bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Analysis Between Pericoronary Fat Attenuation Index and Parameters of Single Plaque
Authors: Nie Ji-Yan , Chen Wen-Xi , Wu Qing-De
Published: February 2024

Objective

The aim of the study is to investigate the relationship between plaque parameters and pericoronary fat attenuation index (FAI).

Methods

A retrospective collection was performed on 227 patients with coronary heart disease who underwent coronary computed tomography angiography examinations in our hospital from May 2021 to April 2023, with a total of 254 right coronary or left anterior descending coronary arteries exhibiting solitary plaques within the FAI measurement area. Based on whether the proximal coronary FAI value was ≥ −70.0 HU, patients and coronary arteries were divided into FAI-positive group (67 cases, 73 coronary arteries) and FAI-negative group (160 cases, 181 coronary arteries). Quantitative parameters of coronary solitary plaques were collected, including stenosis severity, plaque length, plaque volume, plaque composition ratios, minimal luminal area, and calcification score, as well as qualitative parameters such as plaque types and high-risk plaques. Differences in plaque parameters between the FAI-positive and FAI-negative groups were compared.

Results

The proportion of positive remodeling in the FAI-positive group (73 coronary arteries) was higher than that in the FAI-negative group (181 coronary arteries) with statistical significance (89.0% vs 78.5%, P = 0.049). Multivariate analysis revealed that positive remodeling was a risk factor for abnormal FAI values in solitary plaques (odds ratio, 2.271, P = 0.049).

Conclusions

The FAI-positive group had a higher proportion of positive remodeling, and positive remodeling was an independent risk factor for positive FAI values.
Mismatch Between Brain MRIs and 18F-DOPA PET/CT
Authors: Bourbonne Vincent , Dissaux Brieg , Seizeur Romuald , Nguyen Jessica , Querellou Solène
Published: February 2024

After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18F-DOPA uptake. Five additional 18F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.
Multiple Nervous System Involvement of Erdheim-Chester Disease With Responsive Perinephritic Hypermetabolism
Authors: Koç Zehra Pinar , Özcan Pinar Pelin , Tombak Anil , Sönmezoğlu Kerim
Published: February 2024

A 36-year-old man who was at follow-up for histiocytosis had sudden-onset symptoms of unilateral ophthalmic increased pressure. The patient was referred to the FDG PET/CT for determination of involvement with suspicion of Erdheim-Chester disease. The reduction of the FDG uptake in all of the lesions (medial temporal lobes, nasal septum, medulla spinalis in sacral region, as well as perinephritic infiltrations), which were determined by the first PET/CT, was achieved at second imaging.
Unusual Presence of Synchronous Primary Ovarian and Thyroid Extranodal Non-Hodgkin Lymphoma Without Lymph Node Involvement
Authors: Babacan Gündüzalp Buğrahan , Acar Tayyar Merve Nur , Şahin Mehmet Can , Şengiz Erhan Selma , Tamam Müge Öner
Published: February 2024

Extranodal lymphomas without lymph node involvement are rarely observed and create diagnostic challenges. We present the case of a 33-year-old woman who was admitted with abdominal swelling. Ultrasonography findings suggested bilateral ovarian masses. 18F-FDG PET/CT revealed intense uptake on the bilateral pelvic mass and thyroid gland. Following excisional surgery and thyroid fine-needle aspiration biopsy, the patient was diagnosed with diffuse large B-cell lymphoma. This case is exceptionally rare, as it presents 2 synchronous extranodal involvements in the ovaries and the thyroid gland independently while not presenting any lymph node activity, which has not been reported before.
Ultrasound Microbubble-Stimulated miR-145-5p Inhibits Malignant Behaviors of Breast Cancer Cells by Targeting ACTG1
Authors: Ren Liang , Wang Li , Yi Xuelin , Tan Yang , Yi Lingxian , He Jinlan , Li Danping
Published: February 2024

Ultrasound-targeted microbubble destruction (UTMD) technology combines ultrasound with a variety of functional microbubble vectors to enhance the transfection and expression of target genes, and has become a promising noninvasive method for localized gene transfer, which is widely used in gene therapy for cancer. This research aimed to explore the role of UTMD-mediated miR-145-5p on breast cancer (BC) tumorigenesis and the underlying mechanisms. To achieve UTMD-mediated miR-145-5p overexpression, BC cells were cotransfected with microbubbles (MBs) and miR-145-5p mimics. The BC cell malignant phenotypes were assessed through CCK-8, wound healing, and transwell assays. MiR-145-5p and actin gamma 1 (ACTG1) binding relationship was verified through luciferase reporter and RNA pull-down assays. MiR-145-5p and ACTG1 levels in BC cells and tissues were detected through RT-qPCR and Western blotting. ACTG1 was upregulated, whereas miR-145-5p was downregulated in BC cells and tissues. MiR-145-5p targeted ACTG1 and negatively regulated its level in BC cells. Overexpressing miR-145-5p restrained BC cell growth, migration, and invasion. Ultrasound-targeted microbubble destruction improved the overexpression efficiency of miR-145-5p and enhanced the suppressive influence on BC cell malignant phenotypes. In addition, ACTG1 overexpression compromises the repression of UTMD-mediated miR-145-5p on cellular behaviors in BC. Ultrasound-targeted microbubble destruction–delivered miR-145-5p hindered malignant behaviors of BC cells through downregulating ACTG1.
Antifungal activity and potential mechanism of action of Huangqin decoction against Trichophyton rubrum
Authors: Shen Chengying , Luo Zhong , Zhan Ping , Deng Fengyi , Zhang Pei , Shen Baode , Hu Jianxin
Published: February 2024

