Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

The role of pharmacogenomics in precision mental health care.

ABSTRACT: Pharmacogenomics is the study of how genes affect a person's response to medications. This science has given rise to the practice of "precision health care," which combines pharmacology (the study of medication) and genomics (the study of genes and their functions) to inform a more personalized approach. Related considerations include which medications to prescribe to different individuals and what doses will have the most therapeutic effects (with the fewest side effects). A case of recalcitrant depression and anxiety (in the context of chronic inflammatory and autoimmune disease) serves as the basis for discussion of psychopharmacogenomics to inform a more effective treatment approach for psychiatric symptoms. A contemporary understanding of neurobiology and neuropathology, enhanced by genetic and genomic information, supports new models for diagnosis and precision treatment of commonly recurring mental health problems.

Participant perceptions and experiences of a novel community-based respiratory longitudinal sampling method in Liverpool, UK: A mixed methods feasibility study.

Longitudinal, community-based sampling is important for understanding prevalence and transmission of respiratory pathogens. Using a minimally invasive sampling method, the FAMILY Micro study monitored the oral, nasal and hand microbiota of families for 6 months. Here, we explore participant experiences and opinions. A mixed methods approach was utilised. A quantitative questionnaire was completed after every sampling timepoint to report levels of discomfort and pain, as well as time taken to collect samples. Participants were also invited to discuss their experiences in a qualitative structured exit interview. We received questionnaires from 36 families. Most adults and children >5y experienced no pain (94% and 70%) and little discomfort (73% and 47% no discomfort) regardless of sample type, whereas children ≤5y experienced variable levels of pain and discomfort (48% no pain but 14% hurts even more, whole lot or worst; 38% no discomfort but 33% moderate, severe, or extreme discomfort). The time taken for saliva and hand sampling decreased over the study. We conducted interviews with 24 families. Families found the sampling method straightforward, and adults and children >5y preferred nasal sampling using a synthetic absorptive matrix over nasopharyngeal swabs. It remained challenging for families to fit sampling into their busy schedules. Adequate fridge/freezer space and regular sample pick-ups were found to be important factors for feasibility. Messaging apps proved extremely effective for engaging with participants. Our findings provide key information to inform the design of future studies, specifically that self-sampling at home using minimally invasive procedures is feasible in a family context.

Multi-resonant tessellated anchor-based metasurfaces.

In this work, a multi-resonant metasurface that can be tailored to absorb microwaves at one or more frequencies is explored. Surface shapes based on an 'anchor' motif, incorporating hexagonal, square and triangular-shaped resonant elements, are shown to be readily tailorable to provide a targeted range of microwave responses. A metasurface consisting of an etched copper layer, spaced above a ground plane by a thin (< 1/10th of a wavelength) low-loss dielectric is experimentally characterised. The fundamental resonances of each shaped element are exhibited at 4.1 GHz (triangular), 6.1 GHz (square) and 10.1 GHz (hexagonal), providing the potential for single- and multi-frequency absorption across a range that is of interest to the food industry. Reflectivity measurements of the metasurface demonstrate that the three fundamental absorption modes are largely independent of incident polarization as well as both azimuthal and elevation angles.

Multiscale anisotropy analysis of second-harmonic generation collagen imaging of human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a minority (< 10%) of patients surviving five years past diagnosis. This could be improved with the development of new imaging modalities for early differentiation of benign and cancerous fibrosis. This study intends to explore the application of a two-photon microscopy technique known as second harmonic generation to PDAC using the 2D Wavelet Transform Modulus Maxima (WTMM) Anisotropy method to quantify collagen organization in fibrotic pancreatic tissue. Forty slides from PDAC patients were obtained and eight images were captured per each tissue category on each slide. Brownian surface motion and white noise images were generated for calibration and testing of a new variable binning approach to the 2D WTMM Anisotropy method. The variable binning method had greater resistance to wavelet scaling effects and white noise images were found to have the lowest anisotropy factor. Cancer and fibrosis had greater anisotropy factors (Fa) at small wavelet scales than normal and normal adjacent tissue. At a larger scale of 21 µm this relationship changed with normal tissue having a higher Fa than all other tissue groups. White noise is the best representative image for isotropy and the 2D WTMM anisotropy method is sensitive to changes induced in collagen by PDAC.

A Case Report of Clozapine-induced Pleural Effusion in a 28-Year-Old Chinese Male.

