bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci
Authors: Croucher Nicholas J. , Campo Joseph J. , Le Timothy Q. , Pablo Jozelyn V. , Hung Christopher , Teng Andy A. , Turner Claudia , Nosten François , Bentley Stephen D. , Liang Xiaowu , Turner Paul , Goldblatt David
Published: January 2024

Streptococcus pneumoniae (pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. This study characterises the immunoglobulin G (IgG) repertoire recognising pneumococci from birth to 24 months old (mo) in a prospectively-sampled cohort of 63 children using a panproteome array. IgG levels are highest at birth, due to transplacental transmission of maternal antibodies. The subsequent emergence of responses to individual antigens exhibit distinct kinetics across the cohort. Stable differences in the strength of individuals’ responses, correlating with maternal IgG concentrations, are established by 6 mo. By 12 mo, children develop unique antibody profiles that are boosted by re-exposure. However, some proteins only stimulate substantial responses in adults. Integrating genomic data on nasopharyngeal colonisation demonstrates rare pneumococcal antigens can elicit strong IgG levels post-exposure. Quantifying such responses to the diverse core loci (DCL) proteins is complicated by cross-immunity between variants. In particular, the conserved N terminus of DCL protein zinc metalloprotease B provokes the strongest early IgG responses. DCL proteins’ ability to inhibit mucosal immunity likely explains continued pneumococcal carriage despite hosts’ polyvalent antibody repertoire. Yet higher IgG levels are associated with reduced incidence, and severity, of pneumonia, demonstrating the importance of the heterogeneity in response strength and kinetics across antigens and individuals.
Animating hydrogel knotbots with topology-invoked self-regulation
Authors: Zhu Qing Li , Liu Weixuan , Khoruzhenko Olena , Breu Josef , Hong Wei , Zheng Qiang , Wu Zi Liang
Published: January 2024

Steering soft robots in a self-regulated manner remains a grand challenge, which often requires continuous symmetry breaking and recovery steps for persistent motion. Although structural morphology is found significant for robotic functions, geometric topology has rarely been considered and appreciated. Here we demonstrate a series of knotbots, namely hydrogel-based robots with knotted structures, capable of autonomous rolling and spinning/rotating motions. With symmetry broken by external stimuli and restored by self-regulation, the coupling between self-constraint-induced prestress and photothermal strain animates the knotbots continuously. Experiments and simulations reveal that nonequilibrium processes are regulated dynamically and cooperatively by self-constraints, active deformations, and self-shadowing effect of the photo-responsive gel. The active motions enable the knotbots to execute tasks including gear rotation and rod climbing. This work paves the way to devise advanced soft robots with self-regulated sustainable motions by harnessing the topology.
Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation
Authors: Accogli Andrea , Shakya Saurabh , Yang Taewoo , Insinna Christine , Kim Soo Yeon , Bell David , Butov Kirill R. , Severino Mariasavina , Niceta Marcello , Scala Marcello , Lee Hyun Sik , Yoo Taekyeong , Stauffer Jimmy , Zhao Huijie , Fiorillo Chiara , Pedemonte Marina , Diana Maria C. , Baldassari Simona , Zakharova Viktoria , Shcherbina Anna , Rodina Yulia , Fagerberg Christina , Roos Laura Sønderberg , Wierzba Jolanta , Dobosz Artur , Gerard Amanda , Potocki Lorraine , Rosenfeld Jill A. , Lalani Seema R. , Scott Tiana M. , Scott Daryl , Azamian Mahshid S. , Louie Raymond , Moore Hannah W. , Champaigne Neena L. , Hollingsworth Grace , Torella Annalaura , Nigro Vincenzo , Ploski Rafal , Salpietro Vincenzo , Zara Federico , Pizzi Simone , Chillemi Giovanni , Ognibene Marzia , Cooney Erin , Do Jenny , Linnemann Anders , Larsen Martin J. , Specht Suzanne , Walters Kylie J. , Choi Hee-Jung , Choi Murim , Tartaglia Marco , Youkharibache Phillippe , Chae Jong-Hee , Capra Valeria , Park Sung-Gyoo , Westlake Christopher J.
Published: January 2024

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.
Emergence of nodal Bogoliubov quasiparticles across the transition from the pseudogap metal to the d-wave superconductor
Authors: Christos Maine , Sachdev Subir
Published: January 2024

