Research Efforts Research Articles

The Immigration–Crime Nexus: Inner and Outer Containment Buffer or A Push Toward Delinquency

The ongoing debate over the immigration–crime nexus has continued to attract a wide range of research efforts in the criminal justice field. To build on these initiatives, this study not only examines the relationship between immigrants and adolescent crime but also explores attributes derived from containment effects that may contribute to or shield individuals from deviant behavior in America. Results showed that both immigrant and native-born adolescents share similar external attributes rather than internal traits that affect delinquency. For instance, inherent immigration status and identity is relatively more influential on self-reported substance problems among immigrant youth compared to their native-born counterparts. Interestingly, among external attributes, immigrant and native-born adolescents are responsive to legitimate opportunity and neighborhood order in different ways which thrust them into different deviant pathways.

Stevens-Johnson syndrome and toxic epidermal necrolysis-like eruptions in patients treated with immune checkpoint inhibitors: a systematic review.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by targeting immune checkpoints such as PD-1, PDL-1, and CTLA-4, but concerns about severe immune-related adverse events persist. The scarcity of literature on dermatologic implications, especially severe reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), highlights the urgent need for investigation. Our systematic review aims to address the gap in relevant literature by extensively examining the epidemiologic risk factors and management of SJS/TEN-like illnesses in ICI-treated patients to provide insights for risk assessment and clinical care. We identified 158 case reports that detailed the incidence of SJS/TEN in patients being treated with ICIs, examining demographic patterns, type of malignancy, clinical characteristics, and treatments linked to onset. We assessed mortality rates, risk elements, and the effectiveness of interventions to help guide clinical care. Analysis of 158 case reports revealed that SJS/TEN in ICI users is typically seen on average at the age of 63 and is more common in males. PD1 inhibitors such as nivolumab and pembrolizumab are often associated with various mucocutaneous patterns and significant risks with ICI use, especially TEN, which is linked to high morbidity and mortality rates. Our study notes limitations due to the inclusion of case reports or case series, such as potential publication and reporting biases, leading to skewed findings. Additionally, because of the heterogeneous reporting standards, the retrospective nature limits phenotypic precision, control for confounding variables, and data completeness. Our study provides valuable insights into the epidemiology, clinical features, management strategies, and outcomes of ICI-induced SJS/TEN, underscoring the importance of vigilant monitoring and personalized risk assessment in oncology practice. Continued research efforts are essential to optimize patient outcomes and enhance the safety profile of ICIs in cancer therapy.

Implementation of Extreme Learning Machine Method with Particle Swarm Optimization to Classify of Chronic Kidney Disease

Kidney Disease (CKD) appears as a pathological condition due to infection of the kidneys and blockages due to the formation of kidney stones. In the Indonesian context, kidney disease is the second most common disease after heart disease based on BPJS Health data. Notably, in this scenario, medical practitioners and individuals with specialized knowledge in the field are still faced with challenges in effectively classifying CKD cases, thereby making them vulnerable to erroneous diagnostic conclusions. The main objective underlying this particular research effort revolves around increasing the level of accuracy that characterizes the CKD classification process by orchestrating the incorporation of Particle Swarm Optimization (PSO) techniques into the operational framework of Extreme Learning Machines (ELM) with the aim of ensuring optimal results. Configuration of input weights and critical biases to achieve superior diagnostic results. The results obtained from the investigation process include many numerical parameters including but not limited to determining the ideal number of hidden nodes set at 11, population size 80, identification of the most preferred number of iterations denoted by the Best value of 20, aggregate inertia weight assessed at 0.5, along with the constants 1 (c1) and 2 (c2) each registering a value of 1, culminating in the achievement of an accuracy metric pegged at an impressive level of 98.50%. Consequently, the implications obtained from this empirical investigation strengthen the assertion that the use of PSO optimization strategies within the operational framework of ELM has the potential to yield major advances in the classification evaluation domain related to CKD diagnosis.

Exploring the LET dependence of DNA DSB repair kinetics using the DR DNA database.

The repair of DNA double-strand breaks is a crucial yet delicate process which is affected by a multitude of factors. In this study, our goal is to analyse the influence of the linear energy transfer (LET) on the DNA repair kinetics. By utilizing the database of repair of DNA and aggregating the results of 84 experiments, we conduct various model fits to evaluate and compare different hypothesis regarding the effect of LET on the rejoining of DNA ends. Despite the considerable research efforts dedicated to this topic over the past decades, our findings underscore the complexity of the relationship between LET and DNA repair kinetics. This study leverages big data analysis to capture overall trends that single experimental studies might miss, providing a valuable model for understanding how radiation quality impacts DNA damage and subsequent biological effects. Our results highlight the gaps in our current understanding, emphasizing the pressing need for further investigation into this phenomenon.

