bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between body mass index elevation and differentiation in vitamin D receptor gene expression, genetic polymorphism, and oxidative stress in adult Egyptian individuals
Authors: Shaban Nadia Z. , Abdel-Alnaby Mai , Atta Mohamed N. , Abdul-Aziz Ahmed A. , Megahed Fayed
Published: October 2023

Vitamin D plays a central role in maintaining calcium, phosphorus, and bone homeostasis in close interaction with the parathyroid hormone. Obesity is a significant health problem worldwide, particularly in developed nations. The current study was carried out to investigate the possible relationship between body mass index (BMI) elevation and differentiation in 25-hydroxyvitamin D (VD), vitamin D receptor (VDR) gene expression, and genetic polymorphism besides oxidative stress in adult Egyptian individuals. This was done to explore the mechanisms underlying the suggested role of the VD/VDR complex in the pathogenesis of obesity. A total of 70 subjects (30 obese, 25 overweight, and 15 normal, age: 20–50 years, without other chronic diseases) were selected. The study focused on the determination of VD, VDR gene polymorphism, VDR gene expression, alkaline phosphatase, calcium, phosphorus, glucose, lipid profile, oxidative stress including, oxidant (malondialdehyde), and anti-oxidants (reduced glutathione and superoxide dismutase). The results showed that elevation in BMI led to the percentage of the Ff 'allele' becoming predominant, while the percentage of the FF 'allele' was in the normal BMI range. Also, BMI elevation caused significant reductions in VD and VDR expression, with significant elevations in alkaline phosphatase and the levels of calcium and phosphate in serum. Also, oxidative stress increases with increasing BMI. Elevation in BMI causes a reduction in VD concentration and VDR gene expression levels. Also, the percentage of heterozygous mutant genotype Ff 'allele' is predominantly in the obese human, in contrast to normal subjects, where the percentage of homozygous wild genotype FF 'allele' is predominant. In general, the genetic expression and polymorphism of VD and VDR can be used as a genetic marker for predisposition, diagnosis, prognosis, and progression of obesity.
Association between breakthrough infection with COVID-19 and Toxoplasma gondii: a cross-sectional study
Authors: Gouda Marwa A. , AboShabaan Hind S. , Abdelgawad Ahmed S. , Abdel Wahed Aliaa Sabry , A. Abd El-Razik Khaled , Elsaadawy Yara , Abdel-Wahab Ayman. A. , Hawash Yousry
Published: October 2023

The breakthrough infection following COVID-19 vaccination has been a subject of concern recently. Evidence suggests that COVID-19 vaccine efficacy diminishes over time due to multiple factors related to the host, and vaccine. Coinfection with other pathogens was claimed earlier as a contributing cause for this phenomenon. Hence, we aimed to stratify the association of post-COVID-19 vaccination breakthrough coinfection with Toxoplasma gondii (T. gondii) and its impact on disease severity. This cross-sectional study included 330 COVID-19-vaccinated patients confirmed by RT-PCR. They were also screened for anti- T. gondii antibodies using ELISA. Toxoplasma seropositive cases’ whole blood was screened for DNA using PCR to correlate results with COVID-19 severity. Out of 330 COVID-19 vaccinated patients with breakthrough infection, 34.5% (114 patients) showed positivity for Toxoplasma IgG by ELISA, and none of the cases was IgM positive. Eleven patients (9.6%) of the IgG-positive cases were positive by PCR. Positive PCR cases correlated positively with the Toxoplasma IgG titer (P < 0.001), and the Cutoff point was 191.5. Molecular analysis of Toxoplasma and COVID-19 severity showed that 8 (72.7%), 1 (9.1%), and 2 cases (18.2%) had mild, moderate, and severe courses of the disease, respectively, with no significant correlation. Our study reported a heightened prevalence of latent toxoplasmosis among mild cases of COVID-19 breakthrough infection. Nevertheless, a discernible correlation between latent toxoplasmosis and COVID-19 severity is lacking. Hence, implementing studies on a larger scale could provide a more comprehensive comprehension of this association.
Pheromone of grouped female mice impairs genome stability in male mice through stress-mediated pathways
Authors: Glinin Timofey S. , Petrova Marina V. , Shcherbinina Veronika , Shubina Anastasia N. , Dukelskaya Anna V. , Starshova Polina V. , Mamontova Victoria , Burnusuz Alexandra , Godunova Alena O. , Romashchenko Alexander V. , Moshkin Mikhail P. , Khaitovich Philipp , Daev Eugene V.
Published: October 2023

Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the role of chemosignals in the regulation of mouse physiology and behavior in response to social crowding. The pheromone 2,5-dimethylpyrazine (2,5-DMP), which is released by female mice in crowded conditions, induced aversion, glucocorticoid elevation and, when chronic, resulted in reproductive and immune suppression. 2,5-DMP olfaction induced genome destabilization in bone marrow cells in a stress-dependent manner, providing a plausible mechanism for crowding-induced immune dysfunction. Interestingly, the genome-destabilizing effect of 2,5-DMP was comparable to a potent mouse stressor (immobilization), and both stressors led to correlated expression changes in genes regulating cellular stress response. Thus, our findings demonstrate that, in mice, the health effects of crowding may be explained at least in part by chemosignals and also propose a significant role of stress and genome destabilization in the emergence of crowding effects.
Automated 3D liver segmentation from hepatobiliary phase MRI for enhanced preoperative planning
Authors: Oh Namkee , Kim Jae-Hun , Rhu Jinsoo , Jeong Woo Kyoung , Choi Gyu-seong , Kim Jong Man , Joh Jae-Won
Published: October 2023

