bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and risk assessment of novel SXT/R391 integrative and conjugative elements with multidrug resistance in
Proteus mirabilis
isolated from China, 2018–2020
Authors: Han Yun , Gao Yu-Feng , Xu He-ting , Li Jin-Peng , Li Chao , Song Cai-Liang , Lei Chang-Wei , Chen Xuan , Wang Qin , Ma Bo-Heng , Wang Hong-Ning
Published: January 2024

Proteus mirabilis
can transfer transposons, insertion sequences, and gene cassettes to the chromosomes of other hosts through SXT/R391 integrative and conjugative elements (ICEs), significantly increasing the possibility of antibiotic resistance gene (ARG) evolution and expanding the risk of ARGs transmission among bacteria. A total of 103 strains of
P. mirabilis
were isolated from 25 farms in China from 2018 to 2020. The positive detection rate of SXT/R391 ICEs was 25.2% (26/103). All SXT/R391 ICEs positive
P. mirabilis
exhibited a high level of overall drug resistance. Conjugation experiments showed that all 26 SXT/R391 ICEs could efficiently transfer to
Escherichia coli
EC600 with a frequency of 2.0 × 10
−7
to 6.0 × 10
−5
. The acquired ARGs, genetic structures, homology relationships, and conservation sequences of 26 (19 different subtypes) SXT/R391 ICEs were investigated by high-throughput sequencing, whole-genome typing, and phylogenetic tree construction. ICE
Pmi
ChnHBRJC2 carries
erm (42
), which have never been found within an SXT/R391 ICE in
P. mirabilis
, and ICE
Pmi
ChnSC1111 carries 19 ARGs, including clinically important
cfr
,

bla
CTX-M-65

, and
aac(6')-Ib-cr
, making it the ICE with the most ARGs reported to date. Through genetic stability, growth curve, and competition experiments, it was found that the transconjugant of ICE
Pmi
ChnSCNNC12 did not have a significant fitness cost on the recipient bacterium EC600 and may have a higher risk of transmission and dissemination. Although the transconjugant of ICE
Pmi
ChnSCSZC20 had a relatively obvious fitness cost on EC600, long-term resistance selection pressure may improve bacterial fitness through compensatory adaptation, providing scientific evidence for risk assessment of horizontal transfer and dissemination of SXT/R391 ICEs in
P. mirabilis
.

IMPORTANCE

The spread of antibiotic resistance genes (ARGs) is a major public health concern. The study investigated the prevalence and genetic diversity of integrative and conjugative elements (ICEs) in
Proteus mirabilis
, which can transfer ARGs to other hosts. The study found that all of the
P. mirabilis
strains carrying ICEs exhibited a high level of drug resistance and a higher risk of transmission and dissemination of ARGs. The analysis of novel multidrug-resistant ICEs highlighted the potential for the evolution and spread of novel resistance mechanisms. These findings emphasize the importance of monitoring the spread of ICEs carrying ARGs and the urgent need for effective strategies to combat antibiotic resistance. Understanding the genetic diversity and potential for transmission of ARGs among bacteria is crucial for developing targeted interventions to mitigate the threat of antibiotic resistance.
Mechanism for transmission and pathogenesis of carbapenem-resistant Enterobacterales harboring the carbapenemase IMP and clinical countermeasures
Authors: Yang Chengru , Jiang Shan , Wei Chunli , Li Chunjiang , Wang Jianmin , Li Xinhui , Zeng Lingyi , Hu Kewang , Yang Yang , Zhang Jisheng , Zhang Xiaoli
Published: January 2024

Carbapenem-resistant Enterobacterales (CRE) are some of the most important pathogens causing infections, which can be challenging to treat. We identified four
bla
IMP
-carrying CRE isolates and collected clinical data. The transferability and stability of the plasmid were verified by conjugation, successive passaging, and plasmid elimination assays. The IncC
bla
IMP-4
-carrying pIMP4-ECL42 plasmid was successfully transferred into the recipient strain, and the high expression of
traD
may have facilitated the conjugation transfer of the plasmid. Interestingly, the plasmid showed strong stability in clinical isolates. Whole-genome sequencing was performed on all isolates. We assessed the sequence similarity of
bla
IMP
-harboring plasmid from our institution and compared it to plasmids for which sequence data are publicly available. We found that four
bla
IMP
-carrying CRE belonged to four different sequence types. The checkerboard technique and time-kill assays were used to investigate the best antimicrobial therapies for
bla
IMP
-carrying CRE. The time-kill assay showed that the imipenem of 1× minimum inhibitory concentration (MIC) alone had the bactericidal or bacteriostatic effect against IMP-producing strains at 4–12 h
in vitro
. Moreover, the combination of tigecycline (0.5/1/2 × MIC) and imipenem (0.5/1 × MIC) showed a bactericidal effect against the
bla
IMP-26
-carrying CRECL60 strain.