Introduction.
Trichophyton rubrum is a major causative agent of superficial dermatomycoses such as onychomycosis and tinea pedis. Huangqin decoction (HQD), as a classical traditional Chinese medicine formula, was found to inhibit the growth of common clinical dermatophytes such as T. rubrum in our previous drug susceptibility experiments.

Hypothesis/Gap Statement. The antifungal activity and potential mechanism of HQD against T. rubrum have not yet been investigated.

Aim. The aim of this study was to investigate the antifungal activity and explore the potential mechanism of action of HQD against T. rubrum.

Methodology. The present study was performed to evaluate the antifungal activity of HQD against T. rubrum by determination of minimal inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), mycelial growth, biomass, spore germination and structural damage, and explore its preliminary anti-dermatophyte mechanisms by sorbitol and ergosterol assay, HPLC-based ergosterol test, enzyme-linked immunosorbent assay and mitochondrial enzyme activity test.

Results. HQD was able to inhibit the growth of T. rubrum significantly, with an MIC of 3.125 mg ml−1 and an MFC of 12.5 mg ml−1. It also significantly inhibited the hyphal growth, conidia germination and biomass growth of T. rubrum in a dose-dependent manner, and induced structural damage in different degrees for T. rubrum cells. HQD showed no effect on cell wall integrity, but was able to damage the cell membrane of T. rubrum by interfering with ergosterol biosynthesis, involving the reduction of squalene epoxidase (SE) and sterol 14α-demethylase P450 (CYP51) activities, and also affect the malate dehydrogenase (MDH), succinate dehydrogenase (SDH) and ATPase activities of mitochondria.

Conclusion. These results revealed that HQD had significant anti-dermatophyte activity, which was associated with destroying the cell membrane and affecting the enzyme activities of mitochondria.
Loss of function inRBBP5results in a syndromic neurodevelopmental disorder associated with microcephaly
Authors: Huang Yue , Jay Kristy L. , Huang Alden Yen-Wen , Wan Jijun , Jangam Sharayu V. , Chorin Odelia , Rothschild Annick , Barel Ortal , Mariani Milena , Iascone Maria , Xue Han ,   Undiagnosed Diseases Network, Huang Jing , Mignot Cyril , Boris Keren , Saillour Virginie , Mah-Som Annelise Y. , Sacharow Stephanie , Rajabi Farrah , Costin Carrie , Yamamoto Shinya , Kanca Oguz , Bellen Hugo J. , Rosenfeld Jill A. , Palmer Christina G S , Nelson Stanley F. , Wangler Michael F. , Martinez-Agosto Julian A
Published: February 2024

Purpose

Epigenetic dysregulation has been associated with many inherited disorders.RBBP5encodes a core member of the protein complex that methylates histone 3 lysine-4 (H3K4) and has not been implicated in human disease.

Methods

We identify five unrelated individuals withde novoheterozygous pathogenic variants inRBBP5. Three truncating and two missense variants were identified in probands with neurodevelopmental symptoms including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenicDrosophilamodels.

Results

Both missense p.T232I and p.E296D variants affect evolutionarily conserved amino acids and are expected to interfere with the interface between RBBP5 and the histones. InDrosophila,ubiquitous overexpression of humanRBBP5is lethal in the larval developmental stage. Loss ofRbbp5leads to a reduction in brain size, and the human reference, p.T232I, or p.E296D variant transgenes fail to rescue loss ofRbbp5.Expression of either missense variant in anRbbp5null background results in a less severe microcephaly phenotype than the human reference, indicating both p.T232I and p.E296D variants are loss-of-function alleles.

Conclusion

De novoheterozygous variants inRBBP5are associated with a syndromic neurodevelopmental disorder.

Graphical abstract
Large- and Small-Animal Studies of Safety, Pharmacokinetics (PK), and Biodistribution of Inflammasome-Targeting Nanoligomer in the Brain and Other Target Organs
Authors: Risen Sydney , Kusick Breonna , Sharma Sadhana , Gilberto Vincenzo S. , Brindley Stephen , Aguilar Mikayla , Brown Jared M. , McGrath Stephanie , Chatterjee Anushree , Moreno Julie A. , Nagpal Prashant
Published: February 2024

