Search

Objective Cortisol-producing adenoma (CPA) is a major subtype of functional adrenal tumors. CPAs are generally treated with adrenalectomy; however, it is difficult to predict the ideal duration of glucocorticoid replacement after resection. This study explored pre-operative factors predictive of glucocorticoid replacement therapy duration after CPA resection. Mehtods This multicenter retrospective observational study was conducted as part of the Advancing Care and Pathogenesis of Intractable Adrenal Diseases in Japan (ACPA-J) from January 2006 to December 2015. Patients This study was conducted at 10 referral centers and included 124 patients who received hydrocortisone replacement therapy after adrenalectomy for CPA. Results The median duration of replacement therapy was 12 (interquartile range, 5-24) months. In the single regression analysis, the sex (P=0.04), morning ACTH level (P=0.02), morning serum cortisol level (P=0.003), midnight serum cortisol level (P<0.001), serum cortisol level after a 1-mg dexamethasone suppression test (P<0.001), presence of lumbar compression fracture (P=0.015), and Cushingoid appearance (P<0.001) were all significantly associated with the replacement therapy duration. In multiple regression analyses, the midnight serum cortisol level and presence of lumbar compression fracture were significantly correlated with the replacement therapy duration after adjusting for other parameters. Conclusion Our results suggest that high midnight serum cortisol levels, which cause persistent suppression of the HPA axis, contribute to a delay in HPA axis recovery. Lumbar compression fracture is an important symptom that reflects the severity and persistence of cortisol secretion.

Dopamine-secreting paragangliomas is known to be rare. The average annual incidence rate was reported 0.8 per 100,000 person-years. Approximately 1 to 2% of paragangliomas occur in the chest. We describe a patient with a large dopamine-secreting cardiac paraganglioma, right adrenal tumor and carotid body tumor. A 26-year-old man with progressive exertional dyspnea was referred to our hospital for further management of multiple paragangliomas. Positron emission tomography (PET) and PET-computed tomography (CT) detected those three legions. The diameter of cardiac paraganglioma was over 45 mm and was biggest among three tumors. Firstly, therefore, we planned cardiac paraganglioma resection. Through left lateral thoracotomy in the 4th intercostal space via, cardiac paraganglioma was resected under cardiopulmonary bypass and beating heart. Postoperative course was uneventful. Tumor cells were positive for synaptophysin and chromogranin A. Free metanephrines in the serum and urinary fractionated metanephrines normalized after cardiac surgery while the other two tumors remained untreated.

Trace palladium in synthetic materials can be rapidly and inexpensively semiquantified by a catalysis-based fluorometric method that converts resorufin allyl ether to resorufin. However, whether sulfur compounds would interfere with this method has not been systematically studied. Herein, we show that although thiourea in solution interferes with quantification, sulfide, thiol, and thiocarbamate do not. The fluorometric method can also detect palladium bound to sulfur-based scavenger resin and outperform inductively coupled plasma mass spectrometry for detecting trace palladium in ibuprofen.

Background: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment., Methods: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated., Results: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents ( P =0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P =0.022) and adrenalectomy (72% versus 54%; P =0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels., Conclusions: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220., Competing Interests: Disclosures None.

Aldosterone secretion in primary aldosteronism (PA) is often regulated by adrenocorticotropic hormone (ACTH) in addition to its autonomous secretion. However, the clinical characteristics and risk of cardiovascular and cerebrovascular (CCV) events in PA patients with aldosterone responsiveness to ACTH stimulation remain unclear. This study aimed to investigate the prevalence of CCV events in PA patients with high aldosterone responsiveness to ACTH stimulation. A retrospective cross-sectional study was conducted as part of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Disease project. PA patients with adrenal venous sampling (AVS) between January 2006 and March 2019 were enrolled. The ACTH-stimulated plasma aldosterone concentration (PAC) of the inferior vena cava during AVS was used to evaluate aldosterone responsiveness to ACTH. We analyzed the relationship between responsiveness and previous CCV events. Logistic regression analysis demonstrated that the ΔPAC (the difference between the PAC measurements before and after ACTH stimulation) significantly increased the odds of previous CCV events in PA patients after adjusting for classical CCV event risk factors, baseline PAC and duration of hypertension (relative PAC: odds ratio [OR], 2.896; 95% confidence interval [CI], 0.989-8.482; ΔPAC: OR, 2.344; 95% CI, 1.149-4.780; ACTH-stimulated PAC: OR, 2.098; 95% CI, 0.694-6.339). This study clearly demonstrated that aldosterone responsiveness to ACTH is closely related to previous CCV events. The responsiveness of the PAC to ACTH could be useful in predicting CCV event risk.Registration Number in UMIN-CTR is UMIN000032525.

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a "musi-linguistic" continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech.

Background: Clinical practice guidelines recommend the Lateralization Index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Our goal was to identify the optimal LI cut-offs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure., Methods: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1,550 patients with PA who underwent AVS, with and/or without ACTH stimulation. The establishment of optimal cut-offs was informed by a survey of 82 PA patients in Japan, aimed at determining the LI cut-off aligned with patient expectations for a surgical cure rate., Results: The survey revealed that a median cure rate expectation of 80% would motivate PA patients towards undergoing adrenalectomy. The optimal LI cut-offs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on CT imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cut-offs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found., Conclusions and Relevance: The present study clarified the optimal LI cut-offs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Photonic computing is widely used to accelerate the computational performance in machine learning. Photonic decision making is a promising approach utilizing photonic computing technologies to solve the multi-armed bandit problems based on reinforcement learning. Photonic decision making using chaotic mode-competition dynamics has been proposed. However, the experimental conditions for achieving a superior decision-making performance have not yet been established. Herein, we experimentally investigate mode-competition dynamics in a chaotic multimode semiconductor laser in the presence of optical feedback and injection. We control the chaotic mode-competition dynamics via optical injection and observe that positive wavelength detuning results in an efficient mode concentration to one of the longitudinal modes with a small optical injection power. We experimentally investigate two-dimensional bifurcation diagram of the total intensity of the laser dynamics. Complex mixed dynamics are observed in the presence of optical feedback and injection. We experimentally conduct decision making to solve the bandit problem using chaotic mode-competition dynamics. A fast mode-concentration property is observed at positive wavelength detunings, resulting in fast convergence of the correct decision rate. Our findings could be useful in accelerating the decision-making performance in adaptive optical networks using reinforcement learning.