Recent advancements in deep learning have facilitated significant progress in medical image analysis. However, there is lack of studies specifically addressing the needs of surgeons in terms of practicality and precision for surgical planning. Accurate understanding of anatomical structures, such as the liver and its intrahepatic structures, is crucial for preoperative planning from a surgeon’s standpoint. This study proposes a deep learning model for automatic segmentation of liver parenchyma, vascular and biliary structures, and tumor mass in hepatobiliary phase liver MRI to improve preoperative planning and enhance patient outcomes. A total of 120 adult patients who underwent liver resection due to hepatic mass and had preoperative gadoxetic acid-enhanced MRI were included in the study. A 3D residual U-Net model was developed for automatic segmentation of liver parenchyma, tumor mass, hepatic vein (HV), portal vein (PV), and bile duct (BD). The model’s performance was assessed using Dice similarity coefficient (DSC) by comparing the results with manually delineated structures. The model achieved high accuracy in segmenting liver parenchyma (DSC 0.92 ± 0.03), tumor mass (DSC 0.77 ± 0.21), hepatic vein (DSC 0.70 ± 0.05), portal vein (DSC 0.61 ± 0.03), and bile duct (DSC 0.58 ± 0.15). The study demonstrated the potential of the 3D residual U-Net model to provide a comprehensive understanding of liver anatomy and tumors for preoperative planning, potentially leading to improved surgical outcomes and increased patient safety.
Body composition and cardiorespiratory fitness of overweight COVID-19 survivors in different severity degrees: a cohort study
Authors: Perli Victor Augusto Santos , Sordi Ana Flávia , Lemos Maurício Medeiros , Fernandes Jhemilly Scarleth Araujo , Capucho Virgínia Benedetti Nanuncio , Silva Bruno Ferrari , de Paula Ramos Solange , Valdés-Badilla Pablo , Mota Jorge , Branco Braulio Henrique Magnani
Published: October 2023

COVID-19 sequelae are varied, and whether they are temporary or permanent is still unknown. Identifying these sequelae may guide therapeutic strategies to improve these individuals' recovery. This prospective cohort aimed to assess body composition, cardiopulmonary fitness, and long-term symptoms of overweight individuals affected by COVID-19. Participants (n = 90) were divided into three groups according to the severity of acute COVID-19: mild (no hospitalization), moderate (hospitalization, without oxygen support), and severe/critical cases (hospitalized in Intensive Care Unit). We assessed body composition with a tetrapolar multifrequency bioimpedance, hemodynamic variables (heart rate, blood pressure, and peripheral oxygen saturation-SpO2) at rest, and the Bruce test with direct gas exchange. Two assessments with a one-year interval were performed. The most prevalent long-term symptoms were memory deficit (66.7%), lack of concentration (51.7%), fatigue (65.6%), and dyspnea (40%). Bruce test presented a time effect with an increase in the distance walked after 1 year just for severe/critical group (p < 0.05). SpO2 was significantly lower in the severe/critical group up to 5 min after the Bruce test when compared to the mild group, and diastolic blood pressure at the end of the Bruce test was significantly higher in the severe/critical group when compared to mild group (p < 0.05; for all comparisons). A time effect was observed for body composition, with increased lean mass, skeletal muscle mass, fat-free mass, and lean mass just for the severe/critical group after 1 year (p < 0.05). Cardiopulmonary fitness parameters did not differ among the groups, except for respiratory quotient with higher values for the severe/critical group when compared to itself after 1 year. All COVID-19 patients might present long-term sequelae, regardless of the acute disease severity. Reassessing and identifying the most prevalent long-term sequelae are essential to perform more precise health promotion interventions.
Depression by gender and associated factors among older adults in India: implications for age-friendly policies
Authors: Paul Ronak , Muhammad T. , Rashmi Rashmi , Sharma Palak , Srivastava Shobhit , Zanwar Preeti Pushpalata
Published: October 2023

Inspite of implementing policies to control mental health problems, depression remains a severe health concern among older adults in India. We examined self-reported differences in the depression among older men and women in India and examined associated factors for gender differences in depression at the population level. We utilized nationally representative data from the Longitudinal Aging Study in India (LASI) wave I, for years 2017–2019. Our analytical sample comprised of 30,637 older adults ages 60 years and above (14,682 men and 15,655 women). We conducted descriptive statistics and Chi-Square tests followed by binary logistic regression and multivariate decomposition analyses to examine our study objectives. Depression was reported in − 7.4% (95% CI 7.0, 7.8) of older men and 9.5% (CI 9.1, 10.0) of older women. Poor self-rated health, multimorbidity status, physical activity, difficulty in activities of daily living (ADL) and instrumental ADL (IADL) were the significant health-related factors associated with depression among older men and women. Not being satisfied with one’s life, not being satisfied with their present living arrangement, receiving any type of ill-treatment, and being widowed were the significant factors associated with depression among older men and women. We found gender disparity in self-reported depression. Marital status contributed-to 36.7% of the gender gap in depression among older adults. Additionally, ADL and IADL difficulties among men and women contributed to 17.6% and 34.0%, gender gap, self-rated health contributed to 18.8% gap, whereas not having equal social participation (4.4%) and not satisfied in present living arrangements (8.1%) were other factors that contributed to gender gap for depression in India. Depression is a critical and persistent public health problem among—older females in India. Our findings provide a broader framework for policymakers and health practitioners to focus on gender-specific strategies to mitigate this highly emergent problem.
Dopamine D1-like receptors modulate synchronized oscillations in the hippocampal–prefrontal–amygdala circuit in contextual fear
Authors: Stubbendorff Christine , Hale Ed , Bast Tobias , Cassaday Helen J. , Martin Stephen J. , Suwansawang Sopapun , Halliday David M. , Stevenson Carl W.
Published: October 2023

