Ultraclean Interface of Metal Chalcogenides with Metal through Confined Interfacial Chalcogenization.

Acquisition of defect-free transition metal dichalcogenides (TMDs) channels with clean heterojunctions is a critical issue in the production of TMD-based functional electronic devices. Conventional approaches have transferred TMD onto a target substrate, and then apply the typical device fabrication processes. Unfortunately, those processes cause physical and chemical defects in the TMD channels. Here, a novel synthetic process of TMD thin films, named confined interfacial chalcogenization (CIC) is proposed. In the proposed synthesis, a uniform TMDlayer is created at the Au/transition metal (TM) interface by diffusion of chalcogen through the upper Au layer and the reaction of chalcogen with the underlying TM. CIC allows for ultraclean heterojunctions with the metals, synthesis of various homo- and hetero-structured TMDs, and in situ TMD channel formation in the last stage of device fabrication. The mechanism of TMD growth is revealed by the TM-accelerated chalcogen diffusion, epitaxial growth of TMD on Au(111). We demonstrated a wafer-scale TMD-based vertical memristors which exhibit excellent statistical concordance in device performance enabled by the ultraclean heterojunctions and superior uniformity in thickness. CIC proposed in this study represents a breakthrough in in TMD-based electronic device fabrication and marking a substantial step toward practical next-generation integrated electronics.

The effect of integrative Korean medicine treatment on symptomatic lumbar facet joint cysts: A case series.

OBJECTIVE: The optimal treatment for facet joint cysts (FJCs) has remained controversial. Despite a higher success rate than the conservative option, surgical treatments may pose risks of postoperative complications and comorbidities may make the surgical approach difficult. Thus, this study reports four cases of pain amelioration and resorption of FJCs through noninvasive integrative Korean Medicine treatment. METHODS: For intervention, four patients with symptomatic FJCs underwent integrative Korean medicine treatment with acupuncture, herbal medicine, pharmacopuncture, and Chuna manual therapy; after completion of the series of treatment sessions, patients were re-examined with magnetic resonance imaging (MRI). RESULTS: Pain disappeared within 2 months for all four patients; the amelioration of pain was sustained for more than 6 months. Furthermore, the disappearance of FJCs was confirmed by MRI after a certain period from the time of pain disappearance. CONCLUSIONS: This study reported the effectiveness of non-invasive, integrative Korean medicine treatment for patients with FJCs; this method shows promise as a conservative treatment option for patients with FJCs.

ITC-6102RO, a novel B7-H3 antibody-drug conjugate, exhibits potent therapeutic effects against B7-H3 expressing solid tumors.

BACKGROUND: The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors. METHODS: In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo. RESULTS: ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues. CONCLUSIONS: Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

ACURATE: a Guide for Reporting Sham Controls in Trials Using Acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT), which is to be used with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when real and sham acupuncture needles are used in a study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist in the reporting of sham acupuncture procedures and related components.

Conversational Agents for Body Weight Management: Systematic Review.

BACKGROUND: Obesity is a public health issue worldwide. Conversational agents (CAs), also frequently called chatbots, are computer programs that simulate dialogue between people. Owing to better accessibility, cost-effectiveness, personalization, and compassionate patient-centered treatments, CAs are expected to have the potential to provide sustainable lifestyle counseling for weight management. OBJECTIVE: This systematic review aimed to critically summarize and evaluate clinical studies on the effectiveness and feasibility of CAs with unconstrained natural language input for weight management. METHODS: PubMed, Embase, the Cochrane Library (CENTRAL), PsycINFO, and ACM Digital Library were searched up to December 2022. Studies were included if CAs were used for weight management and had a capability for unconstrained natural language input. No restrictions were imposed on study design, language, or publication type. The quality of the included studies was assessed using the Cochrane risk-of-bias assessment tool or the Critical Appraisal Skills Programme checklist. The extracted data from the included studies were tabulated and narratively summarized as substantial heterogeneity was expected. RESULTS: In total, 8 studies met the eligibility criteria: 3 (38%) randomized controlled trials and 5 (62%) uncontrolled before-and-after studies. The CAs in the included studies were aimed at behavior changes through education, advice on food choices, or counseling via psychological approaches. Of the included studies, only 38% (3/8) reported a substantial weight loss outcome (1.3-2.4 kg decrease at 12-15 weeks of CA use). The overall quality of the included studies was judged as low. CONCLUSIONS: The findings of this systematic review suggest that CAs with unconstrained natural language input can be used as a feasible interpersonal weight management intervention by promoting engagement in psychiatric intervention-based conversations simulating treatments by health care professionals, but currently there is a paucity of evidence. Well-designed rigorous randomized controlled trials with larger sample sizes, longer treatment duration, and follow-up focusing on CAs' acceptability, efficacy, and safety are warranted.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when both real and sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting of sham acupuncture procedures and the related components.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

