Search

ObjectiveState-of-the-art invasive brain-machine interfaces (BMIs) have shown significant promise, but rely on external electronics and wired connections between the brain and these external components. This configuration presents health risks and limits practical use. These limitations can be addressed by designing a fully implantable BMI similar to existing FDA-approved implantable devices. Here, a prototype BMI system whose size and power consumption are comparable to those of fully implantable medical devices was designed and implemented, and its performance was tested at the benchtop and bedside.ApproachA prototype of a fully implantable BMI system was designed and implemented as a miniaturized embedded system. This benchtop analogue was tested in its ability to acquire signals, train a decoder, perform online decoding, wirelessly control external devices, and operate independently on battery. Furthermore, performance metrics such as power consumption were benchmarked.Main resultsAn analogue of a fully implantable BMI was fabricated with a miniaturized form factor. A patient undergoing epilepsy surgery evaluation with an electrocorticogram (ECoG) grid implanted over the primary motor cortex was recruited to operate the system. Seven online runs were performed with an average binary state decoding accuracy of 87.0% (lag optimized, or 85.0% at fixed latency). The system was powered by a wirelessly rechargeable battery, consumed  ∼150 mW, and operated for  >60 h on a single battery cycle.SignificanceThe BMI analogue achieved immediate and accurate decoding of ECoG signals underlying hand movements. A wirelessly rechargeable battery and other supporting functions allowed the system to function independently. In addition to the small footprint and acceptable power and heat dissipation, these results suggest that fully implantable BMI systems are feasible.

OBJECTIVE: State-of-the-art invasive brain-machine interfaces (BMIs) have shown significant promise, but rely on external electronics and wired connections between the brain and these external components. This configuration presents health risks and limits practical use. These limitations can be addressed by designing a fully implantable BMI similar to existing FDA-approved implantable devices. Here, a prototype BMI system whose size and power consumption are comparable to those of fully implantable medical devices was designed and implemented, and its performance was tested at the benchtop and bedside. APPROACH: A prototype of a fully implantable BMI system was designed and implemented as a miniaturized embedded system. This benchtop analogue was tested in its ability to acquire signals, train a decoder, perform online decoding, wirelessly control external devices, and operate independently on battery. Furthermore, performance metrics such as power consumption were benchmarked. MAIN RESULTS: An analogue of a fully implantable BMI was fabricated with a miniaturized form factor. A patient undergoing epilepsy surgery evaluation with an electrocorticogram (ECoG) grid implanted over the primary motor cortex was recruited to operate the system. Seven online runs were performed with an average binary state decoding accuracy of 87.0% (lag optimized, or 85.0% at fixed latency). The system was powered by a wirelessly rechargeable battery, consumed  ∼150 mW, and operated for  >60 h on a single battery cycle. SIGNIFICANCE: The BMI analogue achieved immediate and accurate decoding of ECoG signals underlying hand movements. A wirelessly rechargeable battery and other supporting functions allowed the system to function independently. In addition to the small footprint and acceptable power and heat dissipation, these results suggest that fully implantable BMI systems are feasible.

The retrosplenial cortex (RSP) is a complex brain region with multiple interconnected subregions that plays crucial roles in various cognitive functions, including memory, spatial navigation, and emotion. Understanding the afferent and efferent connectivity of the RSP is essential for comprehending the underlying mechanisms of its functions. Here, via viral tracing and fluorescence micro-optical sectioning tomography (fMOST), we systematically investigated the anatomical organisation of the upstream and downstream circuits of glutamatergic and GABAergic neurons in the dorsal and ventral RSP. The cortical connections of the RSP show laminar organisation in which the input neurons are distributed more in the deeper layers of the upstream cortex. Although different types of neurons have similar upstream circuits, GABAergic neurons show bidirectional connections with the hippocampus, whereas glutamatergic neurons only show unidirectional connections. Moreover, GABAergic neurons receive more inputs from the primary sensory cortex than from the prefrontal cortex and association cortex. The dorsal and ventral subregions have preferred circuits such that the dorsal RSP exhibits spatially topological connections with the dorsal visual cortex and lateral thalamus. The systematic study on long-range connections across RSP subregions and cell types may provide useful information for future revealing of RSP working mechanisms.Dissection of long-range circuits of the mouse intermediate retrosplenial cortex reveals preferred circuits of glutamatergic and GABAergic neurons and spatially topological connections in dorsal and ventral subregions. [ABSTRACT FROM AUTHOR]

