bluuebunny/crossref_metadata_2025 huggingface dataset:
Legume-supplemented feed for children hospitalised with severe malnutrition: a phase II trial
Authors: Walsh Kevin , Kiosa Akglinta , Olupot-Olupot Peter , Alaroker Florence , Okiror William , Nakuya Margaret , Tssenyondo Tonny , Aromut Denis , Okalebo Bernard Charles , Muhindo Rita , Mpoya Ayub , George Elizabeth C. , Frost Gary S. , Maitland Kathryn
Published: June 2024

Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not the modification of gut barrier integrity or microbiome which increases the risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. We conducted an open-label phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda, involving 160 children aged 6 months to 5 years with severe malnutrition (mid-upper arm circumference (MUAC) < 11·5 cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n 80) v. WHO standard F75/F100 feeds (n 80). Co-primary outcomes were change in MUAC and mortality to day 90. Secondary outcomes included weight gain (> 5 g/kg/d), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Day 90 MUAC increase was marginally lower in LF v. WHO arm (1·1 cm (interquartile range (IQR) 1·1) v. 1·4 cm (IQR 1·40), P = 0·09); day 90 mortality was similar (11/80 (13·8 %) v. 12/80 (15 %), respectively, OR 0·91 (95 % CI 0·40, 2·07), P = 0·83). There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the LF, ten children switched to WHO feeds. Per-protocol analysis indicated a trend to lower day 90 mortality and readmission rates in the LF (6/60 (10 %) and 2/60(3 %)) v. WHO feeds (12/71(17·5 %) and 4/71(6 %)). Further refinement of LF and clinical trials are warranted, given the poor outcomes in children with severe malnutrition.
On the probability of a Pareto record
Authors: Fill James Allen , Sun Ao
Published: June 2024

Given a sequence of independent random vectors taking values in ${\mathbb R}^d$ and having common continuous distribution function F, say that the $n^{\rm \scriptsize}$th observation sets a (Pareto) record if it is not dominated (in every coordinate) by any preceding observation. Let $p_n(F) \equiv p_{n, d}(F)$ denote the probability that the $n^{\rm \scriptsize}$th observation sets a record. There are many interesting questions to address concerning pn and multivariate records more generally, but this short paper focuses on how pn varies with F, particularly if, under F, the coordinates exhibit negative dependence or positive dependence (rather than independence, a more-studied case). We introduce new notions of negative and positive dependence ideally suited for such a study, called negative record-setting probability dependence (NRPD) and positive record-setting probability dependence (PRPD), relate these notions to existing notions of dependence, and for fixed $d \geq 2$ and $n \geq 1$ prove that the image of the mapping pn on the domain of NRPD (respectively, PRPD) distributions is $[p^*_n, 1]$ (resp., $[n^{-1}, p^*_n]$), where $p^*_n$ is the record-setting probability for any continuous F governing independent coordinates.
Post-adoption experiences of discrimination moderated by sleep quality are associated with depressive symptoms in previously institutionalized youth over and above deprivation-induced depression risk
Authors: Morency Mirinda M. , Donzella Bonny , Reid Brie M. , Lee Richard M. , Dengel Donald R. , Gunnar Megan R.
Published: June 2024

The association of post-adoption experiences of discrimination with depressive symptoms was examined in 93 previously institutionalized (PI) youth (84% transracially adopted). Additionally, we explored whether sleep quality statistically moderated this association. Notably, we examined these associations after covarying a measure of autonomic balance (high/low frequency ratio in heart rate variability) affected by early institutional deprivation and a known risk factor for depression. PI youth exhibited more depressive symptoms and experiences of discrimination than 95 comparison youth (non-adopted, NA) raised in their biological families in the United States. In the final regression model, there was a significant interaction between sleep quality and discrimination, such that at higher levels of sleep quality, the association between discrimination and depression symptoms was non-significant. Despite being cross-sectional, the results suggest that the risk of depression in PI youth involves post-adoption experiences that appear unrelated to the impacts of early deprivation on neurobiological processes associated with depression risk. It may be crucial to examine methods of improving sleep quality and socializing PI youth to cope with discrimination as protection against discrimination and microaggressions.
Biodiversity and Climate Extremes: Known Interactions and Research Gaps
Authors: Mahecha M. D. , Bastos A. , Bohn F. J. , Eisenhauer N. , Feilhauer H. , Hickler T. , Kalesse‐Los H. , Migliavacca M. , Otto F. E. L. , Peng J. , Sippel S. , Tegen I. , Weigelt A. , Wendisch M. , Wirth C. , Al‐Halbouni D. , Deneke H. , Doktor D. , Dunker S. , Duveiller G. , Ehrlich A. , Foth A. , García‐García A. , Guerra C. A. , Guimarães‐Steinicke C. , Hartmann H. , Henning S. , Herrmann H. , Hu P. , Ji C. , Kattenborn T. , Kolleck N. , Kretschmer M. , Kühn I. , Luttkus M. L. , Maahn M. , Mönks M. , Mora K. , Pöhlker M. , Reichstein M. , Rüger N. , Sánchez‐Parra B. , Schäfer M. , Stratmann F. , Tesche M. , Wehner B. , Wieneke S. , Winkler A. J. , Wolf S. , Zaehle S. , Zscheischler J. , Quaas J.
Published: June 2024

