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We investigate many-body properties of equally populated three-component fermions with attractive three-body contact interaction in one dimension. A diagrammatic approach suggests the possible occurrence of Cooper triples at low temperature, which are three-body counterparts of Cooper pairs with a two-body attraction. We develop a minimal framework that bridges the crossover from tightly bound trimers to Cooper triples with increasing chemical potential and show how the formation of Cooper triples occurs in the grand-canonical phase diagram. Moreover, we argue that this nontrivial crossover is similar to the hadron-quark crossover proposed in dense matter. A coexistence of medium-induced triples and the underlying Fermi sea at positive chemical potential is analogous to quarkyonic matter consisting of baryonic excitations and the underlying quark Fermi sea. The comparison with the existing quantum Monte Carlo results implies that the emergence of these kinds of three-body states can be a microscopic origin of the peak of the sound velocity along the crossover.

Competing Interests: The authors declare that they have no conflict of interest.

Objective: Both periodontal disease and obesity are risk factors for dementia, but their links to 1brain function remain unclear. In this study, we examined the effects of oral infection with a periodontal pathogen on cognitive function in a mouse model of obesity, focusing on the roles of microglia., Methods: To create a mouse model of diet-induced obesity and periodontitis, male C57BL/6 J mice were first fed a high-fat diet containing 60% lipid calories for 18 weeks, beginning at 12 weeks of age, to achieve diet-induced obesity. Then, Porphyromonas gingivalis administration in the oral cavity twice weekly for 6 weeks was performed to induce periodontitis in obese mice., Results: Obese mice orally exposed to P. gingivalis showed cognitive impairment in the novel object recognition test. Increased expression levels of inflammatory cytokines (e.g. interleukin-1β and tumor necrosis factor-α) were observed in the hippocampus of P. gingivalis -treated obese mice. Immunohistochemical analysis revealed that microglia cell body size was increased in the hippocampus and prefrontal cortex of P. gingivalis -treated obese mice, indicating microglial activation. Furthermore, depletion of microglia by PLX3397, a colony-stimulating factor 1 receptor inhibitor, ameliorated cognitive dysfunction., Conclusion: These results suggest that microglia mediate periodontal infection-induced cognitive dysfunction in obesity., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Frailty increases the risk of needing nursing care and significantly affects the life and functional prognosis of older individuals. Early detection and tailored interventions are crucial for maintaining and enhancing their life functions. Recognizing distinct clinical phenotypes is essential for devising appropriate interventions. This study aimed to explore diverse frailty phenotypes, focusing on poor nutrition in older Japanese individuals through observational research., Methods: Twenty-one nursing home residents underwent a comprehensive survey covering physical, blood, dietary, cardiac, cognitive, nutritional, nursing care, frailty, agitated behavior, and gut microbiome assessments (high-throughput 16S rRNA gene sequencing). Using clustering analysis with 239 survey items (excluding gut microbiome), participants were classified into subgroups based on clinical phenotypes, and group characteristics were compared through analysis., Results: Individuals with moderate or severe frailty and suspected dementia formed subgroups with distinct clinical phenotypes based on nutritional, defecation, and nursing care statuses. The gut microbiome significantly varied among these groups ( p = 0.007), indicating its correlation with changes in clinical phenotype. Nutritional status differences suggested poor nutrition as a differentiating factor in the core clinical phenotype., Conclusions: This study proposes that the gut microbiome differs based on the clinical phenotype of Japanese older individuals with frailty, and targeted interventions addressing the gut microbiome may contribute to preventing frailty in this population.

Designer receptors exclusively activated by designer drugs (DREADDs) are engineered G-protein-coupled receptors that afford reversible manipulation of neuronal activity in vivo. Here, we introduce size-reduced DREADD derivatives miniD q and miniD i , which inherit the basic receptor properties from the G q -coupled excitatory receptor hM3D q and the G i -coupled inhibitory receptor hM4D i , respectively, while being approximately 30% smaller in size. Taking advantage of the compact size of the receptors, we generated an adeno-associated virus (AAV) vector carrying both miniD q and the other DREADD family receptor (κ-opioid receptor-based inhibitory DREADD [KORD]) within the maximum AAV capacity (4.7 kb), allowing us to modulate neuronal activity and animal behavior in both excitatory and inhibitory directions using a single viral vector. We confirmed that expressing miniD q , but not miniD i , allowed activation of striatum activity in the cynomolgus monkey (Macaca fascicularis). The compact DREADDs may thus widen the opportunity for multiplexed interrogation and/or intervention in neuronal regulation in mice and non-human primates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The human gut environment undergoes substantial changes as a host ages. This investigation centered on the gut microbiome diversity among patients with severe motor and intellectual disabilities (SMID), examining the association between the gut microbiome composition and physical characteristics with varying levels of diversity., Methods: Fourteen subjects were investigated, with physical and defecation status, blood biochemical test, gut microbiome profiling, and fecal metabolites used to divide the patients into a high-diversity group (HD, eight patients) and a low-diversity group (LD, six patients)., Results: Findings indicated that the microbiome of the LD group showed delayed maturation reminiscent of neonates and lactating infants. Analysis of the fecal bile acids (BAs) revealed a markedly diminished proportion of deoxycholic acid in the secondary BAs in the LD group, suggestive of inadequate conversion from primary to secondary BAs. Furthermore, the LD group presented with loose stools. The LD group exhibited a higher degree of physical severity, with all patients bedridden and fed via gastrostomy with only enteral formula received., Conclusions: The composition of the gut microbiome and BAs in the LD group was found to differ from those of healthy individuals and the HD group, indicating a potentially immature gut environment for these individuals.

