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A foil of a metastable β Titanium alloy Ti-15V-3Cr-3Sn-3Al was irradiated at the J-PARC neutrino experimental facility with 1.4 × 1020 30 GeV protons at low temperature (100–130 °C at most), and microstructural characterization and hardness testing were conducted as an initial study on the radiation damage effects of Titanium alloy by the high energy proton beam exposure. Expected radiation damage at the beam center is about 0.06–0.12 displacement per atom. A high density (> 1023 m−3) of a nanometer-sized precipitate was observed by TEM studies, which would be identified as martensite α-phase and athermal ω-phase formed during the solution-treatment process to fabricate metastable β alloy. They did not appear to change substantially after irradiation with protons. In the irradiated specimen, we could not identify an obvious signature of radiation damage distributed along the proton beam profile. Very small, nanometer-scale black dots were present at a low density in the most highly irradiated region, and may be small dislocation loops formed during irradiation. The micro-indentation test indicated that the radiation exposure led to tiny increase in Vickers micro-hardness of ΔHV = 20 at beam center. Atom probe tomography reveals compositional fluctuations that reach a maximum amplitude of 10 at% Ti within a space of

Magnons, quantized spin excitations in magnetic materials, may undergo Bose-Einstein condensation into a macroscopic correlated quantum state at low temperature. Here, the authors demonstrate how magnon condensation in quantum magnet TlCuCl3generates an electrical polarization.

Thermoelectric performances depend on phonon and electron transport. Here, Takahashi et al. show that the large Seebeck coefficient observed in high-purity single-crystal FeSb2 is due to the phonon-drag effect and to the high effective mass of delectrons interacting with quasi-ballistic phonons.

The ferrimagnetic spin-1/2 chain composed of alternating Ising and Heisenberg spins in an arbitrarily oriented magnetic field is exactly solved using the spin-rotation transformation and the transfer-matrix method. It is shown that the low-temperature magnetization process depends basically on a spatial orientation of the magnetic field. A sharp stepwise magnetization curve with a marked intermediate plateau, which emerges for the magnetic field applied along the easy-axis direction of the Ising spins, becomes smoother and the intermediate plateau shrinks if the external field is tilted from the easy-axis direction. The magnetization curve of a polycrystalline system is also calculated by performing powder averaging of the derived magnetization formula. The proposed spin-chain model brings an insight into high-field magnetization data of 3d-4f bimetallic polymeric compound Dy(NO3)(DMSO)2Cu(opba)(DMSO)2, which provides an interesting experimental realization of the ferrimagnetic chain composed of two different but regularly alternating spin-1/2 magnetic ions Dy3+ and Cu2+ that are reasonably approximated by the notion of Ising and Heisenberg spins, respectively.

We report on high-field electron spin resonance (ESR) studies of magnetic excitations in the spin-1/2 triangular-lattice antiferromagnet Cs _2 CuBr _4 . Frequency-field diagrams of ESR excitations are measured for different orientations of magnetic fields up to 25 T. We show that the substantial zero-field energy gap, ${\rm{\Delta }}\approx 9.5$ K, observed in the low-temperature excitation spectrum of Cs _2 CuBr _4 , (Zvyagin et al 2014 Phys. Rev. Lett. http://dx.doi.org/10.1103/PhysRevLett.112.077206 112 http://dx.doi.org/10.1103/PhysRevLett.112.077206 ) is present well above T _N . Noticeably, the transition into the long-range magnetically ordered phase does not significantly affect the size of the gap, suggesting that even below T _N the high-energy spin dynamics in Cs _2 CuBr _4 is determined by short-range-order spin correlations. The experimental data are compared with results of model spin-wave-theory calculations for spin-1/2 triangular-lattice antiferromagnet.

Unconventional high temperature superconductivity as well as three-dimensional bulk Dirac cone quantum states arising from the unique d-orbital topology have comprised an intriguing research area in physics. Here we apply a special analytical approach using a mobility spectrum, in which the carrier number is conveniently described as a function of mobility without any hypothesis, both on the types and the numbers of carriers, for the interpretations of longitudinal and transverse electric transport of high quality single crystal Ba(FeAs) _2 in a wide range of magnetic fields. We show that the majority carriers are accommodated in large parabolic hole and electron pockets with very different topology as well as remarkably different mobility spectra, whereas the minority carriers reside in Dirac quantum states with the largest mobility as high as 70,000 cm ^2 (Vs) $^{-1}$ . The deduced mobility spectra are discussed and compared to the reported sophisticated first principle band calculations.

