Distinct metabolic requirements regulate B cell activation and germinal center responses.

Following infection or vaccination, activated B cells at extrafollicular sites or within germinal centers (GCs) undergo vigorous clonal proliferation. Proliferating lymphocytes have been shown to undertake lactate dehydrogenase A (LDHA)-dependent aerobic glycolysis; however, the specific role of this metabolic pathway in a B cell transitioning from a naïve to a highly proliferative, activated state remains poorly defined. Here, we deleted LDHA in a stage-specific and cell-specific manner. We find that ablation of LDHA in a naïve B cell did not profoundly affect its ability to undergo a bacterial lipopolysaccharide-induced extrafollicular B cell response. On the other hand, LDHA-deleted naïve B cells had a severe defect in their capacities to form GCs and mount GC-dependent antibody responses. In addition, loss of LDHA in T cells severely compromised B cell-dependent immune responses. Strikingly, when LDHA was deleted in activated, as opposed to naïve, B cells, there were only minimal effects on the GC reaction and in the generation of high-affinity antibodies. These findings strongly suggest that naïve and activated B cells have distinct metabolic requirements that are further regulated by niche and cellular interactions.

TBL1XR1 Mutations Drive Extranodal Lymphoma by Inducing a Pro-tumorigenic Memory Fate.

The most aggressive B cell lymphomas frequently manifest extranodal distribution and carry somatic mutations in the poorly characterized gene TBL1XR1. Here, we show that TBL1XR1 mutations skew the humoral immune response toward generating abnormal immature memory B cells (MB), while impairing plasma cell differentiation. At the molecular level, TBL1XR1 mutants co-opt SMRT/HDAC3 repressor complexes toward binding the MB cell transcription factor (TF) BACH2 at the expense of the germinal center (GC) TF BCL6, leading to pre-memory transcriptional reprogramming and cell-fate bias. Upon antigen recall, TBL1XR1 mutant MB cells fail to differentiate into plasma cells and instead preferentially reenter new GC reactions, providing evidence for a cyclic reentry lymphomagenesis mechanism. Ultimately, TBL1XR1 alterations lead to a striking extranodal immunoblastic lymphoma phenotype that mimics the human disease. Both human and murine lymphomas feature expanded MB-like cell populations, consistent with a MB-cell origin and delineating an unforeseen pathway for malignant transformation of the immune system.

A Hyper-IgM Syndrome Mutation in Activation-Induced Cytidine Deaminase Disrupts G-Quadruplex Binding and Genome-wide Chromatin Localization.

Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci promotes antibody class switch recombination (CSR) and somatic hypermutation (SHM), whereas AID targeting of non-Ig loci can generate oncogenic DNA lesions. Here, we examined the contribution of G-quadruplex (G4) nucleic acid structures to AID targeting in vivo. Mice bearing a mutation in Aicda (AIDG133V) that disrupts AID-G4 binding modeled the pathology of hyper-IgM syndrome patients with an orthologous mutation, lacked CSR and SHM, and had broad defects in genome-wide AIDG133V chromatin localization. Genome-wide analyses also revealed that wild-type AID localized to MHCII genes, and AID expression correlated with decreased MHCII expression in germinal center B cells and diffuse large B cell lymphoma. Our findings indicate a crucial role for G4 binding in AID targeting and suggest that AID activity may extend beyond Ig loci to regulate the expression of genes relevant to the physiology and pathology of activated B cells.

Multiflagellarity leads to the size-independent swimming speed of peritrichous bacteria.

To swim through a viscous fluid, a flagellated bacterium must overcome the fluid drag on its body by rotating a flagellum or a bundle of multiple flagella. Because the drag increases with the size of bacteria, it is expected theoretically that the swimming speed of a bacterium inversely correlates with its body length. Nevertheless, despite extensive research, the fundamental size-speed relation of flagellated bacteria remains unclear with different experiments reporting conflicting results. Here, by critically reviewing the existing evidence and synergizing our own experiments of large sample sizes, hydrodynamic modeling, and simulations, we demonstrate that the average swimming speed of Escherichia coli, a premier model of peritrichous bacteria, is independent of their body length. Our quantitative analysis shows that such a counterintuitive relation is the consequence of the collective flagellar dynamics dictated by the linear correlation between the body length and the number of flagella of bacteria. Notably, our study reveals how bacteria utilize the increasing number of flagella to regulate the flagellar motor load. The collective load sharing among multiple flagella results in a lower load on each flagellar motor and therefore faster flagellar rotation, which compensates for the higher fluid drag on the longer bodies of bacteria. Without this balancing mechanism, the swimming speed of monotrichous bacteria generically decreases with increasing body length, a feature limiting the size variation of the bacteria. Altogether, our study resolves a long-standing controversy over the size-speed relation of flagellated bacteria and provides insights into the functional benefit of multiflagellarity in bacteria.

