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In Sun Goak,1,2 Jin A Lee,1,3 Min Ho Jeong,4 Seol Ju Moon,1,3 Min Gul Kim1,3,5 1Department of Pharmacology, School of Medicine, Jeonbuk National University, Jeonju, Republic of Korea; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Republic of Korea; 3Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea; 4Division of Clinical Team, Kingdom Pharmaceutical Co., Ltd, Seoul, Republic of Korea; 5Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, Republic of KoreaCorrespondence: Min Gul Kim, Department of Pharmacology, School of Medicine, Jeonbuk National University, Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Geonji road #20, Deokjin-gu, Jeonju, 54907, Republic of Korea, Tel +82-63-250-3458, Fax +82-63-259-3483, Email mgkim@jbnu.ac.krPurpose: This study was performed to compare the pharmacokinetics of two fixed-dose combination (FDC) formulations of teneligliptin combined with modified-release metformin in healthy Korean subjects under fasting and fed conditions.Patients and Methods: The study was a single-center, open-label, single-dose, 2-way, 2-period, crossover trial. A total of 72 eligible subjects (40 subjects in the fasting state study and 32 subjects in the fed study) were enrolled in the study and were randomized to treatment. After the administration of a single FDC tablet of the investigational products, blood samples were collected at specific time intervals from 0 to 96 hours. The plasma concentrations of teneligliptin and metformin were measured by ultra performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios (test/reference) of the parameters were obtained through analysis of variance of the logarithmically transformed data.Results: The corresponding 90% CIs of area under the plasma concentration-time curve from time zero to the time of last measurable concentration (AUCt) and maximum plasma drug concentration (Cmax) for the test/reference geometric mean ratio (GMR) of teneligliptin were 94.81– 101.32% and 86.03– 97.63%, respectively, under fasting conditions. The corresponding 90% CIs of AUCt and Cmax for the test/reference GMR of metformin were 95.01– 108.36% and 94.69– 108.40%, respectively, under the fasting state and 98.82– 107.56% and 97.25– 106.99%, respectively, after feeding. All adverse events were of mild intensity, and the subjects recovered spontaneously without sequelae.Conclusion: The test FDC drug is equivalent to the reference FDC drug in subjects under fasting and fed conditions within the Korean regulatory bioequivalence criteria. Both formulations were safe and well tolerated, and there were no differences in the safety profiles between the two single FDC formulation drugs.Trial Registration No: Clinicaltrials.gov. KCT0007757, KCT0007759.Keywords: type 2 diabetes mellitus, dipeptidyl peptidase-4 inhibitors, modified release metformin, fixed dose combination

Seol Ju Moon,1,2 Ji-Young Jeon,1 Kyungho Jang,1 Kyung-Sang Yu,2 Yeji Lim,3 Min-Gul Kim1,4–51Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 3Yuhan Research Institute, Yuhan Corporation, Seoul, Republic of Korea; 4Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, Republic of Korea; 5Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of KoreaPurpose: Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers.Patients and methods: An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration versus time curve over dosing interval (AUCτ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax,ss and AUCτ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions.Results: Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Cmax,ss and AUCτ,ss, were 0.9829 (0.8334–1.1590) and 1.0003 (0.9342–1.0710) for telmisartan; 0.9908 (0.9602–1.0223) and 1.0081 (0.9758–1.0413) for amlodipine; and 2.2762 (2.0113–2.5758) and 1.3261 (1.2385–1.4198) for rosuvastatin, respectively.Conclusion: The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.Keywords: drug–drug interactions, pharmacokinetics, phase I, antihypertensive, statins

A series of semi-crystalline, wide band gap (WBG) photovoltaic polymers were synthesized with varying number and topology of fluorine substituents. To decrease intramolecular charge transfer and to modulate the resulting band gap of D-A type copolymers, electron-releasing alkoxy substituents were attached to electron-deficient benzothiadiazole (A) and electron-withdrawing fluorine atoms (0-4F) were substituted onto a 1,4-bis(thiophen-2-yl)benzene unit (D). Intra- and/or interchain noncovalent Coulombic interactions were also incorporated into the polymer backbone to promote planarity and crystalline intermolecular packing. The resulting optical band gap and the valence level were tuned to 1.93-2.15 eV and -5.37 to -5.67 eV, respectively, and strong interchain organization was observed by differential scanning calorimetry, high-resolution transmission electron microscopy and grazing incidence X-ray scattering measurements. The number of fluorine atoms and their position significantly influenced the photophysical, morphological and optoelectronic properties of bulk heterojunctions (BHJs) with these polymers. BHJ photovoltaic devices showed a high power conversion efficiency (PCE) of up to 9.8% with an open-circuit voltage of 0.94-1.03 V. To our knowledge, this PCE is one of the highest values for fullerene-based single BHJ devices with WBG polymers having a band gap of over 1.90 eV. A tandem solar cell was also demonstrated successfully to show a PCE of 10.3% by combining a diketopyrrolopyrrole-based low band gap polymer.

Objectives: Uremic pruritus is common in patients with chronic kidney disease (CKD). The retention of uremic solutes is thought to be associated with uremic pruritus. Meanwhile, activation of protease-activated receptor-2 (PAR-2) has been suggested to play an important role in pruritus. The present study was performed to investigate the effects of uremic solutes on the expression of PAR-2 in the skin. Methods: Indoxyl sulfate (IS), p -cresol (PC), and uremic sera from CKD patients were used to stimulate PAR-2 expression in normal human epidermal keratinocytes (NHEKs). Also, NHEKs were additionally pretreated with soybean trypsin inhibitor to evaluate its inhibitory effect on PAR-2 expression. Patterns of cutaneous PAR-2 expression were investigated in skin samples from five CKD patients and CKD mice. Results: In NHEKs, IS, PC, and sera from CKD patients significantly induced PAR-2 mRNA and protein expression. Soybean trypsin inhibitor significantly decreased PAR-2 mRNA and protein expression in NHEKs treated with IS, PC, and CKD sera. NHEKs treated with IS and PC exhibited significant increases in protease activity. Skin from both CKD patients and mice exhibited marked upregulation of PAR-2 expression compared to control skin. Conclusions: Results from the present study suggest that uremic solutes either directly or indirectly affect PAR-2 expression in the skin of CKD subjects, potentially playing an important role in the pathogenesis of uremic pruritus. [ABSTRACT FROM AUTHOR]

