Background: A large language model is a type of artificial intelligence (AI) model that opens up great possibilities for health care practice, research, and education, although scholars have emphasized the need to proactively address the issue of unvalidated and inaccurate information regarding its use. One of the best-known large language models is ChatGPT (OpenAI). It is believed to be of great help to medical research, as it facilitates more efficient data set analysis, code generation, and literature review, allowing researchers to focus on experimental design as well as drug discovery and development. Objective: This study aims to explore the potential of ChatGPT as a real-time literature search tool for systematic reviews and clinical decision support systems, to enhance their efficiency and accuracy in health care settings. Methods: The search results of a published systematic review by human experts on the treatment of Peyronie disease were selected as a benchmark, and the literature search formula of the study was applied to ChatGPT and Microsoft Bing AI as a comparison to human researchers. Peyronie disease typically presents with discomfort, curvature, or deformity of the penis in association with palpable plaques and erectile dysfunction. To evaluate the quality of individual studies derived from AI answers, we created a structured rating system based on bibliographic information related to the publications. We classified its answers into 4 grades if the title existed: A, B, C, and F. No grade was given for a fake title or no answer. Results: From ChatGPT, 7 (0.5%) out of 1287 identified studies were directly relevant, whereas Bing AI resulted in 19 (40%) relevant studies out of 48, compared to the human benchmark of 24 studies. In the qualitative evaluation, ChatGPT had 7 grade A, 18 grade B, 167 grade C, and 211 grade F studies, and Bing AI had 19 grade A and 28 grade C studies. Conclusions: This is the first study to compare AI and conventional human systematic review methods as a real-time literature collection tool for evidence-based medicine. The results suggest that the use of ChatGPT as a tool for real-time evidence generation is not yet accurate and feasible. Therefore, researchers should be cautious about using such AI. The limitations of this study using the generative pre-trained transformer model are that the search for research topics was not diverse and that it did not prevent the hallucination of generative AI. However, this study will serve as a standard for future studies by providing an index to verify the reliability and consistency of generative AI from a user's point of view. If the reliability and consistency of AI literature search services are verified, then the use of these technologies will help medical research greatly.
Background: Stand-to-sit (StandTS) is an important daily activity widely used in rehabilitation settings to improve strength, postural stability, and mobility. Modifications in movement smoothness and speed significantly influence the kinematics, kinetics, and muscle activation patterns of the movement. Understanding the impact of StandTS speed and smoothness on movement control can provide valuable insights for designing effective and personalized rehabilitation training programs. Research question: How do the smoothness and speed of StandTS movement affect joint kinematics, kinetics, muscle activation patterns, and postural stability during StandTS? Methods: Twelve healthy younger adults participated in this study. There were two StandTS conditions. In the reference condition, participants stood in an upright position with their feet positioned shoulder-width apart on the force plate. Upon receiving a visual cue, participants performed StandTS at their preferred speed. In the smooth condition, participants were instructed to perform StandTS as smoothly as possible, aiming to minimize contact pressure on the seat. Lower leg kinetics, kinematics, and coordination patterns of muscle activation during StandTS were measured: (1) angular displacement of the trunk, knee, and hip flexion; (2) knee and hip extensor eccentric work; (3) muscle synergy pattern derived from electromyography (EMG) activity of the leg muscles; and (4) postural sway in the anterior-posterior (A-P), medio-lateral (M-L), and vertical directions. Results: Compared to the reference condition, the smooth condition demonstrated greater eccentric knee extensor flexion and increased joint work in both the knee and hip joints. Analysis of specific muscle synergy from EMG activity revealed a significant increase in the relative contribution of hip joint muscles during the smooth condition. Additionally, a negative correlation was observed between knee extensor and vertical postural sway, as well as hip extensor work and M-L postural sway. Conclusion: Smooth StandTS facilitates enhanced knee eccentric control and increased joint work at both the hip and knee joints, along with increased involvement of hip joint muscles to effectively manage falling momentum during StandTS. Furthermore, the increased contributions of knee and hip joint work reduced postural sway in the vertical and M-L directions, respectively. These findings provide valuable insights for the development of targeted StandTS rehabilitation training.
Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.
Purpose: Varlitinib is a pan-human epidermal growth (HER) inhibitor targeting epidermal growth factor receptor (EGFR), HER2, and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (IHC) (≥1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median PFS and overall survival (OS) were 3.3 months and 7.9 months, respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), AST/ALT elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion: A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.
Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels muscle metabolism based on frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone rescued muscle quality in aged 24-month-old mice to levels comparable to young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing PGC1α and its co-factor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose to amino acid biogenesis. We also probed the myocyte-specific Lipin1 as non-redundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes to coordinately rescue energy and mass in sarcopenia.
Ovarian Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Stearoyl-CoA Desaturase/metabolism , Stearoyl-CoA Desaturase/antagonists & inhibitors , Proteomics/methods , Biomarkers, Tumor/metabolism
Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.
OBJECTIVES: The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort. METHODS: Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%-45%) by investigator assessment and 35% (19%-55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%-56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%-93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0-8.5) months and 21.3 (11.7-32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3-4, 77%). One patient died from treatment-related hypovolemic shock. CONCLUSIONS: Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status.
BACKGROUND: Congenital dyserythropoietic anemia â ¡ (CDA â ¡) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA â ¡ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis. METHODS: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing. RESULTS: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA â ¡. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS. CONCLUSION: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA â ¡ patients, particularly for those with GS coexisting.
Anemia, Dyserythropoietic, Congenital , Gilbert Disease , Vesicular Transport Proteins , Humans , Anemia, Dyserythropoietic, Congenital/genetics , Anemia, Dyserythropoietic, Congenital/diagnosis , Male , Vesicular Transport Proteins/genetics , Gilbert Disease/genetics , Gilbert Disease/complications , Gilbert Disease/diagnosis , RNA Splicing , Mutation
The objective of this study was to evaluate the leachate and textural characteristics of cooked rice, and the correlations between the leachate properties and texture attributes were also investigated. Cooked waxy rice had much higher total solids and amylopectin amount in leachate than the normal and high-amylose rice. For all varieties, the amylopectin chain length of the leachate was similar, excluding Dodam cultivar. The rheological characteristics of the leachate solutions were highly dependent on the amylopectin amount of the leachate. Regarding the textural characteristics, Dodam had the highest hardness and the lowest adhesiveness. The principal component analysis showed substantial differences in leachate and textural characteristics of Korean cooked rice according to its amylose content. The adhesiveness was positively and negatively correlated with amylopectin amount of leachate and the proportion of long amylopectin chains, respectively. These results indicated that the leachate characteristics of cooked rice significantly influenced its textural attributes. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01446-3.
PURPOSE: The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo. MATERIALS AND METHODS: The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro. ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model. RESULTS: Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogen-activated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels. CONCLUSIONS: These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.
Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.
CRISPR-Cas Systems , Gene Editing , Liposomes , Nanoparticles , Cell Line , Ribonucleoproteins/genetics
OBJECTIVE: To diagnose invasive pulmonary aspergillosis (IPA), galactomannan (GM) detection in serum or bronchoalveolar lavage fluid (BALF) is widely used. However, the utility of proximal airway GM test (from induced sputum or tracheal aspirate) has not been well elucidated. METHODS: In this retrospective cohort study, we evaluated the diagnostic performance of proximal airway GM in diagnosis of IPA including COVID-19 associated pulmonary aspergillosis (CAPA). Between January 2022 and January 2023, patients who had been tested for GM with clinical suspicion or for surveillance from any specimen (serum, induced sputum, tracheal aspirate, and BALF) were screened. IPA was diagnosed using EORTC/MSGERC criteria, and CAPA was diagnosed following the 2020 ECMM/ISHAM consensus criteria. RESULTS: Of 624 patients with GM results, 70 met the criteria for proven/probable IPA and 427 had no IPA. The others included possible IPA and chronic form of aspergillosis. The sensitivities and specificities of serum, proximal airway, and BALF GM for proven/probable IPA versus no IPA were 78.9% and 70.6%, 93.1% and 78.7%, and 78.6% and 91.0%, respectively. Areas under the receiver operating characteristic curve (AUCs) were 0.742 for serum GM, 0.935 for proximal airway GM, and 0.849 for BALF GM (serum GM vs proximal airway GM, p = 0.014; proximal airway GM vs BALF GM, p = 0.334; serum GM vs BALF GM, p = 0.286). CONCLUSION: This study demonstrates that the performance of GM test from non-invasive proximal airway samples is comparable or even better than those from serum and distal airway sample (BALF).
