bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic differentiation within species exhibiting widespread gene flow; phylogeography of the downstream-inhabiting speciesEphemera orientalis(Insecta: Ephemeroptera)
Authors: Takenaka Masaki , Kogawara Hiroaki , Bae Yeon Jae , Tojo Koji
Published: March 2023

Elucidating the mechanism of formation of biota on islands will contribute to our understanding of the evolutionary mechanisms that generate biodiversity. In this study, we focus on the evolutionary history of Ephemera orientalis, which is distributed in East Asia. Phylogenetic analyses were performed using the mitochondrial DNA 16S rRNA, cytochrome oxidase subunit I and the nuclear DNA histone H3 regions. We found that these mayflies exhibit genetic differentiation between the Japanese and Korean populations. The Tsushima population, which is located between the Japanese Islands and the Korean Peninsula, was positioned genetically as a continental clade. The populations of the Fuji-Goko Lakes and Lake Ashino-ko in Central Japan were genetically differentiated from the other populations. The genetic structures over a wide area of the Japanese Islands were confirmed and a loose genetic regionality was observed, which was thought to result from secondary contact of the north-eastern and south-western lineages after their long separation by a geohistorical division event. We have gathered important knowledge regarding the evolutionary history of organisms on islands and investigated the colonization and isolation of biological populations within a species with high dispersal ability.
Faecal immunochemical testing for haemoglobin in detecting bowel polyps in symptomatic patients: multicentre prospective cohort study
Authors: Bath Michael F , Malhi Aman , Ayling Ruth M , Seward Edward , Pritchard-Jones Kathy , Laszlo Helga E , Hackshaw Allan , Machesney Michael R
Published: March 2023

Background

Measurement of faecal haemoglobin using faecal immunochemistry testing is recommended in patients presenting with symptoms suspicious for colorectal cancer, to aid in triage and prioritization of definitive investigations. While its role in colorectal cancer has been extensively investigated, the ability of faecal immunochemistry testing to detect adenomas in symptomatic patients is unclear.

Methods

A multicentre prospective observational study was conducted between April 2017 and March 2019, recruiting adults from 24 hospitals across England and 59 general practices in London who had been urgently referred with suspected colorectal cancer symptoms. Each patient provided a stool sample for faecal immunochemistry testing, in parallel with definitive investigation. A final diagnosis for each patient was recorded, including the presence, size, histology, and risk type of colonic polyps. The outcome of interest was the sensitivity of faecal immunochemistry testing in detecting the presence of adenomas.

Results

Of 3496 patients included in the analysis, 553 (15.8 per cent) had polyps diagnosed. Sensitivity of faecal immunochemistry testing for polyp detection was low across all ranges; with a cut-off for faecal haemoglobin of 4 µg/g or lower, sensitivity was 34.9 per cent and 46.8 per cent for all polyp types and high-risk polyps respectively. The area under the receiver operating characteristic curve in detection probability was relatively low for both intermediate-risk (0.63) and high-risk polyps (0.63).

Conclusion

While faecal immunochemistry testing may be useful in prioritizing investigations to diagnose colorectal cancer, if used as a sole test, the majority of polyps would be missed and the opportunity to prevent progression to colorectal cancer may be lost.
Automatic purse-string suture skill assessment in transanal total mesorectal excision using deep learning-based video analysis
Authors: Kitaguchi Daichi , Teramura Koichi , Matsuzaki Hiroki , Hasegawa Hiro , Takeshita Nobuyoshi , Ito Masaaki
Published: March 2023

Background

Purse-string suture in transanal total mesorectal excision is a key procedural step. The aims of this study were to develop an automatic skill assessment system for purse-string suture in transanal total mesorectal excision using deep learning and to evaluate the reliability of the score output from the proposed system.

Methods

Purse-string suturing extracted from consecutive transanal total mesorectal excision videos was manually scored using a performance rubric scale and computed into a deep learning model as training data. Deep learning-based image regression analysis was performed, and the purse-string suture skill scores predicted by the trained deep learning model (artificial intelligence score) were output as continuous variables. The outcomes of interest were the correlation, assessed using Spearman’s rank correlation coefficient, between the artificial intelligence score and the manual score, purse-string suture time, and surgeon’s experience.

Results

Forty-five videos obtained from five surgeons were evaluated. The mean(s.d.) total manual score was 9.2(2.7) points, the mean(s.d.) total artificial intelligence score was 10.2(3.9) points, and the mean(s.d.) absolute error between the artificial intelligence and manual scores was 0.42(0.39). Further, the artificial intelligence score significantly correlated with the purse-string suture time (correlation coefficient = −0.728) and surgeon’s experience (P< 0.001).

