Journals
2025 EN
DeSantis Paul M. · Basgul Cemile · Spece Hannah
+2 more
ABSTRACT Polyetheretherketone (PEEK) medical devices have been shown to perform well as permanent implants, but the hydrophobicity of PEEK limits its osseointegration ability. Postprocessing techniques are used to improve osseointegration, with ultraviolet (UV) light‐assisted functionalization being one possible method. We hypothesized that UV irradiation of PEEK could be used to graft hydroxyapatite (HAp) to its surface. PEEK samples were created via fused filament fabrication and submerged in 2× simulated body fluid (SBF). Samples were exposed to a 2 W/cm 2 UV light for 6 h and then placed in a water bath set to 37°C for a total of 72 h. After being washed with deionized water and dried, attenuated total reflectance Fourier transform infrared spectroscopy (ATR‐FTIR) was performed on the functionalized samples, control PEEK samples that were not treated, and control samples that were soaked in SBF for 72 h but were not exposed to UV light. Images of the surface of the functionalized samples and controls were obtained using a scanning electron microscope with energy‐dispersive spectroscopy. An in vitro cell study using mouse preosteoblasts was performed to verify if functionalization improves osteoconduction. Normalized alkaline phosphatase activity was used as a marker for osteogenic activity. Analysis revealed that UV‐assisted functionalization successfully applied a layer of calcium phosphate material to the surface of the PEEK. After culturing functionalized surfaces in vitro, the addition of calcium phosphate was found to significantly improve osteogenic activity when compared to nonfunctionalized PEEK samples after 7 and 14 days.
Journals
2025 EN
Derr Tabitha · Basgul Cemile · DeSantis Paul
+2 more
ABSTRACT Silicon nitride (Si 3 N 4 ) is reported to exhibit antibacterial properties and support osteoblast maturation, while polyetherketoneketone (PEKK) is considered to potentially have antibacterial and osseointegrative properties while offering favorable manufacturability through extrusion‐based additive manufacturing compared to traditional ceramics manufacturing. Incorporating silicon nitride into PEKK is hypothesized to enhance its bioactivity while maintaining processability, making Si 3 N 4 ‐PEKK composites promising for medical implants. Our objective was to determine optimal fused filament fabrication (FFF) parameters for PEKK and Si 3 N 4 ‐PEKK. Taguchi optimization (L9 array, n = 5) was performed on PEKK and 15 vol.% Si 3 N 4 ‐PEKK to assess the impact of printing parameters (layer height: 0.1, 0.2, and 0.3 mm; nozzle temperature (PEKK/Si 3 N 4 ‐PEKK): 340/380, 370/400, and 400/420; bed temperature: 130°C, 150°C, and 170°C; and chamber temperature: 110°C, 130°C, and 150°C) on ultimate tensile strength (UTS). Z‐directional tensile specimens were printed on a medical FFF printer. Specimens underwent tensile testing according to ASTM D638. Signal/noise ratios for UTS were calculated and ANOVA (Minitab 21.4.2) was used to assess statistical significance ( p < 0.05). Layer height had the greatest impact on UTS for both PEKK and Si 3 N 4 ‐PEKK. Optimal nozzle and chamber temperatures were 400°C and 130°C, respectively, while the optimal layer height was 0.1 mm for both materials. The optimal bed temperature for PEKK and Si 3 N 4 ‐PEKK was 150°C and 170°C, respectively. For PEKK, differences in all parameters were significant except for bed temperature, while for Si 3 N 4 ‐PEKK all parameters were significant except for nozzle temperature. The specimens with optimum statistically significant parameters showed the highest UTS for both PEKK (91 ± 2 MPa) and Si 3 N 4 ‐PEKK (76 ± 3 MPa). Layer height is the most influential printing variable for both PEKK and Si 3 N 4 ‐PEKK. The optimal PEKK printing condition has a comparable UTS, while Si 3 N 4 ‐PEKK achieved 84% of the injection‐molded value for neat PEKK.
Journals
2025 EN
Wyble Aaron J. · Sethapati V. Rakesh · Post Steven R.
