bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact FGF23 concentration in healthy infants, children, and adolescents, and diagnostic usefulness in patients with X-linked hypophosphatemic rickets
Authors: Baroncelli G. I. , Sessa M. R. , Pelosini C. , Bertelloni S. , Michelucci A. , Toschi B. , Piaggi P. , Peroni D. , Comberiati P.
Published: November 2023

Objective

FGF23 measurement may have a diagnostic role to investigate patients with phosphate disorders. However, normal values for infants, children, and adolescents have not been defined.

Methods

In a total of 282 (males 145, females 137) healthy infants (n = 30), prepubertal (n = 147), pubertal (n = 59), and postpubertal (n = 46), and in twenty patients with X-linked hypophosphatemic rickets (XLH, age 10.2 ± 5.6 years) serum phosphate (automated analyzer), and plasma intact FGF23 (immunochemiluminescent sandwich assay, DiaSorin) concentrations were measured.

Results

Intact FGF23 concentrations were higher in healthy infants than in prepubertal (P < 0.01) and postpubertal subjects (P < 0.05); pubertal subjects showed higher values (P < 0.05) than postpubertal subjects. Serum phosphate concentrations were higher (P < 0.001) in healthy infants than in prepubertal, pubertal, and postpubertal subjects. Pubertal subjects had higher (P < 0.001) serum phosphate concentrations than postpubertal subjects. Intact FGF23 and serum phosphate concentrations did not differ (P = NS) by sex, age of menarche, and time after menarche. In healthy subjects, there was no correlation between intact FGF23 and serum phosphate concentrations. Intact FGF23 concentrations were higher (P < 0.0001) in patients with XLH than in healthy subjects according to chronological age and pubertal development. In all patients, intact FGF23 concentrations were above 40 pg/mL; intact FGF23 concentrations were inversely correlated with serum phosphate concentrations (r = −0.65; P < 0.01).

Conclusion

In healthy subjects, chronological age and puberty were main determinants of intact FGF23 concentrations. Intact FGF23 concentrations may be a useful marker for the early diagnosis of XLH in pediatric patients.
Recent Advances in Bioorthogonal Ligation and Bioconjugation
Authors: Zielke Florian M. , Rutjes Floris P. J. T.
Published: November 2023

The desire to create biomolecules modified with functionalities that go beyond nature’s toolbox has resulted in the development of biocompatible and selective methodologies and reagents, each with different scope and limitations. In this overview, we highlight recent advances in the field of bioconjugation from 2016 to 2023. First, (metal-mediated) protein functionalization by exploiting the specific reactivity of amino acids will be discussed, followed by novel bioorthogonal reagents for bioconjugation of modified biomolecules.
Spinel ferrites for resistive random access memory applications
Authors: Gayakvad Ketankumar , Somdatta Kaushik , Mathe Vikas , Dongale Tukaram , W Madhuri , Patankar Ketaki
Published: November 2023

Cutting edge science and technology needs high quality data storage devices for their applications in artificial intelligence and digital industries. Resistive random access memory (RRAM) is an emerging nonvolatile memory used for recording and reproducing the digital information. Earlier studies on RRAM applications suggest that spinel ferrite is a potential material. We envisage that the spinel ferrite prepared by a particular route, namely spin coating, will in future optimize the essential parameters for optimal functioning of RRAM. An assertion to our assumptions, few researchers have already obtained important findings for spin coated spinel ferrites. Spin coated spinel ferrites, namely zinc ferrite, nickel ferrite, cobalt ferrite and mixed spinel ferrites, have been investigated for their applications as switching layers in RRAM devices. Particularly, spin coated cobalt ferrite, nickel ferrite and doped nickel ferrite were widely used as resistive switching layers. However, it is noticed that there is a tremendous scope for synthesis and resistive switching characterization of spin coated pure and doped zinc ferrite. Proper doping of special element into spinel ferrite can enhance the resistive switching performance of RRAM devices. Insertion of nano structures and metal layers within switching layer uplifts the performance of spin coated spinel ferrite-based RRAM devices. Active layer in RRAM device synthesized by spin coating technique exhibited good resistive switching properties, namely retention of $$10^{3}$$

10
3

to $$10^{5}$$

10
5

s, endurance in the range of $$10^{2}$$

10
2

to 22,500 cycles and memory window of $$10^{2}$$

10
2

to $$10^{6}$$

10
6

. This review article accounts for the optimized parameters obtained especially for the spinel ferrite-based active material synthesized by spin coating justifying the results with appropriate theory. A good co-relation between synthesis parameters and the RRAM functional parameter is separately discussed at the end of review article.
Nutritional aspects, bioactive phytochemicals and biomedical traits of Opuntia spp.: current trends and applications
Authors: Alshaikhi Asmaa Ibrahim , Alzahrani Manar Yahya , Hazzazi Jumanah Samir , Kurdi Jumanah Reda , Ramadan Mohamed Fawzy
Published: November 2023

