Assessing Rectal Cancer Treatment Response Using Coregistered Endorectal Photoacoustic and US Imaging Paired with Deep Learning.

Background Conventional radiologic modalities perform poorly in the radiated rectum and are often unable to differentiate residual cancer from treatment scarring. Purpose To report the development and initial patient study of an imaging system comprising an endorectal coregistered photoacoustic (PA) microscopy (PAM) and US system paired with a convolution neural network (CNN) to assess the rectal cancer treatment response. Materials and Methods In this prospective study (ClinicalTrials.gov identifier NCT04339374), participants completed radiation and chemotherapy from September 2019 to September 2020 and images were obtained with the PAM/US system prior to surgery. Another group's colorectal specimens were studied ex vivo. The PAM/US system consisted of an endorectal imaging probe, a 1064-nm laser, and one US ring transducer. The PAM CNN and US CNN models were trained and validated to distinguish normal from malignant colorectal tissue using ex vivo and in vivo patient data. The PAM CNN and US CNN were then tested using additional in vivo patient data that had not been seen by the CNNs during training and validation. Results Twenty-two patients' ex vivo specimens and five patients' in vivo images (a total of 2693 US regions of interest [ROIs] and 2208 PA ROIs) were used for CNN training and validation. Data from five additional patients were used for testing. A total of 32 participants (mean age, 60 years; range, 35-89 years) were evaluated. Unique PAM imaging markers of the complete tumor response were found, specifically including recovery of normal submucosal vascular architecture within the treated tumor bed. The PAM CNN model captured this recovery process and correctly differentiated these changes from the residual tumor. The imaging system remained highly capable of differentiating tumor from normal tissue, achieving an area under the receiver operating characteristic curve of 0.98 (95% CI: 0.98, 0.99) for data from five participants. By comparison, the US CNN had an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.70, 0.73). Conclusion An endorectal coregistered photoacoustic microscopy/US system paired with a convolutional neural network model showed high diagnostic performance in assessing the rectal cancer treatment response and demonstrated potential for optimizing posttreatment management. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Klibanov in this issue.

Molecular mechanisms of cancer pain.

Pain is the most disruptive influence on the quality of life of cancer patients. Although significant advances are being made in cancer treatment and diagnosis, the basic neurobiology of cancer pain is poorly understood. New insights into these mechanisms are now arising from animal models, and have the potential to fundamentally change the way that cancer pain is controlled.

Case study: the health SmartLibrary experiences in web personalization and customization at the Galter health sciences library, Northwestern University.

QUESTION: How can the user's access to health information, especially full-text articles, be improved? The solution is building and evaluating the Health SmartLibrary (HSL). SETTING: The setting is the Galter Health Sciences Library, Feinberg School of Medicine, Northwestern University. METHOD: The HSL was built on web-based personalization and customization tools: My E-Resources, Stay Current, Quick Search, and File Cabinet. Personalization and customization data were tracked to show user activity with these value-added, online services. MAIN RESULTS: Registration data indicated that users were receptive to personalized resource selection and that the automated application of specialty-based, personalized HSLs was more frequently adopted than manual customization by users. Those who did customize customized My E-Resources and Stay Current more often than Quick Search and File Cabinet. Most of those who customized did so only once. CONCLUSION: Users did not always take advantage of the services designed to aid their library research experiences. When personalization is available at registration, users readily accepted it. Customization tools were used less frequently; however, more research is needed to determine why this was the case.

Evaluation of unmeshed and 1:1 meshed AlloDerm bolsters for stapled rectal anastomoses in a porcine model.

