bluuebunny/crossref_metadata_2025 huggingface dataset:
The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia
Authors: Salama Nadia , Elgedawy Gamalte , Gamal Radwa , Zaki Osama , Khalil Ashraf , Obada Manar
Published: January 2024

Tetrahydrobiopterin deficiency in newborns with atypical hyperphenylalaninemia requires rapid and accurate diagnosis and the ability to distinguish it from the classical type to prevent early irreversible neurological damage. The study aimed to evaluate neopterin and biopterin (products of tetrahydrobiopterin recycling pathway) and amino acid profiles (used in supplementation therapy) in patients with hyperphenylalaninemia after optimizing ultra-performance liquid chromatography coupled with tandem mass spectrometry to simultaneously measure neopterin, biopterin, and amino acids in dried blood spots. The study enrolled preselected infants with classic (n = 46), atypical (n = 14) hyperphenylalaninemia, and a control group (n = 50).

Result Tandem mass spectrometry detected neo/biopterin in the blood with a sensitivity and specificity of 100%. The mean neo/biopterin levels were significantly lower in the atypical cases (4 ± 1 and 3 ± 1 nmol/L) than the classic (49 ± 13 and 50 ± 12 nmol/L) and control (15.2 and 15.3 nmol/L) groups and correlated with phenylalanine and phenylalanine to tyrosine ratio (all P < 0.05). The study compared classic and atypical hyperphenylalaninemia cases with the control group. Both classic and atypical cases exhibited decreased levels of arginine, valine, and leucine compared to controls. Classic cases showed increased levels of citrulline, ornithine, and methionine, while atypical cases showed increased citrulline levels only. Comparing atypical versus classic cases, atypical cases exhibited decreased levels of citrulline, ornithine, methionine, arginine, leucine, and valine (all P < 0.05). Correlation analysis revealed negative associations between ornithine and biopterin and between arginine and neopterin in classic PKU cases. These findings highlight distinct metabolic differences between classic and atypical PKU.

Conclusion The optimized method detected neo/biopterin in the blood with accuracy and precision. The characteristic pattern of neo/biopterin in the blood makes it possible to differentiate between classic and atypical hyperphenylalaninemia with a sensitivity and specificity of 100%. The amino acid profile could add value when treatment with large neutral amino acids is considered.
Ethical Dilemmas in Current Uses of AI in Science Education
Authors: Gouvea Julia Svoboda
Published: January 2024

This installment of Current Insights reviews recently published articles which examine ethical dilemmas concerning the use of artificial intelligence (AI) in science education.
Suicides in degenerative neurocognitive disorders and traumatic brain injuries
Authors: Talaslahti Tiina , Ginters Milena , Palm Anniina , Kautiainen Hannu , Vataja Risto , Elonheimo Henrik , Suvisaari Jaana , Koponen Hannu , Lindberg Nina
Published: January 2024

Background

Neuropsychiatric symptoms in major neurocognitive disorders have been strongly associated with suicidality.

Methods

The objectives were to explore suicide rates in degenerative neurocognitive disorders (DNDs), alcohol-related neurocognitive disorders (ARNDs), and traumatic brain injuries (TBIs). Patients who received these diagnoses between 1998 and 2015 (N = 231,817) were identified from nationwide registers, and their mortality was followed up until December 31, 2018. We calculated incidences of suicides per 100,000 person-years, types of suicides, and suicide rates compared with the general population (standardized mortality ratio [SMR]).

Results

During the follow-up, 0.3% (95% confidence interval [95% CI]: 0.2–0.5) of patients with DNDs, 1.1% (0.7–1.8) with ARNDs, and 1.0% (0.7–1.3) with TBIs committed suicide. Suicide mortality rate was higher in men (58.9, 51.3, to 67.4 per 100,000) than in women (9.8, 7.5, to 12.5 per 100,000). The highest suicide rate was in ARNDs (98.8, 65.1, to 143.8 per 100,000), followed by TBIs (82.0, 62.4, to 105.8 per 100,000), and DNDs (21.2, 18.3, to 24.5 per 100,000). The SMRs (95% CI) were 3.69 (2.53–5.38), 2.99 (2.31–3.86), and 1.31 (1.13–1.51), respectively, and no sex difference emerged. The most common cause of death was self-inflicted injury by hanging or drowning (12.4, 10.3, to 14.8 per 100,000).

Conclusions

Suicide rates were higher in all three patient groups than the general population. Suicide risk remained elevated for more than 10 years after diagnosis. The suicide methods were mostly violent.
Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
Authors: Tobiasson Magnus , Pandzic Tatjana , Illman Johanna , Nilsson Lars , Weström Simone , Ejerblad Elisabeth , Olesen Gitte , Björklund Andreas , Olsnes Kittang Astrid , Werlenius Olle , Lorentz Fryderyk , Rasmussen Bengt , Cammenga Jörg , Weber Duruta , Lindholm Carolin , Wiggh Joel , Dimitriou Marios , Moen Ann Elin , Yip Lundström Laimei , von Bahr Lena , Baltzer-Sollander Karin , Jädersten Martin , Kytölä Soili , Walldin Gunilla , Ljungman Per , Groenbaek Kirsten , Mielke Stephan , Jacobsen Sten Eirik W. , Ebeling Freja , Cavelier Lucia , Smidstrup Friis Lone , Dybedal Ingunn , Hellström-Lindberg Eva
Published: January 2024

PURPOSE

Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.

