Genetic Manipulation and Extended Culture of Human Germinal Center B Cells to Model Lymphomagenesis.

The germinal center (GC) is the stage of B cell differentiation that gives rise to a majority of B cell lymphomas. Here, we present an experimental coculture system for the ex vivo expansion and genetic manipulation of human GC B cells purified from discarded tonsil tissue. This system can be used to investigate the impact of defined genetic alterations, either individually or in combination, upon the growth and survival of human GC B cells in vitro. We provide examples of genetic combinations that lead to the immortalized growth of GC B cells in vitro, and others that result in malignant transformation in immunodeficient mice, allowing the creation of genetically bespoke, synthetic, human lymphoma models.

Deletions Rate-Limit Breast and Ovarian Cancer Initiation.

Optimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germline BRCA1 and BRCA2 (gBRCA1/2) carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors. gBRCA1/2 -driven hereditary and sporadic tumors undergo convergent evolution to develop a similar set of driver deletions, and deletions explain the elevated cancer risk of gBRCA1/2 -carriers. Orthogonal mutation timing analysis identifies deletions of chromosome 17 and 13q as early, recurrent events. Single-cell analyses confirmed deletion rate differences in gBRCA1/2 vs. non-carrier tumors as well as cells engineered to harbor gBRCA1/2 . The centrality of deletion-associated chromosomal instability to tumorigenesis shapes interpretation of the somatic evolution of non-malignant tissue and guides strategies for precision prevention and early detection.

Anxious/depressed individuals exhibit disrupted frontotemporal synchrony during cognitive conflict encoding.

Anxiety and depressive disorders are associated with cognitive control deficits, yet their underlying neural mechanisms remain poorly understood. Here, we used high-resolution stereotactic EEG (sEEG) to determine how anxiety and/or depression modulates neural and behavioral responses when cognitive control is engaged in individuals with medically refractory epilepsy undergoing sEEG monitoring for surgical evaluation. We analyzed sEEG data recorded from frontotemporal regions of 29 participants (age range: 19-55, mean age: 35.5, female: 16/29) while they performed a Multi-Source Interference Task (MSIT) designed to elicit cognitive conflict. Neurobehavioral interviews, symptom rating scales, and clinical documentation were used to categorize participants as demonstrating anxiety and/or depression symptoms (A/D, n=13) or as epilepsy controls (EC, n=16). Generalized linear mixed-effects (GLME) models were used to analyze behavioral and neural data. Models of oscillatory power were used to identify brain regions within conflict-encoding networks in which coherence and phase locking values (PLV) were examined in A/D and EC. A/D participants demonstrated a greater conflict effect (response time slowing with higher cognitive load), without impairment in response time (RT) or accuracy compared to EC. A/D participants also showed significantly enhanced conflict-evoked theta (4-8Hz) and alpha (8-15Hz) power in the dorsolateral prefrontal cortex (dlPFC) and amygdala as well as widespread broadband activity in the lateral temporal lobe (LTL) compared to EC. Additionally, theta coherence and PLV between dlPFC-LTL and dlPFC-amygdala were reduced by conflict in A/D. Our findings suggest individuals with anxiety/depression symptoms exhibit heightened frontotemporal oscillatory activity and disrupted frontotemporal synchrony during cognitive conflict encoding, which may indicate a greater need for cognitive resources due to ineffective cognitive processing. These results highlight a potential role of frontotemporal circuits in conflict encoding that are altered in anxiety/depression, and may further inform future therapeutic interventions aimed at enhancing cognitive control in these populations.

The YTHDF Proteins Shape the Brain Gene Signatures of Alzheimer's Disease.

The gene signatures of Alzheimer's Disease (AD) brains reflect an output of a complex interplay of genetic, epigenetic, epi-transcriptomic, and post-transcriptional regulations. To identify the most significant factor that shapes the AD brain signature, we developed a machine learning model (DEcode-tree) to integrate cellular and molecular factors explaining differential gene expression in AD. Our model indicates that YTHDF proteins, the canonical readers of N6-methyladenosine RNA modification (m6A), are the most influential predictors of the AD brain signature. We then show that protein modules containing YTHDFs are downregulated in human AD brains, and knocking out YTHDFs in iPSC-derived neural cells recapitulates the AD brain gene signature in vitro . Furthermore, eCLIP-seq analysis revealed that YTHDF proteins influence AD signatures through both m6A-dependent and independent pathways. These results indicate the central role of YTHDF proteins in shaping the gene signature of AD brains.

