bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting transonic buffet with incompressible low-frequency oscillations on aerofoils
Authors: Moise Pradeep , Zauner Markus , Sandham Neil D.
Published: February 2024

Self-sustained, low-frequency, coherent flow unsteadiness over rigid, stationary aerofoils in the transonic regime is referred to as transonic buffet. This study examines the role of shock waves in sustaining this transonic phenomenon and its relation to low-frequency oscillations (LFO) that occur in flow over aerofoils in the incompressible regime (Zaman et al., J. Fluid Mech., vol. 202, 1989, pp. 403–442). This is investigated by performing large-eddy simulations of the flow over a NACA0012 profile for a wide range of flow conditions under free-transition conditions. At low Reynolds numbers, zero incidence angle and sufficiently high free-stream Mach numbers,

$M$

, transonic buffet occurs with shock waves present in the flow. However, when

$M$

alone is lowered, self-sustained, periodic oscillations at a low frequency are observed even though shock waves are absent and the entire flow field remains subsonic at all times. At higher incidence angles, the oscillations are sustained at progressively lower

$M$

and are present even at

$M=0.3$

, where compressibility effects are low. A spectral proper orthogonal decomposition (SPOD) shows that the spatial structure of these oscillations is consistent for all cases. The SPOD modes are topologically similar, suggesting a connection between transonic buffet and LFO in the incompressible regime. Comparisons with other studies examining transonic buffet on various aerofoils, under forced-transition and fully turbulent conditions support this hypothesis. Future studies using tools of global linear stability analysis, especially at high free-stream Reynolds numbers are required to examine whether the underlying mechanisms of transonic buffet and incompressible LFO are the same.
Natural Teleology in John Locke’s Ethics
Authors: Zorzi Graedon
Published: February 2024

According to some of the past half-century’s most influential critics of liberalism, John Locke is the pivotal subverter of the pre-modern ethical tradition. Locke’s view of nature and of human nature, the story goes, divorced ethics from natural teleology and so set off an inevitable spiral downward into moral dissolution. This story about Locke remains influential even though the last fifty years of Locke scholarship have brought a cascade of studies treating Locke as operating within the tradition of Reformed natural law. These studies, in part because they embrace a distorted view of Locke’s conception of the person, have failed to address satisfactorily the crux of the story told by the critics of liberalism. This article corrects that distortion and demonstrates how natural teleology operates within Locke’s ethics. I show how Locke sought to identify the teleological ordering of human beings to the supreme good by developing a relational conception of the person, analysing the human being as embedded in and defined by a web of relationships including neighbour and God. The result is a Locke far more in continuity with pre-modern ethical approaches than has hitherto been realized, one who sought to preserve natural teleology for the modern world.
Introduction to Everyday Internationalism: Socialist–South Connections and Mass Culture during the Cold War
Authors: Bodie George
Published: February 2024

This Special Issue brings together scholars working in a variety of contexts to explore the concepts of solidarity and socialist internationalism as a mass phenomenon. While recent scholarship has begun to document linkages between the socialist and (post)colonial world during the Cold War, most of this work has eschewed a focus on the mass, social experience of internationalism, instead emphasizing the transformative role played by small groups of mobile elites. But if the direct experience of socialist internationalism was limited to a privileged few, how then was it experienced by the majority, for whom actual travel outside of their state was a distant possibility? This issue explores how socialist internationalism and its attendant practices of solidarity functioned within and between socialist societies. Where it does take border-transcending groups as its subject, it explores the socio-historical, everyday implications of this transnational story. For much of the Cold War, state and party-led practices of internationalism were a central component of everyday life, but little is known about these practices as they manifested on the ground. To shed light on this, this Special Issue explores how depictions of solidarity manifested in mass culture; how everyday practices emerged out of socialist internationalism and anti-imperialism; and how institutions that sought to bridge gaps between societies through solidarity emerged and then transformed or disappeared after 1989.
Herbage responses and animal performance of nitrogen-fertilized grass and grass-legume grazing systems
Authors: Pereira Neto Jose Diogenes , Dubeux Jose Carlos Batista , Ferreira dos Santos Mércia Virginia , da Silva Santos Erick Rodrigo , Bretas Igor Lima , Jaramillo David M. , Ruiz-Moreno Martin , Rodrigues da Cruz Priscila Junia , Dantas Queiroz Luana Mayara , Tembe Oduor Kenneth , Araujo Bernardini Marilia
Published: February 2024

