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The bioartificial liver (BAL) system can potentially rescue acute liver failure (ALF) patients by providing partial liver function until a suitable donor liver can be found or the native liver has self-regenerated. In this study, we established a suitable cryopreservation process for the development of an off-the-shelf BAL system. The viability of hepatocyte spheroids cryopreserved in liquid nitrogen was comparable to that of fresh primary hepatocyte spheroids. When hepatocyte spheroids were subjected to cryopreservation in a deep freezer, no statistically significant differences were observed in ammonia removal rate or urea secretion rate based on the cryopreservation period. However, the functional activity of the liver post-cryopreservation in a deep freezer was significantly lower than that observed following liquid nitrogen cryopreservation. Moreover, cryopreserving spheroid hydrogel beads in a deep freezer resulted in a significant decrease (approximately 30%) in both ammonia removal and urea secretion rates compared to the group cryopreserved in liquid nitrogen. The viabilities of spheroid hydrogel beads filled into the bioreactor of a BAL system were similar across all four groups. However, upon operating the BAL system for 24 h, the liver function activity was significantly higher in the group comprising hydrogel beads generated after thawing hepatocyte spheroids cryopreserved in liquid nitrogen. Consequently, the manufacturing of beads after the cryopreservation of hepatocyte spheroids is deemed the most suitable method, considering efficiency, economic feasibility, and liver function activity, for producing a BAL system. [ABSTRACT FROM AUTHOR]

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell–neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review. [ABSTRACT FROM AUTHOR]

Aims: This study determined the optimal positive end‐expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). Methods: This prospective observational single‐centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end‐expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end‐expiratory pressure in the prone position was similarly determined. Results: Data from 30 infants were analyzed. The mean value of electrical impedance tomography‐based optimal positive end‐expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p <.001)]. Significant differences were observed between electrical impedance tomography‐ and compliance‐based optimal positive end‐expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. Conclusion: The prone position required higher positive end‐expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end‐expiratory pressure, which needs to be individualized. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS. Key messages: Serum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients. Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS. CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control. Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS. [ABSTRACT FROM AUTHOR]

Rationale: The demand for weight loss products is increasing as slimness emerges as the new aesthetic standard and people's desire to achieve it increases. In addition, the distribution and sale of products containing illegal ingredients, pharmaceuticals, and chemicals for which safety is not guaranteed and that cannot be used as foods or dietary supplements are increasing. Thus, the development of an analytical method that could monitor these illegal products is required. Methods: A high‐performance liquid chromatography‐photodiode array method capable of rapid and reliable qualitative and quantitative analyses of 43 weight loss agents was established and validated. Results: The process involved dividing analytes into three groups for rapid analysis; when bisacodyl was mixed with chlorocyclopentylsibutramine, it decomposed into its metabolites: monoacetyl bisacodyl and bis‐(p‐hydroxypheny)‐pyridyl‐2‐methane. This decomposition was due to NaOH that was used to prepare the chlorocyclopentylsibutramine standard solution. Bisacodyl did not degrade when mixed with neutralized chlorocyclopentylsibutramine, whereas when NaOH was added, it rapidly degraded. We identified the bisacodyl degradation products using liquid chromatography‐quadrupole‐Orbitrap/mass spectrometry. MS2 spectra with proposed structures of fragment peaks were also obtained. Conclusions: The developed method could be used to regulate slimming products that threaten public health, and knowledge of bisacodyl degradation will be used as the basis for developing an analytic method. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of prolonged residual subretinal fluid (SRF) on the outcomes of aflibercept treatment in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods: This retrospective study included patients diagnosed with neovascular AMD or PCV who presented with fovea-involving residual SRF that persisted for a minimum of 6 months while undergoing aflibercept treatment. Changes in best-corrected visual acuity (BCVA) during persistent SRF were evaluated. The factors associated with the risk of visual deterioration during this period were also investigated. Results: In total, 135 patients were included in this study. During this period, the duration of the presence of residual SRF was 17.1 ± 10.3 months and mean injection interval was 2.6 ± 0.7 months. The mean BCVA was changed from 0.30 ± 0.23(Snellen equivalents, 20/39) to 0.36 ± 0.28 (20/45). In 18 (13.3%) patients, ≥2 lines of visual deterioration was noted. The duration of persisting SRF (P = 0.008) and mean height of SRF (P = 0.005) were significantly associated with a high risk of visual deterioration. Among the 80 patients with mean SRF height <100 μm, ≥2 lines of visual deterioration were noted in 4 (5.0%) patients. Among 41 patients with the mean SRF height ≥100 μm and <200 μm and 14 patients with the mean SRF height ≥200 μm, the visual deterioration was noted in 8 (19.5%) and 6 (42.9%) patients, respectively. Conclusions: In cases of neovascular AMD or PCV in which SRF persists without complete resolution during treatment, minimizing the duration of persistent SRF and mean height of SRF is recommended to mitigate the risk of visual deterioration. ClinicalTrials.gov Identifiers: NCT05662943 (https://clinicaltrials.gov/study/NCT05662943?cond=type%201%20macular%20neovascularization&rank=2). [ABSTRACT FROM AUTHOR]

Summary: Given the significant impact of sleep on overall health, radar technology offers a promising, non‐invasive, and cost‐effective avenue for the early detection of sleep disorders, even prior to relying on polysomnography (PSG)‐based classification. In this study, we employed an attention‐based bidirectional long short‐term memory (Attention Bi‐LSTM) model to accurately predict sleep stages using 60 GHz frequency‐modulated continuous‐wave (FMCW) radar. Our dataset comprised 78 participants from an ongoing obstructive sleep apnea (OSA) cohort, recruited between July 2021 and November 2022, who underwent overnight polysomnography alongside radar sensor monitoring. The dataset encompasses comprehensive polysomnography recordings, spanning both sleep and wakefulness states. The predictions achieved a Cohen's kappa coefficient of 0.746 and an overall accuracy of 85.2% in classifying wakefulness, rapid‐eye‐movement (REM) sleep, and non‐REM (NREM) sleep (N1 + N2 + N3). The results demonstrated that the models incorporating both Radar 1 and Radar 2 data consistently outperformed those using only Radar 1 data, indicating the potential benefits of utilising multiple radars for sleep stage classification. Although the performance of the models tended to decline with increasing OSA severity, the addition of Radar 2 data notably improved the classification accuracy. These findings demonstrate the potential of radar technology as a valuable screening tool for sleep stage classification. [ABSTRACT FROM AUTHOR]

