An NK-like CAR T cell transition in CAR T cell dysfunction.

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematological malignancies but remains ineffective in solid tumors, due in part to CAR T cell exhaustion in the solid tumor microenvironment. To study dysfunction of mesothelin-redirected CAR T cells in pancreatic cancer, we establish a robust model of continuous antigen exposure that recapitulates hallmark features of T cell exhaustion and discover, both in vitro and in CAR T cell patients, that CAR dysregulation is associated with a CD8+ T-to-NK-like T cell transition. Furthermore, we identify a gene signature defining CAR and TCR dysregulation and transcription factors, including SOX4 and ID3 as key regulators of CAR T cell exhaustion. Our findings shed light on the plasticity of human CAR T cells and demonstrate that genetic downmodulation of ID3 and SOX4 expression can improve the efficacy of CAR T cell therapy in solid tumors by preventing or delaying CAR T cell dysfunction.

ILD-GAP combined with the monocyte ratio could be a better prognostic prediction model than ILD-GAP in patients with interstitial lung diseases.

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.

There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients <40 y old, we observed that nonphosphorylated CRMP2 was higher than in controls, while phosphorylated CRMP2 remained unchanged from control. In the brain, these changes were associated with dendritic structural abnormalities. The abundance of active CRMP2 with insufficient opposing inactive p-CRMP2 yielded a unique lowering of the p-CRMP2:CRMP2 ratio in SCZ patients, implying a disruption in the normal equilibrium between active and inactive CRMP2. These clinical data suggest that measuring CRMP2 and p-CRMP2 in peripheral blood might reflect intracerebral processes and suggest a rapid, minimally invasive, sensitive, and specific adjunctive diagnostic aid for early SCZ: increased CRMP2 or a decreased p-CRMP2:CRMP2 ratio may help cinch the diagnosis in a newly presenting young patient suspected of SCZ (versus such mimics as mania in bipolar disorder, where the ratio is high).

Inductive effect of SORT1 on odontoblastic differentiation of human dental pulp-derived stem cells.

This study investigated the expression of sortilin 1 (SORT1) in cultured human dental pulp-derived stem cells (hDPSCs) and its role in their odontoblastic differentiation. Permanent teeth were extracted from five patients, and the dental pulp was harvested for explant culture. Fluorescence-activated cell sorting was used to analyze the outgrowth of adherent cells and cells that had migrated from the tissue margin. SORT1 expression was detected in hDPSCs simultaneously expressing the mesenchymal stem cell markers CD44 and CD90. The odontoblastic differentiation potential of SORT1-positive hDPSCs was examined via staining for alkaline phosphatase (ALP), an early odontoblastic differentiation marker. ALP staining was more intense in SORT1-positive than in SORT1-negative hDPSCs. Consistently, the expression of mRNA encoding SORT1 and p75NTR, a binding partner of SORT1, increased in SORT1-positive hDPSCs during odontoblastic differentiation. In addition, pro-nerve growth factor (NGF), a ligand for SORT1-p75NTR co-receptor, promoted ALP expression in SORT1-positive hDPSCs, and the interaction between SORT1 and p75NTR was detected using a coimmunoprecipitation assay. The function of SORT1 in odontoblastic differentiation was examined via RNA interference using shRNA targeting SORT1. ALP staining intensity in SORT1/shRNA-transfected cells was markedly lower than in control/shRNA-transfected cells. SORT1 knockdown decreased JUN phosphorylation and recruitment of phosphorylated JUN to the ALP promoter. Collectively, these results indicate that SORT1 is involved in the odontoblastic differentiation of hDPSCs through the JUN N-terminal kinases (JNK)/JUN signaling pathway and that the binding of SORT1 and p75NTR plays an important role in this process.

A GRU-Based Model for Detecting Common Accidents of Construction Workers.

