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.

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.

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.

Acupuncture ameliorates not only atopic dermatitis-like skin inflammation but also acute and chronic serotonergic itch possibly through blockade of 5-HT2 and 5-HT7 receptors in mice.

Acupuncture has been known to be effective for atopic dermatitis, especially ameliorating itch; however, its mechanisms are still unclear. The aim of this study was to test the anti-itch effects of acupuncture and to investigate its possible mechanisms. Acupuncture was performed at Gok-Ji (LI11) acupoints just before the injection of pruritogens in the mouse cheek model of acute itch and of MC903-induced atopic dermatitis displaying serotonergic chronic itch. Acupuncture significantly reduced acute itch triggered by compound 48/80, chloroquine, or especially serotonin. It also markedly reduced scratching behaviors evoked by the serotonin 5-HT2 receptor agonist α-methylserotonin and selective 5-HT7 receptor agonist LP 44. In addition, acupuncture treatment at LI11 had the preventive and therapeutic effects on persistent itch as well as the robust skin inflammation with epidermal thickening in mice with MC903-induced atopic dermatitis. It also considerably reduced the increased expression of 5-HT2A, 5-HT2B and 5-HT7 receptors in atopic dermatitis-like skin lesions in mice treated with MC903. Taken together, these findings highlight that acupuncture significantly ameliorates not only skin inflammation, but also acute and chronic serotonergic itch, possibly through blockade of serotonin 5-HT2 and 5-HT7 receptors.

Sulfonate Version of OHPAS Linker Has Two Distinct Pathways of Breakdown: Elimination Route Allows Para-Hydroxy-Protected Benzylsulfonate (PHP-BS) to Serve as an Alternative Self-Immolative Group.

Recently we have reported that the ortho-hydroxy-protected aryl sulfate (OHPAS) system can be exploited as a new self-immolative group (SIG) for phenolic payloads. We extended the system to nonphenolic payloads by simply introducing a para-hydroxy benzyl (PHB) spacer. As an additional variation of the system, we explored a benzylsulfonate version of the OHPAS system and found that it has two distinct breakdown pathways, cyclization and 1,4-elimination, the latter of which implies that para-hydroxy-protected (PHP) benzylsulfonate (BS) can also be used as an alternative SIG. The PHP-BS system was found to be stable chemically and in mouse and human plasma, having payload release rates comparable to those of the original OHPAS conjugates.

Aryl Sulfate is a Useful Motif for Conjugating and Releasing Phenolic Molecules: Sulfur Fluorine Exchange Click Chemistry Enables Discovery of Ortho-Hydroxy-Protected Aryl Sulfate Linker.

A new self-immolative linker motif, Ortho Hydroxy-Protected Aryl Sulfate (OHPAS), was devised, and OHPAS-containing antibody drug conjugates (ADC) were tested in vitro and in vivo. Conveniently synthesized using Sulfur Fluorine Exchange (SuFEx) chemistry, it is based structurally on diaryl sulfate, with one aryl acting as a payload and the other as a self-immolative sulfate unit having a latent phenol function at the ortho position. The chemically stable OHPAS linker was stable in plasma samples from 5 different species, yet it can release the payload molecule smoothly upon chemical or biological triggering. The payload release proceeds via intramolecular cyclization, producing a cyclic sulfate coproduct that eventually hydrolyzes to a catechol monosulfate. A set of OHPAS-containing ADCs based on Trastuzumab were prepared with a drug to antibody ratio of ∼2, and were shown to be cytotoxic in 5 different cancer cell lines in vitro and dose-dependently inhibited tumor growth in a NCI-N87 mouse xenograft model. We conclude that OHPAS conjugates will be of considerable use for delivering phenol-containing payloads to tissues targeted for medical intervention.

Introduction of Para-Hydroxy Benzyl Spacer Greatly Expands the Utility of Ortho-Hydroxy-Protected Aryl Sulfate System: Application to Nonphenolic Payloads.

The ortho-hydroxy-protected aryl sulfate (OHPAS) linker is composed of a diaryl sulfate backbone equipped with a latent phenol moiety at the ortho position of one of the aryl units. The Ar-OH released when the ortho phenol undergoes intramolecular cyclization and displaces the second aryl unit can be viewed as a payload. We have shown in the preceding paper that the OHPAS linkers are highly stable chemically and in various plasmas, yet release payloads when exposed to suitable triggering conditions. As an extension of the OHPAS system, we employed a para-hydroxy benzyl (PHB) spacer for coupling to nonphenolic payloads; this tactic again provided a highly stable system capable of smooth release of appended payloads. The PHB modification works beautifully for tertiary amine and N-heterocycle payloads.

Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture.

BACKGROUND: While full disclosure of information on placebo control in participant information leaflets (PILs) in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes. METHODS: Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI) as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model. RESULTS: In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI -0.21 vs. -0.16; p = 0.38). In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference - 0.43 vs. -0.12; p = 0.03), probably due to enhanced expectations. CONCLUSIONS: How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we have few empirical findings on this issue, future studies are needed to determine whether the present findings are relevant to other medical disciplines and at the same time a routine practice of fully disclosing placebo information in PILs calls for reevaluation.

Acupuncture and related interventions for the treatment of symptoms associated with carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is a compressive neuropathic disorder at the level of the wrist. Acupuncture and other methods that stimulate acupuncture points, such as electroacupuncture, auricular acupuncture, laser acupuncture, moxibustion, and acupressure, are used in treating CTS. Acupuncture has been recommended as a potentially useful treatment for CTS, but its effectiveness remains uncertain. We used Cochrane methodology to assess the evidence from randomised and quasi-randomised trials of acupuncture for symptoms in people with CTS. OBJECTIVES: To assess the benefits and harms of acupuncture and acupuncture-related interventions compared to sham or active treatments for the management of pain and other symptoms of CTS in adults. SEARCH METHODS: On 13 November 2017, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL Plus, DARE, HTA, and NHS EED. In addition, we searched six Korean medical databases, and three Chinese medical databases from inception to 30 April 2018. We also searched clinical trials registries for ongoing trials. SELECTION CRITERIA: We included randomised and quasi-randomised trials examining the effects of acupuncture and related interventions on the symptoms of CTS in adults. Eligible studies specified diagnostic criteria for CTS. We included outcomes measured at least three weeks after randomisation. The included studies compared acupuncture and related interventions to placebo/sham treatments, or to active interventions, such as steroid nerve blocks, oral steroid, splints, non-steroidal anti-inflammatory drugs (NSAIDs), surgery and physical therapy. DATA COLLECTION AND ANALYSIS: The review authors followed standard Cochrane methods. MAIN RESULTS: We included 12 studies with 869 participants. Ten studies reported the primary outcome of overall clinical improvement at short-term follow-up (3 months or less) after randomisation. Most studies could not be combined in a meta-analysis due to heterogeneity, and all had an unclear or high overall risk of bias.Seven studies provided information on adverse events. Non-serious adverse events included skin bruising with electroacupuncture and local pain after needle insertion. No serious adverse events were reported.One study (N = 41) comparing acupuncture to sham/placebo reported change on the Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale (SSS) at three months after treatment (mean difference (MD) -0.23, 95% confidence interval (CI) -0.79 to 0.33) and the BCTQ Functional Status Scale (FSS) (MD -0.03, 95% CI -0.69 to 0.63), with no clear difference between interventions; the evidence was of low certainty. The only dropout was due to painful acupuncture. Another study of acupuncture versus placebo/sham acupuncture (N = 111) provided no usable data.Two studies assessed laser acupuncture versus sham laser acupuncture. One study (N = 60), which was at low risk of bias, provided low-certainty evidence of a better Global Symptom Scale (GSS) score with active treatment at four weeks after treatment (MD 7.46, 95% CI 4.71 to 10.22; range of possible GSS scores is 0 to 50) and a higher response rate (risk ratio (RR) 1.59, 95% CI 1.14 to 2.22). No serious adverse events were reported in either group. The other study (N = 25) did not assess overall symptom improvement.One trial (N = 77) of conventional acupuncture versus oral corticosteroids provided very low-certainty evidence of greater improvement in GSS score (scale 0 to 50) at 13 months after treatment with acupuncture (MD 8.25, 95% CI 4.12 to 12.38) and a higher responder rate (RR 1.73, 95% CI 1.22 to 2.45). Change in GSS at two weeks or four weeks after treatment showed no clear difference between groups. Adverse events occurred in 18% of the oral corticosteroid group and 5% of the acupuncture group (RR 0.29, 95% CI 0.06 to 1.32). One study comparing electroacupuncture and oral corticosteroids reported a clinically insignificant difference in change in BCTQ score at four weeks after treatment (MD -0.30, 95% CI -0.71 to 0.10; N = 52).Combined data from two studies comparing the responder rate with acupuncture versus vitamin B12, produced a RR of 1.16 (95% CI 0.99 to 1.36; N = 100, very low-certainty evidence). No serious adverse events occurred in either group.One study of conventional acupuncture versus ibuprofen in which all participants wore night splints found very low-certainty evidence of a lower symptom score on the SSS of the BCTQ with acupuncture (MD -5.80, 95% CI -7.95 to -3.65; N = 50) at one month after treatment. Five people had adverse events with ibuprofen and none with acupuncture.One study of electroacupuncture versus night splints found no clear difference between the groups on the SSS of the BCTQ (MD 0.14, 95% CI -0.15 to 0.43; N = 60; very low-certainty evidence). Six people had adverse events with electroacupuncture and none with splints. One study of electroacupuncture plus night splints versus night splints alone presented no difference between the groups on the SSS of the BCTQ at 17 weeks (MD -0.16, 95% CI -0.36 to 0.04; N = 181, low-certainty evidence). No serious adverse events occurred in either group.One study comparing acupuncture plus NSAIDs and vitamins versus NSAIDs and vitamins alone showed no clear difference on the BCTQ SSS at four weeks (MD -0.20, 95% CI -0.86 to 0.46; very low-certainty evidence). There was no reporting on adverse events. AUTHORS' CONCLUSIONS: Acupuncture and laser acupuncture may have little or no effect in the short term on symptoms of CTS in comparison with placebo or sham acupuncture. It is uncertain whether acupuncture and related interventions are more or less effective in relieving symptoms of CTS than corticosteroid nerve blocks, oral corticosteroids, vitamin B12, ibuprofen, splints, or when added to NSAIDs plus vitamins, as the certainty of any conclusions from the evidence is low or very low and most evidence is short term. The included studies covered diverse interventions, had diverse designs, limited ethnic diversity, and clinical heterogeneity. High-quality randomised controlled trials (RCTs) are necessary to rigorously assess the effects of acupuncture and related interventions upon symptoms of CTS. Based on moderate to very-low certainty evidence, acupuncture was associated with no serious adverse events, or reported discomfort, pain, local paraesthesia and temporary skin bruises, but not all studies provided adverse event data.

