bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel Reconstruction of Vascularized Fibula Autograft for Treatment of Complications after Resection of Malignant Tumor from the Thigh
Authors: Yang Yong , Li Bin , Li Zuchang , Wei Qipei , Li Feng , Shan Huachao , Li Yuan , Duan Fangfang , Niu Xiaohui , Tian Guanglei
Published: August 2023

The authors herein introduce a modification of parallel reconstruction with a vascularized fibula autograft (VFA) for cases of femur allograft complications. Conventional parallel reconstruction, in which the fibula with its vascular pedicle is placed on the medial side of the femur and allogeneic bone, may be an effective means to solve the allograft complications. However, the limited contact area between the fibula and femur/allogeneic bone can affect the bone healing ability. Furthermore, the rigid internal fixation method for the VFA may cause stress shielding and result in bone resorption. The authors propose the use of modified parallel reconstruction of the VFA with fibula expansion and titanium cable fixation for patients with allograft–host junction nonunion, allogeneic bone fracture, and femoral shaft fracture after surgical removal of a malignant tumor from the thigh. The modified parallel reconstruction has been performed on 5 patients (2 patients underwent fibular expansion). All 5 patients with 7 nonunions of the allograft–host junction or fracture were followed up for 33.2 months. The length of fibular graft was 10 to 20 cm, with an average of 15.0 cm. The union rate of allograft–host junction and fracture was 100% (7 of 7), and the union time was 15.9 months. This modified parallel reconstruction technique can achieve satisfactory union in treatment of the above complications.
Reconstruction of Scalp Wounds in Patients With Excoriation Disorder
Authors: Bahraini Anoosh , Samant Sonja , Pogson Kaylyn B. , Khan Kamran , Ogunleye Adeyemi A.
Published: August 2023

Excoriation or skin picking disorder is described as compulsive picking of the skin that cannot be explained by an underlying dermatological condition. There are unfortunately no clear guidelines in the literature for reconstruction of wounds in this patient population. The authors describe the cases of 2 patients with the skin picking disorder who underwent free flap reconstruction for scalp wounds, which were complicated by wound recurrence due to manipulation of the surgical site. The literature is reviewed in detail, and steps to potentially prevent recurrence in this patient population are discussed.
Xenografts Show Signs of Concentric Hypertrophy and Dynamic Left Ventricular Outflow Tract Obstruction After Orthotopic Pig-to-baboon Heart Transplantation
Authors: Längin Matthias , Buttgereit Ines , Reichart Bruno , Panelli Alessandro , Radan Julia , Mokelke Maren , Neumann Elisabeth , Bender Martin , Michel Sebastian , Ellgass Reinhard , Ying Jiawei , Fresch Ann Kathrin , Mayr Tanja , Steen Stig , Paskevicius Audrius , Egerer Stefanie , Bähr Andrea , Kessler Barbara , Klymiuk Nikolai , Binder Uli , Skerra Arne , Ledderose Stephan , Müller Susanna , Walz Christoph , Hagl Christian , Wolf Eckhard , Ayares David , Brenner Paolo , Abicht Jan-Michael
Published: August 2023

Background.

Orthotopic cardiac xenotransplantation has seen substantial advancement in the last years and the initiation of a clinical pilot study is close. However, donor organ overgrowth has been a major hurdle for preclinical experiments, resulting in loss of function and the decease of the recipient. A better understanding of the pathogenesis of organ overgrowth after xenotransplantation is necessary before clinical application.

Methods.

Hearts from genetically modified (GGTA1-KO, hCD46/hTBM transgenic) juvenile pigs were orthotopically transplanted into male baboons. Group I (control, n = 3) received immunosuppression based on costimulation blockade, group II (growth inhibition, n = 9) was additionally treated with mechanistic target of rapamycin inhibitor, antihypertensive medication, and fast corticoid tapering. Thyroid hormones and insulin-like growth factor 1 were measured before transplantation and before euthanasia, left ventricular (LV) growth was assessed by echocardiography, and hemodynamic data were recorded via a wireless implant.

Results.

Insulin-like growth factor 1 was higher in baboons than in donor piglets but dropped to porcine levels at the end of the experiments in group I. LV mass increase was 10-fold faster in group I than in group II. This increase was caused by nonphysiological LV wall enlargement. Additionally, pressure gradients between LV and the ascending aorta developed, and signs of dynamic left ventricular outflow tract (LVOT) obstruction appeared.

Conclusions.

After orthotopic xenotransplantation in baboon recipients, untreated porcine hearts showed rapidly progressing concentric hypertrophy with dynamic LVOT obstruction, mimicking hypertrophic obstructive cardiomyopathy in humans. Antihypertensive and antiproliferative drugs reduced growth rate and inhibited LVOT obstruction, thereby preventing loss of function.
Delayed Graft Function Among Kidney Transplant Recipients Is Associated With an Increased Risk of Urinary Tract Infection and BK Viremia
Authors: Alshaikh Eman A. , Astor Brad C. , Muth Brenda , Jorgenson Margaret , Swanson Kurt , Garg Neetika , Aziz Fahad , Mohamed Maha , Mandelbrot Didier , Parajuli Sandesh
Published: August 2023

Background.

Delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs) is a well-known risk factor for allograft rejection, decreased graft survival, and increased cost. Although DGF is associated with an increased risk of rejection, it is unclear whether it also increases the risk of infection.

Methods.

We reviewed all adult DDKTRs at our center between 2010 and 2018. The primary outcomes of interest were BK viremia, cytomegalovirus viremia, pneumonia, and urinary tract infection (UTI) within the first year of transplant. Additional analysis was made with censoring follow-up at the time of allograft rejection.

Results.

A total of 1512 DDKTRs were included, of whom 468 (31%) had DGF. As expected, several recipient, donor, and baseline immunological characteristics differed by DGF status. After adjustment, DGF was significantly associated with an increased risk of BK viremia (hazard ratio: 1.34; 95% confidence interval, 1.0-1.81; P = 0.049) and UTI (hazard ratio: 1.70; 95% confidence interval, 1.31-2.19; P < 0.001) but not cytomegalovirus viremia or pneumonia. Associations were similar in models censored at the time of rejection.

Conclusions.

DGF is associated with an increased risk of early infectious complications, mainly UTI and BK viremia. Close monitoring and appropriate management are warranted for better outcomes in this unique population.
Co-migration fidelity at a stopover site increases over time in African–European migratory landbirds
Authors: Bellisario Bruno , Cardinale Massimiliano , Maggini Ivan , Fusani Leonida , Carere Claudio
Published: August 2023

Migratory species are changing their timing of departure from wintering areas and arrival to breeding sites (i.e. migration phenology) in response to climate change to exploit maximum food availability at higher latitudes and improve their fitness. Despite the impact of changing migration phenology at population and community level, the extent to which individual and species-specific response affects associations among co-migrating species has been seldom explored. By applying temporal co-occurrence network models on 15 years of standardized bird ringing data at a spring stopover site, we show that African–European migratory landbirds tend to migrate in well-defined groups of species with high temporal overlap. Such ‘co-migration fidelity’ significantly increased over the years and was higher in long-distance (trans-Saharan) than in short-distance (North African) migrants. Our findings suggest non-random patterns of associations in co-migrating species, possibly related to the existence of regulatory mechanisms associated with changing climate conditions and different uses of stopover sites, ultimately influencing the global economy of migration of landbirds in the Palearctic–African migration system.
Energetic consequences of prey type in little penguins (
Eudyptula minor
)
Authors: Petrovski Natalie , Sutton Grace J. , Arnould John P. Y.
Published: August 2023

Investigation of foraging decisions can help understand how animals efficiently gather and exploit food. Prey chase and handling times are important aspects of foraging efficiency, influencing the net energy gain derived from a prey item. However, these metrics are often overlooked in studies of foraging behaviour due to the difficulty in observing them. The present study used animal-borne cameras to investigate the type, duration and energetic consequences of predator–prey interactions in little penguins (
Eudyptula minor
) (
n
= 32) from two colonies in Bass Strait, south-eastern Australia. A total of seven main prey items were observed and consumed by little penguins. Penguins were observed to consume prey types and use strategies that have not been previously documented. These included consumption of bellowsfish (
Macroramphosus scolopax
) and other fish species captured sheltering around jellyfish or extracted dead from the tentacles. Chase and handling time varied with prey type and lasted approximately 2 s for most prey. Profitability varied among prey types, with a greater amount of low profitable prey being consumed, suggesting a trade-off between minimizing energetic costs, and increasing capture rates. These results highlight the use of animal-borne video data loggers to further understand the foraging adaptations of important predators in the marine environment.
Biarticular mechanisms of the gastrocnemii muscles enhance ankle mechanical power and work during running
Authors: Arampatzis Adamantios , Kharazi Mohamadreza , Theodorakis Christos , Mersmann Falk , Bohm Sebastian
Published: August 2023

The objective of the study was to explore how biarticular mechanisms of the gastrocnemii muscles may provide an important energy source for power and work at the ankle joint with increasing running speed. Achilles tendon force was quantified as a proxy of the triceps surae muscle force and the contribution of the monoarticular soleus and the biarticular gastrocnemii to the mechanical power and work performed at the ankle joint was investigated in three running speeds (transition 2.0 m s
−1
, slow 2.5 m s
−1
, fast 3.5 m s
−1
). Although the contribution of the soleus was higher, biarticular mechanisms of the gastrocnemii accounted for a relevant part of the performed mechanical power and work at the ankle joint. There was an ankle-to-knee joint energy transfer in the first part of the stance phase and a knee-to-ankle joint energy transfer during push-off via the gastrocnemii muscles, which made up 16% of the total positive ankle joint work. The rate of knee-to-ankle joint energy transfer increased with speed, indicating a speed-related participation of biarticular mechanisms in running. This energy transfer via the gastrocnemii seems to occur with negligible energy absorption/production from the quadriceps vasti contractile elements and is rather an energy exchange between elastic structures.
The endangered brain: actively preserving
ex-situ
animal behaviour and cognition will benefit
in-situ
conservation
Authors: Clark Fay E. , Greggor Alison L. , Montgomery Stephen H. , Plotnik Joshua M.
Published: August 2023

