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Neuron Nov 2023Working at the intersection of neuroscience and immunology, David Artis shares his lifelong passion for science, starting with harassing Venus flytraps as a child and...
Working at the intersection of neuroscience and immunology, David Artis shares his lifelong passion for science, starting with harassing Venus flytraps as a child and his optimism for science's future. Further, he offers insight into neuroscience and immunology's unique parallelism.
Topics: Child; Humans; Neurosciences
PubMed: 37918350
DOI: 10.1016/j.neuron.2023.10.017 -
Life Sciences Jun 2024Antibody-drug conjugates (ADCs) are immunoconjugates that combine the specificity of monoclonal antibodies with a cytotoxic agent. The most appealing aspects of ADCs... (Review)
Review
Antibody-drug conjugates (ADCs) are immunoconjugates that combine the specificity of monoclonal antibodies with a cytotoxic agent. The most appealing aspects of ADCs include their potential additive or synergistic effects of the innate backbone antibody and cytotoxic effects of the payload on tumors without the severe toxic side effects often associated with traditional chemotherapy. Recent advances in identifying new targets with tumor-specific expression, along with improved bioactive payloads and novel linkers, have significantly expanded the scope and optimism for ADCs in cancer therapeutics. In this paper, we will first provide a brief overview of antibody specificity and the structure of ADCs. Next, we will discuss the mechanisms of action and the development of resistance to ADCs. Finally, we will explore opportunities for enhancing ADC efficacy, overcoming drug resistance, and offer future perspectives on leveraging ADCs to improve the outcome of ADC therapy for cancer treatment.
Topics: Humans; Immunoconjugates; Neoplasms; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Drug Resistance, Neoplasm; Antibody Specificity
PubMed: 38688384
DOI: 10.1016/j.lfs.2024.122676 -
The Lancet. Rheumatology Feb 2024Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle... (Review)
Review
Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle injury. Until recently, there was little insight into the pathogenesis of idiopathic inflammatory myopathies, which challenged the recognition of the breadth of heterogeneity of this group of diseases as well as the development of new therapeutics. However, the landscape of idiopathic inflammatory myopathies is evolving. In the past decade, advances in diagnostic tools have facilitated an enhanced understanding of the underlying disease mechanisms in idiopathic inflammatory myopathies, enabling the expansion of therapeutic trials. The fields of transcriptomics, prot§eomics, and machine learning offer the potential to gain greater insights into the underlying pathophysiology of idiopathic inflammatory myopathies. Harnessing insights gained from these sophisticated tools could contribute to the identification of differences at a molecular level among patients, accelerating the development of targeted, tailored therapies. Bolstered by the validation and standardisation of robust outcome measures, many promising therapies are in clinical trial development. Although challenges remain, there is great optimism in the field due to the progress in innovative diagnostics, outcome measures, and therapeutic approaches. In this Review, we discuss the expanding landscape of idiopathic inflammatory myopathies as the frontier of precision medicine becomes imminent.
Topics: Humans; Myositis; Autoimmune Diseases; Gene Expression Profiling; Machine Learning; Optimism
PubMed: 38267098
DOI: 10.1016/S2665-9913(23)00322-3 -
Journal of Continuing Education in... Sep 2023Optimism is a powerful mindset for leaders and teams, but promoting optimism during extended periods of extreme change and instability is challenging. Futures Thinking...
Optimism is a powerful mindset for leaders and teams, but promoting optimism during extended periods of extreme change and instability is challenging. Futures Thinking is a unique and inherently optimistic set of tools and processes that leaders can use in such times. Looking 10 or more years into the future allows us to step beyond the turmoil of the current moment and apply energy to identifying and planning to create long-term systemic change toward a preferred future. .
