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Parathyroid carcinoma (PC) in cases of secondary or tertiary hyperparathyroidism is relatively uncommon, and only a few case reports have described this entity. Although some papers have reported patients with one or two parathyroid malignancies, multiple PC–especially three or more–have been even more rarely reported. Herein, we report a case of secondary hyperparathyroidism due to multiple PCs in a chronic hemodialysis patient. A 54-year-old man with end-stage kidney disease was referred for hyperparathyroidism. He had been diagnosed with chronic kidney disease in 2001 and had begun hemodialysis in 2009. In laboratory tests, intact parathyroid hormone (iPTH) was markedly elevated to 1,144.1 pg/mL (normal range: 15.0–68.3 pg/mL) and serum calcium was mildly elevated to 10.56 mg/dL (normal range: 8.5–10.3 mg/dL). Ultrasonography showed hypoechoic nodules in the posterior part of both thyroid glands. All three nodules showed increased uptake on a 99mTc sestamibi scan. The patient underwent total parathyroidectomy with autotransplantation to the right forearm. Histopathology findings showed three PCs with capsular invasion and one parathyroid hyperplasia. In the immediate postoperative period, the iPTH level dropped from 1,446.8 to 82.4 pg/dL and, after 1 month, to 4.0 pg/dL. This patient needed oral calcium carbonate and active vitamin D to maintain appropriate serum calcium levels. Although multiple PCs are rare, they can cause secondary hyperparathyroidism. Therefore, clinicians should suspect multiple PCs when patients’ serum iPTH levels are exceptionally high. Additionally, since PCs could occur in multiple glands, autotransplantation of the parathyroid gland after parathyroidectomy should be done carefully.

Background To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM). Methods Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims. Results Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF. Conclusion The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

A numerical feasibility study was conducted to investigate the thermal–hydraulic characteristics of a steam generator with corrugated plates for a small modular reactor. Accordingly, a one-dimensional thermal–hydraulic analysis code was developed based on the existing state-of-the-art thermal–hydraulic models and correlations for corrugated plate heat exchangers. Subsequently, the pressure loss, heat transfer, and instability characteristics of the steam generator with corrugated plates were investigated according to the chevron angle and mass flux. Additionally, the characteristics of rectangular and disk-type corrugated plate steam generators with equivalent heat transfer areas were analyzed. The steam generator with disk-type corrugated plates exhibited better performance in terms of pressure loss and heat transfer rate than the rectangular type. In addition, when the mass flux decreased from the onset of boiling points, reverse gradients of the total pressure change were observed in both types. Thus, it was confirmed that Ledinegg instability could occur in the steam generator with corrugated plates. However, it was dependent on the chevron angle, and the optimal chevron angle to minimize instability was 45° under the conditions of the present analysis.

Abstract Background Ear, nose, and throat involvement are common in eosinophilic granulomatosis with polyangiitis (EGPA). Among otologic manifestation, middle ear effusion (MEE) is less recognized but a problematic condition as it may progress to hearing impairment when left untreated. This study aimed to evaluate the characteristics, risk factors and clinical outcomes of MEE in EGPA patients. Methods This is a case–control study of patients who were diagnosed and treated for EGPA from January 1995 to November 2018. Patients with ear symptoms (ear fullness, ear discharge, tinnitus or hearing loss) were assessed by otologists and were included in the case group (n = 23) if clinically relevant. The other patients without MEE were included in the control group (n = 52). Risk of MEE was calculated using the Cox proportional-hazard model. Results During median follow-up of 9.9 years, 23 (30.7%) out of 75 patients had MEE. In MEE group, 12 (52.2%) patients had hearing loss; conductive type in 10 (10/12, 83.3%) and mixed type in two (2/12, 16.7%). In multivariable regression analysis, major organ involvement at diagnosis (adjusted hazard ratio [aHR] 65.4; 95% confidence interval [CI], 1.50—2838.39; P = 0.030] , early onset of ear symptom after systemic therapy (

Abstract The α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.