Immune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions and multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids offer some relief for systemic inflammation for some organs, many patients never achieve remission and such drugs do not cross the blood-brain barrier making them ineffective for tackling neuroinflammation. Especially in the brain, unintended activation of microglia and astrocytes is hypothesized to be directly or indirectly responsible for Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease (PD), and Alzheimer’s Disease (AD). Recent studies have also shown that targeting inflammasome and specific immune targets can be beneficial for these diseases. Further, our previous studies have shown targeting NF-κB and NLRP3 through brain penetrant Nanoligomer cocktail SB_NI_112 (abbreviated to NI112) can be therapeutic for several neurodegenerative diseases. Here we show safety-toxicity studies, followed by pharmacokinetics (PK) and biodistribution in small- (mice) and large-animal (dog) studies of this inflammasome-targeting Nanoligomer cocktail NI 112. We conducted studies using four different routes of administration: intravenous (IV), subcutaneous (SQ), intraperitoneal (IP), and intranasal (IN), and identified the drug concentration over time using inductively coupled plasma mass spectrometry (ICP-MS) in the blood serum, the brain (including different brain regions), and other target organs like liver, kidney, and colon. Our results indicate the Nanoligomer cocktail has a strong safety profile, and shows high biodistribution (F ∼0.98) and delivery across multiple routes of administration. Further analysis showed high brain bioavailability with a ratio of NI112 in brain tissue to blood serum ∼30%. Our model accurately shows dose scaling, translation between different routes of administration, and interspecies scaling. These results provide an excellent platform for human clinical translation and predicting therapeutic dosage between different routes of administration.
Variability of immune gene expression among different groups within ant colonies show multifaceted response to infection by a non-lethal ectoparasitic fungus
Authors: Orbán-Bakk Kincső , Schultner Eva , Heinze Jürgen , Markó Bálint , Csata Enikő
Published: February 2024

Social insect colonies are known to be targeted by a wide variety of different parasites and pathogens because of their high host abundance. However, within a colony, the level of risk to exposure could vary among individuals depending on their role. Unlike many known parasites, which mostly target specific groups of individuals, e.g. foragers, the myrmecoparasitic fungusRickia wasmanniiinfects entire ant colonies, being linked to subtle changes in physiology, morphology and behaviour. We investigated how different groups within the colonies respond to being exposed to the fungus by measuring the expression of the genesdefensin 1andprophenoloxidase, both vital components of ant immunity. We found that workers, queens and broods varied in their immune response. Workers displayed diverse profiles, with variable responses to infection: in same-age workers, bothprophenoloxidaseanddefensin 1levels exhibited increases in correlation with pathogen loads. Queens exhibited a more pronounced immune response. Highly infected queens had a heightened immune response. Larvae did not show a discernible response. Morphological and physiological characteristics had limited effects on gene expression, except in the case of queens, where larger individuals displayed higherdefensin 1expression. Our study shows that these divergent responses likely stem from the differing physiological needs and priorities of various groups within the colony.

Highlights

In same-age workers,prophenoloxidaseanddefensin 1levels increased with pathogen loads.

Body size affecteddefensin 1expression in a caste-specific manner: larger queens displayed higher expression.

Infection did not elicit any specific response in larvae.

The diverse response to infection likely arise from distinct physiological needs and priorities within colony groups.
Functional genomic screening inKomagataella phaffiienabled by high-activity CRISPR-Cas9 library
Authors: Tafrishi Aida , Trivedi Varun , Xing Zenan , Li Mengwan , Mewalal Ritesh , Culter Sean , Blaby Ian , Wheeldon Ian
Published: February 2024

CRISPR-based high-throughput genome-wide loss-of-function screens are a valuable approach to functional genetics and strain engineering. The yeastKomagataella phaffiiis a host of particular interest in the biopharmaceutical industry and as a metabolic engineering host for proteins and metabolites. Here, we design and validate a highly active 6-fold coverage genome-wide sgRNA library for this biotechnologically important yeast containing 30,848 active sgRNAs targeting over 99% of its coding sequences. Conducting fitness screens in the absence of functional non-homologous end joining (NHEJ), the dominant DNA repair mechanism inK. phaffii, provides a quantitative means to assess the activity of each sgRNA in the library. This approach allows for the experimental validation of each guide’s targeting activity, leading to more precise screening outcomes. We used this approach to conduct growth screens with glucose as the sole carbon source and identify essential genes. Comparative analysis of the called gene sets identified a core set ofK. phaffiiessential genes, many of which relate to protein production, secretion, and glycosylation. The high activity, genome-wide CRISPR library developed here enables functional genomic screening inK. phaffii, applied here to gene essentiality classification, and promises to enable other genetic screens.

Highlights

Designed and validated a high activity genome-wide CRISPR-Cas9 library forK. phaffii

Disabling NHEJ DNA repair enables the generation of genome-wide guide activity profiles

Activity-corrected fitness screens identify a high confidence set of essential genes inK. phaffii

Protein production, secretion, and glycosylation pathways are essential inK. phaffiibut not in other yeasts
Innate floral object identification in the generalist solitary hoverfly pollinatorEristalinus aeneus
Authors: Mishra Aditi , Jain Anupreksha , Iyer Padmapriya S , Suryanarayanan Ashwin , Nordström Karin , Olsson Shannon B.
Published: February 2024

