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While the process of teaching student perfusionists has been in development since the 1950s, the publication of the processes to improve perfusion clinical education has been largely lacking. Publications regarding education from other allied health and medical fields have shown the value of student-centered learning. The use of reflective practice to move perfusion students from thinking about actions after cardiopulmonary bypass (CPB) to reflecting and reacting on actions during CPB is better encouraged by moving from a teacher-centered to a student-centered clinical model. Our institution’s teaching process has developed into a multi-point procedure to make our students into reflective practicing clinicians. Student preceptor evaluations were reversed to allow the students to evaluate themselves first, with feedback from the preceptor given subsequently. Additionally, a biweekly student educational session, where the student chooses a topic and reviews current evidence-based practice, was instituted. The clinical program director serves as the moderator and clinical expert to facilitate problem-based learning during the sessions. Students were also given three skill/experience levels with goals to reach and move through during the rotation. These student levels were also helpful to our preceptors in knowing what each student’s skill level was throughout their rotation. Overall, moving from a teacher-centered to a student-centered clinical rotation has helped make students familiar with reflective practice, self-evaluation, evidence-based practice, and problem-based learning. The incorporation of these processes will hopefully lead students to become lifelong reflective perfusionists.

Sequencing has revealed hundreds of millions of human genetic variants, and continued efforts will only add to this variant avalanche. Insufficient information exists to interpret the effects of most variants, limiting opportunities for precision medicine and comprehension of genome function. A solution lies in experimental assessment of the functional effect of variants, which can reveal their biological and clinical impact. However, variant effect assays have generally been undertaken reactively for individual variants only after and, in most cases long after, their first observation. Now, multiplexed assays of variant effect can characterise massive numbers of variants simultaneously, yielding variant effect maps that reveal the function of every possible single nucleotide change in a gene or regulatory element. Generating maps for every protein encoding gene and regulatory element in the human genome would create an Atlas of variant effect maps and transform our understanding of genetics and usher in a new era of nucleotide-resolution functional knowledge of the genome. An Atlas would reveal the fundamental biology of the human genome, inform human evolution, empower the development and use of therapeutics and maximize the utility of genomics for diagnosing and treating disease. The Atlas of Variant Effects Alliance is an international collaborative group comprising hundreds of researchers, technologists and clinicians dedicated to realising an Atlas of Variant Effects to help deliver on the promise of genomics.

Abstract: Mechanical gradients are often employed in nature to prevent biological materials from damage by creating a smooth transition from strong to weak that dissipates large forces. Synthetic mimics of these natural structures are highly desired to improve distribution of stresses at interfaces and reduce contact deformation in manmade materials. Current synthetic gradient materials commonly suffer from non‐continuous transitions, relatively small gradients in mechanical properties, and difficult syntheses. Inspired by the polychaete worm jaw, we report a novel approach to generate stiffness gradients in polymeric materials via incorporation of dynamic monodentate metal–ligand crosslinks. Through spatial control of metal ion content, we created a continuous mechanical gradient that spans over a 200‐fold difference in stiffness, approaching the mechanical contrast observed in biological gradient materials.

Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Methods: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38–98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Results: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Conclusion: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers. [ABSTRACT FROM AUTHOR]

Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis.

Objective: Older people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group? Methods: We used data from the UK MS Register to characterize demographics and clinical features of late‐onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with adult‐onset MS (AOMS; onset 18–49 years). We performed a pathology study of a separate MS cohort with a later onset (n = 18, mean age of onset 54 years) versus AOMS (n = 23, mean age of onset 29 years). Results: In the Register cohort, there were 1,608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of women, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 vs. 28.3, p < 0.001), and a higher proportion of gait‐related initial symptoms. People with LOMS were less likely to receive a high efficacy disease‐modifying treatment and attained substantial disability sooner. Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset‐age, whereas actively demyelinating lesions and compartmentalized inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalized inflammation, correlated with disability outcomes in older‐onset MS patients. Interpretation: The more progressive nature of older‐onset MS is associated with significant neurodegeneration, but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. ANN NEUROL 2024;95:471–486 [ABSTRACT FROM AUTHOR]

James Neal begins this essay with the introduction of the 1996 paper, "Choosing Our Futures," by calling it a provocation, and a call to arms for the academic library community to challenge complacency and move forward toward fundamental change. Neal writes here that in the context of extraordinary economic pressures, the early transformation of scholarly communication, new thinking about the role and nature of higher education, rampant technological innovation, rapidly shifting user behaviors and expectations, the authors confront the classic debate on the nature of transformation. Will it be incremental, evolutionary, or revolutionary? They also flirt with the prospect of extinction: that is, will it be terminal, the demise of the academic library, or will it be phyletic, the library surviving by progressing to a new species? They call for the systematic application of new knowledge to new resources to produce new goods and new services, responsive to the market. They advocate a process of lowering the costs and increasing the benefits of the work, adding value. They encourage new and deliberate thinking about existing challenges and unmet needs, a focus on solutions. Neal maintains that the "Choosing Our Futures" essay that was an important think piece when it was written in the 1990s remains so today because it translates thoughtful reflection about local practice into a series of observations and thoughts about the future of academic libraries. Neal concludes that this sort of writing still has a place in "College and Research Libraries " today because research libraries must continue to deliberate the past, document and analyze the present, and debate prospects and evolution to grow and remain strong, and relative.