Reinforcement of Positive Electrode-Electrolyte Interface without Using Electrolyte Additives Through Thermoelectrochemical Oxidation of LiPF6 for Lithium Secondary Batteries.

Owing to the limited electrochemical stability window of carbonate electrolytes, the initial formation of a solid electrolyte interphase and surface film on the negative and positive electrode surfaces by the decomposition of the electrolyte component is inevitable for the operation of lithium secondary batteries. The deposited film on the surface of the active material is vital for reducing further electrochemical side reactions at the surface; hence, the manipulation of this formation process is necessary for the appropriate operation of the assembled battery system. In this study, the thermal decomposition of LiPF6 salt is used as a surface passivation agent, which is autocatalytically formed during high-temperature storage. The thermally formed difluorophosphoric acid is subsequently oxidized on the partially charged high-Ni positive electrode surface, which improves the cycleability of lithium metal cells via phosphorus- and fluorine-based surface film formation. Moreover, the improvement in the high-temperature cycleability is demonstrated by controlling the formation process in the lithium-ion pouch cell with a short period of high-temperature storage before battery usage.

Evaluation of bovine coronavirus in Korean native calves challenged through different inoculation routes.

Bovine coronavirus (BCoV) is a pneumoenteric virus that can infect the digestive and respiratory tracts of cattle, resulting in economic losses. Despite its significance, information regarding BCoV pathogenesis is limited. Hence, we investigated clinical signs, patterns of viral shedding, changes in antibody abundance, and cytokine/chemokine production in calves inoculated with BCoV via intranasal and oral. Six clinically healthy Korean native calves (< 30 days old), initially negative for BCoV, were divided into intranasal and oral groups and monitored for 15 days post-infection (dpi). BCoV-infected calves exhibited clinical signs such as nasal discharge and diarrhea, starting at 3 dpi and recovering by 12 dpi, with nasal discharge being the most common symptoms. Viral RNA was detected in nasal and fecal samples from all infected calves. Nasal shedding occurred before fecal shedding regardless of the inoculation route; however, fecal shedding persisted longer. Although the number of partitions was very few, viral RNA was identified in the blood of two calves in the oral group at 7 dpi and 9 dpi using digital RT-PCR analysis. The effectiveness of maternal antibodies in preventing viral replication and shedding appeared limited. Our results showed interleukin (IL)-8 as the most common and highly induced chemokine. During BCoV infection, the levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß were significantly affected, suggesting that these emerge as potential and reliable biomarkers for predicting BCoV infection. This study underscores the importance of BCoV as a major pathogen causing diarrhea and respiratory disease.

Determining lactate concentrations in Korean indigenous calves and evaluating its role as a predictor for acidemia in calf diarrhea.

