bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Th17 T cells at treatment onset predict autoimmune toxicity of PI3Kδ inhibitors
Authors: Gadi Deepti , Martindale Stephen P. , Chiu Pui Yan , Khalsa Jasneet , Chen Pei-Hsuan , Fernandes Stacey M. , Wang Zixu , Tyekucheva Svitlana , Machado John-Hanson , Fisher David C. , Armand Philippe , Davids Matthew S. , Rodig Scott , Sherry Barbara , Brown Jennifer R.
Published: February 2023

PI3Kδ inhibitors are approved for the therapy of B cell malignancies, but their clinical use has been limited by unpredictable autoimmune toxicity, despite promising efficacy and evidence that toxicity is associated with improved clinical outcomes. Prior phenotypic evaluation by CyTOF has identified increases in activated CD8 T cells with activation of Th17 T cells, as well as decreases in Tregs, particularly in patients with toxicity. Here we sought to further understand the effects of idelalisib and duvelisib in vitro, and demonstrate that both idelalisib and duvelisib can inhibit T cell proliferation as well as Th1 and Treg differentiation in vitro, while promoting Th2 and Th17 differentiation. We further demonstrate directly using intracellular flow cytometry that autoimmune toxicity in patients is associated with higher absolute numbers of CD4 and CD8 T cells with Th17 differentiation in peripheral blood prior to therapy, and that gastrointestinal tissues from patients with active autoimmune complications of PI3Kδ inhibitors show infiltration with Th17+ T cells. These same tissues show depletion of Tregs as compared to CLL patients without toxicity, suggesting that loss of Tregs may be permissive for Th17 activation to lead to autoimmune toxicity. Clinical trials to restore this balance are warranted.
Non-canonical functions of spliceosome components in cancer progression
Authors: Ivanova Olga M. , Anufrieva Ksenia S. , Kazakova Anastasia N. , Malyants Irina K. , Shnaider Polina V. , Lukina Maria M. , Shender Victoria O.
Published: February 2023

Dysregulation of pre-mRNA splicing is a common hallmark of cancer cells and it is associated with altered expression, localization, and mutations of the components of the splicing machinery. In the last few years, it has been elucidated that spliceosome components can also influence cellular processes in a splicing-independent manner. Here, we analyze open source data to understand the effect of the knockdown of splicing factors in human cells on the expression and splicing of genes relevant to cell proliferation, migration, cell cycle regulation, DNA repair, and cell death. We supplement this information with a comprehensive literature review of non-canonical functions of splicing factors linked to cancer progression. We also specifically discuss the involvement of splicing factors in intercellular communication and known autoregulatory mechanisms in restoring their levels in cells. Finally, we discuss strategies to target components of the spliceosome machinery that are promising for anticancer therapy. Altogether, this review greatly expands understanding of the role of spliceosome proteins in cancer progression.
3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces cell death through ferroptosis and acts as a trigger of apoptosis in kidney cells
Authors: Park Jung Sun , Kim Dong-Hyun , Choi Hoon-In , Kim Chang Seong , Bae Eun Hui , Ma Seong Kwon , Kim Soo Wan
Published: February 2023

Ferroptosis is a cell death mechanism characterized by intracellular iron accumulation and lipid peroxidation. Effects of uremic toxins on ferroptosis in the kidney are not well understood. We investigated whether protein-bound uremic toxins induce ferroptosis, resulting in cell death, using the bilateral ureteral obstruction (BUO) mouse model and kidney cells. In BUO mice, we observed elevated lipid peroxidation, increased iron concentration, and decreased glutathione peroxidase 4 (GPX4) expression. Levels of transferrin receptor 1 and system Xc-, which are involved in iron transport and storage, were also elevated, while those of ferritin heavy and light chains (FHC and FLC) were reduced. Treatment of HK-2 and NRK49F kidney cells with CMPF decreased GSH levels and the expression of GPX4, FHC, and FLC, and increased levels of ROS, lipid peroxidation, and intracellular iron concentration. CMPF-induced and erastin-induced decreases in GPX4 levels and increases in Bax and cytochrome C levels were counteracted by ferrostatin-1 pretreatment. However, GPX4 mRNA levels, protein abundance, or promoter activity were not restored by Z-VAD-FMK, a multi-caspase inhibitor. These results suggest that ferroptosis induced by CMPF treatment induces apoptosis, and inhibition of ferroptosis reduces apoptosis, suggesting that ferroptosis plays a role in triggering cell death by apoptosis.
Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy
Authors: Trefny Marcel P. , Kirchhammer Nicole , Auf der Maur Priska , Natoli Marina , Schmid Dominic , Germann Markus , Fernandez Rodriguez Laura , Herzig Petra , Lötscher Jonas , Akrami Maryam , Stinchcombe Jane C. , Stanczak Michal A. , Zingg Andreas , Buchi Melanie , Roux Julien , Marone Romina , Don Leyla , Lardinois Didier , Wiese Mark , Jeker Lukas T. , Bentires-Alj Mohamed , Rossy Jérémie , Thommen Daniela S. , Griffiths Gillian M. , Läubli Heinz , Hess Christoph , Zippelius Alfred
Published: February 2023

Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. We here report on a human antigen-specific ex vivo model to explore new therapeutic options for T cell immunotherapies. T cells generated with this model resemble tumor-infiltrating exhausted T cells on a phenotypic and transcriptional level. Using a targeted pooled CRISPR-Cas9 screen and individual gene knockout validation experiments, we uncover sorting nexin-9 (SNX9) as a mediator of T cell exhaustion. Upon TCR/CD28 stimulation, deletion of SNX9 in CD8 T cells decreases PLCγ1, Ca2+, and NFATc2-mediated T cell signaling and reduces expression of NR4A1/3 and TOX. SNX9 knockout enhances memory differentiation and IFNγ secretion of adoptively transferred T cells and results in improved anti-tumor efficacy of human chimeric antigen receptor T cells in vivo. Our findings highlight that targeting SNX9 is a strategy to prevent T cell exhaustion and enhance anti-tumor immunity.
Multi-area recordings and optogenetics in the awake, behaving marmoset
Authors: Jendritza Patrick , Klein Frederike J. , Fries Pascal
Published: February 2023

The common marmoset has emerged as a key model in neuroscience. Marmosets are small in size, show great potential for genetic modification and exhibit complex behaviors. Thus, it is necessary to develop technology that enables monitoring and manipulation of the underlying neural circuits. Here, we describe a novel approach to record and optogenetically manipulate neural activity in awake, behaving marmosets. Our design utilizes a light-weight, 3D printed titanium chamber that can house several high-density silicon probes for semi-chronic recordings, while enabling simultaneous optogenetic stimulation. We demonstrate the application of our method in male marmosets by recording multi- and single-unit data from areas V1 and V6 with 192 channels simultaneously, and show that optogenetic activation of excitatory neurons in area V6 can influence behavior in a detection task. This method may enable future studies to investigate the neural basis of perception and behavior in the marmoset.
Effects of exercise countermeasures on multisystem function in long duration spaceflight astronauts
Authors: Scott Jessica M. , Feiveson Alan H. , English Kirk L. , Spector Elisabeth R. , Sibonga Jean D. , Dillon E. Lichar , Ploutz-Snyder Lori , Everett Meghan E.
Published: February 2023

Exercise training is a key countermeasure used to offset spaceflight-induced multisystem deconditioning. Here, we evaluated the effects of exercise countermeasures on multisystem function in a large cohort (N = 46) of astronauts on long-duration spaceflight missions. We found that during 178 ± 48 d of spaceflight, ~600 min/wk of aerobic and resistance exercise did not fully protect against multisystem deconditioning. However, substantial inter-individual heterogeneity in multisystem response was apparent with changes from pre to postflight ranging from −30% to +5%. We estimated that up to 17% of astronauts would experience performance-limiting deconditioning if current exercise countermeasures were used on future spaceflight missions. These findings support the need for refinement of current countermeasures, adjunct interventions, or enhanced requirements for preflight physiologic and functional capacity for the protection of astronaut health and performance during exploration missions to the moon and beyond.
IFNγ binding to extracellular matrix prevents fatal systemic toxicity
Authors: Kemna Josephine , Gout Evelyne , Daniau Leon , Lao Jessica , Weißert Kristoffer , Ammann Sandra , Kühn Ralf , Richter Matthias , Molenda Christine , Sporbert Anje , Zocholl Dario , Klopfleisch Robert , Schütz Anja , Lortat-Jacob Hugues , Aichele Peter , Kammertoens Thomas , Blankenstein Thomas
Published: February 2023

Interferon-γ (IFNγ) is an important mediator of cellular immune responses, but high systemic levels of this cytokine are associated with immunopathology. IFNγ binds to its receptor (IFNγR) and to extracellular matrix (ECM) via four positively charged C-terminal amino acids (KRKR), the ECM-binding domain (EBD). Across evolution, IFNγ is not well conserved, but the EBD is highly conserved, suggesting a critical function. Here, we show that IFNγ lacking the EBD (IFNγΔKRKR) does not bind to ECM but still binds to the IFNγR and retains bioactivity. Overexpression of IFNγΔKRKR in tumors reduced local ECM binding, increased systemic levels and induced sickness behavior, weight loss and toxicity. To analyze the function of the EBD during infection, we generated IFNγΔKRKR mice lacking the EBD by using CRISPR–Cas9. Infection with lymphocytic choriomeningitis virus resulted in higher systemic IFNγΔKRKR levels, enhanced sickness behavior, weight loss and fatal toxicity. We conclude that local retention of IFNγ is a pivotal mechanism to protect the organism from systemic toxicity during prolonged immune stimulation.
Understanding the role of natural and anthropogenic forcings in structuring the periphytic algal assemblages in a regulated river ecosystem
Authors: Sofi Mohd Sharjeel , Hamid Aadil , Bhat Sami Ullah , Rashid Irfan , Kuniyal Jagdish Chandra
Published: February 2023

Periphytic algal assemblages in the River Sindh of Kashmir Himalaya were studied in relation to environmental factors and anthropogenic alterations like flow regulation for Run-of-River hydropower plants to understand their ecology in a regulated river ecosystem. Sites were sampled from unregulated, regulated, and downstream reaches along the river on a seasonal basis from the year 2017 to 2019. A total of 48 species were identified, spread over 31 genera. Non-metric multidimensional analysis showed clear distinction in periphytic algal assemblage samples based on sites and potentially some more minor distinction based on seasons rendering the sites into two distinct groups (G1 and G2). The ADONIS test showed that the groups (G1 and G2 sites) do not significantly differ in terms of how communities differ from one another, but there is a difference in species compositions based on seasons. However, the betadisper test indicated that groups (G1 and G2 sites) and seasons present homogeneity among group dispersions (compositions vary similarly) while having significantly different compositions. Geo-physical factors (discharge and altitude) accounted for most variations, while the scraper community played a minor role. This study provides scientific insights related to the ecology of a regulated Himalayan river and may provide information relevant to managing the River Sindh sustainably.
Combining accelerometers and direct visual observations to detect sickness and pain in cows of different ages submitted to systemic inflammation
Authors: Ledoux Dorothée , Veissier Isabelle , Meunier Bruno , Gelin Valérie , Richard Christophe , Kiefer Hélène , Jammes Hélène , Foucras Gilles , de Boyer des Roches Alice
Published: February 2023

