bluuebunny/crossref_metadata_2025 huggingface dataset:
Icaritin Sensitizes Thrombin- and TxA2-Induced Platelet Activation and Promotes Hemostasis via Enhancing PLCγ2-PKC Signaling Pathways
Authors: Zhu Zhixiang , Luo Yanggan , Liao Hanjing , Guo Ran , Hao Doudou , Lu Zihan , Huang Manjing , Sun Chenghong , Yao Jingchun , Wei Ning , Zeng Kewu , Tu Pengfei , Zhang Guimin
Published: January 2024

Background Vascular injury results in uncontrollable hemorrhage in hemorrhagic diseases and excessive antithrombotic therapy. Safe and efficient hemostatic agents which can be orally administered are urgently needed. Platelets play indispensable roles in hemostasis, but there is no drug exerting hemostatic effects through enhancing platelet function.

Methods The regulatory effects of icaritin, a natural compound isolated from Herba Epimedii, on the dense granule release, thromboxane A2 (TxA2) synthesis, α-granule release, activation of integrin αIIbβ3, and aggregation of platelets induced by multiple agonists were investigated. The effects of icaritin on tail vein bleeding times of warfarin-treated mice were also evaluated. Furthermore, we investigated the underlying mechanisms by which icaritin exerted its pharmacological effects.

Results Icaritin alone did not activate platelets, but significantly potentiated the dense granule release, α-granule release, activation of integrin αIIbβ3, and aggregation of platelets induced by thrombin and U46619. Icaritin also shortened tail vein bleeding times of mice treated with warfarin. In addition, phosphorylated proteome analysis, immunoblotting analysis, and pharmacological research revealed that icaritin sensitized the activation of phospholipase Cγ2 (PLCγ2)-protein kinase C (PKC) signaling pathways, which play important roles in platelet activation.

Conclusion Icaritin can sensitize platelet activation induced by thrombin and TxA2 through enhancing the activation of PLCγ2-PKC signaling pathways and promote hemostasis, and has potential to be developed into a novel orally deliverable therapeutic agent for hemorrhages.
Alpha-Thalassemia X-Linked Intellectual Disability Syndrome in a Boy with a Strong Family History of Smith–Lemli–Opitz's Syndrome
Authors: Jafar Bedour , Sharma Kamal P. , Maertens Paul
Published: January 2024

Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is a rare disorder characterized by facial dysmorphism, genitourinary tract abnormalities, alpha-thalassemia, and cognitive impairment. Patients present in early infancy with hypotonia, microcephaly, failure to thrive, and delayed milestones. We report a boy with strong family history of the Smith–Lemli–Opitz's syndrome (SLOS) phenotype. All affected family members displayed facial features and presentation identical to those of our patient. None had hypocholesterolemia. All affected family members were boys and have died. Molecular genetic testing in our patient revealed a likely pathogenic mutation in the X-linked recessive ATRX gene. We conclude that SLOS and ATRX syndrome are uncommon disorders sharing similar manifestations. Awareness of such similarity should prompt physicians to explore the possibility of ATRX syndrome in relatives of patients with unproven SLOS.
Structural and functional analysis of Buchanan’s constitutional contract
Authors: Liu Mingyu
Published: January 2024

Buchanan attempted to seek new theoretical construction through the contract method by introducing elements such as ‘individual’, ‘veil of uncertainty’, ‘public choice’, ‘decision costs’, and ‘unanimous agreement principle’. He not only transformed the contract theory model but also interpreted the ideas of consensus politics in an acceptable manner. Specifically, ‘individuals’ are entities of choice and behavior, and the process of choice allows individuals to express different goals and interests. The ‘veil of uncertainty’ prompts individuals to think about issues from a fair point of view when interests cannot be identified and future prospects are unpredictable and to make choices that are beneficial for both themselves and the group. ‘Public choice’ can solve the problem of justice diversity because it does not exclude different or conflicting motivations and goals. ‘Decision costs’ and ‘external costs’ both limit the way collective decisions are made and help identify the normal consequences of constitutional choices. The ‘unanimous agreement principle’ gives everyone equal status, allowing each person the right to pursue their own goals and values and preventing others from abusing their power. The use of the aforementioned theoretical elements not only helps people discuss constitutional choices at a general level but also helps to present the true face of the collective decision-making process, thereby establishing an empirical theory about the actual logic of individual actions in the political system.
Simple method for optical characterization of surface agents on conjugated silver nanoparticles
Authors: Koushki Ehsan , Ghasedi Arman
Published: January 2024

