Human males and females show differences in the incidence of neutrophil-associated diseases and differences in neutrophil responses such as a faster response to the chemorepellent SLIGKV in males. Little is known about the basis of sex-based differences in human neutrophils. We used mass spectrometry to identify proteins and phosphoproteins in unstimulated human neutrophils and in neutrophils incubated with the SLIGKV, a protease activated receptor 2 agonist. There were 132 proteins with higher levels in unstimulated male neutrophils; these proteins tended to be associated with RNA regulation, ribosome, and phosphoinositide signaling pathways, whereas 30 proteins with higher levels in unstimulated female neutrophils were associated with metabolic processes, proteosomes, and phosphatase regulatory proteins. Unstimulated male neutrophils had increased phosphorylation of 32 proteins compared to females. After exposure to SLIGKV, male neutrophils showed a faster response in terms of protein phosphorylation compared to female neutrophils. Male neutrophils have higher levels of proteins and higher phosphorylation of proteins associated with RNA processing and signaling pathways. Female neutrophils have higher levels of proteins associated with metabolism and proteolytic pathways. This suggests that male neutrophils might be more ready to adapt to a new environment, and female neutrophils might be more effective at responding to pathogens.

Iron-sulfur (Fe-S) metalloproteins play vital roles in cellular processes, including DNA replication and repair. Though Fe-S protein dysregulation has been suggested to be associated with developmental and cancerous diseases, only a few Fe-S proteins with genome maintenance roles have been identified experimentally, likely because Fe-S cluster is susceptible to degradation under oxic environment. In vitro, Fe-S clusters could be substituted by other metal ions during protein purification, resulting in misannotation of Fe-S proteins as apoproteins or other metalloproteins. In silico, Fe-S proteins feature cysteines with atypical spacings, rendering motif prediction based solely on sequence signature difficult. Thus, in this study, a three-pronged bioinformatic approach is developed to discover putative [4Fe-4S] proteins in the human proteome: (i) a triamino acid motif involved in Fe-S biogenesis and reconstitution, (ii) cysteine geometric coordinates, and (iii) cysteine mutations with clinical relevance. Here, 21 novel proteins are uncovered as cancer-associated [4Fe-4S] protein candidates while using MUTYH, a known [4Fe-4S] protein, as positive control. Specifically, this study predicts 6 receptor proteins, 3 growth factors, and 5 histone lysine methyltransferases with SET domains to potentially contain [4Fe-4S] metallocofactors. This work establishes a bioinformatic framework for systematic identification of new metalloproteins and discovery of novel disease biomarkers.

Wilms tumor (WT), or nephroblastoma, is a rare pediatric kidney cancer that poses significant clinical challenges. Despite advancements in treatment, WT survivors face the risk of secondary malignant neoplasms (SMNs). This report discusses an 11-year-old girl who developed a secondary juvenile granulosa cell tumor of the ovary eight years after being treated for stage III WT. Initial treatment included nephrectomy, chemotherapy, and radiation. The secondary tumor, identified through imaging and surgery, highlights the importance of extended follow-up. This case underscores the need for vigilance in monitoring WT survivors for late-onset complications, even beyond the typical five-year surveillance period.

High grade dysplastic rectal adenoma in a young patient with Café-au-lait spots: A case reportAli Hamdan1, Razan Abou Zeid2, Jana Khalil3, Karam Karam4, Elias Fiani5*Medical Doctor, Department of Internal Medicine, University of Balamand, Beirut, Lebanon. Email: ali.hamdan.dr@outlook.comMedical student, University of Balamand, Beirut, Lebanon. Email: razan.abouzeid@std.balamand.edu.lbMedical student, University of Balamand, Beirut, Lebanon. Email: jana.khalil@std.balamand.edu.lbMedical doctor, Department of Gastroenterology, University of Balamand, Beirut, Lebanon. Email: Karamek7@gmail.comAssociate Professor, Department of Gastroenterology, University of Balamand, Beirut, Lebanon. Email: Elias.fiani@hotmail.com *CORRESPONDING AUTHORKey Clinical Message: Colorectal cancer screening guidelines typically focus on familial history and age-related risk factors, yet Café-au-lait macules could serve as early indicators for tailored surveillance protocols. This case underscores the importance of considering extracolonic manifestations in young patients presenting with colorectal symptoms. We present a case of a young patient with café-au-lait spots who was diagnosed with rectal tubulo-villous dysplastic adenoma following rectal bleeding.Keywords: Café-au-lait macules; Café-au-lait spots; Tubulo-villous dysplastic adenoma; Extracolonic manifestations; Case report.

