bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Maternal Serum Biomarkers and Uterine Artery and Ductus Venosus Blood Flow Patterns in Early Pregnancy Doppler Ultrasound Study
Authors: Karpów-Greiner Magdalena , Komisarek Oskar , Sekielska Marta , Knypiński Wojciech , Adamczak Rafał , Dubiel Mariusz
Published: April 2023

Background: In this study, we aimed to evaluate the effect of s-FLT-1 and PlGF concentrations in women in the first trimester of pregnancy on the pulsatility index of the ductus venosus and the right and left uterine arteries. Methods: A total of 108 pregnant women in their first trimester were included in the study, with 87 assigned to the experimental group and 21 to the control group. Ultrasound examination were performed to measure the uterine artery pulsatility index, resistance index, ductus venosus pulsatility index, and blood sampling levels of biomarkers such as b-HCG; PAPP-A; s-FLT-1 and PlGF. Results: There was a significant negative relationship between PAPP-A concentration and the risk of fetal growth restriction, and a significant negative relationship between PlGF concentration and the risk of preeclampsia and fetal growth restriction in women in their first trimester of pregnancy. There was also a significant positive relationship between sFLT-1/PLGF ratio and the risk of developing preeclampsia. No significant relationships were found between the concentrations of biomarkers beta-HCG, PAPP-A, sFLT-1, PlGF, and any of the parameters PIUARt, PIUALt, Mean uterine arteries, and DVPI. Summary: In conclusion, this study did not find conclusive evidence to support the hypothesis that beta-HCG, PAPP-A, s-FLT-1, and PlGF concentrations in women in the first trimester of pregnancy have a significant effect on the Pulsatility Index of the ductus venosus and the Right and left Uterine Arteries. Further research is needed to investigate these potential associations.
Torque Teno Virus load predicts opportunistic infections after kidney transplantation but is not associated with maintenance immunosuppression exposure.
Authors: Cañamero Lucía , Benito-Hernandez Adalberto , González Elena , Escagedo Clara , Rodríguez-Vidriales María , García-Saiz María del Mar , Valero Rosalía , Belmar Lara , De Cos María Angeles , Ruiz Juan Carlos , Rodrigo Emilio
Published: April 2023

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculate the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559-0.905, p = 0.023) and between months 3 to 6 (AUC-ROC 0.778, 95%CI 0.599-0.957, p = 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.
SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains
Authors: Mendes-Correa Maria Cassia , Salomão Matias Chiarastelli , Ghilardi Fabio , Tozetto-Mendoza Tania Regina , Santos Vilas Boas Lucy , De Paula Anderson Vicente , Paiao Heuder Gustavo Oliveira , Da Costa Antonio Charlys , Leal Fabio Eudes , Ferraz Andrea de Barros Coscelli , Salles Flavia Cristina , Claro Ingra M. , Ferreira Noely Evangelista , Pereira Geovana M. , Junior Almir Ribeiro , Freire Wilton , Espinoza Evelyn Patricia Sánchez , Manuli Erika R. , Romano Camila , De Jesus Jaqueline Goes , Sabino Ester Cerdeira , Witkin Steven Sol
Published: April 2023

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.
Axillary Artery Transection and Brachial Plexus Injury After Open Inferior Glenohumeral Dislocation
Authors: Huri Gazi , Aksoy Taha , Beydemir Ataberk , Yigit Yigit Aras , Yilmaz Mustafa
Published: April 2023

Case:

A judo athlete presented with an open inferior shoulder dislocation that occurred during competition. Examination revealed a transection of the axillary artery and neuropraxia of the posterior cord. Neuropraxia was resolved within 2 weeks. The axillary artery was repaired with a femoral vein graft. He regained full strength, range of motion, and function at 8 months.

Conclusion:

Inferior glenohumeral dislocations are rare, and their management can be complicated by vascular and neurological injuries. We emphasize the importance of examination, diagnosis, and treatment of neurovascular pathologies to avoid catastrophic outcomes.
Multiple scours and upward fining caused by hydraulic jumps: implications for the recognition of cyclic steps in the deepwater stratigraphic record
Authors: Ono Kenya , Naruse Hajime , Yao Qifeng , Cai Zhirong , Fukuda Sojiro , Yokokawa Miwa
Published: April 2023

