Franklin College

Quantitative protein analysis by surface-enhanced Raman spectroscopy (SERS) remains challenging due to weak and heterogeneous protein adsorption on plasmonic surfaces. Here, we introduce a superspectra-guided SERS framework that leverages chemically distinct interaction environments to enhance quantitative performance. Silver nanorod (AgNR) substrates were functionalized with cysteamine (CM), cysteine (CN), and 6-mercapto-1-hexanol (MCH), together with unmodified (B) AgNRs, to create surfaces that probe complementary aspects of protein-surface interactions through charge- and chemistry-dependent binding. Using bovine serum albumin (BSA) as a model protein, we systematically constructed superspectra by concatenating SERS signals from all single-, pairwise-, triple-, and four-surface combinations and evaluated their performance using support vector regression (SVR) and random forest regression (RFR). Our results reveal that superspectra must be constructed selectively: single-substrate spectra lack sufficient chemical diversity, and superspectra incorporating all four surfaces often degrade accuracy due to noninformative or conflicting features, particularly those introduced by MCH. In contrast, superspectra derived from complementary surface chemistries, especially the CM&CN pair or the B&CM&CN triplet, yield markedly improved quantitative predictions. RFR consistently outperformed SVR, demonstrating superior robustness for integrating chemically heterogeneous spectral inputs. This work establishes, for the first time, design principles for constructing effective superspectra for protein SERS and highlights the importance of analyte-surface interaction complementarity in enabling accurate, scalable protein quantification.

BackgroundHospitalization rates among persons with HIV (PWH) in the US remain substantial, yet regional variations are understudied. This study analyzed insurance claims data to estimate hospitalization incidence among commercially and Medicare-insured PWH across four US regions.Figure 1.Incidence proportion of persons with more than one hospitalizationThe proportion of PWH with ≥1 hospitalization annually was calculated by dividing the number of individuals with ≥1 hospitalization by the total number of individuals with HIV at the beginning of each year. Rates are shown stratified by region of enrollment (red points and error bars) and admitting hospital region (blue points and error bars). From 2018 to 2020, enrollment-based rates were highest in the Northeast and lowest in the West. The Northeast consistently had the highest incidence (0.09 [95% CI: 0.08–0.10] in 2018 and 2019), while the West remained lowest (0.02 [95% CI: 0.02–0.02] in 2018 and 0.02 [95% CI: 0.02–0.03] in 2019 and 2020). In 2020, a slight decrease was observed in the South (from 0.08 to 0.07), while the Northeast and Midwest remained stable. Hospital-based stratification showed a slightly different pattern: the Northeast remained highest, peaking at 0.12 (95% CI: 0.11–0.13) in 2019, while the South had the lowest proportions, decreasing from 0.05 (95% CI: 0.05–0.06) in 2018 to 0.04 (95% CI: 0.04–0.05) in 2020. The West and Midwest showed modest fluctuations, with the West peaking at 0.10 (95% CI: 0.09–0.11) in 2019 before declining to 0.07 (95% CI: 0.06–0.08) in 2020.Figure 2.Incidence proportion of all hospitalizationsB. Incidence proportion of all hospitalizations.Total hospitalizations per regional person-years was calculated by dividing the number of hospitalizations by the total number of individuals with HIV at the beginning of each year. Results are stratified by enrollment region (black points and error bars). From 2018 to 2020, the highest incidence proportions were observed in the Northeast and South (range: 0.12–0.13). The Midwest increased from 0.12 in 2018 to 0.14 in 2019, then declined slightly in 2020. The West consistently had the lowest incidence, remaining at 0.03 each year with narrow confidence intervals.MethodsThis study used MarketScan data (2017-2020) to determine hospitalization incidence in US PWH (ICD-10-CM B20), using 2017 to identify cases for 2018. To ensure complete annual hospitalization capture and minimize loss-to-follow-up bias, the cohort was limited to continuously enrolled individuals (full 12-month coverage/year). For regional analysis across four US Census regions (South, Northeast, Midwest, West, encompassing all 50 states and D.C.), the population was further restricted to enrollees with available regional data. Annual hospitalization incidence was reported as (1) incidence proportion of ≥1 hospitalization, (2) incidence proportion of all hospitalizations, and (3) incidence density, each with 95% confidence intervals.Figure 3.Incidence density of first hospitalizationIncidence density was defined as the number of individuals with a first hospitalization divided by the total person-time at risk (measured as the sum of days prior to first hospitalization or, if no admission occurred, the total follow-up time). Results are stratified by enrollment region (red points and error bars) and hospital region (blue points and error bars). Incidence density declined across all regions from 2018 to 2020. In enrollment-based analyses, the Northeast had the highest rates, dropping from 0.038 (95% CI: 0.036–0.041) in 2018 to 0.017 (95% CI: 0.016–0.019) in 2020. The West had the lowest rates, declining from 0.007 (95% CI: 0.006–0.008) to 0.004 (95% CI: 0.003–0.005). Hospital-based rates followed similar regional trends, with the Northeast consistently highest. While the South and West showed lower rates overall, West region estimates were slightly higher than those based on enrollment.ResultsAmong 90,836 PWH, 13.5% (n=12,287) had ≥1 hospitalization, a stable proportion. Hospitalized individuals were typically 49–50 years old (median), 73% male, and 95% commercially insured, with most experiencing ≥2 annual hospitalizations (3–4-day median stay). The South (39%) and Northeast (29%) accounted for the largest, stable proportions of all hospitalizations. Hospital-based incidence mirrored enrollment trends but showed greater variation, peaking in the Northeast and declining in the South (Fig). Total hospitalization incidence proportions were higher than ≥1 hospitalization proportions, reflecting multiple admissions. Incidence density revealed temporal declines and regional nuances, suggesting reduced hospitalization frequency in the Northeast and South despite stable proportions, and consistently low rates in the West.ConclusionHospitalization patterns varied regionally, with the highest burden in the Northeast and South. While the proportion of individuals hospitalized remained stable, declining incidence density in these regions suggests reduced hospitalization frequency over time. These findings emphasize the need to explore factors such as access to care and comorbidities driving regional disparities.DisclosuresAll Authors: No reported disclosures

