bluuebunny/crossref_metadata_2025 huggingface dataset:
BT08 Mapping UK frameworks for ethical artificial intelligence applied to dermatology
Authors: Shah Syed Fazal Hussein , Matin Rubeta N
Published: June 2023

There is significant enthusiasm to apply artificial intelligence (AI) in dermatology with an emphasis on image-based analyses for risk assessment of suspicious skin lesions. However, the rapid development and deployment of such AI tools raises concerns that ethical issues arising from their widespread, long-term use may not have been adequately considered during design or implementation. Dermatology, in particular, has been identified as lacking sufficient bioethics research that could standardize the approach to regulating AI-assisted applications. Despite significant efforts to develop robust guidelines for ‘ethical AI’ across private, national and international organizations, debate continues surrounding which ethical principles should be included. The 2022 National AI Strategy positions the UK as leading global efforts toward achieving safe and ethical deployment of AI. We sought to systematically review and analyse policy documents to map UK principles for promoting ethical AI as applied to dermatology. Our review identified five UK policy documents relevant to ethical AI published between 2016 and 2022. All included frameworks highlighted the importance of upholding transparency and fairness along the entire lifecycle of AI development and decision-making. The five frameworks also incorporated autonomy through reference to maintaining informed consent, data privacy and human contestability of AI decisions. The principles of accountability and nonmaleficence were each identified in four policy documents, emphasizing the needs for clear definitions of legal and organizational responsibility and for thorough testing of AI tools to avoid unintended/unwanted outcomes. The principles of beneficence (designing AI to promote good on both individual and societal levels) and sustainability (continually monitoring and adjusting AI tools for longevity and efficacy) were each included in two policy documents. Current UK policy frameworks for ethical AI converge around five key values: fairness, transparency, autonomy, nonmaleficence and accountability. The principles of beneficence and sustainability were advanced, although less frequently highlighted. Despite a reassuring level of convergence across policy documents, the practical implementation of these ethical principles in health care and particularly for skin-specific AI tools remains unclear. Furthermore, evidence of real-world integration of these ethical frameworks into developing AI-based skin cancer diagnostic tools is lacking. Future work seeks to address this gap by analysing commercially available skin cancer diagnostic applications using predefined ethical themes to identify case-specific ethical issues and to evaluate the extent to which these issues are addressed within the existing ethical frameworks. This will provide guidance for developers and adopters of these tools, ensuring responsible design and deployment.
BT09 Clinical performance of an artificial intelligence-based medical device deployed within an urgent suspected skin cancer pathway
Authors: Jenkins Rachel , Brewer Christopher Felix , Kalsi Dilraj , Mullarkey Daniel
Published: June 2023

A secondary care trust received over 2800 urgent suspected skin cancer referrals (USCRs) in 2021, 50% more than in 2016 (www.england.nhs.uk/statistics/statistical-work-areas/cancer-waiting-times), < 1 in 10 of which resulted in diagnosis of skin cancer (www.cancerdata.nhs.uk/cwt_conversion_and_detection). Judicious implementation of artificial intelligence (AI) may improve referral accuracy. We conducted a prospective, postdeployment, single-centre clinical performance review of a UK Conformity Assessed Class IIa-approved, AI-based, skin lesion analysis medical device intended for use in the screening, triage and assessment of skin lesions suspicious for skin cancer (AIaMD). The AIaMD is deployed at the trust as a decision-support tool following USCR from primary care, with a second read of all cases by a consultant dermatologist. Patients assessed by the two most recent versions of AIaMD from October 2021 to October 2022 were eligible for inclusion. Outcomes were confirmed from histology reports for cancerous lesions and histology reports or Consultant teledermatology assessment for noncancerous lesions. The AIaMD assessed 1363 lesions with outcomes confirmed, including 51 melanomas, 64 squamous cell carcinomas (SCCs), 96 basal cell carcinomas, 8 rare skin cancers and 244 premalignancies. The AIaMD referral sensitivity for melanoma, all skin cancer and premalignancy was 100% (n = 51/51), 99.5% (n = 218/219) and 96.3% (n = 235/244), respectively. The AIaMD benign lesion specificity was 55.9% (n = 434/777). The negative predictive value (how often AIaMD labelled lesions as premalignant/benign and correctly ruled out cancer) was 99.8% (n = 539/540). The conversion rate (the percentage of lesions classified as high risk by AIaMD that resulted in a diagnosis of melanoma or SCC) was 13.8% (n = 122/886), while the USCR conversion in the local clinical commissioning group was 9.9% in 2020–2021. The service discharged 9.4% (n = 239/2551) of patients during this time without using trust dermatologist capacity, with the potential to have discharged 18.3% (n = 467/2551) without a second read. This postmarket service evaluation reported the clinical outcomes of an AI device used for assessment of skin lesions. The pathway was sensitive, identifying 218 of 219 skin cancers, and specific, correctly identifying over half of benign lesions. Moreover, AIaMD was able to improve the conversion rate of USCRs. The integration of AIaMD into skin cancer diagnostic pathways could significantly improve the accuracy of USCRs.