Objectives: One possible reason for the long-term patency of no-touch (NT) saphenous vein grafts (SVG) is the preservation of the vasa vasorum in the adventitia/perivascular adipose tissue (PAT). We investigated the vasa vasorum of the NT SVG in vivo using frequency-domain optical coherence tomography (FD-OCT), performed qualitative and quantitative analyses and compared them with the conventional SVG., Methods: An FD-OCT study was performed on 14 SVG at the postoperative coronary angiography 1-2 weeks postoperatively (NT group, n = 9; conventional group, n = 5)., Results: Many signal-poor tubular lumen structures that can be recognized in the cross-sectional and longitudinal profiles, which indicates the vasa vasorum, were observed in the adventitial/PAT layer in the NT SVG. In contrast, the vasa vasorum were less abundant in the conventional SVG. The volume of vasa vasorum per millimetre of graft in the no-touch group was significantly higher than in the conventional group [0.0020 (0.0017, 0.0043) mm3 and 0.0003 (0.0000, 0.0006) mm3, P = 0.023]., Conclusions: FD-OCT showed abundant vasa vasorum in the thick adventitia/PAT layer of NT saphenous veins in vivo. In contrast, few vasa vasorum were observed in the conventional SVG., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: We hypothesized that the beneficial effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on diastolic function might depend on baseline left ventricular (LV) systolic function., Methods: To investigate the effects of SGLT2 inhibitors on LV diastolic function in patients with type 2 diabetes mellitus (T2DM), we conducted a post-hoc sub-study of the PROTECT trial, stratifying the data according to LV ejection fraction (LVEF) at baseline. After excluding patients without echocardiographic data at baseline or 24 months into the PROTECT trial, 31 and 38 patients with T2DM from the full analysis dataset of the PROTECT trial who received ipragliflozin or no SGLT2 inhibitor (control), respectively, were included. The primary endpoint was a comparison of the changes in echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels from baseline to 24 months between the two groups stratified according to baseline LVEF., Results: Differences in diastolic functional parameters (e' and E/e') were noted between the two groups. Among the subgroups defined according to median LVEF values, those with higher LVEF (≥60 %) who received ipragliflozin appeared to have a higher e' and lower E/e' than did those who received the standard of care with no SGLT2 inhibitor, indicating longitudinal improvements between baseline and follow up (p = 0.001 and 0.016, respectively)., Conclusions: Ipragliflozin generally improved LV diastolic function in patients with type 2 diabetes, the extent of this improvement might appear to vary with LV systolic function., Competing Interests: Declaration of competing interest TI received lecture fees from JCR Pharmaceuticals and KyowaKirin; and outsourcing fees from Organization for Clinical Medicine Promotion. AT received honoraria from Boehringer Ingelheim Japan and research funding from GlaxoSmithKline, Takeda, Bristol-Myers Squibb, and Novo Nordisk. HT received honoraria from Abbott Medical Japan, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Ono, Mitsubishi Tanabe, and Takeda. MS received grants and personal fees from Mitsubishi Tanabe, Takeda, Daiichi Sankyo, Astellas, Pfizer, Novartis, Boehringer Ingelheim, Bayer, MSD, Kowa, and AstraZeneca. NK has received honoraria from AstraZeneca, Bayer Yakuhin, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Otsuka, Takeda Pharmaceutical; Research grants from Asahi Kasei, Astellas, Boehringer Ingelheim Japan, Fuji Yakuhin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Novartis Pharma, Teijin Pharma; Scholarships from Bayer Yakuhin, Medtronic, Teijin Pharma. All other authors declare no competing interests. AT and KN are Editorial Board members of Cardiovascular Diabetology and were not involved in handling this manuscript during the submission and the review processes., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The effects of daily teriparatide (D-PTH, 20 μg/day), weekly high-dose teriparatide (W-PTH, 56.5 μg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT)., Methods: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment., Results: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %)., Conclusions: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur., Competing Interests: Declaration of competing interest This study was supported by Asahi Kasei Pharma Corporation and Eli Lilly Japan K.K., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Breast metastasis from small cell neuroendocrine carcinoma (SNEC) is very rare. In the present report, we describe a case of a female patient who was initially diagnosed with triple negative primary bilateral breast cancer, but during systemic examination, the diagnosis was bilateral breast metastasis from SNEC., Case Presentation: A 62-year-old woman with no history of smoking presented to the Department of General Medicine with left-sided chest pain, and computed tomography revealed masses in both breasts and left pleural thickening that was further confirmed by mammography and ultrasound of the breasts. A needle biopsy was performed, and triple negative primary bilateral breast cancer was diagnosed. Because progastrin-releasing peptide (ProGRP) 37,300 pg/ml (normal range, 0-81.0 pg/ml) and neuron-specific enolase 35.0 ng/ml (normal range, 0-16.3 ng/ml) levels were elevated, thoracoscopic biopsy was performed, and SNEC was diagnosed. Pathological examinations showed that the bilateral breast masses were also positive for immunohistochemical staining of chromogranin A, synaptophysin, and CD56, leading to a diagnosis of bilateral breast metastasis of neuroendocrine tumor., Conclusion: Although very rare, the possibility of breast metastasis should be considered when malignancy is suspected in other organs., (© 2024. The Author(s).)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Malignant esophageal strictures can mostly be diagnosed successfully by examination of mucosal biopsy specimens. In some cases, that procedure remains nondiagnostic because of significant overlying necrosis. Malignant strictures with normal or fibrotic overlying mucosa, mostly seen after previous mucosal ablative therapies, are uncommon. and mucosal biopsy specimens alone can be misleading. Further evaluation with EUS and analysis of core needle biopsy specimens can be helpful. This report describes the potential role of submucosal tunneling biopsy in selected cases. Submucosal tunneling is a minimally invasive technique that was initially described to perform POEM in patients with achalasia. When it is performed by an experienced operator, there is a low incidence of intraprocedural and postprocedural adverse events. In the past decade, numerous studies have proved the safety and efficacy of this technique in performing myotomies and even resections of subepithelial lesions. Further studies will be required to evaluate the diagnostic utility of submucosal tunneling in obtaining biopsy specimens from luminal strictures and subepithelial lesions. Muhammad Arslan Baig, MD, Interventional Gastroenterologist, Clinical Assistant Professor of Medicine, University of Texas Health Sciences Center at Tyler, Tyler, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Conformational freedom-restricted peptides, such as stapled peptides, play a crucial role in the advancement of functional peptide development. We synthesized stapled octapeptides using α-carbocyclic α,α-disubstituted α-amino acids, particularly 3-allyloxy-1-aminocyclopentane-1-carboxylic acid, as the crosslink motifs. The organocatalytic capabilities of the synthesized stapled peptides were assessed in an asymmetric nucleophilic epoxidation reaction because the catalytic activities are known to be proportional to α-helicity. Despite incorporating side-chain crosslinks, the enantioselectivities of the epoxidation reaction catalyzed by stapled octapeptides were found to be comparable to those obtained using unstapled peptides. Interestingly, the stapled peptides using α-carbocyclic α,α-disubstituted α-amino acids demonstrated higher reactivities and stereoselectivities (up to 99% ee) compared to stapled peptides derived from ( S )-α-(4-pentenyl)alanine, a commonly used motif for stapled peptides. These differences could be attributed to the increased α-helicity of the former stapled peptide in contrast to the latter, as evidenced by the X-ray crystallographic structures of their N - tert -butoxycarbonyl derivatives.

