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Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center.

The growth of omic data presents evolving challenges in data manipulation, analysis and integration. Addressing these challenges, Bioconductor provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming offers a revolutionary data organization and manipulation standard. Here we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analyzing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas, spanning six data frameworks and ten analysis tools.

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P< .01), and stimulated C-peptide levels were lower (P< .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P< .0001), with no insulin independence 12 months posttransplant (P< .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P< .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1–4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays the development of drug resistance. APOBEC mutational signatures are enriched in tumours from patients with lung cancer who progressed after extended responses to targeted therapies. This study shows that induction of A3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that suppression of A3A expression or activity may represent a potential therapeutic strategy in the prevention or delay of acquired resistance to lung cancer targeted therapy.

In this study, Wang et al. show that the inhibition of ATR kinase affords selective lethality to mismatch repair-deficient (MMR-d) cancer cells by promoting MUS81 nuclease- and replication-dependent DNA damage, increasing cytosolic DNA fragments, and activating cGAS signaling. The consequent interferon response potentially stimulates cytotoxic T-cell-dependent antitumor immunity and points to ATR inhibition as a notable strategy to augment PD-1 targeting immunotherapies against MMR-d cancers.

Catch‐and‐release (C&R) ice fishing is a popular form of recreational angling. At present, there is a considerable deficiency in our understanding of how ice angling affects the physiology, behavior, and survival of fish. Thus, the purpose of this review was to summarize our current knowledge of the consequences of winter C&R fishing on fish biology and to identify key knowledge gaps. Our synthesis revealed that in addition to the typical stressors encountered from C&R fishing during the open‐water season, fish that are caught through the ice are subject to several unique challenges, including exposure to subzero air temperatures upon landing as well as unique gear types that are not commonly used in the summer (i.e., passive angling techniques). We currently understand that while C&R angling causes a generalized stress response, cold environments may mute or delay these effects and may also come with additional deleterious consequences, such as tissue freezing. Interestingly, reported mortality can be low following release but can be influenced by gear type, barotrauma, and hooking location. Postrelease behaviors and the spatial ecology of ice‐angled fish are poorly understood, but technologies such as telemetry and biologgers and an intensification of research on the topic are starting to produce new insights in this area. As it stands, research on the consequences of winter C&R angling is largely restricted to a handful of popular sport fish species, and these consequences are likely not being considered in management and conservation contexts. Given the increasing popularity of the sport, furthering our understanding of C&R impacts in the winter represents a timely and important area of inquiry and can be used to develop more informed and effective C&R guidelines and management practices.

Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection. This finding suggests approaches to developing improved therapeutic insulins. Curiously, the receptor displays a continuum of conformations from the symmetric state to a highly asymmetric low-abundance structure that displays coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions.

Black bass fishing tournaments with conventional weigh‐ins tend to displace fish from their capture site and often release fish within close proximity to the weigh‐in site. Tournaments often include Largemouth Bass Micropterus salmoidesand Smallmouth Bass M. dolomieuand occur throughout fishing seasons; however, there have yet to be any systematic congeneric comparisons across different seasons. Objectives of our study were to (1) assess post‐tournament dispersal of Largemouth Bass and Smallmouth Bass (i.e., short‐term stockpiling—accumulation of fish around weigh‐in site <1 month after tournament) across seasons, and (2) determine the success of return to the main basin. Research took place on Big Rideau Lake in eastern Ontario and included a preseason control (N= 30) where fish were captured, acoustically tagged, and released at the site of tournament weigh‐in (Rideau Ferry). Tournament‐caught bass (N= 88 total) were tagged at three tournaments that spanned June (early season), August (midseason), and October (late season). Our results indicated a brief short‐term stockpiling (within 300 m) in all seasons, and all detected fish eventually returned to the main basin. Tournament‐caught Largemouth Bass tended to take longer to disperse from the release site following the midseason tournament (4.6 d); Smallmouth Bass tended to disperse from release site <1 d following all treatments. Similarly, tournament‐caught Largemouth Bass exposed to the midseason tournament tended to take the longest to redistribute to the main basin (238 d) in comparison to other treatments. Although Smallmouth Bass tended to redistribute to the main basin faster than Largemouth Bass, late‐season Smallmouth Bass tended to redistribute the slowest (101 d) following tournament release. Although fish do survive and eventually return to the main basin, displacement may have broader ecological consequences (i.e., large‐scale displacement of top predators, adverse effects on recruitment) such that there would be merit in more catch–weigh–release formatted events.