We report on a simple method to fabricate a magnetic carbon material that contains nitrogen-coordinated transition metals and has a large magnetic moment. Highly chlorinated iron phthalocyanine was used as building blocks and potassium as a coupling reagent to uniformly disperse nitrogen-coordinated iron atoms on the phthalocyanine based carbon material. The iron phthalocyanine based carbon material exhibits ferromagnetic properties at room temperature and the ferromagnetic phase transition occurs at Tc = 490 ± 10K. Transmission electron microscopy observation, X-ray diffraction analysis, and the temperature dependence of magnetization suggest that the phthalocyanine molecules form three-dimensional random networks in the iron phthalocyanine based carbon material. [ABSTRACT FROM AUTHOR]

Spin-1/2 Heisenberg antiferromagnets Cs2CuCl4 and Cs2CuBr4 with distorted triangular-lattice structures are studied by means of electron spin resonance spectroscopy in magnetic fields up to the saturation field and above. In the magnetically saturated phase, quantum fluctuations are fully suppressed, and the spin dynamics is defined by ordinary magnons. This allows us to accurately describe the magnetic excitation spectra in both materials and, using the harmonic spin-wave theory, to determine their exchange parameters. The viability of the proposed method was proven by applying it to Cs2CuCl4, yielding J/kB = 4.7(2) K, J'/kB = 1.42(7) K, [J'/J ≃ 0.30] and revealing good agreement with inelastic neutron-scattering results. For the isostructural Cs2CuBr4, we obtain J/kB = 14.9(7) K, J'/kB = 6.1(3) K, [J'/J ≃ 0.41], providing exact and conclusive information on the exchange couplings in this frustrated spin system. [ABSTRACT FROM AUTHOR]

Reactive oxygen species production might be prevented by xanthine oxidoreductase (XOR) inhibitors, which can cause glomerulosclerosis. We aimed to investigate whether topiroxostat, an XOR inhibitor, prevents diabetic kidney disease development in mice. Six-week-old control Institute of Cancer Research (ICR) mice and type 2 diabetic Nagoya Shibata Yasuda (NSY) mice were divided into the ICR group (ICR mice which received a lard-containing high-fat diet [HFD] based on the AIN-93G diet), NSY control group (NSY mice which received the same aforementioned diet), and NSY + topiroxostat group (NSY mice which received the same aforementioned diet with addition of 0.0012% topiroxostat). After 20 weeks, plasma biomarkers, XOR activity and oxidative stress levels, which were assessed using malondialdehyde (MDA), were measured through enzyme-linked immunosorbent assay or enzymatic methods. Renal pathology was evaluated using periodic acid-Schiff staining. Redox gene and protein expression were determined using RT-qPCR and western blotting, respectively. Plasma XOR activity was lower in NSY mice treated with topiroxostat than those without. Plasma cystatin C and creatinine levels did not differ between the ICR and NSY control groups or between the NSY control and NSY + topiroxostat groups. The NSY + topiroxostat group showed a smaller mesangial area than the NSY control group. The mRNA expression of Sod3, Prdx1, Gpx2, and Gpx3 was higher in the NSY + topiroxostat group than in the NSY control group. Renal MDA levels were lower in the NSY + topiroxostat group than in the NSY control group. Topiroxostat can reduce glomerulosclerosis, and the reduction is associated with renal oxidative markers., Competing Interests: Declaration of competing interest T. Nakmura is an employee of Pharmacological Study Group Pharmaceutical Research Laboratories, and he contributed to providing topiroxostat and determining XOR activity. Commercial organizations, including Pharmacological Study Group Pharmaceutical Research Laboratories, did not fund the study. None of the other authors have conflicts of interest or financial disclosures to the present study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intensified systemic chemotherapy following minimally invasive surgery for patients with unresectable metastatic colorectal cancer is performed to achieve curative resection and improve quality of life. We report a case of initially unresectable rectal cancer with metastases treated with laparoscopic and thoracoscopic staged resections after triplet chemotherapy plus bevacizumab., Case: A 71-year-old man was referred to our hospital to examine the cause of constipation. A circumferential adenocarcinoma with extramural invasion and lateral lymphadenopathy was identified in the lower rectum with simultaneous metastatic liver and lung tumors. Intensified triplet chemotherapy plus bevacizumab was conducted to treat oncologically unresectable rectal cancer to avoid positive radial margins during surgical resection. Eleven cycles of chemotherapy resulted in regression of the tumors with metastases. Laparoscopic low anterior resection with lateral lymph node dissection was performed. Three months later, laparoscopic liver resection of the posterosuperior segment was performed without complications. Finally, the patient underwent thoracoscopic-assisted pulmonary segmentectomy of the right basal lobe. All resected tumors had negative surgical margins, and the patient has been surviving without adjuvant chemotherapy., Conclusion: Minimally invasive staged resection and intensified chemotherapy for the treatment of initially unresectable metastatic colorectal cancer should be performed by a skilled surgical team in coordination with a multidisciplinary team., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Supported decision making (SDM) is a needed focus of policy and practice to enhance opportunities for people with disabilities to exercise self-determination as they are supported to make decisions about their life. This study used content analysis to analyze five focus groups comprised of 27 adults with intellectual and developmental disabilities (IDD) and 16 family members to understand how people with IDD use supports for decision making and how families support decision making. People with IDD and family members described a range of strategies and supports they used for decision making, including engaging trusted supporters, accessing technology, and using early experiences to build decision-making skills. Findings from this research can inform development of practices and policy to enhance use of SDM in research, policy, and practice., (©AAIDD.)