Hydraulic jumps control the bypass, erosion, and depositional processes of Froude-supercritical turbidity currents, so they represent a significant process for understanding the development of submarine geomorphology. Hydraulic jumps actively occur from submarine canyons to fans, where the seafloor slope is relatively steep. Turbidites in such areas comprise large-scale bedforms called cyclic steps, and they exhibit complex internal structures, including localized erosion and the accumulation of coarse-grained fining-upward sequences. However, it is unclear which turbidity-current properties are reflected in the heterogeneous depositional characteristics and grain-size sorting of these deposits. To this end, we conducted flume experiments to reproduce deposits associated with the hydraulic jumps of surge-type flows. Turbidity-current surges were repeatedly generated in an experimental flume with a knickpoint that transitioned from a steep to a gentle slope, resulting in cyclic steps. Overall, the upstream migration of the cyclic steps produced a downstream-upward-fining succession of turbidites. However, hydraulic jumps occurred at several places over the trough to the stoss side of the step in a single flow due to the non-uniform and unsteady flow state of the surge-type turbidite succession. As a result, the reproduced succession exhibited multiple local scours and coarse-grained fill in the lower parts of the turbidites. This suggests that multiple local scours and fining-upward trends are discriminant characteristics of cyclic-step deposits formed by surge-type supercritical turbidity currents.
Stochastic Estimation of Barrels of Oil Equivalent Conversion Factor for Natural Gas Volumes from Offshore Carbonate Fields in Ultradeep Waters
Authors: Silva L. C. , Roque J. V. , Oliveira G. , Souza R. G. , Paulino S. M. , Fonseca C. , Braga D. , Trujillo J.
Published: April 2023

Oil and gas production is measured in different units; therefore, there is a need to use a conversion factor of natural gas (NG) to barrels of oil equivalent (BOE). The SPE unit conversion factor, which is based on a reference oil, is often used. However, BOE conversion factors vary as a function of the high heating value (HHV) calculated for a gas, which in turn, varies as a function of the NG composition. Herein, by using Monte Carlo simulations, HHV and produced volumes of NG measured over the years were used in estimating BOE conversion factors for two offshore carbonate fields in ultradeep waters. Then, the new BOE conversion factors were used to review the production data collected in 2021. By comparing the new production data with the data obtained by using the SPE unit conversion factor, it is seen that the proposed conversion factors are more suitable for the specific assets than the standardized conversion factors.
Outpatient Fully Endoscopic Cervical Unilateral Laminotomy for Bilateral Decompression with Virtual Postoperative Monitoring
Authors: Leyendecker Jannik , Yap Natalie , Prasse Tobias , Bredow Jan , Hofstetter Christoph P.
Published: April 2023

Objective: Cervical endoscopic unilateral laminotomy for bilateral decompression (CE-ULBD) is a promising novel surgical approach. However, to date, there is a paucity of data regarding safety, efficacy, and functional outcomes following CE-ULBD.Methods: The aim of this study was to investigate the outcomes of outpatient CE-ULBD combined with postoperative smartphone-based continuous physiological monitoring and virtual follow-up. Results: We included a total of 23 patients in our study group. The mean age was 69.1±2.5 years. A significant postoperative reduction of the visual analogue scale for neck pain (4.1±0.6 pre- vs. 2.3±0.5 post-surgery; P<0.0001) and upper extremity pain (2.6±0.6 vs. 1.1±0.3; P=0.0012) was reported alongside a significant improvement in the Neck Disability Index (18.6±2.5 vs. 9.1±2.5; p=0.032). Eleven patients were monitored with continuous physiological monitoring via a smartphone app (SPINEHealthie ). Those patients were more likely to be outpatients (p=0.0002) and less likely to have postoperative inpatient clinic utilization (p<0.0001). Continuous physiological monitoring suggested a trend towards higher levels of function in patients following CE-ULBD. Conclusion: : Our early results suggest that outpatient CE-ULBD followed by virtual postoperative monitoring is a safe and efficient therapeutic intervention for symptomatic cervical spinal stenosis.
“Face” in Retrospective: The use of “thanks” and “to thank” in Old Saxon and Old High German
Authors: Concu Valentina
Published: April 2023

Despite being often criticized, the notion of “face” has recently begun to be applied in diachronic pragmatic investigations on directives, requests, apologies, and terms of address. The present study also uses the notion of face to investigate the use of Danke ‘thanks’, Dankbarkeit ‘thankfulness’, and danken ‘to thank’ in expressions of gratitude in Old Saxon and Old High German, laying the foundations to a better understanding of the speech act of thanking in the history of German. The data suggest that, although the manifestation of gratitude was common, the expressions containing Danke, Dankbarkeit, and danken could mostly be found when the addresser was in a lower social position than the addressee. The same situation was observed when these nouns and verbs were used with the meaning of “to reward” and “to praise.” These findings provide evidence to the claim that the effects of a speech act on the speaker’s or hearer’s face are mostly situational rather than being an intrinsic property. They also suggest that, in strictly hierarchical societies such as the Old Saxon and Old High German ones, addressers would threaten their own negative face only if they were in a lower social position than the addressees.
Integrated analysis of robust sex-biased gene signatures in human brain.
Authors: Wapeesittipan Pattama , Joshi Anagha
Published: April 2023

