bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Perineal wound complications after vertical rectus abdominis myocutaneous flap and mesh closure following abdominoperineal surgery and pelvic exenteration of anal and rectal cancers: A meta‐analysis
Authors: Liu Jiang , Fu Chao , Chen Zhiliang , Li Gang
Published: August 2023

A meta‐analysis research was implemented to appraise the perineal wound complications (PWCs) after vertical rectus abdominis myocutaneous (VRAM) flap and mesh closure (MC) following abdominoperineal surgery (AS) and pelvic exenteration (PE) of anal and rectal cancers. Inclusive literature research till April 2023 was done and 2008 interconnected researches were revised. Of the 20 picked researches, enclosed 2972 AS and PE of anal and rectal cancers persons were in the utilized researchers' starting point, 1216 of them were utilizing VRAM flap, and 1756 were primary closure (PC). Odds ratio (OR) and 95% confidence intervals (CIs) were utilized to appraise the consequence of VRAM flap in treating AS and PE of anal and rectal cancers by the dichotomous approach and a fixed or random model. VRAM flap had significantly lower PWCs (OR, 0.64; 95% CI, 0.42–0.98, p < 0.001), and major PWCs (OR, 0.50; 95% CI, 0.32–0.80, p = 0.004) compared to PC in AS and PE of anal and rectal cancers persons. However, VRAM flap and PC had no significant difference in minor PWCs (OR, 1; 95% CI, 0.54–1.85, p = 1.00) in AS and PE of anal and rectal cancer persons. VRAM flap had significantly lower PWCs, and major PWCs, however, no significant difference was found in minor PWCs compared to PC in AS and PE of anal and rectal cancers persons. However, caution needs to be taken when interacting with its values since there was a low sample size of most of the chosen research found for the comparisons in the meta‐analysis.
Physiotherapy assessment in people with neurological conditions—Evidence for the most frequently included domains: A mixed‐methods systematic review
Authors: Garner Jill , Berg Maayken van den , Lange Belinda , Vuu Sally , Lennon Sheila
Published: August 2023

Rationale

There is a lack of consensus in the literature related to what is assessed clinically by physical therapists in people with neurological disorders.

Aims

This mixed‐methods systematic review aimed to identify domains that physiotherapists routinely assess in people with neurological conditions in clinical settings and explored factors influencing assessment domains including country, clinical setting, therapist experience and neurological condition.

Method

Five databases were searched from 1946 to 31st January 2023. Studies with any design reporting on domains assessed by a physiotherapist, in people with neurological conditions in any clinical setting, were included. Independent reviewers assessed eligibility and risk of bias using relevant McMaster critical appraisal tools. Data were extracted and synthesised following the Joanna Briggs Institute approach for mixed systematic reviews.

Results

A total of 23 (16 quantitative, 7 qualitative) studies involving 3134 participants were included. The studies were rated as high (n = 14) or medium (n = 9) quality. The domains of function (n = 14); postural alignment and symmetry (n = 11); gait (n = 11); balance (n = 9), and muscle strength (n = 8) were most frequently included in assessments. Five key themes were identified from the qualitative studies: the clinical reasoning process, clinical use of standardised measures, utilisation of the senses, clinician experience and information gathering. There was minimal data on how country, clinical setting, therapist experience and neurological condition influence inclusion of assessed domains.

Conclusion

Five domains were most frequently included in assessment: function; postural alignment and symmetry; gait; muscle strength; and balance. This limited number of domains is in stark contrast to the full neurological physiotherapy assessment recommended by expert textbooks. Further research is needed to understand the reasons why this might be so.
The impact of targeted interventions aimed to improve quality of life in patients receiving home parenteral nutrition: A systematic literature review
Authors: Carey Sharon , Men Mohan , Cunich Michelle
Published: August 2023

Background

Home parenteral nutrition (HPN) is a specialised therapy offered to people suffering from intestinal failure. Underlying disease, HPN complications and limitations of HPN can significantly impact a person's quality‐of‐life (QOL). The aim of this review was to evaluate the evidence on existing non‐surgical/non‐pharmacological interventions aimed at improving QOL, clinical, patient‐reported and economic outcomes for patients receiving parenteral nutrition therapy at home across adult and paediatric settings.

Methods

Online databases Medline (Ovid), Embase and Cinahl were searched to identify studies published between 1937 and 31 March 2022. Identified studies were appraised using the Cochrane Collaboration risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment.

Results

Nine studies were included in this review. Interventions were focused on education (n = 4), telemedicine (n = 2), preparation of infusion mixtures (n = 1), mindfulness‐based cognitive therapy (n = 1) and a multi‐modal approach (n = 1). Only one study measured QOL before and after the intervention using a validated QOL tool. All studies were assessed at either some, high or critical risk of bias, resulting in low or very low‐quality evidence for the interventions evaluated.

