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Eighty Japanese children, aged 8–12 years, with a spherical equivalent refraction (SER) of − 1.00 to − 6.00 dioptres (D) were randomly allocated into two groups to receive either a combination of orthokeratology (OK) and 0.01% atropine solution (combination group) or monotherapy with OK (monotherapy group). Seventy-three subjects completed the 2-year study. Over the 2 years, axial length increased by 0.29 ± 0.20 mm ( n  = 38) and 0.40 ± 0.23 mm ( n  = 35) in the combination and monotherapy groups, respectively ( P  = 0.03). Interactions between combination treatment and age or SER did not reach significance level (age, P  = 0.18; SER, P  = 0.06). In the subgroup of subjects with an initial SER of − 1.00 to − 3.00 D, axial length increased by 0.30 ± 0.22 mm ( n  = 27) and 0.48 ± 0.22 mm ( n  = 23) in the combination and monotherapy groups, respectively ( P  = 0.005). In the − 3.01 to − 6.00 D subgroup, axial length increased by 0.27 ± 0.15 mm ( n  = 11) and 0.25 ± 0.17 mm ( n  = 12) in the combination and monotherapy groups, respectively ( P  = 0.74). The combination therapy may be effective for slowing axial elongation, especially in children with low initial myopia.

In solving a multi-objective optimization problem by scalarization techniques, solutions to a scalarized problem are, in general, weakly efficient rather than efficient to the original problem. Thus, it is crucial to understand what condition ensures that all weakly efficient solutions are efficient. In this paper, we give a condition to verify when efficiency coincides with weak efficiency, provided that the free disposal hull of a given set is convex. By using this characterization, we obtain various applications to multi-objective optimization problems under some convex conditions. We also apply the main theorem to the least absolute shrinkage and selection operator (LASSO) and show that for a multi-objective version of LASSO, all weakly efficient solutions are efficient. Numerical simulation demonstrates that this equivalence is helpful to accelerate the hyper-parameter search for LASSO.

Purpose To investigate the additive effects of orthokeratology (OK) and atropine 0.01% ophthalmic solution, both of which are effective procedures to slow axial elongation in children with myopia. Study design Prospective randomized clinical trial. Methods Japanese children aged 8–12 years with a spherical equivalent refractive error of − 1.00 to − 6.00 diopters were included. A total of 41 participants who had been wearing the OK lenses successfully for 3 months were randomly allocated into two groups to receive either the combination of OK and atropine 0.01% ophthalmic solution (combination group) or monotherapy with OK (monotherapy group). Subjects in the combination group started to use atropine 0.01% ophthalmic solution once nightly from 3 months after the start of OK. Axial length was measured every 3 months using non-contact laser interferometry (IOLMaster), and the axial length measurement at month 3 of OK therapy was used as the baseline value in both groups. The increase in axial length over 1 year was compared between the two groups. Results A total of 40 consecutive subjects (20 subjects in the combination group and 20 in the monotherapy group) were followed for 1 year. The increase in axial length over 1 year was 0.09 ± 0.12 mm in the combination group and 0.19 ± 0.15 mm in the monotherapy group ( P  = 0.0356, unpaired t test). Conclusion During the 1-year follow-up, the combination of OK and atropine 0.01% ophthalmic solution was more effective in slowing axial elongation than OK monotherapy in children with myopia.

The present study examined whether the perceptual sensitivity and excitability of the primary sensory cortex are modulated by the afferent volley from the digital nerve of a conditioned finger within a short period of time. The perceptual threshold of an electrical stimulus to the index finger (test stimulus) was decreased by a conditioning stimulus to the index finger 4 or 6 ms before the test stimulus, or by a stimulus to the middle or ring finger 2 ms before that. This is explained by the view that the afferent volleys from the digital nerves of the fingers converge in the somatosensory areas, causing spatial summation of the afferent inputs through a small number of synaptic relays, leading to the facilitation of perceptual sensitivity. The N20 component of the somatosensory-evoked potential was facilitated by a conditioning stimulus to the middle finger 4 ms before a test stimulus or to the thumb 2 ms before the test stimulus. This is explained by the view that the afferent volley from the digital nerve of the finger adjacent to the tested finger induces lateral facilitation of the representation of the tested finger in the primary sensory cortex through a small number of synaptic relays.

Lacticaseibacillus paracasei bacteremia associated with probiotic use is rare. We report a 71-year-old man with advanced lung cancer who developed L. paracasei bacteremia while ingesting a commercially available probiotic-fermented milk. Autopsy demonstrated direct tumor invasion and perforation of the mid-esophagus, providing a structural route for bacterial translocation from the gastrointestinal lumen into the bloodstream. Genetic analysis showed that the blood isolate was genetically identical to the probiotic strain contained in the ingested product. Bacteremia resolved with antibiotics, but the patient died of respiratory failure from progression of the malignancy. This case highlights that probiotic organisms, despite an established safety profile, can cause bacteremia when immunocompromise coexists with disruption of the gastrointestinal barrier.