The yes-associated protein (YAP) of the Hippo pathway regulates a variety of target genes involved in cell proliferation, survival, and inflammation. YAP and transcription activator with a PDZ-binding motif (TAZ) proteins act as mediators of the inflammatory response. Still, their role in atopic dermatitis (AD)—particularly, the association with the nuclear factor kappa-B and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways—is not fully understood. In this study, we found that YAP, is upregulated in AD patients and NC/Nga mouse model of AD. In addition, inhibition of YAP significantly reduced epidermal cell proliferation by 58% and mast cell numbers by 51% and attenuated the upregulation of both Th1- and Th2-associated cytokines. Among the JAK-STAT family proteins, the expressions of JAK1 and JAK2 and those of STAT1, STAT2, and STAT3 were also downregulated. These findings may explain the role of YAP in AD and suggest YAP inhibitors as promising therapeutic agents for AD. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the morphology of the three parts of the infraspinatus muscle based on surface landmarks for precise and effective access, and to propose the most effective fine-wire electrode insertion technique and sites. Methods: Fifteen Asian fresh cadavers were used. We investigated the probability of the presence of the superior, middle, and inferior parts in each infraspinatus muscle based on surface landmarks. Based on the positional characteristics of the muscle, we determined the needle insertion method and confirmed its effectiveness by dissection. Results: The superior part was mostly observed near the spine of the scapula. The middle part was broadly observed within the infraspinous fossa. The inferior part showed variable location within the infraspinous fossa. The injection accuracy of the superior, middle, and inferior parts in the infraspinatus muscle was 95.8%, 100%, and 91.7%, respectively. Targeting the superior and middle parts for injection of the infraspinatus muscle is relatively more straightforward than targeting the inferior part. Targeting the inferior part of the infraspinatus muscle in this study was more challenging than targeting the superior and middle parts. Conclusion: Needling for electromyography should be performed with special care to avoid unintended muscle parts, which could lead to inaccurate data acquisition and affect the conclusions about muscle function. [ABSTRACT FROM AUTHOR]

The therapeutic application of cannabinoids has gained traction in recent years. Cannabinoids interact with the human endocannabinoid system in the skin. A large body of research indicates that cannabinoids could hold promise for the treatment of eczema, psoriasis, acne, pruritus, hair disorders, and skin cancer. However, most of the available data are at the preclinical stage. Comprehensive, large-scale, randomized, controlled clinical trials have not yet been fully conducted. In this article, we describe new findings in cannabinoid research and point out promising future research areas. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) are the main contributors to the development and progression of liver fibrosis. Parkin is an E3 ligase involved in mitophagy mediated by lysosomes that maintains mitochondrial homeostasis. Unfortunately, there is little information regarding the regulation of parkin by transforming growth factor-β (TGF-β) and its association with HSC trans-differentiation. This study showed that parkin is upregulated in fibrotic conditions and elucidated the underlying mechanism. Parkin was observed in the cirrhotic region of the patient liver tissues and visualized using immunostaining and immunoblotting of mouse fibrotic liver samples and primary HSCs. The role of parkin-mediated mitophagy in hepatic fibrogenesis was examined using TGF-β-treated LX-2 cells with mitophagy inhibitor, mitochondrial division inhibitor 1. Parkin overexpression and its colocalization with desmin in human tissues were found. Increased parkin in fibrotic liver homogenates of mice was observed. Parkin was expressed more abundantly in HSCs than in hepatocytes and was upregulated under TGF-β. TGF-β-induced parkin was due to Smad3. TGF-β facilitated mitochondrial translocation, leading to mitophagy activation, reversed by mitophagy inhibitor. However, TGF-β did not change mitochondrial function. Mitophagy inhibitor suppressed profibrotic genes and HSC migration mediated by TGF-β. Collectively, parkin-involved mitophagy by TGF-β facilitates HSC activation, suggesting mitophagy may utilize targets for liver fibrosis. [ABSTRACT FROM AUTHOR]

Pectoralis Minor Syndrome (PMS) causes significant discomfort due to the compression of the neurovascular bundle within the retropectoralis minor space. Botulinum neurotoxin (BoNT) injections have emerged as a potential treatment method; however, their effectiveness depends on accurately locating the injection site. In this study, we aimed to identify optimal BoNT injection sites for PMS treatment. We used twenty-nine embalmed and eight non-embalmed human cadavers to determine the origin and intramuscular arborization of the pectoralis minor muscle (Pm) via manual dissection and Sihler's nerve staining techniques. Our findings showed the Pm's origin near an oblique line through the suprasternal notch, with most neural arborization within the proximal three-fourths of the Pm. Blind dye injections validated these results, effectively targeting the primary neural arborized area of the Pm at the oblique line's intersection with the second and third ribs. We propose BoNT injections at the arborized region within the Pm's proximal three-fourths, or the C region, for PMS treatment. These findings guide clinicians towards safer, more effective BoNT injections. [ABSTRACT FROM AUTHOR]

Myofascial pain syndrome caused by myofascial trigger points is a musculoskeletal disorder commonly encountered in clinical practice. The infraspinatus muscle is the region most frequently involved in the myofascial pain syndrome in the scapular region. The characteristics of the myofascial trigger points are that they can be found constantly in the motor endplate zone. However, localizing myofascial trigger points within the motor endplate zone and establishing an accurate injection site of the infraspinatus muscle has been challenging because the anatomical position of the motor endplate zone of the infraspinatus muscle is yet to be described. Therefore, this cadaveric study aimed to scrutinize the motor endplate zone of the infraspinatus muscle, propose potential myofascial trigger points within the muscle, and recommend therapeutic injection sites. Twenty specimens of the infraspinatus muscle for nerve staining and 10 fresh frozen cadavers for evaluation of the injection were used in this study. The number of nerve branches penetrating the infraspinatus muscle and their entry locations were analyzed and photographed. Modified Sihler's staining was performed to examine the motor endplate regions of the infraspinatus muscle. The nerve entry points were mostly observed in the center of the muscle belly. The motor endplate was distributed equally throughout the infraspinatus muscle, but the motor endplate zone was primarily identified in the B area, which is approximately 20–40% proximal to the infraspinatus muscle. The second‐most common occurrence of the motor endplate zone was observed in the center of the muscle. These detailed anatomical data would be very helpful in predicting potential pain sites and establishing safe and effective injection treatment using botulinum neurotoxin, steroids, or lidocaine to alleviate the pain disorder of the infraspinatus muscle. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pelvic-drop exercise (PD) is unilateral weight-bearing exercise that is frequently performed in rehabilitation sessions because its easy application can trigger moderate-to-high gluteus medius (Gmed) activity. Hip rotation has been applied to effectively facilitate Gmed activity during exercise. OBJECTIVE: To determine the effects of PD with three different hip rotations on Gmed, tensor fasciae latae (TFL), gluteus maximus (Gmax) activity, and Gmed:TFL activity ratio in patients with Gmed weakness. METHODS: Eighteen subjects with Gmed weakness participated. Subjects performed three different forms of PD with neutral hip, hip internal rotation, and hip external rotation position. Surface electromyography was performed to quantify the activity of Gmed, TFL, and Gmax. RESULTS: PD with hip internal rotation showed significantly greater Gmed activity than with neutral hip and hip external rotation (P = 0.005 and P = 0.007, respectively). TFL also showed significantly greater activity during PD with hip interna rotation than neutral hip (P = 0.002). There were no significant differences in Gmax activity (P = 0.095) and Gmed:TFL activity ratio (P = 0.254) among different forms of PD. CONCLUSIONS: PD with hip internal rotation is recommended to stimulate greater Gmed activity while preserving Gmed:TFL muscle activity ratio. [ABSTRACT FROM AUTHOR]