BACKGROUND: Calf diarrhea leads to high mortality rates and decreases in growth and productivity, causing negative effects on the livestock industry. Lactate is closely associated with metabolic acidosis in diarrheic calves. However, there have been no reports on lactate concentrations in Korean indigenous (Hanwoo) calves, especially those with diarrhea. This study aimed to determine the reference range of L-lactate and D-lactate concentrations in Hanwoo calves and to better understand the utility of lactate as predictive factors for acidemia in diarrheic calves. RESULTS: L-lactate and D-lactate concentrations were measured in healthy (n = 44) and diarrheic (n = 93) calves, and blood gas analysis was performed on diarrheic calves. The reference range in healthy calves was 0.2-2.25 mmol/L for L-lactate and 0.42-1.38 mmol/L for D-lactate. Diarrheic calves had higher concentrations of L-lactate and D-lactate than healthy calves. In diarrheic calves, L-lactate and D-lactate each had weak negative correlation with pH (r = - 0.31 and r = - 0.35). In diarrheic calves with hyper-L-lactatemia, the combined concentrations of L-lactate and D-lactate had moderate correlation with pH (r = - 0.51) and anion gap (r = 0.55). Receiver operating characteristic analysis showed D-lactate had fair predictive performance (AUC = 0.74) for severe acidemia, with an optimal cut-off value of > 1.43 mmol/L. The combined concentrations of L-lactate and D-lactate showed fair predictive performance for predicting acidemia (AUC = 0.74) and severe acidemia (AUC = 0.72), with cut-off values of > 6.05 mmol/L and > 5.95 mmol/L. CONCLUSIONS: The determined reference ranges for L-lactate and D-lactate in Hanwoo calves enable the identification of hyper-L-lactatemia and hyper-D-lactatemia. Diarrheic calves exhibited increased lactate concentrations correlated with acid-base parameters. While the concentrations of L-lactate and D-lactate have limitations as single diagnostic biomarkers for predicting acidemia or severe acidemia, their measurement remains important, and L-lactate has the advantage of being measurable at the point-of-care. Assessing lactate concentrations should be considered by clinicians, especially when used alongside other clinical indicators and diagnostic tests. This approach can improve calf diarrhea management, contributing positively to animal welfare and providing economic benefits to farms.

Preliminary report of Mycoplasma Wenoynii and Candidatus Mycoplasma haemobos infection in Korean native cattle.

BACKGROUND: Hemotropic mycoplasmas or hemoplasmas are bacteria that attach to the erythrocyte surface and cause bovine hemoplasmosis. Two species, Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, have been identified and shown to be distributed worldwide. However, there is currently no information available on hemoplasmas in cattle in the Republic of Korea. The aim of this study was to investigate the presence of hemoplasmas in Korean native cattle and to evaluate the association between hemoplasma infection and anemia. METHODS: One farm was selected, at which blood samples were collected from 104 Korean native cattle [grazing cattle (n = 89) and housed cattle (n = 15)]. Hemoplasmas were detected via polymerase chain reaction analysis and complete blood counts were also performed. RESULTS: The overall prevalence of hemoplasmas was 34% (35/104); 20.2% (21/104) for M. wenyonii, 3.8% (4/104) for C. M. haemobos, and 9.6% (10/104) for co-infection. Candidatus Mycoplasma haemobos was detected only in grazing cattle. Of red blood cell (RBC) parameters, C. M. haemobos-infected cattle had lower RBC and hematocrit, and higher mean cell volume than hemoplasma-negative cattle, although none of these differences were statistically significant. This is the first study to report the occurrence of M. wenyonii and C. M. haemobos. Mycoplasma wenyonii is more prevalent than C. M. haemobos in Korean native cattle. The results did not show an association between hemoplasma infection and anemia. CONCLUSIONS: Considering the infection rate of hemoplasmas shown in this study, further studies, such as on the pathogenicity and clinical significance of hemoplasmas are necessary.

Reducing contact resistance of MoS2-based field effect transistors through uniform interlayer insertion via atomic layer deposition.

Molybdenum disulfide (MoS2), a semiconducting two-dimensional layered transition metal dichalcogenide (2D TMDC), with attractive properties enables the opening of a new electronics era beyond Si. However, the notoriously high contact resistance (RC) regardless of the electrode metal has been a major challenge in the practical applications of MoS2-based electronics. Moreover, it is difficult to lower RC because the conventional doping technique is unsuitable for MoS2 due to its ultrathin nature. Therefore, the metal-insulator-semiconductor (MIS) architecture has been proposed as a method to fabricate a reliable and stable contact with low RC. Herein, we introduce a strategy to fabricate MIS contact based on atomic layer deposition (ALD) to dramatically reduce the RC of single-layer MoS2 field effect transistors (FETs). We utilize ALD Al2O3 as an interlayer for the MIS contact of bottom-gated MoS2 FETs. Based on the Langmuir isotherm, the uniformity of ALD Al2O3 films on MoS2 can be increased by modulating the precursor injection pressures even at low temperatures of 150 °C. We discovered, for the first time, that film uniformity critically affects RC without altering the film thickness. Additionally, we can add functionality to the uniform interlayer by adopting isopropyl alcohol (IPA) as an oxidant. Tunneling resistance across the MIS contact is lowered by n-type doping of MoS2 induced by IPA as the oxidant in the ALD process. Through a highly uniform interlayer combined with strong doping, the contact resistance is improved by more than two orders of magnitude compared to that of other MoS2 FETs fabricated in this study.