Lumbosacral radiculopathy (LR) is a musculoskeletal disorder or pain syndrome that is generally linked to the compression or irritation of the nerve root. There is a growing interest in the development of efficient acupuncture-based treatments for LR comparable to western medicine. Structured traditional Korean medical treatments including intensified acupuncture stimulus on the EX-B2 point using the G-shaped posture modified from the sitting posture were applied to four LR patients, and the outcomes were evaluated based on objective clinical endpoints including a numeric rating scale (NRS), the Oswestry disability index (ODI), the manual muscle test (MMT), neurological symptoms, and plantar photography. Patients showed improvements in NRS, ODI, MMT, and neurological symptoms without adverse effects during hospitalization and follow-up visits. Moreover, we observed substantial dissolvement of hyperkeratinization and parchedness of the soles of the feet, which was not reported previously. These four cases demonstrate the clinical usefulness of traditional medicine and the diagnostic applicability of plantar photography. However, further randomized controlled trials are required to confirm our findings.

Background Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigated the effect of exogenous DLK1 on muscular atrophy. Methods We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into three groups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1. The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes. Results Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreased expression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reduced expression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscle differentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophy through the myostatin pathway. Conclusion DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrial biogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration.

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

The esophagus exhibits peristalsis via contraction of circularly and longitudinally aligned smooth muscles, and esophageal replacement is required if there is a critical-sized wound. In this study, we proposed to reconstruct esophageal tissues using cell electrospinning (CE), an advanced technique for encapsulating living cells into fibers that allows control of the direction of fiber deposition. After treatment with transforming growth factor-β, mesenchymal stem cell-derived smooth muscle cells (SMCs) were utilized for cell electrospinning or three-dimensional bioprinting to compare the effects of aligned micropatterns on cell morphology. CE resulted in SMCs with uniaxially arranged and elongated cell morphology with upregulated expression levels of SMC-specific markers, including connexin 43, smooth muscle protein 22 alpha (SM22α), desmin, and smoothelin. When SMC-laden nanofibrous patches were transplanted into a rat esophageal defect model, the SMC patch promoted regeneration of esophageal wounds with an increased number of newly formed blood vessels and enhanced the SMC-specific markers of SM22α and vimentin. Taken together, CE with its advantages, such as guidance of highly elongated, aligned cell morphology and accelerated SMC differentiation, can be an efficient strategy to reconstruct smooth muscle tissues and treat esophageal perforation.

Globalization has increased international trade and caused an annual increase in the number of non-native insect pest species found in quarantine sites in Korea. Since over 80% of Korean farms use greenhouses with internal conditions conducive to growing crops and hospitable to exotic pests, efficient pest control is crucial. This study evaluated the efficacy of ethyl formate (EF) against three major exotic insect pests (Aphis gossypii, Frankliniella occidentalis, and Tetranychus urticae) and beneficial organisms (earthworms, honeybees, and silkworms) via EF fumigation experiments at two concentrations. The lethal concentration–time (LCt)99 values of A. gossypii, F. occidentalis, and T. urticae were 8.96, 14.00, and 19.07 g h/m3, respectively. Four hours of fumigation of EF at 15 g/m3 left no residue on the crops or soil after a maximum of 3 h. The beneficial organisms exhibited higher tolerance levels than A. gossypii with regard to LCt99 value, but the higher EF treatment dosage needed to control F. occidentalis and T. urticae could be highly lethal to honeybees. The lower EF dose (4 g/m3) effectively controlled A. gossypii, but 15 g/m3 was needed for F. occidentalis and T. urticae. Phytotoxicity varied in severity with EF concentration. These insights can help in developing a refined disinfestation strategy for greenhouses.

The purpose of this paper is to analyze the seismic response effect caused by the mass eccentricity of individual equipment when conducting base isolation for the improvement of the seismic performance of a nuclear power plant. Recent research has interpreted and confirmed through analysis and testing that base isolation for safety-related equipment in nuclear power plants is an efficient alternative to designing for excessive seismic loads. Depending on the equipment, unavoidable mass eccentricity can occur, which necessitates verification of the response impact caused by eccentricity. In this paper, we analyze the seismic response impact of equipment with mass eccentricity using small base isolators. To do so, sensitivity analysis of the seismic response due to mass eccentricity is conducted for a base-isolated concentrated mass model. Furthermore, three efficient mass eccentricity models suitable for testing are designed and manufactured. Simulation analyses using the finite element method (FEM) models are performed, followed by three-axis shake table tests to validate the seismic response impact of mass eccentricity. In conclusion, it is confirmed that applying small base isolators to equipment with mass eccentricity can affect seismic response impact to some extent when compared for a beyond-design-basis earthquake (BDBE).