The study evaluated forage and livestock performance in different grazing systems over two years. Treatments were three contrasting grazing systems: (I) N-fertilized bahiagrass (Paspalum notatum Flüggé) in the summer overseeded during the winter by N-fertilized ryegrass (Lolium multiflorum) and oat (Avena sativa L.) (Grass + N); (II) unfertilized bahiagrass during the summer overseeded with ryegrass + oat and a blend of clovers (Trifolium spp.) in the winter (Grass + Clover); (III) unfertilized bahiagrass and rhizoma peanut (RP; Arachis glabrata Benth.) mixture during summer, overseeded during winter by ryegrass + oat + clovers mixture (Grass + Clover + RP). Average daily gain (ADG), gain per area (GPA), and stocking rate (SR) in the winter did not differ across treatments and averaged 0.87 kg/d (P = 0.940), 303 kg/ha, and 2.72 AU/ha. In the summer, Grass + Clover + RP had greater ADG than Grass + N (0.34 vs. 0.17 kg/d, respectively). During the summer, the GPA of Grass + Clover + RP was superior to Grass + N (257 vs. 129 kg/ha, respectively), with no difference in SR among treatments at 3.19 AU/ha. Over the entire year, ADG and GPA tended to be greater for Grass + Clover + RP. Annual SR differed between treatments, where Grass + N was greater (3.37 AU/ha) than the other treatments, which averaged 2.76 AU/ha. Integration of legumes into pasture systems in the summer and winter contributes to developing a sustainable grazing system, reducing N fertilizer use by 85% while tending to increase livestock productivity even though SR was decreased by 18%.
A survey involving secondary students with dyslexia studying Latin or a modern foreign language
Authors: Burbank Dora
Published: February 2024

Research in the academic field of Latin and dyslexia is sparse, often outdated, and largely consists of teachers' informal observations, thus lacking empirical evidence. This mixed-methods study aims to address a gap in the literature, exploring the experiences of secondary students with dyslexia learning Latin, French, or Spanish while examining the relationships between dyslexia and examination results in those languages. After purposive sampling, semi-structured interviews with seven dyslexic students, aged 16 to 29, were conducted and 349 GCSE and IB grades, of which 51 were of dyslexic students, were collected from two secondary schools. Reflexive thematic analysis of the interviews revealed seven themes: accessibility, benefits, challenges and barriers, class size, methods and strategies, motivation, and strengths. The results of three chi-square tests showed no significant association for Latin or Spanish, but a significant association between dyslexia and examination results in French. Whereas positive learning experiences for students with dyslexia hinged on the appropriate teaching method and the perceived support rather than the language per se, higher exam achievements were also dependent on the level of orthographic transparency but not on the degree of orality of the language learnt. Future research in the field should explore the experiences and achievements of students at different educational stages and with different learning difficulties doing Latin.
Direct Detection of Ongoing Magnetic Reconnection at Mercury's High‐Latitude Magnetopause
Authors: Wang Rongsheng , Cheng Zihang , Slavin James A. , Lu Quanming , Raines Jim , Lu San , Guo Jin , Gonzalez Walter
Published: February 2024

An ongoing magnetic reconnection event was detected in the Mercury's high latitude magnetopause during a northward interplanetary magnetic field. The reconnection X‐line region was revealed in the Mercury's magnetopause based on the encountered flux ropes ejected away from this region both planetward and tailward. A series of magnetic flux ropes, known as flux transfer event shower were observed tailward of this X‐line region. These flux ropes were probably expanding and deflected as they were ejected away tailward from the X‐line region. Large‐amplitude variations in all three components of the magnetic field and a few small‐scale flux ropes were observed inside the X‐line region, which could be the seed of the flux rope shower at the magnetopause. The observations suggest that magnetic reconnection is highly dynamic and persistent in Mercury's magnetosphere.
Anthropogenic Influence on Tropospheric Reactive Bromine Since the Pre‐industrial: Implications for Arctic Ice‐Core Bromine Trends
Authors: Zhai Shuting , McConnell Joseph R. , Chellman Nathan , Legrand Michel , Opel Thomas , Meyer Hanno , Jaeglé Lyatt , Confer Kaitlyn , Fujita Koji , Wang Xuan , Alexander Becky
Published: February 2024

Tropospheric reactive bromine (Bry) influences the oxidation capacity of the atmosphere by acting as a sink for ozone and nitrogen oxides. Aerosol acidity plays a crucial role in Bry abundances through acid‐catalyzed debromination from sea‐salt‐aerosol, the largest global source. Bromine concentrations in a Russian Arctic ice‐core, Akademii Nauk, show a 3.5‐fold increase from pre‐industrial (PI) to the 1970s (peak acidity, PA), and decreased by half to 1999 (present day, PD). Ice‐core acidity mirrors this trend, showing robust correlation with bromine, especially after 1940 (r = 0.9). Model simulations considering anthropogenic emission changes alone show that atmospheric acidity is the main driver of Bry changes, consistent with the observed relationship between acidity and bromine. The influence of atmospheric acidity on Bry should be considered in interpretation of ice‐core bromine trends.
Machine Learning Emulation of Subgrid‐Scale Orographic Gravity Wave Drag in a General Circulation Model With Middle Atmosphere Extension
Authors: Lu Yixiong , Xu Xin , Wang Lin , Liu Yiming , Wu Tongwen , Jie Weihua , Sun Jian
Published: February 2024