Impact of product packaging messages on consumer perceptions and choice: The role of health claims and bonus pack promotions.

This study used mixed methods to explore the impact of front-of-package health claims and bonus pack messages on consumer evaluations. First, a comprehensive audit of cereal box packages at the world's largest retailer examined how these messages are presented in practice. It was found that negative claims are more frequent and positive claims are less frequent on products with a bonus pack message compared to those without. A subsequent experiment investigated how combinations of health claims and bonus pack messages influence consumer evaluations. It also found that health claims significantly influenced consumer preferences, while bonus pack messages diminished perceptions of food healthiness but increased perceived value. Pairing positive health claims with bonus pack messages, such as "Family Size," improved perceptions of healthiness. Moreover, positive health claims made products seem of lower value, whereas negative health claims did not affect perceived value. Health claims negatively affected value perceptions, even when paired with bonus pack messages like "Large Size." However, the negative effect of health claims on tastiness perceptions was mitigated with "Large Size". The study underscores the complexity of consumer decision-making, and offer insights for food marketers, emphasizing the need of a strategic approach in crafting health-related messaging and promotional strategies for product packaging.

Shallow trochlear groove and narrow medial trochlear width at the proximal trochlea in patients with trochlear dysplasia: A three-dimensional computed tomography analysis.

PURPOSE: Although the Dejour classification is the primary classification system for evaluating trochlear dysplasia, concerns have been raised about its reliability owing to its qualitative criteria and challenges associated with obtaining accurate radiographs. This study aimed to quantify trochlear dysplasia using three-dimensional (3D) computed tomography (CT) reconstruction with novel parameters related to the transepicondylar axis (TEA). METHODS: Sixty patients were enrolled, including 20 with trochlear dysplasia and 40 healthy controls. The 3D CT model was generated using the Materialise Interactive Medical Image Control System software. The following six parameters were measured in eight consecutive planes at 15° intervals (planes 0-105): the distance from the TEA to the most cortical point of the lateral condyle ('LP-TEA', where LP stands for lateral peak), medial condyle ('MP-TEA', MP for medial peak) and deepest point of the trochlea ('TG-TEA', TG for trochlear groove). The distances from the medial epicondyle (MEC) to the corresponding TEA points were measured ('LP-MEC', 'MP-MEC' and 'TG-MEC'). RESULTS: In the dysplasia group, TG-TEA (planes 0, 15 and 30) and MP-MEC (planes 0, 15 and 30) were significantly greater than those in the control group (all p < 0.05 for planes of TG-TEA and MP-MEC). For type A dysplasia, LP-MEC (plane 0) was greater than that in the control group. For type B dysplasia, the MP-MEC (planes 0 and 15) and TG-TEA (planes 0 and 15) were greater than those of the control group. For type D dysplasia, MP-MEC (planes 0, 15 and 30) and TG-TEA (planes 0 and 15) were elevated. CONCLUSION: The 3D CT reconstruction analysis established a reproducible method for quantifying osseous trochlear morphology. Patients with trochlear dysplasia had a shallow TG and narrow medial trochlear width at tracking angles of 0°-30°. This finding corroborates the clinical manifestations of recurrent patellar instability that occur during early flexion. LEVEL OF EVIDENCE: Level III.

Priority-Aware Actuation Update Scheme in Heterogeneous Industrial Networks.