Preeclampsia is characterized by insufficient invasion of extravillous trophoblasts and is a consequence of failed adaption of extravillous trophoblasts to changes in the intrauterine environment developing embryo. Specific miRNAs are implicated in the development of preeclampsia (PE). miR-455-5p is present at low levels in PE but its role is not known. Combining cell and molecular biology methods, we provide evidence of the function and mechanism of miR-455-5p action, and identify its potential target, Shc3, in PE. In vitro, when miR-455-5p was overexpressed in HTR-8/SVneo cells they migrated and invaded more rapidly under hypoxia/reoxygenation (H/R) than in either hypoxic or normoxic conditions. In contrast, apoptosis of HTR-8/SVneo was reduced in H/R. Shc3 was identified as a direct downstream target gene of miR-455-5p. Overexpression of Shc3 reversed the effect of miR-455-5p, promoting apoptosis and suppressing invasion and migration of HTR-8/SVneo under H/R. Shc3 was highly expressed in H/R, but its level was reduced in isolated hypoxic or normoxic environments. Furthermore, we showed Shc3 overexpression is involved in placental inflammation and angiogenesis inhibition. Finally, we showed that the downregulation of miR-455-5p in PE contributes to increased Shc3 in extravillous trophoblasts, thereby limiting extravillous trophoblast cell invasion. Elevated Shc3 is associated with placental inflammation and angiogenesis inhibition. Thus Shc3 serves as a potential biomarker for PE diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Mandarin fish ranavirus (MRV) is a distinctive member among the genus Ranavirus of the family Iridoviridae. The persistently covert infection of MRV was previously observed in a natural outbreak of MRV, but the underlying mechanism remains unclear. Here, we show that mandarin fish peripheral B lymphocytes are implemented as viral reservoirs to maintain the persistent infection. When mandarin fish were infected with a sublethal dosage of MRV under a nonpermissive temperature (19 °C) and a permissive temperature (26 °C), all of the fish in the 19 °C group survived and entered the persistent phase of infection, characterized by a very low viral load in white blood cells, whereas some of the fish died of MRV infection in the 26 °C group, and the survival fish then initiated a persistent infection status. Raising the temperature, vaccination and dexamethasone treatment can reactivate the quiescent MRV to replicate and result in partial mortality. The viral reservoir investigation showed that IgM+-labeled B lymphocytes, but not CD3Δ+-labeled T lymphocytes and MRC-1+-labeled macrophages, are target cells for the persistent infection of MRV. Moreover, the reactivation of the quiescent MRV was confirmed through a non-TLR5 signal pathway manner. Collectively, we demonstrate the presence of the B cell-dependent persistent infection of ranavirus, and provide a new clue for better understanding the complex infection mechanism of vertebrate iridovirus. [ABSTRACT FROM AUTHOR]

Background Social app recruiting–based and peer-led testing strategies have been proven effective in increasing human immunodeficiency virus (HIV) testing among men who have sex with men (MSM), though their combination remains underevaluated. We aimed to assess the efficiency of a combined strategy named "standardly trained peer volunteer–led, social app recruiting–based HIV testing strategy using rapid testing kits" (SPARK). Methods Between March 2020 and December 2021, 177 trained peer volunteers tested 7256 eligible MSM testers. Volunteers primarily recruited testers to undergo HIV testing and counseling in social apps. Volunteers tested testers with HIV rapid antibody tests and interviewed testers while waiting for the results. Moreover, HIV testing data from other testing strategies, both pre- and postimplementation of SPARK, were collected to evaluate the capacity of SPARK to increase HIV testing. Results During this study, MSM testers underwent 10 441 HIV tests; HIV testing volume increased 3-fold from 2020 to 2021. On average, each volunteer recruited 40.99 testers and facilitated 58.99 HIV tests. After SPARK implementation, HIV tests in 2021 increased 1-fold compared with those in 2019; especially for rural MSM testers, the number of HIV tests performed in 2020 and 2021 increased to 2.86 and 5.85 times, respectively, that in 2019. In spatial analysis, most testers sought geographical proximity volunteers for testing; similarly, most testers recruited were from volunteers' own or nearby districts. More than 60% of HIV tests were performed outside of working hours on weekdays, regardless of whether the testers came from urban, periurban, or rural areas. Conclusions SPARK, an MSM-friendly, geographically accessible, and time-flexible testing strategy, has the potential to promote HIV testing among MSM. [ABSTRACT FROM AUTHOR]