+5 more
ABSTRACT In order to reflect patient needs given new treatment options for hematopoietic malignancies, autologous hematopoietic progenitor cell (HPC) collection goals were changed to 10 or 15 × 10 6 CD34+/kg (previously 20 × 10 6 CD34+/kg) for myeloma patients and to 5 × 10 6 CD34+/kg (previously 10 × 10 6 CD34+/kg) for lymphoma patients in March 2023. The minimum number of large volume leukapheresis (LVL) procedures required decreased from two to one. We analyzed the impact of these changes on apheresis and cell therapy laboratory (CTL) services. Data from the post‐implementation period of April through December in 2023 were compared to those from the same 9‐month periods in 2022 and 2021 as controls. The number of patients undergoing autologous HPC collection per month were examined. The numbers of LVL procedures, numbers of cryopreserved bags, and apheresis and CTL staffing hours and costs were determined retrospectively on a per patient and monthly basis. One‐way ANOVA with Tukey's multiple comparison was performed. The per patient averages for LVL procedures, cryopreserved bags, staff hours, and costs in apheresis and CTL services were decreased significantly in 2023 compared to both control periods. However, for monthly analyses, differences were significant between 2023 and 2021; but not between 2023 and 2022. No differences were seen between the two control periods. The changes in autologous HPC collection goals led to a significant decrease in LVL procedures and cryopreserved bags required per patient to meet collection goals, reducing costs and workload for apheresis and CTL.
Journals
2025 EN
AriasSerna María Andrea · CaroLopera Francisco José · Loubes Jean Michel
Abstract Matrix‐variate distribution theory has been instrumental across various disciplines for the past seven decades. However, a comprehensive examination of financial literature reveals a notable gap concerning the application of matrix‐variate extensions to Value‐at‐Risk (VaR). However, from a mathematical perspective, the core requirement for VaR lies in determining meaningful percentiles within the context of finance, necessitating the consideration of matrix c.d.f. This paper introduces the concept of “matrix‐variate VaR” for both Wishart and Gamma distributions. To achieve this, we leverage the theory of hypergeometric functions of matrix argument and integrate over positive definite matrices. Our proposed approach adeptly characterizes a company's exposure by into a comprehensive risk measure. This facilitates a readily computable estimation of the total incurred risk. Notably, this approach enables efficient computation of risk measures under Wishart, exponential, Erlang, gamma, and chi‐square distributions. The resulting risk measures are expressed in closed analytic forms, enhancing their practical utility for day‐to‐day risk management.
Journals
2025 EN
Beutick Steven E. · Lambertini Francesco · Hamlin Trevor A.
+2 more
ABSTRACT We conducted a double‐hierarchical ab initio benchmark and DFT performance study of the organodichalcogenide bonding motif CH 3 Ch 1 Ch 2 (O) n CH 3 with Ch 1 , Ch 2 = S, Se and n = 0, 1, 2. The organodichalcogenide model systems were optimized at ZORA‐CCSD(T)/ma‐ZORA‐def2‐TZVPP. Our ab initio benchmark involved a hierarchical series of all‐electron relativistically contracted variants of the Karlsruhe basis sets (ZORA‐def2‐SVP, ZORA‐def2‐TZVPP, ZORA‐def2‐QZVPP), both with and without diffuse functions (ma‐basis set), in conjunction with a hierarchical series of ZORA‐relativistic quantum chemical methods [HF, MP2, CCSD, and CCSD(T)]. Counterpoise correction was applied to account for the basis set superposition error (BSSE). We assessed the performance of 33 ZORA‐relativistic DFT functionals (ZORA‐[XC functional]/TZ2P//ZORA‐[XC functional]/TZ2P) against our benchmark energies and found that M06 and MN15 furnish accurate geometries and bond energies within a mean absolute error of 1.2 kcal mol −1 relative to our best ab initio reference data.
Journals
2025 EN
Tang Lizhi · Hong Genwei · Xu Tianlv
+4 more
ABSTRACT We investigated crystalline Im‐3m H 3 S at 200 GPa, a pressure regime where H 3 S is generally considered to be an exotic superconductor. Simulated circularly polarized 10 femtosecond (fs) laser pulses were applied and we quantified the effects on the electron dynamics during the application of “pump” and candidate “probe” laser pulses to discover optimal “probe” laser pulses. This is undertaken for the first application of Next Generation Quantum Theory of Atoms in Molecules (NG‐QTAIM) using the Hessian of the “spin‐up” and “spin‐down” contributions to the total electronic charge density ρ ( r ). The optimal “probe” pulse was found to possess a peak electric field E = 10.0 × 10 −4 a.u. compared with the “pump” pulse of E = 200.0 × 10 −4 a.u. Separately considering the spin‐up and spin‐down contributions doubles the values of the chirality‐helicity C helicity function relative to that of the total charge density contribution for the H‐H bonding for the application of the “pump” laser pulse. Within the NG‐QTAIM interpretation, a combination of highly responsive and coherent behaviors is associated with superconductivity. These behaviors were discovered from the very high values of the C helicity function, near‐linear scaling of the bond‐flexing F and bond‐chirality C values with peak E ‐field and all instances of the H‐H bonding possessing R electronic chirality assignments. The “pump” pulse was found to magnify the effects associated with superconductivity within the NG‐QTAIM interpretation. Future applications are discussed including chiral spin selective phenomena and exotic high temperature superconductivity where phonons do not play a significant role.