In this study, a simple formula has been proposed to calculate the refractive index of surface agents of silver nanoparticles (Ag NPs) by using the plasmonic peak of the absorption spectra of dispersed Ag nano-colloids. The basis of the study is the shift in the localized surface plasmon resonance (LSPR) of Ag NPs upon alteration of surface agents. The color changes in a typical metal nano-colloid are mainly due to the shift in the LSPR, which is caused because of electrical interactions of surface agents on the particles. There are some theoretical models to simulate the absorption spectrum, but using these methods to evaluate the plasmonic peak is not facile for a wide range of users. Here, the required simulations were performed for different values of the refractive index of surface agents and particle sizes, and the absorption spectrum and dispersive curves were accordingly plotted. A simple formula was obtained between the wavelength of the plasmonic peak, the refractive index of the shell of surface agents, and the ratio of the hydrodynamic diameter to Feret size of the particles (R0). The refractive index of the surface agents can be calculated by n2=λmax−(202.3R02−748.6R0+947.4)−152.2R02+561.3R0−405.1, where λmax (in nanometer) is the wavelength of the absorption peak due to LSPR. This method can pave the way for experimenters to obtain the refractive index and consequently the type of surface agents around Ag NPs without the need for numerical or mathematical operations. It can also be useful in analyzing the spectral diagnosis of biological agents such as viral antibodies and antigens.
Glycine max acyl–acyl carrier protein thioesterase B gene overexpression alters lipid content and fatty acid profile of Arabidopsis seeds
Authors: Zhao Shihui , Yan Fan , Liu Yajing , Sun Monan , Wang Ying , Li Jingwen , Zhang Xinsheng , Yang Xuguang , Wang Qingyu
Published: January 2024

The fatty acyl–acyl carrier protein thioesterase B (FATB) gene, involved in the synthesis of saturated fatty acids, plays an important role in the content of fatty acid and composition of seed storage lipids. However, the role of FATB in soybeans (Glycine max) has been poorly characterised. This paper presents a preliminary bioinformatics and molecular biological investigation of 10 hypothetical FATB members. The results revealed that GmFATB1B, GmFATB2A and GmFATB2B contain many response elements involved in defense and stress responses and meristem tissue expression. Moreover, the coding sequences of GmFATB1A and GmFATB1B were significantly longer than those of the other genes. Their expression varied in different organs of soybean plants during growth, with GmFATB2A and GmFATB2B showing higher relative expression. In addition, subcellular localisation analysis revealed that they were mainly present in chloroplasts. Overexpression of GmFATB1A, GmFATB1B, GmFATB2A and GmFATB2B in transgenic Arabidopsis thaliana plants increased the seed oil content by 10.3%, 12.5%, 7.5% and 8.4%, respectively, compared to that in the wild-type and led to significant increases in palmitic and stearic acid content. Thus, this research has increased our understanding of the FATB family in soybeans and provides a theoretical basis for subsequent improvements in soybean quality.
CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway
Authors: Hernandez Karla Cano , Shah Akansha M. , Lopez Victor A. , Tagliabracci Vincent S. , Chen Kenian , Xu Lin , Bassel-Duby Rhonda , Olson Eric N. , Liu Ning
Published: January 2024

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high-grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies. CD73 is a 5′ ectonucleotidase that hydrolyzes AMP to adenosine and regulates the purinergic signaling pathway. We found that CD73 is elevated in FN-RMS tumors that express high levels of TWIST2. While high expression of CD73 contributes to the pathogenesis of multiple cancers, its role in FN-RMS has not been investigated. We found that CD73 knockdown decreased FN-RMS cell growth while up-regulating the myogenic differentiation program. Moreover, mutation of the catalytic residues of CD73 rendered the protein enzymatically inactive and abolished its ability to stimulate FN-RMS growth. Overexpression of wildtype CD73, but not the catalytically inactive mutant, in CD73 knockdown FN-RMS cells restored their growth capacity. Likewise, treatment with an adenosine receptor A
2A-B
agonist partially rescued FN-RMS cell proliferation and bypassed the CD73 knockdown defective growth phenotype. These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients.
Early Oligocene kelp holdfasts and stepwise evolution of the kelp ecosystem in the North Pacific
Authors: Kiel Steffen , Goedert James L. , Huynh Tony L. , Krings Michael , Parkinson Dula , Romero Rosemary , Looy Cindy V.
Published: January 2024

Kelp forests are highly productive and economically important ecosystems worldwide, especially in the North Pacific Ocean. However, current hypotheses for their evolutionary origins are reliant on a scant fossil record. Here, we report fossil hapteral kelp holdfasts from western Washington State, USA, indicating that kelp has existed in the northeastern Pacific Ocean since the earliest Oligocene. This is consistent with the proposed North Pacific origin of kelp associated with global cooling around the Eocene–Oligocene transition. These fossils also support the hypotheses that a hapteral holdfast, rather than a discoid holdfast, is the ancestral state in complex kelps and suggest that early kelps likely had a flexible rather than a stiff stipe. Early kelps were possibly grazed upon by mammals like desmostylians, but fossil evidence of the complex ecological interactions known from extant kelp forests is lacking. The fossil record further indicates that the present-day, multi-story kelp forest had developed at latest after the mid-Miocene climate optimum. In summary, the fossils signify a stepwise evolution of the kelp ecosystem in the North Pacific, likely enabled by changes in the ocean-climate system.
Fully-vertical GaN-on-SiC Schottky barrier diode with ultrathin AlGaN buffer layer
Authors: Sun Yuting , Feng Yuxia , Wei Jia , Wang Maojun , Yang Xuelin , Mei Wenkang , Yang Yufei , Shen Bo
Published: January 2024