Introduction: Glucagon-like peptide 1 receptor agonists (GLP1Ras) have emerged as pivotal agents in diabetes management and organ protection. However, their use is limited due to the necessity for injectable administration. The advent of the first oral GLP1Ra (oral semaglutide) in Japan since 2021 is expected to expand its usage. The aim of this study is to survey the efficacy and tolerability of oral semaglutide in clinical practice., Materials and Methods: We retrospectively analyzed 120 outpatients diagnosed with type 2 diabetes mellitus who had received oral semaglutide for >6 months. Changes in clinical parameters during oral semaglutide treatment from baseline to 12 months were analyzed. The inverse probability weighting method using the propensity score was used to evaluate the differences in clinical parameters at 6 months after treatment, based on the patients' obesity levels., Results: Body weight (BW), glycated hemoglobin A 1c (HbA 1c ), and alanine aminotransferase (ALT) levels at baseline decreased significantly after treatment compared with those at 12 months (P < 0.001, P < 0.001, and P = 0.03, respectively). The patients were divided into two groups using a cutoff baseline body mass index (BMI) of 30.3 kg/m 2 . Although no significant difference was observed, changes in body weight and HbA 1c indicated a potentially greater decrease in the BMI ≧ 30.3 group than that in the BMI < 30.3 group (P = 0.07 and 0.13, respectively). Among 206 registered patients, 25 (12.1%) discontinued oral-semaglutide treatment owing to adverse effects, including gastrointestinal symptoms., Conclusions: Oral semaglutide treatment demonstrates efficacy and tolerability for managing type 2 diabetes mellitus in Japan. Significant improvements in metabolic factors induced by oral semaglutide are anticipated, particularly in obese patients., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Ribosome profiling, which is based on deep sequencing of ribosome footprints, has served as a powerful tool for elucidating the regulatory mechanism of protein synthesis. However, the current method has substantial issues: contamination by rRNAs and the lack of appropriate methods to measure ribosome numbers in transcripts. Here, we overcome these hurdles through the development of "Ribo-FilterOut", which is based on the separation of footprints from ribosome subunits by ultrafiltration, and "Ribo-Calibration", which relies on external spike-ins of stoichiometrically defined mRNA-ribosome complexes. A combination of these approaches estimates the number of ribosomes on a transcript, the translation initiation rate, and the overall number of translation events before its decay, all in a genome-wide manner. Moreover, our method reveals the allocation of ribosomes under heat shock stress, during aging, and across cell types. Our strategy of modified ribosome profiling measures kinetic and stoichiometric parameters of cellular translation across the transcriptome., (© 2024. The Author(s).)

The number of patients hospitalized with dementia is increasing, but one symptom, apathy, tends to be overlooked and unaddressed. Thus, this study determines how nurses certified in dementia nursing engage with older patients with dementia who exhibit apathy during hospitalization. A qualitative study using semi-structured interviews with 10 dementia care nurses in Japan was conducted. Through conventional content analysis, 10 categories were generated. They included (1) initiating patient engagement when their physiological or daily-life problems become more pronounced, (2) assessing and identifying the causes of decreased motivation from multiple perspectives, (3) assessing patients from multiple perspectives to determine the best way to start supporting them, (4) providing reassurance through basic dementia care, (5) incorporating pleasant stimuli into the hospital environment, (6) providing care based on patients' circumstances and abilities by collaborating with multiple professionals. Nurses initiate involvement with patients when their daily life problems become more pronounced. They conduct comprehensive assessments from multiple perspectives and collaborate with other professionals to ensure patient care and safety. They also extend their support to patients' families and maintain long-term involvement. Apathetic older patients benefit from basic nursing care practices and a patient-centered approach, which do not require specialization or additional costs and resources.

The sweetpotato whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is challenging to control using chemical pesticides owing to its resistance to many insecticides. Thus, there has been an increasing demand for alternative control measures. Thus, this study evaluated the efficacy of a newly designed pest suction machine to manage whiteflies on tomato plants (Solanum lycopersicum L.) (Solanales: Solanaceae) in greenhouses over 2 seasons. The suction machine comprised a battery-powered cart with a mounted suction unit, an ultrasonic device, and green lights. Ultrasonic irradiation provided non-contact vibration, facilitating the movement of adult whiteflies away from the plants, and green lights attracted them to the suction device. This combination effectively captured whitefly adults, even with a weak suction force, saving electricity consumption. The efficacy of suction machine was further evaluated by measuring the number of whitefly adults caught by the machine and the number of adults and nymphs remaining on the tomato leaves. The whitefly population was considerably lower in the treated blocks than in the non-treated blocks in the autumn trial. The machine reduced the density of whitefly adults without using chemical pesticides. Although a lot of optimizations would be required, suction control is an additional and alternative strategy that may be incorporated in the integrated pest management of whiteflies on greenhouse tomato plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. 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.)

The cyclic peptide cyclo (Val-Leu-Leu-d-Phe-Pro) 2 (peptide 1 ) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within 1 adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4- trans / cis -isomers into 1 , an up-puckering conformation was successfully induced. In the current investigation, introducing hy-droxy-prolines with 4- trans / cis -isomer configurations (tHyp/cHyp) into 1 gave cyclo (Val-Leu-Leu-d-Phe-tHyp) 2 methanol disolvate monohydrate, C 62 H 94 N 10 O 12 ·2CH 4 O·H 2 O ( 4 ), and cyclo (Val-Leu-Leu-d-Phe-cHyp) 2 monohydrate, C 62 H 94 N 10 O 12 ·H 2 O ( 5 ), respectively. However, the puckering of 4 and 5 remained in the down conformation, regardless of the geometric position of the hydroxyl group. Although the backbone structure of 4 with trans -substitution was asymmetric, the asymmetric backbone of 5 with cis -substitution was unexpected. It is speculated that the anti-cipated influence of stress from the geometric positioning, which was expected to affect the puckering, may have been mitigated by inter-actions between the hydroxyl groups of hy-droxy-proline, the solvent mol-ecules, and peptides., (© Asano et al. 2024.)