Conclusions

The findings from this review highlight the lack of high‐quality non‐surgical/non‐pharmacological studies seeking to improve QOL for people on HPN. Because the majority of people receiving HPN are not eligible for surgical or pharmaceutical treatments, higher quality research using clinical trial design, and research focused on improving QOL is needed to inform healthcare managers about the effectiveness (and value) of alternative service delivery models for this vulnerable patient group.
The 2021 KDIGO blood pressure target and the progression of chronic kidney disease: Findings from KNOW‐CKD
Authors: Park Cheol Ho , Kim Hyung Woo , Park Jung Tak , Chang Tae Ik , Yoo Tae‐Hyun , Park Sue Kyung , Kim Yaeni , Jung Ji Yong , Jeong Jong Cheol , Oh Kook‐Hwan , Kang Shin‐Wook , Han Seung Hyeok ,   the KNOW‐CKD (KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease) Investigators
Published: August 2023

Background

The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes.

Methods

The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow‐up period.

Results

Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person‐years of follow‐up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person‐years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause‐specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60–0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13–1.64) for BP above both targets, compared with BP controlled within 2012 target only.

Conclusion

The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline.
Culicidae assemblages of artificial containers and possible biotic interactions affecting Aedes albopictus (Diptera: Culicidae) in Argentina
Authors: Lizuain Arturo Andrés , Maffey Lucia , Leporace Marina , Garzón Maximiliano , Schweigmann Nicolás , Santini María Soledad
Published: August 2023

In Argentina, the distribution of Aedes albopictus (Skuse) is limited to two provinces with a subtropical climate and few records. This study aims to describe and compare assemblies of Culicidae that breed in artificial containers in two areas with different degrees of urbanisation where Ae. albopictus is present and to evaluate possible biotic interactions. We sampled container larval habitats of an urban (Eldorado city) and a rural environment (Colonia Aurora village). We performed generalized linear mixed models to evaluate which variables (containers characteristics or environment) are associated with the presence and abundance of Ae. albopictus, Aedes aegypti Linneaus and Culex quinquefasciatus Say, and the presence of mosquito predators (Lutzia bigoti (Bellardi) and Toxorhynchites spp.). Also, the relationship between the most abundant species was quantified in each environment using Hurlbert's C8 association coefficient. Ae. aegypti was the most abundant species in the urban environment, while Cx. quinquefasciatus and Ae. albopictus were the most abundant in the rural area. Predators were more present in the rural environment and affected the abundance of Aedes mosquitoes. Regarding the C8 index, Ae. aegypti was negatively associated with Ae. albopictus in the urban area, whereas in the rural area these species presented a significantly positive relationship. These results show that in urban environments the high abundance of Ae. aegypti could be affecting the Asian tiger mosquito as evidenced by local studies of food larval competition. Also a greater presence of predators could be affecting Ae. albopictus in rural environments.
Electing presidents: A hidden facet of democratization
Authors: Cheibub José A. , Limongi Fernando , Przeworski Adam
Published: August 2023

A hidden facet of democratization in the world over the past two centuries has been the increased weight of people's voice in electing presidents. On the basis of new data on all presidential elections in the world since 1789, we show that they evolved from systems in which the final decision was made by someone other than voters, to systems in which the choice of voters was decisive only if it generated a majority, to systems in which the final decision is made by voters. This means that in countries where presidents have executive powers, elections may not be the mechanism by which the people, as a collectivity, always selects its rulers, thus violating the fundamental norm of democracy. We document the history of presidential election rules, offer some tentative explanations, and explore the consequences of particular systems.
Physiology and emotions: Within individual associations during caregiver–adolescent conflict
Authors: Siciliano Rachel E. , Anderson Allegra S. , Vreeland Allison J. , Gruhn Meredith A. , Henry Lauren M. , Watson Kelly H. , Liu Qimin , Cole David A. , Ebert Jon , Kuhn Tarah , Compas Bruce E.
Published: August 2023