This review was conducted to fully comprehend the nutritional value of the Opuntia spp., alongside the impact of the bioactive components on health and how well they combat disease. Opuntia ficus-indica fruit is plentiful with the amino acid taurine, a therapeutic compound, alongside vitamins C, E, and K. Opuntia plants are renowned for having a high level of phenolic acids, antioxidants, and pigments like betalains in all of their parts (pulp, roots, cladodes, seeds, and juice). Bioactives content enables Opuntia ficus-indica fruit to generate significant antidepressant effects, an anticancer impact, and the ability to prevent fatty liver disease or hepatic steatosis. Opuntia ficus-indica fruit has a desirable technique of consumption that may be applied as a nutritious component in several edible and value-added items. Fruits and stems may be eaten, making them a great natural energy source and supplement antioxidants and nutritional components that may be added to the diet. Traditionally, Opuntia ficus-indica seed oil is used in various foods, cosmetic products, and medications, mainly for treating chronic disorders, wound healing, and urinary tract infections in traditional folk medicine. In addition, Opuntia fruits could be utilized successfully in various food and nonfood applications.
Transferable and Fixable Proofs
Authors: D'Alessandro William
Published: November 2023

A proof

${\cal P}$

of a theorem T is transferable when it's possible for a typical expert to become convinced of T solely on the basis of their prior knowledge and the information contained in

${\cal P}$

. Easwaran has argued that transferability is a constraint on acceptable proof. Meanwhile, a proof

${\cal P}$

is fixable when it's possible for other experts to correct any mistakes

${\cal P}$

contains without having to develop significant new mathematics. Habgood-Coote and Tanswell have observed that some acceptable proofs are both fixable and in need of fixing, in the sense that they contain non-trivial mistakes. The claim that acceptable proofs must be transferable seems quite plausible. The claim that some acceptable proofs need fixing seems plausible too. Unfortunately, these attractive suggestions stand in tension with one another. I argue that the transferability requirement is the problem. Acceptable proofs need to only satisfy a weaker requirement I call “corrigibility.” I explain why, despite appearances, the corrigibility standard is preferable to stricter alternatives.
Dynamics and scaling of particle streaks in high-Reynolds-number turbulent boundary layers
Authors: Berk Tim , Coletti Filippo
Published: November 2023

Inertial particles in wall-bounded turbulence are known to form streaks, but experimental evidence and predictive understanding of this phenomenon is lacking, especially in regimes relevant to atmospheric flows. We carry out wind tunnel measurements to investigate this process, characterizing the transport of microscopic particles suspended in turbulent boundary layers. The friction Reynolds number$Re_\tau = {O}(10^4)$allows for significant scale separation and the emergence of large-scale motions, while the range of viscous Stokes number$St^+=18$–870 is relevant to the transport of dust and fine sand in the atmospheric surface layer. We perform simultaneous imaging of both carrier and dispersed phases along wall-parallel planes in the logarithmic layer, demonstrating that streamwise particle streaks largely overlap with large-scale low-speed flow regions. The fluid–particle slip velocity indicates that with increasing inertia, the particle streaks outlive the low-speed fluid streaks. Moreover, two-point statistics show that the width of the particle streaks increases linearly with Stokes number, bounded by the size of the coherent flow structures. Finally, the particle-sampled flow topology suggests that particle streaks reside between the legs of hairpin packets. From these observations, we infer a conceptual view of the formation of particle streaks in the frame of the attached eddy model. A scaling for the particle streaks’ width is derived as a function of$Re_\tau$and$St^+$, which reproduces the measured trends and predicts widths${O}(0.1)$m in the atmospheric surface layer, comparable to aeolian streamers observed in the field.
Ideal and non-ideal planar compressible fluid flows in radial equilibrium
Authors: Gajoni Paolo , Guardone Alberto
Published: November 2023

Two-dimensional compressible flows in radial equilibrium are investigated in the ideal dilute-gas regime and the non-ideal single-phase regime close to the liquid–vapour saturation curve and the critical point. Radial equilibrium flows along constant-curvature streamlines are considered. All properties are therefore independent of the tangential streamwise coordinate. A differential relation for the Mach number dependency on the radius is derived for both ideal and non-ideal conditions. For ideal flows, the differential relation is integrated analytically. Assuming a constant specific heat ratio

$\gamma$

, the Mach number is a monotonically decreasing function of the radius of curvature for ideal flows, with

$\gamma$

being the only fluid-dependent parameter. In non-ideal conditions, the Mach number profile also depends on the total thermodynamic conditions of the fluid. For high molecular complexity fluids, such as toluene or hexamethyldisiloxane, a non-monotone Mach number profile is admissible in single-phase supersonic conditions. For Bethe–Zel'dovich–Thompson fluids, non-monotone behaviour is observed in subsonic conditions. Numerical simulations of subsonic and supersonic turning flows are carried out using the streamline curvature method and the computational fluid dynamics software SU2, respectively, both confirming the flow evolution from uniform flow conditions to the radial equilibrium profile predicted by the theory.
Dynamic separation on an accelerating prolate spheroid
Authors: Guo Pengming , Kaiser Frieder , Rival David E.
Published: November 2023

Time-varying flow separation on an accelerating prolate spheroid has been studied at various angles of incidence. Instantaneous pressure and scanning stereoscopic particle image velocimetry were used to shed light on the evolution of cross-flow structures for the Reynolds number (