Gravity wave parameterizations contribute to uncertainties in middle atmosphere modeling. To investigate the potential for using machine learning to represent atmospheric gravity waves and the impact of implementing such schemes in a general circulation model (GCM), we train a random forest (RF) emulator on outputs from an existing complex parameterization scheme for orographic gravity wave drag (GWD). The performance of the RF emulator is then evaluated with a focus on stratospheric climatology and variability in climate simulations from the middle atmosphere resolving Beijing Climate Center Atmospheric Circulation Model. In offline tests, the predicted orographic GWD by the RF agrees remarkably well with the target GWD throughout the troposphere and the middle atmosphere. The RF emulator can reproduce the observed climatology of zonal‐mean wind and air temperature in the GCM simulation, as well as its target scheme. Compared to the target orographic GWD parameterization scheme, the RF emulator can reproduce the breakdown of the polar vortex in the Southern Hemisphere stratosphere. This study demonstrates the feasibility of using machine learning to emulate parameterized orographic GWD for modeling the stratosphere with a GCM.
Night eating in timing, frequency, and food quality and risks of all-cause, cancer, and diabetes mortality: findings from national health and nutrition examination survey
Authors: Wang Peng , Tan Qilong , Zhao Yaxuan , Zhao Jingwen , Zhang Yuzhu , Shi Dan
Published: February 2024

Objective

To investigate the association of timing, frequency, and food quality of night eating with all-cause, cancer, and diabetes mortality.

Methods

This study included 41,744 participants from the US National Health and Nutrition Examination Survey (2002–2018). Night eating information was collected by 24-h dietary recall and the exposures were timing, frequency, and food quality of night eating. Food quality was assessed by latent class analysis. The outcomes were all-cause, cancer, and diabetes mortality, which were identified by the National Death Index and the International Classification of Diseases 10th Revision. Adjusted hazard ratios [aHR] with 95% confidence intervals [CI] were computed by Cox regression.

Results

During a median follow-up of 8.7 years, 6066 deaths were documented, including 1381 from cancer and 206 from diabetes. Compared with no night eating (eating before 22:00), the later timing of night eating was associated with higher risk of all-cause and diabetes mortality (each P-trend <0.05) rather than cancer mortality, with the highest risk of eating being 00:00–1:00 (aHR 1.38, 95% CI 1.02–1.88) and being 23:00–00:00 (aHR 2.31, 95% CI 1.21–4.40), respectively. However, the increased risks were not observed for 22:00-23:00. Likewise, one time or over frequency of night eating was associated with higher all-cause and diabetes mortality (each P < 0.05). That risks were further observed in high-dietary-energy-density group of night eating (all-cause mortality: aHR 1.21 [95% CI 1.06–1.38]; diabetes mortality: aHR 1.97 [95% CI 1.13–3.45]), but not in low-dietary-energy-density group. Finally, correlation analysis found positive associations of night eating with glycohemoglobin, fasting glucose, and OGTT.

Conclusions

Night eating was associated with increased all-cause, cancer and diabetes mortality; however, reduction of excess mortality risk was observed when eating before 23:00 or low-dietary-energy-density foods.
Fulvestrant and everolimus efficacy after CDK4/6 inhibitor: a prospective study with circulating tumor DNA analysis
Authors: Vasseur Antoine , Cabel Luc , Hego Caroline , Takka Wissam , Trabelsi Grati Olfa , Renouf Benjamin , Lerebours Florence , Loirat Delphine , Brain Etienne , Cottu Paul , Sablin Marie-Paule , Pierga Jean-Yves , Callens Céline , Renault Shufang , Bidard François-Clément
Published: February 2024

In a prospective study (NCT02866149), we assessed the efficacy of fulvestrant and everolimus in CDK4/6i pre-treated mBC patients and circulating tumor DNA (ctDNA) changes throughout therapy. Patients treated with fulvestrant and everolimus had their ctDNA assessed at baseline, after 3–5 weeks and at disease progression. Somatic mutations were identified in archived tumor tissues by targeted NGS and tracked in cell-free DNA by droplet digital PCR. ctDNA detection was then associated with clinicopathological characteristics and patients’ progression-free survival (PFS), overall survival (OS) and best overall response (BOR). In the 57 included patients, median PFS and OS were 6.8 (95%CI [5.03–11.5]) and 38.2 (95%CI [30.0-not reached]) months, respectively. In 47 response-evaluable patients, BOR was a partial response or stable disease in 15 (31.9%) and 11 (23.4%) patients, respectively. Among patients with trackable somatic mutation and available plasma sample, N = 33/47 (70.2%) and N = 19/36 (52.8%) had ctDNA detected at baseline and at 3 weeks, respectively. ctDNA detection at baseline and PIK3CA mutation had an adverse prognostic impact on PFS and OS in multivariate analysis. This prospective cohort study documents the efficacy of fulvestrant and everolimus in CDK4/6i-pretreated ER + /HER2- mBC and highlights the clinical validity of early ctDNA changes as pharmacodynamic biomarker.
Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice
Authors: Torres Irizarry Valeria C. , Feng Bing , Yang Xiaohua , Patel Nirali , Schaul Sarah , Ibrahimi Lucas , Ye Hui , Luo Pei , Carrillo-Sáenz Leslie , Lai Penghua , Kota Maya , Dixit Devin , Wang Chunmei , Lasek Amy W. , He Yanlin , Xu Pingwen
Published: February 2024

