A taxonomy of cyber risk taxonomies.

The field of cyber risks is rapidly expanding, yet significant research remains to be conducted. Numerous taxonomy-based systems have been proposed in both the academic literature and industrial practice to classify cyber risk threats. However, the fragmentation of various approaches has resulted in a plethora of taxonomies, often incongruent with one another. In this study, we undertake a comprehensive review of these alternative taxonomies and offer a common framework for their classification based on their scope. Furthermore, we introduce desirable properties of a taxonomy, which enable comparisons of different taxonomies with the same scope. Finally, we discuss the managerial implications stemming from the utilization of each taxonomy class to support decision-making processes.

Green synthesis of biomass-derived carbon quantum dots for photocatalytic degradation of methylene blue.

Water pollution, significantly influenced by the discharge of synthetic dyes from industries, such as textiles, poses a persistent global threat to human health. Among these dyes, methylene blue, particularly prevalent in the textile sector, exacerbates this issue. This study introduces an innovative approach to mitigate water pollution through the synthesis of nanomaterials using biomass-derived carbon quantum dots (CQDs) from grape pomace and watermelon peel. Utilizing the hydrothermal method at temperatures between 80 and 160 °C over periods ranging from 1 to 24 h, CQDs were successfully synthesized. A comprehensive characterization of the CQDs was performed using UV-visible spectroscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, Raman spectroscopy, and luminescence spectroscopy, confirming their high quality. The photocatalytic activity of the CQDs in degrading methylene blue was evaluated under both sunlight and incandescent light irradiation, with measurements taken at 20 min intervals over a 2 h period. The CQDs, with sizes ranging from 1-10 nm, demonstrated notable optical properties, including upconversion and down-conversion luminescence. The results revealed effective photocatalytic degradation of methylene blue under sunlight, highlighting the potential for scalable production of these cost-effective catalytic nanomaterials for synthetic dye degradation.

[Ag(IPr)(bpy)][PF6]: brightness and darkness playing with aggregation induced phosphorescence for light-emitting electrochemical cells.

Heteroleptic silver(I) complexes have recently started to attract attention in thin-film lighting technologies as an alternative to copper(I) analogues due to the lack of flattening distortion upon excitation. However, the interpretation of their photophysical behavior is challenging going from traditional fluorescence/phosphorescence to a temperature-dependent dual emission mechanism and ligand-lock assisted thermally activated delayed fluorescence. Herein, we unveil the photoluminescence behavior of a three-coordinated Ag(I) complex with the N-heterocyclic carbene (NHC) ligand and 2,2'-bipyridine (bpy) as the N^N ligand. In contrast to its low-emissive Cu(I) complex structural analogues, a strong greenish emission was attributed to the presence of aggregates formed by π-π intermolecular interactions as revealed by the X-ray structure and aggregation induced emission (AIE) studies in solution. In addition, the temperature-dependent time-resolved spectroscopic and computational studies demonstrated that the emission mechanism is related to a phosphorescence emission mechanism of two very close lying (ΔE = 0.08 eV) excited triplet states, exhibiting a similar delocalized nature over the bipyridine ligands. Unfortunately, this favourable AIE is lost upon forming homogeneous thin films suitable for lighting devices. Though the films showed very poor emission, the electrochemical stability under device operation conditions is remarkable compared to the prior-art, highlighting the potential of [Ag(NHC)(N^N)][X] complexes in thin-film lighting.

Primary cutaneous EBV+ extranodal NK/T-cell lymphoma of gamma/delta T-cell lineage in the posttransplantation setting.

Posttransplantation primary cutaneous T-cell lymphomas (PT-CTCL) are a rare complication of sustained immunosuppression in the posttransplant setting. When present, PT-CTCLs are typically EBV- and exhibit features of mycosis fungoides/Sézary syndrome or CD30+ lymphoproliferative disorders. We present a case of a 75-year-old individual who developed skin lesions 30 years after liver transplantation. Pathologic evaluation of the skin biopsy revealed involvement by a clonal, EBV+ T-cell population of gamma/delta lineage with no evidence of systemic disease. Comprehensive genomic profiling was performed, confirming focal one-copy loss of 6q23.3, altogether consistent with the extremely rare and unusual diagnosis of primary cutaneous EBV+ extranodal NK/T-cell lymphoma of gamma/delta T-cell lineage in the posttransplantation setting.

Screening of the Skin-Regenerative Potential of Antimicrobial Peptides: Clavanin A, Clavanin-MO, and Mastoparan-MO.