IMPORTANCE

Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat, and infections caused by these microorganisms are often associated with high mortality and limited treatment options. This study aimed to determine the clinical features, molecular characteristics, and plasmid transmissible mechanisms of
bla
IMP
carriage as well as to provide a potential treatment option. Here, we demonstrated that conjugated transfer of the IncC
bla
IMP-4
-carrying plasmid promotes plasmid stability, so inhibition of conjugated transfer and enhanced plasmid loss may be potential ways to suppress the persistence of this plasmid. The imipenem alone or tigecycline-imipenem combination showed a good bactericidal effect against IMP-producing strains. In particular, our study revealed that imipenem alone or tigecycline-imipenem combination may be a potential therapeutic option for patients who are infected with IMP-producing strains. Our study supports further trials of appropriate antibiotics to determine optimal treatment and emphasizes the importance of continued monitoring of IMP-producing strains in the future.
SARS-CoV-2 viral dynamics in a placebo-controlled phase 2 study of patients infected with the SARS-CoV-2 Omicron variant and treated with pomotrelvir
Authors: Borroto-Esoda Katyna , Wilfret David , Tong Xiao , Plummer Andrew , Kearney Brian , Kwong Ann D.
Published: January 2024

Current guidelines recommend that individuals with moderate COVID-19 disease isolate for 5 days after the first appearance of symptoms or a positive SARS-CoV-2 test. It would be useful to understand the time course of infectious virus production and its correlation with virus detection using a rapid antigen test (RAT) or quantitative reverse transcriptase (qRT)-PCR. In a phase 2 study, 242 vaccinated patients with COVID-19 and at low risk for progression to severe disease initiated 5 days of treatment with pomotrelvir (PBI-0451, a SARS-CoV-2 main protease inhibitor) or placebo within 5 days after symptom onset. The primary endpoint, the proportion of subjects with SARS-CoV-2 viral titers below the limit of detection on Day 3 of treatment in the pomotrelvir versus placebo groups, was not met. No between-group differences in SARS-CoV-2 clearance or symptom resolution or alleviation were observed. Additional analyses evaluated the dynamics of SARS-CoV-2 replication in mid-turbinate nasal swabs and saliva samples using infectious virus assay (IVA), RAT, and qRT-PCR. SARS-CoV-2 cleared rapidly, with negative results first determined by IVA (TCID
50
below the limit of detection), followed by the RAT (negative for SARS-CoV-2 N antigen), and qRT-PCR (RNA below the limit of detection), which suggests that delayed initiation of treatment (up to 5 days after symptom onset) may have contributed to the lack of treatment response. Symptom resolution lagged behind viral clearance assessed by IVA and RAT. These data support reliance on a negative RAT to determine when an individual is no longer producing infectious virus and may end isolation.

IMPORTANCE

A phase 2 double-blind, placebo-controlled study was performed evaluating pomotrelvir, a SARS-CoV-2 Mpro inhibitor, compared with placebo in 242 non-hospitalized, vaccinated, symptomatic adults with COVID-19 (Omicron). No improvement in the decrease of viral replication or relief of symptoms was observed between the two groups when treatment was initiated ≥3 days after symptom onset. These results suggest that future COVID-19 antiviral studies using a similar patient population may need to initiate treatment earlier, like influenza studies. This is the first study to prospectively evaluate SARS-CoV-2 viral dynamics and the time to viral clearance in a significant number of patients using concurrently obtained results from an infectious virus assay, a rapid antigen test (RAT), and a qRT-PCR assay over a 15-day time course. These results suggest that a negative RAT assay is a good indicator of loss of infectious virus and the ability to return to normal activities.
Interspecific plant interaction structures the microbiomes of poplar-soil interface to alter nutrient cycling and utilization
Authors: You Yimin , Wang Liran , Liu Xiaoting , Wang Xuelai , Jiang Luping , Ding Changjun , Wang Weina , Zhang Dawei , Zhao Xiyang
Published: January 2024

Terrestrial plants can influence the growth and health of adjacent plants through interspecific interaction. Here, the mechanisms of interspecific plant interaction on microbial function and nutrient utilization in the plant-soil interface (non-rhizosphere soil, rhizosphere soil, and root) were studied by soybean- and potato-poplar intercropping. First, metagenomics showed that soybean- and potato-poplar intercropping influenced the composition and co-occurrence networks of microbial communities in different ecological niches, with higher stability of the microbial community in soybean intercropping. Second, the gene abundance related to carbon metabolism, nitrogen cycling, phosphorus cycling, and sulfur cycling was increased at the poplar-soil interface in soybean intercropping. Moreover, soybean intercropping increased soil nutrient content and enzymatic activity. It showed higher metabolic potential in nutrient metabolism and transportation. Third, functional microorganisms that influenced nutrient cycling and transportation in different intercropping have been identified, namely
Acidobacteria
,
Sphingomonas
,
Gemmatimonadaceae
,
Alphaproteobacteria
, and
Bradyrhizobium
. Therefore, intercropping can construct microbial communities to alter metabolic functions and improve nutrient cycling and absorption. Interspecific plant interactions to influence the microbiome were revealed, opening up a new way for the precise regulation of plant microbiome.