Cheminformatic Identification of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibitors: A Comparative Study of SMILES-Based Supervised Machine Learning Models.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs damages in DNA induced by abortive topoisomerase 1 activity; however, maintenance of genetic integrity may sustain cellular division of neoplastic cells. It follows that Tdp1-targeting chemical inhibitors could synergize well with existing chemotherapy drugs to deny cancer growth; therefore, identification of Tdp1 inhibitors may advance precision medicine in oncology. Current computational research efforts focus primarily on molecular docking simulations, though datasets involving three-dimensional molecular structures are often hard to curate and computationally expensive to store and process. We propose the use of simplified molecular input line entry system (SMILES) chemical representations to train supervised machine learning (ML) models, aiming to predict potential Tdp1 inhibitors. An open-sourced consensus dataset containing the inhibitory activity of numerous chemicals against Tdp1 was obtained from Kaggle. Various ML algorithms were trained, ranging from simple algorithms to ensemble methods and deep neural networks. For algorithms requiring numerical data, SMILES were converted to chemical descriptors using RDKit, an open-sourced Python cheminformatics library. Out of 13 optimized ML models with rigorously tuned hyperparameters, the random forest model gave the best results, yielding a receiver operating characteristics-area under curve of 0.7421, testing accuracy of 0.6815, sensitivity of 0.6444, specificity of 0.7156, precision of 0.6753, and F1 score of 0.6595. Ensemble methods, especially the bootstrap aggregation mechanism adopted by random forest, outperformed other ML algorithms in classifying Tdp1 inhibitors from non-inhibitors using SMILES. The discovery of Tdp1 inhibitors could unlock more treatment regimens for cancer patients, allowing for therapies tailored to the patient's condition.

Classroom to Clinic: Universities Need to Support The Next Generation of Clinical Academics

The General Medical Council’s current version of Outcomes for Doctors sets out three key areas of expertise for tomorrow’s doctors: professional values & behaviours, professional skills, and professional knowledge. (1) Each of these competencies further develops into numerous core skills every student should attain at medical school. While the learning outcomes set under Clinical Research & Scholarship (part of Outcome 3: Professional Knowledge) could usually be attained through numerous instances across a typical medical school curriculum, opportunities to put research skills into practice have remained relatively competitive and scarce. This represents an emerging challenge across the career spectrum, particularly in the UK as the Medical Schools Council warns that the NHS Long Term Workforce Plan 2031-32 could be jeopardised if the number of clinical academics is not maintained.(2) Facilitated by the impacts of an aging workforce alongside years of underinvestment – NHS trusts and medical schools need to work quickly to address barriers in training and retaining the next generation of clinical academics.(3) Clinical Academics are the foundation of the future of medical schools. However, much more must be done to introduce, facilitate, and encourage medical students to consider the option of training as a clinical academic. Investing in opportunities for medical students to get involved in research and teaching early on in their medical career, could be a solution not just to tackle this future workforce challenge but also to offer better career prospects. This is supported by evidence from research on matched-cohort studies conducted in Australia & New Zealand demonstrating an encouraging statistic independent of academic confounding variables. (4,5) Medical students who published research in medical student journals were significantly more likely to be associated with higher degree attainment, PubMed® indexed publications and in some cases, more likely to enter surgical training or their chosen specialty. However, getting involved in clinical research as a medical student remains challenging. Lack of opportunities, competitive funding calls, and fewer supervisors willing to take on the burden of training students are only some of the many barriers students currently face in getting involved. Recent results from a survey by the University of Glasgow’s Medical School demonstrated reassuring enthusiasm for a career in clinical research/teaching among a small sample size of 55 students. Commenting on these findings, Professor Iain McInnes, Head of the College of Medical, Veterinary and Life Sciences, said ‘.... supporting clinical academics at all stages of their career is a top priority for our college and this survey shows that the pipeline for the future of academia is in good health indeed!’. On the balance, the need of the hour must now focus on retaining this enthusiasm by investing in opportunities and offering pathways to ensure medical students can actively engage in academia. Several steps including enhancing funding, fostering stronger mentorship and networking opportunities, promoting interdisciplinary collaboration, and recognizing research efforts by medical students can go a long way in pursuing students to consider a rewarding career in clinical academia.

