bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral and respiratory muscle strength in children and adolescents with CHD: systematic review and meta-analysis
Authors: Niedermeyer Camila da C. , Shizukuishi Maria Luiza Y. , Schaan Camila W. , Lukrafka Janice L.
Published: October 2022

Patients with CHD are less active if compared with controls and have limited functional capacity, related to muscle weakness and fatigue. The aim of this study was to evaluate the peripheral and respiratory muscle strength of children and adolescents with CHD with systematic review and meta-analysis. The review included observational and randomised control trial studies which evaluated peripheral and respiratory muscle strength in children and adolescents with CHD under 18 years old. The peripheral muscle strength was evaluated through dynamometry and respiratory muscle strength through manovacuometry. In studies that compared patients with CHD and respective control groups, it was possible to perform a meta-analysis. A total of 5634 articles met the criteria of eligibility, 15 were included in the systematic review, and 4 were included in the meta-analysis. Twelve studies assessed peripheral muscle strength with a reduction in patients with CHD. In the meta-analysis, patients with CHD had lower muscle strength than controls (−34.07 nm; 95% CI, −67.46 to −0.68; I2 47%; p for heterogeneity = 0.05), and the meta-analysis of the handgrip muscle strength showed no significant difference between patients with CHD and controls (0.08 nm; 95% CI, −6.39 to 6.55; I2 98%; p for heterogeneity <0.00001). The meta-analysis in the present study  showed lower limb muscle strength in patients with CHD in comparison to controls. In contrast, no difference was found regarding hand grip strength. Also, the review showed lower respiratory muscle strength in patients with CHD, yet no meta-analysis was possible to perform.
Close proximity to blast: No long-term or lasting effect on cognitive performance in service members with and without TBI during blast exposure
Authors: Lu L. H. , Reid M. W. , Troyanskaya M. , Scheibel R. S. , Muncy C. , Kennedy J. E.
Published: October 2022

Objective:

Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel.

Method:

One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates.

Results:

No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results.

Conclusion:

No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.
Adverse effects of maternal retinyl palmitate, a vitamin A compound, on the fetal liver
Authors: Aslan Duygu , Soztutar Erdem , Ay Hakan
Published: October 2022

Abstract: Background: Consuming high doses of vitamin A during pregnancy may lead to malformations in the offspring. Some reports state that low doses that do not cause macroscopic abnormalities may result in mental and behavioral disorders. However, there are few studies on the microscopic effects of these doses on the organism. Objective: The aim was to investigate the effects of early prenatal exposure to different doses of oral vitamin A on the fetal liver. Materials and methods: Twenty-five pregnant rats, divided into five groups, received oral vitamin A at doses of 10,000, 50,000, 100,000, and 200,000 IU/kg between days 10 and 12 of gestation. The fetuses were collected on day 19 of gestation, their livers were dissected, and histology, apoptosis, and proliferation were examined by hematoxylin-eosin, TUNEL assay, and Ki67 immunolabeling using stereological methods. Results: Vitamin A decreased fetal liver volume, the number of Ki67-positive cells per unit volume, and the total number of hepatocytes at all doses except 10,000 IU/kg (p<0.001). Consequently, apoptosis was significantly higher in the groups receiving 100,000 and 200,000 IU/kg vitamin A (p<0.001). Conclusion: Our study shows that vitamin A administered during gestation days 10–12 has a suppressive effect on the developing rat liver when the dose exceeds 10,000 IU/kg, probably due to increased apoptosis and suppressed cell division.
Ultrasound-guided venous pressure measurement
Authors: Gutwein Andreas , Thalhammer Christoph
Published: October 2022

Summary: Current standard technique for venous pressure measurement is still invasive, requiring insertion of a catheter. Additionally, clinical estimation of central venous pressure (CVP) has proven unreliable compared to invasive methods. Meanwhile, different non-invasive ultrasound guided modalities may provide a valid alternative to invasive venous pressure measurement. Particularly promising is a novel compression ultrasound (CUS) which combines ultrasound properties with a tissue pressure manometer enabling even further future applications. This review provides an overview using ultrasound guided non-invasive venous pressure measurement (UGPni) in clinical trials so far and focuses on three objectives: (1) To summarize the main methods using UGPni for central venous pressure measurement (2) To outline the key findings of previous clinical trials for UGPni regarding CVP measurement with primary focus on novel compression ultrasound of a forearm vein (3) To point out limitations and possible future clinical implications of these ultrasound modalities UGPni represents an easy-to-perform and safe alternative to invasive “gold standard” diagnostic tools for measuring central venous pressure. After a brief introduction, non-specialist personnel using a portable ultrasound device can apply this method in a feasible way. Of all mentioned methods in this review CUS is the method of choice underscoring its ability to assess a patient’s CVP categories correctly. Furthermore, detection of non-invasive central venous pressure in the emergency room represents an independent predictor for cardiac rehospitalization in patients with decompensated heart failure, thus helping in risk stratification as well as being an additive tool in general hemodynamic management of critically ill patients. This review concludes a significant role for ultrasound guided non-invasive venous pressure measurement suitable for a wide range of everyday clinical practice. However, further studies are warranted to proof a causal relationship in this regard.
The 3‐Machines Energy Transition Model: Exploring the Energy Frontiers for Restoring a Habitable Climate
Authors: Desing Harald , Gerber Andreas , Hischier Roland , Wäger Patrick , Widmer Rolf
Published: October 2022