OBJECTIVE: To promote better reporting quality regarding sham acupuncture in clinical trials for a precise appraisal of the adequacy of the sham acupuncture procedure. METHODS: A three-stage online Delphi survey was conducted to a group of experts. Items with higher than 80% consensus from the initial checklist were selected as the final candidates. Further discussion among the working group was convened to preclude potential redundancy among the items. RESULTS: A total of 23 experts out of 35 (66%) responded to the Delphi process. The final checklist consists of 23 items in six categories: type of sham acupuncture, details of sham acupuncture manipulation, location of sham acupuncture, treatment regimen, practitioner, and protocol and settings. CONCLUSION: This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting sham acupuncture procedures and the related components.

Individualized herbal prescriptions for delayed union: A case series.

Background Bone fractures are important clinical events for both patients and professionals. Active treatment options are limited for delayed unions and for nonunions; surgery is common but not entirely risk-free. This report describes three cases of delayed union successfully treated with herbal decoction. Participants Three patients had trapezoid and 3rd metacarpal bone fractures, 2nd, and 5th metatarsal bone fractures, respectively. All three patients were diagnosed with delayed union by an independent orthopedic surgeon based on computed tomography (CT) scan/radiographic imaging and fracture duration without a healing process. Patients took herbal decoction, Jeopgol-tang, with individually added herbs based on symptom manifestations, twice daily for 56, 85 and 91 days with no additional interventions except for a splint that they had been wearing since fracture diagnosis. Outcomes Improvement of delayed union was evaluated using radiographic imaging or CT during treatment with Jeopgol-tang. Results After taking herbal medicine, callus and bony bridging were confirmed on follow-up imagings and the patients described their experience with pain reduction at an interview after recovery. Conclusions This case series suggests that the herbal decoction Jeopgol-tang warrants further investigation to establish its role as a complementary and integrative medicine treatment option for delayed unions.

Sham Acupuncture Is Not Just a Placebo.

Sham acupuncture should have two distinct features: first, it must be morphologically similar to verum acupuncture for blinding purposes, and second, it must not exert physiologically expected effects of verum acupuncture. While several types of sham acupuncture are currently used, there are on-going debates on which sham acupuncture can meet the criteria for being an appropriate control intervention in acupuncture research. In view of this situation, it is unreasonable to regard the use of sham acupuncture in acupuncture research as the same as the use of placebo drugs in drug research. Given the current research evidence that sham acupuncture can exert not only the originally expected non-specific effects but also sham acupuncture-specific effects, it would be misleading to simply regard sham acupuncture as the same as placebo. Therefore, researchers should be cautious when using the term sham acupuncture in clinical investigations.

Safety of acupuncture by Korean Medicine Doctors: a prospective, practice-based survey of 37,490 consultations.

BACKGROUND: To evaluate safety of acupuncture treatment by Korean Medicine Doctors (KMDs), a prospective, practice-based survey on adverse events (AEs) associated with acupuncture was conducted. METHODS: From July 2016 to October 2017, KMDs were invited to participate in an online survey. Frequency was calculated as the number of AEs per 10,000 treatments; severity was assessed with the Common Terminology Criteria for Adverse Events Grading (Severity) Scale; and causality was evaluated using the World Health Organisation-Uppsala Monitoring Centre system for standardised case causality assessment. Associations between AE occurrence and KMDs' type of practice/clinical experience and patient age/gender/current medication(s) were analysed. RESULTS: Data on 37,490 acupuncture treatments were collected from 222 KMDs. At least one AE was reported from 4,518 acupuncture treatments, giving a frequency rate of 1,205 per 10,000 acupuncture treatments; this increased to 4,768 treatments when administrative problems related to defective devices or medical negligence were added, for a rate of 1,272 per 10,000 acupuncture treatments. Commonly reported AEs were bleeding, needle site pain, and bruising. Approximately 72.9% of AEs/administrative problems were assessed as they certainly occurred by acupuncture treatment in causality assessment. Most AEs/administrative problems were considered mild in severity and two life-threatening AEs were resolved with no sequelae. Compared to males, female patients were more likely to experience AEs and KMDs' clinical experience was not associated with reported AE occurrence. CONCLUSIONS: Although acupuncture-associated AEs occur commonly, they are largely transient and mild. Acupuncture performed by qualified KMDs may serve as a reliable medical treatment with acceptable safety profiles.

A nationwide survey on the management of the COVID-19 pandemic and respiratory disease in South Korea.