Aims: Major trauma patients need adequate nutrition for recovery. This study aimed to evaluate the adequacy of nutritional supply and the correlation between nutritional supply and clinical outcome. Methods: A single‐centre retrospective observational study was undertaken, describing the amounts of energy and proteins provided to 320 critically ill trauma patients during the first 10 days after admission. The data were collected from the electronic medical records of patients admitted to the trauma intensive care unit during the study period and descriptive statistical analyses were performed with the SPSS software. Results: The mean proportion of supplied energy to recommended energy during the first 10 days after admission was 57.5%, and the mean percentage of supplied protein to recommended protein intake was 51.3%. The patients were divided into those who received ≥70% (isocaloric nutrition group) and those who received <70% (hypocaloric nutrition group) of their estimated requirements. Both the duration of ventilator use (12.7 ± 10.5 vs. 16.0 ± 15.8 days, respectively, p = 0.009) and duration of parenteral nutrition (1.1 ± 1.4 vs. 2.0 ± 2.0 days, respectively, p = 0.001) were shorter in the isocaloric nutrition group (n = 83) than in the hypocaloric nutrition group (n = 237). Conclusion: Total energy and the amount of protein supplied were insufficient compared to the recommended amount. The duration of ventilator use was shorter in the isocaloric nutrition group than in the hypocaloric nutrition group. The association between shortened ventilator use and isocaloric nutrition requires further investigation as a potential intervention to reduce the risk of complications such as ventilator‐related pneumonia. [ABSTRACT FROM AUTHOR]

Introduction: Hyperhidrosis, causing excessive sweat, can be treated with Botulinum neurotoxin injection. Botulinum toxin, an effective and safe treatment for hyperhidrosis, unfortunately involves significant pain due to multiple injections. This study aims to propose a more efficient and less painful approach to nerve blocks for relief, by identifying optimal injection points to block the median nerve, thereby enhancing palmar hyperhidrosis treatment. Methods: This study, involving 52 Korean cadaver arms (mean age 73.5 years), measured the location of the median nerve relative to the transverse line at the pisiform level to establish better nerve block injection sites. Results: In between the extensor carpi radialis and palmaris longus, the median nerve was located at an average distance of 47.39 ± 6.43 mm and 29.39 ± 6.43 mm from the transverse line at the pisiform level. Discussion: To minimize discomfort preceding the botulinum neurotoxin injection, we recommend the optimal injection site for local anesthesia to be located 4 cm distal to the transverse line of the pisiform, within the tendons of the palmaris longus and flexor carpi radialis muscles. [ABSTRACT FROM AUTHOR]

Mast cells are an important component of immune responses. Immunoglobulin (Ig) E-sensitized mast cells release substances within minutes of allergen exposure, triggering allergic responses. Until now, numerous pharmacological effects of wheatgrass and aronia have been verified, but the effects of wheatgrass and aronia (TAAR)-mixed extract on allergic reactions have not been identified. Therefore, the aim of this study was to demonstrate the anti-allergic effect of TAAR extract on mast cell activation and cutaneous anaphylaxis. In this study, we investigated the anti-allergic effects and related mechanisms of TAAR extract in IgE-activated mast cells in vitro. We also assessed the ameliorating effect of TAAR extract on IgE-mediated passive cutaneous anaphylaxis mice in vivo. The TAAR extract significantly reduced the expression of β-hexosaminidase, histamine, and pro-inflammatory cytokines, which are mediators related to mast cell degranulation, via the regulation of various signaling pathways. The TAAR extract also regulated oxidative-stress-related factors through the Nrf2 signaling pathway. Additionally, treatment of TAAR extract to the passive cutaneous anaphylaxis mouse model improved ear thickness and local ear pigmentation. Taken together, our results suggest that TAAR extract is a potential candidate natural product to treat overall IgE-mediated allergic inflammation and oxidative-stress-related diseases by suppressing mast cell activity. [ABSTRACT FROM AUTHOR]

Atopic dermatitis represents a complex and multidimensional interaction that represents potential fields of preventive and therapeutic management. In addition to the treatment armamentarium available for atopic dermatitis, novel drugs targeting significant molecular pathways in atopic dermatitis biologics and small molecules are also being developed given the condition's complex pathophysiology. While most of the patients are expecting better efficacy and long-term control, the response to these drugs would still depend on numerous factors such as complex genotype, diverse environmental triggers and microbiome-derived signals, and, most importantly, dynamic immune responses. This review article highlights the challenges and the recently developed pharmacological agents in atopic dermatitis based on the molecular pathogenesis of this condition, creating a specific therapeutic approach toward a more personalized medicine. [ABSTRACT FROM AUTHOR]

Background and objectives: This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. Methods: The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. Results: The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. Conclusion: We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results. [ABSTRACT FROM AUTHOR]

Purpose: The present study aimed to demonstrate the intramuscular nerve distribution of the levator scapulae muscle that is responsible for pain and to use this anatomic data to propose possible injection sites. Methods: Twenty levator scapulae muscles were dissected from 16 Korean embalmed cadavers. The intramuscular nerve distribution of the levator scapulae muscle was identified by whole-mount nerve staining to preserve and stain the nerve fibers without damage. Results: The posterior ramus of spinal nerves C3, C4, and C5 innervated the levator scapulae muscles. When the origin and insertion of the muscle were set to 0% and 100%, respectively, most of the intramuscular nerve terminals were located between 30 and 70%. This area may correspond to the cricoid cartilage of the sixth cervical vertebra. Conclusion: Most intramuscular nerve terminals can be found in the middle and distal portions of the levator scapulae muscle. Our findings improve our understanding of the intramuscular nerve distribution of the levator scapulae muscle and will aid in pain management in clinical practice. [ABSTRACT FROM AUTHOR]

The consumption of food and drugs adulterated with female sex hormones can have an extremely adverse effect on human health. Therefore, developing appropriate monitoring methods for the identification of various exogenous female sex hormones is crucial for minimizing and eliminating the related health risks. Herein, 17 female hormones categorized into two groups: estrogen and progestin, were analyzed using reversed‐phase liquid chromatography coupled to Orbitrap or triple quadrupole mass spectrometry. The fragmentation patterns for all compounds were discovered, and fragmented structures were also derived from them through liquid chromatography–high‐resolution mass spectrometry followed by qualitative sample analysis. In addition, a quantitative analysis of 67 samples of illicit drugs and dietary supplements was performed using the validated liquid chromatography‐tandem mass spectrometry method. Female hormone components were detected in two samples of an unauthorized injectable solution and a tablet‐type drug. Medroxyprogesterone was detected in the samples in the range of 96.4–206 ng/g. Notably, eight components similar in structure to steroids were simultaneously detected as male sex hormones by confirming their fragmentation ion patterns using liquid chromatography–high‐resolution mass spectrometry. The developed methods thus offer a dependable and practically applicable approach for the screening and detection of exogenous female sex hormones in real food and drug samples to ensure public health. [ABSTRACT FROM AUTHOR]