Cattle suffering from inflammatory infection display sickness and pain-related behaviours. As these behaviours may be transient and last only a few hours, one may miss them. The aim of this study was to assess the benefit of combining continuous monitoring of cow behaviour via collar-attached accelerometers with direct visual observations to detect sickness and pain-related behavioural responses after a systemic inflammatory challenge (intravenous lipopolysaccharide injection) in cows of two different ages, proven by clinical, physiological and blood parameters. Twelve cloned Holstein cows (six ‘old’ cows aged 10–15 years old and six ‘young’ cows aged 6 years old) were challenged and either directly observed at five time-points from just before the lipopolysaccharide injection up to 24 h post-injection (hpi) or continuously monitored using collar-attached accelerometers in either control or challenge situations. Direct observations identified specific sickness and pain behaviours (apathy, changes in facial expression and body posture, reduced motivation to feed) expressed partially at 3 hpi and fully at 6 hpi. These signs of sickness and pain behaviours then faded, and quicker for the young cows. Accelerometers detected changes in basic activities (low ingesting, low ruminating, high inactivity) and position (high time standing up) earlier and over a longer period of time than direct observations. The combination of sensors and direct observations improved the detection of behavioural signs of sickness and pain earlier on and over the whole study period, even when direct signs were weak especially in young cows. This system could provide great benefit for better earlier animal care.
Objective analysis of facial bone fracture CT images using curvature measurement in a surface mesh model
Authors: Kim Jeenam , Seo Chaneol , Yoo Jung Hwan , Choi Seung Hoon , Ko Kwang Yeon , Choi Hyung Jin , Lee Ki Hyun , Choi Hyungon , Shin Donghyeok , Kim HyungSeok , Lee Myung Chul
Published: February 2023

The human facial skeleton consists of multiple segments and causes difficulty during analytic processes. We developed image analysis software to quantify the amount of injury and validate the smooth curvature of the surface after facial bone reduction surgery. Three-dimensional computed tomography images of facial bone were obtained from 40 patients who had undergone open reduction surgery to treat unilateral zygomaticomaxillary fractures. Analytic software was developed based on the discrete curvature of a triangular mesh model. The discrete curvature values were compared before and after surgery using two regions of interest. For the inferior orbital rim, the weighted average of curvature changed from 0.543 ± 0.034 to 0.458 ± 0.042. For the anterior maxilla, the weighted average of curvature changed from 0.596 ± 0.02 to 0.481 ± 0.031, showing a significant decrement (P < 0.05). The curvature was further compared with the unaffected side using the Bray–Curtis similarity index (BCSI). The BCSI of the inferior orbital rim changed from 0.802 ± 0.041 to 0.904 ± 0.015, and that for the anterior maxilla changed from 0.797 ± 0.029 to 0.84 ± 0.025, demonstrating increased similarity (P < 0.05). In computational biology, adequate analytic software is crucial. The newly developed software demonstrated significant differentiation between pre- and postoperative curvature values. Modification of formulas and software will lead to further advancements.
Genome-wide transcriptional response of Escherichia coli O157:H7 to light-emitting diodes with various wavelengths
Authors: Khan Shehzad Abid , Kim Min-Jeong , Yuk Hyun-Gyun
Published: February 2023

We investigated the physiological and transcriptomic response of Escherichia coli at the early stationary phase to light-emitting diodes with different wavelengths. The growth and metabolic changes of E. coli O157:H7 were examined under the influence of 465, 520, and 625 nm illuminated light. Under 465 nm illumination, the growth of E. coli O157:H7 was significantly retarded compared to 520 nm and 625 nm illumination and non-illuminated control. Metabolic changes were examined under these illumination and non-illuminated conditions based on transcriptomic reads. Transcriptomic response under 520 nm and 625 nm remained almost similar to control except few up-and down-regulated genes. Carbohydrates metabolic transcriptomic reads were greatly down-regulated under 465 nm illumination compared to 520 nm and 625 nm illumination and non-illuminated control showing depletion of glucose as a sole energy source during the exponential phase. Fatty acid degradation such as fad regulon-related genes was up-regulated in cells under 465 nm illumination revealing the shifting of cells to use fatty acid as a new carbon energy source during the early stationary phase. Exposure of E. coli O157:H7 cells to 465 nm illuminated light down-regulated virulence factor genes such as hlyA, hlyB, hlyC, stx1A, stx2B, paa, and bdm. Under the stress of 465 nm illumination, expression of stress and flagellar motility-related genes were up-regulated causing consumption of energy and reduction in cell growth. Also, oxidative phosphorylated transcriptomic reads were up-regulated under 465 nm illumination probably due to the production of ROS that might involve in the reduction of cell growth during the early stationary phase. These results indicate that pathogenic E. coli O157:H7 respond differentially to a different wavelength of the light-emitting diodes used in this study.
Dynamical behaviors, circuit design, and synchronization of a novel symmetric chaotic system with coexisting attractors
Authors: Qiu Haitao , Xu Xuemei , Jiang Zhaohui , Sun Kehui , Cao Can
Published: February 2023