Conflicts of interest: these were commercial deployments of the AI, and three of the authors are employed by the AI provider.
BT13 MySkinDoctor: lessons learnt from assessing 120 000 teledermatology patients
Authors: Shergill Bav
Published: June 2023

MySkinDoctor is a novel teledermatology platform that enables dermatologists to review images submitted directly by the patient via their smartphone, in addition to any metadata and the standard general practitioner referral. The three sets of data are used to triage or provide advice and guidance to National Health Service patients throughout the south east of England. Since its inception in 2019, the service has completed the assessment of > 120 000 cases. Analysis of the data shows that an unnecessary first appointment has been avoided in 48% of cases. This has led to a sharp reduction in waiting times in the areas in which it is being used (an average of 6 weeks) vs. neighbouring areas where waiting times remain between 27 and 50 weeks. Another benefit of the service is that, on average, each patient using it submits three digital images that are subsequently tagged inter alia with their age, sex, body location and the consultant’s diagnosis. This has resulted in a large, and growing, digital image library with associated dataset of patients that has been used to develop an artificial intelligence platform called ‘dermXai’. Using convolutional neural networks for image identification has produced an accuracy of determination of > 90% for the top 20 conditions seen. We will discuss the implementation schedule and regulatory challenges that need to be met in order for dermXai to support clinical decision-making. There are also environmental and economic benefits associated with using MySkinDoctor. Since its inception, it has saved > 40 000 road miles—over twice Earth’s circumference. This is a CO2 saving of 16 488 kg. The benefit to patients and their carers in terms of saving travel and regaining otherwise lost productivity time is difficult to quantify but could be studied prospectively. Patient-led digital dermatology is the obvious evolution of traditional teledermatology and our successful experience with MySkinDoctor and dermXai in southern England provides a template for a national service that will eliminate backlogs and significantly reduce patient waiting times.

Conflicts of interest: Dr Bav Shergill is the Chief Medical Officer of MySkinDoctor Ltd and a Director of dermXai.
BT17 Patient Assessment Wrap-up Session: the utility of consensus decision-making in teledermatology
Authors: Butt Sanaa , Nahar Sayeda , Gazzani Paul , Shah Farida , Martin-Clavijo Agustin , Akufo-Tetteh Emily , Velangi Shireen
Published: June 2023

In our unit, skin cancer referrals are triaged via teledermatology following high-quality image capture of lesions, including dermoscopic views. Patients are discharged, invited for a face-to-face assessment or listed directly for surgery. Remote and asynchronous consultations are at odds with the traditional clinical training all our consultants underwent, and therefore introduce new uncertainty into our work. As a way to maximize remote discharges, and improve the consistency of and the confidence in our own teledermatology diagnoses, we developed Patient Assessment Wrap-up Session (PAWS). This is an email-based discussion group allowing consensus decision-making on cases with lesions that demonstrate some ambiguity and that individually we would usually bring to a face-to-face appointment. Between March and April 2022, a total of 566 teledermatology cases were allocated to five consultants within the department. In total, 476 (84.1%) were dealt with independently by the allocated consultant. The remaining 90 cases (15.9%) were discussed via PAWS, with 48 (53%) being discharged as a result. On average, four clinicians responded to the PAWS request, and the average time to reach a consensus was 14 h. Of those discharged, two were re-referred within 6 months, one for different lesions and one for the same noncancerous lesion; however, both were discharged again. The additional discharges led to 16 h of clinic time saved, but the PAWS time cost between 12 and 18 h. Although PAWS is currently probably consultant-time neutral, the timing is more flexible than a face-to-face clinic. Additional advantages have also become apparent while using the process. It aids continued professional development and peer assessment while simultaneously providing a service. The patients discharged after PAWS are also saved from a fossil fuel burning visit to the hospital and having to take time off work, and so on. The PAWS also allows for junior colleagues to leverage support from more experienced clinicians when balancing risk and dealing with difficult decision-making. We would like to share our PAWS process as it may also benefit other services using teledermatology.
Severe homozygous HbE disease: the first case report from Nepal
Authors: Bhattarai Urza , Adhikari Dibasha , Gautam Arun , Anand Ayush , Shah Bhupendra , Sharma Sanjib Kumar
Published: June 2023

