bluuebunny/crossref_metadata_2025 huggingface dataset:
MacP bypass variants of
Streptococcus pneumoniae
PBP2a suggest a conserved mechanism for the activation of bifunctional cell wall synthases
Authors: Midonet Caroline , Bisset Sean , Shlosman Irina , Cava Felipe , Rudner David Z. , Bernhardt Thomas G.
Published: October 2023

The peptidoglycan (PG) layer protects bacteria from osmotic lysis and defines their shape. The class A penicillin-binding proteins (aPBPs) are PG synthases that possess both glycan polymerization and crosslinking activities needed for PG biogenesis. In Gram-negative bacteria, aPBPs require activation by outer membrane lipoproteins, which are thought to stimulate their cognate synthase by inducing conformational changes that promote polymerase function. How aPBPs are controlled in Gram-positive bacteria is less clear. One of the few known regulators is MacP in
Streptococcus pneumoniae
(
Sp
). MacP is required for the activity of
Sp
PBP2a, but its mode of action has been obscure. We therefore selected for PBP2a variants capable of functioning in the absence of MacP. Amino acid substitutions that bypassed the MacP requirement for PBP2a function
in vivo
also activated its polymerase activity
in vitro
. Many of these changes mapped to the interface between the transmembrane (TM) helix and polymerase domain in a model PBP2a structure. This region is conformationally flexible in the experimentally determined structures of aPBPs and undergoes a structural transition upon binding the substrate-mimicking drug moenomycin. Our findings suggest that MacP promotes PG polymerization by altering the TM-polymerase domain interface in PBP2a and that this mechanism for aPBP activation may be broadly conserved. Furthermore,
Sp
cells expressing an activated PBP2a variant displayed heterogeneous shapes, highlighting the importance of proper aPBP regulation in cell morphogenesis.

IMPORTANCE

Class A penicillin-binding proteins (aPBPs) play critical roles in bacterial cell wall biogenesis. As the targets of penicillin, they are among the most important drug targets in history. Although the biochemical activities of these enzymes have been well studied, little is known about how they are regulated in cells to control when and where peptidoglycan is made. In this report, we isolate variants of the
Streptococcus pneumoniae
enzyme PBP2a that function in cells without MacP, a partner normally required for its activity. The amino acid substitutions activate the cell wall synthase activity of PBP2a, and their location in a model structure suggests an activation mechanism for this enzyme that is shared with aPBPs from distantly related organisms with distinct activators.
High-quality full genome assembly of historic
Xylella fastidiosa
strains from ICMP collection using a hybrid sequencing approach
Authors: Kant Pragya , Brohier Natasha , Mann Rachel , Rigano Luciano , Taylor Robert , Wong-Bajracharya Johanna , Chapman Toni A. , Kehoe Monica , Roach Rebecca , Rodoni Brendan , Constable Fiona
Published: October 2023

High-quality complete genomes of five
Xylella fastidiosa
strains were assembled by combining Nanopore and Illumina sequencing data. Among these, International Collection of Micro-organisms from Plants (ICMP) 8731, ICMP 8742 and ICMP 8745 belong to subspecies
fastidiosa
while ICMP 8739 and ICMP 8740 were determined as subspecies
multiplex
. The strains were further classified into sequence types.
Metagenome-assembled genomes from sugarcane mill mud
Authors: Uchimiya Minori , Elliott Leah E. , Derito Christopher M. , Hay Anthony G.
Published: October 2023

The genomes of 11 bacteria and 3 archaea were assembled from metagenomic DNA extracted from sugarcane mill mud. These metagenome-assembled genomes ranged from 1.79 to 6.45 Mb, with 2,263 to 5,551 predicted proteins, 80.65% to 100% genome completeness, and 43.19% to 68.02% G+C content.
Draft genomes of 16
Bartonella henselae
strains from cats in Valdivia, Chile
Authors: Sepulveda Paulina , Stegger Marc , Monti Gustavo , Canales Nivia , Mella Armin , Butaye Patrick , Müller Ananda
Published: October 2023

Bartonella henselae
is a primary zoonotic agent, having cats as asymptomatic reservoirs. In humans, it causes cat scratch disease. Here, we report the whole genome sequences of 16 strains isolated from cats in Valdivia city, Southern Chile. Strains showed little variability in the multilocus sequence typing profiles.
Genome sequences of Phasi Charoen-like phasivirus and Fako virus from
Aedes aegypti
mosquitoes collected in coastal Kenya
Authors: Langat Solomon K. , Kerich Gladys , Cinkovich Stephanie , Johnson Jaree , Ambale Janet , Yalwala Santos , Opot Benjamin , Garges Eric , Ojwang Elly , Eyase Fredrick
Published: October 2023

We report the sequencing of two viruses, Phasi Charoen-like phasivirus (PCLV) and Fako virus (FAKV), which were detected in a pool of
Aedes aegypti
from Kenya. Analysis showed a high similarity of PCLV to publicly available PCLV genomes from Kenya. FAKV showed a high genetic divergence from publicly available FAKV genomes.
Rapid bacteriolysis of
Staphylococcus aureus
by lysin exebacase
Authors: Vila-Farres Xavier , Sauve Karen , Oh Jun , Swift Steven , DeJonge Boudewijn , Ambler Jane E. , Schuch Raymond
Published: October 2023