Two-decade battle with myasthenia gravis: A breakthrough case report on the long-term success of eculizumab and ravulizumab treatment

A document by xueting Ma. Click on the document to view its contents.

Abstract: Microalgae are commercially important for the different industries as a natural source of a wide range of food and novel value‐added products. The adaptability of microalgae to produce different kind of pigments is gaining interest as a sustainable source of natural carotenoids. Astaxanthin is a popular ketocarotenoid with many health benefits. Microalgae is the potential source of astaxanthin. However, carotenoids production from microalgae in present time is reliant upon the requirement of strict culture conditions which are hard to maintain. However, the cultural conditions must be optimized first to increase strains’ productivity. In this context, Desmodesmus sp. PLM2 was isolated from the freshwater pond and screened for astaxanthin production under two-stage cultivation. The growth and carotenoid production were increased under optimized culture conditions compared to the control (standard BG-11 media). The optimized culture conditions were: 20 mM sodium nitrate; 3 mM glucose; 32 mM potassium chloride; pH 7, and temperature 27°C. In the second culture stage, the introduction of stress conditions induced the accumulation of orange-red carotenoid, later identified as astaxanthin using UHPLC. These results proved two-stage culture strategy as an effective way to optimise the carotenoid production in the newly isolated Desmodesmus sp. PLM2.

Males and females generally differ in resource investment strategies to maximise reproductive output, sometimes at the expense of important systemic processes such as self-maintenance and immune activity. Here, we used wild Lethrus apterus, a sexually dimorphic beetle with parental care, to investigate the influence of sex roles (e.g., offspring provisioning) on their sex-specific immune gene expression across a pseudo-longitudinal sampling framework. By determining immune gene activation of males and females at five successive moments within the active period, we showed that their sex-specific immune gene expression varies substantially, alternating between male bias and female bias across the active period. However, when pooling all sampling dates together, there was no overall difference in the number of up-regulated immune genes between the sexes. We discuss the potential influence of sex roles on our results and highlight the importance of sequential sampling schemes to understand ecological dynamics in the wild.

The presented paper introduces a design for a phase-locked loop (PLL) that is utilized in frequency synthesis and modulation-demodulation within communication systems and in VLSI applications. The CMOS PLL is designed using 180 nm Fabrication Technology on Cadence Virtuoso Tool with a supply voltage of 1.8 V. The performance is evaluated through simulations and measurements, which demonstrate its ability to track and lock onto the input frequency. The PLL is a frequency synthesizer implemented to generate 2.4 GHz frequency. The input reference clock from a crystal oscillator is 150 MHz square wave. Negative feedback is given by divide-by-16 frequency divider, ensuring the phase and frequency synchronization between the divided signal and the reference signal. The design has essential components such as a phase frequency detector, charge pump, loop filter, current-starved voltage-controlled oscillator (CSVCO), and frequency divider. Through their collaborative operation, the system generates an output frequency that is 16 times the input frequency. The centre frequency of the 3-stage CSVCO is 3.208 GHz at 900 mV input voltage. With an input voltage ranging from 0.4 V to 1.8 V, the VCO offers a tuning range that spans from 1.066 GHz to 3.731 GHz.PLL demonstrates a lock-in range spanning from 70.4 MHz to 173 MHz, with an output frequency range of 1.12 GHz to 2.78 GHz. It achieves a lock time of 260.03 ns and consumes a maximum power of 5.15 mW at 2.4 GHz

In polytypic species, where distinct variants occur in separate populations, few studies to date have quantified intraspecific differences in habitat selection. This can inform us about habitat requirements across different areas and populations, with implications for conservation, and can increase our understanding of the selective pressures acting upon different populations. Here, we investigated differences in habitat selection across six populations of the dyeing poison frog (Dendrobates tinctorius), which are characterized by great phenotypic variation among them, especially in terms of warning coloration, body size, and sexual size dimorphism. We hypothesized that habitat selection differs (1) among populations containing different variants, predicting that frogs in larger-bodied populations are less dependent on structures that retain moisture; (2) among disturbed and pristine areas, predicting frogs in disturbed areas being more reliant on structural diversity and water bodies; and (3) between males and females, predicting stronger differences in habitat selection in populations with greater sexual size dimorphism. We found little support for these hypotheses, with habitat selection being broadly similar among populations. Frogs generally selected for proximity to tree falls, dead woody material (such as fallen/rotting branches, fallen palm bracts, etc.), presence of water pools (phytotelmata and other small bodies of water), and avoided areas with extensive ground vegetation and little canopy cover. We found limited evidence for fine-scale differences in habitat selection between sexes, with males showing a comparatively stronger selection for proximity to water pools and females stronger selection for tree falls. More generally, our results suggest that in polytypic and aposematic species, habitat selection might be less influenced by intersexual niche partitioning and predation risk, and more by resource availability. Our findings provide important baseline data regarding the habitat selection and requirements of this emblematic species, which can be relevant for efficient conservation measures in the future.