There is a strong and growing focus on self-determination in French-speaking countries, and this pilot study reports the technical adequacy of the Self-Determination Inventory: Student Report (SDI:SR) French Translation. Data were collected with 471 French-speaking youth with and without disabilities in Canada (Quebec), Switzerland, France, and Belgium. Key findings showed it was feasible to use 20 (of 21) items to represent the self-determination construct in the French-speaking sample. The same set of items function in the same way across students with and without disabilities, and students with disabilities descriptively scored lower. Overall, this study provides promising evidence for reliability and validity of the SDI:SR French Translation and suggests ongoing development and larger-scale testing of the SDI:SR French Translation is warranted., (©AAIDD.)

A time-saving, one-step polyacrylamide gel preparation method enabling simultaneous preparation of separating and stacking gels was previously reported, but the boundary between the separating and stacking gels was often not well defined. As such, determining whether the gel preparation failed is difficult before SDS-PAGE is carried out. To address this issue, a one-step polyacrylamide gel preparation method was developed in which the stacking gel is colored to allow better visualization of the border between the stacking and separating gels. This new one-step method saves time and achieves comparable performance for SDS-PAGE and western blotting to that obtained with conventional gels., Competing Interests: Declaration of competing interest The author declares no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: SINE-VNTR-Alu (SVA) retrotransposons move from one genomic location to another in a 'copy-and-paste' manner. They continue to move actively and cause monogenic diseases through various mechanisms. Currently, disease-causing SVA retrotransposons are classified into human-specific young SVA_E or SVA_F subfamilies. In this study, we identified an evolutionarily old SVA_D retrotransposon as a novel cause of occipital horn syndrome (OHS). OHS is an X-linked, copper metabolism disorder caused by dysfunction of the copper transporter, ATP7A., Methods: We investigated a 16-year-old boy with OHS whose pathogenic variant could not be detected via routine molecular genetic analyses., Results: A 2.8 kb insertion was detected deep within the intron of the patient's ATP7A gene. This insertion caused aberrant mRNA splicing activated by a new donor splice site located within it. Long-read circular consensus sequencing enabled us to accurately read the entire insertion sequence, which contained highly repetitive and GC-rich segments. Consequently, the insertion was identified as an SVA_D retrotransposon. Antisense oligonucleotides (AOs) targeting the new splice site restored the expression of normal transcripts and functional ATP7A proteins. AO treatment alleviated excessive accumulation of copper in patient fibroblasts in a dose-dependent manner. Pedigree analysis revealed that the retrotransposon had moved into the OHS-causing position two generations ago., Conclusion: This is the first report of a human monogenic disease caused by the SVA_D retrotransposon. The fact that the evolutionarily old SVA_D is still actively transposed, leading to increased copy numbers may make a notable impact on rare genetic disease research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To better characterize the cochlear apex in relation to surgically relevant landmarks to guide surgeons and improve procedural success of apical electrode placement., Study Design: Retrospective image analysis., Setting: Tertiary referral center., Patients: Cochlear implant recipients with available preoperative computed tomography (CT) imaging., Intervention: None., Main Outcome Measure: Cochlear dimensions and cochlear apex distance measures to surgically relevant middle ear landmarks and critical structures., Results: Eighty-two temporal bone CT scans were analyzed utilizing multiplanar reformats. The average lateral width of promontory bone over the cochlear apex was 1.2 mm (standard deviation [SD], 0.3). The anteroposterior distance from the round window (avg, 4.2 mm; SD, 0.5), oval window (avg, 3.3 mm; SD, 0.3), cochleariform process (avg, 2.3; SD, 0.5), and superior-inferior distance from the cochleariform process (avg, -0.9; SD, 0.8) to the cochlear apex were measured. The relationship of the cochlear apex to critical structures was highly variable.A newly developed stapes vector was created and found to mark the posterior/superior boundary of the apex in 94% of patients. When a vector parallel to the stapes vector was drawn through the round window, it marked the anterior/inferior boundary of the cochlear apex in 89% of patients., Conclusions: This study assists in characterizing cochlear apex anatomy and its relation to surrounding structures as a means of improving procedural accuracy and reducing trauma during apical cochleostomy. Understanding both distance relationships and expected boundaries of the apex could help to inform future surgical approaches., Competing Interests: Dr. J Thomas Roland Jr. is a consultant for Cochlear Americas and received research funding for CI-related projects that are not affiliated with this research. Other authors disclose no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