We model the pseudogap state of the hole- and electron-doped cuprates as a metal with hole and/or electron pocket Fermi surfaces. In the absence of long-range antiferromagnetism, such Fermi surfaces violate the Luttinger requirement of enclosing the same area as free electrons at the same density. Using the Ancilla theory of such a pseudogap state, we describe the onset of conventional d-wave superconductivity by the condensation of a charge e Higgs boson transforming as a fundamental under the emergent SU(2) gauge symmetry of a background π-flux spin liquid. In all cases, we find that the d-wave superconductor has gapless Bogoliubov quasiparticles at 4 nodal points on the Brillouin zone diagonals with significant velocity anisotropy, just as in the BCS state. This includes the case of the electron-doped pseudogap metal with only electron pockets centered at wavevectors (π, 0), (0, π), and an electronic gap along the zone diagonals. Remarkably, in this case, too, gapless nodal Bogoliubov quasiparticles emerge within the gap at 4 points along the zone diagonals upon the onset of superconductivity.
Sweet taste receptors play roles in artificial sweetener-induced enhanced urine output in mice
Authors: Cai Shuangfeng , Xie Ningning , Zheng Ling , Li Quan , Zhang Siyu , Huang Qinghua , Luo Wei , Wu Mei , Wang Yidan , Du Yilun , Deng Shao-ping , Cai Lei
Published: January 2024

Sweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear. In this study, we investigated the relationship between urinary excretion and the sweet taste receptor expression in mice after three artificial sweeteners exposure in a higher or lower concentration via animal behavioral studies, western blotting, and real-time quantitative PCR experiment in rodent model. Our results showed that high dose of acesulfame potassium and saccharin can significantly enhance the urine output and there was a positive correlation between K+ and urination volume. The acesulfame potassium administration assay of T1R3 knockout mice showed that artificial sweeteners may affect the urine output directly through the sweet taste signaling pathway. The expression of T1R3 encoding gene can be up-regulated specifically in bladder but not in kidney or other organs we tested. Through our study, the sweet taste receptors, distributing in many tissues as bladder, were indicated to function in the enhanced urine output. Different effects of long-term exposure to the three artificial sweeteners were shown and acesulfame potassium increased urine output even at a very low concentration.
Exploring chronic and transient tumor hypoxia for predicting the efficacy of hypoxia-activated pro-drugs
Authors: Mathur Shreya , Chen Shannon , Rejniak Katarzyna A.
Published: January 2024

Hypoxia, a low level of oxygen in the tissue, arises due to an imbalance between the vascular oxygen supply and oxygen demand by the surrounding cells. Typically, hypoxia is viewed as a negative marker of patients’ survival, because of its implication in the development of aggressive tumors and tumor resistance. Several drugs that specifically target the hypoxic cells have been developed, providing an opportunity for exploiting hypoxia to improve cancer treatment. Here, we consider combinations of hypoxia-activated pro-drugs (HAPs) and two compounds that transiently increase intratumoral hypoxia: a vasodilator and a metabolic sensitizer. To effectively design treatment protocols with multiple compounds we used mathematical micro-pharmacology modeling and determined treatment schedules that take advantage of heterogeneous and dynamically changing oxygenation in tumor tissue. Our model was based on data from murine pancreatic cancers treated with evofosfamide (as a HAP) and either hydralazine (as a vasodilator), or pyruvate (as a metabolic sensitizer). Subsequently, this model was used to identify optimal schedules for different treatment combinations. Our simulations showed that schedules of HAPs with the vasodilator had a bimodal distribution, while HAPs with the sensitizer showed an elongated plateau. All schedules were more successful than HAP monotherapy. The three-compound combination had three local optima, depending on the HAPs clearance from the tissue interstitium, each two-fold more effective than baseline HAP treatment. Our study indicates that the three-compound therapy administered in the defined order will improve cancer response and that designing complex schedules could benefit from the use of mathematical modeling.
Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial
Authors: Verschoor Yara L. , van de Haar Joris , van den Berg José G. , van Sandick Johanna W. , Kodach Liudmila L. , van Dieren Jolanda M. , Balduzzi Sara , Grootscholten Cecile , IJsselsteijn Marieke E. , Veenhof Alexander A. F. A. , Hartemink Koen J. , Vollebergh Marieke A. , Jurdi Adham , Sharma Shruti , Spickard Erik , Owers Emilia C. , Bartels-Rutten Annemarieke , den Hartog Peggy , de Miranda Noel F. C. C. , van Leerdam Monique E. , Haanen John B. A. G. , Schumacher Ton N. , Voest Emile E. , Chalabi Myriam
Published: January 2024

Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46–88%) patients, including 9 (45%, 95% confidence interval 23–68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1)+CD8+ T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835.
Changes in oscillatory patterns of microstate sequence in patients with first-episode psychosis
Authors: Zhou Dong-Dong , Li Hong-Zhi , Wang Wo , Kuang Li
Published: January 2024

We aimed to utilize chaos game representation (CGR) for the investigation of microstate sequences and explore its potential as neurobiomarkers for psychiatric disorders. We applied our proposed method to a public dataset including 82 patients with first-episode psychosis (FEP) and 61 control subjects. Two time series were constructed: one using the microstate spacing distance in CGR and the other using complex numbers representing the microstate coordinates in CGR. Power spectral features of both time series and frequency matrix CGR (FCGR) were compared between groups and employed in a machine learning application. The four canonical microstates (A, B, C, and D) were identified using both shared and separate templates. Our results showed the microstate oscillatory pattern exhibited alterations in the FEP group. Using oscillatory features improved machine learning performance compared with classical features and FCGR. This study opens up new avenues for exploring the use of CGR in analyzing EEG microstate sequences. Features derived from microstate sequence CGR offer fine-grained neurobiomarkers for psychiatric disorders.
Stress field disruption allows gas-driven microdeformation in bentonite to be quantified
Authors: Graham Caroline C. , Harrington Jon F.
Published: January 2024