Skin wound healing is coordinated by a delicate balance between proinflammatory and anti-inflammatory responses, which can be affected by opportunistic pathogens and metabolic or vascular diseases. Several antimicrobial peptides (AMPs) possess immunomodulatory properties, suggesting their potential to support skin wound healing. Here, we evaluated the proregenerative activity of three recently described AMPs (Clavanin A, Clavanin-MO, and Mastoparan-MO). Human primary dermal fibroblasts (hFibs) were used to determine peptide toxicity and their capacity to induce cell proliferation and migration. Furthermore, mRNA analysis was used to investigate the modulation of genes associated with skin regeneration. Subsequently, the regenerative potential of the peptides was further confirmed using an ex vivo organotypic model of human skin (hOSEC)-based lesion. Our results indicate that the three molecules evaluated in this study have regenerative potential at nontoxic doses (i.e., 200 µM for Clavanin-A and Clavanin-MO, and 6.25 µM for Mastoparan-MO). At these concentrations, all peptides promoted the proliferation and migration of hFibs during in vitro assays. Such processes were accompanied by gene expression signatures related to skin regenerative processes, including significantly higher KI67, HAS2 and CXCR4 mRNA levels induced by Clavanin A and Mastoparan-MO. Such findings translated into significantly accelerated wound healing promoted by both Clavanin A and Mastoparan-MO in hOSEC-based lesions. Overall, the data demonstrate the proregenerative properties of these peptides using human experimental skin models, with Mastoparan-MO and Clavanin A showing much greater potential for inducing wound healing compared to Clavanin-MO.

Stable and efficient rare-earth free phosphors based on an Mg(II) metal-organic framework for hybrid light-emitting diodes.

Stable and efficient green hybrid light-emitting diodes (HLEDs) were fabricated from a highly emissive Mg(II)-tetraphenyl ethylene derivative metal-organic framework embedded in a polystyrene matrix (Mg-TBC MOF@PS). The photoluminescence quantum yield (ϕ) of the material, >80%, remains constant upon polymer embedment. The resulting HLEDs featured high luminous efficiencies of >50 lm W-1 and long lifetimes of >380 h, making them among the most stable MOF-based HLEDs. The significance of this work relies on the combination of many features, such as the abundance of the metal ion, the straightforward scalability of the synthetic protocol, the great ϕ reached upon phosphor fabrication, and the state-of-the-art HLED performances.

EDucated: The emergency medicine pharmacotherapy literature of 2023.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2023. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the collective group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 6 guidelines, and 5 meta-analyses covering topics including guideline releases and updates on rapid sequence intubation in the critically ill, managing cardiac arrest or life-threatening toxicity due to poisoning, and management of major bleeding following trauma. Also discussed are ongoing controversies surrounding fluid resuscitation, time and treatment modalities for ischemic stroke, steroid use in community-acquired pneumonia, targeted blood product administration, and much more.

Neurophysiologically Meaningful Motor Imagery EEG Simulation With Applications to Data Augmentation.

Motor imagery-based Brain-Computer Interfaces (MI-BCIs) have gained a lot of attention due to their potential usability in neurorehabilitation and neuroprosthetics. However, the accurate recognition of MI patterns in electroencephalography signals (EEG) is hindered by several data-related limitations, which restrict the practical utilization of these systems. Moreover, leveraging deep learning (DL) models for MI decoding is challenged by the difficulty of accessing user-specific MI-EEG data on large scales. Simulated MI-EEG signals can be useful to address these issues, providing well-defined data for the validation of decoding models and serving as a data augmentation approach to improve the training of DL models. While substantial efforts have been dedicated to implementing effective data augmentation strategies and model-based EEG signal generation, the simulation of neurophysiologically plausible EEG-like signals has not yet been exploited in the context of data augmentation. Furthermore, none of the existing approaches have integrated user-specific neurophysiological information during the data generation process. Here, we present PySimMIBCI, a framework for generating realistic MI-EEG signals by integrating neurophysiologically meaningful activity into biophysical forward models. By means of PySimMIBCI, different user capabilities to control an MI-BCI can be simulated and fatigue effects can be included in the generated EEG. Results show that our simulated data closely resemble real data. Moreover, a proposed data augmentation strategy based on our simulated user-specific data significantly outperforms other state-of-the-art augmentation approaches, enhancing DL models performance by up to 15%.

Plant Virus-Like Particles for RNA Delivery.