In this letter, vertically conductive GaN epilayer on SiC substrate was achieved without the typically used conductive buffer layer. Here, in order to reduce the impacts of band offset of different layers on vertical conductivity and improve the vertical carrier transportation, an ultrathin AlGaN buffer layer was employed to replace the thick conductive buffer layer. Fully-vertical Schottky barrier diode (SBD) based on this vertically conductive epi-stack demonstrated a much lower specific on-resistance of 0.84 mΩ·cm2 with superior thermal stability. Moreover, the SBD also exhibited an on/off ratio of ∼5 × 109 and a nearly unity ideality factor of 1.08. This approach lays the foundation for the heterogeneous integration of GaN/SiC based devices.
Study of Type-B QPOs Observed in Black Hole X-Ray Binary Swift J1728.9-3613
Authors: Kumar Raj
Published: January 2024

We report the detection of type-B quasi-periodic oscillation (QPO) of the black hole X-ray binary Swift J1728.9-3613 observed by NICER during the 2019 outburst. A type-B QPO was observed for the first two days and it disappeared as flux increased, but again appeared at ∼7.70 Hz when flux was dramatically decreased. The source was found in the soft intermediate state during these observations. We further studied the energy dependence of the QPO. We found that QPO was observed only for a higher energy range implying that the origin of QPO is possibly due to the corona emitting higher energy photons by the inverse Compton process. The variation of spectral parameters can be explained with the disk truncation model. The fractional rms was found to be monotonically increased with energy. The phase lag spectrum followed the “U-shaped” curve. The rms and phase lag spectrum are modeled and explained with the single-component Comptonization model vkompthdk.
First operation of an ACHINOS-equipped spherical proportional counter with individual anode read-out
Authors: Herd D. , Katsioulas I. , Knights P. , Manthos I. , Matthews J. , Millins L. , Neep T. , Nikolopoulos K. , Rogers G.
Published: January 2024

The multi-anode sensor ACHINOS revolutionised the capabilities of the spherical proportional counter by enabling large-size, high-pressure, operation and TPC-like reconstruction capabilities through individual anode read-out.
First measurements with an individually read out ACHINOS are performed, which enables improved calibration and response homogenisation. Experimental results demonstrating the improvement in energy resolution brought by the individual anode calibration are presented. These are complemented by detailed simulation studies on the effect of sensor design and manufacturing imperfections, and how they may be corrected both in hardware and analysis.
Computing electronic correlation energies using linear depth quantum circuits
Authors: Chee Chong Hian , Mak Adrian M , Leykam Daniel , Kl Barkoutsos Panagiotis , Angelakis Dimitris G
Published: January 2024

Efficient computation of molecular energies is an exciting application of quantum computing for quantum chemistry, but current noisy intermediate-scale quantum (NISQ) devices can only execute shallow circuits, limiting existing variational quantum algorithms, which require deep entangling quantum circuit ansatzes to capture correlations, to small molecules. Here we demonstrate a variational NISQ-friendly algorithm that generates a set of Hartree–Fock ansatzes using multiple shallow circuits with depth linear in the number of qubits to estimate electronic correlation energies via perturbation theory up to the second order. We tested the algorithm on several small molecules, both with classical simulations including noise models and on cloud quantum processors, showing that it not only reproduces the equilibrium molecular energies but it also captures the perturbative electronic correlation effects at longer bond distances. The number of shallow circuits required for our algorithms scales

O
(

N
5

)

, with N being the system size, thus enabling the study of larger molecules compared to other approaches, where circuit depth or number of qubits required become prohibitive for NISQ devices.
Efficient quantum simulation of nonlinear interactions using SNAP and Rabi gates
Authors: Park Kimin , Marek Petr , Filip Radim
Published: January 2024

Quantum simulations provide means to probe challenging problems within controllable quantum systems. However, implementing or simulating deep-strong nonlinear couplings between bosonic oscillators on physical platforms remains a challenge. We present a deterministic simulation technique that efficiently and accurately models nonlinear bosonic dynamics. This technique alternates between tunable Rabi and SNAP gates, both of which are available on experimental platforms such as trapped ions and superconducting circuits. Our proposed simulation method facilitates high-fidelity modeling of phenomena that emerge from higher-order bosonic interactions, with an exponential reduction in resource usage compared to other techniques. We demonstrate the potential of our technique by accurately reproducing key phenomena and other distinctive characteristics of ideal nonlinear optomechanical systems. Our technique serves as a valuable tool for simulating complex quantum interactions, simultaneously paving the way for new capabilities in quantum computing through the use of hybrid qubit-oscillator systems.
Breast Reconstruction Using the Extended Latissimus Dorsi Myocutaneous Flap—A Long-term Follow-up Utilizing BREAST-Q
Authors: Wyckman Alexander , Assareh Armin , Steinvall Ingrid , Zdolsek Johann
Published: January 2024

Background

The latissimus dorsi (LD) flap is a commonly used method for breast reconstruction after mastectomy. In this study, we present a long-term follow-up and effects of refining surgery on patient satisfaction and quality of life after breast reconstruction with the extended LD flap, using the BREAST-Q questionnaire.