Journals
2025 EN
Jankowski Peter J. · Sandage Steven J. · Davis Don E.
+2 more
ABSTRACT Objective We advanced the virtues of intellectual humility, gratitude, forgiveness, and emotion regulation as relevant to monitoring treatment progress. We did so by exploring the construct validity evidence for differentiation as an indicator of emotion regulation in a psychotherapy context. Method The sample consisted of clients ( N = 117; M age = 37.96; 60.7% female; 69.2% White; 70.1% heterosexual; 70.9% religious identifying) receiving outpatient psychotherapy at a psychodynamic training clinic. First, we conducted exploratory factor analysis to examine the validity evidence for differentiation, as measured by widely used items. Second, we used the factor analytic results to measure differentiation as an indicator of emotion regulation. We modeled the virtues and differentiation as linear and curvilinear combinations predicting depression symptoms and well‐being, using a series of polynomial regressions and response surface analyses. Results The intra‐ and interpersonal aspects of differentiation, reactivity and emotional cutoff, respectively, showed evidence supporting their use as indicators of emotion regulation. Results also showed that the virtues and differentiation were curvilinear predictors of depression symptoms and well‐being, with each of the virtues and reactivity combining to predict initial well‐being, and intellectual humility and emotional cutoff combining to predict later treatment symptom levels. Conclusion Our design limits inference about the directionality of associations, and we used a recently developed self‐report measure of virtues. Nevertheless, our findings point to the use of intellectual humility, gratitude, forgiveness, and differentiation to monitor treatment effectiveness, and potentially guide psychotherapy processes to lower negative emotion (intra‐personal differentiation) and increase positive emotion (gratitude, forgiveness) early in treatment, and enhance prosocial interpersonal responding (intellectual humility, interpersonal differentiation) later in treatment. We highlight that virtues can be indirectly addressed within alliance processes, and addressed via direct interventions.
Journals
2025 EN
Senaldi Giorgio · Mohan Aparna · Zhang Li
+7 more
Abstract Toll‐like receptor (TLR)7 is a pattern recognition receptor that critically contributes to the pathogenesis of systemic lupus erythematosus (SLE). DS‐7011a is an anti‐TLR7 monoclonal antibody that prevents TLR7 from signaling. The aim of this first‐in‐human, double‐blind, randomized, and placebo‐controlled study was to evaluate the safety, pharmacokinetics, immunogenicity, and pharmacodynamics of single ascending intravenous (IV) and subcutaneous (SC) doses of DS‐7011a in healthy subjects (HS) (NCT05203692). On day 1, 80 HS received DS‐7011a or placebo 6:2 in 10 cohorts (7 treated IV and 3 SC) of 8 each and were followed for 8 weeks until day 57. Safety was evaluated by recording treatment‐emergent adverse events (TEAEs), pharmacokinetics by measuring plasma DS‐7011a, immunogenicity by measuring plasma anti‐drug antibodies (ADAs), and pharmacodynamics by evaluating the suppression of interleukin‐6 production ex vivo in whole blood. DS‐7011a was safe and well tolerated across all cohorts. TEAEs were mostly mild in severity and not drug‐related. DS‐7011a exposure increased with the dose but was not dose proportional, as the elimination of lower doses was accelerated by target‐mediated drug disposition. Terminal half‐life was about 15‐17 days and T max upon SC administration was about 5 days. DS‐7011a induced ADAs in about half of HS but with no impact on clinical findings and pharmacokinetics. Pharmacodynamic (PD) response also increased with the dose and at the higher doses was of large extent (>90%), early onset, and lasting duration. DS‐7011a showed favorable safety, pharmacokinetics, immunogenicity, and PD properties that support its development for the treatment of SLE.