Climate extremes are on the rise. Impacts of extreme climate and weather events on ecosystem services and ultimately human well‐being can be partially attenuated by the organismic, structural, and functional diversity of the affected land surface. However, the ongoing transformation of terrestrial ecosystems through intensified exploitation and management may put this buffering capacity at risk. Here, we summarize the evidence that reductions in biodiversity can destabilize the functioning of ecosystems facing climate extremes. We then explore if impaired ecosystem functioning could, in turn, exacerbate climate extremes. We argue that only a comprehensive approach, incorporating both ecological and hydrometeorological perspectives, enables us to understand and predict the entire feedback system between altered biodiversity and climate extremes. This ambition, however, requires a reformulation of current research priorities to emphasize the bidirectional effects that link ecology and atmospheric processes.
Ultra-robust informational metasurfaces based on spatial coherence structures engineering
Authors: Liu Leixin , Liu Wenwei , Wang Fei , Peng Xiaofeng , Choi Duk-Yong , Cheng Hua , Cai Yangjian , Chen Shuqi
Published: June 2024

Optical information transmission is vital in modern optics and photonics due to its concurrent and multi-dimensional nature, leading to tremendous applications such as optical microscopy, holography, and optical sensing. Conventional optical information transmission technologies suffer from bulky optical setup and information loss/crosstalk when meeting scatterers or obstacles in the light path. Here, we theoretically propose and experimentally realize the simultaneous manipulation of the coherence lengths and coherence structures of the light beams with the disordered metasurfaces. The ultra-robust optical information transmission and self-reconstruction can be realized by the generated partially coherent beam with modulated coherence structure even 93% of light is recklessly obstructed during light transmission, which brings new light to robust optical information transmission with a single metasurface. Our method provides a generic principle for the generalized coherence manipulation on the photonic platform and displays a variety of functionalities advancing capabilities in optical information transmission such as meta-holography and imaging in disordered and perturbative media.
The rhythm of mental health: the relationship of chronotype with psychiatric trait dimensions and diurnal variation in psychiatric symptoms
Authors: Balter Leonie J. T. , Holding Benjamin C. , Petrovic Predrag , Axelsson John
Published: June 2024

To advance the emergence of circadian-based therapies, this study characterized how psychiatric symptoms fluctuate across the day and vary between individuals. Using a dimensional approach, we determined how chronotype relates to 13 psychiatric traits, and modeled the temporal development of symptoms throughout the day using generalized additive mixed effects models. In this preregistered study, a subclinical sample completed 13 psychiatric trait scales and a chronotype scale at baseline (N = 515, n = 404 women, 109 men, n = 2 non-binary, M age = 32.4 years, range 18–77), followed by 22 psychiatric symptoms and behaviors rated repeatedly between ~08:00-00:00 (n = 410). Key findings are that 11 out of 13 psychiatric traits were associated with being an evening-type, ranging from depression to obsessive comulsive disorder, social anxiety, and delusional ideation, while only mania was associated with being a morning-type. Four distinct psychiatric trait factors were identified, each predicting worse symptom levels throughout the day. Fatigue-related symptoms exhibited strong time-of-day changes with evening-types experiencing worse fatigue in the morning and morning-types in the evening. Evening-types had considerably lower drive and motivation than morning-types from morning to early evening. Evening-types also had more pronounced negative emotional symptoms and ADHD-type symptoms in the evening, particularly among those high in psychiatric trait factors. These findings identified important research targets that hold promise for improving mental health outcomes, such as strategies to boost morning motivation. Furthermore, the results emphasize the relevance of incorporating circadian factors, including chronotype, into translational psychiatric research and interventions.
Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue
Authors: Kumar Saumya , Basto Afonso P. , Ribeiro Filipa , Almeida Silvia C. P. , Campos Patricia , Peres Carina , Pulvirenti Nadia , Al-Khalidi Sarwah , Kilbey Anna , Tosello Jimena , Piaggio Eliane , Russo Momtchilo , Gama-Carvalho Margarida , Coffelt Seth B. , Roberts Ed W. , Geginat Jens , Florindo Helena F. , Graca Luis
Published: June 2024