Geological disposal of radioactive waste is being planned by many countries. Bentonite clay is often included in facility design, providing a barrier to radionuclide migration. Gas, generated by the waste or corrosion of waste canisters, may disrupt the properties of the bentonite. Robust prediction of this interaction is, therefore, necessary to demonstrate safe facility evolution. In some cases, gas may deform the clay, resulting in localised flow; however, the nature of this deformation has been widely debated. Accurate numerical representation of this behaviour has been limited by a shortage of information on the degree/distribution of deformation. Using experimental data from gas injection tests in bentonite, we show that first order fluctuations in the stress field can provide this information. We show that hundreds of microdeformation events can be detected, with similar characteristics to established fracturing phenomena, including earthquakes and acoustic emissions. We also demonstrate that stress field disruption (i) is spatially localised and (ii) has characteristics consistent with gas pathway ‘opening’ and ‘closure’ as gas enters and exits the clay, respectively. This new methodology offers fundamental insight and a new opportunity to parameterise and constrain gas advection models in clays and shales, substantially improving our capacity for safe facility design.
The biogas upgrading from landfill leachate pretreated with low-frequency ultrasonic: anaerobic digestion performances and energy balance
Authors: Hosseinzadeh Ali , Gitipour Saeid , Mehrdadi Nasser
Published: January 2024

The efficient biogas production from landfill leachate (LL) is one of hot topics in anaerobic digestion systems. Higher bioavailability of LL can be achieved by application a feasible and promising pretreatment technologies in order to utilize as a substrate for anaerobic reactors. Here, the enhanced bioavailabity of LL using the low-frequency ultrasonic process and energy balance in anaerobic digestion process was estimated within incubation period of 24 days. The optimal performance of low-frequency ultrasonic for LL biodegradability index: sCOD and TVFA were estimated under influencing parameters: ultrasonic density (UD) (0.02–0.14 W/mL) and Ultrasonic time (UT) (0–12 min). Moreover, the effects of low-frequency ultrasonic pretreatment process on biogas production in batch mode anaerobic reactors operated at 37 ± 1 °C were surveyed for daily and cumulative methane production, operational performance and energy balance. An increased sCOD (820 mg/L) and TVFA (659 mg/L) were observed under optimum codition: UD (0.1 W/mL) and UT (10 min). The highest methane production (430 mL) was found in reactor 4, where %15 volume ratio of LL pretreated with low frequency ultrasonic were feed in. Energy balance assessment indicated that output energy for anaerobic reactors assissted with ultrasonic in range of + 6.99 and + 7.98 kJ/g VS removed. Therefore, incorporation the low-frequency ultrasonic and digestion process revealed a promising and economic technique to improve biomethane potential and energy balance from LL.
In silico anti-alzheimer study of phytochemicals from Lamiaceae family through GSK3-β inhibition
Authors: Zareei Sara , Pourmand Saeed , Eskandarzadeh Marzieh , Massahi Shokoufeh
Published: January 2024

Glycogen synthase kinase 3-beta (GSK3-β) is a serine-threonine protease expressed in the brain, and its hyperactivity is considered the underlying cause of Alzheimer’s disease. This enzyme requires an ATP molecule in its N-terminal lobe to phosphorylate its substrates, with the most important substrate being the Tau protein. This study focuses on the inhibitory mechanism of four naturally occurring compounds—apigenin, luteolin, rosmarinic acid, and salvianolic acid—from the Laminaceae family against GSK3-β. The orientation of the ligands within the ATP-binding pocket of GSK3-β and their binding energy were determined through molecular docking. Additionally, molecular dynamics simulations was conducted to study the conformational changes induced by the ligands in the protein structure. The results showed that apigenin and salvianolic acid achieved deeper parts of the cavity compared to luteolin and rosmarinic acid and formed stable complexes with the enzyme. In the rosmarinic acid complex, the enzyme exhibited the most exposed conformation. On the other hand, luteolin binding caused a small closure of the opening, suggesting a potentially ATP-competitive role. Our results suggest these compounds as lead candidates for the design of GSK3-β inhibitors.
Investigation of ternary Zn–Co–Fe layered double hydroxide as a multifunctional 2D layered adsorbent for moxifloxacin and antifungal disinfection
Authors: Mahmoud Rehab , Kotb Nada M. , GadelHak Yasser , El-Ela Fatma I. Abo , Shehata Ayman Z. , Othman Sarah I. , Allam Ahmed A. , Rudayni Hassan Ahmed , Zaher Amal
Published: January 2024