Objectives Coping styles refer to cognitive and behavioral patterns used to manage the demands of stressors, and effective coping represents a psychological resource. Some studies have linked coping styles to executive functioning, but less is known about coping styles and their associations with cognition across social groups known to differ in stress exposure and dementia risk. This study aimed to characterize associations between coping styles and cognitive functioning across non-Hispanic Black and non-Hispanic White older adults. Methods Participants were drawn from the Michigan Cognitive Aging Project (N  = 453; age mean (SD) = 63.6 (3.2); 53% non-Hispanic Black). Problem-focused and emotion-focused coping were measured using the Coping Orientation to Problems Experienced Inventory. Global cognition was a composite of 5 cognitive domain scores derived from comprehensive neuropsychological tests. Cross-sectional associations between coping styles and cognition were examined using race-stratified regressions controlling for demographic and health covariates. Results Black older adults reported more emotion-focused coping than White older adults, but there were no race differences in problem-focused coping. Among Black older adults, less problem-focused coping and more emotion-focused coping were each associated with worse cognition. Among White older adults, emotion-focused coping was marginally linked to cognition. Discussion Greater emotion-focused coping among Black older adults may reflect greater exposure to stressors that are uncontrollable. Patterns of racial differences in coping–cognition links are in line with the social vulnerabilities hypothesis. Coping style may be a particularly important psychosocial resource for cognitive health among Black older adults that could be incorporated into culturally relevant interventions. [ABSTRACT FROM AUTHOR]

Objectives: A diagnosis of congenital heart disease (CHD) during fetal life or infancy can be devastating for parents, resulting in significant psychological stressors. The goals of this study were to (1) assess maternal resolution and adaptation to a new diagnosis of CHD, (2) explore how maternal resolution and adaptation relates to psychological well-being and (3) evaluate whether specific illness parameters impact resolution status. Methods: This cross-sectional study evaluated resolution to diagnosis in the first 6 months of life for mothers of children with CHD. Mothers completed a Reaction to Diagnosis Interview (RDI) and psychological surveys assessing stress, depression, and coping skills. The RDI invites parents to discuss the diagnosis, changes in their thoughts and feelings since the diagnosis, and reflections on why they think they have a child with a medical condition. A chart review of the child recording illness parameters was also performed. Results: Thirty-six mothers participated in this study. Twelve of their children had a prenatal diagnosis of CHD (33.3%). Seventeen mothers (47.2%) were unresolved to the diagnosis of CHD in their child, regardless of the timing or severity of the diagnosis. Twenty-four participants (68.6%) had significant or highly significant life stress and 9 participants (25.7%) had clinical concerns or met criteria for Post-Traumatic Stress Disorder. Nineteen mothers (55.9%) were at risk for clinical depression. Mothers unresolved to the diagnosis had higher rates of post-traumatic stress than those resolved to the diagnosis (47.1% vs. 10.5%, p = 0.03). Mothers of infants with a prenatal diagnosis of CHD reported significantly lower rates of life stress despite higher severity of heart defects (p = 0.02). Conclusions for Practice: Mothers of infants with CHD have similar proportions of resolution to diagnosis compared to mothers of children with other chronic diseases. They experience a high rate of symptoms of life stress, post-traumatic stress and clinical depression. Symptoms of post-traumatic stress are higher in mothers unresolved to the diagnosis. Identification of those at highest risk for poor adaptation to the diagnosis may allow for targeted psychological support services for those most vulnerable. Significance Statement: A diagnosis of congenital heart disease can result in significant parental stress and negatively impact parental and child bonding. Our study demonstrates that parents of infants with cardiac disease experience high rates of life stress, post-traumatic stress and clinical depression. Mothers unresolved to the diagnosis have higher rates of post-traumatic stress. Those who received a prenatal diagnosis had lower life stress despite greater disease severity. Identification of mothers at highest risk for poor adaptation to the diagnosis may allow for targeted psychological support services for those most vulnerable. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < −5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07–2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17–2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy. [ABSTRACT FROM AUTHOR]

To use hepatocytes immediately when necessary for hepatocyte transplantation and bioartificial liver (BAL) systems, a serum-free cryopreservation protocol ensuring the high survival of hepatocytes and maintenance of their functions should be developed. We established a serum-free protocol for the cryopreservation of primary hepatocytes, hepatocyte spheroids, and hepatocyte spheroid beads in liquid nitrogen. The serum-free cryopreservation solutions showed a significantly higher performance in maintaining enhanced viability and ammonia removal, urea secretion, and the albumin synthesis of hepatocyte spheroids and spheroid beads. The serum-free thawing medium, containing human serum albumin (HSA) and N-acetylcysteine (NAC), was compared with a fetal bovine serum-containing thawing medium for the development of a serum-free thawing medium. Our results show that hepatocyte spheroids and spheroid beads thawed using a serum-free thawing medium containing HSA and NAC exhibited increased hepatocyte viability, ammonia removal, urea secretion, and albumin synthesis compared to those thawed using the serum-containing medium. Finally, we evaluated the liver functions of the cryopreserved BAL system-applied serum-free cryopreservation process compared to the fresh BAL system. The ammonia removal efficiency of the cryopreserved hepatocyte spheroids BAL was lower than or similar to that of the fresh BAL system. Additionally, the urea concentrations in the media of all three BAL systems were not significantly different during BAL system operation. This cryopreserved spheroid-based BAL system using a serum-free process will be a good candidate for the treatment of patients. [ABSTRACT FROM AUTHOR]

The platysma muscle is a thin superficial muscle that covers the entire neck and lower part of the face. The platysma muscle is the primary target muscle for botulinum neurotoxin injection therapy aimed at treating platysmal band and lower facial lifting. In the procedure of botulinum neurotoxin injection therapy, a lack of knowledge of the anatomy of the platysma muscle and the properties of botulinum neurotoxin can lead to side effects such as dysphagia, dysphonia, and weakness of the neck muscles. Anatomically safe injection sites have been proposed for the platysma muscle, and the appropriate injection technique has been reviewed. We proposed optimal injection sites based on the external anatomical features of the mandible. The aim of these proposal was to standardize the procedure for the effective use of botulinum neurotoxin injections by minimizing the dose unit and injection points and thereby preventing adverse events. [ABSTRACT FROM AUTHOR]

Consumption of foods and dietary supplements (DS) adulterated with unprescribed or non-permitted phosphodiesterase-5 inhibitors (PDE-5i) and their analogs can cause serious risk to human health. This study aims to analyze 93 PDE-5i and their analogs present in adulterated foods and DS using an established and validated method involving high-performance liquid chromatography (HPLC). The method was validated in solid and liquid samples, resulting in a limit of detection and quantitation of 0.03–0.5 and 0.08–1.6 μg/mL, respectively. Using the validated method, a total of 404 samples were screened. It was found that 32% of 404 samples were illegally adulterated with PDE-5i and their analogs; moreover, 16.9% of the adulterated samples were found to contain more than three compounds. HPLC-quadrupole-time-of-flight (TOF)/mass spectrometry (MS) analysis was conducted on all the samples to confirm the detected compounds accurately based on fragmentation ion patterns. In addition, sildenafil and tadalafil were detected from the capsule shells of DS unusually. Subsequently, the detected compounds were identified and quantified using HPLC at concentrations ranging from 0.007 to 370.0 mg/g. NMR analysis was carried out to confirm the accurate chemical structure of a compound found during the TOF/MS analysis, which did not match with the 93 reference standards.; it was identified to be N -desmethylthiosildenafil. In this study, various PDE-5i compounds and their analogs were detected from low to high concentrations in a sample. Therefore, the study sheds light on the misuse of PDE-5i and their analogs in consumable products, which pose a severe threat to public health. [ABSTRACT FROM AUTHOR]