PubMed: 37642446
DOI: 10.3928/00220124-20230816-03 -
The Journal of Hand Surgery, European... Jun 2024This article reviews the history of peripheral nerve (PN) injuries and successive advances in their management by notable pioneers, an interesting topic that I chose for... (Review)
Review
This article reviews the history of peripheral nerve (PN) injuries and successive advances in their management by notable pioneers, an interesting topic that I chose for my Doctoral Thesis in 1990 in Madrid. Mentioning all their names and contributions is an obligatory tribute, and I offer my sincere apologies for inevitably leaving a few out. For half a century I have witnessed microsurgery advances, and also experienced frequent failures in my practice with the use of new techniques; a testimony that we are very far from achieving the 'Holy Grail' of complete PN recovery for these injuries. Our experience is often like a pendulum, from nihilism to optimism and vice versa. Many factors influence the results of PN repair. Fortunately, microsurgery has been a breakthrough but, too often, emergency surgery is carried out by surgeons without enough tools and experience, both very important factors in this field.
Topics: Humans; History, 19th Century; History, 20th Century; History, 21st Century; Microsurgery; Peripheral Nerve Injuries; History, Ancient
PubMed: 37728740
DOI: 10.1177/17531934231198455 -
Lakartidningen Apr 2024In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and... (Review)
Review
In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and substance use disorders. Despite existing treatments being efficacious for many patients, this is not the case for up to a third of the patients with depression. Additionally, treatments are often long and associated with side effects. This review focuses on the psychedelic compound psilocybin, a serotonin-2A-receptor agonist that has been seen to reduce depression and anxiety in patients after administration of only a single dose, with effects lasting several weeks. Recent findings from phase II studies suggest that psilocybin treatment for depression is safe and efficacious. A phase III study is currently recruiting. Whether psychedelics will become a part of standard healthcare remains to be seen, but findings do give rise to cautious optimism.
Topics: Humans; Hallucinogens; Psilocybin; Anxiety Disorders; Psychiatry
PubMed: 38572715
DOI: No ID Found -
Current Opinion in Organ Transplantation Oct 2023Antibody-mediated rejection (AMR) after solid organ transplantation remains an unsolved problem and leads to poor early and late patient outcomes. The complement system... (Review)
Review
PURPOSE OF REVIEW
Antibody-mediated rejection (AMR) after solid organ transplantation remains an unsolved problem and leads to poor early and late patient outcomes. The complement system is a well recognized pathogenic mediator of AMR. Herein, we review the known molecular mechanisms of disease and results from ongoing clinical testing of complement inhibitors after solid organ transplant.
RECENT FINDINGS
Activation and regulation of the complement cascade is critical not only for the terminal effector function of donor-specific antibodies, but also for the regulation of T and B cell subsets to generate the antidonor humoral response. Donor-specific antibodies (DSA) have heterogenous features, as are their interactions with the complement system. Clinical testing of complement inhibitors in transplant patients have shown good safety profiles but mixed efficacy to date.
SUMMARY
The complement cascade is a critical mediator of AMR and clinical trials have shown early promising results. With the steady emergence of novel complement inhibitors and our greater understanding of the molecular mechanisms linking complement and AMR, there is greater optimism now for new prognostic and therapeutic tools to deploy in transplant patients with AMR.
Topics: Humans; Immunity, Humoral; Graft Rejection; Antibodies; Complement Activation; Complement Inactivating Agents; Isoantibodies; HLA Antigens
PubMed: 37582054
DOI: 10.1097/MOT.0000000000001095 -
Gastroenterology & Hepatology Jul 2023Tremendous effort has been put forth over the past 2 decades in understanding the pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis...