METHODS

Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).

RESULTS

Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD–, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).

CONCLUSION

Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662 ).
A new experimental evidence-weighted signaling pathway resource in FlyBase
Authors: Attrill Helen , Antonazzo Giulia , Goodman Joshua L. , Thurmond Jim , Strelets Victor B. , Brown Nicholas H. , the FlyBase Consortium
Published: January 2024

Research in model organisms is central to the characterization of signaling pathways in multicellular organisms. Here, we present the comprehensive and systematic curation of 17 Drosophila signaling pathways using the Gene Ontology framework to establish a dynamic resource that has been incorporated into FlyBase, providing visualization and data integration tools to aid research projects. By restricting to experimental evidence reported in the research literature and quantifying the amount of such evidence for each gene in a pathway, we captured the landscape of empirical knowledge of signaling pathways in Drosophila.
Live tracking of basal stem cells of the epidermis during growth, homeostasis and injury response in zebrafish
Authors: Liu Zhengcheng , Meng Yidan , Ishikura Ayu , Kawakami Atsushi
Published: January 2024

Basal stem cells of the epidermis continuously differentiate into keratinocytes and replenish themselves via self-renewal to maintain skin homeostasis. Numerous studies have attempted to reveal how basal cells undergo differentiation or self-renewal; however, this has been hampered by a lack of robust basal cell markers and analytical platforms that allow single-cell tracking. Here, we report that zebrafish integrin beta 4 is a useful marker for basal cell labelling, irrespective of the body region, stage and regenerative status. We employed Cre-loxP recombination in combination with live cell tracking of single basal clones in the caudal fin and investigated the embryonic origin and behaviour of basal cells during fish growth and homeostasis. Although most basal cells, including those in fins, became quiescent in the adult stage, genetic cell ablation showed that basal cells were reactivated to either self-renew or differentiate, depending on the injured cell type. Our study provides a simple and easy-to-use platform for quantitative in vivo imaging of basal stem cells at wider stages and under various conditions.
Seven-up acts in neuroblasts to specify adult central complex neuron identity and initiate neuroblast decommissioning
Authors: Dillon Noah R. , Manning Laurina , Hirono Keiko , Doe Chris Q.
Published: January 2024

An unanswered question in neurobiology is how are diverse neuron cell types generated from a small number of neural stem cells? In the Drosophila larval central brain, there are eight bilateral Type 2 neuroblast (T2NB) lineages that express a suite of early temporal factors followed by a different set of late temporal factors and generate the majority of the central complex (CX) neurons. The early-to-late switch is triggered by the orphan nuclear hormone receptor Seven-up (Svp), yet little is known about how this Svp-dependent switch is involved in specifying CX neuron identities. Here, we: (1) birth date the CX neurons P-EN and P-FN (early and late, respectively); (2) show that Svp is transiently expressed in all early T2NBs; and (3) show that loss of Svp expands the population of early born P-EN neurons at the expense of late born P-FN neurons. Furthermore, in the absence of Svp, T2NBs fail decommissioning and abnormally extend their lineage into week-old adults. We conclude that Svp is required to specify CX neuron identity, as well as to initiate T2NB decommissioning.
De la fabrication à la fonction des figurines néolithiques de la Thessalie
Authors: Φασούλας Αργύρης
Published: January 2024

Τα νεολιθικά ειδώλια της Θεσσαλίας είναι ένα θέμα που έχει προκαλέσει πολλές συζητήσεις. Στο πλαίσιο μιας έρευνας που εστιάζει έντονα στις μορφολογικές ιδιότητες των ειδωλίων θεωρούμε απαραίτητο, να ασχοληθούμε με μια διαρκώς παραμελημένη πτυχή, την κατασκευή τους. Με βάση τις αρχές της πολιτισμικής τεχνολογίας, στόχος μας είναι όχι μόνο να εντοπίσουμε τις τεχνικές διαδικασίες που εμπλέκονται στην κατασκευή των νεολιθικών ειδωλίων, από την προετοιμασία των πρώτων υλών μέχρι το τελικό προϊόν, αλλά και να επανεξετάσουμε τις φαντασιακές συνδηλώσεις των διαδικασιών αυτών εξετάζοντας τις πολλαπλές πολιτισμικές τους προεκτάσεις. Χρησιμοποιώντας το αναλυτικό εργαλείο της chaîne opératoire, προβήκαμε σε μια τεχνολογική μελέτη ειδωλίων από διάφορες θέσεις της Θεσσαλίας, προκειμένου να ανασυνθέσουμε τις διαδικασίες κατασκευής. Ο προσδιορισμός των συγκεκριμένων chaînes opératoires μας επέτρεψε να περιγράψουμε τη φυσιογνωμία της ειδωλοπλαστικής παραγωγής και στη συνέχεια να ασχοληθούμε με το ζήτημα της λειτουργίας των ειδωλίων. Λαμβάνοντας υπόψη ότι η κατασκευή αποτελεί αναπόσπαστο μέρος της λειτουργίας, θεωρήσαμε απαραίτητο να στραφούμε στην εθνολογία, προκειμένου να αποκτήσουμε παραδείγματα που θα μπορούσαν να χρησιμεύσουν ως αναφορές και να μας βοηθήσουν έτσι να ερμηνεύσουμε τα αρχαιολογικά δεδομένα. Δύο εθνογραφικές έρευνες στο μαροκινό αντιάτλαντα και η προσφυγή στην ανθρωπολογική εμπειρία, μας επέτρεψαν να ανασυνθέσουμε την οργάνωση της παραγωγής των νεολιθικών ειδωλίων της Θεσσαλίας και τις πιθανές λειτουργίες τους.
Der einfluss der rheumatoiden arthritis und funktioneller belastungen auf die physikalischen und mechanischen eigenschaften des mandibulären kondylus in einem transgenen mausmodell
Authors: Κωλέτση Δέσποινα
Published: January 2024