IMPORTANCE

Poplar has the characteristics of wide distribution, strong adaptability, and fast growth, which is an ideal tree species for timber forest. In this study, metagenomics and elemental analysis were used to comprehensively reveal the effects of interspecific plant interactions on microbial communities and functions in different ecological niches. It can provide a theoretical basis for the development and application of the precise management model in poplar.
Double Mizoroki–Heck Arylation of Terminal Alkenes in the Presence of “Ligand-Free” Palladium Catalytic Systems
Authors: Kurokhtina A. A. , Larina E. V. , Lagoda N. A. , Grigoryeva T. A. , Schmidt A. F.
Published: January 2024

One-pot sequential double arylation of terminal alkenes with aryl halides to give trisubstituted derivatives is reported. The proposed approach is more advantageous than the known methods due to the use of a combination of low reactive but available aryl bromides or aryl chlorides and palladium-based “ligand-free” catalytic system.
Prevalence and early surgical outcome of congenital diaphragmatic hernia in the Netherlands: a population-based cohort study from the European Pediatric Surgical Audit
Authors: Teunissen Nadine Maria , Daniels Horst , Schnater J Marco , de Blaauw Ivo , Wijnen René M H
Published: January 2024

Background

Congenital diaphragmatic hernia (CDH) is a rare birth defect with substantial mortality. This study aims to generate a population-based overview of CDH care and outcomes in the Netherlands. Moreover, it assesses interhospital variations between the two Dutch CDH expert centres.

Methods

This study uses data from the Dutch branch of the European Pediatric Surgical Audit, a prospective clinical audit for congenital anomalies. Data of all patients with CDH treated between 2014 and 2021 were included for epidemiological analysis. For comparative analyses, patients presenting after the neonatal period or not treated in the two CDH expert centres were excluded. Identified interhospital variations were assessed using regression analysis.

Results

In the study period, 283 children with CDH were born, resulting in a national prevalence rate of 2.06/10 000 live births. The patient population, treatment and outcomes at 1 year were comparable between the hospitals, except for length of hospital stay. Regression analysis identified the treating hospital as the strongest significant predictor thereof. Other factors associated with longer length of stay include the presence of other malformations, intrathoracic liver position on prenatal ultrasound, extracorporeal membrane oxygenation treatment, patch repair, complicated postoperative course and discharge to home rather than to another care facility.

Conclusion

Outcomes of CDH care throughout the Netherlands are comparable. However, the length of stay differed between the two hospitals, also when adjusting for other covariates. Further qualitative analysis to explain this interhospital variation is indicated. Our findings underscore the potential of clinical auditing as a quality measurement tool in rare conditions.
Ertapenem-induced encephalopathy in a patient with liver abscess and acute kidney injury
Authors: Farooq Shahid , Acosta Allan
Published: January 2024

A man in his late 70s, retired and independent, generally fit and well with a history of normal cognitive function baseline presented with liver abscess and acute kidney injury. He received meropenem 1 g three times a day for 15 days then subsequently changed to ertapenem 1 g one time a day in preparation for outpatient antibiotic treatment. After 2 days of starting ertapenem, the patient developed night-time delirium, decreased orientation and insomnia, loss of appetite, jerking and hallucination. Investigations have been done to investigate the cause of acute delirium, including lumbar puncture, CT brain, MRI brain, repeat CT abdomen and pelvis to monitor the liver abscess, and electroencephalogram but results were all unremarkable. Medication history during admission was reviewed and discontinued one by one the medications that were suspected to have caused the encephalopathy. Two days following the discontinuation of ertapenem, the patient’s symptoms improved with a rapid return to his baseline and without neurological deficit.
Randomised controlled trial on the effect of social support on disease control, mental health and health-related quality of life in people with diabetes from Côte d’Ivoire: the SoDDiCo study protocol
Authors: Ekou Franck Kokora , Eze Ikenna C , Aka Joseph , Kwiatkowski Marek , Merten Sonja , Acka Felix Kouamé , Fink Günther , Utzinger Jürg , Probst-Hensch Nicole
Published: January 2024

Introduction

Diabetes mellitus (DM) and its severe complications contribute significantly to disability and, hence, burden of disease. Poor mental health, a frequent DM consequence, may hinder successful diabetes control in low-income and middle-income countries (LMICs). Evidence suggests social support as a cost-effective tool to improve diabetes self-management, behaviour and mental health. However, its real-world application in LMICs has rarely been tested. We aim to investigate the effect of a social support intervention on disease control, mental health and health-related quality of life in people with diabetes from Côte d’Ivoire (SoDDiCo) through a randomised controlled trial.

