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One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.

The critical requirements in developing clinical-grade human-induced pluripotent stem cells-derived neural precursors (hiPSCs-NPCs) are defined by expandability, genetic stability, predictable in vivo post-grafting differentiation, and acceptable safety profile. Here, we report on the use of manual-selection protocol for generating expandable and stable human NPCs from induced pluripotent stem cells. The hiPSCs were generated by the reprogramming of peripheral blood mononuclear cells with Sendai-virus (SeV) vector encoding Yamanaka factors. After induction of neural rosettes, morphologically defined NPC colonies were manually harvested, re-plated, and expanded for up to 20 passages. Established NPCs showed normal karyotype, expression of typical NPCs markers at the proliferative stage, and ability to generate functional, calcium oscillating GABAergic or glutamatergic neurons after in vitro differentiation. Grafted NPCs into the striatum or spinal cord of immunodeficient rats showed progressive maturation and expression of early and late human-specific neuronal and glial markers at 2 or 6 months post-grafting. No tumor formation was seen in NPCs-grafted brain or spinal cord samples. These data demonstrate the effective use of in vitro manual-selection protocol to generate safe and expandable NPCs from hiPSCs cells. This protocol has the potential to be used to generate GMP (Good Manufacturing Practice)-grade NPCs from hiPSCs for future clinical use.

The objective of this work is to address the need for versatile and effective tissue characterization in abdominal ultrasound diagnosis using a simpler system. We evaluated the backscattering coefficient (BSC) of several tissue-mimicking phantoms utilizing three different ultrasonic probes: a single-element transducer, a linear array probe for clinical use, and a laboratory-made annular array probe. The single-element transducer, commonly used in developing fundamental BSC evaluation methods, served as a benchmark. The linear array probe provided a clinical comparison, while the annular array probe was tested for its potential in high-frequency and high-resolution ultrasonic observations. Our findings demonstrate that the annular array probe meets clinical demands by providing accurate BSC measurements, showcasing its capability for high-frequency and high-resolution imaging with a simpler, more versatile system. [ABSTRACT FROM AUTHOR]

Background Left ventricular pseudoaneurysm (LVPA) is an infrequent but highly lethal complication of myocardial infarction. Early surgical repair with a resection of pseudoaneurysm is often performed, given that medical therapy alone is associated with a high risk of mortality. This report describes a case of a giant LVPA on the lateral wall post-infarction and mitral valve regurgitation that was successfully treated by surgical transatrial closure and mitral valve replacement. Case summary A 77-year-old man with chronic kidney disease and a history of percutaneous coronary interventions for acute myocardial infarction was referred to the cardiac surgeons because of a spontaneous finding of an abnormal mass adjacent to the heart on imaging studies, which was missed on a chest radiograph obtained 3 months earlier. Cardiac studies revealed LVPA and severe mitral regurgitation with poor ejection fraction. Early repair of LVPA and concurrent mitral valve surgery were recommended. Transatrial patch closure and mitral valve replacement were performed using an interatrial approach via median sternotomy. Although the patient's post-operative course was complicated by congestive heart failure and irreversible renal failure, he was discharged with good functional status after 1 month of intermittent renal replacement therapy with haemodialysis. Discussion Transatrial repair of LVPA and concurrent mitral valve replacement can be a treatment of choice for reducing surgical trauma to the left ventricle and protecting the sealing structure from rupture. [ABSTRACT FROM AUTHOR]

Kabuki syndrome (KS) is a genetic disorder caused by gene mutations in either lysine-specific methyltransferase 2D (KMT2D) or lysine demethylase 6A (KDM6A). This congenital disorder exhibits characteristic facial features, developmental delays in psychomotor skills, and skeletal abnormalities. Moreover, it is classified as a congenital immunodeficient disorder under the category of combined immunodeficiency, leading to hypogammaglobulinemia and the onset of autoimmune diseases. Here, we present the first case of KS complicated by idiopathic pulmonary hemosiderosis (IPH). The KS patient, a 2-year-old Japanese girl with a history of hypoplastic left heart syndrome and recurrent bacterial infection, developed severe respiratory distress and anemia. She had autoimmune hemolytic anemia and gouty nephropathy. Hemophagocytic macrophages with hemosiderin ingestion were identified in bronchoalveolar lavage fluid, excluding differential diagnoses and leading to the diagnosis of idiopathic pulmonary hemosiderosis. Intravenous prednisolone (2 mg/kg/day) was administered, but symptoms did not improve. However, pulmonary hemorrhage disappeared with methylprednisolone pulse therapy. IPH warrants consideration in cases where individuals with KS manifest idiopathic pneumonia and concurrent anemia. [ABSTRACT FROM AUTHOR]

A precise understanding of hadronic interactions is essential to interpreting the mass composition of ultra-high energy cosmic rays from the results of air shower experiments. The Large Hadron Collier forward (LHCf) experiment aims to measure forward neutral particles for validation of hadronic interaction models adopted in air shower simulations. We already published the production cross sections of forward photons and neutrons for proton-proton collisions at √s=13 TeV. Recently, we showed a preliminary result of the energy spectrum of forward η mesons for proton-proton collisions at √s=13 TeV. Moreover, in September 2022, we had another data-taking for proton-proton collisions at √s=13.6 TeV. In data taking, we planned to obtain a number of π0 and η candidates ten times larger for precise measurements and to perform the joint operation with ATLAS Roman pots and zero-degree calorimeters. Thanks to the joint operation with the ATLAS Roman pots, we can measure diffractive mass and neutral particles from diffractive dissociation simultaneously. Furthermore, energy resolution for neutrons is expected to be improved from 40% to 20% by combining the LHCf and the ATLAS zero-degree calorimeters. In this work, we report the status and prospects of the LHCf experiment.

Measurements of forward neutrons in pp collisions will allow us to investigate π-p cross-section via one-pion exchange process, which are important for air shower development. However, the precision of these measurements is limited by the energy resolution of the LHCf detectors. To improve it, a joint measurement with the ATLAS ZDC was planned. In 2021, a beam test was conducted to evaluate the performance of the joint measurement of the LHCf-Arm1 and ZDC detectors using proton beams of 350 GeV at SPS. Combining the LHCf data with the ZDC data, we confirmed that the energy resolution improved from about 40% to 21.4%.