Lysins (peptidoglycan hydrolases) are promising new protein-based antimicrobial candidates under development to address rising antibiotic resistance encountered among pathogenic bacteria. Exebacase is an antistaphylococcal lysin and the first member of the lysin class to have entered clinical trials in the United States. In this study, the bacteriolytic activity of exebacase was characterized with time-kill assays, turbidity reduction assays, and microscopy. Three methicillin-susceptible
Staphylococcus aureus
and three methicillin-resistant
S. aureus
isolates were tested in time-kill assays over a range of concentrations from 0.25 to 8 × MIC. Exebacase demonstrated a concentration-dependent killing and showed bactericidal activity (≥3 log
10
kill achieved relative to the starting inoculum) within 3 h at 1 × MIC against all strains tested. Dose-dependent lysis by exebacase was, furthermore, observed in the turbidity reduction assay, wherein decreases in initial OD
600
of 50% were observed within ~15 min at concentrations as low as 4 µg/mL. Membrane dissolution, loss of cytoplasmic material, and lysis were confirmed by video and electron microscopy. The demonstrated rapid bacteriolytic effect of exebacase is an important distinguishing feature of this novel modality.

IMPORTANCE

To guide the development of an investigational new antibacterial entity, microbiological data are required to evaluate the killing kinetics against target organism(s). Exebacase is a lysin (peptidoglycan hydrolase) that represents a novel antimicrobial modality based on degradation of the cell wall of
Staphylococcus aureus
. Killing by exebacase was determined in multiple assay formats including time-kill assays, wherein reductions of viability of ≥3 log
10
colony-forming units/mL were observed within 3 h for multiple different isolates tested, consistent with very rapid bactericidal activity. Rapid reductions in optical density were likewise observed in exebacase-treated cultures, which were visually consistent with microscopic observations of rapid lysis. Overall, exebacase provides a novel antimicrobial modality against
S. aureus
, characterized by a rapid cidal and lytic activity.
Population Dynamics and Distribution of the Lake Smelt, a Dwarf Form of the European Smelt Osmerus eperlanus (Osmeridae), and the Black Sea Sprat Clupeonella cultriventris (Clupeidae) while Cohabiting the Rybinsk Reservoir
Authors: Gerasimov Yu. V. , Komarova A. S. , Tarleva A. F. , Solomatin Yu. I. , Bazarov M. I. , Borisenko E. S.
Published: October 2023

The data for a 23-year period (2000–2022) on the population dynamics and distribution of the lake smelt (a form of the European smelt Osmerus eperlanus) and the Black Sea sprat Clupeonella cultriventris in the Rybinsk Reservoir have been summarized. The lake smelt dominated the reservoir pelagial from the 1950s to the mid-1990s. An anomalously low water level in the reservoir in 1996 and abnormal (for this reservoir) water warming in subsequent years led to elimination of the species from the reservoir ichthyofauna in 2002. The Black-Sea sprat invaded the reservoir in the mid-1990s; its population irruption occurred in the early 2000s (during the depressed state of the smelt population). Currently, this species dominates in the pelagial of the reservoir. Since the early 2000s there were noted two periods when the lake smelt was found in practically all parts of the Rybinsk Reservoir and the sprat abundance was also high. However, high water temperatures in 2010 and 2021, as well as low level in 2014, resulted in almost complete disappearance of the lake smelt disappeared. During the periods of cohabitation of the studied species, a significant similarity in the diet of individuals of both species with the size of up to 80 mm has been noted. The larger smelt fed on larger plankton, and in the summer also on fish. Currently, the main limiting factor negatively affecting the recovery of the smelt population in the Rybinsk Reservoir is the abnormal heating of the water column in some years.
Lipid Profile of the Muscle Tissue of Some Mesopelagic Fish Species of the Families Stomiidae and Myctophidae from Different Depths of the Irminger Sea, North Atlantic
Authors: Voronin V. P. , Artemenkov D. V. , Orlov A. M. , Murzina S. A.
Published: October 2023

For the first time the qualitative and quantitative lipid profile (total lipids and polar and nonpolar lipids) of the muscle tissue of six mesopelagic fish species, which are representatives of two deep-sea families widespread in the World Ocean: Stomiidae and Myctophidae were studied. It was found the species specificity of lipid accumulation for the studied fishes, which indicates differences in the mechanisms of compensatory responses. Triacylglycerols are the main form of lipid storage in the studied species. However, an accumulation of cholesterol esters and waxes (lipid characteristic of vertical migrants) has also been recorded inBorostomias antarcticus. The revealed distinctive features of Myctophidae and Stomiatidae, related to the accumulation of cholesterol and variations in the content of different phospholipid fractions, indicate that the fishes of these families use different mechanisms for regulating and maintaining the physicochemical state (permeability and fluidity) of biological membranes under conditions of change in a set of environmental factors (temperature, salinity, hydrostatic pressure, and specific photoperiod) with increase in the habitat depth.
Obstetric anal sphincter injury (OASI) in the presence of an intact perineum
Authors: Worrall Amy P , O'Leary Bobby D , Salameh Fadi
Published: October 2023