Objectives

The aim of this study was to investigate the patient-reported long-term results after breast reconstruction with the extended LD myocutaneous flap.

Methods

A retrospective cohort study of adult patients (n = 101) who were operated on using the extended LD flap for breast reconstruction at the Linköping University Hospital during 1997 to 2012 was made using data retrieved from medical records. The patients were asked to complete the BREAST-Q questionnaire at 2 different postoperative time points.

Results

Eighty-three patients replied to the first questionnaire, and 56 patients also replied to the second. Mean follow-up was 11.7 years. Higher age and living together with someone correlated to higher BREAST-Q results, while postoperative infection, bilateral LD flaps, smoking, and prior breast surgery had a negative impact on the results. Overall BREAST-Q results increased over time. No independent effect of refining surgery could be shown.

Conclusions

Patient satisfaction after breast reconstruction with the LD flap as measured with the BREAST-Q questionnaire is high and in line with other studies. The overall satisfaction with the reconstruction method seems to increase with time, but no further increase in satisfaction after refining surgery could be established.

Level of Evidence: 3
Imaging chronic active lesions in multiple sclerosis: a consensus statement
Authors: Bagnato Francesca , Sati Pascal , Hemond Christopher C , Elliott Colm , Gauthier Susan A , Harrison Daniel M , Mainero Caterina , Oh Jiwon , Pitt David , Shinohara Russell T , Smith Seth A , Trapp Bruce , Azevedo Christina J , Calabresi Peter A , Henry Roland G , Laule Cornelia , Ontaneda Daniel , Rooney William D , Sicotte Nancy L , Reich Daniel S , Absinta Martina
Published: January 2024

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo.

Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and T2-weighted scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification and monitoring is lacking.

To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a consensus statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this consensus statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.
Surface-mediated dynamic cooperative motions in azobenzene polymer films
Authors: Seki Takahiro
Published: January 2024

Azobenzene (1,2-diphenyldiazene in IUPAC name) is a widely studied, simple, rodlike photochromic molecule. The trans- (E) to cis- (Z) photoisomerization of this molecule was discovered a long time ago (nearly 90 yr). Nevertheless, the allure and utility of this molecule never faded and it has not surrendered a leading position among many other organic photochromic molecules. New applications for photoswitching molecular and macromolecular systems are still being proposed extensively. By linking the azobenzene molecule to liquid crystals (LCs) and polymer systems, a number of fascinating motility functions have been newly realized. This article overviews our research activities using azobenzene-containing monolayers and LC polymer films. The topics range across surface photoalignment of LCs, both from solid surface and free surface; photoalignment of hierarchical structures such as mesohybrids and block copolymers; photomechanical motions and morphological switching in block copolymer monolayers; high-density brushes of azobenzene side chain LC polymers (SCLCPs); photo-triggered mass migrations in azobenzene SCLCP films; and polymer motions via Marangoni flow, etc. Demonstrations of these dynamic photofunctions are expected to provide great opportunities for practical smart applications.
Construction of multi-ring molecules through direct C-H bond transformation
Authors: Nishii Yuji , Hirano Koji , Satoh Tetsuya , Miura Masahiro
Published: January 2024

Transition metal-catalyzed aromatic functionalization reactions are highly important for the construction of various organic fine chemicals. In particular, the direct C(sp2)-H bond transformation of (hetero)aromatics is currently recognized to be highly useful in organic synthesis, as it can realize short-step sequences leading to target molecules. We have been studying aromatic cross-coupling reactions through C-H bond activation/cleavage leading to new C-C and C-heteroatom bonds. The research strategies involve directing group (DG) control and utilization of unique properties of reaction substrates and catalysts, which enable efficient regioselective direct coupling reactions. In this account, our recent work is briefly summarized, mainly focused on the synthetic methods of benzo-fused multi-ring heterocyclic compounds of potent interest in pharmaceutical and material chemistry.
Density-functional tight-binding molecular dynamics study on fixation reaction of CO2 to styrene oxide catalyzed by Mg-MOF-74 metal-organic framework
Authors: Chou Chien-Pin , Sakti Aditya Wibawa , Tsuchiya Yuta , Sekine Yasushi , Nakai Hiromi
Published: January 2024

Carbon capture and utilization is a strategy to reduce CO2 emissions by utilizing them to synthesize fine chemicals. Mg-MOF-74 exhibits exceptional CO2 adsorption capacity and functions as a catalyst in styrene carbonate synthesis from CO2 and styrene oxide. We examined the structural properties and energetics of styrene carbonate synthesis in Mg-MOF-74 at the third-order density-functional tight-binding level. A novel reaction mechanism via the formation of a seven-membered ring intermediate was found to exhibit a lower Gibbs activation energy than the previously proposed mechanism.
Long-term conservation tillage with reduced nitrogen fertilization intensity can improve winter wheat health via positive plant–microorganism feedback in the rhizosphere
Authors: Behr Jan Helge , Kuhl-Nagel Theresa , Sommermann Loreen , Moradtalab Narges , Chowdhury Soumitra Paul , Schloter Michael , Windisch Saskia , Schellenberg Ingo , Maccario Lorrie , Sørensen Søren J , Rothballer Michael , Geistlinger Joerg , Smalla Kornelia , Ludewig Uwe , Neumann Günter , Grosch Rita , Babin Doreen
Published: January 2024