AIM: This study was conducted to describe and compare empowerment, job satisfaction, and organizational commitment between permanent and temporary nurses in Korea. BACKGROUND: Since Korea's economic crisis of 1997, Korea's labor market has been undergoing dramatic modification, and the rate of temporary nurses employed in health care organizations has gradually increased. However, studies focusing on nurses' employment status, which potentially affect the individual and hospital organization, have been rarely conducted. METHODS: This was a descriptive comparative study. The convenient sample of 416 nurses from 19 hospitals in Korea completed a structured questionnaire. RESULTS: Overall, permanent nurses presented higher levels of job satisfaction, organizational commitment, and empowerment than did temporary nurses. CONCLUSIONS: The results of this study indicated that health care administrators should develop strategies to close the gap of perceptions between permanent and temporary nurses in Korea. The results of this study also imply that such opportunities and compensation plans related with administrative recognition should be made available to the temporary nurses to manage their workforces more efficiently. © 2009 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Study Design: Case description. Objectives: To report a rare case of intraosseous malignant peripheral nerve sheath tumors (MPNST), and review the pertinent medical literature. Summary Of Background Data: The spinal MPNST that develops from spinal nerve roots and secondary bony erosion is well-known entity. However, primary intraosseous MPNSTs of the spine are extremely rare. Methods: A 41-year-old male presented with a 1-month history of radiating pain to his right shoulder and arm. Magnetic resonance images showed a large extradural mass extending from C6 to T1 with destruction of the posterior elements of C6, C7, and T1. Complete excision of the tumor and posterior stabilization were performed through a posterior approach. The tumor was noted to originate from the posterior element of C7. Results: The histopathology was diagnostic for a MPNST. Adjuvant chemotherapy was administered after surgery. The patient remained symptom-free for 30 months after surgery without local recurrence or metastasis. Conclusion: We report an intraosseous MPNST of the cervical spine. Complete surgical excision and adjuvant chemotherapy resulted in a good functional outcome. MPNST should be added to the differential diagnosis of primary bone tumors causing spinal cord compression. [ABSTRACT FROM AUTHOR]

Glomerular visceral epithelial cells, namely podocytes, are highly specialized cells and give rise to primary processes, secondary processes, and finally foot processes. The foot processes of neighboring podocytes interdigitate, leaving between them filtration slits. These are bridged by an extracellular substance, known as the slit diaphragm, which plays a major role in establishing size-selective barrier to protein loss. Furthermore, podocytes are known to synthesize matrix molecules to the glomerular basement membrane (GBM), including type IV collagen, laminin, entactin, and agrin. Because diabetic nephropathy is clinically characterized by proteinuria and pathologically by glomerular hypertrophy and GBM thickening with foot process effacement, podocytes have been the focus in the field of research on diabetic nephropathy. As a result, many investigations have demonstrated that the diabetic milieu per se, hemodynamic changes, and local growth factors such as transforming growth factor-beta and angiotensin II, which are considered mediators in the pathogenesis of diabetic nephropathy, induce directly and/or indirectly hypertrophy, apoptosis, and structural changes, and increase type IV collagen synthesis in podocytes. This review explores some of the structural and functional changes of podocytes under diabetic conditions and their role in the development and progression of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors, antidiabetic drugs that reduce blood sugar levels by inhibiting glucose reabsorption in the renal proximal tubules, also ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of SGLT2 inhibition on hepatic steatosis and nonalcoholic steatohepatitis (NASH) using an in vitro model of NAFLD progression. HepG2 cells and a coculture of Hepa1c1c7 and Raw 264.7 cells were treated with 400 μM palmitic acid (PA), followed by treatment with or without 10 μM empagliflozin and dapagliflozin. In HepG2 cells, PA increased hepatic lipid accumulation, the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), exocytosis mediators (VAMP3 and SNAP23), and ER stress markers (GRP78, PERK, IRE1α, ATF6, ATF4, and CHOP), and the gene and protein expression of CD36. SGLT2 inhibitors reversed the effects of PA. SGLT2 inhibition via siRNA reduced proinflammatory-cytokine gene expression in thapsigargin-treated HepG2 cells. Transfection with CD36 siRNA reversed the elevated ATF4 and CHOP expression in PA-treated HepG2 cells. SGLT2 inhibition via an SGTL2 inhibitor and SGLT2 siRNA reduced CD36, Tnf-α, Il-6, Il-1β, Vamp2, Snap23, Atf4, and Chop expression in the PA-treated Hepa1c1c7-Raw 264.7 cell coculture and suppressed Tnf-α release in the Hepa1c1c7-Raw 264.7 cell coculture treated with lipopolysaccharide and PA. These findings indicate that SGLT2 inhibitors inhibited NAFLD progression by reducing hepatic lipid accumulation and inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background/aims: We investigated sudomotor dysfunction, small fiber neuropathy (SFN), and their clinical significance in female fibromyalgia patients., Methods: Fibromyalgia patients and healthy controls (HCs) were recruited. Clinical and laboratory data were measured. Electrochemical skin conductance (ESC) values of hands and feet were assessed by SUDOSCAN. Additionally, several other methods were employed, including nerve conduction study (NCS), electromyography (EMG), and questionnaires. Spearman correlation coefficient was calculated to identify factors associated with ESC values of SUDOSCAN., Results: Twenty-two female fibromyalgia patients and 22 female HCs were recruited. The fibromyalgia group had lower EQ5D and higher Toronto Clinical Neuropathy scores than the HC group. Most of the EMG/NCS findings of motor and proximal sensory nerves were comparable between the fibromyalgia and HC groups, whereas sensory nerve action potential amplitudes of distal sensory nerves were significantly lower in the fibromyalgia group. Mean ESC values of hands and feet were significantly lower in the fibromyalgia group than in the HC group (57.6 ± 16.2 vs. 68.8 ± 10.3 μS, p = 0.010 for hands, 64.9 ± 11.5 vs. 72.0 ± 8.2 μS, p = 0.025 for feet, respectively). Moderate to severe SFN was more common in the fibromyalgia group (68.2%) than in the HC group (68.2 vs. 50%, p = 0.019). Fibromyalgia disease duration was significantly correlated with the ESC values of hands/feet, and tricyclic antidepressant (TCA) responders had higher ESC values than non-responders., Conclusion: SFN was commonly detected in fibromyalgia patients who had normal EMG/NCS findings and was more severe in fibromyalgia patients with longer disease duration. SUDOSCAN may predict response to TCA therapy.