To stabilize the climate, we need to urgently decarbonize our society and remove excess CO2 from the atmosphere. Ambitions for the transformation are ultimately limited by bio‐physical constraints, which cannot be transgressed even if all economic and societal obstacles could be overcome. Even though it is essential to know what transformation pathways are still feasible, there is a lack of studies and models exploring bio‐physical frontiers for climate action. In this paper, we take a first step to explore the energy frontier by introducing the “3‐machines energy transition model.” This simplified representation of the global energy system includes energy feedbacks and is constrained by the maximum renewable energy potential. Simulation experiments with the model show that with most ambitious actions global peak heating may exceed 1.5°C with a chance of 14%. Simultaneously, it is still energetically possible to return to 350 ppm this century, which is considered to be a safe level for atmospheric CO2 concentration. While these energy‐constrained transformation pathways show that the climate can still be stabilized with a fair chance, they also illustrate the urgency and far‐reaching change required in society.
Planning for Climate Migration in Great Lake Legacy Cities
Authors: Van Berkel Derek , Kalafatis Scott , Gibbons Beth , Naud Matthew , Lemos Maria Carmen
Published: October 2022

The possibility that climate change might make the Great Lakes region (GLR) a more attractive place for people to live has gained traction and attracted media attention. Compared with the dry Southwest, the storm‐ridden Gulf region and the sea‐level rise exposed East and West Coasts, the GLR may fare relatively favorably due to an abundance of natural resources and projected climate amenities. While the emergence and character of such migration is still uncertain, it is essential that GLR urban communities proactively prepare and plan for such a potential future. Understanding how these shifts might affect residents of GLR communities will be critical for a just and sustainable future and for avoiding exacerbating existing inequalities and climate vulnerabilities. Here we propose new scalable methodologies for inclusive engagement that enable wide‐reaching knowledge co‐creation (e.g., web‐based engagement) that can meet the emergent and diverse challenges communities will face. These methodologies have the potential to not only broaden participation and improve practitioners' understanding of different GLR communities' preferences, but also to anticipate emerging tensions and potential synergies associated with increased population pressures.
What Can Zircons Tell Us About the Evolution of Plants?
Authors: Tripathy-Lang Alka
Published: October 2022

The versatile mineral could contain evidence of the evolution of land plants and their effect on the sedimentary system.
Cluster Analysis of Dense GNSS Velocity Field Reveals Characteristics Associated With Regional Tectonics in New Zealand
Authors: Takahashi Atsushi , Hashimoto Manabu
Published: October 2022

New Zealand is located in the converging zone between the Australian and Pacific Plates. The Pacific Plate is descending beneath the Australian Plate in the north of New Zealand, while the Australian Plate is descending beneath the Pacific Plate in the south. The contrastive tectonics is connected by the Alpine Fault, the transform fault with NE‐SW strike along most of the length of New Zealand. Recently, previous studies showed that a cluster analysis of dense Global Navigation Satellite System (GNSS) velocity field objectively yields major velocity discontinuities, which may reflect an important tectonic boundary. We applied two different types of clustering algorithms: hierarchical agglomerative clustering (HAC) and Euler pole clustering (EPC), to the dense GNSS horizontal velocity data in New Zealand. Both methods agree that the primary kinematic boundary lies from the northern Wairarapa region to the southwestern end of the Alpine Fault. The HAC introduces a cluster boundary along the North Island Dextral Fault Belt whereas EPC emphasizes the importance of the Taupo Volcanic Zone (TVZ). Since EPC fits the data reasonably well, it indicates the TVZ is an important boundary. This result displays the limitation of the flat earth assumption. The Chatham Islands is identified as an independent cluster by the HAC, but not by the EPC. Further cluster splits illustrate that the relative motion between the two plates is accommodated by distributed deformation in the Marlborough Fault Zone in the South Island whereas the North Island is characterized by local block rotations.
Small‐Scale Spatial Variations of Air‐Sea Heat, Moisture, and Buoyancy Fluxes in the Tropical Trade Winds
Authors: Iyer Suneil , Drushka Kyla , Thompson Elizabeth J. , Thomson Jim
Published: October 2022