$Re$

) range of

$1.0\times 10^6\leq Re \leq 1.5\times 10^6$

. The movement of separation lines is examined for various model accelerations to investigate on the interplay between acceleration and flow separation. The results demonstrate that for axial accelerations, the streamwise pressure distribution in the rear part of the prolate spheroid switches from an adverse to a favourable pressure gradient. At the same time, the circumferential adverse pressure gradient present during steady motion vanishes during said accelerations. In contrast, both streamwise and circumferential adverse pressure gradients strengthen when the model is axially decelerated. These dynamic pressure distributions influence the location of the separation line, which in turn moves closer to the model meridian during accelerations while moving outwards during decelerations. The streamwise vorticity distribution and the streamwise circulation both show how the separation-line position impacts the vortex formation. A high-vorticity region near the model surface is established during acceleration. In contrast, a decelerating model leads to transport of high-vorticity fluid into the outer area of the cross-flow separation. We further assess the memory effects following the near-impulsive velocity changes. The cross-flow retains the memory of moving separation lines shortly after the acceleration. However, the separation recovers quickly to a steady state.
How old is the Ordovician–Silurian boundary at Dob’s Linn, Scotland? Integrating LA-ICP-MS and CA-ID-TIMS U-Pb zircon dates
Authors: Garza Hector K. , Catlos Elizabeth J. , Chamberlain Kevin R. , Suarez Stephanie E. , Brookfield Michael E. , Stockli Daniel F. , Batchelor Richard A.
Published: November 2023

Sedimentary rocks exposed at Dob’s Linn, Scotland, have significantly influenced our understanding of how life evolved over the Ordovician to Early Silurian. The current interpreted chronostratigraphic boundary between the Ordovician and Silurian periods is a Global Boundary Stratotype Section and Point (GSSP), calibrated to 443.8 ± 1.5 Ma (Hirnatian–Rhuddanian age), based on biostratigraphic markers, radioisotopic dates and statistical modelling. However, challenges arise due to tectonic disturbances, complex correlation issues and the lack of systematic dating in Ordovician–Silurian stratigraphic sections. Here, hundreds of zircon grains from three metabentonite ash horizons were dated using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). A subset of the grains were re-analyzed using Chemical Abrasion Isotope Dilution Thermal Ionization Mass Spectrometry (CA-ID-TIMS). We present a high-precision CA-ID-TIMS 238U-206Pb weighted mean date of 440.44 ± 0.55/0.56/0.72 Ma (±analytical/with tracer/with U-decay constant) for the Coronagraptus cyphus biozone. However, the study reports younger, and in certain cases, older LA-ICP-MS zircon dates within the Coronagraptus cyphus, Akidograptus ascensus and Dicellograptus anceps zones, suspected as being influenced by Pb loss and LA-ICP-MS matrix mismatch. The study reports concerns about the suitability of Dob’s Linn as a GSSP section and examines various LA-ICP-MS maximum depositional age (MDA) approaches, suggesting the use of the TuffZirc date and the youngest mode weighted mean (YMWM) as suitable MDA calculations consistent with CA-ID-TIMS results.
“The Teacher of Teachers”: James Mill and the Education of John Stuart Mill
Authors: Loizides Antis
Published: November 2023

John Stuart Mill's account of his education in Autobiography (1873) is typically sifted through three interrelated sets of polarities: nurture/nature; reason/emotion; authority/autonomy. First, the father tried to mold the son's development towards a specific ideal, curbing his spontaneous growth. Second, James relentlessly sharpened John Stuart's analytical prowess to the almost total neglect of his emotional needs. Third, the authoritarianism involved in the design and execution of James Mill's curriculum rendered John Stuart Mill incapable of autonomy. This article argues that the dualities of nurture/nature and reason/emotion are not unambiguous, though ever-present in the reception of the younger Mill's education. Widening our perspective in their examination opens the possibility of a different assessment of that famous education being no education for autonomy.
Perceptual alterations in the relationship between sensory reactivity, intolerance of uncertainty, and anxiety in autistic children with and without ADHD
Authors: Powell Helen J. , He Jason L. , Khalil Nermin , Wodka Ericka L. , DeRonda Alyssa , Edden Richard A. E. , Vasa Roma A. , Mostofsky Stewart H. , Puts Nicolaas A.
Published: November 2023

Sensory differences and anxiety disorders are highly prevalent in autistic individuals with and without ADHD. Studies have shown that sensory differences and anxiety are associated and that intolerance of uncertainty (IU) plays an important role in this relationship. However, it is unclear as to how different levels of the sensory processing pathway (i.e., perceptual, affective, or behavioral) contribute. Here, we used psychophysics to assess how alterations in tactile perception contribute to questionnaire measures of sensory reactivity, IU, and anxiety. Thirty-eight autistic children (aged 8-12 years; 27 with co-occurring ADHD) were included. Consistent with previous findings, mediation analyses showed that child-reported IU fully mediated an association between parent-reported sensory reactivity and parent-reported anxiety and that anxiety partially mediated an association between sensory reactivity and IU. Of the vibrotactile thresholds, only simultaneous frequency discrimination (SFD) thresholds correlated with sensory reactivity. Interestingly, we found that sensory reactivity fully mediated an association between SFD threshold and anxiety, and between SFD threshold and IU. Taken together, those findings suggest a mechanistic pathway whereby tactile perceptual alterations contribute to sensory reactivity at the affective level, leading in turn to increased IU and anxiety. This stepwise association can inform potential interventions for IU and anxiety in autism.
Do normative data specific to Greek Australian older adults improve validity of neuropsychological assessment results?
Authors: Staios Mathew , Kosmidis Mary H. , Tsiaras Yiannis , Nielsen T. Rune , Papadopoulos Alexandra , Kokkinias Arthur , Velakoulis Dennis , March Evrim , Stolwyk Renerus J.
Published: November 2023