Fall accidents in the construction industry have been studied over several decades and identified as a common hazard and the leading cause of fatalities. Inertial sensors have recently been used to detect accidents of workers in construction sites, such as falls or trips. IMU-based systems for detecting fall-related accidents have been developed and have yielded satisfactory accuracy in laboratory settings. Nevertheless, the existing systems fail to uphold consistent accuracy and produce a significant number of false alarms when deployed in real-world settings, primarily due to the intricate nature of the working environments and the behaviors of the workers. In this research, the authors redesign the aforementioned laboratory experiment to target situations that are prone to false alarms based on the feedback obtained from workers in real construction sites. In addition, a new algorithm based on recurrent neural networks was developed to reduce the frequencies of various types of false alarms. The proposed model outperforms the existing benchmark model (i.e., hierarchical threshold model) with higher sensitivities and fewer false alarms in detecting stumble (100% sensitivity vs. 40%) and fall (95% sensitivity vs. 65%) events. However, the model did not outperform the hierarchical model in detecting coma events in terms of sensitivity (70% vs. 100%), but it did generate fewer false alarms (5 false alarms vs. 13).

Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis.

BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple anti-tuberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either catalogue-based approach, wherein one causative mutation suggests resistance, (e.g., WHO catalog) or non-catalogue-based approach using complicated algorithm (e.g., TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the two approaches. METHODS: Following the systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model. RESULTS: Out of 779 articles, 44 articles with 16,821 specimens for meta-analysis and 13 articles not for meta-analysis were adopted. The areas under summary receiver operating characteristic curve suggested "excellent" (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), "very good" (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and "good" (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The non-catalogue-based and catalogue-based approaches had similar ability for all drugs. CONCLUSION: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The two approaches had similar ability.

The cancer epigenome: Non-cell autonomous player in tumor immunity.

Dysregulation of the tumor-intrinsic epigenetic circuit is a key driver event for the development of cancer. Accumulating evidence suggests that epigenetic and/or genetic drivers stimulate intrinsic oncogenic pathways as well as extrinsic factors that modulate the immune system. These modulations indeed shape the tumor microenvironment (TME), allowing pro-oncogenic factors to become oncogenic, thereby contributing to cancer development and progression. Here we review the epigenetic dysregulation arising in cancer cells that disseminates throughout the TME and beyond. Recent CRISPR screening has elucidated key epigenetic drivers that play important roles in the proliferation of cancer cells (intrinsic) and inhibition of antitumor immunity (extrinsic), which lead to the development and progression of cancer. These epigenetic players can serve as promising targets for cancer therapy as a dual (two-in-one)-targeted approach. Considering the interplay between cancer and the immune system as a key determinant of immunotherapy, we discuss a novel lineage-tracing technology that enables longitudinal monitoring of cancer and immune phenotypic heterogeneity and fate paths during cancer development, progression, and therapeutic interventions.

Role of solvophilic moieties of gelators in the thermal stability of organogels.

Affinity analysis using Hansen solubility parameters (HSP) reveals that the gel-sol transition point of binary organogels is correlated with preferential interactions between the solvophilic moiety of gelators and solvents. The decomposition of gelators in HSP analysis can be effectively used for predicting the thermal stability of gels.

Comparative Observation and Analysis of Preference Behavior Based on Three Types of Taxes and Locomotor Activity in the Goldfish, Carassius auratus.

Psychophysiological studies in vertebrates have focused on taxes as indicators of behavioral change. Actually, a considerable number of studies about anxiety-like and anti-anxiety-like behaviors involving geotaxis, scototaxis, and thigmotaxis have been conducted on fish. However, few analyses considering these behaviors based on taxes in fish have been conducted. Here, using goldfish, we measured the time spent in the bright or dark area of a horizontally long rectangular tank (HLRT), in the upper or lower area of a vertically long rectangular tank (VLRT), and in the central or edge area of a circular tank (CT), respectively, for the first 30 min and the last 30 min in a 3-h period after fish had been introduced to tanks. Dark, lower, and edge preference behaviors were observed for the first 30 min in all tanks. While dark and edge preference behaviors were maintained even for the last 30 min, the lower preference was lost. Swimming distance and the number of area crossings in each tank were also compared between the first 30 min and the last 30 min. Both decreased significantly or tended to decrease in the last 30 min in the HLRT and the CT, but no change was observed in the VLRT. These results suggest that, in goldfish, preference behavior is stable for a short time, and that environmental habituation may depend on the shape of the tank and the elapsed time.