Layered double hydroxides have recently gained wide interest as promising multifunctional nanomaterials. In this work, a multifunctional ternary Zn–Co–Fe LDH was prepared and characterized using XRD, FTIR, BET, TEM, SEM, and EDX. This LDH showed a typical XRD pattern with a crystallite size of 3.52 nm and a BET surface area of 155.9 m2/g. This LDH was investigated, for the first time, as an adsorbent for moxifloxacin, a common fluoroquinolones antibiotic, showing a maximum removal efficiency and equilibrium time of 217.81 mg/g and 60 min, respectively. Its antifungal activity, for the first time, was investigated against Penicillium notatum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucor fungi at various concentrations (1000–1.95 µg/mL). This LDH was found to be effective against a variety of fungal strains, particularly Penicillium and Mucor species and showed zones of inhibition of 19.3 and 21.6 mm for Penicillium and Mucor, respectively, with an inhibition of 85% for Penicillium species and 68.3% for Mucormycosis. The highest antifungal efficacy results were obtained at very low MIC concentrations (33.3 and 62 µg/ml) against Penicillium and Mucor, respectively. The results of this study suggest a promising multifunctional potential of this LDH for water and wastewater treatment and disinfection applications.
Biomarkers of axonal damage to favor early diagnosis in variant transthyretin amyloidosis (A-ATTRv)
Authors: González-Moreno Juan , Gragera-Martínez Álvaro , Rodríguez Adrián , Borrachero-Garro Cristina , García-Garrido Sandra , Barceló Carles , Manovel-Sánchez Ana , Ribot-Sansó Maria Antonia , Ibargüen-González Lesly , Gomila Rosa , Muñoz-Beamud Francisco , Losada-López Inés , Cisneros-Barroso Eugenia
Published: January 2024

Early identification of ATTRv amyloidosis disease onset is still often delayed due to the lack of validated biomarkers of this disease. Light chain neurofilament (NfL) have shown promising results in early diagnosis in this disease, but data is still needed, including with alternative measuring methods. Our aim was to study the levels of NfL measured by ELISA. Furthermore, interstitial matrix metalloproteinase type 1 (MMP-1) serum levels were measured as a potential new biomarker in ATTRv. Serum NfL and MMP-1 were measured using ELISA assays in 90 participants (29 ATTR-V30M patients, 31 asymptomatic V30M-TTR variant carriers and 30 healthy controls). Median NfL levels among ATTRv amyloidosis patients were significantly higher (116 pg/mL vs 0 pg/mL in both comparison groups). The AUC comparing ATTRv amyloidosis patients and asymptomatic carriers was 0.90 and the NfL concentration of 93.55 pg/mL yielded a sensitivity of 79% and a specificity of 87%. NfL levels had a significant positive correlation with NIS values among patients. We found a negative significant correlation between eGFR and NfL levels. Finally, MMP1 levels were not different between groups. Evidence of NfL use for early diagnosis of ATTR-PN amyloidosis is growing. ELISA seems a reliable and available technique for it quantification. Decreased GFR could influence NfL plasma levels.
Boil water notices as health-risk communication: risk perceptions, efficacy, and compliance during winter storm Uri
Authors: Day Ashleigh M. , O’Shay Sydney , Islam Khairul , Seeger Matthew W. , Sperone F. Gianluca , McElmurry Shawn P.
Published: January 2024

Winter Storm Uri was a disaster that impacted much of the United States during February of 2021. During and after the storm, Texas and Oklahoma experienced massive power grid failures. This led to cascading impacts, including water system disruptions and many boil water notices (BWNs). The breakdown of some communication channels and the inability to enact protective actions due to power outages, as well as travel limitations on public roads, complicated the dissemination and implementation of notifications. This research examined individuals’ perceptions of risk, water quality, and BWNs during Uri. Additionally, this study sought to understand if previous experience with a BWN influenced compliance during Uri and how perceived efficacy impacted these variables. Surveying 893 Texans and Oklahomans revealed that most Uri-affected respondents believed the risks associated with BWNs were severe. Income and race were two factors that influenced BWN compliance. Age, gender, and level of education did not influence compliance. Previous experience with BWNs did not increase risk perceptions. Higher levels of perceived efficacy correlated to higher levels of compliance, perceptions of risk, and water quality, much of which support propositions of the Extended Parallel Process Model. Results suggest that pre-disaster planning and communication are imperative to helping reduce risk(s) and enhancing efficacy during a disaster, especially for novel disasters that have cascading risks, like Winter Storm Uri.
A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models
Authors: Hall Ashley , Middlehurst Ben , Cadogan Max A. M. , Reed Xylena , Billingsley Kimberley J. , Bubb Vivien J. , Quinn John P.
Published: January 2024