Introduction: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs)., Methods: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy., Results: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose., Conclusion: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.C.K. is a consultant for Afon, Lifecare, Novo, Samsung, embecta, Glucotrack, SynchNeuro, and Thirdwayv. G.F. is CEO of IfDT. G.F./IfDT has/have received research support, speakers’ honoraria or consulting fees in the last three years from Abbott, Ascensia, Berlin Chemie, Boydsense, Dexcom, Glucoset, i-SENS, Lilly, Menarini, Novo Nordisk, Perfood, Pharmasens, Roche, Sinocare, Terumo, Ypsomed. S.P. is an employee of IfDT. B.P.K. declares patent royalties handled by UVA from: DexCom, J&J, Novo Nordisk, and Sanofi; and research support handled by UVA: Dexcom, Novo Nordisk, Tandem Diabetes Care. D.K. has received research support from Abbott Diabetes Care. M.S.D.A. is currently receiving in kind support (CGM devices) from Dexcom Inc for an investigator-initiated clinical study. K.D. receives research funding from Dexcom, Abbott, Sanofi, Viacyte, Insulet, consulting fees from Eli Lilly, Dexcom, Insulet, Oppenheimer, Elsevier, honoraria from Academy for Continued Healthcare Learning, Med Learning Group, Medscape, Impact Education, and royalties from UptoDate. S.M. is in receipt of an investigator-initiated grant from DexCom, has received speaker fees from Sanofi & Lilly, is funded by a Wellcome Trust (223024/Z/21/Z), and is supported by the NIHR Imperial Biomedical Research Centre. A.S. was supported by the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (#1648451). V.N.S. reports receiving personal fees from Sanofi, Embecta, NovoNordisk, Dexcom, Insulet, Tandem Diabetes Care, Ascensia Diabetes Care, Genomelink and LumosFit for consulting, advising or speaking. N.K.T. is a consultant for Roche Diagnostics / Roche Molecular Systems / Radiometer. UC Davis is a Roche Diagnostics Center of Excellence. N.K.T. has received speaking honoraria for Roche Diagnostics, Nova Biomedical, Thermo Fisher, and Radiometer. N.K.T. is also Chair-Elect for the Association for Diagnostic and Laboratory Medicine (ADLM) Critical and Point-of-Care Testing Division, Co-Founder of the Machine Intelligene Learning Optimizer (MILO), Inc, and a member of the International Federation for Clinical Chemistry (IFCC) continuous glucose monitoring workgroup. T.T. is a consultant for Clinical ink. R.E.A. is a consultant for Clinical ink. D.T.A. has received speaker’s honoraria from Abbott, Ascensia Diabetes Care, Insulet, Lilly Diabetes, Mannkind, Novo Nordisk, and Xeris Pharmaceuticals. D.T.A. has received consulting fees from Ascensia Diabetes Care, Lilly Diabetes, and Senseonics. H.K.A. received research grants through University of Colorado from Dexcom, Tandem Diabetes, Medtronic, Mannkind, IM Therapeutics, IAFMS, and received honorarium through University of Colorado for consulting from Dexcom, Tandem Diabetes, and Medtronic. M.E.A.-S. has served on the advisory boards for Abbott, Medtronic, Insulet, VitalAire, Sanofi, Eli Lilly, and Dexcom; has received honoraria for speaking from Abbott, Eli Lilly, Medtronic, Novo Nordisk, Sanofi, VitalAire, and Eli Lilly; and received research support from Medtronic and Sanofi. T.S.B. has received research support from Abbott Rapid Diagnostics, Biolinq, Dexcom, Eli Lilly, Medtronic, Medtrum, Novo Nordisk, Sanofi, Senseonics, and vTv Therapeutics and consulting honoraria from Abbott Diabetes, Abbott Rapid Diagnostics, ACON, CeQur, HagarTech, Intuity Medical, Lifescan, Mannkind, Medtronic, Novo, Perspirion, Sanofi, Sequel Med Tech, and Ypsomed. M.B. currently participates on the Hospital Advisory board with Dexcom and has received research support from Dexcom. L.B. has received research/product support from Dexcom, Ypsomed, and Boehringer Ingelheim; speaker honoraria from Dexcom and Oviva; and participated in advisory boards of Dexcom, Novo Nordisk, Sanofi, Ypsomed, Oviva, and Roche Diabetes Care. Y.M.B. has received honoraria for lectures and scientific advisory from Roche and AstraZeneca in the past 12 months. J.E.B. is on the Speaker’s bureau for Insulet and on the Advisory Board for Cardinal Health and Lifescan. J.E.B. is a consultant for Embecta. J.E.B. receives research support from the Leona M. and Harry B. Helmsley Charitable Trust. E.C. is on the scientific advisory board for Novo Nordisk, Eli-Lilly, Adocia, Arecor, Proventionbio, Portal Insulin, and MannKind. D.C. was a Dexcom employee from August 2018 to May 2024. D.C. is a shareholder of Dexcom, Lilly, Abbott and Tandem. M.C. has received consulting fees from Glooko and research support from Dexcom and Abbott Diabetes Care. G.L.C. is a shareholder of BioTex, Inc., Basepair Biotechnologies Inc., Coordination Centric, Inc., and Shape Memory Medical, Inc. G.L.C. is supported by the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (#1648451). K.K.D. has received honoraria, travel, or fees for advisory boards from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Abbott Diabetes, Menarini, and Sanofi in the last 12 months. J.E. receives federal funding from FDA, NIMHD, and NCATS and is a consultant for Sanofi. C.F. receives royalties from Dexcom and Novo Nordisk managed through her institution. G.A.F. is an advisor for 180 Life Sciences, 89bio, Adocia, Abbott, AdipoPharma, Aerami, Amolyt, Carthera, Catalyst, Cohen Global, CMC Magnetics, Diasome, Eleos, Entera Bio, Enterin, Glyscend, Hagar, Hogan Lovells, IM Therapeutics, Innoneo, Intarcia, Levicure, Lilly Asia Ventures, Lumos, Mars Symbioscience, Melior, metaLead Therapeutics, Microbiotix, MMD, Modular Medical, New Amsterdam, Northwestern, NuSirt, NuVox, Oramed, Pano, Pasithea, PhylloPharma, Pleiogenix, Recordati, Regor, Remodeless, Renaissance, RenovoRx, Rivus, RxMP, Sera Biopharma, Seraxis, Serpin, SFC Fluidics, Skinject, SROne, Stalicla, Surf Bio, TIXiMED, Veroscience, Verthermia, WaveBreak, Zealand Pharma, and Zucara. M.A.L.G. is a consultant for Abbott, Medtronic, Novonordisk, and Roche. R.J.G. received research support from Novo Nordisk, Dexcom and Eli Lilly and consulting fees/advisory fees from Abbott Diabetes Care, Aztra Zeneca, Bayer, Boehringer, Dexcom, Eli Lilly, Novo Nordisk, and Medtronic, outside of this work. R.J.G. is partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Numbers P30DK111024, K23DK123384, R03DK138255, and U2CD137135. A.M.G.-M. reports speaker fees from Novo Nordisk, Sanofi, Elli Lilly, Boehringer Ingelheim, Abbott, and Medtronic. L.H. is a consultant for a number of companies that are developing innovative solutions for the treatment of people with diabetes. N.H. reports Advisory Board member fees from Abbott Diabetes Care and Insulet as well as honoraria for lectures from Berlin-Chemie AG, Becton Dickenson, Sanofi Germany, Roche Diabetes Care, and Dexcom Germany. T.H. serves on the advisory board for Acella and Horizons Therapeutics (no financial compensation). S.H. has served on the advisory board for Tandem, Dexcom, and Medtronic, and received honoraria for nonpromotional educational and/or consultancy work from Abbott, Insulet, Dexcom, Roche, and Sanofi. P.G.J. is a shareholder of Pacific Diabetes Technologies Inc. and serves on the advisory board for Eli Lilly. P.G.J. received grant support from SFC Fluidics and research support from Eli Lilly and Dexcom. J.J. has received fees from lectures and or advisory boards from Abbott, Astra Zeneca, Boeringer Ingelheim, Eli Lilly, Medtronic, Nordic Infucare, Novo Nordisk, and Sanofi. S.R.J is a consultant for USV, Marico, Glenmark, Franco Indian, Twin Health, Biocon, and Zydus Lifesciences. S.R.J. received speaking honoraria from Abbott, Novo Nordisk, MSD, Sanofi, Boehringer Ingelheim, AstraZeneca, Lupin, Bayer Zydus, USV, DRL, Meyer Organics, Servier, Natco. R.A.L. is a consultant for Abbott Diabetes Care, Biolinq, Capillary Biomedical, Deep Valley Labs, Gluroo, PhysioLogic Devices, Portal Insulin, Sanofi, and Tidepool. R.A.L. has served on advisory boards for. ProventionBio and Lilly. R.A.L. receives research support through his institution from Insulet, Medtronic, Tandem, and Sinocare. L.A.L. has received research funding from, has provided CME on behalf of, and/or has acted as an advisor to Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Lexicon, Merck, Novo Nordisk, Pfizer, and Sanofi. M.L. has been a consultant or received honoraria from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Nordic InfuCare, and Novo Nordisk, and has received research grants from Eli Lilly and Novo Nordisk, all outside of the submitted work. J.K.M. is a member of advisory boards of Abbott Diabetes Care, Becton-Dickinson, Biomea Fusion, Eli Lilly, Embecta, Medtronic, NovoNordisk A/S, Roche Diabetes Care, Sanofi-Aventis, and Viatris and received speaker honoraria from A. Menarini Diagnostics, Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtrust, MSD, NovoNordisk A/S, Roche Diabetes Care, Sanofi, Viatris, and Ypsomed. J.K.M. is a shareholder of decide Clinical Software GmbH and elyte Diagnostics. A.M. reports speaker fees from Novo Nordisk. M.M. has an existing research & development relationship with Scientific Bioprocessing, Inc and has been a consultant for Abbott. S.-J.M. is a consultant for Abbott, Curestream, Daewoong, EOFlow, G2e, Huons, iSense, Medtronic, Novo Nordisk, and Sanofi. D.N.O. has served on advisory boards for Abbott Laboratories, Medtronic, Merck Sharp & Dohme, Novo Nordisk, Roche, and Sanofi; received research support from Medtronic, Novo Nordisk, Roche, Eli Lilly and Company, and Sanofi; and received travel support from Novo Nordisk and Merck Sharp & Dohme. F.J.P. has received research support (to Emory University) from Dexcom, Insulet, Novo Nordisk, Tandem, and Ideal Medical Technologies, and has received consulting fees from Dexcom. A.L.P. is on the advisory board of Medscape, Vertex, and Lilly; receives research support from Insulin and Abbott; and has stock options in Omada Health. R.P.-B. receives grant support from Novo Nordisk, Lexicon Pharmaceuticals, and Medtronic and received consulting fees from Bayer, Lexicon Pharmaceuticals, Novo Nordisk, and Roche. C.M.R. has received honoraria and/or grant support from AstraZeneca, Dexcom, Fresenius, and Vifor. D.B.S. is supported by the Intramural Research Program of the National Institutes of Health. S.S. was a Novo Nordisk employee from 2022-2023. S.S. has served as advisor for Novo Nordisk and has received speaker fees from Novo Nordisk and Nordic Infucare within the past three years. G.D.S’s employer, nonprofit International Diabetes Center, HealthPartners Institute, has received educational grant funds from Abbott Diabetes Care, Medscape, and Sanofi-Aventis Groupe. G.D.S receives no personal income/honorarium from these activities. K.S. received grant supports from Arkray, Terumo, and Dexcom. E.K.S. is partly supported by the VA Merit Award (1I01CX001825) from the US Department of Veterans Affairs Clinical Sciences Research and has received unrestricted research support from Dexcom and Tandem Diabetes (to Baltimore VA Medical Center and to University of Maryland) for the conduction of clinical trials. N.L.S. received funding from Novo Nordisk for an investigator-initiated research grant unrelated to the current project. G.E.U. is partly supported by research grants from National Institutes of Health (NIH/NATS UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program, and from National Institutes of Health and National Center for Research Resources (NIH/NIDDK 2P30DK111024-06). G.E.U. has received research support (to Emory University) from Abbott, Bayer, and Dexcom; and has participated in advisory boards for Dexcom and GlyCare. E.W. has received consulting fees from Abbott Diabetes Care, Ascensia, Bayer, Boehringer, Ingelheim, Embecta, GlaxoSmithKline, Lilly, Medtronic, Renalytix, and Sanofi. E.W. has received honoraria from Abbott Diabetes Care, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Lilly, Medtronic, Renalytix, and Sanofi. E.W. is on the Speakers’ Bureau from Abbott Diabetes Care, Bayer, Boehringer, Ingelheim, GlaxoSmithKline, Lilly, Renalytix, and Sanofi. M.Z. is a consultant for DexCom, Inc. M.A.K. is Chief Medical Officer of QuesGen, Inc. C.T., C.L., B.V.H., J.S.K., W.A.L., S.Y.R., J.J.S., K.W., C.W., K.R., C.N.H., A.T.A., A.A., R.R.B., E.M.B., J.G.C., K.Y.C., A.D., N.E., S.K.K., U.M., N.M., C.M., J.H.N., A.P., P.R., S.M.S., B.S., M.V., H.W.V., J.W., A.H.B.W., and S.Y. have nothing to disclose.