In this paper, we introduce a novel three-dimension chaotic system with strange characteristic by applying construction of a 3D chaotic circuit method. Multiple equilibria and abundant coexisting attractors exist in this system. A mathematical model is developed and detailed stability analyses for equilibrium points are executed with obtaining significant results of the period-doubling bifurcation patterns confirmed by phase plane plots and Lyapunov exponent spectra. By varying the initial value and unique controlled parameter, the double-scroll chaotic attractor is broken up into a pair of symmetric singular attractors. Then, the local basins of attraction are investigated concerning the initial condition. Next, the circuit synthesis results generated by Multisim simulation tool validate the self-excitation characteristics of this system. Finally, the feedback control technique is used to study difference synchronization of this system. Main conclusions prove the validity and reliability of difference synchronization.
Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration
Authors: Park Chulo , Lee Jin-Woo , Kim Kiheon , Seen Dong-Seung , Jeong Jae-Yeon , Huh Won-Ki
Published: February 2023

C-X-C chemokine receptor 4 (CXCR4) is widely overexpressed in various types of cancer and is involved in several cancer phenotypes including tumor growth, survival, and metastasis. The roles of histamine and histamine receptor H1 (HRH1) in cancer pathogenesis remain controversial. Here, we show that HRH1 is widely expressed in various cancer cell lines and cancer tissues and that coexpression of CXCR4 and HRH1 is associated with poor prognosis in breast cancer. Using bimolecular fluorescence complementation and bioluminescence resonance energy transfer donor saturation assays, we demonstrate that CXCR4 and HRH1 can assemble into a heteromeric complex. Simultaneous activation of CXCR4 and HRH1 synergistically increases calcium flux in MDA-MB-231 cells that endogenously express CXCR4 and HRH1 but not in cells deficient in CXCR4 or HRH1. Costimulation of CXCR4 and HRH1 also significantly enhances CXCL12-induced MDA-MB-231 cell migration, while histamine alone does not induce cell migration. Synergistic effects on calcium flux and cell migration are inhibited by the Gαi inhibitor pertussis toxin and the Gαq inhibitor YM254890, suggesting that the Gαi and Gαq pathways are involved in the synergy. Enhanced calcium signaling and cell migration are also observed in NCI-H23 and HeLa cells, which coexpress CXCR4 and HRH1. Taken together, our findings demonstrate an interplay between CXCR4 and HRH1, and suggest the possibility of the CXCR4-HRH1 heteromer as a potential therapeutic target for anticancer therapy.
Experiencing sweet taste is associated with an increase in prosocial behavior
Authors: Schaefer Michael , Kühnel Anja , Schweitzer Felix , Rumpel Franziska , Gärtner Matti
Published: February 2023

Taste may be the first sense that emerged in evolution. Taste is also a very important sense since it signals potential beneficial or dangerous effects of foods. Given this fundamental role of taste in our lives, it is not surprising that taste also affects our psychological perception and thinking. For example, previous research demonstrated remarkable psychological effects of sweet taste experiences, suggesting that sweetness may be a source domain for prosocial functioning. Recent research reports that briefly experiencing sweet taste made participants more helpful in their intentions and behavior. The current study aims to test this hypothesis and to examine the neural underpinnings of this effect by using an fMRI approach. Participants were asked to taste sweet, salty, and neutral taste while lying in the fMRI scanner. Subsequently their prosocial behavior was tested by playing the dictator game, a measure of prosocial behavior. Results showed that sweet taste was associated with an increase in prosocial behavior compared with previously experiencing salty taste but did not affect control stimuli ratings. FMRI results revealed a modulation of the dorsal anterior cingulate cortex associated with this sweetness effect. This brain area is known to play a central role for monitoring conflicts and decisions and has been directly linked to selfish and prosocial economic decisions. The results demonstrate that sweet taste has complex psychological effects including positive and socially desirable outcomes. We discuss the results with other studies on psychological sweetness effects and suggest possible implications of these findings.
Longitudinal profiles of the fecal metabolome during the first 2 years of life
Authors: Holzhausen Elizabeth A. , Shen Natalie , Chalifour Bridget , Tran ViLinh , Li Zhenjiang , Sarnat Jeremy A. , Chang Howard H. , Jones Dean P. , Goran Michael I. , Liang Donghai , Alderete Tanya L.
Published: February 2023

During the first 2 years of life, the infant gut microbiome is rapidly developing, and gut bacteria may impact host health through the production of metabolites that can have systemic effects. Thus, the fecal metabolome represents a functional readout of gut bacteria. Despite the important role that fecal metabolites may play in infant health, the development of the infant fecal metabolome has not yet been thoroughly characterized using frequent, repeated sampling during the first 2 years of life. Here, we described the development of the fecal metabolome in a cohort of 101 Latino infants with data collected at 1-, 6-, 12-, 18-, and 24-months of age. We showed that the fecal metabolome is highly conserved across time and highly personalized, with metabolic profiles being largely driven by intra-individual variability. Finally, we also identified several novel metabolites and metabolic pathways that changed significantly with infant age, such as valerobetaine and amino acid metabolism, among others.
Enhanced bacterial clearance in early secondary sepsis in a porcine intensive care model
Authors: Wilske Frida , Skorup Paul , Hanslin Katja , Janols Helena , Larsson Anders , Lipcsey Miklós , Sjölin Jan
Published: February 2023