We present a noninvasive method for quantitative phase imaging through dynamically scattering media. A complex amplitude object, illuminated with coherent light, is captured through a dynamically scattering medium and a variable coded aperture, without the need for interferometric measurements or imaging optics. The complex amplitude of the object is computationally retrieved from intensity images that use multiple coded aperture patterns, employing a stochastic gradient descent algorithm. We demonstrate the proposed method both numerically and experimentally.

We propose a method of computer-generated holography (CGH) using incoherent light emitted from a mobile phone screen. In this method, we suppose a cascade of holograms in which the first hologram is a color image displayed on the mobile phone screen. The hologram cascade is synthesized by solving an inverse problem with respect to the propagation of incoherent light. We demonstrate a three-dimensional color image reproduction using a two-layered hologram cascade composed of an iPhone and a spatial light modulator.

Photonic accelerators have recently attracted soaring interest, harnessing the ultimate nature of light for information processing. Collective decision-making with a laser network, employing the chaotic and synchronous dynamics of optically interconnected lasers to address the competitive multi-armed bandit (CMAB) problem, is a highly compelling approach due to its scalability and experimental feasibility. We investigated essential network structures for collective decision-making through quantitative stability analysis. Moreover, we demonstrated the asymmetric preferences of players in the CMAB problem, extending its functionality to more practical applications. Our study highlights the capability and significance of machine learning built upon chaotic lasers and photonic devices.

Competing Interests: MN has received research grants from the Japan Agency for Medical Research and Development (AMED), the National Center for Global Health and Medicine (Japan), and Japan Ministry of Health, Labour, and Welfare for intractable adrenal diseases; has received consulting fees from Nihon Medi-Physics and honoraria for speakers' bureaus from Recordati Rare Diseases Japan, Roche Diagnostics, Teijin Home Healthcare, FUJIFILM Wako Pure Chemical, Kyowa Kirin, Sumitomo Pharma, FUJIFILM Toyama Chemical, and Daiichi Sankyo, outside the scope of this Comment; and has received honoraria for speakers' bureaus from Ono Pharmaceutical (about metyrosine) and PDRadiopharma (about radiotherapy). WFY has received consulting fees from Crinetics Pharmaceuticals for advisory board participation; and has received consulting fees from AstraZeneca Pharmaceuticals and Bayer AG for participation on a drug safety monitoring board, outside the scope of this Comment.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

With the end of Moore's Law and the increasing demand for computing, photonic accelerators are garnering considerable attention. This is due to the physical characteristics of light, such as high bandwidth and multiplicity, and the various synchronization phenomena that emerge in the realm of laser physics. These factors come into play as computer performance approaches its limits. In this study, we explore the application of a laser network, acting as a photonic accelerator, to the competitive multi-armed bandit problem. In this context, conflict avoidance is key to maximizing environmental rewards. We experimentally demonstrate cooperative decision-making using zero-lag and lag synchronization within a network of four semiconductor lasers. Lag synchronization of chaos realizes effective decision-making and zero-lag synchronization is responsible for the realization of the collision avoidance function. We experimentally verified a low collision rate and high reward in a fundamental 2-player, 2-slot scenario, and showed the scalability of this system. This system architecture opens up new possibilities for intelligent functionalities in laser dynamics., (© 2024. The Author(s).)

Quantitative phase imaging (QPI), such as digital holography, is considered a promising tool in the field of life science due to its noninvasive and quantitative visualization capabilities without the need for fluorescence labeling. However, the popularity of QPI systems is limited due to the cost and complexity of their hardware. In contrast, Zernike phase-contrast microscopy (ZPM) has been widely used in practical scenarios but has not been categorized as QPI, owing to halo and shade-off artifacts and the weak phase condition. Here, we present a single-image phase retrieval method for ZPM that addresses these issues without requiring hardware modifications. By employing a rigorous physical model of ZPM and a gradient descent algorithm for its inversion, we achieve single-shot QPI with an off-the-shelf ZPM system. Our approach is validated in simulations and experiments, demonstrating QPI of a polymer microbead and biological cells. The quantitative nature of our method for single-cell imaging is confirmed through comparisons with observations from an established QPI technique conducted through digital holography. This study paves the way for transforming non-QPI ZPM systems into QPI systems.

Shiitake (Lentinula edodes) contains various beneficial compounds and possesses several notable properties. However, there are few reports on its molecular breeding due to delay in development of its gene-modifying technology. Therefore, here, strain UV30 (pyrG -) was bred from the UV-irradiated protoplasts of strain M2. Strain UV30 was uracil-auxotrophic, and the phenylalanine residue in the active centre of orotidine-5-phosphate decarboxylase encoded by pyrG in the strain was substituted with a serine residue. Next, a recycling marker consisting of the upstream sequence of ku80, a repeat sequence (a portion of the downstream sequence of ku80), pyrG, and the downstream sequence of ku80 was introduced into the strain UV30. Consequently, the prototrophic strain ckp2-1, in which ku80 was replaced with the recycling marker, was obtained. After cultivation in complete medium, mycelia from the edges of ckp2-1 colonies were inoculated into a complete medium containing 5-Fluoroorotic acid (5-FOA). A 5-FOA-resistant strain KaM2, in which pyrG sequence was spliced from the recycling marker sequence via homologous recombination, was obtained. In this study, we developed the first marker recycling system for multigene targeting in L. edodes. Moreover, the resulting ∆ku80 strain may serve as a non-homologous end-joining deficient strain for further genetic manipulations., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

The application of organoids derived from animal tissues and human-induced pluripotent stem cells to safety assessments of environmental chemicals has been introduced over the last decade. One of the objectives of this approach is to develop an alternative method for animal toxicological studies, while another is to focus on the local reactions of chemicals in each organ/tissue. One of the most important goals is bridging the toxicological properties of chemicals between animals and humans, which may be compared on a level playing field using healthy organoids derived from both animals and humans in vitro, excluding species difference in the absorption, distribution, metabolism, and excretion properties of chemicals in vivo. An overview of the application of organoid systems to safety assessments of environmental chemicals, including general toxicology, developmental toxicology, carcinogenicity, and mutagenicity, was provided herein, and bridging strategies using both animal and human organoids are proposed as a future perspective.