Genetically-Encoded Fluorescence Barcodes for Single-Cell Analysis.

Genetically-encoded, single-cell barcodes are broadly useful for experimental tasks such as lineage tracing or genetic screens. For such applications, a barcode library would ideally have high diversity (many unique barcodes), non-destructive identification (repeated measurements in the same cells or population), and fast, inexpensive readout (many cells and conditions). Current nucleic acid barcoding methods generate high diversity but require destructive and slow/expensive readout, and current fluorescence barcoding methods are non-destructive, fast, and inexpensive to readout but lack high diversity. We recently proposed theory for how fluorescent protein combinations may generate a high-diversity barcode library with non-destructive, fast and inexpensive identification. Here, we present an initial experimental proof-of-concept by generating a library of ~150 barcodes from two-way combinations of 18 fluorescent proteins. We use a pooled cloning strategy to generate a barcode library that is validated to contain every possible combination of the 18 fluorescent proteins. Experimental results using single mammalian cells and spectral flow cytometry demonstrate excellent classification performance of individual fluorescent proteins, with the exception of mTFP1, and of most evaluated barcodes, with many true positive rates >99%. The library is compatible with genetic screening for hundreds of genes (or gene pairs) and lineage tracing hundreds of clones. This work lays a foundation for greater diversity libraries (potentially ~10 5 and more) generated from hundreds of spectrally-resolvable tandem fluorescent protein probes.

Perioperative mortality in low-, middle-, and high-income countries: Protocol for a multi-level meta-regression analysis.

BACKGROUND: Surgery is an indispensable component of a functional healthcare system. To date there is limited information regarding how many people die during the perioperative period globally. This study describes a protocol for a systematic review and multilevel meta-regression to evaluate time trends regarding the odds of perioperative mortality among adults undergoing a bellwether surgical procedure while accounting for higher order clustering at the national level. METHODS: Published studies reporting the number of perioperative deaths from bellwether surgical procedures among adults will be identified from MEDLINE, Embase, Cochrane CENTRAL, LILACS and Global Index Medicus. The primary outcome will be the rate of perioperative mortality across time and the secondary outcome will be investigating cause of death over time as a proportion of overall perioperative mortality. Two reviewers will independently conduct full text screening and extract the data. Disagreements will first be resolved via consensus. If consensus cannot be reached a third reviewer will be included to arbitrate. Due to human resource limitations, a risk of bias appraisal will not be conducted. From the included studies a multilevel meta-regression will be constructed to synthesize the results. This model will conceptualize patients as nested in studies which are in turn nested within countries while taking into account potential confounding variables at all levels. DISCUSSION: The systematic review and multilevel meta-regression that will be conducted based on this protocol will provide synthesized global evidence regarding the trends of perioperative mortality. This eventual study may help policymakers and other key stakeholders with benchmarking surgical safety initiatives as well as identify key gaps in our current understanding of global perioperative mortality. TRIAL REGISTRATION: Systematic review registration: PROSPERO registration number 429040.

Shifting from a female-dominated profession: The perceptions and experiences of male students in communication sciences and disorders.

INTRODUCTION: A longstanding aim of the American Speech and Hearing Association is to diversify professional representation. Despite their efforts, a prevalent disparity in male representation persists. The purpose of this study is to explore the experiences of males currently enrolled in a speech-language pathology (SLP) program to better understand barriers to entering the field and identify ways to increase the number of males practicing as speech-language pathologists. METHOD: Twenty-one male students enrolled in an undergraduate or graduate SLP program in the United States participated in four focus group discussions. The 60 minute semi-structured interviews held virtually were recorded and transcribed verbatim. Data were analyzed thematically from an experiential orientation using an inductive approach grounded in the data to explore male experiences and perspectives as an underrepresented student in the program. RESULTS: The analysis generated three themes: (1) Harnessing Heterogeneity, (2) Building Community and a Supportive Infrastructure, and (3) Infectious Attitudes and Perception. The experiences highlight the strengths and shortcomings of the profession and reveal the cultural landscape. CONCLUSIONS: The findings reinforce the need for outreach efforts to increase awareness of the profession and highlight the importance of mentoring programs to provide the support and guidance needed for success.

Mucoadhesion across scales: Towards the design of protein-based adhesives.