Nonsteroidal anti-inflammatory drug (NSAID) use is associated with adverse consequences, including hepatic injury. The detrimental hepatotoxicity of diclofenac, a widely used NSAID, is primarily connected to oxidative damage in mitochondria, which are the primary source of reactive oxygen species (ROS). The primary ROS responsible for inducing diclofenac-related hepatocellular toxicity and the principal antioxidant that mitigates these ROS remain unknown. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-eliminating enzyme in the mitochondria of mammalian cells. Here, we investigated the role of mitochondrial H2O2 and the protective function of PrxIII in diclofenac-induced mitochondrial dysfunction and apoptosis in hepatocytes. Mitochondrial H2O2 levels were differentiated from other types of ROS using a fluorescent H2O2 indicator. Upon diclofenac treatment, PrxIII-knockdown HepG2 human hepatoma cells showed higher levels of mitochondrial H2O2 than PrxIII-expressing controls. PrxIII-depleted cells exhibited higher mitochondrial dysfunction as measured by a lower oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, and caspase activation, and were more sensitive to apoptosis. Ectopic expression of mitochondrially targeted catalase in PrxIII-knockdown HepG2 cells or in primary hepatocytes derived from PrxIII-knockout mice suppressed the diclofenac-induced accumulation of mitochondrial H2O2 and decreased apoptosis. Thus, we demonstrated that mitochondrial H2O2 is a key mediator of diclofenac-induced hepatocellular damage driven by mitochondrial dysfunction and apoptosis. We showed that PrxIII loss results in the critical accumulation of mitochondrial H2O2 and increases the harmful effects of diclofenac. PrxIII or other antioxidants targeting mitochondrial H2O2 could be explored as potential therapeutic agents to protect against the hepatotoxicity associated with NSAID use.

Background: We aimed to investigate the association between the ApoB/ApoA-I ratio and post-stroke cognitive impairment (PSCI) in patients with acute stroke of large artery atherosclerosis etiology. Methods: Prospective stroke registry data were used to consecutively enroll patients with acute ischemic stroke due to large artery atherosclerosis. Cognitive function assessments were conducted 3 to 6 months after stroke. PSCI was defined as a z-score of less than −2 standard deviations from age, sex, and education-adjusted means in at least one cognitive domain. The ApoB/ApoA-I ratio was calculated, and patients were categorized into five groups according to quintiles of the ratio. Logistic regression analyses were performed to assess the association between quintiles of the ApoB/ApoA-I ratio and PSCI. Results: A total of 263 patients were included, with a mean age of 65.9 ± 11.6 years. The median NIHSS score and ApoB/ApoA-I ratio upon admission were 2 (IQR, 1–5) and 0.81 (IQR, 0.76–0.88), respectively. PSCI was observed in 91 (34.6%) patients. The highest quintile (Q5) of the ApoB/ApoA-I ratio was a significant predictor of PSCI compared to the lowest quintile (Q1) (adjusted OR, 3.16; 95% CI, 1.19–8.41; p-value = 0.021) after adjusting for relevant confounders. Patients in the Q5 group exhibited significantly worse performance in the frontal domain. Conclusions: The ApoB/ApoA-I ratio in the acute stage of stroke independently predicted the development of PSCI at 3–6 months after stroke due to large artery atherosclerosis. Further, a high ApoB/ApoA-I ratio was specifically associated with frontal domain dysfunction.

This study proposes self-calibration of capacitor mismatch errors for high-resolution pipeline analog-to-digital converters (ADCs). The proposed calibration circuit recursively amplifies the capacitor mismatch error by re-utilizing a multiplying digital-to-analog converter in a pipeline stage without increasing the circuit complexity, and the amplified error voltage is converted into digital code by utilizing the remaining pipeline stages. Error correction is performed by subtracting the digital code from the ADC output during normal operation. A prototype of a 12-bit pipeline ADC is fabricated in a 0.18 µm standard CMOS process. The ADC comprises eight 1.5-bit stages, followed by a 4-bit flash ADC as the final stage; the capacitor mismatch errors in the first two pipeline stages are corrected by utilizing the proposed self-calibration technique. Although the calibration method is employed in a 1.5-bit stage architecture, which uses a gain-of-two switched-capacitor amplifier, it is applicable to different bit-per-stage architectures. The ADC linearity significantly improves after calibration, and this is verified through simulations and measurements.

