bluuebunny/crossref_metadata_2025 huggingface dataset:
The Current Mismatch Between COVID-19 Clinical Trial Design and the Evolving Profile of Hospitalized Patients: A Retrospective Cohort Analysis
Authors: Montejano Rocio , Soler-Carracedo Alfredo , Borobia Alberto M , Martin-Quiros Alejandro , Grandioso David , Cañada Carlos , Roman Alicia , Arribas Jose R
Published: October 2023

Evaluating 100 adult coronavirus disease 2019 (COVID-19) patients at a Madrid hospital, we identified a mismatch between current clinical trial designs and the evolving profile of hospitalized patients. Most patients were ineligible due to design constraints, suggesting a need to rethink trial criteria for a more accurate representation of the hospitalized COVID-19 cohort.
Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function
Authors: Borrell-Pages Maria , Luquero Aureli , Vilahur Gemma , Padró Teresa , Badimon Lina
Published: October 2023

Aims

There is little information on the regulation of cholesterol homeostasis in the brain. Whether cholesterol crosses the blood–brain barrier is under investigation, but the present understanding is that cholesterol metabolism in the brain is independent from that in peripheral tissues. Lipoprotein receptors from the LDL receptor family (LRPs) have key roles in lipid particle accumulation in cells involved in vascular and cardiac pathophysiology; however, their function on neural cells is unknown.

Methods and results

The expression of LRP5 and the components and targets of its downstream signalling pathway, the canonical Wnt pathway, including β-catenin, LEF1, VEGF, OPN, MMP7, and ADAM10, is analysed in the brains of Wt and Lrp5−/− mice and in a neuroblastoma cell line. LRP5 expression is increased in a time- and dose-dependent manner after lipid loading in neuronal cells; however, it does not participate in cholesterol homeostasis as shown by intracellular lipid accumulation analyses. Neurons challenged with staurosporin and H2O2 display an anti-apoptotic protective role for LRP5.

Conclusions

For the first time, it has been shown that neurons can accumulate intracellular lipids and lipid uptake is performed mainly by the LDLR, while CD36, LRP1, and LRP5 do not play a major role. In addition, it has been shown that LRP5 triggers the canonical Wnt pathway in neuronal cells to generate pro-survival signals. Finally, Lrp5−/− mice have maintained expression of LRP5 only in the brain supporting the biological plausible concept of the need of brain LRP5 to elicit pro-survival processes and embryonic viability.
Outcomes of catheter ablation in high-risk patients with Brugada syndrome refusing an implantable cardioverter defibrillator implantation
Authors: Li Le , Ding Ligang , Zhou Likun , Wu Lingmin , Zheng Lihui , Zhang Zhenhao , Xiong Yulong , Zhang Zhuxin , Yao Yan
Published: October 2023

Aims

The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation.

Methods and results

A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation–triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5–73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012).

Conclusion

Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population.
Dysbiosis of the oral microbiota composition is associated with oral squamous cell carcinoma and the impact of radiotherapy: a pilot study
Authors: Anjali Kanadan , Manzoor Muhammed , Suryavanshi Mangesh Vasant , Rudrapathy Parthiban , Rekha Punchappady Devasya , Das Ranajit , Hameed Asif , Arun Ananthapadmanabha Bhagwath
Published: October 2023

Radiotherapy can potentially influence the diversity and composition of the oral microbiome. We performed a study comparing the composition of oral microbiota in patients with oral squamous cell carcinoma (OSCC) before radiotherapy (n = 6), at three months (n = 6), and six months (n = 6) post-radiotherapy, and controls (n = 6). We profiled the oral microbiome by 16S rRNA gene sequencing using Illumina MiSeq. Alpha diversity (Chao1 index) showed significant differences in species richness between healthy controls and OSCC patients (P = 0.014). Conversely, no noteworthy distinctions were observed in the Chao1 index when comparing the pre-and post-radiation periods at both three and six months. The beta diversity of the oral microbiota differed significantly between the controls and OSCC patients (P = 0.014). However, no significant differences were observed in beta diversity between pre- and post-radiation at three months, whereas a significant difference was observed at six months (P = 0.038). Linear Discriminant Analysis Effect Size (LEfSe) demonstrated lower abundance of Corynebacterium, Actinomyces, Veillonella, and Haemophilus, and higher abundance of Selenomonas and Mycoplasma in OSCC patients than in healthy controls. The oral microbiome composition varied among healthy controls, patients with OSCC, and post-radiation therapy patients with OSCC. The observed recovery in the numerical dominance of specific beneficial oral taxa and the reduction in pathogenic bacteria after radiation therapy highlights the need for further investigations into their clinical implications.
Characterization of a novel ArsR regulates divergent ars operon in Ensifer adhaerens strain ST2
Authors: Zhang Jun , Li Yan-Ning , Shen Jie , Nadar Venkadesh Sarkarai , Chen Jian
Published: October 2023

