Follistatin regulates the specification of the apical cochlea responsible for low-frequency hearing in mammals.

The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in vivo evidence that regional identity in the embryonic cochlea acts as a framework upon which tonotopy-specific properties essential for frequency selectivity in the mature cochlea develop. We found that follistatin (FST) is required for the maintenance of apical cochlear identity, but dispensable for its initial induction. In a fate-mapping analysis, we found that FST promotes expansion of apical cochlear cells, contributing to the formation of the apical cochlear domain. SHH, in contrast, is required both for the induction and maintenance of apical identity. In the absence of FST or SHH, mice produce a short cochlea lacking its apical domain. This results in the loss of apex-specific anatomical and molecular properties and low-frequency-specific hearing loss.

Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts†.

The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.

A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.

Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

Group-Connected Impedance Network of RIS-Assisted Rate-Splitting Multiple Access in MU-MIMO Wireless Communication Systems.

The reconfigurable intelligent surface (RIS) and rate-splitting multiple access (RSMA) are considered as promising technologies for the beyond Fifth-Generation (B5G) and Sixth-Generation (6G) wireless systems by controlling the propagation environment, which attenuates the transmitted signal, and by managing the interference by splitting the user message into common and private messages. Because conventional RIS elements have each impedance connected to the ground, the sum-rate performance improvement of the RIS is limited. Therefore, the new RISs, which have impedance elements connected to each other, have been proposed recently. To be more adaptive to each channel, the optimization of the grouping of the RIS elements is required. Furthermore, since the solution of the optimal rate-splitting (RS) power-splitting ratio is complex, the value should be simply optimized to be more practical in the wireless system. In this paper, the grouping scheme of the RIS elements according to the user scheduling and the solution of the RS power-splitting ratio based on fractional programming (FP) are proposed. The simulation results showed that the proposed RIS-assisted RSMA system achieved a high sum-rate performance compared to the conventional RIS-assisted spatial-division multiple access (SDMA) system. Therefore, the proposed scheme can perform adaptively for the channel and has a flexible interference management. Furthermore, it can be a more suitable technique for B5G and 6G.

Performance of a Double RIS Communication System Aided by Partially Active Elements.

Reconfigurable intelligent surface (RIS) has emerged as a promising technology to enhance the spectral efficiency of wireless communication systems. However, if there are many obstacles between the RIS and users, a single RIS may not provide sufficient performance. For this reason, a double RIS-aided communication system is proposed in this paper. However, this system also has a problem: the signal is attenuated three times due to the three channels created by the double RIS. To overcome these attenuations, an active RIS is proposed in this paper. An active RIS is almost the same as a conventional RIS, except for the included amplifier. Comprehensively, the proposed system overcomes various obstacles and attenuations. In this paper, an active RIS is applied to the second RIS. To reduce the power consumption of active elements, a partially active RIS is applied. To optimize the RIS elements, the sum of the covariance matrix is found by using channels related to each RIS, and the right singular vector is exploited using singular value decomposition for the sum of the covariance matrix. Then, the singular value of the sum of the covariance value is checked to determine which element is the active element. Simulation results show that the proposed system has better sum rate performance compared to a single RIS system. Although it has a lower sum rate performance compared to a double RIS with fully active elements, the proposed system will be more attractive in the future because it has much better energy efficiency.

The Effect of Virtual Presence and Self-Efficacy on Nursing Students' Evaluation of Virtual Simulation Training.

The study aims to determine the effect of virtual simulation practice in nursing students using the Virtual Patient Learning System Evaluation (VPLSE) tool. The study uses descriptive research, centering on correlation and regression analysis. 295 nursing students in Grades 3 and 4 who have experienced virtual simulation practice within the past year were included. The main variables of VPLSE comprise four sub-domains: nursing knowledge improvement, clinical competency development, confidence in nursing performance, and nursing care plan application. In addition to the VPLSE, two other tools, measuring virtual presence and self-efficacy, were utilized. The VPLSE was significantly positively correlated with virtual presence and self-efficacy, respectively. The VPLSE subdomain of "clinical competency development" had a strong positive correlation with virtual presence. To increase the effect of virtual simulation education, it is necessary to maintain the advantages of virtual simulation practice, such as freedom from space and time, repeated learning, psychological stability and application of nursing plans.