Η διδακτορική διατριβή είχε ως ερευνητικό αντικείμενο τη διερεύνηση της επίδρασης της ρευματοειδούς αρθρίτιδας και της λειτουργικής φόρτισης μέσω μεταβολής της δίαιτας (σκληρή/ μαλακή τροφή), στη δομική συνοχή και τις φυσικές και μηχανικές ιδιότητες του οστού/ χόνδρου του κονδύλου της κάτω γνάθου σε διαγονιδιακό μοντέλο μυός (Tg 197 - with rheumatoid arthritis - RA), σε σύγκριση με υγιείς μάρτυρες. Η μηδενική υπόθεση που διαμορφώθηκε ήταν πως δεν υπήρχε διαφορά στις φυσικοχημικές και μηχανικές ιδιότητες του κονδύλου της κάτω γνάθου σε πειραματόζωα που έπασχαν από ρευματοειδή αρθρίτιδα και ελάμβαναν διαφορετικού είδους λειτουργική/ μασητική φόρτιση, σε σχέση με υγιείς μάρτυρες αντίστοιχων ομάδων φόρτισης. Είκοσι τρείς μύες (ΕΚΕΒΕ Φλέμιγκ), ηλικίας 4 εβδομάδων χωρίστηκαν σε 4 ομάδες, οι οποίες έλαβαν σκληρή ή μαλακή τροφή και ήταν διαγονιδιακοί (Tg 197) ή υγιείς και ένα μήνα μετά θυσιάστηκαν για να μελετηθούν οι κόνδυλοι της κάτω γνάθου. Ακολούθησε η αξιολόγηση των δειγμάτων με βάση τις παρακάτω τεχνικές:- υπέρυθρη φασματοσκοπία (micro-attenuated reflection Fourier transform infrared spectroscopy (micro-ATR FTIR)) και reflection FTIR microscopy- ηλεκτρονική μικροσκοπία σάρωσης (scanning electron microscopy/ Energy dispersive x-ray spectroscopy)- μηχανικές δοκιμασίες εκτίμησης μικρο- σκληρότητας (Vickers microhardness, HV 100)Τα συμπεράσματα που προέκυψαν συνοψίζονται ως εξής: 1. σημαντικά χαμηλότερος λόγος (εμβαδό επί τοις εκατό) της α- έλικας προς το αμίδιο Ι για τα διαγονιδιακά πειραματόζωα μετά από στάθμιση για τον παράγοντα της λειτουργικής φόρτισης (διατροφή). 2. οι δείκτες ενασβεστίωσης δε φάνηκε να επηρεάζονται από τη νόσο ή τον τύπο της φόρτισης. 3. μετουσίωση των συστατικών στοιχείων του κολλαγόνου του κονδύλου της κάτω γνάθου στους διαγονιδιακούς μυς, ανεξάρτητα από τη διαφοροποίηση στη φόρτιση. 4. η λειτουργική φόρτιση δε φάνηκε να έχει επίδραση στις μηχανικές ιδιότητες, κάτι το οποίο επηρεάστηκε πρωτίστως από τη νόσο.
A case study on finding efficient monetary policy to solve Shenzhen's excessive-priced housing
Authors: Luo Jiayi
Published: January 2024

Background The real estate market has developed rapidly since 1980s in Shenzhen, China. This study aims to find and investigate an efficient monetary policy to solve the excessive-priced housing problem in Shenzhen. Methods By regulating the contractionary monetary policy which are open market operation, the discount rate and legal reserve deposit can decrease the accelerating rate of excessive housing price in Shenzhen. Firstly, the relationship between housing prices and the other three tools of monetary policy has been analyzed. Then, from collecting the secondary data online, models were established by using the ordinary least square to find the correlation between housing price and money supply from 2011 to 2017. Results This model shows the relationship with the change of the logarithmic form of the amount of M2 and housing index is significantly positive. With the decrease in change of the logarithmic form of the amount of M2, the increase in housing index can be controlled in a relative decelerated rate. Conclusions In the reduced monetary supply, the housing price can be managed to an ideal condition and then it can help the government to achieve the goal of maintaining Shenzhen’s healthy real estate market development.
Women and Power in Zimbabwe: The Need for Feminist Approaches in Considerations of Political Elites
Authors: Mdege Norita
Published: January 2024

