[Academia-Industry Alliance: Recent Trend].

Industry-academia Collaboration is an academic activity within academia(educational institutions such as universities, research institutes, etc.)formed to research and develop new technologies, create new businesses and knowledge, and recruit outsourcing human resources. There is a collaboration between an industry(a private company, a group that engages in broad commercial activities and links research and development directly to economic activity)and academia. Amidst the dramatic changes in the environment surrounding the goals of research and development of new technologies and the creation of new businesses, there are changes in what academia can do complementarily. We will outline the changes and current situation, including the efforts of the Tohoku University Hospital.

Novel Virus Air Sampler Based on Electrostatic Precipitation and Air Sampling of SARS-CoV-2.

The assessment of airborne viruses in air is a critical step in the design of appropriate prevention and control measures. Hence, herein, we developed a novel wet-type electrostatic air sampler using a viral dissolution buffer containing a radical scavenging agent, and verified the concentration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the air of hospital rooms inhabiting coronavirus disease 2019 (COVID-19) patients and public areas. RNA damage caused by corona discharge was negligible when Buffer AVL was used as the collecting electrode. The viral RNA concentration in the air of the room varied by patient: 3.9 × 103 copy/m3 on the 10th day after onset in a mild case and 1.3 × 103 copy/m3 on the 18th day in a severe case. Viral RNA levels were 7.8 × 102 and 1.9 × 102 copy/m3 in the air of the office and food court, respectively, where people removed their masks when eating and talking, but it remained undetected in the station corridor where all the people were wearing masks. The assessment of airborne SARS-CoV-2 RNA using the proposed sampler can serve as a basis for the safe discontinuation of COVID-19 isolation precautions to identify exposure hotspots and alert individuals at increased infection risks.

Incidence of Chronic Subdural Hematoma after Mild Head Trauma in Elderly Patients with or without Pre-traumatic Conditioning of Anti-thrombotic Drugs.

Anti-thrombotic drugs may increase the risk for chronic subdural hematoma (CSDH). However, whether to continue or discontinue/counteract these drugs has not been investigated in patients with mild head trauma. CSDH incidence after mild head trauma, as well as the risk for CSDH in patients with anti-thrombotic drugs, were investigated in this study. The study included 765 consecutive elderly (>65 y.o.) patients with mild head trauma and an initial Glasgow Coma Scale (GCS) score of 14 or 15. All patients received initial CT within 24 hours after trauma and were re-examined 30 days after trauma to detect CSDH formation, repeating for every 30 days to examine symptomatic CSDH progression. Patients were divided into two groups, with anti-thrombotic drugs (n = 195) or without them (n = 263), to investigate the influence of pre-traumatic conditioning with anti-thrombotic drugs on CSDH. The whole sample was 458 out of 765 cases. The incidence of CSDH formation was 91 out of 458 cases (19.9%) after mild head trauma, with no significant difference between with and without anti-thrombotic drugs. CSDH progressed as symptomatic in 21 out of 458 cases (4.6%), with no significant difference between with and without anti-thrombotic drugs. Pre-traumatic conditioning with anti-thrombotic drugs and its continuation after trauma did not affect the incidence of formation or symptomatic progression of CSDH. This finding suggests that discontinuing and/or counteracting anti-thrombotic drugs may be unnecessary in patients with mild head trauma.

Piezo Actuator-Driven Pulsed Water Jet for Neurosurgery: Laboratory Evaluation with the Swine Model and Implications of Mechanical Properties.