Concordance between physiological and emotional responses is central to models of emotion and has been shown to correspond to effective responses and well‐being in adults. A deeper understanding of physiological‐emotional concordance during ecologically relevant scenarios is essential to then determine if these associations predict mental health problems or can serve as a helpful biomarker of risk or resilience in adults and youth. The present study assessed the minute‐to‐minute associations between sympathetic (i.e., skin conductance level [SCL]) and parasympathetic (i.e., respiratory sinus arrhythmia [RSA]) nervous system activity and self‐reported emotions, assessed via video‐mediated recall procedures, during a parent–adolescent conflict discussion task. Associations between emotion ratings and physiological activity were assessed in adolescents (N = 97; ages 10–15) and their adult caregivers (N = 97). Utilizing a multilevel modeling approach, findings demonstrated a significant positive association between SCL and emotion ratings for youth, suggesting that increased engagement and alertness contributed to more positive emotion. RSA was unrelated to emotion ratings. The presence of significant variability in associations indicated the presence of potential moderators. This could include clinically relevant processes (e.g., emotion regulation, relationship quality, and mental health). Future research should continue to build on findings to determine if, when, and for whom, physiological‐emotional concordance occurs, and whether the degree of concordance predicts risk for mental and physical health problems.
The convexity for compressible subsonic cavity flows
Authors: Wang Xiaohui
Published: August 2023

In this paper, we first show that the flow velocity takes its maximum on the free boundary, provided that the nozzle wall and obstacle satisfy some corresponding geometric assumptions. Second, the convexity of the free boundary to the compressible subsonic cavity flows will be established. Finally, the optimal regularity of the free boundary at the detachment point is obtained.
Memory Building and Istitba’ in Divided Societies
Authors: Tabar Paul , Aboultaif Eduardo Wassim
Published: August 2023

This paper studies collective memory in divided societies. To do so, we begin by studying national memory in civil societies, where the nature of this memory is hegemonic. We use Gramsci’s concept of hegemony to explain national memories in civil societies and differentiate it from that of contested memories in divided places. In order to explain memory in divided societies, we apply Ibn Khaldoun’s concepts of ‘aAsabiyah and Istitba’. Societies deeply divided tend to have contested memories at two levels: within a community which creates an internal other and outside the community where groups compete to impose their memory at the state level. We use examples from Lebanon, Northern Ireland and Bosnia‐Herzeogvina to explain the memory dynamics from a Khaldounian perspective.
The politics of street names: Reconstructing Iran’s collective identity
Authors: Kashfi Ehsan
Published: August 2023

With the radical political change in 1979, Iran's revolutionary state assumed the responsibility of re‐rewriting the past history to forge a new sense of belonging, a particularly collective religious (Shia) identity. It launched a complex process of forgetting and remembering to first eliminate the national (Persian), non‐religious memories and heritage, associated and celebrated by the previous regime and then establish a sense of continuity with the country's Shia past; a feeling markedly engendered with a distinguishing symbolic reservoir of Shia traditions and memories, presented in history books, literature, the media, and everyday culture.This paper seeks to examine the role of street names in this process of reconstructing a new religious (Shia) collective memory and identity with particular reference to Tehran, Iran, during the 1979‐2019 period. It seeks to analyze changes in the city's street names and analyze the widespread renaming of streets and public spaces in the city as one means of both ‘de‐commemorating’ the pre‐revolutionary regime and marking the Shia legacy and memories as the signifiers of a widespread political maneuver to articulate a new version of the past and narrative of identity since the 1979 revolution.
Rethinking nationalistic history in China: Towards a multicultural Chinese identity
Authors: Lin Jason Cong
Published: August 2023

In China, the central government enjoys paramount authority in (re)writing national history, and its interpretation is promoted through various channels to shape people's national identity. Over the past two decades, the Chinese government has promoted a nationalistic history to promote a Han‐dominant Chinese identity. This nationalistic approach to Chinese history stands in contrast to China's multicultural society and the government's affirmation of multicultural aims as the core values and future goals of the nation. It was expected that the government would rethink and revise nationalistic history to recognize diverse groups and accommodate their needs in the Xi Jinping era. However, this paper shows that the current government continues to emphasize a version of national history that encourages a nationalistic sentiment and discourse. This approach to Chinese history risks strengthening xenophobic sentiments and behaviour in China, and could become coercive for Chinese people who hold different interpretations or expect a more comprehensive interpretation of national history. I argue that a critical multicultural approach can help develop a more inclusive and balanced national history and identity in China.
Regional organizations and ethnic conflict prevention: The EU and Kosovo conflict
Authors: Vila Jubjana
Published: August 2023

The prevention, management, and resolution of ethnic conflicts comprises an important challenge to the regional peace and stability. This case study explores the role of the EU, as a regional organization, in ethnic conflict prevention in different stages of the Kosovo conflict. It aims to understand the strategies, policies, and mechanisms used by the EU in its engagement throughout different conflict stages. In addition, it offers an evaluation of the capabilities, achievements and failures of the EU in dealing with this type of conflict. The study highlights the efforts of the EU in shifting its strategies to become a leading actor in handling this conflict. The findings of the research reveal progress in the EU’s approach to conflict prevention but highlight the lack of the consensus among member states as an obstacle to EU’s success in conflict prevention.
Identification of three novel HLA‐DRB1 alleles, HLA‐DRB1*07:150, HLA‐DRB1*13:345 and HLA‐DRB1*14:256
Authors: Loginova Maria , Druzhinina Svetlana , Paramonov Igor
Published: August 2023