Conclusion

An automatic purse-string suture skill assessment system using deep learning-based video analysis was shown to be feasible, and the results indicated that the artificial intelligence score was reliable. This application could be expanded to other endoscopic surgeries and procedures.
Multiomics and machine-learning identify novel transcriptional and mutational signatures in amyotrophic lateral sclerosis
Authors: Catanese Alberto , Rajkumar Sandeep , Sommer Daniel , Masrori Pegah , Hersmus Nicole , Van Damme Philip , Witzel Simon , Ludolph Albert , Ho Ritchie , Boeckers Tobias M , Mulaw Medhanie
Published: March 2023

Amyotrophic lateral sclerosis is a fatal and incurable neurodegenerative disease that mainly affects the neurons of the motor system. Despite the increasing understanding of its genetic components, their biological meanings are still poorly understood. Indeed, it is still not clear to which extent the pathological features associated with amyotrophic lateral sclerosis are commonly shared by the different genes causally linked to this disorder. To address this point, we combined multiomics analysis covering the transcriptional, epigenetic and mutational aspects of heterogenous human induced pluripotent stem cell-derived C9orf72-, TARDBP-, SOD1- and FUS-mutant motor neurons as well as datasets from patients’ biopsies. We identified a common signature, converging towards increased stress and synaptic abnormalities, which reflects a unifying transcriptional program in amyotrophic lateral sclerosis despite the specific profiles due to the underlying pathogenic gene. In addition, whole genome bisulphite sequencing linked the altered gene expression observed in mutant cells to their methylation profile, highlighting deep epigenetic alterations as part of the abnormal transcriptional signatures linked to amyotrophic lateral sclerosis. We then applied multi-layer deep machine-learning to integrate publicly available blood and spinal cord transcriptomes and found a statistically significant correlation between their top predictor gene sets, which were significantly enriched in toll-like receptor signalling. Notably, the overrepresentation of this biological term also correlated with the transcriptional signature identified in mutant human induced pluripotent stem cell-derived motor neurons, highlighting novel insights into amyotrophic lateral sclerosis marker genes in a tissue-independent manner. Finally, using whole genome sequencing in combination with deep learning, we generated the first mutational signature for amyotrophic lateral sclerosis and defined a specific genomic profile for this disease, which is significantly correlated to ageing signatures, hinting at age as a major player in amyotrophic lateral sclerosis. This work describes innovative methodological approaches for the identification of disease signatures through the combination of multiomics analysis and provides novel knowledge on the pathological convergencies defining amyotrophic lateral sclerosis.
Understanding and Improving Vaccine Effectiveness Estimates in the Age of Widespread Background Immunity: A Step Toward Improved Science Communication
Authors: Nirenberg Edward , Perencevich Eli N
Published: March 2023

Medical decision making and scientific communication around coronavirus disease 2019 (COVID-19) vaccines and booster doses requires proper understanding of how vaccine effectiveness estimates are determined and the potential biases inherent in current estimates. The importance of background immunity from prior infection is reviewed along with ideas for improving the vaccine effectiveness estimates.
CD4/CD8 Ratio During Human Immunodeficiency Virus Treatment: Time for Routine Monitoring?
Authors: Ron Raquel , Moreno Elena , Martínez-Sanz Javier , Brañas Fátima , Sainz Talía , Moreno Santiago , Serrano-Villar Sergio
Published: March 2023

In the last decade, studies in persons with HIV (PWH) on antiretroviral therapy (ART) have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low CD4/CD8 ratio reflects increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of the CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cutoff points, associated clinical events, effects of treatments, and how the CD4/CD8 ratio could improve decision making in the clinic. Here, we critically review the literature, identify knowledge gaps, and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.
Thorstein Veblen’s Absentee Ownership in the Age of the Anthropocene: Law, Technology and Climate Crisis
Authors: Plotkin Sidney
Published: March 2023

This paper reconsiders Veblen’s Absentee Ownership on the centennial of its publication in 1923. It offers a reading of the work in relation to climate change in the new geologic age of the Anthropocene. The central finding is that Veblen’s analysis of the power implications of finance capital and law stand up well as guides to understanding the inertia of US energy policy. However, the book’s concept of ‘the industrial system’ is found seriously wanting. Conceiving of ‘the industrial system’ as a balanced whole of inter-connected mechanical processes, Veblen’s model fails to grasp how that industrial logic might be open to the environment and thus a major source of de-stabilising climate warming gases. More, this outcome is a result of industrial processes, regardless of which social group exercises control of the system: e.g. financiers, communists, or technicians. That is, while Veblen well understands the impact of technology on society, he tends not to envision how industrial technology itself can change Nature in unanticipated and destructive ways. The weaknesses of Veblen’s concept are traced back to his understanding of Nature as a structure of brute forces, scientific knowledge of which permits its effective technological control.
High Burden of Obesity and Low Rates of Weight Loss Pharmacotherapy in Inflammatory Bowel Disease: 10-Year Trend
Authors: Elangovan Abbinaya , Shah Raj , Ali Sajjadh M J , Katz Jeffry , Cooper Gregory S
Published: March 2023

Background

The prevalence of obesity and inflammatory bowel disease (IBD) has increased in the last decade. There is a paucity of data on the recent trend of obesity and the utilization of anti-obesity pharmacotherapy in IBD. We aimed to use a population-level database to analyze their trends.

