Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.

Triple-Phase Computed Tomography May Replace Dual-Energy X-ray Absorptiometry Scan for Evaluation of Osteoporosis in Liver Transplant Candidates.

Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual-energy X-ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual-energy abdominal triple-phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA-based osteoporosis was defined as a T score ≤-2.5 at the hip or spine. BCT-based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3 . Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2 . Using DXA as the clinical reference, sensitivity of BCT to detect DXA-defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple-phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.

Efficacy and Safety of Endoscopic Balloon Placement for Weight Loss in Patients With Cirrhosis Awaiting Liver Transplantation.

The efficacy and safety of a fluid-filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m2 and on the waiting list for IGB placement endoscopically for a maximum of 6 months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End-Stage Liver Disease-sodium (MELD-Na) scores 14.1 ± 3.4 experienced weight reduction (146 ± 22.2 kg versus 127 ± 21.6 kg [P = 0.005] with IGB in place and 130 ± 24.6 kg [P = 0.014] at 6 months), with a total body weight loss of 12.2% ± 8.8% with IGBs in place and 10.9% ± 8.9% at 6 months. Body fat decreased from 48.6% ± 5.8% to 40.6% ± 6.4% (P = 0.001) and lean mass increased from 51.3% ± 6% to 59.4% ± 6.4% (P = 0.001). No change in MELD-Na scores occurred (P = 0.770). Early balloon retrieval was attributed to accommodative symptoms (n = 2) and liver decompensation (n = 1). Mallory Weiss tears (n = 3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short-term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow-up are required.

Effect of Integrated Gastroenterology Specialists in a Primary Care Setting: a Retrospective Cohort Study.

BACKGROUND: Gastrointestinal (GI) complaints are common in primary care practices. The patient-centered medical home (PCMH) may improve coordination and collaboration by facilitating coordination across healthcare settings and within the community, enhancing communication between providers, and focusing on quality of care delivery. OBJECTIVE: To investigate the effect of integrated community gastroenterology specialists (ICS-GI) model within a large primary care practice. DESIGN: Retrospective cohort with propensity-matched historic controls. PATIENTS: We identified 265 patients who had a visit with one of our ICS-GI specialists and matched them (1:2) to 530 similar patients seen prior to the implementation of the ICS-GI model. MAIN MEASURES: Frequency of diagnostic testing for GI indications, visits to our outpatient GI referral practice, emergency department and hospital utilization, and time to access of specialty care for the whole population and by GI condition group. KEY RESULTS: Patients seen in our ICS-GI model had similar outpatient care utilization (OR = 1.0, 95% CI 0.7-1.4, p = 0.90), were more likely to have visits in primary care (OR OR=1.5, 95% CI 1.1-2.2, p = 0.02), and were less likely to have visits to our GI outpatient referral practice (OR = 0.3, 95% CI 0.2-0.7, p < 0.0001). Condition-specific analyses show that all GI conditions experienced decreased visits to the outpatient GI referral practice outside of patients with GI neoplasm. Populations did not differ in emergency department, hospital, or diagnostic utilization. CONCLUSIONS: We observed that an embedded specialist in primary care model is associated with improved care coordination without compromising patient safety. The PCMH could be extended to include subspecialty care.

Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses.

BACKGROUND AND AIMS: Detection and characterization of focal liver lesions (FLLs) is key for optimizing treatment for patients who may have a primary hepatic cancer or metastatic disease to the liver. This is the first study to develop an EUS-based convolutional neural network (CNN) model for the purpose of identifying and classifying FLLs. METHODS: A prospective EUS database comprising cases of FLLs visualized and sampled via EUS was reviewed. Relevant still images and videos of liver parenchyma and FLLs were extracted. Patient data were then randomly distributed for the purpose of CNN model training and testing. Once a final model was created, occlusion heatmap analysis was performed to assess the ability of the EUS-CNN model to autonomously identify FLLs. The performance of the EUS-CNN for differentiating benign and malignant FLLs was also analyzed. RESULTS: A total of 210,685 unique EUS images from 256 patients were used to train, validate, and test the CNN model. Occlusion heatmap analyses demonstrated that the EUS-CNN model was successful in autonomously locating FLLs in 92.0% of EUS video assets. When evaluating any random still image extracted from videos or physician-captured images, the CNN model was 90% sensitive and 71% specific (area under the receiver operating characteristic [AUROC], 0.861) for classifying malignant FLLs. When evaluating full-length video assets, the EUS-CNN model was 100% sensitive and 80% specific (AUROC, 0.904) for classifying malignant FLLs. CONCLUSIONS: This study demonstrated the capability of an EUS-CNN model to autonomously identify FLLs and to accurately classify them as either malignant or benign lesions.