Background: Sexual dimorphism is highly prominent in mammals with many physiological and behavioral differences between male and female form of the species. Accordingly, the fundamental social and cultural stratification factors for humans is sex. The sex differences are thought to emerge from a combination of genetic and environmental factors. It distinguishes individuals most prominently on the reproductive traits, but also affects many of the other related traits and manifest in different disease susceptibilities and treatment responses across sexes. Sex differences in brain have raised a lot of controversy due to small and sometimes contradictory sex-specific effects. Many studies have been published to identify sex-biased genes in one or several brain regions but the assessment of the robustness of these studies is missing. We therefore collected huge amount of publicly available transcriptomic data to first estimate whether consistent sex differences exist and further explore their likely origin and functional significance.
Results and Conclusion: In order to systematically characterise sex specific differences across human brain regions, we collected transcription profiles for more than 16,000 samples from about fifty datasets across eleven brain regions. By systematic integration of the data from multiple studies, we identified robust transcription level differences in human brain across to identify male-biased and female-biased genes in each brain region. Firstly, both male and female-biased genes were highly conserved across primates and showed a high overlap with sex-biased genes in other species. Female-biased genes were enriched for neuron-associated processes while male-biased genes were enriched for membranes and nuclear structures. Male-biased genes were enriched on the Y chromosome while female-biased genes were enriched on the X chromosome, which included X chromosome inactivation escapees explaining the origins of some sex differences. Male-biased genes were enriched for mitotic processes while female-biased genes were enriched for synaptic membrane and lumen. Finally, sex-biased genes were enriched for drug-targets and more female-biased genes were affected by adverse drug reactions than male-biased genes. In summary, by building a comprehensive resource of sex differences across human brain regions at gene expression level, we explored their likely origin and functional significance. We have also developed a web resource to make the entire analysis available for the scientific community for further exploration, available at https://joshiapps.cbu.uib.no/SRB app/.
Influence of femoral anteversion angle and neck-shaft angle on muscle forces and joint loading during walking
Authors: Kainz Hans , Mindler Gabriel T. , Kranzl Andreas
Published: April 2023

Femoral deformities, e.g. increased or decreased femoral anteversion (AVA) and neck-shaft angle (NSA), can lead to pathological gait patterns, altered joint loads, and degenerative joint diseases. The mechanism how femoral geometry influences muscle forces and joint load during walking is still not fully understood. Hence, we conducted a comprehensive musculoskeletal modelling study to investigate the influence of femoral AVA and NSA on muscle forces and joint loads during walking. We created 25 musculoskeletal models with a variety of NSA and AVA. For each model we calculated moment arms, muscle forces, muscle moments, and joint loads based on motion capture data of a healthy person with a typical gait pattern. We found a significant increase in co-contraction of hip and knee joint spanning muscles in models with increasing AVA and NSA, which led to a substantial increase in hip and knee joint contact forces. Decreased AVA and NSA had a minor impact on muscle and joint contact forces. Neglecting an individual’s femoral geometry when estimating joint contact forces can lead to errors above five times body weight. Knowing the influence of femoral geometry on muscle forces and joint loads can help clinicians to improve treatment strategies in patients with femoral deformities.
Geobody Estimation by Bhattacharyya Method Utilizing Nonlinear Inverse Modeling of Magnetic Data in Baba-Ali Iron Deposit, NW Iran
Authors: Kianoush Pooria , Khah Nasser Keshavarz Faraj , Hosseini Seyed Aliakbar , Jamshidi Emad , Afzal Peyman , Ebrahimabadi Arash
Published: April 2023

Geophysical investigations are one of the leading efforts in any exploration project that must be performed ahead of time due to the high excavation expenditures, heavy machinery, and cost reduction. One of the essential geophysical concerns is the estimation of the physical and geometrical parameters of the reserve (geobody), which is done by exploiting the nonlinear inverse modeling of magnetic data. These parameters include depth, volume, shape factor, and type of storage. The present investigation aims to prepare and model magnetic data for proposed drilling sites in the Baba Ali Iron ore deposit in the Hamedan province of Iran. The areal and depth extent of the iron ore geobody was unknown. The Bhattacharyya method by MATLAB software coding was used to minimize the target function and potential field data and create the best fit for the magnetic data. The residual anomaly and model graphs exhibited an excellent two-dimensional conformation in this modeling. Also, 3D modeling correctly reconstructs the properties of the productive resources of anomalies. After preparing full magnetic maps, the magnetic lenses distinguished in four anomalies of surface depths, 20, 50, and deeper than 50 meters for this zone. This magnetite lens for the first zone was estimated based on filters applied on the entire magnetic map so that the lens's depth is trivial and almost zero. Their specific gravity is calculated as 4.77 t/m3, and their initial storage capacity is suggested to be about 95,400 tones at most. Finally, to complete the preliminary explorations of the specified area, exploratory drilling is suggested for three points by inverse modeling.
Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases
Authors: Peyvandi Flora , Seidizadeh Omid , Cairo Andrea , Baronciani Luciano , Valenti Luca
Published: April 2023