Contextual fear conditioning (CFC) is mediated by a neural circuit that includes the hippocampus, prefrontal cortex, and amygdala, but the neurophysiological mechanisms underlying the regulation of CFC by neuromodulators remain unclear. Dopamine D1-like receptors (D1Rs) in this circuit regulate CFC and local synaptic plasticity, which is facilitated by synchronized oscillations between these areas. In rats, we determined the effects of systemic D1R blockade on CFC and oscillatory synchrony between dorsal hippocampus (DH), prelimbic (PL) cortex, basolateral amygdala (BLA), and ventral hippocampus (VH), which sends hippocampal projections to PL and BLA. D1R blockade altered DH–VH and reduced VH–PL and VH–BLA synchrony during CFC, as inferred from theta and gamma coherence and theta-gamma coupling. D1R blockade also impaired CFC, as indicated by decreased freezing at retrieval, which was characterized by altered DH–VH and reduced VH–PL, VH–BLA, and PL–BLA synchrony. This reduction in VH–PL–BLA synchrony was not fully accounted for by non-specific locomotor effects, as revealed by comparing between epochs of movement and freezing in the controls. These results suggest that D1Rs regulate CFC by modulating synchronized oscillations within the hippocampus–prefrontal–amygdala circuit. They also add to growing evidence indicating that this circuit synchrony at retrieval reflects a neural signature of learned fear.
Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma
Authors: Lyu Su Ir , Popp Felix C. , Simon Adrian Georg , Schultheis Anne Maria , Zander Thomas , Fretter Caroline , Schröder Wolfgang , Bruns Christiane J. , Schmidt Thomas , Quaas Alexander , Knipper Karl
Published: October 2023

Esophageal adenocarcinoma exhibits one of the highest mortality rates among all cancer entities. Multimodal therapy strategies have improved patients’ survival significantly. However, patients in early stages are currently limited to receiving only local therapies, even though some patients within this group showcase short survival periods. Until now, there has been no widely established clinically used biomarker to detect these high-risk patients. Telomerase reverse transcriptase (TERT), a gene encoding a crucial subunit of the telomerase enzyme, plays a significant role in establishing cancer cell immortality and is under suspicion for its potential contribution to tumor progression. Therefore, we aimed to evaluate the clinical relevance of the TERT amplification status. We included 643 patients with esophageal adenocarcinoma, who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. The TERT amplification status was characterized using fluorescence in situ hybridization. Clinicopathological values and patients’ overall survival were compared between patients with and without TERT amplification. Further sub-cohort analyses were conducted for patients with pT1N0-3 tumor stage. Eighty-One patients (12.6%) exhibited TERT amplification. Patients with amplified TERT showed significantly worse overall survival (median OS: 22.6 vs. 36.8 months, p = 0.009). Interestingly, TERT amplification could be characterized as an independent risk factor for worse overall survival in multivariate analysis in patients with pT1N0-3 tumor stage (HR = 2.440, 95% CI 1.095–5.440, p = 0.029). In this study, we describe the TERT amplification status as an independent risk factor for worse survival in patients diagnosed with esophageal adenocarcinoma at pT1N0-3 tumor stage, encompassing cases involving tumor infiltration of the lamina propria, muscularis mucosae, and/or submucosa. Based on our findings, we put forth the proposition that evaluating the TERT amplification status may serve as a valuable tool in identifying a specific subgroup of patients, namely those with TERT amplification and pT1N0-3 tumor-stage esophageal adenocarcinoma. The patients of this subgroup could potentially benefit from enhanced follow-up protocols, more aggressive treatment approaches, or possible targeted TERT inhibition therapies, all aimed at improving their overall clinical outcomes.
Regular exercise delays microvascular endothelial dysfunction by regulating antioxidant capacity and cellular metabolism
Authors: Scarfò Giorgia , Daniele Simona , Chelucci Elisa , Rizza Antonio , Fusi Jonathan , Freggia Giancarlo , Costa Barbara , Taliani Sabrina , Artini Paolo , Martini Claudia , Franzoni Ferdinando
Published: October 2023