To investigate the correlation between the aggregated state and photoluminescence (PL) mechanism of dual fluorescent (FL) and phosphorescent (PH) polyimides (PIs), the photophysical processes of FL-type BP-PI , PH-type DBrBP-PI , and their corresponding imide model compounds ( BP-MC and DBrBP-MC ) dispersed in poly(methyl methacrylate) (PMMA) films were analyzed at elevated pressures up to 8 GPa using a diamond anvil cell. Dibromo-substituted DBrBP-MC demonstrated a shorter wavelength absorption than BP-MC owing to the larger dihedral angle in the biphenyl moiety. Both MCs exhibited red-shifts in their absorption spectra with increasing pressure, indicating planarization occurred at the biphenyl moieties associated with the compression of the free volume in PMMA. The PL intensity of BP-MC increased with increasing pressure, while its quantum yield (Φ PL ) decreased sharply due to the enhanced energy transfer via the Förster mechanism. In contrast, the PH quantum yield (Φ PH ) of DBrBP-MC monotonically increased at lower pressures, while it showed excitation wavelength-dependent behaviors at higher pressures: Φ PH remained unchanged under excitation at 340 nm but gradually increased under excitation at 365 nm. This fact suggests that, at higher pressures, 365 nm excitation promoted intersystem crossing (ISC) from excited singlet states at higher energy levels. Using this phenomenon, a significant pressure-induced PH enhancement (PIPE) was observed for DBrBP-PI up to 0.9 GPa upon excitation at 365 nm, which is a rare phenomenon for organic polymers. This study indicates that even in colorless and optically transparent amorphous polymers, an enhancement of PH due to restricted molecular motion and intensified ISC outweighs the deactivation due to intermolecular energy transfer under certain pressures, leading to an increase in Φ PH .

Pasteurellosis is a common zoonotic infection that occurs after an animal bite or scratch (B/S). We compared the clinical features of six patients with non-B/S pasteurellosis with those of 14 patients with B/S infections. Pasteurella multocida was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in all six non-B/S infections, whereas 13 of the 14 B/S infections were identified with diagnostic kits. The non-B/S infections were pneumonia (n = 3), skin and soft tissue infections (n = 2), and bacteremia (n = 1). Pneumonia occurred in two patients with underlying pulmonary disease, whereas ventilator-associated pneumonia developed in one patient with cerebral infarction. Pasteurella multocida was isolated from a blood specimen and nasal swab from a patient with liver cirrhosis (Child-Pugh class C) and diabetes. Cellulitis developed in one patient with diabetes and normal-pressure hydrocephalus, who had an open wound following a fall, and in one patient with diabetes and a foot ulcer. Three patients with non-B/S infections had no pet and no episode of recent animal contact. The rate of moderate-to-severe comorbidities was significantly higher in patients with non-B/S infections than in those with B/S infections (100% and 14.3%, respectively, p < 0.001). In conclusion, non-B/S infections can develop in patients with chronic pulmonary disease, invasive mechanical ventilation, or open wounds, or who are immunocompromised, irrespective of obvious animal exposure. In contrast to B/S infections, non-B/S pasteurellosis should be considered opportunistic., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m 2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.

Nursing management activities are important in influencing staff nurses' action to prevent or withdraw physical restraints. However, limited studies have been conducted empirically to determine the nursing management activities required for minimizing physical restraints. Therefore, there is a need for basic standards of nursing management activities to minimize physical restraints in acute care settings. This study aimed to develop nursing management indicators to minimize physical restraint (MaIN-PR) in hospitalized older adult patients in an acute care setting. It was conducted between June and October 2021 in Japan using a Delphi consensus approach. Fifty nurses working at top or middle management levels or as certified nurse specialists in gerontological nursing enrolled as participants. The potential indicators obtained from the literature review and interviews were organized inductively to develop two types of draft indicators: (1) 35 items for top management and (2) 33 items for middle management. We asked the nursing managers and certified nurse specialists in gerontological nursing to assess the validity of each indicator in three rounds. Of the 50 initial panelists, 12 from top management and 13 from middle management continued till the third round. MaIN-PR contained 35 indicators for top management and 28 indicators for middle management and were classified into the following six metrics: planning, motivating, training, commanding, organizing, and controlling. To the best of our knowledge, the current MaIN-PR are the first set of nursing management indicators for minimizing physical restraint, including perspectives on geriatric nursing in acute care settings. These indicators could guide both top and middle nursing management, thus supporting staff nurses' judgment in minimizing physical restraints to enhance the quality of older adult patient care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Minamizaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: We aimed to evaluate the influence of easing COVID-19 preventive measures following its downgrading to a common infectious disease on COVID-19 occurrence among hospitalized patients., Methods: Nosocomial occurrence of COVID-19 was compared between periods with national infectious disease category 5 versus the preceding category 2 equivalent. Changes in the revised manual included a shorter duration of work restrictions for infected health care practitioners (HCPs); no work restriction for HCPs exposed to SARS-CoV-2 with a negative test on days 1, 3 and 5; discontinuation of universal pre-admission screening; and pre-emptive isolation of patients without screening. Wearing an N95 mask and face shield was required in procedure/care with moderate-to high-risk contact., Results: Although the mean monthly number of infected HCPs increased from 8.1 to 12.7 in the category 5 period (p = 0.034) and that of pre-admission screening decreased to one-fourth, the COVID-19 incidence in hospitalized patients remained similar between the two study periods (1.60 ± 5.59/month versus 1.40 ± 2.63/month, p = 0.358). Clusters, defined as ≥3 COVID-19 patients on the ward, were experienced twice in the preceding period and only once in the category 5 period. The index cases causing nosocomial SARS-CoV-2 transmission mostly involved rehabilitation therapists in the preceding period; five of six index cases were patients in the category 5 period. Following the expanded indication for N95 masks, neither SARS-CoV-2 transmission to patients nor transmission from infected patients was observed in HCPs for 1 year., Conclusion: With sustained, enhanced standard precautions, easing prevention strategies could limit nosocomial SARS-CoV-2 infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU., (© 2024 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Thrombin activatable fibrinolysis inhibitor (TAFI) is one of the most important physiological fibrinolysis inhibitors. Its inhibitory efficacy under physiological conditions remains uncertain., Objectives: Elucidate the role of soluble thrombomodulin (sTM)/TAFI axis in the regulation of fibrinlysis., Methods: Since thrombin is required to generate activated TAFI (TAFIa) that targets the C-terminal lysine of partially digested fibrin, a clot lysis assay is suitable for evaluating its function. Using tissue-type plasminogen activator-induced plasma clot lysis time (tPA-PCLT) together with TAFIa inhibitor and recombinant sTM (rsTM), we evaluated the specific function of TM/TAFI in the plasma milieu., Results: tPA-PCLT values were significantly shortened by the TAFIa inhibitor. rsTM supplementation prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor to a time similar to that obtained without rsTM and with the TAFIa inhibitor. Plasma obtained from patients treated with rsTM showed prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor but not further prolonged by rsTM. However, no significant correlation was observed between tPA-PCLT and parameters of TM/TAFI system in the plasma., Conclusion: The role of the TM/TAFI system in regulating fibrinolysis was successfully evaluated using TAFIa inhibitor and rsTM. Trace amounts of soluble TM in normal plasma appeared sufficient to activate TAFI and inhibit fibrinolysis. Further, a therapeutic dose of rsTM appeared sufficient to activate TAFI and regulate fibrinolysis in the plasma milieu., (© 2024 The Author(s).)