Screening for Major Depressive Disorder Using a Wearable Ultra-Short-Term HRV Monitor and Signal Quality Indices.

To encourage potential major depressive disorder (MDD) patients to attend diagnostic sessions, we developed a novel MDD screening system based on sleep-induced autonomic nervous responses. The proposed method only requires a wristwatch device to be worn for 24 h. We evaluated heart rate variability (HRV) via wrist photoplethysmography (PPG). However, previous studies have indicated that HRV measurements obtained using wearable devices are susceptible to motion artifacts. We propose a novel method to improve screening accuracy by removing unreliable HRV data (identified on the basis of signal quality indices (SQIs) obtained by PPG sensors). The proposed algorithm enables real-time calculation of signal quality indices in the frequency domain (SQI-FD). A clinical study conducted at Maynds Tower Mental Clinic enrolled 40 MDD patients (mean age, 37.5 ± 8.8 years) diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 29 healthy volunteers (mean age, 31.9 ± 13.0 years). Acceleration data were used to identify sleep states, and a linear classification model was trained and tested using HRV and pulse rate data. Ten-fold cross-validation showed a sensitivity of 87.3% (80.3% without SQI-FD data) and specificity of 84.0% (73.3% without SQI-FD data). Thus, SQI-FD drastically improved sensitivity and specificity.

Correlation between pain catastrophizing in acute herpes zoster and postherpetic neuralgia: a retrospective analysis.

PURPOSE: The objective of this study was to examine the association between pain catastrophizing in acute phase herpes zoster and the development of postherpetic neuralgia. METHODS: The medical records of all patients diagnosed with herpes zoster between February 2016 and December 2021 were retrieved. Inclusion criteria were patients aged > 50 years who visited our pain center within 60 days after rash onset and reported a pain intensity of ≥ 3 in a numerical rating scale. Patients with a score of 30 or more in the pain catastrophizing scale at baseline were assigned to the catastrophizer group, and those with a score < 30 were assigned to the non-catastrophizer group. We defined patients with "postherpetic neuralgia" and "severe postherpetic neuralgia" as those with a numerical rating scale score of 3 or more and 7 or more at 3 months after baseline, respectively. RESULTS: Data of 189 patients were available for complete analysis. Age, baseline numerical rating scale, and prevalence of anxiety and depression were significantly higher in the catastrophizer than those in the non-catastrophizer group. Incidence of postherpetic neuralgia did not differ significantly between the groups (p = 0.26). Multiple logistic regression analysis showed that age, severe pain at baseline, and immunosuppressive state were the factors which were independently associated with developing postherpetic neuralgia. Severe pain at baseline was the only factor related to developing severe postherpetic neuralgia. CONCLUSION: Pain catastrophizing in the acute phase of herpes zoster may not be related to the development of postherpetic neuralgia.

Single Virus Detection on Silicon Photonic Crystal Random Cavities.

On-chip silicon microcavity sensors are advantageous for the detection of virus and biomolecules due to their compactness and the enhanced light-matter interaction with the analyte. While their theoretical sensitivity is at the single-molecule level, the fabrication of high quality (Q) factor silicon cavities and their integration with optical couplers remain as major hurdles in applications such as single virus detection. Here, label-free single virus detection using silicon photonic crystal random cavities is proposed and demonstrated. The sensor chips consist of free-standing silicon photonic crystal waveguides and do not require pre-fabricated defect cavities or optical couplers. Residual fabrication disorder results in Anderson-localized cavity modes which are excited by a free space beam. The Q ≈105 is sufficient for observing discrete step-changes in resonance wavelength for the binding of single adenoviruses (≈50 nm radius). The authors' findings point to future applications of CMOS-compatible silicon sensor chips supporting Anderson-localized modes that have detection capabilities at the level of single nanoparticles and molecules.