INTRODUCTION: The major morbidity of colorectal anastomoses is leaks. The concept of staple-line reinforcement is a growing area of interest. In this study, we evaluated the feasibility and effect of utilizing AlloDerm to bolster end-to-end stapled rectal anastomoses in a porcine model. METHODS: A total of 30 female 45-kg domestic pigs were studied, and each served as its own control by creating a bolstered and unbolstered anastomosis in each animal. All anastomoses were created with a 29-mm end-to-end stapling device. Bolstered anastomoses were randomized to proximal and distal positions along the rectum, and each rectorectal anastomosis was separated by an average of 10 cm. In 20 pigs, an unmeshed bolster of a 0.5-0.7-mm thickness was used. The remaining 10 pigs had a 1:1 meshed bolster that was 0.34-0.51 mm thick. The animals were survived for 14 days. Barium enemas were then performed and the two anastomotic sites harvested, and each anastomosis underwent burst testing. The internal diameter of each anastomosis was measured and a biochemical analysis was performed for matrix metalloproteinase (MMP), elastin and collagen content. RESULTS: The unmeshed bolstered anastomoses burst fewer times than the unbolstered anastomoses (P=0.004) and had higher burst pressures (P=0.023), though their anastomotic circumferences were smaller (P=0.007). Meshed bolsters offered no strength advantage to anastomoses and were significantly (P=0.009) smaller than unbolstered anastomoses in the same animal. No difference in elastin, collagen, or MMP content was observed between bolstered and unbolstered groups. No animals had clinical or radiographic leaks. CONCLUSIONS: The routine use of unmeshed and 1:1 meshed AlloDerm bolsters is safe and does not appear to inhibit healing in elective colorectal surgery on healthy subjects. AlloDerm may have a role as a tissue bolster in select patients who are more prone to develop anastomotic leaks.

Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program.

A combined analysis of genome scans was performed for adult height in the NHLBI Family Blood Pressure Program. Height data were available on 6752 individuals. Linkage analysis was performed first separately for each of the eight ethnic groups in the four networks using the variance component method. To increase the power to detect the common genetic components affecting height for all the individuals, a linkage analysis was performed subsequently for the combined data set by pooling the average allele-sharing IBD () for all groups. By combining the data, we replicated evidence for a QTL influencing adult height on chromosome 7 (7q31) (LOD=2.46), which has been reported in two previous studies. Suggestive linkage (LOD>1) was found in another six regions in our combined analysis. Evidence for linkage for two of these regions (2p12, 20p11) has also been reported previously.

A genome-wide affected sibpair linkage analysis of hypertension: the HyperGEN network.

Results are reported here from a genome-wide linkage analysis of hypertension in a large sample of hypertensive (affected) sibpairs (650 African American and 915 white sibpairs) recruited by the HyperGEN Network of the National Heart, Lung and Blood Institute (NHLBI) Family Blood Pressure Program (FBPP). Analysis using MAPMAKER/SIBS suggests one interesting region with a LOD score of 2.08 at 63 cM from the p telomere on chromosome 2 in the African American sibpairs, which may harbor hypertension susceptibility genes.

A gene expression and systems pathway analysis of the effects of clozapine compared to haloperidol in the mouse brain implicates susceptibility genes for schizophrenia.

Clozapine has markedly superior clinical properties compared to other antipsychotic drugs but the side effects of agranulocytosis, weight gain and diabetes limit its use. The reason why clozapine is more effective is not well understood. We studied messenger RNA (mRNA) gene expression in the mouse brain to identify pathways changed by clozapine compared to those changed by haloperidol so that we could identify which changes were specific to clozapine. Data interpretation was performed using an over-representation analysis (ORA) of gene ontology (GO), pathways and gene-by-gene differences. Clozapine significantly changed gene expression in pathways related to neuronal growth and differentiation to a greater extent than haloperidol; including the microtubule-associated protein kinase (MAPK) signalling and GO terms related to axonogenesis and neuroblast proliferation. Several genes implicated genetically or functionally in schizophrenia such as frizzled homolog 3 (FZD3), U2AF homology motif kinase 1 (UHMK1), pericentriolar material 1 (PCM1) and brain-derived neurotrophic factor (BDNF) were changed by clozapine but not by haloperidol. Furthermore, when compared to untreated controls clozapine specifically regulated transcripts related to the glutamate system, microtubule function, presynaptic proteins and pathways associated with synaptic transmission such as clathrin cage assembly. Compared to untreated controls haloperidol modulated expression of neurotoxic and apoptotic responses such as NF-kappa B and caspase pathways, whilst clozapine did not. Pathways involving lipid and carbohydrate metabolism and appetite regulation were also more affected by clozapine than by haloperidol.