A sheet of glassy polymers placed in a solvent shows swelling behaviors quite different from that of soft polymers (rubbers and gels). (1) Non-Fickian diffusion (called case II diffusion): As solvent permeates into the sample, a sharp front is created between the swollen part and the glassy part, and it moves toward the center at constant speed. (2) Nonmonotonous swelling: The thickness of the sample first increases and then decreases toward the equilibrium value. Here we propose a theory to explain such anomalous behavior by extending the previous theory for swelling of soft gels. We regard the material as a continuum mixture of a glassy polymer network and solvent. We assume that the polymer network is a viscoelastic gel of glassy polymers, and its relaxation time depends strongly on solvent concentration. We show that this theory explains the above two characteristics of glassy polymers in a simple and unified framework. The theory predicts how the permeation speed of the solvent and the characteristic times of the swelling process depend on material parameters and experimental conditions, which can be checked experimentally.

Background: Superior mesenteric venous thrombosis (SMVT) is mostly treated with anticoagulation therapy; however, SMVT can lead to irreversible bowel ischemia and require bowel resection in the acute or subacute phase., Case Presentation: We report four cases of SMVT that required careful observation and bowel resection. Case 1: A 71-year-old man presented with abdominal pain, diarrhea, and vomiting that showed a completely occluded SMV with thrombus and small bowel ischemia. Case 2: A 47-year-old man presented with abdominal pain, peritoneal irritation symptoms, and a completely occluded SMV with thrombus, ischemia of the small bowel, and massive ascites. Case 3: A 68-year-old man presented with abdominal pain and vomiting for several days and showed a partially occluded SMV with a thrombus, bowel ischemia, and massive ascites. Case 4: A 68-year-old man presented with acute abdominal pain and a partially occluded SMV with thrombus and bowel edema without ischemic changes. Anticoagulation therapy was administered; however, 3 days later, abdominal pain and bowel ischemia worsened. Bowel resection was performed in all cases., Conclusions: Most idiopathic SMVT cases can be treated with anticoagulation therapy or endovascular thrombectomy. However, in cases with peritoneal irritation signs, these treatments may be ineffective, and bowel resection may be required., (© 2024. The Author(s).)

Species specificity of commercial human DNA quantification kits and short tandem repeat (STR) profiling kits was examined using primate DNA samples. These samples comprised 33 individuals from eight primate species, each with gender and kinship data, including human (Homo sapiens), chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), and orangutan (Pongo pygmaeus) of Hominidae family, and Japanese macaque (Macaca fuscata), long-tailed macaque (Macaca fascicularis), hamadryas baboon (Papio hamadryas), and savannah monkey (Chlorocebus sp.) of Cercopithecidae family. The findings revealed varying levels of cross-species amplifications in all non-human DNA samples that correlated with their evolutionary proximity to humans, both kit types. Moreover, cross-species amplification, including female DNA samples, was observed in a Y-chromosomal STR profiling kit. Additionally, species specificity differed among the commercial kits examined. The cross-species amplification data presented in this study offer valuable assistance in interpreting the results of individual human identification in forensic cases involving non-human primates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fairy chemicals (FCs), such as 2-azahypoxanthine (AHX), are a potential new class of plant hormones that are naturally present in plants and produced via a novel purine metabolic pathway. FCs support plant resilience against various stresses and regulate plant growth. In this study, we developed a four-step method for synthesising AHX from 2-cyanoacetamide, achieving a good yield. Oxime was obtained from 2-cyanoacetamide via the oximation reaction. Cascade-type one-pot selective Pt/C-catalysed reduction of oxime, followed by a coupling reaction with formamidine acetate, yielded intermediate 5-amino-1 H -imidazole-4-carboxamide (AICA). For the synthesis of AICA from oxime, we used modern fine bubble technology, affording AICA in 69% yield. Subsequently, we synthesised 4-diazo-4 H -imidazole-5-carboxamide (DICA) from AICA via the diazotisation reaction. Notably, the synthesis of DICA from AICA was achieved, and the stability of previously known less stable DICA in the solid state was confirmed. Finally, PhI(OAc) 2 (0.5 mol%) catalysed the intramolecular cyclisation of DICA in the green solvent water to yield AHX (overall yield of 47%). This study's innovative techniques and substantial discoveries highlight its potential influence and significance in FC science, thereby establishing a new standard for subsequent research.

We report herein that supported gold catalysts efficiently promote the borylation of stable C(sp 3 )-O bonds of alkyl esters. The use of a disilane as an electron source and gold nanoparticles as a single-electron transfer catalyst is the key to generating alkyl radicals via the homolysis of stable C(sp 3 )-O bonds, thereby enabling cross-coupling between bis(pinacolato)diboron and linear and cyclic alkyl esters to afford the diverse alkyl boronates.

