bluuebunny/crossref_metadata_2025 huggingface dataset:
Zinc finger proteins and ATP‐binding cassette transporter‐dependent multidrug resistance
Authors: Barzegar Sanaz , Pirouzpanah Saeed
Published: November 2023

Background

Multidrug resistance (MDR) remains a significant challenge in cancer treatment, leading to poor clinical outcomes. Dysregulation of ATP‐binding cassette (ABC) transporters has been identified as a key contributor to MDR. Zinc finger proteins (ZNPs) are key regulators of transcription and have emerged as potential contributors to cancer drug resistance. Bridging the knowledge gap between ZNPs and MDR is essential to understand a source of heterogeneity in cancer treatment. This review sought to elucidate how different ZNPs modulate the transcriptional regulation of ABC genes, contributing to resistance to cancer therapies.

Methods

The search was conducted using PubMed, Google Scholar, EMBASE and Web of Science.

Results

In addition to ABC‐blockers, the transcriptional features regulated by ZNP are expected to play a role in reversing ABC‐mediated MDR and predicting the efficacy of anticancer treatments. Among the ZNP‐induced epithelial to mesenchymal transition, SNAIL, SLUG and Zebs have been identified as important factors in promoting MDR through activation of ATM, NFκB and PI3K/Akt pathways, exposing the metabolism to potential ZNP‐MDR interactions. Additionally, nuclear receptors, such as VDR, ER and PXR have been found to modulate certain ABC regulations. Other C2H2‐type zinc fingers, including Kruppel‐like factors, Gli and Sp also have the potential to contribute to MDR.

Conclusion

Besides reviewing evidence on the effects of ZNP dysregulation on ABC‐related chemoresistance in malignancies, significant markers of ZNP functions are discussed to highlight the clinical implications of gene‐to‐gene and microenvironment‐to‐gene interactions on MDR prospects. Future research on ZNP‐derived biomarkers is crucial for addressing heterogeneity in cancer therapy.
Perspectives on virtual interviews for dental school admissions
Authors: Hilton Edward , Song Crystal , Park Sang E.
Published: November 2023

Introduction

Admissions interviews are an integral part of the dental school application process. In light of the COVID‐19 pandemic, interviews had to adapt and become a part of the virtual realm. The purpose of the study was to evaluate the perspectives of interviewees and interviewers in this process.

Methods

Admission data for all prospective students were compiled for the classes of 2016 through 2025 to compare in‐person to virtual interview scores. Additionally, surveys were sent to members of the admissions committee as well as interviewees asking questions regarding the virtual interview experience. A Likert scale was used for the majority of questions and free responses were also an option.

Results

The comparison data showed that the virtual candidates may have had higher overall undergraduate and application scores, in addition to better interview scores compared to in‐person candidates. Interviewees and interviewers both agreed in their top three rankings of what was enjoyable about the virtual interviews, specifically the lower cost for applicants, the convenience, and the safety during the pandemic. There was also agreement with their top three aspects that were least desirable in the interview process, specifically the absence of visual cues/lack of body language, lack of personal contact, and connectivity issues. Around 74% of committee members would recommend virtual interviews in the future whereas only 49% of interviewees would recommend virtual interviews in the future.

Conclusion

The pandemic brought about many changes, including the way admissions interviews were conducted. While this was a change made of necessity, it was valuable to explore the appropriateness of implementing virtual interviews in the future as a part of dental school admissions processes.
Natural swimming holes, at the crossroad between conservation and recreation
Authors: Acuña Vicenç , Auró Mar , Campillo Ventura , Petrovic Mira , Pueyo Josep , Freixa Anna
Published: November 2023

Natural swimming holes (NSH) are commonly the only habitats with water throughout the year in semi‐arid climates, thus becoming refuges for freshwater biota. However, human crowds also gather in NSH during the warm season, threatening biodiversity.

Our goal was to analyse the drivers of recreation (e.g., distance to roads, river flow) in NSH, assess the relationship between visitation and impacts on water quality (dissolved organic carbon, ammonium, caffeine, and the sunscreen agent 2‐ethylhexyl 4‐methoxycinnamate) and bacterial biodiversity (as indicator of biodiversity), and to develop a method to determine the carrying capacity (i.e. maximum number of visitors per day to avoid an impact in biodiversity) of each NSH.

Results suggest that recreation impacts both water quality and biodiversity, and that changes in biodiversity were especially fast when increasing recreation from none to low.

Although the study is limited by the low number of case‐studies, and the consideration of only bacterial biodiversity, we believe that recreation should be banned or severely restricted in those NSH with high conservation value, whereas a recreation cap using river flow and upstream water quality should be used for those NSH with lower conservation value.
Forest reorganisation effects on fuel moisture content can exceed changes due to climate warming in wet temperate forests
Authors: Brown Tegan P. , Duff Thomas J. , Inbar Assaf , Lane Patrick N. J. , Sheridan Gary J.
Published: November 2023