Hydrogen peroxide (H₂O₂) is a widely used oxidant in wastewater treatment, disinfection, and industrial processes. Conventional anthraquinone production process is complex and energy intensive, and produces highly concentrated H₂O₂ that is unsafe and expensive to transport. As an alternative, distributed electrochemical synthesis of H₂O₂ via the two-electron oxygen reduction reaction (2e⁻ ORR) provides a more sustainable approach, enabling on-site production from air and electricity. In this study, we explore a series of monoclinic transition metal 3:4 selenides (M₃Se₄, M = Fe, Co, Ni), including Co₃Se₄, FeCo₂Se₄, Fe₂CoSe₄, and Fe₃Se₄, as potential electrocatalysts for 2e⁻ ORR. Systematic hydrothermal synthesis of this series of compounds and structural characterization are conducted. Then their activity and selectivity for 2e⁻ ORR are evaluated using rotating ring-disk electrode (RRDE) measurements. The Fe:Co ratio in (Fe x Co1-x )₃Se₄ is further adjusted to investigate its effect on their electronic structure and catalytic behaviors. The results show that FeCo₂Se₄ exhibits the best activity and selectivity for 2e⁻ ORR across a broad potential range, demonstrating the potential of M₃Se₄ as electrocatalysts for electrochemical H₂O₂ production. This study provides insights into rational design of transition metal chalcogenides for electrocatalysis and contributes to the development of sustainable H₂O₂ electrosynthesis.

A robust immune response and regenerative capacity are both essential for survival after injury. In plants, salicylic acid (SA) is essential for activating immunity but simultaneously suppresses regenerative capacity. The mechanisms coordinating the trade-off between immunity and regeneration remain poorly understood. Here, we identify proline transporters as key regulators of this balance. Mutations in two wound-induced proline transporters, ProT2 and ProT3, rescued exogenous proline-induced suppression of de novo root regeneration (DNRR) and enhanced DNRR. ProTs are required for SA–mediated suppression of regeneration, without affecting SA-dependent defense responses. Mechanistically, a ProT3–CPK1 complex modulates the dynamics of wound-induced reactive oxygen species (ROS), sustaining a ROS level that restricts DNRR after wounding. Notably, pharmacological inhibition of proline transport rescued SA-mediated suppression of regeneration and enhanced regeneration across multiple plant species. These findings establish proline transporter as a regulatory hub integrating stress-induced proline metabolism, SA signaling, and ROS homeostasis to balance immunity and regeneration, and highlight chemical inhibition of proline transport as a strategy to improve crop regeneration under biotic stresses without compromising disease resistance.