Objective:

This study aimed to compare Greek Australian and English language normative data with regard to impairment rates yielded within a healthy Greek Australian older adult sample. We also examined whether optimal cut scores could be identified and capable of sensitively and specifically distinguishing between healthy Greek Australians from those with a diagnosis of Alzheimer’s disease (AD).

Method:

Ninety healthy Greek Australian older adults and 20 demographically matched individuals with a diagnosis of AD completed a range of neuropsychological measures, including the Wechsler Adult Intelligence Scale-Fourth Edition, Greek Adaptation (WAIS-IV GR), verbal and visual memory, language and naming, and executive functions. Impairment rates derived from the use of either Greek Australian or English language normative data were calculated and compared, using a 1.5 standard deviation criterion to denote impairment. Receiver operating characteristics curve analysis was used to investigate the sensitivity and specificity of alternate cut scores.

Results:

Impairment rates derived from the Greek Australian normative data showed that rates of impairment generally fell within the expected 7% range. In contrast, impairment rates for all tests derived using English language normative data were significantly higher and ranged from 11%–66%. Comparisons between healthy and AD participants with moderate dementia showed significant differences across all measures. Area under the curve results ranged from .721 to .999 across all measures, with most tests displaying excellent sensitivity and specificity.

Conclusions:

English language normative data were found to be inappropriate for use with Greek Australian elders, potentially leading to erroneous diagnostic outcomes. The use of minority group specific normative data and associated cut points appear to partially ameliorate this issue. Clinical implications are discussed alongside future research directions.
Inaccurate forecasting of a randomized controlled trial
Authors: Ahrenshop Mats , Golden Miriam , Gulzar Saad , Sonnet Luke
Published: November 2023

We report the results of a forecasting experiment about a randomized controlled trial that was conducted in the field. The experiment asks Ph.D. students, faculty, and policy practitioners to forecast (1) compliance rates for the RCT and (2) treatment effects of the intervention. The forecasting experiment randomizes the order of questions about compliance and treatment effects and the provision of information that a pilot experiment had been conducted which produced null results. Forecasters were excessively optimistic about treatment effects and unresponsive to item order as well as to information about a pilot. Those who declare themselves expert in the area relevant to the intervention are particularly resistant to new information that the treatment is ineffective. We interpret our results as suggesting that we should exercise caution when undertaking expert forecasting, since experts may have unrealistic expectations and may be inflexible in altering these even when provided new information.
Future Global Population Exposure to Record‐Breaking Climate Extremes
Authors: Li Bohao , Liu Kai , Wang Ming , Wang Qianzhi , He Qian , Li Chenxia
Published: November 2023

The increase in record‐breaking extreme events caused by climate change poses a threat to human health and well‐being. Understanding the future impacts of such events on global populations can provide decision‐making support for policies aiming to mitigate climate change. Here, we investigated the population exposure to eight climate extreme indices and drivers of exposure trajectories based on National Aeronautics and Space Administration Earth Exchange Global Daily Downscaled Projections Coupled Model Intercomparison Project 6 and population projection data under four shared socioeconomic pathway scenarios at a spatial resolution of 0.25° × 0.25°. The results show that by the mid‐twenty‐first century, most regions worldwide, especially Africa and South America, will continue to experience record‐breaking temperatures and compound drought and heatwaves (CDHWs). Regarding population exposure, under SSP3‐7.0 in the late twenty‐first century, the mean value of the multimodel median expected annual exposure (EAE) of all extreme temperature indices and CDHW reaches 8.12 billion persons per year. Population exposure hotspots will be concentrated in Central Africa, South Asia, Southeast Asia, and East Asia, mostly in developing countries, where 55.01%–87.42% of the EAE is found. The drivers of exposure trajectories are spatially heterogeneous. The increase in record‐breaking probability contributes more than population growth to EAE growth in most regions of the world except Central Asia, the Middle East, and most of Africa. These findings reveal the future trajectories of record‐breaking probabilities and population exposures for climate extremes, which can inform understanding of the intersections between climate change and population change and future risk management.
Role of Atmospheric Indices in Describing Shoreline Variability Along the Atlantic Coast of Europe
Authors: Masselink Gerd , Castelle Bruno , Scott Tim , Konstantinou Aikaterini
Published: November 2023

