generation of dual-target compounds using artificial intelligence.

Drugs that interact with multiple therapeutic targets are potential high-value products in polypharmacology-based drug discovery, but the rational design remains a formidable challenge. Here, we present artificial intelligence (AI)-based methods to design the chemical structures of compounds that interact with multiple therapeutic target proteins. The molecular structure generation is performed by a fragment-based approach using a genetic algorithm with chemical substructures and a deep learning approach using reinforcement learning with stochastic policy gradients in the framework of generative adversarial networks.

Blood glucose levels in out-of-hospital cardiac arrest undergoing targeted temperature management and ECPR.

Aim: Targeted temperature management (TTM) for patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) has not been fully studied. This study aimed to investigate the association between blood glucose levels during TTM and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing ECPR.

Methods: This was a secondary analysis of the SAVE-J II study, a retrospective, multicenter study of OHCA patients treated with ECPR in Japan.

Downregulation of semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis.

Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown.

Imaging using diffusion-weighted whole-body imaging with background signal suppression for methotrexate-associated lymphoproliferative disorder: A case report.

Patients with rheumatoid arthritis (RA) receiving immunosuppressive therapy including methotrexate (MTX), are at risk of developing lymphoproliferative disorder (LPD). Herein, we report the case of a 61-year-old man who has been treated with MTX and sulfasalazine for seropositive RA since the age of 52. He underwent diffusion-weighted whole-body imaging with background signal suppression (DWIBS), which revealed high-intensity lesions in the affected lymph nodes of the cervical, clavicular, and axillary regions.

Association between Polypharmacy and Adverse Events in Patients with Alzheimer's Disease: An Analysis of the Japanese Adverse Drug Event Report Database (JADER).

: Alzheimer's disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer's disease treatment combinations, the number of concomitant medications, and the occurrence of AEs.

Intraoperative neuromonitoring of visual evoked potentials in a pregnant patient with meningioma: a case report.

Background: Meningioma in the parasellar region may lead to visual impairment, so intraoperative neurological monitoring is essential for enucleation surgery. However, intraoperative neurological monitoring in pregnant women is challenging, as the anesthesia management must consider the effects and risks to the fetus. Remimazolam is a newly introduced intravenous anesthetic that has little effect on blood pressure.

A case of minimum invasive debranch thoracic endovascular aortic repair for isolated left vertebral artery: complete revascularization without artificial vessels via a single small incision.

Isolated left vertebral artery (ILVA) is one of the most frequent vertebral abnormalities. When performing thoracic endovascular aortic repair (TEVAR), the ILVA may have to be closed depending on the position of the stent graft; in these cases, the decision to reconstruct the ILVA depends on the state of cerebral blood flow. Here, we report a case of a 68-year-old male, in whom the Willis arterial circle was incomplete; we therefore performed a reconstructive method during zone 2-landing TEVAR that ensured ILVA and left subclavian artery blood flow without the use of artificial vessels.

Safety, pharmacokinetics, and pharmacodynamics of ART-648, a PDE4 inhibitor in healthy subjects: A randomized, placebo-controlled phase I study.

Phosphodiesterase 4 (PDE4) inhibitor is associated with a broad-spectrum anti-inflammatory mechanism. However, securing clinically efficacious doses with sufficient safety margins remains challenging due to class specific adverse events that are often unavoidable in the clinic. ART-648 is an orally available PDE4 inhibitor being developed for the treatment of inflammatory diseases.

Modified colored three-dimensional posterior and temporal cranial fossa model with mobility of the joint between C1 and occipital condyle.

Background: Skull base surgery requires anatomical knowledge and appropriate surgical technique in bone drilling. We developed a newly modified three-dimensional (3D) model of the posterior cranial fossa as a learning tool that improves knowledge of skull base anatomy and surgical approaches, including skull base drilling techniques.

Methods: This bone model of the posterior cranial fossa was created based on computed tomography data using a 3D printer, and incorporates artificial cranial nerves, cerebral vessels, bony structures, dura mater, and cerebellar tentorial dura.

Effects of cardiac rehabilitation on in vivo nailfold microcirculation in patients with cardiovascular disease.

This study aimed to explore the impact of cardiac rehabilitation (CR) on in vivo and ex vivo microcirculation, exercise capacity, and oxidative stress in patients with cardiovascular disease (CVD). The study included patients with acute coronary syndrome (ACS; n = 45; age, 69.0 ± 14.

Effects of early surgery for cervical fracture dislocation on 30-day mortality using the Japanese Diagnosis Procedure Combination database.

Study Design: Retrospective study of data abstracted from the Diagnosis Procedure Combination (DPC) database.

Purpose: This study aimed to investigate the effects of surgery in the early phase.

Overview Of Literature: The optimal timing of surgery for cervical fracture dislocation (CFD) remains unclear because only a few clinical studies with approximately 100 patients have been published.

Association between the hypokalaemia index based on area over the serum potassium concentration curve and occurrence of acute kidney injury in patients administered liposomal amphotericin B.

Background: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L-AMB).

Objectives: Because excess potassium (K) leakage occurs during renal tubular injury caused by L-AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L-AMB than hypokalaemia identified from a one-point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated.

Giant Left Ventricular Thrombus Rapidly Developing in an Extremely Short Period of Time in a Patient With Severe Systolic Dysfunction.

Although left ventricular thrombi (LVTs) are closely related to the prognosis of patients with systolic dysfunction, anticoagulation therapy is not recommended for the primary prevention of LVTs in patients with sinus rhythm heart failure. We report a case of a patient with systolic dysfunction who developed a giant LVT in an extremely short period of time (one month) after an infection. The LVT led to acute limb ischemia, gangrene, and death.

Timing of Assessment of Humoral and Cell-Mediated Immunity after Influenza Vaccination.

Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing of immunological assessments after vaccination using markers of humoral and cell-mediated immunity.