Opportunities and challenges for immunosuppression in the context of pig-to-human xenotransplantation.

The transplantation of organ(s) across species may alleviate the shortage of available donor kidneys for an ever-growing number of patients on transplant waiting lists. However, this potential remains limited by uncharacterized physiologic and immune effects of xenotransplants in recipients, which Pan et al.1 investigated in the current study.

Parallel patterns of cognitive aging in marmosets and macaques.

As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain's susceptibility to the effects of aging. As such, non-human primates are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary non-human primate model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical working memory task. Our results demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, highlighting the value of the marmoset as a model for cognitive aging research within the neuroscience community.

Assessing the safety and efficacy of prescribing psychologists in New Mexico and Louisiana.

This study aimed to compare patient outcomes between prescribing psychologists, psychiatrists, and primary care physicians (PCPs). Private insurance claims (2005-2021; n = 307,478) were used to conduct an active comparator, new user longitudinal cohort study developed using target trial emulation. Inverse propensity for treatment weighting was used to adjust for baseline differences in a range of sociodemographic, clinical, and contextual patient factors. Differences in the 1-year rate of health care visits for adverse drug events (ADEs), psychiatric emergency department (ED) utilization, medication adherence, and psychotropic polypharmacy were identified between prescribing psychologists and the other provider types using doubly robust Cox proportional hazards models. Compared to patients of psychiatrists, patients of prescribing psychologists had a 24% lower rate of ADEs (95% CI [0.60, 0.96]), a 20% lower rate of psychotropic polypharmacy (95% CI [0.74, 0.86]), and similar rates of psychiatric ED utilization and medication nonadherence. Compared to patients of PCPs, patients of prescribing psychologists had 138% higher rates of psychiatric ED utilization (95% CI [1.67, 3.39]), 175% higher rates of psychotropic polypharmacy (95% CI [2.53, 2.99]), 28% lower rates of medication nonadherence (95% CI [0.66, 0.78]), and similar rates of ADEs. Using robust pharmacoepidemiological methods, we noted that among mental health specialists, prescribing psychologists appear to be as safe and efficacious as psychiatrists in a large sample of privately insured patients. Notable differences in safety and efficacy when compared to PCPs may be attributable to differences between specialty and primary care. Future research on prescribing psychologists should move toward studies of care quality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Reduced Nephrin Tyrosine Phosphorylation Enhances Insulin Secretion and Increases Glucose Tolerance With Age.

BACKGROUND: Nephrin is a transmembrane protein with well-established signaling roles in kidney podocytes, and a smaller set of secretory functions in pancreatic ß cells are implicated in diabetes. Nephrin signaling is mediated in part through its 3 cytoplasmic YDxV motifs, which can be tyrosine phosphorylated by high glucose and ß cell injuries. Although in vitro studies demonstrate these phosphorylated motifs can regulate ß cell vesicle trafficking and insulin release, in vivo evidence of their role in this cell type remains to be determined. METHODS: To further explore the role of nephrin YDxV phosphorylation in ß cells, we used a mouse line with tyrosine to phenylalanine substitutions at each YDxV motif (nephrin-Y3F) to inhibit phosphorylation. We assessed islet function via primary islet glucose-stimulated insulin secretion assays and oral glucose tolerance tests. RESULTS: Nephrin-Y3F mice successfully developed pancreatic endocrine and exocrine tissues with minimal structural differences. Unexpectedly, male and female nephrin-Y3F mice showed elevated insulin secretion, with a stronger increase observed in male mice. At 8 months of age, no differences in glucose tolerance were observed between wild-type (WT) and nephrin-Y3F mice. However, aged nephrin-Y3F mice (16 months of age) demonstrated more rapid glucose clearance compared to WT controls. CONCLUSION: Taken together, loss of nephrin YDxV phosphorylation does not alter baseline islet function. Instead, our data suggest a mechanism linking impaired nephrin YDxV phosphorylation to improved islet secretory ability with age. Targeting nephrin phosphorylation could provide novel therapeutic opportunities to improve ß cell function.