Beaches are highly variable environments and respond to changes in wave forcing, themselves modulated by climate variability. Here, we analyze three high‐quality beach profile data sets to robustly investigate, for the first time, the link between shoreline change, wave forcing and climate variability along the Atlantic coast of Europe. Winter wave conditions are strongly associated with North Atlantic Oscillation (NAO) and Western Europe Pressure Anomaly (WEPA), with WEPA explaining 50%–80% of the winter wave power variability. Shoreline variability during winter is also strongly linked to NAO and WEPA, with WEPA explaining 25% of the winter shoreline variability. Winter wave conditions and associated shoreline variability are both unrelated to El Nino Southern Oscillation. In addition to the atmospherically‐forced beach morphological response, shoreline change also depends strongly on the antecedent morphology as evidenced by significant correlations between summer/winter shoreline response and the shoreline position at the start of each season.
A case of infantile spasms with three possibly pathogenic de novo missense variants in NF1 and GABBR1
Authors: Watanabe Kazuki , Kubota Kazuo , Nakashima Mitsuko , Saitsu Hirotomo
Published: November 2023

Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. Here, we report a unique case of a patient with typical NF1 findings and infantile spasms who had three possibly pathogenic de novo variants, c.3586C>T, p.(Leu1196Phe) and c.3590C>T, p.(Ala1197Val) in NF1 located in cis and c.1042G>C, p.(Ala348Pro) in GABBR1. This study contributes to our understanding of the effect of two cis variants on NF1 phenotypes and GABBR1-related neuropsychiatric disorders.
Prenatal hypertension as the risk of eclampsia, HELLP syndrome, and critical obstetric hemorrhage
Authors: Akaishi Tetsuya , Tarasawa Kunio , Hamada Hirotaka , Iwama Noriyuki , Tomita Hasumi , Akaishi Miho , Fushimi Kiyohide , Fujimori Kenji , Yaegashi Nobuo , Saito Masatoshi
Published: November 2023

Critical bleeding is a common cause of maternal mortality in obstetric patients. However, the non-obstetric factors underlying critical obstetric bleeding remain uncertain. Therefore, this study aimed to clarify the impact of chronic hypertension on obstetric hemorrhage by evaluating a nationwide administrative database in Japan. Women who gave birth between 2018 and 2022 were enrolled. The primary outcome was critical hemorrhage requiring massive red blood cell (RBC) transfusion during childbirth. In total, 354, 299 eligible women were selected from the database. The maternal mortality rate was >1.0% among those who received a massive RBC transfusion (≥4000 cc), and this amount was used as the cutoff of the outcome. Critical hemorrhage was less frequent with elective Caesarean section (CS) compared with vaginal childbirth or emergent CS (odds ratio [OR], 0.38; 95% confidence interval, 0.30–0.47). Multiple logistic regression analysis adjusting for these obstetric risks revealed that a higher maternal age (adjusted OR [aOR] per 1 year, 1.07 [1.05–1.09]); oral medications with prednisolone (aOR, 2.5 [1.4–4.4]), anti-coagulants (aOR, 10 [5.4–19]), and anti-platelets (aOR, 2.9 [1.3–6.4]); and a prenatal history of hypertension (aOR, 2.5 [1.5–4.4]) and hypoproteinemia (aOR, 5.8 [1.7–20]) are the risks underlying critical obstetric hemorrhage. Prenatal history of hypertension was significantly associated with obstetric disseminated intravascular coagulation (OR, 1.9 [1.5–2.4]); Hemolysis, Elevated Liver enzymes, and Low platelet count (HELLP) syndrome (OR, 3.3 [2.7–4.2]); and eclampsia (OR, 6.1 [4.6–8.1]). In conclusion, a maternal prenatal history of hypertension is associated with the development of HELLP syndrome, eclampsia, and resultant critical hemorrhage.
Hopfion rings in a cubic chiral magnet
Authors: Zheng Fengshan , Kiselev Nikolai S. , Rybakov Filipp N. , Yang Luyan , Shi Wen , Blügel Stefan , Dunin-Borkowski Rafal E.
Published: November 2023

Magnetic skyrmions and hopfions are topological solitons1—well-localized field configurations that have gained considerable attention over the past decade owing to their unique particle-like properties, which make them promising objects for spintronic applications. Skyrmions2,3 are two-dimensional solitons resembling vortex-like string structures that can penetrate an entire sample. Hopfions4–9 are three-dimensional solitons confined within a magnetic sample volume and can be considered as closed twisted skyrmion strings that take the shape of a ring in the simplest case. Despite extensive research on magnetic skyrmions, the direct observation of magnetic hopfions is challenging10 and has only been reported in a synthetic material11. Here we present direct observations of hopfions in crystals. In our experiment, we use transmission electron microscopy to observe hopfions forming coupled states with skyrmion strings in B20-type FeGe plates. We provide a protocol for nucleating such hopfion rings, which we verify using Lorentz imaging and electron holography. Our results are highly reproducible and in full agreement with micromagnetic simulations. We provide a unified skyrmion–hopfion homotopy classification and offer insight into the diversity of topological solitons in three-dimensional chiral magnets.
Sequential appetite suppression by oral and visceral feedback to the brainstem
Authors: Ly Truong , Oh Jun Y. , Sivakumar Nilla , Shehata Sarah , La Santa Medina Naymalis , Huang Heidi , Liu Zhengya , Fang Wendy , Barnes Chris , Dundar Naz , Jarvie Brooke C. , Ravi Anagh , Barnhill Olivia K. , Li Chelsea , Lee Grace R. , Choi Jaewon , Jang Heeun , Knight Zachary A.
Published: November 2023