Microbes evolved resistance determinates for coping with arsenic toxicity are commonly regulated by a variety of transcriptional repressors (ArsRs). Ensifer adhaerens strain ST2 was previously shown tolerance to environmental organoarsenical methylarsenite (MAs(III)), which has been proposed to be a primordial antibiotic. In E. adhaerens strain ST2 chromosomal ars operon, two MAs(III) resistance genes, arsZ, encoding MAs(III) oxidase, and arsK, encoding MAs(III) efflux transporter, are controlled by a novel ArsR transcriptional repressor, EaArsR. It has two conserved cysteine pairs, Cys91-92 and Cys108-109. Electrophoretic mobility shift assays (EMSAs) demonstrate that EaArsR binds to two inverted-repeat sequences within the ars promoter between arsR and arsZ to repress ars operon transcription and that DNA binding is relieved upon binding of As(III) and MAs(III). Mutation of either Cys91 or Cys92 to serine (or both) abolished these mutants binding to the ars promoter. In contrast, both C108S and C109S mutants kept responsiveness to As(III) and MAs(III). These results suggest that cysteine pair Cys91-Cys92 and either Cys108 or Cys109 contribute to form arsenic binding site. Homology modeling of EaArsR indicates the binding site consisted of Cys91-Cys92 pair from one monomer and Cys108-Cys109 pair from the other monomer, which displays the diverse evolution of arsenic binding site in the ArsR metalloregulators.
ABC superfamily transporter Rv1273c of Mycobacterium tuberculosis acts as a multidrug efflux pump
Authors: Adhikary Anwesha , Chatterjee Debasmita , Ghosh Anindya Sundar
Published: October 2023

Efflux pump-mediated drug resistance in bacteria is a common occurrence effective for the general survival of the organism. The Mycobacterium tuberculosis genome has an abundance of adenosine triphosphate (ATP) dependent cassette transporter genes but only a handful of them are documented for their contribution to drug resistance. In this study, we inspected the potential of an ABC transporter Rv1273c from M. tuberculosis as a multidrug efflux pump and a contributor to intrinsic drug resistance. Expression of Rv1273c in Escherichia coli and M. smegmatis conferred tolerance to various structurally unrelated antibiotics. Lower accumulation of fluoroquinolones in intact E. coli and M. smegmatis cells expressing the transporter implied its active efflux activity. Energy-dependent efflux by Rv1273c was observed in real time using the lipophilic dye Nile Red. Expression of Rv1273c also resulted in an increase in biofilm formation by E. coli and M. smegmatis cells. Overall, the results indicate the possibility that Rv1273c might be a multidrug transporter with a wide substrate range and a probable contributor to biofilm formation.
Titanium dioxide E171 consumption exacerbates Listeria monocytogenes infection in mice
Authors: Teng Yue , Wang Ailin , Zhao Dongyun , Li Guopeng , Liu Longze , Zou Yue , Xia Xiaodong
Published: October 2023

The food additive titanium dioxide is commonly utilized to enhance the appearance and flavor of food products. However, this substance has been linked to gastrointestinal disorders. The aim of this study was to investigate the impact of dietary exposure of titanium dioxide E171 on Listeria monocytogenes infection in mice. Mice were mainly divided into the control, LM group (L. monocytogenes infection), and E171+LM groups (E171 supplementation before L. monocytogenes infection). Pre-exposure to E171 resulted in increased bacterial counts in the liver, spleen, ileum, colon, mesenteric lymph nodes, and feces of mice after L. monocytogenes infection. Moreover, E171 exposure increased the levels of pro-inflammatory cytokines while attenuating the levels of anti-inflammatory cytokines in mice infected with L. monocytogenes. Meanwhile, mice in the E171+LM group exhibited considerably more severe colonic inflammation and worse intestinal barrier function than mice in the LM group. The 16S rRNA gene sequencing revealed a shift in the composition of the gut microbiota of mice in the E171+LM group, characterized by a decrease in the relative abundance of Firmicutes and a decrease in the Firmicutes-to-Bacteroidetes ratio. The levels of acetate, butyrate, and isobutyrate were markedly decreased within the cecum of mice in the E171+LM group in comparison to mice in the LM group. In conclusion, these results suggest that E171 exposure could exacerbate L. monocytogenes infection in mice, which may provide useful information for future risk assessment of this commonly used food additive.
Seismic imaging of the Northern Andean subduction zone from teleseismic tomography: a torn and fragmented Nazca slab
Authors: Rodríguez E E , Beck S L , Ruiz M , Meltzer A , Portner D E , Hernández S , Segovia M , Agurto-Detzel H , Charvis P
Published: October 2023