The distributions of vegetation and fire activity are changing rapidly in response to climate warming. In many regions, climate effects on dead fuel moisture content (FMC) are expected to increase future wildfire activity. However, forest FMC is largely driven by microclimate conditions, which are moderated from open weather by vegetation canopies. As shifts in vegetation increase under climate warming, the extent to which future fire activity will be driven by climate directly or associated vegetation shifts remains unresolved. Here, we present a study aimed at quantifying the relative magnitudes of (i) direct climate warming, and (ii) vegetation change, on FMC. Field sites to evaluate these effects were established in a natural laboratory of altered forest states to mature wet temperate forest in south‐eastern Australia. FMC was estimated using a process‐based model and 48 years of reconstructed climate data. Canopy effects on microclimate were captured by transferring inputs from climate to microclimate using models parameterised with field observations. To evaluate the relative magnitude of climate and vegetation effects, we calculated the maximum difference in mean annual FMC across annual climate replicates and compared this to FMC differences across reorganising forest sites. Our results show vegetation effects on FMC can exceed those related to expected climate change. Changes to forest structure and composition increased (+15.7%) and decreased (−12.3%) mean annual FMC, with a larger negative effect when forest cover was completely removed (−18.5%). In contrast, the largest climate effect on FMC was −6.6% across 48‐years of data. Our study demonstrates that the magnitude of vegetation effects on FMC can exceed expected climate change effects. Models of future fire activity that do not account for changing vegetation effects on microclimate are omitting a key biophysical control on FMC and therefore may not be accurately predicting future fire activity.
Interdental cleaning and periodontal status among older Koreans: Findings from KNHANES VII
Authors: Son Ji‐Young , Kim Eun‐Jeong
Published: November 2023

Objective

To assess the association between the usage of interdental cleaning and periodontal status among older people in Korea.

Background

In order to maintain oral health in older people, it is very important to use interdental cleaning devices. However, there is a lack of research on periodontal status and interdental cleaning device use in older people.

Methods

This study used data collected from the 7th National Health Nutrition Survey (KNHANES VII: 2016–2018). A total of 3426 older people adults aged 65 years or older were selected from 16 489 participants. Data on sociodemographic status (sex, age, level of education, income, residential area), personal health practice (subjective health status, smoking, physical activity, hypertension, and diabetes mellitus), oral health practice (subjective oral health status, tooth brushing frequency, dental visits, and chewing problem), the number of teeth and periodontitis were collected. Periodontitis was defined as having a World Health Organisation community periodontal index (CPI) code greater than or equal to three, and severe periodontitis was defined as a CPI code 4. Participants having a CPI code of 3 or 4 were considered to have periodontal disease in this study. Logistic regression analysis investigated the association between interdental cleaning devices usage and periodontitis controlling the confounding factors.

Results

Those who do not use dental floss had a higher rate of periodontal disease (AOR = 1.47, 95% confidence interval [CI]: 1.05 to 2.1). However, there were no significant differences by interdental brush use. In those with 20 or more teeth, non‐users of dental floss had a higher risk of periodontitis in all models. Conversely, in those with fewer than 20 teeth, no significant differences were observed.

Conclusions

Older people with mostly intact dentitions have better periodontal health if they clean between their teeth.
CD41+ extracellular vesicles produced by avian thrombocytes contain microRNAs
Authors: Sugimoto Kenkichi , Nishikawa Takamasa , Sugiyama Toshie
Published: November 2023

Avians have thrombocytes in their blood circulation rather than mammalian platelets. However, many details of thrombocyte characteristics have not been determined. Here, chicken thrombocytes were isolated, and extracellular vesicle (EV) production was investigated. The thrombocyte‐specific markers cd41 and cd61 were expressed in the yolk sac at 24 h. According to the embryonic developmental stage, the cd41‐expressing tissues changed from the yolk sac to the bone marrow and spleen. Accordingly, the bone marrow and spleen were the main tissues producing thrombocytes in adult chickens. Avian thrombocytes were separated from adult spleen cells through a combination of discontinuous density gradient centrifugation, phagocytic cell removal, and fluorescence‐activated cell sorting. Isolated thrombocytes produced CD41+ EVs (CD41+ EVs), and the CD41+ EVs also expressed CD9. Microarray analysis revealed that CD41+ EVs contain many microRNAs. Macrophage lines (RAW264.7) phagocytosed CD41+ EVs, and their phagocytosis and migration activity were suppressed. Microarray analysis also revealed that EVs altered gene expression in macrophages. These data indicated that the CD41+ EV was a carrier of microRNAs produced from thrombocytes and affected the cell characteristics of the received cells. Therefore, the CD41+ EVs of avians worked as a communication tool.
Visible light induced self‐cleaning performance of iron‐doped TiO2 nanoparticles for surface applications
Authors: Hasanuzzaman Muhammad , Islam Mohammad Johirul , Mokammel Mohammad Arif
Published: November 2023

This study aimed to enhance the visible light photosensitivity of TiO2 nanoparticles for self‐cleaning applications by doping with Fe3+. Nanocrystalline undoped and Fe‐doped TiO2 (Ti1 − xFexO2, x = .01–.04) were synthesized via sol–gel method. The results demonstrated that Fe‐doped TiO2 nanoparticles exhibited visible light sensitivity and self‐cleaning properties. An increased Fe concentration resulted in a red shift in the absorption band edge. Fe0.03‐doped TiO2 with an average particle size of ∼21 nm, a crystallite size of ∼12 nm, and a band gap of ∼2.86 eV showed the highest photocatalytic activity (60% methylene blue degradation) and super‐hydrophilicity (water droplet contact angle 9°) under visible light radiation. These findings highlight the potential of Fe‐doped TiO2 nanoparticles as a promising material for self‐cleaning applications.
Some Results from an Automated Statewide Comparison among Attempted, Committed, and Nonsuicidal Patients
Authors: Sletten Ivan W. , Evenson Richard C. , Brown Marjorie L.
Published: November 2023