Methods and analysis

The trial will take place in the Centre Antidiabétique d’Abidjan, Institut National de Santé Publique, Abidjan, Côte d’Ivoire. We will prospectively randomise up to 1500 people with newly diagnosed diabetes into two parallel arms: intervention (routine care+family supporter accompanying clinical management) and control (routine care), using gender-stratified blocked randomisation with random block sizes of 10, 16, 20 and 24. Participants will undergo baseline, 3-month and 12-month postrandomisation assessments. The primary study outcome will be glycated haemoglobin (HbA1c). Secondary outcomes will include glycaemic control (HbA1c<7.0%), presence at follow-up visits, mental health and quality of life scores. Using intention-to-treat framework, we will assess the impact of the family support intervention on these endpoints over the course of the 1-year follow-up. Effect modification by baseline social capital will be assessed.

Ethics and dissemination

The SoDDiCo trial was approved by the Ethikkommission Nordwest- und Zentralschweiz (ref: AO_2021-00041; approved: 12 July 2021) and by Comité National d'Éthique des Sciences de la Vie et de la Santé (ref: 049-22/MSHPCMU/CNESVS-kp; approved: 20 April 2022). The randomised intervention trial will follow good clinical practice guidelines. All results will be made available to the public through abstracts at conferences as well as through peer-reviewed articles. International guidelines for authorship will be respected.

Trial registration number

ISRCTN10901121, ISRCTN registry.
ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo
Authors: Schulz-Kuhnt Anja , Rühle Katharina , Javidmehr Asal , Döbrönti Michael , Biwank Jana , Knittel Selina , Neidlinger Peter , Leupold Jannik , Liu Li-Juan , Dedden Mark , Taudte Regina Verena , Gessner Arne , Fromm Martin F , Mielenz Dirk , Kreiss Lucas , Waldner Maximilian J , Schürmann Sebastian , Friedrich Oliver , Dietel Barbara , López-Posadas Rocío , Plattner Christina ,   The TRR241 IBDome Consortium, Zundler Sebastian , Becker Christoph , Atreya Raja , Neurath Markus F , Atreya Imke
Published: January 2024

Objective

Mucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we here focus on the enzyme ATP citrate lyase (ACLY) in mucosal T cell immunometabolism and its relevance for IBD.

Design

ACLY expression and its immunometabolic impact on colitogenic T cell function were analysed in mucosal T cells from patients with IBD and in two experimental colitis models.

Results

ACLY was markedly expressed in colon tissue under steady-state conditions but was significantly downregulated in lamina propria mononuclear cells in experimental dextran sodium sulfate-induced colitis and in CD4+and to a lesser extent in CD8+T cells infiltrating the inflamed gut in patients with IBD. ACLY-deficient CD4+T cells showed an impaired capacity to induce intestinal inflammation in a transfer colitis model as compared with wild-type T cells. Assessment of T cell immunometabolism revealed that ACLY deficiency dampened the production of IBD-relevant cytokines and impaired glycolytic ATP production but enriched metabolites involved in the biosynthesis of phospholipids and phosphatidylcholine. Interestingly, the short-chain fatty acid butyrate was identified as a potent suppressor of ACLY expression in T cells, while IL-36α and resolvin E1 induced ACLY levels. In a translational approach, in vivo administration of the butyrate prodrug tributyrin downregulated mucosal infiltration of ACLYhighCD4+T cells and ameliorated chronic colitis.

Conclusion

ACLY controls mucosal T cell immunometabolism and experimental colitis. Therapeutic modulation of ACLY expression in T cells emerges as a novel strategy to promote the resolution of intestinal inflammation.
Indian childhood cirrhosis: a retrospective study –redefining the older myths!
Authors: Goyal Surbhi , Singh Akanksha , Gangwar Shivanshu , Goyal Aditi , Sakhuja Puja , Kapoor Seema
Published: January 2024

Aims

This retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management.

Methods

This study was done on liver archival tissue of our department from the period of January 2016 to December 2022. Of these, cases of copper overload on paediatric biopsies were retrieved. The histopathological features were scrutinised independently by three pathologists, correlating with their clinico-radiological investigations.

Results

Five children in infancy to middle childhood presented with features of chronic liver disease in the form of jaundice and abdominal distention, were included in the study. Characteristic ﬁrm hepatomegaly with sharp margins and transaminitis was noted in all cases. Autoimmune, viral and metabolic workup were negative in all these patients except one which showed positive autoimmunity and another whose Coomb’s test was positive. Normal ceruloplasmin levels and unremarkable slit lamp examination excluded the possibility of Wilson’s disease. The histological features of marked ballooning degeneration with diffuse Mallory Denk, pericellular fibrosis, absence of steatosis and panlobular copper deposits clinched the diagnosis of ICC.