Early secondary sepsis (ESS), occurring after recent inflammatory activation is associated with a reduced inflammatory response. If this attenuation also is associated with decreased bacterial killing, the need for antibiotic efficacy might be greater than in primary sepsis (PS). This prospective, randomised interventional study compares bacterial killing in ESS and PS in a large animal intensive care sepsis model. 38 pigs were intravenously administered live Escherichia coli for 3 h. Before baseline ESS was pre-exposed to endotoxin 24 h, whereas PS was not. Bacterial growth was measured in organs immediately post-mortem, repeatedly during 6 h in blood in vivo and for blood intrinsic bactericidal capacity ex vivo. Splenic growth was lower in ESS animals, than in PS animals (3.31 ± 0.12, vs. 3.84 ± 0.14 log10 CFU/mL, mean ± SEM) (p < 0.01) with a similar trend in hepatic growth (p = NS). Blood bacterial count at 2 h correlated with splenic bacterial count in ESS (ESS: r = 0.71, p < 0.001) and to blood killing capacity in PS (PS: r = 0.69, p < 0.001). Attenuated inflammation in ESS is associated with enhanced antibacterial capacities in the spleen. In ESS blood bacterial count is related to splenic killing and in PS to blood bactericidal capacity. The results suggest no increased need for synergistic antibiotic combinations in ESS.
Maternal immune activation affects socio-communicative behavior in adult rats
Authors: Gzieło Kinga , Piotrowska Diana , Litwa Ewa , Popik Piotr , Nikiforuk Agnieszka
Published: February 2023

A wide body of evidence suggests a relationship between maternal immune activation (MIA) and neurodevelopmental disorders such as autism spectrum disorder (ASD). Since social and communicative deficits are included in the first diagnostic criterion of ASD, we aimed to characterize socio-communicative behaviors in the MIA model based on prenatal exposure to poly(I:C). Our previous studies demonstrated impaired socio-communicative functioning in poly(I:C)-exposed adolescent rats. Therefore, the current study sought to clarify whether these changes would persist beyond adolescence. For this purpose, we analyzed behavior during the social interaction test and recorded ultrasonic vocalizations (USVs) accompanying interactions between adult poly(I:C) rats. The results demonstrated that the altered pattern of social behavior in poly(I:C) males was accompanied by the changes in acoustic parameters of emitted USVs. Poly(I:C) males also demonstrated an impaired olfactory preference for social stimuli. While poly(I:C) females did not differ from controls in socio-positive behaviors, they displayed aggression during the social encounter and were more reactive to somatosensory stimulation. Furthermore, the locomotor pattern of poly(I:C) animals were characterized by repetitive behaviors. Finally, poly(I:C) reduced parvalbumin and GAD67 expression in the cerebellum. The results showed that prenatal poly(I:C) exposure altered the pattern of socio-communicative behaviors of adult rats in a sex-specific manner.
Large-scale geological structures of the Egyptian Nubian Shield
Authors: Hamimi Zakaria , Eldosouky Ahmed M. , Hagag Wael , Kamh Samir Z.
Published: February 2023

Integration of potential field- and structural data make it possible to trace surface and subsurface large-scale geological structures of the Egyptian Nubian Shield (ENS). Obtained results indicate that the Northern Eastern Desert (NED) of the ENS is dominated by relatively younger (c. 580 Ma) E–W and NE–SW trending extensional structures that were controlled by the evolution and retreat of the Cadomian Arc. Density of such extensional structures increases with depth as displayed by the potential data. The prevailing structural trends in the Central Eastern Desert (CED) are NW–SE and WNW–ESE. Both trends are highly prompted by the timing of deformation upon the Najd Fault System, and are themselves dissected by a relatively younger NE–SW shearing trend. Lineament density in the CED is subordinate for both subsurface and near surface structures. The South Eastern Desert exhibits compressional and extrusion-related structures of two main prominent trends; WNW-to-NW (to the western part) and the N-, NNE- to NE (to the eastern part). The previously mentioned Neoproterozoic trends are remarkably influenced by the Oligocene–Miocene Red Sea-Gulf of Suez rift related fractures in the vicinity of the rift shoulder. The remarkable change in trends and densities of structural trends, especially in the NED, is interpreted in terms of concealing of the older structures by the younger extensional structures which in turns reflect an N-ward progressive deformation in the entire ENS. Gravity data are more appropriate in delineating the structural trends compared to the magnetic data which are largely affected by lithological variations and/or alteration zones and magnetic mineralogy.
Social isolation in patients with chronic limb-threatening ischemia: a cross-sectional study
Authors: Takahara Mitsuyoshi , Iida Osamu , Ohura Norihiko , Soga Yoshimitsu , Yamaoka Terutoshi , Azuma Nobuyoshi
Published: February 2023