Von Willebrand disease (VWD) is a common bleeding disorder caused by mutations in the von Willebrand factor gene (VWF). The true global prevalence of VWD has not been accurately established. We estimated the worldwide and within-population prevalence of inherited VWD by analyzing exome and genome data of 141,456 individuals gathered by the genome Aggregation Database (gnomAD). We also extended our data deepening by mining the main databases containing VWF variants i.e., the Leiden Open Variation Database (LOVD) and the Human Gene Mutation Database (HGMD) with the goal to explore the global mutational spectrum of VWD. A total of 4,313 VWF variants were identified in the gnomAD population, of which 505 were predicted to be pathogenic or already reported to be associated with VWD. Among the 282,912 alleles analyzed, 31,785 were affected by the aforementioned variants. The global prevalence of dominant VWD in 1000 individuals was established to be 74 for type 1, 3 for 2A, 3 for 2B and 6 for 2M. The global prevalences for recessive VWD forms (type 2N and type 3) were 0.03 and 3 in 1000 individuals, respectively. This comprehensive analysis provided a global mutational landscape of VWF by means of 927 already reported variants in the HGMD and LOVD datasets and 287 novel pathogenic variants identified in the gnomAD. Our results reveal that there is a considerably higher than expected prevalence of putative disease alleles and variants associated with VWD and suggest that a large number of VWD patients are undiagnosed.
Evolutionary Algorithm for Optimized CNN Architecture Search Applied to Real-Time Boat Detection in Aerial Images
Authors: Zerrouk Ilham , Moumen Younes , Khiati Wassim , Habchi Ali El , Berrich Jamal , Bouchentouf Toumi
Published: April 2023

When processing the detection of boats in aerial images by neural networks, we have always been concerned about the execution time of these networks in the equipment on board the Unmanned Aerial Vehicle (UAV). Throughout its mission, the UAV will capture images that must be processed in real time. For this purpose, a network optimized for execution time is essential. This article proposes an enhanced Network Architecture Search (NAS) method for searching for time-optimized detection networks, for a given dataset, using an evolutionary algorithm. The search uses mutations as a mechanism of evolution that affect the structure of the network and the hyper-parameters of its layers. Its original fitness function allows the choice of architectures that are not very greedy in terms of operations, specifically favouring small networks whose advantages are to be fast and quick to train, thus accelerating the search algorithm. Using this method, we were able to obtain detection networks with an improved mean Average Precision (mAP) compared to the initial network (parent) but with much fewer FLoating-point OPerations (Flops): 68% of operations reduction. This induces considerable gain in terms of execution time with 50 Frames Processed per Second (FPS) in an embedded environment on a drone.
Long-term Energy System Modelling for a Clean Energy Transition in Egypt's Energy Sector
Authors: Gibson Anna , Makuch Zen , Yeganyan Rudolf , Tan Naomi , Cannone Carla , Howells Mark
Published: April 2023

Egypt has the potential to generate significant amounts of renewable energy, in particular solar PV, concentrated solar power (CSP), and onshore and offshore wind. The energy sector is reliant on fossil fuels, particularly natural gas, for electricity production and is at risk of locking itself into a high carbon pathway. Globally, reducing greenhouse gas (GHG) emissions associated with national energy sectors is a target outlined in the UN’s Paris Agreement. To reduce carbon dioxide (CO2) emissions associated with a higher dependence on fossil fuels, Egypt must consider upscaling renewable energy technologies (RET) to achieve a clean energy transition (CET).

This research modelled six scenarios using OSeMOSYS to identify the technologies and policy target improvements that are needed to upscale RETs within Egypt’s energy sector. The results showed that solar PV and onshore wind are key technologies to be upscaled to contribute towards Egypt’s CET. The optimal renewable target is the International Renewable Energy Agency’s (IRENA) 53% of electricity to be sourced from RETs by 2030, which will cost $16.4 billion more up to 2035 than Egypt’s current Integrated Sustainable Energy Strategy (ISES) target of 42% by 2035; it also saves 732.0 Mt of CO2 over the entire modelling period to 2070.

Socio-economic barriers to this transition are considered, such as recent discoveries of natural gas reserves combined with a history of energy insecurity, political instability impacting investor confidence, and a lack of international climate funding. The paper concludes with policy recommendations that would enable Egypt to progress towards achieving a CET.
Increased nationwide use of greenspace in Norway during the COVID-19 pandemic
Authors: Ulset Vidar , Venter Zander , Kozák Michal , Nordbø Emma Charlott Andersson , von Soest Tilmann
Published: April 2023