The Nazca-South America subduction zone in Ecuador is characterized by a complicated along-strike geometry as the slab transitions from flat slab subduction in the south, with the Peruvian flat slab, to what has been characterized as ‘normal’ dipping subduction beneath central Ecuador. Plate convergence additionally changes south to north as the trench takes on a convex shape. Highly heterogeneous bathymetry at the trench, including the aseismic oceanic Carnegie Ridge (CR), and sparse intermediate-depth seismicity has led many to speculate about the behaviour of the downgoing plate at depth. In this study, we present a finite-frequency teleseismic P-wave tomography model of the northern Andes beneath Ecuador and Colombia from 90 to 1200 km depth. Our model builds on prior tomography models in South America by adding relative traveltime residuals recorded at stations in Ecuador. The complete data set is comprised of 114 096 relative traveltime residuals from 1133 stations across South America, with the added data serving to refine the morphology of the Nazca slab in the mantle beneath the northern Andes. Our tomography model shows a Nazca slab with a fragmented along-strike geometry and the first teleseismic images of several proposed slab tears in this region. At the northern edge of the Peruvian flat slab in southern Ecuador, we image a shallow tear at 95–200 km depth that appears to connect mantle flow from beneath the flat slab to the Ecuadorian Arc. Beneath central Ecuador at the latitudes of the CR, the Nazca slab is continuous into the lower mantle. Beneath southern Colombia, the Malpelo Tear breaks the Nazca slab below ∼200 km depth.
Identification of conserved skeletal enhancers associated with craniosynostosis risk genes
Authors: He(何璇) Xuan Anita , Berenson Anna , Bernard Michelle , Weber Chris , Cook Laura E , Visel Axel , Fuxman Bass Juan I , Fisher Shannon
Published: October 2023

Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15%–20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. We hypothesized that the two noncoding genomic regions identified by a GWAS for craniosynostosis contain distal regulatory elements for the risk genes BMPER and BMP2. To identify such regulatory elements, we surveyed conserved noncoding sequences from both risk loci for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous expression of bmper and bmp2. For each locus, we also found a skeletal enhancer that also contains a sequence variant associated with craniosynostosis risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. The same enhancer is active in mouse skeletal tissues, demonstrating evolutionarily conserved activity. Using enhanced yeast one-hybrid assays, we identified transcription factors that bind each enhancer and observed differential binding between alleles, implicating multiple signaling pathways. Our findings help unveil the genetic mechanism of the two craniosynostosis risk loci. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms.
Morphological and functional alterations of neuromuscular synapses in a mouse model of ACTA1 congenital myopathy
Authors: Liu Yun , Lin Weichun
Published: October 2023

Mutations in skeletal muscle α-actin (Acta1) cause myopathies. In a mouse model of congenital myopathy, heterozygous Acta1 (H40Y) knock-in (Acta1+/Ki) mice exhibit features of human nemaline myopathy, including premature lethality, severe muscle weakness, reduced mobility, and the presence of nemaline rods in muscle fibers. In this study, we investigated the impact of Acta1 (H40Y) mutation on the neuromuscular junction (NMJ). We found that the NMJs were markedly fragmented in Acta1+/Ki mice. Electrophysiological analysis revealed a decrease in amplitude but increase in frequency of miniature end-plate potential (mEPP) at the NMJs in Acta1+/Ki mice, compared with those in wild type (Acta1+/+) mice. Evoked end-plate potential (EPP) remained similar at the NMJs in Acta1+/Ki and Acta1+/+ mice, but quantal content was increased at the NMJs in Acta1+/Ki, compared with Acta1+/+ mice, suggesting a homeostatic compensation at the NMJs in Acta1+/Ki mice to maintain normal levels of neurotransmitter release. Furthermore, short-term synaptic plasticity of the NMJs was compromised in Acta1+/Ki mice. Together, these results demonstrate that skeletal Acta1 H40Y mutation, albeit muscle-origin, leads to both morphological and functional defects at the NMJ.
Performance of Metagenomic Next-Generation Sequencing of Cell-Free DNA From Vitreous and Aqueous Humor for Diagnoses of Intraocular Infections
Authors: Qian Zhuyun , Xia Han , Zhou Jiemin , Wang Ruifeng , Zhu Dan , Chen Li , Kang Hao , Feng Jing , Hu Xiaofeng , Wang Lu , Xu Songtao , Lou Zheng , Tao Yong
Published: October 2023

Background

Delayed diagnosis and improper therapy for intraocular infections usually result in poor prognosis. Due to limitations of conventional culture and polymerase chain reaction methods, most causative pathogens cannot be identified from vitreous humor (VH) or aqueous humor (AH) samples with limited volume.

Methods

Patients with suspected intraocular infections were enrolled from January 2019 to August 2021. Metagenomic next-generation sequencing (mNGS) was used to detected causative pathogens.

Results

This multicenter prospective study enrolled 488 patients, from whom VH (152) and AH (336) samples were respectively collected and analyzed using mNGS of cell-free DNA (cfDNA). Taking final comprehensive clinical diagnosis as the gold standard, there were 39 patients with indefinite final diagnoses, whereas 288 and 161 patients were diagnosed as definite infectious and noninfectious diseases, respectively. Based on clinical adjudication, the sensitivity (92.2%) and total coincidence rate (81.3%) of mNGS using VH samples were slightly higher than those of mNGS using AH samples (85.4% and 75.4%, respectively).