Assistance by family members or friends plays important roles in the course of treating patients with chronic limb-threatening ischemia (CLTI), both during hospitalization and after discharge. The aim of this study was to reveal the prevalence of social isolation and to explore relevant clinical backgrounds in patients with CLTI presenting with tissue loss and requiring revascularization. We analyzed 413 patients registered in a multicenter study in whom revascularization were scheduled for CLTI with tissue loss. Social isolation was analyzed by assessing the residence status of the patients and the involvement of a trusted family member or friend in their daily lives and during hospitalization. Patients living alone accounted for 24.5% (95% confidence interval [CI] 20.1–28.8%) of the study population. Patients receiving welfare were more likely to live alone (P < 0.001). For patients living alone, 21.8% (95% CI 12.8–30.8%) met a trusted family member or friend in their daily lives less than once per year. Younger age and receiving welfare were independently associated with lower frequency of meeting the trusted person in their daily lives (both P < 0.05). The adjusted odds ratio of age and receiving welfare was 0.44 (95% CI 0.29–0.67) per 10-year increase and 3.47 (95% CI 1.43–8.44), respectively. During hospitalization, 9.9% (95% CI 6.8–13.0%) of the patients had no hospital visits by a trusted family member or friend on three key occasions: the patient’s first hospital visit, the preoperative explanation regarding the planned operation, and the day of the operation. Younger age and receiving welfare were independently associated with lower frequency of hospital visits by a family member or friend (both P < 0.05). The adjusted odds ratio of age and receiving welfare for no visit versus ≥ 1 visit was 0.51 (0.36–0.74) per 10-year increase and 5.29 (2.46–11.4), respectively. In conclusion, social isolation is common among patients with CLTI, especially younger patients and those on welfare. Practical countermeasures against social isolation are warranted in the management of CLTI.
Molecular characterization and antimicrobial susceptibility profiles of Thai Mycoplasma synoviae isolates
Authors: Limpavithayakul Kriengwich , Sasipreeyajan Jiroj , Pakpinyo Somsak
Published: February 2023

Mycoplasma synoviae(MS) infection is mainly controlled by pathogen-free flocks’ maintenance, medication in infected flocks, and vaccination in high-risk flocks. The effective control strategy requires convenient approach for detecting and differentiating MS strains and reliable drug susceptible evidence for deciding on reasonable antimicrobial usage. This study aimed to characterize the partialvlhAgene of nine Thai MS isolates circulated in chickens in 2020, to verify the PCR-RFLP assay for strain differentiation, and to determine the eight antimicrobial susceptibility profiles using microbroth dilution method. Based on sequence analysis of the partialvlhAgene, Thai MS isolates in 2020 were classified as types E and L with 19 and 35 amino acid lengths, respectively. The developed PCR-RFLP assay could detect and differentiate vaccine and Thai field strains. Most Thai MS isolates in this study were susceptible to tylosin, tylvalosin, tiamulin, doxycycline, oxytetracycline, tilmicosin, and lincomycin-spectinomycin at MIC50values of 0.0391, 0.0098, 0.0781, 0.1563, 0.1563, 0.625 and 0.625 μg/mL, respectively; and resistance to enrofloxacin at MIC50value of 10 μg/mL. In conclusion, this study revealed diagnostic assays for differentiating MS strains and the antimicrobial susceptibility profiles of Thai MS,which are necessary to design suitable MS control procedures for poultry flocks.
The use of kiosks to improve triage efficiency in the emergency department
Authors: Joseph Michael Jose , Summerscales Matthew , Yogesan Saieesha , Bell Anthony , Genevieve Michele , Kanagasingam Yogesan
Published: February 2023

Triage is a system used to prioritise patients as they enter the emergency department (ED) based on their need for urgent care. In recent decades, EDs have becoming increasingly overcrowded, leading to longer pre-triage waiting times for patients. E-triage interventions like kiosks have been proposed as a solution to overcrowding. We conducted a literature review into the effectiveness of kiosks in improving triage efficiency. After rigorously searching five biomedical databases and screening candidate articles in Endnote, we identified nine papers pertaining to the introduction of kiosks in emergency departments. Six articles had positive findings—with E-triage interventions improving some aspect of the triage process—such as reducing pre-triage times. Conversely, only three articles reported negative findings, such as low uptake. Consequently, EDs should consider introducing kiosks to complement the current nurse-led triage process and thereby promote better patient outcomes.
A tablet-based game for the assessment of visual motor skills in autistic children
Authors: Perochon Sam , Matias Di Martino J. , Carpenter Kimberly L. H. , Compton Scott , Davis Naomi , Espinosa Steven , Franz Lauren , Rieder Amber D. , Sullivan Connor , Sapiro Guillermo , Dawson Geraldine
Published: February 2023

Increasing evidence suggests that early motor impairments are a common feature of autism. Thus, scalable, quantitative methods for measuring motor behavior in young autistic children are needed. This work presents an engaging and scalable assessment of visual-motor abilities based on a bubble-popping game administered on a tablet. Participants are 233 children ranging from 1.5 to 10 years of age (147 neurotypical children and 86 children diagnosed with autism spectrum disorder [autistic], of which 32 are also diagnosed with co-occurring attention-deficit/hyperactivity disorder [autistic+ADHD]). Computer vision analyses are used to extract several game-based touch features, which are compared across autistic, autistic+ADHD, and neurotypical participants. Results show that younger (1.5-3 years) autistic children pop the bubbles at a lower rate, and their ability to touch the bubble’s center is less accurate compared to neurotypical children. When they pop a bubble, their finger lingers for a longer period, and they show more variability in their performance. In older children (3-10-years), consistent with previous research, the presence of co-occurring ADHD is associated with greater motor impairment, reflected in lower accuracy and more variable performance. Several motor features are correlated with standardized assessments of fine motor and cognitive abilities, as evaluated by an independent clinical assessment. These results highlight the potential of touch-based games as an efficient and scalable approach for assessing children’s visual-motor skills, which can be part of a broader screening tool for identifying early signs associated with autism.
Constructing coarse-grained skyrmion potentials from experimental data with Iterative Boltzmann Inversion
Authors: Ge Yuqing , Rothörl Jan , Brems Maarten A. , Kerber Nico , Gruber Raphael , Dohi Takaaki , Kläui Mathias , Virnau Peter
Published: February 2023

