Search

Polylactic acid modified with graphene oxide (PLA/GO) is proposed to interact with ZnO through 6 different schemes. Density functional theory at B3LYP/LANL2DZ level was utilized to calculate total dipole moment (TDM), HOMO/LUMO energy gap (ΔE) and to map the molecular electrostatic potential (MESP). Results indicated that PLA/GO interacted with ZnO through O-atom forming PLA/GO/OZn composite. This composite interacts with methane, hydrogen sulfide, humidity (H 2 O), carbon dioxide and ethanol. The same gases were supposed to interact further with PLA/GO/Cu 2 O. Adsorption energy for the interaction between each composite and the proposed gases were calculated. Both PLA/GO/OZn and PLA/GO/Cu 2 O composites interacted favorably with H 2 O. Adsorption energy for interaction of other gases with studied structures are generally low compared to H 2 O. PLA/GO/OZn have adsorption energy slightly higher than that of PLA/GO/Cu 2 O. PLA/GO/OZn has higher TDM values than those of PLA/GO/Cu 2 O, indicating a more polar material. Conversely, PLA/GO/Cu 2 O exhibited larger ΔE values than those of PLA/GO/OZn. TDM and energy gap results for both studied structures indicated good sensing capabilities. Further insights come from analyzing the calculated density of states (DOS) and partial density of states (PDOS). PLA/GO/Cu 2 O exhibited high peak for copper in its DOS and PDOS spectra compared to zinc and oxygen in case of PLA/GO/OZn. This means a higher density of available electronic states associated with Cu., (© 2024. The Author(s).)

Background: Applications of large language models such as ChatGPT are increasingly being studied. Before these technologies become entrenched, it is crucial to analyze whether they perpetuate racial inequities., Methods: We asked Open AI's ChatGPT-3.5 and ChatGPT-4 to simplify 750 radiology reports with the prompt "I am a ___ patient. Simplify this radiology report:" while providing the context of the five major racial classifications on the U.S. census: White, Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or other Pacific Islander. To ensure an unbiased analysis, the readability scores of the outputs were calculated and compared., Results: Statistically significant differences were found in both models based on the racial context. For ChatGPT-3.5, output for White and Asian was at a significantly higher reading grade level than both Black or African American and American Indian or Alaska Native, among other differences. For ChatGPT-4, output for Asian was at a significantly higher reading grade level than American Indian or Alaska Native and Native Hawaiian or other Pacific Islander, among other differences., Conclusion: Here, we tested an application where we would expect no differences in output based on racial classification. Hence, the differences found are alarming and demonstrate that the medical community must remain vigilant to ensure large language models do not provide biased or otherwise harmful outputs., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Enhanced health literacy in children has been empirically linked to better health outcomes over the long term; however, few interventions have been shown to improve health literacy. In this context, we investigate whether large language models (LLMs) can serve as a medium to improve health literacy in children. We tested pediatric conditions using 26 different prompts in ChatGPT-3.5, ChatGPT-4, Microsoft Bing, and Google Bard (now known as Google Gemini). The primary outcome measurement was the reading grade level (RGL) of output as assessed by Gunning Fog, Flesch-Kincaid Grade Level, Automated Readability Index, and Coleman-Liau indices. Word counts were also assessed. Across all models, output for basic prompts such as "Explain" and "What is (are)," were at, or exceeded, the tenth-grade RGL. When prompts were specified to explain conditions from the first- to twelfth-grade level, we found that LLMs had varying abilities to tailor responses based on grade level. ChatGPT-3.5 provided responses that ranged from the seventh-grade to college freshmen RGL while ChatGPT-4 outputted responses from the tenth-grade to the college senior RGL. Microsoft Bing provided responses from the ninth- to eleventh-grade RGL while Google Bard provided responses from the seventh- to tenth-grade RGL. LLMs face challenges in crafting outputs below a sixth-grade RGL. However, their capability to modify outputs above this threshold, provides a potential mechanism for adolescents to explore, understand, and engage with information regarding their health conditions, spanning from simple to complex terms. Future studies are needed to verify the accuracy and efficacy of these tools., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Background The complex medical terminology of radiology reports may cause confusion or anxiety for patients, especially given increased access to electronic health records. Large language models (LLMs) can potentially simplify radiology report readability. Purpose To compare the performance of four publicly available LLMs (ChatGPT-3.5 and ChatGPT-4, Bard [now known as Gemini], and Bing) in producing simplified radiology report impressions. Materials and Methods In this retrospective comparative analysis of the four LLMs (accessed July 23 to July 26, 2023), the Medical Information Mart for Intensive Care (MIMIC)-IV database was used to gather 750 anonymized radiology report impressions covering a range of imaging modalities (MRI, CT, US, radiography, mammography) and anatomic regions. Three distinct prompts were employed to assess the LLMs' ability to simplify report impressions. The first prompt (prompt 1) was "Simplify this radiology report." The second prompt (prompt 2) was "I am a patient. Simplify this radiology report." The last prompt (prompt 3) was "Simplify this radiology report at the 7th grade level." Each prompt was followed by the radiology report impression and was queried once. The primary outcome was simplification as assessed by readability score. Readability was assessed using the average of four established readability indexes. The nonparametric Wilcoxon signed-rank test was applied to compare reading grade levels across LLM output. Results All four LLMs simplified radiology report impressions across all prompts tested ( P < .001). Within prompts, differences were found between LLMs. Providing the context of being a patient or requesting simplification at the seventh-grade level reduced the reading grade level of output for all models and prompts (except prompt 1 to prompt 2 for ChatGPT-4) ( P < .001). Conclusion Although the success of each LLM varied depending on the specific prompt wording, all four models simplified radiology report impressions across all modalities and prompts tested. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Rahsepar in this issue.