Methods

A retrospective analysis of population-level data from 2010 to 2019 was performed among individuals ≥18 years of age using a commercial database, IBM Explorys. The prevalence and trends of obesity, diabetes mellitus type 2 (DM2), essential hypertension, dyslipidemia and/or hyperlipidemia, sleep apnea, and anti-obesity pharmacotherapy were studied. Univariate analysis using chi-square test and trend analysis using the Cochrane Armitage test were performed.

Results

Among 39 717 520 adults, 37.3% of IBD patients have a diagnosis of obesity (Crohn’s disease 36.9% vs ulcerative colitis 38.5%, P < .0001). The proportion of IBD adults with obesity and metabolic comorbidities increased from 2010 to 2019: obesity (19.7%–30.1%), DM2 (8.3%–12.5%), hypertension (25.1%–33.9%), hyperlipidemia (22.1%–32.2%), and sleep apnea (4.1%–10.8%). All comparisons were statistically significant (P < .0001). Only 2.8% of eligible adults with obesity were prescribed anti-obesity pharmacotherapy in the last 10 years, with trends increasing from 1.4% to 3.6%, 2010–2019.

Conclusions

With obesity being a harbinger for metabolic syndrome, the increase in obesity in IBD patients was accompanied by a concomitant increase in the diseases associated with obesity in the past decade. However, this alarming rise in obesity was accompanied by a disproportionately small increase in anti-obesity pharmacotherapy similar to general population.
General practice trainees’ telehealth use during the COVID-19 pandemic: a cross-sectional study
Authors: Fisher Katie , Tapley Amanda , Ralston Anna , Davey Andrew , Fielding Alison , van Driel Mieke , Holliday Elizabeth , Ball Jean , Dizon Jason , Spike Neil , Clarke Lisa , Magin Parker
Published: March 2023

Background

Prompted by the COVID-19 pandemic, remuneration was introduced for Australian general practice telehealth consultations. General practitioner (GP) trainees’ telehealth use is of clinical, educational, and policy importance. The aim of this study was to assess the prevalence and associations of telehealth versus face-to-face consultations amongst Australian GP registrars (vocational GP trainees).

Methods

Cross-sectional analysis of data from the Registrar Clinical Encounters in Training (ReCEnT) study, from 2020 to 2021 (three 6-month terms), including registrars in 3 of Australia’s 9 Regional Training Organisations. In ReCEnT, GP registrars record details of 60 consecutive consultations, 6 monthly. The primary analysis used univariate and multivariable logistic regression, with outcome of whether the consultation was conducted via telehealth (phone and videoconference) or face-to-face.

Results

1,168 registrars recorded details of 102,286 consultations, of which 21.4% (95% confidence interval [CI]: 21.1%–21.6%) were conducted via telehealth. Statistically significant associations of a telehealth consultation included shorter consultation duration (odds ratio [OR] 0.93, 95% CI: 0.93–0.94; and mean 12.9 versus 18.7 min); fewer problems addressed per consultation (OR 0.92, 95% CI: 0.87–0.97); being less likely to seek assistance from a supervisor (OR 0.86, 95% CI: 0.76–0.96) while being more likely to generate learning goals (OR 1.18, 95% CI: 1.02–1.37); and being more likely to arrange a follow-up consultation (OR 1.18, 95% CI: 1.02–1.35).

Conclusions

That telehealth consultations were shorter, with higher rates of follow-up, has GP workforce/workload implications. That telehealth consultations were less likely to involve in-consultation supervisor support, but more likely to generate learning goals, has educational implications.
Temperature and interspecific interactions drive differences in carbon use efficiencies and biomass stoichiometry among aquatic fungi
Authors: Tomczyk Nathan J , Rosemond Amy D , Whiteis Ally M , Benstead Jonathan P , Gulis Vladislav
Published: March 2023

Saprotrophic fungi play important roles in transformations of carbon (C), nitrogen (N), and phosphorus (P) in aquatic environments. However, it is unclear how warming will alter fungal cycling of C, N, and P. We conducted an experiment with four aquatic hyphomycetes (Articulospora tetracladia, Hydrocina chaetocladia, Flagellospora sp., and Aquanectria penicillioides), and an assemblage of the same taxa, to test how temperature alters C and nutrient use. Specifically, we evaluated biomass accrual, C:N, C:P, δ13C, and C use efficiency (CUE) over a 35-d experiment with temperatures ranging from 4ºC to 20ºC. Changes in biomass accrual and CUE were predominantly quadratic with peaks between 7ºC and 15ºC. The C:P of H. chaetocladia biomass increased 9× over the temperature gradient, though the C:P of other taxa was unaffected by temperature. Changes in C:N were relatively small across temperatures. Biomass δ13C of some taxa changed across temperatures, indicating differences in C isotope fractionation. Additionally, the 4-species assemblage differed from null expectations based on the monocultures in terms of biomass accrual, C:P, δ13C, and CUE, suggesting that interactions among taxa altered C and nutrient use. These results highlight that temperature and interspecific interactions among fungi can alter traits affecting C and nutrient cycling.
Description ofDefluviimonas salinarumsp. nov. with the potential of benzene-degradation isolated from saltern in the Yellow Seacoast
Authors: Lee Yunjeong , Kim Jong-Hwa , Yoon Jung-Hoon , Lee Jung-Sook , Sukhoom Ampaitip , Kim Wonyong
Published: March 2023

