Non-tuberculosis Mycobacterial Pulmonary Disease Caused by Mycobacterium kiyosense, a New Species.

Non-tuberculosis mycobacterial (NTM) pulmonary disease (NTM-PD) is quite common, and newly identified species are being reported increasingly frequently thanks to advances in identification technologies. A 56-year-old woman had mild sputum production showed bronchiectasis with multiple small nodules, consistent with NTM-PD, on chest computed tomography. Mycobacterial species were isolated from the specimens; however, conventional methods could not identify the species. We conducted whole-genome sequencing and identified the NTM isolates as Mycobacterium kiyosense, a species newly registered in 2023 from Japan. She was diagnosed with NTM-PD caused by M. kiyosense and received watchful waiting.

Does the superior ophthalmic vein dilate in acute intracranial hypertension due to hemorrhagic stroke?

A 65-year-old man presented with coma. The cranial computed tomography (CT) revealed a massive hematoma in the left cerebral hemisphere, accompanied by intraventricular hemorrhage (IVH) and ventriculomegaly. Contrast examination revealed ectatic superior ophthalmic veins (SOVs). The patient underwent emergent hematoma evacuation. Contrast CT performed on postoperative day (POD) 2 showed a remarkable reduction in the diameters of both SOVs. A second patient, a 53-year-old man, presented with consciousness disturbance and right hemiparesis. CT revealed a large hematoma in the left thalamus, accompanied by massive IVH. Contrast CT demonstrated the bold delineation of the SOVs. The patient underwent endoscopic IVH removal. Contrast CT performed on POD 7 showed a remarkable reduction in the diameters of both SOVs. A third patient, a 72-year-old woman, presented with severe headache. CT revealed diffuse subarachnoid hemorrhage and ventriculomegaly. Contrast CT demonstrated a saccular aneurysm on the internal carotid artery-anterior choroidal artery branching site with the bold delineation of the SOVs. The patient underwent microsurgical clipping. Contrast CT performed on POD 68 showed a remarkable reduction in the diameters of both SOVs. The SOVs may function as an alternative venous drainage pathway in the setting of acute intracranial hypertension due to hemorrhagic stroke.

Inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein from bland thrombus using gadoxetic acid-enhanced magnetic resonance imaging.

PURPOSE: To assess inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein (TIV) from bland thrombus on gadoxetic acid-enhanced magnetic resonance imaging (Gx-MRI). Secondarily, to determine whether a multi-feature model improves accuracy compared to LI-RADS. METHODS: We retrospectively identified consecutive patients at risk for hepatocellular carcinoma with venous occlusion(s) reported on Gx-MRI. Five radiologists independently classified each occlusion as TIV or bland thrombus using the LI-RADS TIV criterion (enhancing soft tissue in vein). They also evaluated imaging features suggestive of TIV or bland thrombus. Intra-class correlation coefficient (ICC) was calculated for individual features. A multi-feature model was developed based on consensus scores of features with > 5% consensus prevalence and > 0.40 ICC. Sensitivity and specificity of the LI-RADS criterion and of the cross-validated multi-feature model were compared. RESULTS: Ninety-eight patients with 103 venous occlusions (58 TIV, 45 bland thrombus) were included. The LI-RADS criterion provided 0.63 ICC and, depending on the reader, 0.62-0.93 sensitivity and 0.87-1.00 specificity. Five other features had > 5% consensus prevalence and > 0.40 ICC, including three LI-RADS suggestive features and two non-LI-RADS features. The optimal multi-feature model incorporated the LI-RADS criterion and one LI-RADS suggestive feature (occluded or obscured vein contiguous with malignant parenchymal mass). After cross-validation, the multi-feature model did not improve sensitivity or specificity compared to the LI-RADS criterion (P = 0.23 and 0.25, respectively). CONCLUSION: Using Gx-MRI, the LI-RADS criterion for TIV provides substantial inter-observer agreement, variable sensitivity, and high specificity for differentiating TIV from bland thrombus. A cross-validated multi-feature model did not improve diagnostic performance.