Plant viruses such as brome mosaic virus and cowpea chlorotic mottle virus are effectively purified through PEG precipitation and sucrose cushion ultracentrifugation. Increasing ionic strength and an alkaline pH cause the viruses to swell and disassemble into coat protein subunits. The coat proteins can be reassembled into stable virus-like particles (VLPs) that carry anionic molecules at low ionic strength and through two-step dialysis from neutral pH to acidic buffer. VLPs have been extensively studied due to their ability to protect and deliver cargo, particularly RNA, while avoiding degradation under physiological conditions. Furthermore, chemical functionalization of the surface of VLPs allows for the targeted drug delivery. VLPs derived from plants have demonstrated great potential in nanomedicine by offering a versatile platform for drug delivery, imaging, and therapeutic applications.

"R" you getting this? Factors contributing to the public's understanding, evaluation, and use of basic reproduction numbers for infectious diseases.

BACKGROUND: We (1) examined the effects of evaluative labels and visual aids on people's understanding, evaluation, and use of the COVID-19 reproduction number (or "r-number"), (2) examined whether people's perceived susceptibility and (intended) adherence to preventive measures changed after being exposed to the r-number, and (3) explored whether these effects and changes depended on people's numeracy skills. METHODS: In an online experiment, participants from a large Dutch representative sample (N = 1,168) received information about the COVID-19 r-number displayed on the corona dashboard of the Dutch Ministry of Health, Welfare and Sport. The r-number was either presented with or without a categorical line display (i.e., evaluative label) and with or without an icon-based tree diagram (i.e., visual aid) explaining how the number works. Regarding people's use of the statistic, we measured perceived susceptibility to COVID-19 and adherence (intention) to five preventive measures before and after exposure to the r-number. After exposure, we also measured participants' understanding, perceived usefulness, affective and cognitive evaluation, and objective numeracy. RESULTS: About 56% of participants correctly interpreted the r-number, with highly numerate people having better understanding than less numerate people. Information about the r-number was perceived as more useful when presented with a visual aid. There were no differences across experimental conditions in people's understanding, affective, and cognitive evaluations. Finally, independent of experimental conditions, intention to adhere to preventive measures was higher after seeing the r-number, but only among highly numerate people. CONCLUSIONS: Although evaluative labels and visual aids did not facilitate people's understanding and evaluation of the r-number, our results show that the statistic is perceived as useful and may be used to stimulate adherence to preventive measures. Policy makers and public health communicators are advised to clearly explain why they are giving these numbers to - especially - the less numerate people, but also how people could use them for behavior change to combat the spread of virus during a pandemic.

JNK signaling and its impact on neural cell maturation and differentiation.

C-Jun-N-terminal-kinases (JNKs), members of the mitogen-activated-protein-kinase family, are significantly linked with neurological and neurodegenerative pathologies and cancer progression. However, JNKs serve key roles under physiological conditions, particularly within the central-nervous-system (CNS), where they are critical in governing neural proliferation and differentiation during both embryogenesis and adult stages. These processes control the development of CNS, avoiding neurodevelopment disorders. JNK are key to maintain the proper activity of neural-stem-cells (NSC) and neural-progenitors (NPC) that exist in adults, which keep the convenient brain plasticity and homeostasis. This review underscores how the interaction of JNK with upstream and downstream molecules acts as a regulatory mechanism to manage the self-renewal capacity and differentiation of NSC/NPC during CNS development and in adult neurogenic niches. Evidence suggests that JNK is reliant on non-canonical Wnt components, Fbw7-ubiquitin-ligase, and WDR62-scaffold-protein, regulating substrates such as transcription factors and cytoskeletal proteins. Therefore, understanding which pathways and molecules interact with JNK will bring knowledge on how JNK activation orchestrates neuronal processes that occur in CNS development and brain disorders.

It is, uh, very likely? The impact of prosodic uncertainty cues on the perception and interpretation of spoken verbal probability phrases.

People typically use verbal probability phrases when discussing risks ("It is likely that this treatment will work"), both in written and spoken communication. When speakers are uncertain about risks, they can nonverbally signal this uncertainty by using prosodic cues, such as a rising, question-like intonation or a filled pause ("uh"). We experimentally studied the effects of these two prosodic cues on the listener's perceived speaker certainty and numerical interpretation of spoken verbal probability phrases. Participants (N = 115) listened to various verbal probability phrases that were uttered with a rising or falling global intonation and with or without a filled pause before the probability phrase. For each phrase, they gave a point estimate of their numerical interpretation in percentages and indicated how certain they thought the speaker was about the correctness of the probability phrase. Speakers were perceived as least certain when the verbal probability phrases were spoken with both prosodic uncertainty cues. Interpretation of verbal probability phrases varied widely across participants, especially when rising intonation was produced by the speaker. Overall, high probability phrases (e.g., "very likely") were estimated as lower (and low probability phrases, such as "unlikely," as higher) when they were uttered with a rising intonation. The effects of filled pauses were less pronounced, as were the uncertainty effects for medium probability phrases (e.g., "probable"). These results stress the importance of nonverbal communication when verbally communicating risks and probabilities to people, for example, in the context of doctor-patient communication.