Conclusions

ICC once believed to be extinct has still not vanished and remains underdiagnosed in routine practice. It is a rapidly fatal disease with a debatable pattern of inheritance and controversial role of copper as etiological agent. The clinical presentation is often deceptive and lack of awareness leads to misdiagnosis. Histopathological attributes are pathognomonic and possibility of ICC should be kept in all cases of cryptogenic cirrhosis.
Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients
Authors: Ali Rola H , Almanabri Mohamad , Ali Nawal Y , Alsaber Ahmad R , Khalifa Nisreen M , Hussein Rania , Alateeqi Mona , Mohammed Eiman M A , Jama Hiba , Almarzooq Ammar , Benobaid Noelle , Alqallaf Zainab , Ahmed Amir A , Bahzad Shakir , Almurshed Maryam
Published: January 2024

Aims

Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait.

Methods

We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations.

Results

Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2–17.6) and 21 adult patients (median 37 years; 18.9–89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs.

Conclusion

The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.
Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank
Authors: Casanova Francesco , Tian Qu , Atkins Janice L , Wood Andrew R , Williamson Daniel , Qian Yong , Zweibaum David , Ding Jun , Melzer David , Ferrucci Luigi , Pilling Luke C
Published: January 2024

Background

Brain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter.

Methods

We analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer’s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia.

Results

In Europeans, higher genetically predicted TSAT increased genetic liability to dementia (Odds Ratio [OR]: 1.15, 95% Confidence Intervals [CI] 1.04 to 1.26, p=0.0051), non-AD dementia (OR: 1.27, 95% CI 1.12 to 1.45, p=0.00018) and vascular dementia (OR: 1.37, 95% CI 1.12 to 1.69, p=0.0023), but not AD (OR: 1.00, 95% CI 0.86 to 1.15, p=0.97). Higher TSAT was also associated with increased risk of non-AD dementia in participants of African, but not South Asian groups. In survival analysis using a TSAT polygenic score, the effect was independent of apolipoprotein-E ε4 genotype (with adjustment subdistribution Hazard Ratio: 1.74, 95% CI 1.33 to 2.28, p=0.00006). Genetically predicted TSAT was associated with lower grey matter volume in caudate, putamen and thalamus, and not in other areas of interest.

Discussion

Genetic evidence supports a causal relationship between higher TSAT and risk of clinically defined non-AD and vascular dementia, in European and African groups. This association appears to be independent of apolipoprotein-E ε4.
Personalism and boosting organ ResERVOirs: a consideration of euthanasia by removal of vital organs in the Canadian context
Authors: Grunwald Jamie
Published: January 2024

Canada’s decriminalisation of assisted death has elicited significant ethical implications for the use of assisted death in healthcare contexts. Euthanasia by removal of vital organs (ERVO) is a theoretical extension of medically assisted death with an increased plausibility of implementation in light of the rapid expansion of assisted death eligibility laws and criteria in Canada. ERVO entails removing organs from a living patient under general anaesthesia as the mechanism of death. While ERVO is intended to maximise the viability of organs procured from the euthanised patient for donation to recipients, ending the lives of patient donors in this manner solely to benefit ill or dying recipient patients merits further ethical consideration. Specifically, the paper explores the application of personalist bioethics in determining whether the means of procuring organs through assisted death justifies the end of improving the lives of those who would benefit from receiving them. Further, by discussing the medical, social and ethical implications of ERVO, I will explicate a broader philosophical understanding of the influences of legalising assisted death on human dignity and conscience.
Single case of lymphogranuloma venereum on the tongue
Authors: Sobral-Costas Tristan Gabriel , López-Alcázar Sergio , Escudero-Tornero Rafael , Servera-Negre Guillermo , Montenegro Pascual David Manuel , Quiles-Melero Inmaculada , Sendagorta Cudós Elena
Published: January 2024

Traditionally, lymphogranuloma venereum (LGV) has been associated with disease of the genital area. However, atypical presentations and proctitis are increasingly observed. We report a case of LGV affecting the dorsum of the tongue, which presented as a very painful ulcer. The response to doxycycline (100 mg two times per day for 21 days) was satisfactory. This case may represent a paradigm shift in the differential diagnosis of lingual ulcers.
Nicotine beliefs and perceptions of low nicotine labels and mitigating statements among people who do and do not smoke: a cross-sectional study from Aotearoa New Zealand
Authors: Gendall Philip , Popova Lucy , Thrasher James , Hoek Janet
Published: January 2024

Background

Aotearoa New Zealand proposed a new maximum nicotine content of 0.8 mg/g for smoked tobacco products, although the new government plans to repeal this legislation. Requiring ‘Very low nicotine’ (VLN) messages on cigarettes meeting this standard may reinforce misperceptions that they are less harmful than cigarettes currently sold.

Methods

To explore knowledge of nicotine and very low nicotine cigarettes (VLNCs), and perceptions of cigarette packs featuring different low nicotine messages (eg, ‘Very low nicotine’) and mitigating statements (eg, ‘No cigarettes are safe’), we surveyed 354 people who smoked, 142 who formerly smoked, and 214 people who had never smoked regularly.