Mucoadhesion is a special case of bioadhesion in which a material adheres to soft mucosal tissues. This review elucidates our current understanding of mucoadhesion across length, time, and energy scales by focusing on relevant structural features of mucus. We highlight the importance of both covalent and non-covalent interactions that can be tailored to maximize mucoadhesive interactions, particularly concerning proteinaceous mucoadhesives, which have been explored only to a limited extent so far in the literature. In particular, we highlight the importance of thiol groups, hydrophobic moieties, and charged species inherent to proteins as key levers to fine tune mucoadhesive performance. Some aspects of protein surface modification by grafting specific functional groups or coupling with polysaccharides to influence mucoadhesive performance are examined. Insights from this review offer a physicochemical roadmap to inform the development of biocompatible, protein-based mucoadhesive systems that can fulfil dual roles for both adhesion and delivery of actives, enabling the fabrication of advanced biomedical, nutritional and allied soft material technologies.

Data-Driven Approach to Development of a Risk Score for Periprosthetic Joint Infections in Total Joint Arthroplasty Using Electronic Health Records.

BACKGROUND: Periprosthetic joint infection (PJI) is an uncommon, but serious complication in total joint arthroplasty. Personalized risk prediction and risk factor management may allow better preoperative assessment and improved outcomes. We evaluated different data-driven approaches to develop surgery-specific PJI prediction models using large-scale data from the electronic health records. METHODS: A large institutional arthroplasty registry was leveraged to collect data from 58,574 procedures of 41,844 patients who underwent at least one primary and/or revision hip and/or knee arthroplasty between 2000 and 2019. The registry dataset was augmented with additional clinical, procedural, and laboratory data from the electronic health records for more than 100 potential predictor variables. The main outcome was PJI within the first year after surgery. We implemented both traditional and machine learning methods for model development (lasso regression, relaxed lasso regression, ridge regression, random forest, stepwise regression, extreme gradient boosting, neural network) and used 10-fold cross-validation to calculate measures of model performance in terms of discrimination (c-statistic), cross-entropy loss, and calibration. RESULTS: All models performed similarly in predicting PJI risk, with negligible differences of less than 0.08 between the best and worst-performing models. The relaxed and fully relaxed lasso models using the Cox model structure outperformed the other models with concordances of 0.787 in primary hip arthroplasty and 0.722 in revision hip arthroplasty, with the number of predictors ranging from nine to 41. The concordances with the relaxed lasso models were 0.681 in primary and 0.699 in revision knee arthroplasty, with a higher number of predictors in the models. Predictors included in the models varied substantially across the four surgical groups. CONCLUSIONS: The incorporation of additional data from the electronic health records offers limited improvement in PJI risk stratification. Furthermore, improvement in PJI risk prediction was modest with the machine learning approaches and may not justify the added complexity.

An IL-2 mutein increases regulatory T cell suppression of dendritic cells via IL-10 and CTLA-4 to promote T cell anergy.

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3+ regulatory T (TR) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated TR population with elevated proliferation, a transcriptional program associated with Stat5- and T cell receptor-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface major histocompatibility complex class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 co-stimulatory ligands from maturing cDCs to TR cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes, resulting in T cell anergy. Thus, IL-2 mutein-expanded TR cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.

Rapid Whole-Plate Cell and Tissue Micropatterning Using a Budget 3D Resin Printer.

The ability to precisely pattern cells and proteins is crucial in various scientific disciplines, including cell biology, bioengineering, and materials chemistry. Current techniques, such as microcontact stamping, 3D bioprinting, and direct photopatterning, have limitations in terms of cost, versatility, and throughput. In this Article, we present an accessible approach that combines the throughput of photomask systems with the versatility of programmable light patterning using a low-cost consumer LCD resin printer. The method involves utilizing a bioinert hydrogel, poly(ethylene glycol) diacrylate (PEGDA), and a 405 nm sensitive photoinitiator (LAP) that are selectively cross-linked to form a hydrogel upon light exposure, creating specific regions that are protein and cell-repellent. Our result highlights that a low-cost LCD resin printer can project virtual photomasks onto the hydrogel, allowing for reasonable resolution and large-area printing at a fraction of the cost of traditional systems. The study demonstrates the calibration of exposure times for optimal resolution and accuracy and shape corrections to overcome the inherent challenges of wide-field resin printing. The potential of this approach is validated through widely studied 2D and 3D stem cell applications, showcasing its biocompatibility and ability to replicate complex tissue engineering patterns. We also validate the method with a cell-adhesive polymer (gelatin methacrylate; GelMA). The combination of low cost, high throughput, and accessibility makes this method broadly applicable across fields for enabling rapid and precise fabrication of cells and tissues in standard laboratory culture vessels.