Women politicians in Africa often find themselves in precarious positions as they negotiate their place in men-dominated environments. Their positions are further complicated because political power remains weakly institutionalised in most parts of Africa and highly dependent on informal links between individuals/groups and their respective networks. Given this, this paper looks at both formal and informal networks and relationships, as shaped by local political culture and contexts, to advance the search for a way to provide a more reliable picture of the realities of women politicians within the African context. It advances the elite theory by demonstrating how a feminist approach helps provide a way of understanding political elites that accounts for contextualised gendered power dynamics and experiences. It does so using Zimbabwe’s Joice Mujuru as a case study. The paper combines an African feminist approach and discourse analysis to trace the various debates and discourses around Joice Mujuru’s power to influence policies and decisions, her reputation, and her precarious position in Zimbabwe’s men-dominated political spaces. The paper concludes that a feminist perspective in considerations of political elites helps to better comprehend how various political cultures and contexts shape the understanding of women’s roles and positions in political groups and networks and their relationship to power centres. Such comprehension can shed light on contextual factors to take into account when considering effective ways of promoting women’s political leadership. Ultimately, the paper proposes an African feminist method to help create a path to further explorations of African elite groups and networks in gender-sensitive and context-based ways.
The role of selected polymorphisms in regulation of gene CD38 expression and their effect on the clinical picture of autism spectrum disorders – preliminary study
Authors: Wilczyński Krzysztof Maria , Auguściak-Duma Aleksandra , Cichoń Lena , Stasik Aleksandra , Janas-Kozik Małgorzata
Published: January 2024

Cel pracy

Efekty kliniczne obserwowane w przypadku niedoboru oksytocyny mogą być również obecne w przypadku zaburzeń w mechanizmach odpowiedzialnych np. za jej sekrecję. W przypadku oksytocyny funkcję tą pełni miedzy innymi antygen różnicowania komórkowego 38 (CD38). Istniejące dane literaturowe jak również związki białka CD38 z sekrecją oksytocyny budzą zainteresowanie w kontekście ich możliwego powiązania z obrazem klinicznym i rozwojem objawów ze spektrum autyzmu (ASD). Celem prezentowanego badania była analiza związku pomiędzy polimorfizmami rs3796863 oraz rs6449197 w genie CD38, poziomem ekspresji genu a obrazem klinicznym i ryzykiem uzyskania diagnozy ASD.

Metoda

Badanie objęło 59 osób w wieku średnio 15,05 lat z IQ>90. Uczestnicy byli podzieleni na dwie grupy: badaną obejmująca 37 osób z potwierdzoną diagnozą ASD oraz kontrolą obejmującą 22 osoby neurotypowe. Weryfikacja diagnozy dokonywana była przy użyciu protokołu ADOS-2.

Wyniki

W analizie porównawczej z populacją wzorcową opartą o bazę 1000Genomes z występowaniem istotnego kliniczne nasilenia cech ASD związek wykazywały allele „T” polimorfizmów rs3796863 oraz rs6449197, które wykazują wyższą częstość w populacji ogólnej i traktowane są jako „dzikie”. W przypadku analizy międzygrupowej tego typu zależność była słabsza zaś genotyp grupy kontrolnej był niejako pośredni pomiędzy grupą badaną a populacją wzorcową. W analize ∆∆Ct znormalizowana wartość względnego poziomu ekspresji genu CD38 wskazywała, iż w grupie badanej poziom ekspresji był o około 1,1-1,2 razy wyższy niż w grupie kontrolnej.

Wnioski

Uzyskane wyniki wskazują, iż istotny związek z nasileniem cech zaburzeń ze spektrum autyzmu obserwowany jest przede wszystkim w przypadku nosicieli wariantów dzikich badanych polimorfizmów u których obserwuje się także, powiązany z nimi, wzrost ekspresji genu CD38.
Lviv lectures of Kant's criticism
Authors: Ingarden Roman Witold
Published: January 2024

Lectures read and transcribed from the original by:

Radosław Kuliniak University of WrocławORCID: 0000-0002-0090-6609e-mail: kornik90@poczta.onet.pl

Mariusz PanduraUniversity of WrocławORCID: 0000-0001-5875-2705e-mail: mariusz.pandura@uwr.edu.pl
Product Development in Crowdfunding: Theoretical and Empirical Analysis
Authors: Candoğan Sıdıka Tunç , Cornelius Philipp B. , Gokpinar Bilal , Körpeoğlu Ersin , Tang Christopher S.
Published: January 2024

Problem definition: Crowdfunding goes beyond raising funds. Entrepreneurs often use crowdfunding to solicit feedback from customers to improve their products and may therefore prefer to launch their crowdfunding campaigns using basic versions of their products with fewer features. However, customers may not be persuaded by a campaign if the product appears to be underdeveloped. In view of this tradeoff, a key question for entrepreneurs is how much to develop a product before launching a crowdfunding campaign. Methodology/results: Analyzing a game-theoretical model and testing its predictions empirically, we study (1) how the development level of a product at campaign launch, measured by the initial number of product features, influences whether customers will make comments that help entrepreneurs improve the product; (2) whether entrepreneurs continue to improve the product during the campaign; and (3) whether the campaign is successful. We show that, as the number of product features at campaign launch increases, the likelihood that customers will make comments and that the product will be improved during the campaign first increases but then decreases. Furthermore, the likelihood of campaign success first increases but then decreases with the number of product features at campaign launch. Finally, by analyzing the interactions between customer feedback, product improvement, and campaign success, we show that customer feedback motivates entrepreneurs to improve the product during the campaign. Moreover, entrepreneurs should take account of the initial number of features and customer feedback when improving the product, because otherwise product improvements can harm campaign success. Managerial implications: Our study provides practical insights on how entrepreneurs can use crowdfunding to aid product development and improvement. Specifically, entrepreneurs should avoid overdeveloping their products before crowdfunding campaigns because, as well as decreasing the chance of campaign success, this could hinder their ability to save development costs (e.g., market research costs) through involving customers in product development.