Background: Now that it is possible to efficiently classify and save tissue images of laboratory animals using whole-slide imaging, many diagnostic models are being developed through transfer learning with Convolutional Neural Network (CNN). In this study, transfer learning was performed to gain toxicopathological knowledge using CNN models such as InceptionV3 and Xception. For the classification of tubular basophilia and mineralization, two representative background lesions that commonly occur in toxicological studies, accuracies of diagnosis were compared using MobileNetV2, Xception and InceptionV3. For the simultaneous detection of the two lesions, the accuracy was analysed using You Only Look Once version 4 (YOLOv4). Results: The accuracy of the classification models was as follows: MobileNetV2 (epoch 50, accuracy: 98.57%) > Xception (epoch 70, accuracy: 97.47%) > InceptionV3 (epoch 70, accuracy: 89.62%). In the case of object detection, the accuracy of YOLOv4 was 98.62% at epoch 3000. Conclusions: Among the classification models, MobileNetV2 had the best accuracy despite applying a lower epoch than InceptionV3 and Xception. The object detection model, YOLOv4, accurately and simultaneously diagnosed tubular basophilia and mineralization, with an accuracy of 98.62% at epoch 3000. [ABSTRACT FROM AUTHOR]

Rationale: With the development of the Internet and social network services, the public access to or use of illegal products has been increased via on/offline black markets. Steroids refer to the compounds yielding strong treatment effects on some diseases or muscle building, and are classified as the pharmaceutical compounds that are prohibited for personal use without a prescription. The prohibition is made for their potential risk to cause serious adverse effects along with their efficacies. Methods: To monitor the distribution of illicit products containing steroids, a simple and reliable analytical method was established and validated, allowing rapid and simultaneous determination of 54 steroids in them. During the screening, LC‐Q‐Orbitrap/MS was performed first followed by quantitative analysis using LC–MS/MS. For the accurate and reliable analysis, the samples were extracted using QuEChERS to reduce the matrix effect. Results: After the screening of 617 illegal samples advertised as being effective in alleviating various diseases or improving athletic performance with the established LC‐Q‐Orbitrap/MS method, the validated LC–MS/MS method was used to perform the quantitative analysis of the detected steroids. Of these, 142 samples were adulterated with steroids, and several samples with two or more steroids were detected. Due to the lack of previous studies on the toxicity of these illicit products, the side effects of consuming them are unpredictable and could be harmful. Conclusions: The development of LC‐Q‐Orbitrap/MS method accompanied by LC–MS/MS could be successfully applied to the inspection of illegal steroid products for public health, enabling the rapid and accurate detection of analytes and incorporation of non‐analyte components. [ABSTRACT FROM AUTHOR]

The phenotypes of atopic dermatitis (AD) are diverse, and ethnic differences have been suggested. To date, few studies have explored large-scale national data on the treatment patterns of AD in Asians. Therefore, we aimed to examine real-world treatment patterns for AD, including the probability of discontinuation of AD treatment and restart after discontinuation. A retrospective observational study was conducted using the nationwide healthcare database in South Korea between January 1, 2016 to July 31, 2020. We identified 944,559 pediatric patients and 1,066,453 adults with AD. Topical corticosteroids and antihistamines were the most commonly prescribed medications in all age groups. The frequency of topical corticosteroid prescription decreased as the age increased. Although immunosuppressive drugs were not widely used in both children and adults, cyclosporine was the most frequently prescribed immunosuppressant, particularly among those aged 12 years or more (1–2%). Pediatric patients were more likely to discontinue treatment than adult patients. Treatment restart for moderate-to-severe AD was earlier than that for overall AD. In conclusion, significant differences were observed in the treatment patterns of AD between pediatric and adult patients. These findings will improve our understanding of the latest treatment patterns for AD, which may contribute to decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

In order to effectively and quickly monitor such illegal food and drugs, simultaneous screening and quantitative analysis for multiple compounds are needed. In this study, we established a method of identifying fragmentation ions of 45 compounds for weight loss using liquid chromatography and high‐resolution mass spectrometry and developed a quantitation method through liquid chromatography and tandem mass spectrometry. Note that, 656 samples selected as health functional food, food, and illegal drug were applied. The detection rate of banned weight loss compounds in health functional food, food, and illegal drug was showed as 19.2, 27.3, 40.7%, respectively. Among them, sibutramine, sennoside A and B, ephedrine were most frequently detected in 237 samples that contained weight loss compounds. The detection range about sibutramine was 0.03–159.3 mg/g, sennoside was 0.1–97.6 mg/g, and ephedrine was 0.1–587.7 mg/g in the detected 237 samples. In addition, the unknown compounds not included in our simultaneous analysis method in some samples were identified as furosemide and chlorpheniramine. High selectivity of high resolution mass spectrometry combined with these fragmentation pathways and tandem mass spectrometry methods can be successfully applied to screening and identifying 45 weight loss compounds for continuous blocking and supervision of illegally distributed health functional food, food, and illegal drug. [ABSTRACT FROM AUTHOR]

• Isolation of human monoclonal antibodies (mAbs) against MERS-CoV RBD through phage display. • Development of potent bispecific antibodies (bsAbs) targeting the MERS-CoV RBD. • The efficacy of the parental mAb is surpassed by the enhanced neutralization of MERS-CoV achieved by the bsAb K207.C. • The dual-targeting strategy for the effective management of MERS-CoV. The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization. [Display omitted] [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin injections near the lateral canthal rhytids are commonly used in cosmetic settings; however, there is a lack of thorough anatomical knowledge, and an effective way to treat them with accumulating knowledge is needed. The anatomical characteristics concerning the injection of botulinum neurotoxin into the orbicularis oculi muscle were evaluated in this review. Current knowledge on the identification of botulinum neurotoxin injection points from recent anatomical research was assessed. The lateral canthal lines are involved with the orbicularis oculi muscle and nearby anatomical structures, and the injection points can be more precisely defined. The best possible injection sites were provided, and the injection procedure was described. This review proposes evidence for injection sites associated with the surface anatomy of the orbicularis oculi muscles to enhance the effectiveness of easing lateral canthal rhytids. [ABSTRACT FROM AUTHOR]

Aim: Once the periodontal ligament (PDL) is damaged, it is difficult to regenerate its characteristic structure. Copine7 (CPNE7) reportedly plays a functional role in supporting periodontal attachment and PDL alignment. Here we demonstrate the regulatory mechanism of CPNE7 coordination with cytoskeleton reorganization and cementum attachment protein (CAP)‐mediated attachment in PDL regeneration. Materials and Methods: The expression and localization of CPNE7, α‐TUBULIN, ACTIN, and microtubule associated protein tau (TAU) were investigated in vitro. The effects of recombinant CPNE7 (rCPNE7) and CPNE7‐derived peptides (CPNE7‐DP) on the regulation of CAP were analysed in vitro, and PDL repair capacity was analysed in vivo. Results: CPNE7 co‐localized with F‐ACTIN and induced α‐TUBULIN expansion to the edge of human PDL cells (hPDLCs). ACTIN and α‐TUBULIN protein expressions were not elevated in rCPNE7‐treated hPDLCs. rCPNE7 elevated the protein expression of TAU, which co‐localized with F‐ACTIN and α‐TUBULIN. Replantation studies on mice revealed that well‐attached and well‐aligned PDLs were repaired in the rCPNE7 group. CPNE7‐DP directly up‐regulate the expression of CAP in vitro and promote PDL regeneration in three‐wall defect canine models in vivo. Conclusions: Our findings suggest that CPNE7 helps in PDL repair by supporting PDL alignment through TAU‐mediated cytoskeleton reorganization and direct regulation of CAP‐mediated PDL attachments of PDLCs. [ABSTRACT FROM AUTHOR]