A retrospective study of perianesthetic and sedation deaths in dogs and cats submitted to Canadian veterinary diagnostic laboratories.

Background: Perianesthetic death or sedation death in companion animals is an infrequent but devastating complication. Few studies have investigated the pathology associated with these deaths. Objective: To determine clinical features and postmortem findings for submissions to multiple Canadian diagnostic laboratories from perianesthetic/sedation deaths in dogs and cats. Animals and procedure: Laboratory Information Management Systems were retrospectively reviewed for cases of perianesthetic/sedation death in dogs and cats. Inclusion criteria were: i) whole-body submissions and ii) death within 7 d after the procedure. Results: Pathology reports determined the cause of death in 43% of dogs (73/168) and 34% of cats (50/147). Spay/neuter surgeries were the most common procedure for which animals were submitted (dogs: n = 72, 31%; cats: n = 111, 58%). The American Society of Anesthesiologists physical status in these animals was low (ASA status I or II) in 94% of dogs (68/72) and 93% of cats (103/111). Clinical history was considered incomplete in 60.3% of cases (242/401). Conclusion and clinical relevance: These results had similar trends to those in previous studies that identified an important proportion of submissions for perianesthetic/sedation deaths lacked significant lesions to explain the cause of death. This study also identified spay/neuter procedures were involved in the largest proportion of submissions, despite their low pre-anesthetic/sedation risk.

Étude rétrospective des décès par anesthésie et sédation chez les chiens et les chats soumis aux laboratoires de diagnostic vétérinaire canadiens. Contexte: La mort par anesthésie ou par sédation chez les animaux de compagnie est une complication rare mais dévastatrice. Peu d'études ont examiné la pathologie associée à ces décès. Objectif: Déterminer les caractéristiques cliniques et les trouvailles post-mortem des soumissions à plusieurs laboratoires de diagnostic canadiens à partir de décès par anesthésie/sédation chez les chiens et les chats. Animaux et procédure: Les systèmes de gestion des informations de laboratoire ont été examinés rétrospectivement pour les cas de décès par anesthésie/sédation chez les chiens et les chats. Les critères d'inclusion étaient : i) soumissions du corps entier et ii) décès dans les 7 jours suivant la procédure. Résultats: Les rapports de pathologie ont déterminé la cause du décès chez 43 % des chiens (73/168) et 34 % des chats (50/147). Les chirurgies de stérilisation étaient la procédure la plus courante pour laquelle les animaux étaient soumis (chiens : n = 72, 31 %; chats : n = 111, 58 %). L'état physique de ces animaux était pauvre selon les critères de l'American Society of Anesthesiologists (statut ASA I ou II) chez 94 % des chiens (68/72) et 93 % des chats (103/111). L'histoire clinique était considérée comme incomplète dans 60,3 % des cas (242/401). Conclusion et pertinence clinique: Ces résultats présentaient des tendances similaires à celles d'études précédentes qui avaient identifié une proportion importante de soumissions pour décès périanesthésiques/sédations qui manquaient de lésions significatives pour expliquer la cause du décès. Cette étude a également identifié que les procédures de stérilisation étaient impliquées dans la plus grande proportion de soumissions, malgré leur faible risque préanesthésique/sédation.(Traduit par Dr Serge Messier).

Public Board Score Reporting Undermines Holistic Review for Residency Selection.

Holistic review has become the gold standard for residency selection. As a result, many programs are de-emphasizing standardized exam scores and other normative metrics. However, if standardized exam scores predict passing of an initial certifying exam, this may lead to an increase in board failure rates within specific residency training programs who do not emphasize test scores on entry. Currently, the board pass rates of residency programs from many of the American Board of Medical Subspecialities (ABMS) are publicly reported as a rolling average. In theory, this should create accountability but may also create pressure and distort the way residency program selects applicants. The risk to programs of having a lower board pass rate publicly reported incentivizes programs to focus increasingly on standardized test scores, threatening holistic review. All programs do not recruit students entering residency with an identical chance of passing boards. Therefore, we believe the ABMS member boards should stop publicly reporting raw certifying exam rates above a certain threshold for normative comparison. We strongly encourage the use of learning analytics to create a residency "expected board pass rate" that would be a better metric for program evaluation and accreditation.