Supplemental Material: The online appendices are available at https://doi.org/10.1287/msom.2022.0344 .
Work Devotion as Identity Armor? How Single Professionals with Relationship Aspirations Use Career Decisions to Manage Their Identities
Authors: Oelberger Carrie
Published: January 2024

Although scholarship has established how people with a partner, child, or other domestic obligations account for these responsibilities when making career decisions, we lack conceptual apparatus around how career decision making is informed by personal aspirations. Following a cohort of 89 international aid workers over eight years, I draw on in-depth interview (n = 126), survey (n = 551), and job transition data (n = 228) to detail how career decision making serves as a platform for identity management for single professionals who have aspirations for a long-term intimate relationship. I introduce the possibility space, which conveys how the ability to realize relationship aspirations is constrained for work-devoted professionals, especially for straight women and lesbian, gay, bisexual, and queer (LGBQ) people. Yet, they resist scaling back work. I detail why, presenting the three types of career decisions they made: (1) work devotion as identity armor, protecting and affirming their current aid worker identity; (2) temporary work alterations as identity diversification, carving out time to hopefully realize their desired relationship while postponing the affirmation of their aid worker identity; and (3) durable work alterations as identity restructuring, removing the aid worker identity from their identity network. This article’s model of career decision making as identity management and the broader theoretical explanation of how different behavioral practices can manage temporally distinct identities offers important contributions to scholarship on identity, the work-nonwork interface, labor market inequalities, and career decision making.

Funding: This research was supported by the University of Minnesota’s Grant-in-Aid of Research, Artistry and Scholarship and a Stanford University Dissertation Support Grant.
Unravelling Beau's lines as a potential indicator of severe immune response in COVID-19 and reinfection
Authors: Agouridis Aris P. , Ntzani Evangelia E. , Anastasiou Georgia , Barkas Fotios , Rizos Evangelos C.
Published: January 2024

Background: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix. These rare nail disorders can be triggered mostly by infections or systemic diseases. Case Description: We describe a 65-year-old man who presented with nail changes on all fingernails. The patient, a non-smoker with no medication history, had severe immune responses during two hospitalisations, 9 and 4 months ago, for COVID-19. Both hospitalisations were accompanied by markedly elevated interleukin-6 levels, and treatment with tocilizumab on top of dexamethasone was required. The present examination revealed Beau's lines which were associated with both prior COVID-19 infections. Conclusions: Although nail changes look harmless, seeking Beau's lines during the physical examination might indicate past severe COVID-19 infection and a higher probability for reinfection and rehospitalisation.
Opioid-free anaesthesia
Authors: Weir Andrew
Published: January 2024

Adverse effects of perioperative opioids have led to the pursuit of ‘opioid-free anaesthesia’. While early studies have shown that effective analgesia can be achieved without using opioids, with some reduction in unwanted effects, further research is needed to elucidate which patients may benefit most and how.
Exploring Practical Pedagogy in High School Biology Education: A Qualitative Study of Pre-Service Biology Teachers’ Experiences in Vietnam
Authors: Diem Huynh Thi Thuy , Thinh Mai Phuc , Lam Vo Thi Thao
Published: January 2024

This qualitative study examines the experiences of pre-service high school biology teachers in the Mekong Delta, Vietnam, focusing on the challenges and transformative learning experiences encountered during their school-based internship. It aims to explore the dichotomy between specialized biology knowledge and practical applicability in high school teaching and uncover the significance of fostering student engagement through innovative strategies and the role of mentor teachers in guiding pre-service teachers. Semi-structured interviews were used to collect data from pre-service biology teachers who completed a school-based internship in the Mekong Delta. Thematic analysis was employed to analyze the interview data. The study highlights the challenges of bridging the gap between theoretical knowledge and classroom practice, emphasizing the importance of innovative teaching strategies for student engagement. It recognizes the role of mentor teachers in guiding and enhancing the skills of pre-service teachers in creating effective learning environments. Findings suggest the need for curriculum reforms that balance specialized biology knowledge and practical pedagogical skills. The study emphasizes the importance of experiential learning through teaching apprenticeships to better prepare pre-service teachers for their professional journey.
Investigating the Effectiveness of Artificial Intelligence Chatbots in Enhancing Digital Dialogue Skills for Students
Authors: Alwazzan Mona Saleh
Published: January 2024