ABSTRACT: In the Missouri Division of Mental Health statewide automated Standard System of Psychiatry, 151 patients who had attempted suicide were compared with 424 who had not and with 97 who had committed suicide. Much of the data was provided from relatives using an automated history. Compared with nonattempters, attempters were younger and more often female, depressed, assaultive, and had a family history of suicide. Actual suicides were more often male, better educated, and in general more resembled the attempters than nonattempters.
Patient perspectives of recovery from myalgic encephalomyelitis/chronic fatigue syndrome: An interpretive description study
Authors: Hasan Zara , Kuyvenhoven Cassandra , Chowdhury Mehreen , Amoudi Lana , Zeraatkar Dena , Busse Jason W. , Sadik Marina , Vanstone Meredith
Published: November 2023

Aims and Objectives

Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome (CFS), is characterised by persistent fatigue, postexertional malaise, and cognitive dysfunction. It is a complex, long‐term, and debilitating illness without widely effective treatments. This study describes the treatment choices and experiences of ME/CFS patients who have experienced variable levels of recovery.

Method

Interpretive description study consisting of semi‐structured qualitative interviews with 33 people who met the US Centers for Disease Control (2015) diagnostic criteria for ME/CFS and report recovery or symptom improvement.

Results

Twenty‐six participants endorsed partial recovery, and seven reported full recovery from ME/CFS. Participants reported expending significant time and energy to identify, implement, and adapt therapeutic interventions, often without the guidance of a medical practitioner. They formulated individualised treatment plans reflecting their understanding of their illness and personal resources. Most fully recovered participants attributed their success to mind‐body approaches.

Conclusion

Patients with ME/CFS describe independently constructing and managing treatment plans, due to a lack of health system support. Stigmatised and dismissive responses from clinicians precipitated disengagement from the medical system and prompted use of other forms of treatment.
An absence of imperfections: A proposed framework for defining, assessing, and achieving skin glow
Authors: Goodman Greg J. , Armour Katherine , Ong David , Tienthavorn Tanongkiet , Wu Yan , Chen Pei‐Chun , Tam Elias , Ong Amanda , Messiha Gina , Telfer Tara , Avelar Luiz E. T.
Published: November 2023

Background

Skin glow is a subcomponent of skin quality. It has become entrenched in the cosmeceuticals and aesthetics lexicons as a synonym for health and youth, but is not well‐defined as a scientific metric.

Aims

To examine the concept of skin glow and determine if it is an objective concept that can be defined and quantified.

Methods

Literature review was used to develop a survey on current concepts relating to skin quality. The survey results were analyzed descriptively and presented to a focus group comprising five dermatologists and four aesthetic physicians. This group then discussed the concept of skin glow, how to define it and what metrics could be used to assess it.

Results

Surveyed practitioners (n = 38) ranked skin quality as the fourth most important factor related to a person's overall aesthetic first impression. Almost all (95%) respondents reported routinely assessing skin quality, citing serial photography (83%), and visual inspection (67%) as the main means of achieving this. The focus group defined skin glow as even reflectance from an unaffected papillary and reticular dermal collagen layer, which is created only when skin does not exhibit any characteristics that detract from this even reflectance. Due to its complexity, the focus group proposed a hierarchal framework for assessment, encompassing patient self‐rating, practitioner severity rating, and supplemental use of validated measurement devices.

Conclusions

Skin glow can be defined and quantified. More work is warranted to develop a practical skin glow assessment tool suitable for use in the clinic setting.
Building a resilient organization through a pre‐shock strategic emphasis on innovation
Authors: Engelen Andreas , Huesker Constantin , Rieger Verena , Berg Victoria
Published: November 2023

Why are some firms more resilient when systemic shocks like the Global Financial Crisis (GFC) or COVID‐19 pandemic set in? We approach this question by arguing that a firm's pre‐shock strategic emphasis on innovation can mitigate the consequences of such shocks by facilitating stability and flexibility, major components of organizational resilience, as the shock sets in. We test our arguments empirically by analyzing data from 2003 to 2011 on as many as 994 firms from the S&P 1500 to identify the causes of their resilience during the 2008 GFC. Our findings indicate that pre‐shock product introductions and, to some extent, top management's focus on innovation can facilitate stability and flexibility when a shock occurs, while R&D intensity and patents, other dimensions of a strategic emphasis on innovation, do so only when firm profitability before the shock is low. In this way, we direct innovation research's attention to the additional performance benefits of innovation activities when shocks occur and reveal which dimensions of a strategic emphasis on innovation buffer the negative consequences of a shock, thus providing insights into how innovation helps firms be resilient. Further, our theorizing and empirical findings unveil an intriguing paradox: While existing research tends to find positive associations between innovation and profitability in “regular” times, strong pre‐shock profitability impairs innovation's ability to unfold its effects fully at shock onset.
Vaccination for the prevention of equine herpesvirus‐1 disease in domesticated horses: A systematic review and meta‐analysis
Authors: Osterrieder Klaus , Dorman David C. , Burgess Brandy A. , Goehring Lutz S. , Gross Peggy , Neinast Claire , Pusterla Nicola , Hussey Gisela Soboll , Lunn David P.
Published: November 2023

Background

Equine herpes virus type 1 (EHV‐1) infection in horses is associated with respiratory and neurologic disease, abortion, and neonatal death.

