bluuebunny/crossref_metadata_2025 huggingface dataset:
Epistemic language in news headlines shapes readers’ perceptions of objectivity
Authors: Chuey Aaron , Luo Yiwei , Markman Ellen M.
Published: May 2024

How we reason about objectivity—whether an assertion has a ground truth—has implications for belief formation on wide-ranging topics. For example, if someone perceives climate change to be a matter of subjective opinion similar to the best movie genre, they may consider empirical claims about climate change as mere opinion and irrelevant to their beliefs. Here, we investigate whether the language employed by journalists might influence the perceived objectivity of news claims. Specifically, we ask whether factive verb framing (e.g., "Scientists know climate change is happening") increases perceived objectivity compared to nonfactive framing (e.g., "Scientists believe [...]"). Across eight studies (N = 2,785), participants read news headlines about unique, noncontroversial topics (studies 1a–b, 2a–b) or a familiar, controversial topic (climate change; studies 3a–b, 4a–b) and rated the truth and objectivity of the headlines’ claims. Across all eight studies, when claims were presented as beliefs (e.g., “Tortoise breeders believe tortoises are becoming more popular pets”), people consistently judged those claims as more subjective than claims presented as knowledge (e.g., “Tortoise breeders know…”), as well as claims presented as unattributed generics (e.g., “Tortoises are becoming more popular pets”). Surprisingly, verb framing had relatively little, inconsistent influence over participants’ judgments of the truth of claims. These results demonstrate how, apart from shaping whether we believe a claim is true or false, epistemic language in media can influence whether we believe a claim has an objective answer at all.
Energetic cost of biosynthesis is a missing link between growth and longevity in mammals
Authors: Hou Chen
Published: May 2024

The comparative studies of aging have established a negative correlation between Gompertz postnatal growth constant and maximum lifespan across mammalian species, but the underlying physiological mechanism remains unclear. This study shows that the Gompertz growth constant can be decomposed into two energetic components, mass-specific metabolic rate and the energetic cost of biosynthesis, and that after controlling the former as a confounder, the negative correlation between growth constant and lifespan still exists due to a 100-fold variation in the latter, revealing that the energetic cost of biosynthesis is a link between growth and longevity in mammals. Previously, the energetic cost of biosynthesis has been thought to be a constant across species and therefore was not considered a contributor to the variation in any life history traits, such as growth and lifespan. This study employs a recently proposed model based on energy conservation to explain the physiological effect of the variation in this energetic cost on the aging process and illustrates its role in linking growth and lifespan. The conventional life history theory suggested a tradeoff between growth and somatic maintenance, but the findings in this study suggest that allocating more energy to biosynthesis may enhance the somatic maintenance and extend lifespan and, hence, reveal a more complex nature of the tradeoff.
MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites
Authors: Han Yue , Li Min , Zhao Bingqing , Wang Huichao , Liu Yan , Liu Zhijun , Xu Jiaxi , Yang Rui
Published: May 2024

Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here, we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a unique kinesin-based mechanism for polarized transport of vesicles to dendrites.
A finely balanced order–disorder equilibrium sculpts the folding–binding landscape of an antibiotic sequestering protein
Authors: Natarajan Lawanya , De Sciscio Maria Laura , Nardi Alessandro Nicola , Sekhar Ashok , Del Giudice Alessandra , D’Abramo Marco , Naganathan Athi N.
Published: May 2024

TipA, a MerR family transcription factor from
Streptomyces lividans
, promotes antibiotic resistance by sequestering broad-spectrum thiopeptide-based antibiotics, thus counteracting their inhibitory effect on ribosomes. TipAS, a minimal binding motif which is expressed as an isoform of TipA, harbors a partially disordered N-terminal subdomain that folds upon binding multiple antibiotics. The extent and nature of the underlying molecular heterogeneity in TipAS that shapes its promiscuous folding–function landscape is an open question and is critical for understanding antibiotic-sequestration mechanisms. Here, combining equilibrium and time-resolved experiments, statistical modeling, and simulations, we show that the TipAS native ensemble exhibits a pre-equilibrium between binding-incompetent and binding-competent substates, with the fully folded state appearing only as an excited state under physiological conditions. The binding-competent state characterized by a partially structured N-terminal subdomain loses structure progressively in the physiological range of temperatures, swells on temperature increase, and displays slow conformational exchange across multiple conformations. Binding to the bactericidal antibiotic thiostrepton follows a combination of induced-fit and conformational-selection-like mechanisms, via partial binding and concomitant stabilization of the binding-competent substate. These ensemble features are evolutionarily conserved across orthologs from select bacteria that infect humans, underscoring the functional role of partial disorder in the native ensemble of antibiotic-sequestering proteins belonging to the MerR family.
ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin
Authors: Goto Naoki , Suke Kazuma , Yonezawa Nao , Nishihara Hidenori , Handa Tetsuya , Sato Yuko , Kujirai Tomoya , Kurumizaka Hitoshi , Yamagata Kazuo , Kimura Hiroshi
Published: May 2024