Strain CAU 1641T was isolated from saltern collected in Ganghwa Island, Republic of Korea. The bacterium was an aerobic, Gram-negative, catalase-positive, oxidase-positive, motile, and rod-shaped bacterium. Cell of strain CAU 1641T could grow at 20–40°C and pH 6.0–9.0 with 1.0–3.0% (w/v) NaCl. Stain CAU 1641T shared high 16S rRNA gene sequence similarities with Defluviimonas aquaemixtae KCTC 42108T (98.0%), Defluviimonas denitrificans DSM 18921T (97.6%), and Defluviimonas aestuarii KACC 16442T (97.5%). Phylogenetic trees based on the 16S rRNA gene and the core-genome sequences indicated that strain CAU 1641T belonged to genus Defluviimonas. Strain CAU 1641T contained ubiquinone-10 (Q-10) as the sole respiratory quinone and and summed feature 8 (C18:1ω6c and/or C18:1ω7c) as the predominant fatty acid (86.1%). The pan-genome analysis indicated that the genomes of the strain CAU 1641T and 15 reference strains contain a small core genome. The Average Nucleotide Identity and digital DNA–DNA hybridization values among strain CAU 1641T and reference strains of the genus Defluviimonas were in the range of 77.6%–78.8% and 21.1–22.1%, respectively. The genome of strain CAU 1641T has several genes of benzene degradation. The genomic G + C content was 66.6%. Based on polyphasic and genomic analyses, strain CAU 1641T represents a novel species of the genus Defluviimonas, for which the name Defluviimonas salinarum sp. nov., is proposed. The type strain is CAU 1641T ( = KCTC 92081T = MCCC 1K07180T).
Between metropole and colony: Bordels militaires de campagne in colonial Morocco and France in the twentieth century
Authors: Phipps Catherine
Published: March 2023

Bordels militaires de campagne (BMCs) were French military brothels in North Africa under colonial occupation. This system was extended to metropolitan France during the First and Second World Wars due to fears of sexual violence or consensual relationships between Moroccan men and French women. Even after brothels were banned in metropolitan France in 1946, French military authorities illegally brought hundreds of Moroccan women to France to work in BMCs because of the Moroccan soldiers still present in the metropole. With poor living conditions, underage labour and a high workload, French military brothels exploited Moroccan women to theoretically ‘protect’ European women against sexual violence from Moroccan men. This was based on a racialized understanding of Moroccan masculinity. This article uses the experiences of these Moroccan women and details of the sex work system in Morocco to understand the systemic cruelty behind the operation of these French military brothels.
Perspectives on the Relationship Between Copyright and Design Law after Cofemel/G-Star – The Australian Regulation of Copyright/Design Overlap as a Role Model for European Law?
Authors: Jänich Volker Michael
Published: March 2023

The relationship between copyright and design law has again come more into focus as a result of the Court of Justice of the European Union’s (CJEU) decision in the Cofemel/G-Star case. EU law enables dual protection of designs both through copyright and through design law. Australian copyright law tries to exclude or at least limit dual protection. This article considers the advantages and disadvantages of dual protection and outlines a suggestion for sharpening the distinction between copyright and design law.
Antitrust Unchained: The EU’s Case Against Self-Preferencing
Authors: Colangelo Giuseppe
Published: March 2023

Self-preferencing is the symbol of the competition policy Zeitgeist in digital markets. Large online platforms acting as gatekeepers to their ecosystems and engaging in a dual mode intermediation are accused of taking advantage of their hybrid business model by granting preferential treatment to their own products and services. Alongside the recent legislative initiatives undertaken around the world to impose a neutrality regime over digital gatekeepers by targeting different forms of self-preferencing, this practice is also emerging in Europe as a new antitrust theory of harm advanced by courts and competition authorities. In the aftermath of the General Court’s decision in Google Shopping and against the risk that the new label may merely provide antitrust enforcers with the opportunity to skip the legal standards and evidentiary burdens required to prove traditional anticompetitive behavior, this paper investigates whether and to what extent self-preferencing could be considered a new standalone offence in EU competition law.
Health literacy and associated factors among undergraduate health sciences students in western Nepal: a cross-sectional study
Authors: Gairhe Samikshya , Gyawali Bishal , Pahari Sandip , Jnawali Kalpana , Poudel Arati , Khatri Dhurba , Paneru Damaru Prasad
Published: March 2023