Simple Summary: The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). Imatinib, the treatment of choice for GISTs, shows a lower response in KIT/PDGFRA wild-type GISTs. Neurotrophic tyrosine receptor kinase (NTRK) fusion, which can be treated with an NTRK target agent, has been reported in KIT/PDGFRA wild-type GISTs, and, therefore, the Yonsei Cancer Center analyzed NTRK fusion incidence in KIT/PDGFRA wild-type GISTs. At the Yonsei Cancer Center, NTRK fusion was confirmed in 16% of cases. Confirmation of NTRK fusion in KIT/PDGFRA wild-type GISTs provides important information for improving therapeutic outcomes. NTRK fusion was confirmed in 16% of KIT/PDGFRA wild-type GIST cases at the Yonsei Cancer Center. Confirmation of NTRK fusion in KIT/PDGFRA wild-type GISTs will improve therapeutic outcomes. The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). GISTs with non-canonical mutations are a heterogeneous group. Here, we examined tropomyosin-related kinase (TRK) fusion in GIST cases without KIT/PDGFRA mutations (KIT/PDGFRA wild-type (WT) GISTs). We retrospectively analyzed patients who were diagnosed with GISTs at the Yonsei Cancer Center, Severance Hospital, between January 1998 and December 2016. Thirty-one patients with KIT/PDGFRA WT GISTs were included in the analysis. TRK expression in tumor samples was assessed by pan-TRK immunohistochemistry (IHC), and the neurotrophic tyrosine receptor kinase (NTRK: the gene encoding TRK) rearrangement was analyzed by fluorescence in situ hybridization (FISH). IHC analyses revealed that five cases in this cohort exhibited a weak to moderate TRK expression. NTRK1 fusions were detected in three tumor samples, and two samples harbored NTRK3 fusions. The remaining 26 samples did not harbor NTRK fusions. Two types of NTRK fusions were detected, and the overall NTRK fusion frequency in KIT/PDGFRA WT GIST cases was 16% (5/31). Our data provide insights into the molecular alterations underpinning KIT/PDGFRA WT GISTs. More effort should be devoted to improve methods to identify this distinct disease subtype within the KIT/PDGFRA WT GIST group. [ABSTRACT FROM AUTHOR]

A hollow temple may give rise to a false impression of early facial aging. This is corrected with dermal fillers that are injected into the hollow temple area to produce a smoother facial contour. However, various complications of this procedure have been reported, with the most common being the inadvertent injection of the filler material into the superficial temporal artery (STA). The aim of this study was to investigate the topographic anatomy of the STA and zygomatico-orbital artery (ZOA) to provide essential anatomical information to aid in various clinical procedures involving the temporal region. The superficial arterial distribution of the temple area was studied in 43 hemisectioned Korean cadavers. The courses of the STA and ZOA were identified and classified based on the line connecting the tragus and the superciliary arch (TR-SA line). The ZOA was present in 85.2% of cases and bifurcated from the frontal branch of the STA, after which it ran along the TR-SA line. In this study, the STA pattern was classified into a typical pattern where the ZOA coexists with the STA and a lower pattern where the ZOA was absent. The current findings suggested that the ZOA ran close to the TR-SA line. Therefore, to minimize vascular complications during invasive procedures, injection into this area should be avoided. In addition, clinicians should verify the existence of ZOA and the course of STA before performing various clinical procedures. [ABSTRACT FROM AUTHOR]

Background: High‐intensity focused ultrasound (HIFU) has been recently introduced as a non‐invasive therapeutic modality for controlling excessive subcutaneous fat. Objective: The efficacy and safety of the HIFU device for sculpting the abdomen, upper arm, and thigh were evaluated. Materials and Methods: Ten subjects with more than 10 mm of subcutaneous fat in the abdomen, upper arm, and/or thigh were recruited. We evaluate mean change in the thickness and circumference of subcutaneous fat of each treated area measured using ultrasound 12 weeks after the procedure, the degree of pain, and subject and practitioner satisfaction 12 weeks after the procedure. Results: The mean change of subcutaneous fat thickness in the abdomen, upper arm, and thigh measured using ultrasound 12 weeks after the procedure was −4.33 ± 2.42, −1.86 ± 1.35, and −1.86 ± 1.35 mm, respectively. Compared with pretreatment, subcutaneous fat thickness of the abdomen and upper arm was significantly reduced (p = 0.0020 and p = 0.0004, respectively), but not in the thigh (p = 0.0716). Highest patient satisfaction was for the abdomen. Pain was generally tolerable. Conclusion: The results from the present study indicate HIFU can be an effective and safe therapeutic modality for removing excessive subcutaneous fat in humans. [ABSTRACT FROM AUTHOR]

Introduction: The role of liver compression in predicting fluid responsiveness in children with a single ventricle has never been evaluated. The purpose of this study was to assess whether blood pressure changes during liver compression predict fluid responsiveness in children with single ventricle physiology. Methods: This prospective, interventional study included children aged 3 months to 5 years who underwent surgery for bidirectional cavopulmonary shunt or extracardiac Fontan operation. Before fluid loading, the right upper abdomen was compressed at 30 mmHg for 10 s, and changes in the blood pressure waves were recorded before administering 10 ml kg−1 of crystalloid solution. Systolic arterial pressure, diastolic arterial pressure, central venous pressure, pleth variability index, respiratory variation in aortic blood flow peak velocity, and stroke volume were measured before and after fluid loading. A volume responder was defined as a patient with >15% increase in stroke volume index. Results: Thirty patients underwent bidirectional cavopulmonary shunt (15 responders and 15 non‐responders), and 32 underwent Fontan surgery (17 responders and 15 non‐responders). In children with bidirectional cavopulmonary shunt, Δsystolic arterial pressure > 8 mmHg (sensitivity 76.9% and specificity 93.3%), Δdiastolic arterial pressure > 7 mmHg (sensitivity 69.2% and specificity 93.3%), and Δmean arterial pressure > 7 mmHg (sensitivity 69.2% and specificity 100%) during liver compression predicted fluid responsiveness. The areas under the receiver operating characteristic curves of Δsystolic arterial pressure, Δdiastolic arterial pressure, and Δmean arterial pressure were 0.928, 0.859, and 0.874 (all p <.001). In children who underwent Fontan surgery, only Δsystolic arterial pressure > 16 mmHg was predictive of fluid responsiveness (sensitivity of 41.2% and specificity of 100%), with the areas under the receiver operating characteristic curves curve of 0.786 (p <.001). Pleth variability index and respiratory variation in aortic blood flow peak velocity had no predictive value for fluid responsiveness after both types of surgeries. Discussion: In BCPS patients, liver compression increases the inferior vena cava flow which directly leads to an increase in preload. On the other hand, blood flow from the liver drains directly into the pulmonary arteries in Fontan circulation. Because of this characteristics for preload determination, the clinical application of liver compression to monitor hemodynamic changes might be more useful in patients with bidirectional cavopulmonary shunt than those with Fontan circulation. Conclusion: Increase in blood pressure induced by liver compression is predictive of fluid responsiveness in children with single ventricle physiology. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin injection surrounding the nose area is frequently used in aesthetic settings. However, there is a shortage of thorough anatomical understanding that makes it difficult to treat wrinkles in the nose area. In this study, the anatomical aspects concerning the injection of botulinum neurotoxin into the nasalis, procerus, and levator labii superioris alaeque muscles are assessed. In addition, the present knowledge on localizing the botulinum neurotoxin injection point from a newer anatomy study is assessed. It was observed that, for the line-associated muscles in the nose region, the injection point may be more precisely defined. The optimal injection sites are the nasalis, procerus, and levator labii superioris alaeque muscles, and the injection technique is advised. We advise the best possible injection sites in association with anatomical standards for commonly injected muscles to increase efficiency in the nose region by removing the wrinkles. Similarly, these suggestions support a more precise procedure. [ABSTRACT FROM AUTHOR]