Hemoglobin E (HbE) is the most prevalent hemoglobinopathy in the eastern Indian subcontinent. We presented the case of a 53-year-old male from Nepal with a history of multiple blood transfusions who presented with abdominal fullness for 15 years and easy fatigability for 2 months. He had pallor and massive splenomegaly. Laboratory parameters showed pancytopenia with microcytic anemia, indirect hyperbilirubinemia, target cells in the peripheral smear and iron overload. A computed tomography scan of the abdomen showed multiple splenic infarcts. Hemoglobin electrophoresis was suggestive of HbE homozygous disease. Based on these findings, we made a diagnosis of HbE homozygous disease. We provided symptomatic treatment and folic acid supplementation and counseled him for splenectomy and genetic screening. Our case highlighted the uncommon presentation of Hb E disease.
Bioinformatics Analysis of the Regulatory lncRNA–miRNA–mRNA Network and Drug Prediction in Patients with Pulmonary Arterial Hypertension
Authors: Jin Xiao , Jin Ling , Han Li , Zhu Shiping
Published: June 2023

Objective:

Pulmonary arterial hypertension (PAH) is a cardiovascular disease caused by primary proliferative lesions in pulmonary arterioles. Competing endogenous RNAs (ceRNAs) have been reported to act as sponges for microRNAs (miRNAs). To date, however, the mechanisms underlying ceRNA involvement in PAH have not been investigated. This study aimed to construct a PAH-related ceRNA network to further explore the mechanisms of PAH.

Methods:

A probe reannotation was conducted to identify the long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in PAH. Based on the reannotation results, the “limma” package was used to identify the differentially expressed genes (DEGs) and lncRNAs. The miRcode database was used to predict the lncRNA–miRNA interactions. Then, the mRNAs targeted by the miRNAs were predicted by using TargetScan, miRTarBase, and miRDB. Based on the above interactions, a ceRNA network was constructed, which was mapped and visualized with Cytoscape 3.6.1 software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the database. To predict possible drugs or molecules that may mitigate PAH, C-Map analysis was applied to find relevant molecular compounds that can reverse the expression of DEGs in cell lines.

Results:

The ceRNA network consisted of 174 nodes and 304 links, which included 10 lncRNAs, 23 miRNAs, and 53 mRNAs. The hub genes of the ceRNA network for PAH included hsa-miR-17-5p, hsa-miR-20b-5p, MEG3, HCP5, hsa-miR-27a-3p, hsa-miR-107, hsa-miR-142-3p, hsa-miR-363-3p, hsa-miR-301b-3p, and hsa-miR-23b-3p. Calprotectin, irinotecan, and medrysone were found to be the 3 significant compounds.

Conclusion:

This study found that hsa-miR-17-5p, hsa-miR-20b-5p, MEG3, HCP5, hsa-miR-27a-3p, hsa-miR-107, hsa-miR-142-3p, hsa-miR-363-3p, hsa-miR-301b-3p, and hsa-miR-23b-3p maybe the underlying biomarkers and targets for diagnosis and treatment of PAH.
War-related urethral and penile injuries' management and short-term outcomes: Experience from war in Yemen
Authors: Elkady Amr , Abdullah Abdulfattah Mohammed , Lotfi Mohamed Amr , Rammah Ahmed M. , Torad Hesham , Abdel-Rassoul Mohammed , El Ghoneimy Mohamed
Published: June 2023

Objectives

To investigate the mechanisms of injury, wound patterns, surgical management, and outcomes of urethral and penile injuries caused by firearms and explosives during the ongoing war in Yemen.

Materials and methods

The present prospective descriptive study included 46 patients who sustained penile and/or urethral injuries during the ongoing Yemeni war. The patients received primary surgical care in Yemen and were referred for definitive treatment in Egypt between October 2018 and October 2020. Patient demographics, cause of injury, site and severity of injury, and associated injuries were evaluated together with management outcomes.

Results

The median age was 28 years (range, 18–50 years); 27 patients (58.7%) had posterior urethral injuries, 11 (23.9%) of whom had posterior urethral distraction defect injuries, 5 (10.9%) had a posterior urethral distraction defect injuries associated with urethrorectal fistulas, and the remaining 11 patients developed posterior urethral strictures; 9 patients (19.6%) sustained anterior urethral injuries, and 10 (21.7%) had isolated penile tissue injuries. Injuries to the penis (90%) and anterior urethra (67%) were primarily due to improvised explosive devices, whereas injuries to the posterior urethra (85%) were mostly caused by firearms. During the posttreatment follow-up period (6–12 months), 4 patients (8.7%) developed recurrent urethral strictures.

