Essential Role Research Articles

Multiple images captured from a single encounter do not promote face learning.

Viewing multiple images of a newly encountered face improves recognition of that identity in new instances. Studies examining face learning have presented high-variability (HV) images that incorporate changes that occur from moment-to-moment (e.g., head orientation and expression) and over time (e.g., lighting, hairstyle, and health). We examined whether low-variability (LV) images (i.e., images that incorporate only moment-to-moment changes) also promote generalisation of learning such that novel instances are recognised. Participants viewed a single image, six LV images, or six HV images of a target identity before being asked to recognise novel images of that identity in a face matching task (training stimuli remained visible) or a memory task (training stimuli were removed). In Experiment 1 (n = 71), participants indicated which image(s) in 8-image arrays belonged to the target identity. In Experiment 2 (n = 73), participants indicated whether sequentially presented images belonged to the target identity. Relative to the single-image condition, sensitivity to identity improved and response biases were less conservative in the HV condition; we found no evidence of generalisation of learning in the LV condition regardless of testing protocol. Our findings suggest that day-to-day variability in appearance plays an essential role in acquiring expertise with a novel face.

Keeping Corporations in the Courts: A Framework for Addressing Jurisdiction over Corporate Defendants in Class Action Litigation

In a series of recent cases, the Supreme Court has made it significantly more difficult for plaintiffs to seek legal redress against corporations by limiting the power of courts to exercise personal jurisdiction over corporate defendants. Beginning in 2011, the Supreme Court limited the inquiry around where a corporation might be subject to general, all-purpose jurisdiction for claims against it. Then, in 2017, in Bristol-Myers Squibb v. Superior Court of California (“BMS”), the Court constrained the ability of plaintiffs to join together to sue a corporation when those plaintiffs were harmed by the corporation in different states. Importantly, these decisions left open whether these jurisdictional constraints apply to class actions. This Note argues that because of the important role that class actions play in corporate accountability, it is essential that these limitations not be extended to the class action form. In summary, if the Rule 23 class action certification criteria are met and if the court has jurisdiction over the defendant with respect to class representatives’ claims under current personal jurisdiction doctrine, then the court should impute jurisdiction over that defendant with respect to the claims of class members. Part II of the Note details the scope of the aforementioned string of cases and discusses the scholarly, judicial, and popular responses to the potential applicability of BMS to class actions. Part III identifies the problems with applying BMS to class actions, focusing on the importance of private enforcement in maintaining corporate accountability and the essential role that the class action form plays in that process. Finally, Part IV considers the legal, policy, and normative considerations associated with limiting the scope of BMS and proposes solutions for how to limit BMS in the class action context.

Wear Reduction on the Roller–Shoe Mechanism at High Operation Loads

The roller–shoe mechanism is a classic mechanical assembly with an essential role in motion transmission. Common rail high-pressure pumps are an example of a complex assembly that uses such a mechanism to transform the rotation motion into a translation one. The rolling element of the mechanism is represented by a cylindrical roller. Although it can carry heavy loads due to its design, a proper surface profile could significantly increase the life of the entire mechanism. A better solution can be achieved using a logarithmic profile. The shoe is the second base element of the mechanism. It is a part with an inner cylindrical surface and it is separated from the roller by a thin lubricant film. Considering this, increasing the hardness of the roller–shoe contact surface can be obtained using a suitable coating. The positive results of this coating are highlighted using endurance tests to which high-pressure pumps are subjected. Therefore, the roller profile and the shoe coating represent two directions for improving the contact between the mechanism transmission elements, in terms of wear reduction. The purpose of this paper is to identify a suitable roller profile and to highlight its impact on the shoe coating.