Obstetric anal sphincter injury (OASI) in the absence of concurrent injury to the perineal skin is not a common diagnosis. A primiparous woman delivered a healthy male infant by spontaneous vertex delivery. At time of delivery, a compound presentation of the fetal hand with the head was noted. Initial examination revealed a presumed second-degree tear; however, a small laceration above the anal verge was noted, which on exploration revealed a perineal injury through the anal sphincter complex. In the operating theatre, the perineal skin was incised to reveal a 3c OASI, which was repaired appropriately. While atypical OASI has been reported previously, this specific injury has never been described in detail in the literature. Awareness of atypical perineal injuries is needed and while careful perineal examination is required in all cases, this is especially important where the perineal skin appears intact to ensure appropriate diagnosis of any concurrent OASI.
Colo-colonic intussusception secondary to a lipomatous lesion in an asymptomatic patient
Authors: Kyaw Pan Su Pyae , Eliezer Dilharan Dhivakanth , Sutherland Andrew
Published: October 2023

Colo-colonic intussusception is a rare clinical condition in adults. The predominant aetiology of intussusception in adults is a pathological lead point, with malignant lesions being the most common type. Lipomas are benign tumours of adipocytes that can sometimes be difficult to diagnose without histopathological confirmation as we highlight with this case report. We report a case of an asymptomatic female patient in her 50s who presented with an intussusception due to a giant colonic lipoma. Her CT imaging showed the possibility of a low-grade liposarcomatous component or atypical lipomatous tumour component. A laparoscopic right hemicolectomy was performed due to intussusception with the possibility of leading to colonic obstruction as well as diagnostic uncertainty of the risk of malignancy. Histopathology confirmed the diagnosis of a lipomatous lesion. In cases such as this, early surgical management is appropriate to rule out malignancy and prevent emergency presentation and surgery.
Pulmonary function after lobectomy in children: a systematic review and meta-analysis
Authors: Liu Chenyu , Liu Jie , Yuan Miao , Cheng Kaisheng , Luo Dengke , Zeng Li , Xu Chang
Published: October 2023

Background

The influence of lobectomy on pulmonary function in children was still controversial. A systematic review and meta-analysis were essential to explore whether pulmonary function was impaired after lobectomy in children.

Methods

PubMed, Embase and Web of Science were searched from 1 January 1946 to 1 July 2022. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and total lung capacity were extracted from the studies as the primary analysis indicators. Subgroup analyses were performed between the congenital lung malformation (CLM) group and other diseases group, early surgery and late surgery group (1 year old as the dividing line).

Results

A total of 5302 articles were identified through the search strategy; finally, 10 studies met the inclusion criteria. Through the meta-analysis, we found a mild obstructive ventilatory disorder in children who underwent lobectomy. However, a normal pulmonary function could be found in young children with CLM who underwent lobectomy, and the time of operation had no significant influence on their pulmonary function.

Conclusions

The overall result of pulmonary function after lobectomy in children was good. Surgeons may not need to be excessively concerned about the possibility of lung surgery affecting pulmonary function in children, particularly in patients with CLM.

PROSPERO registration number

CRD42022342243.
Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma
Authors: Clingan Philip , Ladwa Rahul , Brungs Daniel , Harris Dean Laurence , McGrath Margaret , Arnold Susan , Coward Jermaine , Fourie Samuel , Kurochkin Andriy , Malan Daniel R , Mant Andrew , Sharma Vinay , Shue Hong , Tazbirkova Andrea , Berciano-Guerrero Miguel-Angel , Charoentum Chaiyut , Dalle Stéphane , Dechaphunkul Arunee , Dudnichenko Oleksandr , Koralewski Piotr , Lugowska Iwona , Montaudié Henri , Muñoz-Couselo Eva , Sriuranpong Virote , Oliviero James , Desai Jayesh
Published: October 2023

Background

Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors. It is an unmodified immunoglobulin G1 subtype with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Here, we present results of the pivotal study of patients with metastatic CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial of cosibelimab.

Methods

In this trial, participants with metastatic CSCC received cosibelimab 800 mg intravenously every 2 weeks. Primary endpoint was objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, V.1.1. Secondary endpoints included duration of response (DOR) and safety.

Results

Objective response was observed in 37 of 78 participants (47.4% (95% CI: 36.0% to 59.1%)), with median follow-up of 15.4 months (range: 0.4 to 40.5) as of data cut-off. Median DOR was not reached (range: 1.4+ to 34.1+ months), with response ongoing in 73.0% of participants. Common treatment-emergent AEs (≥15%) were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Eighteen participants (23.1%) experienced immune-related AEs (grade 3: n=2 (2.6%); no grade 4/5). No treatment-related deaths were reported.