Aging is the basis for several unfavorable conditions, including cardiovascular diseases (CVDs). In this sense, regular physical activity (regular PA) has been proven to delay cellular aging and prevent endothelial dysfunction related to CVDs. Despite numerous studies involving athletes, little is known about cellular and molecular mechanisms of regular PA among master athletes. The present study aimed at evaluating the effects of regular PA on local microcirculatory functions in elderly athletes as compared to age-matched sedentary controls. Moreover, molecular/epigenetic mechanisms (nitric oxide, oxidative stress, PGC-1α, SIRT1 and miR29) were also assessed. The results of the present study showed that regular PA significantly increased local blood flow in post-ischemia and post-heating conditions, as well as NO plasma concentrations, denoting a better endothelial function/microcirculatory efficiency. Moreover, athletes presented a greater plasma antioxidant and increased transcriptional levels of the metabolism regulator PGC-1α. Finally, regular PA enhanced plasma level of SIRT1 and miR29, suggested as epigenetic regulators of redox balance and cellular metabolism. In addition, stimulated local blood flow was directly related to plasma antioxidant capacity, and SIRT1 and miR29 levels. Overall, our data confirm the beneficial effects of regular PA on the cardiovascular profile in elderly athletes and shed light on molecular signals involved in the positive adaptations to exercise.
Experimental, analytical, and simulation studies of modified concrete mix for radiation shielding in a mixed radiation field
Authors: Nabil Islam M. , El-Samrah Moamen G. , Omar Ahmed , Tawfic A. F. , El Sayed A. F.
Published: October 2023

The current study assessed two concrete mixes prepared using dolomite and barite/limonite aggregates to shield against both energetic photons and neutrons. After that, a designed mix which comprised barite/goethite aggregates plus fine-powdered boron carbide additive, was proposed to improve the overall radiation shielding properties and in the same time, doesn’t compromise or even improve the physic-mechanical properties of the mature concrete. The assessment started first with intensive experimental investigations to investigate the prepared mixes’ shielding capabilities against both γ-rays and fast neutrons. Then, analytical computations were performed via number of reliable software programs such as; Phy-X, NXCom, MRCsC, JANIS-4, and MCNP5, in order to confirm the experimental results and to validate the created Monte-Carlo models. Finally, an intensive radiation shielding assessment for all concrete mixes understudy using, mainly, the validated MCNP models, was performed. The obtained results have revealed the superiority of barite mixes over the dolomite mix concerning attenuating photons moreover, the proposed designed mix has shown superiority over the other two prepared mixes considering shielding against; energetic photons, fast/thermal neutrons, and secondary emitted γ-rays, which nominates this mix to be a suitable universal shield that can be used even in mixed radiation fields.
Evaluating service needs for veno-venous extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome in Saskatchewan
Authors: Saha Barsa , Drapak Savannah , Mailman Jonathan F. , Kassir Sandy , Sy Eric
Published: October 2023

To determine the number of patients with acute respiratory distress syndrome (ARDS) who would be eligible to receive veno-venous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective observational study of ARDS patients admitted to Regina General Hospital Intensive Care Unit (ICU). VV-ECMO eligibility was assessed using selection criteria from the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Syndrome trial (EOLIA), the Extracorporeal Life Support Organization (ELSO), New South Wales (NSW), Critical Care Services Ontario (CCSO) and a Regina-restrictive criteria. Of 415 patients admitted between October 16, 2018, and January 21, 2021, 103 (25%) had mild, 175 (42%) had moderate, and 64 (15%) had severe ARDS. Of the cohort, 144 (35%) had bacterial pneumonia, 86 (21%) had viral pneumonia (including COVID-19), and 72 (17%) had aspiration pneumonia. Using the EOLIA, ELSO, NSW, CCSO and Regina-restrictive criteria, 7/415 (1.7%), 6/415 (1.5%), 19/415 (4.6%), 26/415 (6.3%) and 12/415 (2.9%) were eligible for VV-ECMO, respectively. Of all ECMO-eligible patients, only one (2.4%) actually received VV-ECMO, 20/42 (48%) received prone positioning and 21/42 (50%) received neuromuscular blockade. There is potential for service expansion of VV-ECMO in Regina; however, there is still a need to improve the delivery of evidence-based ARDS therapies.
Effects of thermal treatment of food using barbecue fuels on ambient air and beach sands within recreation facilities
Authors: Kuś Sebastian , Jelonek Iwona , Jelonek Zbigniew
Published: October 2023

Organised bathing areas located within leisure facilities, in addition to the function typical of their purpose, allow in most cases the use of their own barbecue facilities. This type of cooking of food before consumption is very popular during leisure time at the waterfront. However, cooking food on a barbecue produces fumes emitted from both the fuel being burned and the food being grilled. In addition, the fat from the grilled food falls on the hearth, contributing to the release of further toxic compounds and, in many cases, together with other exhaust fumes, causing considerable smoke and the summer smog effect. Such cumulative gases emitted by irregularly dispersed barbecues repeatedly irritate the respiratory tract of beachgoers in the area of these devices, and the residue of unburned barbecue fuel contaminates the resting area. Small pieces of charcoal of various textures tend to sink into the sand when exposed to the elements and can pose a risk to young children playing on the beach by causing choking and minor injuries. The study revealed an assumed range of exposure to dust and gases emitted from barbecuing that extended up to 40 m from the hearth. Additionally, it was demonstrated that the thermal processing of food using barbecue fuels could lead to increased contamination of beach sands from the fuel itself and food storage materials. Therefore, taking into account the studies carried out showing the adverse effects of active barbecues on beach sands and, above all, the atmospheric air and directly on beachgoers, administrators of recreational facilities should strive to concentrate these devices at a distance (up to several tens of metres) from beaches and bathing areas.
Development of immersive learning framework (ILF) in achieving the goals of higher education: measuring the impact using a pre–post design
Authors: Devassy Saju Madavanakadu , Scaria Lorane , Metzger Jed , Thampi Kiran , Jose Jitto , Joseph Binoy
Published: October 2023