PSLBI-4 Influence of gender on animal science research funding from the National Institute of Food and Agriculture

Abstract According to the National Academies of Sciences, Engineering, and Medicine, females and males in science disciplines obtain bachelor’s degrees at or near parity, yet females are not equally represented in academic faculty positions. This is true for agricultural fields including the animal sciences. The USDA’s National Institute of Food and Agriculture (NIFA) administers the Agriculture and Food Research Initiative (AFRI), a flagship competitive grants program that funds research, education, and extension efforts with a total appropriation of $445 million in 2024. Our objective was to determine the difference between genders for submission rates (i.e., number of standard and seed grant applications submitted), peer reviewers of grant applications, and success rates (i.e., number of grant awards/number of applications submitted) in the main animal related AFRI program area priorities. All applications submitted to AFRI programs in animal genomics, reproduction, health, nutrition and growth, and welfare during yr 2013-2022 were evaluated. Gender was assigned to Project Directors (PD) and peer reviewers using first names as input into Gender API software (Gender-API.com; Passau, Germany) with ≥ 95% accuracy and ≥ 20 database occurrences used as quality filters and binary outcomes only (i.e., male or female). Effect of gender on submission rates, peer review panel compositions, and success rates were then analyzed using Pearson’s Chi-squared tests with P ≤ 0.05 considered significant. Results: A total of 3,757 applications were submitted, of which 2,761 (73%) PD genders were assigned and analyzed further. Overall, the proportional submission rate for females was 28% and for males was 72%. Submission rates for females increased (P = 0.0614) over time ranging from 22% in 2013 to 33% in 2021. Submission rates differed by gender across programs (P < 0.0001) and ranged from 23% female in animal reproduction to 48% female in animal welfare. Across 48 panels, 41% of panelists were female; no differences were identified for the proportion of female panelists over time (P = 0.9509) or by program (P = 0.9298). Overall, the funding success rate for females was 23% and for males was 22%. Success rates did not differ between genders over time (P = 0.9080) or by program (P = 0.9094). Females submitted less than one-half as many applications as did males, but the proportion of submissions by females increased over time. This trend remained consistent despite challenges of relocation of NIFA and COVID-19 during this time. Overall, the proportion of NIFA panelists who were female exceeded the proportion of applications submitted by females. Funding success rates did not differ by gender and increased for both genders over time. These results indicate that although differences in gender existed for application submission rate and panel composition, these differences did not impact funding success rate of applications in animal science programs at NIFA, which did not differ between genders.

PSXIII-16 Kinematics and viability of spermatozoa from Criollo and Angus bulls in a low-input system

Abstract The Chihuahuan Criollo cattle is a genetic resource with special adaptive characteristics to rough, arid and semi-arid ecosystems. There is a great interest in incorporating such adaptations into beef production systems as one of the strategies for sustainable production to face the climate change challenge. Reproductive success is determinant to achieve sustainability in animal production systems. Most research efforts to improve reproductive efficiency have focused on the study of females. However, it has been shown that much of the economic losses caused by embryonic deaths are due to the bull. The aim of this study was to evaluate the quality of thawed semen from Angus and Criollo bulls kept in a low-input system. Thirteen healthy bulls (n = 7 Angus and 6 = Chihuahuan Criollo), with an average age of 4.3 ± 0.48 yr, grazing in the same rangeland and subjected to natural pasture conditions, were studied. Semen obtained by electroejaculation, were frozen and subsequently thawed for analyses. Characteristics of motility, vitality (V), morphology (M) and plasma membrane integrity (PMI) were evaluated in fresh and thawed semen, whereas movement kinetics (MK) and acrosome reaction (AR) were evaluated in thawed semen. Statistical analysis was performed using the PROC GLM of SAS Studio 2022 including the fixed effects of breed, semen condition and their interaction for variables of progressive motility (PM), V, M, PMI and the effect of breed for variables of MK and AR. As expected, PM and V were less (P < 0.05) in thawed (57.93 ± 4.1 and 53.69 ± 2.7) compared with fresh (72.64 ± 3.9 and 74.98 ± 2.6) semen, whereas no differences (P > 0.05) were found in M. However, the interaction between semen condition and breed for PMI tended to the significance (P = 0.08) with a PMI of 68.95 ± 4.6 and 58.98 ± 4.3 for Criollo and Angus, respectively, in fresh semen, whereas in thawed semen this difference was inverted (52.08 ± 4.6 and 58.40 ± 4.6). It is important to note that the semen retained quality traits with values above the minimum accepted for use in artificial insemination, despite the scarcity of resources of the system in which the animals were kept. There were no differences by breed in the main MK variables; however, AR reported as live unreacted sperm was less (P < 0.05) in Criollo (40.49 ± 4.49) compared with Angus bulls (58.48 ± 4.49). In conclusion, it is important to incorporate the assessment of membrane integrity and acrosome reaction in thawed semen evaluation to obtain a more accurate prediction of the potential fertility of samples, even if motility parameters appear to be optimal.

