The Amphibian Genomics Consortium: advancing genomic and genetic resources for amphibian research and conservation.

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomics resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomics resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, antipredator strategies, and resilience and adaptive responses. They also serve as critical models for understanding widespread genomic characteristics, including evolutionary genome expansions and contractions given they have the largest range in genome sizes of any animal taxon and multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The advent of long-read sequencing technologies, along with computational techniques that enhance scaffolding capabilities and streamline computational workload is now enabling the ability to overcome some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC) in early 2023. This burgeoning community already has more than 282 members from 41 countries (6 in Africa, 131 in the Americas, 27 in Asia, 29 in Australasia, and 89 in Europe). The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and outline how the AGC can enable amphibian genomics research to "leap" to the next level.

Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment.

Cancer cells show altered antioxidant defense systems, dysregulated redox signaling, and increased generation of reactive oxygen species (ROS). Targeting cancer cells through ROS-mediated mechanisms has emerged as a significant therapeutic strategy due to its implications in cancer progression, survival, and resistance. Extensive research has focused on selective generation of H2O2 in cancer cells for selective cancer cell killing by employing various strategies such as metal-based prodrugs, photodynamic therapy, enzyme-based systems, nano-particle mediated approaches, chemical modulators, and combination therapies. Many of these H2O2-amplifying approaches have demonstrated promising anticancer effects and selectivity in preclinical investigations. They selectively induce cytotoxicity in cancer cells while sparing normal cells, sensitize resistant cells, and modulate the tumor microenvironment. However, challenges remain in achieving selectivity, addressing tumor heterogeneity, ensuring efficient delivery, and managing safety and toxicity. To address those issues, H2O2-generating agents have been combined with other treatments leading to optimized combination therapies. This review focuses on various chemical agents/approaches that kill cancer cells via H2O2-mediated mechanisms. Different categories of compounds that selectively generate H2O2 in cancer cells are summarized, their underlying mechanisms and function are elucidated, preclinical and clinical studies as well as recent advancements are discussed, and their prospects as targeted therapeutic agents and their therapeutic utility in combination with other treatments are explored. By understanding the potential of these compounds, researchers can pave the way for the development of effective and personalized cancer treatments.

Environmental factors influence cross-talk between a heat shock protein and an oxidative stress protein modification in the lizard Gallotia galloti.

Better understanding how organisms respond to their abiotic environment, especially at the biochemical level, is critical in predicting population trajectories under climate change. In this study, we measured constitutive stress biomarkers and protein post-translational modifications associated with oxidative stress in Gallotia galloti, an insular lizard species inhabiting highly heterogeneous environments on Tenerife. Tenerife is a small volcanic island in a relatively isolated archipelago off the West coast of Africa. We found that expression of GRP94, a molecular chaperone protein, and levels of protein carbonylation, a marker of cellular stress, change across different environments, depending on solar radiation-related variables and topology. Here, we report in a wild animal population, cross-talk between the baseline levels of the heat shock protein-like GRP94 and oxidative damage (protein carbonylation), which are influenced by a range of available temperatures, quantified through modelled operative temperature. This suggests a dynamic trade-off between cellular homeostasis and oxidative damage in lizards adapted to this thermally and topologically heterogeneous environment.

Humans in the loop: Community science and machine learning synergies for overcoming herbarium digitization bottlenecks.

Premise: Among the slowest steps in the digitization of natural history collections is converting imaged labels into digital text. We present here a working solution to overcome this long-recognized efficiency bottleneck that leverages synergies between community science efforts and machine learning approaches. Methods: We present two new semi-automated services. The first detects and classifies typewritten, handwritten, or mixed labels from herbarium sheets. The second uses a workflow tuned for specimen labels to label text using optical character recognition (OCR). The label finder and classifier was built via humans-in-the-loop processes that utilize the community science Notes from Nature platform to develop training and validation data sets to feed into a machine learning pipeline. Results: Our results showcase a >93% success rate for finding and classifying main labels. The OCR pipeline optimizes pre-processing, multiple OCR engines, and post-processing steps, including an alignment approach borrowed from molecular systematics. This pipeline yields >4-fold reductions in errors compared to off-the-shelf open-source solutions. The OCR workflow also allows human validation using a custom Notes from Nature tool. Discussion: Our work showcases a usable set of tools for herbarium digitization including a custom-built web application that is freely accessible. Further work to better integrate these services into existing toolkits can support broad community use.

Unified and pluralistic ideals for data sharing and reuse in biodiversity.