Despite the importance of health literacy for health promotion, Nepalese undergraduate students are largely unaware of its importance. The present study assessed the health literacy levels of undergraduate health sciences students and explored various sociodemographic, clinical and health information-related factors associated with health literacy at Pokhara University in the Kaski district of western Nepal. A cross-sectional web-based observational study was conducted among 406 undergraduate students university students from five faculties at the School of Health and Allied Sciences affiliated with Pokhara University. Data on sociodemographic information, clinical characteristics and sources of health information were collected. Health literacy was assessed using the 44-item measure that captures the concept of health literacy across nine distinct domains. Associated factors were examined using a one-way analysis of variance followed by stepwise backward multiple linear regression analysis at the level of significance of 0.05. The mean score for the health literacy questionnaire was 3.13 ± 0.26. Outcomes of multivariable analyses demonstrated various factors associated with health literacy scores, including age (β = 0.10; p = 0.001), physical exercise (β = −0.13; p < 0.001), monthly household income (β = 0.05; p = 0.029) and routine health checkup (β = −0.14; p < 0.001). The study showed that there is a need to understand and address sociodemographic factors and clinical factors, including age, physical exercise, monthly household income and routine health checkups to improve health literacy levels among undergraduate students in western Nepal. More research, including longitudinal studies, is needed to better understand factors that influence health literacy among undergraduate students in Nepal.
Social network and health behaviors among Japanese older adults: a three-wave longitudinal study
Authors: Harada Kazuhiro , Masumoto Kouhei , Okada Shuichi
Published: March 2023

Identifying modifiable determinants of behavior is essential for developing effective strategies to promote health behaviors among older adults. Although social networks are potentially modifiable determinants of health behaviors, their longitudinal associations have not been established in previous studies. The present study examined whether a larger social network is associated with higher dietary variety, longer time spent exercising and shorter time spent viewing TV among older adults. This is a longitudinal study. The data of 908 Japanese older adults were obtained through a three-wave questionnaire survey (Wave 1, December 2017 to January 2018; Wave 2, after 1 year; Wave 3, after 3 years) and analyzed. In each wave of the survey, dietary variety (dietary variety score), exercise time (hours per day), TV viewing time (hours per day) and social network (family and friend subscales of the Japanese version of the abbreviated Lubben Social Network Scale) were measured. The present study used latent growth, cross-lagged and simultaneous effect models to investigate the longitudinal associations of family and friend social networks with dietary variety, exercise time and TV viewing time. However, these models did not show clear and robust associations. Whether social networks are determinants of health behaviors among older adults remains inconclusive.
Salud postpandemia: influencia supranacional y coordinación regulatoria
Authors: Benavides Reverditto Ximena
Published: March 2023

The dominant position of the U.S. Food and Drug Administration (FDA) as the most influential regulator in the world has been particularly salient during the COVID-19 pandemic, in the context of COVID-19 vaccines’ emergency use authorizations. In the context of adjustment toward a post-COVID-19 regulatory order of harmonization for medicines approval, this essay proposes a critical reflection about the justifications and political dynamics behind the FDA’s power and its impact in latinamerican countries’ regulatory systems, considering the already regulatory reliance on the FDA. In particular, this essay asks whether regulatory ‘agility’ and ‘coordination’ will benefit countries of the region in addressing the problems of scarcity and inequitable access to medicines that have become evident with the pandemic.
Heat- and Wave-Type Equations with Nonlocal Operators, I. Compact Lie Groups
Authors: de Moraes Wagner A A , Restrepo Joel E , Ruzhansky Michael
Published: March 2023

We prove existence and uniqueness and give the analytical solution of heat and wave type equations on a compact Lie group $G$ by using a nonlocal (in time) differential operator and a positive left invariant operator (maybe unbounded) acting on the group. For heat type equations, solutions are given in $L^q(G)$ for data in $L^p(G)$ with $1<p\leqslant 2\leqslant q<+\infty $. We also provide some asymptotic estimates (large-time behavior) for the solutions. Some examples are given. Also, for wave-type equations, we give the solution on some suitable Sobolev spaces over $L^2(G)$. We complement our results, by studying a multi-term heat-type equation as well.
The primary pharmacology of ceftazidime/avibactam: microbiology from clinical studies, and development of resistance during treatment
Authors: Nichols Wright W , Bradford Patricia A , Stone Gregory G
Published: March 2023