Conclusions

Using mNGS of cfDNA, an era with clinical experience for more rapid, independent, and impartial diagnosis of bacterial and other intraocular infections can be expected.
RTS,S/AS02A Malaria Vaccine-Induced IgG Responses Equally Recognize Native-Like Fucosylated and Nonfucosylated Plasmodium falciparum Circumsporozoite Proteins
Authors: Jairoce Chenjerai , Macià Dídac , Torres-Yaguana Jorge P , Mayer Leonie , Vidal Marta , Santano Rebeca , Hurtado-Guerrero Ramón , Reiter Karine , Narum David L , Lopez-Gutierrez Borja , Hamerly Timothy , Sacarlal Jahit , Aguilar Ruth , Dinglasan Rhoel R , Moncunill Gemma , Izquierdo Luis , Dobaño Carlota
Published: October 2023

The RTS,S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O-fucosylated on the sporozoite surface. We determined whether RTS,S/AS02A-induced immunoglobulin G (IgG) antibodies recognize vaccine-like nonfucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS,S/AS02A vaccination induced high anti-PfCSP IgG levels associated with malaria protection. IgG recognition of nonfucosylated and fucosylated PfCSP was equivalent, suggesting that PfCSP fucosylation does not affect antibody recognition.

Clinical Trials Registration. NCT00197041.
Phylogeny and systematics of the “Pronophila clade,” with 2 new genera to resolve the formerly polyphyletic genus Pseudomaniola (Lepidoptera: Nymphalidae: Satyrinae)
Authors: Pyrcz Tomasz W , Willmott Keith R , Lachowska-Cierlik Dorota , Mrozek Artur , Florczyk Klaudia , Mahecha-J Oscar , Espeland Marianne
Published: October 2023

Analysis of a target enrichment molecular dataset confirms the monophyly of the Neotropical montane butterfly group known as the Pronophila Westwood clade, 1 of 2 major lineages of the satyrine subtribe Pronophilina. The Pronophila clade comprises 18–20 recognized genera and some 125 species. Within this group, the genus Pseudomaniola Röber appears as paraphyletic, and is split here into 3 genera, Pseudomaniola sensu novum with 6 species, including 4 previously considered as subspecies of P. phaselis (Hewitson), the monobasic Fahraeusia Pyrcz n. gen. for Catargynnis asuba Thieme, n. comb., and Boyeriana Pyrcz, Espeland & Willmott n. gen., with 9 species. The adults of all 3 genera can be recognized by their wing color patterns, but the strongest synapomorphies are found in the genitalia, especially those of the male, supporting the above systematic decisions. Notable differences are also found in scale organization and morphology. A divergence time analysis suggests that Fahraeusia diverged from Pseudomaniola + Boyeriana in the mid-Miocene, around 12 Mya, and the subsequent separation of the last 2 genera occurred at the start of the Pliocene at around 5 Mya.
Research on key technologies for intelligent and fine-grained construction of earth–rock dams based on artificial intelligence
Authors: Liu Biao , Gong Xiaohui , Meng Tao , Zhao Yufei
Published: October 2023

High dam construction is continuing to develop with new requirements for intelligent dam construction. New information technology capabilities are providing paths for improved intelligent dam construction. This paper provides a comprehensive overview of the key technologies employed in the intelligent construction process of earth–rock dams. Starting with the multidimensional perception technologies and equipment utilized in earth–rock dam filling construction, it covers various aspects, such as the fine-grained management of unit construction based on building information modeling, rapid detection and qualification testing of dam materials’ physical characteristics, fast perception technology for material compaction, and unmanned driving technology for dam compaction equipment. Additionally, this paper highlights an overview of the existing technical challenges and future prospects in intelligent construction for earth–rock dams. These research results provide important references and lessons for the construction and development of high earth–rock dam engineering.
Mutations in ompK36 differentially impact in vitro synergy of meropenem/vaborbactam and ceftazidime/avibactam in combination with other antibiotics against KPC-producing Klebsiella pneumoniae
Authors: Rogers Tara M , Kline Ellen G , Griffith Marissa P , Jones Chelsea E , Rubio Abigail M , Squires Kevin M , Shields Ryan K
Published: October 2023

Objectives

Ceftazidime/avibactam and meropenem/vaborbactam are preferred agents for Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections and are often used in combination with other agents. We aimed to characterize the synergy of combinations against KPC-Kp with varying ompK36 genotypes.

Methods

KPC-Kp that harboured ompK36 WT, IS5 or glycine-aspartic acid duplication (GD) genotypes were selected. MICs were determined in triplicate. Synergy was assessed by time-kill assays for ceftazidime/avibactam and meropenem/vaborbactam in combination with colistin, gentamicin, tigecycline, meropenem or fosfomycin against 1 × 108 cfu/mL KPC-Kp.