Hypothesis

Vaccines decrease the occurrence of clinical disease in EHV‐1‐infected horses.

Methods

A systematic review was performed searching multiple databases to identify relevant studies. Selection criteria were original peer‐reviewed research reports that investigated the in vivo use of vaccines for the prevention of disease caused by EHV‐1 in domesticated horses. Main outcomes of interest included pyrexia, abortion, neurologic disease, viremia, and nasal shedding. We evaluated risk of bias, conducted exploratory meta‐analyses of incidence data for the main outcomes, and performed a GRADE evaluation of the quality of evidence for each vaccine subtype.

Results

A total of 1018 unique studies were identified, of which 35 met the inclusion criteria. Experimental studies accounted for 31/35 studies, with the remainder being observational studies. Eight vaccine subclasses were identified including commercial (modified‐live, inactivated, mixed) and experimental (modified‐live, inactivated, deletion mutant, DNA, recombinant). Risk of bias was generally moderate, often because of underreporting of research methods, and sample sizes were small leading to imprecision in the estimate of the effect size. Several studies reported either no benefit or minimal vaccine efficacy for the primary outcomes of interest. Meta‐analyses revealed significant heterogeneity was present, and our confidence in the quality of evidence for most outcomes was low to moderate.

Conclusions and Clinical Importance

Our review indicates that commercial and experimental vaccines minimally reduce the incidence of clinical disease associated with EHV‐1 infection.
Realities and ideals: Experiences and needs of pediatric oncology nurses in communication processes with children and their families at the end‐of‐life period: A photovoice qualitative study
Authors: Özdemir Koyu Hazal , Algül Gökce , Kilicarslan Törüner Ebru
Published: November 2023

Effective communication in end‐of‐life care for pediatric cancer patients is crucial. Yet, limited research focuses on the communication experiences of pediatric oncology nurses during this period. This study aims to investigate the communication experiences and needs of these nurses with children and their families during the end‐of‐life period. A qualitative study design with photo voice methodology was followed. The research was conducted with 16 pediatric oncology nurses working in the pediatric oncology wards of a university hospital between January and May 2023. Data were collected the “Characteristic Information Form”, “Semi‐Structured Interview Form”, and photovoice methodology. Data were analyzed through reflexive thematic analysis. Most of the nurses are at the undergraduate level, and their working experience in pediatric oncology wards ranges from 4 months to 17 years. Seven main themes emerged: Optimistic Communication‐Interaction, Mindfulness, Active Coping, Behavioral Actions, Death Uncertainty Dilemma, Interpersonal and Environmental Factors, and Discrepancy between Ideals and Reality. The study sheds light on the importance of pediatric oncology nurses' ideals versus realities upstream approach in communicating with end‐of‐life children and their families, empowering pediatric oncology nurses on the journey to ideal end‐of‐life care.
Liquid and solid gastric emptying and correlation with clinical characteristics in pediatric patients with dyspepsia
Authors: Santucci Neha R. , Corsiglia Joshua , El‐Chammas Khalil , Shumeiko Oleksandr , Liu Chunyan , Kaul Ajay
Published: November 2023

Background

There is limited data on gastric emptying in dyspeptic children. We aimed to determine solid and liquid emptying rates in dyspeptic children and correlate with clinical characteristics.

Methods

Charts of dyspeptic children undergoing 4‐hour dual‐phase gastric scintigraphy were reviewed for demographics, symptoms, and comorbidities.

Key Results

In 1078 dyspeptic patients (65% females, median age 13 years) vomiting (55%), nausea (53%), and abdominal pain (52%) were the most common symptoms. The most common comorbidities were mental health (32%), neurologic (27%), and hypermobility spectrum disorders (20%). Solid and liquid emptying rates were aligned in 61.23%. Delayed solid with normal liquid emptying were noted in 2.5%, compared to delayed liquid with normal solid emptying in 26.16%. Abdominal pain had a trend for association with delayed or normal solid emptying (p = 0.06). Nausea was mostly reported with normal solid emptying (p < 0.0001) and underreported in patients <12 years with vomiting (29%). Abnormal solid emptying (rapid and delayed) was noted more frequently in children with mental health disorders (p = 0.027). Rapid liquid emptying was more common in children with genetic disorders (p = 0.032).