This paper describes the findings of an independent peer review of the modeling tools used by the Volpe National Transportation Systems Center to forecast national vehicle miles traveled (VMT) over the next 30 years. Overall, the VMT forecasting models, which use autoregressive distributed lag models for light-duty vehicle, single-unit truck, and combination truck VMT, work well to estimate travel demand. All model estimations were reviewed, and all models perform well against several validation and testing techniques. The study team was supported by an expert panel selected from academia, government, and industry with experience in econometric methods, transportation and economic data, and modeling methods. The panel reviewed model documentation as well as the report assessing the VMT forecasting models and provided insight into alternative model research. The paper is an effort to synthesize the approaches and the validation methods used. A complementary literature search was also conducted to test the validity and comparability of several estimated variable coefficients. The paper concludes by summarizing the key findings and making recommendations on future model improvements.

The premise of catch‐and‐release recreational angling is that postrelease survival is high. Therefore, it is common for anglers, management agencies, and conservation organizations to share information on handling practices and other strategies that are believed to improve the welfare and survival of fish that are released. A recent surge in popularity has sensationalized the use of carbonated beverages to treat bleeding fish—an intervention that is purported to stop bleeding but has yet to be validated scientifically. We captured Northern Pike Esox luciusvia hook and line and experimentally injured their gills in a standardized manner. Gill injuries were treated with Mountain Dew, Coca‐Cola, or carbonated lake water. The duration and intensity of bleeding as well as overall blood loss (using gill color as a proxy) were observed while the fish were held in a lake water bath. As a control, we used a group of experimentally injured fish that did not have liquid poured over their gills before the observation period. All treatments and the control were conducted at two different water temperatures (11–18°C and 24–27°C) to determine whether the effects of pouring carbonated beverages over injured gills are seasonally dependent. When compared to the control, we found that the duration and intensity of bleeding increased regardless of the type of carbonated beverage used in this study, and there was no effect of season. Use of chilled versus ambient‐temperature beverages similarly had no influence on outcomes. As such, there is no scientific evidence to support the use of carbonated beverages for reducing or stopping blood loss in fish that receive gill injuries during recreational angling based on the context studied here. Our study reinforces the need to scientifically test angler anecdotes and theories regarding best practices for catch‐and‐release fishing.

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5–10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2–46?Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0–7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n?=?16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n?=?530) and glioblastoma (n?=?171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n?=?10), TSC cortical tubers (n?=?15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3;and TFs IRF6and EOMESwere all expressed >12-fold higher in SEGAs (FDR/q-value?

In live‐release angling tournaments, fish are captured and typically held within onboard live‐well systems, where they are subsequently “culled” (i.e., released) as larger fish are captured. Anglers often mark individual fish to easily identify them based on weight and to reduce handling time. However, there is limited information about the physiological consequences of using different culling apparatus on fish. This study examined the physiological consequences associated with using four different types of culling apparatus (i.e., metal stringer through the jaw, pincher on the jaw, lasso around the caudal peduncle, and zippered mesh bag) on Largemouth Bass Micropterus salmoidesrelative to controls during a 2‐h live‐well retention period. Blood samples were taken afterwards and were analyzed for blood glucose, blood lactate, plasma cortisol, and osmolality. Compared to the baseline control (i.e., fish that were captured, subjected to blood sampling, and immediately released), blood parameters (except osmolality) were significantly elevated in all treatments. The pincher and lasso treatments tended to yield higher physiological disturbances than the other treatments, including fish that were held in the live well without any culling apparatus. Moreover, the lasso culling apparatus appeared to cause noticeable injury relative to the other culling devices. Our research provides valuable information to help guide the selection of culling gear that maintains the welfare status of retained fish during tournaments.