Submerged aquatic vegetation (macrophytes) can provide prey with refuges from predators and may perform a similar role for interactions with other natural enemies such as parasites. This could occur by interfering with the ability of free-swimming parasite infectious stages to locate or move towards hosts, reducing infections. Alternatively, infections may increase if macrophytes reduce host anti-parasite behaviours such as detection or evasion. Both scenarios could be affected by macrophyte density and structural complexity. Here we investigated whether experimental infection of tadpoles (Rana sylvatica and R. pipiens) by parasitic flatworms (the trematodes Ribeiroia ondatrae and Echinostoma sp.) was affected by the presence of artificial vegetation with varying density and complexity (simple vs. branching), as well as tadpole activity in these conditions. Macrophyte presence significantly reduced tadpole infection loads only in the highest density treatment, but there was no effect of structural complexity. Related to this, tadpoles spent significantly more time near aquatic vegetation when it was dense but showed no preference for either structural type. Our results indicate that aquatic vegetation can reduce parasite transmission in certain scenarios, with further studies needed to explore how structural complexity in natural systems can affect host-parasite interactions considering the massive physical alterations possible through eutrophication and the introduction of invasive plant species.

This article is focused on the design of an LMI-based observer for the class of disturbance-affected nonlinear systems. Two novel LMI conditions are derived by deploying a more general form of the matrix multiplier compared to the one used in the literature. The first method is based on the use of the H ∞ criterion, while the second one utilises an ISS notion. Both LMIs are developed by employing the reformulated Lipschitz property, a well-known LPV approach and the new variant of Young inequality. The key element of the proposed LMI conditions is the incorporation of the novel matrix multipliers which allow us to include some additional decision variables as compared to the methods proposed in the literature. These additional variables add extra degrees of freedom, thus enhancing the LMI feasibility. Furthermore, the effectiveness of the proposed methodologies is showcased through a numerical example.

Global climate change exerts great effort for plants distributions. However the response of P. mira, one of the most important species for ecological protection in the southeast of Qinghai-Tibet Plateau, to climate change remains unclear. To explore the ecological factors on the distribution of P. mira in context of global climate change, the MaxENT model is used to predict the suitable habitats for P. mira. Our study indicated that the distribution of P. mira is primarily influenced by temperature rather than precipitation, warming can facilitate the growth of P. mira. When the temperature seasonality (bio4) ranges from 134 to 576 and the mean temperature of coldest quarter (bio11) ranges from -2.6°C to 2.7°C, it is most conducive to the growth of P. mira. Among the four climate scenarios, the optimal habitat for P. mira is predominantly concentrated in river valley areas and is expected to expand into higher altitude regions, particularly in the north and southeast. SSP245 and SSP370 climate pathways are conducive to the growth and spatial expansion of P. mira. Our findings highlight the significant impact of temperature not precipitation on the distribution of P. mira, and this insight is crucial for the stability and conservation of this ecologically significant plant species.

Recently, antiferroelectric and antiferroelectric-like materials have regained interest for electronic devices, such as field-effect transistors, memory, and transducers. Particularly, in micro/nano-electromechanical coupling systems, such as actuators, these innovative materials, with their peculiar phase transition between antiferroelectric and ferroelectric phases, show promise in offering large electro-strain, fast response, and low power consumption devices. However, compared to the numerous computational models of ferroelectric actuators, numerical modeling of antiferroelectric and antiferroelectric-like actuators remains relatively unexplored. In this paper, we propose a phenomenological model of a uni-axial antiferroelectric and antiferroelectric-like actuators based on their switching polarization behavior. Specifically, both the double hysteresis loop of antiferroelectric materials and the pinched hysteresis loop of antiferroelectric-like materials can be captured by two hyperbolic tangent functions. This allows us to cast a polarization-dependent strain and piezoelectric tensor into the constitutive laws. The proposed model is then implemented into a finite element framework, in which the voltage-induced deformation can be solved using the Newton-Raphson procedure. Numerical examples of both antiferroelectric and antiferroelectric-like actuators are illustrated and compared with experimental data, showing our proposed model can serve as a useful tool for the design and development of antiferroelectric and antiferroelectric-like actuators.