Conclusions

Cosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile.

Trial registration number

NCT03212404.
COVID-19 prognosis in systemic lupus erythematosus compared with rheumatoid arthritis and spondyloarthritis: results from the CONTROL-19 Study by the Italian Society for Rheumatology
Authors: Scirocco Chiara , Ferrigno Sara , Andreoli Laura , Fredi Micaela , Lomater Claudia , Moroni Luca , Mosca Marta , Raffeiner Bernd , Carrara Greta , Landolfi Gianpiero , Rozza Davide , Zanetti Anna , Scirè Carlo Alberto , Sebastiani Gian Domenico
Published: October 2023

Introduction

Data concerning SARS-CoV-2 in patients affected by SLE are contradicting.

The aim of this study was to investigate disease-related differences in COVID-19 prognosis of patients affected by rheumatic diseases before vaccination; we tested the hypothesis that patients with SLE may have a different outcome compared with those with rheumatoid arthritis (RA) or spondyloarthritis (SPA).

Methods

We analysed data from the national CONTROL-19 Database with a retrospective, observational design, including rheumatic patients affected by COVID-19. The principal outcome measure was hospitalisation with death or mechanical ventilation. Differences between SLE, RA and SPA were analysed by univariable and multivariable logistic regression models.

Results

We included 103 patients with SLE (88.2% female, mean age 48.9 years, 50.4% active disease), 524 patients with RA (74.4% female, mean age 60.6 years, 59.7% active disease) and 486 patients with SPA (58.1% female, mean age 53.2 years, 58% active disease).

Outcome prevalence was not different between patients with SLE and those with RA (SLE 24.5%, RA 25.6%), while patients with SPA showed a more favourable outcome compared with those with SLE (SPA 15.9%); data from the multivariable analysis confirmed this result.

In SLE, age >65 years (OR 17.3, CI 5.51 to 63.16, p<0.001), hypertension (OR 6.2, CI 2.37 to 17.04, p<0.001) and prednisone (PDN) use (OR 3.8, CI 1.43 to 11.39, p=0.01) were associated with severe outcomes, whereas hydroxychloroquine use was found to be protective (OR 0.3, CI 0.14 to 0.91, p=0.03).

Conclusion

Our data suggest that patients with SLE and RA do not show a different COVID-19 outcome, while patients with SPA have a more favourable disease course compared with those with SLE. Risk of hospitalisation with ventilation or death was associated with age >65 years, hypertension and PDN use in patients with SLE.
Dysanapsis is not associated with exertional dyspnoea in healthy male and female never-smokers aged 40 years and older
Authors: Molgat-Seon Yannick , Sawatzky Mathieu A.T. , Dominelli Paolo B. , Kirby Miranda , Guenette Jordan A. , Bourbeau Jean , Tan Wan C. , Sheel A. William
Published: October 2023

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%–37% smaller (all p < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p < 0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p < 0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r < 0.34; all p > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea.
Quasinormal modes of phantom Reissner-Nordström-de Sitter black holes
Authors: Liu Hang
Published: October 2023

In this paper, we investigate some characteristics of phantom Reissner-Nordström-de Sitter (RN-dS) black holes. The peculiar features of phantom field render this kind of black holes quite different from their counterparts. We can only find at most two horizons in this spacetime, i.e. event horizon and cosmological horizon. For the black hole charge parameter, we find that it is not bounded from below. We calculate quasinormal modes (QNMs) frequencies of massless neutral scalar field perturbation in this black hole spacetime, and some properties related to the large charge parameter are disclosed.
Optical soliton for (2+1)-dimensional coupled integrable NLSE using Sardar-subequation method
Authors: Rehman Hamood Ur , Yasin Sadia , Iqbal Ifrah
Published: October 2023

The [Formula: see text]-dimensional coupled nonlinear Schrödinger equation has versatile applications for modeling nonlinear waves in different areas such as optics, atmospheric science, fluid dynamics, and plasma physics. This study focuses on the propagation of optical solitons and their interaction within various mediums such as multi-mode fiber and fiber arrays. The Sardar-subequation method is applied to achieve the bright, dark, combined bright–dark, periodic, combined dark-singular and singular optical solitons solutions. The 3D, contour and 2D profiles for some of the assimilation solutions are also plotted to show the physical behavior of the solutions. The obtained results demonstrate the effectiveness of the adopted methodology in obtaining traveling wave solutions and have many applications in applied mathematics and engineering. The novelty of our work lies in the successful application of Sardar-subequation method in obtaining diverse soliton solutions and exploring their physical behavior. This study goes beyond previous efforts in the literature by presenting a comprehensive analysis of soliton dynamics. This ability to describe and predict the behavior of optical solitons in diverse mediums opens up new opportunities for investigating the existing systems.
Optical properties of the proton-implanted waveguide in the Dy3+-doped Y3Al5O12 transparent ceramic
Authors: Wang Zi-Hao , Zhao Jie , Fu Li-Li , Zhang Liao-Lin , Liu Chun-Xiao
Published: October 2023

