treated with specific matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) inhibitor. The expression of autophagic markers, glycocalyx, MMP-2, and MMP-9 was measured. Results: LSS impacted the expression of endothelium autophagy markers, increasing the expression of LC3II.LC3I−1 and Beclin−1, and decreasing the levels of p62, accompanied by glycocalyx disturbance. Moreover, LSS upregulated the expression of MMP-2 and MMP-9 and downregulated the levels of syndecan-1 and heparan sulfate (HS). Additionally, expression of MMP-2 and MMP-9 was increased by an autophagy promoter but was decreased by autophagy inhibitor treatment under LSS. Autophagy and MMP-2 and MMP-9 further caused glycocalyx disruption. Conclusion: LSS promotes autophagy, leading to glycocalyx disruption. Autophagy increases the expression of MMP-2 and MMP-9, which are correlated with the glycocalyx destruction induced by LSS.
Postoperative Ileus after Minimally Invasive Colorectal Surgery: A Summary of Current Strategies for Prevention and Management
Authors: Abernethy Eve K. , Aly Emad H.
Published: March 2024

Background: Postoperative ileus (POI) is one of the most common postoperative complications after colorectal surgery and prolongs hospital stays. Minimally invasive surgery (MIS) has reduced POI, but it remains common. This review explores the current methods for preventing and managing POI after MIS. Summary: Preoperative interventions, including optimising nutrition, preoperative medicationn, and mechanical bowel preparation with oral antibiotics, may have a role in preventing POI. Transversus abdominis plane blocks and lidocaine could replace epidural analgesia in MIS. Fluid overload should be avoided; in some cases, goal-directed fluid therapy may aid in achieving this. Pharmacological agents, such as prucalopride and dexmedetomidine, could target mechanisms underlying POI. New strategies to stimulate vagal nerve activity may promote postoperative gastrointestinal motility. Preoperative bowel stimulation could potentially reduce POI following loop ileostomy closure. However, the evidence base for several interventions remains weak and requires further corroboration with robust studies. Key Messages: Despite the increasing use of MIS, POI remains a major issue following colorectal surgery. Further strategies to prevent POI are rapidly emerging. Studies using standardised definitions and perioperative care will help validate these interventions and remove barriers to accurate meta-analysis. Future studies should focus on establishing the impact of these interventions on POI after MIS specifically.
Solitary Clear Cell Renal Cell Carcinoma Metastasis to the Eyelid: A Case Report
Authors: Zrinšćak Ognjen , Kasumović Armin , Krolo Iva , Ivekovic Renata , Malenica Ravlić Maja , Tomašković Igor , Vatavuk Zoran
Published: March 2024

Introduction: This study is a case of solitary clear cell renal cell carcinoma (ccRCC) eyelid metastasis in a 66-year-old man as the first sign of a primary tumor. ccRCC usually spreads to the lungs, mediastinum, bones, liver, and brain, while ocular metastases are rare. Case Presentation: Solitary metastasis presented as a solid mass in the central third of the upper eyelid, which has been growing for 3 weeks. Treatment included tumor removal and blepharoplasty. Histopathological examination showed metastasis of clear cell renal carcinoma. A thorough examination revealed a primary tumor on the lower pole of the right kidney. A right nephrectomy was performed, and histopathology showed ccRCC. Postoperative examinations showed no signs of local or systemic disease. Sunitinib malate was administered to the patient. Conclusion: The eyelid metastasis in this case was still solitary and had been discovered before the existence of the primary tumor was known. Ocular metastasis of renal carcinoma is a rare initial manifestation of the disease and therefore requires a multidisciplinary approach in the treatment of these patients.
Less Invasive Surfactant Administration Compared to Intubation, Surfactant, Rapid Extubation Method in Preterm Neonates: An Umbrella Review
Authors: Kuitunen Ilari , Räsänen Kati
Published: March 2024

