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ObjectiveThe purpose of this study was to predict the four cold–heat patterns in patients who have the subjective symptoms of the cold–heat pattern described in the International Classification of Diseases Traditional Medicine Conditions – Module 1 by applying a machine learning algorithm.MethodsSubjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern.ResultsWe included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold–heat pattern.ConclusionWe developed a prediction model on cold–heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold–heat pattern diagnosis by the physician.

We previously reported that a high HbA1c level 3 months before vitrectomy for vitreous hemorrhage or a large preoperative decrease in the HbA1c level over 3 months tended to increase the risk of rebleeding in diabetic retinopathy patients evaluated between 2010 and 2014. Here, we aimed to confirm these results with an extended study period and an increased number of operated eyes. This study included 121 diabetic patients who were admitted to Osaka University Hospital between 2010 and 2019 and who underwent vitrectomy for vitreous hemorrhage. Binomial logistic regression analysis was performed with the presence of postoperative bleeding as the outcome. The present study showed that the duration of the operation was associated with rebleeding (odds ratio = 1.02, p = 0.0016). A high HbA1c level just before vitrectomy tended to be associated with the bleeding (odds ratio = 1.27, p = 0.05), while preoperative HbA1c changes were not associated with rebleeding. The results of this study suggest that a high preoperative HbA1c level just before vitrectomy, not a decrease in HbA1c levels, in addition to the duration of the operation may increase the risk of postoperative bleeding after vitrectomy in diabetic retinopathy patients.

Abstract Background The relationship between plasma tenofovir (TFV) concentration at the beginning of tenofovir disoproxil fumarate (TDF) administration and the development of renal dysfunction during long-term administration of TDF has not been demonstrated yet. The objective of the present study was to determine whether plasma TFV trough concentrations during early TDF administration could serve as an indicator of renal dysfunction when TDF is administered for long periods. Methods We included 149 HIV-1 infected Japanese patients who were prescribed TDF. We investigated the relationship between plasma TFV trough concentrations and the rate of discontinuation due to the development of renal dysfunction for up to five years after the start of TDF administration. We also examined how the decrease in renal function over time due to TDF administration was related to factors associated with high TFV levels and plasma TFV trough concentrations. Results The median TFV trough concentration in the TDF discontinuation group was 88 ng/mL, which was significantly higher (p = 0.0041), than that in the continuation group (72 ng/mL). Further, using an ROC curve, the cut-off value for TFV trough concentration at which TDF discontinuation was significantly high was found to be 98 ng/mL. Logistic multivariate analysis of factors associated with discontinuation of TDF due to renal function-related adverse events showed that being ≥ 50 years old (OR = 2.96; 95% CI, 1.01–8.64), having eGFR

Abstract Developing a safe and potent repellent of mosquitoes applicable to human skins is an effective measure against the spread of mosquito-borne diseases. Recently, we have identified that hydrophobic solutions such as low viscosity polydimethylsiloxane (L-PDMS) spread on a human skin prevent mosquitoes from staying on and biting it. This is likely due to the ability of L-PDMS in wetting mosquito legs and exerting a capillary force from which the mosquitoes attempt to escape. Here we show three additional functions of L-PDMS that can contribute to repel Aedes albopictus, by combining physicochemical analysis and behavioral assays in both an arm cage and a virtual flight arena. First, L-PDMS, when mixed with topical repellents and applied on a human skin, enhances the effect of topical repellents in reducing mosquito bites by efficiently transferring them to mosquito legs upon contact. Second, L-PDMS applied to mosquito tarsi compromises visual object tracking during flight, exerting an influence outlasting the contact. Finally, L-PDMS applied to mosquito tarsi acts as an aversive reinforcer in associative learning, making mosquitoes avoid the conditioned odor. These results uncover a multifaceted potential of L-PDMS in altering a sequence of mosquito behaviors from biting a human skin, visual object tracking following takeoff, to the response to an odor linked with L-PDMS.