Microbiome-based solutions are regarded key for sustainable agroecosystems. However, it is unclear how agricultural practices affect the rhizosphere microbiome, plant–microorganism interactions and crop performance under field conditions. Therefore, we installed root observation windows in a winter wheat field cultivated either under long-term mouldboard plough (MP) or cultivator tillage (CT). Each tillage practice was also compared at two nitrogen (N) fertilization intensities, intensive (recommended N-supply with pesticides/growth regulators) or extensive (reduced N-supply, no fungicides/growth regulators). Shoot biomass, root exudates and rhizosphere metabolites, physiological stress indicators, and gene expression were analyzed together with the rhizosphere microbiome (bacterial/archaeal 16S rRNA gene, fungal ITS amplicon, and shotgun metagenome sequencing) shortly before flowering. Compared to MP, the rhizosphere of CT winter wheat contained more primary and secondary metabolites, especially benzoxazinoid derivatives. Potential copiotrophic and plant-beneficial taxa (e.g. Bacillus, Devosia, and Trichoderma) as well as functional genes (e.g. siderophore production, trehalose synthase, and ACC deaminase) were enriched in the CT rhizosphere, suggesting that tillage affected belowground plant–microorganism interactions. In addition, physiological stress markers were suppressed in CT winter wheat compared to MP. In summary, tillage practice was a major driver of crop performance, root deposits, and rhizosphere microbiome interactions, while the N-fertilization intensity was also relevant, but less important.
Examination of Hibiscus sabdariffa’s bioactive arsenal: pharmacological prospects and comprehensive insights into catalysing health and wellness through its therapeutic attributes—an exposition
Authors: Bhandare Saurabh Dilip , Malode Sarika Shivaji
Published: January 2024

This study signifies the rich pharmacological potential of Hibiscus sabdariffa, exploring its bioactive components and their therapeutic implications for health and wellness. Despite the promising insights, a comprehensive critical analysis is essential to ensure scientific rigour. To address this, the study establishes clear aims and objectives, aiming to scrutinise the study findings through a meticulous assessment. In conclusion, this study, upon addressing these key points, aspires to offer a robust contribution to scientific research, by advancing the understanding of H. sabdariffa’s therapeutic attributes and promoting the adoption of sustainable methodologies in scientific research.
Rapid, economical diagnostic classification of ATRT molecular subgroup using NanoString nCounter platform
Authors: Ho Ben , Arnoldo Anthony , Zhong Yvonne , Lu Mei , Torchia Jonathon , Yao Fupan , Hawkins Cynthia , Huang Annie
Published: January 2024

Background

Despite genomic simplicity, recent studies have reported at least 3 major atypical teratoid rhabdoid tumor (ATRT) subgroups with distinct molecular and clinical features. Reliable ATRT subgrouping in clinical settings remains challenging due to a lack of suitable biological markers, sample rarity, and the relatively high cost of conventional subgrouping methods. This study aimed to develop a reliable ATRT molecular stratification method to implement in clinical settings.

Methods

We have developed an ATRT subgroup predictor assay using a custom genes panel for the NanoString nCounter System and a flexible machine learning classifier package. Seventy-one ATRT primary tumors with matching gene expression array and NanoString data were used to construct a multi-algorithms ensemble classifier. Additional validation was performed using an independent gene expression array against the independently generated dataset. We also analyzed 11 extra-cranial rhabdoid tumors with our classifier and compared our approach against DNA methylation classification to evaluate the result consistency with existing methods.

Results

We have demonstrated that our novel ensemble classifier has an overall average of 93.6% accuracy in the validation dataset, and a striking 98.9% accuracy was achieved with the high-prediction score samples. Using our classifier, all analyzed extra-cranial rhabdoid tumors are classified as MYC subgroups. Compared with the DNA methylation classification, the results show high agreement, with 84.5% concordance and up to 95.8% concordance for high-confidence predictions.

Conclusions

Here we present a rapid, cost-effective, and accurate ATRT subgrouping assay applicable for clinical use.
How to Detect Antibodies Against Babesia divergens in Human Blood Samples
Authors: Tijani Muyideen Kolapo , Svensson Joel , Adlerborn Paula , Danielsson Lena , Teleka Alexandra , Lövmar Matilda Ljungqvist , Lindgren Per-Eric , Forsberg Pia , Persson Kristina E M
Published: January 2024

Background

Today only indirect fluorescent antibody assays (IFAs) are commercially available to detect antibodies against Babesia divergens in humans. IFA is subjective and requires highly experienced staff. We have therefore developed an enzyme-linked immunosorbent assay (ELISA)–based method for measuring anti–B. divergens immunoglobulin G antibodies in human blood samples.