Engineering strategies for broad application of TCR-T- and CAR-T-cell therapies.

Adoptive-cell therapy, including the transfer of tumor-infiltrating T lymphocytes after in vitro expansion or T cells redirected to tumor antigens using antigen-specific transgenic T-cell receptor T cells (TCR-T cells) or chimeric antigen receptor T cells (CAR-T cells), has shown a significant clinical impact. Particularly, several types of CAR-T-cell therapies have been approved for the treatment of hematological malignancies. The striking success of CAR-T-cell therapies in hematological malignancies motivates their further expansion to a wide range of solid tumors, yet multiple obstacles, including the lack of proper target antigens exhibiting a tumor-specific expression pattern and the immunosuppressive tumor microenvironment (TME) impairing the effector functions of adoptively transferred T cells, have prevented clinical application. Gene engineering technologies such as the CRISPR/Cas9 system have enabled flexible reprogramming of TCR/CAR-T-cell signaling or loading genes that are targets of the tumor immunosuppression as a payload to overcome the difficulties. Here, we discuss recent advances in TCR/CAR-T-cell engineering: various promising approaches to enhance the anti-tumor activity of adoptively transferred T cells in the TME for maximizing the efficacy and the safety of adoptive-cell therapy are now being tested in the clinic, especially targeting solid tumors.

Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study.

BACKGROUND: This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. METHODS: This prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2. RESULTS: Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels. CONCLUSIONS: Liquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.

Phase-Separated Nanodroplets Formed below the Cloud Point for the Aqueous Solution of Stereo-Controlled Poly(N-isopropylacrylamide).

The relationship between dehydration of polymer chains and the nanodroplet formation through the macroscopic liquid-liquid phase separation (LLPS) has been investigated for the aqueous solution of stereocontrolled poly(N-isopropylacrylamide) (PNiPAm) and poly(N-diethylacrylamide) (PNdEAm). The fluorescent probe method reveals that the temperature range of dehydration for PNiPAm chains is much narrower than that for PNdEAm. The sharp dehydration of polymer chains may give rise to the characteristic thermoresponsive behavior of PNiPAm in water. For meso-rich PNiPAms, the dehydration point (Tdh), which is defined as the temperature where the single chains start assembling in the solution, locates far from the cloud point (Tc). That is, the dehydration of the chain occurs antecedently before the system undergoes a macroscopic LLPS. For PNdEAm, however, the dissociation between Tdh and Tc is not found. For the aqueous solution of PNiPAm with 52% of the meso content, the fluorescence correlation spectroscopy has revealed that nano-order droplets (ca. 45 nm of the hydration radius) are stabilized in the intermediate state between Tdh and Tc. The sharp dehydration of PNiPAm chains may enable an acute condensation of polymers in droplets, causing a viscoelastic hindrance in the coalescence of droplets.

Use of Systemic Corticosteroids for Reasons Other than Asthma in Subjects with Asthma.

BACKGROUNDS: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. OBJECTIVES: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. METHOD: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. RESULTS: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. CONCLUSIONS: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.

Multidimensional Vibrational Circular Dichroism Apparatus Equipped with Quantum Cascade Laser and Its Use for Investigating Some Peptide Systems Containing d-Amino Acids.

We developed a multidimensional vibrational circular dichroism system with a positional coordinate, making it possible to move in both x- and y-directions using an automatic stage. Quantum cascade laser (QCL) was used as a light source to achieve high intensity and narrow focusing. The QCL emitted light in the wavenumber range of 1500-1740 cm-1, which encompassed absorption bands assigned to the stretching vibrations of amides I and II. The operation of the instrument was analyzed for samples containing amide groups. An aqueous solution of Gly-l-Leu or Gly-d-Leu was measured under the background absorbance as high as 3.5 due to the water medium. The spectra were recorded by scanning at 1.0 cm-1 steps. The time required for performing measurement at each wavenumber was less than 1 s. The mirror-image relation was maintained between the optical antipodes. A peak assigned to amide II appeared clearly at around 1580 cm-1. In the case of KBr pellets containing the same compounds, peaks assigned to amide I and II were observed. For two-dimensional pattering, a KBr pellet comprising two domains of amino acids (or l-Ala and d-Ser) was investigated. The distribution of each component within the pellet was obtained under the two-dimensional alignment at the spatial interval of 2.5 mm.