Results

KPC-Kp harboured ompK36 WT (n = 5), IS5 (n = 5) or GD (n = 5); 11 were KPC-2 and 4 were KPC-3. All were susceptible to ceftazidime/avibactam and meropenem/vaborbactam. In time-kill analysis, ceftazidime/avibactam and meropenem/vaborbactam 1 × MIC exhibited mean 24 h log-kills of −2.01 and −0.84, respectively. Ceftazidime/avibactam was synergistic in combination with colistin independent of ompK36 genotype. Ceftazidime/avibactam combinations impacted by porin mutations (compared to WT) were meropenem (−5.18 versus −6.62 mean log-kill, P < 0.001) and fosfomycin (−3.98 versus −6.58, P = 0.058). Mean log-kills with meropenem/vaborbactam were greatest in combination with gentamicin (−5.36). In the presence of porin mutations, meropenem/vaborbactam killing activity was potentiated by the addition of colistin (−6.65 versus −0.70, P = 0.03) and fosfomycin (−3.12 versus 1.54, P = 0.003).

Conclusions

Our results shed new light on the synergy of ceftazidime/avibactam and meropenem/vaborbactam combinations against KPC-Kp with or without porin mutations. Killing activity of ceftazidime/avibactam with other cell wall active agents was decreased against isolates with porin mutations. On the other hand, some meropenem/vaborbactam combinations demonstrated enhanced killing in the presence of porin mutations.
Evaluating the incidence of ampC-β-lactamase genes, biofilm formation, and antibiotic resistance among hypervirulent and classical Klebsiella pneumoniae strains
Authors: Haddadi Mohammad Hossein , Khoshnood Saeed , Koupaei Maryam , Heidary Mohsen , Moradi Melika , Jamshidi Ali , Behrouj Hamid , Movahedpour Ahmad , Maleki Mohammad Hassan , Ghanavati Roya
Published: October 2023

Aim

Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae).

Materials and methods

Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC β-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates.

Results

For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers.

Conclusion

Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated.
Occurrence of high-risk clones of Klebsiella pneumoniae ST11, ST340, and ST855 carrying the blaKPC-2, blaNDM-1, blaNDM-5, and blaNDM-7 genes from colonized and infected patients in Brazil
Authors: de Oliveira Érica Maria , Beltrão Elizabeth Maria Bispo , Pimentel Maria Izabely Silva , Lopes Ana Catarina de Souza
Published: October 2023

Aims

Determine which sequence type (ST) clones were carrying the blaKPC, blaNDM, blaVIM, blaIMP, and blaGES genes and their variants in clinical isolates of multidrug-resistant Klebsiella pneumoniae.

Methods and Results

Ten K. pneumoniae isolates were obtained from the colonized and infected patients in a public hospital in the city of Recife-PE, in northeastern Brazil, and were further analyzed. The detection of carbapenem resistance genes and the seven housekeeping genes [for multilocus sequence typing (MLST) detection] were done with PCR and sequencing. The blaKPC and blaNDM genes were detected concomitantly in all isolates, with variants being detected blaNDM-1, blaNDM-5, blaNDM-7, and blaKPC-2. The blaKPC-2 and blaNDM-1 combination being the most frequent. Molecular typing by MLST detected three types of high-risk ST clones, associated with the clonal complex 258, ST11/CC258 in eight isolates, and ST855/CC258 and ST340/CC258 in the other two isolates.

Conclusions

These findings are worrying, as they have a negative impact on the scenario of antimicrobial resistance, and show the high genetic variability of K. pneumoniae and its ability to mutate resistance genes and risk of dissemination via different ST clones.
Improve coati optimization algorithm for solving constrained engineering optimization problems
Authors: Jia Heming , Shi Shengzhao , Wu Di , Rao Honghua , Zhang Jinrui , Abualigah Laith
Published: October 2023

The coati optimization algorithm (COA) is a meta-heuristic optimization algorithm proposed in 2022. It creates mathematical models according to the habits and social behaviors of coatis: (i) In the group organization of the coatis, half of the coatis climb trees to chase their prey away, while the other half wait beneath to catch it and (ii) Coatis avoidance predators behavior, which gives the algorithm strong global exploration ability. However, over the course of our experiment, we uncovered opportunities for enhancing the algorithm’s performance. When confronted with intricate optimization problems, certain limitations surfaced. Much like a long-nosed raccoon gradually narrowing its search range as it approaches the optimal solution, COA algorithm exhibited tendencies that could result in reduced convergence speed and the risk of becoming trapped in local optima. In this paper, we propose an improved coati optimization algorithm (ICOA) to enhance the algorithm’s efficiency. Through a sound-based search envelopment strategy, coatis can capture prey more quickly and accurately, allowing the algorithm to converge more rapidly. By employing a physical exertion strategy, coatis can have a greater variety of escape options when being chased, thereby enhancing the algorithm’s exploratory capabilities and the ability to escape local optima. Finally, the lens opposition-based learning strategy is added to improve the algorithm’s global performance. To validate the performance of the ICOA, we conducted tests using the IEEE CEC2014 and IEEE CEC2017 benchmark functions, as well as six engineering problems.
Undecidability of admissibility in the product of two Alt logics
Authors: Balbiani Philippe , Gencer Çiğdem
Published: October 2023