Background: This study aimed to explore individual prevalence of respiratory symptoms and to describe the Korean population's treatment approaches, preventive health behaviors, and mental health conditions during the pandemic. Methods: We analyzed responses from an online nationwide survey, conducted between February 2021 to May 2021, about people's experiences during the pandemic. Statistical analysis was also performed to see if there were any significant differences in treatment and prevention strategies between different groups of respondents (between those had respiratory symptoms, compared with those who did not, and between those tested positive for COVID-19, compared with those who did not). Results: A total of 2,177 survey respondents completed the survey and, of these, only 142 had experienced symptoms. The most frequently reported respiratory infections related symptoms were runny or blocked nose (47.6%), cough (45.5%), fever (44.1%), sore throat (42.0%), and fatigue (30.1%). More than half of the respondents (53.1%) used complementary and alternative medicine (CAM) approaches as means of preventive measures. In terms of preventive behaviors, the more emphasized behaviors were mask-wearing (58.9%) and hand-washing after coming home (42.7%). The majority of the respondents (64.9%) did not show signs of mental health issues. Conclusion: In South Korea, conventional medicine was mainly used for COVID-19 treatment whereas CAM was commonly used as preventive measures. COVID-19 was also found to have less impact on the general population's mental health. The findings of this study may shed light on how the pandemic impacted the general population.

Safety of acupotomy in a real-world setting: A prospective pilot and feasibility study.

OBJECTIVE: Acupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs). METHODS: This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured. RESULTS: A total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point. CONCLUSION: The findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0002849 (https://cris.nih.go.kr/cris/search/detailSearch.do/11487).

Reporting quality of sham needles used as controls in acupuncture trials: a methodological evaluation.

OBJECTIVE: The description of controls is important in acupuncture clinical trials to interpret its effectiveness without fallacy. This paper aims to evaluate the reporting quality of acupuncture studies on the characteristics of sham needles. STUDY DESIGN AND SETTING: Using a checklist developed from previously published reporting guidelines, the distribution of reported items and changes of reporting rates over time were investigated. Two-way ANOVA and linear regression were conducted. RESULTS: Original articles of RCTs of any design involving sham needles as controls were eligible for assessment. 117 trials from three 2-year time periods between 2009 and 2018 were included. Seven items out of 25 were reported in more than 50% of the studies. While significant differences of reporting scores among categories were observed, there were no significant differences among time periods; no significant improvement was observed over time. CONCLUSIONS: Low reporting qualities of sham needles used in acupuncture studies may influence how researchers understand the effectiveness of acupuncture. This study evaluated previous publications from 2009 to 2018 and found that reporting qualities on sham needles did not improve over time. Further studies are required to validate the items used in this study to endorse better reporting of controls in acupuncture trials.

Hybrid Deep Learning Crystallographic Mapping of Polymorphic Phases in Polycrystalline Hf0.5 Zr0.5 O2 Thin Films.

By controlling the configuration of polymorphic phases in high-k Hf0.5 Zr0.5 O2 thin films, new functionalities such as persistent ferroelectricity at an extremely small scale can be exploited. To bolster the technological progress and fundamental understanding of phase stabilization (or transition) and switching behavior in the research area, efficient and reliable mapping of the crystal symmetry encompassing the whole scale of thin films is an urgent requisite. Atomic-scale observation with electron microscopy can provide decisive information for discriminating structures with similar symmetries. However, it often demands multiple/multiscale analysis for cross-validation with other techniques, such as X-ray diffraction, due to the limited range of observation. Herein, an efficient and automated methodology for large-scale mapping of the crystal symmetries in polycrystalline Hf0.5 Zr0.5 O2 thin films is developed using scanning probe-based diffraction and a hybrid deep convolutional neural network at a 2 nm2 resolution. The results for the doped hafnia films are fully proven to be compatible with atomic structures revealed by microscopy imaging, not requiring intensive human input for interpretation.

Ferroelastic-Ferroelectric Multiferroicity in van der Waals Rhenium Dichalcogenides.

2D multiferroics with combined ferroic orders have gained attention owing to their novel functionality and underlying science. Intrinsic ferroelastic-ferroelectric multiferroicity in single-crystalline van der Waals rhenium dichalcogenides, whose symmetries are broken by the Peierls distortion and layer-stacking order, is demonstrated. Ferroelastic switching of the domain orientation and accompanying anisotropic properties is achieved with 1% uniaxial strain using the polymer encapsulation method. Based on the electron localization function and bond dissociation energy of the Re-Re bonds, the change in bond configuration during the evolution of the domain wall and the preferred switching between the two specific orientation states are explained. Furthermore, the ferroelastic switching of ferroelectric polarization is confirmed using the photovoltaic effect. The study provides insights into the reversible bond-switching process and potential applications based on 2D multiferroicity.