Three novel HLA‐DRB1 alleles, HLA‐DRB1*07:150, HLA‐DRB1*13:345 and HLA‐DRB1*14:256, were identified.
Isoclinism of skew braces
Authors: Letourmy T. , Vendramin L.
Published: August 2023

We define isoclinism of skew braces and present several applications. We study some properties of skew braces that are invariant under isoclinism. For example, we prove that right nilpotency is an isoclinism invariant. This result has application in the theory of set‐theoretic solutions to the Yang–Baxter equation. We define isoclinic solutions and study multipermutation solutions under isoclinism.
Influence of Wire Feed Speed and Torch Speed on the Mechanical Properties of Wire Arc Additively Manufactured Stainless Steel
Authors: Terrenoir Laurent , Lartigau Julie , Arjunan Arun , Laguna Salvado Laura , Merlo Christophe
Published: August 2023

Wire arc additive manufacturing (WAAM) enables 3D printing of large high-value metal components. However, integrating WAAM into production lines requires a critical understanding of the influence of process parameters on the resulting material characteristics. As such, this research investigates the relationship between WAAM wire feed speed (WFS) and torch speed (TS) on the resulting mechanical characteristics of 316LSi thick parts (2.5 cm (0.98 in.)). The experimental procedure is informed by a training matrix that allows parametric analysis of WFS and TS on the ultimate tensile strength (σult), yield strength (σy), elastic modulus (E), failure strain (εf), hardness (HV0.5), and dimensional accuracy (Da) of the printed samples. The research found that WAAM-processed 316LSi parts feature isotropic material properties despite variations in WFS and TS. The surrogate model developed in this study offers five significant polynomial models capable of accurately predicting the influence of WAAM process parameters on σult, σy, εf, E, and Da. The research found TS to be the most significant WAAM process parameter in comparison to WFS for σult and εf. On the contrary, σy, E, and Da were found to be primarily driven by WFS as opposed to TS. Overall, the paper for the first time presents an accurate surrogate model to predict the mechanical characteristics of WAAM 316LSi thick parts informed by wire feed speed and torch speed. The study demonstrates that the mechanical properties of WAAM-processed steel are primarily influenced by the underlying process parameters offering significant potential for tunable performance.
Hybrid Laser-Arc Welding-Induced Distortion Analysis of Large-Scale Thin-Walled Cruise Ship Structures
Authors: Li Liangfeng , Zhang Yansong
Published: August 2023

In recent years, there has been increasing use of thin-walled structures with a plate thickness of 6–10 mm in the construction of cruise ships. As one of the important processes of cruise ship construction, hybrid laser-arc welding, combining the advantages of laser welding and arc welding, is increasingly applied in thin-walled cruise ships with the objective of reducing panel deformation. However, due to the weak stiffness of the thin-walled structure with a continuous weld length of 4–16 m, complex welding deformation, e.g., buckling deformation, will be prone to occur. This paper analyzed the deformation behavior of large-scale thin-walled cruise ship structures with the change of weld length, structural width, and plate thickness in the hybrid laser-arc welding process. The buckling mode induced by the welding deformation is predicted based on the combination method of thermal elastic–plastic and inherent strain, as well as experimental verification. By analyzing the deformation behavior with the weld length of 5–15 m, when the continuous weld length exceeds 7.5 m during butt welding of large thin-walled cruise ship structures, the welding deformation mode will change from bending deformation to buckling deformation, while the maximum deformation will be reduced by about 50%. Compared with the buckling mode of the traditional thick-walled structures, with the decrease of plate thickness, the buckling mode of large ship structures will change from wave buckling deformation of the whole structure to wave buckling at the edge of structures.
Effect of Bending Rigidity and Nonlinear Strains on Free Vibration of Hemi-Ellipsoidal Shells
Authors: Chanto K. , Pulngern T. , Tangbanjongkij C. , Jiammeepreecha W. , Chucheepsakul S.
Published: August 2023

