Personalized treatment using predictive biomarkers in solid organ malignancies: A review.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.

(1) Background: The neddylation pathway assumes a pivotal role in the initiation and progression of cancer. MLN4924, a potent small-molecule inhibitor of the NEDD8-activating enzyme (NAE), effectively intervenes in the early stages of the neddylation pathway. By instigating diverse cellular responses, such as senescence and apoptosis in cancer cells, MLN4924 also exerts regulatory effects on non-malignant cells within the tumor microenvironment (TME) and tumor virus-infected cells, thereby impeding the onset of tumors. Consequently, MLN4924 has been widely acknowledged as a potent anti-cancer drug. (2) Recent findings: Nevertheless, recent findings have illuminated additional facets of the neddylation pathway, revealing its active involvement in various biological processes detrimental to the survival of cancer cells. This newfound understanding underscores the dual role of MLN4924 in tumor therapy, characterized by both anti-cancer and pro-cancer effects. This dichotomy is herein referred to as the "double-edged effects" of MLN4924. This paper delves into the intricate relationship between the neddylation pathway and cancer, offering a mechanistic exploration and analysis of the causes underlying the double-edged effects of MLN4924-specifically, the accumulation of pro-cancer neddylation substrates. (3) Perspectives: Here, the objective is to furnish theoretical support and novel insights that can guide the development of next-generation anti-cancer drugs targeting the neddylation pathway.

Acceptability of Mobile App-Based Motivational Interviewing and Preferences for App Features to Support Self-Management in Patients With Type 2 Diabetes: Qualitative Study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) experience multiple barriers to improving self-management. Evidence suggests that motivational interviewing (MI), a patient-centered communication method, can address patient barriers and promote healthy behavior. Despite the value of MI, existing MI studies predominantly used face-to-face or phone-based interventions. With the growing adoption of smartphones, automated MI techniques powered by artificial intelligence on mobile devices may offer effective motivational support to patients with T2DM. OBJECTIVE: This study aimed to explore the perspectives of patients with T2DM on the acceptability of app-based MI in routine health care and collect their feedback on specific MI module features to inform our future intervention. METHODS: We conducted semistructured interviews with patients with T2DM, recruited from public primary care clinics. All interviews were audio recorded and transcribed verbatim. Thematic analysis was conducted using NVivo. RESULTS: In total, 33 patients with T2DM participated in the study. Participants saw MI as a mental reminder to increase motivation and a complementary care model conducive to self-reflection and behavior change. Yet, there was a sense of reluctance, mainly stemming from potential compromise of autonomy in self-care by the introduction of MI. Some participants felt confident in their ability to manage conditions independently, while others reported already making changes and preferred self-management at their own pace. Compared with in-person MI, app-based MI was viewed as offering a more relaxed atmosphere for open sharing without being judged by health care providers. However, participants questioned the lack of human touch, which could potentially undermine a patient-provider therapeutic relationship. To sustain motivation, participants suggested more features of an ongoing supportive nature such as the visualization of milestones, gamified challenges and incremental rewards according to achievements, tailored multimedia resources based on goals, and conversational tools that are interactive and empathic. CONCLUSIONS: Our findings suggest the need for a hybrid model of intervention involving both app-based automated MI and human coaching. Patient feedback on specific app features will be incorporated into the module development and tested in a randomized controlled trial.

Complements and Their Role in Systemic Disorders.

The complement system is critical to the body's innate defense against exogenous pathogens and clearance of endogenous waste, comprising the classical, alternative, and lectin pathways. Although tightly regulated, various congenital and acquired diseases can perturb the complement system, resulting in specific complement deficiencies. Systemic rheumatic, neurological, ophthalmological, renal, and hematological disorders are some prototypical complement-mediated diseases. An adequate understanding of the mechanisms of the normal complement system and the pathophysiology of complement dysregulation is critical for providing diagnostic clues and appropriately managing these conditions. This review guides clinicians in understanding the role of complement factors in systemic diseases and what diagnostic and therapeutic options are available for complement-mediated disorders.

Thromboembolic phenomena in patients with nephrotic syndrome: pathophysiology, risk factors, prophylaxis and treatment.