Limited Sampling Strategies Fail to Accurately Predict Mycophenolic Acid Area Under the Curve in Kidney Transplant Recipients and the Impact of Enterohepatic Recirculation.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is challenging due to difficulties in measuring the area under the curve (AUC). Limited sampling strategies (LSSs) have been developed for MPA therapeutic drug monitoring but come with risk of unacceptable performance. The authors hypothesized that the poor predictive performance of LSSs were due to the variability in MPA enterohepatic recirculation (EHR). This study is the first to evaluate LSSs models performance in the context of EHR. METHODS: Adult kidney transplant recipients (n = 84) receiving oral mycophenolate mofetil underwent intensive MPA pharmacokinetic sampling. MPA AUC0-12hr and EHR were determined. Published MPA LSSs in kidney transplant recipients receiving tacrolimus were evaluated for their predictive performance in estimating AUC0-12hr in our full cohort and separately in individuals with high and low EHR. RESULTS: None of the evaluated LSS models (n = 12) showed good precision or accuracy in predicting MPA AUC0-12hr in the full cohort. In the high EHR group, models with late timepoints had better accuracy but low precision, except for 1 model with late timepoints at 6 and 10 hours postdose, which had marginally acceptable precision. For all models, the good guess of predicted AUC0-12hr (±15% of observed AUC0-12hr) was highly variable (range, full cohort = 19%-61.9%; high EHR = 4.5%-65.9%; low EHR = 27.5%-62.5%). CONCLUSIONS: The predictive performance of the LSS models varied according to EHR status. Timepoints ≥5 hours postdose in LSS models are essential to capture EHR. Models and strategies that incorporate EHR during development are required to accurately ascertain MPA exposure.

Materials descriptors for advanced water dissociation catalysts in bipolar membranes.

The voltage penalty driving water dissociation (WD) at high current density is a major obstacle in the commercialization of bipolar membrane (BPM) technology for energy devices. Here we show that three materials descriptors, that is, electrical conductivity, microscopic surface area and (nominal) surface-hydroxyl coverage, effectively control the kinetics of WD in BPMs. Using these descriptors and optimizing mass loading, we design new earth-abundant WD catalysts based on nanoparticle SnO2 synthesized at low temperature with high conductivity and hydroxyl coverage. These catalysts exhibit exceptional performance in a BPM electrolyser with low WD overvoltage (ηwd) of 100 ± 20 mV at 1.0 A cm-2. The new catalyst works equivalently well with hydrocarbon proton-exchange layers as it does with fluorocarbon-based Nafion, thus providing pathways to commercializing advanced BPMs for a broad array of electrolysis, fuel-cell and electrodialysis applications.

Spectral degradation and carrier sentences increase age-related temporal processing deficits in a cue-specific manner.

Advancing age is associated with decreased sensitivity to temporal cues in word segments, particularly when target words follow non-informative carrier sentences or are spectrally degraded (e.g., vocoded to simulate cochlear-implant stimulation). This study investigated whether age, carrier sentences, and spectral degradation interacted to cause undue difficulty in processing speech temporal cues. Younger and older adults with normal hearing performed phonemic categorization tasks on two continua: a Buy/Pie contrast with voice onset time changes for the word-initial stop and a Dish/Ditch contrast with silent interval changes preceding the word-final fricative. Target words were presented in isolation or after non-informative carrier sentences, and were unprocessed or degraded via sinewave vocoding (2, 4, and 8 channels). Older listeners exhibited reduced sensitivity to both temporal cues compared to younger listeners. For the Buy/Pie contrast, age, carrier sentence, and spectral degradation interacted such that the largest age effects were seen for unprocessed words in the carrier sentence condition. This pattern differed from the Dish/Ditch contrast, where reducing spectral resolution exaggerated age effects, but introducing carrier sentences largely left the patterns unchanged. These results suggest that certain temporal cues are particularly susceptible to aging when placed in sentences, likely contributing to the difficulties of older cochlear-implant users in everyday environments.