This paper focuses on free vibration of hemi-ellipsoidal shells with the consideration of the bending rigidity and nonlinear terms in strain energy. The appropriate form of the energy functional is formulated based on the principle of virtual work and the fundamental form of surfaces. Natural frequencies and their corresponding mode shapes are determined using the modified direct iteration method. The obtained results, which show a close agreement with previous research, are compared with those obtained based on the membrane theory. The effect of the support condition, thickness, size ratio, and volume constraint condition on frequency parameters and mode shapes is demonstrated. With the bending rigidity, shell thickness has a significant impact on the frequency, especially in higher vibration modes and in shells with a considerable thickness but the frequency parameter converges to that determined by using the membrane theory while the reference radius-to-thickness ratio is increasing. In addition, accounting for the bending rigidity solves the issue of determining natural frequencies and mode shapes of the shells using the membrane theory without the volume constraint condition. The obtained results also indicate that the free vibration analysis with bending is essential for the hemi-ellipsoidal shell with a base radius-to-thickness ratio of less than 100, which gives over 2.84% difference compared with that of the shell derived by membrane theory, and this allows engineers to perform the analysis in more applications.
Topological defects law for migrating banded vegetation patterns in arid climates
Authors: Pinto-Ramos D. , Clerc M. G. , Tlidi M.
Published: August 2023

Self-organization and pattern formation are ubiquitous processes in nature. We study the properties of migrating banded vegetation patterns in arid landscapes, usually presenting dislocation topological defects. Vegetation patterns with dislocations are investigated in three different ecosystems. We show through remote sensing data analysis and theoretical modeling that the number of dislocations
N
(
x
) decreases in space according to the law
N
∼ log(
x
/
B
)/
x
, where
x
is the coordinate in the opposite direction to the water flow and
B
is a suitable constant. A sloped topography explains the origin of banded vegetation patterns with permanent dislocations. Theoretically, we considered well-established approaches to describe vegetation patterns. All the models support the law. This contrasts with the common belief that the dynamics of dislocations are transient. In addition, regimes with a constant distribution of defects in space are predicted. We analyze the different regimes depending on the aridity level and water flow speed. The reported decay law of defects can warn of imminent ecosystem collapse.
Repetitive mRNA vaccination is required to improve the quality of broad-spectrum anti–SARS-CoV-2 antibodies in the absence of CXCL13
Authors: Azarias Da Silva Marne , Nioche Pierre , Soudaramourty Calaiselvy , Bull-Maurer Anne , Tiouajni Mounira , Kong Dechuan , Zghidi-Abouzid Ouafa , Picard Morgane , Mendes-Frias Ana , Santa-Cruz André , Carvalho Alexandre , Capela Carlos , Pedrosa Jorge , Castro António Gil , Loubet Paul , Sotto Albert , Muller Laurent , Lefrant Jean-Yves , Roger Claire , Claret Pierre-Géraud , Duvnjak Sandra , Tran Tu-Anh , Tokunaga Kenzo , Silvestre Ricardo , Corbeau Pierre , Mammano Fabrizio , Estaquier Jérôme
Published: August 2023

Since the initial spread of severe acute respiratory syndrome coronavirus 2 infection, several viral variants have emerged and represent a major challenge for immune control, particularly in the context of vaccination. We evaluated the quantity, quality, and persistence of immunoglobulin G (IgG) and IgA in individuals who received two or three doses of messenger RNA (mRNA) vaccines, compared with previously infected vaccinated individuals. We show that three doses of mRNA vaccine were required to match the humoral responses of preinfected vaccinees. Given the importance of antibody-dependent cell-mediated immunity against viral infections, we also measured the capacity of IgG to recognize spike variants expressed on the cell surface and found that cross-reactivity was also strongly improved by repeated vaccination. Last, we report low levels of CXCL13, a surrogate marker of germinal center activation and formation, in vaccinees both after two and three doses compared with preinfected individuals, providing a potential explanation for the short duration and low quality of Ig induced.
Cell-autonomous diversification in bacteria arises from calcium dynamics self-organizing at a critical point
Authors: Meyer Christian T. , Kralj Joel M.
Published: August 2023

How dynamic bacterial calcium is regulated, with kinetics faster than typical mechanisms of cellular adaptation, is unknown. We discover bacterial calcium fluctuations are temporal-fractals resulting from a property known as self-organized criticality (SOC). SOC processes are poised at a phase transition separating ordered and chaotic dynamical regimes and are observed in many natural and anthropogenic systems. SOC in bacterial calcium emerges due to calcium channel coupling mediated via membrane voltage. Environmental or genetic perturbations modify calcium dynamics and the critical exponent suggesting a continuum of critical attractors. Moving along this continuum alters the collective information capacity of bacterial populations. We find that the stochastic transition from motile to sessile lifestyle is partially mediated by SOC-governed calcium fluctuations through the regulation of c-di-GMP. In summary, bacteria co-opt the physics of phase transitions to maintain dynamic calcium equilibrium, and this enables cell-autonomous population diversification during surface colonization by leveraging the stochasticity inherent at a boundary between phases.
Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling
Authors: Chiaranunt Pailin , Burrows Kyle , Ngai Louis , Tai Siu Ling , Cao Eric Y. , Liang Helen , Hamidzada Homaira , Wong Anthony , Gschwend Julia , Flüchter Pascal , Kuypers Meggie , Despot Tijana , Momen Abdul , Lim Sung Min , Mallevaey Thierry , Schneider Christoph , Conway Tyrrell , Imamura Hiromi , Epelman Slava , Mortha Arthur
Published: August 2023

Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism.
The M2 proteins of bat influenza A viruses reveal atypical features compared to conventional M2 proteins
Authors: Thompson Danielle , Cismaru Christiana Victoria , Rougier Jean-Sebastien , Schwemmle Martin , Zimmer Gert
Published: August 2023

The influenza A virus (IAV) M2 protein has proton channel activity, which plays a role in virus uncoating and may help to preserve the metastable conformation of the IAV hemagglutinin (HA). In contrast to the highly conserved M2 proteins of conventional IAV, the primary sequences of bat IAV H17N10 and H18N11 M2 proteins show remarkable divergence, suggesting that these proteins may differ in their biological function. We, therefore, assessed the proton channel activity of bat IAV M2 proteins and investigated its role in virus replication. Here, we show that the M2 proteins of bat IAV did not fully protect acid-sensitive HA of classical IAV from low pH-induced conformational change, indicating low proton channel activity. Interestingly, the N31S substitution not only rendered bat IAV M2 proteins sensitive to inhibition by amantadine but also preserved the metastable conformation of acid-sensitive HA to a greater extent. In contrast, the acid-stable HA of H18N11 did not rely on such support by M2 protein. When mutant M2(N31S) protein was expressed in the context of chimeric H18N11/H5N1(6:2) encoding HA and NA of avian IAV H5N1, amantadine significantly inhibited virus entry, suggesting that ion channel activity supported virus uncoating. Finally, the cytoplasmic domain of the H18N11 M2 protein mediated rapid internalization of the protein from the plasma membrane leading to low-level expression at the cell surface. However, cell surface levels of H18N11 M2 protein were significantly enhanced in cells infected with the chimeric H18N11/H5N1(6:2) virus. The potential role of the N1 sialidase in arresting M2 internalization is discussed.

IMPORTANCE

Bat IAV M2 proteins not only differ from the homologous proteins of classical IAV by their divergent primary sequence but are also unable to preserve the metastable conformation of acid-sensitive HA, indicating low proton channel activity. This unusual feature may help to avoid M2-mediated cytotoxic effects and inflammation in bats infected with H17N10 or H18N11. Unlike classical M2 proteins, bat IAV M2 proteins with the N31S substitution mediated increased protection of HA from acid-induced conformational change. This remarkable gain of function may help to understand how single point mutations can modulate proton channel activity. In addition, the cytoplasmic domain was found to be responsible for the low cell surface expression level of bat IAV M2 proteins. Given that the M2 cytoplasmic domain of conventional IAV is well known to participate in virus assembly at the plasma membrane, this atypical feature might have consequences for bat IAV budding and egress.
Perceived influence of commercial milk formula labelling on mothers’ feeding choices in Great Britain: a qualitative study
Authors: Conway Rana , Ritchie Isabel , Esser Sara , Steptoe Andrew , Smith Andrea D , Llewellyn Clare
Published: August 2023

Objective

To understand how mothers use commercial milk formula (CMF) labels to inform their feeding choices and explore mothers’ understanding of differences between CMF products.

Design

Qualitative study with recruitment via social media. Online semistructured interviews, including a product mapping exercise and thematic analysis.

Participants

Mothers (n=25) using CMF for children <3 years living in Great Britain (GB).

Results

Mothers were drawn to brands they recognised from years of exposure to CMF advertising. CMF products were assumed to vary according to brand and stage, but participants found on-pack information did not explain how. This added to anxiety about choosing ‘the best one’ and mothers would have liked guidance from healthcare professionals (HCPs). Wide availability of CMF for older infants and children, and on-pack messaging suggesting progression from one product to the next, led many to believe these products were necessary. There was confusion over the appropriate use of specialist products. While mothers rarely mentioned on-pack health and nutrition claims, they were attracted to the overall appearance of packs and messaging relating to science, research and nature. References to breast milk and a logo perceived to represent a breastfeeding mother were taken as indicators of closer similarity to breast milk.