Background/aims: Interstitial lung disease (ILD) is a potentially serious but underdiagnosed manifestation of primary Sjögren's syndrome (pSS). This observational study investigated the prevalence and clinical course of ILD in pSS, together with prognostic factors., Methods: A multicenter, retrospective longitudinal study was performed using findings from baseline and follow-up pulmonary function tests and chest computed tomography. Predisposing factors for the development of ILD and acute exacerbation (AE) were identified using a logistic regression model. The risk factors for a significant decline of pulmonary function were determined by the Cox proportional hazard model., Results: A total of 1,306 patients with pSS were included in this study (female, 98%; mean age, 54 years). Among them, 79 patients with pSS were comorbid with ILD. ILD was more frequently found in male, older patients. Nonspecific interstitial pneumonia was the most prevalent imaging pattern in pSS-ILD (51%), followed by usual interstitial pneumonia (22%). At diagnosis with pSS-ILD, 54% of patients had restrictive pulmonary function, and 41% of patients initiated pharmacological treatment. During the median 4-year follow-up period, AE, a significant decline in pulmonary function, and death occurred in 19%, 29%, and 9% of patients with pSS-ILD, respectively. The neutrophil-to-lymphocyte ratio (NLR) increased 3 months prior to AE, and it was associated with AE. Older age at pSS-ILD diagnosis was a prognostic factor for a significant decline in pulmonary function., Conclusions: ILD accounted for 6% of the comorbidity of pSS. AE was associated with a significant decline in pulmonary function, and the NLR may predict AE.

