Efficacy, Safety, and Continuation of Biological Therapy in Older Patients with Asthma in a Real-World Setting: A Retrospective Observational Study.

Background: Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma. Methods: In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated. Results: Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group. Conclusion: Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma.

Pembrolizumab-induced asthma exacerbation with hypereosinophilia and elevated interleukin-5 in endometrial cancer: A case report.

Pembrolizumab is an anti-programmed cell death-1 (PD-1) antibody used to treat various cancer types. Treatments with such immune checkpoint inhibitors cause immune-related adverse events. However, airway inflammation caused by immune-related adverse events has rarely been reported. A 54-year-old woman with endometrial cancer experienced asthma exacerbation, and increased blood eosinophil counts 3 months after pembrolizumab administration. Although asthma exacerbation improved, the resumption of pembrolizumab caused the recurrence of dry cough and hypereosinophilia. The discontinuation of pembrolizumab improved her symptoms. Serum interleukin-5 levels increased during pembrolizumab treatment but decreased upon discontinuation. The blockade of PD-1 and its ligand may exacerbate asthma through eosinophilic inflammation.

Correction: The Li + CaF → Ca + LiF chemical reaction under cold conditions.

Correction for 'The Li + CaF → Ca + LiF chemical reaction under cold conditions' by Humberto da Silva Jr et al., Phys. Chem. Chem. Phys., 2023, 25, 14193-14205, https://doi.org/10.1039/D3CP01464A.

The Clinical Characteristics of Allergic Bronchopulmonary Mycosis Differ Among Pathogenic Fungi.

Background: Allergic bronchopulmonary mycosis (ABPM) occurs with fungi, other than Aspergillus fumigatus. However, the clinical characteristics of ABPM caused by non-Aspergillus species are unspecified. Methods: We retrospectively reviewed all patients with ABPM who visited to our hospital between April 2005 and December 2020. The causative fungi and clinical characteristics were analyzed. Patients were divided into the Aspergillus group and the non-Aspergillus group. Results: Fourteen patients and five patients were included in the Aspergillus group and the non-Aspergillus group, respectively. Compared to the Aspergillus group, the non-Aspergillus group had a significantly low serum immunoglobulin E level and low forced vital capacity. In addition, the non-Aspergillus group had a lower rate of the requirement for oral corticosteroid treatment and a low frequency of recurrence. Conclusion: Patients with non-Aspergillus ABPM had lower type 2 inflammation than did patients with allergic bronchopulmonary aspergillosis.

The Li + CaF → Ca + LiF chemical reaction under cold conditions.

The calcium monofluoride (CaF) molecule has emerged as a promising candidate for precision measurements, quantum simulation, and ultracold chemistry experiments. Inelastic and reactive collisions of laser cooled CaF molecules in optical tweezers have recently been reported and collisions of cold Li atoms with CaF are of current experimental interest. In this paper, we report ab initio electronic structure and full-dimensional quantum dynamical calculations of the Li + CaF → LiF + Ca chemical reaction. The electronic structure calculations are performed using the internally contracted multi-reference configuration-interaction method with Davidson correction (MRCI + Q). An analytic fit of the interaction energies is obtained using a many-body expansion method. A coupled-channel quantum reactive scattering approach implemented in hyperspherical coordinates is adopted for the scattering calculations under cold conditions. Results show that the Li + CaF reaction populates several low-lying vibrational levels and many rotational levels of the product LiF molecule and that the reaction is inefficient in the 1-100 mK regime allowing sympathetic cooling of CaF by collisions with cold Li atoms.

Signatures of Non-universal Quantum Dynamics of Ultracold Chemical Reactions of Polar Alkali Dimer Molecules with Alkali Metal Atoms: Li(2S) + NaLi(a3Σ+) → Na(2S) + Li2(a3Σu+).