All animals must locate and identify food for their survival. Most insects are solitary. Newly emerged solitary insects must therefore employ innate identification of food cues to locate relevant nutritive objects from a distance. Innate preferences for food cues should be both specific enough to allow discrimination between food and non-food objects and general enough to allow for the variety of food objects relevant to each species’ ecology. How insects with small nervous systems are able to encode these cues innately is an area of intense study for ecologists and neuroscientists alike. Here, we used the solitary generalist pollinatorEristalinus aeneusto understand how the innate search template used to identify multiple floral species can arise through a small number of sensory cues spanning multiple modalities. We found that innate floral choices of the hoverflyE. aeneusare a product of contextual integration of broad, plant-based olfactory cues and visual cues, where a combination of radial symmetry and reflection in the 500-700 nm wavelength range was particularly important. Our study, therefore, shows how tiny brains can efficiently encode multimodal cues to identify multiple relevant objects without prior experience.
Program Directors’ Perspectives on Duty Hours Following the Physicians’ Work Style Reforms in Japan
Authors: Shikino Kiyoshi , Nishizaki Yuji , Nagasaki Kazuya , Kobayashi Hiroyuki , Kataoka Koshi , Shimizu Taro , Tokuda Yasuharu
Published: February 2024

Background

In anticipation of Japan’s physician work style reforms scheduled for April 2024, which will restrict physicians’ overtime duty hours to under 960 (Level A) or 1920 (Level C-1) hours per year, this study evaluates the potential impact on clinical resident physicians’ training environments through the lens of residency program directors.

Methods

A cross-sectional survey was administered to program directors from 701 facilities associated with the 2023 General Medicine-In Training Examination (GM-ITE), capturing responses regarding their planned level of overtime, perceptions of optimal working hours for training efficacy, and items considered as duty hours.

Results

Out of the 701 facilities, 254 responded (36.2% response rate), with a predominant inclination towards adopting Level A (83.5%). A consensus emerged favoring 40 overtime duty hours per month as optimal, significantly lower than previous suggestions of 60–65 hours per week. The study also delineated the classification of activities as duty hours, with patient procedures and mandatory educational sessions identified as such, while self-improvement was largely not considered duty.

Discussion

The findings indicate a substantial shift from previously recommended optimal duty hours towards a more conservative approach. This shift may reflect a proactive adaptation to upcoming regulatory changes and raises questions about the potential impact on the quality of clinical training. The distinction between educational activities and duty hours underscores the need for clarity within the impending work style reforms.
Fine-grained neural coding of bodies and body parts in human visual cortex
Authors: Garcia Ramirez Jesus , Vanhoyland Michael , Apurva Murty Ratan N. , Decramer Thomas , Van Paesschen Wim , Bracci Stefania , Op de Beeck Hans , Kanwisher Nancy , Janssen Peter , Theys Tom
Published: February 2024

The visual image of a human body provides a valuable source of socially relevant information. However, our understanding of the neuronal mechanisms underlying body perception in humans remains limited given the spatiotemporal constraints of functional imaging. Here we recorded multi-unit spiking activity in two neurosurgical patients in or near the extrastriate body area (EBA), a critical region for body perception. Our recordings revealed a strong preference for human bodies over a large range of control stimuli. Notably, this preference was driven by a distinct selectivity for body parts. Moreover, the observed body selectivity generalized to non-photographic depictions of bodies such as silhouettes and stick figures. Overall, our study provides an unprecedented access into the representation of bodies in the human visual cortex to bridge the gap between human neuroimaging and macaque electrophysiology studies, and form a solid basis for computational models of human body processing.
Antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) against influenza A virus
Authors: Lim Chie Min , Lal Sunil Kumar , Isa Nurulfiza Mat , Omar Abdul Rahman , Choo Wee Sim
Published: February 2024

Seasonal influenza affects millions of lives worldwide, with influenza A virus (IAV) responsible for pandemics and annual epidemics, causing the most severe illnesses resulting in patient hospitalizations or death. With IAV threatening the next global influenza pandemic, it is a race against time to search for antiviral drugs. Betacyanins are unique nitrogen-containing and water-soluble reddish-violet pigments that have been reported to possess antiviral properties against dengue virus. The objective of this study was to examine the antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) on IAV-infected lung epithelial A549 cells. HPLC and LC-MS analysis of extracted betacyanin showed four betacyanins in the betacyanin fraction, namely phyllocactin, hylocerenin, betanin, and isobetanin. Cytotoxicity assay showed that betacyanin fractions were not cytotoxic to A549 cells at concentrations below 100 µg/mL. Betacyanin fraction concentrations of 12.5, 25.0, and 50.0 µg/mL prevented the formation of viral cytopathic effect and reduced virus titer in IAV-infected cells up to 72 h. A downregulation of protein and mRNA nucleoprotein expression levels was observed after treatment with 25.0 and 50.0 µg/mL of betacyanin fraction after 24 h, thereby providing evidence for the anti-viral activity of betacyanin from red pitahaya against IAVin vitro.
Human color constancy in cast shadows
Authors: Morimoto Takuma , Sato Masayuki , Sunaga Shoji , Uchikawa Keiji
Published: February 2024