Observations from two autonomous Wave Gliders and six Lagrangian Surface Wave Instrument Float with Tracking drifters in the northwestern tropical Atlantic during the January–February 2020 NOAA Atlantic Tradewind Ocean‐atmosphere Mesoscale Interaction Campaign (ATOMIC) are used to evaluate the spatial variability of bulk air‐sea heat, moisture, and buoyancy fluxes. Sea surface temperature (SST) gradients up to 0.7°C across 10–100 km frequently persisted for several days. SST gradients were a leading cause of systematic spatial air‐sea sensible heat flux gradients, as variations over 5 Wm−2 across under 20 km were observed. Wind speed gradients played no significant role and air temperature adjustments to SST gradients sometimes acted to reduce spatial flux gradients. Wind speed, air temperature, and air humidity caused high‐frequency spatial and temporal flux variations on both sides of SST gradients. A synthesis of observations demonstrated that fluxes were usually enhanced on the warm SST side of gradients compared to the cold SST side, with variations up to 10 Wm−2 in sensible heat and upward buoyancy fluxes and 50 Wm−2 in latent heat flux. Persistent SST gradients and high‐frequency air temperature variations each contributed up to 5 Wm−2 variability in sensible heat flux. Latent heat flux was instead mostly driven by air humidity variability. Atmospheric gradients may result from convective structures or high‐frequency turbulent fluctuations. Comparisons with 0.05°‐resolution daily satellite SST observations demonstrate that remote sensing observations or lower‐resolution models may not capture the small‐scale spatial ocean variability present in the Atlantic trade wind region.
Evaluation of CMIP6 GCMs Over the CONUS for Downscaling Studies
Authors: Ashfaq Moetasim , Rastogi Deeksha , Kitson Joy , Abid Muhammad Adnan , Kao Shih‐Chieh
Published: October 2022

Despite the necessity of Global Climate Models (GCMs) sub‐selection in downscaling studies, an objective approach for their selection is currently lacking. Building on the previously established concepts in GCMs evaluation frameworks, we develop a weighted averaging technique to remove the redundancy in the evaluation criteria and rank 37 GCMs from the sixth phase of the Coupled Models Intercomparison Project over the contiguous United States. GCMs are rated based on their average performance across 66 evaluation measures in the historical period (1981–2014) after each metric is weighted between zero and one, depending on its uniqueness. The robustness of the outcome is tested by repeating the process with the empirical orthogonal function analysis in which each GCM is ranked based on its sum of distances from the reference in the principal component space. The two methodologies work in contrasting ways to remove the metrics redundancy but eventually develop similar GCMs rankings. A disparity in GCMs' behavior related to their sensitivity to the size of the evaluation suite is observed, highlighting the need for comprehensive multi‐variable GCMs evaluation at varying timescales for determining their skillfulness over a region. The sub‐selection goal is to use a representative set of skillful models over the region of interest without substantial overlap in their future climate responses and modeling errors in representing historical climate. Additional analyses of GCMs' independence and spread in their future projections provide the necessary information to objectively select GCMs while keeping all aspects of necessity in view.
The Use of Satellite Data‐Based “Critical Relative Humidity” in Cloud Parameterization and Its Role in Modulating Cloud Feedback
Authors: Wang Xiaocong , Miao Hao , Liu Yimin , Bao Qing , He Bian , Li Jinxiao , Zhao Yaxin
Published: October 2022

The critical relative humidity (RHc), which approximately measures the subgrid‐scale variability of moisture, is important to cloud parameterization. Based on the diagnostics from CloudSat/CALIPSO satellite data, we propose an improved RHc formula that incorporates geographic dependence and allows for non‐monotonic variations in the vertical. With the parameterized RHc, a cloud macrophysics scheme is constructed in which fractional cloudiness and subgrid‐scale condensation are synergistically solved, with the latter being calculated using two different approaches. Results show the new scheme largely alleviates the underestimation of high‐ and mid‐level clouds in the default model. The performance is also superior to the simulations applying a globally uniform RHc as conventionally used in the literature. Varying RHc and the techniques for computing subgrid‐scale condensation leads to a marked diversity in cloud feedback, which nearly replicates the range of uncertainty found in Coupled Model Intercomparison Project Phase 6 models. Using smaller RHc leads to larger spread than using larger ones. And the spread caused by different techniques for calculating subgrid‐scale condensation is larger than that caused by the choice of RHc. While many previous studies have emphasized the diversity of cloud feedback due to low clouds, varying RHc and its implementation leads to diversity of cloud feedback being mainly due to optically thick clouds. These results highlight the importance of RHc in inducing uncertainty of cloud feedback, as well as notes of caution to modelers when using RHc to tune models.
Single-cell view of deep-sea microbial activity and intracommunity heterogeneity
Authors: Arandia-Gorostidi N , Parada A E , Dekas A E
Published: October 2022

Microbial activity in the deep sea is cumulatively important for global elemental cycling yet is difficult to quantify and characterize due to low cell density and slow growth. Here, we investigated microbial activity off the California coast, 50–4000 m water depth, using sensitive single-cell measurements of stable-isotope uptake and nucleic acid sequencing. We observed the highest yet reported proportion of active cells in the bathypelagic (up to 78%) and calculated that deep-sea cells (200–4000 m) are responsible for up to 34% of total microbial biomass synthesis in the water column. More cells assimilated nitrogen derived from amino acids than ammonium, and at higher rates. Nitrogen was assimilated preferentially to carbon from amino acids in surface waters, while the reverse was true at depth. We introduce and apply the Gini coefficient, an established equality metric in economics, to quantify intracommunity heterogeneity in microbial anabolic activity. We found that heterogeneity increased with water depth, suggesting a minority of cells contribute disproportionately to total activity in the deep sea. This observation was supported by higher RNA/DNA ratios for low abundance taxa at depth. Intracommunity activity heterogeneity is a fundamental and rarely measured ecosystem parameter and may have implications for community function and resilience.
Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity
Authors: Wang Ruru , Shang Yajing , Chen Bin , Xu Feng , Zhang Jie , Zhang Zhaoyang , Zhao Xipeng , Wan Xiangbo , Xu An , Wu Lijun , Zhao Guoping
Published: October 2022

Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER) enzyme that mediates the formation of disulfide bonds, and is also a therapeutic target for cancer treatment. Our previous studies found that PDI mediates apoptotic signaling by inducing mitochondrial dysfunction. Considering that mitochondrial dysfunction is a major contributor to autophagy, how PDI regulates autophagy remains unclear. Here, we provide evidence that high expression of PDI in colorectal cancer tumors significantly increases the risk of metastasis and poor prognosis of cancer patients. PDI inhibits radio/chemo-induced cell death by regulating autophagy signaling. Mechanistically, the combination of PDI and GRP78 was enhanced after ER stress, which inhibits the degradation of AKT by GRP78, and eventually activates the mTOR pathway to inhibit autophagy initiation. In parallel, PDI can directly interact with the mitophagy receptor PHB2 in mitochondrial, then competitively blocks the binding of LC3II and PHB2 and inhibits the mitophagy signaling. Collectively, our results identify that PDI can reduce radio/chemo-sensitivity by regulating autophagy, which could be served as a potential target for radio/chemo-therapy.
Dispersive transport dynamics in porous media emerge from local correlations
Authors: Meigel Felix J. , Darwent Thomas , Bastin Leonie , Goehring Lucas , Alim Karen
Published: October 2022

Understanding and controlling transport through complex media is central for a plethora of processes ranging from technical to biological applications. Yet, the effect of micro-scale manipulations on macroscopic transport dynamics still poses conceptual conundrums. Here, we demonstrate the predictive power of a conceptual shift in describing complex media by local micro-scale correlations instead of an assembly of uncorrelated minimal units. Specifically, we show that the non-linear dependency between microscopic morphological properties and macroscopic transport characteristics in porous media is captured by transport statistics on the level of pore junctions instead of single pores. Probing experimentally and numerically transport through two-dimensional porous media while gradually increasing flow heterogeneity, we find a non-monotonic change in transport efficiency. Using analytic arguments, we built physical intuition on how this non-monotonic dependency emerges from junction statistics. The shift in paradigm presented here broadly affects our understanding of transport within the diversity of complex media.
The immune factors driving DNA methylation variation in human blood
Authors: Bergstedt Jacob , Azzou Sadoune Ait Kaci , Tsuo Kristin , Jaquaniello Anthony , Urrutia Alejandra , Rotival Maxime , Lin David T. S. , MacIsaac Julia L. , Kobor Michael S. , Albert Matthew L. , Duffy Darragh , Patin Etienne , Quintana-Murci Lluís ,   Milieu Intérieur Consortium, Abel Laurent , Alcover Andres , Aschard Hugues , Bousso Philippe , Bourke Nollaig , Brodin Petter , Bruhns Pierre , Cerf-Bensussan Nadine , Cumano Ana , d’Enfert Christophe , Deriano Ludovic , Dillies Marie-Agnès , Di Santo James , Dromer Françoise , Eberl Gérard , Enninga Jost , Fellay Jacques , Gomperts-Boneca Ivo , Hasan Milena , Hedestam Gunilla Karlsson , Hercberg Serge , Ingersoll Molly A. , Lantz Olivier , Kenny Rose Anne , Ménager Mickaël , Michel Frédérique , Mouquet Hugo , O’Farrelly Cliona , Pellegrini Sandra , Rausell Antonio , Rieux-Laucat Frédéric , Rogge Lars , Fontes Magnus , Sakuntabhai Anavaj , Schwartz Olivier , Schwikowski Benno , Shorte Spencer , Tangy Frédéric , Toubert Antoine , Touvier Mathilde , Ungeheuer Marie-Noëlle , Zimmer Christophe , Quintana-Murci Lluis
Published: October 2022

Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping. We show that DNA methylation differs substantially between naïve and memory T cells, supporting the need for adjustment on these cell-types. By doing so, we find that latent cytomegalovirus infection drives DNA methylation variation and provide further support that the increased dispersion of DNA methylation with aging is due to epigenetic drift. Finally, our results indicate that cellular composition and DNA sequence variation are the strongest predictors of DNA methylation, highlighting critical factors for medical epigenomics studies.
Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry
Authors: Dixon Tom , MacPherson Derek , Mostofian Barmak , Dauzhenka Taras , Lotz Samuel , McGee Dwight , Shechter Sharon , Shrestha Utsab R. , Wiewiora Rafal , McDargh Zachary A. , Pei Fen , Pal Rajat , Ribeiro João V. , Wilkerson Tanner , Sachdeva Vipin , Gao Ning , Jain Shourya , Sparks Samuel , Li Yunxing , Vinitsky Alexander , Zhang Xin , Razavi Asghar M. , Kolossváry István , Imbriglio Jason , Evdokimov Artem , Bergeron Louise , Zhou Wenchang , Adhikari Jagat , Ruprecht Benjamin , Dickson Alex , Xu Huafeng , Sherman Woody , Izaguirre Jesus A.
Published: October 2022