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HTDRN neurons from naïve female mice. Notably, this higher sensitivity was blunted by 17β-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERα and ERβ are expressed in 5-HTDRN neurons, whereas ERα agonist depolarizes and ERβ agonist hyperpolarizes 5-HTDRN neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HTDRN neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs’ inhibitory effects on ethanol-induced burst firing of 5-HTDRN neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERα- or ERβ-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERα/β to prevent alcohol-induced activation of 5-HTDRN neurons, which in return leads to higher binge alcohol drinking.
Nickel-catalyzed electrophiles-controlled enantioselective reductive arylative cyclization and enantiospecific reductive alkylative cyclization of 1,6-enynes
Authors: Liu Wenfeng , Xing Yunxin , Yan Denghong , Kong Wangqing , Shen Kun
Published: February 2024

Transition metal-catalyzed asymmetric cyclization of 1,6-enynes is a powerful tool for the construction of chiral nitrogen-containing heterocycles. Despite notable achievements, these transformations have been largely limited to the use of aryl or alkenyl metal reagents, and stereoselective or stereospecific alkylative cyclization of 1,6-enynes remains unexploited. Herein, we report Ni-catalyzed enantioselective reductive anti-arylative cyclization of 1,6-enynes with aryl iodides, providing enantioenriched six-membered carbo- and heterocycles in good yields with excellent enantioselectivities. Additionally, we have realized Ni-catalyzed enantiospecific reductive cis-alkylative cyclization of 1,6-enynes with alkyl bromides, furnishing chiral five-membered heterocycles with high regioselectivity and stereochemical fidelity. Mechanistic studies reveal that the arylative cyclization of 1,6-enynes is initiated by the oxidative addition of Ni(0) to aryl halides and the alkylative cyclization is triggered by the oxidative addition of Ni(0) to allylic acetates. The utility of this strategy is further demonstrated in the enantioselective synthesis of the antiepileptic drug Brivaracetam.
Impact of population aging on future temperature-related mortality at different global warming levels
Authors: Chen Kai , de Schrijver Evan , Sivaraj Sidharth , Sera Francesco , Scovronick Noah , Jiang Leiwen , Roye Dominic , Lavigne Eric , Kyselý Jan , Urban Aleš , Schneider Alexandra , Huber Veronika , Madureira Joana , Mistry Malcolm N. , Cvijanovic Ivana ,   MCC Collaborative Research Network, Armstrong Ben , Schneider Rochelle , Tobias Aurelio , Astrom Christofer , Guo Yuming , Honda Yasushi , Abrutzky Rosana , Tong Shilu , de Sousa Zanotti Stagliorio Coelho Micheline , Saldiva Paulo Hilario Nascimento , Correa Patricia Matus , Ortega Nicolás Valdés , Kan Haidong , Osorio Samuel , Orru Hans , Indermitte Ene , Jaakkola Jouni J. K. , Ryti Niilo , Pascal Mathilde , Katsouyanni Klea , Analitis Antonis , Mayvaneh Fatemeh , Entezari Alireza , Goodman Patrick , Zeka Ariana , Michelozzi Paola , de’Donato Francesca , Hashizume Masahiro , Alahmad Barrak , Diaz Magali Hurtado , De la Cruz Valencia César , Overcenco Ala , Houthuijs Danny , Ameling Caroline , Rao Shilpa , Carrasco-Escobar Gabriel , Seposo Xerxes , da Silva Susana Pereira , Holobaca Iulian Horia , Acquaotta Fiorella , Kim Ho , Lee Whanhee , Íñiguez Carmen , Forsberg Bertil , Ragettli Martina S. , Guo Yue-Liang Leon , Pan Shih-Chun , Li Shanshan , Colistro Valentina , Zanobetti Antonella , Schwartz Joel , Dang Tran Ngoc , Van Dung Do , Carlsen Hanne Krage , Cauchi John Paul , Achilleos Souzana , Raz Raanan , Gasparrini Antonio , Vicedo-Cabrera Ana M.
Published: February 2024

Older adults are generally amongst the most vulnerable to heat and cold. While temperature-related health impacts are projected to increase with global warming, the influence of population aging on these trends remains unclear. Here we show that at 1.5 °C, 2 °C, and 3 °C of global warming, heat-related mortality in 800 locations across 50 countries/areas will increase by 0.5%, 1.0%, and 2.5%, respectively; among which 1 in 5 to 1 in 4 heat-related deaths can be attributed to population aging. Despite a projected decrease in cold-related mortality due to progressive warming alone, population aging will mostly counteract this trend, leading to a net increase in cold-related mortality by 0.1%–0.4% at 1.5–3 °C global warming. Our findings indicate that population aging constitutes a crucial driver for future heat- and cold-related deaths, with increasing mortality burden for both heat and cold due to the aging population.
Volcano generated tsunami recorded in the near source
Authors: Ripepe M. , Lacanna G.
Published: February 2024

Volcano sector collapse and pyroclastic density currents are common phenomena on active volcanoes and potentially a fatal source of tsunami waves which constitute a serious hazard for local as well as distant coastal population. Several examples in recent history, warn us on the urgent need to improve our mitigation counter-actions when tsunamis have volcanic origin. However, instrumental record of tsunami generated by mass movement along a volcano flank are still rare and not well understood yet. Small tsunamis (≤1 m) induced by pyroclastic density currents associated to violent explosions of Stromboli volcano were recorded in near-source conditions (<1.6 km). We show how tsunami waveform remains unaltered regardless of the two orders of variability in the landslide volume and dynamics. This unprecedented record is also providing the lesson to develop unconventional warning strategies necessary when the tsunamigenic source is expected to be very close (<10 minutes) to densely populated coasts and with a limited time to issue an alert based on simulation of wave propagation and inundation.
The emergence of circadian timekeeping in the intestine
Authors: Parasram Kathyani , Zuccato Amy , Shin Minjeong , Willms Reegan , DeVeale Brian , Foley Edan , Karpowicz Phillip
Published: February 2024