Bronchoalveolar Lavage Fluid , Galactose , Invasive Pulmonary Aspergillosis , Mannans , Sensitivity and Specificity , Humans , Galactose/analogs & derivatives , Mannans/blood , Mannans/analysis , Invasive Pulmonary Aspergillosis/diagnosis , Retrospective Studies , Male , Female , Middle Aged , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/microbiology , Aged , COVID-19/diagnosis , Sputum/microbiology , Adult , SARS-CoV-2/isolation & purification , ROC Curve
BACKGROUND: Physically modified starches can be classified as natural ingredients on food labels and clean label products. Thus, the market demand for physically modified starch is increasing. Potato, tapioca, and corn starches were physically modified by mild heat treatment in an alcoholic solution to enhance their gelling property and freeze-thaw stability. RESULTS: During mild heating of starch suspension (40% w/w) in 10% ethanol solution at the onset gelatinization temperature, granular swelling of starch occurred, followed by amylose leaching with medication of the surface structure of the starch granules. All treated starches exhibited increased gelatinization and pasting temperatures and decreased breakdown for pasting due to improved stability against shear and heat. The treated starches had higher hardness, cohesiveness, and springiness of gel than the respective native starches, and these gel properties were more pronounced in potato starch than in tapioca and corn starches. The treated starches showed substantially reduced gel syneresis during freeze-thawing. CONCLUSION: Physical modification of starch by mild heat treatment in an alcoholic solution substantially improved its gelation ability and freeze-thaw stability. This article is protected by copyright. All rights reserved.
BACKGROUND/AIM: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinum-resistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. PATIENTS AND METHODS: We retrospectively divided patients with PR-ROC into two groups: bevacizumab plus chemotherapy (BEV-CT group) and chemotherapy alone (CT group). Progression-free survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. RESULTS: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. CONCLUSION: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity.
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Ovarian Neoplasms , Humans , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Female , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Aged , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Treatment Outcome , Prognosis , Retrospective Studies , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/mortality , Platinum/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/administration & dosage
Purpose: Cervical insufficiency is a significant risk factor for preterm birth and miscarriage during the second trimester; cervical cerclage is a treatment option. This study seeks to evaluate the predictive roles of various clinical factors and to develop predictive models for immediate and long-term outcomes after rescue cerclage. Methods: We conducted a multicenter retrospective study on patients who underwent rescue cerclage at 14 to 26 weeks of gestation. Data were collected from the Electronic Medical Record systems of participating hospitals. Outcomes were dichotomized into immediate failure (inability to maintain pregnancy for at least 48 hours post-cerclage, gestational latency < 2 days) and long-term success (maintenance of pregnancy until at least 28 weeks of gestation). Clinical factors influencing these outcomes were analyzed. Results: The study included 98 patients. Immediate failure correlated with longer prolapsed membrane lengths, elevated C-reactive protein levels at admission, and extended operation time. The successful maintenance of pregnancy until at least 28 weeks was associated with earlier gestational age at diagnosis, negative AmniSure test results, longer lengths of the functional cervix, and smaller cervical dilatation at the time of cerclage. Binary logistic regression models for immediate failure and long-term success exhibited excellent and good predictive abilities, respectively (AUROC = 0.912, 95% CI: 0.834-0.989; and AUROC = 0.872, 95% CI: 0.788-0.956). Conclusion: The developed logistic regression models offer a valuable tool for the prognostic assessment of patients undergoing rescue cerclage, enabling informed clinical decision-making.
Cerclage, Cervical , Female , Humans , Pregnancy , Clinical Decision-Making , Gestational Age , Retrospective Studies , Treatment Outcome
Genetic variations in the glucocorticoid receptor (GR) gene NR3C1 can impact metabolism. The single nucleotide polymorphism (SNP) rs6190 (p.R23K) has been associated in humans with enhanced metabolic health, but the SNP mechanism of action remains completely unknown. We generated a transgenic knock-in mice genocopying this polymorphism to elucidate how the mutant GR impacts metabolism. Compared to non-mutant littermates, mutant mice showed increased muscle insulin sensitivity and strength on regular chow and high-fat diet, blunting the diet-induced adverse effects on weight gain and exercise intolerance. Overlay of RNA-seq and ChIP-seq profiling in skeletal muscle revealed increased transactivation of Foxc1 and Arid5A genes by the mutant GR. Using adeno-associated viruses for in vivo overexpression in muscle, we found that Foxc1 was sufficient to transcriptionally activate the insulin response pathway genes Insr and Irs1. In parallel, Arid5a was sufficient to transcriptionally repress the lipid uptake genes Cd36 and Fabp4, reducing muscle triacylglycerol accumulation. Collectively, our findings identify a muscle-autonomous epigenetic mechanism of action for the rs6190 SNP effect on metabolic homeostasis, while leveraging a human nuclear receptor coding variant to unveil Foxc1 and Arid5a as novel epigenetic regulators of muscle metabolism.