How should billions of species observations worldwide be shared and made reusable? Many biodiversity scientists assume the ideal solution is to standardize all datasets according to a single, universal classification and aggregate them into a centralized, global repository. This ideal has known practical and theoretical limitations, however, which justifies investigating alternatives. To support better community deliberation and normative evaluation, we develop a novel conceptual framework showing how different organizational models, regulative ideals and heuristic strategies are combined to form shared infrastructures supporting data reuse. The framework is anchored in a general definition of data pooling as an activity of making a taxonomically standardized body of information available for community reuse via digital infrastructure. We describe and illustrate unified and pluralistic ideals for biodiversity data pooling and show how communities may advance toward these ideals using different heuristic strategies. We present evidence for the strengths and limitations of the unification and pluralistic ideals based on systemic relationships of power, responsibility and benefit they establish among stakeholders, and we conclude the pluralistic ideal is better suited for biodiversity data.

Right Heart Failure Following Left Ventricular Device Implantation: Natural History, Risk Factors, and Outcomes: An Analysis of the STS INTERMACS Database.

BACKGROUND: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. METHODS: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. RESULTS: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P<0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P<0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P=0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P=0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P<0.001). CONCLUSIONS: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Fatal Allograft Rejection and Cardiac Allograft Vasculopathy After Treatment With Pembrolizumab for Metastatic Melanoma in a Heart Transplant Recipient: A Case Report.

Checkpoint inhibitors decrease the progression of many cancers. However, the experience in immunosuppressed patients is limited, with reports of possible serious adverse events. We present a heart transplant recipient treated with pembrolizumab for metastatic melanoma who developed fatal rejection. The patient was a 29 year-old man who underwent heart transplantation at the age of 10 years for congenital heart disease. Seventeen years after transplant, he was diagnosed with scalp melanoma pT3a, N2a, M0, Stage IIIA, positive for BRAF V600E mutation treated with excision, which metastasized to his lungs and brain a year later. Dabrafenib and trametinib were started with transient response. Additional options and their risks were discussed, and pembrolizumab was started 4 months later due to the incomplete response to previous therapy. Five days after initiation the patient presented with moderate cellular rejection and possible antibody mediated rejection (ISHLT Grade 2R, pAMR 1H). Pembrolizumab was discontinued, and he was treated with steroids. Seven months later he presented in cardiogenic shock and severe coronary allograft vasculopathy. Biopsy was negative for cellular rejection, but suspicious for antibody mediated rejection (ISHLT Grade 0R, pAMR 1H), and he had a new serum alloantibody. Despite steroids and plasmapheresis he remained in refractory cardiogenic shock and died of cardiac arrest.

Identifying gaps in the photographic record of the vascular plant flora of the Americas.

Field photographs of plant species are crucial for research and conservation, but the lack of a centralized database makes them difficult to locate. We surveyed 25 online databases of field photographs and found that they harboured only about 53% of the approximately 125,000 vascular plant species of the Americas. These results reflect the urgent need for a centralized database that can both integrate and complete the photographic record of the world's flora.

Quality of Life in Patients With Heart Failure With Recovered Ejection Fraction.

Importance: Heart failure with recovered ejection fraction (HFrecEF) is a recently recognized phenotype of patients with a history of reduced left ventricular ejection fraction (LVEF) that has subsequently normalized. It is unknown whether such LVEF improvement is associated with improvements in health status. Objective: To examine changes in health-related quality of life in patients with heart failure with reduced ejection fraction (HFrEF) whose LVEF normalized, compared with those whose LVEF remains reduced and those with HF with preserved EF (HFpEF). Design, Setting, and Participants: This prospective cohort study was conducted at a tertiary care hospital from November 2016 to December 2018. Consecutive patients seen in a heart failure clinic who completed patient-reported outcome assessments were included. Clinical data were abstracted from the electronic health record. Data analysis was completed from February to December 2020. Main Outcomes and Measures: Changes in Kansas City Cardiomyopathy Questionnaire overall summary score, Visual Analog Scale score, and Patient-Reported Outcomes Measurement Information System domain scores on physical function, fatigue, depression, and satisfaction with social roles over 1-year follow-up. Results: The study group included 319 patients (mean [SD] age, 60.4 [15.5] years; 120 women [37.6%]). At baseline, 212 patients (66.5%) had HFrEF and 107 (33.5%) had HFpEF. At a median follow-up of 366 (interquartile range, 310-421) days, LVEF had increased to 50% or more in 35 patients with HFrEF (16.5%). Recovery of systolic function was associated with heart failure-associated quality-of-life improvement, such that for each 10% increase in LVEF, the Kansas City Cardiomyopathy Questionnaire score improved by an mean (SD) of 4.8 (1.6) points (P = .003). Recovery of LVEF was also associated with improvement of physical function, satisfaction with social roles, and a reduction in fatigue. Conclusions and Relevance: Among patients with HFrEF in this study, normalization of left ventricular systolic function was associated with a significant improvement in health-related quality of life.