Genome sequence of the coffee root-knot nematode Meloidogyne exigua.

Root-knot nematodes (Meloidogyne spp.) cause serious damages on most crops. Here, we report a high-quality genome sequence of Meloidogyne exigua (population Mex1, Costa Rica), a major pathogen of coffee. Its mitogenome (20,974 bp) was first assembled and annotated. The nuclear genome was then constructed consisting of 206 contigs, with an N50 length of 1.89 Mb and a total assembly length of 42.1 Mb.

Diagnosis and Management of Genetic Iron Overload Disorders.

Iron overload disorders lead to excess iron deposition in the body, which can occur as a result of genetic or secondary causes. Genetic iron overload, referred to as hereditary hemochromatosis, may present as a common autosomal recessive mutation or as one of several uncommon mutations. Secondary iron overload may result from frequent blood transfusions, exogenous iron intake, or certain hematological diseases such as dyserythropoietic syndrome or chronic hemolytic anemia. Iron overload may be asymptomatic, or may present with significant diseases of the liver, heart, endocrine glands, joints, or other organs. If treated appropriately prior to end-organ damage, life expectancy has been shown to be similar compared to matched populations. Alongside clinical assessment, diagnostic studies involve blood tests, imaging, and in some cases liver biopsy. The mainstay of therapy is periodic phlebotomy, although oral chelation is an option for selected patients.

Calcium-binding proteins that are type B″ regulatory subunits of phosphatase 2A in Giardia intestinalis.

Giardia intestinalis is a protozoan parasite that colonizes the upper part of the small intestine of its mammalian hosts. The trophozoite, which is the replicative stage, has a complex cytoskeleton that allows it to move and adhere to intestinal cells. It has been proposed that protein phosphatase 2A (PP2A) participates in the regulation of changes to the parasite cytoskeleton during its life cycle. However, how PP2A is involved in this regulation remains unclear since its substrates and regulators have not been characterized. In this work, we report the bioinformatic and experimental analysis of two potential regulatory B″ subunits of PP2A in Giardia, both of which are calcium-binding proteins. In this work, in silico and experimental evidence of the binding of both proteins to calcium is presented; the proteins are shown to interact with the catalytic PP2A subunit in the trophozoite stage, and they exhibit different subcellular localization patterns. Because PP2A is a heterotrimer, homology analysis of the different subunits of PP2A indicates that fewer holoenzyme combinations can be formed in this parasite than in other organisms. Our results suggest that the localization of PP2A may be associated with calcium-dependent signaling through its B″ type regulatory subunits.

Longterm clinical and radiological follow-up of living liver donors.

Although short-term risks of living donor hepatectomy have been well defined, little is known about the longterm impact. We aimed to perform a systematic follow-up to screen for unanticipated health consequences of liver donation. All donors who were more than 1 year from donation were invited for a systematic evaluation including physical and laboratory assessment, quality of life questionnaire, and magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP). Those unable to return were offered the questionnaire and laboratory assessment at home. Out of our total of 97 donors, 45 returned for a full assessment and 23 completed labs and survey locally (total n = 68; 70%) after a median of 5.5 years (1.5-10.9 years) after donation. The only laboratory abnormality was a significant decrease in platelet count (median 198 ×10(9) /L versus 224 ×10(9) /L before donation; P < 0.001), whereas 93% of patients were still above normal limits. No late biliary strictures or other structural abnormalities were found on MRI/MRCP. Liver regeneration was complete. Spleen volume did significantly increase (median 278 cm(3) versus 230 cm(3) before donation; P < 0.001) without resulting in lowered platelets (P = 0.73). The most common complaints were persistent incisional numbness and changed bowel habits. Seven donors (11%) reported problems obtaining insurance. The vast majority (97%) would have donated again. In conclusion, longterm outcome following liver donation appears satisfactory. None of our donors have developed occult biliary strictures, failure of regeneration, abnormal liver function, or other important health consequences after a median of 5.5 years from surgery. These findings can be used when counseling potential donors in the future. Liver Transplantation 22 934-942 2016 AASLD.