Ultracold chemical reactions of weakly bound triplet-state alkali metal dimer molecules have recently attracted much experimental interest. We perform rigorous quantum scattering calculations with a new ab initio potential energy surface to explore the chemical reaction of spin-polarized NaLi(a3Σ+) and Li(2S) to form Li2(a3Σu+) and Na(2S). The reaction is exothermic and proceeds readily at ultralow temperatures. Significantly, we observe strong sensitivity of the total reaction rate to small variations of the three-body part of the Li2Na interaction at short range, which we attribute to a relatively small number of open Li2(a3Σu+) product channels populated in the reaction. This provides the first signature of highly non-universal dynamics seen in rigorous quantum reactive scattering calculations of an ultracold exothermic insertion reaction involving a polar alkali dimer molecule, opening up the possibility of probing microscopic interactions in atom+molecule collision complexes via ultracold reactive scattering experiments.

Analysis of individual matrix particles in the Allende meteorite by high-resolution FIB-TOF-SIMS.

The matrix in the "Allende meteorite" was analyzed by high-spatial-resolution focused ion beam time-of-flight secondary ion mass spectrometry (FIB-TOF-SIMS), and consisted of fine grains with sizes of several micrometers. It is difficult to analyze the matrix particles individually. As FIB-TOF-SIMS has a high spatial resolution, it can analyze the matrix individually. In addition, if the sample can be smoothed, no other pretreatment is required. By this method, it was clarified that Al, Cr, etc., which were conventionally detected as trace components in mass spectra, existed as fine particles between the matrix particles, rather than as impurities within them. The Al-rich particles did not match the minerals already found in the Allende meteorite matrix. Although the identity of the aluminum-rich particles has not been clarified, the abundance and localization could be observed correctly. Al-rich particles are likely to be affected by metamorphism and have important information to clarify the metamorphism process.

Specialized Pro-Resolving Mediators Do Not Inhibit the Synthesis of Inflammatory Mediators Induced by Tumor Necrosis Factor-α in Synovial Fibroblasts.

Background: Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, is involved in the pathogenesis of rheumatoid arthritis (RA). The omega-3 unsaturated fatty acid-derived metabolites resolvin (Rv) D1, RvE1, and maresin-1 (MaR1) have been reported as anti-inflammatory lipid mediators and are known as specialized pro-resolving mediators (SPMs). In this study, we aimed to investigate the anti-inflammatory effects of SPMs on TNF-α-induced responses in synovial fibroblasts. Methods: We investigated the effects of SPMs on gene expression and/or production of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), interleukin (IL)-6, and matrix metalloproteinase (MMP)-3, which are involved in TNF-α-induced synovitis in RA or OA synovial fibroblasts, by quantitative real-time PCR. We also investigated the effects of SPMs on the mitogen-activated protein kinase (MAPK) signaling pathway by western blotting. Anti-inflammatory effects of SPMs were evaluated by applying SPMs to cultured synovial fibroblasts, followed by TNF-α stimulation. Results: The induction of COX-2, mPGES-1, IL-6, and MMP-3 by TNF-α in synovial fibroblasts was not suppressed by omega 3-derived SPMs regardless of their origin such as RA or OA. SPMs had no effect on lipid mediator receptor gene expression induce by TNF-α and did not inhibit the TNF-α-activated MAPK signaling pathway. The production of COX-2 and IL-6 protein was significantly decreased by p38 inhibitor. Conclusion: Despite reports on the anti-inflammatory effect of omega 3-derived SPMs, its anti-inflammatory effect on TNF-α-induced responses was not observed in synovial fibroblasts. The reason may be that SPMs have no suppressive effect on p38 activation, which plays an important role in the production of inflammatory cytokines in synovial fibroblasts.

Role of Low Energy Resonances in the Stereodynamics of Cold He + D2 Collisions.

