Type 1 diabetes prevention clinical trial simulator: Case reports of model-informed drug development tool.

Clinical trials seeking to delay or prevent the onset of type 1 diabetes (T1D) face a series of pragmatic challenges. Despite more than 100 years since the discovery of insulin, teplizumab remains the only FDA-approved therapy to delay progression from Stage 2 to Stage 3 T1D. To increase the efficiency of clinical trials seeking this goal, our project sought to inform T1D clinical trial designs by developing a disease progression model-based clinical trial simulation tool. Using individual-level data collected from the TrialNet Pathway to Prevention and The Environmental Determinants of Diabetes in the Young natural history studies, we previously developed a quantitative joint model to predict the time to T1D onset. We then applied trial-specific inclusion/exclusion criteria, sample sizes in treatment and placebo arms, trial duration, assessment interval, and dropout rate. We implemented a function for presumed drug effects. To increase the size of the population pool, we generated virtual populations using multivariate normal distribution and ctree machine learning algorithms. As an output, power was calculated, which summarizes the probability of success, showing a statistically significant difference in the time distribution until the T1D diagnosis between the two arms. Using this tool, power curves can also be generated through iterations. The web-based tool is publicly available: https://app.cop.ufl.edu/t1d/. Herein, we briefly describe the tool and provide instructions for simulating a planned clinical trial with two case studies. This tool will allow for improved clinical trial designs and accelerate efforts seeking to prevent or delay the onset of T1D.

Circulating cell-free (cf)DNA analysis: Current technologies and applications in gynecologic cancer.

Cell-free DNA (cfDNA) analysis has several promising clinical applications in the management of cancer patients, with clinical validity established in different types of solid tumors (e.g., lung, breast, and colon cancer). Cancers harbor unique genetic alterations that can be detected in the plasma and other bodily fluids of cancer patients, constituting an alternate source of tumor-derived DNA. Technologic advances and wide-spread availability of next-generation sequencing (NGS) have made sequencing analysis of circulating tumor DNA (ctDNA) possible, employing both off-the-shelf and personalized tumor-informed panels. Tumor size, disease burden and high-grade histologic types have been shown to correlate with ctDNA levels across multiple solid cancer types. Detection of tumor-derived genetic alterations in plasma-derived cfDNA can facilitate diagnosis, guide treatment selection, and serve as a biomarker for treatment response and prognostication. Molecular residual disease (MRD) is at the forefront of cfDNA analysis, with implications in treatment de-escalation/ escalation in the neoadjuvant and adjuvant settings. The development of cfDNA analysis in early detection of cancers is under active investigation. Proof-of-principles studies in gynecologic cancers have demonstrated feasibility and potential for innovation in cancers lacking specific biomarkers, including the tracking of human papillomavirus (HPV) cfDNA in patients with cervical cancer. In this review, we outline the assays currently available for cfDNA sequencing/ ctDNA detection, the role of cfDNA analysis in clinical decision-making and the current status and potential clinical uses of cfDNA research in gynecologic cancers.

Outcomes of Radical Hysterectomy for Early-Stage Cervical Carcinoma, with or without Prior Cervical Excision Procedure.

OBJECTIVE: To investigate the impact of a prior cervical excisional procedure on the oncologic outcomes of patients with apparent early-stage cervical carcinoma undergoing radical hysterectomy. METHODS: The National Cancer Database (2004-2015) was accessed, and patients with FIGO 2009 stage IB1 cervical cancer who had a radical hysterectomy with at least 10 lymph nodes (LNs) removed and a known surgical approach were identified. Patients who did and did not undergo a prior cervical excisional procedure (within 3 months of hysterectomy) were selected for further analysis. Overall survival (OS) was evaluated following the generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control a priori-selected confounders. RESULTS: A total of 3159 patients were identified; 37.1% (n = 1171) had a prior excisional procedure. These patients had lower rates of lymphovascular invasion (29.2% vs. 34.9%, p = 0.014), positive LNs (6.7% vs. 12.7%, p < 0.001), and a tumor size >2 cm (25.7% vs. 56%, p < 0.001). Following stratification by tumor size, the performance of an excisional procedure prior to radical hysterectomy was associated with better OS even after controlling for confounders (aHR: 0.45, 95% CI: 0.30, 0.66). The rate of minimally invasive surgery was higher among patients who had a prior excisional procedure (61.5% vs. 53.2%, p < 0.001). For these patients, performance of minimally invasive radical hysterectomy was not associated with worse OS (aHR: 1.37, 95% CI: 0.66, 2.82). CONCLUSIONS: For patients undergoing radical hysterectomy, preoperative cervical excision may be associated with a survival benefit. For patients who had a prior excisional procedure, minimally invasive radical hysterectomy was not associated with worse overall survival.