Roller compaction: Measuring ribbon porosity by terahertz spectroscopy and machine learning.

Roller compaction is a crucial unit operation in pharmaceutical manufacturing, with its ribbon porosity widely recognised as a critical quality attribute. Terahertz spectroscopy has emerged as a fast and non-destructive technique to measure porosity in pharmaceutical products. From a sensing perspective, the irregular shape and uneven surface of fragmented ribbon pieces can affect the accuracy and precision of the measurements, particularly for techniques that probe only a small sampling volume. It is known that the porosity is not uniform within the ribbon structure, with variations expected across the width of the ribbon and in the microstructure corresponding to its surface texture. However, typical pharmaceutical analysis methods, such as envelope density, only report an average bulk porosity, are slow to operate and limited in accuracy. To address this challenge, we developed and trained convolutional neural network models using THz spectra as input to classify four types of topography typically encountered in ribbons: ridge, valley, flat plane and edge points. The classifiers achieved 91% validation accuracy in both identifying outliers and differentiating between ribbons of smooth and knurled surfaces. For the more challenging task of distinguishing between the ridges and valleys of knurled surfaces, an 81% testing accuracy was achieved. Once each measurement is paired with its topography, resolving the density distribution within the sample is possible. This data can be combined to arrive at an average bulk porosity value compatible with conventional pharmaceutical analysis.

Venous thromboembolism in adolescents and young adults with acute lymphoblastic leukemia treated on a pediatric-inspired regimen.

Asparaginase (ASP)-containing regimens for acute lymphoblastic leukemia (ALL) are associated with venous thromboembolism (VTE). We evaluated the prevalence, risk factors, role of prophylaxis and clinical impact of VTE among adolescents and young adult (AYA) patients (15-50 years) treated on Dana-Farber Cancer Institute (DFCI) ALL protocols. The 1- and 2-year cumulative incidence of VTE were 31.9% (95% CI: 27.0%, 36.9%) and 33.5% (95% CI: 28.5%, 38.5%) respectively, with most events occurring during ASP-based consolidation phase (68.6%). VTE was more frequent in patients with overweight/obese vs. normal BMI (39.2% vs. 29.0%, p = 0.048). In a 1-year landmark analysis, the 4-year overall survival was 91.5%, without difference between patients with vs. without VTE (93.8% vs. 90.0%, p = 0.93). Relapse and non-relapse mortality rates were also similar. Among patients treated at Dana-Farber/Harvard Cancer Center, cerebral sinus vein thrombosis occurred in 3.6% of patients (8.5% of VTE events) in comparison to pulmonary embolism (32.9%) and deep vein thromboses (58.6%, 24.4% line-associated). In a Cox regression model for VTE free-time, elevated BMI was associated with shorter VTE free-time (HR 1.94 [95% CI 1.13-3.35], p = 0.018), while low molecular weight heparin (LMWH) prophylaxis as time-varying covariate was not. In conclusion, we found that VTE was frequent in AYAs treated on DFCI ALL protocols but did not impact survival outcomes. Overweight/obese BMI increased risk for VTE.

The NIH Pain Common Data Elements: A Great Start but a Long Way to the Finish Line.

BACKGROUND: The NIH Pain Common Data Elements (CDEs) provide a standardized framework for pain research, but their implementation and interpretation present challenges. OBJECTIVES: To review the NIH CDE Program's selected pain domains, provide best practices for implementing required questions, and offer a checklist for appropriate CDE use in clinical trials and secondary data analysis. METHODS: This work analyzed the ten core pain research domains selected by the NIH CDE Program and discuss their limitations and considerations for use. RESULTS: The manuscript provides an overview of the ten core pain research domains, including pain intensity, interference, physical function, sleep, catastrophizing, depression, anxiety, global impression of change, substance use screening, and quality of life. It offers sample scenarios for implementing required questions and presents a checklist to guide researchers in using pain CDEs effectively for clinical trials and secondary data analysis. DISCUSSION: Key challenges identified include contextual variability, lack of validation across all pain conditions and populations, and potential misuse or misinterpretation of measures. This work proposes solutions such as supplementary measures, context-specific guidance, comprehensive training programs, and ongoing refinement of the CDE framework. CONCLUSION: While NIH Pain CDEs are valuable tools for standardizing pain assessment in research, addressing challenges in their implementation and interpretation is crucial for improving the consistency, validity, and interpretability of pain research data, ultimately advancing the field and enhancing patient care.