Conclusions

CMF legislation in GB should be updated to restrict brand advertising and the use of on-pack text and images that mothers perceive as indicating products have a closer similarity to breast milk. Greater input from HCPs was desired by new mothers and would support them to make more informed choices about CMF.
Adult multisystem Langerhans cell histiocytosis with cutaneous involvement manifesting as extensive flexural erosions
Authors: Lau Lachlan Dat Wah , Vu Mi , Nirenberg Alex , Scardamaglia Laura
Published: August 2023

Langerhans cell histiocytosis is a great imitator of other diseases with an often-delayed diagnosis leading to a concerning delay in commencing treatment. We present the case of a male who was previously diagnosed with Hailey-Hailey disease, in whom several treatment options had failed, was referred to the dermatology team for evaluation of a 3-month atypical, extensive, painful and pruritic cutaneous flexural eruption. On systems review, he reported a 2-year history of polyuria and polydipsia. Repeat skin biopsy revealed a prominent histiocytic infiltrate on histopathology with corresponding positive expression of Langerin (CD207), S100, CyclinD1 and p-ERK on immunohistochemistry staining. An MRI of the brain demonstrated posterior pituitary enhancement. The clinical presentation, biopsy and investigations confirmed a diagnosis of a multisystem Langerhans cell histiocytosis, which resulted in longstanding patient morbidity. With considerable multidisciplinary teamwork, a gradual and sustained resolution of his lesions, pain, polyuria and polydipsia was achieved.
Tophaceous spinal gout in a young man with complete spinal cord injury
Authors: Okoroafor Francois , Ghazali Sorfina , Bhattacharyya Debapriya
Published: August 2023

Gout is a common inflammatory arthritis, caused by monosodium urate crystal deposition in the joints. Gout typically affects peripheral joints but less commonly it affects the spine. We report a case of a man in his 30s with chronic gout who presented acutely with thoracic back pain and flaccid paralysis of his lower limbs. CT showed abnormal facet joints at T8/9 with lucency suggestive of septic arthritis and MRI showed signal changes suggestive of epidural collection. The patient underwent emergency spinal surgery to evacuate the collection, followed by broad-spectrum antibiotic treatment. Cultures were negative; however, histopathology was suggestive of gout tophi. The patient was subsequently treated for spinal gout with prednisolone, allopurinol and colchicine and saw significant improvement in symptoms though he sustained a complete spinal cord injury. This case demonstrates that spinal gout is an important differential to consider in patients with chronic gout, presenting with acute back pain.
Enolase represents a metabolic checkpoint controlling the differential exhaustion programmes of hepatitis virus-specific CD8+T cells
Authors: Winkler Frances , Hipp Anna V , Ramirez Carlos , Martin Bianca , Villa Matteo , Neuwirt Emilia , Gorka Oliver , Aerssens Jeroen , Johansson Susanne E , Rana Nisha , Llewellyn-Lacey Sian , Price David A , Panning Marcus , Groß Olaf , Pearce Erika L , Hermann Carl M , Schumann Kathrin , Hannibal Luciana , Neumann-Haefelin Christoph , Boettler Tobias , Knolle Percy , Hofmann Maike , Wohlleber Dirk , Thimme Robert , Bengsch Bertram
Published: August 2023

Objective

Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction.

Design

Metabolic state, exhaustion and transcriptome of virus-specific CD8+T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52)were determinedex vivoand during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were testedin vitro. Intrahepatic virus-specific CD8+T cells were analysed by scRNA-Seq in a HBV-replicating murinein vivomodel of acute and chronic infection.

Results

HBV-specific (core18-27, polymerase455-463) and HCV-specific (NS31073-1081, NS31406-1415, NS5B2594-2602) CD8+T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase455-463-specific CD8+T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core18-27-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8+T cells in a murine model of chronic infection.

Conclusion

Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.
Cumulative exposure to extreme heat and trajectories of cognitive decline among older adults in the USA
Authors: Choi Eun Young , Lee Haena , Chang Virginia W
Published: August 2023

Background

The projected increase in extreme heat days is a growing public health concern. While exposure to extreme heat has been shown to negatively affect mortality and physical health, very little is known about its long-term consequences for late-life cognitive function. We examined whether extreme heat exposure is associated with cognitive decline among older adults and whether this association differs by race/ethnicity and neighbourhood socioeconomic status.

Methods

Data were drawn from seven waves of the Health and Retirement Study (2006–2018) merged with historical temperature data. We used growth curve models to assess the role of extreme heat exposure on trajectories of cognitive function among US adults aged 52 years and older.

Results

We found that high exposure to extreme heat was associated with faster cognitive decline for blacks and residents of poor neighbourhoods, but not for whites, Hispanics or residents of wealthier neighbourhoods.