Introduction: In spontaneously breathing neonates, surfactant can be administered via thin catheter while enabling the own breathing (less invasive surfactant administration [LISA]). Alternatively, the neonate is intubated for surfactant delivery (intubation, surfactant, rapid extubation [INSURE]). Thus, the aim was to provide an overview of the efficacy of the LISA compared to INSURE. Methods: We performed an umbrella review of previous meta-analyses including randomized controlled trials. We searched PubMed, Scopus, and Web of Science in July 2023. Two authors screened the search results, and systematic reviews with meta-analyses that focused on LISA versus INSURE were included. One author extracted, and another author validated the extracted data. AMSTAR-2 and ROBIS evaluations were performed by two authors independently. Results: A total of 9 systematic reviews with meta-analyses were included. The quality according to AMSTAR-2 was high in one, moderate in one, low in three, and critically low in four. According to ROBIS, the risk of bias was low in three and high in six of the reviews. LISA was more effective than INSURE in preventing mechanical ventilation (8/8 reviews), death or BPD (4/4 reviews), death (3/9 reviews), and BPD (3/9 reviews). Conclusions: All the included systematic reviews and meta-analyses reported LISA to be more effective than INSURE in terms of need for mechanical ventilation and death or BPD. However, the quality of the published systematic reviews has been mostly deficient. Future systematic reviews should focus on reporting quality.
Die translationale Revolution bei der atopischen Dermatitis: Der Paradigmenwechsel von der Pathogenese zur Behandlung
Authors: Facheris Paola , Jeffery Jane , Del Duca Ester , Guttman-Yassky Emma
Published: March 2024

Die atopische Dermatitis (AD) ist die häufigste entzündliche Haut­erkrankung und gilt als komplexe und heterogene Erkrankung. Kürzlich wurden verschiedene AD-Phänotypen beschrieben, die nach dem Alter des Patienten zu Beginn, dem ethnischen Hintergrund, der Krankheitsdauer und anderen Krankheitsmerkmalen definiert wurden und der Notwendigkeit eines personalisierten Behandlungsansatzes zugrunde liegen. Jüngste Fortschritte beim Verständnis der AD-Pathogenese führten zu einer echten translationalen Revolution und zu einer exponentiellen Erweiterung der therapeutischen Pipeline. Die Untersuchung von Biomarkern in klinischen Studien zu neuen Behandlungen trägt dazu bei, die Rolle jedes Zytokins und Immunwegs bei der AD zu klären und wird es ermöglichen, den einzigartigen immunologischen Fingerabdruck jeder AD-Untergruppe zu adressieren. Die personalisierte Medizin wird das ultimative Ziel dieser gezielten translationalen Forschung sein. In dieser Übersichtsarbeit diskutieren wir die Veränderungen in den Konzepten sowohl der Pathogenese als auch des Behandlungsansatzes für AD, heben die wissenschaftliche Begründung für jede zielgerichtete Behandlung hervor und berichten über die neuesten klinischen Daten zur Wirksamkeit.
Diagnostic Performance of Angiography-Derived Quantitative Flow Ratio in Complex Coronary Lesions
Authors: Wu Xianpeng , Wang Kan , Li Guohua , Wu Jie , Jiang Jun , Gao Feng , Zhu Lingjun , Xu Qiyuan , Wang Xinhong , Xu Mengxi , Chen Hui , Ma Longhui , Han Xianjun , Luo Nan , Tu Shengxian , Wang Jian’an , Hu Xinyang
Published: March 2024

BACKGROUND:

Quantitative flow ratio derived from computed tomography angiography (CT-QFR) and invasive coronary angiography (Murray law–based quantitative flow ratio [μQFR]) are novel approaches enabling rapid computation of fractional flow reserve without the use of pressure guidewires and vasodilators. However, the feasibility and diagnostic performance of both CT-QFR and μQFR in evaluating complex coronary lesions remain unclear.