Thromboembolic events resulting from disturbances in the body's balance of thrombotic and antithrombotic abilities are among the most life-threatening complications of nephrotic syndrome. Certain causes of nephrotic syndrome leave the patient particularly susceptible to thromboembolism. The severity of proteinuria and degree of hypoalbuminaemia are other common predictors of risk. Timely initiation of prophylactic therapy can help prevent morbidity and mortality associated with this complication in patients with nephrotic syndrome. The duration of treatment and choice of therapeutic agent depends on several factors, including the degree of hypoalbuminaemia, risk factors for thrombosis and risk of bleeding. This article reviews current understanding of the pathophysiology and risk factors for thromboembolism associated with nephrotic syndrome, and summarises recommendations and strategies for preventing and treating thromboembolic events in patients with nephrotic syndrome.

Prevalence and factors associated with fatigue in patients with axial spondyloarthritis: a systematic review and meta-analysis.

Objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease associated with significant morbidity. Fatigue, a widely recognized disease manifestation, has considerable impacts on patients' work productivity, physical function and mental well-being. However, the reported prevalence of fatigue varies across studies, and pooled data are currently lacking. We aimed to characterize the prevalence of fatigue in patients with axSpA and to identify factors associated with fatigue. Methods: A systematic review and a meta-analysis were conducted to determine the global prevalence of fatigue in patients with axSpA. Databases including CINAHL, Embase, Medline, Cochrane Library, PubMed and Google Scholar were searched from inception until April 2023. Data were extracted, and the quality of studies was assessed. A pooled prevalence of fatigue was determined by using a random-effects model. Meta-analyses were used to determine the observed heterogeneity via subgroup analysis and associations between relevant predictors and the presence of fatigue. Results: Thirty eligible articles were included in the study, including 7893 patients with axSpA. The pooled prevalence of fatigue in patients with axSpA was 0.56 (95% CI: 0.49, 0.63; I2 = 94.6%), with significant levels of heterogeneity. Among the factors of heterogeneity explored, the geographical region of the study (P = 0.0013) was significant for being a possible source. Poorer quality of life was associated with more fatigue (P < 0.05). Conclusion: More than half of patients with axSpA experience fatigue, with poorer quality of life being associated with more fatigue.

Iridium-Catalyzed Enantioselective and Diastereoselective Allylation of Dioxindoles: A One-Step Synthesis of 3-Allyl-3-hydroxyoxindoles.

An iridium-catalyzed asymmetric allylation of dioxindoles, 3-hydroxyoxindoles, regulated by prosthetic groups has been accomplished under mild conditions. The methodology is applicable to a diverse array of 3-hydroxyoxindole and cinnamyl acetate substrates. A range of 3-allyl-3-hydroxyoxindoles containing vicinal tetrasubstituted and trisubstituted stereocenters can be efficiently synthesized in one-step with excellent enantioselectivity (up to >99% enaniomeric excess (ee)) and good diastereoselectivity (up to 11:1 diastereomeric ratio (dr)).

δ-Selective Functionalization of Alkanols Enabled by Visible-Light-Induced Ligand-to-Metal Charge Transfer.

We demonstrate the application of ligand-to-metal charge transfer (LMCT) excitation to the direct catalytic generation of energetically challenging alkoxy radicals from alcohols through a coordination-LMCT-homolysis process with an abundant and inexpensive cerium salt as the catalyst. This catalytic manifold provides a simple and efficient way to utilize the characteristic reactivity and selectivity of transient alkoxy radicals for δ-selective C-H bond functionalization. Under mild redox-neutral conditions without the need for prefunctionalization, this method provides a versatile platform to access molecular complexity from simple and abundant alcohols.

Photocatalytic C-C Bond Cleavage and Amination of Cycloalkanols by Cerium(III) Chloride Complex.

A general strategy for the cleavage and amination of C-C bonds of cycloalkanols has been achieved through visible-light-induced photoredox catalysis utilizing a cerium(III) chloride complex. This operationally simple methodology has been successfully applied to a wide array of unstrained cyclic alcohols, and represents the first example of catalytic C-C bond cleavage and functionalization of unstrained secondary cycloalkanols.

Oxidative coupling of methylamine with an aminyl radical: direct amidation catalyzed by I2/TBHP with HCl.

Oxidative coupling of methylamines with an aminyl radical to construct amides was developed in the presence of an I2/TBHP catalyst under acidic conditions via the two cleavages of the sp(3) C-N bond of aryl-methylamines and the sp(2) C-N bond of N-substituted formamides respectively. This transition-metal-free protocol provides a novel synthetic tool for the construction of N-substituted amides and a series of arylamides can be easily obtained with good yields.