The central focus of this study is exploring the potential of Artificial Intelligence (AI) Chatbots in enhancing digital dialogue for students. The study investigates the key attributes of Chatbots that can contribute to the feasibility of facilitating digital dialogue to improve students' communication skills through discussions and dialogues. The study employed a descriptive method using a questionnaire to gather the perspectives of 35 educational experts on the use of AI Chatbots in digital dialogue skills. This study revealed that using AI Chatbots plays a crucial role in enhancing digital dialogue skills and can be effectively integrated into instructional practices to facilitate meaningful dialogue among students. Finally, the study recommends that educational technology specialists leverage new technologies, such as Al Chatbots to help improve student performance and facilitate digital dialogue in education.
Randomized controlled trial comparing traditional versus enhanced-fixation designs of a novel cemented total knee arthroplasty tibial component
Authors: Turgeon Thomas R. , Vasarhelyi Edward , Howard James , Teeter Matthew , Righolt Christiaan H. , Gascoyne Trevor , Bohm Eric
Published: January 2024

Aims

A novel enhanced cement fixation (EF) tibial implant with deeper cement pockets and a more roughened bonding surface was released to market for an existing total knee arthroplasty (TKA) system.This randomized controlled trial assessed fixation of the both the EF (ATTUNE S+) and standard (Std; ATTUNE S) using radiostereometric analysis.

Methods

Overall, 50 subjects were randomized (21 EF-TKA and 23 Std-TKA in the final analysis), and had follow-up visits at six weeks, and six, 12, and 24 months to assess migration of the tibial component. Low viscosity bone cement with tobramycin was used in a standardized fashion for all subjects. Patient-reported outcome measure data was captured at preoperative and all postoperative visits.

Results

The patient cohort mean age was 66 years (SD seven years), 59% were female, and the mean BMI was 32 kg/m2 (SD 6 kg/m2). Mean two-year subsidence of the EF-TKA was 0.056 mm (95% confidence interval (CI) 0.025 to 0.086) versus 0.006 mm (95% CI -0.029 to 0.040) for the Std-TKA, and the two-year maximum total point motion (MTPM) was 0.285 mm (95% upper confidence limit (UCL) ≤ 0.363) versus 0.346 mm (95% UCL ≤ 0.432), respectively, for a mean difference of -0.061 mm (95% CI -0.196 to 0.074). Inducible displacement also did not differ between groups. The MTPMs between 12 and 24 months for each group was below the published threshold of 0.2 mm for predicting early aseptic loosening (p < 0.001 and p = 0.001, respectively).

Conclusion

Both the enhanced fixation and the standard tibial implant design showed fixation with a predicted low risk of long-term aseptic loosening.

Cite this article: Bone Jt Open 2024;5(1):20–27.
Robust single-shot 3D fluorescence imaging in scattering media with a simulator-trained neural network
Authors: Alido Jeffrey , Greene Joseph , Xue Yujia , Hu Guorong , Gilmore Mitchell , Monk Kevin J. , DiBenedictis Brett T. , Davison Ian G. , Tian Lei , Li Yunzhe
Published: January 2024

Imaging through scattering is a pervasive and difficult problem in many biological applications. The high background and the exponentially attenuated target signals due to scattering fundamentally limits the imaging depth of fluorescence microscopy. Light-field systems are favorable for high-speed volumetric imaging, but the 2D-to-3D reconstruction is fundamentally ill-posed, and scattering exacerbates the condition of the inverse problem. Here, we develop a scattering simulator that models low-contrast target signals buried in heterogeneous strong background. We then train a deep neural network solely on synthetic data to descatter and reconstruct a 3D volume from a single-shot light-field measurement with low signal-to-background ratio (SBR). We apply this network to our previously developed computational miniature mesoscope and demonstrate the robustness of our deep learning algorithm on scattering phantoms with different scattering conditions. The network can robustly reconstruct emitters in 3D with a 2D measurement of SBR as low as 1.05 and as deep as a scattering length. We analyze fundamental tradeoffs based on network design factors and out-of-distribution data that affect the deep learning model’s generalizability to real experimental data. Broadly, we believe that our simulator-based deep learning approach can be applied to a wide range of imaging through scattering techniques where experimental paired training data is lacking.
Beating the spectroscopic Rayleigh limit via post-processed heterodyne detection
Authors: Krokosz Wiktor , Mazelanik Mateusz , Lipka Michał , Jarzyna Marcin , Wasilewski Wojciech , Banaszek Konrad , Parniak Michał
Published: January 2024

Quantum-inspired superresolution methods surpass the Rayleigh limit in imaging, or the analogous Fourier limit in spectroscopy. This is achieved by carefully extracting the information carried in the emitted optical field by engineered measurements. An alternative to complex experimental setups is to use simple homodyne detection and customized data analysis. We experimentally investigate this method in the time-frequency domain and demonstrate the spectroscopic superresolution for two distinct types of light sources: thermal and phase-averaged coherent states. The experimental results are backed by theoretical predictions based on estimation theory.
A major endogenous glycoside hydrolase mediating quercetin uptake in Bombyx mori
Authors: Waizumi Ryusei , Hirayama Chikara , Tomita Shuichiro , Iizuka Tetsuya , Kuwazaki Seigo , Jouraku Akiya , Tsubota Takuya , Yokoi Kakeru , Yamamoto Kimiko , Sezutsu Hideki
Published: January 2024