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5–10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2–46 Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0–7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n= 16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n= 530) and glioblastoma (n= 171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n= 10), TSC cortical tubers (n= 15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3;and TFs IRF6and EOMESwere all expressed >12-fold higher in SEGAs (FDR/q-value < 0.05). Immunohistochemistry supported the specificity of IRF6, VAX1, SIX3 for SEGAs in comparison to other tumor entities and normal brain. We conclude that SEGAs have an extremely low somatic mutation rate, suggesting that TSC1/TSC2loss is sufficient to drive tumor growth. The unique and highly expressed SEGA-specific TFs likely reflect the neuroepithelial cell of origin, and may also contribute to the transcriptional and epigenetic state that enables SEGA growth following two-hit loss of TSC1or TSC2and mTORC1 activation.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is Available in the Text.

Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium against ischemia-reperfusion injury. We sought to compare major adverse cardiovascular events (MACE) for patients who received RIC before PCI for ST-segment–elevation myocardial infarction (STEMI) compared with standard care.

Supplemental Digital Content is Available in the Text.

Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins—a human des-octapeptide insulin analog—as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24–PheB25–TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.

•Diagnostic and relapse diffuse large B-cell lymphoma (DLBCL) biopsies reveal increased mutational burden/loss of heterozygosity in HLA-A.•Serially sampled tumor biopsies provide insight into therapeutic targets and evolutionary divergence in relapsed/refractory DLBCL.

In recreational fisheries it is understood that individual fish that exhibit bolder personality traits have a tendency to be removed from the population (i.e., fishing mortality via harvest or catch‐and‐release mortality), while more timid individuals remain. The use of aquatic protected areas (APAs) has been promoted as a means of offsetting the negative consequences that are associated with fishing mortality by protecting the full suite of phenotypes. However, little work has investigated whether APAs are able to maintain heterogeneity in behavioral traits in wild fish. We attempted to address this question by using wild Bluegill Lepomis macrochirusfrom Lake Opinicon, a freshwater system consisting of both an APAand heavily fished areas. The Bluegill were obtained via angling from three zones in the lake: the main lake area (i.e., fished), the APA(which has been in place since the 1940s), and a transitional zone between these two areas. In the laboratory, the Bluegill were subjected to two behavioral assessments, a Z‐maze and a flight‐initiation‐distance (FID) test, to address differences in boldness and risk‐taking between these populations. No significant effects of capture zone were detected for any of the behavioral metrics that were assessed in the maze trial. However, individuals that originated from the main lake population had significantly higher FIDscores than the fish from the transitional zone and the APAdid, indicating that they were more timid. Our results suggest that fisheries activities may only be acting only on specific traits, which may explain some of the null results that are presented here. Nevertheless, our study provides evidence that APAs are providing a reservoir of less timid individuals, which is consistent with an evolutionarily enlightened management strategy.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZand TOB1, focal deletions in BRD4and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

Slower reaction times to targets presented at a previously cued or attended location are often attributed to inhibition of return (IOR). It has been suggested that IOR affects a process at the output end of processing continuum when it is generated while the oculomotor system is activated. Following the path set by Kavyani, Farsi, Abdoli, and Klein (2017)we used the locus of slack logic embedded in the psychological refractory period (PRP) paradigm to test this idea. We generated what we expected would be the output form of IOR by beginning each with participants making a target directed saccade which was followed by two tasks. Task 1, was a 2-choice auditory discrimination task and Task 2 was a 2-choice visual localization task. We varied the interval between the onsets of the two targets associated with these two tasks (using TTOAs of 200, 400, or 800 msec). As expected the visual task suffered from a robust PRP effect (substantially delayed RTs at the shorter TTOAs). There was also a robust IOR effect with RTs to localize visual targets being slower when the targets were presented at a previously fixated location. Importantly, and in striking to our previous results wherein we generated the input form of IOR, in the present study there was an additive effect between IOR and TTOA on RT2. As implied by the locus of slack logic, we therefore conclude that the form of IOR generated when the oculomotor system is activated affects a late stage of processing. Converging evidence for this conclusion, from a variety of neuroscientific methods, is presented and the dearth of such evidence about the input form of IOR is noted.