Background: The success of liver resection relies on the ability of the remnant liver to regenerate. Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies, and data on humans are scarce. Additionally, there is limited knowledge about the preoperative factors that influence postoperative regeneration., Aim: To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regeneration., Methods: A total of 268 patients who received partial hepatectomy were enrolled. Patients were grouped into right hepatectomy/trisegmentectomy (RH/Tri), left hepatectomy (LH), segmentectomy (Seg), and subsegmentectomy/nonanatomical hepatectomy (Sub/Non) groups. The regeneration index (RI) and late regeneration rate were defined as (postoperative liver volume)/[total functional liver volume (TFLV)] × 100 and (RI at 6-months - RI at 3-months)/RI at 6-months, respectively. The lower 25 th percentile of RI and the higher 25 th percentile of late regeneration rate in each group were defined as "low regeneration" and "delayed regeneration". "Restoration to the original size" was defined as regeneration of the liver volume by more than 90% of the TFLV at 12 months postsurgery., Results: The numbers of patients in the RH/Tri, LH, Seg, and Sub/Non groups were 41, 53, 99 and 75, respectively. The RI plateaued at 3 months in the LH, Seg, and Sub/Non groups, whereas the RI increased until 12 months in the RH/Tri group. According to our multivariate analysis, the preoperative albumin-bilirubin (ALBI) score was an independent factor for low regeneration at 3 months [odds ratio (OR) 95%CI = 2.80 (1.17-6.69), P = 0.02; per 1.0 up] and 12 months [OR = 2.27 (1.01-5.09), P = 0.04; per 1.0 up]. Multivariate analysis revealed that only liver resection percentage [OR = 1.03 (1.00-1.05), P = 0.04] was associated with delayed regeneration. Furthermore, multivariate analysis demonstrated that the preoperative ALBI score [OR = 2.63 (1.00-1.05), P = 0.02; per 1.0 up] and liver resection percentage [OR = 1.02 (1.00-1.05), P = 0.04; per 1.0 up] were found to be independent risk factors associated with volume restoration failure., Conclusion: Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score. This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Main Conclusion: Two glycosyltransferase genes belonging to UGT88 family were identified to have 6'-deoxychalcone 4'-glucosyltransferase activity in dahlia. 6'-Deoxychalcones (isoliquiritigenin and butein) are important pigments for yellow and orange to red flower color. 6'-Deoxychalcones are glucosylated at the 4'-position in vivo, but the genes encoding 6'-deoxychalcone 4'-glucosyltransferase have not yet been identified. In our previous study, it was indicated that snapdragon (Antirrhinum majus) chalcone 4'-O-glucosyltransferase (Am4'CGT) has isoliquiritigenin 4'-glucosylation activity. Therefore, to identify genes encoding 6'-deoxychalcone 4'-glucosyltransferase in dahlia (Dahlia variabilis), genes expressed in ray florets that shared high homology with Am4'CGT were explored. As a result, c34671&#95;g1&#95;i1 and c35662&#95;g1&#95;i1 were selected as candidate genes for 6'-deoxychalcone 4'-glucosyltransferases in dahlia. We conducted transient co-overexpression of three genes (c34671&#95;g1&#95;i1 or c35662&#95;g1&#95;i1, dahlia aldo-keto reductase1 (DvAKR1) or soybean (Glycine max) chalcone reductase5 (GmCHR5), and chili pepper (Capsicum annuum) MYB transcription factor (CaMYBA)) in Nicotiana benthamiana by agroinfiltration. Transient overexpression of c34671&#95;g1&#95;i1, DvAKR1, and CaMYBA resulted in increase in the accumulation of isoliquiritigenin 4'-glucosides, isoliquiritigenin 4'-O-glucoside, and isoliquiritigenin 4'-O-[6-O-(malonyl)-glucoside]. However, transient overexpression of c35662&#95;g1&#95;i1, DvAKR1, and CaMYBA did not increase accumulation of isoliquiritigenin 4'-glucosides. Using GmCHR5 instead of DvAKR1 showed similar results suggesting that c34671&#95;g1&#95;i1 has isoliquiritigenin 4'-glucosyltransferase activity. In addition, we conducted co-overexpression of four genes (c34671&#95;g1&#95;i1, c35662&#95;g1&#95;i1 or Am4'CGT, DvAKR1 or GmCHR5, CaMYBA, and chalcone 3-hydroxylase from dahlia). Accumulation of butein 4'-O-glucoside and butein 4'-O-[6-O-(malonyl)-glucoside] was detected for c35662&#95;g1&#95;i1, suggesting that c35662&#95;g1&#95;i1 has butein 4'-glucosyltransferase activity. Recombinant enzyme analysis also supported butein 4'-glucosyltransferases activity of c35662&#95;g1&#95;i1. Therefore, our results suggested that both c34671&#95;g1&#95;i1 and c35662&#95;g1&#95;i1 are 6'-deoxychalcone 4'-glucosyltransferases but with different substrate preference., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pungent capsaicinoid is synthesized only in chili pepper (Capsicum spp.). The production of vanillylamine from vanillin is a unique reaction in the capsaicinoid biosynthesis pathway. Although putative aminotransferase (pAMT) has been isolated as the vanillylamine synthase gene, it is unclear how Capsicum acquired pAMT. Here, we present a phylogenetic overview of pAMT and its homologs. The Capsicum genome contained 5 homologs, including pAMT, CaGABA-T1, CaGABA-T3, and two pseudogenes. Phylogenetic analysis indicated that pAMT is a member of the Solanaceae cytoplasmic GABA-Ts. Comparative genome analysis found that multiple copies of GABA-T exist in a specific Solanaceae genomic region, and the cytoplasmic GABA-Ts other than pAMT are located in the region. The cytoplasmic GABA-T was phylogenetically close to pseudo-GABA-T harboring a plastid transit peptide (pseudo-GABA-T3). This suggested that Solanaceae cytoplasmic GABA-Ts occurred via duplication of a chloroplastic GABA-T ancestor and subsequent loss of the plastid transit signal. The cytoplasmic GABA-T may have been translocated from the specific Solanaceae genomic region during Capsicum divergence, resulting in the current pAMT locus. A recombinant protein assay demonstrated that pAMT had higher vanillylamine synthase activity than those of other plant GABA-Ts. pAMT was expressed exclusively in the placental septum of mature green fruit, whereas tomato orthologs SlGABA-T2/4 exhibit a ubiquitous expression pattern in plants. These findings suggested that both the increased catalytic efficiency and transcriptional changes in pAMT may have contributed to establish vanillylamine synthesis in the capsaicinoid biosynthesis pathway. This study provides insights into the establishment of pungency in the evolution of chili peppers., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: The Coccomyxa sp. strain KJ (Coccomyxa KJ), a microalga found in Japan, has a potential function in controlling viral infections. Recently, its dry powder has been marketed as a health food product., Objectives: This pilot study investigated the effects of Coccomyxa KJ powder tablet intake on allergic reactions and immune functions in healthy participants., Material and Methods: Nine healthy volunteers (4 males and 5 females) who expressed interest in foods containing Coccomyxa KJ, and were willing to undergo blood tests, were recruited. Each individual was asked to take 2 Coccomyxa KJ powder tablets (0.3 g) before breakfast once a day for 4 weeks. The salivary immunoglobulin A (IgA) level and blood parameters (white blood cell (WBC) count, eosinophil and lymphocyte counts and percentages, natural killer (NK) cell activity, interleukin (IL)-6 level, and T helper (Th)1/Th2 cell ratio) were evaluated at baseline and weeks 2 and 4., Results: The 4-week intake of Coccomyxa KJ did not affect salivary IgA levels, WBC count, eosinophil and lymphocyte counts and percentages, or the Th1/Th2 ratio. There were significant differences in the NK cell activity after 4 weeks, with an average increase of 11.78 (95% confidence interval (95% CI): 6.80-16.76). None of the patients experienced adverse reactions during or after the study., Conclusions: Long-term Coccomyxa KJ intake improved NK cell activity without causing adverse effects on the indicators of local immunity, systemic inflammation and immune response balance. This study suggests that Coccomyxa KJ powder tablets can induce beneficial immune modifications without causing any adverse effects.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor, and more than 90% of feline MCC cases test positive for Felis catus papillomavirus type 2 (FcaPV2). In the present study, basal cell markers p40, p63, and p73 and the stem cell marker SOX2 and cytokeratin 14 (CK14) were immunohistochemically examined in normal fetal, infant, and adult feline skin tissues. The expression of these proteins was examined in tumors positive for FcaPV2, including MCC, basal cell carcinoma (BCC), Bowenoid in situ carcinoma (BISC), and squamous cell carcinoma (SCC). Infant and adult feline skin tissues had mature Merkel cells, which were CK14-, CK18+, CK20+, SOX2+, synaptophysin+ and CD56+, while fetal skin tissue had no mature Merkel cells. MCC was immunopositive for p73, CK18, and SOX2 in 32/32 cases, and immunonegative for CK14 in 31/32 cases and for p40 and p63 in 32/32 cases. These results indicate that MCC exhibits different immunophenotypes from Merkel cells (p73-) and basal cells (p40+, p63+, and SOX2-). In contrast, all 3 BCCs, 1 BISC, and 2 SCCs were immunopositive for the basal cell markers p40, p63, and p73. The life cycle of papillomavirus is closely associated with the differentiation of infected basal cells, which requires the transcription factor p63. Changes in p63 expression in FcaPV2-positive MCC may be associated with unique cytokeratin expression patterns (CK14-, CK18+, and CK20+). Furthermore, SOX2 appears to be involved in Merkel cell differentiation in cats, similar to humans and mice.