What intrinsic factors influence responsiveness to acupuncture in pain?: a review of pre-clinical studies that used responder analysis.

BACKGROUND: Not many studies have investigated individual sensitivity to acupuncture. To explore the intrinsic factors related to individual responses to acupuncture, we reviewed published pre-clinical studies using responder analysis on pain. METHODS: We searched the PubMed and EMBASE databases to June 2015. We included pre-clinical reports describing responders and non-responders to anti-nociceptive and analgesic effects of acupuncture in animal study. We identified the potential intrinsic factors which might be related with the response to acupuncture. RESULTS: Totally, 216 potentially relevant articles were retrieved and 14 studies met our inclusion criteria. Rat (n = 1348) and rabbit (n = 56) were used, and only electroacupuncture (EA) was applied as an intervention. Results showed that high levels of cholecystokinin-8 and receptors were associated with poor responsiveness to EA. Endogenous opioids including ß-endorphin and met-enkephalin, descending inhibitory norepinephrine and serotonin system, and hypothalamic 5'-AMP-activated protein kinase seemed to be associated with high-level responses. Spinal levels of neurotransmitters and pro-inflammatory cytokines were also differentially expressed depending on the EA sensitiveness. In the central nervous system, hypothalamus, periaqueductal grey, pituitary gland, and spinal cord were suggested to be involved in the EA responsiveness. Identified individual variations did not seem to be accidental, as the responsiveness to EA was replicated over time. However, methodological issues such as reproducibility, cut-off criteria, and clinical relevance need to be further elaborated. CONCLUSION: Our study suggests that the identification of the biological factors differentiating responders from non-responders is necessary and it may aid in understanding how acupuncture modulates pain.

Self-Aligned Multichannel Graphene Nanoribbon Transistor Arrays Fabricated at Wafer Scale.