Targeted Demethylation of FOXP3-TSDR Enhances the Suppressive Capacity of STAT6-deficient Inducible T Regulatory Cells.

In vitro induced T regulatory cells (iTregs) are promising for addressing inflammation-driven diseases. However, current protocols for the generation and expansion of iTregs fail to induce extensive demethylation of the Treg-specific demethylated region (TSDR) within the FOXP3 gene, recognized as the master regulator for regulatory T cells (Tregs). This deficiency results in the rapid loss of Foxp3 expression and an unstable regulatory phenotype. Nevertheless, inhibition of STAT6 signaling effectively stabilizes Foxp3 expression in iTregs. Thus, this study aimed to develop a protocol combining epigenetic editing with STAT6 deficiency to improve iTregs' ability to maintain stable suppressive function and a functional phenotype. Our findings demonstrate that the combination of STAT6 deficiency (STAT6-/-) with targeted demethylation of the TSDR using a CRISPR-TET1 tool leads to extensive demethylation of FOXP3-TSDR. Demethylation in STAT6-/- iTregs was associated with enhanced expression of Foxp3 and suppressive markers such as CTLA-4, PD-1, IL-10, and TGF-ß. Furthermore, the edited STAT6-/- iTregs exhibited an increased capacity to suppress CD8+ and CD4+ lymphocytes and could more efficiently impair Th1-signature gene expression compared to conventional iTregs. In conclusion, the deactivation of STAT6 and TSDR-targeted demethylation via CRISPR-TET1 is sufficient to induce iTregs with heightened stability and increased suppressive capacity, offering potential applications against inflammatory and autoimmune diseases.

CD8 T cells are dispensable for experimental autoimmune prostatitis induction and chronic pelvic pain development.

Introduction: Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied. Methods: We herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals. Results: We found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions. Discussion: Our results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.

Molecular determinants for brain targeting by peptides: a meta-analysis approach with experimental validation.

Blood-brain barrier (BBB) peptide-shuttles (BBBpS) are able to translocate the BBB and reach the brain. Despite the importance of brain targeting in pharmacology, BBBpS are poorly characterized. Currently, their development relies on the empiric assumption that cell-penetrating peptides (CPPs), with proven ability to traverse lipid membranes, will likewise behave as a BBBpS. The relationship between CPPs/BBBpS remains elusive and, to the best of our knowledge, has not hitherto been subject to thorough experimental scrutiny. In this work, we have identified/quantified the main physicochemical properties of BBBpS and then searched for CPPs with these properties, hence potential BBBpS. The specific features found for BBBpS are: (i) small size, (ii) none or few aromatic residues, (iii) hydrophobic, and (iv) slight cationic nature. Then, we selected the 10 scoring best in an ordinary least squares analysis, and tested them in vitro and in vivo. Overall, we identified the molecular determinants for brain targeting by peptides, devised a methodology that can be used to assist in the design of peptides with potential brain penetration from amino acid residue sequences, and found four new BBBpS within the CPP library.

Atypical Presentation of Retroperitoneal Fibrosis Causing Colonic Obstruction: A Case Report.