Object Pulsed water jet is an emerging surgical instrumentation intended to achieve both maximal lesion resection and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The piezo actuator-driven pulsed water jet (ADPJ) is a new technology that can deliver a precisely controlled uniform and efficient pulsed water jet with minimum water flow. The present study evaluated the ADPJ system in preclinical animal studies in the swine brain, and investigated breaking strength, one of the parameters for mechanical properties, to elucidate the mechanism of tissue selectivity for tissue dissection by the water jet. Methods This system consisted of a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle (internal diameter: 0.15 mm). The water was supplied at 6 ml/min. The relationship between input voltage (3-25 V at 400 Hz) and peak pressure was measured using a pressure sensor through a sensing hole. Temporal profile of dissection depth during moving application was evaluated using gelatin brain phantom and swine brain. The dissected specimens were evaluated histologically. The mechanical property (breaking strength) of swine brain was measured by a compact table-top universal tester. Results Peak pressure increased linearly with increase in the input voltage, which reflected dissection depth in both the gelatin brain phantom and swine brain. Small arteries were preserved, and minimum damage to surrounding tissues occurred. The breaking strength of arachnoid membrane (0.12 ± 0.014 MPa) was significantly higher compared to gray matter (0.030 ± 0.010 MPa) and white matter (0.056 ± 0.009 MPa) (p < 0.05). The breaking strength of gray matter corresponded to that of 3 wt% gelatin, and that of white matter corresponded to a value between those of 3.5 and 4 wt% gelatin, and the dissection depth seemed to be estimated by 3-4 wt% gelatin. Conclusion The present study suggests that the ADPJ system has the potential to achieve accurate tissue dissection with preservation of blood vessels in neurosurgery. The difference in breaking strength may explain the tissue selectivity between brain parenchyma and tissue protected by the arachnoid membrane.

Totally Organic Hydrogel-Based Self-Closing Cuff Electrode for Vagus Nerve Stimulation.

An intrinsically soft organic electrode consisting of poly(3,4-ethylenedioxythiophene)-modified polyurethane (PEDOT-PU) is embedded into a bilayer film of polyvinyl alcohol (PVA) hydrogels for developing a self-closing cuff electrode for neuromodulation. The curled form of the PVA hydrogel is prepared by releasing internal stress in the bilayer structure. The inner diameter of the cuff electrode is set to less than 2 mm for immobilization to the vagus nerve (VN) of humans and pigs. The stability of the immobilization is examined, while the pressure applied to a nerve bundle is at a harmless level (≈200 Pa). Since the electrode is totally organic, MRI measurements can be conducted without image artifacts. The large electric capacitance of the PEDOT-PU (≈27 mF cm-2 ) ensures a safe stimulation of living tissues without Faradaic reactions. The practical performance of the cuff electrode for VN stimulation is demonstrated by observation of bradycardia induction in a pig.

Effectiveness of an actuator-driven pulsed water jet for removal of softened carious dentin.

The aim of this study was to assess the utility of an actuator-driven pulsed water jet (ADPJ) as a hardness-dependent carious dentin removal device by using different outputs. Thirty-six plane surface dental caries samples were treated with the ADPJ at 150, 200, and 250 voltage (12 teeth each). The Knoop hardness number (KHN) and Ca/P mass ratio were measured at 70 µm from the deepest point of the removing groove. Furthermore, three other teeth samples were manually treated with the ADPJ at the three above mentioned voltages (one tooth each) for 1 min. The KHN and Ca/P mass ratio were measured at 70 µm from the surface of the residual dentin part. In both the KHN and Ca/P mass ratio, higher residual dentin depended on the applied voltage of ADPJ. The ADPJ enabled the removal of softened carious dentin in an applied voltage-dependent manner.

Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator.

OBJECTIVE: We developed an actuator-driven pulsed water jet (ADPJ) device to achieve maximal lesion dissection with minimal risk of normal structural damage. Despite the unique dissection characteristics, there is a risk of dissemination of tissue dispersion; however, there is no established method to quantify the dispersion. Hence, this study aimed to assess the factors associated with dispersion and propose a simple experimental method using spectrophotometry to evaluate the degree of dispersion in a wet field. RESULTS: Methylene blue-stained brain phantom gelatin was immersed in a chamber with distilled water solution and dissected with an ADPJ. The dispersed gelatin solution was stirred and warmed to dissolve. The absorbance of the solution was measured spectrophotometrically. First, a reference standard curve was constructed to confirm the relationship between the absorbance and the amount of the dispersed gelatin. A clear proportional correlation was observed, which indicated that absorbance measurements can help evaluate the amount of dispersion. Using this method, we revealed that a high dissection force, insufficient suction, and inappropriate long distance between the nozzle tip and the target were associated with increased dispersion. This method might constitute a versatile and reliable approach to evaluate dispersion and aid in the development of surgical devices.