The accuracy of classical force fields (FFs) has been shown to be limited for the simulation of cation-protein systems despite their importance in understanding the processes of life. Improvements can result from optimizing the parameters of classical FFs or by extending the FF formulation by terms describing charge transfer (CT) and polarization (POL) effects. In this work, we introduce our implementation of the CTPOL model in OpenMM, which extends the classical additive FF formula by adding CT and POL. Furthermore, we present an open-source parametrization tool, called FFAFFURR, that enables the (system-specific) parametrization of OPLS-AA and CTPOL models. The performance of our workflow was evaluated by its ability to reproduce quantum chemistry energies and by molecular dynamics simulations of a zinc-finger protein.

Study Design: This was a retrospective cohort study., Purpose: This study investigated the influence of preoperative mental health on patient-reported outcome measures (PROMs) and minimal clinically important difference (MCID) among workers' compensation (WC) recipients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF)., Overview of Literature: No studies have evaluated the impact of preoperative mental functioning on outcomes following MIS TLIF among WC claimants., Methods: WC recipients undergoing single-level MIS TLIF were identified. PROMs of Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), 12-item Short Form Physical and Mental Composite Scale (SF-12 PCS/MCS), and Patient-Reported Outcomes Measurement Information System Physical Function evaluated subjects preoperatively/postoperatively. Subjects were grouped according to preoperative SF-12 MCS: <41 vs. ≥41. Demographic/perioperative variables, PROMs, and MCID were compared using inferential statistics. Multiple regression was used to account for differences in spinal pathology., Results: The SF-12 MCS <41 and SF-12 MCS ≥41 groups included 48 and 45 patients, respectively. Significant differences in ΔPROMs were observed at SF-12 MCS at all timepoints, except at 6 months (p≤0.041, all). The SF-12 MCS <41 group had worse preoperative to 6-months SF-12 MCS, 12-weeks/6-months VAS back, 12-week VAS leg, and preoperative to 6-months ODI (p≤0.029, all). The SF-12 MCS <41 group had greater MCID achievement for overall ODI and 6-weeks/1-year/overall SF-12 MCS (p≤0.043, all); the SF-12 MCS ≥41 group had greater attainment for 6-month VAS back (p=0.004)., Conclusions: Poorer mental functioning adversely affected the baseline and intermediate postoperative quality-of-life outcomes pertaining to mental health, back pain, and disability among WC recipients undergoing lumbar fusion. However, outcomes did not differ 1-2 years after surgery. While MCID achievement for pain and physical function was largely unaffected by preoperative mental health score, WC recipients with poorer baseline mental health demonstrated higher rates of overall clinically meaningful improvements for disability and mental health.