In recent years, there has been growing concern about the decline in human greenspace use and nature-based recreation in Western countries. While some evidence suggests that the COVID-19 pandemic led to increased recreational mobility in urban greenspaces, it is unclear whether the pandemic led to nationwide changes in greenspace use in both densely and less densely populated neighborhoods, and whether social inequalities in greenspace use were reinforced or attenuated. To address these questions, we used daily nationwide aggregated mobility data from more than 2 million cell phone subscribers in 14,331 geographical grids across Norway to examine potential changes in mobility to greenspaces measured by the Normalized Difference Vegetation Index (NDVI) during the pandemic, while controlling for weather conditions, holidays, and neighborhood sociodemographic characteristics. Results from linear mixed model analyses showed a 9.4% increase in recreational dwells in the greenest spaces during the pandemic. Notably, this increase was most prominent in neighborhoods of low socioeconomic status and was observed in both high and low population density neighborhoods, although the increase was somewhat stronger in neighborhoods with low population density. Our study findings suggest that the COVID-19 pandemic has played a role in increasing nationwide greenspace use in Norway and potentially narrowing the gap of green inequality, highlighting the importance of preserving and promoting green spaces as a public health resource, particularly in disadvantaged neighborhoods.
Physics-Informed Neural Networks for Solving Time-Dependent Mode-Resolved Phonon Boltzmann Transport Equation
Authors: Luo Tengfei , Zhou Jiahang , Li Ruiyang
Published: April 2023

The phonon Boltzmann transport equation (BTE) is a powerful tool for modeling and understanding micro-/nanoscale thermal transport in solids, where Fourier's law can fail due to non-diffusive effect when the characteristic length/time is comparable to the phonon mean free path/relaxation time. However, numerically solving phonon BTE can be computationally costly due to its high dimensionality, especially when considering mode-resolved phonon properties and time dependency. In this work, we demonstrate the effectiveness of physics-informed neural networks (PINNs) in solving time-dependent mode-resolved phonon BTE. The PINNs are trained by minimizing the residual of the governing equations, and boundary/initial conditions to predict phonon energy distributions, without the need for any labeled training data. The results obtained using the PINN framework demonstrate excellent agreement with analytical and numerical solutions. Moreover, after offline training, the PINNs can be utilized for online evaluation of transient heat conduction, providing instantaneous results, such as temperature distribution. It is worth noting that the training can be carried out in a parametric setting, allowing the trained model to predict phonon transport in arbitrary values in the parameter space, such as the characteristic length. This efficient and accurate method makes it a promising tool for practical applications such as the thermal management design of microelectronics.
Water-soluble ions (WSIs) in the aerosols from Central Asia via transboundary transport measured in Jimunai in 2020
Authors: Wang Lin , Zhang Xin , Wang Feiteng , Ming Jing
Published: April 2023

Air pollution is a global issue that often transcends national borders, leading to disputes over environmental concerns and climate-mitigation responsibilities. Between March and July 2020, we collected aerosol samples in Jimunai, a town in western China neighboring Kazakhstan, to assess transboundary air pollution in the region. Our analysis focused on major water-soluble ions, with Ca2+ and SO42− accounting for almost 60% of the total ion loading. The ratio of cations to anions was greater than one, indicating alkaline aerosols during the sampling period. Our results suggest that the pollutants measured were primarily sourced from Kazakhstan, as demonstrated by local meteorological data, air-mass trajectory analysis, and pollutant emission inventories in Kazakhstan. Correlation and primary component analysis indicated that NH4+ played an important role in neutralizing NO3− and SO42−, while Cl− was significantly depleted by the probable reaction HNO3↑ + NaCl = HCl↑ + NaNO3. These findings highlight the need for continued monitoring and regulation of air pollution sources in the region to address transboundary air pollution.
Development of a robust induced pluripotent stem cell atrial cardiomyocyte differentiation protocol to model atrial arrhythmia
Authors: Thorpe Jordan , Perry Matthew D , Contreras Osvaldo , Hurley Emily , Parker George , Harvey Richard P , Hill Adam P , Vandenberg Jamie I
Published: April 2023