The cumulative toxicity of volatile organic compounds (VOCs) cause many medical diseases. We analyzed the evidence of association between VOCs and risk of metabolic syndrome in the Korean population using 1771 participants from the 2023 National Health and Nutrition Examination Survey. The creatinine-corrected urinary concentrations of BMA, 2-MHA, PGA, SPMA, 3-HPMA, BPMA and DHBMA were higher in the metabolic syndrome group than in the non-metabolic syndrome group. Urine N-Acetyl-S-(phenyl)-L-cysteine (SPMA) levels were significantly associated with metabolic syndrome after adjusting for confounders (odds ratio: 1.71). 2-MHA (OR 1.29, P=0.035) and SPMA (OR 2.84, P<0.001) were associated with the risk of elevated FBG impairment and SPMA (OR 1.57) was positively connected with the high blood pressure (P=0.016). In conclusion, the findings indicated significant association between the metabolic syndrome and a number of VOCs. Among them, there was a substantial positive correlation between the urinary SPMA levels and metabolic syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Maternal nutrition significantly influences fetal development and postnatal outcomes. This study investigates the impact of maternal overfeeding during mid to late pregnancy on gene expression in the round and sirloin muscles of Hanwoo neonatal calves. Eight cows were assigned to either a control group receiving standard nutrition (100%) or a treated group receiving overnutrition (150%). After birth, tissue samples from the round and sirloin muscles of neonatal calves were collected and subjected to RNA sequencing to assess differentially expressed genes (DEGs). RNA sequencing identified 43 DEGs in round muscle and 15 in sirloin muscle, involving genes related to myogenesis, adipogenesis, and energy regulation. Key genes, including PPARGC1A, THBS1, CD44, JUND, CNN1, ENAH, and RUNX1, were predominantly downregulated. Gene ontology (GO) enrichment analyses revealed terms associated with muscle development, such as "biological regulation," "cellular process," and "response to stimulus." Protein-protein interaction networks highlighted complex interactions among DEGs. Random Forest analysis identified ARC, SLC1A5, and GNPTAB as influential genes for distinguishing between control and treated groups. Overall, maternal overnutrition during mid-to-late pregnancy results in the downregulation of genes involved in muscle development and energy metabolism in neonatal Hanwoo calves. These findings provide insights into the molecular effects of maternal nutrition on muscle development., (© 2024. The Author(s).)

Background and Objectives: Cochlear schwannomas, which are categorized into intracochlear and intravestibulocochlear schwannomas (ICs and IVCs, respectively) are rare and may cause hearing loss (HL). The affected region is invariably correlated with tumor location, which can be detected on magnetic resonance imaging (MRI). We describe the cochleovestibular manifestations of ICs and IVCs., Subjects and Methods: The study included 31 patients with ICs or IVCs. Tumor extent and exact locations were delineated using MRI. Types of HL were subcategorized into the low-to-mid frequency (250 Hz to 1 kHz), mid-to-high frequency (>1 kHz), and all-frequency (universal) HL groups., Results: The tumors involved the entire cochlear turn (two ICs) or extended beyond the cochleae (nine IVCs) in 11 patients, and 20 ICs were located in specific locations as follows: 14 in the basal, 3 in the middle, and 3 in the middle and apical turns. No patient showed tumor invasion of the internal auditory canal or middle ear. The pattern of HL usually reflects the location or extent of a tumor. We observed HL at all frequencies, at low-to-mid frequencies, and at mid-to-high frequencies in 13, 4, and 14 patients, respectively. Dizziness or tinnitus was observed in >50% of patients. Surgical tumor removal was performed in 10 patients, and the remaining patients are undergoing annual monitoring., Conclusions: Cochlear schwannomas may be associated with HL, which may worsen over time and reflect tumor location. Therefore, these lesions should be considered in the differential diagnosis in patients who present with idiopathic, fluctuating, progressive or sudden HL.

Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.