Most natural scenes contain cast shadows to a varying extent. Illuminant conditions inside and outside the shadow typically differ largely both in intensity and in chromaticity. Nevertheless, our daily experiences suggest that colored materials appear to have the same color in shadows even though the reflected light from the material might be very different. Two experiments were conducted to reveal mechanisms that support human color constancy in cast shadows. In all experiments we built a real scene that consisted of colored hexagons illuminated by two independent liquid crystal projectors simulating “sunlight” and “skylight”, respectively. A part of the scene included a cast shadow under which observers were instructed to change the luminance and the chromaticity of a test field so that it appeared as a full-white paper under the shadow. The color of the skylight was manipulated, testing if our visual system uses a prior that the skylight is typically bluish or yellowish to achieve color constancy. We also created a condition where a cast shadow is not recognized as a shadow. Results showed that color constancy generally holds well in shadows and changing skylight color had little effect. Recognizing a cast shadow as a shadow also had no effect. Overall, these results are consistent with our daily experiences that we stably judge objects’ color even in shadows, providing a key step to reveal mechanisms of color perception in real-world scenes where lighting conditions spatially vary.
Characterization of the common genetic variation in the Spanish population of Navarre
Authors: Maillo Alberto , Huergo Estefania , Apellániz-Ruiz María , UrruDa Edurne , Miranda María , Salgado Josefa , Pasalodos-Sánchez Sara , Delgado-Mora Luna , Teijido Óscar , Goicoechea Ibai , Carmona Rosario , Perez-Florido Javier , Aquino Virginia , Lopez-Lopez Daniel , Peña-Chilet María , Beltrán Sergi , Dopazo Joaquín , Lasa Iñigo , Beloqui Juan José ,   NAGEN-scheme, Alonso Ángel , Gomez-Cabrero David
Published: February 2024

Purpose

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain).

Methods

Genome sequencing data from 358 unrelated individuals of Spanish origin from the Navarrese population were used.

Results

Our analysis revealed 61,410 biallelic exonic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1,069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1,069 SNVs as common in Navarre.

Conclusion

This study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants.
Protocol for a prospective, multicentre, cross-sectional cohort study to assess personal light exposure
Authors: Guidolin Carolina , Aerts Sam , Agbeshie Gabriel Kwaku , Akuffo Kwadwo Owusu , Aydin Sema Nur , Baeza Moyano David , Bolte John , Broszio Kai , Cantarero-García Guadalupe , Didikoglu Altug , González-Lezcano Roberto Alonso , Joosten-Ma Hongli , Melero-Tur Sofia , Nilsson Tengelin Maria , Pérez Gutiérrez María Concepción , Stefani Oliver , Svensson Ingemar , Udovicic Ljiljana , Zauner Johannes , Spitschan Manuel
Published: February 2024

Light profoundly impacts many aspects of human physiology and behaviour, including the synchronization of the circadian clock, the production of melatonin, and cognition. These effects of light, termed the non-visual effects of light, have been primarily investigated in laboratory settings, where light intensity, spectrum and timing can be carefully controlled to draw associations with physiological outcomes of interest. Recently, the increasing availability of wearable light loggers has opened the possibility of studying personal light exposure in free-living conditions where people engage in activities of daily living, yielding findings associating aspects of light exposure and health outcomes, supporting the importance of adequate light exposure at appropriate times for human health. However, comprehensive protocols capturingenvironmental(e.g., geographical location, season, climate, photoperiod) andindividualfactors (e.g., culture, personal habits, behaviour, commute type, profession) contributing to the measured light exposure are currently lacking. Here, we present a protocol that combines smartphone-based experience sampling (experience sampling implementing Karolinska Sleepiness Scale, KSS ratings) and high-quality light exposure data collection at three body sites (near-corneal plane between the two eyes mounted on spectacle, neck-worn pendant/badge, and wrist-worn watch-like design) to capture daily factors related to individuals’ light exposure. We will implement the protocol in an international multi-centre study to investigate the environmental and socio-cultural factors influencing light exposure patterns in Germany, Ghana, Netherlands, Spain, Sweden, and Turkey (minimum n=15, target n=30 per site, minimum n=90, target n=180 across all sites). With the resulting dataset, lifestyle and context-specific factors that contribute to healthy light exposure will be identified. This information is essential in designing effective public health interventions.
Pathways in the brain, heart and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: anin silicostudy hinting cancer incidence
Authors: Chatterjee Shrabonti , Mahata Joydeep , Kateriya Suneel , Anirudhan Gireesh
Published: February 2024

The influence of SARS-CoV-2 non-structural protein in the host’s tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs – the brain, heart, and lungin silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of proteins regulated after SARS-CoV-2 infection and that are interacting with NSP6 interacting proteins. Pathway enrichment analyses provided global insights into biological pathways governed by differentially regulated genes in the three tissues after COVID-19 infection. Many drugs targeting hub genes of tissue-specific protein interactome were found that could be candidates for COVID-19 management. MiRNA-gene network for the tissue-specific regulated proteins was also deduced and comparing gene list targeted by SARS-CoV-2 regulated miRNAs, we found three and two common genes in the brain and lung respectively. Among the five common proteins revealed as potential therapeutic targets across the three tissues, Galectin3 (LGALS3) that was upregulated in the heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer positively and is found in multiple cancers. COVID-19 infection also causes myocardial inflammation and heart failure (HF). HF is observed to be increasing cancer incidence. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies in this direction and cancer surveillance especially with the present scenario of long COVID-19 and recurrent COVID-19 infections.