Digital cognitive assessments as low-burden markers for predicting future cognitive decline and tau accumulation across the Alzheimer's spectrum.

Digital cognitive assessments, particularly those that can be done at home, present as low burden biomarkers for participants and patients alike, but their effectiveness in diagnosis of Alzheimer's or predicting its trajectory is still unclear. Here, we assessed what utility or added value these digital cognitive assessments provide for identifying those at high risk for cognitive decline. We analyzed >500 ADNI participants who underwent a brief digital cognitive assessment and Aß/tau PET scans, examining their ability to distinguish cognitive status and predict cognitive decline. Performance on the digital cognitive assessment were superior to both cortical Aß and entorhinal tau in detecting mild cognitive impairment and future cognitive decline, with mnemonic discrimination deficits emerging as the most critical measure for predicting decline and future tau accumulation. Digital assessments are effective in identifying at-risk individuals, supporting their utility as low-burden tools for early Alzheimer's detection and monitoring.

Eccentric muscle-damaging exercise in the heat lowers cellular stress prior to and immediately following future exertional heat exposure.

Muscle-damaging exercise (e.g., downhill running [DHR]) or heat exposure bouts potentially reduce physiological and/or cellular stress during future exertional heat exposure; however, the true extent of their combined preconditioning effects is unknown. Therefore, this study investigated the effect of muscle-damaging exercise in the heat on reducing physiological and cellular stress during future exertional heat exposure. Ten healthy males (mean ± Standard Definition; age, 23 ± 3 years; body mass, 78.7 ± 11.5 kg; height, 176.9 ± 4.7 cm) completed this study. Participants were randomly assigned into two preconditioning groups: (a) DHR in the heat (ambient temperature [Tamb], 35 °C; relative humidity [RH], 40%) and (b) DHR in thermoneutral (Tamb, 20 °C; RH, 20%). Seven days following DHR, participants performed a 45-min flat run in the heat (FlatHEAT [Tamb, 35 °C; RH, 40%]). During exercise, heart rate and rectal temperature (Trec) were recorded at baseline and every 5-min. Peripheral blood mononuclear cells were isolated to assess heat shock protein 72 (Hsp72) concentration between conditions at baseline, immediately post-DHR, and immediately pre-FlatHEAT and post-FlatHEAT. Mean Trec during FlatHEAT between hot (38.23 ± 0.38 °C) and thermoneutral DHR (38.26 ± 0.38 °C) was not significantly different (P = 0.68), with no mean heart rate differences during FlatHEAT between hot (172 ± 15 beats min-1) and thermoneutral conditions (174 ± 8 beats min-1; P = 0.58). Hsp72 concentration change from baseline to immediately pre-FlatHEAT was significantly lower in hot (-51.4%) compared to thermoneutral (+24.2%; P = 0.025) DHR, with Hsp72 change from baseline to immediately post-FlatHEAT also lower in hot (-52.6%) compared to thermoneutral conditions (+26.3%; P = 0.047). A bout of muscle-damaging exercise in the heat reduces cellular stress levels prior to and immediately following future exertional heat exposure.

Dermatologic needs of transgender and gender diverse youth: A retrospective cohort study.

Several dermatologic concerns are known to disproportionally affect transgender and gender-diverse (TGD) adults, but little is known about dermatologic conditions in TGD youth. This study assesses the prevalence of acne, androgenic alopecia, scarring from gender-affirming procedures, and eczema in pediatric TGD patients seen at Boston Children's Hospital between April 2021 and April 2022. The results demonstrate that, for TGD youth, the studied dermatologic concerns are common, referral rates to dermatology are low, and acne is significantly associated with testosterone use. Future studies should examine additional dermatologic concerns and barriers to accessing dermatologic care for this historically underserved population.