Objective: To compare patient-reported outcome measure (PROM) scores and minimum clinically important difference (MCID) achievement rates among patients undergoing single-level anterior cervical discectomy and fusion (ACDF) in patients with varying severity of preoperative visual analog scale (VAS) neck score., Methods: Patients with ACDF were grouped: severity of preoperative VAS neck score ≤8 or >8. Demographic/perioperative variables and PROMs (Patient-Reported Outcomes Measurement Information System Physical Function [PROMIS PF] score, 12-Item Short Form [SF-12] Mental Component Score [MCS], VAS neck/arm score, and Neck Disability Index [NDI]) were collected preoperatively/postoperatively. MCID attainment comparison by grouping was evaluated using χ 2 analysis., Results: A total of 137 patients were included (103 VAS neck preoperative score ≤8; 34 VAS neck preoperative score >8). The VAS neck preoperative score ≤8 cohort did not improve: 6 weeks PROMIS-PF score, 6 weeks SF-12 Physical Component Score [PCS], 12 weeks/1 year/2 years SF-12 MCS, 2 years VAS neck score, and 1 years/2 years VAS arm score (P ≤ 0.015, all). VAS neck preoperative score >8 did not improve: 6 weeks/12 weeks/2 years PROMIS-PF score, all time points SF-12 PCS, 6 weeks/12 weeks/1 year/2 years SF-12 MCS, and 2 years VAS arm score (P ≤ 0.013, all). VAS neck preoperative score >8 had inferior PROMIS-PF scores all time points except 1 year (P ≤ 0.036, all), lower SF-12 PCS 6 weeks/6 months (P ≤ 0.043, both), inferior SF-12 MCS at preoperative to 6 months (P ≤ 006, all), higher VAS neck score from preoperative to 6 months (P ≤ 0.018), higher VAS arm score preoperative/12 weeks/6 months (P ≤ 0.020, all), and higher NDI at preoperative/12 weeks/6 months (P ≤ 0.030, all). MCID attainment rates for VAS neck preoperative score >8 were greater for NDI 2 years (P = 0.040), lower for PROMIS-PF score 2 years, and overall (P = 0.018), lower for SF-12 MCS 12 weeks (P = 0.046), lower for VAS neck score 12 weeks to 1 year and overall (P ≤ 0.032, all), and lower for VAS arm score 6 weeks/1 year (P ≤ 0.030, both)., Conclusions: Patients with single-level ACDF presenting with greater baseline neck pain showed poorer physical function/pain/disability/mental health at preoperative/intermediate postoperative time points, but had comparable long-term PROMs by 2 years. MCID attainment was lower among patients with greater preoperative neck pain; MCID among the VAS neck score >8 cohort were only significantly inferior for neck pain., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite impressive advances in the treatment of prostate cancer with various efficacious inhibitors along the androgen/androgen receptor axis, eventual development of incurable metastatic Castration-Resistant Prostate Cancer (mCRPC) is inevitable and remains a major clinical challenge. Constitutively active androgen receptor (AR) spliced variants have emerged as primary means of resistance to anti-androgens and androgen synthesis inhibitors. The alternatively spliced AR variant, ARv7, has attracted significant interest due to its constitutively active status in CRPC that drives androgen-independence. Factors that are involved in regulating ARv7 levels in CRPC are not clearly known. We recently demonstrated that a protein kinase, T-LAK cell-originated protein kinase (TOPK) level correlates with the aggressiveness of prostate cancer and its invasive behavior. In this study, we investigated whether TOPK plays a role in driving androgen-independence in prostate cancer cells. Our data demonstrate that TOPK overexpression in androgen-dependent LNCaP and VCaP induces ARv7 and drives androgen-independent growth. On the other hand, pharmacological inhibition of TOPK in androgen-independent LNCaP95 and 22Rv1 represses AR transactivation, and AR stability. In summary, this study illustrates a direct role of TOPK in regulating ARv7 and driving androgen-independence in prostate cancer cells., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Explicit description of atomic polarizability is critical for the accurate treatment of inter-molecular interactions by force fields (FFs) in molecular dynamics (MD) simulations aiming to investigate complex electrostatic environments such as metal-binding sites of metalloproteins. Several models exist to describe key monovalent and divalent cations interacting with proteins. Many of these models have been developed from ion-amino-acid interactions and/or aqueous-phase data on cation solvation. The transferability of these models to cation-protein interactions remains uncertain. Herein, we assess the accuracy of existing FFs by their abilities to reproduce hierarchies of thousands of Ca 2+ -dipeptide interaction energies based on density-functional theory calculations. We find that the Drude polarizable FF, prior to any parameterization, better approximates the QM interaction energies than any of the non-polarizable FFs. Nevertheless, it required improvement in order to address polarization catastrophes where, at short Ca 2+ -carboxylate distances, the Drude particle of oxygen overlaps with the divalent cation. To ameliorate this, we identified those conformational properties that produced the poorest prediction of interaction energies to reduce the parameter space for optimization. We then optimized the selected cation-peptide parameters using Boltzmann-weighted fitting and evaluated the resulting parameters in MD simulations of the N-lobe of calmodulin. We also parameterized and evaluated the CTPOL FF, which incorporates charge-transfer and polarization effects in additive FFs. This work shows how QM-driven parameter development, followed by testing in condensed-phase simulations, may yield FFs that can accurately capture the structure and dynamics of ion-protein interactions.