Endangered species have small, unsustainable population sizes that are geographically or genetically restricted.
Ex-situ
conservation programmes are therefore faced with the challenge of breeding sufficiently sized, genetically diverse populations earmarked for reintroduction that have the behavioural skills to survive and breed in the wild. Yet, maintaining historically beneficial behaviours may be insufficient, as research continues to suggest that certain cognitive-behavioural skills and flexibility are necessary to cope with human-induced rapid environmental change (HIREC). This paper begins by reviewing interdisciplinary studies on the ‘captivity effect’ in laboratory, farmed, domesticated and feral vertebrates and finds that captivity imposes rapid yet often reversible changes to the brain, cognition and behaviour. However, research on this effect in
ex-situ
conservation sites is lacking. This paper reveals an apparent mismatch between
ex-situ
enrichment aims and the cognitive-behavioural skills possessed by animals currently coping with HIREC. After synthesizing literature across neuroscience, behavioural biology, comparative cognition and field conservation, it seems that
ex-situ
endangered species deemed for reintroduction may have better chances of coping with HIREC if their natural cognition and behavioural repertoires are actively preserved. Evaluating the effects of environmental challenges rather than captivity
per se
is recommended, in addition to using targeted cognitive enrichment.
YOKENELLA REGENSBURGEI URINARY TRACT INFECTION IN AN IMMUNOCOMPETENT PATIENT: A CASE REPORT
Authors: V Annie Sheeba , Suji Thangamani , Jayanth Selvin Theodore , Sahni Rani Diana
Published: August 2023

Yokenella regensburgei, belonging to the order Enterobacterales, is a rare and emerging human pathogen reported to cause both superficial and invasive infections. The 13 case reports in literature worldwide highlight blood, bone and wound infections.  To our knowledge this is the first case description of Yokenella regensburgei causing UTI in a 69-year old immunocompetent patient which was isolated in 2 separate specimens and identified using MALDI-TOF MS (bioMérieux, Version 3.2, France). It was found to be susceptible to most antimicrobials but resistant to penicillin, amoxicillin-clavulanate, cefoxitin, colistin. Inducible chromosomal ampC resistance was demonstrated on disk approximation test and blaYOC-1 Class C beta-lactamase, beta lactamase superfamily and MBL fold metallo-hydrolase genes were found on whole genome sequencing.
Isolation and genome sequencing of cytomegaloviruses from Natal multimammate mice (Mastomys natalensis)
Authors: Hansen Frederick , Vučak Matej , Nichols Jenna , Hughes Joseph , Bane Sidy , Camiolo Salvatore , da Silva Filipe Ana , Ostermann Eleonore , Staliunaite Laura , Chan Baca , Mauch Thekla , Sogoba Nafomon , Streblow Daniel N. , Voigt Sebastian , Oestereich Lisa , Ehlers Bernhard , Redwood Alec J. , Feldmann Heinz , Brune Wolfram , Rosenke Kyle , Jarvis Michael A. , Davison Andrew J.
Published: August 2023

Distinct cytomegaloviruses (CMVs) are widely distributed across their mammalian hosts in a highly host species-restricted pattern. To date, evidence demonstrating this has been limited largely to PCR-based approaches targeting small, conserved genomic regions, and only a few complete genomes of isolated viruses representing distinct CMV species have been sequenced. We have now combined direct isolation of infectious viruses from tissues with complete genome sequencing to provide a view of CMV diversity in a wild animal population. We targeted Natal multimammate mice (Mastomys natalensis), which are common in sub-Saharan Africa, are known to carry a variety of zoonotic pathogens, and are regarded as the primary source of Lassa virus (LASV) spillover into humans. Using transformed epithelial cells prepared from M. natalensis kidneys, we isolated CMVs from the salivary gland tissue of 14 of 37 (36 %) animals from a field study site in Mali. Genome sequencing showed that these primary isolates represent three different M. natalensis CMVs (MnatCMVs: MnatCMV1, MnatCMV2 and MnatCMV3), with some animals carrying multiple MnatCMVs or multiple strains of a single MnatCMV presumably as a result of coinfection or superinfection. Including primary isolates and plaque-purified isolates, we sequenced and annotated the genomes of two MnatCMV1 strains (derived from sequencing 14 viruses), six MnatCMV2 strains (25 viruses) and ten MnatCMV3 strains (21 viruses), totalling 18 MnatCMV strains isolated as 60 infectious viruses. Phylogenetic analysis showed that these MnatCMVs group with other murid viruses in the genus Muromegalovirus (subfamily Betaherpesvirinae, family Orthoherpesviridae), and that MnatCMV1 and MnatCMV2 are more closely related to each other than to MnatCMV3. The availability of MnatCMV isolates and the characterization of their genomes will serve as the prelude to the generation of a MnatCMV-based vaccine to target LASV in the M. natalensis reservoir.
Gain-of-function MARK4 variant associates with pediatric neurodevelopmental disorder and dysmorphism
Authors: Samra Simran , Sharma Mehul , Vaseghi-Shanjani Maryam , Del Bel Kate L. , Byres Loryn , Lin Susan , Dalmann Joshua , Salman Areesha , Mwenifumbo Jill , Modi Bhavi P. , Biggs Catherine M. , Boelman Cyrus , Clarke Lorne A. , Lehman Anna , Turvey Stuart E.
Published: August 2023

Microtubule affinity regulating kinase 4 (MARK4) is a serine/threonine kinase that plays a key role in tau phosphorylation and regulation of the mTOR pathway. Abnormal tau phosphorylation and dysregulation of the mTOR pathway are implicated in neurodegenerative and neurodevelopmental disorders.