Feasibility, reliability, and validity of the 12-item World Health Organization Disability Assessment Schedule 2.0 in patients attending the pain clinic.

PURPOSE: In the cohort of patients attending pain clinic, the primary goal has been shifting from pain reduction to improving activities of daily living and functional status. The 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is one of the useful tools for assessment of functional status across all psychiatric and medical diseases; however, its feasibility, reliability, and validity have not been assessed in these patients. Thus, in this study, we evaluated the feasibility, reliability, and validity of the 12-item WHODAS 2.0 in patients attending the pain clinic at our university hospital. METHODS: This is a prospective observational study including the patients aged 50 years or older who were attending the pain clinic at Nara Medical University between April 2019 and May 2019. Patient-related outcomes including functional status and activities of daily living were assessed with the 12-item WHODAS 2.0, EuroQol-5 dimension 5 levels, and the Tokyo Metropolitan Institute of Gerontology Index. RESULTS: The response rate was 99.7%. The 12-item WHODAS2.0 had a floor effect but no ceiling effect and its Cronbach's α coefficient was 0.909. The correlation coefficients between the 12-item WHODAS 2.0 score and the EuroQol-5 dimension 5 levels and the Tokyo Metropolitan Institute of Gerontology Index were -0.66 and -0.67, respectively. CONCLUSIONS: The 12-item WHODAS 2.0 is a useful measurement tool to assess disability of pain patients with high reliability and validity.

The short-term effect of COVID-19 pandemic on disability, pain intensity, psychological status, and exercise habits in patients with chronic pain.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has affected the lives of people worldwide. The first declaration of a state of emergency in Japan, based on the Act on Special Measures for the Prevention and Control of the Novel Coronavirus, was issued from 16 April 2020 to 14 May 2020 to reduce person-to-person contact. Restrictions on going out, participating in community activities, and visiting hospitals were in place. This study investigates the short-term effects of the COVID-19 pandemic on patients with chronic pain. METHODS: This study included outpatients with chronic pain undergoing treatment at the Pain Center of Nara Medical University Hospital. The patients had completed questionnaires for a disability during the study period, from 1 July to 30 September 2019 (baseline), 1 October to 31 December 2019 (pre-pandemic), and 1 July to 30 September 2020 (during the pandemic). The questionnaire covered changes in disability, pain intensity, health-related quality of life (QOL), anxiety, depression, catastrophic thinking, and the presence/absence of exercise habits at baseline, pre-pandemic, and during the pandemic. RESULTS: Of the 245 eligible patients, there was no significant disability difference between baseline, pre-pandemic, and during the pandemic (p = 0.14). Similarly, pain intensity, health-related QOL, anxiety, depression, and the presence/absence of exercise habits did not significantly differ between baseline, pre-pandemic, and during the pandemic either. The current study observed significant differences in terms of catastrophic thinking (p = 0.02). CONCLUSION: The effects of the COVID-19 pandemic on patients with chronic pain were not apparent in the short-term. Clinical trail registration: UMIN000043174.

pH-sensitive GaInAsP photonic crystal fractal band-edge laser.

The light emission characteristics of GaInAsP semiconductors in aqueous solutions are modified by the surface charge, depending on the balance between radiative and nonradiative recombination. This Letter demonstrates the application of a GaInAsP photonic crystal band-edge laser in sensing a solution pH, which reflects the surface charge. The sensitivity is enhanced by a hybrid of fractal honeycomb and close-packed structures with a large surface-to-volume ratio and a high quality factor (Q), which allows a low threshold carrier density. We experimentally obtained a maximum pH sensitivity of 1.9 dB/pH near the threshold and a signal-to-noise ratio of 52/pH (pH resolution of 0.019) at a pump power 2.4 times the threshold where the intensity noise diminished.