The circadian clock is a molecular timekeeper, present from cyanobacteria to mammals, that coordinates internal physiology with the external environment. The clock has a 24-h period however development proceeds with its own timing, raising the question of how these interact. Using the intestine of Drosophila melanogaster as a model for organ development, we track how and when the circadian clock emerges in specific cell types. We find that the circadian clock begins abruptly in the adult intestine and gradually synchronizes to the environment after intestinal development is complete. This delayed start occurs because individual cells at earlier stages lack the complete circadian clock gene network. As the intestine develops, the circadian clock is first consolidated in intestinal stem cells with changes in Ecdysone and Hnf4 signalling influencing the transcriptional activity of Clk/cyc to drive the expression of tim, Pdp1, and vri. In the mature intestine, stem cell lineage commitment transiently disrupts clock activity in differentiating progeny, mirroring early developmental clock-less transitions. Our data show that clock function and differentiation are incompatible and provide a paradigm for studying circadian clocks in development and stem cell lineages.
Multi-night cortico-basal recordings reveal mechanisms of NREM slow-wave suppression and spontaneous awakenings in Parkinson’s disease
Authors: Anjum Md Fahim , Smyth Clay , Zuzuárregui Rafael , Dijk Derk Jan , Starr Philip A. , Denison Timothy , Little Simon
Published: February 2024

Sleep disturbance is a prevalent and disabling comorbidity in Parkinson’s disease (PD). We performed multi-night (n = 57) at-home intracranial recordings from electrocorticography and subcortical electrodes using sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography in four PD participants and one with cervical dystonia (clinical trial: NCT03582891). Cortico-basal activity in delta increased and in beta decreased during NREM (N2 + N3) versus wakefulness in PD. DBS caused further elevation in cortical delta and decrease in alpha and low-beta compared to DBS OFF state. Our primary outcome demonstrated an inverse interaction between subcortical beta and cortical slow-wave during NREM. Our secondary outcome revealed subcortical beta increases prior to spontaneous awakenings in PD. We classified NREM vs. wakefulness with high accuracy in both traditional (30 s: 92.6 ± 1.7%) and rapid (5 s: 88.3 ± 2.1%) data epochs of intracranial signals. Our findings elucidate sleep neurophysiology and impacts of DBS on sleep in PD informing adaptive DBS for sleep dysfunction.
Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies
Authors: Gupta Pragya , Goswami Sangam Giri , Kumari Geeta , Saravanakumar Vinodh , Bhargava Nupur , Rai Akhila Balakrishna , Singh Praveen , Bhoyar Rahul C. , Arvinden V. R. , Gunda Padma , Jain Suman , Narayana Vanya Kadla , Deolankar Sayali C. , Prasad T. S. Keshava , Natarajan Vivek T. , Scaria Vinod , Singh Shailja , Ramalingam Sivaprakash
Published: February 2024

Ex vivo cellular system that accurately replicates sickle cell disease and β-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and β-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells. Additionally, these cellular models recapitulate pathological conditions associated with both the diseases. Hydroxyurea and pomalidomide treatment enhanced fetal hemoglobin levels. Notably, we introduce a therapeutic strategy for the above diseases by recapitulating the HPFH3 genotype, which reactivates fetal hemoglobin levels and rescues the disease phenotypes, thus making these lines a valuable platform for studying and developing new therapeutic strategies. Altogether, we demonstrate our disease cellular systems are physiologically relevant and could prove to be indispensable tools for disease modeling, drug screenings and cell and gene therapy-based applications.
Global fungal-host interactome mapping identifies host targets of candidalysin
Authors: Zhang Tian-Yi , Chen Yao-Qi , Tan Jing-Cong , Zhou Jin-An , Chen Wan-Ning , Jiang Tong , Zha Jin-Yin , Zeng Xiang-Kang , Li Bo-Wen , Wei Lu-Qi , Zou Yun , Zhang Lu-Yao , Hong Yue-Mei , Wang Xiu-Li , Zhu Run-Ze , Xu Wan-Xing , Xi Jing , Wang Qin-Qin , Pan Lei , Zhang Jian , Luan Yang , Zhu Rui-Xin , Wang Hui , Chen Changbin , Liu Ning-Ning
Published: February 2024

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.
Deep learning infers clinically relevant protein levels and drug response in breast cancer from unannotated pathology images
Authors: Liu Hui , Xie Xiaodong , Wang Bin
Published: February 2024