Effective antibody responses are essential to generate protective humoral immunity. Different inflammatory signals polarize T cells towards appropriate effector phenotypes during an infection or immunization. Th1 and Th2 cells have been associated with the polarization of humoral responses. However, T follicular helper cells (Tfh) have a unique ability to access the B cell follicle and support the germinal center (GC) responses by providing B cell help. We investigated the specialization of Tfh cells induced under type-1 and type-2 conditions. We first studied homogenous Tfh cell populations generated by adoptively transferred TCR-transgenic T cells in mice immunized with type-1 and type-2 adjuvants. Using a machine learning approach, we established a gene expression signature that discriminates Tfh cells polarized towards type-1 and type-2 response, defined as Tfh1 and Tfh2 cells. The distinct signatures of Tfh1 and Tfh2 cells were validated against datasets of Tfh cells induced following lymphocytic choriomeningitis virus (LCMV) or helminth infection. We generated single-cell and spatial transcriptomics datasets to dissect the heterogeneity of Tfh cells and their localization under the two immunizing conditions. Besides a distinct specialization of GC Tfh cells under the two immunizations and in different regions of the lymph nodes, we found a population of Gzmk+ Tfh cells specific for type-1 conditions. In human individuals, we could equally identify CMV-specific Tfh cells that expressed Gzmk. Our results show that Tfh cells acquire a specialized function under distinct types of immune responses and with particular properties within the B cell follicle and the GC.
Highly confined epsilon-near-zero and surface phonon polaritons in SrTiO3 membranes
Authors: Xu Ruijuan , Crassee Iris , Bechtel Hans A. , Zhou Yixi , Bercher Adrien , Korosec Lukas , Rischau Carl Willem , Teyssier Jérémie , Crust Kevin J. , Lee Yonghun , Gilbert Corder Stephanie N. , Li Jiarui , Dionne Jennifer A. , Hwang Harold Y. , Kuzmenko Alexey B. , Liu Yin
Published: June 2024

Recent theoretical studies have suggested that transition metal perovskite oxide membranes can enable surface phonon polaritons in the infrared range with low loss and much stronger subwavelength confinement than bulk crystals. Such modes, however, have not been experimentally observed so far. Here, using a combination of far-field Fourier-transform infrared (FTIR) spectroscopy and near-field synchrotron infrared nanospectroscopy (SINS) imaging, we study the phonon polaritons in a 100 nm thick freestanding crystalline membrane of SrTiO3 transferred on metallic and dielectric substrates. We observe a symmetric-antisymmetric mode splitting giving rise to epsilon-near-zero and Berreman modes as well as highly confined (by a factor of 10) propagating phonon polaritons, both of which result from the deep-subwavelength thickness of the membranes. Theoretical modeling based on the analytical finite-dipole model and numerical finite-difference methods fully corroborate the experimental results. Our work reveals the potential of oxide membranes as a promising platform for infrared photonics and polaritonics.
Direct observation of photoinduced sequential spin transition in a halogen-bonded hybrid system by complementary ultrafast optical and electron probes
Authors: Jiang Yifeng , Hayes Stuart , Bittmann Simon , Sarracini Antoine , Liu Lai Chung , Müller-Werkmeister Henrike M. , Miyawaki Atsuhiro , Hada Masaki , Nakano Shinnosuke , Takahashi Ryoya , Banu Samiran , Koshihara Shin-ya , Takahashi Kazuyuki , Ishikawa Tadahiko , Miller R. J. Dwayne
Published: June 2024

A detailed understanding of the ultrafast dynamics of halogen-bonded materials is desired for designing supramolecular materials and tuning various electronic properties by external stimuli. Here, a prototypical halogen-bonded multifunctional material containing spin crossover (SCO) cations and paramagnetic radical anions is studied as a model system of photo-switchable SCO hybrid systems using ultrafast electron diffraction and two complementary optical spectroscopic techniques. Our results reveal a sequential dynamics from SCO to radical dimer softening, uncovering a key transient intermediate state. In combination with quantum chemistry calculations, we demonstrate the presence of halogen bonds in the low- and high-temperature phases and propose their role during the photoinduced sequential dynamics, underscoring the significance of exploring ultrafast dynamics. Our research highlights the promising utility of halogen bonds in finely tuning functional properties across diverse photoactive multifunctional materials.
Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration
Authors: Bixel M. Gabriele , Sivaraj Kishor K. , Timmen Melanie , Mohanakrishnan Vishal , Aravamudhan Anusha , Adams Susanne , Koh Bong-Ihn , Jeong Hyun-Woo , Kruse Kai , Stange Richard , Adams Ralf H.
Published: June 2024