Netakimab in the treatment of psoriatic erythroderma

Psoriasis is considered as system immunoassociated disease of the multifactorial nature with dominating value in development of genetic factors. Suffer псориазом from 2 to 7% of inhabitants of a planet. Psoriasis it is started, when environment factors activate plasmocytoid dentrid cages that leads to development numerous proinflammatory citokines, including the factor некроза to a tumour FNO-α, interferon (IFN) γ, interleukin (IL) 17, IL-22, IL-23 and IL-1β. Many of these citokines stimulate hyperproliferation keratinocyes which supports a chronic inflammation. The heaviest form psoriasis – psoriatic erythroderma, results adverse экзогенных from the factors, irritating treatment. Develops erythroderma at 1.5–3% of patients псориазом which amazes all surface of an integument. All skin cover gets brightly red colour, with a brown shade, is strained. Taking into account recent achievements in understanding of the inflammatory nature psoriatic research efforts have been concentrated to finding-out of a role specific proinflammatory cytokines which participate in pathogenesis diseases, for the purpose of working out of new purposeful methods of treatment. For treatment psoriatic erythroderma in medicine there is a wide spectrum of external and system means. Undoubtedly, psoriatic erythroderma has all indications to appointment of biological therapy, especially when does not give in traditional methods. Authors of article have presented a therapy material psoriatic erythroderma, a domestic preparation of genno-engineering biological therapy of (netakimab). The good clinical effect that opens prospect of application of this preparation is gained. The concrete clinical example of successful treatment is resulted.

323 Advances in using membrane vesicles for studying intestinal functions

Abstract Enterocytes are the major cell lineage of the small intestinal epithelia along the crypt-villus axis in gut mucosa. Enterocytes participate in the gut terminal nutrient digestion and absorption; and have essential roles in nutrient and metabolite recycling and efflux, nutrient and hormonal sensing, interactions with symbiotic microbiome and binding to infectious viruses, thus influencing the host homeostasis and whole-body physiological status. Intestinal membrane vesicles have been widely used for studying various gut functions in the past several decades. Villus enterocytic brush border membrane and the apical membrane vesicles along the crypt-villus axis in gut mucosa can be prepared and isolated by Mg2+- and Ca2+-precipitation and differential centrifugation procedures. Whereas, gut mucosal basolateral membrane vesicles can be prepared, fractionated and differentiated from other intracellular organelles such as the mitochondrial inner membrane by the Percoll gradient ultracentrifugation. Nutrient transport and exchange activities in the membrane vesicles in vitro are conducted often by rapid hand filtration, and in excess, in an automated fast sampling apparatus. Nutrient transport and exchange activity kinetics are derived according to the well-established classic Michaelis-Menten and the tracer inhibitory kinetic models with a simple linear diffusional component. Physiological and biochemical properties associated with various nutrient uptake systems such as pH optimum, requirements for co-transported ions (e.g., Na+, K+, Cl-), transporter affinity and substrate specificity can be effectively investigated in vitro with the membrane vesicles by altering the compositions of uptake buffers and intra-vesicular pre-loading buffers. Some of the fundamental gut functions are established via using the membrane vesicles in different mammalian species. And these include H+-peptide cotransport, Na+-cotransport and Na+-independent systems of hexose uptake across the apical membrane and the low-affinity Na+-independent hexose bidirectional uptake across the basolateral membrane that were characterized in rodents; Na+-dependent cotransport and Na+-independent systems of amino acid (AA) transport across the apical membrane that were revealed in rodents and pigs; as well as the Na+-hexose and AA cotransport and the co-expression of the coronavirus SARS-CoV-2 host epithelial apical membrane binding receptor, i.e., the angiotensin-converting enzyme-2 (ACE2), along the gut crypt-villus axis that were identified in liquid formula-fed piglets. In the post genomic and metagenomic sequencing era, further research efforts need to pursue understanding of expression and various functionality of the gut terminal hydrolases, nutrient transporters, nutrient exchangers, nutrient sensors, substrate and particle receptors, taste receptors, viral binding receptors such as ACE2 and hormonal receptors and their interactions with luminal factors such as nutrient, metabolites, symbiotic bacterial outer membrane vesicles etc., along the longitudinal and crypt-villus axes, through using the mammalian primary enterocytic apical and the basolateral membrane vesicles under various research settings.