Conclusion

Extreme heat exposure can disproportionately undermine cognitive health in later life for socially vulnerable populations. Our findings underscore the need for policy actions to identify and support high-risk communities for increasingly warming temperatures.
Pre-eclampsia in a first pregnancy and subsequent pregnancy outcomes: a nationwide cohort study
Authors: Havers-Borgersen Eva , Fosbøl Emil , Johansen Marianne , Køber Lars , Morris Jonathan M , Seeho Sean K M
Published: August 2023

Background

For women whose first pregnancy was complicated by pre-eclampsia (PE), particularly if severe and requiring early birth, the risk of recurrence and maternal and neonatal outcomes at subsequent birth are important considerations.

Methods

In this observational cohort study, all primiparous women who gave birth in Denmark between 1997 and 2016 were identified using nationwide registries. Women were stratified by whether they developed PE and followed from date of birth until subsequent birth, emigration, death or end of study (December 2016). The cumulative incidences of subsequent birth among women with versus without PE were assessed using the Aalen-Johansen estimator. Subsequent outcomes including PE recurrence and maternal and neonatal morbidity and mortality were also examined. Factors associated with subsequent birth and recurrent PE were examined using multivariable Cox regression models.

Results

Among 510 615 primiparous women with singleton pregnancies, 21 683 (4.2%) developed PE, with 1819 (0.4%) being early-onset PE (birth <34 weeks). Women with PE had a lower subsequent birth rate (57.4%) compared with women without PE (61.2%), and it was considerably lower among women with early-onset PE (49.4%). Among women with PE who had a subsequent birth, the overall recurrence rate of PE was 15.8% and higher among those with early-onset PE (31.5%). The gestational age increased with a median of 3 days (IQR −5 to 14) overall and 50 days (IQR 35–67) among those with early-onset PE. Moreover, neonatal and maternal morbidity and mortality were substantially improved in a subsequent pregnancy.

Conclusions

Primiparous women with PE have a significantly lower rate of a subsequent birth than women without PE, yet the absolute difference was modest. Although the overall risk of recurrent PE is 1 in 6, maternal and neonatal morbidity and mortality at subsequent birth are substantially improved.
On the ethical permissibility ofin situreperfusion in cardiac transplantation after the declaration of circulatory death
Authors: Kreitmair Karola Veronika
Published: August 2023

Transplant surgeons in the USA have begun performing a novel organ procurement protocol in the setting of circulatory death. Unlike traditional donation after circulatory death (DCD) protocols,in situnormothermic perfusion DCD involves reperfusing organs, including the heart, while still contained in the donor body. Some commentators, including the American College of Physicians, have claimed thatin situreperfusion after circulatory death violates the widely accepted Dead Donor Rule (DDR) and conclude thatin situreperfusion is ethically impermissible. In this paper I argue that, in terms of respecting the DDR,in situreperfusion cardiac transplantation does not differ from traditional DCD cardiac transplantation. I do this by introducing and defending a refined conception of circulatory death, namelyvegetative state function permanentism. I also argue against the controversial brain occlusion feature of thein situreperfusion DCD protocol, on the basis that it is ethically unnecessary and generates the problematic appearance of ethical dubiousness.
GermlineHPF1retrogene insertion inRB1gene involved in cancer predisposition
Authors: Le Gall Jessica , Dehainault Catherine , Boutte Matteo , Petitalot Ambre , Caputo Sandrine M , Courtois Laura , Vacher Sophie , Bieche Ivan , Radvanyi François , Pacquement Hélène , Doz François , Lumbroso-Le Rouic Livia , Gauthier Villars Marion , Stoppa-Lyonnet Dominique , Lallemand François , Houdayer Claude , Golmard Lisa
Published: August 2023

About half of the human genome is composed of repeated sequences derived from mobile elements, mainly retrotransposons, generally without pathogenic effect. Familial forms of retinoblastoma are caused by germline pathogenic variants inRB1gene. Here, we describe a family with retinoblastoma affecting a father and his son. No pathogenic variant was identified after DNA analysis ofRB1gene coding sequence and exon-intron junctions. However,RB1mRNA analysis showed a chimeric transcript with insertion of 114 nucleotides fromHPF1gene insideRB1gene. This chimeric transcript led to an insertion of 38 amino acids in functional domain of retinoblastoma protein. Subsequent DNA analysis inRB1intron 17 revealed the presence of a full-lengthHPF1retrogene insertion in opposite orientation. Functional assay shows that this insertion has a deleterious impact on retinoblastoma protein function. This is the first report of a full-length retrogene insertion involved in human Mendelian disease leading to a chimeric transcript and a non-functional chimeric protein. Some retrogene insertions may be missed by standard diagnostic genetic testing, so contribution of retrogene insertions to human disease may be underestimated. The increasing use of whole genome sequencing in diagnostic settings will help to get a more comprehensive view of retrogenes.