The product of two $\textbf {Alt}$ logics possesses the polynomial product finite model property and its membership problem is $\textbf {coNP}$-complete. Using a reduction from an undecidable domino-tiling problem, we prove that its admissibility problem is undecidable.
Neuroethics guidance documents: principles, analysis, and implementation strategies
Authors: O’Shaughnessy Matthew R , Johnson Walter G , Tournas Lucille Nalbach , Rozell Christopher J , Rommelfanger Karen S
Published: October 2023

Innovations in neurotechnologies have ignited conversations about ethics around the world, with implications for researchers, policymakers, and the private sector. The human rights impacts of neurotechnologies have drawn the attention of United Nations bodies; nearly 40 states are tasked with implementing the Organization for Economic Co-operation and Development’s principles for responsible innovation in neurotechnology; and the United States is considering placing export controls on brain-computer interfaces. Against this backdrop, we offer the first review and analysis of neuroethics guidance documents recently issued by prominent government, private, and academic groups, focusing on commonalities and divergences in articulated goals; envisioned roles and responsibilities of different stakeholder groups; and the suggested role of the public. Drawing on lessons from the governance of other emerging technologies, we suggest implementation and evaluation strategies to guide practitioners and policymakers in operationalizing these ethical norms in research, business, and policy settings.
DNA double-strand breaks enhance brassinosteroid signaling to activate quiescent center cell division in Arabidopsis
Authors: Takahashi Naoki , Suita Kazuki , Koike Toshiya , Ogita Nobuo , Zhang Ye , Umeda Masaaki
Published: October 2023

In Arabidopsis roots, the quiescent center (QC), a group of slowly dividing cells located at the center of the stem cell niche, functions as an organizing center to maintain the stemness of neighboring cells. Recent studies have shown that they also act as a reservoir for backup cells, which replenish DNA-damaged stem cells by activating cell division. The latter function is essential for maintaining stem cells under stressful conditions, thereby guaranteeing post-embryonic root development in fluctuating environments. In this study, we show that one of the brassinosteroid receptors in Arabidopsis, BRASSINOSTEROID INSENSITIVE1-LIKE3 (BRL3), plays a major role in activating QC division in response to DNA double-strand breaks. SUPPRESSOR OF GAMMA RESPONSE 1, a master transcription factor governing DNA damage response, directly induces BRL3. DNA damage-induced QC division was completely suppressed in brl3 mutants, whereas QC-specific overexpression of BRL3 activated QC division. Our data also showed that BRL3 is required to induce the AP2-type transcription factor ETHYLENE RESPONSE FACTOR 115, which triggers regenerative cell division. We propose that BRL3-dependent brassinosteroid signaling plays a unique role in activating QC division and replenishing dead stem cells, thereby enabling roots to restart growing after recovery from genotoxic stress.
Evaluation of TIB Molbiol LightMix® assays for detection of Mycoplasma genitalium and key resistance mutations for macrolides and fluoroquinolones
Authors: Balgovind Prisha , Atchison Steph , Danielewski Jennifer , Garland Suzanne M , Costa Anna-Maria , Bodiyabadu Kaveesha , Murray Gerald L
Published: October 2023

The LightMix® Modular Mycoplasma Macrolide and LightMix® Modular parC Fluoroquinolone Resistance assays (TIB Molbiol) were evaluated using sequential Mycoplasma genitalium positive (n = 125) and negative (n = 93) clinical samples. Results were compared to the results of an established commercial assay (ResistancePlus MG assay, SpeeDx Pty Ltd) or Sanger sequencing (for parC). Detection of M. genitalium by the TIB Molbiol assay had a high agreement with the reference assay, with a positive percent agreement (PPA) of 97.6 [95% confidence interval (CI): 93.1–99.5] and negative percent agreement (NPA) of 95.7 (95% CI: 89.5–98.8). From 105 positive samples, macrolide resistance detection had a PPA of 100% (95% CI: 93.7–100) and NPA of 81.3% (95% CI: 67.4–91.1). For the detection of fluroquinolone resistance mutation G248T/S83I or “other mutation” in the quinolone resistance determinant region, from 95 samples there was 100% (95% CI: 86.3–100) sensitivity and 100% (95% CI: 94.5–100) specificity. The understanding of the basis for fluoroquinolone treatment failure is still developing; it is therefore important to use the output of parC-based resistance assays with caution to avoid the inappropriate use of antibiotic therapies, especially considering the limited number of alternative treatments.
Imaging
Authors: Costa Guido , Lanza Ezio , Donadon Matteo , Torzilli Guido
Published: October 2023

Liver imaging represents an essential resource in the surgical treatment of liver diseases. Over the years, a shift has occurred in the role of liver imaging which has moved forward from the classical preoperative aetiological definition of a liver lesion. Nowadays, liver imaging aids the surgeon in the assessment of liver anatomy for optimal surgical planning, in the detection and characterization of focal liver lesions and biliary tract disorders in both the preoperative and intraoperative setting, and in the evaluation of the postoperative course and follow-up. This chapter provides an up-to-date review on the major imaging modalities that aid the surgeon in the surgical treatment of liver diseases.
Fatty liver in liver surgery
Authors: Goldaracena Nicolas , McCormack Lucas
Published: October 2023