Emerging technological tools like Artificial Intelligence-based Chatbots, digital educational alternatives and market-driven educational systems pose a challenge to the fundamental aim of the higher education system; comprehensive education for well-being. Therefore, this research aims to devise and evaluate strategies to impart new-age competencies to innovate socially and morally appropriate solutions in a modern competitive innovative society. The 8-month-long immersive learning framework (ILF), was designed based on the volatility, uncertainty, complexity, and ambiguity (VUCA) paradigm. The framework was evaluated with 133 newly joined postgraduate students doing their science or arts programmes from a higher education institution in Kerala, India. The outcome variables included well-being, depressive symptoms, personality patterns, and sub-domains of philosophy of human nature. The follow-up scores showed a significant improvement in well-being (Mean difference: 1.15, p = 0.005), trustworthiness (Mean difference: 14.74, p = 0.000), strength of will (Mean difference: 10.11, p = 0.000), altruism (Mean difference: 12.85, p = 0.000), and independence (Mean difference: 11.93, p = 0.000). Depression scores did not improve significantly. However, the intervention shielded them from the adjustment issues that often accompany any transition. The ILF framework can help students develop their personal and professional selves if it is implemented collaboratively in a reflective setting. It can also instil moral rectitude and a prosocial mindset.
Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder
Authors: Ellul Pierre , Maruani Anna , Vantalon Valérie , Humeau Elise , Amestoy Anouck , Anchordoqui Andrea , Atzori Paola , Baleyte Jean-Marc , Benmansour Safiyah , Bonnot Olivier , Bouvard Manuel , Cartigny Ariane , Coulon Nathalie , Coutelle Romain , Da Fonseca David , Demily Caroline , Givaudan Marion , Gollier-Briant Fanny , Guénolé Fabian , Koch Andrea , Leboyer Marion , Lefebvre Aline , Lejuste Florian , Levy Charlotte , Mendes Eugénie , Robert Natalia , Schroder Carmen M. , Speranza Mario , Zante Elodie , Peyre Hugo , Rosenzwajg Michelle , Klatzmann David , Tchitchek Nicolas , Delorme Richard
Published: October 2023

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA-). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother–child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.
Fine conductive line printing of high viscosity CuO ink using near field electrospinning (NFES)
Authors: Rahman Md. Khalilur , Lee Jin-Sol , Kwon Kye-Si
Published: October 2023

Modern printed electronics applications require patterning of fine conductive lines of sufficient thickness. However, the two requirements for pattern width and thickness are a trade-off. To print fine pattern at a micrometer size, the nozzle diameter must be approximately the size of the pattern width, so only low-viscosity inks are used. As a result, the pattern is likely to be very thin and multiple overlapping printing is required for sufficient conductance. In order to use high viscosity ink for fine patterning, near field electrospinning (NFES) is attracting attention because it can print very thin and thick patterns using large nozzles (high-viscosity ink). Until now, silver paste ink has been used for microconductive patterning using electrospinning. However, Ag nanoparticle (NP) inks are expensive. In this study, we report the use of a relatively inexpensive CuO NP ink for electrospinning-based printing. For implementation, the material preparation, printing and post-processing process are discussed. For post-processing, a continuous wave (CW) green laser with a 532 nm wavelength was used to reduce the CuO to Cu and sinter the nanoparticles. After sintering, the 50 μm width and 1.48 μm thick Cu conductive line exhibited a resistivity of 5.46 μΩ·cm, which is 3.25 times of the bulk resistivity of Cu.
Application of single wrist-wearable accelerometry for objective motor diary assessment in fluctuating Parkinson’s disease
Authors: Löhle Matthias , Timpka Jonathan , Bremer Alexander , Khodakarami Hamid , Gandor Florin , Horne Malcom , Ebersbach Georg , Odin Per , Storch Alexander
Published: October 2023