This study examined the similarities/differences between the social phenotypes of Williams syndrome (WS) and autism spectrum disorder (ASD). As cultural norms may affect symptom evaluation, this study administered the Social Responsiveness Scale-2 to Japanese individuals with WS (n = 78, 4.4-44.0 years) and ASD (n = 75, 4.7-55.4 years). The scores for Social Motivation and Social Communication were significantly more severe in the ASD than WS group. Overall, the similarities and differences between the social phenotypes of the syndromes were consistent with the findings of a recent study conducted in the UK, except for the social awareness subscale score. This highlights the importance of cross-cultural investigations of WS and ASD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA., Methods: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics ® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported., Results: Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6-17 years., Conclusion: Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events., Competing Interests: MH, SP, EGM and KR are employees and stockholders of Takeda Development Center Americas, Inc. VD, SM and MD are employees of IQVIA, which received funding for this study from Takeda Development Center Americas, Inc. CS is an employee of AlphaNet; has grants paid to the Medical University of South Carolina from Adverum Biotechnologies, Arrowhead Pharmaceuticals, AstraZeneca, CSA Medical, Grifols, Krystal, Mereo BioPharma, National Institutes of Health, Novo Nordisk, Nuvaira, Takeda and Vertex Pharmaceuticals; and has consulted for Bronchus, CSL Behring, Dicerna Pharmaceuticals, GlaxoSmithKline, PulManage and Vertex Pharmaceuticals for alpha-1 and/or chronic obstructive pulmonary disease. The authors report no other conflicts of interest in this work., (© 2024 Takeda Development Center America Inc.)