SINE-VNTR-Alu (SVA) retrotransposons represent mobile regulatory elements that have the potential to influence the surrounding genome when they insert into a locus. Evolutionarily recent mobilisation has resulted in loci in the human genome where a given retrotransposon might be observed to be present or absent, termed a retrotransposon insertion polymorphism (RIP). We previously observed that an SVA RIP ~ 2 kb upstream of LRIG2 on chromosome 1, the ‘LRIG2 SVA’, was associated with differences in local gene expression and methylation, and that the two were correlated. Here, we have used CRISPR-mediated deletion of the LRIG2 SVA in a cell line model to validate that presence of the retrotransposon is directly affecting local expression and provide evidence that is suggestive of a modest role for the SVA in modulating nearby methylation. Additionally, in leveraging an available Hi-C dataset we observed that the LRIG2 SVA was also involved in long-range chromatin interactions with a cluster of genes ~ 300 kb away, and that expression of these genes was to varying degrees associated with dosage of the SVA in both CRISPR cell line and population models. Altogether, these data support a regulatory role for SVAs in the modulation of gene expression, with the latter potentially involving chromatin looping, consistent with the model that RIPs may contribute to interpersonal differences in transcriptional networks.
Sick leave one year after COVID-19 infection: a nationwide cohort study during the first wave in Sweden
Authors: Abzhandadze Tamar , Westerlind Emma , Palstam Annie , Sunnerhagen Katharina S. , Persson Hanna C.
Published: January 2024

This study aimed to investigate the patterns of sick leave, as well as factors associated with sick leave due to COVID-19 during one year after the COVID-19 diagnosis, and sex-related aspects on sick leave. This nationwide study involved 11,902 individuals who received sickness benefits for COVID-19 during the first wave of the pandemic. Data from three Swedish registries were analyzed for sick leave that commenced between March 1 and August 31, 2020, with a follow-up period of 12 months. Sick leave due to COVID-19 was counted as the number of days with sickness benefits and required to include at least one registered COVID-19 diagnosis. The median duration of sick leave was 35 days, and 347 (2.9%) individuals continued their sick leave during the entire follow-up period. Furthermore, 1 year later, the cumulative incidence of sick leave was slightly higher in males (3.5%) compared to females (2.7%). Older age, being single with no children, diagnosed with the virus, medium income level, history of sick leave, and need for inpatient care were significantly associated with a higher duration of sick leave due to COVID-19, both in the total population and when stratified by sex. These results indicated that three out of 100 (3%) patients were still on sick leave 1 year after their COVID-19 diagnosis. Aspects regarding the importance of sick leave duration differed between males and females and comprised sociodemographic characteristics and need for inpatient care. The results indicated the complexity of sick leave due to COVID-19.
A multi-stage anticipated surprise model with dynamic expectation for economic decision-making
Authors: Chan Ho Ka , Toyoizumi Taro
Published: January 2024

There are many modeling works that aim to explain people’s behaviors that violate classical economic theories. However, these models often do not take into full account the multi-stage nature of real-life problems and people’s tendency in solving complicated problems sequentially. In this work, we propose a descriptive decision-making model for multi-stage problems with perceived post-decision information. In the model, decisions are chosen based on an entity which we call the ‘anticipated surprise’. The reference point is determined by the expected value of the possible outcomes, which we assume to be dynamically changing during the mental simulation of a sequence of events. We illustrate how our formalism can help us understand prominent economic paradoxes and gambling behaviors that involve multi-stage or sequential planning. We also discuss how neuroscience findings, like prediction error signals and introspective neuronal replay, as well as psychological theories like affective forecasting, are related to the features in our model. This provides hints for future experiments to investigate the role of these entities in decision-making.
Deep learning-based identification of eyes at risk for glaucoma surgery
Authors: Wang Ruolin , Bradley Chris , Herbert Patrick , Hou Kaihua , Ramulu Pradeep , Breininger Katharina , Unberath Mathias , Yohannan Jithin
Published: January 2024

To develop and evaluate the performance of a deep learning model (DLM) that predicts eyes at high risk of surgical intervention for uncontrolled glaucoma based on multimodal data from an initial ophthalmology visit. Longitudinal, observational, retrospective study. 4898 unique eyes from 4038 adult glaucoma or glaucoma-suspect patients who underwent surgery for uncontrolled glaucoma (trabeculectomy, tube shunt, xen, or diode surgery) between 2013 and 2021, or did not undergo glaucoma surgery but had 3 or more ophthalmology visits. We constructed a DLM to predict the occurrence of glaucoma surgery within various time horizons from a baseline visit. Model inputs included spatially oriented visual field (VF) and optical coherence tomography (OCT) data as well as clinical and demographic features. Separate DLMs with the same architecture were trained to predict the occurrence of surgery within 3 months, within 3–6 months, within 6 months–1 year, within 1–2 years, within 2–3 years, within 3–4 years, and within 4–5 years from the baseline visit. Included eyes were randomly split into 60%, 20%, and 20% for training, validation, and testing. DLM performance was measured using area under the receiver operating characteristic curve (AUC) and precision-recall curve (PRC). Shapley additive explanations (SHAP) were utilized to assess the importance of different features. Model prediction of surgery for uncontrolled glaucoma within 3 months had the best AUC of 0.92 (95% CI 0.88, 0.96). DLMs achieved clinically useful AUC values (> 0.8) for all models that predicted the occurrence of surgery within 3 years. According to SHAP analysis, all 7 models placed intraocular pressure (IOP) within the five most important features in predicting the occurrence of glaucoma surgery. Mean deviation (MD) and average retinal nerve fiber layer (RNFL) thickness were listed among the top 5 most important features by 6 of the 7 models. DLMs can successfully identify eyes requiring surgery for uncontrolled glaucoma within specific time horizons. Predictive performance decreases as the time horizon for forecasting surgery increases. Implementing prediction models in a clinical setting may help identify patients that should be referred to a glaucoma specialist for surgical evaluation.
Predicting the subjective intensity of imagined experiences from electrophysiological measures of oscillatory brain activity
Authors: Arnold Derek H. , Saurels Blake W. , Anderson Natasha , Andresen Isabella , Schwarzkopf Dietrich S.
Published: January 2024