BackgroundTuberculosis persists today in many resource-limited countries in the southern hemisphere because unobserved transmission of M. tuberculosis occurs in undefined contact networks of infectious cases.MethodsTo study the transmission dynamics of M. tuberculosis in an African city with endemic tuberculosis, we built out a sociocentric network in the Lubaga Division of Kampala, Uganda, using the personal networks of 130 index cases and 123 community controls frequency-matched by age, sex, and parish. Clusters of genetically related strains were identified using whole genome sequencing was from 99 isolates of the cases. The social distance between cases with related pairs was estimated from the sociocentic network.FindingsWe found that characteristics of this sociocentric network account, in part, for tuberculosis persistence. These characteristics included highly connected network members, or hubs, where mixing among contacts may occur; predominant transmission among contacts with weak, or distant, ties to the index case; and geographic structural holes in the network that may link cases with these unknown contacts.InterpretationThese findings suggest that active case finding within the social networks of index cases may result in marginal gains in reducing transmission of tuberculosis. To achieve greater gains, transmission in the community may be reduced through population-based strategies that disrupt transmission in geographic hubs of transmission where mixing may occur between infectious cases and community contacts.FundingThis research was conducted with support from the National Institute of Health (AI093856, AI147319, P30 AI 68386, D43TW010045, D43TW012481).

Material-sparing tablet development (MSTD) describes an approach to tablet formulation development that uses the active pharmaceutical ingredient's (API) material properties to guide formulation design. The work presented here expands on this methodology and demonstrates its application for any API. Four APIs were randomly selected from the Boehringer Ingelheim opnMe platform to demonstrate the universal applicability of the MSTD regardless of the API properties. Small batches of each API (<20 g of API) were used to mimic early-phase development. Each API was analyzed for particle morphology, flowability, density, and compression behavior. Formulations were then designed to complement these API properties using standard tableting excipients. The powder blends were tested for flowability (≤ 12 mm Flodex) and tensile strength (> 2 MPa) to ensure manufacturability. Tablet disintegration (< 15 min) and friability (NMT 0.8 % loss) were tested to verify tablets met current federal performance standards. Stability testing was done to determine excipient compatibility and overall drug product stability (NMT 0.3 % API loss). This work demonstrated that for a wide variety of different APIs, formulations could be designed and tested for critical manufacturing attributes, and possible failure points could be determined using less than 20 g of API in less than 14 days.

As brackish turbid waters exit San Francisco Bay, one of the largest estuaries in the U.S. West Coast, they form the San Francisco Bay Plume (SFBP), which spreads offshore and influences the Gulf of the Farallones (GoF), an ecologically significant region in the California Current System that is also home to three National Marine Sanctuaries. This paper provides the first observationally based investigation of the spatio-temporal variability of the SFBP, using a plume tracking algorithm applied to more than two decades (2002-2023) of ocean color data from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor onboard satellites Aqua and Terra. The turbid SFBP spreads radially, extending 10-20 km offshore around 50% of the time, and during extreme discharge events (&amp;lt;1% of the time), the plume can reach nearly 60 km offshore to the shelf break. The greatest variability in frequency of plume occurrence was observed 10-20 km offshore and it was largely explained by the seasonal cycle (80% of total variance), linked primarily to seasonal changes in river discharge. Largest plume areas (determined by summing up all pixel areas weighted by their respective fraction of plume occurrence) were observed during winter and smallest during summer, occupying on average 24% and 1.5% of GoF area, respectively. Beyond 20-30 km offshore, variability in frequency of plume occurrence was dominated by the intraseasonal band (50-80% of total variance), attributed to plume response to synoptic wind-forcing and/or filaments and eddies, while the interannual band played a secondary role in the plume variability (&amp;lt;20% of total variance). Finally, a multivariable linear regression model of the turbid SFBP area was created to explore the potential predictability of the plume’s influence in the GoF. The model included the annual and semi-annual cycles and discharge anomalies (deseasoned and detrended), and despite its simplicity, it explained over 78% of total variance of the turbid SFBP area. Therefore, it could be a useful tool for scientists and stakeholders to better understand how management actions on freshwater supply can have consequences offshore beyond the Golden Gate and help guide future management decisions in this ecologically important region.