In heterogeneous wireless networked control systems (WNCSs), the age of information (AoI) of the actuation update and actuation update cost are important performance metrics. To reduce the monetary cost, the control system can wait for the availability of a WiFi network for the actuator and then conduct the update using a WiFi network in an opportunistic manner, but this leads to an increased AoI of the actuation update. In addition, since there are different AoI requirements according to the control priorities (i.e., robustness of AoI of the actuation update), these need to be considered when delivering the actuation update. To jointly consider the monetary cost and AoI with priority, this paper proposes a priority-aware actuation update scheme (PAUS) where the control system decides whether to deliver or delay the actuation update to the actuator. For the optimal decision, we formulate a Markov decision process model and derive the optimal policy based on Q-learning, which aims to maximize the average reward that implies the balance between the monetary cost and AoI with priority. Simulation results demonstrate that the PAUS outperforms the comparison schemes in terms of the average reward under various settings.

Effects of Sling-Suspension-Based Active Shoulder Joint Exercise on Shoulder Joint Subluxation, Pain, Muscle Strength, and Upper Limb Function in Patients with Subacute Stroke.

Background and Objectives: We investigated the effects of sling-suspension-based active shoulder joint exercise training on shoulder joint subluxation, pain, muscle strength, and upper extremity function in patients with subacute stroke. Materials and Methods: Twenty-eight patients with subacute stroke were randomly assigned to either the sling-suspension-based active shoulder joint exercise (SASE) group (n = 14) or the motorized upper extremity exercise (MUEE) group (n = 14). The SASE group actively performed shoulder joint flexion, extension, abduction, adduction, external and internal rotation, and horizontal abduction and adduction using a sling suspension system, whereas the MUEE group underwent an exercise program using a motorized upper extremity exercise machine. All participants underwent a 4-week intervention with 30 min of exercise once a day for 5 days a week. Additionally, both groups received general physical therapy and functional electrical stimulation for 30 min twice a day for 5 days a week. Shoulder joint subluxation was measured by radiographic examination before and after training, and pain was evaluated in the splenius, upper trapezius, and infraspinatus muscles using pressure parameters. In addition, a manual muscle tester was used to assess the muscle strength of the shoulder joint flexors, extensors, abductors, adductors, and external and internal rotators, and the Fugl-Mayer Assessment (FMA) and Manual Functional Test (MFT) were used to evaluate upper extremity function. Results: A significant group-time interaction was observed for pain, with F-values of F(1, 26) = 7.470, p < 0.011 for the splenius and F(1, 26) = 9.623, p < 0.005 for the upper trapezius. A significant time-group interaction was observed for the muscle strength of the shoulder, with F-values of F(1, 26) = 13.211, p < 0.001; F(1, 26) = 4.974, p = 0.035 and F(1, 26) = 9.674, p = 0.004 for flexors, abductors, and external rotators, respectively. A significant time-group interaction was observed in the FMA, with F-values of F(1, 26) = 13.243, p < 0.001. When comparing the interaction effects between time and group for MFT scores, a significant difference was observed, with F-values of F(1, 26) = 32.386, p < 0.001. Conclusions: This study confirmed that sling-suspension-based active shoulder joint exercises are effective in improving shoulder joint subluxation, pain, muscle strength, and upper extremity function in patients with subacute stroke.

Comparison between arthroscopic suture anchor fixation and open plate fixation in the greater tuberosity fracture of the proximal humerus.

INTRODUCTION: The purpose of this study is to compare the clinical and radiological outcomes of patients undergoing open reduction and internal fixation (OR/IF) using a plate or patients undergoing an arthroscopic suture anchor fixation for the greater tuberosity (GT) fracture of the proximal humerus. The purpose of this study is to compare the clinical and radiological outcomes of patients undergoing OR/IF or an arthroscopic suture anchor fixation for the GT fracture. MATERIALS AND METHODS: Between January, 2010 and December, 2020, 122 patients with GT fracture underwent operative fixation. Either OR/IF using proximal humeral locking plate (50 patients) or arthroscopic suture anchor (72 patients) fixation was performed. Fourteen patients were lost to follow-up and finally, 108 patients were enrolled in this study. We divided these patients into two groups: (1) OR/IF group (Group I: 44 patients) and arthroscopic anchor fixation group (Group II: 64 patients). The primary outcome was subjective shoulder function (shoulder functional scale). Secondary outcomes were range of motion, and complications including GT fixation failure, fracture migration, or neurologic complication. Also, age, sex, BMI, operation time, shoulder dislocation, fracture comminution, AP (anteroposterior), SI (superoinferior) size and displacement were evaluated and compared between two groups. RESULTS: Both groups showed satisfactory clinical and radiological outcomes at mid-term follow-up. Between 2 groups, there were no significant differences in age, sex, BMI, presence of shoulder dislocation or comminution. Group II showed higher clinical scores except VAS score (p < 0.05) and longer surgical times (95.3 vs. 61.5 min). Largest fracture displacement (Group I vs. II: SI displacement: 40 vs. 13 mm, and AP displacement: 49 vs. 11 mm) and higher complication rate (p = 0.049) was found in Group I. CONCLUSIONS: Both arthroscopic anchor fixation and open plate fixation methods showed satisfactory outcomes at mid-term follow-up. Among them, OR/IF is preferred for larger fracture displacement (> 5 mm) and shorter operation time However, arthroscopic anchor fixation group showed better clinical outcomes and less complications than the OR/IF group. LEVEL OF EVIDENCE: Level 4, Case series with subgroup analysis.