Background
Atrial fibrillation (AF) is the most common arrhythmia syndrome and causes significant morbidity and mortality. Current therapeutics, however, have limited efficacy. Notably, many therapeutics shown to be efficacious in animal models have not proved effective in humans. Thus, there is a need for a drug screening platform based on human tissue. The aim of this study was to develop a robust protocol for generating atrial cardiomyocytes from human-induced pluripotent stem cells.
Methods
A novel protocol for atrial differentiation, with optimized timing of retinoic acid during mesoderm formation, was compared to two previously published methods. Each differentiation method was assessed for successful formation of a contractile syncytium, electrical properties assayed by optical action potential recordings and multi-electrode array electrophysiology, and response to the G-protein-gated potassium channel activator, carbamylcholine. Atrial myocyte monolayers, derived using the new differentiation protocol, were further assessed for cardiomyocyte purity, gene expression, and the ability to form arrhythmic rotors in response to burst pacing.
Results
Application of retinoic acid at day 1 of mesoderm formation, resulted in a robust differentiation of atrial myocytes with contractile syncytium forming in 16/18 differentiations across two cell lines. Atrial-like myocytes produced have shortened action potentials and field potentials, when compared to standard application of retinoic acid at the cardiac mesoderm stage. Day 1 retinoic acid produced atrial cardiomyocytes are also carbamylcholine sensitive, indicative of active Ikach currents, which was distinct from ventricular myocytes and standard retinoic addition in matched differentiations. A current protocol utilizing reduced activin A and BMP4 can produce atrial cardiomyocytes with equivalent functionality but with reduced robustness of differentiation; only 8/17 differentiations produced a contractile syncytium.
The day 1 retinoic acid protocol was successfully applied to 6 iPSC lines (3 male and 3 female) without additional optimization or modification. Atrial myocytes produced could also generate syncytia with rapid conduction velocities, >40 cm/s, and form rotor style arrhythmia in response to burst pacing.
Conclusions
This method combines an enhanced atrial-like phenotype with robustness of differentiation, which will facilitate further research in human atrial arrhythmia and myopathies, whilst being economically viable for larger anti-arrhythmic drug screens.
Thyroid Hormones and Frailty in Older Adults: Systematic Review and Dose–Response Meta-Analysis
Authors: Chia Wen-Chun , Chen Yang-Ching , Xiu Shuang-ling , Wang Sen-Te
Published: April 2023

Objective To investigate (1) whether the association of thyroid hormone with frailty risk is linear or nonlinear and (2) what level of thyroid hormones or thyroid stimulating hormone (TSH) is most suitable for preventing frailty in older adults.Design: Systematic review and dose–response meta-analysisMethods Medical electronic databases were searched for cross-sectional or longitudinal studies, published from database inception to February 2022. We focused on the relationship between TSH and frailty. Data on TSH reference range, TSH exposure categories, sample size of each exposure category, and adjusted odds ratios (ORs) for frailty with 95% confidence interval (CI) were extracted. In the dose–response meta-analysis, we set the OR for frailty as 1 at 0.3 mIU/L TSH.Results The systematic review included 10 studies, whereas the meta-analysis included 3 studies (n = 6388). TSH levels ranged from 0.3 to 4.8 mIU/L, and the dose–response meta-analysis revealed a significant J-shaped association (p = 0.0071). Frailty OR (95% CI) increased from 1.30 (1.06–1.59) for 2.7 mIU/L TSH to 2.06 (1.18–3.57) for 4.8 mIU/L TSH.Conclusions A significant nonlinear, J-shaped association was noted between TSH level and frailty. TSH levels within the upper half (2.7-4.8mIU/L) of reference range was noted to significantly increase frailty risk; by contrast, those in the lower half (0.6–1.5 mIU/L) had a lower frailty risk, though nonsignificantly so.
Impact of cancer stem cell marker expression in vestibular schwannoma progression
Authors: Klause Clara Helene , Schildhauer Paola , Strauss Christian , Rampp Stefan , Scheller Christian , Leisz Sandra
Published: April 2023

Background: Vestibular schwannoma (VS), a benign tumor originating from the Schwann cells surrounding the 8th cranial nerve, is one of the most common intracranial tumors. Affected patients suffer from symptoms such as impaired hearing, dizziness and dysfunction of surrounding cranial nerves, which increase with the size of the VS. Although various factors influencing VS growth have been investigated, the molecular causes remain unclear. Cancer stem cells (CSC) are already known from malignant tumor entities to have the ability to self-renew and differentiate to generate and drive tumor growth. Therefore, our study investigated the influence of the expression of cancer stem cell markers in the VS progression.
Methods: An exploratory study of eleven CSC markers was performed in 165 VS of different tumor volume by quantitative real-time polymerase chain reaction and correlated with preoperative tumor volume. In addition, we investigated the CSC markers Nestin, Nanog, CD44 and CD45 in selected VS primary cultures by immunofluorescence and flow cytometry. Finally, a copy number variation analysis of 26 tumor samples was performed to investigate gain or loss of CSC markers at DNA level.
Results: Our results showed a strong correlation among CSC marker expression and a correlation of the tumor volume with eight CSC markers. In the VS, in particular, the expression of the markers CXCR4, CD44, CD45, Nestin, and CD133 were related to volume increase, whereas expression of SOX2, c-myc and Klf4 showed a negative correlation with the tumor volume. Using flow cytometry and immunofluorescence analysis, population of cells were detected expressing CD44 and CD45 as well as Nestin and Nanog simultaneously.
Conclusion: This suggests that there is a not previously described subpopulation of CSC in VS, which is associated with an increasing tumor volume. Due to the limited treatment options available for VS, these findings could offer the possibility of targeting CSC pharmacologically to prevent tumor progression in the VS.
Trial registration: The study was approved by the ethics committee of the Martin-Luther-University Halle-Wittenberg (approval number 2020-122) and ensures written informed consent of all patients.
Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry
Authors: Yamamoto Tsuyoshi , Terada Chisato , Oh Kaho , Tsubaki Ryutaro , Chan Bun , Aibara Nozomi , Ohyama Kaname , Shibata Masa-Aki , Wada Takehiko , Harada-Shiba Mariko , Yamayoshi Asako
Published: April 2023