Graphical Abstract
Phages reconstitute NAD+to counter bacterial immunity
Authors: Osterman Ilya , Samra Hadar , Rousset Francois , Loseva Elena , Itkin Maxim , Malitsky Sergey , Yirmiya Erez , Millman Adi , Sorek Rotem
Published: February 2024

Bacteria defend against phage infection via a variety of antiphage defense systems. Many defense systems were recently shown to deplete cellular nicotinamide adenine dinucleotide (NAD+) in response to infection, by breaking NAD+to ADP-ribose (ADPR) and nicotinamide. It was demonstrated that NAD+depletion during infection deprives the phage from this essential molecule and impedes phage replication. Here we show that a substantial fraction of phages possess enzymatic pathways allowing reconstitution of NAD+from its degradation products in infected cells. We describe NAD+reconstitution pathway 1 (NARP1), a two-step pathway in which one enzyme phosphorylates ADPR to generate ADPR-pyrophosphate (ADPR-PP), and the second enzyme conjugates ADPR- PP and nicotinamide to generate NAD+. Phages encoding the NARP1 pathway can overcome a diverse set of defense systems, including Thoeris, DSR1, DSR2, SIR2-HerA, and SEFIR, all of which deplete NAD+as part of their defensive mechanism. Phylogenetic analyses show that NARP1 is primarily encoded on phage genomes, suggesting a phage- specific function in countering bacterial defenses. A second pathway, NARP2, allows phages to overcome bacterial defenses by building NAD+via metabolites different than ADPR-PP. Our findings report a unique immune evasion strategy where viruses rebuild molecules depleted by defense systems, thus overcoming host immunity.
Antivirals for Monkeypox Virus: Proposing an Effective Machine/Deep Learning Framework
Authors: Hashemi S. Morteza , Zabihian Arash , Hajsaeedi Masih , Hooshmand Mohsen
Published: February 2024

Monkeypox is one of the infectious viruses which caused morbidity and mortality problems in these years. Despite its danger to public health, there is no approved drug to stand and handle Monkeypox. On the other hand, drug repurposing is a promising screening method for the low-cost introduction of approved drugs for emerging diseases and viruses which utilizes computational methods. Therefore, drug repurposing is a promising approach to suggesting approved drugs for the monkeypox virus. This paper proposes a computational framework for monkeypox antiviral prediction. To do this, we have geenrated a new virus-antiviral dataset. Moreover, we applied several machine learning and one deep learning method for virus-antiviral prediction. The suggested drugs by the learning methods have been investigated using docking studies. To the best of our knowledge, this work is the first work to study deep learning methods for the prediction of monkeypox antivirals. The screening results confirm that Tilorone, Valacyclovir, Ribavirin, Favipiravir, and Baloxavir marboxil are effective drugs for monkeypox treatment.
Sociodemographic and health-related differences in non-diabetic hyperglycaemia and undiagnosed type 2 diabetes in the Health Survey for England 2013-2019
Authors: Campbell Emma , Macey Ellie , Kneebone-Hopkins Caitlin , Shine Chris , Nafilyan Vahé , Brown Nicholas , White Martin , Jones Ross , Khunti Kamlesh , Finning Katie
Published: February 2024

Background

Type 2 diabetes is a leading cause of morbidity and mortality but is often undiagnosed. Non-diabetic hyperglycaemia increases T2D risk, and its prevalence is increasing. Understanding the scale of undiagnosed T2D and NDH and identifying at-risk groups is important for detection and intervention.

Methods

We used the 2013-2019 Health Survey for England, an annual, nationally representative, cross-sectional survey. Respondents aged 16+who were not pregnant and had valid HbA1c measurements were included. Outcomes were undiagnosed T2D (HbA1c ≥48 mmol/mol (6·5%) and no T2D diagnosis), and NDH (HbA1c 42-47 mmol/mol (6·0-6·4%) and no diagnosis). Age-adjusted prevalence was estimated across sociodemographic and health-related characteristics. Independent associations were assessed using logistic regression.

Findings

An estimated 2·25% (95% confidence interval 2·05-2·45) of adults had undiagnosed T2D and 11·54% (11·11-11·97) had NDH; an estimated 999,700 and 5,121,800 adults respectively. Prevalence was higher in those with known risk factors for T2D, such as older age or Black or Asian ethnicity. Among those with T2D, 30·21% (28·13-32·28) were undiagnosed. Younger adults and those self-reporting better health were most likely to be undiagnosed. For women, lower BMI, and waist circumference, not being prescribed antidepressants, and living in rural areas, were associated with increased likelihood of being undiagnosed.