Despite the positive effects of botulinum neurotoxin (BoNT) injection into the neural arborized area, there is no anatomical evidence in the literature regarding the neural arborization of the supraspinatus muscle. The present study aimed to define the intramuscular neural arborized pattern of the supraspinatus muscle using the modified Sihler's staining method to facilitate the establishment of safe and effective injection sites in patients with myofascial pain in the supraspinatus muscle. Seventeen supraspinatus muscles from 15 embalmed cadavers were dissected. Precise suprascapular nerve entry locations were also observed. Intramuscular neural arborization was visualized by Sihler's staining. The supraspinatus muscle was divided into four portions named A, B, C, and D. The nerve entry points were observed in 88.2% (15 of 17 cases) of section B and 76.5% (13 of 17 cases) of section C of the supraspinatus muscle, respectively. The concentration of intramuscular neural arborization was highest in section B of the supraspinatus muscle, which was the center of the supraspinatus muscle. When the clinician performs a trigger point and a BoNT injection into the supraspinatus muscle, injection within the medial 25–75% of the supraspinatus muscle will lead to optimal results when using small amounts of BoNT and prevent undesirable paralysis. [ABSTRACT FROM AUTHOR]

Natural-derived steroids and their analogues are present in various plants and insects. To minimize the chance of missing a positive doping test and avoiding potentially serious health problems, adequate screening methods are necessary for the detection of a wide range of natural-derived steroids and their analogues in dietary supplements. In this study, an accurate and simple liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine and quantify the natural-derived steroids and their analogues according to the International Conference on Harmonization of technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The validation results indicating excellent extraction efficiency and low matrix effects show that the LC-MS/MS method is reliable for the detection of natural-derived steroids and their analogues. In addition, we established the ion fragmentation of turkesterone and ion fragmentation of four natural-derived steroids and their analogues. The validated method was applied to 60 dietary supplements purchased online and in person from international vendors in 2020. Ecdysterone and 5α-hydroxylaxogenin were detected respectively in 3 and 14 of 60 dietary supplements. Especially, a high amount of 5α-hydroxylaxogenin, an FDA-unapproved ingredient, was detected in two of dietary supplements (44.4 and 32.3 mg/g). This component should be controlled since it may cause unexpected side effects if administered excessively. Thus, this method will be helpful for the continuous control and supervision of unlicensed dietary supplements containing natural-derived steroids and their analogues. [ABSTRACT FROM AUTHOR]

Meso- and macrozooplankton play crucial roles in the trophic web and the biological carbon pump in the ocean by transferring energy from lower to higher trophic levels and vertically exporting carbon from the surface to the deep ocean and seabed. In this study, zooplankton community structures in the Ross Sea, Antarctica, were analyzed using metabarcoding methods. Both regular barcode (RB) (using a PacBio Sequel system) and mini barcode (MB) (using the Illumina MiSeq platform) methods were utilized. As the result of a combination of the two bioinformatic pipelines used in the RB, 55 reliable haplotypes were obtained from the pooled zooplankton net samples, whereas 183 amplicon sequence variants (ASVs) were isolated from the MB metabarcoding analyses of 14 individual stations. Among these, 39 (70.9%) and 125 (90.6%) showed higher than 99% sequence identity to the database, indicating that there were sufficient reference sequences to employ metabarcoding analysis—except for several taxa, including small-sized copepods, cnidarians, and pneumodermatids. A high degree of shared taxa showed that both metabarcoding analyses were feasible for use in the analysis of zooplankton assemblages in the Ross Sea. However, RB would be more useful for the construction of a reference database due to its relatively high cost, whereas MB would be more economic for ecological surveys due to its relatively low cost (albeit, only if reference sequences were well documented using RB). Zooplankton assemblages were highly diverse in each sample site, presumably due to the narrow covered volumes of the vertical net-towed samples from polynyas in the Ross Sea. As metabarcoding data accumulate, we will gain better insights into zooplankton communities and their ecological implications in the Ross Sea. [ABSTRACT FROM AUTHOR]

Background: Perioperative central venous catheters are required but may be associated with various complications. Aims: The purpose of our study was to assess the incidence and perioperative risk factors for catheter‐related internal jugular vein thrombosis in pediatric surgical patients. Methods: This prospective observational study included children under 6 years of age who were scheduled to undergo central venous catheterization of the right internal jugular vein under general anesthesia. A central venous catheter was inserted under real‐time ultrasound guidance. An investigator examined for thrombosis using ultrasonography at predetermined time points. The primary aim was the incidence of catheter‐related thrombosis from insertion until the 5th day postoperatively or the removal of the central venous catheter. The secondary aim was the determination of the risk factors for thrombosis. Results: Eighty patients completed the study. Internal jugular vein thrombi were found in 31 patients (38.8%, 95% CI 28.0–49.4). On multiple logistic regression analyses, the number of insertion attempts was the only influencing factor for catheter‐related thrombosis (p <.001). More than two insertion attempts increased the risk of thrombosis (odds ratio 5.6; 95% CI 1.7 – 18.7, p =.004). Anesthesia time (p =.017; mean difference 166.4 min; 95% CI 55.7–277.1), intraoperative red blood cell transfusion (p =.001; median difference 21.1 ml kg−1; 95% CI 6.6–34.4), and intensive care unit stay (p =.001; median difference 100.0 h; 95% CI 48–311) differed between patients with transient thrombosis and those with thrombosis lasting for more than 3 days. Conclusion: Internal jugular vein thrombosis was frequently detected by ultrasound following central venous catheterization in pediatric surgical patients. Multiple insertion attempts may be associated with the incidence of thrombosis. The clinical relevance of thrombi detected via ultrasound surveillance has not been determined. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin injection for treating glabellar frown lines is a commonly used method; however, side effects, such as ptosis and samurai eyebrow, have been reported due to a lack of comprehensive anatomical knowledge. The anatomical factors important for the injection of the botulinum neurotoxin into the corrugator supercilii muscle has been reviewed in this study. Current understanding on the localization of the botulinum neurotoxin injection point from newer anatomy examination was evaluated. We observed that for the glabellar-frown-line-related muscles, the injection point could be more accurately demarcated. We propose the injection method and the best possible injection sites for the corrugator supercilii muscle. We propose the optimal injection sites using external anatomical landmarks for the frequently injected muscles of the face to accelerate effective glabellar frown line removal. Moreover, these instructions would support a more accurate procedure without adverse events. [ABSTRACT FROM AUTHOR]