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1–4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.
Distinguishing cells using electro-acoustic spinning
Authors: Saghaei Tayebeh , Weber Andreas , Reimhult Erik , van Oostrum Peter D. J.
Published: November 2023

Many diseases, including cancer and covid, result in altered mechanical and electric properties of the affected cells. These changes were proposed as disease markers. Current methods to characterize such changes either provide very limited information on many cells or have extremely low throughput. We introduce electro-acoustic spinning (EAS). Cells were found to spin in combined non-rotating AC electric and acoustic fields. The rotation velocity in EAS depends critically on a cell's electrical and mechanical properties. In contrast to existing methods, the rotation is uniform in the field of view and hundreds of cells can be characterized simultaneously. We demonstrate that EAS can distinguish cells with only minor differences in electric and mechanical properties, including differences in age or the number of passages.
Evaluating the effectiveness of stain normalization techniques in automated grading of invasive ductal carcinoma histopathological images
Authors: Voon Wingates , Hum Yan Chai , Tee Yee Kai , Yap Wun-She , Nisar Humaira , Mokayed Hamam , Gupta Neha , Lai Khin Wee
Published: November 2023

Debates persist regarding the impact of Stain Normalization (SN) on recent breast cancer histopathological studies. While some studies propose no influence on classification outcomes, others argue for improvement. This study aims to assess the efficacy of SN in breast cancer histopathological classification, specifically focusing on Invasive Ductal Carcinoma (IDC) grading using Convolutional Neural Networks (CNNs). The null hypothesis asserts that SN has no effect on the accuracy of CNN-based IDC grading, while the alternative hypothesis suggests the contrary. We evaluated six SN techniques, with five templates selected as target images for the conventional SN techniques. We also utilized seven ImageNet pre-trained CNNs for IDC grading. The performance of models trained with and without SN was compared to discern the influence of SN on classification outcomes. The analysis unveiled ap-value of 0.11, indicating no statistically significant difference in Balanced Accuracy Scores between models trained with StainGAN-normalized images, achieving a score of 0.9196 (the best-performing SN technique), and models trained with non-normalized images, which scored 0.9308. As a result, we did not reject the null hypothesis, indicating that we found no evidence to support a significant discrepancy in effectiveness between stain-normalized and non-normalized datasets for IDC grading tasks. This study demonstrates that SN has a limited impact on IDC grading, challenging the assumption of performance enhancement through SN.
Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
Authors: Bai Wenya , Huo Siying , Li Junjie , Yang Yuan , Zhou Guilin , Shao Jianlin
Published: November 2023

Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats involved in anti-CIRI effects of Biliverdin, providing experimental foundation for searching specific marker proteins. Rat model of MCAO/R was established, HE staining, TTC staining, TUNEL staining, and neurological behavioral examination, corner turning test, adhesive removal test, were performed to validate the effects of Biliverdin, and the results indicated that Biliverdin plays a significant role in alleviating CIRI. Furthermore, proteomic analysis of brain tissues of rats subjected to CIRI following Biliverdin treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology to clarify the comprehensive mechanisms of Biliverdin in CIRI. First, we conducted strict quality control data for TMT experiments. Finally, a total of 7366 proteins were identified, of which 95 proteins were differentially expressed (DEPs) between the CIRI group and the Sham group and 52 between the CIRI and BV groups. In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.
Design of high bulk moduli high entropy alloys using machine learning
Authors: Kandavalli Manjunadh , Agarwal Abhishek , Poonia Ansh , Kishor Modalavalasa , Ayyagari Kameswari Prasada Rao
Published: November 2023

In this work, the authors have demonstrated the use of machine learning (ML) models in the prediction of bulk modulus for High Entropy Alloys (HEA). For the first time, ML has been used for optimizing the composition of HEA to achieve enhanced bulk modulus values. A total of 12 ML algorithms were trained to classify the elemental composition as HEA or non-HEA. Among these models, Gradient Boosting Classifier (GBC) was found to be the most accurate, with a test accuracy of 78%. Further, six regression models were trained to predict the bulk modulus of HEAs, and the best results were obtained by LASSO Regression model with an R-square value of 0.98 and an adjusted R-Square value of 0.97 for the test data set. This work effectively bridges the gap in the discovery and property analysis of HEAs. By accelerating material discovery via providing alternate means for designing virtual alloy compositions having favourable bulk modulus for respective applications, this work opens new avenues of applications of HEAs.
Genetic architecture of individual meiotic crossover rate and distribution in Atlantic Salmon
Authors: Brekke Cathrine , Johnston Susan E. , Knutsen Tim M. , Berg Peer
Published: November 2023