Histone H3 lysine36 dimethylation (H3K36me2) is generally distributed in the gene body and euchromatic intergenic regions. However, we found that H3K36me2 is enriched in pericentromeric heterochromatin in some mouse cell lines. We here revealed the mechanism of heterochromatin targeting of H3K36me2. Among several H3K36 methyltransferases, NSD2 was responsible for inducing heterochromatic H3K36me2. Depletion and overexpression analyses of NSD2-associating proteins revealed that NSD2 recruitment to heterochromatin was mediated through the imitation switch (ISWI) chromatin remodeling complexes, such as BAZ1B-SMARCA5 (WICH), which directly binds to AT-rich DNA via a BAZ1B domain-containing AT-hook-like motifs. The abundance and stoichiometry of NSD2, SMARCA5, and BAZ1B could determine the localization of H3K36me2 in different cell types. In mouse embryos, H3K36me2 heterochromatin localization was observed at the two- to four-cell stages, suggesting its physiological relevance.
Tail length and E525K dilated cardiomyopathy mutant alter human β-cardiac myosin super-relaxed state
Authors: Duno-Miranda Sebastian , Nelson Shane R. , Rasicci David V. , Bodt Skylar M.L. , Cirilo Joseph A. , Vang Duha , Sivaramakrishnan Sivaraj , Yengo Christopher M. , Warshaw David M.
Published: May 2024

Dilated cardiomyopathy (DCM) is a condition characterized by impaired cardiac function, due to myocardial hypo-contractility, and is associated with point mutations in β-cardiac myosin, the molecular motor that powers cardiac contraction. Myocardial function can be modulated through sequestration of myosin motors into an auto-inhibited “super-relaxed” state (SRX), which may be further stabilized by a structural state known as the “interacting heads motif” (IHM). Here, we sought to determine whether hypo-contractility of DCM myocardium results from reduced function of individual myosin molecules or from decreased myosin availability to interact with actin due to increased IHM/SRX stabilization. We used an established DCM myosin mutation, E525K, and characterized the biochemical and mechanical activity of wild-type and mutant human β-cardiac myosin constructs that differed in the length of their coiled-coil tail, which dictates their ability to form the IHM/SRX state. We found that short-tailed myosin constructs exhibited low IHM/SRX content, elevated actin-activated ATPase activity, and fast velocities in unloaded motility assays. Conversely, longer-tailed constructs exhibited higher IHM/SRX content and reduced actomyosin ATPase and velocity. Our modeling suggests that reduced velocities may be attributed to IHM/SRX-dependent sequestration of myosin heads. Interestingly, longer-tailed E525K mutants showed no apparent impact on velocity or actomyosin ATPase at low ionic strength but stabilized IHM/SRX state at higher ionic strength. Therefore, the hypo-contractility observed in DCM may be attributable to reduced myosin head availability caused by enhanced IHM/SRX stability in E525K mutants.
Development of high conducting phosphorous doped nanocrystalline thin silicon films for silicon heterojunction solar cells application
Authors: Bhattacharya Shrestha , Pandey Ashutosh , Alam Shahnawaz , Komarala Vamsi Krishna
Published: May 2024

We have investigated the plasma-enhanced chemical vapor deposition growth of the phosphorus-doped hydrogenated nanocrystalline silicon (n-nc-Si:H) film as an electron-selective layer in silicon heterojunction (SHJ) solar cells. The effect of power densities on the precursor gas dissociation are investigated using optical emission spectra and the crystalline fraction in n-nc-Si:H films are correlated with the dark conductivity. With the P
d of 122 mW cm−2 and ∼2% phosphorus doping, we observed Raman crystallinity of 53%, high dark conductivity of 43 S cm−1, and activation energy of ∼23 meV from the ∼30 nm n-nc-Si:H film. The n-nc-Si:H layer improves the textured c-Si surface passivation by two-fold to ∼2 ms compared to the phosphorus-doped hydrogenated amorphous silicon (n-a-Si:H) layers. An enhancement in the open-circuit voltage and external quantum efficiency (from >650 nm) due to the better passivation at the rear side of the cell after integrating the n-nc-Si:H layer compared to its n-a-Si:H counterpart. An improvement in the charge carrier transport is also observed with an increase in fill factor from ∼71% to ∼75%, mainly due to a reduction in electron-selective contact resistivity from ∼271 to ∼61 mΩ-cm2. Finally, with the relatively better c-Si surface passivation and carrier selectivity, a power conversion efficiency of ∼19.90% and pseudo-efficiency of ∼21.90% have been realized from the SHJ cells.
Thickness dependence of the room-temperature ethanol sensor properties of Cu2O polycrystalline films
Authors: Aparicio-Huacarpuma B D , H Aragón F F , Villegas-Lelovsky L , Soncco C M , Pacheco-Salazar D G , Guerra J A , Morais P C , da Silva S W , Coaquira J A H
Published: May 2024