In patients with bilateral cleft lip and palate (BCLP) with protrusion and/or torsion of the premaxilla, achieving a favorable outcome with adequate facial and maxillary development remains challenging. In the present study, we report a retrospective cohort of patients with complete BCLP who were treated between 2017 and 2020 at a single center in Japan. We investigated the effects and complications of primary vomerine osteotomy (PVO) with gingivoperiosteoplasty (GPP) following pre-surgical orthodontics (PSO) for premaxillary protrusion and/or torsion. For patients with residual premaxillary protrusion and/or torsion after PSO, PVO, and GPP were performed. The distances and angles of the premaxilla were measured on dental casts before PSO, on the day of PVO, after PVO, and on the day of palatoplasty after cheiloplasty. We further assessed postoperative complications. From a total of 36 patients with complete BCLP after PSO, seven patients underwent PVO with GPP. Proper positioning of the premaxilla was achieved in all seven patients. The distance between the anterior edge of the premaxilla and the anterior edge of the lateral segment and the length of the premaxillary-lateral segment on both sides continued to decrease over time. Loosening of GPP sutures occurred in two cases, although no major complications such as necrosis of the premaxilla or fistula formation occurred. Vomerine osteotomy with GPP before primary cheiloplasty is a potential treatment option in BCLP when the premaxilla still protrudes despite PSO or because PSO cannot be applied., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The design of a simple approach enabling the detection of bisphenol A (BPA) in water samples without the need for large amounts of solvents is of utmost importance. This paper reports a simple method for the separation, concentration, and quantification of BPA in water samples using high-performance liquid chromatography with fluorescence detection (HPLC-FLD) after its microextraction into an in situ formed organic ion-associate (IA) liquid phase (LP). Novel IA phase components without conjugated double bonds, such as benzene rings, were investigated. Ethylhexyloxypropylamine hydrochloride and sodium dodecyl sulfate solutions were added to the water samples to form IAs. The aqueous phase and ion-associate liquid phase (IALP) were separated by centrifugation. The aqueous phase was removed, and the liquid phase was recovered and measured using HPLC-FLD or HPLC-electrochemical detection (ECD). The concentrated phase (IALP) had a relatively low viscosity and could be injected directly into the chromatograph without dissolving it in organic solvents. The detection limits for BPA by HPLC-FLD and HPLC-ECD were 0.009 and 0.3 µg L -1 , respectively.

We present a method for speckle-correlation imaging with an extended field of view to observe spatially non-sparse objects. In speckle-correlation imaging, an object is recovered from a non-invasively captured image through a scattering medium by assuming shift-invariance of the optical process called the memory effect. The field of view of speckle-correlation imaging is limited by the size of the memory effect, and it can be extended by extrapolating the speckle correlation in the reconstruction process. However, spatially sparse objects are assumed in the inversion process because of its severe ill-posedness. To address this issue, we introduce a deep image prior, which regularizes the image statistics by using the structure of an untrained convolutional neural network, to speckle-correlation imaging. We experimentally demonstrated the proposed method and showed the possibility of extending the method to imaging through scattering media.

Retrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that RTL5 and RTL6 (also known as sushi-ichi retrotransposon homolog 8 ( SIRH8 ) and SIRH3 ) are microglial genes that play important roles in the brain's innate immunity against viruses and bacteria through their removal of double-stranded RNA and lipopolysaccharide, respectively. In this work, we addressed the function of RTL9 (also known as SIRH10 ). Using knock-in mice that produce RTL9-mCherry fusion protein, we examined RTL9 expression in the brain and its reaction to fungal zymosan. Here, we demonstrate that RTL9 plays an important role, degrading zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Furthermore, in Rtl9 knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost. Thus, RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system: RTL9 , RTL5 and RTL6 , responding to fungi, viruses and bacteria, respectively.

Background: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation., Objectives: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal., Methods: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference. The accuracy of different values of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity, was examined., Results: We found prominent differences in RASI values distribution between patients with and without unilateral primary aldosteronism. The diagnostic accuracy of RASI values estimated by the area under receiver operating characteristic curves was 0.714 and 0.855, respectively, in the responsible and the contralateral side; RASI values >2.55 and ≤0.96 on the former and the latter side furnished the highest accuracy for detection of surgically cured unilateral primary aldosteronism. Moreover, in the patients without unilateral primary aldosteronism, only 20% and 16% had RASI values ≤0.96 and >2.55., Conclusions: With the strength of a large real-life data set and use of the gold reference entailing an unambiguous diagnosis of unilateral primary aldosteronism, these results indicate the feasibility of identifying unilateral primary aldosteronism using unilaterally selective adrenal vein sampling results., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01234220., Competing Interests: Disclosures None.

We present a diffractive optics design for incoherent imaging with an extendable field-of-view. In our design method, multiple layers of diffractive optical elements (DOEs) are synthesized so that images on the input plane illuminated with spatially incoherent light are reproduced upright on the output plane. In addition, our method removes the need for an approximation of shift invariance, which has been assumed in conventional optical designs for incoherent imaging systems. Once the DOE cascade is calculated, the field-of-view can be extended by using an array of such DOEs without further calculation. We derive the optical condition to calculate the DOEs and numerically demonstrate the proposed method with the condition.

Collective decision-making plays a crucial role in information and communication systems. However, decision conflicts among agents often impede the maximization of potential utilities within the system. Quantum processes have shown promise in achieving conflict-free joint decisions between two agents through the entanglement of photons or the quantum interference of orbital angular momentum (OAM). Nonetheless, previous studies have shown symmetric resultant joint decisions, which, while preserving equality, fail to address disparities. In light of global challenges such as ethics and equity, it is imperative for decision-making systems to not only maintain existing equality but also address and resolve disparities. In this study, we investigate asymmetric collective decision-making theoretically and numerically using quantum interference of photons carrying OAM or entangled photons. We successfully demonstrate the realization of asymmetry; however, it should be noted that a certain degree of photon loss is inevitable in the proposed models. We also provide an analytical formulation for determining the available range of asymmetry and describe a method for obtaining the desired degree of asymmetry., (© 2023. Springer Nature Limited.)