Combination Antifungal Therapy for Invasive Mucormycosis in Immunocompromised Hosts: A Single-Center Experience.

Combination antifungal therapy for invasive mucormycosis remains controversial and is inconsistently defined in prior studies. In a cohort of patients with immunocompromised status and invasive mucormycosis, we found no difference in 6-week mortality with up-front or salvage combination therapy as compared with monotherapy.

Long-term olfactory loss post-COVID-19: Pathobiology and potential therapeutic strategies.

An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the early phases of the COVID-19 pandemic. In most COVID-19 patients, olfaction recovers over the course of a few weeks. However, a lasting partial or complete loss of smell, often associated with distorted olfactory perceptions termed parosmia, has emerged as a widespread problem impacting at least 5%-10% of those who experience anosmia due to COVID-19. Our inability to offer effective therapies to this hyposmic or anosmic population, comprising millions of patients, highlights an enormous unmet need for the medical system. Here, we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS-CoV-2 infection, focusing on how the virus interacts with the peripheral olfactory system, a major site of viral infection. We also explore the problem of long-COVID olfactory dysfunction, which may accompany other persistent systemic disorders collectively termed postacute sequelae of COVID-19. Specifically, we discuss an emerging model focused on unresolved immune cell activity driving ongoing dysfunction. Finally, we review current and future therapeutic approaches aimed at restoring olfactory function.

MEMO: dataset and methods for robust multimodal retinal image registration with large or small vessel density differences.

The measurement of retinal blood flow (RBF) in capillaries can provide a powerful biomarker for the early diagnosis and treatment of ocular diseases. However, no single modality can determine capillary flowrates with high precision. Combining erythrocyte-mediated angiography (EMA) with optical coherence tomography angiography (OCTA) has the potential to achieve this goal, as EMA can measure the absolute RBF of retinal microvasculature and OCTA can provide the structural images of capillaries. However, multimodal retinal image registration between these two modalities remains largely unexplored. To fill this gap, we establish MEMO, the first public multimodal EMA and OCTA retinal image dataset. A unique challenge in multimodal retinal image registration between these modalities is the relatively large difference in vessel density (VD). To address this challenge, we propose a segmentation-based deep-learning framework (VDD-Reg), which provides robust results despite differences in vessel density. VDD-Reg consists of a vessel segmentation module and a registration module. To train the vessel segmentation module, we further designed a two-stage semi-supervised learning framework (LVD-Seg) combining supervised and unsupervised losses. We demonstrate that VDD-Reg outperforms existing methods quantitatively and qualitatively for cases of both small VD differences (using the CF-FA dataset) and large VD differences (using our MEMO dataset). Moreover, VDD-Reg requires as few as three annotated vessel segmentation masks to maintain its accuracy, demonstrating its feasibility.

Aspirin as a chemopreventive agent for cutaneous melanoma: a literature review.

Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin's role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin's complexities in melanoma prevention. A PubMed search using "Aspirin" AND "Cutaneous melanoma" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It's crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin's impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention.

Role of systematic lymphadenectomy at the time of interval debulking surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection.

OBJECTIVE: To evaluate the role of systematic lymphadenectomy at the time of interval cytoreductive surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection. METHODS: The National Cancer DataBase was accessed, and patients diagnosed between 2010 and 2015 with advanced-stage ovarian carcinoma who underwent interval cytoreductive surgery and achieved complete gross resection were identified. Patients who did not undergo lymphadenectomy and those who underwent systematic lymphadenectomy (defined as at least 20 lymph nodes removed) were selected for further analysis. Median overall survival was compared with the log-rank test and controlled for a priori selected confounders. RESULTS: A total of 1060 patients were identified. Systematic lymphadenectomy was performed for 125 (11.8%) patients with a median of 29 lymph nodes (range 20-72) removed. Rate of lymph node metastasis was 62.4%. Patients who underwent systematic lymphadenectomy had higher rate of unplanned readmission (8.9% vs 1.6%, p<0.001), and median hospital stay (6 vs 4 days, p<0.001). Median overall survival for patients who did and did not undergo systematic lymphadenectomy was 44.2 and 40.4 months, respectively, p=0.40. After controlling for confounders, performance of systematic lymphadenectomy was not associated with better survival (HR=0.98, 95% CI 0.80 to 1.19). CONCLUSION: Systematic lymphadenectomy is rarely performed at the time of interval cytoreductive surgery and not associated with a survival benefit for patients who achieved complete gross resection.