Global Analysis of Natural Products Biosynthetic Diversity Encoded in Fungal Genomes.

Fungal secondary metabolites (SMs) represent an invaluable source of therapeutic drugs. Genomics-based approaches to SM discovery have revealed a vast and largely untapped biosynthetic potential within fungal genomes. Here, we used the publicly available fungal genome sequences from the NCBI public database, as well as tools such as antiSMASH, BIG-SLiCE, etc., to analyze a total of 11,598 fungal genomes, identifying 293,926 biosynthetic gene clusters (BGCs), which were subsequently categorized into 26,825 gene cluster families (GCFs). It was discovered that only a tiny fraction, less than 1%, of these GCFs could be mapped to known natural products (NPs). Some GCFs that only contain a single BGC internally are crucial for the biodiversity of fungal biosynthesis. Evident patterns emerged from our analysis, revealing popular taxa as prominent sources of both actual and potential biosynthetic diversity. Our study also suggests that the genus rank distribution of GCF is generally consistent with NP diversity. It is noteworthy that genera Xylaria, Hypoxylon, Colletotrichum, Diaporthe, Nemania, and Calonectria appear to possess a higher potential for SM synthesis. In addition, 7213 BGCs match possible known compound structures, and homologous gene clusters of well-known drugs can be located in different genera, facilitating the development of derivatives that share structural similarity to these drugs and may potentially possess similar biological activity. Our study demonstrated the various types of fungi with mining potential, assisting researchers in prioritizing their research efforts and avoiding duplicate mining of known resources to further explore fungal NP producers.

The anti-biofilm efficacy of copper and zinc doped borate bioactive glasses.

Aim: Healthcare-acquired infections (HAIs) pose significant challenges in medical settings due to their resistance to conventional treatment methods. The role of bacterial biofilms in exacerbating these infections is well-documented, making HAIs particularly difficult to eradicate. Despite numerous research efforts, an effective solution to combat these infections remains elusive. This study aims to explore the potential of metal-ion (copper and zinc) doped borate bioactive glasses (BBGs) as a novel treatment modality to inhibit bacterial species commonly implicated in HAIs: Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa.Methods: The study analyzed the efficacy of both direct and indirect applications of BBGs on severe biofilms pre-formed under static and dynamic growth conditions; a comprehensive predictive modeling was developed, simulating diverse clinically relevant conditions.Results: Results demonstrate more than 4 log reduction in bacterial growth within 2days for direct application and 3days for indirect application of copper and zinc-doped BBGs. These findings were consistent across the three bacterial species, in both static and dynamic conditions.Conclusion: Copper and zinc-doped BBGs can be an effective approach in combating HAIs complicated by biofilms.

350 Awardee Talk: Beef cattle mineral nutrition: What do we know and where do we go from here

Abstract Trace minerals are pivotal in enhancing cattle growth and ensuring profitability in beef production. Historically, supplementation strategies have aimed at preventing deficiencies, significantly improving growth and reproductive performance. However, as cattle breeding has evolved to achieve remarkable growth rates, the challenges related to health and stress during the feeding period have intensified. This presentation explores refined trace mineral recommendations, focusing on zinc’s “stress requirement” for cattle undergoing transit and health challenges, and its impact on performance. The segmented nature of the beef industry, necessitating multiple transports, induces physiological stress and oxidative stress, highlighting the need for tailored mineral supplementation. Further, when recognizing feedlot cattle as the high-performing athletes they are, the potential benefits of adjusted trace mineral concentrations become apparent. Preliminary findings suggest that optimal zinc concentrations may exceed current National Academies of Sciences, Engineering, and Medicine (NASEM) 2016 recommendations, whereas for other minerals like copper and manganese, the existing guidelines remain appropriate. This presentation will explore the differential effects of increasing dietary zinc and copper in conjunction with various growth-promoting technologies. Preliminary data indicates that increasing zinc concentrations can linearly enhance average daily gain (ADG) and hot carcass weight (HCW), especially when using potent anabolic implants, while the response to increased copper concentrations exhibits a more quadratic relationship with performance. Building upon the foundational work of pioneering researchers in the field of mineral nutrition, this presentation advocates for the continuous refinement and optimization of trace mineral supplementation strategies. By integrating cutting-edge technologies and fostering collaborative research efforts, we aim to further enhance the sustainability of the beef industry. A deeper understanding of trace mineral requirements in the face of modern production challenges will pave the way for more precise and effective nutritional strategies.