This study investigates the fabrication process of copper thin films via thermal evaporation, with precise control over film thickness achieved through Z-position adjustment. Analysis of the as-fabricated copper films reveals a discernible relationship between grain size (〈D〉) and Z-position, characterized by a phenomenological equation

〈
D

〉
XRD
n

(
Z
)
=
〈
D

〉
0
n

1
+

3
2

r
Z

2

+

15
8

r
Z

4

, which is further supported by a growth exponent (n) of 0.41 obtained from the analysis. This value aligns well with findings in the literature concerning the growth of copper films, thus underlining the validity and reliability of our experimental outcomes. The resulting crystallites, ranging in size from 20 to 26 nm, exhibit a resistivity within the range of 3.3–4.6 μΩ · cm. Upon thermal annealing at 200 °C, cuprite Cu2O thin films are produced, demonstrating crystallite sizes ranging from ∼9 to ∼24 nm with increasing film thickness. The observed monotonic reduction in Cu2O crystallites relative to film thickness is attributed to a recrystallization process, indicating amorphization when oxygen atoms are introduced, followed by the nucleation and growth of newly formed copper oxide phase. Changes in the optical bandgap of the Cu2O films, ranging from 2.31 to 2.07 eV, are attributed mainly to the quantum confinement effect, particularly important in Cu2O with size close than the Bohr exciton diameter (5 nm) of the Cu2O. Additionally, correlations between refractive index and extinction coefficient with film thickness are observed, notably a linear relationship between refractive index and charge carrier density. Electrical measurements confirm the presence of a p-type semiconductor with carrier concentrations of ∼1014 cm−3, showing a slight decrease with film thickness. This phenomenon is likely attributed to escalating film roughness, which introduces supplementary scattering mechanisms for charge carriers, leading to a resistivity increase, especially as the roughness approaches or surpasses the mean free path of charge carriers (8.61 nm). Moreover, ab-initio calculations on the Cu2O crystalline phase to investigate the impact of hydrostatic strain on its electronic and optical properties was conducted. We believe that our findings provide crucial insights that support the elucidation of the experimental results. Notably, thinner cuprite films exhibit heightened sensitivity to ethanol gas at room temperature, indicating potential for highly responsive gas sensors, particularly for ethanol breath testing, with significant implications for portable device applications.
Full color control and patterned display device from cyan/magenta/yellow water-dispersed electrochromic polymer nanoparticles systems
Authors: Lv Xiaojing , Liu Chunyan , Shao Mingfa , Li Jin , Xia Minao , Cui Jiankun , Dong Juncheng , Ouyang Mi , Zhang Cheng
Published: May 2024

Electrochromic polymers (ECPs) have great application potential in flexible displays, and there is an increasing expectation of using green methods to form ECP films. Herein, we propose a modified microemulsion method to prepare cyan/magenta/yellow (C/M/Y) water-dispersed electrochromic polymer nanoparticles (WDEN) systems. Three polymer films (WDECP-C/M/Y) maintain similar electrochemical properties compared to their corresponding organic solvent-based polymer films. It is intriguing that WDECP-C/M/Y exhibit better electrochromic properties in terms of higher cycling stability (97.24%, 95.05%, and 52.84%, respectively) and faster switching time (0.94 s, 1.09 s, and 1.34 s for coloring time, respectively) due to the introduction of nanoparticles. In addition, it can achieve various desired colors by blending the C/M/Y WDEN systems in different ratios. The calculated chromaticity coordinates of the blending polymer films show close values to the experimental observation, and the calculated ΔE