Microseismic Velocity Inversion Based on Deep Learning and Data Augmentation

Microseismic monitoring plays an essential role for reservoir characterization and earthquake disaster monitoring and early warning. The accuracy of the subsurface velocity model directly affects the precision of event localization and subsequent processing. It is challenging for traditional methods to realize efficient and accurate microseismic velocity inversion due to the low signal-to-noise ratio of field data. Deep learning can efficiently invert the velocity model by constructing a mapping relationship from the waveform data domain to the velocity model domain. The predicted and reference values are fitted with mean square error as the loss function. To reduce the feature mismatch between the synthetic and real microseismic data, data augmentation is also performed using correlation and convolution operations. Moreover, a hybrid training strategy is proposed by combining synthetic and augmented data. By testing real microseismic data, the results show that the Unet is capable of high-resolution and robust velocity prediction. The data augmentation method complements more high-frequency components, while the hybrid training strategy fully combines the low-frequency and high-frequency components in the data to improve the inversion accuracy.

Investigating the Influence of Stakeholders' Collaboration on Open Innovation in Healthcare

This article investigates the impact of stakeholder collaboration on open innovation in healthcare, focusing on diverse case studies across countries. It highlights the essential role of collaboration in generating new solutions and overcoming barriers in healthcare innovation. The study utilizes a multiple case study method to analyze four healthcare projects in different countries, examining collaboration processes, outcomes, challenges, and opportunities. The results emphasize the importance of trust-building, user involvement, regulatory support, and incentives in fostering successful collaboration and innovation outcomes. The findings underscore the need for transparent governance, sustained commitment, and tailored policy interventions to promote multi-stakeholder cooperation and drive sustainable innovation in healthcare.

BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.

Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment. We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and examined the relationship between SHH, BMP4, GREM1, and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4, and GREM1 treatment. Corpora cavernosa of Peyronie's disease (control), prostatectomy, and diabetic ED patients were obtained (N= 30). Adult Sprague Dawley rats (n = 90) underwent (1) CN crush (1-7days) or sham surgery; (2) CN injury and BMP4, GREM1, or mouse serum albumin (control) treatment via Affi-Gel beads or peptide amphiphile (PA) for 14days; (3) 5E1 SHH inhibitor, IgG, or phosphate-buffered saline (control) treatment for 2 to 4days; or (4) CN crush with mouse serum albumin or SHH for 9days. Immunohistochemical and Western analysis for BMP4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed. BMP4 and GREM1 proteins were identified in corpora cavernosa smooth muscle of prostatectomy, diabetic, and Peyronie's patients, and in rat smooth muscle, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Collagen decreased 25.4% in rats with CN injury and BMP4 treatment (P = .02) and increased 61.3% with CN injury and GREM1 treatment (P = .005). Trichrome stain showed increased collagen in rats treated with GREM1. Western analysis identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased the monomer form of BMP4 and GREM1, altering their range of signaling. A better understanding of penile remodeling and how fibrosis occurs with loss of innervation is essential for development of novel ED therapies. The relationship between SHH, BMP4, GREM1, and collagen is complex in the penis. BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED.

Will Nigella sativa oil protect parotid glands of rats against cranium gamma irradiation? Histological and immunohistochemical evaluation

BackgroundRadiation plays an essential role in treating malignancies. Radiation exposure of salivary glands often results in permanent loss of their functions; therefore, their protection against radiation is crucial. Nigella sativa oil (NSO) is a useful antioxidant against free radicals. The purpose of this study was to investigate the radio-protective effect of NSO on oxidative injury of parotid glands of gamma-irradiated rats. Methods: Twenty-eight male albino rats were divided into four groups (n = 7): Group 1: Neither NSO nor radiation, Group 2: Rats received NSO 400 mg/kg, Group 3: Rats received 15 Gy cranium gamma irradiation & Group 4: Rats received gamma irradiation and NSO. Rats were sacrificed two weeks after the last NSO dose. Histological sections of parotid glands were stained with H&E, Masson’s trichrome and anti-TGF-β antibodies. Area percentage of Masson’s trichrome and TGF-β expression was morphometrically examined. Results: Parotid glands of control and NSO groups revealed normal morphology. Gamma-irradiated glands showed loss of normal acinar architecture and slight acinar shrinkage. NSO treatment of gamma-irradiated glands preserved acinar outline and architecture. Masson’s trichrome stained samples revealed trace amounts of collagen fibers in control and NSO groups, and excessive amounts of collagen fibers in gamma-irradiated group, in addition to few collagen fibers for gamma-irradiated glands treated with NSO. Additionally, control and NSO groups showed negative TGF-β expression. Gamma-irradiated group showed high TGF-β expression, while NSO treated gamma-irradiated group showed moderate TGF-β expression. Conclusions: Gamma-irradiation adversely affected parotid glands, and in contrast, NSO seemed to positively counteract this adverse effect.