Albiflorin Promotes Osteoblast Differentiation and Healing of Rat Femoral Fractures Through Enhancing BMP-2/Smad and Wnt/ß-Catenin Signaling.

Fracture healing is related to osteogenic differentiation and mineralization. Recently, due to the unwanted side effects and clinical limitations of existing treatments, various natural product-based chemical studies have been actively conducted. Albiflorin is a major ingredient in Paeonia lactiflora, and this study investigated its ability to promote osteogenic differentiation and fracture healing. To demonstrate the effects of albiflorin on osteoblast differentiation and calcified nodules, alizarin red S staining and von Kossa staining were used in MC3T3-E1 cells. In addition, BMP-2/Smad and Wnt/ß-catenin mechanisms known as osteoblast differentiation mechanisms were analyzed through RT-PCR and western blot. To investigate the effects of albiflorin on fracture healing, fractures were induced using a chainsaw in the femur of Sprague Dawley rats, and then albiflorin was intraperitoneally administered. After 1, 2, and 3 weeks, bone microstructure was analyzed using micro-CT. In addition, histological analysis was performed by staining the fractured tissue, and the expression of osteogenic markers in serum was measured. The results demonstrated that albiflorin promoted osteoblastogenesis and the expression of RUNX2 by activating BMP-2/Smad and Wnt/ß-catenin signaling in MC3T3-E1 cells. In addition, albiflorin upregulated the expression of various osteogenic genes, such as alkaline phosphatase, OCN, bone sialoprotein, OPN, and OSN. In the femur fracture model, micro-CT analysis showed that albiflorin played a positive role in the formation of callus in the early stage of fracture recovery, and histological examination proved to induce the expression of osteogenic genes in femur tissue. In addition, the expression of bone-related genes in serum was also increased. This suggests that albiflorin promotes osteogenesis, bone calcification and bone formation, thereby promoting the healing of fractures in rats.

Unveiling the Origin of Robust Ferroelectricity in Sub-2 nm Hafnium Zirconium Oxide Films.

HfO2-based ferroelectrics are highly expected to lead the new paradigm of nanoelectronic devices owing to their unexpected ability to enhance ferroelectricity in the ultimate thickness scaling limit (≤2 nm). However, an understanding of its physical origin remains uncertain because its direct microstructural and chemical characterization in such a thickness regime is extremely challenging. Herein, we solve the mystery for the continuous retention of high ferroelectricity in an ultrathin hafnium zirconium oxide (HZO) film (∼2 nm) by unveiling the evolution of microstructures and crystallographic orientations using a combination of state-of-the-art structural analysis techniques beyond analytical limits and theoretical approaches. We demonstrate that the enhancement of ferroelectricity in ultrathin HZO films originates from textured grains with a preferred orientation along an unusual out-of-plane direction of (112). In principle, (112)-oriented grains can exhibit 62% greater net polarization than the randomly oriented grains observed in thicker samples (>4 nm). Our first-principles calculations prove that the hydroxyl adsorption during the deposition process can significantly reduce the surface energy of (112)-oriented films, thereby stabilizing the high-index facet of (112). This work provides new insights into the ultimate scaling of HfO2-based ferroelectrics, which may facilitate the design of future extremely small-scale logic and memory devices.

The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis.

While mast cells (MCs) are previously well-known as a pathological indicator of pain, their role in alleviating pain is recently emerged in acupuncture research. Thus, this study systematically reviews the role of MC in acupuncture analgesia. Animal studies on MC changes associated with the acupuncture analgesia were searched in PubMed and EMBASE. The MC number, degranulation ratio and pain threshold changes were collected as outcome measures for meta-analyses. Twenty studies were included with 13 suitable for meta-analysis, most with a moderate risk of bias. A significant MC degranulation after acupuncture was indicated in the normal and was significantly higher in the pain model. In the subgroup analysis by acupuncture type, manual (MA) and electrical (EA, each P < .00001) but not sham acupuncture had significant MC degranulation. Meta-regression revealed the linear proportionality between MC degranulation and acupuncture-induced analgesia (P < .001), which was found essential in MA (P < .00001), but not in EA (P = .45). MC mediators, such as adenosine and histamine, are involved in its mechanism. Taken together, skin MC is an essential factor for acupuncture-induced analgesia, which reveals a new aspect of MC as a pain alleviator. However, its molecular mechanism requires further study. PERSPECTIVE: This systematic review synthesizes data from studies that examined the contribution of skin MC in acupuncture analgesia. Current reports suggest a new role for skin MC and its mediators in pain alleviation and explain a peripheral mechanism of acupuncture analgesia, with suggesting the need of further studies to confirm these findings.