*

ab
values range from 2.6 to 10.3, which may provide theoretical guidance for precisely color control. Finally, large-scale and patterned devices were assembled, which can achieve colored-to-colorless reversible electrochromism at a low driving voltage of 0–1.5 V. This work puts forward a universal and environmentally sustainable strategy to prepare WDEN systems, demonstrating their wide range of applications in display devices and electronic tags.
Uncertainties of nuclear level density estimated using Bayesian neural networks*
Authors: Wang 王 Xinyu 馨钰 , Cui 崔 Ying 莹 , Tian 田 Yuan 源 , Zhao 赵 Kai 凯 , Zhang 张 Yingxun 英逊
Published: May 2024

Nuclear level density (NLD) is a critical parameter for understanding nuclear reactions and the structure of atomic nuclei; however, accurate estimation of NLD is challenging owing to limitations inherent in both experimental measurements and theoretical models. This paper presents a sophisticated approach using Bayesian neural networks (BNNs) to analyze NLD across a wide range of models. It uniquely incorporates the assessment of model uncertainties. The application of BNNs demonstrates remarkable success in accurately predicting NLD values when compared to recent experimental data, confirming the effectiveness of our methodology. The reliability and predictive power of the BNN approach not only validates its current application but also encourages its integration into future analyses of nuclear reaction cross sections.
Correlation between the charge radii difference in mirror partner nuclei and thesymmetry energy slope*
Authors: Ma 马 Xiao-Rong 小荣 , Sun 孙 Shuai 帅 , An 安 Rong 荣 , Cao 曹 Li-Gang 李刚
Published: May 2024

A correlation between the charge radii difference of mirror partner nuclei

and the slope parameter L of symmetry energy has been built to ascertain the equation of state of isospin asymmetric nuclear matter. In this work, the influences of pairing correlations and isoscalar compression modulus on the

are systematically investigated based on the Skyrme energy density functional theory. The calculated results suggest that the linear correlation between

and L is decreased by the surface pairing correlations. The slope parameter deduced from the difference of charge radii of mirror-pair nuclei 32Ar-32Si, 36Ca-36S, 38Ca-38Ar, and 54Ni-54Fe falls into the range of

−

MeV, that is, the rather soft equation of state of asymmetric nuclear matter. Besides, the range of the slope parameter can also be influenced by the effective forces classified by various isoscalar incompressibility coefficients.
Triply degenerate semimetal PtBi2 as van der Waals contact interlayer in two-dimensional transistor
Authors: Wei Bohan , Li Yun , Yun Tinghe , Li Yang , Gui Tianhu , Yu Wenzhi , Mu Hanran , Cui Nan , Chen Weiqiang , Lin Shenghuang
Published: May 2024

The low-energy electronic excitations in topological semimetal yield a plethora of a range of novel physical properties. As a relatively scarce branch, the research of triple-degenerate semi-metal is mostly confined to the stage of physical properties and theoretical analysis, there are still challenges in its practical application. This research showcases the first application of the triply degenerate semimetal PtBi2 in electronic devices. Leveraging a van der Waals transfer method, PtBi2 flakes were used as interlayer contacts for metal electrodes and WS2 in transistors. The transistor achieved a switching ratio above 106 and average mobility can reach 85 cm2V−1 s−1, meeting integrated circuit requirements. Notably, the excellent air stability of PtBi2 simplifies the device preparation process and provides more stable device performance. Transfer process reduces the Schottky barrier between metal electrodes and semiconductors while avoiding Fermi pinning during metal deposition to achieve excellent contact. This groundbreaking work demonstrates the practical applicability of PtBi2 in the field of electronic devices while opening new avenues for the integration of novel materials in semiconductor technology, setting a precedent for future innovations.
Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial
Authors: Richard Nicolas , Arab-Hocine Nadia , Vannier Margot , Leblanc-Boubchir Rachida , Pelaquier Agnès , Boruchowicz Arnaud , Musikas Marietta , Amil Morgane , Fumery Mathurin , Nahon Stéphane , Arotcarena Ramuntcho , Gelsi Eve , Maurin Arnaud , Hébuterne Xavier , Savoye Guillaume
Published: May 2024

Background

Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied.

Aims

This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB.

Methods

This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9–11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180.

Results

From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups.

Conclusions

Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).
Establishing hemolysis, icterus, and lipemia interference limits for body fluid chemistry analytes measured on the Roche cobas instrument
Authors: Block Darci R , Lasho Michael A , Donato Leslie J , Meeusen Jeffrey W
Published: May 2024

Objectives

The aims of this study were to (1) establish the maximum allowable interference limits for hemolysis, lipemia, and icterus for chemistry analytes tested in body fluid samples and (2) assess the effectiveness of serial dilution to mitigate spectral interferences.