The high-quality waveguide structure in the Dy[Formula: see text]-doped Y3Al5O[Formula: see text] transparent ceramic is of significance for the application of integrated micro-light elements. However, there have been no reports on the preparation of optical waveguides by ion implantation in the Dy[Formula: see text]-doped Y3Al5O[Formula: see text] transparent ceramic. The work reports on the formation of optical planar waveguides by using the proton implantation in the Dy[Formula: see text]-doped Y3Al5O[Formula: see text] transparent ceramic. The acceleration energy and the dose of the protons are 400[Formula: see text]keV and [Formula: see text] ions/cm2, respectively. The structure of the fabricated waveguide is captured with the high-res/mag images by a metallurgical microscope. The dark-mode spectrum and the refractive index distribution are gained by the prism coupling system and the RCM software, respectively. The measurement and simulation of the near-field intensity distribution indicate the propagation of light field in the waveguide. The results are of potential to the compact devices in the photonics.
Focusing on Refinement Typing
Authors: Economou Dimitrios J. , Krishnaswami Neel , Dunfield Jana
Published: October 2023

We present a logically principled foundation for systematizing, in a way that works with any computational effect and evaluation order, SMT constraint generation seen in refinement type systems for functional programming languages. By carefully combining a focalized variant of call-by-push-value, bidirectional typing, and our novel technique of value-determined indexes, our system generates solvable SMT constraints without existential (unification) variables. We design a polarized subtyping relation allowing us to prove our logically focused typing algorithm is sound, complete, and decidable. We prove type soundness of our declarative system with respect to an elementary domain-theoretic denotational semantics. Type soundness implies, relatively simply, the total correctness and logical consistency of our system. The relative ease with which we obtain both algorithmic and semantic results ultimately stems from the proof-theoretic technique of focalization.
Passages
Authors: Groce Alex
Published: October 2023

Sydney Padua's The Thrilling Adventures of Lovelace and Babbage violates the rules of Passages in a technical sense; the book was published in 2015, so cannot be a classic, right? I could excuse cheating on the grounds that covering this delightful book is so important that I can't wait until 2025. After all, I might be hit by a bus; ACM SIGSOFT might dissolve; rogue AI might go all Skynet and murder us all; less catastrophically, I might tire of doing these columns or you might tire of reading them. A much better excuse,however, is that Padua's book really dates from a throwaway cartoon she posted on the web in 2009. In any case, this month's column is a review of Sydney Padua's 2015 book,
The Thrilling Adventures of Lovelace and Babbage - with Interesting Curious Anecdotes of Celebrated and Distinguished Characters, Fully Illustrating a Variety of Instructive and Amusing Scenes; As Performed Within and Without the Remarkable Difference Engine (Embellished with Portraits and Scientific Diagrams).
Report on the 4th International Workshop on Engineering and Cybersecurity of Critical Systems (EnCyCriS - 2023)
Authors: Esnoul Coralie , Sánchez-Gordón Mary , Jee Eunkyoung , Colomo-Palacios Ricardo , Chockalingam Sabarathinam , Eidar Simensen John , Bae Doo-Hwan
Published: October 2023

Critical Infrastructures (CIs) are vital for modern societies, encompassing diverse sectors such as healthcare, banking, emergency services, energy, water distribution, oil and gas, and transportation. Over time, these CIs have become increasingly reliant on technology to ensure their seamless operations. The reliable and secure operation of these CIs holds paramount importance for a nation's economy and the well-being of society. This paper presents the findings and discussions from the 4th International Workshop on Engineering and Cybersecurity of Critical Systems (EnCyCriS - 2023). The main purpose of this EnCyCriS workshop is to collect contributions from practitioners and researchers working on challenges and solutions for engineering and cybersecurity of critical systems in the Fourth Revolution (4IR). The 2023 edition has accepted and presented six papers. In addition, there was a keynote talk from a Senior Research Scientist in safety and security of digital technologies within safety critical industries in addition to an open discussion about the "Future of IT and OT". This workshop was colocated with the 45th International Conference on Software Engineering (ICSE - 2023), which took place on 20th May 2023.
Genetic Improvement @ ICSE 2023
Authors: Langdon William B. , Nowack Vesna , Petke Justyna , Wagner Markus , Lee Hyeonseok , Fredericks Erik M. , An Gabin , Blot Aymeric
Published: October 2023

Following the formal presentations, which included keynotes by Prof. Myra B. Cohen of Iowa State University and Dr. Sebastian Baltes of SAP as well as six papers (which are recorded in the pro- ceedings) there was a wide ranging discussion at the twelfth inter- national Genetic Improvement workshop, GI-2023 @ ICSE held on Saturday 20th May 2023 in Melbourne and online via Zoom. Topics included GI to improve testing, and remove unpleasant surprises in cloud computing costs, incorporating novelty search, large language models (LLM ANN) and GI benchmarks.
Robust Embedded Autonomous Driving Positioning System Fusing LiDAR and Inertial Sensors
Authors: He Zhijian , Xue Bohuan , Hu Xiangcheng , Shen Zhaoyan , Zeng Xiangyue , Liu Ming
Published: October 2023