Meiotic recombination through chromosomal crossovers ensures proper segregation of homologous chromosomes during meiosis, while also breaking down linkage disequilibrium and shuffling alleles at loci located on the same chromosome. Rates of recombination can vary between species, but also between and within individuals, sex and chromosomes within species. Indeed, the Atlantic salmon genome is known to have clear sex differences in recombination with female biased heterochiasmy and markedly different landscapes of crossovers between males and females. In male meiosis, crossovers occur strictly in the telomeric regions, whereas in female meiosis crossovers tend to occur closer to the centromeres. However, little is known about the genetic control of these patterns and how this differs at the individual level. Here, we investigate genetic variation in individual measures of recombination in > 5000 large full-sib families of a Norwegian Atlantic salmon breeding population with high-density SNP genotypes. We show that females had 1.6 × higher crossover counts (CC) than males, with autosomal linkage maps spanning a total of 2174 cM in females and 1483 cM in males. However, because of the extreme telomeric bias of male crossovers, female recombination is much more important for generation of new haplotypes with 8 × higher intra-chromosomal genetic shuffling than males. CC was heritable in females (h2 = 0.11) and males (h2 = 0.10), and shuffling was also heritable in both sex but with a lower heritability in females (h2 = 0.06) than in males (h2 = 0.11). Inter-sex genetic correlations for both traits were close to zero, suggesting that rates and distribution of crossovers are genetically distinct traits in males and females, and that there is a potential for independent genetic change in both sexes in the Atlantic Salmon. Together, these findings give novel insights into the genetic architecture of recombination in salmonids and contribute to a better understanding of how rates and distribution of recombination may evolve in eukaryotes more broadly.
Small peptide formulas versus standard polymeric formulas in critically ill patients with acute gastrointestinal injury: a systematic review and meta-analysis
Authors: Wang Youquan , Li Yanhua , Li Hongxiang , Li Yuting , Li Xinyu , Zhang Dong
Published: November 2023

Small peptide formulas versus standard polymeric formulas for enteral nutrition in critically ill patients with acute gastrointestinal injury (AGI) have been a topic of debate. A systematic review and meta-analysis were conducted to compare their clinical and nutritional outcomes. Relevant studies from January 1980 to June 2022 were searched in PubMed, Cochrane, and Embase databases. Randomized controlled trials involving AGI grade I-IV patients were included, while children, non-AGI patients, and non-critically ill patients were excluded. Results indicated no significant difference in all-cause mortality. Patients receiving small peptide formulas showed higher daily protein intake, greater albumin growth, and higher prealbumin levels. They also had shorter lengths of stay in the intensive care unit and hospital. Conversely, patients receiving standard polymeric formulas had a higher daily calorie intake. In conclusion, the choice of formula may not affect mortality in critically ill patients with AGI. Small peptide formulas were more conducive to increase daily protein intake, decrease intensive care unit and hospital length of stay. Further large-scale randomized controlled trials evaluating the effects of these two nutritional formulas on clinical and nutritional outcomes in critically ill patients with AGI are needed to confirm these results.
Validation of a modified visual analogue scale to measure user-perceived comfort of a lower-limb exoskeleton
Authors: Mohammed El Husaini Mohammed , Maberry Axl , Martin Anne E.
Published: November 2023

User perceived exoskeleton comfort is likely important for device acceptance, but there is currently no validated instrument to measure it. The Visual Analogue Scale (VAS) is an existing tool to measure subjective human feedback by asking the user to mark a point on a line with each end of the line representing an opposing anchor statement. It can be modified to show the previous response, allowing the subject to directly indicate if the current condition is better or worse than the previous one. The goal of this study was to determine how well the modified VAS could measure user-perceived comfort as the exoskeleton control parameters were varied. To validate the survey, 14 healthy subjects walked in a pair of ankle exoskeletons with approximately ten distinct sets of control parameters tested in a prescribed order. Each set of control parameters was tested twice. After each trial, user-perceived comfort was measured using a two-question VAS survey. The repeatability coefficient was approximately 40 mm, similar to the total range of responses. The results were also inconsistent, with relative rankings between consecutive pairs of conditions matching for approximately 50% of comparisons. Thus, as tested, the VAS was not repeatable or consistent. It is possible that subject adaptation within the trial and over the course of the experiment may have impacted the results. Additional work is needed to develop a repeatable method to measure comfort and to determine how perceived comfort varies as subjects’ gain exoskeleton experience.
Diagnostic implications of lncRNA NORAD in breast cancer
Authors: Zhang Yaping , Fan Xiaowei , Hong Jianfeng , Yang Enyu , Xuan Cheng , Fang Hongming , Ding Xianfeng
Published: November 2023