Most people can conjure images and sounds that they experience in their minds. There are, however, marked individual differences. Some people report that they cannot generate imagined sensory experiences at all (aphantasics) and others report that they have unusually intense imagined experiences (hyper-phantasics). These individual differences have been linked to activity in sensory brain regions, driven by feedback. We would therefore expect imagined experiences to be associated with specific frequencies of oscillatory brain activity, as these can be a hallmark of neural interactions within and across regions of the brain. Replicating a number of other studies, relative to a Resting-State we find that the act of engaging in auditory or in visual imagery is linked to reductions in the power of oscillatory brain activity across a broad range of frequencies, with prominent peaks in the alpha band (8–12 Hz). This oscillatory activity, however, did not predict individual differences in the subjective intensity of imagined experiences. For audio imagery, these were rather predicted by reductions within the theta (6–9 Hz) and gamma (33–38 Hz) bands, and by increases in beta (15–17 Hz) band activity. For visual imagery these were predicted by reductions in lower (14–16 Hz) and upper (29–32 Hz) beta band activity, and by an increase in mid-beta band (24–26 Hz) activity. Our data suggest that there is sufficient ground truth in the subjective reports people use to describe the intensity of their imagined sensory experiences to allow these to be linked to the power of distinct rhythms of brain activity. In future, we hope to combine this approach with better measures of the subjective intensity of imagined sensory experiences to provide a clearer picture of individual differences in the subjective intensity of imagined experiences, and of why these eventuate.
Association between gestational weight gain and chronic disease risks in later life
Authors: Kamihara Yuki , Ogawa Kohei , Morisaki Naho , Arata Naoko , Wada Seiji
Published: January 2024

To assess the association between gestational weight gain (GWG) and the risk of developing chronic diseases in later life, this historical cohort study of 318 non-overweight women was conducted between April 2017 and November 2020 at a hospital in Tokyo. Data about GWG in the last pregnancy and the development of any chronic diseases of the subjects were retrieved from the women’s Maternal and Child Health Handbooks and through a questionnaire survey, respectively. The outcomes were chronic diseases, such as diabetes mellitus (DM), hypertension, hyperlipidemia, and being overweight (body mass index [BMI] ≥ 25 kg/m2). Association between GWG and outcomes were assessed using a logistic regression analysis.

There were significant positive linear associations between GWG and the risks of developing DM, hypertension, and being overweight (P = 0.013, 0.050, and 0.017, respectively). After adjusting for later-life BMI, a significant association between GWG and DM (P = 0.025) remained, but the association between GWG and hypertension disappeared. GWG was significantly associated with DM, hypertension, and being overweight later in life. Although the association between GWG and DM was partially independent of BMI later in life, the association between GWG and hypertension was influenced by being overweight later in life.
Radiation-induced changes in energy metabolism result in mitochondrial dysfunction in salivary glands
Authors: Buss Lauren G. , Rheinheimer Brenna A. , Limesand Kirsten H.
Published: January 2024

Salivary glands are indirectly damaged during radiotherapy for head and neck cancer, resulting in acute and chronic hyposalivation. Current treatments for radiation-induced hyposalivation do not permanently restore function to the gland; therefore, more mechanistic understanding of the damage response is needed to identify therapeutic targets for lasting restoration. Energy metabolism reprogramming has been observed in cancer and wound healing models to provide necessary fuel for cell proliferation; however, there is limited understanding of alterations in energy metabolism reprogramming in tissues that fail to heal. We measured extracellular acidification and oxygen consumption rates, assessed mitochondrial DNA copy number, and tested fuel dependency of irradiated primary salivary acinar cells. Radiation treatment leads to increases in glycolytic flux, oxidative phosphorylation, and ATP production rate at acute and intermediate time points. In contrast, at chronic radiation time points there is a significant decrease in glycolytic flux, oxidative phosphorylation, and ATP production rate. Irradiated salivary glands exhibit significant decreases in spare respiratory capacity and increases in mitochondrial DNA copy number at days 5 and 30 post-treatment, suggesting a mitochondrial dysfunction phenotype. These results elucidate kinetic changes in energy metabolism reprogramming of irradiated salivary glands that may underscore the chronic loss of function phenotype.
Unsupervised learning-based approach for detecting 3D edges in depth maps
Authors: Aggarwal Ayush , Stolkin Rustam , Marturi Naresh
Published: January 2024