Semiaromatic polyestersderived from petroleum are an importantclass of polymers that encompass a wide variety of thermal and mechanicalproperties. Unfortunately, replacing the aromatic component with cost-competitivebioderived monomers is an ongoing challenge. This work describes thesynthesis of nine different polyesters made from AB monomers thatcan be derived from lignin, starting with phloretic, coumaric, andferulic acids and similar derivatives. The polyesters were synthesizedat >50 g scale, and full characterization of the thermal, mechanical,and rheological properties is included. The polymers exhibit excellentthermal stability, a Tg range of 16–65°C, tensile moduli ranging from 4.6 to 1200 MPa, and elongationat break ranging from 7.5% to greater than 3800%. To examine the effectsof structural permutations among the polymer series, TTS master curveswere constructed for seven polyesters using melt rheology. Propertiessuch as packing length and characteristic ratio are described andcompared among the series. Finally, it is demonstrated that thesepolyesters are easily chemically recycled to monomer in high yield.

Background:While isavuconazole (ISA) has demonstrated non-inferiority to voriconazole (VCZ) for invasive aspergillosis (IA) in clinical trials, real-world comparisons are limited.Objectives:To compare treatment completion, adverse events, hospitalizations, and healthcare costs in patients treated with VCZ versus ISA for IA.Design:Retrospective cohort study using Merative MarketScan claims data (2017–2020).Methods:Adults (⩾18 years) diagnosed with IA (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes) who received VCZ or ISA monotherapy were included. Treatment completion was defined as ⩾42 days of therapy. Descriptive statistics and logistic regression were used to assess outcomes and predictors of antifungal selection, adverse events, hospitalizations, and treatment completion.Results:Among 335 patients, 84% (n = 282) received VCZ and 16% (n = 53) received ISA. Baseline characteristics were comparable, although the VCZ group had higher Medicaid enrollment, and the ISA group had more patients with malignancy. Treatment completion rates were comparable (92% each, p = 1), as were median treatment durations (VCZ: 120 days, ISA: 112 days, p = 0.95). Adverse event rates were not significantly different (VCZ: 49%, ISA: 60%, p = 0.18), but CNS-related events occurred more frequently with ISA (16% vs 9%, p = 0.32). VCZ was associated with lower outpatient pharmacy costs (median $1,596.68 vs $11,000.66, p < 0.001) and total hospitalization costs (median $40,681.89 vs $121,545.89, p = 0.01). Malignancy was associated with lower odds of receiving VCZ (OR 0.30, p = 0.001), and younger age predicted higher odds of treatment incompletion (OR 0.97, p = 0.035). Female sex was associated with increased adverse event risk. Notably, VCZ use was not associated with increased adverse events or treatment incompletion.Conclusion:VCZ was prescribed five times more frequently than ISA for IA, despite similar treatment durations and completion rates. VCZ was associated with lower costs and did not increase the risk of adverse events or treatment discontinuation. These findings suggest that VCZ remains commonly used and potentially more cost-effective treatment option for IA.

This study investigates the association between thromboembolic events (TE) and castration-resistant prostate cancer (CRPC) patients receiving oral androgen receptor pathway inhibitors (ARPi) compared to those undergoing chemotherapy, both with and without a pre-existing history of cardiovascular disease (CVD). A total of 2779 men diagnosed with CRPC were identified using the Surveillance, Epidemiology, and End Results (SEER) Medicare Linked Database from 2012 to 2016. Patients were stratified based on their CVD history. Within each CVD stratum (pre-existing CVD vs. no pre-existing CVD), patients were further categorized into two treatment groups: those receiving oral ARPi and those undergoing chemotherapy. Unadjusted and inverse probability treatment weight (IPTW)-adjusted proportional hazards models, using Fine and Gray's method, were applied to evaluate the potential association between ARPi treatment and TE. Patients with pre-existing CVD treated with ARPi exhibited a significantly lower crude hazard ratio (HR) for TE compared to chemotherapy (HR 0.39, 95% CI 0.27-0.58, p < 0.001). However, after adjustment using IPTW, this association was no longer significant (adjusted hazard ratio [AHR] 1.00, 95% CI 0.75-1.32, p = 0.99). For patients without CVD, ARPi use was also associated with a reduced risk of TE in the crude analysis (HR 0.53, 95% CI 0.32-0.87, p = 0.01), but this effect was not statistically significant after IPTW adjustment (HR 0.99, 95% CI 0.69-1.41, p = 0.94). ARPi demonstrated no significant effect on TE risk compared to chemotherapy, regardless of pre-existing CVD status. Similarly, when excluding patients with a prior history of TE, ARPi use remained non-significantly associated with new TE in the IPTW-adjusted competing risk analysis, highlighting the need for further investigation.