Methods

Crude merozoite extract from in vitro cultures of a new B. divergens isolate was used in ELISA to detect antibodies in different sets of samples: Borrelia burgdorferi–positive samples, healthy individuals, tick-bitten individuals including follow-up samples 3 months later, positive control samples from patients with an active Babesia infection, and samples from malaria-endemic regions. As a reference, IFA was used to detect antibodies in the tick-bitten samples. Western blot was used to evaluate reactions against specific bands in extracts with/without parasites.

Results

Using IFA as the reference method, the sensitivity and specificity of the ELISA were 86% (12/14) and 100% (52/52). There was a very high correlation (r = −0.84; P = .0004) between IFA dilution factors and ELISA absorbances among the samples classified as positive. Five percent of the B. burgdorferi–positive samples were judged as weakly positive and 5% as strongly positive in our ELISA. Western blot showed that the immunodominant antigens (∼120 kDa) were from merozoites and not from erythrocytes.

Conclusions

This ELISA can detect antibodies directed against B. divergens, and it can be a useful and easy assay to handle compared with IFA. The ELISA can also measure high and low levels of antibodies, which could give insight into the recency of a B. divergens infection.
Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose‐stimulated insulin secretion
Authors: Shimizu Kahori , Ono Moe , Mikamoto Takenari , Urayama Yuya , Yoshida Sena , Hase Tomomi , Michinaga Shotaro , Nakanishi Hiroki , Iwasaki Miho , Terada Tomoyuki , Sakurai Fuminori , Mizuguchi Hiroyuki , Shindou Hideo , Tomita Koji , Nishinaka Toru
Published: January 2024

Postprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated. LPLAT10 expression is low in the liver, the main organ that regulates metabolism, under normal conditions. Here, we investigated whether overexpression of LPLAT10 in the liver leads to improved glucose metabolism. For overexpression, we generated an LPLAT10‐expressing adenovirus (Ad) vector (Ad‐LPLAT10) using an improved Ad vector. Postprandial hyperglycemia was suppressed by the induction of glucose‐stimulated insulin secretion in Ad‐LPLAT10‐treated mice compared with that in control Ad vector‐treated mice. Hepatic and serum levels of phosphatidylcholine 40:7, containing C18:1 and C22:6, were increased in Ad‐LPLAT10‐treated mice. Serum from Ad‐LPLAT10‐treated mice showed increased glucose‐stimulated insulin secretion in mouse insulinoma MIN6 cells. These results indicate that changes in hepatic phosphatidylcholine species due to liver‐specific LPLAT10 overexpression affect the pancreas and increase glucose‐stimulated insulin secretion. Our findings highlight LPLAT10 as a potential novel therapeutic target for T2DM.
Military Veteran Matriculation in US Physician Associate/Assistant Programs
Authors: Broughton Adam , Landry Alexis , Showstark Mary , Barry Carey L. , Najmabadi Shahpar , Rolls Joanne , Honda Trenton
Published: January 2024

Introduction

This study aims to determine whether veterans have differential access to physician associate/assistant (PA) education by examining likelihood of matriculation relative to nonveteran peers. We explore associations between veteran status and likelihood of matriculation for change over time and whether effects differ among active duty versus non–active-duty applicants.

Methods

Multivariate logistic regression was used to investigate associations between self-identified military status and likelihood of PA program matriculation in five Centralized Applicant Services for Physician Assistants admissions cycles (2012–2013, 2014–2015, 2016–2017, 2018–2019, 2020–2021). Models controlled for age, sex, race/ethnicity, patient care experience hours, total undergraduate grade point average, and number of applications submitted and applied a Bonferroni correction for alpha inflation.

Results

Veteran applicant numbers were small across the study time frame but increased from 2012 (n = 708) to 2020 (n = 978), representing a 38% increase over the lookback period. Despite growth, the proportion of veterans in the matriculant pool has decreased from 4.2% in 2012 to 3.0% in 2020. In unadjusted models, military status was not strongly associated with odds of matriculation. In adjusted models, both veteran and active-duty status were associated with higher odds of matriculation, although this increase was not statistically significant at the 0.005 level for applicants on active-duty.

Discussion

Military veterans and active-duty military personnel have higher likelihood of matriculation into US PA programs relative to nonveteran peers. The proportion of veterans in the matriculant pool has decreased over time. This suggests that while PA programs seems to value previous military experience, further efforts to evaluate and address barriers to military veterans in applying for admissions is needed.
Effects of Ziprasidone or Haloperidol on Theory of Mind in Patients With Schizophrenia: A 16-week Pilot Trial
Authors: Zhong Jie , Jia Yuan , Zhu Hong , Wang Dan , Jia Hongxiao
Published: January 2024

Objectives:

Schizophrenia is associated with impairment in theory of mind (ToM), which is defined as the ability to make judgments about mental states and is related to medial prefrontal cortical activity. Ziprasidone, but not haloperidol, is known to have a protective effect in the medial prefrontal cortex. Thus, we hypothesized that these 2 drugs would have different efficacy in improving ToM task performance in patients with schizophrenia.