Liver steatosis is considered as a clinically important feature that influences patient morbidity and mortality after hepatic resection and liver transplantation. Surgeons should take the presence of injured livers into account when planning the extent and type of hepatic surgery. Preoperative and perioperative interventions should be considered in these patients to minimize postoperative complications. Each multidisciplinary team should decide the best algorithm based on current evidence tailored to each patient to reach similar rates of morbidity and mortality compared to patients with healthy livers. Further randomized trials should focus on the evaluation of novel preoperative strategies, such as short-term intensive medical treatment of hepatic steatosis and preoperative portal vein embolization, to minimize risk in these patients.
Cystic lesions of the liver
Authors: Martin David , Melloul Emmanuel
Published: October 2023

Cystic lesions of the liver represent a heterogeneous group of fluid-filled lesions. Most of these lesions are benign and discovered incidentally. A minority can cause symptoms and rarely may be associated with complications. Hepatic cysts can be subdivided into simple and complex cysts, based on their characteristics. Ultrasound is typically the first-line imaging modality. Computed tomography scanning or magnetic resonance imaging gives more detailed information about location, surrounding structures, nodularity, septations, and calcification within the cyst. There are still controversies about the definitions and classifications of cysts. Furthermore, no consensus has been achieved on the optimal treatment of patients with symptoms. This chapter provides an overview of the diagnosis and management of the most commonly observed hepatic cystic lesions.
Primary neoplasms of the liver
Authors: Muiesan Paolo , Schlegel Andrea , Grimaldi Chiara , Bici Kejd
Published: October 2023

Liver tumours represent around 2% of paediatric solid tumours. Among liver malignancies hepatoblastoma is the most frequent (80%), followed by hepatocellular carcinoma and other rare tumours. In the last decade, the management of hepatoblastoma has significantly evolved, leading to constant improvements in long-term outcome. In fact, the disease-free survival has increased from 30% in the prechemotherapy era to 70–80% in recent reports. As far as complete tumour resection remains the standpoint of treatment, multimodality and multispecialist management is the key for the constant amelioration of results. New cooperative groups like the Children’s Hepatic tumours International Collaboration (CHIC) allowed the collection of data from large series to introduce a new, simplified risk staging system and more data will be obtained with the institution of the Pediatric Hepatic International Tumor Trial (PHITT) protocol to optimize chemotherapy treatments. In this chapter, pre- and intraoperative management of HB are detailed, along with the most recent advances and challenges in the approach to patients with HB to give a complete and deep overview of the topic.
Non-operative management of liver lesions
Authors: Deepa Shree T. , Botcha Sandeep
Published: October 2023

Liver malignancies are the second leading cause of cancer-related mortality worldwide. Transplantation and surgical resection of the liver remain the gold standard curative treatment options; however, a limited number (15–20%) of patients are suitable candidates for these procedures due to advanced liver disease and associated comorbidities. A variety of image-guided percutaneous ablative and catheter-based locoregional techniques have been developed and intensively investigated in patients with inoperable primary and secondary liver lesions. They are useful to downstage and bridge patients for surgical and transplant interventions, definitive curative intent in smaller lesions, and as primary palliative management improving survival outcomes and quality of life with increasing importance in treating postsurgical tumour recurrence. This chapter summarizes various currently available non-operative minimally invasive interventional oncology treatments along with their techniques of use in planning and managing liver lesions.
Endoscopic diagnostic and treatment modalities of the biliary system
Authors: Gubler Christoph , Oliver Frans
Published: October 2023

Parallel to the evolution of radiological imaging, endosonography and endoscopic retrograde cholangiopancreatography (ERCP) have evolved into important diagnostic and therapeutic modalities in biliary disease. ERCP has shifted to an almost solely therapeutic intervention whereas endosonography gained grounds in both diagnostics and therapy. Beside characterizing and staging lesions, endosonography allows acquisition of tissue to confirm a diagnosis. Therapeutically, endosonography enables gaining access to the biliary system in altered anatomy or when other methods fail. ERCP remains the intervention of choice in stone and most stricturing bile duct diseases regardless of the aetiology. Through-the-endoscope (dilatation) balloons, baskets, stents, radiofrequency ablation catheters, cholangioscopes, and electrohydraulic/laser lithotripsy catheters have expended the therapeutic possibilities.
Acute and chronic cholecystitis
Authors: Goumard Claire , Scatton Olivier
Published: October 2023

In the era of minimally invasive surgery, cholecystitis remains the main risk factor for bile duct injury during cholecystectomy, irrespective of the surgical approach—laparoscopic or open. This chapter reviews, according to the most recent recommendations, the indications, surgical technique, and alternative strategies in the case of cholecystitis depending on its severity. It emphasizes the importance of obtaining the critical view of safety, and describes the recommended ‘bail-out’ procedures in case it is impossible to safely obtain the critical view of safety. Dome-down cholecystectomy or partial cholecystectomy must be considered early to prevent any bile duct or vascular injury in case of severe inflammation. Open conversion remains a safe option in case of unclear anatomy, but does not always prevent biliary or vascular injuries, as the experience of surgeons has shifted from open to laparoscopic techniques in the last decades.
Biliary fistula, gallstone ileus, and Mirizzi syndrome
Authors: Palavecino Martin , Pekolj Juan
Published: October 2023