Bone regeneration requires a well-orchestrated cellular and molecular response including robust vascularization and recruitment of mesenchymal and osteogenic cells. In femoral fractures, angiogenesis and osteogenesis are closely coupled during the complex healing process. Here, we show with advanced longitudinal intravital multiphoton microscopy that early vascular sprouting is not directly coupled to osteoprogenitor invasion during calvarial bone regeneration. Early osteoprogenitors emerging from the periosteum give rise to bone-forming osteoblasts at the injured calvarial bone edge. Microvessels growing inside the lesions are not associated with osteoprogenitors. Subsequently, osteogenic cells collectively invade the vascularized and perfused lesion as a multicellular layer, thereby advancing regenerative ossification. Vascular sprouting and remodeling result in dynamic blood flow alterations to accommodate the growing bone. Single cell profiling of injured calvarial bones demonstrates mesenchymal stromal cell heterogeneity comparable to femoral fractures with increase in cell types promoting bone regeneration. Expression of angiogenesis and hypoxia-related genes are slightly elevated reflecting ossification of a vascularized lesion site. Endothelial Notch and VEGF signaling alter vascular growth in calvarial bone repair without affecting the ossification progress. Our findings may have clinical implications for bone regeneration and bioengineering approaches.
Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis
Authors: Ma Yu-Lan , Kong Chun-Yan , Guo Zhen , Wang Ming-Yu , Wang Pan , Liu Fang-Yuan , Yang Dan , Yang Zheng , Tang Qi-Zhu
Published: June 2024

Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.
Picosecond reactions of excited radical ion super-reductants
Authors: Pfund Björn , Gejsnæs-Schaad Deyanira , Lazarevski Bruno , Wenger Oliver S.
Published: June 2024

Classical photochemistry requires nanosecond excited-state lifetimes for diffusion-controlled reactions. Excited radicals with picosecond lifetimes have been implied by numerous photoredox studies, and controversy has arisen as to whether they can actually be catalytically active. We provide direct evidence for the elusive pre-association between radical ions and substrate molecules, enabling photoinduced electron transfer beyond the diffusion limit. A strategy based on two distinct light absorbers, mimicking the natural photosystems I and II, is used to generate excited radicals, unleashing extreme reduction power and activating C(sp2)―Cl and C(sp2)―F bonds. Our findings provide a long-sought mechanistic understanding for many previous synthetically-oriented works and permit more rational future photoredox reaction development. The newly developed excitation strategy pushes the current limits of reactions based on multi-photon excitation and very short-lived but highly redox active species.
The FRESHAIR4Life study: Global implementation research on non-communicable disease prevention targeting adolescents’ exposure to tobacco and air pollution in disadvantaged populations
Authors: Hoffman Charlotte M. , Versluis Anke , Chirila Sergiu , Kirenga Bruce J. , Khan Amina , Saeed Saima , Sooronbaev Talant , Tsiligianni Ioanna , Arvind D. K. , Bauld Linda C. , van den Brand Floor A. , Chavannes Niels H. , Pinnock Hilary , Powell Pippa D. , van der Schans Jurjen , Siddiqi Kamran , Williams Siân , van der Kleij M. J. J. Rianne
Published: June 2024

The FRESHAIR4Life study aims to reduce the non-communicable disease (NCD) burden by implementing preventive interventions targeting adolescents’ exposure to tobacco use and air pollution (AP) worldwide. This paper presents the FRESHAIR4Life methodology and initial rapid review results. The rapid review, using various databases and PubMed, aimed to guide decision-making on risk factor focus, target areas, and populations. It showed variable NCD mortality rates related to tobacco use and AP across the participating countries, with tobacco as the main risk factor in the Kyrgyz Republic, Greece, and Romania, and AP prevailing in Pakistan and Uganda. Adolescent exposure levels, sources, and correlates varied. The study will continue with an in-depth situational analysis to guide the selection, adaptation, and integration of evidence-based interventions into the FRESHAIR4Life prevention package. This package will be implemented, evaluated, assessed for cost-effectiveness, and iteratively refined. The research places a strong emphasis on co-creation, capacity building, and comprehensive communication and dissemination.
Chromosome-level genome assembly of ridgetail white shrimp Exopalaemon carinicauda
Authors: Wang Jiajia , Lv Jianjian , Shi Miao , Ge Qianqian , Wang Qiong , He Yuying , Li Jian , Li Jitao
Published: June 2024