Background: Limited reports exist regarding postoperative recurrent non-small cell lung cancer (NSCLC) without major driver mutations [epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements] treated with immune checkpoint inhibitors (ICIs) when programmed cell death ligand 1 (PD-L1) is expressed in a real-world setting. The aim of this study was to evaluate the effect of ICIs for those NSCLC., Methods: We enrolled 255 patients with postoperative recurrent NSCLC lacking EGFR mutations or ALK rearrangements who underwent lobectomy or more extensive resection between 2012 and 2021. Factors associated with post-recurrence survival (PRS) were determined using the Cox proportional hazards model. PRS was analyzed using Kaplan-Meier curves and compared using the log-rank test., Results: Multivariable analysis demonstrated that squamous cell carcinoma, pathological stage III, and an Eastern Cooperative Oncology Group (ECOG) performance status ≥2 were significantly associated with worse PRS. Conversely, ICI use at first line was associated with improved PRS. Patients who used ICIs during the first line and subsequent therapies had better PRS than those who received chemotherapy alone. Among patients who used ICIs, there was no significant difference in response rate at the first line, nor in PRS among those with PD-L1 expression ≥50%, 1-49%, and <1% in surgically resected specimens., Conclusions: ICI use at any treatment line improved the PRS of NSCLC patients without major driver mutations, irrespective of PD-L1 expression, in a real-world setting., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-237/coif). N.I. reports the relationship with AstraZeneca, Chugai pharma, Pfeizer, Taiho pharma, MSD, Boehringer Ingelheim, Eli Lilly, Ono pharma, Teiji n, Nihon Mediphysics, Fuji film, Johnson & Johnson, Bristol-Meyers, Olympus, Medtronics that includes: speaking and lecture fees. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Anticoagulant therapy with heparin is the first-line treatment for acute mesenteric vein thrombosis and is effective in improving outcomes. Conversely, patients with failed early anticoagulant therapy occasionally develop bowel infarction requiring surgery. The efficacy of long-term anticoagulant therapy on recanalizing mesenteric vein thrombosis in patients with failed early anticoagulant therapy remains unclear. Herein, we report a patient who achieved recanalization of port-superior mesenteric vein thrombosis treated with anticoagulant therapy for 10 years after failed early anticoagulant therapy, followed by bowel resection., Case Presentation: A 38-year-old male patient visited an outpatient clinic due to acute exacerbation of abdominal pain that had persisted for a month. He was diagnosed with port-superior mesenteric vein thrombosis on contrast-enhanced computed tomography (CT) scan and was transferred to our institution. Although he presented with abdominal pain, his respiration and circulation were stable upon hospital arrival. Anticoagulant therapy with heparin was started, and the patient was admitted to the intensive care unit. However, the patient's abdominal pain worsened, and he began to develop signs of peritonitis. Repeat CT scan revealed bowel infarction. Thus, the patient underwent bowel resection 6 h after admission. The initial surgery was completed with open abdomen management. Bowel anastomosis was performed on the second-look surgery on the first postoperative day. Finally, the abdomen was closed on the third postoperative day after confirming the absence of bowel ischemia progression. The patient had prolonged impaired bowel function with paralytic ileus, but was discharged on the 60th postoperative day. He was then diagnosed with protein C and S deficiency based on the tests performed. Anticoagulant therapy with warfarin was initiated. He also received anticoagulant therapy in the outpatient setting. The patient's port-superior mesenteric vein thrombosis had improved gradually with warfarin during the follow-up period. At 10 years after surgery, total occlusion of the port-superior mesenteric vein was recanalized with improvement of the portal collateral vessels. In addition, no gastric or esophageal varices were observed., Conclusions: Long-term anticoagulation therapy could affect the recanalization of extensive thrombus in multiple segments in patients with mesenteric venous thrombosis., (© 2024. The Author(s).)

Domains in a crystal, which have crystallographic uniformity and are geometrically segmented, typically arise from various phase transitions. The physical properties within individual domains are inherently the same as those in the homogeneous bulk. As a result, sufficiently large domains have little influence on the bulk properties. However, as the domains decrease in size to the nanoscale, for instance, due to multiple phase instabilities or spatial inhomogeneities, then the materials often acquire exceptional functionalities that are unattainable without these domains. This effect is exemplified by the ultrahigh dielectric and piezoelectric responses observed in ferroelectric oxides with nanoscale polar domains as well as in ferroelectric relaxors with polar nanoclusters. Here, we demonstrate that hashed nanoscale domains in an antiferroelectric material are also capable of boosting dielectric permittivity in an unconventional way. This discovery has been made in an antiferroelectric titanite-type oxide, CaTi(Si 1- x Ge x )O 5 , in which the permittivity significantly increases when the antiferroelectric order becomes short-range. Our transmission electron microscopy observations have clarified that polar regions simultaneously appear around antiphase boundaries in the antiferroelectric phase of CaTi(Si 1- x Ge x )O 5 . As the concentration of the antiphase boundary increases, the polar regions become denser and play a crucial role in boosting the permittivity. At the composition of x = 0.5, the value of the permittivity finally reaches double that in the bulk and shows excellent linearity, at least until an electric field of 500 kV/cm is applied. The present findings highlight the promise of domain engineering for boosting the permittivity in antiferroelectrics as a way to develop materials with excellent dielectric properties.