The computational pathology has been demonstrated to effectively uncover tumor-related genomic alterations and transcriptomic patterns. Although proteomics has indeed shown great potential in the field of precision medicine, few studies have focused on the computational prediction of protein levels from pathology images. In this paper, we assume that deep learning-based pathological features imply the protein levels of tumor biomarkers that are indicative of prognosis and drug response. For this purpose, we propose wsi2rppa, a weakly supervised contrastive learning framework to infer the protein levels of tumor biomarkers from whole slide images (WSIs) in breast cancer. We first conducted contrastive learning-based pre-training on tessellated tiles to extract pathological features, which are then aggregated by attention pooling and adapted to downstream tasks. We conducted extensive evaluation experiments on the TCGA-BRCA cohort (1978 WSIs of 1093 patients with protein levels of 223 biomarkers) and the CPTAC-BRCA cohort (642 WSIs of 134 patients). The results showed that our method achieved state-of-the-art performance in tumor diagnostic tasks, and also performed well in predicting clinically relevant protein levels and drug response. To show the model interpretability, we spatially visualized the WSIs colored the tiles by their attention scores, and found that the regions with high scores were highly consistent with the tumor and necrotic regions annotated by a 10-year experienced pathologist. Moreover, spatial transcriptomic data further verified that the heatmap generated by attention scores agrees greatly with the spatial expression landscape of two typical tumor biomarker genes. In predicting the response to drug trastuzumab treatment, our method achieved a 0.79 AUC value which is much higher than the previous study reported 0.68. These findings showed the remarkable potential of computational pathology in the prediction of clinically relevant protein levels, drug response, and clinical outcomes.
Gait impairment-related axonal degeneration in Parkinson’s disease by neurite orientation dispersion and density imaging
Authors: Wei Xuan , Wang Shiya , Zhang Mingkai , Yan Ying , Wang Zheng , Wei Wei , Tuo Houzhen , Wang Zhenchang
Published: February 2024

Microstructural alterations in the brain networks of Parkinson’s disease (PD) patients are correlated with gait impairments. Evaluate microstructural alterations in the white matter (WM) fiber bundle tracts using neurite orientation dispersion and density imaging (NODDI) technique in PD versus healthy controls (HC). In this study, 24 PD patients and 29 HC were recruited. NODDI and high-resolution 3D structural images were acquired for each participant. The NODDI indicators, including the intracellular neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), were compared between the two groups. Diffusion-weighted (DW) images were preprocessed using MRtrix 3.0 software and the orientation distribution function to trace the main nerve fiber tracts in PD patients. Quantitative gait and clinical assessment scales were used to compare the medication “ON” and “OFF” states of PD patients. The NDI, ODI, and ISO values of the WM fiber bundles were significantly higher in PD patients compared to HC. Fiber bundles, including the anterior thalamic radiation, corticospinal tract, superior longitudinal fasciculus, forceps major, cingulum, and inferior longitudinal fasciculus, were found to be significantly affected in PD. The NDI changes of PD patients were well correlated with stride lengths in the “ON” state; ODI changes were correlated with the stride time in the “ON” and “OFF” states and ISO changes were correlated with the stride time and cadence in the “ON” state. In conclusion, combination of NODDI technique and gait parameters can help detect gait impairment in PD patients early and accurately.
ReptTraits: a comprehensive dataset of ecological traits in reptiles
Authors: Oskyrko Oleksandra , Mi Chunrong , Meiri Shai , Du Weiguo
Published: February 2024

Trait datasets are increasingly being used in studies investigating eco-evolutionary theory and global conservation initiatives. Reptiles are emerging as a key group for studying these questions because their traits are crucial for understanding the ability of animals to cope with environmental changes and their contributions to ecosystem processes. We collected data from earlier databases, and the primary literature to create an up-to-date dataset of reptilian traits, encompassing 40 traits from 12060 species of reptiles (Archelosauria: Crocodylia and Testudines, Rhynchocephalia, and Squamata: Amphisbaenia, Sauria, and Serpentes). The data were gathered from 1288 sources published between 1820 and 2023. The dataset includes morphological, physiological, behavioral, and life history traits, as well as information on the availability of genetic data, IUCN Red List assessments, and population trends.
Phytochemical variations antioxidant, and antibacterial activities among zebaria sumac (Rhus coriaria var. zebaria) populations in Iraq
Authors: Shahrivari Saba , Zeebaree Saeed Mizgeen Saeed , Alizadeh-Salteh Saeideh , Feizy Hadar S. , Morshedloo Mohammad Reza
Published: February 2024

Sumac (Rhus coriaria L.) is one of the medicinal plants of Anacardiaceae family and widely used as a spice in Iran and Arab countries. Rhus coriaria var. zebaria is a small tree or large shrub, wildly growing in Iraq and described as a new variety with special characteristics. These increase the importance of studying sumac in these areas. Here, the phytochemical variations and the antibacterial activity of 50 accessions of this variety from five different climatic conditions was evaluated in order to identify the best accession to use and the best area for its cultivation. This is the most comprehensive study on this plant. Essential oil compounds were identified using GC–MS method and according to the results, Z, E-2,13-octadecadien, caryophyllene oxide, 2,4-decadienal, E-caryophyllene and nonanoic acid were among the main compounds. Also, the variety is a rich source of minerals including K, Ca, Mg, Na, P, and N. Sumac fruit extract from Akre Xerds had the highest anthocyanin and the lowest amount was from Kavilca region. The radical scavenging effect of extract from Dostic area in the concentration of 400 µg/mL is closer to the effect of ascorbic acid. The largest inhibition was found in the sumac extracted oil of Xasto Zhere area against S. aureus in compared with penicillin and amoxicillin and enrofloxacin antibiotics.
Robot therapy aids mental health in patients with hematological malignancy during hematopoietic stem cell transplantation in a protective isolation unit
Authors: Yamada Akiko , Akahane Daigo , Takeuchi Shiho , Miyata Kaori , Sato Takako , Gotoh Akihiko
Published: February 2024