Quercetin is a common plant flavonoid which is involved in herbivore–plant interactions. Mulberry silkworms (domestic silkworm, Bombyx mori, and wild silkworm, Bombyx mandarina) take up quercetin from mulberry leaves and accumulate the metabolites in the cocoon, thereby improving its protective properties. Here we identified a glycoside hydrolase, named glycoside hydrolase family 1 group G 5 (GH1G5), which is expressed in the midgut and is involved in quercetin metabolism in the domestic silkworm. Our results suggest that this enzyme mediates quercetin uptake by deglycosylating the three primary quercetin glycosides present in mulberry leaf: rutin, quercetin-3-O-malonylglucoside, and quercetin-3-O-glucoside. Despite being located in an unstable genomic region that has undergone frequent structural changes in the evolution of Lepidoptera, GH1G5 has retained its hydrolytic activity, suggesting quercetin uptake has adaptive significance for mulberry silkworms. GH1G5 is also important in breeding: defective mutations which result in discoloration of the cocoon and increased silk yield are homozygously conserved in 27 of the 32 Japanese white-cocoon domestic silkworm strains and 12 of the 30 Chinese ones we investigated.
Perceptions and experiences of daily and long-acting pre-exposure prophylaxis (PrEP) among MSM in India
Authors: Agarwal Harsh , Núñez Ivania , Hill Lauren M. , Dubé Karine , Knoble Abigail , Pamilerin Oluwamuyiwa
Published: January 2024

Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy with high efficacy. An increased willingness to use PrEP among at-risk Indian men who have sex with men (MSM) population has been reported; however, little is known about their real experiences that guide their key motivators, facilitators, and barriers with using oral and Long-Acting (LA) Injectable PrEP. We recruited participants (n = 18) through active MSM social media networks. The interviews were conducted using teleconferencing software. Interview topics included participants’ sources of knowledge, experiences accessing daily PrEP, safe-sex behaviors while on PrEP, barriers and facilitators around PrEP, long-term goals with PrEP, perceptions around LA PrEP, and discussion around decision-making to switch from oral PrEP to LA PrEP. Transcripts were coded according to interview topics, and key themes were analyzed using a topical data analysis approach. Participants (median age 28 years, ranging from 18 to 40) reported a high perceived risk of HIV. This increased perceived risk was a key motivator for oral PrEP uptake. Most participants shared that they accessed PrEP through non-profit organizations serving the MSM community, where doctor consultations and medication were either free or subsidized. Even when participants reported high adherence to oral PrEP, they expressed discontent with the requirement to take it daily. High condom usage was reported concomitantly with PrEP use among most participants, except for a few who preferred bareback sex. Participants shared that they would prefer to continue PrEP until they are in a monogamous, exclusive relationship. The cost and affordability remained recurring themes, and while participants could afford oral PrEP, they wished it was cheaper, making it more accessible to the community at large. Most participants did not have prior knowledge of LA injectable PrEP but welcomed the intervention, alluding to cost and availability as the key decision-making factors affecting switching. MSM from India we interviewed adopted oral PrEP as an additional HIV prevention strategy to condoms through non-profit and private channels. Cost and broader access remains a concern among the MSM community. More acceptability research about long-acting PrEP is needed among MSM in the Indian context, and it is recommended for government interventions to include oral PrEP groups at higher risk of HIV acquisition.
Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort
Authors: Wedderburn Catherine J. , Bondar Julia , Lake Marilyn T. , Nhapi Raymond , Barnett Whitney , Nicol Mark P. , Goddard Liz , Zar Heather J.
Published: January 2024

Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality. There is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort study. Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0–6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0–6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was associated with increased incidence rates of hospitalisation in infants (IRR 1.63 [95% CI 1.29–2.05]) and longer hospital admission (p = 0.004). Prematurity (HR 2.82 [95% CI 2.28–3.49]), delayed infant vaccinations (HR 1.43 [95% CI 1.12–1.82]), or raised maternal HIV viral load in HEU infants were risk factors for hospitalisation; breastfeeding was protective (HR 0.69 [95% CI 0.53–0.90]). In conclusion, children in SSA experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at greater risk of hospitalisation in infancy compared to HUU children. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have additional impact in reducing hospitalisation.
Prevalence and factors associated with early resumption of sexual intercourse among postpartum women: Systematic review and meta-analysis
Authors: Abebe Gelaw Kelemu , Atalay Yibeletal Assefa , Yeshambel Adisu , Adella Getachew Asmare , Walle Belete Gelaw , Zeleke Liknaw Bewket , Gebeyehu Natnael Atnafu
Published: January 2024

Introduction

Postpartum sexual health is indicated by a resumption of sexual activity as well as arousal, desire, orgasm, and sexual satisfaction. The issue of resuming sexual intercourse after childbirth has received limited attention because healthcare professionals rarely provide adequate care to postnatal women. The present study aimed to ascertain the overall prevalence of early resumption of sexual intercourse among most women.

Methods

Searches were conducted in PubMed, Web of Science, Science Direct, Google Scholar, African Journals Online, and the Cochrane Library. Data were extracted using Microsoft Excel, and STATA version 14 was used for analysis. Publication bias was checked by funnel plot, Egger, and Begg regression tests. A p-value of 0.05 was regarded to indicate potential publication bias. Using I2 statistics, the heterogeneity of the studies was evaluated. By country, a subgroup analysis was conducted. A sensitivity analysis was carried out to determine the effect of each study’s findings on the overall estimate. The random effects model was used to assess the overall effect of the study and then measured using prevalence rates and odds ratio with 95% CI.