The serratus anterior muscle is commonly involved in myofascial pain syndrome and is treated with many different injective methods. Currently, there is no definite injection point for the muscle. This study provides a suggestion for injection points for the serratus anterior muscle considering the intramuscular neural distribution using the whole-mount staining method. A modified Sihler method was applied to the serratus anterior muscles (15 specimens). The intramuscular arborization areas were identified in terms of the anterior (100%), middle (50%), and posterior axillary line (0%), and from the first to the ninth ribs. The intramuscular neural distribution for the serratus anterior muscle had the largest arborization patterns in the fifth to the ninth rib portion of between 50% and 70%, and the first to the fourth rib portion had between 20% and 40%. These intramuscular neural distribution-based injection sites are in relation to the external anatomical line for the frequently injected muscles to facilitate the efficiency of botulinum neurotoxin injections. Lastly, the intramuscular neural distribution of serratus anterior muscle should be considered in order to practice more accurately without the harmful side effects of trigger-point injections and botulinum neurotoxin injections. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic and its restrictions have led to a shift in how people connect with others. This study investigated (a) profiles of social contact change across social ties and modes of contact, (b) predictors of these profiles, and (c) the association between these profiles and mental health during the pandemic. Participants (N = 2,098; Age mean = 50.94, range = 18–98; 48.3% female) were surveyed online twice, once prior to the pandemic (January 31–February 10, 2020) and again early in the outbreak (March 18–29, 2020). A latent profile analysis identified profiles of social contact change across social ties and communication methods. Additional analyses identified predictors of group membership and their association with mental health. Three latent groups were identified: (1) the "majority group" (77%) slightly restricted in‐person contact and had a small increase in phone and text use, (2) the "high technology use group" (13%) restricted in‐person contact and increased the use of all technology‐based methods, and (3) the "isolated group" (10%) decreased in both in‐person and technology‐based contact. Compared to the majority group, the high technology use group reported higher depression and anxiety, whereas the isolated group reported higher loneliness. There were three distinct profiles of how adults in the United States changed their communication patterns with others early in the pandemic that were linked to distinct patterns of mental health. The results have implications for the development and the delivery of mental health treatment in times of social (physical) distancing. [ABSTRACT FROM AUTHOR]

Background: The Bland-Altman plot with the limits of agreement has been widely used as an absolute index for assessing test-retest reliability or reproducibility between two measurements. We have observed that in the settings where the relative index such as concordance correlation coefficient (CCC) or intraclass correlation coefficient is employed, the limits of agreement approach may be inconsistent with the scaled index. Particularly, the broad width of the limits of agreement may indicate a lack of agreement when the two measurements are highly concordant but an acceptable difference is not known and the common variance of the data is large. This research aims to create a novel, CCC-based guidance for graphical evaluation of reproducibility or reliability.Methods: The concordance correlation coefficient is used to create a 100(1-α)% reference band from two measurements. Simulation studies and real examples, including the peak expiratory flow rate data in Bland and Altman's paper and the test-retest reproducibility data of the Radiomics study, are implemented to assess the use of the reference band.Results: In the absence of an acceptable difference between measurements, we found that the limits of agreement may not be consistent with the concordance correlation coefficient. Our simulation study results and real data application show that the proposed method can provide practitioners with a novel graphical evaluation that is consistent with results from the concordance correlation coefficient.Conclusions: Our proposed novel scaled index-based guidance can be used for the graphical evaluation of reproducibility or reliability and may have advantages over the limits of agreement in settings where the concordance correlation coefficient is employed. [ABSTRACT FROM AUTHOR]

Chest X-ray (CXR), computed tomography (CT), and positron emission tomography–computed tomography (PET-CT) are noninvasive imaging techniques widely used in human and veterinary pulmonary research and medicine. These techniques have recently been applied in studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed non-human primates (NHPs) to complement virological assessments with meaningful translational readouts of lung disease. Our review of the literature indicates that medical imaging of SARS-CoV-2-exposed NHPs enables high-resolution qualitative and quantitative characterization of disease otherwise clinically invisible and potentially provides user-independent and unbiased evaluation of medical countermeasures (MCMs). However, we also found high variability in image acquisition and analysis protocols among studies. These findings uncover an urgent need to improve standardization and ensure direct comparability across studies. In non-human primates (NHPs), characteristic radiographic abnormalities (best observed by high-resolution imaging), combined with concordant immunological, virological, and lung histopathological findings, mirror mild-to-moderate human disease. Noninvasive medical imaging can visualize otherwise 'silent' disease at high resolution and generates quantifiable measurements that are particularly important in sublethal models, providing an essential complement to standard immunological, virological, and pathological assays, which can only be performed as snapshots (not longitudinally) or may be difficult to perform. The incorporation of advanced medical imaging tools in NHP studies for coronavirus disease 2019 (COVID-19) research is not without challenges, including high experimental costs due to the limited availability of equipment in high containment environments, frequency of anesthesia events required for imaging, and the number of animals that can practically be imaged at a single time point. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether in vivo MR-electrical properties tomography (MR-EPT) is feasible in musculoskeletal tissues by evaluating the conductivity of muscle, cartilage, and peripheral nerve around the knee joint, and to explore whether these measurements change after exercise. This prospective study was approved by the institutional review board. On February 2020, ten healthy volunteers provided written informed consent and underwent MRI of the right knee using a three-dimensional balanced steady-state free precession (bSSFP) sequence. To test the effect of loading, the subjects performed 60 squatting exercises after baseline MRI, immediately followed by post-exercise MRI with the same sequences. After reconstruction of conductivity map based on the bSSFP sequence, conductivity of muscles, cartilages, and nerves were measured. Measurements between the baseline and post-exercise MRI were compared using the paired t-test. Test–retest reliability for baseline conductivity was evaluated using the intraclass correlation coefficient. The baseline and post-exercise conductivity values (mean ± standard deviation) [S/m] of muscles, cartilages, and nerves were 1.73 ± 0.40 and 1.82 ± 0.50 (p = 0.048), 2.29 ± 0.47 and 2.51 ± 0.37 (p = 0.006), and 2.35 ± 0.57 and 2.36 ± 0.57 (p = 0.927), respectively. Intraclass correlation coefficient for the baseline conductivity of muscles, cartilages, and nerves were 0.89, 0.67, and 0.89, respectively. In conclusion, in vivo conductivity measurement of musculoskeletal tissues is feasible using MR-EPT. Conductivity of muscles and cartilages significantly changed with an overall increase after exercise. [ABSTRACT FROM AUTHOR]