Safety and Outcomes of Percutaneous Biopsy of 61 Hepatic Adenomas.

OBJECTIVE: Given the recent classification of hepatic adenoma (HA) into subtypes and recognition of imperfect specificity of MRI to differentiate HA from focal nodular hyperplasia (FNH), there is a resurgent interest in the role of biopsy to diagnose HA. The purpose of this study was to determine the safety and outcomes of biopsy of HAs. MATERIALS AND METHODS: A retrospective review of the electronic medical records of all patients who underwent hepatic mass biopsy revealing HA from 2000 through 2013 was performed. The biopsy procedure parameters were evaluated. Complications were graded using the Common Terminology Criteria for Adverse Events. Pathology-specific outcomes related to the diagnosis of HA were assessed. RESULTS: Sixty patients (52 women and eight men) were identified with a mean age of 42 ± 13 (SD) years and a mean follow-up of 2.3 ± 3.0 years after biopsy. One patient had two HAs biopsied during the same procedure, resulting in a total of 61 biopsy-proven HAs. Of the 60 patients, one patient (2%) had a single major complication, which involved bleeding that resulted in a blood transfusion, and six patients (10%) had a minor complication. A total of six (10%) discordant biopsy results were found: Four biopsy-proven HAs (7%) revealed FNH on surgical resection or repeat biopsy, one HA (2%) showed well-differentiated hepatocellular carcinoma (HCC) at subsequent biopsy, and one HA (2%) showed findings suggestive of HCC on follow-up imaging. CONCLUSION: Complications after biopsy of HAs are uncommon. Although uncommon, discordant pathology results between biopsy and surgical resection may occur.

Performance of 2-Dimensional Ultrasound Shear Wave Elastography in Liver Fibrosis Detection Using Magnetic Resonance Elastography as the Reference Standard: A Pilot Study.

OBJECTIVES: To investigate the correlation between 2-dimensional (2D) ultrasound shear wave elastography (SWE) and magnetic resonance elastography (MRE) in liver stiffness measurement and the diagnostic performance of 2D SWE for liver fibrosis when imaging from different intercostal spaces and using MRE as the reference standard. METHODS: Two-dimensional SWE was performed on 47 patients. One patient was excluded from the study. Each of the remaining 46 patients underwent same-day MRE for clinical purposes. The study was compliant with the Health Insurance Portability and Accountability Act and approved by the Institutional Review Board. Informed consent was obtained from each patient. Two-dimensional SWE measurements were acquired from the ninth, eighth, and seventh intercostal spaces. The correlation with MRE was calculated at each intercostal space and multiple intercostal spaces combined. The performance of 2D SWE in diagnosing liver fibrosis was evaluated by receiver operating characteristic curve analysis using MRE as the standard. RESULTS: The 47 patients who initially underwent 2D SWE included 22 female and 25 male patients (age range, 19-77 years). The highest correlation between 2D SWE and MRE was from the eighth and seventh intercostal spaces (r = 0.68-0.76). The ranges of the areas under the receiver operating characteristic curves for separating normal or inflamed livers from fibrotic livers using MRE as the clinical reference were 0.84 to 0.92 when using the eighth and seventh intercostal spaces individually and 0.89 to 0.90 when combined. CONCLUSIONS: The results suggest that 2D SWE and MRE are well correlated when SWE is performed at the eighth and seventh intercostal spaces. The ninth intercostal space is less reliable for diagnosing fibrosis with 2D SWE. Combining measurements from multiple intercostal spaces does not significantly improve the performance of 2D SWE for detection of fibrosis.