3D bioprinting: a review and potential applications for Mohs micrographic surgery.

Mohs Micrographic Surgery (MMS) is effective for treating common cutaneous malignancies, but complex repairs may often present challenges for reconstruction. This paper explores the potential of three-dimensional (3D) bioprinting in MMS, offering superior outcomes compared to traditional methods. 3D printing technologies show promise in advancing skin regeneration and refining surgical techniques in dermatologic surgery. A PubMed search was conducted using the following keywords: "Three-dimensional bioprinting" OR "3-D printing" AND "Mohs" OR "Mohs surgery" OR "Surgery." Peer-reviewed English articles discussing medical applications of 3D bioprinting were included, while non-peer-reviewed and non-English articles were excluded. Patients using 3D MMS models had lower anxiety scores (3.00 to 1.7, p < 0.0001) and higher knowledge assessment scores (5.59 or 93.25% correct responses), indicating better understanding of their procedure. Surgical residents using 3D models demonstrated improved proficiency in flap reconstructions (p = 0.002) and knowledge assessment (p = 0.001). Additionally, 3D printing offers personalized patient care through tailored surgical guides and anatomical models, reducing intraoperative time while enhancing surgical. Concurrently, efforts in tissue engineering and regenerative medicine are being explored as potential alternatives to address organ donor shortages, eliminating autografting needs. However, challenges like limited training and technological constraints persist. Integrating optical coherence tomography with 3D bioprinting may expedite grafting, but challenges remain in pre-printing grafts for complex cases. Regulatory and ethical considerations are paramount for patient safety, and further research is needed to understand long-term effects and cost-effectiveness. While promising, significant advancements are necessary for full utilization in MMS.

Hospital water environment and antibiotic use: Key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens.

BACKGROUND: The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). Here, we report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS: The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analyzed. . RESULTS: The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics were associated with acquisition of KPC-SM (p < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION: Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant microorganisms, underscoring the necessity of enhancing infection control practices in these areas.

Telemedicine: Does it have a place in surgical oncology practice?

BACKGROUND: Telemedicine has gained traction in surgical subspecialties, particularly since the COVID-19 pandemic. This study aims to identify whether telemedicine can be appropriately integrated within surgical oncology practice. METHODS: This retrospective study evaluated patients who received either telemedicine or office follow-up after undergoing surgical oncology operations between 2016 and 2021. The telemedicine group (TG) and office group (OG) received a 15-question survey regarding their satisfaction with their care. Patient outcomes and responses were analyzed utilizing propensity-score matching in 1:1 fashion. RESULTS: Telemedicine group and OG each had 21 patients. Length of stay, complication frequency, follow-up frequency, and readmissions frequency within 90-days were comparable between groups. Telemedicine group expressed comparable satisfaction with postoperative care relative to OG (95.2% vs. 85.7%, p = 0.61). All telemedicine patients said they would utilize telemedicine again in the future and would recommend its use to others. CONCLUSION: Patient satisfaction with postoperative telemedicine follow-up is comparable to those with in-person follow-up.

EMBARK: A Randomized, Controlled Trial Comparing Three Approaches to Reducing Diabetes Distress and Improving HbA1c in Adults With Type 1 Diabetes.