The Phe-incorporated cyclic peptide [cyclo(-Phe 1 -oxazoline 2 -d-Val 3 -thiazole 4 -Ile 5 -oxazoline 6 -d-Val 7 -thiazole 8 -)] is in a conformational equilibrium between square and folded forms in solution. In the folded form, a CH⋯π interaction between the Phe 1 aromatic ring and the Oxz 2 methyl group is observed. We endeavored to control the local conformation and thus modulate the CH⋯π interaction and flexibility of the Phe 1 side chain by controlling the electronic substituent effects at the 4-position of the aromatic ring of the Phe 1 residue. The effect of the 4-substituent on the global conformation was indicated by the linear relationship between the conformational free energies (Δ G o ) determined through NMR-based quantification and the Hammett constants ( σ ). Electron-donating substituents, which had relatively strong CH⋯π interactions, promoted peptide folding by restraining the loss in entropy. Local control by the 4-substituent effects suggested that the Phe side chain exerts an entropic influence on the folding of these cyclic peptides., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: It remains unclear whether clopidogrel is better suited than aspirin as the long-term antiplatelet monotherapy following dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI)., Objectives: This study compared clopidogrel monotherapy following 1 month of DAPT (clopidogrel group) with aspirin monotherapy following 12 months of DAPT (aspirin group) after PCI for 5 years., Methods: STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy 2) is a multicenter, open-label, adjudicator-blinded, randomized clinical trial conducted in Japan. Patients who underwent PCI with cobalt-chromium everolimus-eluting stents were randomized in a 1-to-1 fashion either to clopidogrel or aspirin groups. The primary endpoint was a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) or major bleeding (TIMI major or minor bleeding)., Results: Among 3,005 study patients (age: 68.6 ± 10.7 years; women: 22.3%; acute coronary syndrome: 38.3%), 2,934 patients (97.6%) completed the 5-year follow-up (adherence to the study drugs at 395 days: 84.7% and 75.9%). The clopidogrel group compared with the aspirin group was noninferior but not superior for the primary endpoint (11.75% and 13.57%, respectively; HR: 0.85; 95% CI: 0.70-1.05; P noninferiority  < 0.001; P superiority  = 0.13), whereas it was superior for the cardiovascular outcomes (8.61% and 11.05%, respectively; HR: 0.77; 95% CI: 0.61-0.97; P = 0.03) and not superior for major bleeding (4.44% and 4.92%, respectively; HR: 0.89; 95% CI: 0.64-1.25; P = 0.51). By the 1-year landmark analysis, clopidogrel was numerically, but not significantly, superior to aspirin for cardiovascular events (6.79% and 8.68%, respectively; HR: 0.77; 95% CI: 0.59-1.01; P = 0.06) without difference in major bleeding (3.99% and 3.32%, respectively; HR: 1.23; 95% CI: 0.84-1.81; P = 0.31)., Conclusions: Clopidogrel might be an attractive alternative to aspirin with a borderline ischemic benefit beyond 1 year after PCI., Competing Interests: Funding Support and Author Disclosures STOPDAPT-2 is funded by Abbott. The funder had no role in the design, data analysis, interpretation, or writing of the report. Dr Watanabe has received personal fees from Abbott; and has received personal fees from Amgen, Pfizer, and Daiichi-Sankyo outside the submitted work. Dr Morimoto has received lecturer’ fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Board for Novartis and Teijin outside the submitted work. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Hibi has received a scholarship donation from Abbott. Dr Kimura has received research grants from Abbott Vascular and Boston Scientific; and serves as an Advisory Board member for Abbott Vascular and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The circadian fluctuation of body temperature is one of the most prominent and stable outputs of the circadian clock and plays an important role in maintaining optimal day-night energy homeostasis. The body temperature of homothermic animals is not strictly constant, but it shows daily oscillation within a range of 1-3 °C, which is sufficient to synchronize the clocks of peripheral tissues throughout the body. The thermal entrainment mechanisms of the clock are partly mediated by the action of the heat shock transcription factor and cold-inducible RNA-binding protein-both have the ability to affect clock gene expression. Body temperature in the poikilotherms is not completely passive to the ambient temperature change; they can travel to the place of preferred temperature in a manner depending on the time of their endogenous clock. Based on this behavior-level thermoregulation, flies exhibit a clear body temperature cycle. Noticeably, flies and mice share the same molecular circuit for the controlled body temperature; in both species, the calcitonin receptors participate in the formation of body temperature rhythms during the active phase and exhibit rather specific expression in subsets of clock neurons in the brain. We summarize knowledge on mutual relationships between body temperature regulation and the circadian clock., (© 2024. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