Exopalaemon carinicauda, a eurythermal and euryhaline shrimp, contributes one third of the total biomass production of polyculture ponds in eastern China and is considered as a potential ideal experimental animal for research on crustaceans. We conducted a high-quality chromosome-level genome assembly of E. carinicauda combining PacBio HiFi and Hi-C sequencing data. The total assembly size was 5.86 Gb, with a contig N50 of 235.52 kb and a scaffold N50 of 138.24 Mb. Approximately 95.29% of the assembled sequences were anchored onto 45 pseudochromosomes. BUSCO analysis revealed that 92.89% of 1,013 single-copy genes were highly conserved orthologs. A total of 44, 288 protein-coding genes were predicted, of which 70.53% were functionally annotated. Given its high heterozygosity (2.62%) and large proportion of repeat sequences (71.49%), it is one of the most complex genome assemblies. This chromosome-scale genome will be a valuable resource for future molecular breeding and functional genomics research on E. carinicauda.
Chromosome-level genome assembly of Solanum pimpinellifolium
Authors: Han Hongyu , Li Xiuhong , Li Tianze , Chen Qian , Zhao Jiuhai , Zhai Huawei , Deng Lei , Meng Xianwen , Li Chuanyou
Published: June 2024

Solanum pimpinellifolium, the closest wild relative of the domesticated tomato, has high potential for use in breeding programs aimed at developing multi-pathogen resistance and quality improvement. We generated a chromosome-level genome assembly of S. pimpinellifolium LA1589, with a size of 833 Mb and a contig N50 of 31 Mb. We anchored 98.80% of the contigs into 12 pseudo-chromosomes, and identified 74.47% of the sequences as repetitive sequences. The genome evaluation revealed BUSCO and LAI score of 98.3% and 14.49, respectively, indicating high quality of this assembly. A total of 41,449 protein-coding genes were predicted in the genome, of which 89.17% were functionally annotated. This high-quality genome assembly serves as a valuable resource for accelerating the biological discovery and molecular breeding of this important horticultural crop.
EW-7197, transforming growth factor β inhibitor, combined with irreversible electroporation for improving skin wound in a rat excisional model
Authors: Zeng Chu Hui , Kang Jeon Min , Kim Song Hee , Park Yubeen , Shim Soyeon , Kim Dae-Kee , Shin Ji Hoon , Park Jung-Hoon
Published: June 2024

To evaluate the safety and efficacy of combining EW-7197 with irreversible electroporation (IRE) for improving wound healing, 16 male Sprague–Dawley rats were randomly divided into four groups of four rats each after dorsal excisional wound induction: sham control group; oral administration of EW-7197 for 7 days group; one-time application of IRE group; and one-time application of IRE followed by oral administration of EW-7197 for 7 days group. Measurement of wound closure rate, laser Doppler scanning, histological staining (hematoxylin and eosin and Masson’s trichrome), and immunohistochemical analyses (Ki-67 and α-SMA) were performed to evaluate the efficacy. Fifteen of 16 rats survived throughout the study. Statistically significant differences in wound closure rates were observed between the combination therapy group and the other three groups (all P < 0.05). The degrees of inflammation, α-SMA, and Ki-67 were reduced in the EW-7197 and IRE monotherapy groups; however, not statistically significant. The fibrosis score exhibited significant reduction in all three treatment groups, with the most prominent being in the combination therapy group. This study concludes that oral administration of EW-7197 combined with IRE demonstrated effectiveness in improving skin wound in a rat excisional model and may serve as a potential alternative for promoting healing outcomes.
Immunomodulation profile of the biosimilar trastuzumab MYL-1401O in a bioequivalence phase I study
Authors: Audran R. , Chtioui H. , Thierry A. C. , Mayor C. E. , Vallotton L. , Dao K. , Rothuizen L. E. , Maghraoui A. , Pennella E. J. , Brunner-Ferber F. , Buclin T. , Spertini F.
Published: June 2024

The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin® and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin® similarly secreted IL-6, TNF-α, IL-1β, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals.
Dorsal pulvinar inactivation leads to spatial selection bias without perceptual deficit
Authors: Kaduk Kristin , Wilke Melanie , Kagan Igor
Published: June 2024