In recent experiments using the Stark-induced adiabatic Raman passage technique, Zhou et al. ( J. Chem. Phys. 2021, 154, 104309; Science 2021, 374, 960-964) measured the product's angular distribution for the collisions between He and aligned D2 molecules at cold collision energies. The signatures of the angular distributions were attributed to an [Formula: see text] = 2 resonance that governs scattering at low energies. A first-principles quantum mechanical treatment of this problem is presented here using a highly accurate interaction potential for the He-H2 system. Our results predict a very intense [Formula: see text] = 1 resonance at low energies, leading to angular distributions that differ from those measured in the experiment. A good agreement with the experiment is achieved only when the [Formula: see text] = 1 resonance is artificially removed, for example, by excluding the lowest energies present in the experimental velocity distribution. Our analysis revealed that neither the position nor the intensity of the [Formula: see text] = 1 resonance significantly changes when the interaction potential is modified within its predicted uncertainties. Energy-resolved measurements may help to resolve the discrepancy.

Human Papillomavirus Vaccination as an Adjuvant Therapy for Recurrent Respiratory Papillomatosis: Additional Case Series.

Prevention of the recurrence of recurrent respiratory papillomatosis (RRP), a neoplasm of the respiratory tract, is a challenge. Human papillomavirus (HPV) vaccine has been expected to suppress the aggressiveness of RRP. However, there has been insufficient data to verify whether HPV vaccination can serve as an adjuvant therapy option for RRP. The aim of this study was to add our data on the efficacy of HPV vaccination for RRP to the academic discipline. Twenty-four RRP patients were treated with a combination therapy of surgery and three sessions of quadrivalent HPV vaccine. The patients' clinical courses, which were HPV infection status changes, intersurgical interval, and disease severity score (Derkay's site score), were statistically analyzed before and after combination therapy. Twelve of the 24 (52.5%) RRP patients who were HPV-DNA positive turned negative after the combination therapy. The mean of intersurgical interval was significantly extended from 6.85 ± 4.49 months to 30.5 ± 27.6 months after the therapy (P <0.01). The median of Derkay's score of the participants also significantly decreased from 7.5 (interquartile range, 5-12) to 1 (interquartile range, 0-4.25) after the therapy (P <0.01). Thus, combination therapy comprising of surgery and HPV vaccination can postpone the recurrence and lessen the severity of RRP.

Myasthenic crisis appearing after resection of intracardiac ectopic thymoma with superior vena cava syndrome.

BACKGROUND: We describe herein an extremely rare case of intracardiac ectopic thymoma-only two pure cases have been reported to date-associated with myasthenia gravis, an infrequent complication of ectopic thymoma. CASE PRESENTATION: A 71-year-old woman with superior vena cava syndrome was found to have a large mass mainly located in the right atrium. Tumor resection under cardiopulmonary bypass was performed. The pathological diagnosis was type AB ectopic thymoma. The postoperative course was complicated by progressive respiratory failure, and she was diagnosed with myasthenic crisis based on clinical signs and the edrophonium test. The patient recovered and was weaned from prolonged mechanical ventilation after receiving intravenous immunoglobulin, and was subsequently discharged uneventfully. CONCLUSIONS: This is the first report of myasthenic crisis due to intracardiac ectopic thymoma. Residual thymoma is a risk factor for the development of post-thymectomy myasthenia gravis, and long-term follow-up is required.

Systematic Studies on the Effect of Fluorine Atoms in Fluorinated Tolanes on Their Photophysical Properties.