In an effort to understand skyrmion behavior on a coarse-grained level, skyrmions are often described as 2D quasiparticles evolving according to the Thiele equation. Interaction potentials are the key missing parameters for predictive modeling of experiments. Here, the Iterative Boltzmann Inversion technique commonly used in soft matter simulations is applied to construct potentials for skyrmion-skyrmion and skyrmion-magnetic material boundary interactions from a single experimental measurement without any prior assumptions of the potential form. It is found that the two interactions are purely repulsive and can be described by an exponential function for micrometer-sized skyrmions in a ferromagnetic thin film multilayer stack. This captures the physics on experimental length and time scales that are of interest for most skyrmion applications and typically inaccessible to atomistic or micromagnetic simulations.
Reactivity and Mechanism in Organic Chemistry
Authors: Zipse Hendrik
Published: February 2023

Completely revised and updated, this 2nd Edition of Reactivity and Mechanism in Organic Chemistry is an ideal introduction to the quantitative description of organic reactivity for students in undergraduate and masters chemistry programmes. The book proceeds logically from qualitative molecular orbital theory as a tool for the description of bonding phenomena to combining this with thermochemical data to rationalise concepts such as molecular strain and hyperconjugation. Next, transition state theory, for examining organic reactivity phenomena, is introduced and its relation to energy surfaces and simple rate equations is discussed. On this basis more specific reactivity concepts commonly used in organic chemistry are explored such as the Bell–Evans–Polanyi principle, Marcus theory, HSAB principle, Hammett correlations, the Mayr–Patz equation, and FMO theory. How these reactivity models are applied is demonstrated for pericyclic reactions and selected rearrangement reactions involving transient intermediates such as radicals, diradicals, or carbocations, and for reactions involving classical electrophile/nucleophile combinations.
Exploring Materials through Patent Information
Authors: Segal David
Published: February 2023

Many advances in technology are due to the development of new materials and by using patent literature we can monitor how technology has advanced. Exploring Materials through Patent Information describes how different technologies have evolved through the development of their patents, providing students with a guide on how to use patents as a source of information in their research and studies.

The first chapter provides practical advice on searching for patents and using patents, followed by individual chapters covering different material systems where the technical information in the patent literature demonstrates the developments in the technology. The materials discussed includes light-emitting diodes, quantum dots, organic light-emitting diodes (OLEDs), liquid crystals and liquid crystal displays, 3d printing, healthcare, block copolymers, aerogels, ionic liquids, flame retardants, graphene, hydrogels, and superhydrophobic materials.

The book is aimed at students in chemistry, materials science and engineering to show how patent information is an important source of information alongside other sources of information.
Sticking Together: The Science of Adhesion
Authors: Abbott Steven
Published: February 2023

This popular science title covers adhesion science in an easily accessible entertaining manner. As well as outlining types of adhesion and their importance in everyday life, the book covers interesting future applications of adhesion and inspiration taken from nature. Ideal for students and the scientifically minded reader this book provides a fascinating introduction to the science of what makes things stick.
The Case of the Poisonous Socks: Tales from Chemistry
Authors: Brock William H
Published: February 2023

In 1868, The Times reported that poisons contained in dyes were affecting the public's health. A doctor informed a London magistrate that brilliantly coloured socks had caused severe "constitutional and local complaint" to several of his patients. In one case, a patient's foot had become so swollen that his boots had to be cut off. Respected chemist, William Crookes, offered to identify the poison if doctors would send him samples of the deadly socks. The story of how he solved the mystery gives this book its title and forms the basis of the first chapter. Written by a respected science historian and established author, this collection of essays contains 42 tales of chemists and their discoveries from the nineteenth and twentieth centuries. Other topics covered include: the quirky beliefs of American philanthropist, George Hodgkins; the development of the chemical laboratory since the 1830s, and the career of C.P. Snow before he became a novelist. Its broad coverage and modern approach makes it of interest to chemists, teachers, historians and laypeople with an interest in science. Written with a light style and presented in a series of unconnected vignettes the book is easy to dip into at leisure.
Isotope Dilution Mass Spectrometry
Authors: Alonso Jose , Gonzalez Pablo
Published: February 2023

Isotope Dilution Mass Spectrometry (IDMS) has become an essential tool in research laboratories and is increasingly used in routine analysis labs (including environmental, food safety and clinical applications). This is the first textbook to present a comprehensive and instructive view of the theory and applications of this growing technique.

The main objective of this book is to cover the theory and applications of Isotope Dilution in Analytical Chemistry. The scope is comprehensive to include elemental analysis, speciation analysis, organic analysis and biochemical and clinical analysis together with applications in metabolism studies and traceability of goods. Until now there have been no books published with the same general scope (only book chapters on particular applications). This is a textbook focused at post-graduate level covering the basic knowledge required for doctoral studies in this field. Isotope Dilution Mass Spectrometry will also outline practical applications of interest for routine testing laboratories where isotope dilution procedures are implemented or can be implemented in the future. This unique book covers all the theoretical and practical aspects of Isotope Dilution Mass Spectrometry (IDMS). Due to the increasing application of IDMS in many research laboratories and the increasing implementation of IDMS methodologies in routine testing laboratories, scientists in industry and working in or affiliated to this area will this an invaluable source of information. Concerning the theoretical aspects, the authors present a uniform theoretical background which grows from previous developments in Organic, Speciation and Elemental analysis both in their own laboratory and in other laboratories around the world. This general approach will be simpler and will also include new emerging fields such as quantitative proteomics and metabolism studies.
A minireview of recent developments in ozone detection using optical chemodosimeters
Authors: Manna Saikat Kumar , Kuilya Debajyoti , Adhikary Ashok , Maiti Aindrila , Mondal Sanchita
Published: February 2023