Interpretation

Nearly a third of T2D cases were undiagnosed. Some groups less likely to have T2D were most likely to be undiagnosed. NDH is prevalent across all groups, even those considered low risk. Findings highlight the burden of T2D and NDH and emphasise the need for awareness across the population.
Intermittent low-intensity far-UVC irradiation inhibits growth of common mold below threshold limit value
Authors: Mogensen Emilie Hage , Holm Christian Kanstrup
Published: February 2024

Mold infestations in buildings pose significant challenges to human health, affecting both private residences and hospitals. While molds commonly trigger asthma and allergies in the immunocompetent, they can cause life-threatening diseases in the immunocompromised. Currently, there is an unmet need for new strategies to reduce or prevent mold infestations. Far-UVC technology can inactivate microorganisms while remaining safe for humans. This study investigates the inhibitory efficacy of far-UVC light at 222 nm on the growth of common mold-producing fungi, specificallyPenicillium candidum, when delivered in low-dose on-off duty cycles, a configuration consistent with its use in real-world settings. The inhibitory effect of the low-dose duty cycles was assessed on growth induced by i) an adjacent spore-producingP. candidumdonor and ii)P. candidumspores seeded directly onto agar plates. In both setups, the far-UVC light significantly inhibited both vertical and horizontal growth ofP. candidum, even when the UV doses were below the Threshold Value Limit of 23 mJ/cm2. These results suggest that far-UVC light holds the potential to improve indoor air quality by reducing or preventing mold growth, also when people are present.
Comparison of two automated CT perfusion software packages in patients with ischemic stroke presenting within 24 hours of onset
Authors: Kim Nak-Hoon , Ha Sue Young , Park Gihoon , Park Jong-Hyeok , Kim Dongmin , Sunwoo Leonard , Kye Min-Surk , Baik Sung Hyun , Jung Cheolkyu , Ryu Wi-Sun , Kim Beom Joon
Published: February 2024

Background

We compared the ischemic core and hypoperfused tissue volumes estimated by RAPID and JBS-10K, a newly developed automated CT perfusion (CTP) analysis package. We also assessed agreement between ischemic core volumes by two software packages against early follow-up infarct volumes on diffusion-weighted images (DWI).

Methods

This retrospective study analyzed 327 patients admitted to a single stroke center in Korea from January 2021 to May 2023, who underwent CTP scans within 24 hours of onset. The concordance correlation coefficient and Bland-Altman plots were utilized to compare the volumes of ischemic core and hypoperfused tissue volumes between the software packages. Agreement with early (within 3 hours from CTP) follow-up infarct volumes on diffusion-weighted imaging (n=217) was also evaluated.

Results

The mean age was 70.7±13.0 and 137 (41.9%) were female. Ischemic core volumes by JBS-10K and RAPID in the threshold of relative cerebral blood flow (rCBF) < 30% had excellent agreement (ρ = 0.958 [95% CI, 0.949 to 0.966]). Excellent agreement was also observed for time to a maximum of the residue function (Tmax) > 6 seconds between JBS-10K and RAPID (ρ = 0.835 [95% CI, 0.806 to 0.863]). Although early follow-up infarct volume showed substantial agreement in both packages (JBS-10K ρ = 0.751 and RAPID ρ = 0.632), ischemic core volumes at the threshold of rCBF <30% tended to overestimate ischemic core volumes.

Conclusion

JBS-10K and RAPID demonstrated remarkable concordance in estimating the volumes of the ischemic core and hypoperfused area based on CTP within 24 hours from onset.
Targeted Viromes and Total Metagenomes Capture Distinct Components of Bee Gut Phage Communities
Authors: Sbardellati Dino Lorenzo , Vannette Rachel Lee
Published: February 2024

Despite being among the most abundant biological entities on earth, bacteriophage (phage) remain an understudied component of host-associated systems. One limitation to studying host-associated phage is the lack of consensus on methods for sampling phage communities. Here, we compare paired total metagenomes and viral size fraction metagenomes (viromes) as methods for investigating the dsDNA viral communities associated with the GI tract of two bee species: the European honey beeApis melliferaand the eastern bumble beeBombus impatiens. We find that viromes successfully enriched for phage, thereby increasing phage recovery, but only in honey bees. In contrast, for bumble bees, total metagenomes recovered greater phage diversity. Across both bee species, viromes better sampled low abundance and low occupancy phage, while total metagenomes were biased towards sampling temperate phage and the most prominent phage. Additionally, many of the phage captured by total metagenomes were absent altogether from viromes. Comparing between bees, we show that phage communities in commercially reared bumble bees are significantly reduced in diversity compared to honey bees, likely reflecting differences in bacterial titer and diversity. In a broader context, these results highlight the complementary nature of total metagenomes and targeted viromes, especially when applied to host-associated environments. Overall, we suggest that studies interested in assessing total communities of host-associated phage should consider using both approaches. However, given the constraints of virome sampling, total metagenomes may serve to sample phage communities with the understanding that they will preferentially sample dominant and temperate phage.
RNAformer: A Simple yet Effective Model for Homology-Aware RNA Secondary Structure Prediction
Authors: Franke Jörg K.H. , Runge Frederic , Köksal Ryan , Matus Dominika , Backofen Rolf , Hutter Frank
Published: February 2024