Here, we report a novel gain-of-function variant inMARK4in two siblings with childhood-onset neurodevelopmental disability and dysmorphic features.

The siblings carry a germline heterozygous missenseMARK4variant c.604T>C; p.Phe202Leu, located in the catalytic domain of the kinase, which they inherited from their unaffected, somatic mosaic mother. Functional studies show that this amino acid substitution has no impact on protein expression but instead increases the ability of MARK4 to phosphorylate tau isoforms found in the fetal and adult brain. TheMARK4variant also increases phosphorylation of ribosomal protein S6, indicating upregulation of the mTORC1 pathway.

This is the first study to link a germline monoallelicMARK4variant to a childhood-onset neurodevelopmental disorder characterized by global developmental delay, intellectual disability, behavioral abnormalities, and dysmorphic features.
Interrogating basal ganglia circuit function in Parkinson’s disease and dystonia
Authors: Sumarac S , Spencer KA , Steiner LA , Fearon C , Haniff E , Kühn AA , Hodaie M , Kalia SK , Lozano AM , Fasano A , Hutchison WD , Milosevic L
Published: August 2023

Background

The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology.

Objective

Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.

Results

GPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate, and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression.

Conclusion

We substantiated claims of hyper-versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.
Bushfire alters the gut microbiome in endangered Kangaroo Island echidnas (Tachyglossus aculeatus multiaculeatus)
Authors: Perry Tahlia , Lu Amy , McKelvey Michael W. , Rismiller Peggy D. , Grützner Frank
Published: August 2023

Kangaroo Island experienced extensive bushfires in December 2019 and January 2020, affecting almost half of the island. This impacted several threatened species including the Kangaroo Island echidnas (Tachyglossus aculeatus multiaculeatus). Echidnas can often survive fires, however, changes in soil chemistry and food availability raises questions about the impact on echidna gut health and foraging behaviours. Due to local participation in the citizen science project, EchidnaCSI, echidna scats were collected before and after the fires to directly assess how fire affects their gut microbiomes. Metabarcoding of scat microbiota (n = 13) revealed substantial changes in bacterial composition of echidna faeces post-bushfire when compared to samples collected prior to bushfires. Before the fires, echidna gut microbiomes were more variable and contained mostly soil-associated bacteria, whereas post-fire samples shifted to uniform bacterial communities consisting of lactic acid and gut commensal bacteria. Interestingly, changes were observed in scats collected in both burnt and unburnt regions of the island, suggesting echidnas are foraging between these areas. This is the first study to document changes in gut microbiome of any mammal following bushfires. More work is needed to investigate if the gut bacterial communities continue to change as areas recover from fires.
Neural computation in the brainstem for visceral sensation-driven haemodynamics
Authors: Lee Jiho , Mun Junseung , Park Sung-Min
Published: August 2023

The brainstem serves as an intermediary processor of haemodynamic sensations via nucleus tractus solitaries (NTS) in regulating circulatory system. After sensing visceral inputs, the NTS relays information to efferent pathways to modulate peripheral viscera. However, the neural computation mechanism underlying how the NTS processes viscerosensory input remains unknown. Here, we show the computational principles embedded inside the NTS of rats, producing haemodynamic modulation in concert. Our findings demonstrate that the collective dynamics leveraging from neuronal population within the NTS neural circuit encode input-driven haemodynamics. The NTS exhibits the neural trajectory, the dynamical trace of neural states, which is confined to low-dimensional latent space and may represent haemodynamic perturbations. Surprisingly, by normalizing neural trajectory of rats, we found the across-rat common rules for the viscerosensory-information processing by the NTS. Furthermore, the common rules allowed to identify inter-subject variable haemodynamics by quantifying the computational mechanisms in neuro-haemodynamic axis. Our findings provide pioneering insights into understanding the neural computation involved in regulation of visceral functions by the autonomic nervous system.
CLOCK Mediates Delay in Cardiac Myofibroblast Formation and Attenuates Progression of Myocardial Fibrosis through Inhibition of Smad 3 Transcriptional Activity
Authors: Zhou Yongqiao , Liao Minqi , Chen Lihua , Yao Yongzhao , Huang Zhichao , Yang Yanhua , Su Shaohui , Liang Guangzhu , Wu Zhihao , Ouyang Shumin , Guo Suxia
Published: August 2023

Introduction

Myocardial fibrosis, characterized by excessive extracellular matrix deposition, leading to adverse cardiac remodeling and impaired function. The differentiation of cardiac fibroblasts into myofibroblasts plays a pivotal role in this process. The involvement of the core clock protein CLOCK in the formation of cardiac myofibroblasts and the advancement of myocardial fibrosis is not well understood. This study aims to investigate how CLOCK modulates cardiac myofibroblast differentiation and attenuates myocardial fibrosis by inhibiting Smad3 transcriptional activity.