Frequency of actionable secondary findings in 7472 Korean genomes derived from the National Project of Bio Big Data pilot study.

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.

Critical Factors to Understanding the Electrochemical Performance of All-Solid-State Batteries: Solid Interfaces and Non-Zero Lattice Strain.

All-solid-state lithium batteries have been developed to secure safety by substituting a flammable liquid electrolyte with a non-flammable solid electrolyte. However, owing to the nature of solids, interfacial issues between cathode materials and solid electrolytes, including chemical incompatibility, electrochemo-mechanical behavior, and physical contact, pose significant challenges for commercialization. Herein, critical factors for understanding the performance of all-solid-state batteries in terms of solid interfaces and non-zero lattice strains are identified through a strategic approach. The initial battery capacity can be increased via surface coating and electrode-fabrication methods; however, the increased lattice strain causes significant stress to the solid interface, which degrades the battery cycle life. However, this seesaw effect can be alleviated using a more compacted electrode microstructure between the solid electrolyte and oxide cathode materials. The compact solid interfaces contribute to low charge-transfer resistance and a homogeneous reaction between particles, thereby leading to improved electrochemical performance. These findings demonstrate, for the first time, a correlation between the uniformity of the electrode microstructure and electrochemical performance through the investigation of the reaction homogeneity among particles. Additionally, this study furthers the understanding of the relationship between electrochemical performance, non-zero lattice strain, and solid interfaces.

A graphitic nano-onion/molybdenum disulfide nanosheet composite as a platform for HPV-associated cancer-detecting DNA biosensors.

An electrochemical DNA sensor that can detect human papillomavirus (HPV)-16 and HPV-18 for the early diagnosis of cervical cancer was developed by using a graphitic nano-onion/molybdenum disulfide (MoS2) nanosheet composite. The electrode surface for probing DNA chemisorption was prepared via chemical conjugation between acyl bonds on the surfaces of functionalized nanoonions and the amine groups on functionalized MoS2 nanosheets. The cyclic voltammetry profile of an 1:1 nanoonion/MoS2 nanosheet composite electrode had an improved rectangular shape compared to that of an MoS2 nanosheet elecrode, thereby indicating the amorphous nature of the nano-onions with sp2 distancing curved carbon layers that provide enhanced electronic conductivity, compared to MoS2 nanosheet only. The nanoonion/MoS2 sensor for the DNA detection of HPV-16 and HPV-18, respectively, was measured at high sensitivity through differential pulse voltammetry (DPV) in the presence of methylene blue (MB) as a redox indicator. The DPV current peak was lowered after probe DNA chemisorption and target DNA hybridization because the hybridized DNA induced less effective MB electrostatic intercalation due to it being double-stranded, resulting in a lower oxidation peak. The nanoonion/MoS2 nanosheet composite electrodes attained higher current peaks than the MoS2 nanosheet electrode, thereby indicating a greater change in the differential peak probably because the nanoonions enhanced conductive electron transfer. Notably, both of the target DNAs produced from HPV-18 and HPV-16 Siha and Hela cancer cell lines were effectively detected with high specificity. The conductivity of MoS2 improved by complexation with nano-onions provides a suitable platform for electrochemical biosensors for the early diagnosis of many ailments in humans.