In this minireview, we have provided a summary of the recent advancements in optical chemodosimeters for ozone detection from 2009 to 2022.
The facile activation of graphite for the improved determination of dopamine, rutin and acetamidophenol
Authors: Xu Yanxue , Chen Guihua , Qin Yunting , Xiao Dan
Published: February 2023

A glassy carbon electrode (GCE) was modified with graphite powder (G/GCE), and then treated with a solution of sodium peroxide for several minutes to prepare an oxidized G/GCE (OG/GCE).
Physico-chemical properties of functionally adhesive spider silk nanofibres
Authors: Joel Anna-Christin , Rawal Aditya , Yao Yin , Jenner Andrew , Ariotti Nicholas , Weissbach Margret , Adler Lewis , Stafstrom Jay , Blamires Sean J.
Published: February 2023

In nano-scale spider silk fibres, typically secondary protein structures are lost and the silk becomes very compliant. Additionally, due to a changed amino acid composition, a suit of new functionalities can be gained.
A new boronate ester-based crosslinking strategy allows the design of nonswelling and long-term stable dynamic covalent hydrogels
Authors: Lagneau N. , Terriac L. , Tournier P. , Helesbeux J-J. , Viault G. , Séraphin D. , Halgand B. , Loll F. , Garnier C. , Jonchère C. , Rivière M. , Tessier A. , Lebreton J. , Maugars Y. , Guicheux J. , Le Visage C. , Delplace V.
Published: February 2023

Testing libraries of phenylboronic acid derivatives and diols revealed a new crosslinking couple for the formation of viscoelastic hydrogels with tunable properties and long-term stability.
Hot-band absorption assisted single-photon frequency upconversion luminescent nanophotosensitizer for 808 nm light triggered photodynamic immunotherapy of cancer
Authors: Yu Hui , Wang Qing , Zhang Xinmiao , Tiemuer Aliya , Wang Jing , Zhang Yuanyuan , Sun Xiaolian , Liu Yi
Published: February 2023

We propose upconversion luminescent phthalocyanine nanophotosensitizer PdPc NPs with anti-Stokes emission at 748 nm triggered by 808 nm laser. After synergizing with anti-PDL1, the system could achieve prominent photodynamic sensitized immunotherapy.
Camptothecin loaded casein nanosystem for tuning the therapeutic efficacy against highly metastatic triple-negative breast cancer cells
Authors: Khatun Sajmina , Pebam Monika , Putta Chandra Lekha , Rengan Aravind Kumar
Published: February 2023

The heterogenicity of TNBC can be tackled by casein-based nanosystem with high therapeutic efficacy.
A multi-enzyme-like activity exhibiting mussel-inspired nanozyme hydrogel for bacteria-infected wound healing
Authors: Zhu Junrun , Han Qinqin , Li Qiulan , Wang Fang , Dong Miaodan , Liu Nuoya , Li Xiao , Chen Dan , Yang Dezhi , Song Yuzhu , Yang Yaling
Published: February 2023

A multi-enzyme-like activity exhibiting nanozyme hydrogel with oxidase and catalase-like activity was designed for wound healing, which exhibited excellent antibacterial performance. The catalase-like activity of the nanozyme provides adequate O2 for hypoxia abatement.
The location of metastatic lymph nodes and the evaluation of lymphadenectomy by near-infrared photoacoustic imaging with iridium complex nanoparticles
Authors: Yang Qi , Yu Yajun , Tang Chaojie , Gao Yucong , Wang Wu , Zhou Zhiguo , Yang Shiping , Yang Hong
Published: February 2023

Near-infrared iridium(iii) complex nanoparticles (IrCy-FA NPs) can serve as an effective photoacoustic imaging agent for pre-operative imaging analysis of the lymph node status and the postoperative evaluation of lymphadenectomy in vivo.
3D bioprinting of heterogeneous tissue-engineered skin containing human dermal fibroblasts and keratinocytes
Authors: Li Meng , Sun Lei , Liu Zixian , Shen Zhizhong , Cao Yanyan , Han Lu , Sang Shengbo , Wang Jianming
Published: February 2023

Three-dimensional (3D) printed skin substitutes have great potential for wound healing.
In situ electrochemical construction of Co/CoP crystalline-amorphous hetero-phase catalysts for highly efficient electrocatalytic hydrogen evolution
Authors: Wu Yali , Gao Di , Huang Lu , Shi Huihui , Yang Peixin , Guo Jiangna , Zhou Ming , Xiao Peng , Zhang Yunhuai
Published: February 2023

Co/CoP crystalline-amorphous hetero-phase electrocatalysts with superior alkaline HER performance are successfully synthesized by a facile and environmentally friendly one-step electrochemical approach.
Modified preparation of Si@C@TiO2 porous microspheres as anodes for high-performance lithium-ion batteries
Authors: Luo Jian , Xiao Peng , Li Yangjie , Xiong Jiangzhi , Zhou Peng , Pang Liang , Xie Xilei , Li Yang
Published: February 2023

Intact Si@C@TiO2 porous microspheres were synthesized by a modified etching and sol–gel method. The well-designed materials show good cycling performance and rate capability, and can maintain the original mechanical structure after cycling.