As one of a series of thematically linked reviews of the primary pharmacology of the β-lactam/β-lactamase inhibitor combination, ceftazidime/avibactam, this article reviews the microbiological findings in drug-exposed patients. Earlier articles in the series focused on basic in vitro and in vivo translational biology (J Antimicrob Chemother 2022; 77: 2321–40 and 2341–52) and the development and mechanisms of resistance in vitro (J Antimicrob Chemother 2023: Epub ahead of print. doi: 10.1093/jac/dkac449). In clinical trials of ceftazidime/avibactam, combined favourable microbiological responses for evaluable patients infected at baseline by susceptible Enterobacterales or Pseudomonas aeruginosa were 86.1% (851/988). The corresponding percent favourable among patients infected by ceftazidime/avibactam-resistant pathogens was 58.8% (10/17), noting that the majority (15/17) of the resistant examples were P. aeruginosa. Microbiological response rates to comparator treatments in the same clinical trials ranged between 64% and 95%, depending on the type of infection and the analysis population. Uncontrolled case studies over a wide range of patients infected by antibiotic multiresistant Gram-negative bacteria have demonstrated that ceftazidime/avibactam can elicit microbiological clearance of ceftazidime/avibactam-susceptible strains. In case studies where a matched cohort of patients had been treated with antibacterial agents other than ceftazidime/avibactam, microbiological outcomes were comparable between treatments, mostly being observationally more favourable for ceftazidime/avibactam (recognizing that numbers were too small for definitive superiority assessments). Development of resistance to ceftazidime/avibactam during therapy is reviewed. The phenomenon has been reported multiple times, mostly in difficult-to-treat patients infected by KPC-producing Enterobacterales. Molecular mechanisms, when determined, have frequently been observed previously in vitro, such as the ‘Ω-loop’ D179Y (Asp179Tyr) substitution found in KPC variant enzymes. In human volunteers exposed to therapeutic levels of ceftazidime/avibactam, faecal numbers of Escherichia coli, other enterobacteria, lactobacilli, bifidobacteria, clostridia and Bacteroides spp. decreased. Clostridioides difficile was detected in the faeces, but this was of uncertain significance, because no unexposed controls were studied.
Identification of a novel carbapenem-hydrolysing class D β-lactamase RAD-1 inRiemerella anatipestifer
Authors: Li Pei , Yang Zhishuang , Lei Ting , Dai Yujie , Zhou Yang , Zhu Dekang , Luo Hongyan
Published: March 2023

Objectives

To elucidate the role of a novel carbapenem-hydrolysing class D β-lactamase (RAD-1) from Riemerella anatipestifer.

Methods

We applied WGS and bioinformatic analysis to screen putative β-lactamase genes in R. anatipestifer SCVM0004. A putative class D β-lactamase gene was cloned into pET24a and transferred into Escherichia coli BL21 (DE3) for antibiotic susceptibility determination and protein purification. Meanwhile, the purified native protein was used to determine the enzymatic activities.

Results

A class D β-lactamase, RAD-1, was identified in the genome of R. anatipestifer SCVM0004. It was distinct from all characterized class D β-lactamases (≤42% amino acid sequence identity). Searching in GenBank showed that blaRAD-1 was widely disseminated among R. anatipestifer. Genomic environment analysis indicated that the chromosomal structures of blaRAD-1-located regions were relatively conserved. Expression of RAD-1 in E. coli results in elevated MICs for various β-lactam antibiotics, including penicillins, extended-spectrum cephalosporins, a monobactam and carbapenems. Moreover, kinetic analysis of purified RAD-1 revealed: (i) high-level activity against penicillins; (ii) highest affinity for carbapenems; (iii) moderate hydrolysis of extended-spectrum cephalosporins and a monobactam; and (iv) no activity for oxacillin and cefoxitin.

Conclusions

This study identified a novel chromosomally located class D carbapenemase RAD-1 (Bush–Jacoby functional group 2def) in R. anatipestifer SCVM0004. Moreover, bioinformatic analysis confirmed that the RAD-1 was widely prevalent and conserved in R. anatipestifer.
Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies
Authors: Körner Elena , Lorentz Axel
Published: March 2023

As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score, quality of life measured by the lBS quality of life scale, and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient’s microbiota profile shifted toward their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient’s own stool, placebo capsules, or bowel cleansing. Moreover, optimal donor selection, frequency, dosage, and route of delivery still need to be defined.
Transcriptomic characterization of Lonrf1 at the single-cell level under pathophysiological conditions
Authors: Li Dan , Wang Teh-Wei , Aratani Sae , Omori Satotaka , Tamatani Maho , Johmura Yoshikazu , Nakanishi Makoto
Published: March 2023

The LONRF family of proteins consists of three isozymes, LONRF1–3, which harbors RING (really interesting new gene) domain and Lon substrate binding domain. We have recently identified LONRF2 as a protein quality control ubiquitin ligase that acts predominantly in neurons. LONRF2 selectively ubiquitylates misfolded or damaged proteins for degradation. LONRF2−/− mice exhibit late-onset neurological deficits. However, the physiological implications of other LONRF isozymes remain unclear. Here, we analysed Lonrf1 expression and transcriptomics at the single-cell level under normal and pathological conditions. We found that Lonrf1 was ubiquitously expressed in different tissues. Its expression in LSEC and Kupffer cells increased with age in the liver. Lonrf1high Kupffer cells showed activation of regulatory pathways of peptidase activity. In normal and NASH (nonalcoholic steatohepatitis) liver, Lonrf1high LSECs showed activation of NF-kB and p53 pathways and suppression of IFNa, IFNg and proteasome signalling independent of p16 expression. During wound healing, Lonrf1high/p16low fibroblasts showed activation of cell growth and suppression of TGFb and BMP (bone morphogenetic protein) signalling, whereas Lonrf1high/p16high fibroblasts showed activation of WNT (wingless and Int-1) signalling. These results suggest that although Lonrf1 does not seem to be associated with senescence induction and phenotypes, LONRF1 may play a key role in linking oxidative damage responses and tissue remodelling during wound healing in different modes in senescent and nonsenescent cells.
Food and feeding strategies of the deep-sea shrimpHeterocarpus woodmasoni, Alcock 1901 (Decapoda: Pandalidae) from southwestern India
Authors: Ambatt Padmanabhan Gayathri , Chakraborty Rekha Devi , Lakshman Sreesanth
Published: March 2023