The incidence of atrial fibrillation (AF) and risk of cardiovascular events are reportedly higher in patients with primary aldosteronism (PA) than essential hypertension. However, associated factors of comorbid AF and cardiovascular events in PA patients after PA treatment remain unclear. This nationwide registration study included PA patients ≥20 years old. Incident cardiovascular events were observed with a mean follow-up of approximately 3 years. A total of 3654 patients with PA were included at the time of analysis. Prevalence of AF was 2.4%. PA patients with AF were older, more frequently male and had longer duration of hypertension than those without AF. No significant difference in basal plasma and adrenal venous aldosterone concentration, renin activity, potassium concentration, confirmatory tests of PA, laterality or surgery rate were seen between groups. Logistic regression analysis showed age, male sex, cardiothoracic ratio, past history of coronary artery disease and heart failure were independent factors associated with AF. PA patients with AF showed a higher frequency of cardiovascular events than those without AF (P < 0.001). Multivariate Cox analyses demonstrated AF in addition to older age, duration of hypertension, body mass index and chronic kidney disease as independent prognostic factors for cardiovascular events after PA treatment. Incidence of cardiovascular events were significantly lower in PA patients with AF than AF patients from the Fushimi registry during follow-up after adjusting age, sex and systolic blood pressure. Early diagnosis of PA may prevent AF and other cardiovascular events in PA patients by shortening the duration of hypertension and appropriate PA treatment., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We assessed the feasibility of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) human adult clinical exercise protocols, while also documenting select cardiovascular, metabolic, and molecular responses to these protocols. After phenotyping and familiarization sessions, 20 subjects (25 ± 2 yr, 12 M, 8 W) completed an endurance exercise bout ( n = 8, 40 min cycling at 70% V̇o 2max ), a resistance exercise bout ( n = 6, ∼45 min, 3 sets of ∼10 repetition maximum, 8 exercises), or a resting control period ( n = 6, 40 min rest). Blood samples were taken before, during, and after (10 min, 2 h, and 3.5 h) exercise or rest for levels of catecholamines, cortisol, glucagon, insulin, glucose, free fatty acids, and lactate. Heart rate was recorded throughout exercise (or rest). Skeletal muscle (vastus lateralis) and adipose (periumbilical) biopsies were taken before and ∼4 h following exercise or rest for mRNA levels of genes related to energy metabolism, growth, angiogenesis, and circadian processes. Coordination of the timing of procedural components (e.g., local anesthetic delivery, biopsy incisions, tumescent delivery, intravenous line flushes, sample collection and processing, exercise transitions, and team dynamics) was reasonable to orchestrate while considering subject burden and scientific objectives. The cardiovascular and metabolic alterations reflected a dynamic and unique response to endurance and resistance exercise, whereas skeletal muscle was transcriptionally more responsive than adipose 4 h postexercise. In summary, the current report provides the first evidence of protocol execution and feasibility of key components of the MoTrPAC human adult clinical exercise protocols. Scientists should consider designing exercise studies in various populations to interface with the MoTrPAC protocols and DataHub. NEW & NOTEWORTHY This study highlights the feasibility of key aspects of the MoTrPAC adult human clinical protocols. This initial preview of what can be expected from acute exercise trial data from MoTrPAC provides an impetus for scientists to design exercise studies to interlace with the rich phenotypic and -omics data that will populate the MoTrPAC DataHub at the completion of the parent protocol.

Cycling exercise in older individuals is beneficial for the cardiovascular system and quadriceps muscles, including partially reversing the age-related loss of quadriceps muscle mass. However, the effect of cycling exercise on the numerous other lower limb muscles is unknown. Six older men (74 ± 8 years) underwent MRI before and after 12-weeks of progressive aerobic cycle exercise training (3-4 days/week, 60-180 min/week, 60%-80% heart rate reserve, VO 2 max: +13%) for upper (rectus femoris, vastii, adductor longus, adductor magnus, gracilis, sartorius, biceps femoris long head, biceps femoris short head, semimembranosus, semitendinosus) and lower (anterior tibial, posterior tibialis, peroneals, flexor digitorum longus, lateral gastrocnemius, medial gastrocnemius, soleus) leg muscle volumes. In the upper leg, cycle exercise training induced hypertrophy (p ≤ 0.05) in the vastii (+7%) and sartorius (+6%), with a trend to increase biceps femoris short head (+5%, p = 0.1). Additionally, there was a trend to decrease muscle volume in the adductor longus (-6%, p = 0.1) and biceps femoris long head (-5%, p = 0.09). In the lower leg, all 7 muscle volumes assessed were unaltered pre- to post-training (-2% to -3%, p > 0.05). This new evidence related to cycle exercise training in older individuals clarifies the specific upper leg muscles that are highly impacted, while revealing all the lower leg muscles do not appear responsive, in the context of muscle mass and sarcopenia. This study provides information for exercise program development in older individuals, suggesting other specific exercises are needed for the rectus femoris and adductors, certain hamstrings, and the anterior and posterior lower leg muscles to augment the beneficial effects of cycling exercise for older adults., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Matrix multiplication is important in various information-processing applications, including the computation of eigenvalues and eigenvectors, and in combinatorial optimization algorithms. Therefore, reducing the computation time of matrix products is essential to speed up scientific and practical calculations. Several approaches have been proposed to speed up this process, including GPUs, fast matrix multiplication libraries, custom hardware, and efficient approximate matrix multiplication (AMM) algorithms. However, research to date has yet to focus on accelerating AMMs for general matrices on GPUs, despite the potential of GPUs to perform fast and accurate matrix product calculations. In this paper, we propose a method for improving Monte Carlo AMMs. We also give an analytical solution for the optimal values of the hyperparameters in the proposed method. The proposed method improves the approximation of the matrix product without increasing the computation time compared to the conventional AMMs. It is also designed to work well with parallel operations on GPUs and can be incorporated into various algorithms. Finally, the proposed method is applied to a power method used for eigenvalue computation. We demonstrate that, on an NVIDIA A100 GPU, the computation time can be halved compared to the conventional power method using cuBLAS.