Advanced Parkinson’s disease (PD) is characterized by motor fluctuations including unpredictable oscillations remarkably impairing quality of life. Effective management and development of novel therapies for these response fluctuations largely depend on clinical rating instruments such as the widely-used PD home diary, which are associated with biases and errors. Recent advancements in digital health technologies provide user-friendly wearables that can be tailored for continuous monitoring of motor fluctuations. Their criterion validity under real-world conditions using clinical examination as the gold standard remains to be determined. We prospectively examined this validity of a wearable accelerometer-based digital Parkinson’s Motor Diary (adPMD) using the Parkinson’s Kinetigraph (PKG®) in an alternative application by converting its continuous data into one of the three motor categories of the PD home diary (Off, On and Dyskinetic state). Sixty-three out of 91 eligible participants with fluctuating PD (46% men, average age 66) had predefined sufficient adPMD datasets (>70% of half-hour periods) from 2 consecutive days. 92% of per-protocol assessments were completed. adPMD monitoring of daily times in motor states showed moderate validity for Off and Dyskinetic state (ICC = 0.43–0.51), while inter-rating methods agreements on half-hour-level can be characterized as poor (median Cohen’s κ = 0.13–0.21). Individualization of adPMD thresholds for transferring accelerometer data into diary categories improved temporal agreements up to moderate level for Dyskinetic state detection (median Cohen’s κ = 0.25–0.41). Here we report that adPMD real-world-monitoring captures daily times in Off and Dyskinetic state in advanced PD with moderate validities, while temporal agreement of adPMD and clinical observer diary data is limited.
The neonatal southern white rhinoceros ovary contains oogonia in germ cell nests
Authors: Appeltant Ruth , Hermes Robert , Holtze Susanne , Modina Silvia Clotilde , Galli Cesare , Bjarkadottir Briet. D. , Adeniran Babatomisin V. , Wei Xi , Swegen Aleona , Hildebrandt Thomas Bernd , Williams Suzannah A.
Published: October 2023

The northern white rhinoceros is functionally extinct with only two females left. Establishing methods to culture ovarian tissues, follicles, and oocytes to generate eggs will support conservation efforts using in vitro embryo production. To the best of our knowledge, this is the first description of the structure and molecular signature of any rhinoceros, more specifically, we describe the neonatal and adult southern white rhinoceros (Ceratotherium simum simum) ovary; the closest relation of the northern white rhinoceros. Interestingly, all ovaries contain follicles despite advanced age. Analysis of the neonate reveals a population of cells molecularly characterised as mitotically active, pluripotent with germ cell properties. These results indicate that unusually, the neonatal ovary still contains oogonia in germ cell nests at birth, providing an opportunity for fertility preservation. Therefore, utilising ovaries from stillborn and adult rhinoceros can provide cells for advanced assisted reproductive technologies and investigating the neonatal ovaries of other endangered species is crucial for conservation.
Scanning single molecule localization microscopy (scanSMLM) for super-resolution volume imaging
Authors: Basumatary Jigmi , Baro Neptune , Joshi Prakash , Mondal Partha Pratim
Published: October 2023

Over the last decade, single-molecule localization microscopy (SMLM) has developed into a set of powerful techniques that have improved spatial resolution over diffraction-limited microscopy and demonstrated the ability to resolve biological features down to a few tens of nanometers. We introduce a single molecule-based scanning SMLM (scanSMLM) system that enables rapid volume imaging. Along with epi-illumination, the system employs a scanning-based 4f detection for volume imaging. The 4f system comprises a combination of an electrically-tunable lens and high NA detection objective lens. By rapidly changing the aperture (or equivalently the focus) of an electrically-tunable lens (ETL) in a 4f detection system, the selectivity of the axial object plane is achieved, for which the image forms in the image/detector plane. So, in principle, one can scan the object volume by just altering the aperture of ETL. Two schemes were adopted to carry out volume imaging: cyclic scan and conventional scan. The cyclic scheme scans the volume in each scan cycle, whereas plane-wise scanning is performed in the conventional scheme. Hence, the cyclic scan ensures uniform dwell time on each frame during data collection, thereby evenly distributing photobleaching throughout the cell volume. With a minimal change in the system hardware (requiring the addition of an ETL lens and related electronics for step-voltage generation) in the existing SMLM system, volume scanning (along the z-axis) can be achieved. To calibrate and derive critical system parameters, we imaged fluorescent beads embedded in a gel-matrix 3D block as a test sample. Subsequently, scanSMLM is employed to visualize the architecture of actin-filaments and the distribution of Meos-Tom20 molecules on the mitochondrial membrane. The technique is further exploited to understand the clustering of Hemagglutinin (HA) protein single molecules in a transfected cell for studying Influenza-A disease progression. The system, for the first time, enabled 3D visualization of HA distribution that revealed HA cluster formation spanning the entire cell volume, post 24 hrs of transfection. Critical biophysical parameters related to HA clusters (density, the number of HA molecules per cluster, axial span, fraction of clustered molecules, and others) are also determined, giving an unprecedented insight into Influenza-A disease progression at the single-molecule level.
Single-cell chromatin accessibility and transcriptomic characterization of Behcet’s disease
Authors: Shi Wen , Ye Jinguo , Shi Zhuoxing , Pan Caineng , Zhang Qikai , Lin Yuheng , Liang Dan , Liu Yizhi , Lin Xianchai , Zheng Yingfeng
Published: October 2023