Purpose: Numerous patients experience long-term complications after hematopoietic stem cell transplantation (HSCT). This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses., Materials and Methods: We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases, 10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis., Results: A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation-based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, total body irradiation-based conditioning regimen, and non-antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus., Conclusion: The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

Background: The prevalence of type 1 diabetes (T1D) is increasing worldwide, with a much higher proportion of adult patients. However, achieving stable glycemic control is difficult in these patients., Objective: After periodic implementation of structured education for patients with T1D through the Home and Self-Care Program, a pilot home health care project promoted by the Korean government, we evaluated the program's effects on glycemic control., Methods: This study was conducted from April 2020 to March 2023. We analyzed 119 participants with T1D aged >15 years. Nursing and nutrition education were provided separately up to 4 times per year, with physician consultation up to 6 times per year. A distinguishing feature of this study compared with previous ones was the provision of remote support using a general-purpose smartphone communication app offered up to 12 times annually on an as-needed basis to enhance the continuity of in-person education effects. Patients were followed up on at average intervals of 3 months for up to 24 months. The primary end point was the mean difference in glycated hemoglobin (HbA 1c ) at each follow-up visit from baseline. For continuous glucose monitoring (CGM) users, CGM metrics were also evaluated., Results: The mean HbA 1c level of study participants was 8.6% at baseline (mean duration of T1D 10.02, SD 16.10 y). The HbA 1c level reduction in participants who received at least 1 structured educational session went from 1.63% (SD 2.03%; P<.001; adjustment model=1.69%, 95% CI 1.24%-2.13% at the first follow-up visit) to 1.23% (SD 1.31%; P=.01; adjustment model=1.28%, 95% CI 0.78%-1.79% at the eighth follow-up visit). In the adjustment model, the actual mean HbA 1c values were maintained between a minimum of 7.33% (95% CI 7.20%-7.46% at the first follow-up visit) and a maximum of 7.62% (95% CI 7.41%-7.82% at the sixth follow-up visit). Among CGM users, after at least 1 session, the mean time in the target range was maintained between 61.59% (adjusted model, 95% CI 58.14%-65.03% at the second follow-up visit) and 54.7% (95% CI 50.92%-58.48% at the eighth follow-up visit), consistently staying above 54.7% (corresponding to an HbA 1c level of <7.6%). The mean time below the target range (TBR) also gradually improved to the recommended range (≤4% for TBR of <70 mg/dL and ≤1% for TBR of <54 mg/dL)., Conclusions: The Home and Self-Care Program protocol for glycemic control in patients with T1D is effective, producing significant improvement immediately and long-term maintenance effects, including on CGM indexes., (©Dae-Jeong Koo, Sun-Joon Moon, Suhyeon Moon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee, Cheol-Young Park. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.09.2024.)

Aim: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin., Materials and Methods: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24., Results: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection., Conclusions: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone., (© 2024 John Wiley & Sons Ltd.)

This study presents the development of a ferrite core inductively coupled plasma (ICP) radio frequency (RF) ion source designed to improve the lifetime of ion sources in commercial ion implanters. Unlike existing DC methods, this novel approach aims to enhance the performance and lifetime of the ion source. We constructed a high-vacuum evaluation chamber to thoroughly examine RF ion source characteristics using a Langmuir probe. Comparative experiments assessed the extraction current of two upgraded ferrite core RF ion sources in a commercial ion implanter setting. Additionally, we tested the plasma lifetime of the ICP source and took temperature measurements of various components to verify the operational stability and efficiency of the innovative design. This study confirmed that the ICP RF ion source operated effectively under a high vacuum of 10 -5 torr and in a high-voltage environment of 30 kV. We observed that the extraction current increased linearly with RF power. We also confirmed that BF 3 gas, which presents challenging conditions, was stably ionized in the ICP RF ion sources., Competing Interests: The authors declare no conflicts of interest.

Backgruound: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes., Methods: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models., Results: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity., Conclusion: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Background: This study demonstrates the difference between glucose management indicator (GMI) and glycated hemoglobin (HbA 1c ) according to sensor mean glucose and HbA 1c status using 2 continuous glucose monitoring (CGM) sensors in people with type 1 diabetes., Methods: A total of 275 subjects (117 Dexcom G6 [G6] and 158 FreeStyle Libre 1 [FL]) with type 1 diabetes was included. The G6 and FL sensors were used, respectively, over 90 days to analyze 682 and 515 glycemic profiles that coincide with HbA 1c ., Results: The mean HbA 1c was 6.6% in Dexcom G6 and 7.2% in FL profiles. In G6 profiles, GMI was significantly higher than HbA 1c irrespective of mean glucose (all P < .001, mean difference: 0.58% ± 0.49%). The GMI was significantly higher than the given HbA 1c when HbA 1c was below 8.0% (all P < .001). The discordance was the highest at 0.9% for lower HbA 1c values (5.0%-5.9%). The proportion of discordance >0.5% improved from 60.1% to 30.9% when using the revised GMI equation in G6 profiles. In FL profile, the overall mean difference between GMI and HbA 1c was 0 ( P = .966). The GMI was significantly lower by 0.9% than HbA 1c of 9.0% to 9.9% and higher by 0.5% in HbA 1c of 5.0% to 5.9% (all P < .001)., Conclusions: The GMI is overestimated in G6 users, particularly those with well-controlled diabetes, but the GMI and HbA 1c discordance improved with a revised equation from the observed data. The FL profile showed greater discordance for lower HbA 1c levels or higher HbA 1c levels., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Taste buds, the neuroepithelial organs responsible for the detection of gustatory stimuli in the oral cavity, arise from stem/progenitor cells among nearby basal keratinocytes. Using genetic lineage tracing, Lgr5 and Lgr6 were suggested as the specific markers for the stem/progenitor cells of taste buds, but recent evidence implied that taste buds may arise even in the absence of these markers. Thus, we wanted to verify the genetic lineage tracing of lingual Lgr5 - and Lgr6 -expressing cells. Unexpectedly, we found that antibody staining revealed more diverse Lgr5 -expressing cells inside and outside the taste buds of circumvallate papillae than was previously suggested. We also found that, while tamoxifen-induced genetic recombination occurred only in cells expressing the Lgr5 reporter GFP, we did not see any increase in the number of recombined daughter cells induced by consecutive injections of tamoxifen. Similarly, we found that cells expressing Lgr6 , another stem/progenitor cell marker candidate and an analog of Lgr5 , also do not generate recombined clones. In contrast, Lgr5 -expressing cells in fungiform papillae can transform into Lgr5- negative progeny. Together, our data indicate that lingual Lgr5 - and Lgr6 -expressing cells exhibit diversity in their capacity to transform into Lgr5 - and Lgr6 -negative cells, depending on their location. Our results complement previous findings that did not distinguish this diversity., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: This study compared the pharmacokinetics (PK), immunogenicity, and safety of candidate tocilizumab biosimilar, CT-P47, administered via auto-injector (CT-P47 AI) or pre-filled syringe (CT-P47 PFS), in healthy Asian adults., Research Design and Methods: In this phase I, multicenter, open-label study, participants were randomized 1:1 to receive a single 162 mg/0.9 mL dose of CT-P47 via AI or PFS. Primary endpoints were area under the concentration - time curve from time zero to infinity (AUC 0-inf ) and maximum serum concentration (C max ). PK equivalence was determined if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK parameters, immunogenicity, and safety outcomes were also assessed., Results: Of 314 participants randomized (155 CT-P47 AI; 159 CT-P47 PFS), 310 received the study drug (153 CT-P47 AI; 157 CT-P47 PFS). Primary and secondary PK results, immunogenicity and safety were similar between groups. Ninety percent CIs for the ratio of gLSMs were within the predefined equivalence margin for AUC 0-inf (85.87-102.94) and C max (82.98-98.16)., Conclusions: PK equivalence between CT-P47 AI and CT-P47 PFS was demonstrated in healthy Asian adults, with comparable immunogenicity and safety between the two devices., Trial Registration: ClinicalTrials.gov: NCT05617183.