We investigate theoretically the effect of quantum confinement on high harmonic generation (HHG) in semiconductors by systematically varying the width of a model quantum nanowire. Our analysis reveals a reduction in ionization and a concurrent growth in HHG efficiency with increasing confinement. The drop in ionization results from an increase in the band gap due to stronger confinement. The increase in harmonic efficiency comes as a result of the confinement restricting the spreading of the transverse wave packet. As a result, intense laser driven 1D and 2D nanosystems present a potential pathway to increasing yield and photon energy of HHG in solids.

Continued reliance on androgen receptor (AR) signaling is a hallmark of prostate cancer, including the development of castration-resistant prostate cancer (CRPC), making it an attractive therapeutic target for prostate cancer treatment. Mahanine is a novel carbazole alkaloid derived from the leaves of Murraya koenigii, commonly known as the curry leaf plant, which grows widely across East-Asia. We show here that mahanine possesses the ability to inhibit ligand-dependent and -independent AR transactivation, leading to a prominent decline in AR target gene expression. Mahanine treatment causes a time- and dose-dependent decline in AR protein levels, including truncated AR splice variants, in a panel of androgen-responsive and -independent prostate cancer cells. The decrease in AR levels induced by mahanine occurs posttranslationally by proteasomal degradation, without any change in the AR gene expression. Mahanine treatment induces an outward movement of the AR from the nucleus to the cytoplasm, leading to an initial increase in cytoplasmic AR levels, followed by a gradual decline in the AR levels in both cellular compartments. Ligand-induced AR phosphorylation at Ser-81, a phospho-site associated with prostate cancer cell growth and AR transactivity, is greatly diminished in the presence of mahanine. The decline in AR phosphorylation at Ser-81 by mahanine occurs via the inactivation of mitotic kinase CDK1. Collectively, our data demonstrate that mahanine strongly disrupts AR signaling and inhibits the growth of androgen-dependent and -independent prostate cancer cells, thereby implicating a therapeutic role of mahanine in prostate cancer treatment.