Methods:

Patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia matched for sex, duration of illness, and education were randomized to receive ziprasidone (n=30) or haloperidol (n=30). All patients were assessed using the Positive and Negative Syndrome Scale and the Personal and Social Functioning Scale. ToM was assessed using a first-order false belief task, a second-order false belief task, the faux-pas task, and the Reading the Mind in the Eyes Task, in order of developmental complexity and difficulty. The primary outcome was change in ToM performance from baseline to 16 weeks of treatment.

Results:

For the first-order false belief task, there were no significant differences between the groups (P>0.05). For the second-order false belief task, the interaction effect was significant (P<0.05), and the simple effect of time showed a significant difference only in the ziprasidone group (P<0.001). For the faux-pas task, the interaction effect was not significant (P>0.05). For the Reading the Mind in the Eyes Task, the interaction effect was significant (P<0.05), and the simple effect of time showed a significant difference only in the ziprasidone group (P<0.001). The Positive and Negative Syndrome Scale results were similar between the groups. The ziprasidone group performed better than the haloperidol group on the Personal and Social Functioning Scale. There were no major safety concerns or adverse events.

Conclusions:

The findings of this study suggest that ziprasidone could improve ToM and might be superior to haloperidol for improving complex ToM as well as personal and social functioning in patients with schizophrenia.

Trial Registration Chinese Clinical Trial Register:

ChiCTR2200060542.
Patient and Caregiver Depression in Jordan After a First Stroke
Authors: Aldabbour Belal , Al Qawasmeh Majdi , Elamassie Samah , Abuabada Amal , Abdelrahman Khalid , Zahran Mohammad , Khweileh Mays , El-Salem Khalid
Published: January 2024

Background:

Poststroke depression among patients is well-recognized, while caregiver depression is understudied. The interaction between patient and caregiver depression is also unclear.

Methods:

This cross-sectional and follow-up study recruited 108 patient-caregiver dyads after the first-ever stroke. Demographic and clinical data, stroke severity (NIH Stroke Scale score), functional outcome (Barthel Index), and residual disability (modified Rankin Score) were documented. Using the self-reported Patient Health Questionnaire-9, we screened patients and caregivers for depressive symptoms upon admission and after 1 month. Changes in the prevalence and severity of depression were calculated. The Pearson correlation test and logistic regression analysis were conducted to evaluate both the correlation between both groups and significant predictors of depression.

Results:

In total, 89 patients and 96 caregivers responded to both screenings. Depression was reported by 13.5% and 27.0% of patients on admission and after 1 month, and 9.4% and 18.8% of caregivers, respectively. Caregiver depression on admission was significantly correlated with patient depression on admission (P=0.031). In addition, depression in caregivers after 1 month was a significant predictor of patient depression (P=0.008). Predictors of caregiver depression after 1 month were female caregivers (P=0.026), caring for a male patient (P=0.045), higher mRS scores after 1 month (P=0.013), longer admissions (P=0.017), caregiver between 17 and 35 years of age compared with 54 to 70 years of age (P=0.030), and caring for a patient with poststroke depression at 1 month poststroke (P=0.003).

Conclusions:

Both stroke survivors and their caregivers are at high risk for depression, with a potential interaction between depression in the 2 groups.
Bridging Neuroscience and Clinical Assessment in a Patient with Alcohol Use Disorder, Anxiety, and Trauma
Authors: GOPALDAS MANESH , FLOOK ELIZABETH A. , BLACKFORD JENNIFER URBANO
Published: January 2024

This article presents a unique framework that combines insights from neuroscience with clinical assessment to evaluate individuals who have co-occurring alcohol use disorder, anxiety, and trauma. Through the use of a case study, the authors demonstrate the practical application of this framework and contextualize the relevant neurocircuitry associated with alcohol withdrawal, maladaptive fear and anxiety, and chronic stress. By integrating these perspectives, they provide a comprehensive approach for assessing and treating patients with complex psychiatric histories, particularly those presenting with anxiety symptoms, offering valuable insights for practitioners.
Pupil size and eye movements differently index effort in both younger and older adults
Authors: Herrmann Björn , Ryan Jennifer D.
Published: January 2024

The assessment of mental effort is increasingly relevant in neuro-cognitive and lifespan domains. Pupillometry, the measure of the pupil size, is often used to assess effort but has disadvantages. Analysis of eye movements may provide an alternative, but research has been limited to easy and difficult task demands in younger adults. An effort measure must be sensitive to the whole effort profile, including ‘giving up’ effort investment, and capture effort in different age groups. The current study comprised three experiments in which younger (N=66) and older adults (N=44) listened to speech masked by background babble at different signal-to-noise ratios associated with easy, difficult, and impossible speech comprehension. We expected individuals to invest little effort for easy and impossible speech (‘giving up’) but to exert effort for difficult speech. Indeed, pupil size was largest for difficult, but lower for easy and impossible speech. In contrast, gaze dispersion decreased with increasing speech masking in both age groups. Critically, gaze dispersion during difficult speech returned to levels similar to easy speech after sentence offset, when acoustic stimulation was similar across conditions, whereas gaze dispersion during impossible speech continued to be reduced. These findings show that a reduction in eye movements is not a byproduct of acoustic factors, but instead suggest that neuro-cognitive processes, different from arousal-related systems regulating the pupil size, drive reduced eye movements during high task demands. The current data thus show that effort in one sensory domain (audition) differentially impacts distinct functional properties in another sensory domain (vision).