Reservoir computing is a machine learning paradigm that uses a structure called a reservoir, which has nonlinearities and short-term memory. In recent years, reservoir computing has expanded to new functions such as the autonomous generation of chaotic time series, as well as time series prediction and classification. Furthermore, novel possibilities have been demonstrated, such as inferring the existence of previously unseen attractors. Sampling, in contrast, has a strong influence on such functions. Sampling is indispensable in a physical reservoir computer that uses an existing physical system as a reservoir because the use of an external digital system for the data input is usually inevitable. This study analyzes the effect of sampling on the ability of reservoir computing to autonomously regenerate chaotic time series. We found, as expected, that excessively coarse sampling degrades the system performance, but also that excessively dense sampling is unsuitable. Based on quantitative indicators that capture the local and global characteristics of attractors, we identify a suitable window of the sampling frequency and discuss its underlying mechanisms., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

In Japan, the standard method for measuring plasma aldosterone concentration (PAC) for primary aldosteronism (PA) diagnosis was changed from radioimmunoassay (RIA) to a novel chemiluminescent enzyme immunoassay (CLEIA). The purpose of this study is to simulate the possible impact of the change on PA diagnosis. This retrospective study assessed 2,289 PA patients. PACs measured by conventional RIA were transformed to estimated PACs (CLEIA) as follows: RIA (pg/mL) = 1.174 × CLEIA (pg/mL) + 42.3. We applied the estimated PAC (CLEIA) to the conventional cut-off of aldosterone-to-renin activity ratio ≥200 for screening and captopril challenge test (CCT) and PAC ≥60 pg/mL for saline infusion test (SIT). Application of the estimated PAC to screening and confirmatory tests decreased the number of PA diagnoses by 36% (743/2,065) on CCT and 52% (578/1,104) on SIT (discrepant cases). Among the discrepant cases, 87% (548/628) of CCT and 87% (452/522) of SIT were bilateral on adrenal venous sampling (AVS). Surgically treatable aldosterone-producing adenomas (APAs) were observed in 6% (36/579) and 5% (23/472) of discrepant cases on CCT and SIT, respectively; most were characterized by hypokalemia and/or adrenal nodule on CT imaging. Application of the PAC measured by the novel CLEIA to conventional cut-offs decreases the number of PA diagnoses. Although most discrepant cases were bilateral on AVS, there are some APA cases that were characterized by hypokalemia and/or adrenal tumor on CT. Further studies which evaluate PACs measured by both RIA and CLEIA for each patient are needed to identify new cut-offs for PAC measured by CLEIA.

Quantum walks (QWs) have a property that classical random walks (RWs) do not possess-the coexistence of linear spreading and localization-and this property is utilized to implement various kinds of applications. This paper proposes RW- and QW-based algorithms for multi-armed-bandit (MAB) problems. We show that, under some settings, the QW-based model realizes higher performance than the corresponding RW-based one by associating the two operations that make MAB problems difficult-exploration and exploitation-with these two behaviors of QWs.

In patients with clefts, the affection of other congenital malformations on the feeding is unclear. We investigated the other congenital malformations and nutritional intake of neonates with cleft lip and/or palate and examined their relationships associated with cleft type and laterality. The participants included 126 infants under treatment with a presurgical naso-alveolar molding (PNAM) or a Hotz-type plate. The survey items were gender, cleft type and side, presence and nature of other congenital malformations, birth weight and nutritional method at age of the fifth day. The number of infants was 36 (28.6%) of cleft lip and alveolus, 82 (65.1%) of cleft lip and palate, and 8 (6.3%) of cleft palate only. Forty-three patients (34.1%) had other various congenital malformations. The nutritional method included oral intake in 78.6% (n = 99) of cases and tube feeding with/without oral intake in 21.4% (n = 27) of cases. The rate of tube feeding was higher for right-sided clefts than that for left-sided clefts. This observation was consistent with the fact that right-sided clefts were associated with more significant other congenital malformations than those on the left-side. The nutritional method for infants with cleft lip and/or palate was related to the presence of other congenital malformations, not to cleft laterality or oral cleft itself under early treatment with PNAM plate. These results proposed that screening the general condition is essential for neonates with right-sided cleft lip with/without cleft palate compared to left-sided clefts, which should be conducted immediately after birth for planning the appropriate nutritional method., (© 2023 Japanese Teratology Society.)

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs., Competing Interests: Declaration of interests DT has received personal honoraria for lectures and consulting and support for meeting attendance from Advanced Accelerator Applications and Novartis. CL-L has received personal honoraria for lectures and support for meeting attendance from Ipsen. SN has received research grant to their institution from German Research Foundation. LA has received personal honoraria for lectures from Servier and Ipsen. ALE has received fees for consulting from WL Gore and fees for participation on an advisory board from Artivion. ML has received research grants to their institution from Arbor, Bristol Myers Squibb, Accuray, Biohaven, and Urogen; honoraria for research consulting from VBI Vaccines, InCephalo Therapeutics, Merck, Pyramid Bio, Insightec, Biohaven, Sanianoia, Hemispherian, Novocure, Noxxon, InCando, Century Therapeutics, and CraniUs; honoraria for non-research consulting from Stryker; is a shareholder of Egret Therapeutics; holds patents for the combination of immunotherapy and local chemotherapy to treat malignancies (10864180) and focused radiation to augment immune-based strategies against cancer (9132281); and is a member of the data and safety monitoring board of Cellularity. ELP has received fees for participation on an advisory board from Vysioneer. RTC has received personal honoraria for lectures from Novartis, support for meeting attendance from Ipsen, and serves as a board member for the Society for Endocrinology clinical committee and the UK and Ireland Neuroendocrine Tumour Society clinical committee. JKL has received honoraria for lectures from and is a consultant for Stryker. ERM has received fees for consulting and personal honoraria for lectures from MSD. NN has received an intramural research grant from the National Institutes of Health. NP-T has received research grants to their institution from Innervate, Clarity pharma; fees for consulting from Progenics, Lantheus, and Innervate Lifesciences. NP-T is a member of the data and safety monitoring board of Progenics and Lantheus, and serves as a board member for Society of Nuclear Medicine and Molecular Imaging. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We present a method for computer-generated holography (CGH) in which different images are reproduced on both sides of a hologram with a single illumination source. In the proposed method, we use a transmissive spatial light modulator (SLM) and a half mirror (HM) located downstream of the SLM. The light modulated by the SLM is partially reflected by the HM, and the reflected light is modulated again by the SLM for the double-sided image reproduction. We derive an algorithm for double-sided CGH and experimentally demonstrate it.