Communication between Mast Cells and Group 2 Innate Lymphoid Cells in the Skin.

The skin is a dynamic organ with a complex immune network critical for maintaining balance and defending against various pathogens. Different types of cells in the skin, such as mast cells (MCs) and group 2 innate lymphoid cells (ILC2s), contribute to immune regulation and play essential roles in the early immune response to various triggers, including allergens. It is beneficial to dissect cell-to-cell interactions in the skin to elucidate the mechanisms underlying skin immunity. The current manuscript concentrates explicitly on the communication pathways between MCs and ILC2s in the skin, highlighting their ability to regulate immune responses, inflammation, and tissue repair. Furthermore, it discusses how the interactions between MCs and ILC2s play a crucial role in various skin conditions, such as autoimmune diseases, dermatological disorders, and allergic reactions. Understanding the complex interactions between MCs and ILC2s in different skin conditions is crucial to developing targeted treatments for related disorders. The discovery of shared pathways could pave the way for novel therapeutic interventions to restore immunological balance in diseased skin tissues.

Recent Advances in Hydrodeoxygenation of Lignin‐Derived Phenolics over Metal‐Zeolite Bifunctional Catalysts

AbstractThe hydrodeoxygenation (HDO) reaction provides a promising catalytic strategy to remove oxygen in biomass‐derived bio‐oil to produce renewable transportation fuels and value‐added chemicals. The development of highly efficient and stable HDO catalysts plays an essential role in biomass valorization. Metal‐zeolite bifunctional catalysts have been well‐developed as the effective HDO catalysts in upgrading lignin‐derived phenolics due to their excellent activity, selectivity, and thermal and hydrothermal stability. However, clarifying the roles of the active sites and their synergistic effect, and establishing effective structure‐performance relationships in the HDO process still face challenges. In this review, we first survey the conventional catalysts applied in the HDO of bio‐oil, followed by thoroughly discussing the roles of metal centers, acid sites, supports, and their impacts on the HDO process of phenolic model compounds or bio‐oil. Finally, a discussion on the stability and deactivation of metal‐zeolite catalysts, especially in the aqueous‐phase HDO reaction, is provided. This critical review offers new insights into the development of state‐of‐the‐art metal‐zeolite bifunctional catalysts with well‐defined porosity and metal‐acid properties for viable biomass valorization.

Boko Haram insurgency and sustainable development in north-east, Nigeria, 2014-2022

The problem of insecurity and terrorism became heightened in 2014 after a series of attacks by Boko Haram on individuals, properties; government installations, etc. especially in North-East Nigeria. The study examines Boko Haram Insurgency and sustainable development in North East Nigeria, using the thematic approach of Insurgency and sustainable development. Qualitative analysis was strictly used based on purposive sampling gathered from four states of the northeastern part of Nigeria; Borno, Yobe, Bauchi, and Gombe. The Sustainable Development Theory was used to analyze the Insurgency's impact on economic, social, and human development, and the climate/environmental challenges. The researcher used both primary and secondary sources to collect information. The research findings indicate that the North East region and its people suffered grievous economic and political damages from the activities of the insurgents, with the catastrophic collapse of economic, social, and political structures, and processes, and a likelihood of the State itself collapsing and breaking into fragments if the insurgency had continued unabated for a more extended period. The study recommended that the provision of immediate and comprehensive mental health diagnosis, treatment, and counselling will play an essential and critical role in helping people exposed to insurgency recover quickly from the emotional pains and trauma that come with such exposure.