The "double bipolar method" (DBM) in robotic surgery has been widely used in Japanese general surgery and gynecology; however, it is not commonly used in the field of urology. A 55-year-old female was diagnosed with stage IA endometrial cancer. A 2-cm cystic lesion was incidentally observed at the dome of the bladder on magnetic resonance imaging. A simultaneous robot-assisted total hysterectomy and partial cystectomy using the da Vinci Xi system was planned. The gynecological procedure was first performed with the DBM, and the DBM was also used in the partial cystectomy without additional instruments to reduce surgical costs. Maryland bipolar forceps was used to excise the peritoneum, fat, and bladder wall without bleeding, enabling delicate and precise resection using the forceps' tips. Robot-assisted partial cystectomy using the DBM was feasible. When performing combined surgeries with other departments, if the DBM is already being utilized, it is worthwhile to attempt to decrease surgical cost., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hamasaki et al.)

Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics ® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.

DNA methylation is a pivotal epigenetic modification that defines cellular identity. While cell deconvolution utilizing this information is considered useful for clinical practice, current methods for deconvolution are limited in their accuracy and resolution. In this study, we collected DNA methylation data from 945 human samples derived from various tissues and tumor-infiltrating immune cells and trained a neural network model with them. The model, termed MEnet, predicted abundance of cell population together with the detailed immune cell status from bulk DNA methylation data, and showed consistency to those of flow cytometry and histochemistry. MEnet was superior to the existing methods in the accuracy, speed, and detectable cell diversity, and could be applicable for peripheral blood, tumors, cell-free DNA, and formalin-fixed paraffin-embedded sections. Furthermore, by applying MEnet to 72 intrahepatic cholangiocarcinoma samples, we identified immune cell profiles associated with cancer prognosis. We believe that cell deconvolution by MEnet has the potential for use in clinical settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Cancer.)

Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Hiruta et al.)

Alveolar type 2 (AT2) epithelial cells are tissue stem cells capable of differentiating into alveolar type 1 (AT1) cells for injury repair and maintenance of lung homeostasis. However, the factors involved in human AT2-to-AT1 cell differentiation are not fully understood. Here, we established SFTPC GFP and AGER mCherry-HiBiT dual-reporter induced pluripotent stem cells (iPSCs), which detected AT2-to-AT1 cell differentiation with high sensitivity and identified factors inducing AT1 cell differentiation from AT2 and their progenitor cells. We also established an "on-gel" alveolar epithelial spheroid culture suitable for medium-throughput screening. Among the 274 chemical compounds, several single compounds, including LATS-IN-1, converted AT1 cells from AT2 and their progenitor cells. Moreover, YAP/TAZ signaling activation and AKT signaling suppression synergistically recapitulated the induction of transcriptomic, morphological, and functionally mature AT1 cells. Our findings provide novel insights into human lung development and lung regenerative medicine., Competing Interests: Declaration of interests Y.O., A.M., and T.S. are employees, received research funding from, and are shareholders of Kyorin Pharmaceutical. R.M., T.H., M.H., and S.G. received research funding from Kyorin Pharmaceutical. S.G. and M.H. are founders and shareholders of HiLung. S.G. is an external board member of HiLung. S.G. is listed as one of the inventors of Kyoto University’s patents related to the method of generating alveolar organoids: WO2014168264A1 and WO2016143803A1., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Photoemission orbital tomography (POT) from photoelectron momentum maps (PMMs) is a powerful technique that visualizes the shape of the molecular orbitals (MOs) of molecular films. For further utilization of POT, a simple and low-cost method of POT is highly required. Here, we propose a new POT method based on the PhaseLift algorithm (PhaseLift POT). This method utilizes a lifting procedure to convert the PMM, which is a second-order polynomial of MO coefficients, into a first-order polynomial of the lifted MO coefficients and further relaxes the equality constraint for a given PMM. We also established a method to improve the accuracy of phase retrieval from the noisy PMM data by using sparsity for MO coefficients (sparse PhaseLift POT). These methods make it possible to reconstruct the three-dimensional MOs, including phases of the wave function, directly from a single experimental PMM. This method can also precisely determine the adsorption-induced molecular deformations with an accuracy of 0.05 [Å]. Furthermore, the robust sparse PhaseLift POT is robust against unavoidable noise in the experimental PMMs due to the relaxation of the matching condition for a given PMM. Therefore, this will be an innovative tool for POT, especially for analyzing the dynamics of the molecules during the chemical reaction and excitation processes.