Olfactory Dysfunction and its Course in Patients With Nasal Bone Fracture.

PURPOSE: Nasal bone fractures are the most common facial bone fractures. Although olfactory dysfunction is one of the most common complications in patients with nasal bone fractures, few studies on olfactory dysfunction in nasal bone fractures have been reported. The authors attempted to find the frequency and course of olfactory dysfunction and hypothesize its mechanism in patients with nasal bone fractures. METHODS: Sixty-six patients who underwent closed reduction were examined using the Korean version of Sniffin' Sticks test (KVSS) II at preoperation, 1 month and 6 months postoperation. We categorized 30 points or more as "normosmia," 15 points or less as "anosmia," and the scores between them as "hyposmia." The authors only performed test in patients who subjectively complained of their loss of sense of smell at 1 and 6 months postoperation. RESULTS: The authors classified the patients as "olfactory dysfunction" or "normal olfaction" using the Threshold-Discrimination-Identification score and subjective complaint of symptom. Olfactory dysfunction was seen on 31 of 66 patients (46.9%) preoperatively. Twenty-four patients (36.3%) showed olfactory dysfunction at 1 month postoperation, and 4 patients (6.0%) showed olfactory dysfunction at 6 months postoperation. Twelve of the 35 patients (34.3%) with normosmia shown in the preoperation had new olfactory dysfunction after the surgery. CONCLUSION: Olfactory dysfunction is common complication in nasal bone fracture. However, this complication was recovered in most cases (93.9%). In addition, patients should receive explanations about the possibility of iatrogenic olfactory impairment after surgery, and a gentle maneuver is helpful for preventing iatrogenic damage.

Multiscale Cumulative Residual Dispersion Entropy with Applications to Cardiovascular Signals.

Heart rate variability (HRV) is used as an index reflecting the adaptability of the autonomic nervous system to external stimuli and can be used to detect various heart diseases. Since HRVs are the time series signal with nonlinear property, entropy has been an attractive analysis method. Among the various entropy methods, dispersion entropy (DE) has been preferred due to its ability to quantify the time series' underlying complexity with low computational cost. However, the order between patterns is not considered in the probability distribution of dispersion patterns for computing the DE value. Here, a multiscale cumulative residual dispersion entropy (MCRDE), which employs a cumulative residual entropy and DE estimation in multiple temporal scales, is presented. Thus, a generalized and fast estimation of complexity in temporal structures is inherited in the proposed MCRDE. To verify the performance of the proposed MCRDE, the complexity of inter-beat interval obtained from ECG signals of congestive heart failure (CHF), atrial fibrillation (AF), and the healthy group was compared. The experimental results show that MCRDE is more capable of quantifying physiological conditions than preceding multiscale entropy methods in that MCRDE achieves more statistically significant cases in terms of p-value from the Mann-Whitney test.

Sclerostin in periodontal ligament: Homeostatic regulator in biophysical force-induced tooth movement.

AIM: To study the role of sclerostin in periodontal ligament (PDL) as a homeostatic regulator in biophysical-force-induced tooth movement (BFTM). MATERIALS AND METHODS: BFTM was performed in rats, followed by microarray, immunofluorescence, in situ hybridization, and real-time polymerase chain reaction for the detection and identification of the molecules. The periodontal space was analysed via micro-computed tomography. Effects on osteoclastogenesis and bone resorption were evaluated in the bone-marrow-derived cells in mice. In vitro human PDL cells were subjected to biophysical forces. RESULTS: In the absence of BFTM, sclerostin was hardly detected in the periodontium except in the PDL and alveolar bone in the furcation region and apex of the molar roots. However, sclerostin was up-regulated in the PDL in vivo by adaptable force, which induced typical transfiguration without changes in periodontal space as well as in vitro PDL cells under compression and tension. In contrast, the sclerostin level was unaffected by heavy force, which caused severe degeneration of the PDL and narrowed periodontal space. Sclerostin inhibited osteoclastogenesis and bone resorption, which corroborates the accelerated tooth movement by the heavy force. CONCLUSIONS: Sclerostin in PDL may be a key homeostatic molecule in the periodontium and a biological target for the therapeutic modulation of BFTM.