Autonomous driving emphasizes precise multi-sensor fusion positioning on limit resource embedded systems. LiDAR-centered sensor fusion system serves as a mainstream navigation system due to its insensitivity to illumination and viewpoint change. However, these types of systems suffer from handling large-scale sequential LiDAR data using limited resources on board, leading LiDAR-centralized sensor fusion unpractical. As a result, hand-crafted features such as plane and edge are leveraged in majority mainstream positioning methods to alleviate this unsatisfaction, triggering a new cornerstone in LiDAR Inertial sensor fusion. However, such super light weight feature extraction, although it achieves real-time constraint in LiDAR-centered sensor fusion, encounters severe vulnerability under high speed rotational or translational perturbation. In this paper, we propose a sparse tensor based LiDAR Inertial fusion method for autonomous driving embedded system. Leveraging the power of sparse tensor, the global geometrical feature is fetched so that the point cloud sparsity defect is alleviated. Inertial sensor is deployed to conquer the time-consuming step caused by the coarse level point-wise inlier matching. We construct our experiments on both representative dataset benchmarks and realistic scenes. The evaluation results show the robustness and accuracy of our proposed solution compared to classical methods.
Tight Sum-of-squares Lower Bounds for Binary Polynomial Optimization Problems
Authors: Kurpisz Adam , Leppänen Samuli , Mastrolilli Monaldo
Published: October 2023

For binary polynomial optimization problems of degree
2d
with
n
variables Sakaue, Takeda, Kim, and Ito [
33
] proved that the

\(\lceil \frac{n+2d-1}{2}\rceil\)

th semidefinite (SDP) relaxation in the SoS/Lasserre hierarchy of SDP relaxations provides the exact optimal value. When
n
is an odd number, we show that their analysis is tight, i.e., we prove that

\(\frac{n+2d-1}{2}\)

levels of the SoS/Lasserre hierarchy are also necessary.

Laurent [
24
] showed that the Sherali-Adams hierarchy requires
n
levels to detect the empty integer hull of a linear representation of a set with no integral points. She conjectured that the SoS/Lasserre rank for the same problem is
n
-1. In this article, we disprove this conjecture and derive lower and upper bounds for the rank.
Multi-task Pre-training Language Model for Semantic Network Completion
Authors: Li Da , Zhu Boqing , Yang Sen , Xu Kele , Yi Ming , He Yukai , Wang Huaimin
Published: October 2023

Semantic networks, exemplified by the knowledge graph, serve as a means to represent knowledge by leveraging the structure of a graph. While the knowledge graph exhibits promising potential in the field of natural language processing, it suffers from incompleteness. This article focuses on the task of completing knowledge graphs by predicting linkages between entities, which is fundamental yet critical. Traditional methods based on translational distance struggle when dealing with unseen entities. In contrast, semantic matching presents itself as a potential solution due to its ability to handle such cases. However, semantic matching-based approaches necessitate large-scale datasets for effective training, which are typically unavailable in practical scenarios, hindering their competitive performance. To address this challenge, we propose a novel architecture for knowledge graphs known as LP-BERT, which incorporates a language model. LP-BERT consists of two primary stages: multi-task pre-training and knowledge graph fine-tuning. During the pre-training phase, the model acquires relationship information from triples by predicting either entities or relations through three distinct tasks. In the fine-tuning phase, we introduce a batch-based triple-style negative sampling technique inspired by contrastive learning. This method significantly increases the proportion of negative sampling while maintaining a nearly unchanged training time. Furthermore, we propose a novel data augmentation approach that leverages the inverse relationship of triples to enhance both the performance and robustness of the model. To demonstrate the effectiveness of our proposed framework, we conduct extensive experiments on three widely used knowledge graph datasets: WN18RR, FB15k-237, and UMLS. The experimental results showcase the superiority of our methods, with LP-BERT achieving state-of-the-art performance on the WN18RR and FB15k-237 datasets.
Who Should be Credited for the Gouy-Chapman Model?
Authors: Ivanov Vladimir D.
Published: October 2023

The Gouy-Chapman theory is well known to all electrochemists. However, examining the works of Gouy and Chapman, one can find that the current mathematical basis of this theory notably differs from the original concept. The Poisson-Boltzmann equation is at the heart of this model in its present form. However, not only did neither Gouy nor Chapman solve this equation, they did not even formulate it. Concerning the diffuse double layer, this equation was solved for the first time by Karl Herzfeld Phys. Z.
21, 28, (1920). Please note that this exact solution of the Poisson-Boltzmann equation predates the Debye-Hückel approximation. Unfortunately, the scientific community is currently ignoring Karl Herzfeld’s contributions to this theory. This paper is an analysis of the mathematical apparatus of the Gouy, Chapman, and Herzfeld versions of the double layer theory. The author presented the equations they derived as close as possible to the original.
Efficacy of an Insect-Based Diet with Addition of Probiotics on Growth, Proximate Composition, Enzymatic Efficiency, and Immune Response of Nile Tilapia
Authors: Naveed Muhammad , Mateen Abdul , Dureshahwar  , Majeed Waqar , Naeem Muhammad , Khattab Yassir , Hedfi Amor , Ansir Fareeha , Ali Manel Ben
Published: October 2023