Methods

Residual body fluids from clinically ordered testing were mixed (<10% by volume) with stock solutions of interferent (spiked) and compared with a control spiked with an equal volume of 0.9% saline. The analytes were measured on the Roche cobas c501 instrument. Difference and percentage difference were calculated and compared with allowable total error limits. A subset of samples were serially diluted with 0.9% saline. Mean (SD) difference and percentage difference were calculated.

Results

The interference thresholds were lower than the package insert for lactate dehydrogenase, cholesterol, triglycerides, and total protein for hemolysis; amylase, cholesterol, and total protein for icterus; and albumin for lipemia. Only cholesterol and triglyceride results returned to baseline upon dilution of icteric samples.

Conclusions

Interference thresholds in body fluids were lower than blood for 6 analytes. Diluting interferences that surpass these limits does not produce reliable results that are comparable to the baseline results before spiking in the interferent.
GSScore: a novel Graphormer-based shell-like scoring method for protein–ligand docking
Authors: Guo Linyuan , Wang Jianxin
Published: May 2024

Protein–ligand interactions (PLIs) are essential for cellular activities and drug discovery. But due to the complexity and high cost of experimental methods, there is a great demand for computational approaches to recognize PLI patterns, such as protein–ligand docking. In recent years, more and more models based on machine learning have been developed to directly predict the root mean square deviation (RMSD) of a ligand docking pose with reference to its native binding pose. However, new scoring methods are pressingly needed in methodology for more accurate RMSD prediction. We present a new deep learning-based scoring method for RMSD prediction of protein–ligand docking poses based on a Graphormer method and Shell-like graph architecture, named GSScore. To recognize near-native conformations from a set of poses, GSScore takes atoms as nodes and then establishes the docking interface of protein–ligand into multiple bipartite graphs within different shell ranges. Benefiting from the Graphormer and Shell-like graph architecture, GSScore can effectively capture the subtle differences between energetically favorable near-native conformations and unfavorable non-native poses without extra information. GSScore was extensively evaluated on diverse test sets including a subset of PDBBind version 2019, CASF2016 as well as DUD-E, and obtained significant improvements over existing methods in terms of RMSE, $R$ (Pearson correlation coefficient), Spearman correlation coefficient and Docking power.
Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia
Authors: Yang Xiyue , Liu Naici , Sun Hui , Li Xing , Li Hongwei , Gong Qiyong , Lui Su
Published: May 2024

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.
Study on the specific photodegradation performance of Fe3O4@SiO2@TiO2@MIPs for berberine hydrochloride
Authors: Xiong Junfu , Tian Hao , Li Xicheng , Wang Changzheng , Xu Shoufang
Published: May 2024

Adsorption is crucial for the performance of photocatalysts in degrading new pollutants. Here, we report a magnetic molecularly imprinted material Fe3O4@SiO2@TiO2@MIPs with a semiconductor/insulator/semiconductor structure, which achieved up to 81% preferential degradation of berberine hydrochloride (BH). The significant enhancement of catalytic performance can be attributed to the interaction between BH and the imprinted cavity, as well as size matching, which proposes new solutions to address the current problem of difficult degradation of new pollutants.
Hybrid photocatalyst constructed using polymerized metal complexes and semiconductor powders for photocatalytic carbon dioxide reduction
Authors: Yamazaki Yasuomi , Maruyama Riku , Kumagai Hiromu , Maeda Kazuhiko , Tsubomura Taro
Published: May 2024

Hybrid photocatalysts prepared by the adsorption of metal complexes on semiconductors via anchoring groups are among notable photocatalysts for selective CO2 reduction using abundant electron donors. However, their photocatalytic activities are limited by their low adsorption amounts and strength. In this study, we demonstrate the reductive polymerization of vinyl groups in metal complexes triggered by excited electrons on semiconductors as a new immobilization method. This approach significantly enhanced the adsorption amount and durability, thus increasing the photocatalytic performance.
Synthesis of hydroxy acids via the light-driven carboxylation of epoxides with CO2
Authors: Maeda Chihiro , Kumemoto Ren , Tanaka Rio , Ema Tadashi
Published: May 2024

Light-driven ring-opening carboxylation of epoxides with CO2 provided β-hydroxy acids via sequential single electron transfer (SET), followed by reaction with CO2. This reaction condition was applicable to aryl epoxides and oxetanes with (hetero)polycyclic aromatics to give the corresponding β- and γ-hydroxy acids, respectively, with high chemoselectivity.
Development of Simultaneous HPTLC Method and Validation for the Quality Assessment of Ayurvedic Formulation—Ayush Kvatha Churna by Using Marker Compound Rosmarinic Acid, Trans-Cinnamaldehyde and Piperine
Authors: Sahu Umakant , Chauhan Nagendra Singh , Parihar Arun Kumar Singh , Karbhal Kamleshwar Singh , Inchulkar Shrikant R , Gupta Prashant Kumar , Singh Rajesh Kumar
Published: May 2024