Aims/hypothesis: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP)., Methods: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA 1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates., Results: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA 1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group., Conclusions/interpretation: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP., Trial Registration: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Hanwoo traceability system currently utilizes 11 dinucleotide repeat microsatellite (MS) markers. However, dinucleotide repeat markers are known to have a high incidence of polymerase chain reaction (PCR) artifacts, such as stutter bands, which can complicate the accurate reading of alleles. In this study, we examined the polymorphisms of the 11 dinucleotide repeat MS markers currently employed in traceability systems. Additionally, we explored four trinucleotide repeat MS markers and one tetranucleotide repeat MS marker in a sample of 1,106 Hanwoo cattle. We also assessed the potential utility of the tri- and tetranucleotide repeat MS markers. The polymorphic information content (PIC) of the five tri- and tetranucleotide repeat markers ranged from 0.663 to 0.767 (mean: 0.722), sufficiently polymorphic and slightly higher than the mean (0.716) of the current 11 dinucleotide repeat markers. Using all 16 markers, the mean PIC was 0.718. The estimated probability of identity (PI) was 3.13 × 10 -12 using the 11 dinucleotide repeat markers, 7.03 × 10 -6 using the five tri- and tetranucleotide repeat markers, and 2.39 × 10 -17 using all 16 markers; the respective PI half-sibs values were 2.69 × 10 -9 , 1.29 × 10 -4 , and 3.42 × 10 -13 ; and the respective PIsibs values were 3.89 × 10 -5 , 9.6 × 10 -3 , and 3.69 × 10 -7 . The probability of exclusion 1 (PE 1 ) was 0.999864 for the 11 dinucleotide repeat markers, 0.981141 for five of the tri- and tetranucleotide repeat markers, and > 0.99 for all 16 markers; the respective PE 2 values were 0.994632, 0.901369, and > 0.99; and the respective PE 3 values were 0.998702, > 0.99, and > 0.99. The five investigated tri- and tetranucleotide repeat MS markers can be used in combination with the 11 existing MS markers to improve the accuracy of individual identification and paternity testing in Hanwoo., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

Background: Hyperuricemia could be a risk for various chronic diseases, and it could be largely corrected by diet control. This study was a nationwide cross-sectional study to investigate the association between serum uric acid level and dietary fiber intake., Methods: This study analyzed data based on the Korean National Health and Nutrition Examination Survey conducted from 2016 to 2018. Adults over 20 years of age with normal renal function, defined as an estimated glomerular filtration rate (eGFR) over 30mL/min/1.73m 2 , were included. The criteria for hyperuricemia were ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Data regarding dietary intake were obtained using the 24-hour recall method., Results: A total of 15,278 subjects (6,455 males/8,823 females) were analyzed. The prevalence of hyperuricemia was 19.3% in men and 6.8% in women. There were significant, negative associations between serum uric acid and total fiber intake in both men and women. Consuming more than 27.9 g of dietary fiber in men and 20.7 g in women reduced the risk of hyperuricemia by approximately 30% with odds ratios of 0.72 (0.62-0.83) and 0.71 (0.56-0.88) in men and women, respectively. With regard to the risk reduction by the type of dietary fiber, cereal fiber was significantly identified in both men and women, while fruit fiber was only significant in men. In the subgroup analysis, this association remained significantly in young and metabolically healthy populations with normal weight., Conclusions: Dietary fiber intake was inversely associated with serum uric acid levels. This relationship was particularly significant in metabolically healthy young adults., (© 2024. The Author(s).)

Thin transparent oxide layers are typically patterned for use in electronic products including semiconductors, displays, and solar cells for applications such as transparent electrodes, insulating films, and encapsulation films. Conventional patterning methods have traditionally been used in photolithography and lift-off processes. Photolithography employs the wet development process, which has disadvantages such as potential undercut effects, swelling, chemical contamination, and high process costs. On the other hand, laser ablation, which has the advantages of high accuracy, high speed, a noncontact nature, and selective processing, can be used to pattern thin films. However, absorption in transparent oxide films is usually low. In this study, experiments were conducted to determine the ablation characteristics of mask layers. The factors affecting ablation, including beam radii, fluences, overlap ratios, and coating thicknesses, were examined; and the parameters characteristic of residue-free ablation, namely the ablation threshold, minimum fluence, and minimum ablation linewidth, were also examined. The experimental results revealed that the beam radius was an important parameter in determining the resolutions of transparent films and substrates.

Backgruound: Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea., Methods: We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs., Results: A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049)., Conclusion: In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP- 4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.