Laundry detergents and surfactants-induced eosinophilic airway inflammation by increasing IL-33 expression and activating ILC2s.

INTRODUCTION: Epidemiological studies demonstrated that cleaning work and frequent use of cleaning products are risk factors for asthma. Laundry detergents have been reported to have epithelial barrier-opening effects. However, whether laundry detergents directly induce airway inflammation and its mechanisms in vivo remain to be elucidated. METHODS: Two commercial laundry detergents and two commonly used surfactants for cleaning and cosmetics (sodium lauryl sulfate and sodium dodecyl benzene sulfonate) were intranasally administered to mice. Lungs were analyzed using flow cytometry, histology, ELISA, and quantitative PCR. Human bronchial epithelial cells were stimulated with laundry detergents and analyzed using quantitative PCR and western blotting. Involvement of oxidative stress was assessed using an antioxidant. Dust samples from homes were analyzed to determine their detergent content by measuring their critical micelle concentration (CMC). RESULTS: The administered laundry detergents and surfactants-induced eosinophilic airway inflammation accompanied by increased IL-33 expression and activation of group 2 innate lymphoid cells (ILC2s). Detergent-induced eosinophilic airway inflammation was significantly attenuated in Rag2-/- Il2rg-/- , Il33-/- mice, and also in wild-type mice treated with NAC. Detergent-induced IL-33 expression in airways was attenuated by NAC treatment, both in vivo and in vitro. CMCs were found in all of the tested dust extracts, and they differed significantly among the homes. CONCLUSION: The laundry detergents and surfactants-induced eosinophilic airway inflammation in vivo through epithelial cell and ILC2 activation. They induced IL-33 expression in airway epithelial cells through oxidative stress. Furthermore, detergent residues were present in house dust and are presumably inhaled into the airway in daily life.

Analytical and Physical Investigation on Source Resistance in InxGa1-xAs Quantum-Well High-Electron-Mobility Transistors.

We present a fully analytical model and physical investigation on the source resistance (RS) in InxGa1-xAs quantum-well high-electron mobility transistors based on a three-layer TLM system. The RS model in this work was derived by solving the coupled quadratic differential equations for each current component with appropriate boundary conditions, requiring only six physical and geometrical parameters, including ohmic contact resistivity (ρc), barrier tunneling resistivity (ρbarrier), sheet resistances of the cap and channel regions (Rsh_cap and Rsh_ch), side-recessed length (Lside) and gate-to-source length (Lgs). To extract each model parameter, we fabricated two different TLM structures, such as cap-TLM and recessed-TLM. The developed RS model in this work was in excellent agreement with the RS values measured from the two TLM devices and previously reported short-Lg HEMT devices. The findings in this work revealed that barrier tunneling resistivity already played a critical role in reducing the value of RS in state-of-the-art HEMTs. Unless the barrier tunneling resistivity is reduced considerably, innovative engineering on the ohmic contact characteristics and gate-to-source spacing would only marginally improve the device performance.

STAT6 gain-of-function variant exacerbates multiple allergic symptoms.

BACKGROUND: Allergic diseases were long considered to be complex multifactorial disorders. However, recent findings indicate that severe allergic inflammation can be caused by monogenic immune defects. OBJECTIVES: We sought to clarify the molecular pathogenesis of a patient with early-onset multiple allergic diseases, a high serum IgE level, hypereosinophilia, treatment-resistant severe atopic dermatitis with increased dermal collagen fiber deposition, and eosinophilic gastrointestinal disorder with numerous polypoid nodules. METHODS: A missense variant in STAT6 was identified, and its function was examined using peripheral blood, transfected HEK293 cells, lymphoblastoid cell lines, and knock-in mice with the corresponding mutation. RESULTS: Whole-exome sequencing identified a de novo heterozygous missense variant in signal transducer and activator of transcription 6 (STAT6) (p.Asp419Asn). Luciferase reporter assay revealed that the transcriptional activity of this STAT6 mutant was upregulated even without IL-4 stimulation. Phosphorylation of STAT6 was not observed in either the patient's TH2 cells or lymphoblastoid cell lines without stimulation, whereas it was induced more strongly in both by IL-4 stimulation compared with healthy controls. STAT6 protein was present in the nuclear fraction of the lymphoblastoid cell lines of the patient even in the absence of IL-4 stimulation. The patient's gastric mucosa showed upregulation of STAT6-, fibrosis-, and germinal center formation-related molecules. Some of the knock-in mice with the corresponding mutation spontaneously developed dermatitis with skin thickening and eosinophil infiltration. Moreover, serum IgE levels and mRNA expression of type 2 cytokines were increased in the knock-in mice-with or without development of spontaneous dermatitis-compared with the wild-type mice. CONCLUSIONS: A novel STAT6 gain-of-function variant is a potential cause of primary atopic disorders.