With an increase in the international trade of agricultural and non-agricultural products, there is an increase in the possibility of introducing hitchhiking insect pests such as Halyomorpha halys, which has been detected on imported vehicles and agricultural machinery. Although methyl bromide (MB) is provisionally used to control invasive pests, it is classified as a restricted chemical owing to its potential to deplete the ozone layer and pose health risks to humans in cases of inadequate ventilation, as well as concerns regarding consumer safety. Therefore, this study investigated ethyl formate’s (EF’s) efficacy against H. halys and its efficacy and sorption, as an alternative to MB, on main electronic components, including alternators, ignition coils, and motors. Fumigation with 35 and 70 g/m3 EF for 4 h at 15 °C had no damage on the main electronic components as evaluated using various operation tests. In a commercial trial, H. halys infestation was effectively controlled with 35 g/m3 EF fumigated for 4 h at 23 °C using a 30 m3 polyvinyl chloride tarpaulin fumigation chamber. After ventilation, the EF concentration decreased below the safety level within 10 min and reached the zero level within 40 min for worker safety. This novel sanitary treatment using EF fumigation on imported agricultural machinery could be an effective method without causing mechanical damage.

Climate change is affecting all regions of the world with different climates, and the scale of damage is increasing due to the occurrence of various natural disasters. In particular, maize production is highly affected by abnormal climate events such as heat waves and droughts. Increasing temperatures can accelerate growth and shorten the growing season, potentially reducing productivity. Additionally, enhanced temperatures during the ripening period can accelerate the process, reducing crop yields. In addition, drought stress due to water deficit can greatly affect seedling formation, early plant growth, photosynthesis, reproductive growth, and yield, so proper water management is critical to maize growth. Maize, in particular, is tall and broad-leaved, so extreme drought stress at planting can cause leaves to curl and stunt growth. It is important to understand that severe drought can have a detrimental effect on the growth and reproduction of maize. In addition, high temperatures caused by drought stress can inhibit the induction of flowering in male flowers and cause factors that interfere with pollen development. It is therefore important to increase the productivity of all food crops, including maize, while maintaining them in the face of persistent drought caused by climate change. This requires a strategy to develop genetically modified crops and drought-tolerant maize that can effectively respond to climate change. The aim of this paper is to investigate the effects of climate change and drought tolerance on maize growth. We also reviewed molecular breeding techniques to develop drought-tolerant maize varieties in response to climate change.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is generally developed with excessive accumulation of lipids in the liver. Ketogenesis is an efficient pathway for the disposal of fatty acids in the liver and its metabolic benefits have been reported. In this review, we examined previous studies on the association between ketogenesis and MAFLD and reviewed the candidate mechanisms that can explain this association.

This study evaluated the feasibility of ionizing radiation combined with coagulation–sedimentation and Fenton oxidation as a treatment method for landfill leachate. The experiments revealed a positive correlation between pollutant removal efficiency and increased ionizing radiation intensity. Remarkable pollutant removal efficiencies were achieved under ionizing radiation at 50 kGy, with a maximum of 27% removal of total organic carbon (TOC), 61% removal of total nitrogen, 51% removal of total phosphorus, and an impressive 93% removal of NO3−-N. With the addition of coagulation–sedimentation and Fenton oxidation, the treatment efficiency further increased by 33% nitrogen, 18% SCOD, and 8% phosphate. The most significant observation from the study was that for all the different treatment methods, the results were always better for leachate samples treated with ionizing radiation than for the untreated samples. Subsequently, biological treatment was applied as a post-treatment method to remove residual organic carbon and nitrogen, which found that the best removal efficiencies were only for the low salt concentration (0.5%) and the removal decreased with increasing salt concentration. These experimental results conclusively demonstrated that when treating leachate wastewater, it was more appropriate to employ physicochemical methods rather than a biological treatment, primarily due to the high salt concentration present.