Title: Hypersensitivity reaction to rivaroxaban with a successful switch to apixaban; a case reportShort title/running head: Rivraxoaban-induced hypersensitivity reaction

Reward-related brain activity has most often been examined during monetary reward paradigms, but it has also been examined in response to other types of reward (e.g., social reward) that often necessitate modifications to procedure and task design. It is important to investigate whether task factors impact the ability to assess the neural response common across different types of reward (i.e., domain-general) and specific to each type of reward (i.e., domain-specific). The present study involved a sample of 303 18-year-olds (49.5% female) who completed the Monetary Doors task and two social tasks: Social Reward, which was designed to be analogous to Monetary Doors, and Island Getaway, which differed procedurally from the other two tasks. Using electroencephalography to measure the time-domain reward positivity (RewP) and time-frequency delta and theta activity, we found that all three tasks elicited a RewP and greater delta activity to favorable outcomes (i.e., monetary win, social like/acceptance), and greater theta activity to unfavorable outcomes (i.e., monetary loss, social dislike/rejection). The RewP was positively correlated across all three tasks, indicating the ability to measure domain-general neural response, but the neural responses during Monetary Doors and Social Reward were more strongly correlated compared to the other task pairwise correlations for the RewP and delta activity. The present study suggests that different monetary and social reward tasks can elicit both domain-general and domain-specific brain activity but are influenced by task design. Recommendations are made regarding factors to consider when attempting to examine domain-general and domain-specific neural response to reward.

A document by Moushami Singh. Click on the document to view its contents.

Purpose: This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of SHR6508 injection, a new calcimimetic agent, in healthy Chinese subjects following single dose. Methods: This study utilized a placebo-controlled, single-dose and dose-escalation design with four dose groups (0.5 mg, 2.5 mg, 5 mg, 10 mg). The trial started with a low dose and continuing to the next dose after completion of the out-of-group safety assessment of the previous dose group. Blood samples were collected at 15 time points to measure pharmacokinetic and pharmacodynamic parameters. Safety was assessed by therapeutic emergency adverse events (TEAEs), clinical laboratory tests, vital signs, electrocardiograms (ECGs), and physical examination. Results: Of the 22 subjects who completed this study, 16 received SHR6508 Injection and 6 received placebo. In the 0.5-5 mg group Tmax was 0.033 - 0.058 h, and t1/2z was 8.8 h-28.3 h. Cmax and AUC increased proportionally with dose. PD results showed that SHR6508 dose-dependently decreased iPTH and blood calcium levels in subjects in the 0.5-5 mg dose range; blood phosphorus levels in subjects in the 5 mg group tended to be elevated compared to those in the placebo group. 21 TEAEs occurred in 12 subjects (54.5%), and no serious or severe TEAE occurred. Conclusion: The overall safety and tolerability of a single intravenous dose of 0.5-5 mg SHR6508 in healthy subjects was favorable, exhibiting dose-dependent PK and PD properties.

We performed a retrospective cohort analysis comparing the trends in low global warming potential (GWP) inhaler prescribing in primary care in England, Scotland, Wales and Northern Ireland between 2018 and 2024. Over the study period there was little change in low GWP inhalers in England and Northern Ireland, a reduction from 35% to 30.9% in Scotland and an increase from 31.7% to 38.7% in Wales. Only in Wales was there a simultaneous reduction in high GWP inhalers and an increase in low GWP inhalers in line with published national goals. These findings suggest that the approach taken in Wales to promote inhaler switching was effective and could be adopted in the other nations.

The aim of this study was to carry out a cross-cultural adaptation and validation of the Spanish version of the Recovery Process Inventory (RPI-S) and to provide empirical evidence on the importance of hope and social support for the personal recovery. A preliminary Spanish version of the RPI was first produced through a standardized process, ensuring semantic, linguistic, and contextual equivalence with respect to the original instrument. The psychometric properties were then examined in sample of 267 participants with severe mental disorders. The recommendations included in the STROBE checklist for cross-sectional studies were followed. Confirmatory factor analysis supported a structure consisting of four key dimensions for assessing personal recovery. Correlations between scores on the RPI-S and scores on the Spanish version of the Questionnaire about the Process of Recovery and on the Spanish version of the Maryland Assessment of Recovery Scale showed the expected direction and magnitude, supporting convergent validity. Internal consistency of RPI-S scores was adequate (McDonald’s ω ranging between .70 and .88), as was temporal stability over a one-week interval (Pearson correlation coefficients ranging between .71 and .77) for all the dimensions. In addition, people with greater hope and social support reported better levels of personal recovery on all dimensions assessed by the RPI-S. The results suggest that the RPI-S is a valid and reliable instrument for assessing personal recovery among Spanish people with severe mental disorders and demonstrate the importance of hope and social support as essential factors within the conceptual framework of recovery.