Conclusion and Inferences

Over half of children with dyspepsia had delayed liquid gastric emptying, and one quarter had delayed liquid with normal solid emptying. Dual‐phase gastric emptying studies may help target therapy in dyspeptic children. Nausea is not a reliable symptom for dyspepsia in younger children. Given the significant association of abnormal gastric emptying in children with mental health disorders, we recommend screening and treating children with dyspepsia.
Metabarcoding read abundances of orchid mycorrhizal fungi are correlated to copy numbers estimated using ddPCR
Authors: Wang Deyi , Trimbos Krijn B. , Gomes Sofia I. F. , Jacquemyn Hans , Merckx Vincent S. F. T.
Published: November 2023

Quantifying the abundances of fungi is key to understanding natural variation in mycorrhizal communities in relation to plant ecophysiology and environmental heterogeneity. High‐throughput metabarcoding approaches have transformed our ability to characterize and compare complex mycorrhizal communities. However, it remains unclear how well metabarcoding read counts correlate with actual read abundances in the sample, potentially limiting their use as a proxy for species abundances.

Here, we use droplet digital PCR (ddPCR) to evaluate the reliability of ITS2 metabarcoding data for quantitative assessments of mycorrhizal communities in the orchid species Neottia ovata sampled at multiple sites. We performed specific ddPCR assays for eight families of orchid mycorrhizal fungi and compared the results with read counts obtained from metabarcoding.

Our results demonstrate a significant correlation between DNA copy numbers measured by ddPCR assays and metabarcoding read counts of major mycorrhizal partners of N. ovata, highlighting the usefulness of metabarcoding for quantifying the abundance of orchid mycorrhizal fungi. Yet, the levels of correlation between the two methods and the numbers of false zero values varied across fungal families, which warrants cautious evaluation of the reliability of low‐abundance families.

This study underscores the potential of metabarcoding data for more quantitative analyses of mycorrhizal communities and presents practical workflows for metabarcoding and ddPCR to achieve a more comprehensive understanding of orchid mycorrhizal communities.
A Brief History of General‐to‐specific Modelling*
Authors: Hendry David F.
Published: November 2023

We review key stages in the development of general‐to‐specific modelling (Gets). Selecting a simplified model from a more general specification was initially implemented manually, then through computer programs to its present automated machine learning role to discover a viable empirical model. Throughout, Gets applications faced many criticisms, especially from accusations of ‘data mining’—no longer pejorative—with other criticisms based on misunderstandings of the methodology, all now rebutted. A prior theoretical formulation can be retained unaltered while searching over more variables than the available sample size from non‐stationary data to select congruent, encompassing relations with invariant parameters on valid conditioning variables.
Cost of implementing HIV pre‐exposure prophylaxis at community‐based clinics in Indonesia
Authors: Siregar Adiatma Yudistira Manogar , Juwita Mery Nurma , Hardiawan Donny , Akbar Adhadian , Rachman Zulfa Haitan , Haekal Muhammad Dzaki Fahd , Marwah Yuvi Siti , Putri Tarinanda Adzani , Rakhmat Fani Fadillah , Pohan Mawar Nita , Handayani Miasari , Budiarty Tri Indah , Afriana Nurhalina , Prabowo Bagus Rahmat , Wisaksana Rudi
Published: November 2023

Introduction

Currently, Indonesia still has one of the highest rates of new HIV/AIDS infections among countries in Asia and the Pacific region. The WHO has recommended pre‐exposure prophylaxis (PrEP) as an additional HIV epidemic prevention step, which has been applied globally and related to the reduction in the number of HIV cases. However, information on the cost of implementing PrEP is rarely available in developing countries, especially in Southeast Asia. Designing a cost‐effective approach to scale up PrEP and to estimate the potential budget impact requires information on the cost of implementing PrEP. This study aims to estimate the cost of implementing PrEP at community‐based clinics in Indonesia.

Methods

We collected healthcare and non‐healthcare/client costs from nine community‐based clinics in various cities/districts in Indonesia. The healthcare costs included data on resource utilisation and costs to deliver PrEP, divided into recurrent and capital costs using a discount rate of 3%. Non‐healthcare costs included out‐of‐pocket costs (e.g., transportation, meals) and productivity loss by clients and accompanying person(s) in accessing PrEP. On average, we interviewed 27 clients/clinic.

Results

The annual cost of providing PrEP per client is US $365.03, 39% lower than the yearly cost of antiretroviral treatment (ART) per person (approximately US $600). Drugs and non‐healthcare costs contribute approximately 67% of the cost. The cost of PrEP amounts to US $292,756.45/year, covering 802 clients. The non‐healthcare cost per visit at all sites never reaches more than 10% of the average monthly household expenditure.

Conclusions

The cost of providing PrEP per person is approximately US $365 and is 39% lower than the annual cost of ART per person. Lowering the cost of PrEP ARV drugs would reduce the cost. Scaling up PrEP should recognise this cost structure and strive to reach economies of scale as the intervention gains more clients while simultaneously controlling new HIV infections.
Autoimmune anti‐D in an RhD‐positive young infant: Learning from a rare case
Authors: Malhotra Sheetal , Roy Manisha , Parchure Disha , Kaba Munira , Jain Ashish , Kulkarni Swati , Bansal Deepak , Sharma Ratti Ram
Published: November 2023

Background and Objectives

Anti‐D is usually immune in nature and is formed in individuals lacking D antigen or having variants/altered D phenotypes. In the Indian population, 93.8% are RhD positive, and R1R1 is the commonest Rh phenotype. Here we report a rare and interesting case of autoimmune anti‐D in an RhD‐positive 3‐month‐old infant leading to warm autoimmune haemolytic anaemia.