Conclusions

Urethral injuries caused by firearms and improvised explosive devices showed a greater association with urethrorectal fistulas or penile tissue injuries than what is typically observed in our practice. Management of these injuries by highly experienced urologists enhances patient outcomes and minimizes future complications.
Open fractures: Current treatment perspective
Authors: Minehara Hiroaki , Maruo Akihiro , Amadei Rafael , Contini Achille , Braile Adriano , Kelly Michael , Jenner Lydia , Schemitsch Geoffrey W. , Schemitsch Emil H. , Miclau Theodore
Published: June 2023

Severe open fractures present challenges to orthopaedic surgeons worldwide, with increased risks of significant complications. Although different global regions have different resources and systems, there continue to be many consistent approaches to open fracture care. Management of these complex injures continues to evolve in areas ranging from timing of initial operative debridement to the management of critical-sized bone defects. This review, compiled by representative members of the International Orthopaedic Trauma Association, focuses on several critical areas of open fracture management, including antibiotic administration, timing of debridement, bone loss, soft tissue management, and areas of need for future investigation.
Trinickia mobilis sp. nov. and Trinickia acidisoli sp. nov., isolated from soil
Authors: Wang You-qi , Zhao Bing-nan , Guo Xiu-yin , Wu Ke-cheng , Qiu Li-hong
Published: June 2023

Two novel Gram-stain-negative, aerobic and rod-shaped bacterial strains, designated DHG64T and 4D114T, were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. DHG64T grew at 12–37 °C (optimum 33 °C), pH 4.5–10.0 (optimum 6.5–7.5) and in the presence of 0–2.0 % NaCl (w/v); while 4D114T grew at 12–37 °C (optimum 20–33 °C), pH 4.0–7.0 (optimum 4.5–6.0) and in the presence of 0–1.0 % NaCl (w/v). DHG64T and 4D114T showed 97.1–98.0 and 97.5–98.4 % 16S rRNA gene sequence similarities with seven species of the genus

Trinickia

with validly published names, respectively. In the phylogenetic trees based on 16S rRNA gene and genome sequences, both strains formed a clade with the members of genus

Trinickia

but well separated from each other. The average nucleotide identity and digital DNA–DNA hybridisation values for the novel strains to all species of the genus

Trinickia

with validly published names were in the ranges of 80.6–85.0 and 22.4–28.0 %, respectively. DHG64T contained C16 : 0, C17 : 0 cyclo and C19 : 0 cyclo ω8c, while 4D114T had C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c and summed feature 2 (iso-C16 : 1 I and/or C14 : 0 3-OH) as the major cellular fatty acids. The major polar lipids for strains DHG64T and 4D114T were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C contents of DHG64T and 4D114T were 63.0 and 62.8 mol%, respectively. Genomic analyses indicated that DHG64T and 4D114T may have potential for various applications, such as developing drugs against certain health problems and restoring environments polluted with metal ions and/or benzoate. On the basis of the results of morphological, physiological, biochemical and phylogenetic analyses, strains DHG64T and 4D114T were classified as representing two novel species of the genus

Trinickia

, for which the names Trinickia mobilis sp. nov. (type strain DHG64T = KACC 21223T = GDMCC 1.1282T) and Trinickia acidisoli sp. nov. (type strain 4D114T = KCTC 82876T = GDMCC 1.2131T) are proposed.
Brain Dopamine Receptor System is Not Altered in Obesity: Bayesian and Frequentist Meta-Analyses
Authors: Pak Kyoungjune , Nummenmaa Lauri
Published: June 2023

Background

Feeding induces dopamine release in the striatum, and a dysfunction of the dopaminergic reward system can lead to overeating, and obesity. Studies have reported inconsistent findings of dopamine receptor (DR) positron emission tomography (PET) scans in obesity. Here we investigated the association between DR availability and overweight/obesity using Bayesian and frequentist meta-analysis.

Methods

We performed a systematic search of Embase, Medline, Scopus and Web of Science for studies which compared striatal DR availability between lean subjects and overweight/obese subjects. The standardized mean difference (Hedge’s g) of DR availability was calculated after extraction of data from each study. Studies were divided into two groups according to the definition of overweight/obese subjects (BMI cutoff of 25 and 30kg/m2). Both Bayesian and conventional meta-analysis was done in R Statistical Software version 4.2.2 (The R Foundation for Statistical Computing).

Results

Nine studies were eligible for inclusion in this study. Three studies with C11-raclopride, one with C11-PNHO, two with F18-fallypride, one with I123-IBZM, one with C11-NMB and one with both C11-raclopride and C11-PNHO were included. In Bayesian meta-analysis, the standardized mean difference of DR availability between lean and overweight/obese subjects markedly overlapped with zero regardless of BMI cutoff for obesity. In frequentist meta-analysis the pooled standardized mean difference of DR availability did not show the significant difference between lean and overweight/obese subjects. There was an effect of the radiopharmaceutical on the standardized mean difference of DR availability in meta-analysis of BMI cutoff of 25 kg/m2.