Increasing reports have appeared of pleural effusion and peripheral eosinophilia associated with clozapine treatment. These reports describe the onset of pleural effusion from 2 to 5 weeks after initiation of clozapine. Here, we describe a case of a 28-year-old Chinese male who presented with pleural effusion and peripheral eosinophilia ∼17 weeks after initiation of clozapine. We discuss this delayed presentation and examine the potential significance of the patient's East Asian ethnicity. We recommend clinicians consider ethnicity and other factors that can affect the metabolism of clozapine when choosing a clozapine titration schedule and when monitoring during clozapine treatment.

Polysaccharide utilization loci in Bacteroides determine population fitness and community-level interactions.

Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably Bacteroides, contain numerous PULs that enable glycan utilization and shape ecological dynamics. To investigate the role of PULs on fitness and inter-species interactions, we develop a CRISPR-based genome editing tool to study 23 PULs in Bacteroides uniformis (BU). BU PULs show distinct glycan-degrading functions and transcriptional coordination that enables the population to adapt upon loss of other PULs. Exploiting a BU mutant barcoding strategy, we demonstrate that in vitro fitness and BU colonization in the murine gut are enhanced by deletion of specific PULs and modulated by glycan availability. PULs mediate glycan-dependent interactions with butyrate producers that depend on the degradation mechanism and glycan utilization ability of the butyrate producer. Thus, PULs determine community dynamics and butyrate production and provide a selective advantage or disadvantage depending on the nutritional landscape.

Evaluation of the Usage and Dosing of Guideline-Directed Medical Therapy for Heart Failure With Reduced Ejection Fraction Patients in Clinical Practice.

BACKGROUND: Although strategies for optimization of pharmacologic therapy in patients with heart failure with reduced ejection fraction (HFrEF) are scripted by guidelines, data from HF registries suggests that guideline-directed medical therapies (GDMT) are underutilized among eligible patients. Whether this discrepancy reflects medication intolerance, contraindications, or a quality of care issue remains unclear. OBJECTIVE: The objective of this initiative was to identify reasons for underutilization and under-dosing of HFrEF therapy in patients at a large, academic medical center. METHODS: Among 500 patients with HFrEF enrolled in a quality improvement project at a tertiary center, we evaluated usage and dosing of 4 categories of GDMT: ACE inhibitors/Angiotensin Receptor Blockers (ACE-i/ARB), Angiotensin Receptor-Neprilysin Inhibitors (ARNi), beta blockers, and Mineralocorticoid Receptor Antagonists (MRA). Reasons for nonprescription and usage of suboptimal doses were abstracted from notes in the chart and from telephone review of previous medication trials with the patient. RESULTS: Of 500 patients identified, 472 subjects had complete data for analysis. Among eligible patients, ACE-i/ARB were prescribed in 81.4% (293 of 360) and beta blockers in 94.4% (442 of 468). Of these patients, 10.6% were prescribed target doses of ACE-i/ARB and 12.4% were prescribed target doses of beta blockers. Utilization of other categories of GDMT was lower, with 54% of eligible patients prescribed MRAs and 27% prescribed an ARNi. In most cases, the reasons for nonprescription or under-dosing of GDMT were not apparent on review of the health record or discussion with the patient. CONCLUSION: Clear rationale for nonprescription and under-dosing of GDMT often cannot be ascertained from detailed review and is only rarely related to documented medication intolerance or contraindications, suggesting an opportunity for quality improvement.

Design of synthetic human gut microbiome assembly and butyrate production.

The capability to design microbiomes with predictable functions would enable new technologies for applications in health, agriculture, and bioprocessing. Towards this goal, we develop a model-guided approach to design synthetic human gut microbiomes for production of the health-relevant metabolite butyrate. Our data-driven model quantifies microbial interactions impacting growth and butyrate production separately, providing key insights into ecological mechanisms driving butyrate production. We use our model to explore a vast community design space using a design-test-learn cycle to identify high butyrate-producing communities. Our model can accurately predict community assembly and butyrate production across a wide range of species richness. Guided by the model, we identify constraints on butyrate production by high species richness and key molecular factors driving butyrate production, including hydrogen sulfide, environmental pH, and resource competition. In sum, our model-guided approach provides a flexible and generalizable framework for understanding and accurately predicting community assembly and metabolic functions.

Absorption modes of Möbius strip resonators.

In this work, the electromagnetic response of a mathematically interesting shape-a Möbius strip-is presented, along with a ring resonator for comparison. Both resonators consist of a central lossy dielectric layer bounded by perfectly conducting layers. For the case of the Möbius strips, the computational results show that there are a family of half-integer wavelength modes within the dielectric layer. These additional modes result in increased absorption, and a corresponding reduction in the radar cross section. Interestingly, rotational scans show that these modes can be excited over a large angular range. This investigation gives an understanding of the electromagnetic response of these structures, paving the way for future experiments on Möbius strip resonators.