Unknown interactions between drugs remain the limiting factor for clinical application of drugs, and the induction and inhibition of drug-metabolizing CYP enzymes are considered the key to examining the drug-drug interaction (DDI). In this study, using human HepaRG cells as an in vitro model system, we analyzed the potential DDI based on the expression levels of CYP3A4 and CYP1A2. Rifampicin and omeprazole, the potent inducers for CYP3A4 and CYP1A2, respectively, induce expression of the corresponding CYP enzymes at both the mRNA and protein levels. We noticed that, in addition to inducing CYP1A2, omeprazole induced CYP3A4 mRNA expression in HepaRG cells. However, unexpectedly, CYP3A4 protein expression levels were not increased after omeprazole treatment. Concurrent administration of rifampicin and omeprazole showed an inhibitory effect of omeprazole on the CYP3A4 protein expression induced by rifampicin, while its mRNA induction remained intact. Cycloheximide chase assay revealed increased CYP3A4 protein degradation in the cells exposed to omeprazole. The data presented here suggest the potential importance of broadening the current DDI examination beyond conventional transcriptional induction and enzyme-activity inhibition tests to include post-translational regulation analysis of CYP enzyme expression.

Temperature-dependent translational control of the core clock gene Per2 plays an important role in establishing entrainment of the circadian clock to physiological body temperature cycles. Previously, we found an involvement of the phosphatidylinositol 3-kinase (PI3K) in causing Per2 protein expression in response to a warm temperature shift (WTS) within a physiological range (from 35 to 38.5 °C). However, signaling pathway mediating the Per2 protein expression in response to WTS is only sparsely understood. Additional factor(s) other than PI3K remains unknown. Here we report the identification of eukaryotic initiation factor 2α (eIF2α) kinases, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), as a novel mediator of WTS-dependent Per2 protein expression. Canonically, eIF2α has been regarded as a major downstream target of PERK and PKR. However, we found that PERK and PKR mediate WTS response of Per2 in a manner not involving eIF2α. We observed that PERK and PKR serve as an upstream regulator of PI3K rather than eIF2α in the context of WTS-dependent Per2 protein expression. There have been studies reporting PI3K activation occurring depending on PERK and PKR, while its physiological contribution has remained elusive. Our finding therefore not only helps to enrich the knowledge of how WTS affects Per2 protein expression but also extends the region of cellular biology involving the PERK/PKR-mediated PI3K activation to include entrainment-mechanism of the circadian clock.

Objective: Due to the lack of information on the effects of nutritional guidance focused on leucine intake in patients undergoing maintenance cardiac rehabilitation, this study investigated on plasma leucine concentrations, lean body mass, and muscle strength., Methods: Nutritional guidance, focused on leucine (intervention group) or general nutritional guidance (control group), was provided for six months to patients participating in cardiac rehabilitation. Body composition, grip strength, hematological test results, and diet of both groups were compared before and after the intervention., Results: Seven patients in the intervention group (53.2 ± 18.2 years) and 7 patients in the control group (58.6 ± 15.3 years) were included. Dietary survey results showed that the six-month intervention significantly (p < 0.05) increased protein intake and estimated leucine intake only in the intervention group. There was no significant difference in the rate of change in plasma leucine concentration between the two groups. The rate of change in lean body mass was significantly higher in the intervention group compared to the control group (p = 0.035). The rate of change in plasma leucine concentration and that in lean body mass was positively correlated only in the intervention group (r = 0.777, p = 0.040), and the rate of change in plasma leucine concentration was also positively correlated with the rate of change in grip strength (ρ = 0.857, p = 0.014)., Conclusions: In the patients undergoing maintenance cardiac rehabilitation, increased plasma leucine concentration by nutritional guidance focused on leucine increased lean body mass without any increasing the training load., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 The Juntendo Medical Society.)

Background: Glycogen storage disease (GSD) is a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. GSD type Ia is a congenital deficiency of the enzyme responsible for the final step in glucose production by glycolysis, resulting in impaired carbohydrate metabolism., Case Presentation: A 14-year-old boy with GSD type Ia was scheduled for a maxillary cystectomy under general anesthesia. He was taking oral sugars such as uncooked cornstarch regularly to prevent hypoglycemia. Perioperatively, glucose was administered via the peripheral vein for fasting; however, severe lactic acidosis occurred. He also developed hypercapnia because of intraoperative poor ventilation caused by hepatomegaly., Conclusions: We experienced a child with GSD type Ia who developed severe lactic acidosis despite continuous glucose infusion. Further studies are required to determine appropriate perioperative management for patients with GSD, including fasting glucose administration., (© 2023. The Author(s).)