Insects are potential alternative protein sources to replace fish meal (FM) in aqua feed. The role of insect species as replacements in the aqua industry has been a hot debate in the current era. The present study evaluated the influence of FM replacement with insect-based meals (black soldier fly (BSF) and maggot fly) in the feed of Nile tilapia. Eight diets with graded replacement levels of FM were formulated along with basal diet as T0 (control group having basal diet), T1 (25% maggot meal (MM) with 2% probiotics), T2 (50% MM + 2% probiotics), T3 (75% MM + 2% probiotics), T4 (100% MM + 2% probiotics), T5 (25% BSF meal (BSFM) + 2% probiotics), T6 (50% BSFM + 2% probiotics), T7 (75% BSFM + 2% probiotics), and T8 (100% BSFM + 2% probiotics). Fish having an initial body weight of 7 g were fed on formulated feed for 16 weeks. Growth parameters, including weight, length, feed conversion ratio, specific growth rate, and survival rate, were observed weekly, and significant (

p
<
0.05

) results were attained up to 75% replacement level with no adverse effect on growth. However, at 100% replacement of FM, fish growth was retarded. Maximum survival rate was observed in T1 and T5 and minimal in T4 and T8. Body composition, including crude protein, fat, moisture, and ash, showed significant (

p
<
0.05

) results. Similarly, digestive enzyme (protease, lipase, and amylase) activity was measured at the end of the trial. Fish in T1 and T5 groups had the highest digestive enzyme activity, which slightly decreased with the inclusion of insect-based meals and probiotics. Statistically significant (

p
<
0.05

) results were observed for antioxidant enzyme activity in catalase, glutathione peroxidase, and superoxide dismutase. The most vigorous immune response was shown in T1 and T5, with higher white blood cells and high levels of IgM. The present research showed that FM could be replaced with BSF meal and MM with probiotics up to 50% for better fish health performance; however, 75% replaced FM without compromising growth and health status.
Live Microalgae-Based Diets as Enrichment to Improve the Nutritional Profile of the Calanoid Copepod Acartia tonsa (Dana, 1849) Nauplii
Authors: Martino Andrea , Montero Daniel , Roo Javier , Holt William Vincent , Lavorano Silvia , Narizzano Riccardo , Otero Ferrer Francisco
Published: October 2023

Most emerging species in marine aquaculture and the aquarium industry have a sensitive and small-mouthed larval stage, and their culture is very challenging due to a lack of appropriate early feeding protocols. The use of copepods has been widely recognized as a good alternative to traditional fish live feeds (rotifers and Artemia spp.), especially for new species targeted for the multibillion-dollar marine aquarium trade. However, most copepod culture trials are focused on biomass production, while their nutritional requirements and enrichment protocols remain scarcely known. The main objective of this study was to determine the dietary contribution of three microalgae-based diets, provided as a mono R (Rhodomonas salina) or binary I–R (Isochrysis galbana + R. salina) and T–R (Tetraselmis suecica + R. salina), on the biochemical composition (proximate and fatty acids (FAs)) and survival of the calanoid copepod Acartia tonsa (nauplii) versus the conventional rotifer Brachionus plicatilis throughout 96 hr exposure. Both live preys were characterized by the highest protein and total n-3 long-chain polyunsaturated FAs (LC-PUFAs) content when fed with the binary diet I–R compared to other treatments, although the nutritional value of A. tonsa nauplii was always much higher compared to B. plicatilis. In general, there was a wide difference in proximate and FAs composition between the two preys, denoting A. tonsa as better live feed in terms of capacity to retain n-3 LC-PUFAs, especially eicosapentanoic acid (20 : 5n-3) and docosahexanoic acid (22 : 6n-3). The present study highlights the nutritional profile of enriched A. tonsa nauplii and contributes to the production of high-quality live feeds, which may be able to reach the nutritional needs of new marine fish species during their larval development, as well as contributing to the improvement of A. tonsa culture.
Moringa oleifera Use in Maintaining Oral Health and Its Potential Use in Regenerative Dentistry
Authors: Shafiq Nada E. , Mahdee Anas F.
Published: October 2023

Phytomedicine refers to the use of naturally derived products to cure and mitigate human conditions. Natural products have the advantages of causing minimum side effects, being biocompatible, available, and economical, with a wide array of biological activities. Reports have described the use of natural products with antimicrobial and anti-inflammatory properties to treat oral conditions and promote wound healing. Moringa oleifera, known as the “drumstick” or “horseradish” tree, is believed to have medicinal properties regarding a range of medical conditions, though there is limited information on its use in oral medicine. This narrative review focuses on the use of Moringa extracts in the management of oral conditions, including oral infections, inflammatory conditions, the remineralization of hard tissues, oral wound healing, and tissue regeneration, drawing from both in vitro and in vivo studies which indicate that the potential of Moringa extracts in supporting dentin-pulp regeneration after caries or trauma is worthy of more careful consideration.
The Impact of Biofloc Technology on Water Quality in Aquaculture: A Systematic Meta-Analysis
Authors: Ahmed Alkhamis Yousef , Sultana Airin , Tareq Arafat Shaikh , Abdur Rouf Muhammad , Mustafizur Rahman Sheikh , Thomas Mathew Roshmon , Ganesan Nagarajan , Sultana Afrin , Saleh Alngada Rashid , Abdul Whed Raed , Abdulaziz Aljaafari Nouh , Moshiur Rahman Md.
Published: October 2023