Behect’s disease is a chronic vasculitis characterized by complex multi-organ immune aberrations. However, a comprehensive understanding of the gene-regulatory profile of peripheral autoimmunity and the diverse immune responses across distinct cell types in Behcet’s disease (BD) is still lacking. Here, we present a multi-omic single-cell study of 424,817 cells in BD patients and non-BD individuals. This study maps chromatin accessibility and gene expression in the same biological samples, unraveling vast cellular heterogeneity. We identify widespread cell-type-specific, disease-associated active and pro-inflammatory immunity in both transcript and epigenomic aspects. Notably, integrative multi-omic analysis reveals putative TF regulators that might contribute to chromatin accessibility and gene expression in BD. Moreover, we predicted gene-regulatory networks within nominated TF activators, including AP-1, NF-kB, and ETS transcript factor families, which may regulate cellular interaction and govern inflammation. Our study illustrates the epigenetic and transcriptional landscape in BD peripheral blood and expands understanding of potential epigenomic immunopathology in this disease.
Determinants of species-specific utilization of ACE2 by human and animal coronaviruses
Authors: Wang Qingxing , Noettger Sabrina , Xie Qinya , Pastorio Chiara , Seidel Alina , Müller Janis A. , Jung Christoph , Jacob Timo , Sparrer Konstantin M. J. , Zech Fabian , Kirchhoff Frank
Published: October 2023

Utilization of human ACE2 allowed several bat coronaviruses (CoVs), including the causative agent of COVID-19, to infect humans directly or via intermediate hosts. However, the determinants of species-specific differences in ACE2 usage and the frequency of the ability of animal CoVs to use human ACE2 are poorly understood. Here we applied VSV pseudoviruses to analyze the ability of Spike proteins from 26 human or animal CoVs to use ACE2 receptors across nine reservoir, potential intermediate and human hosts. We show that SARS-CoV-2 Omicron variants evolved towards more efficient ACE2 usage but mutation of R493Q in BA.4/5 and XBB Spike proteins disrupts utilization of ACE2 from Greater horseshoe bats. Variations in ACE2 residues 31, 41 and 354 govern species-specific differences in usage by coronaviral Spike proteins. Mutation of T403R allows the RaTG13 bat CoV Spike to efficiently use all ACE2 orthologs for viral entry. Sera from COVID-19 vaccinated individuals neutralize the Spike proteins of various bat Sarbecoviruses. Our results define determinants of ACE2 receptor usage of diverse CoVs and suggest that COVID-19 vaccination may protect against future zoonoses of bat coronaviruses.
Platicon dynamics in photonic molecules
Authors: Rebolledo-Salgado Israel , Quevedo-Galán Clara , Helgason Óskar Bjarki , Lööf Anton , Ye Zhichao , Lei Fuchuan , Schröder Jochen , Zelan Martin , Torres-Company Victor
Published: October 2023

Coherent dissipative structures known as platicons can be reliably generated in photonic molecules, resulting in deterministic and reproducible microcombs derived from a continuous-wave pump. However, the supermode spectrum of standard photonic molecules displays numerous avoided mode crossings, distorting the spectral envelope of platicon microcombs. Here, we obtain a platicon microcomb using a photonic molecule configuration based on two coupled microcavities, whose size differs by an order of magnitude. This results in an engineered microcomb spectrum that closely resembles the one generated in an ideal single microresonator with just one frequency mode shift. We observe the coupling between the repetition rate of the platicon microcomb with the frequency of the pump laser, an effect originating from the dispersive-wave recoil induced by mode crossings. Using two identical platicon microcombs, we make use of such coupling to realize dual-comb interferometry. These results contribute to understanding dissipative structures in normal-dispersion microresonators and offer an alternative to applications such as spectroscopy and metrology.
The overall-subshear and multi-segment rupture of the 2023 Mw7.8 Kahramanmaraş, Turkey earthquake in millennia supercycle
Authors: Xu Liuwei , Mohanna Saeed , Meng Lingsen , Ji Chen , Ampuero Jean-Paul , Yunjun Zhang , Hasnain Masooma , Chu Risheng , Liang Cunren
Published: October 2023

On February 6, 2023, an Mw7.8 earthquake hit the East Anatolian Fault (EAF) and Narlı Fault (NF), followed by an Mw7.5 event on the Sürgü Fault. We combine multiple seismic datasets, global navigation satellite system recordings, and radar satellite images with finite fault inversion and slowness enhanced back-projection to study the rupture kinematics. Our analysis reveals that the rupture originated on the NF, propagating 120 km northeast at 3.05 km/s and 200 km southwest at 3.11 km/s after reaching the EAF junction, exhibiting overall subshear speeds. Further Mach wave analysis confirms the subshear rupture, matching the prediction using close-Rayleigh speeds. The unexpectedly-large slip on some EAF segments suggests a supercycle lasting ≥900 years. The EAF geometry is similar to the San Andreas-San Jacinto Fault system, while the latter has higher slip rates but without large earthquakes on its southern segments since 1857, carrying the potential of an M8 earthquake.
Microbial growth in actual martian regolith in the form of Mars meteorite EETA79001
Authors: Naz Neveda , Harandi Bijan F. , Newmark Jacob , Kounaves Samuel P.
Published: October 2023

Studies to understand the growth of organisms on Mars are hampered by the use of simulants to duplicate martian mineralogy and chemistry. Even though such materials are improving, no terrestrial simulant can replace a real martian sample. Here we report the use of actual martian regolith, in the form of Mars meteorite EETA79001 sawdust, to demonstrate its ability to support the growth of four microorganisms,E. coli. Eucapsissp.,Chr20-20201027-1, andP. halocryophilus, for up to 23 days under terrestrial conditions using regolith:water ratios from 4:1 to 1:10. If the EETA79001 sawdust is widely representative of regolith on the martian surface, our results imply that microbial life under appropriate conditions could have been present on Mars in the past and/or today in the subsurface, and that the regolith does not contain any bactericidal agents. The results of our study have implications not only for putative martian microbial life but also for building bio-sustainable human habitats on Mars.
Net-spinning caddisflies create denitrifier-enriched niches in the stream microbiome
Authors: Bertagnolli Anthony D , Maritan Andrew J , Tumolo Benjamin B , Fritz Samuel F , Oakland Hayley C , Mohr Elizabeth J , Poole Geoffrey C , Albertson Lindsey K , Stewart Frank J
Published: October 2023