Argonaute and Dicer are essential for communication between Trichoderma atroviride and fungal hosts during mycoparasitism.

Trichoderma species are known for their mycoparasitic activity against phytopathogenic fungi that cause significant economic losses in agriculture. During mycoparasitism, Trichoderma spp. recognize molecules produced by the host fungus and release secondary metabolites and hydrolytic enzymes to kill and degrade the host's cell wall. Here, we explored the participation of the Trichoderma atroviride RNAi machinery in the interaction with six phytopathogenic fungi of economic importance. We determined that both Argonaute-3 and Dicer-2 play an essential role during mycoparasitism. Using an RNA-Seq approach, we identified that perception, detox, and cell wall degradation depend on the T. atroviride-RNAi when interacting with Alternaria alternata, Rhizoctonia solani AG2, and R. solani AG5. Furthermore, we constructed a gene co-expression network that provides evidence of two gene modules regulated by RNAi, which play crucial roles in essential processes during mycoparasitism. In addition, based on small RNA-seq, we conclude that siRNAs regulate amino acid and carbon metabolism and communication during the Trichoderma-host interaction. Interestingly, our data suggest that siRNAs might regulate allorecognition (het) and transport genes in a cross-species manner. Thus, these results reveal a fine-tuned regulation in T. atroviride dependent on siRNAs that is essential during the biocontrol of phytopathogenic fungi, showing a greater complexity of this process than previously established.IMPORTANCEThere is an increasing need for plant disease control without chemical pesticides to avoid environmental pollution and resistance, and the health risks associated with the application of pesticides are increasing. Employing Trichoderma species in agriculture to control fungal diseases is an alternative plant protection strategy that overcomes these issues without utilizing chemical fungicides. Therefore, understanding the biocontrol mechanisms used by Trichoderma species to antagonize other fungi is critical. Although there has been extensive research about the mechanisms involved in the mycoparasitic capability of Trichoderma species, there are still unsolved questions related to how Trichoderma regulates recognition, attack, and defense mechanisms during interaction with a fungal host. In this work, we report that the Argonaute and Dicer components of the RNAi machinery and the small RNAs they process are essential for gene regulation during mycoparasitism by Trichoderma atroviride.

Unraveling the Intraday Variations in the Tear Fluid Proteome.

Tear fluid is a complex and dynamic biological fluid that plays essential roles in maintaining ocular homeostasis and protecting against the external environment. Owing to the small sample volume, studying the tear proteome is challenging. However, advances in high-resolution mass spectrometry have expanded tear proteome profiling, revealing >500 unique proteins. Tears are emerging as a noninvasive source of biomarkers for both ocular and systemic diseases; nevertheless, intraday variability of proteins in tear fluid remains questionable. This study investigates intraday variations in the tear fluid proteome to identify stable proteins that could act as candidate biomarkers. Tear samples from 15 individuals at four time points (10 am, 12 pm, 2 pm, and 4 pm) were analyzed using mass spectrometry to evaluate protein variation during these intervals. Technical variation was assessed by analyzing pooled samples and was subtracted from the total variation to isolate biological variability. Owing to high technical variation, low-abundant proteins were filtered, and only 115 proteins met the criteria for further analysis. These criteria include being detected at all four time points in at least eight subjects, having a mean peptide-spectrum match count greater than 5, and having a technical variation less than 0.10. Lactotransferrin, lipocalin-1, and several immunoglobulins were among the 51 stable proteins (mean biological coefficient of variation < 0.10). Additionally, 43 proteins displayed significant slopes across the 4 time points, with 17 increasing and 26 decreasing over time. These findings contribute to the understanding of tear fluid dynamics and further expand our knowledge of the tear proteome.

Protective effect of SERCA2a-SUMOylation by SUMO-1 on diabetes-induced atherosclerosis and aortic vascular injury.