Journals
2025 EN
Randell Rachel L. · GelineauMorel Rose · Thomas Sydney
+3 more
Abstract The limited number of researchers with expertise necessary toaddress treatment gaps for children presents an ongoing challenge. The NationalInstitutes of Health established a national Pediatric Clinical Pharmacology T32Training Program in 2012 to train a multidisciplinary, collaborative pediatricclinical pharmacology workforce. We surveyed all current T32 trainees andgraduates since inception to identify strengths and opportunities to enhanceworkforce development. A total of 85 out of 155 (55%) responded, with themajority of respondents being female gender (61%), white race (75%), andworking in academia (75%). Nearly all (97%) reported using clinicalpharmacology in their current position, with 88% planning to remain in clinicalpharmacology in the long term, reinforcing current training efforts. Lifestylefactors and student debt appeared to influence career decisions. Mentors werecritical for introduction and future success in the field. Time and fundinglimitations were perceived as barriers to successful training. There was also apressing need to improve diversity. For workforce development, we suggestsupporting: (1) trainees' lifestyle, by offsetting financial pressures ofresearch training and expanding the geographic footprint of pediatric clinicalpharmacology training; (2) mentorship, by identifying mentors in the field andproviding dedicated support for mentorship; (3) efficiency, by evaluatingcurrent training activities and focusing on activities that maximizeopportunities for future funding; and (4) diversity, by examining barriers todiversity in the workforce in general and expanding early enrichmentopportunities.
Journals
2025 EN
Tran Steven D. · Forrest Noah J. · Guggilla Vijeeth
+5 more
ABSTRACT Background Cancer‐associated cachexia can inhibit immune checkpoint inhibitor (ICI) therapy efficacy. Cachexia's effect on ICI therapy has not been studied in large cohorts of cancer patients aside from lung cancer. We studied associations between real‐world routinely collected clinical cachexia markers and disability‐free, hospitalization‐free and overall survival of cancer patients. Methods A retrospective study was conducted of electronic health records (EHR) of patients with lung, renal cell, melanoma and other cancers treated with ICI therapy at Northwestern Medicine of Chicago, IL, United States, between March 2011 and January 2022. Weight, body mass index, absolute neutrophil and lymphocyte counts, albumin and C‐reactive protein (CRP) measures were analysed to calculate the Fearon consensus criteria for cachexia, weight loss grading system (WLGS) score, neutrophil‐lymphocyte ratio (NLR), Prognostic Nutritional Index (PNI) and modified Glasgow Prognostic Score (mGPS) at ICI therapy initiation. Kaplan–Meier and Cox proportional hazards analyses were used to determine associations between these metrics and disability‐free, hospitalization‐free and overall survival. Results EHR analysis uncovered 3285 cancer patients on ICI therapy (54% > 65 years of age, 50.7% male, 77.7% White). At ICI therapy initiation, 1282 (39.0%) patients had cachexia (consensus criteria), 1641 (50.0%) had a WLGS score ≥ 2, 1806 (55.0%) had an NLR > 3, 1087 (33.1%) had albumin < 3.5 g/dL and 1318 (40.1%) had a PNI < 44. Missing measurements included CRP missing for 98.2% and mGPS missing for 98.6% of patients. Disability‐free ( n = 1373), hospitalization‐free ( n = 2374) and overall survival ( n = 1599) events were analysed with 1‐year rates of 65% (64%–67%), 35% (34%–37%) and 65% (63%–66%), respectively. Multivariate Cox model analyses showed hazard ratios (HR) for cachexia at 1.58 (95% CI 1.38–1.80), 1.47 (95% CI 1.33–1.63) and 1.97 (95% CI 1.75–2.23) for disability, hospitalization and death, respectively. HRs for WLGS ≥ 2 were 1.45 (95% CI 1.28–1.66), 1.37 (95% CI 1.24–1.51) and 1.91 (95% CI 1.69–2.17). HRs for NLR > 3 were 1.57 (95% CI 1.35–1.83), 1.40 (95% CI 1.25–1.58) and 1.95 (95% CI 1.67–2.27). HRs for albumin < 3.5 g/dL were 1.33 (95% CI 1.15–1.54), 1.67 (95% CI 1.50–1.86) and 2.09 (95% CI 1.84–2.36). HRs for PNI < 44 were 1.60 (95% CI 1.39–1.84), 1.46 (95% CI 1.31–1.63) and 2.07 (95% CI 1.80–2.37). Conclusions Fearon consensus criteria, WLGS, NLR, albumin and PNI were routinely collected at ICI initiation in regular clinical practice and predictive of worse disability‐free, hospitalization‐free and overall survival in cancer patients receiving ICI therapy. These routine clinical measures may aid prognostication and decision‐making in cancer patients with cachexia.
Springer Science+Business Media