Results

Around half of all respondents believed VLNCs were less harmful than regular cigarettes and around two-thirds incorrectly thought nicotine causes most of the related health problems resulting from smoking. Nearly a third thought VLNCs would belessharmful than regular cigarettes; 34% believed they would be just as harmful. Mitigating statements did not affect perceptions of people who smoked, although people who formerly, or who had never smoked regularly, perceived mitigating statements referring to poisons and cancer as significantly more likely than the VLN message to discourage smoking.

Conclusions

Misunderstanding of VLNCs as less harmful than regular cigarettes is widespread; VLN messages may reinforce this misperception, which mitigating statements did not correct among people who smoke. As an alternative to VLN messages, policy makers could consider introducing VLNCs on a specified date and developing public information campaigns; these measures would avoid phase-in confusion and obviate the need for VLN messaging.
The effect of pre-exercise oral hyperhydration on endurance exercise performance, heart rate, and thermoregulation: a meta-analytical review
Authors: McCubbin Alan J. , Irwin Christopher
Published: January 2024

This study aimed to determine the effect of pre-exercise hyperhydration on endurance performance (primary outcome), heart rate, thermoregulation, and perceptual responses (secondary outcomes). Six academic databases were searched to February 2023. Only studies reporting differences in hydration between intervention and placebo/control were included. Meta-analysis determined overall effect size (Hedges’ g), and meta-regression the influence of independent moderators (ambient temperature, hyperhydration agent, exercise mode, extent of hyperhydration). Overall, 10 publications generating 19 effect estimates for primary outcomes, and 11 publications reporting 48 effect estimates for secondary outcomes, were included. A small-to-moderate improvement in time-to-exhaustion (TTE) (Hedges’ g = 0.31, 95% CI: 0.13–0.50, p = 0.001) and time trial (TT) ( g = 0.25, 95% CI: 0.002–0.51, p = 0.049) but not total work (TW) tasks ( p = 0.120) was found following hyperhydration. No moderating effects were observed. No effect of hyperhydration was found for heart rate following steady state (SS) exercise ( p = 0.069) or the performance task ( p = 0.072), nor for body temperature post-SS ( p = 0.132) or post-performance task ( p = 0.349), but meta-regression of sodium versus glycerol showed lower body temperature post-performance task with sodium ( g = 0.80, t (5) = 2.65, p = 0.046). No effects were found for perceived exertion or thermal comfort. Study heterogeneity was low, lacking representation of elite and female athletes, and weight-bearing (i.e., running) exercise modalities. These results suggest pre-exercise hyperhydration provides a small-to-moderate benefit to endurance performance in TTE and TT, but not TW performance tasks. While no moderating effects were observed, lack of heterogeneity makes it difficult to generalise these findings.
Compaction, strength, and volume change characteristics of excavated clayey soil stabilized with composite admixture of cement and autoclaved aerated concrete powder
Authors: Wang Ziang , Zhan Liangtong , Zhang Haihua , Zheng Liangfeng , Kang Ting
Published: January 2024

Low-strength and highly compressible excavated clayey soils are common in geotechnical engineering, which cannot serve as a bearing stratum and typically end up being disposed of in landfills. Autoclaved aerated concrete powder (AACP) is a lightweight and porous waste material, with its stockpiles rapidly accumulating worldwide. To promote sustainable development in geotechnical engineering, a type of composite admixture consisting of cement and AACP was developed to modify clayey soils in this study. The physical and mechanical properties of untreated and the composite admixture-treated soil samples were investigated via Atterberg limits, compaction, bender element, constraint compression, free swell, and unconfined compressive strength (UCS) tests. The physicochemical and microstructural observations, including soil pH, scanning electron microscopy, and mercury intrusion porosimetry analyses, were conducted to interpret the macroscopic mechanical behaviors. Test results showed that the incorporation of AACP improved the workability of clayey soils, while cement further enhanced their mechanical properties. Hydration compounds primarily filled the voids with a diameter ranging from 0.1 to 1 µm. From the perspective of volume change behavior, 8% cement content was recommended. Shear wave velocity showed a strong correlation with the UCS, demonstrating that the bender element technique was an effective non-destructive tool for assessing the strength of compacted samples.
Uncovering the link between diabetes and cardiovascular diseases: insights from adipose-derived stem cells
Authors: Meechem Megan B. , Jadli Anshul S. , Patel Vaibhav B.
Published: January 2024

Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. The escalating global occurrence of obesity and diabetes mellitus (DM) has led to a significant upsurge in individuals afflicted with CVDs. As the prevalence of CVDs continues to rise, it is becoming increasingly important to identify the underlying cellular and molecular mechanisms that contribute to their development and progression, which will help discover novel therapeutic avenues. Adipose tissue (AT) is a connective tissue that plays a crucial role in maintaining lipid and glucose homeostasis. However, when AT is exposed to diseased conditions, such as DM, this tissue will alter its phenotype to become dysfunctional. AT is now recognized as a critical contributor to CVDs, especially in patients with DM. AT is comprised of a heterogeneous cellular population, which includes adipose-derived stem cells (ADSCs). ADSCs resident in AT are believed to regulate physiological cardiac function and have potential cardioprotective roles. However, recent studies have also shown that ADSCs from various adipose tissue depots become pro-apoptotic, pro-inflammatory, less angiogenic, and lose their ability to differentiate into various cell lineages upon exposure to diabetic conditions. This review aims to summarize the current understanding of the physiological roles of ADSCs, the impact of DM on ADSC phenotypic changes, and how these alterations may contribute to the pathogenesis of CVDs.
On generating r-uniform subspaces with the isometric mapping method
Authors: Antipin K. V.
Published: January 2024