Background: Hypermethylation of the promoter of the tumor suppressor gene RASSF1A silences its expression and has been found to be associated with advanced grade prostatic tumors. The DNA methyltransferase (DNMT) family of enzymes are known to be involved in the epigenetic silencing of gene expression, including RASSF1A, and are often overexpressed in prostate cancer. The present study demonstrates how mahanine, a plant-derived carbazole alkaloid, restores RASSF1A expression by down-regulating specific members of the DNMT family of proteins in prostate cancer cells., Results: Using methylation-specific PCR we establish that mahanine restores the expression of RASSF1A by inducing the demethylation of its promoter in prostate cancer cells. Furthermore, we show that mahanine treatment induces the degradation of DNMT1 and DNMT3B, but not DNMT3A, via the ubiquitin-proteasome pathway; an effect which is rescued in the presence of a proteasome inhibitor, MG132. The inactivation of Akt by wortmannin, a PI3K inhibitor, results in a similar down-regulation in the levels DNMT1 and DNMT3B. Mahanine treatment results in a decline in phospho-Akt levels and a disruption in the interaction of Akt with DNMT1 and DNMT3B. Conversely, the exogenous expression of constitutively active Akt inhibits the ability of mahanine to down-regulate these DNMTs, suggesting that the degradation of DNMT1 and DNMT3B by mahanine occurs via Akt inactivation., Conclusions: Taken together, we show that mahanine treatment induces the proteasomal degradation of DNMT1 and DNMT3B via the inactivation of Akt, which facilitates the demethylation of the RASSF1A promoter and restores its expression in prostate cancer cells. Therefore, mahanine could be a potential therapeutic agent for advanced prostate cancer in men when RASSF1A expression is silenced.

Epigenetic events significantly impact the transcriptome of cells and often contribute to the onset and progression of human cancers. RASSF1A (Ras-association domain family 1 isoform A), a well-known tumor suppressor gene, is frequently silenced by epigenetic mechanisms such as promoter hypermethylation in a wide range of cancers. In the past decade a vast body of literature has emerged describing the silencing of RASSF1A expression in various cancers and demonstrating its ability to reverse the cancerous phenotype when re-expressed in cancer cells. However, the mechanisms by which RASSF1A exerts its tumor suppressive properties have not been entirely defined. RASSF1A appears to mediate three important cellular processes: microtubule stability, cell cycle progression, and the induction of apoptosis through specific molecular interactions with key factors involved in these processes. Loss of function of RASSF1A leads to accelerated cell cycle progression and resistance to apoptotic signals, resulting in increased cell proliferation. In this review, we attempt to summarize the current understanding of the biological functions of RASSF1A and provide insight that the development of targeted drugs to restore RASSF1A function holds promise for the treatment of prostate cancer.

Acute myelogenous leukemia with minimal differentiation (AML-M0) is a rare subtype of acute leukemia in which blasts fail to show morphologic differentiation and conventional cytochemical stains and myeloid markers are negative. Acute myelogenous leukemia (AML) presents primarily with peripheral blood and/or bone marrow involvement. Presentation in extramedullary sites, including the head and neck region, is not uncommon. Acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5) have had the highest incidence of associated oral infiltrates. We report a case of a 58-year-old gentleman, with no prior history of acute leukemia, presenting with a solitary palatal swelling. Initial morphologic examination favored high-grade non-Hodgkin's lymphoma (NHL). Conventional cytochemical and immunohistochemical stains were negative for lymphoid and myeloid markers. Subsequent immunophenotyping via flow cytometry performed on peripheral blood and bone marrow aspirate demonstrated myeloid lineage without lymphoid differentiation, confirming the diagnosis of AML-M0.To our knowledge, this subtype of AML-M0 has not been previously reported involving the oral cavity. With absence of morphologic differentiation, and negative findings on conventional cytochemical and immunohistochemical stains, this subtype of leukemia may be misdiagnosed as non-Hodgkin's lymphoma (NHL). Flow cytometry is useful in detecting the myeloid lineage of this leukemia.

The level of fructose, NEFA, triglycerides and lipase activity were determined in the semen of 17 normozoospermic, 10 oligozoospermic and 10 azoospermic men. This was done immediately and 2 hours after seminal liquefaction. The levels of fructose and NEFA were significantly decreased while triglycerides show significant increase. These phenomena were more marked in normozoospermic, less marked in oligozoospermic and absent in azoospermic men. These results may indicate that both fructose and free fatty acids are utilized by sperms to supply energy or incorporated by them into triglycerides. No lipase activity was detected by the method used in the present work.