Diet composition and feeding strategies of deep-sea caridean shrimp Heterocarpus woodmasoniAlcock,1901 are described from gut contents of 4,116 specimens collected from the southwestern coast of India. Knowledge of the species diet plays a prime effect on its biological aspects and its role in the ecological energetics of the community. All the analyses were performed in accordance with ecological (season) and biological factors (sex, size, and gonadal stages). The species was found to prey on diversified components such as detritus, foraminiferans, other crustaceans, molluscs, echinoderms, and fishes in their declining order of preponderance. Multivariate analysis of variance showed a significant difference (P<0.05) in the diet components according to the combination of sex along with season and gonadal stages. Values of the gastro-somatic index (GSI) showed a positive correlation with feeding activity, and its intensity. GSI, feeding intensity, and activity reached their peak values during the post-monsoon season. High vacuity index was recorded in almost all conditions, which is a highlighted feature of this species. These observations provide fundamental information on the feeding pattern of H. woodmasoni, which aims to develop suitable fishing strategies in the future.
Life After Conviction at the International Criminal Tribunal for the former Yugoslavia
Authors: Strupinskienė Lina
Published: March 2023

Of the 92 persons convicted at the International Criminal Tribunal for the former Yugoslavia (ICTY), 60 have already served their sentences and been released. Even though in post-conflict environments, the public behaviour of perpetrators can help counter (atrocity crime) denial, establish an authoritative version of the truth and contribute to sustainable reconciliation, we still know little about what happens once they return to their communities. This article is one of the first attempts to systematically map and understand what pathways the ICTY convicts take after release, and why. It finds that those who promote nationalist interpretations of the past and deny their responsibility and involvement in crimes are often hailed by receptive domestic audiences across the Western Balkans. They successfully use certain support networks, such as dominant political parties or military and war veterans’ organizations, to take back their place in public life. On the other hand, those convicts who have admitted their guilt and responsibility and do not promote a nationalist interpretation of the past often find themselves ostracized, living in poverty and seclusion.
Reforming Shareholder Claims in Investor-State Dispute Settlement
Authors: Arato Julian , Claussen Kathleen , Lee Jaemin , Zarra Giovanni
Published: March 2023

Investor-state dispute settlement (ISDS) stands alone in empowering shareholders to bring claims for shareholder reflective loss (SRL)—meaning claims over harms allegedly inflicted upon the company, but which somehow affect share value. National systems of corporate law and public international law regimes generally bar SRL claims for strong policy reasons bearing on the efficiency and fairness of the corporate form. However, ISDS tribunals allow shareholders broad and regular access to seek relief for reflective loss. The availability of SRL claims in ISDS ultimately harms States and investors alike, imposing surprise ex post costs on States and various corporate stakeholders (particularly creditors), and creating perverse incentives likely to raise the cost of doing business ex ante. The article sets out the harms caused by allowing ISDS claims for reflective loss, as well as the possible justifications for allowing such claims in this specific context. Concluding that any potential benefits of SRL can be realized through less invasive means, we then canvas a number of plausible reform options, with an eye to their trade-offs.
Parent Perspectives of School/Daycare Experiences in Young Children Newly Diagnosed With Diabetes
Authors: Stern Alexa , Duran Brenda , Streisand Randi , Wang Christine H , Tully Carrie , Clary Lauren , Gallagher Katherine , Cogen Fran , Karaviti Lefkothea , Monaghan Maureen , Hilliard Marisa E
Published: March 2023

Objective

A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child’s school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child’s T1D diagnosis.

Methods

As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 months) T1D reported on their child’s school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods design to describe and contextualize parents’ experiences with school/daycare. Qualitative data were collected via open-ended responses, and quantitative data were collected from a demographic/medical from.

Results

While most children were enrolled in school/daycare at all time points, over 50% of parents endorsed that T1D affected their child’s enrollment, rejection, or removal from school/daycare at 9 or 15 months. We generated five themes related to parents’ school/daycare experiences: Child factors, Parent factors, School/Daycare factors, Cooperation between Parents and Staff, and Socio-historical factors. Parents of younger children and those with lower subjective socioeconomic status were significantly more likely to endorse challenges with school/daycare enrollment.