Patients with hematological malignancy experience physical and psychological pain, such as a sense of isolation and confinement due to intensive chemotherapy in a protective isolation unit (PIU). We examined whether the intervention of a robotic puppy, aibo (manufactured by Sony), could improve patients' mental health as an alternative therapy for pet therapy, which is not feasible in PIU. This study included 21 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (n = 16) or autologous HSCT (n = 5). The patients were randomly divided into the aibo and control groups. Psychological effects were regularly assessed by measuring the levels of salivary stress hormone chromogranin A (CgA), serum oxytocin, and serum cortisol and the quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores. The aibo group demonstrated a significant decrease in CgA level, while the control group showed the opposite trend. In addition, changes in serum oxytocin and cortisol levels indicated that aibo helped reduce stress. There was no significant difference in the QIDS-SR scores between the two groups; however, the psychomotor activity in the aibo group improved significantly. These findings suggest that aibo intervention during a stay in a PIU can improve the mental health of patients with hematological malignancies who have undergone HSCT.
Influence of inclined magnetic field and heat transfer on the peristaltic flow of Rabinowitsch fluid model in an inclined channel
Authors: Elmhedy Y. , Abd-Alla A. M. , Abo-Dahab S. M. , Alharbi F. M. , Abdelhafez M. A.
Published: February 2024

The recent study is focused on discussion of heat transfer and magnetic field results of peristaltic flow of Rabinowitsch fluid model in an Inclined Channel. In this piece of research, peristalsis’s fundamental problem with heat transfer in the presence of a magnetic field is checked. An incompressible Rabinowitsch fluid is present in an inclined channel, which is considered as the reference for this research. The solutions are devised with the assumptions of long wavelength and low Reynolds number approximations. The resulting equations are then solved exactly by implementing various command of MATHEMATICA subject to relevant boundary conditions. Results are discussed for various flow quantities like temperature, velocity, tangential stress, pressure gradient and rise, and friction force. Computational simulations are performed to determine the flow quantities. This investigation goes beyond mere calculations and examines particle motion to gain deeper insights into flow quantities. Furthermore, this investigates how magnetic field and heat transfer parameters influence these peristaltic flow phenomena. The outcomes of important parameters were plotted and scrutinized. There is amultitude of medical implementations derived from the current consideration, such as the depiction of the gastric juice motion in the small intestine when an endoscope is inserted through it.
Markovian noise modelling and parameter extraction framework for quantum devices
Authors: Brand Dean , Sinayskiy Ilya , Petruccione Francesco
Published: February 2024

In recent years, Noisy Intermediate Scale Quantum (NISQ) computers have been widely used as a test bed for quantum dynamics. This work provides a new hardware-agnostic framework for modelling the Markovian noise and dynamics of quantum systems in benchmark procedures used to evaluate device performance. As an accessible example, the application and performance of this framework is demonstrated on IBM Quantum computers. This framework serves to extract multiple calibration parameters simultaneously through a simplified process which is more reliable than previously studied calibration experiments and tomographic procedures. Additionally, this method allows for real-time calibration of several hardware parameters of a quantum computer within a comprehensive procedure, providing quantitative insight into the performance of each device to be accounted for in future quantum circuits. The framework proposed here has the additional benefit of highlighting the consistency among qubit pairs when extracting parameters, which leads to a less computationally expensive calibration process than evaluating the entire device at once.
SlumberNet: deep learning classification of sleep stages using residual neural networks
Authors: Jha Pawan K. , Valekunja Utham K. , Reddy Akhilesh B.
Published: February 2024

Sleep research is fundamental to understanding health and well-being, as proper sleep is essential for maintaining optimal physiological function. Here we present SlumberNet, a novel deep learning model based on residual network (ResNet) architecture, designed to classify sleep states in mice using electroencephalogram (EEG) and electromyogram (EMG) signals. Our model was trained and tested on data from mice undergoing baseline sleep, sleep deprivation, and recovery sleep, enabling it to handle a wide range of sleep conditions. Employing k-fold cross-validation and data augmentation techniques, SlumberNet achieved high levels of overall performance (accuracy = 97%; F1 score = 96%) in predicting sleep stages and showed robust performance even with a small and diverse training dataset. Comparison of SlumberNet's performance to manual sleep stage classification revealed a significant reduction in analysis time (~ 50 × faster), without sacrificing accuracy. Our study showcases the potential of deep learning to facilitate sleep research by providing a more efficient, accurate, and scalable method for sleep stage classification. Our work with SlumberNet further demonstrates the power of deep learning in mouse sleep research.
Spatial analysis of 10-year predicted risk and incident atherosclerotic cardiovascular disease: the CoLaus cohort
Authors: Jordan Guillaume , Ridder David , Joost Stephane , Vollenweider Peter , Preisig Martin , Marques-Vidal Pedro , Guessous Idris , Vaucher Julien
Published: February 2024