Objective: Switching biologic and targeted synthetic DMARD (b/tsDMARD) medications occurs commonly in RA patients, however data are limited on the reasons for these changes. The objective of the study was to identify and categorize reasons for b/tsDMARD switching and investigate characteristics associated with treatment refractory RA., Methods: In a multi-hospital RA electronic health record (EHR) cohort, we identified RA patients prescribed ≥1 b/tsDMARD between 2001 and 2017. Consistent with the EULAR "difficult to treat" (D2T) RA definition, we further identified patients who discontinued ≥2 b/tsDMARDs with different mechanisms of action. We performed manual chart review to determine reasons for medication discontinuation. We defined "treatment refractory" RA as not achieving low disease activity (<3 tender or swollen joints on <7.5 mg of daily prednisone equivalent) despite treatment with two different b/tsDMARD mechanisms of action. We compared demographic, lifestyle, and clinical factors between treatment refractory RA and b/tsDMARD initiators not meeting D2T criteria., Results: We identified 6040 RA patients prescribed ≥1 b/tsDMARD including 404 meeting D2T criteria. The most common reasons for medication discontinuation were inadequate response (43.3 %), loss of efficacy (25.8 %), and non-allergic adverse events (13.7 %). Of patients with D2T RA, 15 % had treatment refractory RA. Treatment refractory RA patients were younger at b/tsDMARD initiation (mean 47.2 vs. 55.2 years, p < 0.001), more commonly female (91.8% vs. 76.1 %, p = 0.006), and ever smokers (68.9% vs. 49.9 %, p = 0.005). No RA clinical factors differentiated treatment refractory RA patients from b/tsDMARD initiators., Conclusions: In a large EHR-based RA cohort, the most common reasons for b/tsDMARD switching were inadequate response, loss of efficacy, and nonallergic adverse events (e.g. infections, leukopenia, psoriasis). Clinical RA factors were insufficient for differentiating b/tsDMARD responders from nonresponders., Competing Interests: Declaration of competing interest MEW reports research support from Bristol Myers Squibb, Aqtual, Abbvie, and Janssen; consultancy for Abbvie, Aclaris, Amgen, Aqtual, Bristol Myers Squibb, CorEvitas, Glaxo Smith Kline, Gilead, Horizon, Johnson & Johnson, Lilly, Pfizer, Rani, Revolo, Saniofi, Scipher, Sci Rhom, Set Point, and Tremeau; and stock or stock options from Canfite, Inmedix, Scipher. Other authors report no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Placing dental implants in areas with low bone density or in conditions where bone healing is suppressed is challenging for clinicians. An experiment using a rodent model was performed with the aim of determining the efficacy of host modulation by increasing the systemic level of cholesterol sulfate (CS) using Irosustat in the context of the bone healing process around dental implants., Methods: In 16 ovariectomised female Sprague-Dawley rats, 2 implant fixtures were placed in the tibial bones (1 fixture on each side). At 1 week after surgery, the high-CS group (n=8) received Irosustat-mixed feed, while the control group (n=8) was fed conventionally. Block specimens were obtained at 5 weeks post-surgery for histologic analysis and the data were evaluated statistically ( P <0.05)., Results: Unlike the high-CS group, half of the specimens in the control group demonstrated severe bone resorption along with a periosteal reaction in the cortex. The mean percentages of bone-to-implant contact (21.5%) and bone density (28.1%) near the implant surface were significantly higher in the high-CS group than in the control group ( P <0.05), as was the number of Haversian canals (by 5.3)., Conclusions: Host modulation by increasing the CS level may enhance the osseointegration of dental implants placed under conditions of impaired bone healing., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Academy of Periodontology.)

This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet of 4.5 kg of concentrate and 6.5 kg of rice straw daily, resulting in intake levels of 8.42 kg DMI, 5.69 kg TDN, and 0.93 kg CP-higher than the control group (6.07 kg DMI, 4.07 kg TDN, and 0.65 kg CP), with respective NEm values of 9.56 Mcal and 6.68 Mcal. Following birth, newly born calves were euthanized humanely as per ethical guidelines, and SAT and liver samples from newborn calves were collected for RNA extraction and analysis. RNA sequencing identified 192 genes that were differentially expressed in the SAT (17 downregulated and 175 upregulated); notably, HSPA6 emerged as the most significantly upregulated gene in the SAT and as the singular upregulated gene in the liver (adj- p value < 0.05). Additionally, differential gene expression analysis highlighted extensive changes across genes associated with adipogenesis, fibrogenesis, and stress response. The functional enrichment pathway and protein-protein interaction (PPI) unraveled the intricate networks and biological processes impacted by overnutrition, including extracellular matrix organization, cell surface receptor signaling, and the PI3K-Akt signaling pathway. These findings underscore maternal overnutrition's substantial influence on developmental pathways, suggesting profound cellular modifications with potential lasting effects on health and productivity. Despite the robust insights that are provided, the study's limitations (sample size) underscore the necessity for further research.

Continuous glucose monitoring (CGM) has been shown to improve glycemic control and self-monitoring, as well as to reduce the risk of hypoglycemia. Integrated CGM (iCGM) FDA-cleared systems with published performance data are established nonadjunctive and accurate CGM tools that can directly inform decision-making in the treatment of diabetes (i.e., insulin dosing). Studies have assessed accuracy and safety data of CGMs that were eventually cleared for iCGM by the FDA and that informed the recommendation for their nonadjunctive use. Subsequent robust clinical trials and real-world studies demonstrated clinical effectiveness with improvements in a range of patient outcomes. In recent years, a number of non-iCGM-approved CGM devices have entered the market outside the United States worldwide. Some of these non-iCGM-approved CGM devices require additional user verification of blood glucose levels to be performed for making treatment decisions, termed adjunctive. Moreover, in many non-iCGM-approved CGM devices, accuracy studies published in peer-reviewed journals are scarce or have many limitations. Consequently, non-iCGM-approved CGM devices cannot be automatically perceived as having the same performance or quality standards than those approved for iCGM by the FDA. As a result, although these devices tend to cost less than iCGMs that carry FDA clearance and could therefore be attractive from the point of view of a health care payer, it must be emphasized that evaluation of costs should not be limited to the device (such as the usability preference that patients have for nonadjunctive sensors compared to adjunctive sensors) but to the wider value of the total benefit that the product provides to the patient., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DCK is a consultant for Afon, Atropos Health, Glucotrack, Lifecare, Nevro, Novo, Samsung, and Thirdwayv. MG is a consultant for Abbott, Medtronic, Novo, Roche. SJM is consultant for Abbott, Curestream, Daewoong, EOFlow, G2e, Huons, iSense, Medtronic, Novonodisk, and Sanofi. EGW has received personal fees from Abbott, AstraZeneca, Dexcom, Eli Lilly, Embecta, Insulet, Medtronic, Novo Nordisk, Roche, Sanofi, Ypsomed and research support from Abbott, Embecta, Insulet, Novo Nordisk, Sanofi.

The primary performance limitation in inverted perovskite-based solar cells is the interface between the fullerene-based electron transport layers and the perovskite. Atomic layer deposited thin aluminum oxide (AlO X ) interlayers that reduce nonradiative recombination at the perovskite/C 60 interface are developed, resulting in >60 millivolts improvement in open-circuit voltage and 1% absolute improvement in power conversion efficiency. Surface-sensitive characterizations indicate the presence of a thin, conformally deposited AlO x layer, functioning as a passivating contact. These interlayers work universally using different lead-halide-based absorbers with different compositions where the 1.55 electron volts bandgap single junction devices reach >23% power conversion efficiency. A reduction of metallic Pb 0 is found and the compact layer prevents in- and egress of volatile species, synergistically improving the stability. AlO X -modified wide-bandgap perovskite absorbers as a top cell in a monolithic perovskite-silicon tandem enable a certified power conversion efficiency of 29.9% and open-circuit voltages above 1.92 volts for 1.17 square centimeters device area., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)