3D edge features, which represent the boundaries between different objects or surfaces in a 3D scene, are crucial for many computer vision tasks, including object recognition, tracking, and segmentation. They also have numerous real-world applications in the field of robotics, such as vision-guided grasping and manipulation of objects. To extract these features in the noisy real-world depth data, reliable 3D edge detectors are indispensable. However, currently available 3D edge detection methods are either highly parameterized or require ground truth labelling, which makes them challenging to use for practical applications. To this extent, we present a new 3D edge detection approach using unsupervised classification. Our method learns features from depth maps at three different scales using an encoder–decoder network, from which edge-specific features are extracted. These edge features are then clustered using learning to classify each point as an edge or not. The proposed method has two key benefits. First, it eliminates the need for manual fine-tuning of data-specific hyper-parameters and automatically selects threshold values for edge classification. Second, the method does not require any labelled training data, unlike many state-of-the-art methods that require supervised training with extensive hand-labelled datasets. The proposed method is evaluated on five benchmark datasets with single and multi-object scenes, and compared with four state-of-the-art edge detection methods from the literature. Results demonstrate that the proposed method achieves competitive performance, despite not using any labelled data or relying on hand-tuning of key parameters.
Classification of tropical cyclone rain patterns using convolutional autoencoder
Authors: Kim Dasol , Matyas Corene J.
Published: January 2024

Heavy rainfall produced by tropical cyclones (TCs) frequently causes wide-spread damage. TCs have different patterns of rain depending on their development stage, geographical location, and surrounding environmental conditions. However, an objective system for classifying TC rain patterns has not yet been established. This study objectively classifies rain patterns of North Atlantic TCs using a Convolutional Autoencoder (CAE). The CAE is trained with 11,991 images of TC rain rates obtained from satellite precipitation estimates during 2000−2020. The CAE consists of an encoder which compresses the original TC rain image into low-dimensional features and a decoder which reconstructs an image from the compressed features. Then, TC rain images are classified by applying a k-means method to the compressed features from the CAE. We identified six TC rain patterns over the North Atlantic and confirmed that they exhibited unique characteristics in their spatial patterns (e.g., area, asymmetry, dispersion) and geographical locations. Furthermore, the characteristics of rain patterns in each cluster were closely related to storm intensity and surrounding environmental conditions of moisture supply, vertical wind shear, and land interaction. This classification of TC rain patterns and further investigations into their evolution and spatial variability can improve forecasts and help mitigate damage from these systems.
Starch mediates and cements densely magnetite-coating of talc, giving an efficient nano-catalyst for three-component synthesis of imidazo[1,2-c]quinazolines
Authors: Hosseinzadeh Hedyeh , Rad-Moghadam Kurosh , Mehrdad Morteza , Rouhi Somayeh
Published: January 2024

Hot-water-soluble starch (HWSS) was used as a powerful cementing material to produce nano-size conglomerates of talc and magnetite nanoparticles. Coordination of HWSS hydroxyl groups to iron atoms at surface of magnetite leads to grafting and encapsulation of its nanoparticles. The resulting nano-complex showed a higher loading capacity on talc than pristine magnetite nanoparticles. Only a minute amount of HWSS was detected in the fabricated nano-composite Talc\HWSS@Fe3O4. XPS study suggests a considerable interaction between HWSS and Fe3O4 nanoparticles, upon which some of the Fe+3 atoms on surface of Fe3O4 are reduced into Fe+2 atoms. ATR FT-IR spectra of the nano-composite revealed significant delamination of talc sheets on interaction with HWSS-coated Fe3O4 nanoparticles. The nano-composite displayed an efficient catalytic activity in the synthesis of new imidazo[1,2-c]quinazoline derivatives via Grobke–Blackburn–Bienaymé three-component reaction of 4-aminoquinazoline, arylaldehydes and isocyanide. The efficiency of the method was exemplified by synthesizing 7 new products in fairly high yields (68–83%) within short reaction times (24–30 min) using a catalytic amount of the catalyst under solvent-free condition at 120 °C. Clean and fast synthesis of the products and convenient separation of the robust nano-catalyst are the prominent advantages of the present method. The nano-catalyst was properly characterized.
Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis
Authors: Naveed Muhammad , Ali Urooj , Aziz Tariq , Jabeen Khizra , Arif Muhammad Hammad , Alharbi Metab , Alasmari Abdullah F. , Albekairi Thamer H.
Published: January 2024