Pathogenic variants in WDR45 on chromosome Xp11 cause neurodegenerative disorder beta-propeller protein-associated neurodegeneration (BPAN). Currently, there is no effective therapy for BPAN. Here we report a 17-year-old female patient with BPAN and show that antisense oligonucleotide (ASO) was effective in vitro. The patient had developmental delay and later showed extrapyramidal signs since the age of 15 years. MRI findings showed iron deposition in the globus pallidus and substantia nigra on T2 MRI. Whole genome sequencing and RNA sequencing revealed generation of pseudoexon due to inclusion of intronic sequences triggered by an intronic variant that is remote from the exon-intron junction: WDR45 (OMIM #300526) chrX(GRCh37):g.48935143G > C, (NM&#95;007075.4:c.235 + 159C > G). We recapitulated the exonization of intron sequences by a mini-gene assay and further sought antisense oligonucleotide that induce pseudoexon skipping using our recently developed, a dual fluorescent splicing reporter system that encodes two fluorescent proteins, mCherry, a transfection marker designed to facilitate evaluation of exon skipping and split eGFP, a splicing reaction marker. The results showed that the 24-base ASO was the strongest inducer of pseudoexon skipping. Our data presented here have provided supportive evidence for in vivo preclinical studies., (© 2024. The Author(s).)

Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown. Here we characterize distinct features of tumor-infiltrating Treg cells by global analyses of the transcriptome and chromatin landscape. They exhibited activated phenotypes with enhanced Foxp3-dependent transcriptional regulation, yet being distinct from activated Treg cells in secondary lymphoid organs. Such differences may be attributed to the extensive clonal expansion of tumor-infiltrating Treg cells. Moreover, we found that TCF7 and LEF1 were specifically downregulated in tumor-infiltrating Treg cells both in mice and humans. These factors and Foxp3 co-occupied Treg suppressive function-related gene loci in secondary lymphoid organ Treg cells, whereas the absence of TCF7 and LEF1 accompanied altered gene expression and chromatin status at these gene loci in tumor-infiltrating Treg cells. Functionally, overexpression of TCF7 and LEF1 in Treg cells inhibited the enhancement of Treg suppressive function upon activation. Our results thus show the downregulation of TCF7 and LEF1 as markers of highly suppressive Treg cells in tumors and suggest that their absence controls the augmentation of Treg suppressive function in tumors. These molecules may be potential targets for novel cancer immunotherapy with minimum effects on immune homeostasis., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Lung squamous cell carcinoma (LUSC) usually shows expansive growth with large tumor nests; few reports on invasive growth patterns (INF) in LUSC have been associated with poor prognosis in gastrointestinal and urothelial cancers. In this study, we examine the association between INF and the prognosis of LUSC., Materials and Methods: We analyzed INF as a potential prognostic factor in 254 consecutive patients with LUSC who underwent complete surgical resection at our hospital between 2008 and 2017. INF was classified into 3 categories based on the structure of the tumor other than the large round solid nest of tumor cells., Results: INF was categorized as INFa in 59 patients (23 %) with only well-demarcated large solid tumor cell nests, INFb in 89 patients (35 %) with medium to small, alongside large solid nests, and INFc in 98 patients (39 %) with cord-like/small nests or isolated cells plus large or medium solid nests. No significant lymph node metastasis differences were observed between INFc and INFa/b tumors. However, in patients with p-stage I, INFc had a poorer prognosis with regard to recurrence-free survival (RFS), with a 5-year RFS rate of 53.3 %, compared to 74.9 % for INFa/b (p = 0.010)., Conclusion: Our study highlights a novel pathological concept of INF in LUSC, and contributed to the proposal that it is a factor indicating an unfavorable prognosis in patients with early-stage LUSC. A prospective multicenter study is warranted for INFc patients, as careful follow-up and adjuvant chemotherapy might lead to the early detection and prevention of recurrence., Competing Interests: Declaration of competing interest Norihiko Ikeda reports a relationship with Astra Zeneca, Chugai pharma, Pfeizer, Taiho pharma, MSD, Boehringer Ingelheim, Eli Lilly, Ono pharma, Teijin, Nihon Mediphysics, Fuji film, Johnson & Johnson, Bristol-Meyers, Olympus, Medtronics that includes: speaking and lecture fees. The other authors declare no competing interests., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