During the cultivation of button mushrooms, the green mold epidemic, which causes a decrease in productivity, is a very important problem. The environmental harm of chemicals used in the control of such epidemics and the demand of consumers for organic products without chemicals have brought environmentally friendly biological control to the fore. Biological control can be achieved by the use of antagonistic microorganisms and their metabolites. In this study, the effectiveness of Bacillus and Pseudomonas spp. for the biological control of the green mold disease agent Trichoderma aggressivum subsp. in Agaricus bisporus cultivation was examined. For this purpose, the antifungal effects of Bacillus and Pseudomonas spp. against T. aggressivum strains were examined by an in vitro dual culture test and the agar well diffusion method. Then, it was determined whether the bacterial strains showing antifungal activity showed antagonistic activity against A. bisporus. Although none of the Pseudomonas spp. showed antifungal activity against T. aggressivum strains, most of the Bacillus spp. were found to have high activity. It has been concluded that Bacillus sp. Ö-4-82, which shows high antifungal activity against T. aggressivum subsp. and low antagonism against A. bisporus, may be potential biological control agents for button mushroom cultivation.

Esophageal cancer (ESCA) has the sixth highest mortality rate worldwide and its incidence is increasing every year. Alterations in genes and poor dietary habits may induce ESCA. In addition, the tumor immune microenvironment is one of the most common factors involved in the tumorigenesis and development of ESCA, which may be mediated by tumor-associated macrophages, but the molecular mechanism underlying this is unclear. Therefore, in this study, CIBERSORT was used to understand the distribution of innate-immune cells in ESCA and normal tissues using TCGA database. Weighted gene co-expression network (WGCNA) analysis was used to analyze hub genes linked to M1, M2, and M0, which were the top three enriched cells in ESCA. Gene Set Enrichment Analysis (GSEA) displayed that three signal pathways linked to inflammation were enriched in ESCA: NF-κB regulatory pathway genes for TNF response, IFNα signaling pathway genes, and the energy metabolism-related oxidative phosphorylation pathway. Then, multiple hub genes were identified that had several forms of genetic alterations in ESCA, and many patients exhibited more than two of these alterations simultaneously. The risk assessment showed that three hub genes, CMA1, FGF5, and VEGFD, were identified as independent risk factors for ESCA (p<0.05). The overall 5- and 10-year survival rates were lower in patients with altered FGF5 and VEGFD

Several insect groups exhibit the phenomenon of cannibalism, preying upon individuals of the same species. Cannibalism is an intriguing behavior but often poorly understood. Cannibalism is thought to be influenced by the sex, life history stage, and physiological condition as well as ecological and social contexts in which it occurs. Here we review cannibalism in a carnivorous insect order Odonata (dragonflies and damselflies), on the adult stage of their life cycles, based on primary and secondary data. We collected primary data from our field work (mostly from opportunistic observation) spanning eight years from three countries (India, Bangladesh and Australia) and secondary data including published literature and observations from global citizen science portals. In total, we retrieved 86 instances of cannibalism and metadata (developmental stage and sex of the individuals involved in cannibalism) of 63 cannibalistic instances. We found that, Odonata families with most reported cannibalism cases were Coenagrionidae (n=50) and Libellulidae (n=31) followed by Lestidae (n=2), Aeshnidae, Calopterygidae and Euphaediae each with one example. We classified the cannibalism in odonates into four patterns, 1) Females cannibalizing males, 2) males cannibalizing females, 3) intrasexual cannibalism and, 4) mature individuals cannibalizing tenerals. We found, female cannibalizing males was higher in proportions, compared to males cannibalizing females, and intrasexual cannibalism. We further found that, individuals involved in Anisopteran cannibalism were mostly matures, but in case of Zygoptera, mostly matures individuals were canabilising tenerals. We discuss that species recognition errors, intrasexual competition for mating, and mating harassment avoiding strategies are major driving factors of cannibalism in odonates. We provide a comprehensive insight into the cannibalistic behavior of adult odonates and highlight that experimental evidences are required to understand the mechanisms of cannibalism.

Rare acute pulmonary thromboembolism after internal fixation for isolated multiple rib fractures: a case report