OBJECTIVE: To compare the effectiveness of three interventions to reduce diabetes distress (DD) and improve HbA1c among adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Individuals with T1D (n = 276) with elevated DD (a score >2 on the total Type 1 Diabetes Distress Scale) and HbA1c (>7.5%) were recruited from multiple settings and randomly assigned to one of three virtual group-based programs: 1) Streamline, an educator-led education and diabetes self-management program; 2) TunedIn, a psychologist-led program focused exclusively on emotional-focused DD reduction; or 3) FixIt, an integration of Streamline and TunedIn. Assessments of the primary outcomes of DD and HbA1c occurred at baseline and at 3, 6, and 12 months. RESULTS: All three programs demonstrated substantive and sustained reductions in DD (Cohen's d = 0.58-1.14) and HbA1c (range, -0.4 to -0.72) at 12-month follow-up. TunedIn and FixIt participants reported significantly greater DD reductions compared with Streamline participants (P = 0.007). Streamline and TunedIn participants achieved significantly greater HbA1c reductions than did FixIt participants (P = 0.006). CONCLUSIONS: DD can be successfully reduced among individuals with T1D with elevated HbA1c using both the educational/behavioral and emotion-focused approaches included in the study. Although both approaches are associated with significant and clinically meaningful reductions in DD and HbA1c, TunedIn, the emotion-focused program, had the most consistent benefits across both DD and HbA1c. The study findings suggest the overall value of group-based, fully virtual, and time-limited emotion-focused strategies, like those used in TunedIn, for adults with T1D.

Pancreaticoduodenectomy for trauma in an adolescent female with complex pancreatic and duodenal injuries: Case report and review of the literature.

Background: We present a successful staged surgical repair of an adolescent who sustained a high grade combined pancreaticoduodenal injury following a high-speed motor vehicle collision. Methods: We discuss our case as well as provide a thorough literature review made on databases such as PubMed, Google Scholar, and Embase. Summary: A fifteen-year-old female presented after a motor vehicle collision with abdominal pain and imaging suggestive of pancreatic and duodenal injuries. Emergent exploratory laparotomy confirmed a transection of the pancreatic neck in addition to disruption of the second portion of the duodenum. She sustained other injuries including an injury to the portal vein and a right colonic perforation. A damage control strategy was employed, and the patient underwent duodenal repair, wide drainage of the pancreatic injury, primary portal vein repair, right hemicolectomy, and temporary abdominal closure using negative pressure wound dressing placement. She remained stable overnight in the ICU and was taken back to the operating room for a pylorus-preserving pancreaticoduodenectomy with a hepatobiliary surgeon the following afternoon. The patient required additional surgery for fixation of an unstable vertebral fracture but was discharged to inpatient rehab within two weeks of presentation. She did not require TPN, and the only long-term sequelae have been admissions for acute uncomplicated pancreatitis that have been treated medically. Conclusion: Combined pancreatic and duodenal injury in the pediatric population is uncommon. We discuss our case of a patient requiring a pancreaticoduodenectomy. Despite postoperative pancreatitis and limited information in this field, we believe we provided the optimal surgical care, and this is a potential area for future investigation.

When it's not ovarian cancer: A case of a massive leiomyoma with hydropic change.

Background: Uterine leiomyomas are benign tumors characterized by pelvic pain and abnormal bleeding. Their evolution can lead to degenerative changes, occasionally mimicking malignancies on imaging, presenting diagnostic challenges. Case presentation: A 31-year-old nulliparous woman presented with symptoms of bloating, cramping, and abdominal distension. Imaging suggested an advanced ovarian malignancy, showing a complex adnexal mass and elevated CA-125 levels. During exploratory laparotomy, what was suspected to be ovarian cancer was instead identified as a large uterine mass on pathologic evaluation revealing a benign leiomyoma with extensive hydropic change. Conclusion: This case highlights the diagnostic intricacies associated with large complex adnexal masses and illustrates how benign conditions like leiomyomas with hydropic degeneration can mimic ovarian cancer. This emphasizes the importance of comprehensive preoperative and intraoperative assessments to tailor management and avoid unindicated radical procedures.

Five multivariate Duchenne muscular dystrophy progression models bridging six-minute walk distance and MRI relaxometry of leg muscles.