There is some evidence that the age-associated change in skeletal muscle mass is muscle specific, yet the number of specific muscles that have been studied to form our understanding in this area is limited. In addition, few aging investigations have examined multiple muscles in the same individuals. This longitudinal investigation compared changes in skeletal muscle size via computed tomography of the quadriceps (rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius), hamstrings (biceps femoris short and long heads, semitendinosus, and semimembranosus), psoas, rectus abdominis, lateral abdominals (obliques and transversus abdominis), and paraspinal muscles (erector spinae and multifidi) of older individuals from the Health, Aging, and Body Composition (Health ABC) study at baseline and 5.0 ± 0.1 years later ( n = 469, 73 ± 3 yr and 78 ± 3 yr, 49% women, 33% black). Skeletal muscle size decreased ( P < 0.05) in quadriceps (-3.3%), hamstrings (-5.9%), psoas (-0.4%), and rectus abdominis (-7.0%). The hamstrings and rectus abdominis atrophied approximately twice as much as the quadriceps ( P < 0.05), whereas the quadriceps atrophied substantially more than the psoas ( P < 0.05). The lateral abdominals (+5.9%) and paraspinals (+4.3%) hypertrophied ( P < 0.05) to a similar degree ( P > 0.05) over the 5 years. These data suggest that older individuals experience skeletal muscle atrophy and hypertrophy in a muscle group-specific fashion in the eighth decade, a critical time period in the aging process. A broader understanding of muscle group-specific skeletal muscle aging is needed to better guide exercise programs and other interventions that mitigate decrements in physical function with aging. NEW & NOTEWORTHY These longitudinal analyses of six muscle groups in septuagenarians provide novel information on the muscle group-specific aging process. Although the quadriceps, hamstrings, psoas, and rectus abdominis atrophied with different magnitudes, the lateral abdominals and paraspinals hypertrophied over the 5 years. These findings contribute to a better understanding of the skeletal muscle aging process and highlight the need to complete studies in this area with a muscle-specific focus.

Age-related skeletal muscle atrophy appears to be a muscle group-specific process, yet only a few specific muscles have been investigated and our understanding in this area is limited. This review provides a comprehensive summary of the available information on age-related skeletal muscle atrophy in a muscle-specific manner, nearly half of which comes from the quadriceps. Decline in muscle-specific size over ∼50 yr of aging was determined from 47 cross-sectional studies of 982 young (∼25 yr) and 1,003 old (∼75 yr) individuals and nine muscle groups: elbow extensors (-20%, -0.39%/yr), elbow flexors (-19%, -0.38%/yr), paraspinals (-24%, -0.47%/yr), psoas (-29%, -0.58%/yr), hip adductors (-13%, -0.27%/yr), hamstrings (-19%, -0.39%/yr), quadriceps (-27%, -0.53%/yr), dorsiflexors (-9%, -0.19%/yr), and triceps surae (-14%, -0.28%/yr). Muscle-specific atrophy rate was also determined for each of the subcomponent muscles in the hamstrings, quadriceps, and triceps surae. Of all the muscles included in this review, there was more than a fivefold difference between the least (-6%, -0.13%/yr, soleus) to the most (-33%, -0.66%/yr, rectus femoris) atrophying muscles. Muscle activity level, muscle fiber type, sex, and timeline of the aging process all appeared to have some influence on muscle-specific atrophy. Given the large range of muscle-specific atrophy and the large number of muscles that have not been investigated, more muscle-specific information could expand our understanding of functional deficits that develop with aging and help guide muscle-specific interventions to improve the quality of life of aging women and men.

Chronic inflammation is associated with a decline in aging skeletal muscle health. Inflammation also seems to interfere with the beneficial skeletal muscle adaptations conferred by exercise training in older individuals. We hypothesize that the cyclooxygenase pathway is partially responsible for this negative inflammatory influence on aging skeletal muscle health and plasticity., (Copyright © 2023 by the American College of Sports Medicine.)

Aspirin is one of the most commonly consumed cyclooxygenase (COX)-inhibitors and anti-inflammatory drugs and has been shown to block COX-produced regulators of inflammation and aging skeletal muscle size. We used propensity score matching to compare skeletal muscle characteristics of individuals from the Health ABC study that did not consume aspirin or any other COX-inhibiting drugs (non-consumers, n = 497, 74 ± 3 year, 168 ± 9 cm, 75.1 ± 13.8 kg, 33.1 ± 7.4% body fat, 37% women, 34% black) to those that consumed aspirin daily (and not any other COX-inhibiting drugs) and for at least 1 year (aspirin consumers, n = 515, 74 ± 3 year, 168 ± 9 cm, 76.2 ± 13.6 kg, 33.8 ± 7.1% body fat, 39% women, 30% black, average aspirin consumption: 6 year). Subjects were matched (p > 0.05) based on age, height, weight, % body fat, sex, and race (propensity scores: 0.33 ± 0.09 vs. 0.33 ± 0.09, p > 0.05). There was no difference between non-consumers and aspirin consumers for computed tomography-determined muscle size of the quadriceps (103.5 ± 0.9 vs. 104.9 ± 0.8 cm 2 , p > 0.05) or hamstrings (54.6 ± 0.5 vs. 54.9 ± 0.5 cm 2 , p > 0.05), or quadriceps muscle strength (111.1 ± 2.0 vs. 111.7 ± 2.0 Nm, p > 0.05). However, muscle attenuation (i.e., density) was higher in the aspirin consumers in the quadriceps (40.9 ± 0.3 vs. 44.4 ± 0.3 Hounsfield unit [HU], p < 0.05) and hamstrings (27.7 ± 0.4 vs. 33.2 ± 0.4 HU, p < 0.05). These cross sectional data suggest that chronic aspirin consumption does not influence age-related skeletal muscle atrophy, but does influence skeletal muscle composition in septuagenarians. Prospective longitudinal investigations remain necessary to better understand the influence of chronic COX regulation on aging skeletal muscle health., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Multiscale entropy (MSE) has been widely used to examine nonlinear systems involving multiple time scales, such as biological and economic systems. Conversely, Allan variance has been used to evaluate the stability of oscillators, such as clocks and lasers, ranging from short to long time scales. Although these two statistical measures were developed independently for different purposes in different fields, their interest lies in examining the multiscale temporal structures of physical phenomena under study. We demonstrate that from an information-theoretical perspective, they share some foundations and exhibit similar tendencies. We experimentally confirmed that similar properties of the MSE and Allan variance can be observed in low-frequency fluctuations (LFF) in chaotic lasers and physiological heartbeat data. Furthermore, we calculated the condition under which this consistency between the MSE and Allan variance exists, which is related to certain conditional probabilities. Heuristically, natural physical systems including the aforementioned LFF and heartbeat data mostly satisfy this condition, and hence, the MSE and Allan variance demonstrate similar properties. As a counterexample, we demonstrate an artificially constructed random sequence, for which the MSE and Allan variance exhibit different trends., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