Tremendous effort has been put forth over the past 2 decades in understanding the pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH). Although multiple potential targets for drug development exist, there have been no approved therapies for NAFLD/NASH. Lipotoxicity, owing to increased delivery of fatty acids to the liver, and hepatic de novo lipogenesis are key drivers of disease pathogenesis. Moreover, genetics, environmental factors, and comorbid conditions converge to determine disease progression in individual patients. Given the complexity and heterogeneity of disease pathogenesis, numerous therapeutic targets have emerged and have been tested in clinical trials. Early trial failures have provided key lessons and foundational insights to move the field forward. Current ongoing phase 3 trials and emerging phase 2 trials are reasons for optimism, and 2 drugs, obeticholic acid and resmetirom, are being evaluated for accelerated approval by the US Food and Drug Administration this year. This article highlights key features of NASH pathophysiology and drug targets, the lessons learned from completed trials, and the current landscape of phase 2 and 3 clinical trials in NASH.
PubMed: 37771619
DOI: No ID Found -
BMC Psychiatry Aug 2023Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience...
BACKGROUND
Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience poor mental health, some traumatized people are grown to be more resilient than others. Few studies have examined the association between childhood maltreatment and adult resilience. This study aimed to determine different relationships between specific types and features of childhood maltreatment with adult resilience among Chinese with Major Depressive Disorder (MDD) and healthy controls (HCs).
METHODS
A total of 101 patients with MDD and 116 participants in the healthy control (HC) group from Zhumadian Psychiatric Hospital and its nearby communities were included in this analysis. Childhood maltreatment was assessed retrospectively using Childhood Trauma Questionnaire (CTQ). Adults' resilience was assessed by the Connor-Davidson Resilience Scale (CD-RISC). Generalized linear models were applied between childhood maltreatment (specific types and features) and resilience adjusting for covariates.
RESULTS
The total score of CD-RISC and factor scores of strength, optimism, and tenacity in the HC group were higher than those in the MDD group. CTQ total score had a negative association with optimism score among participants in MDD (β=-0.087, P < 0.001) and HC (β=-0.074, P = 0.023) groups. Higher emotional neglect (EN) score (β=-0.169, P = 0.001) and physical neglect (PN) score (β=-0.153, P = 0.043) were related to a worse optimism score in MDD group. Emotional abuse (EA) score was associated with a worse tenacity score (β=-0.674, P = 0.031) in MDD group. For participants in HC group, higher EN and PN scores were related to worse resilience scores (tenacity, strength, and optimism).
CONCLUSIONS
Patients with MDD showed lower optimism than HCs. Childhood maltreatment, especially childhood negect, independently contributed to optimism, with more severe childhood maltreatment predictive of worse performance of optimism. EA in childhood was also linked to worse tenacity in adult patients with MDD.
Topics: Adult; Child; Humans; Adverse Childhood Experiences; Depressive Disorder, Major; Emotional Abuse; Retrospective Studies; East Asian People
PubMed: 37648984
DOI: 10.1186/s12888-023-05124-w -
Frontiers in Psychiatry 2023This study aimed to investigate and compare the therapeutic outcomes of psychological capital between narrative therapy, cognitive-behavioral therapy, and play therapy...
AIM
This study aimed to investigate and compare the therapeutic outcomes of psychological capital between narrative therapy, cognitive-behavioral therapy, and play therapy in the context of hikikomori.
METHODS
This study included 502 hikikomori. Correlation analysis was performed to investigate the relationship between the three forms of therapy and psychological capital, while one-way ANOVA and independent samples -tests were performed to determine the differences in the outcomes of psychological capital between the three forms of therapies.
RESULTS
Results indicated that all three forms of therapy were significantly positively related to psychological capital. Moreover, while cognitive-behavioral therapy performed better in psychological capital (overall score) than the other two, cognitive-behavioral therapy performed better in the subscales "self-efficacy" and "resilience," while narrative therapy performed better in the "hope" and "optimism" subscales. Also, combining features of play therapy helped enhance the outcomes of narrative therapy and cognitive-behavioral therapy on psychological capital.
CONCLUSION
Owing to the varied outcomes of psychological capital among different therapies, the differential use of therapies to deal with the unique needs resultant of hikikomori helps achieve optimal results.
PubMed: 37608996
DOI: 10.3389/fpsyt.2023.1114170