Atypical convexity meningioma presenting with photophobia and skull erosion.

A 41-year-old man presented with photophobia. The patient showed a choked disc and right-sided quadrantanopia with an intact sphincter reaction to light stimulation. Computed tomography revealed an isodense mass in the right frontal convexity, accompanied by extensive perifocal brain edema and smooth-contoured skull erosion. On cerebral magnetic resonance imaging, the tumor was dural-based, appeared inhomogeneous intensity on both T1- and T2-weighted sequences, and was intensely enhanced. Magnetic resonance angiography revealed unusually ectatic right-sided middle meningeal and superficial temporal arteries. The tumor, which was elastic hard, highly vascular, and severely adhered to the frontal cortices, was completely resected. The microscopic findings of the resected specimen were consistent with angiomatous meningioma. The patient's photophobia resolved after surgery, with resolution of the optic chiasm compression. Meningiomas arising in the frontal convexity may cause photophobia. Angiomatous meningioma should be considered when a broad-based tumor is found in the cerebral convexity accompanied by skull erosion and extensive perifocal edema.

Explicit Thermal Resistance Model of Self-Heating Effects of AlGaN/GaN HEMTs with Linear and Non-Linear Thermal Conductivity.

We presented an explicit empirical model of the thermal resistance of AlGaN/GaN high-electron-mobility transistors on three distinct substrates, including sapphire, SiC, and Si. This model considered both a linear and non-linear thermal resistance model of AlGaN/GaN HEMT, the thickness of the host substrate layers, and the gate length and width. The non-linear nature of channel temperature-visible at the high-power dissipation stage-along with linear dependency, was constructed within a single equation. Comparisons with the channel temperature measurement procedure (DC) and charge-control-based device modeling were performed to verify the model's validity, and the results were in favorable agreement with the observed model data, with only a 1.5% error rate compared to the measurement data. An agile expression for the channel temperature is also important for designing power devices and monolithic microwave integrated circuits. The suggested approach provides several techniques for investigation that could otherwise be impractical or unattainable when utilizing time-consuming numerical simulations.

A hyperechoic mass in femoral vein.

Here, we present a case of fat embolism syndrome (FES) in which ultrasound sonography and computed tomography successfully visualized fat embolus in the femoral vein. A multimodality approach was particularly useful for early and specific diagnosis.

Eating behaviour characteristics and dietary intake among Japanese junior high school students: A cross-sectional study.

BACKGROUND: Psychological characteristics of eating behaviour may be related to dietary habits. AIM: We investigated the association between eating behaviour characteristics and nutrition and food intake adequacy in Japanese adolescents. METHODS: This cross-sectional survey was conducted among 136 junior high school students (boys: 90, girls: 46) at a junior high school in Tokyo, Japan. Eating behaviour was categorised into three types (emotional, external, and restrained) using scores on the Japanese version of the Dutch Eating Behaviour Questionnaire. Dietary intake was assessed using a validated, brief self-administered diet history questionnaire. Inadequate nutrient intake was determined by counting the number of nutrients not meeting the dietary reference intake (DRI) for the Japanese population. The statistical analyses included Wilcoxon signed-rank tests, Spearman's rank correlation coefficient, and multiple regression analysis using JMP ver.14 (SAS Institute Inc., Cary, NC, USA). All reported p values are two-tailed, and p < 0.05 was regarded as statistically significant. RESULTS: Multiple regression analysis showed that restrained eating score was inversely associated with the number of nutrients not meeting the DRI (ß = - 0.28; p = 0.0027) and with total weight of snack intake (ß = - 0.30; p = 0.0010). Neither emotional nor external eating was significantly associated with the number of nutrients not meeting the DRI and with total weight of snack intake. CONCLUSIONS: These results suggest that adolescents with low restrained eating scores may have less self-control over their eating behaviour and may therefore have inadequate dietary intake.