This study aimed to assess the expression levels of non-coding RNA activated by DNA damage (NORAD) in the cells, tissues, and serum of breast cancer (BRCA) patients and benign breast nodules and investigate its association with clinicopathological characteristics and prognosis in BRCA. NORAD was analyzed using TCGA-BRCA, GSE77308, Cellminer, and Sangerbox databases, revealing its significance in BRCA prognosis, immune microenvironment, and cell function. Serum samples from 38 BRCA patients, 80 patients with benign breast nodules (50 fibroadenoma and 30 breast adenosis cases), and 42 healthy individuals were collected from Zhejiang Xiaoshan Hospital. NORAD expression was quantified using quantitative reverse transcription PCR (RT-qPCR). Differential NORAD expression between benign and malignant breast nodules and its relationship to clinicopathological characteristics were assessed. NORAD demonstrated elevated expression in BRCA patient serum compared to healthy individuals and those with benign breast nodules (P < 0.05). Moreover, its expression correlated with TNM-stage, lymph node metastasis, and luminal classification. These findings highlight the elevated NORAD expression in BRCA patient serum and its correlation with clinicopathological characteristics, providing insights into its potential as a diagnostic biomarker or therapeutic target.
Environmental DNA-based biomonitoring of Cuban Crocodylus and their accompanying vertebrate fauna from Zapata Swamp, Cuba
Authors: Pérez-Fleitas Etiam , Milián-García Yoamel , Sosa-Rodríguez Gustavo , Amato George , Rossi Natalia , Shirley Matthew H. , Hanner Robert H.
Published: November 2023

Crocodylians globally face considerable challenges, including population decline and extensive habitat modification. Close monitoring of crocodylian populations and their habitats is imperative for the timely detection of population trends, especially in response to management interventions. Here we use eDNA metabarcoding to identify the Critically EndangeredCrocodylus rhombiferand the VulnerableC. acutus, as well as vertebrate community diversity, in Cuba’s Zapata Swamp. We tested four different primer sets, including those used previously inCrocodyluspopulation genetic and phylogenetic research, for their efficiency at detecting crocodylian eDNA. We detectedC. rhombifereDNA in 11 out of 15 sampled locations within its historical geographic distribution. We found that data analyses using the VertCOI primers and the mBRAVE bioinformatics pipeline were the most effective molecular marker and pipeline combination for identifying this species from environmental samples. We also identified 55 vertebrate species in environmental samples across the four bioinformatics pipelines— ~ 85% known to be present in the Zapata ecosystem. Among them were eight species previously undetected in the area and eight alien species, including known predators of hatchling crocodiles (e.g.,Clariassp.) and egg predators (e.g.,Mus musculus). This study highlights eDNA metabarcoding as a powerful tool for crocodylian biomonitoring within fragile and diverse ecosystems, particularly where fast, non-invasive methods permit detection in economically important areas and will lead to a better understanding of complex human-crocodile interactions and evaluate habitat suitability for potential reintroductions or recovery programs for threatened crocodylian species.
PBK correlates with prognosis, immune escape and drug response in LUAD
Authors: Ma Hongyu , Zhang Jing , Shi Yan , Wang Ziqiang , Nie Wenhu , Cai Jingjing , Huang Yinglong , Liu Bin , Wang Xiaojing , Lian Chaoqun
Published: November 2023

PBK (PDZ-binding kinase) is a protein-coding gene that encodes a serine/threonine protein kinase associated with the dual-specific mitogen-activated protein kinase (MAPKK) family. Overexpression of this gene is closely linked to tumor development. In this study, we aimed to investigate the role of PBK in lung adenocarcinoma (LUAD) progression, prognosis, and immune evasion. We conducted a pan-cancer analysis of PBK to examine its expression and prognostic value. In the LUAD cohort, we analyzed PBK expression, prognosis, mutational features, and immune infiltration in groups with different PBK expression levels. We constructed a PBK-associated genomic model, integrated it into a nomogram, and compared high and low-risk subgroups. In our pan-cancer analysis, PBK was significantly upregulated, particularly in LUAD patients, and displayed poor prognosis. The high PBK expression group had many deletion mutations but still showed gene upregulation. Immune infiltration analysis indicated that PBK-triggered immune escape in the high expression group might relate to antigen presentation, dendritic cell, and CD8+ T cell infiltration. We constructed a 5-gene prognostic model and a nomogram to quantify individual survival probabilities. The PBK-associated gene prognostic model reliably predicted patient prognosis and drug response. Our findings offer new insights into PBK-induced immune escape and targeted therapy during LUAD development, providing valuable suggestions for clinical treatment approaches.
NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma
Authors: Wang Naixue , Zhu Dantong , Liu Yao , Wu Jingran , Wang Meiling , Jin Shanxiu , Fu Fangwei , Li Baolei , Ji Hongjuan , Du Cheng , Zheng Zhendong
Published: November 2023

Few prognostic biomarkers exist for lung squamous cell carcinoma (LUSC), which has a poor five-year survival rate. Using bioinformatics, this study evaluated NPLOC4 as a prognostic marker for patients with lung squamous cell carcinoma. Shorter survival periods and tumor growth were linked to high NPLOC4 expression.Disulfiram (DSF) combined with copper (Cu) targets NPLOC4 to achieve antitumor effects in lung squamous cell carcinoma. Thus, we investigated the effects of DSF with Cu in LUSC. Gene-set enrichment analysis identified ubiquitin-mediated proteolysis as the NPLOC4-associated mechanism influencing LUSC prognosis. In SK-MES-1 cell lines, DSF + Cu increased K48-linked ubiquitinated protein expression and apoptosis. This study identified NPLOC4 as a prognostic biomarker and a potential therapeutic target for LUSC.