With the advent of increasingly sophisticated organoids, there is growing demand for technology to replicate the interactions between multiple tissues or organs. This is challenging to achieve, however, due to the varying culture conditions of the different cell types that make up each tissue. Current methods often require complicated microfluidic setups, but fragile tissue samples tend not to fare well with rough handling. Furthermore, the more complicated the human system to be replicated, the more difficult the model becomes to operate. Here, we present the development of a multi-tissue chip platform that takes advantage of the modularity and convenient handling ability of a CUBE device. We first developed a blood-brain barrier-in-a-CUBE by layering astrocytes, pericytes, and brain microvascular endothelial cells in the CUBE, and confirmed the expression and function of important tight junction and transporter proteins in the blood-brain barrier model. Then, we demonstrated the application of integrating Tissue-in-a-CUBE with a chip in simulating the in vitro testing of the permeability of a drug through the blood-brain barrier to the brain and its effect on treating the glioblastoma brain cancer model. We anticipate that this platform can be adapted for use with organoids to build complex human systems in vitro by the combination of multiple simple CUBE units., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest: The authors disclose no conflicts of interest.

Under the Individuals With Disabilities Education Act, individualized education program (IEP) annual goals are required to enable students with disabilities to be involved in and make progress in the general education curriculum and to address other educational needs. This study reports findings from a content analysis of the annual goals in 88 IEPs for K-12 students with extensive support needs. Results reflect a lack of comprehensive academic content goals to promote involvement and progress in the general education curriculum, and limited opportunities for students to develop skills associated with self-determination. Findings also show a focus within goals on student compliance rather than the development of meaningful skills and knowledge. Implications for research and practice are provided., (©AAIDD.)

Purpose: With the current study, we aimed to reveal the similarities and differences in sensory profiles between Williams syndrome (WS) and autism spectrum disorder., Methods: Using the sensory profile questionnaire completed by the caregivers, we analyzed the WS (n = 60, 3.4-19.8 years) and autistic (n = 39, 4.2-14.0 years) groups., Results: The Severity Analysis revealed a significant group difference in Sensory Sensitivity but not in Low Registration, Sensation Seeking, and Sensation Avoiding subscales. Age can modulate the subscale scores differently across groups. For Sensation Seeking, the scores of both groups decreased with development. However, the scores of Sensory Sensitivity decreased with age in the autistic group but not in the WS group. Sensation Avoiding scores increased with development in the WS group but not in the autistic group. No significant developmental changes were observed in Low Registration., Conclusion: This study highlights the cross-syndrome similarities and differences in sensory profiles and developmental changes in autistic individuals and individuals with WS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Complexity of quantum phases of matter is often understood theoretically by using gauge structures, as is recognized by the [Formula: see text] and U(1) gauge theory description of spin liquids in frustrated magnets. Anomalous Hall effect of conducting electrons can intrinsically arise from a U(1) gauge expressing the spatial modulation of ferromagnetic moments or from an SU(2) gauge representing the spin-orbit coupling effect. Similarly, in insulating ferro and antiferromagnets, the magnon contribution to anomalous transports is explained in terms of U(1) and SU(2) fluxes present in the ordered magnetic structure. Here, we report thermal Hall measurements of MnSc 2 S 4 in an applied field up to 14 T, for which we consider an emergent higher rank SU(3) flux, controlling the magnon transport. The thermal Hall coefficient takes a substantial value when the material enters a three-sublattice antiferromagnetic skyrmion phase, which is in agreement with the linear spin-wave theory. In our description, magnons are dressed with SU(3) gauge field, which is a mixture of three species of U(1) gauge fields originating from the slowly varying magnetic moments on these sublattices., (© 2024. The Author(s).)