Dynamic Regulation of SARS-Cov-2 Binding and Cell Entry Mechanisms in Remodeled Human Ventricular Myocardium.

Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that mRNA expression of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cardiac myocyte receptor ACE2 is up-regulated with remodeling and with reverse remodeling down-regulates into the normal range. The proteases responsible for virus-cell membrane fusion were expressed but not regulated with remodeling. In addition, a new candidate for SARS-CoV-2 cell binding and entry was identified, the integrin encoded by ITGA5. Up-regulation in ACE2 in remodeled left ventricles may explain worse outcomes in patients with coronavirus disease 2019 who have underlying myocardial disorders, and counteracting ACE2 up-regulation is a possible therapeutic approach to minimizing cardiac damage.

Impact of Shared Care in Remote Areas for Patients With Left Ventricular Assist Devices.

OBJECTIVES: The aim of this study was to evaluate the impact of a shared-care model on outcomes in patients with left ventricular assist devices (LVADs) living in remote locations. BACKGROUND: Health care delivery through shared-care models has been shown to improve outcomes in patients with chronic diseases. However, the impact of shared-care models on outcomes in patients with LVAD is unknown. METHODS: LVAD recipients in the authors' program (2007 to 2018) were classified based on the levels of care provided and training and resources used: level 1, was defined as outpatient primary care without LVAD-specific care; level 2 was level 1 services and outpatient LVAD-specific care; level 3 was level 2 services and inpatient LVAD-specific care and implantation center (IC). The Kaplan-Meier method was used to compare rates of survival, bleeding, pump thrombosis, infection, neurologic events, and readmissions among levels of care. RESULTS: A total of 336 patients were included, with 255 patients (75.9%) cared for in shared-care facilities. Median follow-up was 810 (interquartile range: 321 to 1,096) days. In comparison to patients cared for by IC, patients at levels 2 and 3 shared-care centers had similar rates of death, bleeding, neurologic events, pump thromboses, and infections. However, the rates of death, pump thromboses, and infections were higher for level 1 patients than in IC patients. CONCLUSIONS: Shared health care is an effective strategy to deliver care to patients with LVAD living in remote locations. However, patients in shared-care facilities unable to provide LVAD-specific care are at higher risk of unfavorable outcomes. Availability of LVAD-specific care should be strongly considered during patient selection and every effort made to ensure LVAD-specific training and resources are available at shared-care facilities.

Decentralized but Globally Coordinated Biodiversity Data.

Centralized biodiversity data aggregation is too often failing societal needs due to pervasive and systemic data quality deficiencies. We argue for a novel approach that embodies the spirit of the Web ("small pieces loosely joined") through the decentralized coordination of data across scientific languages and communities. The upfront cost of decentralization can be offset by the long-term benefit of achieving sustained expert engagement, higher-quality data products, and ultimately more societal impact for biodiversity data. Our decentralized approach encourages the emergence and evolution of multiple self-identifying communities of practice that are regionally, taxonomically, or institutionally localized. Each community is empowered to control the social and informational design and versioning of their local data infrastructures and signals. With no single aggregator to exert centralized control over biodiversity data, decentralization generates loosely connected networks of mid-level aggregators. Global coordination is nevertheless feasible through automatable data sharing agreements that enable efficient propagation and translation of biodiversity data across communities. The decentralized model also poses novel integration challenges, among which the explicit and continuous articulation of conflicting systematic classifications and phylogenies remain the most challenging. We discuss the development of available solutions, challenges, and outline next steps: the global effort of coordination should focus on developing shared languages for data signal translation, as opposed to homogenizing the data signal itself.

Correction: Sequential analysis of myocardial gene expression with phenotypic change: Use of cross-platform concordance to strengthen biologic relevance.

[This corrects the article DOI: 10.1371/journal.pone.0221519.].

Sequential analysis of myocardial gene expression with phenotypic change: Use of cross-platform concordance to strengthen biologic relevance.