Retroperitoneal fibrosis (RPF), also referred to as Ormond's disease, is a rare fibroinflammatory condition characterized by abnormal fibrous tissue deposition in the retroperitoneal space, which traditionally presents with ureteral obstruction. Nonetheless, our case report showcases an exceptional instance involving a 70-year-old female patient who presented with symptoms suggestive of colonic obstruction, an unusual presentation that is not commonly associated with RPF. Although RPF has established associations with autoimmune conditions such as immunoglobulin G4-related disease and systemic lupus erythematosus, its connection to colonic obstruction remains undocumented in the medical literature. Our patient is a 70-year-old female who presented with constipation, anemia, and fecal occult blood. Her past medical history included a hysterectomy due to fibroids, right breast lumpectomy, type 2 diabetes mellitus, subclinical hyperthyroidism, hypertension, and obesity. Upon physical examination, the patient's abdomen appeared protuberant but was non-tender to palpation. Bowel sounds were normal, and there was no distension. Notably, there was no tenderness in the right or left costovertebral angles, nor was there any guarding. Workup with colonoscopy could not be completed due to the inability to pass a colonoscope beyond the rectosigmoid junction. Further workup with barium enema confirmed an apple core lesion seen in the rectosigmoid concerning for a neoplastic or inflammatory process. Finally, a computed tomography scan of the abdomen and pelvis showed a 7.1 cm right pelvic mass attached to the bladder and cecum, moderate right hydroureteronephrosis, and a 5.2 cm left adnexal mass with soft tissue changes narrowing the sigmoid colon. The next step was to take the patient for an exploratory laparotomy. During exploratory laparotomy, extensive adhesions and desmoplastic reactions were observed in the pelvic region, involving the sigmoid colon, bladder, cecum, and appendix. Two firm masses were identified in the retroperitoneum, one located in the left lower quadrant (LLQ) adherent to the posterior wall of the sigmoid colon and one in the right lower quadrant (RLQ) adherent to the posterior wall of the cecum. Three specimens were sent to pathology for further examination: a portion of the sigmoid colon, a resection from the RLQ mass, and a resection from the LLQ mass. Pathology reported dense fibrotic masses with abscess-like formation, reactive in nature and of unclear etiology, and negative for malignancy. They were negative for fibromatosis (ß-catenin negative), and IgG4+/IgG+ was approximately 5%. Interestingly, the LLQ mass also contained remnants of the fallopian tube and ovary and benign cystic changes. This case report presents a unique and atypical presentation of RPF, deviating from the conventional presentation of ureteral obstruction. The patient's initial symptoms suggested colonic obstruction, a clinical scenario rarely linked to RPF. This case underscores the significance of considering diverse clinical presentations when diagnosing RPF, thereby expanding our comprehension of the condition's clinical spectrum and ultimately refining patient care and management.

Simple Sol-Gel Protein Stabilization toward Rainbow and White Lighting Devices.

Fluorescent proteins (FPs) are heralded as a paradigm of sustainable materials for photonics/optoelectronics. However, their stabilization under non-physiological environments and/or harsh operation conditions is the major challenge. Among the FP-stabilization methods, classical sol-gel is the most effective, but less versatile, as most of the proteins/enzymes are easily degraded due to the need of multi-step processes, surfactants, and mixed water/organic solvents in extreme pH. Herein, sol-gel chemistry with archetypal FPs (mGreenLantern; mCherry) is revisited, simplifying the method by one-pot, surfactant-free, and aqueous media (phosphate buffer saline pH = 7.4). The synthesis mechanism involves the direct reaction of the carboxylic groups at the FP surface with the silica precursor, generating a positively charged FP intermediate that acts as a seed for the formation of size-controlled mesoporous FP@SiO2 nanoparticles. Green-/red-emissive (single-FP component) and dual-emissive (multi-FPs component; kinetic studies not required) FP@SiO2 are prepared without affecting the FP photoluminescence and stabilities (>6 months) under dry storage and organic solvent suspensions. Finally, FP@SiO2 color filters are applied to rainbow and white bio-hybrid light-emitting diodes featuring up to 15-fold enhanced stabilities without reducing luminous efficacy compared to references with native FPs. Overall, an easy, versatile, and effective FP-stabilization method is demonstrated in FP@SiO2 toward sustainable protein lighting.

The use of a selective, nontoxic dual-acting peptide for breast cancer patients with brain metastasis.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of commonly targeted receptors. Unspecific chemotherapy is currently the main therapeutic option, with poor results. Another major challenge is the frequent appearance of brain metastasis (BM) associated with a significant decrease in patient overall survival. The treatment of BM is even more challenging due to the presence of the blood-brain barrier (BBB). Here, we present a dual-acting peptide (PepH3-vCPP2319) designed to tackle TNBC/BM, in which a TNBC-specific anticancer peptide (ACP) motif (vCPP2319) is joined to a BBB peptide shuttle (BBBpS) motif (PepH3). PepH3-vCPP2319 demonstrated selectivity and efficiency in eliminating TNBC both in monolayers (IC50≈5.0 µM) and in spheroids (IC50≈25.0 µM), with no stringent toxicity toward noncancerous cell lines and red blood cells (RBCs). PepH3-vCPP2319 was also able to cross the BBB in vitro and penetrate the brain in vivo, and was stable in serum with a half-life above 120 min. Tumor cell-peptide interaction is fast, with quick peptide internalization via clathrin-mediated endocytosis without membrane disruption. Upon internalization, the peptide is detected in the nucleus and the cytoplasm, indicating a multi-targeted mechanism of action that ultimately induces irreversible cell damage and apoptosis. In conclusion, we have designed a dual-acting peptide capable of brain penetration and TNBC cell elimination, thus expanding the drug arsenal to fight this BC subtype and its BM.