[Monitoring and Neurocritical Care of Severe Traumatic Brain Injury].

The main objectives of critical care of severe traumatic brain injury(TBI)are the prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure, and optimization of cerebral oxygenation. The critical care management of severe TBI will be discussed with a focus on the monitoring and avoidance or minimization of secondary brain insults, with emphasis on understanding the underlying physiology and pathophysiology. The evolution of critical care of severe traumatic brain injury will also be discussed along with the accumulating knowledge and experience.

Effect of endoscope flexibility on tissue dissection profile assessed with pulsed water jet device: ensuring safety, efficacy, and handling of thin devices for neuroendoscopic surgery.

OBJECTIVE: We developed an actuator-driven pulsed water jet device (ADPJ) for flexible neuroendoscopy to achieve effective tissue dissection with vasculature preservation. Although flexibility is a strong advantage for minimally invasiveness, the effect of the ductile curvature on the dissection profiles remains unknown. The purpose of this study was to clarify the impact of the curvature change of the ADPJ connecting tube on the dissection safety and efficacy. RESULTS: Three ADPJ connecting tubes with different inner diameters (1.0, 0.75, 0.5 mm) were used to dissect the brain phantom. They were bent at 3 angles: 0°, 60°, and 120°. The dissection profiles were evaluated using the mean depth and coefficient of variation (CV) for efficacy and safety, respectively.The larger inner diameter connecting tube dissected more deeply. The dissection depth was not changed regardless of the curvature degree in each tube. There was no significant difference in CVs regardless of inner diameter and curvature. The ductile curvature of the flexible neuroendoscope did not affect the efficacy and safety of the ADPJ dissection profile. Among the numerous instruments, tube-formed devices, including suction and injecting devices such as ADPJ, can be used safely and effectively without flexibility-related limitations.

Totally transparent hydrogel-based subdural electrode with patterned salt bridge.

A totally transparent subdural electrode was developed by embedding a conductive poly (vinyl alcohol) (PVA)-filled microchannel made of poly(dimethylsiloxane) (PDMS) into an another PVA hydrogel substrate. Tight bonding between the PVA substrate and the PDMS microchannel (salt bridge) was achieved by mechanical interlocking utilizing the microprotrusions formed on the microchannel. This simple method of bonding without the use of any additives such as silane molecules or nanofibers is very suitable for constructing biomedical devices. The salt bridge electrode (total thickness, ca. 1.5 mm) was sufficiently soft, and showed superior shape conformability that makes it an excellent choice as a subdural electrode used on the brain surface. In vivo measurement proved that the salt bridge electrode makes close contact to the exposed porcine brain and can record brain wave signals of frequencies 1 ~ 15 Hz. In addition, the high transparency of the electrode provided a clear view of the brain surface that would assist the effective surgical operation and optogenetic research.

Raman image-activated cell sorting.

The advent of image-activated cell sorting and imaging-based cell picking has advanced our knowledge and exploitation of biological systems in the last decade. Unfortunately, they generally rely on fluorescent labeling for cellular phenotyping, an indirect measure of the molecular landscape in the cell, which has critical limitations. Here we demonstrate Raman image-activated cell sorting by directly probing chemically specific intracellular molecular vibrations via ultrafast multicolor stimulated Raman scattering (SRS) microscopy for cellular phenotyping. Specifically, the technology enables real-time SRS-image-based sorting of single live cells with a throughput of up to ~100 events per second without the need for fluorescent labeling. To show the broad utility of the technology, we show its applicability to diverse cell types and sizes. The technology is highly versatile and holds promise for numerous applications that are previously difficult or undesirable with fluorescence-based technologies.

The effectiveness of an actuator-driven pulsed water jet for the removal of artificial dental calculus: a preliminary study.