Study Design and Methods

Auto‐anti‐D was detected serologically by immunohaematological techniques such as direct antiglobulin test, antibody detection and identification, dithiothreitol, enzyme treatment, antibody titration and elution. Molecular studies were performed to rule out genetic variants of RhD.

Results

Anti‐D was confirmed in eluate and blood group post elution was B RhD positive. On genotyping using the Indian‐specific RHD genotyping assay, the sample was found to be negative for the RHD*01W.150 (most common RhD variant in Indians) but positive for RHD exon 5 and RHD exon 10 along with glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). The sample was further sequenced for RHD exons 1–10 by Sanger sequencing and found to be a wild type, thus, ruling out the presence of an RhD variant.

Conclusion

This case is of interest because of the rare occurrence of autoimmune anti‐D in an RhD‐positive patient of such a young age (3 months). To the best of our knowledge, only two case reports have been published on autoimmune anti‐D in infancy (in 1961 and 1964).
A note on lc‐trivial fibrations
Authors: Hashizume Kenta
Published: November 2023

For every lc‐trivial fibration from an lc pair, we prove that after a base change, there exists a positive integer , depending only on the dimension of , the Cartier index of , and the sufficiently general fibers of , such that is linearly equivalent to the pullback of a Cartier divisor.
Joined up Thinking: Aggregating archaeological datasets at an international scale
Authors:   University of York, Richards Julian D.
Published: November 2023

The archaeological research community was an early adopter of digital tools for data acquisition, organisation, analysis, and presentation of research results of individual projects. However, the provision of e-infrastructure and services for data sharing, discovery, access, and reuse has lagged behind. The ARIADNE Research Infrastructure has sought to address this situation. Developed with European funding, ARIADNE has created an e-infrastructure that enables data providers to register and provide access to their digital resources through the ARIADNE data portal, facilitating discovery, access, and research. ARIADNE has aggregated resources from over 45 data providers, spanning over 40 countries and 4 continents. The portal now provides online access to over 3.9 million research resources. It is based upon Linked Open Data technologies and is underpinned by a flexible and extensible architecture, enabling multiple combinations and presentations of the same underpinning data. We have been keen not to 'make a great heap' of all the data and, learning from previous data aggregation projects, we have defined a subset of the CIDOC CRM to be used as a strict ontology and paid close attention to data standards and controlled vocabularies to achieve a high degree of interoperability. This article discusses some of the challenges of large-scale data integration and describes the approaches adopted to ensure that the ARIADNE Knowledge Base is an effective tool for archaeological heritage management and research at a national and international level.
Multi-Fidelity Physics-Informed Generative Adversarial Network for Solving Partial Differential Equations
Authors: Taghizadeh Mehdi , Nabian Mohammad Amin , Alemazkoor Negin
Published: November 2023

We propose a novel method for solving partial differential equations using multi-fidelity physics-informed generative adversarial networks. Our approach incorporates physics supervision into the adversarial optimization process to guide the learning of the generator and discriminator models. The generator has two components: one that approximates the low-fidelity response of the input and another that combines the input and low-fidelity response to generate an approximation of high-fidelity responses. The discriminator identifies whether the input–output pairs accord not only with the actual high-fidelity response distribution, but also with physics. The effectiveness of the proposed method is demonstrated through numerical examples and compared to existing methods.
The Influence of a Warm-Up on Vigilance in University Students
Authors: González-Fernández Francisco Tomás , Castillo-Rodriguez Alfonso , González-Víllora Sixto , Hortigüela-Alcalá David
Published: November 2023

The present study aimed to analyze the effects of conducting a warm-up (WC) or not (WWC) on students of the Science Degree in Physical Activity and Sport before starting a practical class. Thirty-two students of the Science Degree in Physical Activity and Sport (age: 22.38 ± 1.81 years; height: 176.09 ± 8.52 cm; weight: 22.38 ± 1.81 kg; body fat: 25.17 ± 3.20%) participated in a counterbalanced cross-sectional study in which three conditions were tested: (a) basal lineal, (b) WC, and (c) WWC. Participants recorded longer times (worse performance) in the Illinois dribbling test (basal lineal condition [20.17 ± 1.35], WWC [20.13 ± 1.37], and WC [19.32 ± 1.35]) and the Psychomotor Vigilance Task test (basal lineal condition [397.88 ± 75.98 ms]; WWC [412.19 ± 91.39 ms], and WC [368.53 ± 68.65 ms]). The warm-up prior to physical activity classes had positive effects on vigilance linked to executive functioning, and physical performance. In this sense, more research on different types of warm-up may be in order to contrast them with each other, as well as to carry out attention measurements according to the content to be imparted after the warm-ups. The present study represents a big opportunity for all physical education teachers due to warm-up is a crucial aspect that occurs in all practical sessions, also linked to the attention processes and motivational factors of the students.
Jumbo phages are active against extensively drug-resistant eyedrop-associated
Pseudomonas aeruginosa
infections
Authors: Cobián Güemes Ana Georgina , Ghatbale Pooja , Blanc Alisha N. , Morgan Chase J. , Garcia Andrew , Leonard Jesse , Huang Lina , Kovalick Grace , Proost Marissa , Chiu Megan , Kuo Peiting , Oh Joseph , Karthikeyan Smruthi , Knight Rob , Pogliano Joe , Schooley Robert T. , Pride David T.
Published: November 2023