Abstract Optogenetics enables precise regulation of intracellular signaling in target cells. However, the application of optogenetics to induce the differentiation of precursor cells and generate mature cells with specific functions has not yet been fully explored. Here, we focused on osteoclasts, which play an important role in bone remodeling, to develop a novel optogenetics tool, Opto-RANK, which can manipulate intracellular signals involved in osteoclast differentiation and maturation using blue light. We engineered Opto-RANK variants, Opto-RANKc and Opto-RANKm, and generated stable cell lines through retroviral transduction. Differentiation was induced by blue light, and various assays were conducted for functional analysis. Osteoclast precursor cells expressing Opto-RANK differentiated into multinucleated giant cells on light exposure and displayed upregulation of genes normally induced in differentiated osteoclasts. Furthermore, the differentiated cells exhibited bone-resorbing activities, with the possibility of spatial control of the resorption by targeted light illumination. These results suggested that Opto-RANK cells differentiated by light possess the features of osteoclasts, both morphological and functional. Thus, Opto-RANK should be useful for detailed spatiotemporal analysis of intracellular signaling during osteoclast differentiation and the development of new therapies for various bone diseases.

Abstract Background The sarcomatous variant of carcinoma is relatively rare in intrahepatic cholangiocarcinoma (ICC). Sarcomatous ICC (SICC) is associated with a poorer prognosis compared with ICC. SICC is rarely diagnosed before surgery due to non-descriptive findings; it progresses rapidly, resulting in miserable prognosis. Here, we report a case of rapidly progressing SICC that showed a clinically significant tumor growth rate. Case presentation A 77-year-old woman who had undergone ileocecal resection for cecal cancer 5 years previously was found to have elevated levels of the tumor marker carbohydrate antigen 19-9. Although an abdominal computed tomography (CT) scan did not detect any liver mass lesions until 3 months before this serum examination, the subsequent CT scan revealed a hypodensity 20 mm mass lesion in the right anterior section. Contrast-enhanced CT and magnetic resonance imaging revealed peripheral enhancement in the arterial-to-equilibrium phase. Fluorodeoxyglucose positron emission tomography revealed uptake in the lesion. None of the imaging modalities showed lymph node swelling or distant metastases. She underwent hepatectomy under the diagnosis of ICC or an atypical metastasis from previous cecal cancer. Although preoperative images showed no suspicious lymph node metastasis 3 weeks prior, the hilar lymph node swelled 3 cm and contained adenocarcinoma. Consequently, the patient underwent right anterior sectionectomy and lymph node dissection of the hepatoduodenal ligament. Histopathological examination revealed that the liver tumor was a poorly differentiated adenocarcinoma with sarcomatous pattern. While the patient received adjuvant gemcitabine and S-1 therapy, lymph node metastasis appeared in the mediastinum 13 months after the surgery. She received gemcitabine + cisplatin + S-1 therapy but died 20 months after surgery. Conclusion SICC and lymph node metastasis clinically appeared within 3 months and 3 weeks, respectively. Suspected ICC that rapidly progresses should be considered SICC and treated with early resection. SICC is often missed in clinical diagnosis and has a poor prognosis, even after curative resection. While an alternative strategy involving preoperative biopsy and neoadjuvant therapy may be beneficial, it should be approached with discretion due to the potential risks of tumor progression and peritoneal dissemination.

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic disease that can rapidly deteriorate into circulatory collapse when complicated by comorbidities. We herein describe a case involving a 43‐year‐old woman with class III obesity (body mass index of 63 kg/m2) and severe CTEPH associated with total occlusion of the left main pulmonary artery who subsequently developed circulatory collapse along with multiple comorbidities, including acute kidney injury, pulmonary tuberculosis, and catastrophic antiphospholipid syndrome. The patient was successfully treated with two sessions of rescue balloon pulmonary angioplasty with veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) support under local anesthesia without sedation, at cannulation and during the V‐A ECMO run, to avoid invasive mechanical ventilation. This case suggests the potential usefulness of rescue balloon pulmonary angioplasty under awake V‐A ECMO support for rapidly deteriorating, inoperable CTEPH in a patient with class III obesity complicated with multiple comorbidities.