Multiple genes for essential-hypertension susceptibility on chromosome 1q.

Essential hypertension, defined as elevated levels of blood pressure (BP) without any obvious cause, is a major risk factor for coronary heart disease, stroke, and renal disease. BP levels and susceptibility to development of essential hypertension are partially determined by genetic factors that are poorly understood. Similar to other efforts to understand complex, non-Mendelian phenotypes, genetic dissection of hypertension-related traits employs genomewide linkage analyses of families and association studies of patient cohorts, to uncover rare and common disease alleles, respectively. Family-based mapping studies of elevated BP cover the large intermediate ground for identification of genes with common variants of significant effect. Our genomewide linkage and candidate-gene-based association studies demonstrate that a replicated linkage peak for BP regulation on human chromosome 1q, homologous to mouse and rat quantitative trait loci for BP, contains at least three genes associated with BP levels in multiple samples: ATP1B1, RGS5, and SELE. Individual variants in these three genes account for 2-5-mm Hg differences in mean systolic BP levels, and the cumulative effect reaches 8-10 mm Hg. Because the associated alleles in these genes are relatively common (frequency >5%), these three genes are important contributors to elevated BP in the population at large.

Individual differences in responsivity to a neurobehavioural examination predict crying patterns of 1-week-old infants at home.

Unexplained crying in infants aged 1 to 3 months is a common concern for Western parents and health services. This study examined the hypothesis that the crying is due to high infant responsivity, and provides evidence about the types of stimulation that trigger crying in infants who present with high responsivity. The sample included 93 eight-day-old infants from a community sample (47 females, 46 males; mean birthweight 3457g; mean gestation 39.4 weeks; mean Apgar scores 8.28 at 1 minute and 9.59 at 5 minutes). Infants were tested for their response to two standard, mildly challenging, procedures: a neurobehavioural test involving undressing, putting down, and handling, and the Guthrie test, involving a painful heel prick to obtain a blood sample. The infants' crying over 24 hours was recorded in parental diaries. Newborn infants who exhibited high responsivity during the neurobehavioural assessment cried, rather than fussed, the most at home. High responsivity during the neurobehavioural assessment also predicted those infants who cried a lot and met a definition of 'colic' at home. The findings support the responsivity hypothesis and show that infants with high responsivity are upset by undressing, putting down, and sustained handling. Explanations for this and implications for the management of infant crying and colic are discussed.

Evaluating the Health SmartLibrary.

The Health SmartLibrary (HSL), supported by the National Library of Medicine (Information Systems grant # 1 G08 LM07051-01A1), is a web-based system designed to target resources relevant to the users' information needs. Faculty and librarians collaborated to build tools that would make access to information resources easy and efficient. These tools include current awareness; a metasearch engine; a file cabinet; personalization features; and discipline-based resource collections.

A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.

Familial hypercholesterolemia results from mutations in the low-density lipoprotein (LDL) receptor or apolipoprotein B genes. We have previously reported the identification of a Utah autosomal-dominant hypercholesterolemia pedigree (kindred 1173) that did not show linkage to either of these loci (Hunt et al. 2000). Expansion of the pedigree and increased marker density within the region of interest have resulted in a multipoint LOD score of 9.6 and enabled us to decrease the size of the linked region to approximately 7.5 Mbp. In addition, we were able to identify additional families sharing the same microsatellite haplotype. While all haplotype carriers in kindred 1173 (K1173) are affected, the haplotype carriers within the newly identified families are unaffected, suggesting that the causal mutation in K1173 had occurred after divergence of these pedigrees from a common ancestor. Mutation screening of genes in the region identified a single nucleotide variant (G-->T) present on the K1173 haplotype that was not present on the same haplotype in the other kindreds. This variant results in a D374Y missense change in the gene PCSK9.