Antibiotic-resistant bacteria present an emerging challenge to human health. Their prevalence has been increasing across the globe due in part to the liberal use of antibiotics that has pressured them to develop resistance. Those bacteria that acquire mobile genetic elements are especially concerning because those plasmids may be shared readily with other microbes that can then also become antibiotic resistant. Serious infections have recently been related to the contamination of preservative-free eyedrops with extensively drug-resistant (XDR) isolates of
Pseudomonas aeruginosa
, already resulting in three deaths. These drug-resistant isolates cannot be managed with most conventional antibiotics. We sought to identify alternatives to conventional antibiotics for the lysis of these XDR isolates and identified multiple bacteriophages (viruses that attack bacteria) that killed them efficiently. We found both jumbo phages (>200 kb in genome size) and non-jumbo phages that were active against these isolates, the former killing more efficiently. Jumbo phages effectively killed the three separate XDR
P. aeruginosa
isolates both on solid and liquid medium. Given the ongoing nature of the XDR
P. aeruginosa
eyedrop outbreak, the identification of phages active against them provides physicians with several novel potential alternatives for treatment.
Enhancing the antibacterial function of probiotic
Escherichia coli
Nissle: when less is more
Authors: Bartram Emma , Asai Masanori , Gabant Philippe , Wigneshweraraj Sivaramesh
Published: November 2023

Probiotic bacteria confer multiple health benefits, including preventing the growth, colonization, or carriage of harmful bacteria in the gut. Bacteriocins are antibacterial peptides produced by diverse bacteria, and their production is tightly regulated and coordinated at the transcriptional level. A popular strategy for enhancing the antibacterial properties of probiotic bacteria is to retrofit them with the ability to overproduce heterologous bacteriocins. This is often achieved from non-native constitutive promoters or in response to host or pathogen signal from synthetic promoters. How the dysregulated overproduction of heterologous bacteriocins affects the fitness and antibacterial efficacy of the retrofitted probiotic bacteria is often overlooked. We have conferred the prototypical probiotic
Escherichia coli
strain Nissle (EcN) the ability to produce microcin C (McC) from the wild-type promoter and two mutant promoters that allow, relative to the wild-type promoter, high and low amounts of McC production. This was done by introducing specific changes to the sequence of the wild-type promoter driving transcription of the McC operon while ensuring that the modified promoters respond to native regulation. By studying the transcriptomic responses and antibacterial efficacy of the retrofitted EcN bacteria in a
Galleria mellonella
infection model of enterohemorrhagic
E. coli
, we show that EcN bacteria that produce the lowest amount of McC display the highest antibacterial efficacy with little-to-none undesired collateral impact on their fitness. The results highlight considerations researchers may take into account when retrofitting probiotic bacteria with heterogenous gene products for therapeutic, prophylactic, or diagnostic applications.

Bacteria that resist killing by antibiotics are a major risk to modern medicine. The use of beneficial “probiotic” bacteria to make antibiotic-like compounds at the site of infection in the body is emerging as a popular alternative to the use of conventional antibiotics. A potential drawback of engineering probiotic bacteria in this way is that producing antibiotic-like compounds could impart undesired side effects on the performance of such bacteria, thereby compromising their intended use. This study highlights considerations researchers may take into account when engineering probiotic bacteria for therapeutic, prophylactic, or diagnostic applications.
Implication of amino acid metabolism and cell surface integrity for the thermotolerance mechanism in the thermally adapted acetic acid bacterium
Acetobacter pasteurianus
TH-3
Authors: Matsumoto Nami , Matsutani Minenosuke , Tanimoto Yoko , Nakanishi Rina , Tanaka Shuhei , Kanesaki Yu , Theeragool Gunjana , Kataoka Naoya , Yakushi Toshiharu , Matsushita Kazunobu
Published: November 2023

An acetic acid bacterium,
Acetobacter pasteurianus
SKU1108, was adapted to higher growth temperatures through an experimental evolution approach under acetic acid fermentation conditions. The thermally adapted strain, TH-3, exhibited significantly increased growth and fermentation ability compared with the wild-type strain at higher temperatures (M. Matsutani, M. Nishikura, N. Saichana, T. Hatano, et al., J Biotechnol 165:109–119, 2013,
https://doi.org/10.1016/j.jbiotec.2013.03.006
). A previous study showed that the TH-3 strain has a total of 11 mutations in the genome, of which
marR
has been shown to be involved in a higher acetic acid fermentation ability, but mutations related to thermotolerance have not yet been elucidated. In this study, we identified almost all of the mutated genes and found that mutation of three genes,
ans
(asparagine permease),
dct
(dicarboxylate transporter), and
glnD
(uridylyltransferase PII), with
ans
and
dct
becoming dysfunctional but
glnD
seemingly functionally modified, was sufficient to reproduce the increased thermotolerance of the TH-3 strain. In addition, these mutations induced two phenotypic changes in TH-3: altered intracellular amino acid pool and cell size reduction. We further observed cell surface modification in TH-3, including increased phospholipid and lipopolysaccharide contents, as well as increased respiratory activities with reduced intracellular reactive oxygen species generation. These results suggest that mutation of the three genes enabled the TH-3 strain to be more thermotolerant by increasing the cell surface integrity and energy generation, which could be caused by increased membrane components and altered membrane protein synthesis via changes in the intracellular amino acid pool, together with the cell size reduction, which may enhance nutrient or oxygen availability.