Methods

In vivo, adeno-associated virus 9 was utilized for overexpression or silencing of the CLOCK gene via mice intravenous injection. In vitro experiments were conducted using primary cultures of cardiac fibroblasts isolated from mouse hearts to examine the expression levels of molecular markers associated with myofibroblast differentiation, such as α-smooth muscle actin (α-SMA) and collagen I. Additionally, a Smad3 luciferase reporter gene experiment was employed to assess the transcriptional activity of Smad3 under CLOCK regulation.

Results

The results demonstrate that CLOCK overexpression significantly reduces the expression of α-SMA and collagen I in cardiac fibroblasts, indicating a suppression of myofibroblast formation. Conversely, CLOCK knockdown enhances the expression of these fibrotic markers. Interestingly, CLOCK was found to negatively regulate the transcriptional activity of Smad3, suggesting a potential mechanism by which CLOCK exerts its inhibitory effect on cardiac fibrosis. Specifically, CLOCK interacts with Smad3, inhibiting its nuclear translocation and subsequent activation of fibro genic gene expression.

Conclusion

These findings highlight the crucial role of CLOCK in the regulation of cardiac myofibroblast formation and the progression of myocardial fibrosis. CLOCK appears to exert an inhibitory effect on fibrotic signaling pathways, partially through the inhibition of Smad3 transcriptional activity. This study provides novel insights into the molecular mechanisms underlying cardiac fibrosis and emphasizes the therapeutic potential of targeting CLOCK-mediated pathways for treating myocardial fibrosis.
Wastewater-based surveillance is an efficient monitoring tool for tracking influenza A virus in the community
Authors: Kirsi-Maarit Lehto , Rafiqul Hyder , Annika Länsivaara , Oskari Luomala , Anssi Lipponen , Hokajärvi Anna-Maria , Annamari Heikinheimo , Tarja Pitkänen , Sami Oikarinen ,   WastPan Study Group
Published: August 2023

Around the world, influenza A virus has caused severe pandemics, and the risk of future pandemics remains high. Currently, influenza A virus surveillance is based on the clinical diagnosis and reporting of disease cases. In this study, we apply wastewater-based surveillance to monitor the incidence of the influenza A virus at the population level. We report incidence data of the influenza A virus in 10 wastewater treatment plant catchment areas covering 40% of the Finnish population. Altogether, 141 monthly composite influent wastewater samples (collected between April 2020 and May 2021) were analysed from supernatant fraction using influenza A virus specific RT-qPCR method. During the study period, an influenza A virus epidemic occurred in two waves in Finland. This study shows that the influenza A virus can be detected from the supernatant fraction of 24 h composite influent wastewater samples. The influenza A virus gene copy number in wastewater correlated with the number of confirmed disease cases in the Finnish National Infectious Diseases Register. The Kendall’s τ correlation strength was over 0.600 in all wastewater treatment plants, save for one, which was 0.459. The strongest correlations were 0.761 and 0.833. Wastewater-based surveillance of the influenza A virus is an unbiased method and cost-efficiently reflects the circulation of the virus in the entire population. Thus, wastewater monitoring complements the available, but often too sparse, information from individual testing and improves health care and public health preparedness for influenza A virus pandemics.
Uncoupling interferons and the interferon signature explain clinical and transcriptional subsets in SLE
Authors: Gómez-Bañuelos Eduardo , Goldman Daniel W. , Andrade Victoria , Darrah Erika , Petri Michelle , Andrade Felipe
Published: August 2023

Interferons (IFN) are thought to be key players in systemic lupus erythematosus (SLE). The unique and interactive roles of the different IFN families in SLE pathogenesis, however, remain poorly understood. Using reporter cells engineered to precisely quantify IFN-I, IFN-II and IFN-III activity levels in serum/plasma, we found that while IFNs play essential role in SLE pathogenesis and disease activity, they are only significant in specific subsets of patients. Interestingly, whereas IFN-I is the main IFN that governs disease activity in SLE, clinical subsets are defined by the co-elevation of IFN-II and IFN-III. Thus, increased IFN-I alone was only associated with cutaneous lupus. In contrast, systemic features, such as nephritis, were linked to co-elevation of IFN-I plus IFN-II and IFN-III, implying a synergistic effect of IFNs in severe SLE. Intriguingly, while increased IFN-I levels were strongly associated with IFN-induced gene expression (93.5%), in up to 64% of cases, the IFN signature was not associated with IFN-I. Importantly, neither IFN-II nor IFN-III explained IFN-induced gene expression in patients with normal IFN-I levels, and not every feature in SLE was associated with elevated IFNs, suggesting IFN-independent subsets in SLE. Together, the data suggest that, unlike the IFN signature, direct quantification of bioactive IFNs can identify pathogenic and clinically relevant SLE subsets amenable for precise anti-IFN therapies. Since IFN-I is only elevated in a subset of SLE patients expressing the IFN signature, this study explains the heterogeneous response in clinical trials targeting IFN-I, where patients were selected based on IFN-induced gene expression rather than IFN-I levels.
Antimicrobial efficacy ofin-situplasma-generated ozone againstPseudomonas aeruginosabiofilms in drains and water-submerged surfaces
Authors: Pajak-Zajac Malgorzata Z. , Dowdell Adam , Buckley Anthony , Potts Hugh E. , Smith Andrew , Diver Declan A.
Published: August 2023

Aims

To demonstrate a novel method of gaseous disinfection that can eradicate biofilms inhabiting elusive regions of plumbing systems.