Conclusions

School/daycare settings present challenges for parents of young children with T1D. Changes may need to occur across contexts to support early childhood education, including advocacy resources for parents to navigate school policies, increased training for school staff, and healthcare team outreach initiatives to parents and schools.
Estimation of temperature-dependent growth profiles for the assessment of time of hatching in forensic entomology
Authors: Pigoli Davide , Ferraty Frédéric , Aston John A D , Mazumder Anjali , Richards Cameron , Hall Martin J R
Published: March 2023

Forensic entomology contributes important information to criminal investigations. This paper proposes a novel method to estimate the hatching time of fly larvae based on the temperature profile at the crime scene and on experimental data on larval development, where larvae are exposed to a constant temperature. We develop a dynamic model to estimate the growth curve under time-varying temperature profiles and the corresponding hatching time at the crime scene. Asymptotic properties are provided for the proposed estimators, and we explore their robustness via simulations. The proposed methodology is demonstrated on data from two criminal cases from the UK.
Supraclavicular metastasis from prostate cancer: unusual case and literature review
Authors: Ascio Noelani-Mei , Qureshi Abid , Banayan Elliot , Asarian Armand , Genato Romulo , Xiao Philip
Published: March 2023

Prostate cancer is the most common cancer among men, with the most common metastatic sites in bone, regional lymph nodes, liver and thorax. It is most commonly diagnosed in the early stages with clinical findings of enlarged prostate on digital rectal exam and positive prostate specific antigen. Distant metastases associated with prostate cancer commonly occur to bone. It is imperative to be cautious in assuming primary breast, lung or head and neck malignancy in patients presenting with lymphadenopathy in the upper aerodigestive pathways. Cervical lymphadenopathy due to prostate cancer is becoming more prevalent since previously reported. Here we present a case of prostate cancer recurrence found through metastasis to supraclavicular lymph nodes and we also highlight homeobox protein CDX2 as a potential clinico-pathological marker in metastatic prostate cancer.
Perforated mediastinal gastric volvulus: an uncommon complication of hiatal hernia
Authors: Schneider Mateus Henrique , Solis-Pazmino Paola , Maldonado Pedro , Hamaoui Mohamed
Published: March 2023

A woman in her 50s was admitted to the emergency department with a 3-day history of abdominal pain, mainly in the right hypochondrium, radiating to the back, associated with postprandial vomiting and dysphagia. The abdominal ultrasound study found no abnormalities. Laboratory tests showed increased C-reactive protein levels, creatinine and high white blood cell count without a left shift. Abdominal computed tomography scan exhibited mediastinal herniation, twist and perforation of the gastric fundus associated with air-fluid levels in the lower mediastinum. The patient underwent diagnostic laparoscopy requiring laparotomy conversion due to hemodynamic instability related to the pneumoperitoneum. During the intensive care unit (ICU) stay, thoracoscopy with pulmonary decortication was performed to treat complicated pleural effusion. After ICU and standard infirmary bed recovery, the patient was discharged from the hospital. This report illustrates a case of perforated gastric volvulus as the cause of nonspecific abdominal pain.
Rare dual surgical pathology at emergency laparotomy: a case report of concurrent small bowel obstruction and appendicitis
Authors: Tully Dylan S , Balasooriya Janaka , Lim James
Published: March 2023

Dual surgical pathology at emergency laparotomy is an uncommon finding outside of trauma scenarios. There is a scarcity of case reports of concomitant small bowel obstruction and appendicitis at laparotomy, likely in part because of advancements in investigative tools, diagnostic processes and the ready availability of medical care, which is demonstrated by harrowing statistics from developing nations where these factors are lacking. However, despite these advancements, initial diagnosis of dual pathology can be difficult. We report a case of concurrent small bowel obstruction and occult appendicitis discovered at emergency laparotomy in a previously well female with a virgin abdomen.
Newly diagnosed cirrhosis secondary to gastrointestinal bleed due to portal hypertensive colopathy
Authors: Sabat Nestor , Schulze Bettina
Published: March 2023

Portal hypertensive colopathy (PHC) is a colonic phenomenon commonly causing chronic gastrointestinal bleeding or less commonly a life-threatening acute colonic hemorrhage. An otherwise well, 58-year-old female presents general surgeons a diagnostic dilemma for symptomatic anemia. An interesting case where the rare and elusive PHC was diagnosed on colonoscopy, which led to the diagnosis of liver cirrhosis without evidence of oesophageal varices. Although PHC is most common in patients with cirrhosis, it is likely still underdiagnosed, given the current stepwise treatment approach of these cirrhotic patients often leads to treatment of the PHC alongside PHG without establishing a diagnosis. Instead, this case presents a generalised approach to patients with underlying portal and sinusoidal hypertension due to a variety of causes, and the endoscopic and radiological findings, which lead to their successful diagnosis and medical management of the gastrointestinal bleeding.