More than 95% of patients fall victim to primary amoebic meningoencephalitis (PAM), a fatal disease attacking the central nervous system. Naegleria fowleri, a brain-eating microorganism, is PAM's most well-known pathogenic ameboflagellate. Despite the use of antibiotics, the fatality rate continues to rise as no clinical trials have been conducted against this disease. To address this, we mined the UniProt database for pathogenic proteins and selected assumed epitopes to create an mRNA-based vaccine. We identified thirty B-cell and T-cell epitopes for the vaccine candidate. These epitopes, secretion boosters, subcellular trafficking structures, and linkers were used to construct the vaccine candidate. Through predictive modeling and confirmation via the Ramachandran plot (with a quality factor of 92.22), we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: 0.394, instability index: 38.99, antigenicity: 0.8). The theoretical model of immunological simulations indicated favorable responses from both innate and adaptive immune cells, with memory cells expected to remain active for up to 350 days post-vaccination, while the antigen was eliminated from the body within 24 h. Notably, strong interactions were observed between the vaccine construct and TLR-4 (− 11.9 kcal/mol) and TLR-3 (− 18.2 kcal/mol).
Molecular detection and identification of hemotropic Mycoplasma species in dogs and their ectoparasites in Iran
Authors: Beus Kimia , Goudarztalejerdi Ali , Sazmand Alireza
Published: January 2024

Hemotropic Mycoplasma species are vector-borne bacteria that attach and grow on the surface of erythrocytes in various mammals, yet reports of canine hemoplasmosis in Iran are scarce. The aim of this study was molecular detection and identification of hemoplasmas in the blood of dogs (n = 370) from five provinces of Iran and ectoparasites infesting them including Ctenocephalides canis and Pulex irritans fleas, Rhipicephalus sanguineus sensu lato ticks, Heterodoxus spiniger lice and Hippobosca longipennis keds. Hemotropic Mycoplasma spp. pathogens were detected using genus-specific conventional PCRs, and subsequently identified using species-specific PCRs for Mycoplasma haemocanis (Mhc), and Candidatus Mycoplasma haematoparvum (CMhp). Sanger sequencing was then performed to confirm the species. Correlation of infection and risk factors (geographical area, keeping condition, body condition, sex, age, ectoparasite infestation) were analyzed. In total, 210 dogs (56.7%) were tested PCR-positive for hemotropic Mycoplasma spp. Species-specific PCR and sequencing revealed infection with Mhc in 17.8%, with CMhp in 7.02% and co-infection in 31.9% of dogs. Flea infestation, poor body condition, and being older than 3-years-old correlated with hemoplasmosis. In ectoparasites, DNA of hemoplasmas were detected only in fleas i.e. Mhc in P. irritans, CMhp in P. irritans and C. canis, and co-infection in C. canis. To our knowledge, this is the first large-scale molecular epidemiology study of canine hemoplasmosis in Iran. Considering the high prevalence of canine hemoplasmosis all over the country including potentially zoonotic CMhp, effective ectoparasite control strategies, regular examination of dogs, successful chemoprophylaxis and public awareness strategies are advocated.
Surgical site infection after trochanteric and subtrochanteric fractures: a single centre retrospective analysis
Authors: Sator Thomas , Binder Harald , Payr Stephan , Pichler Lorenz , Frenzel Stephan , Hajdu Stefan , Presterl Elisabeth , Tiefenboeck Thomas Manfred
Published: January 2024

Surgical site infection (SSI) following osteosynthesis of trochanteric or subtrochanteric fractures is a rare but serious complication with incidence rate ranging from 1 to 3%. SSIs are associated with higher mortality and increased length of hospital stay resulting in higher healthcare costs and loss of life quality. In this retrospective analysis all patients with SSI following osteosynthesis of trochanteric or subtrochanteric fractures at the Department of Trauma Surgery were identified. We included all surgical procedures performed from 1992 to 2018, using data from electronic health records and SSI-Trauma-Registry. The aim was to describe epidemiological data, as well as to identify parameters correlating with the occurrence of SSI and mortality. Of 2753 patients, 53 (1.9%) developed SSI. Longer operative time was demonstrated among patients with SSI (P = 0.008). Mortality during the first postoperative year was significantly higher in the SSI group (32.1% vs. 19.1%; P = 0.018), with detection of methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA; HR 4.13, CI 95% 1.24–13.80; P = 0.021) or Enterococcus spp. (HR 5.58, CI 95% 1.67–18.65; P = 0.005) being independent risk factors. Male sex (HR 2.25, 95% CI 1.86–2.73; P < 0.001) and higher mean age (HR 1.05, 95% CI 1.04–1.06; P < 0.001) were found to be predictors for 1-year mortality in non-infected patients. SSI rate was low with 1.9% and longer duration of surgery was associated with infection. Patients with SSI had a higher 1-year mortality, with detection of MSSA, MRSA and enterococci significantly increasing the risk of dying. Male sex and higher age were risk factors for one-year mortality in patients without SSI.