Bioconductor is a widely used R-based platform for genomics, but its host of complex genomic data structures places a cognitive burden on the user. For most tasks, the GRanges object would suffice, but there are gaps in the API that prevent its general use. By recognizing that the GRanges class follows “tidy” data principles, we create a grammar of genomic data transformation, defining verbs for performing actions on and between genomic interval data and providing a way of performing common data analysis tasks through a coherent interface to existing Bioconductor infrastructure. We implement this grammar as a Bioconductor/R package called plyranges.

Innovative sensors can provide new capabilities to monitor and understand the behavior of soil, rock, and geo-structures and help geotechnical engineers make informed decisions about the construction and maintenance of geo-structures. This study introduced, calibrated, and validated one such sensor, the Surface Stress Sensitive Film (S3F) point sensor, for both normal and shear stress measurements in soil and along the soil–structure interface. The measurements of the S3F sensor rely on the deformation of an elastic film that is monitored by a magnetic floating element embedded in the elastic film and a Hall effect sensor. This sensor provides measurements of the 3-D deformation of the film, which are converted to normal and shear stresses using an a priori calibration. The calibrations of the S3F sensor were performed considering the effect of the loading areas, loading and unloading conditions, and soil particle sizes. Then, the performance of the S3F sensor to measure the normal stresses in soil and shear stresses at the soil–wooden block interface under static tension and pull-out conditions was evaluated. It was found that the normal stress calibration curves depended on the sizes of the loading areas because of the stiff housing boundary effect. However, the shear stress calibration curves were independent of the loading areas. The S3F sensor showed an ability to measure normal stresses in three different types of soils, including two silica sands from Ottawa, Illinois, with particle sizes ranging between sieve No. 20 and 30 (Ottawa 20/30 sand) and sieve No. 50 and 70 (Ottawa 50/70 sand) and finely ground silica silt (Sil-Co-Sil). The S3F sensor also showed an ability to measure the shear stresses at the soil–structure interface, which match well with the theoretical shear stresses. The S3F sensor has potential for stress measurements at the soil–structure interfaces in foundations, tunnels, pipes, and retaining systems.

G-Quadruplexes are noncanonical nucleic acid structures made up of stacked guanosine tetrads connected by short loops. They are frequently used building blocks in synthetic biology and thought to play widespread biological roles. Multimerization can change the functional properties of G-quadruplexes, and understanding the factors that modulate this process remains an important goal. Here, we report the discovery of a novel mechanism by which the formation of multimeric G-quadruplexes can be controlled using GTP. We show that GTP likely inhibits multimer formation by becoming incorporated into a tetrad in the monomeric form of the structure and define the sequence requirements of G-quadruplexes that form GTP-dependent structures. These experiments provide new insights into the small molecule control of G-quadruplex multimerization. They also suggest possible roles for GTP-dependent multimeric G-quadruplexes in both synthetic and natural biological systems.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR–Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines. The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.

TLR4 blockade with TAK-242, a small molecular inhibitor, protects islets from sterile inflammation-mediated stress in a syngeneic transplant model using a marginal mass of islets transplanted intraportally into mice with streptozotocin-induced diabetes. Supplemental digital content is available in the text.

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KITmutations, increased immune infiltration, globally demethylated DNA, and decreased KRAScopy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.

High‐quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet‐enriched microRNAs (miRNAs) ‐375 and ‐200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR‐375, miR‐200c, and C‐peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplantation glycemic control was monitored through C‐peptide, hemoglobin A1c, insulin requirement, and SUITOindex. The amount of miR‐375 released was significantly higher during enzymatic digestion followed by the islet bagging (P <.001). Mir‐200c mirrored these changes, albeit at lower concentrations. In contrast, the C‐peptide amount was significantly higher in the purification and bagging steps (P <.001). Lower amounts of miR‐375 were associated with a lower 6‐month insulin requirement (P =.01) and lower hemoglobin A1c(P =.04). Measurement of the absolute quantity of miRNA‐375 and ‐200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNAis indicative of posttransplantation endocrine function in TPIATpatients. Quantification of microRNA‐375 released during islet isolation procedures demonstrates islet damage and indicates posttransplant endocrine function in patients undergoing total pancreatectomy with islet autotransplantation.