Powdery mildew and two-spotted spider mite are detrimental to strawberry plants and are controlled with traditional pesticides. To accommodate consumer demand, eco-friendly methods of pest control are required. Strawberries were cultivated (in soil and in a hydroponic system) for two years, and ultraviolet B (UV-B) irradiation was used as an alternative pest control during the harvesting season. Three varieties were grown (Seolhyang, Kingsberry, and Durihyang), and four UV-B lamp/mulch (black, green, and light reflection sheet [LRS]) combinations were used during harvesting: UV-B+black or green mulch, UV-B+black or green+LRS, no UV-B+black or green, and no UV-B+black or green+LRS. In all varieties, powdery mildew was 65% more controlled when UV-B irradiation was used. The adult two-spotted spider mite density was lowest in the UV-B lamp+black or green+LRS treatments. Therefore, UV-B irradiation during the strawberry harvesting season could effectively control powdery mildew and two-spotted spider mite with little side effect on the plants.

Abstract The skin has a protective barrier against the external environment, making the transdermal delivery of active macromolecules very difficult. Cell-penetrating peptides (CPPs) have been accepted as useful delivery tools owing to their high transduction efficiency and low cytotoxicity. In this study, we evaluated the hydrophobic peptide, macromolecule transduction domain 1067 (MTD 1067) as a CPP for the transdermal delivery of protein cargoes of various sizes, including growth hormone-releasing hexapeptide-6 (GHRP-6), a truncated form of insulin-like growth factor-I (des(1-3)IGF-I), and platelet-derived growth factor BB (PDGF-BB). The MTD 1067-conjugated GHRP-6 (MTD-GHRP-6) was chemically synthesized, whereas the MTD 1067-conjugated des(1-3)IGF-I and PDGF-BB proteins (MTD-des(1-3)IGF-I and MTD-PDGF-BB) were generated as recombinant proteins. All the MTD 1067-conjugated cargoes exhibited biological activities identical or improved when compared to those of the original cargoes. The analysis of confocal microscopy images showed that MTD-GHRP-6, MTD-des(1-3)IGF-I, and MTD-PDGF-BB were detected at 4.4-, 18.8-, and 32.9-times higher levels in the dermis, respectively, compared to the control group without MTD. Furthermore, the MTD 1067-conjugated cargoes did not show cytotoxicity. Altogether, our data demonstrate the potential of MTD 1067 conjugation in developing functional macromolecules for cosmetics and drugs with enhanced transdermal permeability.

Background Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate. Methods The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed. Results In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (P

Background : Electronic moxibustion (EM) was developed to minimize the side effects of traditional moxibustion, such as burns, and to overcome therapeutic compliances such as smoke or smell. Objectives: To investigate distributions and thermal stimulation of EM at various depths using silicon phantom and to compare this methodology to traditional indirect moxibustion (TIM). Methods : A silicon phantom composed of polydimethylsiloxane was heated and immersed in a hot plate containing warm water to set the phantom’s temperature to that of biological tissue. K-type thermocouples were inserted into the phantom at depths of 0, 2, 5, 7, and 10 mm to measure temperature changes with thermal stimulation of EM or TIM placed on top of the phantom. Results : At the surface of the phantom, the peak temperature after applying TIM (55.04 ± 0.92℃ [Δ23.79 ± 0.96℃]) was significantly higher than after EM (43.25 ± 1.95℃ [Δ13.00 ± 2.23℃]), with both interventions reaching the highest temperature after 2 minutes. The temperature increase for TIM was also statistically significant compared to EM when measured at a depth of 2 mm. For the experimental setting with TIM, after reaching peak surface temperature, a rapid decrease was observed at the surface and 2 mm while EM showed a much more gradual decline. There was no significant difference in temperature change between the groups at depths of 5, 7, and 10 mm. Conclusion : TIM resulted in a higher temperature rise compared to EM at the surface and at a 2 mm depth reaching over 50℃, which creates risk of burns. Thermal stimulation with EM had a lower risk of burns with temperature increment not being statistically different from TIM below the depth of 5 mm.

Chimeric antigen receptor T cells represent a breakthrough treatment in hematologic malignancies, but insufficient level of cytotoxicity and persistence of T cells might compromise success. Authors show here that a recombinant long acting form of interleukin-7 enhances proliferation, persistence and cytotoxicity of the engineered T cells, resulting in long term disease remission.