Ayurveda emphasizes the propagation of nature in maintaining health. In the present scenario, we have seen the faith of people in herbal drugs during the Covid 19 outbreak. The raises in the number of peoples have been using herbal drugs to boost immunity against infectious diseases shows the popularity of this ancient system of medicine. The standardization of Ayush Kvatha Churna (AKC), work set out to establish a straightforward, accurate and sensitive HPTLC method for the identification and quantification of marker compounds. The Rosmarinic acid, trans-Cinnamaldehyde and Piperine were used for the estimation of markers in Ayush Kvatha Churna by using HPTLC with a solvent system, consisting of Toluene: Ethyl acetate: Ethyl alcohol: Formic acid (5.6:2.4:2: 0.3 v/v/v/v). The Rf value 0.33 for Rosmarinic Acid, 0.69 for Piperine and 0.77 for trans-Cinnamaldehyde was observed and it is exactly complying with the corresponding bands in Ayush Kvatha Churna. The technique has been effectively verified and validated, enabling it to be used for the standardization or quantitative analysis of Rosmarinic acid, trans-Cinnamaldehyde and piperine in Ayush Kvatha Churna.
Cardiovascular magnetic resonance in the identification of extra-cardiac causes of myocarditis: a case series
Authors: Sakhi Hichem , Reverdito Guillaume , Soulat Gilles , Mousseaux Elie
Published: May 2024

Background

Myocarditis is challenging to diagnose due to its varied presentations. Endomyocardial biopsy is the gold standard for diagnosis, but its invasive nature has led to alternative non-invasive modalities, notably cardiovascular magnetic resonance (CMR). Identifying the precise aetiology of myocarditis is crucial for effective treatment, yet extra-cardiac causes are often overlooked. In this paper, we spotlight the underexplored role of CMR in diagnosing extra-cardiac aetiologies, utilizing three insightful cases for illustration.

Case summary

The first case is a 31-year-old patient with myocarditis secondary to a pyogenic liver abscess, identified through CMR, who improved after abscess drainage. The second case involves a 54-year-old patient with myocarditis attributed to adult T-cell leukaemia–lymphoma, with the loco-regional thickening process identified thanks to CMR. This patient had an unfavourable disease progression due to the underlying malignancy. The third case concerns a 23-year-old patient suffering from myocarditis associated with pneumonia, again illustrated effectively through CMR imaging, who recovered after antibiotic treatment.

Discussion

These cases underline the overlooked potential of CMR in diagnosing extra-cardiac aetiologies of myocarditis, even though such causes are rare. Despite current guidelines recognizing the importance of identifying the aetiology of myocarditis, they do not explicitly address the role of CMR in diagnosing extra-cardiac aetiologies. This article, therefore, proposes that future guidelines could emphasize the utility of CMR in exploring these causes, potentially leading to more accurate diagnoses and improved patient outcomes. It also advocates for a comprehensive, multidisciplinary approach to myocarditis diagnosis, encouraging vigilance for potential loco-regional causes, and calls for further research in this area.
Transcriptomic Signatures of Progression to Tuberculosis Disease Among Close Contacts in Brazil
Authors: Mendelsohn Simon C , Andrade Bruno B , Mbandi Stanley Kimbung , Andrade Alice M S , Muwanga Vanessa M , Figueiredo Marina C , Erasmus Mzwandile , Rolla Valeria C , Thami Prisca K , Cordeiro-Santos Marcelo , Penn-Nicholson Adam , Kritski Afranio L , Hatherill Mark , Sterling Timothy R , Scriba Thomas J ,   the RePORT–South Africa and RePORT–Brazil Consortia, Bilek Nicole , Cloete Yolundi , Erasmus Mzwandile , Fisher Michelle , Hadley Katie , Hassiem Rieyaat , Hatherill Mark , Jaxa Lungisa , Mbandi Stanley Kimbung , Mendelsohn Simon C , Meyer Faheemah , Muwanga Vanessa M , Nombida Onke , Penn-Nicholson Adam , Raphela Rodney , Scriba Thomas J , September Alison , Sterling Timothy R , Thami Prisca K , Veldsman Ashley , Andrade Alice , Andrade Bruno B , Carvalho Brenda , Cordeiro-Santos Marcelo , Figueiredo Marina Cruvinel , Gomes Adriano , Kritski Afranio L , Rolla Valeria C , Sterling Timothy R
Published: May 2024

Background

Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease.