Larval net-spinning caddisflies (Hydropsychidae) function as ecosystem engineers in streams where they construct protective retreats composed of organic and inorganic material affixed with silk filtration nets that alter streambed hydrology. We hypothesized that hydropsychid bio-structures (retreats, nets) are microhabitats for microbes with oxygen-sensitive metabolisms, and therefore increase the metabolic heterogeneity of streambed microbial assemblages. Metagenomic and 16 S rRNA gene amplicon analysis of samples from a montane stream (Cherry Creek, Montana, USA) revealed that microbiomes of caddisfly bio-structures are taxonomically and functionally distinct from those of the immediately adjacent rock biofilm (~2 cm distant) and enriched in microbial taxa with established roles in denitrification, nitrification, and methane production. Genes for denitrification, high oxygen affinity terminal oxidases, hydrogenases, oxidative dissimilatory sulfite reductases, and complete ammonia oxidation are significantly enriched in caddisfly bio-structures. The results suggest a novel ecosystem engineering effect of caddisflies through the creation of low-oxygen, denitrifier-enriched niches in the stream microbiome. Facilitation of metabolic diversity in streambeds may be a largely unrecognized mechanism by which caddisflies alter whole-stream biogeochemistry.
Extracellular vesicles are the main contributor to the non-viral protected extracellular sequence space
Authors: Lücking Dominik , Mercier Coraline , Alarcón-Schumacher Tomas , Erdmann Susanne
Published: October 2023

Environmental virus metagenomes, commonly referred to as “viromes”, are typically generated by physically separating virus-like particles (VLPs) from the microbial fraction based on their size and mass. However, most methods used to purify VLPs, enrich extracellular vesicles (EVs) and gene transfer agents (GTAs) simultaneously. Consequently, the sequence space traditionally referred to as a “virome” contains host-associated sequences, transported via EVs or GTAs. We therefore propose to call the genetic material isolated from size-fractionated (0.22 µm) and DNase-treated samples protected environmental DNA (peDNA). This sequence space contains viral genomes, DNA transduced by viruses and DNA transported in EVs and GTAs. Since there is no genetic signature for peDNA transported in EVs, GTAs and virus particles, we rely on the successful removal of contaminating remaining cellular and free DNA when analyzing peDNA. Using marine samples collected from the North Sea, we generated a thoroughly purified peDNA dataset and developed a bioinformatic pipeline to determine the potential origin of the purified DNA. This pipeline was applied to our dataset as well as existing global marine “viromes”. Through this pipeline, we identified known GTA and EV producers, as well as organisms with actively transducing proviruses as the source of the peDNA, thus confirming the reliability of our approach. Additionally, we identified novel and widespread EV producers, and found quantitative evidence suggesting that EV-mediated gene transfer plays a significant role in driving horizontal gene transfer (HGT) in the world’s oceans.
Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe
Authors: Zhang Le , Antonacci Michael , Burant Alex , McCallister Andrew , Kelley Michele , Bryden Nicholas , McHugh Christian , Atalla Sebastian , Holmes Leah , Katz Laurence , Branca Rosa Tamara
Published: October 2023

Background

Absolute temperature measurements of tissues inside the human body are difficult to perform non-invasively. Yet, for brown adipose tissue (BAT), these measurements would enable direct monitoring of its thermogenic activity and its association with metabolic health.

Methods

Here, we report direct measurement of absolute BAT temperature in humans during cold exposure by magnetic resonance (MR) with laser polarized xenon gas. This methodology, which leverages on the sensitivity of the chemical shift of the 129Xe isotope to temperature-induced changes in fat density, is first calibrated in vitro and then tested in vivo in rodents. Finally, it is used in humans along with positron emission tomography (PET) scans with fluorine-18-fluorodeoxyglucose to detect BAT thermogenic activity during cold exposure.

Results

Absolute temperature measurements, obtained in rodents with an experimental error of 0.5 °C, show only a median deviation of 0.12 °C against temperature measurements made using a pre-calibrated optical temperature probe. In humans, enhanced uptake of 129Xe in BAT during cold exposure leads to background-free detection of this tissue by MR. Global measurements of supraclavicular BAT temperature, made over the course of four seconds and with an experimental error ranging from a minimum of 0.4 °C to more than 2 °C, in case of poor shimming, reveal an average BAT temperature of 38.8° ± 0.8 °C, significantly higher (p < 0.02 two-sided t test) than 37.7 °C. Hot BAT is also detected in participants with a PET scan negative for BAT.

Conclusions

Non-invasive, radiation-free measurements of BAT temperature by MRI with hyperpolarized 129Xe may enable longitudinal monitoring of human BAT activity under various stimulatory conditions.