This study aimed to develop a machine-learning algorithm to diagnose aldosterone-producing adenoma (APA) for predicting APA probabilities. A retrospective cross-sectional analysis of the Japan Rare/Intractable Adrenal Diseases Study dataset was performed using the nationwide PA registry in Japan comprised of 41 centers. Patients treated between January 2006 and December 2019 were included. Forty-six features at screening and 13 features at confirmatory test were used for model development to calculate APA probability. Seven machine-learning programs were combined to develop the ensemble-learning model (ELM), which was externally validated. The strongest predictive factors for APA were serum potassium (s-K) at first visit, s-K after medication, plasma aldosterone concentration, aldosterone-to-renin ratio, and potassium supplementation dose. The average performance of the screening model had an AUC of 0.899; the confirmatory test model had an AUC of 0.913. In the external validation, the AUC was 0.964 in the screening model using an APA probability of 0.17. The clinical findings at screening predicted the diagnosis of APA with high accuracy. This novel algorithm can support the PA practice in primary care settings and prevent potentially curable APA patients from falling outside the PA diagnostic flowchart., (© 2023. The Author(s).)

Fully pairing all elements of a set while attempting to maximize the total benefit is a combinatorically difficult problem. Such pairing problems naturally appear in various situations in science, technology, economics, and other fields. In our previous study, we proposed an efficient method to infer the underlying compatibilities among the entities, under the constraint that only the total compatibility is observable. Furthermore, by transforming the pairing problem into a traveling salesman problem with a multi-layer architecture, a pairing optimization algorithm was successfully demonstrated to derive a high-total-compatibility pairing. However, there is substantial room for further performance enhancement by further exploiting the underlying mathematical properties. In this study, we prove the existence of algebraic structures in the pairing problem. We transform the initially estimated compatibility information into an equivalent form where the variance of the individual compatibilities is minimized. We then demonstrate that the total compatibility obtained when using the heuristic pairing algorithm on the transformed problem is significantly higher compared to the previous method. With this improved perspective on the pairing problem using fundamental mathematical properties, we can contribute to practical applications such as wireless communications beyond 5G, where efficient pairing is of critical importance. As the pairing problem is a special case of the maximum weighted matching problem, our findings may also have implications for other algorithms on fully connected graphs.

Objective: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized., Design: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated., Results: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers., Conclusions: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

High-fat intake by young Asian women impacts the risk of breast cancer. Understanding the underlying molecular mechanisms may be essential for disease prevention in Asia as well as globally. We aimed to examine the effects of corn oil- and animal fat-based high-fat diets (32.9 and 31.4%, respectively, of fat energy ratio as compared to 12.3% in the standard diet) on mammary carcinogenesis and alterations in gene expression and epigenetic statuses in the mammary gland during the growth stages in a rat model. An increased incidence of carcinomas was observed after the cessation of high-fat feeding. In addition, rapid tumor growth and elevations in Celsr2 expression, which may be a result of DNA hypomethylation patterns in the 3' untranslated region of the gene were noted in the animal fat group. In the human breast carcinoma cell line MCF7, a marginal decrease in cell viability was observed following the knockdown of Celsr2 , suggesting that the animal fat-associated risk of cancer is partly due to the deregulation of mammary cell proliferation via non-metabolic gene functions. The present results will contribute to the development of strategies for controlling the food-associated risk of breast cancer, particularly in younger age groups.

Allan variance has been widely utilized for evaluating the stability of the time series generated by atomic clocks and lasers, in time regimes ranging from short to extremely long. This multiscale examination capability of the Allan variance may also be beneficial in evaluating the chaotic oscillating dynamics of semiconductor lasers- not just for conventional phase stability analysis. In the present study, we demonstrated Allan variance analysis of the complex time series generated by a semiconductor laser with delayed feedback, including low-frequency fluctuations (LFFs), which exhibit both fast and slow dynamics. While the detection of LFFs is difficult with the conventional power spectrum analysis method in the low-frequency regime, the Allan variance approach clearly captured the appearance of multiple time-scale dynamics, such as LFFs. This study demonstrates that Allan variance can help in understanding and characterizing diverse laser dynamics, including LFFs, spanning a wide range of timescales.