The study aimed to provide quantitative information on the utilization of MRI transverse relaxation time constant (MRI-T2) of leg muscles in DMD clinical trials by developing multivariate disease progression models of Duchenne muscular dystrophy (DMD) using 6-min walk distance (6MWD) and MRI-T2. Clinical data were collected from the prospective and longitudinal ImagingNMD study. Disease progression models were developed by a nonlinear mixed-effect modeling approach. Univariate models of 6MWD and MRI-T2 of five muscles were developed separately. Age at assessment was the time metric. Multivariate models were developed by estimating the correlation of 6MWD and MRI-T2 model variables. Full model estimation approach for covariate analysis and five-fold cross validation were conducted. Simulations were performed to compare the models and predict the covariate effects on the trajectories of 6MWD and MRI-T2. Sigmoid Imax and Emax models best captured the profiles of 6MWD and MRI-T2 over age. Steroid use, baseline 6MWD, and baseline MRI-T2 were significant covariates. The median age at which 6MWD is half of its maximum decrease in the five models was similar, while the median age at which MRI-T2 is half of its maximum increase varied depending on the type of muscle. The models connecting 6MWD and MRI-T2 successfully quantified how individual characteristics alter disease trajectories. The models demonstrate a plausible correlation between 6MWD and MRI-T2, supporting the use of MRI-T2. The developed models will guide drug developers in using the MRI-T2 to most efficient use in DMD clinical trials.

Unraveling diffusion behavior in Cu-to-Cu direct bonding with metal passivation layers.

Cu/SiO2 hybrid bonding presents a promising avenue for achieving high-density interconnects by obviating the need for microbumps and underfills. Traditional copper bonding methods often demand temperatures exceeding 400 °C, prompting recent endeavors to mitigate bonding temperatures through investigations into metal passivation bonding. In this study, we scrutinized the diffusion behavior associated with various metal passivation layers (Platinum, Titanium, Tantalum, and Chromium) in the context of low-temperature direct copper bonding and delved into the essential bonding mechanisms. We observed a deviation from conventional metal-metal bonding factors, such as surface roughness and grain size, in the diffusion behavior. Remarkably, our analysis revealed a pronounced correlation between the crystallinity of the metal passivation layers and diffusion behavior, surpassing the influence of other experimental factors. Subsequent post-bonding examinations corroborated consistent diffusion behavior in Pt and Cr passivation samples with disparate crystallinities, reinforcing the significance of crystallinity in the bonding process. Our findings underscore crystallinity as a pivotal factor governing diffusion behavior, even under varied bonding conditions. These insights are instrumental in achieving exceptional bonding characteristics at lower temperatures in Cu/SiO2 hybrid bonding. Implications of this study extend to the prospect of advancing highly integrated systems through die-to-wafer bonding, marking a substantial stride toward future applications.

ARIA II: a randomized controlled trial of near-infrared Angiography during RectosIgmoid resection and Anastomosis in women with ovarian cancer.

BACKGROUND: Ovarian cancer with extensive metastatic disease involving pelvic structures often requires rectosigmoid resection for complete gross resection; however, it is associated with increased surgical morbidity. There are limited data, and none in ovarian cancer, on near-infrared assessment of perfusion in rectosigmoid resections with anastomosis. PRIMARY OBJECTIVE: To compare the rate of pelvic complications (pelvic abscesses, anastomotic leaks, and infections) within 30 days of surgery with and without near-infrared assessment of perfusion at time of rectosigmoid resection and re-anastomosis in patients undergoing cytoreductive surgery for ovarian cancer. STUDY HYPOTHESIS: We hypothesize the use of near-infrared technology (intravenous indocyanine green and endoscopic near-infrared fluorescence imaging), compared with standard intra-operative assessment, to evaluate anastomotic perfusion at time of rectosigmoid resection and re-anastomosis will result in lower rates of post-operative pelvic complications. TRIAL DESIGN: This is a planned multicenter randomized controlled trial. Patients who undergo rectosigmoid resection as part of their ovarian cytoreductive surgery will be randomized 1:1 to standard assessment of anastomosis with the surgeon's usual technique (control arm) or assessment with near-infrared angiography using indocyanine green and endoscopic fluorescence imaging (experimental arm). Randomization will occur after rectosigmoid resection has been completed and the surgeon declares their plan to create a diverting ostomy. Randomization will be stratified by plan for diverting ostomy. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria include patients with primary or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are scheduled for cytoreductive surgery with suspected need for low-anterior rectosigmoid resection. PRIMARY ENDPOINT: Rate of 30-day post-operative pelvic complications. SAMPLE SIZE: 310 (155 per arm) ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Q2 2027 and Q4 2027, respectively. TRIAL REGISTRATION: NCT04878094.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine.

Peptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self-assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug-loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor-mediated endocytosis and cell-penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease-specific targeting for diagnostics and therapeutics in diseases such as cancer.