In this paper, we propose a compositional approach to construct subspaces consisting entirely of r-uniform states, i.e. states with each reduction to r subsystems being maximally mixed. The approach generates new objects from old ones by combining encoding isometries of pure quantum error correcting codes with entangled multipartite states and subspaces. Such a scheme allows for construction of states in heterogeneous systems, i.e. those having unequal local dimensions. The presented methods can be also used to obtain new pure quantum error correcting codes from certain combinations of old ones. The approach is illustrated with various examples including constructions of 2-, 3-, 4- and 5-uniform subspaces.
Behavior of spin-0 scalar particles in Eddington-inspired Born–Infeld gravity global monopole with harmonic oscillator potential
Authors: Ahmed Faizuddin , Güvendi Abdullah
Published: January 2024

In this paper, we investigate the behavior of a scalar bosonic field within the backdrop of Eddington-inspired Born–Infeld gravity with a global monopole configuration. Additionally, we consider the presence of both scalar and vector potentials. To introduce the scalar potential, we perform a transformation on the mass term, replacing [Formula: see text] with [Formula: see text]. For the vector potential, we apply a minimal coupling scheme, transforming [Formula: see text] within the relativistic Klein–Gordon equation. We opt for a harmonic oscillator scenario where the scalar and vector potentials are equal, i.e. [Formula: see text]. Through this setup, we analytically solve the wave equation using the confluent Heun equation form. Subsequently, we delve into the quantum system in the absence of any potential, determining the permissible values for bound-state relativistic energy levels and the scalar field’s wave function. Our analysis reveals that the energy levels and wave function are influenced by various parameters present in the eigenvalue expression.
Identifying the Root Causes of DBMS Suboptimality
Authors: Currim Sabah , Snodgrass Richard T. , Suh Young-Kyoon
Published: January 2024

The query optimization phase within a database management system (DBMS) ostensibly finds the fastest query execution plan from a potentially large set of enumerated plans, all of which correctly compute the same result of the specified query. Sometimes the cost-based optimizer selects a slower plan, for a variety of reasons. Previous work has focused on increasing the performance of specific components, often a single operator, within an individual DBMS. However, that does not address the fundamental question: from where does this suboptimality arise, across DBMSes generally? In particular, the contribution of each of many possible factors to DBMS suboptimality is currently unknown. To identify the root causes of DBMS suboptimality, we first introduce the notion of
empirical suboptimality
of a query plan chosen by the DBMS, indicated by the existence of a query plan that performs more efficiently than the chosen plan, for the same query. A crucial aspect is that this can be measured externally to the DBMS, and thus does not require access to its source code. We then propose a novel
predictive model
to explain the relationship between various factors in query optimization and empirical suboptimality. Our model associates suboptimality with the factors of complexity of the schema, of the underlying data on which the query is evaluated, of the query itself, and of the DBMS optimizer. The model also characterizes concomitant interactions among these factors. This model induces a number of specific hypotheses that were tested on multiple DBMSes. We performed a series of experiments that examined the plans for thousands of queries run on four popular DBMSes. We tested the model on over a million of these query executions, using correlational analysis, regression analysis, and causal analysis, specifically Structural Equation Modeling (SEM). We observed that the dependent construct of empirical suboptimality prevalence correlates positively with nine specific constructs characterizing four identified factors that explain in concert much of the variance of suboptimality of two extensive benchmarks, across these disparate DBMSes. This predictive model shows that it is the common aspects of these DBMSes that predict suboptimality,
not
the particulars embedded in the inordinate complexity of each of these DBMSes. This paper thus provides a new methodology to study mature query optimizers, identifies underlying DBMS-independent causes for the observed suboptimality, and quantifies the relative contribution of each of these causes to the observed suboptimality. This work thus provides a roadmap for fundamental improvements of cost-based query optimizers.
The Art of Cybercrime Community Research
Authors: Hughes Jack , Pastrana Sergio , Hutchings Alice , Afroz Sadia , Samtani Sagar , Li Weifeng , Santana Marin Ericsson
Published: January 2024