Calvarial angiomatous meningioma developed in the diploe.

Background: Angiomatous meningioma is a rare subtype of meningiomas. To the best of our knowledge, there have been no reports of intradiploic angiomatous meningioma. Case Description: A 53-year-old previously healthy woman was diagnosed with a calvarial lesion during a brain checkup. Cerebral magnetic resonance imaging showed an intradiploic tumor, 11 × 14 × 12 mm, in the right parietal bone. It was an enhancing, lobular tumor presenting as isointensity on T1- and hyperintensity on T2-weighted sequences, with an intense enhancement of the adjacent dura mater. Computed tomography revealed bone erosion at the tumor site, extending predominantly into the inner side, and sclerotic changes in the surrounding bone. Total resection was performed. Microscopically, the tumor tissue comprised cells with low-grade meningioma and intervening prominent vasculatures, consistent with angiomatous meningioma. Conclusion: Angiomatous meningioma should be considered as a differential diagnosis when an intradiploic tumor shows a lobular structure, intense enhancement of the adjacent dura mater, and sclerotic changes in the surrounding skull. These findings can support prompt tumor resection.

Oculomotor nerve palsy presumably caused by cisternal drain during microsurgical clipping.

Background: Oculomotor nerve palsy can be caused by diverse etiologies, but no report has yet documented its association with a cisternal drain. Case Description: A 35-year-old woman presented with severe headache. The patient did not exhibit oculomotor nerve palsy at presentation. Cranial computed tomography (CT) revealed diffuse subarachnoid hemorrhage. The patient underwent open microsurgical clipping of a ruptured middle cerebral artery aneurysm. During surgery, a cisternal drain was placed in the basal cistern at the medial aspect of the clinoidal portion of the internal carotid artery. The patient presented with the left oculomotor nerve palsy immediately after surgery. CT revealed displacement of the cisternal drain to the lateral aspect of the anterior clinoid process. The patient's mydriasis and sluggish light reaction recovered after 7 days, while extraocular movements persisted for 50 days. The constructive interference steady-state sequence detected the left oculomotor nerve coursing adjacent to the clinoidal internal carotid artery. Conclusion: Oculomotor nerve palsy can be caused by collision with a thin silastic tube placed during surgery for aneurysmal subarachnoid hemorrhage. Withdrawal of the drain as early as possible is recommended when drain-associated oculomotor nerve palsy is suspected.

Subsequent bilateral intracerebral hemorrhages in the putamen and thalamus: A report of four cases.

Background: Subsequent bilateral intracerebral hemorrhage (SBICH) in the putamen and thalamus is a rare condition. Herein, we report four such cases. Case Description: Case 1: A 47-year-old woman presented with the left hemiparesis and elevated blood pressure. Neuroimaging revealed a right thalamic hemorrhage and a small left thalamic hemorrhage accompanying the hyperdense rim on computed tomography (CT) and the hypointense rim on gradient-echo T2*-weighted imaging (T2*WI). Case 2: A 53-year-old man presented with a disturbance of consciousness and elevated blood pressure. Neuroimaging revealed a left putaminal hemorrhage and a small right thalamic hemorrhage that appeared hyperdense on CT and hypointense on T2*WI. Case 3: A 65-year-old woman presented with the right hemiparesis and elevated blood pressure. Neuroimaging revealed a left putaminal hemorrhage and a small right thalamic hemorrhage accompanied by a hyperdense rim on CT and a hypointense rim on T2*WI. Case 4: A 75-year-old woman presented with the right hemiparesis and elevated blood pressure. Neuroimaging revealed a left thalamic hemorrhage and small hemorrhages in the right thalamus and cerebellar hemisphere. These hemorrhages appeared hyperdense on CT and hypointense on T2*WI. Conclusion: SBICHs are rare bilateral hemorrhages that may present with asymptomatic microbleeds in the putamen or thalamus coupled with symptomatic, subsequent hemorrhages in the contralateral counterparts. The latter hemorrhage may develop during the subacute phase of microbleeds in the putamen or thalamus.