The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect symptoms, including an overt spatial saccade bias during free choices. However, it remains unclear whether disrupting the dorsal pulvinar during target selection that relies on a perceptual decision leads to a perceptual impairment or a more general spatial orienting and choice deficit. To address this question, we reversibly inactivated the unilateral dorsal pulvinar by injecting GABA-A agonist THIP while two macaque monkeys performed a color discrimination saccade task with varying perceptual difficulty. We used Signal Detection Theory and simulations to dissociate perceptual sensitivity (d-prime) and spatial selection bias (response criterion) effects. We expected a decrease in d-prime if dorsal pulvinar affects perceptual discrimination and a shift in response criterion if dorsal pulvinar is mainly involved in spatial orienting. After the inactivation, we observed response criterion shifts away from contralesional stimuli, especially when two competing stimuli in opposite hemifields were present. Notably, the d-prime and overall accuracy remained largely unaffected. Our results underline the critical contribution of the dorsal pulvinar to spatial orienting and action selection while showing it to be less important for visual perceptual discrimination.
Lie symmetry analysis and solitary wave solution of biofilm model Allen-Cahn
Authors: Shakeel Muhammad , Abbas Naseem , Rehman Muhammad Junaid U. , Alshammari Fehaid Salem , Al-Yaari Abdullah
Published: June 2024

The investigation presented in this study delves into the analysis of Lie symmetries for the bistable Allen-Cahn (BAC) equation with a quartic potential, specifically applied to the biofilm model. By employing the Lie symmetry method, we have acquired the Lie infinitesimal generators for the considered model. Using a transformation method, the nonlinear partial differential equations (NPDEs) are converted into various nonlinear ordinary differential equations (NLODEs), providing the numerous closed-form solitary wave solutions. The obtained solutions manifest in various forms including dark, bright, kink, anti-kink, and periodic types using diverse strategies. To enhance the physical interpretation, the study presents 3D, 2D, and contour plots of the acquired solutions. Every graph’s wave-like structure contains information about the structural behaviour of the bacteria that build biofilms on surfaces where rectangles have different densities. This analysis enhances comprehension of the complex dynamics present in areas like fluid dynamics, fiber optics, biology, ocean physics, coastal engineering, and nonlinear complex physical systems.
Exploring the potential mechanisms of Danshen against COVID-19 via network pharmacology analysis and molecular docking
Authors: Zhang Qiang , Liang Zongsuo , Wang Xiaoqing , Zhang Siyu , Yang Zongqi
Published: June 2024

Danshen, a prominent herb in traditional Chinese medicine (TCM), is known for its potential to enhance physiological functions such as blood circulation, immune response, and resolve blood stasis. Despite the effectiveness of COVID-19 vaccination efforts, some individuals still face severe complications post-infection, including pulmonary fibrosis, myocarditis arrhythmias and stroke. This study employs a network pharmacology and molecular docking approach to investigate the potential mechanisms underlying the therapeutic effects of candidate components and targets from Danshen in the treatment of complications in COVID-19. Candidate components and targets from Danshen were extracted from the TCMSP Database, while COVID-19-related targets were obtained from Genecards. Venn diagram analysis identified common targets. A Protein–Protein interaction (PPI) network and gene enrichment analysis elucidated potential therapeutic mechanisms. Molecular docking evaluated interactions between core targets and candidate components, followed by molecular dynamics simulations to assess stability. We identified 59 potential candidate components and 123 targets in Danshen for COVID-19 treatment. PPI analysis revealed 12 core targets, and gene enrichment analysis highlighted modulated pathways. Molecular docking showed favorable interactions, with molecular dynamics simulations indicating high stability of key complexes. Receiver operating characteristic (ROC) curves validated the docking protocol. Our study unveils candidate compounds, core targets, and molecular mechanisms of Danshen in COVID-19 treatment. These findings provide a scientific foundation for further research and potential development of therapeutic drugs.
Influence of fermentation conditions, and the blends of sorghum and carrot pulp supplementation on the nutritional and sensory quality of tef injera
Authors: Suraj Mohammed , Abewaa Mikiyas , Mengistu Ashagrie , Bultosa Geremew , Bussa Nigussie
Published: June 2024