Methods & Results

Highly biocidal ozone is generatedin-situusing the ambient air inside a model sink and drain, via portable plasma discharge, with the plasma device sealing the treated area, ensuring no ozone escape to the external environment. Subsequent bacterial recovery illustrates an approximate bioburden reduction of 5log10for biofilms suspended in the drain, and 6log10for biofilms placed in the sink.

Conclusions

Plasma-generated ozone is a safe and effective method for controlling bioburden in periodically wetted, otherwise inaccessible pipework and drains, both above and below the water line.

Significance and Impact of Study

The ozone generation system described has potential for controlling healthcare associated infections (HAIs) and infections linked to closed environments, such as cruise ships, from bacteria arising from waste water systems by aerosolization or splash-back. The method has additional benefits provided by an absence of toxic residues after application, reducing risks to users and the waste water system. Cost effectiveness is high, requiring minimal energy input from the electrical supply and only ambient air (no additional feedstock gas is necessary) to generate ozone.
A simple method for developing lysine targeted covalent protein reagents
Authors: Gabizon Ronen , Tivon Barr , Reddi Rambabu N. , van den Oetelaar Maxime C. M. , Amartely Hadar , Cossar Peter J. , Ottmann Christian , London Nir
Published: August 2023

There is a growing demand for covalent tool compounds and chemical probes to investigate and perturb protein function and dysregulation. The combination of a covalent electrophile with a peptide or protein-based scaffold with an extended binding footprint enables the targeting of shallow protein surfaces, not typically addressable using small molecules. However, to fully exploit the potential of electrophilic proteins or peptides there is a need for versatile approaches to convert native peptide sequences into covalent binders that can target a broad range of residues. Here we report protein-based thio-methacrylate esters - electrophiles with a diverse reactivity profile that can be installed easily on unprotected peptides and proteins via cysteine side chains, and react efficiently and selectively with cysteine and lysine side chains on the target. Guided by computational modeling, we designed and synthesized methacrylate phosphopeptides derived from 14-3-3-binding proteins and demonstrated these peptides irreversibly label 14-3-3σ via either lysine or cysteine residues, depending on the position of the electrophile. Methacrylate peptides targeting a conserved lysine residue exhibited pan-isoform binding of 14-3-3 proteins, and efficiently labeled 14-3-3 proteins in lysates, as well as secreted 14-3-3 extracellularly. The irreversible binding to the predicted target lysines were confirmed by proteomics and X-ray crystallography of the complexes. Finally, we applied this approach to develop protein-based covalent binders. A methacrylate-modified variant of the colicin E9 immunity protein irreversibly bound to the E9 DNAse, resulting in significantly higher thermal stability relative to the non-covalent complex. Our approach offers a simple and versatile route to convert peptides and proteins into potent covalent binders.
Limb regeneration is blastema dependent in a ladybird beetle,Cheilomenes sexmaculata(Fabricius)
Authors: Rawat Saumya , Rai Shriza , Mishra Geetanjali
Published: August 2023

Holometabolous insects undergoes metamorphosis which involves an intercalated pupal stage between larva and adult. The body plan of the adult is established during pupal stage and larval systems are de-differentiated and reorganized in insects undergoing complete metamorphosis. In ladybird beetles, limbs amputated in larval stages are regenerated in adults. This occurs during pupation. Given that changes in pupa are akin to embryogenesis, does the lost limbs are redeveloped as a part of metamorphosis or has some pre-patterning initiated prior pupation? To study this we hypothesised that limb regeneration in a holometabolous ladybird beetles,Cheilomenes sexmaculatais the result of the recapitulation of the embryonic gene programs in the pupa. To test this, we exposed third larval stages ofC. sexmaculatato amputation and prior to amputation the tissues on the amputated site was scraped off every 24hrs. It was found that limb regeneration does not occur in the treatment where scrapping was done. Assuming that these epidermal cells correspond to blastema, for limb regeneration in ladybird beetles blastema is essential and does not occur in its absence.
Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria
Authors: van den Biggelaar Robin H.G.A. , Walburg Kimberley V. , van den Eeden Susan , van Doorn Cassandra L.R. , Meiler Eugenia , de Ries Alex S. , Fusco M. Chiara , Meijer Annemarie H. , Ottenhoff Tom H.M. , Saris Anno
Published: August 2023