A technique called biofloc technology (BFT) is an environmentally friendly method for aquaculture in which a successful growing cycle depends on the maintenance and monitoring of water quality parameters. Studies have revealed that improving water quality in BFT and maintaining the safety range of the parameters can help to increase the growth performance of cultured species. Following a systematic review of the literature, a meta-analysis was performed to explore how some important water parameters such as pH, dissolved oxygen (DO), nitrite (NO2–N), nitrate (NO3–N), ammonia (NH3–N), total ammonia nitrogen (TAN), total suspended solids (TSS), and alkalinity were influenced by different BFT systems. The PRISMA screening process was followed, and 33 studies were eligible for the meta-analysis. The meta-analyses showed that NO2–N and TSS were significantly affected by BFT, while pH, DO, NO3–N, NH3–N, TAN, and alkalinity were not significantly influenced by this system. The analyses revealed that NO2–N had a significant negative effect size due to BFT, whereas TSS showed a significant positive effect size. The study also revealed some publication bias in which few experiments of some studies showed extremely positive and negative effect sizes due to BFT application in the system. Overall, the findings suggest clear evidence of the profound influence of BFT on the water quality parameters in different aquaculture systems, suggesting the future development of BFT for sustainable and environmentally friendly aquaculture production.
Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: October 2023

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis–associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1–4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation–associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.

Significance:

The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.
The Effect of Diet on Breast Cancer Recurrence: The DIANA-5 Randomized Trial
Authors: Berrino Franco , Villarini Anna , Gargano Giuliana , Krogh Vittorio , Grioni Sara , Bellegotti Manuela , Venturelli Elisabetta , Raimondi Milena , Traina Adele , Zarcone Maurizio , Amodio Rosalba , Mano Maria Piera , Johansson Harriet , Panico Salvatore , Santucci de Magistris Maria , Barbero Maggiorino , Gavazza Cristina , Mercandino Angelica , Consolaro Elena , Galasso Rocco , Del Riccio Luciana , Bassi Maria Chiara , Simeoni Milena , Premoli Paolo , Pasanisi Patrizia , Bonanni Bernardo , Bruno Eleonora
Published: October 2023

Purpose:

The DIANA-5 randomized controlled trial assessed the effectiveness of a diet based on Mediterranean and macrobiotic traditions (macro-Mediterranean diet) in reducing breast cancer recurrence.

Patients and Methods:

The DIANA-5 study involved 1,542 patients with breast cancer at high risk of recurrence because of estrogen receptor–negative cancer, or metabolic syndrome, or high plasma levels of insulin or testosterone. Women were randomly assigned to an active dietary intervention (IG) or a control group (CG). Both groups received the 2007 American Institute for Cancer Research/World Cancer Research Fund recommendations for cancer prevention. The intervention consisted of meetings with kitchen classes, community meals, and dietary recommendations. Recommended foods included whole grain cereals, legumes, soy products, vegetables, fruit, nuts, olive oil, and fish. Foods to be avoided were refined products, potatoes, sugar and desserts, red and processed meat, dairy products, and alcoholic drinks. A compliance Dietary Index was defined by the difference between recommended and discouraged foods.

Results:

Over the 5 years of follow-up, 95 patients of the IG and 98 of the CG developed breast cancer recurrence [HR = 0.99; 95% confidence interval (CI): 0.69–1.40]. The analysis by compliance to the dietary recommendations (IG and CG together) showed that the women in the upper tertile of Dietary Index change had an HR of recurrence of 0.59 (95% CI: 0.36–0.92) compared with women in the lower tertile.

Conclusions:

The DIANA-5 dietary intervention trial failed to show a reduction in breast cancer recurrence, although self-reported diet at year 1 in IG and CG combined showed a protective association with the higher Dietary Index change.

See related commentary by McTiernan, p. 931
Immunologic Targets in AML
Authors: Ritz Jerome
Published: October 2023

In this issue of Blood Cancer Discovery, Nelde and colleagues used a sensitive mass spectrometry-based immunopeptidomics approach to characterize the antigenic landscape of acute myeloid leukemia (AML) and were able to identify immunogenic peptides presented by both leukemia stem cells (LSC) and bulk primary AML blasts. These immunogenic peptides elicit primarily CD4 T-cell responses and the diversity of the HLA class II immunopeptidome and presence of CD4 memory T-cell responses were both associated with improved clinical outcome.

See related article by Nelde et al., p. 468 (1) .