Abstract

Predicting RNA secondary structure is essential for understanding RNA function and developing RNA-based therapeutics. Despite recent advances in deep learning for structural biology, its application to RNA secondary structure prediction remains contentious. A primary concern is the control of homology between training and test data. Moreover, deep learning approaches often incorporate complex multi-model systems, ensemble strategies, or require external data. Here, we present theRNAformer, a scalable axial-attention-based deep learning model designed to predict secondary structure directly from a single RNA sequence without additional requirements. We demonstrate the benefits of this lean architecture by learning an accurate biophysical RNA folding model using synthetic data. Trained on experimental data, our model overcomes previously reported caveats in deep learning approaches with a novel homology-aware data pipeline. The RNAformer achieves state-of-the-art performance on RNA secondary structure prediction, out-performing both traditional non-learning-based methods and existing deep learning approaches, while carefully considering sequence and structure similarities.
SpoIIDMP-driven peptidoglycan rearrangement is crucial for ribosome translocation into the spore
Authors: Iwańska Olga , Latoch Przemysław , Kovalenko Mariia , Lichocka Małgorzata , Hołówka Joanna , Serwa Remigiusz , Grzybowska Agata , Zakrzewska-Czerwińska Jolanta , Starosta Agata L.
Published: February 2024

In a spore-forming bacteriumBacillus subtilistranscription and translation are uncoupled and the translational machinery is located at the cell poles. During sporulation the cell undergoes morphological changes including asymmetric septation and chromosome translocation. However, the fate of translational machinery during sporulation has not been described. Here, using a combination of microscopic assays and mass spectrometry, we are tracking the ribosome localisation during sporulation inB. subtilisWT and mutants. We show that the ribosomes are associated with the asymmetric septum which is a functionally important organelle and that peptidoglycan rearrangement is essential for ribosome packing into the forespore. We also show that the feeding tube channel SpoIIIA-SpoIIQ is not required for the ribosome translocation, but is essential for maintaining the chromosome inside the spore.

One-Sentence Summary

Movement of ribosomes into the spore ofB. subtilisfollows chromosome transport and is precisely orchestrated in the cell.
Transcriptional and post-transcriptional mechanisms modulate cyclopropane fatty acid synthase through small RNAs inEscherichia coli
Authors: Bianco Colleen M. , Caballero-Rothar Nancy N. , Ma Xiangqian , Farley Kristen R. , Vanderpool Carin K.
Published: February 2024

The small RNA (sRNA) RydC strongly activatescfa, which encodes the cyclopropane fatty acid synthase. Previous work demonstrated that RydC activation ofcfaincreases conversion of unsaturated fatty acids to cyclopropanated fatty acids in membrane lipids and changes the biophysical properties of membranes, making cells more resistant to acid stress. The conditions and regulators that control RydC synthesis had not previously been identified. In this study, we demonstrate that RydC regulation ofcfais important for resistance to membrane-disrupting conditions. We identify a GntR-family transcription factor, YieP, that repressesrydCtranscription and show that YieP indirectly regulatescfathrough RydC. YieP positively autoregulates its own transcription. We further identify additional sRNA regulatory inputs that contribute to control of RydC andcfa. The translation ofyiePis repressed by the Fnr-dependent sRNA, FnrS, making FnrS an indirect activator ofrydCandcfa.Conversely, RydC activity oncfais antagonized by the OmpR-dependent sRNA OmrB. Altogether, this work illuminates a complex regulatory network involving transcriptional and post-transcriptional inputs that link control of membrane biophysical properties to multiple environmental signals.

Importance

Bacteria experience many environmental stresses that challenge their membrane integrity. To withstand these challenges, bacteria sense what stress is occurring and mount a response that protects membranes. Previous work documented the important roles of small RNA (sRNA) regulators in membrane stress responses. One sRNA, RydC, helps cells cope with membrane-disrupting stresses by promoting changes in the types of lipids incorporated into membranes. In this study, we identified a regulator, YieP, that controls when RydC is produced, and additional sRNA regulators that modulate YieP levels and RydC activity. These findings illuminate a complex regulatory network that helps bacteria sense and respond to membrane stress.
Scalable approach to quantum simulation via projection-based embedding
Authors: Ralli Alexis , Williams de la Bastida Michael , Coveney Peter V.
Published: February 2024

Owing to the computational complexity of electronic structure algorithms running on classical digital computers, the range of molecular systems amenable to simulation remains tightly circumscribed even after many decades of work. Many believe quantum computers will transcend such limitations although in the current era the size and noise of these devices militates against significant progress. Here we describe a chemically intuitive approach that permits a subdomain of a molecule's electronic structure to be calculated accurately on a quantum device, while the rest of the molecule is described at a lower level of accuracy using density functional theory running on a classical computer. We demonstrate that this approach produces improved results for molecules that cannot be simulated fully on current quantum computers but which can be resolved classically at a cheaper level of approximation. The algorithm is tunable, so that the size of the quantum simulation can be adjusted to run on available quantum resources. Therefore, as quantum devices become larger, this method will enable increasingly large subdomains to be studied accurately.

Published by the American Physical Society
2024