Significance statement

The assessment of mental effort is increasingly relevant in many domains. Here, we investigated the sensitivity of a novel measure of effort - the spatial dispersion of eye movements - and compared it to pupillometry, which is a more common effort-assessment tool. Individuals listened to speech masked by background babble at levels associated with easy, difficult, and impossible speech comprehension. Pupil size was largest for difficult, but lower for easy and impossible speech conditions (giving up listening). In contrast, the spatial dispersion of eye movements decreased with increasing speech masking, but this effect was independent of acoustic factors. Instead, the current results suggest that neuro-cognitive processes, different from arousal-related systems regulating the pupil size, drive reduced eye movements during high task demands.
Excess Mortality in the United States, 2020-21: County-level Estimates for Population Groups and Associations with Social Vulnerability
Authors: Kandula Sasikiran , Keyes Katherine M. , Yaari Rami , Shaman Jeffrey
Published: January 2024

To assess the excess mortality burden of Covid-19 in the United States, we estimated sex, age and race stratified all-cause excess deaths in each county of the US during 2020 and 2021. Using spatial Bayesian models trained on all recorded deaths between 2003-2019, we estimated 463,187 (95% uncertainty interval (UI): 426,139 – 497,526) excess deaths during 2020, and 544,105 (95% UI: 492,202 – 592,959) excess deaths during 2021 nationally, with considerable geographical heterogeneity.

Excess mortality rate (EMR) nearly doubled for each 10-year increase in age and was consistently higher among men than women. EMR in the Black population was 1.5 times that of the White population nationally and as high as 3.8 times in some states. Among the 25-54 year population excess mortality was highest in the American Indian/Alaskan Native (AI/AN) population among the four racial groups studied, and in a few states was as high as 6 times that of the White population.

Strong association of EMR with county-level social vulnerability was estimated, including positive associations with prevalence of disability (standardized effect: 40.6 excess deaths per 100,000), older population (37.6), poverty (23.6), and unemployment (18.5), whereas population density (−50), higher education (−38.6), and income (−35.4) were protective.

Together, these estimates provide a more reliable and comprehensive understanding of the mortality burden of the pandemic in the US thus far. They suggest that Covid-19 amplified social and racial disparities. Short-term measures to protect more vulnerable groups in future Covid-19 waves and systemic corrective steps to address long-term societal inequities are necessary.

Significance Statement

All-cause excess mortality estimates, the difference between observed all-cause deaths and deaths expected in the absence of a pandemic, can help more fully assess the pandemic’s burden than direct Covid-19 mortality. Our estimates, based on a 17-year record of all deaths in the US and a Bayesian spatial model, quantify the differences in excess mortality across counties and by population age, race and sex, as well as between the first and second years of the pandemic. Furthermore, our results indicate that population-level socioeconomic indicators such as poverty, unemployment and educational attainment had considerable effect on excess mortality during the pandemic. Sustained efforts to protect vulnerable populations during future waves of Covid-19 (and other public health emergencies) remain vital.
Feasibility, usability, acceptability and Efficacy of a novel leg strengthening device (S-Press) for strengthening leg muscles and improving physical impairment during hospital admission
Authors: Maden-Wilkinson TM. , Griffiths C. , Lakkappa B. , Walker K. , Kennerley CL , Turner JJ.
Published: January 2024

Background

Deconditioning due to in-patients’ stays is predictive of delayed discharges and readmissions; preserving muscle mass and strength in order for patients to remain independent should be of utmost priority. Progressive resistance training offers the most cost-effective way of doing this; however, it is not routinely done.

Objective

To examine the feasibility, usability and acceptability of a novel in-bed strength training device (S-Press) by patients and staff members within an in-patient rehabilitation ward in the NHS.

Methods

Using a mixed methods approach, 6 patients who performed resistance training on the S-Press device and, alongside 3 healthcare professionals, were interviewed. Data were thematically analysed to examine individuals’ perspectives and perceptions on the feasibility, useability and acceptability of the S-Press. In addition, measures of sit to stand and muscle ultrasound were conducted before use and before discharge. For indications of safety, heart rate and blood pressure measures were taken during each session.

Results

Patients found the S-Press easy and comfortable to use and enjoyed using it as an adjunct therapy during in-patient stay. Healthcare professionals using the S-Press noted that it improved mobility allowing patients to gradually build up muscle strength in a safe and motivating way. All participants improved sit to stand performance with use of the S-Press. There were no significant differences observed in heart rate or blood pressure during each session, indicating the safety of S-Press use.

Conclusion

From this proof-of-concept study, use of the S-Press to improve muscle strength and physiological function in in-patients is feasible and an acceptable intervention. Further work should focus on use with wider patient demographics and conditions.