Conclusions

Brain DR availability is not different between lean and overweight/obese subjects. However, the effect is dependent on the radiopharmaceutical and the degree of obesity. Further studies with multi-radiopharmaceutical in the same individuals are need to understand the association between DR and obesity.
Short-term thinning effect on inter- and intra-annual radial increment of Mediterranean Scots pine-oak mixed forest
Authors: Aldea J. , del Río M. , Cattaneo N. , Riofrío J. , Ordóñez C. , Uzquiano S. , Bravo F.
Published: June 2023

Thinning treatment and mixed forest stands have been suggested as possible adaptation strategies to cope to climate change but there is still scarce knowledge about the combination of both subjects. In this study, we aim to better understand the thinning effect and the growth differences between two coexisting species on inter- and intra-annual cumulative radial increment patterns. We studied radial increment of a Scots pine-oak (Pinus sylvestris-Quercus pyrenaica) Mediterranean mixed forest during two climatically contrasted years (2016-2017) in north-western Spain. Data came from a thinning trial consisting in a randomized block experimental design with a control and two thinning treatments from below: a moderate and heavy thinning removing 25% and 50 % of initial basal area respectively focused on both species. Tree radial increment was analyzed based on bi-weekly readings from band dendrometers installed in 90 oak and pine trees. Non-linear mixed model based on double-Richards curve was fitted to show thinning and species differences in intra-annual cumulative radial increment patterns. Inter-annual basal area increment at species and stand levels were estimated using the model previously fitted at tree level and aggregating the results for exploring thinning effects at these levels. Scots pine leaded the tree and stand growth, and had also a better respond to early spring drought compared to oak. Heavy thinning increased tree radial increment for both species at the expense of decreased stand basal area. At species level, basal area increment decreased for Scots pine, however, heavy thinning generated the same oak basal area increment than control. Thus, heavy thinning may be good strategy towards a conversion from overaged coppice stands into high forests to conform a stable mixed forest stand.

Highlights

Scots pine leaded growth at tree and stand level

Scots pine trees may take advantage during early spring droughts

Heavy thinning increased tree radial increment for both species

Heavy thinning decreases stand basal area growth
A non-invasive photoactivatable split-Cre recombinase system for genome engineering in zebrafish
Authors: Elsaid Ramy , Mikdache Aya , Diabangouaya Patricia , Gros Gwendoline , Hernández Pedro P.
Published: June 2023

The cyclic recombinase (Cre)/loxPrecombination system is a powerful technique forin vivocell labeling and tracking. However, achieving high spatiotemporal precision in cell tracking using this system is challenging due to the requirement for reliable tissue-specific promoters. In contrast, light-inducible systems offer superior regional confinement, tunability and non-invasiveness compared to conventional lineage tracing methods. Here, we took advantage of the unique strengths of the zebrafish to develop an easy-to-use highly efficient, genetically encoded, Magnets-based, light-inducible transgenic Cre/loxPsystem. Our system relies on the reassembly of split Cre fragments driven by the affinity of the Magnets and is controlled by the zebrafishubiquitinpromoter. We demonstrate that our system does not exhibit phototoxicity or leakiness in the dark, and it enables efficient and robust Cre/loxPrecombination in various tissues and cell types at different developmental stages through noninvasive illumination with blue light. Our newly developed tool is expected to open novel opportunities for light-controlled tracking of cell fate and migrationin vivo.

Highlights

zPA-Cre is a novel zebrafish transgenic optogenetic split-Cre tool

zPA-Cre allows loxP-mediated DNA recombination in various tissues and cell types

It enables light-induced DNA recombination at different developmental stages.

It allows spatio-temporal DNA recombination in a specific tissue region with high resolution
Catching a wave: on the suitability of traveling-wave solutions in epidemiological modeling
Authors: Langmüller Anna M. , Hermisson Joachim , Murdock Courtney C. , Messer Philipp W.
Published: June 2023