IMPORTANCE

Acetobacter pasteurianus
, an industrial vinegar-producing strain, is suffered by fermentation stress such as fermentation heat and/or high concentrations of acetic acid. By an experimental evolution approach, we have obtained a stress-tolerant strain, exhibiting significantly increased growth and acetic acid fermentation ability at higher temperatures. In this study, we report that only the three gene mutations of ones accumulated during the adaptation process,
ansP
,
dctD
, and
glnD
, were sufficient to reproduce the increased thermotolerance of
A. pasteurianus
. These mutations resulted in cell envelope modification, including increased phospholipid and lipopolysaccharide synthesis, increased respiratory activity, and cell size reduction. The phenotypic changes may cooperatively work to make the adapted cell thermotolerant by enhancing cell surface integrity, nutrient or oxygen availability, and energy generation.
Regulation of the general stress response sigma factor σ
T
by Lon-mediated proteolysis
Authors: Akar Roya , Fink Matthias J. , Omnus Deike J. , Jonas Kristina
Published: November 2023

The Lon protease is widely conserved in both prokaryotic and eukaryotic organisms and fulfills important regulatory functions. Nevertheless, the number of identified Lon substrates is limited in most organisms, and the precise role of Lon in regulating these proteins is poorly understood. Here, we describe the α-proteobacterial general stress response sigma factor σ
T
as a novel Lon substrate in
Caulobacter crescentus
. Based on previously published quantitative proteomics data, we find σ
T
to be a promising putative Lon substrate and confirm a direct role of Lon in degrading σ
T
. We show that Lon contributes to the downregulation of σ
T
abundance under optimal conditions and during recovery from sucrose-induced osmotic stress. Furthermore, the presence of the Lon activity regulator LarA enhances Lon-mediated degradation of σ
T
in vitro
and reduces σ
T
levels
in vivo
indicating a role of LarA in modulating Lon-mediated degradation of σ
T
. Together, our results highlight the importance of Lon during the recovery phase following stress exposure by adjusting the concentrations of critical regulators of stress responses.

IMPORTANCE

Regulated protein degradation is a critical process in all cell types, which contributes to the precise regulation of protein amounts in response to internal and external cues. In bacteria, protein degradation is carried out by ATP-dependent proteases. Although past work revealed detailed insights into the operation principles of these proteases, there is limited knowledge about the substrate proteins that are degraded by distinct proteases and the regulatory role of proteolysis in cellular processes. This study reveals a direct role of the conserved protease Lon in regulating σ
T
, a transcriptional regulator of the general stress response in α-proteobacteria. Our work is significant as it underscores the importance of regulated proteolysis in modulating the levels of key regulatory proteins under changing conditions.
SARS-CoV-2 NSP12 associates with TRiC and the P323L substitution acts as a host adaption
Authors: Alruwaili Muhannad , Armstrong Stuart , Prince Tessa , Erdmann Maximillian , Matthews David A. , Luu Lisa , Davidson Andrew , Aljabr Waleed , Hiscox Julian A.
Published: November 2023

SARS-CoV-2 emerged in the human population in late 2019, and human-to-human transmission has dominated the evolutionary landscape and driven the selection of different lineages. The first major change that resulted in increased transmission was the D614G substitution in the spike protein. This was accompanied by the P323L substitution in the viral RNA-dependent RNA polymerase (NSP12). Together with D614G, these changes are the root of the predominant global SARS-CoV-2 landscape. Here, we found that NSP12 formed an interactome with cellular proteins. The functioning of NSP12 was dependent on the T-complex protein ring complex, a molecular chaperone. In contrast, there was a differential association between NSP12 variants and components of a phosphatase complex (PP2/PP2A and STRN3). The virus expressing NSP12
L323
was less sensitive to perturbations in PP2A and supports the paradigm that ongoing genotype to phenotype adaptation of SARS-CoV-2 in humans is not exclusively restricted to the spike protein.

IMPORTANCE

SARS-CoV-2 has caused a worldwide health and economic crisis. During the course of the pandemic, genetic changes occurred in the virus, which have resulted in new properties of the virus—particularly around gains in transmission and the ability to partially evade either natural or vaccine-acquired immunity. Some of these viruses have been labeled Variants of Concern (VoCs). At the root of all VoCs are two mutations, one in the viral spike protein that has been very well characterized and the other in the virus polymerase (NSP12). This is the viral protein responsible for replicating the genome. We show that NSP12 associates with host cell proteins that act as a scaffold to facilitate the function of this protein. Furthermore, we found that different variants of NSP12 interact with host cell proteins in subtle and different ways, which affect function.