Tef [Eragrostis tef (Zucc.) Trotter], an ancient cereal primarily grown in Ethiopia, is becoming increasingly popular worldwide due to its high iron content and gluten-free nature. However, it has been reported that injera produced only with tef flour lack certain vital nutrients. Therefore, this specific study was conducted to supplement tef injera with other food materials of better nutritional value and compensate its expensive market price with sorghum cereal flour. The effect of fermentation conditions, and the sorghum and carrot pulp blending ratio on the nutritional value and sensory quality of tef injera was investigated. The factorial approach of the experimental design was conducted considering the nutritional value and sensory quality of the injera made of three main blending ratios of tef, sorghum, and carrot (60% tef: 30% sorghum: 10% carrot pulp, 45% tef: 45% sorghum: 10% carrot pulp and 30% tef: 60% sorghum: 10% carrot pulp) as experiential variables. The raw materials and injera were characterised for their proximate composition, physicochemical property, mineral composition, microbial analysis, and sensory attributes, using standard methods. The results of the study show that fermentation conditions and blending ratios have a significant effect on the nutritional, anti-nutritional, mineral content, microbial quality, and sensory properties of blended injera products, where higher values of ash, crude protein, crude fat, Total titratable acidity (TTA), Fe, Zn, and Ca (2.30%, 11.34%, 2.62%, 3.53, 32.97 mg/100 g, 2.98 mg/100 g and 176.85 mg/100 g, respectively) were analyzed for the co-fermented injera sample. In addition, a lower microbial count was observed in co-fermented injera samples, whereas microbial counts in injera samples prepared from carrot pulp-supplemented dough after the co-fermentation of tef and sorghum flours were observed to be higher. The injera product made using blending ratio of 60% tef: 30%sorghum: 10% carrot co-fermented was found to be the optimum result due to its very good nutritional improvement (i.e., reduction of some anti-nutritional factors, microbial contents, pH and increased contents of some minerals, crude protein, crude fat, TTA and improved most of the sensory quality of the supplemented injera product). According to this study, sorghum and carrot supplementation on tef could improve the nutritional value of injera while also providing an instant remedy for the growing price of tef.
Enzymatic chemonucleolysis for lumbar disc herniation—an assessment of historical and contemporary efficacy and safety: a systematic review and meta-analysis
Authors: Schol Jordy , Ambrosio Luca , Tamagawa Shota , Joyce Kieran , Ruiz-Fernández Clara , Nomura Akira , Sakai Daisuke
Published: June 2024

Lumbar disc herniation (LDH) is often managed surgically. Enzymatic chemonucleolysis emerged as a non-surgical alternative. This systematic review and meta-analysis aims to assess the efficacy and safety of chemonucleolytic enzymes for LDH. The primary objective is to evaluate efficacy through “treatment success” (i.e., pain reduction) and severe adverse events (SAEs) rates. Additionally, differences in efficacy and safety trends among chemonucleolytic enzymes are explored. Following our PROSPERO registered protocol (CRD42023451546) and PRISMA guidelines, a systematic search of PubMed and Web of Science databases was conducted up to July 18, 2023. Inclusion criteria involved human LDH treatment with enzymatic chemonucleolysis reagents, assessing pain alleviation, imaging changes, and reporting on SAEs, with focus on allergic reactions. Quality assessment employed the Cochrane Source of Bias and MINORS tools. Meta-analysis utilized odds ratios (OR) with 95% confidence intervals (CI). Among 62 included studies (12,368 patients), chemonucleolysis demonstrated an 79% treatment success rate and significantly outperformed placebo controls (OR 3.35, 95% CI 2.41–4.65) and scored similar to surgical interventions (OR 0.65, 95% CI 0.20–2.10). SAEs occurred in 1.4% of cases, with slightly higher rates in chymopapain cohorts. No significant differences in “proceeding to surgery” rates were observed between chemonucleolysis and control cohorts. Limitations include dated and heterogeneous studies, emphasizing the need for higher-quality trials. Further optimization through careful patient selection and advances in therapy implementation may further enhance outcomes. The observed benefits call for wider clinical exploration and adoption. No funding was received for this review.
Investigating the causal relationship between thyroid dysfunction diseases and osteoporosis: a two-sample Mendelian randomization analysis
Authors: Qi Weihui , Wang Dong , Hong Yihu , Yao Jun , Wang Huang , Zhu Li , Pan Hao
Published: June 2024

The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.
Cost-effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia
Authors: Adawiyah Rabiah Al , Bradshaw Catriona S. , Vodstrcil Lenka A. , Fairley Christopher K. , Zhang Lei , Ong Jason J.
Published: June 2024