In this study, we synthesized a series of fluorinated and non-fluorinated tolanes, in which one or more fluorine atoms were systematically introduced into one aromatic ring of a tolane scaffold, and systematically evaluated their photophysical properties. All the tolanes with or without fluorine substituents were found to have poor photoluminescence (PL) in tetrahydrofuran (THF) solutions. On the other hand, in the crystalline state, non-fluorinated and fluorinated tolanes with one or four fluorine atoms were less emissive, whereas fluorinated tolanes with three or five fluorine atoms exhibited high PL efficiencies (ФPL) up to 0.51. X-ray crystallographic analyses of the emissive fluorinated tolanes revealed that the position of the fluorine substituent played a key role in achieving a high ФPL. Fluorine substituents at the ortho (2/6) and para (4) positions led to tight and rigid packing due to plural π-π stacking and/or hydrogen bonding interactions, resulting in enhanced ФPL caused by the suppression of non-radiative deactivation. Additionally, fluorinated tolanes with three fluorine atoms exhibited notable aggregation-induced PL emission enhancement in THF/water mixed solvents. This demonstrates that the PL characteristics of small PL materials can be tuned depending on the usage requirements.

Rainbow scattering in rotationally inelastic collisions of HCl and H2.

We examine rotational transitions of HCl in collisions with H2 by carrying out quantum mechanical close-coupling and quasi-classical trajectory (QCT) calculations on a recently developed globally accurate full-dimensional ab initio potential energy surface for the H3Cl system. Signatures of rainbow scattering in rotationally inelastic collisions are found in the state resolved integral and differential cross sections as functions of the impact parameter (initial orbital angular momentum) and final rotational quantum number. We show the coexistence of distinct dynamical regimes for the HCl rotational transition driven by the short-range repulsive and long-range attractive forces whose relative importance depends on the collision energy and final rotational state, suggesting that the classification of rainbow scattering into rotational and l-type rainbows is effective for H2 + HCl collisions. While the QCT method satisfactorily predicts the overall behavior of the rotationally inelastic cross sections, its capability to accurately describe signatures of rainbow scattering appears to be limited for the present system.

Evaluation of Internal Distribution and Extracellular Action of the Cell via TOF-SIMS.

Cisplatin is one of the most popular and traditional platinum-based anti-cancer drugs. Additionally, it is known for its effect on different types of cancers. To clarify the reaction mechanism of anti-cancer drugs in a cell, the visualization of drugs in a single cell is required. In this study, we investigated a secondary ion species obtained from cisplatin, which was bounded to the nucleus in a cell and its intensity. PtCl2- was mainly detected via SIMS during an analysis of pure cisplatin reagent. In contrast, a high-intensity signal for PtCN- was detected from cultured cells that were administered cisplatin. However, this signal was not detected from cisplatin in the reagent state. Chlorine in the cisplatin structure is replaced with water when it is combined with the cell nucleus. Therefore, PtCN- was mainly detected from the intracellular region because the structure was changed by cisplatin binding to the nucleus and which exhibits anti-cancer activity. The results showed that the cisplatin selectively combined with the nucleus. Through TOF-SIMS, we achieved a visual distribution of the cisplatin intracellular nucleus.

Stereodynamics of ultracold rotationally inelastic collisions.

Recent experiments on rotational quenching of HD in the v = 1, j = 2 rovibrational state in collisions with H2, D2, and He near 1 K have revealed strong stereodynamic preference stemming from isolated shape resonances. So far, the experiments and subsequent theoretical analyses have considered the initial HD rotational state in an orientation specified by the projection quantum number m or a coherent superposition of different m states. However, it is known that such stereodynamic control is generally not effective in the ultracold energy regime due to the dominance of the incoming s-wave (l = 0, partial wave). Here, we provide a detailed analysis of the stereodynamics of rotational quenching of HD by He with both m and m' resolution, where m' refers to the inelastically scattered HD. We show the existence of a significant m dependence in the m'-resolved differential and integral cross sections even in the ultracold s-wave regime with a factor greater than 60 for j = 2 → j' = 1 and a factor greater than 1300 for j = 3 → j' = 2 transitions. In the helicity frame, however, the integral cross section has no initial orientation (k) dependence in the ultracold energy regime, even resolving with respect to the final orientation (k'). The distribution of final rotational state orientations (k') is found to be statistical (uniform), regardless of the initial orientation.