Ordinary differential equation models such as the classical SIR model are widely used in epidemiology to study and predict infectious disease dynamics. However, these models typically assume that populations are homogeneously mixed, ignoring possible variations in disease prevalence due to spatial heterogeneity. To address this issue, reaction-diffusion models have been proposed as an alternative approach to modeling spatially continuous populations in which individuals move in a diffusive manner. In this study, we explore the conditions under which such spatial structure must be explicitly considered to accurately predict disease spread, and when the assumption of homogeneous mixing remains adequate. In particular, we derive a critical threshold for the diffusion coefficient below which disease transmission dynamics exhibit spatial heterogeneity. We validate our analytical results with individual-based simulations of disease transmission across a two-dimensional continuous landscape. Using this framework, we further explore how key epidemiological parameters such as the probability of disease establishment, its maximum incidence, and its final epidemic size are affected by incorporating spatial structure into SI, SIS, and SIR models. We discuss the implications of our findings for epidemiological modeling and identify design considerations and limitations for spatial simulation models of disease dynamics.
The microenvironment dictates glycocalyx construction and immune surveillance
Authors: Tharp Kevin M. , Park Sangwoo , Timblin Greg A. , Richards Alicia L. , Berg Jordan A. , Twells Nicholas M. , Riley Nicholas M. , Peltan Egan L. , Shon D. Judy , Stevenson Erica , Tsui Kimberly , Palomba Francesco , Lefebvre Austin E. Y. T. , Soens Ross W. , Ayad Nadia M.E. , ten Hoeve-Scott Johanna , Healy Kevin , Digman Michelle , Dillin Andrew , Bertozzi Carolyn R. , Swaney Danielle L. , Mahal Lara K. , Cantor Jason R. , Paszek Matthew J. , Weaver Valerie M.
Published: June 2023

Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built within vitromodels that do not match the microenvironmental characteristics of human tissues. Usingin vitromodels which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium.

Key Points

Culture medium dictates cellular mechanoresponse signatures in vitro

Epithelial glycocalyx construction is mediated by Heat Shock Factor 1 (HSF1)

Sialic acid topology dictates Natural Killer cell cytotoxicity

Physiological microenvironments reveal distinct glycobiology
Fluorogenesis: Inducing Fluorescence in a Non-Fluorescent Protein Through Photoinduced Chromophore Transfer of a Genetically Encoded Chromophore
Authors: Kumar Yashwant , Singh Reman Kumar , Ojha Manisha , Pushpavanam Karthik
Published: June 2023

Fluorescent proteins, while essential for bioimaging, are limited to visualizing cellular localization without offering additional functionality. We report for the first time a strategy to expand the chemical, structural, and functional diversity of fluorescent proteins by harnessing light to induce red fluorescence in a previously non-fluorescent protein. We accomplish this by inducing the transfer of the genetically encoded chromophore from a photocleavable protein (PhoCl1) to a non-fluorescent kinase (MjRibK) inducing red fluorescence in the latter. We have employed analytical and spectroscopic techniques to validate the presence of red fluorescence inMjRibK. Furthermore, molecular dynamics simulations were carried out to investigate the amino acid residues ofMjRibK involved in the generation of red fluorescence. Finally, we demonstrate the ability of the red fluorescentMjRibK to operate as a cyclable high-temperature sensor. We anticipate that this light-induced chromophore transfer strategy will open new possibilities for developing multifunctional genetically encoded fluorescent sensors.
PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities
Authors: Đukić Nina , Strømland Øyvind , Munnur Deeksha , Zhu Kang , Schuller Marion , Chatrin Chatrin , Kar Pulak , Rack Johannes Gregor Matthias , Baretić Domagoj , Schüler Herwig , Wijngaarden Sven , Filippov Dmitri V. , Sanyal Sumana , Smith Rebecca , Ahel Dragana , Ahel Ivan
Published: June 2023

PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. Here we show that PARP14 is dual function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a dramatic increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylationin vitroand in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.

Teaser

PARP14 is an antiviral PARP that combines ADP-ribosylation writer, reader and eraser functions in one polypeptide.
Dynamic ParB-DNA interactions initiate and maintain a partition condensate for bacterial chromosome segregation
Authors: Tišma Miloš , Janissen Richard , Antar Hammam , Gonzalez Alejandro Martin , Barth Roman , Beekman Twan , van der Torre Jaco , Michieletto Davide , Gruber Stephan , Dekker Cees
Published: June 2023

In most bacteria, chromosome segregation is driven by the ParABSsystem where the CTPase protein ParB loads at theparSsite to trigger the formation of a large partition complex. Here, we presentin vitrostudies of the partition complex forBacillus subtilisParB, using single-molecule fluorescence microscopy and AFM imaging to show that transient ParB-ParB bridges are essential for forming DNA condensates. Molecular Dynamics simulations confirm that condensation occurs abruptly at a critical concentration of ParB and show that multimerization is a prerequisite for forming the partition complex. Magnetic tweezer force spectroscopy on mutant ParB proteins demonstrates that CTP hydrolysis at the N-terminal domain is essential for DNA condensation. Finally, we show that transcribing RNA polymerases can steadily traverse the ParB-DNA partition complex. These findings uncover how ParB forms a stable yet dynamic partition complex for chromosome segregation that induces DNA condensation and segregation while enabling replication and transcription.
Vacuolar H+-ATPase Determines Daughter Cell Fates through Asymmetric Segregation of the Nucleosome Remodeling and Deacetylase Complex
Authors: Xie Zhongyun , Chai Yongping , Zhu Zhiwen , Shen Zijie , Guo Zhengyang , Zhao Zhiguang , Xiao Long , Du Zhuo , Ou Guangshuo , Li Wei
Published: June 2023

Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs inCaenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.
Packaging journey from retail to home: how the meaning of sustainability for colour transforms
Authors: Sekki Sanna , Kauppinen-Räisänen Hannele , Kylkilahti Eliisa , Autio Minna
Published: June 2023

Purpose

Research has largely disregarded consumer–packaging interaction in contexts other than retail. Focusing on the powerful cue of colour and consumers’ pleas for sustainability and drawing on the customer journey and moments of consumption, this study investigates how packaging colour meanings are redefined from retail to home and how the meaning of sustainability for colour transforms.

Design/methodology/approach

A qualitative methodology was employed with 27 informants, who were interviewed in pairs or in small groups of three.

Findings

First, colour meanings emerge outside the retail context, confirming the idea of the packaging journey. Colours are dynamic, as meanings are redefined throughout the voyage. In retail, colour conveys brand, product, environmental and origin-related meanings, while at home it conveys product, food- and health-related meanings. At the end of the journey, colour communicates disposal, environmental, health and origin-related meanings. Second, the meaning of sustainability for colour transforms during the voyage from being conveyed by a colour hue to being perceived as a material and, therefore, as a waste and recycling concern.

Originality/value

The study adds insight into the role of colour in the packaging life cycle, wherein colour transforms from a visual packaging cue to an issue of materiality. The recyclability of colours is a prevailing sustainability issue that deserves attention within the packaging industry. The study argues that although the consumer–packaging interaction in the retail context is essential, managers should recognise that the interaction continues with colours from in-store purchase decisions to consumers’ homes (use and recycling).
Baseline knee osteoarthritis radiographic severity as a predictor of symptom response to diet and exercise program: A secondary analysis
Authors: Dissanayaka Thusharika D. , Deveza Leticia A. , Heller Gillian , Robbins Sarah R. , Hunter David J.
Published: June 2023

Objective

To investigate whether baseline joint space narrowing (JSN) predicted disease remission, knee pain, and physical function changes in persons with knee osteoarthritis (OA).

Methods

This study is a secondary analysis of a two‐armed randomized controlled trial. Participants were aged ≥50 years (n = 171) with a body mass index ≥28 kg/m2 and radiographic medial tibiofemoral OA. Participants in the intervention group received diet and exercise programs and special treatment (cognitive behavioral therapy, knee brace, and muscle strengthening exercises) according to the disease remission. Remission of pain and remission of patient global assessment of disease activity and/or functional impairment were used to define the disease remission. The control group were provided with an education pamphlet. The primary outcome was disease remission at 32 weeks, and the secondary outcomes were the changes in knee pain and physical function at 20 and 32 weeks. Baseline JSN was scored from 0 to 3, and the association between baseline JSN and outcomes was assessed using multiple regression.

Results

There was no association of baseline JSN with disease remission at 32 weeks when the disease remission has been achieved. The baseline JSN grade 3 was associated with changes in knee pain at 20 weeks (p < .05). There was no association between baseline JSN and physical function.

Conclusion

Baseline JSN severity predicted changes in knee pain but not the disease remission or changes in physical functions. Identification of baseline radiographic severity may be helpful in identifying differences in response to diet and exercise programs in knee OA.
Increasing rates of sars‐cov‐2 infection in newborns during the omicron variant epoch
Authors: Eid Joe , Post Sara , Guhde Heather , Basuray Rakhi Gupta , Sanchez Pablo J. , Costantine Maged M. , Rood Kara M.
Published: June 2023

Problem

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) from infected pregnant individuals to the fetus or newborn occurs from 1.2% to 4.3%. Our aim was to determine the rate of positivity among newborns delivered to infected mothers during epochs of different variants predominance.

Method of study

This is a single academic center retrospective cohort study where we reviewed the electronic health records of pregnant individuals who tested positive for SARS‐CoV‐2 infection and their newborns from March 2020 through January 2022. Infants born to SARS‐CoV‐2‐positive mothers at the time of delivery or within 10 days of admission were tested for SARS‐CoV‐2 infection at 24–36 h of age.