Impact of multiple transarterial chemoembolization treatments on hepatocellular carcinoma for patients awaiting liver transplantation.

Transarterial chemoembolization (TACE) is a common treatment for patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (LT). The aim of this study was to assess the impact of multiple TACE treatments on tumor necrosis, tumor recurrence, and survival in these patients. A retrospective analysis was performed for 104 consecutive patients undergoing LT for HCC from January 2002 to December 2009 who were treated with TACE before LT. The number of TACE treatments was not associated with tumor necrosis in the explant. After a median follow-up of 69 months (range = 0-123 months), 14 of the 104 patients (13%) developed recurrent HCC after LT. Recurrence had a significant relationship with a short interval between the diagnosis of HCC and LT (≤6 months) in univariate and multivariate analyses [P = 0.029, odds ratio (OR) = 19.2]. Patients subjected to a single TACE treatment were more likely to experience recurrence, although this finding was not confirmed in the multivariate analysis. No significant relationship was observed between tumor necrosis in the explant and recurrence. The mean overall survival was 102.8 months (95% confidence interval = 94.9-110.8 months) with 1-, 3-, and 5-year survival rates of 91%, 89%, and 84% respectively. In the univariate survival analysis, the presence of ascites before TACE, a waiting time ≤ 9 months, and tumor characteristics at the pathological examination were statistically associated with shorter survival. In the multivariate analysis, only vascular invasion (P < 0.001, OR = 7.99) remained independently associated with shorter survival. The number of TACE treatments was not associated with survival. In conclusion, multiple TACE treatments were not associated with a higher risk of recurrence or shorter survival. Continued use of TACE should be considered as indicated if the patient and lesions are suitable for retreatment. A shorter waiting time before LT is related to an increased risk of recurrence and decreased survival after LT for HCC. These data could reflect the presence of more aggressive tumor biology and may be useful for guiding organ allocation policy to consider a minimum observation period before LT for regions with shorter wait times.

Impact of fibrosis progression on clinical outcome in patients treated for post-transplant hepatitis C recurrence.

BACKGROUND & AIMS: Patients who achieve sustained virological response (SVR) following the treatment of post-liver transplant (LT) recurrence of hepatitis C virus (HCV) infection have improved outcomes. The full impact of eradication of HCV on allograft histology is, however, not clearly known. METHODS: We studied allograft histology in protocol-based paired liver biopsies in consecutive LT recipients who underwent post-LT treatment of recurrence of HCV. RESULTS: A total of 116 patients were treated with interferon-based therapy for recurrent HCV. Paired pre-treatment baseline biopsies and post-treatment biopsies were available in 83.2% of patients. SVR was achieved in 37.9% of patients. Among the patients who achieved SVR, 20.5% had progression of fibrosis on post-treatment biopsies vs. 65.5% of patients with non-response/relapse (P < 0.001). The impact of virological response on fibrosis progression was sustained and a similar outcome was observed in the subset of patients who had 4-5 year post-treatment biopsies available. In the SVR group, 12.8% progressed to fibrosis stage ≥3 on post-treatment biopsies vs. 37.9% in the non-response/relapse group (P = 0.001). The 5-year survival in patients with progression of fibrosis 86% vs. 98% among patients who had improvement/stable fibrosis [P = 0.003; HR 3.8 (1.2-11.8)]. A small subset of patients who achieve SVR unfortunately still experience progression of fibrosis, most commonly associated with plasma cell hepatitis. CONCLUSIONS: In post-transplant patients treated for HCV, SVR is associated with improved graft survival and also with sustained and significant improvement in histological outcome. Importantly, progression of fibrosis still occurred in a small subset of patients who achieved SVR.

Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Several studies have shown that statins could have chemopreventive effects on HCC. We performed a systematic review and meta-analysis of studies that evaluated the effects of statins on the risk of HCC. METHODS: We conducted a systematic search of MEDLINE, Embase, and Web of Science through May 2012 and manually reviewed the literature. Studies were included if they evaluated and clearly defined exposure to statins, reported the incidence of HCC, and reported relative risks or odds ratios (ORs) or provided data for their estimation. Ten studies reporting 4298 cases of HCC in 1,459,417 patients were analyzed. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random effects model. Statistical heterogeneity was assessed with the Cochran's Q statistic and I(2) statistic. RESULTS: Statin users were less likely to develop HCC than statin nonusers (adjusted OR, 0.63; 95% CI, 0.52-0.76), although the results were heterogeneous (P = .01, I(2) = 59%). This heterogeneity could be accounted for by study location (Asian population [n = 4]: adjusted OR, 0.52; 95% CI, 0.42-0.64; Western population [n = 6]: adjusted OR, 0.67; 95% CI, 0.53-0.85) and design (observational studies [n = 7]: adjusted OR, 0.60; 95% CI, 0.49-0.73; clinical trials [n = 3]: adjusted OR, 0.95; 95% CI, 0.62-1.45). CONCLUSIONS: Based on meta-analysis, statin use is associated with a reduced risk of HCC, most strongly in Asian but also in Western populations. Randomized clinical trials in populations at high risk for HCC (especially in Asian populations with hepatitis B) are warranted.

A new clinically based staging system for perihilar cholangiocarcinoma.

OBJECTIVES: Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials. METHODS: Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system. RESULTS: Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1-2.6), 3.1 (2.0-4.7), and 8.7 (5.2-14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival. CONCLUSIONS: This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials.

Noninvasive assessment of liver fibrosis using ultrasound-based shear wave measurement and comparison to magnetic resonance elastography.

OBJECTIVES: Magnetic resonance elastography (MRE) has excellent performance in detecting liver fibrosis and is becoming an alternative to liver biopsy in clinical practice. Ultrasound techniques based on measuring the propagation speed of the shear waves induced by acoustic radiation force also have shown promising results for liver fibrosis staging. The objective of this study was to compare ultrasound-based shear wave measurement to MRE. METHODS: In this study, 50 patients (28 female and 22 male; age range, 19-81 years) undergoing liver MRE examinations were studied with an ultrasound scanner modified with shear wave measurement functionality. For each patient, 27 shear wave speed measurements were obtained at various locations in the liver parenchyma away from major vessels. The median shear wave speed from all measurements was used to calculate a representative shear modulus (µ) for each patient. Magnetic resonance elastographic data processing was done by a single analyst blinded to the ultrasound measurement results. RESULTS: Ultrasound and MRE measurements were correlated (r = 0.86; P < .001). Receiver operating characteristic (ROC) analysis was applied to the ultrasound measurement results with the MRE diagnosis as the "ground truth." The area under the ROC curve for separating patients with minimum fibrosis (defined as µ(MRE) ≤2.9 kPa) was 0.89 (95% confidence interval, 0.77-0.95), and the area under the ROC curve for separating patients with advanced fibrosis (defined as µ(MRE) ≥5.0 kPa) was 0.96 (95% confidence interval, 0.87-0.99). CONCLUSIONS: Results indicate that the ultrasound-based shear wave measurement correlates with MRE and is a promising method for liver fibrosis staging.

Non-Fungible Tokens for Organoids: Decentralized Biobanking to Empower Patients in Biospecimen Research.