Two-center analysis of cannabis on venous thromboembolism risk after traumatic injury: A matched analysis.

BACKGROUND: Conflicting evidence exists evaluating associations between cannabis (THC) and post-traumatic DVT. METHODS: Retrospective analysis (2014-2023) of patients ≥15yrs from two Level I trauma centers with robust VTE surveillance and prophylaxis protocols. Multivariable hierarchical regression assessed the association between THC and DVT risk. THC â€‹+ â€‹patients were direct matched to other drug use categories on VTE risk markers and hospital length of stay. RESULTS: Of 7365 patients, 3719 were drug-, 575 were THC â€‹+ â€‹only, 2583 were other drug+, and 488 were TCH+/other drug+. DVT rates by exposure group did not differ. TCH â€‹+ â€‹only patients had higher GCS scores, shorter hospital length of stay, and the lowest pelvic fracture and mortality rates. A total of 458 drug-, 453 other drug+, and 232 THC+/other drug â€‹+ â€‹patients were matched to 458, 453, and 232 THC â€‹+ â€‹only patients. There were no differences in DVT event rates in any paired sub-cohort set. Additionally, iteratively adjusted paired models did not show an association between THC and DVT. CONCLUSIONS: THC does not appear to be associated with increased DVT risk in patients with strict trauma chemoprophylaxis. Toxicology testing is useful for identifying substance abuse intervention opportunities, but not for DVT risk stratification in THC â€‹+ â€‹patients.

Demographics and clinical characteristics of patients of prescribing psychologists, psychiatrists, and primary care physicians.

To describe the characteristics of patients receiving psychotropic medication from prescribing psychologists, psychiatrists, and primary care physicians. This descriptive study was conducted using private insurance claims of patients from New Mexico and Louisiana receiving psychotropic medications (anticonvulsants, antidepressants, antipsychotics, hypotensive agents, anxiolytics/sedatives/hypnotics, and stimulants) from 2004 to 2021 (N = 307,478). Patient characteristics were captured during the 6 months prior to their first psychotropic medication using administrative information, diagnosis and procedure codes, and medication data. Logistic regression models estimated the associations of patient characteristics with prescriber type. Additional logistic regression models estimated the association of prescriber type with medication classes prescribed. Patients were most likely to see specialists (psychologists or psychiatrists) if they had bipolar disorder (average marginal effect and 95% CI 0.214 [0.196, 0.231]), schizophrenia/psychotic disorders (0.118 [0.097, 0.138]), or had 1-4 visits of psychotherapy (0.267 [0.258, 0.026]). Specialist patients were most likely to see a prescribing psychologist if they had 1-4 visits of psychotherapy (0.196 [0.183, 0.210]) or had insomnia (0.309 [0.203, 0.415]). Prescribing psychologists were more likely to prescribe antidepressants (0.028 [0.011, 0.045]) and less likely to prescribe antipsychotics (-0.016 [-0.020, -0.012]) than psychiatrists. Primary care physicians were less likely to prescribe all psychotropic medications except antidepressants (0.011 [0.002, 0.019]) and anxiolytics (0.074 [0.067, 0.080]). Prescribing psychologists treat patients who are more similar to those of psychiatrists than patients of primary care physicians; they are less likely to prescribe antipsychotics and more likely to prescribe antidepressants. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cold seep formation from salt diapir-controlled deep biosphere oases.