Targeted protein degradation (TPD) is a promising approach in drug discovery for degrading proteins implicated in diseases. A key step in this process is the formation of a ternary complex where a heterobifunctional molecule induces proximity of an E3 ligase to a protein of interest (POI), thus facilitating ubiquitin transfer to the POI. In this work, we characterize 3 steps in the TPD process. (1) We simulate the ternary complex formation of SMARCA2 bromodomain and VHL E3 ligase by combining hydrogen-deuterium exchange mass spectrometry with weighted ensemble molecular dynamics (MD). (2) We characterize the conformational heterogeneity of the ternary complex using Hamiltonian replica exchange simulations and small-angle X-ray scattering. (3) We assess the ubiquitination of the POI in the context of the full Cullin-RING Ligase, confirming experimental ubiquitinomics results. Differences in degradation efficiency can be explained by the proximity of lysine residues on the POI relative to ubiquitin.
The Donnan potential revealed
Authors: Aydogan Gokturk Pinar , Sujanani Rahul , Qian Jin , Wang Ye , Katz Lynn E. , Freeman Benny D. , Crumlin Ethan J.
Published: October 2022

Selective transport of solutes across a membrane is critical for many biological, water treatment and energy conversion and storage systems. When a charged membrane is equilibrated with an electrolyte, an unequal distribution of ions arises between phases, generating the so-called Donnan electrical potential at the solution/membrane interface. The Donnan potential results in the partial exclusion of co-ion, providing the basis of permselectivity. Although there are well-established ways to indirectly estimate the Donnan potential, it has been widely reported that it cannot be measured directly. Here we report the first direct measurement of the Donnan potential of an ion exchange membrane equilibrated with salt solutions. Our results highlight the dependence of the Donnan potential on external salt concentration and counter-ion valence, and show a reasonable agreement with current theoretical models of IEMs, which incorporate ion activity coefficients. By directly measuring the Donnan potential, we eliminate ambiguities that arise from limitations inherent in current models.
Involvement of striatal motoric subregions in familial frontotemporal dementia with parkinsonism harboring the C9orf72 repeat expansions
Authors: Liu Li , Liu Shuying , Chu Min , Wang Jingjuan , Xie Kexin , Cui Yue , Ma Jinghong , Nan Haitian , Cui Chunlei , Qiao Hongwen , Rosa-Neto Pedro , Chan Piu , Wu Liyong
Published: October 2022

The chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood. To explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews, physical examinations, genetic testing, [18F]-fluorodeoxyglucose PET/MRI, and [18F]-dihydrotetrabenazine PET/CT. Voxel-wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Patient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy. These findings imply that parkinsonism in FTDP may be associated with the degeneration and dopaminergic dysfunction of the striatal motor subregion, which might be attributed to C9orf72 repeat expansions.
Local and global energy barriers for chiral domain walls in synthetic antiferromagnet–ferromagnet lateral junctions
Authors: Yoon Jiho , Yang See-Hun , Jeon Jae-Chun , Migliorini Andrea , Kostanovskiy Ilya , Ma Tianping , Parkin Stuart. S. P.
Published: October 2022

Of great promise are synthetic antiferromagnet-based racetrack devices in which chiral composite domain walls can be efficiently moved by current. However, overcoming the trade-off between energy efficiency and thermal stability remains a major challenge. Here we show that chiral domain walls in a synthetic antiferromagnet–ferromagnet lateral junction are highly stable against large magnetic fields, while the domain walls can be efficiently moved across the junction by current. Our approach takes advantage of field-induced global energy barriers in the unique energy landscape of the junction that are added to the local energy barrier. We demonstrate that thermal fluctuations are equivalent to the magnetic field effect, thereby, surprisingly, increasing the energy barrier and further stabilizing the domain wall in the junction at higher temperatures, which is in sharp contrast to ferromagnets or synthetic antiferromagnets. We find that the threshold current density can be further decreased by tilting the junction without affecting the high domain wall stability. Furthermore, we demonstrate that chiral domain walls can be robustly confined within a ferromagnet region sandwiched on both sides by synthetic antiferromagnets and yet can be readily injected into the synthetic antiferromagnet regions by current. Our findings break the aforementioned trade-off, thereby allowing for versatile domain-wall-based memory, and logic, and beyond.
Intra-beat biomarker for accurate continuous non-invasive blood pressure monitoring
Authors: Abiri Arash , Chou En-Fan , Qian Chengyang , Rinehart Joseph , Khine Michelle
Published: October 2022