We present a novel method for fabricating large-area field-effect transistors (FETs) based on densely packed multichannel graphene nanoribbon (GNR) arrays using advanced direct self-assembly (DSA) nanolithography. The design of our strategy focused on the efficient integration of the FET channel and using fab-compatible processes such as thermal annealing and chemical vapor deposition. We achieved linearly stacked DSA nanopattern arrays with sub-10 nm half-pitch critical dimensions (CD) by controlling the thickness of topographic Au confinement patterns. Excellent roughness values (∼10% of CD) were obtained, demonstrating the feasibility of integrating sub-10 nm GNRs into commercial semiconductor processes. Based on this facile process, FETs with such densely packed multichannel GNR arrays were successfully fabricated on 6 in. silicon wafers. With these high-quality GNR arrays, we achieved FETs showing the highest performance reported to date (an on-to-off ratio larger than 10(2)) for similar devices produced using conventional photolithography and block-copolymer lithography.

Reconfigurable van der Waals Heterostructured Devices with Metal-Insulator Transition.

Atomically thin two-dimensional (2D) materials range from semimetallic graphene to insulating hexagonal boron nitride to semiconducting transition-metal dichalcogenides. Recently, metal-insulator-semiconductor field effect transistors built from these 2D elements were studied for flexible and transparent electronics. However, to induce ambipolar characteristics for alternative power-efficient circuitry, ion-gel gating is often employed for high capacitive coupling, limiting stable operation at ambient conditions. Here, we report reconfigurable MoTe2 optoelectronic transistors with all 2D components, where the device can be reconfigured by both drain and gate voltages. Eight different configurations for each fixed voltage are spatially resolved by scanning photocurrent microscopy. In addition, metal-insulator transitions are observed in both electron and hole carriers under 2 V due to strong Coulomb interaction in the system. Furthermore, the vertical tunneling photocurrent through multiple van der Waals layers between the gate and source contacts is measured. Our reconfigurable devices offer potential building blocks for system-on-a-chip optoelectronics.

Anti-angiogenic activity of thienopyridine derivative LCB03-0110 by targeting VEGFR-2 and JAK/STAT3 Signalling.

Vascular endothelial growth factor receptor-2 (VEGFR-2) and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signalling are important for tumor angiogenesis and metastasis. In this study, we identified (3-(2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-ylamino)phenol (LCB03-0110) as a potent angiogenesis inhibitor. LCB03-0110 inhibited VEGFR-2 and JAK/STAT3 signalling in primary cultured human endothelial cells and cancer cells. An in vitro kinase assay and molecular modelling revealed that LCB03-0110 inhibited VEGFR-2, c-SRC and TIE-2 kinase activity via preferential binding at the ATP-binding site of their kinases. LCB03-0110 successfully occupied the hydrophobic pocket of VEGFR-2, c-SRC and TIE-2. LCB03-0110 also inhibited hypoxia-induced HIF/STAT3 and EGF- or angiopoietin-induced signalling cascades. In addition, LCB03-0110 inhibited VEGF-induced proliferation, viability, migration and capillary-like tube formation. LCB03-0110 also suppressed the sprouting of endothelial cells in the rat aorta and the formation of new blood vessels in the mouse Matrigel plug assay, but also suppressed pulmonary metastasis and tumor xenograft in mice. Our results suggest that LCB03-0110 is a potential candidate small molecule for blocking angiogenesis mediated by aberrant activation of VEGFR-2 and JAK/STAT3 signalling.

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.

Drug trials are more likely to disclose full placebo control information than non-drug trials: A cross-sectional study of participant information leaflets of placebo-controlled trials.

Background: This study aimed to investigate whether placebo control is differently disclosed in drug and non-drug randomised clinical trial (RCT) participant information leaflets (PILs) and how this might affect participant blinding and direction of study outcomes. Methods: PILs were obtained from trials registered in the International Standard Randomised Controlled Trial Number database via email. Placebo descriptions in PILs were categorised as Full Disclosure (FD), Partial Disclosure (PD), or Missing Information (MI). Associations between intervention type (drug or non-drug)/placebo disclosure (FD or PD/MI) and participant blinding success/trial outcome direction (positive or non-positive) were examined using a two-sided Fisher's exact test. Results: Of 116 collected PILs, 56 % were for drug trials and 44 % were for non-drug trials. Among them, 88 PILs had the corresponding publications available and 68 reports specified primary outcomes. Drug trials were more likely to fully disclose placebo information than non-drug trials (92.3 % vs. 74.5 %, p < 0.05). However, the success rate of blinding was only reported in 3 out of 88 trial publications (3.4 %), precluding further analysis. Furthermore, there was no significant association between the direction of trial results and the type of intervention or placebo disclosure. Conclusion: Our study findings suggest that drug and non-drug RCTs might differ in the way they reveal placebo control information. Further research is warranted to understand what leads to more common PD of placebo information in non-drug trials than drug trials and to determine the optimal placebo control disclosure in specific trial context.