Advancing microRNA target site prediction with transformer and base-pairing patterns.

MicroRNAs (miRNAs) are short non-coding RNAs involved in various cellular processes, playing a crucial role in gene regulation. Identifying miRNA targets remains a central challenge and is pivotal for elucidating the complex gene regulatory networks. Traditional computational approaches have predominantly focused on identifying miRNA targets through perfect Watson-Crick base pairings within the seed region, referred to as canonical sites. However, emerging evidence suggests that perfect seed matches are not a prerequisite for miRNA-mediated regulation, underscoring the importance of also recognizing imperfect, or non-canonical, sites. To address this challenge, we propose Mimosa, a new computational approach that employs the Transformer framework to enhance the prediction of miRNA targets. Mimosa distinguishes itself by integrating contextual, positional and base-pairing information to capture in-depth attributes, thereby improving its predictive capabilities. Its unique ability to identify non-canonical base-pairing patterns makes Mimosa a standout model, reducing the reliance on pre-selecting candidate targets. Mimosa achieves superior performance in gene-level predictions and also shows impressive performance in site-level predictions across various non-human species through extensive benchmarking tests. To facilitate research efforts in miRNA targeting, we have developed an easy-to-use web server for comprehensive end-to-end predictions, which is publicly available at http://monash.bioweb.cloud.edu.au/Mimosa.

Text mining method to unravel long COVID’s clinical condition in hospitalized patients

Long COVID is characterized by persistent that extends symptoms beyond established timeframes. Its varied presentation across different populations and healthcare systems poses significant challenges in understanding its clinical manifestations and implications. In this study, we present a novel application of text mining technique to automatically extract unstructured data from a long COVID survey conducted at a prominent university hospital in São Paulo, Brazil. Our phonetic text clustering (PTC) method enables the exploration of unstructured Electronic Healthcare Records (EHR) data to unify different written forms of similar terms into a single phonemic representation. We used n-gram text analysis to detect compound words and negated terms in Portuguese-BR, focusing on medical conditions and symptoms related to long COVID. By leveraging text mining, we aim to contribute to a deeper understanding of this chronic condition and its implications for healthcare systems globally. The model developed in this study has the potential for scalability and applicability in other healthcare settings, thereby supporting broader research efforts and informing clinical decision-making for long COVID patients.

Review of the Use of Metals in Biomedical Applications: Biocompatibility, Additive Manufacturing Technologies, and Standards and Regulations

Advanced manufacturing techniques such as Additive Manufacturing (AM) have grown rapidly in major industries such as aerospace, automotive, and biomedical device manufacturing. Biomedical industry has benefitted immensely from AM because of its flexibility in design and its rapid production cycle. Powder bed processes are the major production technique for metal-based AM implants. This paper serves as a comprehensive review on the research efforts being made using AM to develop new patient centered medical devices. This review focuses on AM of the most common metals for biomedical applications, Magnesium alloys, Cobalt-Chromium alloys, pure Titanium, Titanium alloys. Several different aspects are discussed including biocompatibility and osseointegration, application of specific metals in different types of implants, their advantages and disadvantages, mechanical properties in comparison to bone, and their production technologies. Regulatory and quality assurance hurdles that are facing new innovations made using AM are discussed.

Integrating Novel Agents Into the Clinical Management of Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) is highly curable at all stages. Research efforts over the past few decades have largely focused on interim PET-adapted strategies for therapy de-escalation or intensification. The overarching goals have been to increase cure rates, minimize potential therapy-related effects, and optimize survivorship. Better understanding of the biology of cHL has led to the development and approval of effective novel agents including the antibody-drug conjugate brentuximab vedotin and the checkpoint inhibitor immunotherapies. In this review, we discuss recent trial results and how these agents are integrated into clinical practice with the goal of further optimizing outcomes.