Diabetes is a major risk factor for cardiovascular disease. However, the exact mechanism by which diabetes contributes to vascular damage is not fully understood. The aim of this study was to investigate the role of SUMO-1 mediated SERCA2a SUMOylation in the development of atherosclerotic vascular injury associated with diabetes mellitus.ApoE-/- mice were treated with streptozotocin (STZ) injection combined with high-fat feeding to simulate diabetic atherosclerosis and vascular injury. Human aortic vascular smooth muscle cells (HAVSMCs) were treated with high glucose (HG, 33.3 mM) and palmitic acid (PA, 200 µM) for 24h to mimic a model of diabetes-induced vascular injury in vitro. Aortic vascular function, phenotypic conversion, migration, proliferation, intracellular Ca2+ concentration, the levels of small ubiquitin-like modifier type 1 (SUMO1), SERCA2a and SUMOylated SERCA2a were detected.Diabetes-induced atherosclerotic mice presented obvious atherosclerotic plaques and vascular injury, companied by significantly lower levels of SUMO1 and SERCA2a in aorta. HG and PA treatment in HAVSMCs reduced the expressions of SUMO1, SERCA2a and SUMOylated SERCA2a, facilitated the HAVSMCs phenotypic transformation, proliferation and migration, attenuated the Ca2+ transport, and increased the resting intracellular Ca2+ concentration. We also confirmed that SUMO1 directly bound to SERCA2a in HAVSMCs. Overexpression of SUMO1 restored the function and phenotypic contractile ability of HAVSMCs by upregulating SERCA2a SUMOylation, thereby alleviating HG and PA-induced vascular injury.These observations suggest an essential role of SUMO1 to protect diabetes-induced atherosclerosis and aortic vascular injury by the regulation of SERCA2a-SUMOylation and calcium homeostasis.

The occurrence and distribution characteristics of microbial necromass carbon in lake sediments

As a critical component of SOC, microbial necromass carbon (MNC) has been well studied in forest, farmland, and grassland ecosystems. However, the distribution, forms, and storage of MNC, which bound to the sediments in lakes, remain unclear. Herein, the lake sediments in the West Dongting Lake have been collected to investigate the distributions of MNC in sediments, particulated organic matter (POM), and mineral-associated organic matter (MAOM). The contribution of MNC to the sedimentary organic carbon was 20–30 %, which was lower than the average value of 50 % in other ecosystems. The reasons might be related to the selective migration of soil particles with uneven distribution of MNC and the accelerated mineralization of MNC prior to sedimentation. The results revealed that MNCmaom was the predominant form of MNC, accounting for 61–73 % of the total MNC. In addition, the MNC content in the sediments ranged from 2.03 g kg−1 to 4.33 g kg−1, showing an increasing trend along the direction of the water flow from the lake shore to the center. The redundancy analyses and the partial least square path model analyses indicated that sediment organic carbon, total nitrogen, silt and MAOM had a substantial impact on the MNC. Silt played an essential role in regulating the distributions of MNC in lake sediments by promoting MNC sedimentation and providing protection from degradation. These findings revealed that the accumulation of MNC in lake sedimentwas mainly affected by sediment particles, which differed from other non-lake ecosystems. The presented findings provided essential insights into the accumulation of MNC in lake sediments, highlighting the importance of the MNC in lake sediments and a more profound understanding of the role of MNC in lake carbon cycling.

In Situ Generation of a Gel Polymer Electrolyte via the Controlled Formation of Ethylene Carbonate in a Poly(ethylene carbonate)‐Hydrogenated Nitrile Butadiene Rubber Solid Polymer Electrolyte