Off-target interactions between antisense oligonucleotides (ASOs) with state-of-the-art modifications and biological components still pose clinical safety liabilities. To prevent both hybridization-dependent and -independent off-target interactions, a novel nanoarchitecture called BRace On a THERapeutic aSo (BROTHERS or BRO) consisting of typical gapmer ASO and partially complementary peptide nucleic acid (PNA) strand was devised. This non-canonical ASO/PNA hybrids have been shown to have non-specific protein-binding repellent characteristics. Feasible optimization of the structural and thermodynamic characteristics of this duplex system was also demonstrated to elicit in vivo operative toehold-mediated strand displacement (TMSD) reaction, which can reduce hybridization to RNA off-targets. The optimized BROs dramatically mitigated hepatotoxicity while maintaining the on-target knockdown activity of their parent ASOs in vivo. This new technique will not only bring a novel BRO class of drugs that would have a transformative impact on the extrahepatic delivery of ASOs, but also help uncover the toxicity mechanism of ASOs.
Breaking the fast: First report of dives and ingestions events in molting Southern elephant seals
Authors: Charlanne Laura , Chaise Laureline , Sornette Damien , Piot Erwan , McCafferty Dominic , Ancel André , Gilbert Caroline
Published: April 2023

Southern elephant seals experience a “catastrophic molt”, an energetically costly physiological event characterized by the total renewal of hair and epidermis and that requires a high peripheral vascular circulation. Molting individuals are therefore constrained by high metabolic heat loss. Molting animals have an extended period of fasting and in this species the molt period was previously thought to be spent entirely on land.
We therefore investigated movement-patterns and stomach temperature of female Southern elephant seals during the molting period. In contrast to previous predictions, our data demonstrated for the first time that molting females, conversely to what has been hypothesized, do travel at sea, and ingest water and/or prey items, despite the cost of cold exposure during their critical molt period.
We conclude that the paradigm of exclusive fasting during the molt in this species should be reconsidered as well as the possible fitness consequences of this behavior.
Drought triggers and sustains overnight fires in North America
Authors: Luo Kaiwei , Wang Xianli , de Jong Mark , Flannigan Mike
Published: April 2023

Overnight fires are emerging in North America with yet unknown drivers and implications. This phenomenon is significant as it challenges the traditional understanding of the “active day, quiet night” paradigm of the diurnal fire cycle and current fire management practices. Here we show that ~20% of all large fires (≥1000ha) in North America observed during 2017-2020 using geostationary satellite images and terrestrial fire records burned through a total of 1,084 nights. Overnight burning was characterized by early onset after ignition, high persistence, and a tendency to mutually reinforce extreme fires. While warming weakens the climatological barrier to general nighttime fires1, we found the major driver of overnight burning was the accumulated fuel dryness and fuel availability (i.e., drought conditions), rather than fast-reacting day-night weather fluctuations. Drought conditions tended to sustain overnight burning for periods of multiple days, and even weeks. Moreover, we show that daytime drought indicators can be used to predict overnight burning events, which could facilitate early detection and management of nighttime fires. Recently observed and predicted future increasing trends in conditions conducive to overnight burning indicate that disruption of the diurnal fire cycle may accelerate, leading to larger, more intense, and extreme fires in future.
Ileoileal knotting a rare cause of double loop small bowel obstruction, diagnostic and intraoperative challenge at Ethiopian Leku district hospital,sidama region, April 2023 ,case report
Authors: Kibret Asfaw
Published: April 2023

Baground: Intestinal obstruction is common cause for abdominal surgeries. Among the causes for intestinal obstruction ileal knotting is the unusual and rare cause with very few case reports in the globe and in Ethiopia. Almost all cases were intraoperative surprises. We report a case of strangulated closed small bowel loop obstruction caused by ileoileal knotting at distal ileum near to ileocecal junction, its diagnostic and management challenges and the role of the “Integrated Emergency surgical officers(IESO)’’ for early emergency surgical interventions in district primary hospitals in Ethiopia where there is scarce general specialist surgeon.
Case presentation: Here we discuss a 78yrs old male Ethiopian patient presented to our district hospital with sign symptoms of strangulated small bowel obstruction and exploratory laparatomy was done with intraoperative surprise of ileoileal knot with gangrenous closed loop obstruction at ileocecal junction. The gangrenous segment was resected and ileo-ascending colon anastomosis was done.The post operative stay was uneventful and patient discharged on his 7th post operation date.
Conclusion: Here we present this case to highlight difficulty of preoperative diagnosis and the need of high index of suspicion as well as the management challenges of resection anastomosis when the knot is near to ileocecal junction and the undeniable role of emergency surgical officers for early interventions of such emergency cases who need early interventions.
Physically inactive as a risk factor for obesity and reduced physical function in young adults
Authors: Rachmawati Maria Regina , Kusumaningsih Widjaja Laksmi , Suhartini Sri Mukti
Published: April 2023