Biliary fistula, gallstone ileus, and Mirizzi syndrome are clinical scenarios related to a prolonged history of gallstone disease. Preoperative diagnosis is crucial for correct treatment and is still challenging. Computed tomography scan and magnetic resonance cholangiopancreatography have high diagnostic sensitivity, specificity, and accuracy. Biliary fistula is an abnormal communication between the gall bladder and another organ. The most common is a cholecystoduodenal fistula. Gallstone ileus is a mechanical bowel obstruction due to an impacted gallstone. This is a high morbidity and mortality scenario. The main therapeutic objective is to release the obstruction. Surgical enterolithotomy is the most frequently used procedure. Two-stage and one-stage surgery have selective indications. The laparoscopic approach is increasing its applicability in these complex cases and is safe and effective when performed by experienced surgeons. The endoscopic approach has selective indications in some gastroduodenal and colonic obstructions. Mirizzi syndrome is a fistula between the gall bladder and the main biliary duct. It has four different types and each one has an adequate technique for treatment. The laparoscopic approach is preferable when feasible and performed by surgeons with expertise in complex biliary surgery.
Acute cholangitis, recurrent cholangitis, and management of common bile duct calculi
Authors: Triki Haitham , Boudjema Karim
Published: October 2023

Acute cholangitis is an acute inflammation and infection in the bile ducts leading to systemic infectious disease. It can be life-threatening. The most common cause is a bile duct calculus. Adequate resuscitation, broad-spectrum parenteral antibiotics, and biliary decompression are the key principles of the management. Biliary decompression can be achieved by endoscopic or percutaneous means. Surgery should be used only as a last resort. Recurrent cholangitis is often associated with intrahepatic lithiasis. Its management is challenging and aims to reduce the risk of recurrence and long-term complications including biliary cirrhosis and cholangiocarcinoma. Common bile duct calculi are generally related to the migration of stones from the gallbladder. It should be removed to reduce the risk of complications over time. In case of previous cholecystectomy, endoscopic treatment is the best option. Otherwise, the management of both common bile duct and gallbladder stones can be performed either by a combined endoscopy–surgical approach or by an exclusively surgical approach.
Heparins, fondaparinux, hirudin, bivalirudin, argatroban, and danaparoid
Authors: Olie Renske H. , ten Cate Hugo
Published: October 2023

Several parenteral anticoagulants are available for thromboprophylaxis as well as for treatment of both venous and arterial thrombosis. In this chapter, the mechanism of action, pharmacology, administration, and monitoring of heparin, low-molecular-weight heparins, fondaparinux, hirudin, bivalirudin, argatroban, and danaparoid are discussed. Indications and adverse effects are summarized, as well as reversal of effect in case of bleeding complications or urgent surgery. Heparin-induced thrombocytopenia is a rare but feared reaction to heparin treatment and requires discontinuation of the drug and alternative treatment with non-heparin anticoagulants such as argatroban, danaparoid or fondaparinux.
Thought Insertion, Mental Affordances, and Affectivity
Authors: Maiese Michelle
Published: October 2023

Subjects ordinarily have a sense that our thoughts are afforded or solicited by aspects of our environment, or by our existing mental states. However, in cases of thought insertion, thoughts are not experienced as afforded. They seem so foreign and alien that subjects claim that they have been inserted in their mind by another source. Subjectivity and ownership remain intact in the sense that the thoughts are first-personally accessible via introspection; however, the subject lacks both a sense of ownership and a sense of agency. To make sense of how thoughts ordinarily are experienced as afforded, and how this ordinary experience is disrupted in cases of thought insertion, this chapter appeals to McClelland’s (2019) notion of ‘mental affordance’ and Dings’ (2018) observations about the phenomenology of affordance-responsiveness. It is argued that affectivity is central to our experience of affordances and that a disruption to ‘affective framing’ plays a central role in thought insertion.
Thought Insertion Delusion
Authors: Vilatta Emilia
Published: October 2023

Thought insertion is a type of delusion that involves experiencing one’s thoughts as if they were someone else’s. In this chapter, it is argued that in order to understand what the delusional experience consists of, and how it is different from other alien thoughts, several factors need to be considered: (i) the occurrence of thoughts that appear as intrusive because of their unpleasant content and by the effect of the compartmentalization of the mind; (ii) a pattern of experiential avoidance that implies a pathological way of relating with the disturbing thoughts; (iii) phenomenological alterations in the sense of agency; and (iv) a number of cognitive biases that affect the process of adoption and evaluation of beliefs. The upshot is that a multifactorial approach is needed to explain how thought insertion delusion can arise.