Accurate continuous non-invasive blood pressure (CNIBP) monitoring is the holy grail of digital medicine but remains elusive largely due to significant drifts in signal and motion artifacts that necessitate frequent device recalibration. To address these challenges, we developed a unique approach by creating a novel intra-beat biomarker (Diastolic Transit Time, DTT) to achieve highly accurate blood pressure (BP) estimations. We demonstrated our approach’s superior performance, compared to other common signal processing techniques, in eliminating stochastic baseline wander, while maintaining signal integrity and measurement accuracy, even during significant hemodynamic changes. We applied this new algorithm to BP data collected using non-invasive sensors from a diverse cohort of high acuity patients and demonstrated that we could achieve close agreement with the gold standard invasive arterial line BP measurements, for up to 20 min without recalibration. We established our approach's generalizability by successfully applying it to pulse waveforms obtained from various sensors, including photoplethysmography and capacitive-based pressure sensors. Our algorithm also maintained signal integrity, enabling reliable assessments of BP variability. Moreover, our algorithm demonstrated tolerance to both low- and high-frequency motion artifacts during abrupt hand movements and prolonged periods of walking. Thus, our approach shows promise in constituting a necessary advance and can be applied to a wide range of wearable sensors for CNIBP monitoring in the ambulatory and inpatient settings.
Chronic liver disease and hepatic calcium-oxalate deposition in patients with primary hyperoxaluria type I
Authors: Recker Pia , Beck Bodo Bernhard , Sikora Przemyslaw , Göbel Heike , Kemper Markus Josef , Nazco Angel , Martin-Higueras Cristina , Hoppe Bernd
Published: October 2022

Patients with primary hyperoxaluria type I (PH I) are prone to develop early kidney failure. Systemic deposition of calcium-oxalate (CaOx) crystals starts, when renal function declines and plasma oxalate increases. All tissue, but especially bone, heart and eyes are affected. However, liver involvement, as CaOx deposition or chronic hepatitis/fibrosis has never been reported. We examined liver specimen from 19 PH I patients (aged 1.5 to 52 years at sample collection), obtained by diagnostic biopsy (1), at autopsy (1), or transplantation (17). With polarization microscopy, birefringent CaOx crystals located in small arteries, but not within hepatocytes were found in 3/19 patients. Cirrhosis was seen in one, fibrosis in 10/19 patients, with porto-portal and nodular fibrosis (n = 1), with limitation to the portal field in 8 and/or to central areas in 5 patients. Unspecific hepatitis features were observed in 7 patients. Fiber proliferations were detectable in 10 cases and in one sample transformed Ito-cells (myofibroblasts) were found. Iron deposition, but also megakaryocytes as sign of extramedullary erythropoiesis were found in 9, or 3 patients, respectively. Overall, liver involvement in patients with PH I was more pronounced, as previously described. However, CaOx deposition was negligible in liver, although the oxalate concentration there must be highest.
Regulation of serine palmitoyl-transferase and Rac1–Nox2 signaling in diabetic retinopathy
Authors: Alka Kumari , Mohammad Ghulam , Kowluru Renu A.
Published: October 2022

Hyperlipidemia is considered as one of the major systemic factors associated with the development of diabetic retinopathy, and animal models have documented that its presence in a hyperglycemic environment exacerbates cytosolic ROS production (via activation of the Rac1–Nox2 axis) and mitochondrial damage. Hyperglycemia also accelerates Rac1 transcription via dynamic DNA methylation–hydroxymethylation of its promoter. In diabetes, ceramide metabolism in the retina is impaired and its accumulation is increased. Our aim was to investigate the effect of inhibition of the rate limiting enzyme of the de novo ceramide biosynthesis, serine palmitoyl-transferase (SPT), on Rac1 activation in diabetic retinopathy. Using human retinal endothelial cells, transfected with SPT-siRNA, and incubated in 20 mM d-glucose in the presence or absence of 50 µM palmitate (glucolipotoxic and glucotoxic, respectively), activities of Rac1 and Nox2, and ROS levels were quantified. For Rac1 transcriptional activation, 5 hydroxymethyl cytosine (5hmC) levels at its promoter were quantified. Key parameters were confirmed in retinal microvessels from streptozotocin-induced diabetic mice on a normal diet (type 1 diabetic model) or on a high-fat diet (45% kcal, type 2 diabetic model), injected intravitreally with SPT-siRNA. Compared to normal glucose, cells in high glucose, with or without palmitic acid, had increased Rac1–Nox2–ROS signaling, Rac1 transcripts and 5hmC levels at its promoter. Inhibition of SPT by SPT-siRNA or myriocin prevented glucotoxic- and glucolipotoxic-induced increase in Rac1–Nox2–ROS signaling and 5hmC at the Rac1 promoter. Similarly, in both type 1 and type 2 diabetic mouse models, SPT-siRNA attenuated the increase in the Rac1–Nox2–ROS axis and 5hmC at the Rac1 promoter. Thus, inhibition of the rate limiting enzyme of ceramide de novo biosynthesis, SPT, regulates activation of DNA methylation–hydroxymethylation machinery and prevents increased Rac1 transcription. This ameliorates the activation of Rac1–Nox2 signaling and protects the mitochondria from damaging cytosolic ROS, which prevents accelerated capillary cell loss. These results further raise the importance of regulating lipid levels in diabetic patients with dyslipidemia.
Retinal vascular assessment in psoriatic patients with and without metabolic syndrome using optical coherence tomography angiography
Authors: Tolba Doaa Ahmed , Amin Rana Hussein , Alorbani Aya Magdi , Mamdouh Esmat Sara
Published: October 2022