Abstract Background Total knee arthroplasty (TKA) is an important management strategy for patients with knee osteoarthritis (OA) refractory to conservative management. Postoperative range of motion (ROM) exercise is important to recover patients’ activities of daily living. Continuous passive motion (CPM) is a machine that provides passive ROM exercises of the knee joint in a pre-defined arc of motion. The short- and long-term effects of CPM exercise are controversial. We hypothesized that the inconsistent results of the CPM exercise are due to poor fitting of CPM machines and measurement errors. This study aims to present a protocol for investigating a new type of CPM machine that could be applied in a sitting position in comparison with the conventional type of CPM machine for patients with unilateral TKAs. Methods This study presents the protocol of a prospective, multicenter, single-blinded, three-armed randomized controlled trial (RCT). One hundred and twenty-six patients receiving unilateral TKAs will be recruited at the physical medicine and rehabilitation clinics of two urban tertiary medical hospitals. The patients were randomly divided into three groups with a 1:1:1 allocation. The intervention group will receive two weeks of post-operative rehabilitation using a new type of CPM machine. The control group will receive 2 weeks of post-operative rehabilitation using conventional CPM machines. The third group will receive post-operative rehabilitation with both types of CPM machines. The primary outcome will be the change in the passive ROM of the affected knee joint from baseline to 2 weeks after baseline assessment. The secondary outcomes will be pain and functional measurements, and will include patient-reported outcomes and performance tests surveyed at multiple time points up to 3 months after TKA. Discussion This is the first RCT to investigate the effect of a new type of CPM machine. The results of this RCT will determine whether the position of the patients during CPM exercise is important in post-operative rehabilitation protocols after TKAs and will provide evidence for the development of proper rehabilitation guidelines after TKAs. Trial registration Clinical Research Information Service of Republic of Korea, KCT0005520, Registered on 21 October 2020, https://cris.nih.go.kr/cris/search/detailSearch.do/21750

Abstract Objective Electrocardiogram (ECG) patterns can change, especially in patients with central nervous system disorders such as spontaneous subarachnoid hemorrhage. However, the association between the prognosis of traumatic brain injury (TBI) and ECG findings is unknown. Therefore, this study aimed to compare and to analyze ECG findings to predict early mortality in patients with TBI. Methods This retrospective observational study included patients with severe trauma and TBI who were admitted to the emergency department (ED) between January 2018 and December 2020. TBI was defined as an abbreviated injury scale score of the head of ≥3. We examined ECG findings, including PR prolongation (≥ 200 ms), QRS complex widening (≥ 120 ms), corrected QT interval prolongation (QTP, ≥ 480 ms), ST-segment elevation, and ST-segment depression (STD) at ED arrival. The primary outcome was 48-h mortality. Results Of the total patients with TBI, 1024 patients were included in this study and 48-h mortality occurred in 89 patients (8.7%). In multivariate analysis, QTP (odds ratio [OR], 2.017; confidence interval [CI], 1.203–3.382) and STD (OR, 8.428; 95% CI, 5.019–14.152) were independently associated with 48-h mortality in patients with TBI. The areas under the curve (AUCs) of the revised trauma score (RTS), injury severity score (ISS), QTP, STD, and the combination of QTP and STD were 0.790 (95% CI, 0.764–0.815), 0.632 (95% CI, 0.602–0.662), 0.605 (95% CI, 0.574–0.635), 0.723 (95% CI, 0.695–0.750), and 0.786 (95% CI, 0.759–0.811), respectively. The AUC of the combination of QTP and STD significantly differed from that of ISS, QTP, and STD, but not RTS. Conclusion Based on the ECG findings, QTP and STD were associated with 48-h mortality in patients with TBI.

Abstract Background Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. Methods We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients’ tissues. Results We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. Conclusions Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.