Determining the inner structure of the molecular torus around an active galactic nucleus is essential for understanding its formation mechanism. However, spatially resolving the torus is difficult because of its small size. To probe the clump conditions in the torus, we therefore perform the systematic velocity-decomposition analyses of the gaseous ^12 CO rovibrational absorption lines ( v = 0 → 1, Δ J = ±1) at λ ∼ 4.67 μ m observed toward four (ultra)luminous infrared galaxies using the high-resolution ( R ∼ 5000–10,000) spectroscopy from the Subaru Telescope. We find that each transition has two to five distinct velocity components with different line-of-sight (LOS) velocities ( V _LOS ∼ −240 to +100 km s ^−1 ) and dispersions ( σ _V ∼ 15–190 km s ^−1 ), i.e., the components (a), (b), ⋯, beginning with the broadest one in each target, indicating that the tori have clumpy structures. By assuming a hydrostatic disk ( ${\sigma }_{V}\propto {R}_{\mathrm{rot}}^{-0.5}$ ), we find that the tori has dynamic inner structures, with the innermost component (a) outflowing with velocity ∣ V _LOS ∣ ∼ 160–240 km s ^−1 , and the outer components (b) and (c) outflowing more slowly or infalling with ∣ V _LOS ∣ ≲ 100 km s ^−1 . In addition, we find that the innermost component (a) can be attributed to collisionally excited hot (≳530 K) and dense ( $\mathrm{log}({n}_{{{\rm{H}}}_{2}}/{\mathrm{cm}}^{-3})\gtrsim 6$ ) clumps, based on the level populations. Conversely, the outer component (b) can be attributed to cold (∼30–140 K) clumps radiatively excited by a far-infrared-to-submillimeter background with a brightness temperature higher than ∼20–400 K. These observational results demonstrate the clumpy and dynamic structure of tori in the presence of background radiation.

We investigate the physical origins of the Balmer decrement anomalies in GS-NDG-9422 and RXCJ2248-ID galaxies at z ∼ 6 whose H α /H β values are significantly smaller than 2.7, the latter of which also shows anomalous H γ /H β and H δ /H β values beyond the errors. Because the anomalous Balmer decrements are not reproduced under the Case B recombination, we explore the nebulae with optical depths smaller and larger than the Case B recombination by physical modeling. We find two cases quantitatively explaining the anomalies: (1) density-bounded nebulae that are opaque only up to around Ly γ –Ly8 transitions and (2) ionization-bounded nebulae partly/fully surrounded by optically thick excited H i clouds. The case of (1) produces more H β photons via Ly γ absorption in the nebulae, requiring fine tuning in optical depth values, while this case helps ionizing photon escape for cosmic reionization. The case of (2) needs the optically thick excited H i clouds with N _2 ≃ 10 ^12 −10 ^13 cm ^−2 , where N _2 is the column density of the hydrogen atom with the principal quantum number of n = 2. Interestingly, the high N _2 values qualitatively agree with the recent claims for GS-NDG-9422 with the strong nebular continuum requiring a number of 2 s -state electrons and for RXCJ2248-ID with the dense ionized regions likely coexisting with the optically thick clouds. While the physical origin of the optically thick excited H i clouds is unclear, these results may suggest gas clouds with excessive collisional excitation caused by an amount of accretion and supernovae in the high- z galaxies.

Reducing the average Al composition of Al _x Ga _1− _x N/Al _y Ga _1− _y N multiple quantum wells (MQWs) is an effective approach to increase the current injection efficiencies of far-UV-C LEDs (far-UVC LEDs). A reduction can be realized by decreasing the Al-composition differentiation between the well and barrier layers. Compared to conventional MQWs, a 230 nm wavelength far-UVC LED equipped with a single-Al-composition and a 39 nm thick light-emitting layer exhibits a higher external quantum efficiency (EQE). The EQE of far-UVC LEDs with low Al-composition differentiation (∼1%) is enhanced to approximately 0.6% and 1.4% under continuous wave operations at 230 nm and 236 nm wavelengths, respectively.