Introduction: Scientists use donated biospecimens to create organoids, which are miniature copies of patient tumors that are revolutionizing precision medicine and drug discovery. However, biobanking platforms remove donor identifiers to protect privacy, precluding patients from benefiting from their contributions or sharing information that may be relevant to research outcomes. Decentralized biobanking (de-bi) leverages blockchain technology to empower patient engagement in biospecimen research. We describe the creation of the first de-bi prototype for an organoid biobanking use case. Methods: We designed and developed a proof-of-concept non-fungible tokens (NFTs) framework for an organoid research network of patients, physicians, and scientists within a synthetic dataset modeled on a real-world breast cancer organoid ecosystem. Our implementation deployed multiple smart contracts on Ethereum test networks, minting NFTs representing each stakeholder, biospecimen, and organoid. The system architecture was designed to be composable with established biobanking programs. Results: Our de-bi prototype demonstrated how NFTs representing patients, physicians, scientists, and organoids may be united in a privacy-preserving platform that builds upon relationships and transactions of existing biobank research networks. The mobile application simulated key features, enabling patients to track their biospecimens, view organoid images and research updates from scientists, and allow physicians to participate in peer-to-peer communications with basic scientists and patients alike, all while ensuring compliance with de-identification requirements. Discussion: We demonstrate proof-of-concept for a web3 platform engaging patients, physicians, and scientists in a dynamic research community, unlocking value for a model organoid ecosystem. This initial prototype is a critical first step for advancing paradigm-shifting de-bi technology that provides unprecedented transparency and suggests new standards for equity and inclusion in biobanking. Further research must address feasibility and acceptability considering the ethical, legal, economic, and technical complexities of organoid research and clinical translation.

Biperiden reverses the increase in 50-kHz ultrasonic vocalizations but not the increase in locomotor activity induced by cocaine.

Cocaine use disorder (CUD) is a worldwide public health problem, associated with severe psychosocial and economic impacts. Currently, no FDA-approved treatment is available for CUD. However, an emerging body of evidence from clinical and preclinical studies suggests that biperiden, an M1 muscarinic receptor antagonist, presents potential therapeutic use for CUD. These studies have suggested that biperiden may reduce the reinforcing effects of cocaine. It is well established that rodents emit 50-kHz ultrasonic vocalizations (USV) in response to natural rewards and stimulant drugs, including cocaine. Nonetheless, the effects of biperiden on the cocaine-induced increase of 50-kHz USV remains unknown. Here, we hypothesized that biperiden could antagonize the acute effects of cocaine administration on rat 50-kHz USV. To test this hypothesis, adult male Wistar rats were divided into four experimental groups: saline, 5 mg/kg biperiden, 10 mg/kg cocaine, and biperiden/cocaine (5 and 10 mg/kg, i.p., respectively). USV and locomotor activity were recorded in baseline and test sessions. As expected, cocaine administration significantly increased the number of 50-kHz USV. Biperiden administration effectively antagonized the increase in 50-kHz USV induced by cocaine. Cocaine administration also increased the emission of trill and mixed 50 kHz USV subtypes and this effect was antagonized by biperiden. Additionally, we showed that biperiden did not affect the cocaine-induced increase in locomotor activity, although biperiden administration per se increased locomotor activity. In conclusion, our findings indicate that administering biperiden acutely reduces the positive affective effects of cocaine, as demonstrated by its ability to inhibit the increase in 50-kHz USV.

Haitian coffee agroforestry systems harbor complex arabica variety mixtures and under-recognized genetic diversity.

Though facing significant challenges, coffee (Coffea arabica) grown in Haitian agroforestry systems are important contributors to rural livelihoods and provide several ecosystem services. However, little is known about their genetic diversity and the variety mixtures used. In light of this, there is a need to characterize Haitian coffee diversity to help inform revitalization of this sector. We sampled 28 diverse farms in historically important coffee growing regions of northern and southern Haiti. We performed KASP-genotyping of SNP markers and HiPlex multiplex amplicon sequencing for haplotype calling on our samples, as well as several Ethiopian and commercial accessions from international collections. This allowed us to assign Haitian samples to varietal groups. Our analyses revealed considerable genetic diversity in Haitian farms, higher in fact than many farmers realized. Notably, genetic structure analyses revealed the presence of clusters related to Typica, Bourbon, and Catimor groups, another group that was not represented in our reference accession panel, and several admixed individuals. Across the study areas, we found both mixed-variety farms and monovarietal farms with the historical and traditional Typica variety. This study is, to our knowledge, the first to genetically characterize Haitian C. arabica variety mixtures, and report the limited cultivation of C. canephora (Robusta coffee) in the study area. Our results show that some coffee farms are repositories of historical, widely-abandoned varieties while others are generators of new diversity through genetic mixing.