METHODS:

Between September 2014 and September 2021, 240 patients with 30% to 90% coronary diameter stenosis who underwent both coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve within 60 days were retrospectively enrolled. The diagnostic performance of CT-QFR and μQFR in detecting functional ischemia among all lesions, especially complex coronary lesions, was analyzed using fractional flow reserve as the reference standard.

RESULTS:

CT-QFR and μQFR analyses were performed on 309 and 289 vessels, respectively. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for CT-QFR in all lesions at the per-vessel level were 91% (with a 95% CI of 84%–96%), 92% (95% CI, 88%–95%), 83% (95% CI, 75%–90%), 96% (95% CI, 93%–98%), and 92% (95% CI, 88%–95%), with values for μQFR of 90% (95% CI, 81%–95%), 97% (95% CI, 93%–99%), 92% (95% CI, 84%–97%), 96% (95% CI, 92%–98%), and 94% (95% CI, 91%–97%), respectively. Among bifurcation, tandem, and moderate-to-severe calcified lesions, the diagnostic values of CT-QFR and μQFR showed great correlation and agreement with those of invasive fractional flow reserve, achieving an area under the receiver operating characteristic curve exceeding 0.9 for each complex lesion at the vessel level. Furthermore, the accuracies of CT-QFR and μQFR in the gray zone were 85% and 84%, respectively.

CONCLUSIONS:

Angiography-derived quantitative flow ratio (CT-QFR and μQFR) demonstrated remarkable diagnostic performance in complex coronary lesions, indicating its pivotal role in the management of patients with coronary artery disease.
Cardiac Magnetic Resonance to Predict Cardiac Mass Malignancy: The CMR Mass Score
Authors: Paolisso Pasquale , Bergamaschi Luca , Angeli Francesco , Belmonte Marta , Foà Alberto , Canton Lisa , Fedele Damiano , Armillotta Matteo , Sansonetti Angelo , Bodega Francesca , Amicone Sara , Suma Nicole , Gallinoro Emanuele , Attinà Domenico , Niro Fabio , Rucci Paola , Gherbesi Elisa , Carugo Stefano , Mushtaq Saima , Baggiano Andrea , Pavon Anna Giulia , Guglielmo Marco , Conte Edoardo , Andreini Daniele , Pontone Gianluca , Lovato Luigi , Pizzi Carmine
Published: March 2024

BACKGROUND:

Multimodality imaging is currently suggested for the noninvasive diagnosis of cardiac masses. The identification of cardiac masses’ malignant nature is essential to guide proper treatment. We aimed to develop a cardiac magnetic resonance (CMR)-derived model including mass localization, morphology, and tissue characterization to predict malignancy (with histology as gold standard), to compare its accuracy versus the diagnostic echocardiographic mass score, and to evaluate its prognostic ability.

METHODS:

Observational cohort study of 167 consecutive patients undergoing comprehensive echocardiogram and CMR within 1-month time interval for suspected cardiac mass. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, by histology or radiological resolution after adequate anticoagulation treatment. Logistic regression was performed to assess CMR-derived independent predictors of malignancy, which were included in a predictive model to derive the CMR mass score. Kaplan-Meier curves and Cox regression were used to investigate the prognostic ability of predictors.

RESULTS:

In CMR, mass morphological features (non-left localization, sessile, polylobate, inhomogeneity, infiltration, and pericardial effusion) and mass tissue characterization features (first-pass perfusion and heterogeneity enhancement) were independent predictors of malignancy. The CMR mass score (range, 0–8 and cutoff, ≥5), including sessile appearance, polylobate shape, infiltration, pericardial effusion, first-pass contrast perfusion, and heterogeneity enhancement, showed excellent accuracy in predicting malignancy (areas under the curve, 0.976 [95% CI, 0.96–0.99]), significantly higher than diagnostic echocardiographic mass score (areas under the curve, 0.932;
P
=0.040). The agreement between the diagnostic echocardiographic mass and CMR mass scores was good (κ=0.66). A CMR mass score of ≥5 predicted a higher risk of all-cause death (
P
<0.001; hazard ratio, 5.70) at follow-up.