To evaluate the retinal vasculature in psoriasis patients and detect if metabolic syndrome is an additional risk factor. This cross-sectional analytic study was carried out on 80 eyes of 80 subjects; 28 eyes with psoriasis only (PS group), 12 eyes with additional metabolic syndrome to psoriasis (PMS group) and 40 eyes healthy controls (HS). The retinal capillary plexuses were evaluated by OCTA. The disease activity was evaluated by the Psoriasis Area and Severity Index (PASI) score and extent. The superficial capillary plexus (SCP) vascular density was significantly lower in PS group than HS while in PMS it was significantly lower only in whole image and superior and temporal perifoveal areas (p-value = 0.020, 0.030, 0.001 respectively). The changes correlated with the disease duration. The vascular density of the deep capillary plexus (DCP) was significantly lower in both PS and PMS groups (p-value < 0.001). Psoriatic patients are at a higher risk of developing retinal vascular complications even without evident clinical ocular disease. It was noted that the presence of metabolic syndrome contributes as an additional risk factor in possible visual loss secondary to ischemic changes that are likely to start in the DCP and progress to involve all levels.
Gut microbiota shift in layer pullets fed on black soldier fly larvae-based feeds towards enhancing healthy gut microbial community
Authors: Ndotono Evalyne W. , Khamis Fathiya M. , Bargul Joel L. , Tanga Chrysantus M.
Published: October 2022

Globally, most gut microbiota-related studies have focused on broilers due to their diverse microbial communities compared to that of layer chicken. However, in Africa few studies have been undertaken despite the increasing benefits to the poultry industry. The utilization of Insect-Based diets to improve the gastrointestinal function and gut health in poultry is increasingly gaining global attention. Here, we evaluated the potential roles of commercial black soldier fly larvae-based feeds (BSFLF) in reshaping the abundance, composition and diversity of the gut microbiota of layer chickens using high throughput Oxford nanopore Minion sequencing of the full length bacterial 16S rRNA gene. Two hundred and fifty ISA Brown layer chicks were reared in pens for a period of 20 weeks. The layer pullets were allotted 5 dietary treatments that were formulated as follows: control diet (T1): 100% FM + 0% BSFL, T2: 25% BSFL + 75% FM; T3: 50% BSFL + 50% FM; T4: 75% BSFL + 25% FM, and T5: 100% BSFL + 0% FM. Sampling was done from the eight major regions including oesophagus, crop, proventriculus, gizzard, duodenum, ileum, large intestines and ceca. Out of the 400,064 classified reads analyzed, the most dominant phyla identified across the feed treatments were Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. The diet treatment with 100% inclusion levels of BSFL showed the highest intra-species alpha diversity and richness according to Chao1 and Shannon index. Intra-species beta diversity assessment revealed that the diet types significantly influenced the abundance of the microbiota, but differences between most abundant taxa were similar. There was increase in abundance of potentially beneficial bacteria (Lactobacillus, Bacteroides and Enterococcus) with increased inclusion levels of BSFLF in layer pullets diets. Across the different gut segments, Lactobacillus dominated all the eight regions and the ceca was the most diverse segment. Our findings unravel complex gut microbial shift in laying hen fed BSFLF and therefore underpins the potential roles of beneficial bacteria as promising prebiotics and probiotics in reshaping of the gut microbiota to maintain good gut health.
Quantifying the relationship between specialisation and reputation in an online platform
Authors: Livan Giacomo , Pappalardo Giuseppe , Mantegna Rosario N.
Published: October 2022

Online platforms implement digital reputation systems in order to steer individual user behaviour towards outcomes that are deemed desirable on a collective level. At the same time, most online platforms are highly decentralised environments, leaving their users plenty of room to pursue different strategies and diversify behaviour. We provide a statistical characterisation of the user behaviour emerging from the interplay of such competing forces in Stack Overflow, a long-standing knowledge sharing platform. Over the 11 years covered by our analysis, we represent the interactions between users and topics as bipartite networks. We find such networks to display nested structures akin to those observed in ecological systems, demonstrating that the platform’s user base consistently self-organises into specialists and generalists, i.e., users who focus on narrow and broad sets of topics, respectively. We relate the emergence of these behaviours to the platform’s reputation system with a series of data-driven models, and find specialisation to be statistically associated with a higher ability to post the best answers to a question. We contrast our findings with observations made in top-down environments—such as firms and corporations—where generalist skills are consistently found to be more successful.
Field evolved insecticide resistance in the cotton mealybug Phenacoccus solenopsis and its direct and indirect impacts on the endoparasitoid Aenasius arizonensis
Authors: Shankarganesh Karuppan , Ricupero Michele , Sabtharishi Subramanian
Published: October 2022

Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) an invasive mealybug on cotton is primarily controlled by conventional insecticides. An endoparasitoid Aenasius arizonenesis (Girault) (Hymenoptera: Encyrtidae) is a potential biocontrol agent of this pest. We assessed the susceptibility in field populations of P. solenopsis and A. arizonensis to commonly used insecticides: profenofos, imidacloprid and thiodicarb. Reproductive traits of the parasitoid and Environmental Risk Assessment (ERA) parameters viz., Reduction coefficient, Descriptive analysis, Risk Index (RI), Selectivity ratio and Hazard quotient were measured to assess the direct and indirect effects of these insecticides on the parasitoid. Probit analysis revealed heterogeneity in the insecticide resistance development for both the cotton mealybug and its parasitoid. The field populations of P. solenopsis exhibited resistance to profenofos (18.87–59.86 folds) and thiodicarb (20.07 folds) and susceptibility to imidacloprid. Development of resistance to profenofos was observed in field populations of A. arizonensis. Exposure to lethal doses of imidacloprid and profenofos caused a reduction in parasitization (19–23%) and adult emergence (62–69%) of the parasitoid. Profenofos, thiodicarb and imidacloprid were found to be hazardous, non-selective and harmful to the endoparasitoid, A. arizonensis. There is an urgent need for optimizing insecticide applications for sustainable management of this invasive mealybug in cotton.
The ratio of 12α to non-12-hydroxylated bile acids reflects hepatic triacylglycerol accumulation in high-fat diet-fed C57BL/6J mice
Authors: Iwasaki Wakana , Yoshida Ryo , Liu Hongxia , Hori Shota , Otsubo Yuki , Tanaka Yasutake , Sato Masao , Ishizuka Satoshi
Published: October 2022

In our previous study, enterohepatic 12α-hydroxylated (12α) bile acid (BA) levels were found to be correlated with hepatic triacylglycerol concentration in rats fed high-fat (HF) diet. Since BA composition is diverse depending on animal species, we evaluated whether such a relationship is applicable in mice in response to an HF diet. C57BL/6JJmsSLC (B6) male mice were fed HF diet for 13 weeks and analyzed for triacylglycerol, cholesterol, oxysterols, and other metabolites in the liver. The BA composition was determined in the liver, small intestinal contents, portal plasma, aortic plasma, and feces. Neutral sterols were also measured in the feces. The ratio of 12α BA/non-12 BA increased in the liver, portal plasma, small intestinal contents, and feces of HF-fed B6 mice. Moreover, a positive correlation was observed between the ratio of fecal 12α BAs/non-12 BAs and hepatic triacylglycerol concentration. The concentration of 7α-hydroxycholesterol was increased in the liver of HF-fed B6 mice, whereas no increase was observed in the hepatic expression of cytochrome P450 family 7 subfamily A member 1. The present study showed that the ratio of 12α BA/non-12 BA in feces is closely associated with hepatic triacylglycerol accumulation in B6 mice fed HF diet.
Destruction of mesoscopic chemically modulated domains in single phase high entropy alloy via plastic deformation
Authors: Miyajima Yoji , Nagata Tomohiro , Takeda Kohei , Yoshida Shuhei , Yasuno Satoshi , Watanabe Chihiro , Kazuhiro Ishikawa , Adachi Hiroki , Tsuji Nobuhiro
Published: October 2022

Chemically modulated mesoscopic domains in a fcc single phase CrMnFeCoNi equi-atomic high entropy alloy (HEA) are detected by small angle diffraction performed at a synchrotron radiation facility, whereas the mesoscopic domains cannot be detected by conventional X-ray diffraction and 2D mappings of energy dispersive X-ray spectroscopy by scanning electron microscopy and scanning transmission electron microscopy. The mesoscopic domains are deformed and shrieked, and finally destructed by plastic deformation, which is supported by the comprehensive observations/measurements, such as electrical resistivity, Vickers hardness, electron backscattering diffraction, and hard X-ray photoemission spectroscopy. The destruction of the mesoscopic domains causes the decrease in electrical resistivity via plastic deformation, so called K-effect, which is completely opposite to the normal trend of metals. We confirmed that the presence and the size of local chemical ordering or short-range order domains in the single phased HEA, and furthermore, Cr and Mn are related to form the domains.
Nonlinear effects in Thomas precession due to the interplay of Lorentz contraction and Thomas–Wigner rotation
Authors: Di Lorenzo Antonio
Published: October 2022

It is demonstrated that the 3-vector $$\varvec{S}$$

S

currently associated to the spin in an inertial frame does not contract, but rather dilates, in the direction of the velocity. The correct vector $$\varvec{T}$$

T

is individuated. The equation of motion for the two vectors is shown to contain two terms, a common linear rotation, identified with Thomas precession, and also a nonlinear rotation depending on the direction of the spin itself.