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.

Moxibustion in the management of irritable bowel syndrome: systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Many patients suffer from IBS that can be difficult to treat, thus complementary therapies which may be effective and have a lower likelihood of adverse effects are being sought.This systematic review and meta-analysis aimed at critically evaluating the current evidence on moxibustion for improving global symptoms of IBS. METHODS: We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, AMED, CINAHL, and CNKI databases for randomised controlled trials (RCTs) of moxibustion comparing with sham moxibustion, pharmacological medications, and other active treatments in patients with IBS. Trials should report global symptom improvement as an outcome measure. Risk of bias for each RCT was assessed according to criteria by the Cochrane Collaboration, and the dichotomous data were pooled according to the control intervention to obtain a risk ratio (RR) of global symptom improvement after moxibustion, with 95% confidence intervals (CI). RESULTS: A total of 20 RCTs were eligible for inclusion (n = 1625). The risk of bias was generally high. Compared with pharmacological medications, moxibustion significantly alleviated overall IBS symptoms but there was a moderate inconsistency among studies (7 RCTs, RR 1.33, 95% CI [1.15, 1.55], I² = 46%). Moxibustion combined with acupuncture was more effective than pharmacological therapy but a moderate inconsistency among studies was found (4 RCTs, RR 1.24, 95% CI [1.09, 1.41], I² = 36%). When moxibustion was added to pharmacological medications or herbal medicine, no additive benefit of moxibustion was shown compared with pharmacological medications or herbal medicine alone. One small sham-controlled trial found no difference between moxibustion and sham control in symptom severity (mean difference 0.35, 95% CI [-0.77, 1.47]). Moxibustion appears to be associated with few adverse events but the evidence is limited due to poor reporting. CONCLUSIONS: This systematic review and meta-analysis suggests that moxibustion may provide benefit to IBS patients although the risk of bias in the included studies is relatively high. Future studies are necessary to confirm whether this finding is reproducible in carefully-designed and conducted trials and to firmly establish the place of moxibustion in current practice.

Acupuncture for ankle sprain: systematic review and meta-analysis.

BACKGROUND: Ankle sprain is one of the most frequently encountered musculoskeletal injuries; however, the efficacy of acupuncture in treating ankle sprains remains uncertain. We therefore performed a systematic review to evaluate the evidence regarding acupuncture for ankle sprains. METHODS: We searched 15 data sources and two trial registries up to February 2012. Randomized controlled trials of acupuncture were included if they involved patients with ankle sprains and reported outcomes of symptom improvement, including pain. A Cochrane risk of bias assessment tool was used. Risk ratio (RR) or mean difference (MD) was calculated with 95% confidence intervals (CIs) in a random effects model. Subgroup analyses were performed based on acupuncture type, grade of sprain, and control type. Sensitivity analyses were also performed with respect to risk of bias, sample size, and outcomes reported. RESULTS: Seventeen trials involving 1820 participants were included. Trial quality was generally poor, with just three reporting adequate methods of randomization and only one a method of allocation concealment. Significantly more participants in acupuncture groups reported global symptom improvement compared with no acupuncture groups (RR of symptoms persisting with acupuncture = 0.56, 95% CI 0.42-0.77). However, this is probably an overestimate due to the heterogeneity (I2 = 51%) and high risk of bias of the included studies. Acupuncture as an add-on treatment also improved global symptoms compared with other treatments only, without significant variability (RR 0.61, 95% CI 0.51-0.73, I2 = 1%). The benefit of acupuncture remained significant when the analysis was limited to two studies with a low risk of bias. Acupuncture was more effective than various controls in relieving pain, facilitating return to normal activity, and promoting quality of life, but these analyses were based on only a small number of studies. Acupuncture did not appear to be associated with adverse events. CONCLUSIONS: Given methodological shortcomings and the small number of high-quality primary studies, the available evidence is insufficient to recommend acupuncture as an evidence-based treatment option. This calls for further rigorous investigations.

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.

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.