ACR Appropriateness Criteria® Imaging of Suspected Intracranial Hypotension.

The clinical syndrome of intracranial hypotension refers to the symptoms caused by cerebrospinal fluid hypovolemia and is primarily characterized by postural headaches, but can be associated with a multitude of other neurological symptoms. Imaging plays a critical role in helping to establish a diagnosis of intracranial hypotension, localize the source of cerebrospinal fluid leak, and assist in directing targeted treatments. Using the best available evidence, this document provides diagnostic imaging recommendations for the workup of intracranial hypotension across various clinical presentations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Thoracic Back Pain.

Thoracic back pain is a common site for inflammatory, neoplastic, metabolic, infectious, and degenerative conditions, and may be associated with significant disability and morbidity. Uncomplicated acute thoracic back pain and/or radiculopathy does not typically warrant imaging. Imaging may be considered in those patients who have persistent pain despite 6 weeks of conservative treatment. Early imaging may also be warranted in patients presenting with "red flag" history or symptoms, including those with a known or suspected history of cancer, infection, immunosuppression, or trauma; in myelopathic patients; or in those with a history of prior thoracic spine fusion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Heuristic machine learning approaches for identifying phishing threats across web and email platforms.

Life has become more comfortable in the era of advanced technology in this cutthroat competitive world. However, there are also emerging harmful technologies that pose a threat. Without a doubt, phishing is one of the rising concerns that leads to stealing vital information such as passwords, security codes, and personal data from any target node through communication hijacking techniques. In addition, phishing attacks include delivering false messages that originate from a trusted source. Moreover, a phishing attack aims to get the victim to run malicious programs and reveal confidential data, such as bank credentials, one-time passwords, and user login credentials. The sole intention is to collect personal information through malicious program-based attempts embedded in URLs, emails, and website-based attempts. Notably, this proposed technique detects URL, email, and website-based phishing attacks, which will be beneficial and secure us from scam attempts. Subsequently, the data are pre-processed to identify phishing attacks using data cleaning, attribute selection, and attacks detected using machine learning techniques. Furthermore, the proposed techniques use heuristic-based machine learning to identify phishing attacks. Admittedly, 56 features are used to analyze URL phishing findings, and experimental results show that the proposed technique has a better accuracy of 97.2%. Above all, the proposed techniques for email phishing detection obtain a higher accuracy of 97.4%. In addition, the proposed technique for website phishing detection has a better accuracy of 98.1%, and 48 features are used for analysis.

Fibromyalgia is associated with increased odds of prior pain-precipitated relapse among non-treatment-seeking individuals with opioid use disorder.

BACKGROUND/OBJECTIVES: Chronic pain is an opioid use disorder (OUD) treatment barrier and associated with poor outcomes in OUD treatment including relapse. Fibromyalgia is a chronic pain condition related to central nervous system substrates that overlap with the brain disease model of OUD. We know of no studies that have looked at non-treatment seeking individuals, to see if fibromyalgia might represent a barrier to OUD treatment. Given many non-treatment-seeking individuals previously attempted recovery before experiencing relapse, and chronic pain is a known precipitant of relapse, fibromyalgia might be a currently unappreciated modifiable factor in OUD relapse and, potentially, a barrier to treatment reengagement among those not currently seeking treatment. This study aimed to determine if fibromyalgia is associated with greater odds of agreeing that 'I have tried to stop using opioids before, but pain caused me to relapse' among non-treatment seeking individuals with OUD. METHODS: This cross-sectional study recruited non-treatment-seeking individuals with OUD (n = 141) from a syringe service program. Ordinal logistic regression was used to determine if the presence of fibromyalgia increased the odds of agreement with prior pain-precipitated relapse. RESULTS: Fibromyalgia was identified in 35% of study participants and associated with 125% greater odds of strongly agreeing that pain had previously caused them to relapse, even after accounting for relevant covariates, including age, sex, depression, anxiety, OUD severity, and pain severity. CONCLUSIONS: This study provides early evidence that the presence of fibromyalgia may be associated with increased odds of pain-precipitated OUD relapse.

Fibromyalgia may be uniquely related to pain­precipitated relapse of OUD.