Methods

Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up.

Results

Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up.

Conclusions

Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration.
Review of Current Tuberculosis Human Infection Studies for Use in Accelerating Tuberculosis Vaccine Development: A Meeting Report
Authors: Balasingam Shobana , Dheda Keertan , Fortune Sarah , Gordon Stephen B , Hoft Daniel , Kublin James G , Loynachan Colleen N , McShane Helen , Morton Ben , Nambiar Sujatha , Sharma Nimisha Raj , Robertson Brian , Schrager Lewis K , Weller Charlotte L
Published: May 2024

Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment among key stakeholders. In March 2023, the Wellcome Trust and the International AIDS Vaccine Initiative convened international experts involved in developing both TB and bacillus Calmette-Guérin (BCG) human infection studies (including mucosal and intradermal challenge routes) to discuss the status of each of the models and the key enablers to move the field forward. This report provides a summary of the presentations and discussion from the meeting. Discussions identified key issues, including demonstrating model validity, to provide confidence for vaccine developers, which may be addressed through demonstration of known vaccine effects (eg, BCG vaccination in specific populations), and by comparing results from field efficacy and human infection studies. The workshop underscored the importance of establishing safe and acceptable studies in high-burden settings, and the need to validate >1 model to allow for different scientific questions to be addressed as well as to provide confidence to vaccine developers and regulators around use of human infection study data in vaccine development and licensure pathways.
Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production
Authors: Xu Hongke , Chen Yanfei , Li Jingzhi , Li Mengyu , Sun Miao , Chen Jian , Li Ling , Xue Qinghong , Ma Hongwei
Published: May 2024

Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgG production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgG production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgG production exhibited TIP (duration < 60 days) and PIP (duration > 368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were coimmunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgG production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.
Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19
Authors: Zhou Xiao-Jian , Horga Arantxa , Puri Adeep , Winchester Lee , Montrond Maureen , Pietropaolo Keith , Belanger Bruce , Fletcher Courtney V , Hammond Janet
Published: May 2024

Background

Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved.

Objectives

This Phase 1 study in healthy subjects aimed to assess the bronchopulmonary pharmacokinetics, safety and tolerability of repeated doses of bemnifosbuvir.

Methods

A total of 24 subjects were assigned to receive bemnifosbuvir twice daily at doses of 275, 550 or 825 mg for up to 3.5 days.

Results

AT-511, the free base of bemnifosbuvir, was largely eliminated from the plasma within 6 h post dose in all dosing groups. Antiviral drug levels of bemnifosbuvir were consistently achieved in the lungs with bemnifosbuvir 550 mg twice daily. The mean level of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, measured in the epithelial lining fluid of the lungs was 0.62 µM at 4–5 h post dose. This exceeded the target in vitro 90% effective concentration (EC90) of 0.5 µM for antiviral drug exposure against SARS-CoV-2 replication in human airway epithelial cells. Bemnifosbuvir was well tolerated across all doses tested, and most treatment-emergent adverse events reported were mild in severity and resolved.

Conclusions

The favourable pharmacokinetics and safety profile of bemnifosbuvir demonstrates its potential as an oral antiviral treatment for COVID-19, with 550 mg bemnifosbuvir twice daily currently under further clinical evaluation in persons with COVID-19.
Sedimentation field-flow fractionation for rapid phenotypic antimicrobial susceptibility testing: a pilot study
Authors: Gauthier Audrey , Tlili Linda , Battu Serge , Le Moan Coline , Ploy Marie-Cécile , Lalloue Fabrice , Bégaud Gaëlle , Barraud Olivier
Published: May 2024

Background

The increase in antibiotic resistance is a major public health issue. The development of rapid antimicrobial susceptibility testing (AST) methods is becoming a priority to ensure early and appropriate antibiotic therapy.

Objectives

To evaluate sedimentation field-flow fractionation (SdFFF) as a method for performing AST in less than 3 h.

Methods

SdFFF is based on the detection of early biophysical changes in bacteria, using a chromatographic-type technology. One hundred clinical Escherichia coli strains were studied. A calibrated bacterial suspension was incubated for 2 h at 37°C in the absence (untreated) or presence (treated) of five antibiotics used at EUCAST breakpoint concentrations. Bacterial suspensions were then injected into the SdFFF machine. For each E. coli isolate, retention times and elution profiles of antibiotic-treated bacteria were compared with retention times and elution profiles of untreated bacteria. Algorithms comparing retention times and elution profiles were used to determine if the strain was susceptible or resistant. Performance evaluation was done according to CLSI and the ISO standard 20776-2:2021 with broth microdilution used as the reference method.