OBJECTIVES: To investigate the biologic relevance of cross-platform concordant changes in gene expression in intact human failing/hypertrophied ventricular myocardium undergoing reverse remodeling. BACKGROUND: Information is lacking on genes and networks involved in remodeled human LVs, and in the associated investigative best practices. METHODS: We measured mRNA expression in ventricular septal endomyocardial biopsies from 47 idiopathic dilated cardiomyopathy patients, at baseline and after 3-12 months of ß-blocker treatment to effect left ventricular (LV) reverse remodeling as measured by ejection fraction (LVEF). Cross-platform gene expression change concordance was investigated in reverse remodeling Responders (R) and Nonresponders (NR) using 3 platforms (RT-qPCR, microarray, and RNA-Seq) and two cohorts (All 47 subjects (A-S) and a 12 patient "Super-Responder" (S-R) subset of A-S). RESULTS: For 50 prespecified candidate genes, in A-S mRNA expression 2 platform concordance (CcpT), but not single platform change, was directly related to reverse remodeling, indicating CcpT has biologic significance. Candidate genes yielded a CcpT (PCR/microarray) of 62% for Responder vs. Nonresponder (R/NR) change from baseline analysis in A-S, and ranged from 38% to 100% in S-R for PCR/microarray/RNA-Seq 2 platform comparisons. Global gene CcpT measured by microarray/RNA-Seq was less than for candidate genes, in S-R R/NR 17.5% vs. 38% (P = 0.036). For S-R global gene expression changes, both cross-cohort concordance (CccT) and CcpT yielded markedly greater values for an R/NR vs. an R-only analysis (by 22 fold for CccT and 7 fold for CcpT). Pathway analysis of concordant global changes for R/NR in S-R revealed signals for downregulation of multiple phosphoinositide canonical pathways, plus expected evidence of a ß1-adrenergic receptor gene network including enhanced Ca2+ signaling. CONCLUSIONS: Two-platform concordant change in candidate gene expression is associated with LV biologic effects, and global expression concordant changes are best identified in an R/NR design that can yield novel information.

Post-transplant outcome in patients bridged to transplant with temporary mechanical circulatory support devices.

BACKGROUND: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS. METHODS: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes. RESULTS: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time. CONCLUSIONS: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant.

A data management workflow of biodiversity data from the field to data users.

PREMISE: Heterogeneity of biodiversity data from the collections, research, and management communities presents challenges for data findability, accessibility, interoperability, and reusability. Workflows designed with data collection, standards, dissemination, and reuse in mind will generate better information across geopolitical, administrative, and institutional boundaries. Here, we present our data workflow as a case study of how we collected, shared, and used data from multiple sources. METHODS: In 2012, we initiated the collection of biodiversity data relating to Michigan prairie fens, including data on plant communities and the federally endangered Poweshiek skipperling (Oarisma poweshiek). RESULTS: Over 23,000 occurrence records were compiled in a database following Darwin Core standards. The records were linked with media and biological, chemical, and geometric measurements. We published the data as Global Biodiversity Information Facility data sets and in Symbiota SEINet portals. DISCUSSION: We highlight data collection techniques that optimized transcription time, including the use of predetermined and controlled vocabulary, Darwin Core terms, and data dictionaries. The validity and longevity of our data were supported by voucher specimens, metadata with measurement records, and published manuscripts detailing methods and data sets. Key to our data dissemination was cooperation among partners and the utilization of dynamic tools. To increase data interoperability, we need flexible and customizable data collection templates, coding, and enhanced communication among communities using biodiversity data.

Novel Model to Predict Gastrointestinal Bleeding During Left Ventricular Assist Device Support.

BACKGROUND: Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients. METHODS AND RESULTS: CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure <18 mm Hg, and fasting glucose >107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0-1 points) 4.8%, intermediate (2-4) 39.8%, and high risk (5-9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74). CONCLUSIONS: The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.

Microvascular Loss and Diastolic Dysfunction in Severe Symptomatic Cardiac Allograft Vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV. METHODS AND RESULTS: The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness ( P<0.05). CONCLUSIONS: Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.

Use of globally unique identifiers (GUIDs) to link herbarium specimen records to physical specimens.

With the advent of the U.S. National Science Foundation's Advancing Digitization of Biodiversity Collections program and related worldwide digitization initiatives, the rate of herbarium specimen digitization in the United States has expanded exponentially. As the number of electronic herbarium records proliferates, the importance of linking these records to the physical specimens they represent as well as to related records from other sources will intensify. Although a rich and diverse literature has developed over the past decade that addresses the use of specimen identifiers for facilitating linking across the internet, few implementable guidelines or recommended practices for herbaria have been advanced. Here we review this literature with the express purpose of distilling a specific set of recommendations especially tailored to herbarium specimen digitization, curation, and management. We argue that associating globally unique identifiers (GUIDs) with physical herbarium specimens and including these identifiers in all electronic records about those specimens is essential to effective digital data curation. We also address practical applications for ensuring these associations.