Results

Twenty-one studies with 4,482 postpartum women participants were included in the study. The pooled prevalence of early resumption sexual intercourse among post-partum women was 57.26% (95% CI 50.14, 64.39) with significant heterogeneity between studies (I2  =  99.2%; P-value ≤ 0.000) observed. Current contraceptive use (AOR = 1.48, 95%CI = 1.03, 6.21), primipara (AOR = 2.88, 95%CI = 1.41, 5.89), and no history of severe genital injury on the last delivery (AOR = 2.27, 95%CI = 1.05, 4.93) were significantly associated with early resumption of sexual intercourse.

Conclusion

This study found that more than half of women resumed sexual intercourse early after giving birth. This suggests that a significant number of women may be at higher risk of unwanted pregnancies, short birth intervals, and postpartum sepsis. Thus, stakeholders should improve the integration of postpartum sexual education with maternal health services to reduce the resumption of postpartum sexual intercourse.
The changes in health service utilisation in Malawi during the COVID-19 pandemic
Authors: She Bingling , Mangal Tara D. , Adjabeng Anna Y. , Colbourn Tim , Collins Joseph H. , Janoušková Eva , Li Lin Ines , Mnjowe Emmanuel , Mohan Sakshi , Molaro Margherita , Phillips Andrew N. , Revill Paul , Smith Robert Manning , Twea Pakwanja D. , Nkhoma Dominic , Manthalu Gerald , Hallett Timothy B.
Published: January 2024

Introduction

The COVID-19 pandemic and the restriction policies implemented by the Government of Malawi may have disrupted routine health service utilisation. We aimed to find evidence for such disruptions and quantify any changes by service type and level of health care.

Methods

We extracted nationwide routine health service usage data for 2015–2021 from the electronic health information management systems in Malawi. Two datasets were prepared: unadjusted and adjusted; for the latter, unreported monthly data entries for a facility were filled in through systematic rules based on reported mean values of that facility or facility type and considering both reporting rates and comparability with published data. Using statistical descriptive methods, we first described the patterns of service utilisation in pre-pandemic years (2015–2019). We then tested for evidence of departures from this routine pattern, i.e., service volume delivered being below recent average by more than two standard deviations was viewed as a substantial reduction, and calculated the cumulative net differences of service volume during the pandemic period (2020–2021), in aggregate and within each specific facility.

Results

Evidence of disruptions were found: from April 2020 to December 2021, services delivered of several types were reduced across primary and secondary levels of care–including inpatient care (-20.03% less total interactions in that period compared to the recent average), immunisation (-17.61%), malnutrition treatment (-34.5%), accidents and emergency services (-16.03%), HIV (human immunodeficiency viruses) tests (-27.34%), antiretroviral therapy (ART) initiations for adults (-33.52%), and ART treatment for paediatrics (-41.32%). Reductions of service volume were greatest in the first wave of the pandemic during April-August 2020, and whereas some service types rebounded quickly (e.g., outpatient visits from -17.7% to +3.23%), many others persisted at lower level through 2021 (e.g., under-five malnutrition treatment from -15.24% to -42.23%). The total reduced service volume between April 2020 and December 2021 was 8 066 956 (-10.23%), equating to 444 units per 1000 persons.

Conclusion

We have found substantial evidence for reductions in health service delivered in Malawi during the COVID-19 pandemic which may have potential health consequences, the effect of which should inform how decisions are taken in the future to maximise the resilience of healthcare system during similar events.
Pathobiology of Candida auris infection analyzed by multiplexed imaging and single cell analysis
Authors: Chadwick Chrystal , De Jesus Magdia , Ginty Fiona , Martinez Jessica S.
Published: January 2024

Fungal organisms contribute to significant human morbidity and mortality and Candida auris (C. auris) infections are of utmost concern due to multi-drug resistant strains and persistence in critical care and hospital settings. Pathogenesis and pathology of C. auris is still poorly understood and in this study, we demonstrate how the use of multiplex immunofluorescent imaging (MxIF) and single-cell analysis can contribute to a deeper understanding of fungal infections within organs. We used two different neutrophil depletion murine models (treated with either 1A8—an anti-Ly6G antibody, or RB6-8C5—an anti-Ly6G/Ly6C antibody; both 1A8 and RB6-8C5 antibodies have been shown to deplete neutrophils) and compared to wildtype, non-neutropenic mice. Following pathologist assessment, fixed samples underwent MxIF imaging using a C. albicans antibody (shown to be cross-reactive to C. auris) and immune cell biomarkers—CD3 (T cells), CD68 (macrophages), B220 (B cells), CD45 (monocytes), and Ly6G (neutrophils) to quantify organ specific immune niches. MxIF analysis highlighted the heterogenous distribution of C. auris infection within heart, kidney, and brain 7 days post-infection. Size and number of fungal abscesses was greatest in the heart and lowest in brain. Infected mice had an increased count of CD3+, CD68+, B220+, and CD45+ immune cells, concentrated around C. auris abscesses. CD68+ cells were predominant in wildtype (non-neutropenic mice) and CD3+/CD45+ cells were predominant in neutropenic mice, with B cells being the least abundant. These findings suggest a Th2 driven immune response in neutropenic C. auris infection mice models. This study demonstrates the value of MxIF to broaden understanding of C. auris pathobiology, and mechanistic understanding of fungal infections.