CONCLUSIONS:

A CMR-derived model, including mass morphology and tissue characterization, showed excellent accuracy, superior to echocardiography, in predicting cardiac masses malignancy, with prognostic implications.
Local agricultural by-products for rearing superworm larvae (Zophobas morio): a Greek example
Authors: Gourgouta M. , Rumbos C.I. , Oonincx D.G.A.B. , Adamaki-Sotiraki C. , Karapanagiotidis I.T. , Athanassiou C.G.
Published: March 2024

As the industrial insect production sector is rapidly growing, the high production cost of insects forms a constraint for the further growth of the insect industry. One of the main factors that greatly contributes to the total insect production cost and affects the profitability of insect farms is feed costs. Various agricultural by-products have been successfully evaluated and proposed as low-cost, alternative, insect feedstocks. In this context, this study evaluates a variety of Greek agricultural by-products as feeding substrates for Zophobas morio (F.) (Coleoptera: Tenebrionidae) larvae. More specifically, eleven agricultural by-products derived from the seed cleaning process of barley, oats, peas and vetch and the production of cotton, sugar beet and sunflower, were utilized singly and as components of compound isonitrogenous diets at two nitrogen levels (2.7% and 3.2% on dry matter basis). The results showed that larvae reared on sunflower meal, oat and barley (class II) by-products performed well in terms of larval growth and survival. In contrast, for most other diets tested high mortality rates were recorded, indicating the necessity for the formulation of diets that meet the nutritional requirements of the larvae. Our study highlights the potential of locally available by-products for the rearing of Z. morio larvae and contributes to determining their nutrient requirements.
A revision of Megagraphydrus Hansen (Coleoptera, Hydrophilidae): synonymization with Agraphydrus Régimbart and description of seven new species
Authors: MINOSHIMA YÛSUKE N. , KOMAREK ALBRECHT , ÔHARA MASAHIRO
Published: March 2024

The genus Megagraphydrus Hansen, 1999 is revised. Eleven of the twelve previously described species are recognized as valid, with Megagraphydrus wangi Hebauer, 2000 syn. nov. found to be a junior synonym of M. politus Hansen, 1999. Most significantly, Megagraphydrus itself is found to be a junior synonym of Agraphydrus Régimbart, 1903. The species are assigned to the subgenus Agraphydrus. This nomenclatural act results in the following new combinations: Agraphydrus (Agraphydrus) anhuianus (Hebauer, 2000) comb. nov., A. (A.) attenuatus (Hansen, 1999) comb. nov., A. (A.) jaechi (Hansen, 1999) comb. nov., A. (A.) luteilateralis (Minoshima & Fujiwara, 2009) comb. nov., A. (A.) malayanus (Hebauer, 2000) comb. nov., A. (A.) politus (Hansen, 1999) comb. nov., A. (A.) puzhelongi (Jia, 2010) comb. nov., A. (A.) regularis (Hansen, 1999) comb. nov., A. (A.) siamensis (Hansen, 1999) comb. nov., A. (A.) superans (Hebauer, 2000) comb. nov., and A. (A.) uvaensis (Hebauer, 2000) comb. nov. All species are redescribed with the exclusion of A. superans, A. luteilateralis, and A. puzhelongi. Seven new species are described: Agraphydrus (Agraphydrus) biprojectus sp. nov., A. (A.) coronarius sp. nov., A. (A.) decipiens sp. nov., A. (A.) insidiator sp. nov., A. (A.) masatakai sp. nov., A. (A.) montanus sp. nov., A. (A.) thaiensis sp. nov. Digital and SEM photographs are provided, and the male and female genital segments are illustrated and described.