We introduce a novel model to spectroscopically constrain the mid-infrared (MIR) extinction/attenuation curve from 3–17 μ m, using polycyclic aromatic hydrocarbon (PAH) emission drawn from an AKARI–Spitzer extragalactic cross-archival data set. Currently proposed MIR extinction curves vary significantly in their slopes toward the near-infrared, and the variation in the strengths and shapes of the 9.7 μ m and 18 μ m silicate absorption features make MIR spectral modeling and interpretation challenging, particularly for heavily obscured galaxies. By adopting the basic premise that PAH bands have relatively consistent intrinsic ratios within dusty starbursting galaxies, we can, for the first time, empirically determine the overall shape of the MIR attenuation curve by measuring the differential attenuation at specific PAH wavelengths. Our attenuation model shows PAH emission in most (ultra)luminous infrared galaxies is unambiguously subjected to attenuation, and we find strong evidence that PAH bands undergo differential attenuation as obscuration increases. Compared to preexisting results, the MIR attenuation curve derived from the model favors relatively gray continuum absorption from 3–8 μ m and silicate features with intermediate strength at 9.7 μ m but with stronger than typical 18 μ m opacity.

Objective: Although reports of endovascular treatment for intracranial arterial stenosis have been increasing recently, their efficacy remains to be elucidated. This study aimed to investigate the changes in cerebral hemodynamics of severe middle cerebral artery (MCA) stenosis patients by performing CT perfusion (CTP) after endovascular treatment., Methods: Subjects were those who underwent balloon angioplasty and stenting for symptomatic MCA M1 stenosis refractory to medical therapy at our hospital between 2008 and 2022. We included 36 patients (mean age 63.69 ± 15.24 years, 20 males) who underwent CTP before and within three weeks after treatment. The CTP parameters such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) were calculated as ipsilateral values divided by contralateral value., Results: Endovascular treatment consisted of 26 balloon angioplasty and 10 stenting procedures performed at an average of 1 month from onset. CTP was performed at an average of 5.5 days postoperatively. The mean overall stenosis rate decreased from 79.0% to 30.3%. In the balloon angioplasty group, it decreased from 77.6% to 35.3%, and in the stent group, it decreased from 82.7% to 17.5%. After treatment, rCBF and rMTT measured by CTP improved significantly (both p  < 0.001), whereas there was no significant change in rCBV. The improvement rates of rCBF and rMTT were mild higher in the stent group, but not significantly so., Conclusion: Balloon angioplasty and stenting for symptomatic MCA improved cerebral hemodynamics, resulting in significantly increased rCBF and decreased rMTT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Distinguishing human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy from hereditary spastic paraplegia in patients infected with HTLV-1 is challenging due to overlapping clinical symptoms. The aim of this study was to explore the possibility that hereditary spastic paraplegia is inherently present in patients diagnosed with HTLV-1-associated myelopathy., Methods: We performed whole-genome sequencing on 315 unrelated patients registered in the HTLV-1-Associated Myelopathy patient registry "HAM-net," from 2013 to 2022 in Japan. CSF inflammatory biomarkers, including CXCL10, were measured., Results: We identified 5 patients with pathogenic variants in the genes RTN2 , SPAST , VCP , and UBAP1 , which are the known causes of hereditary spastic paraplegia. These patients had no family history of hereditary spastic paraplegia. The levels of CSF inflammatory biomarkers were lower than expected in these patients, compared with disease severity., Discussion: Genetic analysis is useful for the differentiation of hereditary spastic paraplegia patients from HTLV-1-associated myelopathy patients, especially for the patients with low levels of CSF inflammatory markers. Here we report the presence of hereditary spinal cord diseases in patients diagnosed with HTLV-1-associated myelopathy and provides evidence that genetic analysis would be helpful in the diagnostic workflow., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)