Spinal anesthesia for muscle biopsy in an infant with a suspected neuromuscular disorder: a case report.

BACKGROUND: Neuromuscular disorders (NMDs) occur in different forms and are generally diagnosed using muscle biopsy. Among the available anesthetic management options for infants with a suspected NMD are general anesthesia (GA) and regional anesthesia (RA), including spinal anesthesia (SA). Anesthesia selection is often challenging from the point of potential airway risks and anesthetic drug-related complications. CASE PRESENTATION: A 6-month-old male infant repeatedly underwent endotracheal intubation and extubation after birth because of respiratory muscle weakness and copious secretions. He was suspected of having NMD and was scheduled for muscle biopsy. His generalized hypotonia and decreased respiratory function presented a potentially difficult airway and complicated the selection of an appropriate anesthetic method. We selected SA and dexmedetomidine, which are safe for infants. CONCLUSION: We report the successful and effective anesthetic management of SA and dexmedetomidine in an infant with a suspected NMD.

Stereodynamics of rotationally inelastic scattering in cold He + HD collisions.

Stereodynamics of cold collisions has become a fertile ground for sensitive probe of molecular collisions and control of the collision outcome. A benchmark system for stereodynamic control of rotational transition is He + HD. This system was recently probed experimentally by Perreault et al. by examining quenching from j = 2 to j' = 0 state in the v = 1 vibrational manifold of HD. Here, through explicit quantum scattering calculations on a highly accurate ab initio interaction potential for He + H2, we reveal how a combination of two shape resonances arising from l = 1 and l = 2 partial waves controls the stereodynamic outcome rather than a single l = 2 partial wave attributed in the experiment. Furthermore, for collision energies below 0.5 cm-1, it is shown that stereodynamic preference for the integral cross section follows a simple universal trend.

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules.

Pure organic phosphorescent molecules are attractive alternatives to transition-metal-complex-based phosphores for biomedical and technological applications owing to their abundance and nontoxicity. This article discloses the design, synthesis, and photophysical properties of fluorinated benzil and bisbenzil derivatives as potential pure organic room-temperature phosphorescent molecules. These compounds were separately converted from the corresponding fluorinated bistolanes via PdCl2-catalyzed oxidation by dimethyl sulfoxide, while nonfluorinated bistolane provided the corresponding bisbenzil derivatives exclusively in a similar manner. Intensive investigations of the photophysical properties of the benzil and bisbenzil derivatives in toluene at 25 °C showed both fluorescence with a photoluminescence (PL) band at a maximum wavelength (λPL) of around 400 nm and phosphorescence with a PL band at a λPL of around 560 nm. Interestingly, intersystem crossing effectively caused fluorinated benzils to emit phosphorescence, which may arise from immediate spin-orbit coupling involving the 1(n, π)→3(π, π) transition, unlike the case of fluorinated or nonfluorinated bisbenzil analogues. These findings offer a useful guide for developing novel pure organic room-temperature phosphorescent materials.

A Time-of-Flight Range Sensor Using Four-Tap Lock-In Pixels with High near Infrared Sensitivity for LiDAR Applications.

In this paper, a back-illuminated (BSI) time-of-flight (TOF) sensor using 0.2 µm silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) technology is developed for long-range laser imaging detection and ranging (LiDAR) application. A 200 µm-thick bulk silicon in the SOI substrate is fully depleted by applying high negative voltage at the backside for higher quantum efficiency (QE) in a near-infrared (NIR) region. The proposed SOI-based four-tap charge modulator achieves a high-speed charge modulation and high modulation contrast of 71% in a NIR region. In addition, in-pixel drain function is used for short-pulse TOF measurements. A distance measurement up to 27 m is carried out with +1.8~-3.0% linearity error and range resolution of 4.5 cm in outdoor conditions. The measured QE of 55% is attained at 940 nm which is suitable for outdoor use due to the reduced spectral components of solar radiation.