Calvarial Langerhans cell histiocytosis in an adult presenting rapid growth.

Background: Langerhans cell histiocytosis (LCH) arising in the skull is rare in adulthood. Case Description: A 58-year-old woman experienced a durable headache. Cerebral magnetic resonance imaging (MRI) at presentation showed no abnormalities; however, MRI and computed tomography (CT) performed 6 weeks later revealed the emergence of a well-demarcated, heterogeneously enhancing calvarial tumor accompanied by irregular-shaped bone erosion. On MRI, the temporalis muscle and subcutaneous tissue adjacent to the tumor were extensively swollen and enhanced. The patient underwent en bloc resection. The microscopic appearance of the tumor was consistent with that of LCH. Postoperative systemic 18F-fluorodeoxyglucose positron emission tomography/CT did not detect any abnormal accumulation. Conclusion: LCH may develop within a short period. It should be considered as a differential diagnosis when a rapidly growing calvarial tumor is encountered, even when the patient is an adult. Prompt histological verification is recommended in such cases.

Are bone erosion and peripheral feeding vessels hallmarks of intracranial solitary fibrous tumor/hemangiopericytoma?

An 86-year-old man sustained progressive motor weakness in the left lower extremity for 1 month. Cranial computed tomography (CT) revealed an isodense mass in the right parietal lobe, with a smooth-contoured focal erosion in the adjacent parietal bone. The extra-axial tumor appeared isointense on T1- and hyperintense on T2-weighted magnetic resonance imaging with intense enhancement. On three-dimensional CT angiography, the ectatic left occipital artery coursed into the right parietal foramina and connected with a dilated meningeal vessel supplying the tumor. The focal erosion formed in the inner parietal bone was located adjacent to the feeding vessel. A total tumor resection was achieved. The microscopic findings of the resected specimen were consistent with a World Health Organization grade III hemangiopericytoma (HPC). Bone erosion and peripheral feeding vessels may be characteristic findings of intracranial solitary fibrous tumor (SFT)/HPC. Careful interpretation of neuroimages could help detect clues for distinguishing an SFT/HPC masquerading as a meningioma from a true meningioma.

Prominent hyperintense areas in swollen optic pathway: An indicator of congestive glymphatic pathway?

A 34-year-old woman presented with progressive visual impairment for 2 months. Computed tomography and magnetic resonance imaging (MRI) revealed a suprasellar cyst. The patient underwent endoscopic endonasal surgery, which resulted in gross total resection with a diagnosis of craniopharyngioma. Postoperatively, the patient's visual function improved. The constructive interference steady-state (CISS) sequence revealed a remarkable resolution of hyperintense areas in the swollen optic nerve and tract. A 36-year-old woman sustained an abrupt visual loss. She had been diagnosed with cavernous malformations (CMs) in the right frontal lobe and suprasellar region 11 years ago, with an intact optic tract. Cerebral MRI at presentation revealed marked enlargement of the suprasellar CM and swelling of the right optic tract, accompanied by predominant hyperintense areas in the optic pathway. The patient's visual function showed significant improvement with conservative management. The CISS sequence performed 3 months later showed remarkable resolution of hyperintensity in the optic pathway. Prominent hyperintense areas in the optic pathway may indicate congestion of glymphatic flow. Reduction in such areas may be a radiological biomarker reflecting the improvement of visual impairment.

Successful Resuscitation of Cardiac Arrest After Refeeding Syndrome Associated with Hiatal Hernia: A Case Report.