Results

A total of 195 mothers were positive at delivery or within 10 days of admission and had their newborns tested for SARS‐CoV‐2. Seven newborns (3.6%) were positive. All positive infants were asymptomatic and born to unvaccinated mothers. Newborn positivity for SARS‐CoV‐2 was highest during the Omicron epoch (9.4%, p = .01).

Conclusion

Increasing positivity rate was seen during the Omicron variant predominance. This could be attributed to postnatal acquisition of the virus, as Omicron has been associated with higher transmissibility in older children and adults.
Metabolic characterization of human sperm cells using the Seahorse metabolic flux analyzer
Authors: Freitas‐Martins Artur , Sousa Maria Inês , Cristo Maria Inês , Ramalho‐Santos João , Amaral Sandra
Published: June 2023

Background

The concerning trend on male infertility global prevalence, together with the unexplainable causes in half of those cases, highlights that there are still aspects of this disease to be understood and solved. To address this issue, one should not only be aware of the limitations of the implemented diagnostic tools, but also understand the sperm cell in depth, structurally, biochemically, molecularly in order to develop reliable and ready‐to‐be new/improved diagnostic tools. In this sense, the sperm cells metabolism, highly related to its functionality, seems to be a promising aspect to explore. Though there is much information on the human sperm metabolism, there is still a lack of a quick integrated and comprehensive analysis that may be introduced with the potential to reveal innovative clinically relevant information.

Objectives

Find metabolic details on human sperm that can be accessed easily, in real time and using few cells, relying on the bivalent potential of the Seahorse flux analyzer (SFA).

Results

We have obtained standard records on human sperm cells’ oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), that together with the metabolic metrics provided information on sperm cells’ oxidative and glycolytic metabolism. Furthermore, a metabolic interindividual variation was observed.

Discussion and conclusion

Although the comparison with other species or cell types is not linear and warrant further studies, the metabolic profile of human sperm cells seems to be similar to that of other species. Altogether our results corroborate the value of SFA for metabolic human sperm cell analysis, warranting new studies, and anticipating several applications in the male infertility field.
‘Staying Close’: Enabling social interdependence for young people leaving residential care in England
Authors: Allen Dan
Published: June 2023

Applying social interdependence theory as a framework for document analysis, this paper considers eight evaluations of an extended care scheme in England known as ‘Staying Close’. Findings suggest that for extended care projects like ‘Staying Close’ to work, any service offer designed to support the transition from residential care to independent living must be seen by the young person, the carer, and the wider social network, as a continuation of earlier efforts to build and nurture a genuinely committed relationship. A new interrelations model for extended care is introduced and implications are discussed for strategic responses that enable young people, their carers and wider social network to promote opportunities for social interdependence.
Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct
Authors: Nalwa Aasma , Nakra Tripti , Yadav Rajni , Walia Ritika , Agarwala Sandeep , Jana Manisha , Jain Deepali , Das Prasenjit , Mathur Sandeep R. , Iyer Venkateswaran K.
Published: June 2023

Introduction

Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC.

Methods

Cases diagnosed with HCC on ultrasound‐guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi‐ or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra‐medullary haematopoiesis, monomorphism, and nuclear overlapping.

Results

Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha‐fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases.

Conclusions

Ultrasound‐guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.
A simple ATTR‐CM score to identify transthyretin amyloid cardiomyopathy burden in HFpEF patients
Authors: Ye Min , Liu Xiao , Gu Zhenbang , Sun Junyi , Dong Yugang , Chen Yili , Liu Chen , Wu Zexuan , Zhu Wengen
Published: June 2023

Background

Transthyretin amyloid cardiomyopathy (ATTR‐CM) is often found in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence regarding ATTR‐CM and prognosis in HFpEF remains scarce. This study sought to determine whether the ATTR‐CM burden was associated with clinical outcomes in HFpEF patients.

Methods

We evaluated the associations of baseline ATTR‐CM score with adverse outcomes in HFpEF patients from the TOPCAT trial using the Cox proportional hazards model or the competing risk regression model. The discriminatory ability of the ATTR‐CM score was assessed using the area under the time‐dependent receiver operating characteristic curve (AUC).

Results

We included 870 HFpEF patients, 18.9% of which had an ATTR‐CM score ≥6. Per 1 increment in the ATTR‐CM score was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.12–1.27) with an AUC of 0.652 (0.594–0.711), whereas patients with ATTR‐CM score ≥6 presented higher risks of the primary outcome (adjusted HR 2.20, 95% CI 1.65–2.95). Similar results were observed toward the secondary outcomes.

Conclusions

The simple ATTR‐CM score identified an 18.9% ATTR‐CM burden in HFpEF patients, and a higher ATTR‐CM burden might predict adverse outcomes with moderate discriminatory abilities in HFpEF.