In the last decade, cybercrime has risen considerably. One key factor is the proliferation of online cybercrime communities, where actors trade products and services, and also learn from each other. Accordingly, understanding the operation and behavior of these communities is of great interest, and they have been explored across multiple disciplines with different, often quite novel, approaches. This survey explores the challenges inherent to the field and the methodological approaches researchers used to understand this space. We note that, in many cases, cybercrime research is more of an art than a science. We highlight the good practices and propose a list of recommendations for future cybercrime community scholars, including taking steps to verify and validate results, establishing privacy and ethical research practices, and mitigating the challenge of ground truth data.
Towards an Integrative Framework for Robot Personality Research
Authors: Dobrosovestnova Anna , Reinboth Tim , Weiss Astrid
Published: January 2024

Within human-robot interaction (HRI), research on robot personality has largely drawn on trait theories and models, such as the Big Five and OCEAN. We argue that reliance on trait models in HRI has led to a limited understanding of robot personality as a question of stable traits that can be designed into a robot plus how humans with certain traits respond to particular robots. However, trait-based approaches exist alongside other ways of understanding personality, including approaches focusing on more dynamic constructs such as adaptations and narratives. We suggest that a deep understanding of robot personality is only possible through a cross-disciplinary effort to integrate these different approaches. We propose an Integrative Framework for Robot Personality Research (IF), wherein robot personality is defined not as a property of the robot, nor of the human perceiving the robot, but as a complex assemblage of components at the intersection of robot design and human factors. With the IF, we aim to establish a common theoretical grounding for robot personality research that incorporates personality constructs beyond traits and treats these constructs as complementary and fundamentally interdependent.
Asymmetric Learning for Graph Neural Network based Link Prediction
Authors: Yao Kai-Lang , Li Wu-Jun
Published: January 2024

Link prediction is a fundamental problem in many graph-based applications, such as protein-protein interaction prediction. Recently, graph neural network (GNN) has been widely used for link prediction. However, existing GNN-based link prediction (GNN-LP) methods suffer from scalability problem during training for large-scale graphs, which has received little attention from researchers. In this paper, we first analyze the computation complexity of existing GNN-LP methods, revealing that one reason for the scalability problem stems from their symmetric learning strategy in applying the same class of GNN models to learn representation for both head nodes and tail nodes. We then propose a novel method, called
a
sym
m
etric
l
earning (AML), for GNN-LP. More specifically, AML applies a GNN model to learn head node representation while applying a multi-layer perceptron (MLP) model to learn tail node representation. To the best of our knowledge, AML is the first GNN-LP method to adopt an asymmetric learning strategy for node representation learning. Furthermore, we design a novel model architecture and apply a row-wise mini-batch sampling strategy to ensure promising model accuracy and training efficiency for AML. Experiments on three real large-scale datasets show that AML is 1.7×∼7.3× faster in training than baselines with a symmetric learning strategy while having almost no accuracy loss.
Corrosion Resistance, Composition, and Stratification of Passive Films: Ni-22Cr and Ni-22Cr-6Mo Alloys Passivated and Exposure Aged in Acidic Chloride Solutions
Authors: Orson Keithen , Romanovskaia Elena , Costine Anna , Han Junsoo , Ogle Kevin , Scully John R. , Reinke Petra
Published: January 2024

Ni-Cr based super-alloys have exceptional corrosion resistance, which is further improved with Mo alloying. The correlation between passive layer performance and composition was studied to gain a deeper mechanistic understanding of the role of Mo by comparing the behavior of Ni-22Cr to Ni-22Cr-6Mo (wt%) alloys. The passive layers were formed using galvanostatic holds to create fast and slow growth conditions using high and low current densities. A potentiostatic hold was added to initiate exposure aging. The passive film was characterized using electrochemical impedance spectroscopy (EIS), linear sweep voltammetry (LSV), atomic emission spectro-electrochemistry (AESEC), and X-ray photoelectron spectroscopy (XPS). Combined electrochemical and XPS characterization offered insight in cation concentrations and stratification, bonding states (oxide, hydroxide), and their modulation as a function of electrochemical conditions and performance. Most importantly: (i) Mo addition enhanced Cr(III) bound in oxide, (ii) fast growth conditions resulted in less corrosion resistant films, and (iii) exposure aging increased Cr-enrichment and reduced stratification of Mo-cations. The correlation between passive film performance and Cr, Ni, and Mo oxidation states, bonding, oxide-hydroxide contributions, and stratification is discussed. Generally accepted correlations, such as Cr-cation concentration and performance of the passive layer, have to be reexamined in order to account for the complex chemical make-up of the passive layer.
Maternal GLP-1 receptor activation inhibits fetal growth
Authors: Qiao Liping , Lu Cindy , Zang Tianyi , Dzyuba Brianna , Shao Jianhua
Published: January 2024

Our study reveals a progressive decline in maternal blood glucagon-like peptide 1 (GLP-1) concentration. GLP-1 receptor agonist injection in late pregnancy significantly reduced fetal body weight, even after restoration of maternal blood glucose concentration. GLP-1 receptor activation significantly reduced the placental labyrinth area, expression of some nutrient transporters, and capillary development. Our study indicates that reducing maternal blood GLP-1 levels is a physiological adaptation process that benefits placental development and fetal growth.