BACKGROUND: While hand and ultrasonic scalers are the primary tools used for the removal of dental calculus in periodontal treatment, many studies have shown that they also damage the enamel surface. We have developed a novel actuator-driven pulsed water jet (ADPJ) system, which has the ability to selectively remove materials depending on their stiffness. Considering the different material properties between teeth and dental calculus, it might be possible to develop the ADPJ to remove dental calculus without damage to the tooth's enamel surface using a suitable jet pressure. Therefore, the aim of this study was to assess the effectiveness of the ADPJ in removing dental calculus, and the surface features of the teeth after its use. METHODS: A total of 93 artificial teeth coated with artificial dental calculus were examined in this study. The weights of 90 teeth were measured before and after the use of ADPJ, which had an applied voltage setting of 150, 200, or 240 V. The three remaining teeth were instrumented with a conventional hand scaler, ultrasonic scaler, or ADPJ (set at 240 V). Damage to the artificial tooth surfaces was evaluated using 5% Evans blue dye under an optical microscope. Furthermore, apatite pellets, which are utilized as experimental substitutes for natural teeth, were assessed after the use of ADPJ and both conventional scalers. RESULTS: The ADPJ significantly reduced the amount of artificial calculus, and the removal rate was dependent on the applied voltage. No damage was observed on the surface of the artificial tooth and apatite pellet following the use of ADPJ, in contrast to the conventional scalers. CONCLUSIONS: The results of this study demonstrate the in vitro effectiveness of ADPJ in the removal of dental calculus, without causing damage to tooth surfaces.

Intelligent image-activated cell sorting 2.0.

The advent of intelligent image-activated cell sorting (iIACS) has enabled high-throughput intelligent image-based sorting of single live cells from heterogeneous populations. iIACS is an on-chip microfluidic technology that builds on a seamless integration of a high-throughput fluorescence microscope, cell focuser, cell sorter, and deep neural network on a hybrid software-hardware data management architecture, thereby providing the combined merits of optical microscopy, fluorescence-activated cell sorting (FACS), and deep learning. Here we report an iIACS machine that far surpasses the state-of-the-art iIACS machine in system performance in order to expand the range of applications and discoveries enabled by the technology. Specifically, it provides a high throughput of ∼2000 events per second and a high sensitivity of ∼50 molecules of equivalent soluble fluorophores (MESFs), both of which are 20 times superior to those achieved in previous reports. This is made possible by employing (i) an image-sensor-based optomechanical flow imaging method known as virtual-freezing fluorescence imaging and (ii) a real-time intelligent image processor on an 8-PC server equipped with 8 multi-core CPUs and GPUs for intelligent decision-making, in order to significantly boost the imaging performance and computational power of the iIACS machine. We characterize the iIACS machine with fluorescent particles and various cell types and show that the performance of the iIACS machine is close to its achievable design specification. Equipped with the improved capabilities, this new generation of the iIACS technology holds promise for diverse applications in immunology, microbiology, stem cell biology, cancer biology, pathology, and synthetic biology.

Questionnaire survey on the prescription of renal replacement therapy for acute phase patients on maintenance dialysis who developed cerebrovascular disease.

BACKGROUND: There is limited information about acute phase renal replacement therapy (RRT) for maintenance hemodialysis patients after the onset of cerebrovascular disease. This study aimed to investigate which modality of renal replacement therapy is currently selected in practice. METHODS: We conducted a mail-based survey in 317 dialysis facilities that were certified by three academic societies that focus on dialysis, neurology, and neurosurgery in Japan. RESULTS: We received responses from 103 facilities (32.5%). In cases of cerebral infarction (CI) and intracerebral hemorrhage (ICH), more than 80% of the facilities selected only intermittent RRT, and 22.3% (CI)/8.7% (ICH) of the facilities selected intermittent HD which is the same setting in normal conditions. Although continuous hemodiafiltration and peritoneal dialysis are recommended in the Japanese guidelines, these were selected in only a few facilities: 16.5% and 0% in CI, 16.5% and 1% in ICH, respectively. RRT on the day of onset tended to be avoided, irrespective of the duration following the last HD session. Furthermore, physicians preferred to modify anticoagulants and reduce dialysis performance in the acute phase. CONCLUSION: This questionnaire survey uncovered a gap between guidelines and actual practice, even in hospitals accredited as educational facility, which is a novel and important finding. Further studies with larger sample sizes are needed to determine the optimal modality of RRT for the acute phase of cerebrovascular disease.

Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.