Results

AST results from SdFFF were obtained in less than 3 h. SdFFF showed high categorical agreement (99.8%), sensitivity (99.5%) and specificity (100.0%) with broth microdilution. Results for each antimicrobial were also in agreement with the ISO 20776-2 recommendations, with sensitivity and specificity of ≥95.0%.

Conclusions

This study showed that SdFFF can be used as a rapid, accurate and reliable phenotypic AST method with a turnaround time of less than 3 h.
Pharmacist roles in antimicrobial stewardship: a qualitative study from India, South Africa and the United Kingdom
Authors: Nampoothiri Vrinda , Mbamalu Oluchi , Mendelson Marc , Singh Sanjeev , Charani Esmita
Published: May 2024

Objective

To explore pharmacist roles in antimicrobial stewardship (AMS) in India, South Africa (SA), United Kingdom (UK) and the factors that contribute to their participation in the programme in these countries.

Methods

Data were collected between April 2019 and March 2022 through semi-structured interviews with key AMS stakeholders from India (Kerala); SA (Western Cape province) and the UK (England). Interviews were conducted face to face or via Zoom and Skype platforms, audio recordings were transcribed verbatim and thematically analysed using a grounded theory approach aided by NVivo 12 software.

Results

We interviewed 38 key AMS stakeholders (pharmacists and doctors). India and the UK have dedicated AMS pharmacists (Doctor of Pharmacy and Master of Pharmacy graduates with opportunities for additional post-graduate qualifications respectively). Pharmacists in the UK lead AMS programmes, while in India, predominantly in the private sector, pharmacists drive AMS in collaboration with clinicians. In SA, pharmacists (Bachelor of Pharmacy graduates) participate in AMS out of their own commitment in addition to their pharmacy responsibilities. Private sector pharmacists drive AMS while public sector pharmacists participate in clinician-led AMS programmes. Current pharmacy curricula do not provide adequate training in AMS, and this limitation shapes pharmacist roles and acceptance in AMS among clinicians in India and SA. Support of mentors (doctors/senior pharmacists) and self-motivated learning are key factors for effective pharmacist involvement in AMS.

Conclusions

A contextually developed, standardized and accessible AMS training programme along with pharmacy curricula modification to include AMS, may facilitate prominent pharmacist roles in AMS.
Heat stress alters hematological parameters in barrows and gilts
Authors: Rudolph Tori E , Roths Melissa , Freestone Alyssa D , White-Springer Sarah H , Rhoads Robert P , Baumgard Lance H , Selsby Joshua T
Published: May 2024

The purpose of this investigation was to establish the role biological sex plays in circulating factors following heat stress (HS). Barrows and gilts (36.8 ± 3.7 kg body weight) were kept in either thermoneutral (TN; 20.8 ± 1.6 °C; 62.0% ± 4.7% relative humidity; n = 8/sex) conditions or exposed to HS (39.4 ± 0.6 °C; 33.7% ± 6.3% relative humidity) for either 1 (HS1; n = 8/sex) or 7 (HS7; n = 8/sex) d. Circulating glucose decreased as a main effect of the environment (P = 0.03). Circulating non-esterified fatty acid (NEFA) had an environment × sex interaction (P < 0.01) as HS1 barrows had increased NEFA compared to HS1 gilts (P = 0.01) and NEFA from HS7 gilts increased compared to HS1 gilts (P = 0.02) and HS7 barrows (P = 0.04). Cortisol, insulin, glucagon, T3, and T4 were reduced as a main effect of environment (P ≤ 0.01). Creatinine was increased in HS1 and HS7 animals compared to TN (P ≤ 0.01), indicative of decreased glomerular filtration rate. White blood cell populations exhibited differential patterns based on sex and time. Neutrophils and lymphocytes had an environment × sex interaction (P ≤ 0.05) as circulating neutrophils were increased in HS1 barrows compared to TN and HS7 barrows, and HS1 gilts (P ≤ 0.01) and HS7 barrows had less neutrophils compared to TN barrows (P = 0.01), whereas they remained similar in gilts. In contrast, barrow lymphocyte numbers were similar between groups, but in HS7 gilts they were decreased compared to TN and HS1 gilts (P ≤ 0.04). In total, these data demonstrate that HS alters a host of circulating factors and that biological sex mediates, at least in part, the physiological response to HS.