Physical inactivity is associated with increased rates of noncommunicable diseases (NCDs). Some of the factors that indicate a person has risk for future NCDs are obesity and reduced measures of physical performance, such as appendicular muscle mass (ASM), hand grip strength (HGS), and gait speed (GS).
Objectives: Study to analyze the risk of physical inactivity for obesity and physical performance in young adults.
Method: The cross-sectional study included 419 young adults consisting of 206 (49.2%) men and 213 (50.8%) women. Physical activity (PA) values were determined using the International PA Questionnaire (IPAQ), with an inactive score <600 METs and an obesity standard ≥ 25 kg/m2. The values of lower ASM, HGS, and GS were based on the 2019 AWGS criteria.
Results: Physical inactivity rates were 327 (78%), 154 (47%) in men and 173 (53%) in women (p=0.125). Obesity rates were 162 (39%); however, in men, they were slightly higher than in women: 101 (62.3%) vs 61 (37.7%) (p<0.001). The low ASM rates were 104 (25%), i.e., in men were lower than in women; 34 (32.7%) vs 70 (67.3%) (p<0.001). The low HGS rates were 32 (8%), which was relatively similar between genders, 18 (56.3%) and 14 (43.8%) (p=0.464), and the low GS rates were 55 (13%), which was also similar between genders, 23 (42%) and 32 (58%) (p=0.25). Physically inactive was a risk factor for obesity in men (OR (95% CI)=1.2 (0.6-2)) and in women (OR (95% CI) = 1.5 (0.7-3)), for lower ASM (OR (95% CI) = 1.6 (0.9-3)), and for lower HGS (OR (95% CI) = 1.6 (0.6-4.2)). Physically inactive was not a risk factor for lower GS of OR (95% CI= 1 (0.6-2)).
Conclusion: Most young adults were physically inactive, thus increasing the risk of obesity and decreasing muscle mass and muscle strength.
The perception of locals on commercialisation and value addition of non-Timber Forest products in forest adjacent communities in Ghana
Authors: Asamoah Obed , Danquah Jones Abrefa , Bamsiegwe Dastan , Verter Nahanga , Acheampong Emmanuel , Boateng Charles Mario , Kuittinen Suvi , Appiah Mark , Pappinen Ari
Published: April 2023

Residents living adjacent to forests commonly gather non-timber forest products (NTFPs) for income, nourishment, ailment treatment, firewood, religious reasons, and artefacts. This study focused on the locals’ perception of NTFP value addition in forest-adjacent communities in Ghana. To determine which NTFPs are collected, we interviewed 732 residents about their perception of value addition to the NTFPs collected and if value addition has impacted the commercialisation and quality of the products obtained from the forest. We found that 97.5% of those surveyed frequently visited the forest to gather different NTFPs. For example, mushrooms, snails, honey and others were the most collected. Also, most interviewees do not process or add value to the NTFPs collected from the forest; thus, adding value to these NTFPs could increase incomes in the future. Future research should focus on educating locals about the value addition to NTFPs, and processes for increasing the price of NTFPs by adding value and commercialising these products. Proper commercialising of NTFPs will help improve the lives of the locals.
Efficient CO 2 Absorption through Wet Membrane Falling Film Contactors: Insights from Modeling and Simulation
Authors: Ghasem Nayef
Published: April 2023

This study investigates the use of wet membrane falling liquid film contactors to enhance the absorption of carbon dioxide (CO2) in a monoethanolamine (MEA) aqueous solution. Simulation and modeling analysis were performed to assess the effectiveness of the contactors in capturing CO2. The study analyzed the membrane surface area, flow rates, gas-liquid contact time, and solvent loading to investigate the CO2 absorption process in a falling film membrane contactor (FFMC). The results show that using FFMC significantly increases the CO2 capture rate compared to wet membranes. The study provides valuable insights into the use of contactors for CO2 capture and can serve as a basis for further research in this field. The study employed the finite element analysis method-based COMSOL Multiphysics 6.1 simulation software to conduct a numerical simulation of the CO2 mass transfer process in the FFMC system. The simulation model's accuracy was tested by comparing the simulated CO2 absorption efficiency and flux values in the MEA solution with experimental data. The results showed a favorable agreement between the predicted and experimental values, with an average relative error of approximately 4.3%. These findings suggest that the falling film membrane contactor approach holds significant potential for commercial applications in CO2 capture.