BACKGROUND Refeeding syndrome (RFS) is a life-threatening syndrome, which can cause sudden death. RFS has been reported frequently in young patients with anorexia without organic disease; however, there are few reports in elderly patients with organic disease. Herein, we report a case of cardiac arrest after refeeding syndrome associated with hiatal hernia. CASE REPORT We report the case of a 59-year-old woman who had a diagnosis of RFS during treatment for anorexia secondary to hiatal hernia. She was hospitalized with hypothermia, anemia, and hypovolemic shock and treated with electrolytes, hydration, and transfusion at the Emergency Department. Upper gastrointestinal endoscopy revealed hiatal hernia with severe reflux esophagitis. We initiated parenteral nutrition (8.7 kcal/kg/day). However, QTc prolongation caused pulseless ventricular tachycardia. Temporary cardiac pacing was performed to prevent recurrence. Her nutritional status steadily improved, and she was transferred to another hospital without complications. CONCLUSIONS Patients with gastrointestinal comorbidities are more likely to have inadequate food intake and to be undernourished on admission and therefore should be carefully started on nutritional therapy, considering their risk of RFS.

A Clinically Applicable Prediction Model to Improve T Cell Collection in Chimeric Antigen Receptor T Cell Therapy.

As chimeric antigen receptor (CAR) T cell therapy targeting CD19 has shown favorable outcomes in patients with relapsed or refractory (r/r) mature B cell lymphomas and B cell acute lymphoblastic leukemia (B-ALL), an increasing number of patients are waiting to receive these treatments. Optimized protocols for T cell collection by lymphapheresis for chimeric antigen receptor (CAR) T cell therapy are urgently needed to provide CAR T cell therapy for patients with refractory and progressive disease and/or a low number of lymphocytes owing to prior chemotherapy. The predicted efficiency of CD3+ cell collection in apheresis can guide protocols for apheresis, but a clinically applicable model to produce reliable estimates has not yet been established. In this study, we prospectively analyzed 108 lymphapheresis procedures for tisagenlecleucel therapy at 2 centers. The apheresis procedures included 20 procedures in patients with B cell acute lymphoblastic leukemia and 88 procedures in patients with diffuse large B cell lymphoma, with a median age at apheresis of 58 years (range, 1 to 71 years). After lymphapheresis with a median processing blood volume of 10 L (range, 3 to 16 L), a median of 3.2 × 109 CD3+ cells (range, .1 to 15.0 × 109 cells) were harvested. Collection efficiency 2 (CE2) for CD3+ cells was highly variable (median, 59.3%; range, 11.0% to 199.8%). Multivariate analyses revealed that lower hemoglobin levels, higher circulating CD3+ cell counts, and higher platelet counts before apheresis significantly decreased apheresis CE2. Based on multivariate analyses, we developed a novel formula that estimates CE2 from precollection parameters with high accuracy (r = .56; P < .01), which also suggests the necessary processing blood volume. Our strategy for lymphapheresis should help reduce collection failure, as well as achieve efficient utilization of medical resources in clinical practice, thereby allowing delivery of CAR T cell therapy to more patients in a timely manner.

A large cystic meningioma incidentally detected during general examination for breast cancer.

A 57-year-old woman who underwent needle biopsy for a subcutaneous mass in the breast was diagnosed with invasive ductal carcinoma. General examination incidentally revealed an intracranial tumor. At presentation, the patient showed memory disturbance but no focal neurological deficits. Cranial computed tomography (CT) revealed a large, hypodense cyst in the left frontotemporal region, involving a tumor with extensive hyperostotic changes in the left sphenoid and frontal bones. Magnetic resonance imaging showed that the tumor was attached to the dura mater of the pterional region and extensively enhanced, with involvement of the frontal and sphenoid bones. The less vascular tumor was removed en bloc by drilling the affected sphenoid and frontal bones as much as possible. The microscopic findings of the tumor were consistent with meningothelial meningioma with invasion into the dura mater and bone. Cystic meningioma should be considered when encountered with a dural-based cystic tumor, even in patients with cancer. In such circumstances, prompt and preferential resection may be indicated for intracranial tumors for timely initiation of the long-term treatment of cancer.

Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. METHODS: Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared. RESULTS: HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and ß adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs. CONCLUSIONS: Overexpression of HCN4 showed enhancement of If current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.