The emergence of antimicrobial resistance has created an urgent need for alternative treatment strategies against deadly bacterial species. In this study, we investigated the potential of kinase inhibitors as host-directed therapies (HDTs) for combating infectious diseases caused by intracellular bacteria, specificallySalmonellaTyphimurium (Stm) andMycobacterium tuberculosis(Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models forStmandMtb, based on human cell lines and primary macrophages. Additionally, thein vivoefficacy of the compounds was assessed using zebrafish embryo infection models. Our kinase inhibitor screen identified 14 hit compounds forStmand 19 hit compounds forMtbthat were effective against intracellular bacteria and non-toxic for host cells. Further validation experiments showed the high efficacy of mostStmhit compounds and their ability to fully clear the intracellular infection both in cell lines and primary human macrophages. From these, two structurally relatedStmhit compounds, GSK1379738A and GSK1379760A, exhibited significant effectiveness againstStmin infected zebrafish embryos. Compounds that were active against intracellularMtbincluded morpholino-imidazo/triazolo-pyrimidinones that specifically target the kinases PIK3CB and PIK3CD as well as 2-aminobenzimidazoles targeting BLK, ABL1 and TRKA. Overall, this study provided insight into critical kinase targets acting at the host-pathogen interface and identified novel kinase inhibitors as potential HDTs for intracellular bacterial infections.
Morphogen gradients can convey position and time in growing tissues
Authors: Vetter Roman , Iber Dagmar
Published: August 2023

During development, cells need to make fate decisions according to their position and the developmental timepoint. Morphogen gradients provide positional information, but how timing is controlled has remained elusive. Here, we show that in morphogen gradients with constant decay length, cells experience transient, hump-shaped concentration profiles if the morphogen source expands in parallel with the uniformly growing tissue. This transient signal can convey time. We further show that opposing steady-state morphogen gradients with equal decay length, as found in the vertebrate neural tube, can synchronise cell fate decisions along the entire expanding patterning axis, because the product of the two opposing concentration gradients is constant along it. In case of an increasing amplitude, cells experience a transient hump signal, while in case of constant gradient amplitudes, the concentration product declines continuously as the tissue expands — a hallmark of a depletion timer. Once the tissue reaches a critical size and the concentrations a critical value, a cell fate switch can be triggered. Timers based on morphogen gradients offer a simple mechanism for the simultaneous control of position and time and might apply in many patterning systems, as uniform growth is observed widely in development.
Extracellular Matrix Proteins Changes in the Left Ventricular Unloading and Overloading after Myocardial Infarction
Authors: Mavropoulos Spyros A. , Sakata Tomoki , Mazurek Renata , Ravichandran Anjali J. , Marx Jonas M. , Ishikawa Kiyotake
Published: August 2023

Background

The cardiac extracellular matrix (ECM) is a dynamic scaffold that transmits and responds to forces that act on the heart during the cardiac cycle. While acute left ventricle (LV) unloading by percutaneous LV assist device (pLVAD) is now a therapeutic option, its impact on ECM is unknown. We hypothesize that the composition of LV ECM proteins changes in response to reduced wall stress with mechanical LV unloading.

Methods

Ten Yorkshire pigs underwent myocardial infarction, and one week later were subjected to either 2 hours of LV unloading with pLVAD or 2 hours of LV overloading by mechanically-induced acute aortic regurgitation. Non-ischemic remote myocardium was processed for ECM specific proteomics. Volcano plots were constructed to determine differentially expressed proteins between the groups. Gene ontology (GO) analysis was performed to identify associated molecular processes and biological functions. Immunofluorescence microscopy was performed to validate differential protein expression.

Results

Of the 986 proteins analyzed, 39 were significantly differentially expressed between overloaded and unloaded myocardium. GO analysis by molecular function revealed that differences tending towards RNA binding and lipid binding proteins. Analysis by biological process showed that cell differentiation, vesicle transport, and programmed cell death were the processes most affected. Staining for three of the identified differentially expressed proteins had results congruent with proteomic analysis.

Conclusions

There were significant differences in the protein composition of the cardiac ECM between acutely unloaded and overloaded myocardium, suggesting that it actively responds to altered LV load.
Identifying key factors that encourage vegetable intake by young adults: using the health belief model
Authors: Hartwell Heather , Bray Jeff , Lavrushkina Natalia , Lacey Jodie , Rodrigues Vanessa Mello , Fernandes Ana Carolina , Bernardo Greyce Luci , Martinelli Suellen Secchi , Cavalli Suzi Barletto , Proença Rossana Pacheco da Costa
Published: August 2023

Purpose

Adequate vegetable consumption is fundamental to a healthy balanced diet; however, global compliance with recommendations is poor which is particularly important for young adults as they form food consumption habits. There is a growing interest in the circular economy of hospitality and sustainability of current dietary patterns in light of climate change and an expanding global population. The food value chain needs to be considered both vertically and horizontally where the research and development (R&D) investment is optimised by being “joined up” and not fragmentary; in addition, consumer trade-offs of health vs for example sensory appeal are taken into consideration. The purpose of this study was to identify factors predicting acceptance of vegetable dishes by young adults and present a roadmap that can be used for dish development and healthful marketing.