Perioperative Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome Aggravated by Hepatopulmonary Syndrome in Deceased Donor Liver Transplantation: A Case Report.

Background: Extracorporeal membrane oxygenation (ECMO) is an accommodation of the cardiopulmonary bypass technique that can support gas exchange and hemodynamic stability. It is used as a salvage maneuver in patients with life-threatening respiratory or cardiac failure that does not respond to conventional treatment. There are few case reports of successful perioperative use of ECMO, especially preoperatively, in liver transplantation (LT). Here, we report an experience of successful anesthetic management in deceased donor liver transplantation (DDLT) by applying perioperative veno-venous (VV) ECMO support in the setting of acute respiratory distress syndrome (ARDS) aggravated by hepatopulmonary syndrome (HPS). Case: A 25-year-old female (156.0 cm, 65.0 kg), without any underlying disease, was referred to our emergency department for decreased mentality. Based on imaging and laboratory tests, she was diagnosed with acute liver failure of unknown cause combined with severe ARDS aggravated by HPS. Since the patient faced life-threatening hypoxemia with a failure of conventional ventilation maneuvers, preoperative VV ECMO was initiated and maintained during the operation. The patient remained hemodynamically stable throughout DDLT, and ARDS showed gradual improvement after the administration of VV ECMO. As ARDS improved, the patient's condition alleviated, and VV ECMO was weaned on postoperative day 6. Conclusions: This case demonstrates that VV ECMO may be a useful therapeutic option not only during the intraoperative and postoperative periods but also in the preoperative period for patients with liver failure combined with reversible respiratory failure.

Using metal substrates to enhance the reactivity of graphene towards Diels-Alder reactions.

The Diels-Alder (DA) reaction, a classic cycloaddition reaction involving a diene and a dienophile to form a cyclohexene, is among the most versatile organic reactions. Theories have predicted thermodynamically unfavorable DA reactions on pristine graphene owing to its low chemical reactivity. We hypothesized that metals like Ni could enhance the reactivity of graphene towards DA reactions through charge transfer. The results indeed showed that metal substrates enhanced the reactivity of graphene in the DA reactions with a diene, 2,3-dimethoxy butadiene (DMBD), and a dienophile, maleic anhydride (MAH), with the activity enhancement in the order of Ni > Cu, and both are more reactive than graphene supported on silicon wafer. The rate constants were estimated to be two times higher for graphene supported on Ni than on silicon wafer. The computational results support the experimentally obtained rate trend of Ni > Cu, both predicted to be greater than unsupported graphene, which is explained by the enhanced graphene-substrate interaction reflected in charge transfer effects with the strongly interacting Ni. This study opens up a new avenue for enhancing the chemical reactivity of pristine graphene through substrate selection.

Efficient User-Serving Scheme in the User-Centric Cell-Free Massive MIMO System.

A cell-free massive multiple input multiple output (MIMO) system is an attractive network model that is in the spotlight in 5G and future communication systems. Despite numerous advantages, the cell-free massive MIMO system has a problem in that it is difficult to operate in reality due to its vast amount of calculation. The user-centric cell-free massive MIMO model has a more feasible and scalable benefit than the cell-free massive MIMO model. However, this model has the disadvantage that as the number of users in the area increases, there are users who do not receive the service. In this paper, the proposed scheme creates connections for unserved users under a user-centric scheme without additional access point (AP) installation and disconnection for existing users. A downlink user-centric cell-free massive MIMO system model in which the APs are connected to the central processing unit (CPU) and the APs and users are geographically distributed is considered. First, the downlink spectral efficiency formula is derived and applied to the user-centric cell-free massive MIMO system. Then, the proposed scheme and power control algorithm are applied to the derived formula. The simulation results show that the unserved users within the area disappear by using the proposed scheme, while the bit error rate (BER) performance and sum rate improve compared to the existing scheme. In addition, it is shown that the proposed scheme works well even with a very large number of users in the area, and a significant service performance improvement for the worst 10% of users and the overall improvement of per-user throughput for the bottom 70% of users are ensured.