Deep sea cold seeps are sites where hydrogen sulfide, methane, and other hydrocarbon-rich fluids vent from the ocean floor. They are an important component of Earth's carbon cycle in which subsurface hydrocarbons form the energy source for highly diverse benthic micro- and macro-fauna in what is otherwise vast and spartan sea scape. Passive continental margin cold seeps are typically attributed to the migration of hydrocarbons generated from deeply buried source rocks. Many of these seeps occur over salt tectonic provinces, where the movement of salt generates complex fault systems that can enable fluid migration or create seals and traps associated with reservoir formation. The elevated advective heat transport of the salt also produces a chimney effect directly over these structures. Here, we provide geophysical and geochemical evidence that the salt chimney effect in conjunction with diapiric faulting drives a subsurface groundwater circulation system that brings dissolved inorganic carbon, nutrient-rich deep basinal fluids, and potentially overlying seawater onto the crests of deeply buried salt diapirs. The mobilized fluids fuel methanogenic archaea locally enhancing the deep biosphere. The resulting elevated biogenic methane production, alongside the upward heat-driven fluid transport, represents a previously unrecognized mechanism of cold seep formation and regulation.

Identification of Nonfunctional Alternatively Spliced Isoforms of STING in Human Acute Myeloid Leukemia.

Lack of robust activation of Stimulator of Interferon Genes (STING) pathway and subsequent induction of type I IFN responses is considered a barrier to antitumor immunity in acute myeloid leukemia (AML). Using common human AML cell lines as in vitro tools to evaluate the efficacy of novel STING agonists, we found most AML lines to be poor producers of IFNs upon exposure to extremely potent agonists, suggesting cell-intrinsic suppression of STING signaling may occur. We observed unexpected patterns of response that did not correlate with levels of STING pathway components or of known enzymes associated with resistance. To identify a genetic basis for these observations, we cloned and sequenced STING from the cDNA of human AML cell lines and found both frequent mutations and deviations from normal RNA splicing. We identified two novel spliced isoforms of STING in these lines and validated their expression in primary human AML samples. When transduced into reporter cells, these novel STING isoforms exhibited complete insensitivity to agonist stimulation. These observations identify alternative splicing as a mechanism of STING pathway suppression and suggest that most AML silences the STING pathway through direct modification rather than through engagement of external inhibitory factors. SIGNIFICANCE: We find that AML acquires resistance to innate immune activation via the STING pathway through aberrant splicing of the STING transcript including two novel forms described herein that act as dominant negatives. These data broaden understanding of how cancers evolve STING resistance, and suggest that the AML tumor microenvironment, not the cancer cell, should be the target of therapeutic interventions to activate STING.

Implementing vanadium peroxides as direct air carbon capture materials.

Direct air capture (DAC) removal of anthropogenic CO2 from the atmosphere is imperative to slow the catastrophic effects of global climate change. Numerous materials are being investigated, including various alkaline inorganic metal oxides that form carbonates via DAC. Here we explore metastable early d0 transition metal peroxide molecules that undergo stabilization via multiple routes, including DAC. Specifically here, we describe via experiment and computation the mechanistic conversion of A3V(O2)4 (tetraperoxovanadate, A = K, Rb, Cs) to first a monocarbonate VO(O2)2(CO3)3-, and ultimately HKCO3 plus KVO4. Single crystal X-ray structures of rubidium and cesium tetraperoxovanadate are reported here for the first time, likely prior-challenged by instability. Infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), 51V solid state NMR (nuclear magnetic resonance), tandem thermogravimetry-mass spectrometry (TGA-MS) along with calculations (DFT, density functional theory) all converge on mechanisms of CO2 capture and release that involve the vanadium centre, despite the end product of a 300 days study being bicarbonate and metavanadate. Electron Paramagnetic Resonance (EPR) Spectroscopy along with a wet chemical assay and computational studies evidence the presense of ∼5% adventitous superoxide, likely formed by peroxide reduction of vanadium, which also stabilizes via the reaction with CO2. The alkalis have a profound effect on the stability of the peroxovanadate compounds, stability trending K > Rb > Cs. While this translates to more rapid CO2 capture with heavier alkalis, it does not necessarily lead to capture of more CO2. All compounds capture approximately two equivalents CO2 per vanadium centre. We cannot yet explain the reactivity trend of the alkali peroxovanadates, because any change in speciation of the alkalis from reactions to product is not quantifiable. This study sets the stage for understanding and implementing transition metal peroxide species, including peroxide-functionalized metal oxides, for DAC.

Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.

The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.

Nurse-Led Models of Care: Practice and Policy to Support Aging in Place.

PURPOSE: Research demonstrates that aging in place is the goal of most adults aged >50 years. Unfortunately, multiple barriers to aging in place continue to exist, especially for vulnerable populations. Achieving this goal will require innovative nurse-led models of care and new policies for RN reimbursement. The current article describes a nurse-led clinic implemented in one community. METHOD: Using an evidence-based nurse-led model of care, a team of university faculty, students, and a family nurse practitioner designed and implemented a nurse-led clinic for a religious community in the Pacific Northwest. RESULTS: Today, the nurse-led clinic offers care coordination and primary care to support aging in place and is one example of a nurse-led model well-positioned to address the aging in place needs of vulnerable populations. CONCLUSION: Replication and sustainability of this nurse-led model requires sweeping policy change, including consideration of requiring all nurses to attain a National Provider Identification number to expand RN reimbursement and ultimately increase access to care. [Journal of Gerontological Nursing, 50(3), 13-17.].

'If I Knew More I Would Feel Less Worried': Filipino Americans' Attitudes and Knowledge of Genetic Disease, Counseling, and Testing.

INTRODUCTION: The field of genetics is rapidly expanding and people are increasingly utilizing genetic testing and counseling services. However, the current literature on genetic health topics and Filipinos remains limited, as many minority populations are not adequately studied. This study describes Filipino Americans' attitudes and knowledge of genetic disease, genetic testing, and genetic counseling. To address these knowledge gaps and reduce the burden of health disparities, the informational needs of Filipino Americans regarding genetic disease and genetic services must be understood in order to better tailor these services and outreach methods. METHODS: Fifteen semi-structured, qualitative interviews were held with individuals who self-identified as Filipino American between November 2022 and January 2023. Interviews were transcribed and coded using an iterative process. RESULTS: Most participants were familiar with genetic disease and believed that factors such as biology, as well as cultural factors such as upbringing and food, contributed to its development. The majority of participants had previously heard of genetic testing; however, most participants either did not know much or were only familiar with ancestry direct-to-consumer genetic testing (DTC-GT). Most participants had not heard of genetic counseling and those that had heard of genetic counseling before did not understand its purpose. Overall, most participants had a positive attitude toward genetic testing and counseling. Participants identified the benefits of these services including genetic disease prevention, management, and treatment. Participants stressed the importance of educating the Filipino community and shared their ideas for how to implement outreach efforts. DISCUSSION/CONCLUSION: This study found that Filipino Americans generally had a positive outlook on genetic testing and genetic counseling. We propose participant-generated ideas for outreach and education that may help inform future public health efforts that aim to educate this population about genetic disease, testing and counseling.

A Bayesian framework for modeling COVID-19 case numbers through longitudinal monitoring of SARS-CoV-2 RNA in wastewater.

Wastewater-based surveillance has become an important tool for research groups and public health agencies investigating and monitoring the COVID-19 pandemic and other public health emergencies including other pathogens and drug abuse. While there is an emerging body of evidence exploring the possibility of predicting COVID-19 infections from wastewater signals, there remain significant challenges for statistical modeling. Longitudinal observations of viral copies in municipal wastewater can be influenced by noisy datasets and missing values with irregular and sparse samplings. We propose an integrative Bayesian framework to predict daily positive cases from weekly wastewater observations with missing values via functional data analysis techniques. In a unified procedure, the proposed analysis models severe acute respiratory syndrome coronavirus-2 RNA wastewater signals as a realization of a smooth process with error and combines the smooth process with COVID-19 cases to evaluate the prediction of positive cases. We demonstrate that the proposed framework can achieve these objectives with high predictive accuracies through simulated and observed real data.