Design/methodology/approach

This study used the health belief model (HBM) as framework to investigate key factors that encourage vegetable intake by young adults using an online questionnaire sample of 444 enrolled in undergraduate programs at universities in Brazil.

Findings

Structural modelling showed that vegetable consumption frequency was positively influenced by Health concerns, Naturalness and Self-efficacy (including cooking skills), whereas Sensory factors and Familiarity demonstrated a negative loading that might be related to unpleasantness.

Originality/value

Globally, there is a strong need to promote the consumption of vegetables as a public health policy priority but also to ameliorate barriers to action that could be facilitated by availability, dish development and healthful marketing in hospitality operations.
Now what? An assessment of perceived legacies post-Olympic cycle
Authors: Feller Rodrigo , Turick Robert M. , Walker Khirey B. , Downs Benjamin J.
Published: August 2023

Purpose

The purpose of this study is to examine the post-event perceptions of Rio de Janeiro residents regarding the legacies left to them from hosting the 2016 Olympic Games. Additionally, this study examines how perceptions of Olympic legacies differed amongst demographic groups.

Design/methodology/approach

Utilizing a mixed-methods approach, participants were asked to complete a survey questionnaire and answer three open-ended questions. An adapted version of Fredline et al. (2003)'s General Scale to Measure Social Impacts (GSMSI) was selected for this study. In total, 156 useable responses were collected. An exploratory factor analysis was utilized for the survey items while the three open-ended questions were coded abductively as positive, negative or mixed feelings.

Findings

The quantitative results shows that Rio residents believe that hosting the 2016 Olympic Games had a mostly negative impact on their perception of legacies. Through reading open-ended responses, participants expressed disappointment over the legacies left to them. These findings suggest that hosting the Olympic Games may not have been beneficial to the life of Rio de Janeiro residents, and it may have been particularly worse for members of the middle class.

Originality/value

Due to the recency of the Rio 2016 Olympic Games, a few studies have explored the long-term legacies left to the local population. However, the uniqueness of this study lays on the perceptions of legacies from hosting the Rio 2016 after a full Olympic cycle has passed.
Readiness of lean sustainability in healthcare organizations
Authors: Thomas Albi , Suresh M.
Published: August 2023

Purpose

This paper aims to “identify,” “analyse” and “categorise” the readiness factors of lean sustainability in health-care organisation using total interpretive structural modelling (TISM).

Design/methodology/approach

To obtain the data, a closed-ended questionnaire was used in addition to a scheduled interview. To identify how the factors interact, the TISM approach was used, and the matriced’ impacts croise’s multiplication applique’e a UN classement (MICMAC) analysis was used to rank and categorise the lean sustainability readiness factors.

Findings

This study identified ten lean sustainability readiness factors for health-care organisation. The identified factors are resources utilization practice (F1), management commitment and leadership (F2), operational flexibility (F3), workforce engagement and time commitment (F4), sustainability motivational factors (F5), awareness of lean and sustainable practice (F6), hospital design (F7), energy efficiency practices in hospitals (F8), responsible autonomy (F9) and new system adoptability training (F10). The key/driving factors are identified in this study are operational flexibility, sustainability motivational factors, management commitment and leadership, new system adoptability training.

Research limitations/implications

The study focussed primarily on lean sustainability factors for the health-care sector.

Practical implications

This research will aid key stakeholders and academics in the better understanding the readiness factors that influence lean sustainability in health-care organisation. This study emphasises the factors that must be considered when applying lean sustainable practices in health care as a real-world application in a health-care organisation. These readiness factors for lean sustainability can be used by an organization to comprehend more about the concept and the components that contribute to health-care lean sustainability.

Originality/value

This study proposes the TISM technique for health care, which is a novel attempt in the subject of lean sustainability in this sector.
What do we know about real earnings management in the GCC?
Authors: Alghemary Mahmoud , Al-Najjar Basil , Polovina Nereida
Published: August 2023

Purpose

The authors empirically investigate the association between acquisition, ownership structure and accrual earnings management (AEM) on real earnings management (REM) using Gulf Cooperation Council (GCC)-listed firms' context.

Design/methodology/approach

The authors' sample consists of 1,892 firm-year observations for the period from 2007–2017, and the authors adopt a panel data approach in investigating the interrelationships in this study. The authors employ different econometrics approach to test the authors' hypotheses.

Findings

The findings reveal that acquiring companies engage more in AEM if compared to REM. In terms of ownership structure, institutional ownership and state ownership mitigate the engagement in REM, whereas foreign ownership is found to be an ineffective mechanism in reducing engagement in REM. The authors report similar findings on ownership structure for AEM. The authors also find that the GCC firms engage more in REM when the firms engage in AEM, suggesting a complementary relation between these two earnings management techniques. These findings are robust after controlling for different aspects including any endogeneity issue in the authors' models.

Originality/value

The authors' research highlights the importance of understanding REM and AEM dynamics in GCC context. Also, the authors' findings on ownership structure suggest that GCC-listed firms can gain from institutional and state ownership which restricts earnings management, improving firm transparency and subsequently impacting firm performance.