AbstractElectrolytes play an essential role in electrochemical energy storage devices. Liquid electrolytes have good ionic conductivity but tend to be flammable, prompting some of the safety concerns that are associated with these devices. Solid polymer electrolytes (SPEs) are presented as a potential solution to this problem. These materials have higher mechanical stability and can be formulated to be non‐flammable. However, ionic conductivity in solid polymer electrolytes tends to be several orders of magnitude lower than that of liquid electrolytes, significantly limiting device performance making electrolyte safety and performance difficult to optimize simultaneously. However, gel electrolytes which combine lower flammability, higher mechanical strength, and adequate ionic conductivity may present a solution to this challenge. To this end, the melt processing of hydrogenated nitrile rubber (HNBR) with poly(ethylene carbonate) (PEC) followed by the in situ formation of ethylene carbonate (EC) is reported. Conversion of PEC to EC is confirmed via NMR spectroscopy. Electrochemical testing reveals improved ionic conductivity following the conversion of the solid polymer electrolyte to the gel polymer electrolyte. Improvements in ionic conductivity, relative to the initial SPE, are attributed to decreased salt‐polymer interactions in favor of salt‐EC interactions as observed via differential scanning calorimetry, Fourier transform infrared, and nuclear magnetic resonance spectroscopy.

WOX2 functions redundantly with WOX1 and WOX4 to positively regulate seed germination in Arabidopsis.

WOX family gene WOX2 is highly expressed during seed development, which functions redundantly with WOX1 and WOX4 to positively regulate seed germination. WOX (WUSCHEL-related homeobox) is a family of transcription factors in plants. They play essential roles in the regulation of plant growth and development, but their function in seed germination is not well understood. In this report, we show that WOX1, WOX2, and WOX4 are close homologues in Arabidopsis. WOX2 has a redundant function with WOX1 and WOX4, respectively, in seed germination. WOX2 is highly expressed during seed development, from the globular embryonic stage to mature dry seeds, and its expression is decreased after germination. Loss of function single mutant wox2, and double mutants wox1 wox2 and wox2 wox4-1 show decreased germination speed. WOX2 and WOX4 are essential for hypocotyl-radicle zone elongation during germination, potentially by promoting the expression of cell wall-related genes. We also found that WOX2 and WOX4 regulate germination through the gibberellin (GA) pathway. These results suggest that WOX2 and WOX4 integrate the GA pathway and downstream cell wall-related genes during germination.

GhCTSF1, a short PPR protein with a conserved role in chloroplast development and photosynthesis, participates in intron splicing of rpoC1 and ycf3-2 transcripts in cotton

Cotton is one of the most important textile fibers worldwide. As crucial agronomic traits, leaves play an essential role in the growth, disease resistance, fiber quality, and yield of cotton plants. Pentatricopeptide repeat (PPR) proteins are a large family of nuclear-encoded proteins involved in organellar or nuclear RNA metabolism. Using a virus-induced gene silencing assay, we found that cotton plants displayed variegated yellow leaf phenotypes with decreased chlorophyll content when expression of the PPR gene GhCTSF1 was silenced. GhCTSF1 encodes a chloroplast-localized protein that contains only two PPR motifs. Disruption of GhCTSF1 substantially reduces the splicing efficiency of rpoC1 intron 1 and ycf3 intron 2. Loss of function of the GhCTSF1 ortholog EMB1417 causes splicing defects in rpoC1 and ycf3-2, leading to impaired chloroplast structure and decreased photosynthetic rates in Arabidopsis. We also found that GhCTSF1 interacts with two splicing factors, GhCRS2 and GhWTF1. Defects in GhCRS2 and GhWTF1 severely affect intron splicing of rpoC1 and ycf3-2 in cotton, leading to defects in chloroplast development and a reduction in photosynthesis. Our results suggest that GhCTSF1 is specifically required for splicing rpoC1 and ycf3-2 in cooperation with GhCRS2 and GhWTF1.