The First Report of Sphaerirostris picae Infection in the Oriental Magpie (Pica serica) in Beijing, China.

Background: Sphaerirostris picae is a parasitic species known for its ability to infect and transmit between hosts in the gastrointestinal tracts of wild avian species. However, there is limited information on its presence and impact on urban avian populations, particularly in China. Materials and Methods: In this study, morphological observations were conducted to detect the presence of Sphaerirostris sp. within the intestinal tract of the Oriental Magpie (Pica serica) collected in Beijing, China. Further confirmation of the parasite's identity was achieved through phylogenetic analysis using COX1 gene sequencing to compare with previously documented Sphaerirostris picae isolates. Results: The morphological and molecular analyses confirmed the presence of Sphaerirostris picae in the Oriental Magpie. Phylogenetic analysis indicated a close relationship with known Sphaerirostris picae isolates. This represents the first reported case of Sphaerirostris picae infection in magpies from Beijing, China. Conclusion: The findings highlight the potential health hazards posed by Sphaerirostris picae to urban avian populations and public health. The study suggests that additional research and surveillance efforts are necessary to better understand the risks associated with this parasite and to develop effective mitigation strategies.

Roadmap to a Global Template for Implementation of Ototoxicity Management for Cancer Treatment.

Ototoxicity is among the adverse events related to cancer treatment that can have far-reaching consequences and negative impacts on quality-of-life for cancer patients and survivors of all ages. Ototoxicity management (OtoM) comprises the prevention, diagnosis, monitoring, and treatment, including rehabilitation and therapeutic intervention, of individuals who experience hearing loss, tinnitus, or balance/vestibular difficulties following exposures to ototoxic agents, including platinum chemotherapy (cisplatin, carboplatin) and cranial radiation. Despite the well-established physical, socioeconomic, and psychological consequences of hearing and balance dysfunction, there are no widely adopted standards for clinical management of cancer treatment-related ototoxicity. Consensus recommendations and a roadmap are needed to guide development of effective and feasible OtoM programs, direct research efforts, address the needs of caregivers and patients at all stages of cancer care and survivorship. Here we review current evidence and propose near-term to longer-term goals to advance OtoM in five strategic areas: (1) beneficiary awareness, empowerment, and engagement, (2) workforce enhancement, (3) program development, (4) policy, funding, and sustainability, and (5) research and evaluation. The goal is to identify needs and establish a roadmap to guide worldwide adoption of standardized OtoM for cancer treatment and improved outcomes for patients and survivors.

The G Protein-First Mechanism for Activation of the Class B Glucagon-like Peptide 1 Receptor Coupled to N-Terminal Domain-Mediated Conformational Progression.

Recently, there has been a great deal of excitement about new glucagon-like peptide 1 receptor (GLP-1R) agonists (e.g., semaglutide and tirzepatide) that have received FDA approval for type 2 diabetes and obesity. Although effective, these drugs come with side effects that limit their use. While research efforts continue to focus intensively on long-lasting, orally administered GLP-1R medications with fewer side effects, a major impediment to developing improved GLP-1R medications is that the mechanism by which an agonist activates GLP-1R to imitate signaling is not known. Here we present and validate the G protein (GP)-first mechanism for the GLP-1R supported by extensive atomistic simulations. We propose that GLP-1R is preactivated through the formation of a GLP-1R-GP precoupled complex at the cell membrane prior to ligand binding. Despite a transmembrane helix 6 (TM6)-bentout conformation characteristic of activated GLP-1R, this precoupled complex remains unactivated until an agonist binds to elicit signaling. Notably, this new hypothesis offers a unified and predictive model for the activities of a series of full and partial agonists, including the peptides ExP5, GLP-1(7-36), and GLP-1(9-36). Most surprisingly, our simulations reveal an N-terminus domain (NTD)-swing/agonist-insertion mechanism wherein the long extracellular NTD of GLP-1R tightly holds the C-terminal half of the peptide agonist and progressively shifts the N-terminal head of the peptide to facilitate insertion into the orthosteric pocket. Our findings provide novel mechanistic insights into the activation and function of class B GPCRs and should provide a realistic basis for structure-based ligand design.