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, effectively treats EGFR-mutated non-small cell lung cancer. Drug-induced interstitial lung disease, a potentially fatal complication of osimertinib, involves an increase in lymphocytes in the bronchoalveolar lavage fluid (BALF). As the precise role of these lymphocytes is unknown, we investigated the pathogenesis of osimertinib-induced pneumonitis using BALF obtained from patients, and an osimertinib-induced pneumonitis mouse model. Mass cytometry revealed the presence of CCR7+ CD45RA+ naïve T cells in the BALF of patients with osimertinib-induced pneumonitis. Body weight measurements, BALF analysis, histopathological evaluation and RNA sequencing of mouse lung tissue were performed to investigate immune cell involvement and the mechanisms underlying osimertinib-induced pneumonitis. In the mouse model, administration of osimertinib after naphthalene-induced damage to the bronchiolar epithelium exacerbated lung inflammation and resulted in significant weight loss. Immunofluorescence staining revealed the infiltration of CCR7+ cells into the lungs of mice treated with naphthalene and osimertinib. Bulk RNA sequencing identified an upregulation of chemokine-related biological processes, with increased expression of C–C motif chemokine ligand 21 (Ccl21) and C–C motif chemokine ligand 8 (Ccl8) in the lung tissue. Additionally, immunofluorescence staining confirmed elevated expression of Ccl21 and Ccl8 in the distal bronchiolar epithelium. This study provides insights into the mechanisms underlying osimertinib-induced pneumonitis.

Background/Objectives: When manipulating an object placed on the palm, the eyes and fingers move together. To perform this task precisely, coordination of the eyes and fingers is needed. Based on this view, the present study examined the three-way interaction among the central motor drives to the eyes, index finger, and little finger. Methods: Healthy male participants abducted the right index and/or little finger with or without concomitant saccadic eye movement to the right in response to a visual cue, while the forearm was in the pronated or supinated position. We measured the reaction time (RT), velocity, and amplitude of the eye movements, as well as the RT and amplitude of the electromyographic (EMG) responses in the prime movers for the independent and dependent finger movements. Results: The velocity, amplitude, and RT of the eye movement were not changed by the additional involvement of the finger movement, indicating that the central motor drive to the finger does not influence the eye motor excitability and central motor drive to the eyes. On the one hand, the RT of the finger was not changed by the eye movement, indicating that the central motor drive to the eyes does not influence the central motor drive to the finger muscle. On the other hand, the EMG amplitude in the first dorsal interosseous muscle at the movement onset decreased during the concomitant eye movement, indicating that the central motor drive to the eyes suppresses the motor excitability of the independent finger muscle. The RT increased and EMG amplitude decreased in one finger muscle when the other finger concurrently moved, indicating that the central motor drive to one finger muscle suppresses the motor excitability of and central motor drive to the other finger muscle. The change in the RT and EMG amplitude in one finger muscle caused by the concomitant execution of the other finger movement and/or eye movement varied with forearm position, indicating that forearm proprioception influences the interaction of the motor execution processes among the fingers and eyes. Conclusions: The central motor drive to the eyes or finger muscles suppresses the motor excitability of the other finger muscles and the central motor drive to that muscle, but the central motor drive to the finger muscles does not influence those for the eyes. Forearm proprioception influences the motor excitability of the finger muscle and central motor drive to that muscle.

Under certain conditions, tactile stimulus to the head induces movement of the head away from the stimulus, and this is thought to be caused by a defense mechanism. In this study, we tested our hypothesis that predicting the stimulus site of the head in a quiet stance activates the defense mechanism, causing a body sway to keep the head away from the stimulus. Fourteen healthy males aged 31.2 ± 6.8 years participated in this study. A visual cue predicting the forthcoming stimulus site (forehead, left side of the head, right side of the head, or back of the head) was given. Four seconds after this cue, an auditory or electrical tactile stimulus was given at the site predicted by the cue. The cue predicting the tactile stimulus site of the head did not induce a body sway. The cue predicting the auditory stimulus to the back of the head induced a forward body sway, and the cue predicting the stimulus to the forehead induced a backward body sway. The cue predicting the auditory stimulus to the left side of the head induced a rightward body sway, and the cue predicting the stimulus to the right side of the head induced a leftward body sway. These findings support our hypothesis that predicting the auditory stimulus site of the head induces a body sway in a quiet stance so as to keep the head away from the stimulus. The right gastrocnemius muscle contributes to the control of the body sway in the anterior-posterior axis related to this defense mechanism.

Purpose A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). Study design This was a prospective, open-label, multicenter study. Patients and methods We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. Results We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg ( P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg ( P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by – 2.0 ± 1.8 mmHg ( P < 0.0001) and –1.9 ± 1.4 mmHg ( P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. Conclusions BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.

Immune checkpoint inhibitor (ICI)-related myositis is a rare, potentially fatal condition that warrants further studies. Its incidence, clinical features, and prognosis remain poorly understood. To address these gaps, we conducted a systematic review and meta-analysis to evaluate the risk of myositis associated with ICI for solid tumors by analyzing phase III randomized controlled trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). To complement this analysis with clinical data, we evaluated published ICI case reports along with cases from our institutional registry. This registry comprised 422 patients treated with ICIs alone or in combination from September 2014 to June 2021. The analysis revealed an incidence of ICI-related myositis in 6,838 patients in 18 randomized controlled trials of 0.38% (odds ratio 1.96; 95% confidence interval 1.02–3.75) for patients receiving ICIs compared with controls. Detailed analysis of 88 cases from the literature search and our registry showed that myositis induced by PD-1 inhibitors was more frequent than that induced by anti-CTLA-4 agents, revealing a clinically diverse trend including myasthenia gravis and myocarditis. Importantly, having ptosis at the time of onset was significantly associated with the development of concomitant myocarditis (odds ratio 3.81; 95% CI 1.48–9.83), which is associated with poor prognosis. Regarding treatment, most patients received glucocorticoids, and some received immunosuppressants. Our study revealed the incidence of ICI-mediated myositis and the clinical features of myocarditis, highlighting the need for recognition and early intervention.