Objective: Primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing syndrome, is often diagnosed as a bilateral adrenal incidentaloma with subclinical cortisol production. Circulating microRNAs (miRNAs) are a characteristic of adrenocortical adenomas, but miRNA expression in PBMAH has not been investigated. We aimed to evaluate the circulating miRNA expression in patients with PBMAH and compare them with those in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA)., Methods: miRNA profiling of plasma samples from four, five, and five patients with NFA, CPA, and PBMAH, respectively, was performed. Selected miRNA expressions were validated using quantitative RT-PCR., Results: PBMAH samples showed distinct miRNA expression signatures on hierarchical clustering while NFA and CPA samples were separately clustered. PBMAH was distinguished from the adenoma group of NFA and CPA by 135 differentially expressed miRNAs. Hsa-miR-1180-3p, hsa-miR-4732-5p, and hsa-let-7b-5p were differentially expressed between PBMAH and adenoma ( P = 0.019, 0.006, and 0.003, respectively). Furthermore, PBMAH could be classified into two subtypes based on miRNA profiling: subtype 1 with a similar profile to those of adenoma and subtype 2 with a distinct profile. Hsa-miR-631, hsa-miR-513b-5p, hsa-miR-6805-5p, and hsa-miR-548av-5p/548k were differentially expressed between PBMAH subtype 2 and adenoma ( P = 0.027, 0.027, 0.027, and 1.53E-04, respectively), but not between PBMAH, as a whole, and adenoma., Conclusion: Circulating miRNA signature was identified specific for PBMAH. The existence of subtype-based miRNA profiles may be associated with the pathophysiological heterogeneity of PBMAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hara, Murakami, Niitsu, Takeuchi, Horino, Shiba, Tsujimoto, Komiya, Ikeda, Tsuiki, Tanabe, Tanaka, Yokoyama, Fujii, Naruse and Yamada.)

Photonic artificial intelligence has attracted considerable interest in accelerating machine learning; however, the unique optical properties have not been fully used for achieving higher-order functionalities. Chaotic itinerancy, with its spontaneous transient dynamics among multiple quasi-attractors, can be used to realize brain-like functionalities. In this study, we numerically and experimentally investigate a method for controlling the chaotic itinerancy in a multimode semiconductor laser to solve a machine learning task, namely, the multiarmed bandit problem, which is fundamental to reinforcement learning. The proposed method uses chaotic itinerant motion in mode competition dynamics controlled via optical injection. We found that the exploration mechanism is completely different from a conventional searching algorithm and is highly scalable, outperforming the conventional approaches for large-scale bandit problems. This study paves the way to use chaotic itinerancy for effectively solving complex machine learning tasks as photonic hardware accelerators.

Irregular spatial distribution of photon transmission through a photochromic crystal photoisomerized by a local optical near-field excitation was previously reported, which manifested complex branching processes via the interplay of material deformation and near-field photon transfer therein. Furthermore, by combining such naturally constructed complex photon transmission with a simple photon detection protocol, Schubert polynomials, the foundation of versatile permutation operations in mathematics, have been generated. In this study, we demonstrated an order recognition algorithm inspired by Schubert calculus using optical near-field statistics via nanometre-scale photochromism. More specifically, by utilizing Schubert polynomials generated via optical near-field patterns, we showed that the order of slot machines with initially unknown reward probability was successfully recognized. We emphasized that, unlike conventional algorithms, the proposed principle does not estimate the reward probabilities but exploits the inversion relations contained in the Schubert polynomials. To quantitatively evaluate the impact of Schubert polynomials generated from an optical near-field pattern, order recognition performances were compared with uniformly distributed and spatially strongly skewed probability distributions, where the optical near-field pattern outperformed the others. We found that the number of singularities contained in Schubert polynomials and that of the given problem or considered environment exhibited a clear correspondence, indicating that superior order recognition is attained when the singularity of the given situations is presupposed. This study paves way for physical computing through the interplay of complex natural processes and mathematical insights gained by Schubert calculus., (© 2022. The Author(s).)

Aims: This study sought to determine whether not sleeping soundly in early infancy predicted poor development. This complemented earlier studies of children aged 12 months or older., Methods: Sleep/wake patterns of 35 Japanese infants (23 males) with a gestational age of 37< weeks were recorded at home using actigraphy. Families were registered with a laboratory-based database for infant research. Follow-up recordings were conducted at 3, 4, 6, 12, and 24 months. Crawling was rated by mothers at 12 months and used to create regular and irregular crawling groups. Temperament was scaled using the Japanese Infant Behaviour Questionnaire-Revised Questionnaire and the Japanese Early Childhood Behaviour Questionnaire., Results: At 4 months, infants with regular crawling style had shorter night-time sleep than infants with irregular crawling style. However, at 12 months, the former had longer motionless sleep at night compared to the latter. Before 6 months, infants with regular crawling style showed lower sleep efficiency, especially during the day, compared to those with irregular crawling style. In addition, the amount of night-time active sleep at 3 and 4 months were positively correlated with day-time activity, but not at 6 months., Conclusion: Short fragmental sleep in early infancy did not always predict poor development., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

mRNA vaccines for SARS-CoV-2 have been widely used and saving millions of people in the world. How efficiently proteins are produced from exogenous mRNAs in the embryonic brain, however, is less known. Here we show that protein expression occurs highly efficiently in neural stem cells, in a very narrow time window after mRNA electroporation in the embryonic mouse brain, where plasmids have been successfully transfected. Protein expression is detected 1 h and 12 h after the electroporation of mRNAs and plasmids, respectively. The delivery of exogenous mRNAs may be useful for not only vaccines but also functional analysis in the brain., (© 2022. The Author(s).)

Little is known regarding the association of blood pressure (BP) after treatment for primary aldosteronism (PA) (i.e., adrenalectomy and mineralocorticoid receptor antagonists) with long-term renal outcomes, and whether the association is independent of BP before treatment. Using a dataset from a nationwide registry of PA in Japan, we assessed whether achieved BP levels 6 months after treatment for PA are associated with annual changes in estimated glomerular filtration rate (eGFR), rapid eGFR decline, and incident chronic kidney disease (CKD) during the 5-year follow-up period. The cohort included 1266 PA patients. In multivariable linear regression including systolic BP (SBP) levels before treatment for PA, estimates (95% confidence interval [CI]) for annual changes in eGFR after month 6 associated with one-standard deviation (1-SD) higher SBP at month 6 were -0.08 (-0.15, -0.02) mL/min/1.73 m 2 /year. After multivariable adjustment, the estimate (95% CI) for annual changes in eGFR after month 6 was -0.12 (-0.21, -0.02) for SBP ≥ 130 mmHg vs. SBP < 130 mmHg at month 6. Among 537 participants without CKD at baseline, a 1-SD higher SBP was associated with a higher risk for incident CKD events (hazard ratio [95% CI]: 1.40 [1.00, 1.94]). Higher SBP after treatment for PA was associated with a higher risk for kidney dysfunction over time, independently of BP levels before treatment. Achieving SBP lower than 130 mmHg after treatment for PA may be linked to better kidney outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)