Author Correction: A practical guide to intelligent image-activated cell sorting.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Hydrogel-Based Organic Subdural Electrode with High Conformability to Brain Surface.

A totally soft organic subdural electrode has been developed by embedding an array of poly(3,4-ethylenedioxythiophene)-modified carbon fabric (PEDOT-CF) into the polyvinyl alcohol (PVA) hydrogel substrate. The mesh structure of the stretchable PEDOT-CF allowed stable structural integration with the PVA substrate. The electrode performance for monitoring electrocorticography (ECoG) was evaluated in saline solution, on ex vivo brains, and in vivo animal experiments using rats and porcines. It was demonstrated that the large double-layer capacitance of the PEDOT-CF brings low impedance at the frequency of brain wave including epileptic seizures, and PVA hydrogel substrate minimized the contact impedance on the brain. The most important unique feature of the hydrogel-based ECoG electrode was its shape conformability to enable tight adhesion even to curved, grooved surface of brains by just being placed. In addition, since the hydrogel-based electrode is totally organic, the simultaneous ECoG-fMRI measurements could be conducted without image artifacts, avoiding problems induced by conventional metallic electrodes.

Arterial blood pressure correlates with 90-day mortality in sepsis patients: a retrospective multicenter derivation and validation study using high-frequency continuous data.

OBJECTIVE: To identify the outcome of patients with sepsis using high-frequency blood pressure data. MATERIALS AND METHODS: This retrospective observational study was conducted at a university hospital ICU (derivation study) and at two urban hospitals (validation study) with data from adult sepsis patients who visited the centers during the same period. The area under the curve (AUC) of blood pressure falling below threshold was calculated. The predictive 90-day mortality (primary endpoint) area under threshold (AUT) and critical blood pressure were calculated as the maximum area under the curve of the receiver operating characteristic curve (AUCROC) and the threshold minus average AUT (derivation study), respectively. For the validation study, the derived 90-day mortality AUCROC (using critical blood pressure) was compared with Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and APACHE III. RESULTS: Derivation cohort (N = 137): the drop area from the mean blood pressure of 70 mmHg at 24-48 hours most accurately predicted 90-day mortality [critical blood pressure, 67.8 mmHg; AUCROC, 0.763; 95% confidence interval (CI), 0.653-0.890]. Validation cohort (N = 141): the 90-day mortality AUCROC (0.776) compared with the AUCROC for SOFA (0.711), SAPSII (0.771), APACHE II (0.745), and APACHE III (0.710) was not significantly different from the critical blood pressure 67.8 mmHg (P = 0.420). CONCLUSION: High-frequency arterial blood pressure data of the period and extent of blood pressure depression can be useful in predicting the clinical outcomes of patients with sepsis.

A practical guide to intelligent image-activated cell sorting.

Intelligent image-activated cell sorting (iIACS) is a machine-intelligence technology that performs real-time intelligent image-based sorting of single cells with high throughput. iIACS extends beyond the capabilities of fluorescence-activated cell sorting (FACS) from fluorescence intensity profiles of cells to multidimensional images, thereby enabling high-content sorting of cells or cell clusters with unique spatial chemical and morphological traits. Therefore, iIACS serves as an integral part of holistic single-cell analysis by enabling direct links between population-level analysis (flow cytometry), cell-level analysis (microscopy), and gene-level analysis (sequencing). Specifically, iIACS is based on a seamless integration of high-throughput cell microscopy (e.g., multicolor fluorescence imaging, bright-field imaging), cell focusing, cell sorting, and deep learning on a hybrid software-hardware data management infrastructure, enabling real-time automated operation for data acquisition, data processing, intelligent decision making, and actuation. Here, we provide a practical guide to iIACS that describes how to design, build, characterize, and use an iIACS machine. The guide includes the consideration of several important design parameters, such as throughput, sensitivity, dynamic range, image quality, sort purity, and sort yield; the development and integration of optical, microfluidic, electrical, computational, and mechanical components; and the characterization and practical usage of the integrated system. Assuming that all components are readily available, a team of several researchers experienced in optics, electronics, digital signal processing, microfluidics, mechatronics, and flow cytometry can complete this protocol in ~3 months.