Whether cardiovascular risk scores geographically aggregate and inform on spatial development of atherosclerotic cardiovascular diseases (ASCVD) remains unknown. Our aim is to determine the spatial distribution of 10-year predicted cardiovascular risk and ASCVD, and to compare the overlap of the resulting spatial distributions. Using prospective data from the CoLaus|PsyCoLaus cohort study (2003–2021) we computed SCORE2 in participants free from ASCVD. Geographical distributions of predicted risk and events were determined using the Gi* Getis-Ord autocorrelation statistic. 6203 individuals (54% women, mean age 52.5 ± SD 10.7, ASCVD incidence rate 5.7%) were included. We identified clusters of high versus low predicted risk (4%, 6%, respectively) and ASCVD (5%, 5% respectively) at baseline. They persisted at follow-up. Overlap of SCORE2 and ASCVD clusters was marginal. Body-mass index and alcohol consumption explained most of the predicted risk distribution. For ASCVD, high clusters persisted or were reinforced after multivariate adjustment, while low incidence clusters were reduced, multifactorial determinants. Incidence rate of ASCVD was 2.5% higher (IC 95%, 1.4–3.7) in clusters of higher incidence of ASCVD. To develop up-to-date, geographically targeted prevention strategies, there is a need to study novel geographically risk factors affecting ASCVD and to update commonly used prediction models for a population approach.
First detection and genetic characterization of canine bufavirus in domestic dogs, Thailand
Authors: Charoenkul Kamonpan , Thaw Yu Nandi , Phyu Eaint Min , Jairak Waleemas , Nasamran Chanakarn , Chamsai Ekkapat , Chaiyawong Supassama , Amonsin Alongkorn
Published: February 2024

Canine bufavirus (CBuV) was reported in domestic dogs worldwide. We conducted a survey of canine bufavirus in domestic dogs in Thailand from September 2016 to October 2022. Rectal swab samples (n = 531) were collected from asymptomatic dogs and dogs with gastroenteritis signs. The samples were tested for CBuV using PCR with specific primers to the VP1/VP2 gene, and 9.42% (50/531) was CBuV positive. Our findings showed that CBuVs could be detected in both symptomatic and healthy dogs. The Thai CBuVs were found in dogs from different age groups, with a significant presence in those under 1 year (12.60%) and dogs aged 1–5 years (7.34%) (p < 0.05), suggesting a high prevalence of Thai CBuVs in dogs under 5 years of age. We performed complete genome sequencing (n = 15) and partial VP1/VP2 sequencing (n = 5) of Thai CBuVs. Genetic and phylogenetic analyses showed that whole genomes of Thai CBuVs were closely related to Chinese and Italian CBuVs, suggesting the possible origin of Thai CBuVs. The analysis of VP1 and VP2 genes in Thai CBuVs showed that 18 of them were placed in subgroup A, while only 2 belonged to subgroup B. This study is the first to report the detection and genetic characterization of CBuVs in domestic dogs in Thailand. Additionally, surveillance and genetic characterization of CBuVs in domestic animals should be further investigated on a larger scale to elucidate the dynamic, evolution, and distribution of CBuVs.
Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension
Authors: Al-Daghestani Hiba , Qaisar Rizwan , Al Kawas Sausan , Ghani Nurhafizah , Rani K. G. Aghila , Azeem Muhammad , Hasnan Hijaz Kamal , Kassim Nur Karyatee , Samsudin A. R.
Published: February 2024

Hindlimb suspension (HLS) mice exhibit osteoporosis of the hindlimb bones and may be an excellent model to test pharmacological interventions. We investigated the effects of inhibiting endoplasmic reticulum (ER) stress with 4-phenyl butyrate (4-PBA) on the morphology, physicochemical properties, and bone turnover markers of hindlimbs in HLS mice. We randomly divided 21 male C57BL/6J mice into three groups, ground-based controls, untreated HLS group and 4-PBA treated group (HLS+4PBA) (100mg/kg/day, intraperitoneal) for 21 days. We investigated histopathology, micro-CT imaging, Raman spectroscopic analysis, and gene expression. Untreated HLS mice exhibited reduced osteocyte density, multinucleated osteoclast-like cells, adipocyte infiltration, and reduced trabecular striations on micro-CT than the control group. Raman spectroscopy revealed higher levels of ER stress, hydroxyproline, non-collagenous proteins, phenylalanine, tyrosine, and CH2Wag as well as a reduction in proteoglycans and adenine. Furthermore, bone alkaline phosphatase and osteocalcin were downregulated, while Cathepsin K, TRAP, and sclerostin were upregulated. Treatment with 4-PBA partially restored normal bone histology, increased collagen crosslinking, and mineralization, promoted anti-inflammatory markers, and downregulated bone resorption markers. Our findings suggest that mitigating ER stress with 4-PBA could be a therapeutic intervention to offset osteoporosis in conditions mimicking hindlimb suspension.