The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin. However, the prevalence of macrolide resistance for M. genitalium has increased to more than 50% worldwide. In 2013, Australia introduced a resistance-guided therapy (RGT) strategy to manage M. genitalium infections. This study assesses the cost-effectiveness of the RGT approach compared to no RGT (i.e., without macrolide resistance profile test) in women, men who have sex with men (MSM), and men who have sex with women (MSW) in Australia. We constructed dynamic transmission models of M. genitalium infections in women, MSM, and MSW in Australia, each with a population of 100,000. These models compared the costs and quality-adjusted life-years (QALYs) gained between RGT and no RGT scenarios from a healthcare perspective over ten years. All costs are reported in 2022 Australian dollars (Australian $). In our model, RGT is cost saving in women and MSM, with the incremental net monetary benefit of $1.3 million and $17.9 million, respectively. In MSW, the RGT approach is not cost-effective, with an incremental cost-effectiveness ratio of -$106.96 per QALY gained. RGT is cost saving compared to no RGT for M. genitalium infections in women and MSM, supporting its adoption as the national management strategy for these two population groups.
Winter diet of bats in working forests of the southeastern U.S. Coastal Plain
Authors: Perea Santiago , Meinecke Colton D. , Larsen-Gray Angela L. , Greene Daniel U. , Villari Caterina , Gandhi Kamal J. K. , Castleberry Steven B.
Published: June 2024

Working forests comprise a large proportion of forested landscapes in the southeastern United States and are important to the conservation of bats, which rely on forests for roosting and foraging. While relationships between bat ecology and forest management are well studied during summer, winter bat ecology remains understudied. Hence, we aimed to identify the diet composition of overwintering bats, compare the composition of prey consumed by bat species, and determine the potential role of forest bats as pest controllers in working forest landscapes of the southeastern U.S. Coastal Plain. During January to March 2021–2022, we captured 264 bats of eight species. We used DNA metabarcoding to obtain diet composition from 126 individuals of seven bat species identifying 22 orders and 174 families of arthropod prey. Although Coleoptera, Diptera, and Lepidoptera were the most consumed orders, we found that bats had a generalist diet but with significant differences among some species. We also documented the consumption of multiple insect pests (e.g.,Rhyacionia frustrana)and disease vectors (e.g.,Culexspp). Our results provide important information regarding the winter diet of bats in the southeastern U.S. Coastal Plain and their potential role in controlling economically relevant pest species and disease vectors.
Use of Viscous medium to study anthelmintic drug action in Caenorhabditis elegans
Authors: Hellinga Jacqueline R. , Krücken Jürgen , Schulenburg Hinrich , von Samson-Himmelstjerna Georg
Published: June 2024

Caenorhabditis elegans is an appealing tool for experimental evolution and for working with antiparasitic drugs, from understanding the molecular mechanisms of drug action and resistance to uncover new drug targets. We present a new methodology for studying the impact of antiparasitic drugs in C. elegans. Viscous medium was initially designed for C. elegans maintenance during long-term evolution experiments. Viscous medium provides a less structured environment than the standard nematode growth media agar, yet the bacteria food source remains suspended. Further, the Viscous medium offers the worm population enough support to move freely, mate, and reproduce at a rate comparable to standard agar cultures. Here, the Viscous medium was adapted for use in antiparasitic research. We observed a similar sensitivity of C. elegans to anthelmintic drugs as in standard liquid media and statistical difference to the standard agar media through a larval development assay. Using Viscous medium in C. elegans studies will considerably improve antiparasitic resistance research, and this medium could be used in studies aimed at understanding long-term multigenerational drug activity.
Circulating tumor cells are a good predictor of tumor recurrence in clinical patients with gastric cancer
Authors: Li Wenxing , Zhang Xin , Yang Yanqi , Lin Jinhe , Zhou Kai , Sun Ruifang , Dang Chengxue , Diao Dongmei
Published: June 2024

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101–0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169–8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071–0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28–80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.
Representations of imaginary scenes and their properties in cortical alpha activity
Authors: Stecher Rico , Kaiser Daniel
Published: June 2024

Imagining natural scenes enables us to engage with a myriad of simulated environments. How do our brains generate such complex mental images? Recent research suggests that cortical alpha activity carries information about individual objects during visual imagery. However, it remains unclear if more complex imagined contents such as natural scenes are similarly represented in alpha activity. Here, we answer this question by decoding the contents of imagined scenes from rhythmic cortical activity patterns. In an EEG experiment, participants imagined natural scenes based on detailed written descriptions, which conveyed four complementary scene properties: openness, naturalness, clutter level and brightness. By conducting classification analyses on EEG power patterns across neural frequencies, we were able to decode both individual imagined scenes as well as their properties from the alpha band, showing that also the contents of complex visual images are represented in alpha rhythms. A cross-classification analysis between alpha power patterns during the imagery task and during a perception task, in which participants were presented images of the described scenes, showed that scene representations in the alpha band are partly shared between imagery and late stages of perception. This suggests that alpha activity mediates the top-down re-activation of scene-related visual contents during imagery.