Progranulin and neuropathological features of Alzheimer’s disease: longitudinal study

BackgroundProgranulin is an anti-inflammatory protein that plays an essential role in the synapse function and the maintenance of neurons in the central nervous system (CNS). It has been shown that the CSF level of progranulin increases in Alzheimer’s disease (AD) patients and is associated with the deposition of amyloid-beta (Aβ) and tau in the brain tissue. In this study, we aimed to assess the longitudinal changes in cerebrospinal fluid (CSF) progranulin levels during different pathophysiological stages of AD and investigate associated AD pathologic features.MethodsWe obtained the CSF and neuroimaging data of 1001 subjects from the ADNI database. The participants were classified into four groups based on the A/T/N framework: A + /TN + , A + /TN−, A−/TN + , and A−/TN−.ResultsBased on our analysis there was a significant difference in CSF progranulin (P = 0.001) between ATN groups. Further ANOVA analysis revealed that there was no significant difference in the rate of change of CSF-progranulin ATN groups. We found that the rate of change of CSF progranulin was associated with baseline Aβ-PET only in the A−/TN + group. A significant association was found between the rate of change of CSF progranulin and the Aβ-PET rate of change only in A−/TN + ConclusionOur findings revealed that an increase in CSF progranulin over time is associated with faster formation of Aβ plaques in patients with only tau pathology based on the A/T/N classification (suspected non-Alzheimer’s pathology). Together, our findings showed that the role of progranulin-related microglial activity on AD pathology can be stage-dependent, complicated, and more prominent in non-AD pathologic changes. Thus, there is a need for further studies to consider progranulin-based therapies for AD treatment.

Patient and public involvement in the development of the digital tool MyBoT to support communication between young people with a chronic condition and care providers.

To guide good practices in patient and public involvement (PPI), several calls have been made to share detailed accounts of practical experiences. We describe our collaboration with young people with a chronic condition (YPCC) in the development, testing and implementation of the digital communication tool MyBoT (Map your Burden of Treatment). MyBoT was developed by a team of academic researchers, some of whom were practising care providers, YPCC and designers. In addition to the two co-researchers in the research team, various groups of YPCC were involved in decision-making through participation in a design session, workshops and a dialogue session. The Involvement Matrix was used to reflect on the PPI of all YPCC. Initially, the two co-researchers were involved in the roles of informer and co-thinker, but their decision-making power within the study increased over time. In the final stages of the study, the co-researchers and researchers became partners. The other YPCC who participated in the different sessions and workshops were co-thinkers in all stages of the study. The PPI of two YPCCsas co-researchers within the research team ensured continuous involvement, whereas the PPI of various groups of YPCCsguaranteed a representative and inclusive approach. Researchers play an essential role in bringing all perspectives together, integrating them within the technical and financial constraints and ultimately building a tool that is tailored to its users' needs. YPCC played a significant role in the present study. Two YPCC-who are also co-authors of this paper-were involved in all stages of this project as members of the research team. In addition, various YPCCswere involved in the development, testing and implementation stage of MyBoT by organizing design sessions, workshops and a dialogue session.

Dihalogenated nitrophenols in drinking water: Prevalence, resistance to household treatment, and cardiotoxic impact on zebrafish embryo

Dihalogenated nitrophenols (2,6-DHNPs), an emerging group of aromatic disinfection byproducts (DBPs) detected in drinking water, have limited available information regarding their persistence and toxicological risks. The present study found that 2,6-DHNPs are resistant to major drinking water treatment processes (sedimentation and filtration) and households methods (boiling, filtration, microwave irradiation, and ultrasonic cleaning). To further assess their health risks, we conducted a series of toxicology studies using zebrafish embryos as the model organism. Our findings reveal that these emerging 2,6-DHNPs showed lethal toxicity 248 times greater than that of the regulated DBP, dichloroacetic acid. Specifically, at sublethal concentrations, exposure to 2,6-DHNPs generated reactive oxygen species (ROS), caused apoptosis, inhibited cardiac looping, and induced cardiac failure in zebrafish. Remarkably, the use of a ROS scavenger, N-acetyl-l-cysteine, considerably mitigated these adverse effects, emphasizing the essential role of ROS in 2,6-DHNP-induced cardiotoxicity. Our findings highlight the cardiotoxic potential of 2,6-DHNPs in drinking water even at low concentrations of 19 μg/L and the beneficial effect of N-acetyl-l-cysteine in alleviating the 2,6-DHNP-induced cardiotoxicity. This study underscores the urgent need for increased scrutiny of these emerging compounds in public health discussions.