Abstract We investigated the association of extracorporeal circuit-based devices with temperature management and neurological outcome in out-of-hospital cardiac arrest survivors who underwent targeted temperature management. Patients with extracorporeal membrane oxygenation and/or continuous renal replacement therapy were classified as the extracorporeal group. We calculated the cooling rate during the induction period and time-weighted core temperatures (TWCT) during the maintenance period. We defined the sum of TWCT above or below 33 °C as positive and negative TWCT, respectively, and the sum of TWCT above 33.5 °C or below 32.5 °C as undercooling or overcooling, respectively. The primary outcome was the negative TWCT. The secondary outcomes were positive TWCT, cooling rate, undercooling, overcooling, and poor neurological outcomes, defined as Cerebral Performance Category 3–5. Among 235 patients, 150 (63.8%) had poor neurological outcomes and 52 (22.1%) were assigned to the extracorporeal group. The extracorporeal group (β, 0.307; p

Abstract Purpose To assess the performance of the post-cardiac arrest (CA) prognostication strategy algorithm recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) in 2020. Methods This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0. Unconscious patients without confounders at day 4 (72–96 h) after return of spontaneous circulation (ROSC) were included. The association between the prognostic factors included in the prognostication strategy algorithm, except status myoclonus and the neurological outcome, was investigated, and finally, the prognostic performance of the prognostication strategy algorithm was evaluated. Poor outcome was defined as cerebral performance categories 3–5 at 6 months after ROSC. Results A total of 660 patients were included in the final analysis. Of those, 108 (16.4%) patients had a good neurological outcome at 6 months after CA. The 2020 ERC/ESICM prognostication strategy algorithm identified patients with poor neurological outcome with 60.2% sensitivity (95% CI 55.9–64.4) and 100% specificity (95% CI 93.9–100) among patients who were unconscious or had a GCS_M score ≤ 3 and with 58.2% sensitivity (95% CI 53.9–62.3) and 100% specificity (95% CI 96.6–100) among unconscious patients. When two prognostic factors were combined, any combination of prognostic factors had a false positive rate (FPR) of 0 (95% CI 0–5.6 for combination of no PR/CR and poor CT, 0–30.8 for combination of No SSEP N20 and NSE 60). Conclusion The 2020 ERC/ESICM prognostication strategy algorithm predicted poor outcome without an FPR and with sensitivities of 58.2–60.2%. Any combinations of two predictors recommended by ERC/ESICM showed 0% of FPR.

Abstract The current status of 2D organic–inorganic hybrid perovskites for use in photovoltaic (PV) and light-emitting diode (LED) applications lags far behind their 3D counterparts. Here, we propose a computational strategy for discovering novel perovskites with as few computing resources as possible. A tandem optimization algorithm consisting of an elitism-reinforced nondominated sorting genetic algorithm (NSGA-II) and a multiobjective Bayesian optimization (MOBO) algorithm was used for density functional theory (DFT) calculations. The DFT-calculated band gap and effective mass were taken as objective functions to be optimized, and the constituent molecules and elements of a Ruddlesden–Popper (RP) structure (n = 2) were taken as decision variables. Fourteen previously unknown RP perovskite candidates for PV and LED applications were discovered as a result of the NSGA-II/MOBO algorithm. Thereafter, more accurate DFT calculations based on the HSE06 exchange correlation functional and ab initio molecular dynamics (AIMD) were conducted for the discovered 2D perovskites to ensure their validity.

Abstract Oligonol is a low‐molecular‐weight polyphenol product derived from lychee (Litchi chinensis Sonn.) fruits. This study was focused on the effects of oligonol on the skeletal muscle of ovariectomized rats. We randomly divided female Sprague–Dawley rats into three groups: a sham surgery control group (Sham), an ovariectomy (OVX) group, and an OVX group treated with oligonol (OVX + Oligonol). Oligonol was intraperitoneally administrated at 30 mg/kg daily for 6 weeks. Oligonol treatment after OVX decreased body weight and fat mass, regulated lipid metabolism in skeletal muscle, without loss of lean mass and bone. Bone turnover was not affected by oligonol. In protein synthesis and degradation, oligonol increased the levels of the mammalian target of rapamycin and its downstream targets, eukaryotic initiation factor 4E‐binding protein 1 and 70‐kDa ribosomal protein S6 kinase, and it stimulated the expression of ubiquitin‐proteasome pathway proteins, the forkhead box transcription factors of the class O and the muscle ring‐finger protein‐1. Moreover, oligonol treatment enhanced mitochondrial biogenesis and dynamics. Thus, our results indicated that oligonol treatment had beneficial effects on the skeletal muscle in an estrogen‐deficiency rat model.