Simple Summary: The adherent and suspension cell culture methods have their own advantages. Adherent culture involves both straightforward steps and inexpensive consumables, and the even spread of cells on the substrate facilitates clear observation of the cell morphology, growth status, and cytopathic effects using a microscope. By comparison, the ability to form a high-density cell population and the ease of scaling up make suspension culture valuable for industrial production, such as vaccine development, bio-pharmaceutical manufacture, medicine screening, and food production. However, very few cell lines can grow in suspension naturally, and the typical commercially used suspension cell culture systems are all mammalian in origin, making them not suitable for a lot of aquatic cases. To meet the needs of aquatic industries, a new ES culture system of aquatic origin was developed through explant outgrowth and enzyme-digesting passaging. The ES cells can adapt to suspension growth naturally and conduct transformation reversibly between the adherent and suspension modes. This culture model was confirmed to be susceptible to different fatal aquatic viruses and suitable for gene engineering as well. As a suspension culture system with no need for microcarriers and special additives, ES cells may be useful for the development of new aquatic serum-free production systems in a bioreactor or become a promising tool for the aquatic vaccine industry. Suspension growth can greatly increase the cell density and yield of cell metabolites. To meet the requirements of aquatic industries, a culture model derived from Anguilla anguilla skin was developed using the explant outgrowth and enzyme-digesting passaging methods. These cells were kept in vitro continuously for over 12 months and subcultured 68 times. This heteroploid cell line, designated as ES, can naturally adapt to adherent and suspension growth reversibly under certain temperatures, serum percentages, and inoculum densities, without the need for any microcarriers or special medium additives. The ES cells can continue being highly productive under a temperature range of 15–37 °C and a serum percentage ranging from 3 to 15%. An inoculum density higher than 5 × 105 cells·mL−1 is necessary for the ES cells to turn into suspension efficiently. The green fluorescent protein (GFP) reporter gene was successfully expressed in the ES cells. The ES cells demonstrated susceptibility to Anguillid herpesvirus (AngHV) and red-spotted grouper nervous necrosis virus (RGNNV). ES is the first natural suspension growth model of aquatic origin; it does not require the processes of suspension domestication and carrier dissolution, making it a promising and cost-effective model for vaccine production, bio-pharmaceutical manufacturing, and cellular agriculture. [ABSTRACT FROM AUTHOR]

Motivation Neuroscientists have long endeavored to map brain connectivity, yet the intricate nature of brain networks often leads them to concentrate on specific regions, hindering efforts to unveil a comprehensive connectivity map. Recent advancements in imaging and text mining techniques have enabled the accumulation of a vast body of literature containing valuable insights into brain connectivity, facilitating the extraction of whole-brain connectivity relations from this corpus. However, the diverse representations of brain region names and connectivity relations pose a challenge for conventional machine learning methods and dictionary-based approaches in identifying all instances accurately. Results We propose BioSEPBERT, a bio medical pre-trained model based on s tart- e nd position p ointers and BERT. In addition, our model integrates specialized identifiers with enhanced self-attention capabilities for preceding and succeeding brain regions, thereby improving the performance of named entity recognition and relation extraction in neuroscience. Our approach achieves optimal F1 scores of 85.0%, 86.6%, and 86.5% for named entity recognition, connectivity relation extraction, and directional relation extraction, respectively, surpassing state-of-the-art models by 2.6%, 1.1%, and 1.1%. Furthermore, we leverage BioSEPBERT to extract 22.6 million standardized brain regions and 165 072 directional relations from a corpus comprising 1.3 million abstracts and 193 100 full-text articles. The results demonstrate that our model facilitates researchers to rapidly acquire knowledge regarding neural circuits across various brain regions, thereby enhancing comprehension of brain connectivity in specific regions. Availability and implementation Data and source code are available at: http://atlas.brainsmatics.org/res/BioSEPBERT and https://github.com/Brainsmatics/BioSEPBERT. [ABSTRACT FROM AUTHOR]

Abstract Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (

While prior noninvasive (e.g., electroencephalographic) studies suggest that the human primary motor cortex (M1) is active during gait processes, the limitations of noninvasive recordings make it impossible to determine whether M1 is involved in high-level motor control (e.g., obstacle avoidance, walking speed), low-level motor control (e.g., coordinated muscle activation), or only nonmotor processes (e.g., integrating/relaying sensory information). This study represents the first invasive electroneurophysiological characterization of the human leg M1 during walking. Two subjects with an electrocorticographic grid over the interhemispheric M1 area were recruited. Both exhibited generalized γ-band (40-200 Hz) synchronization across M1 during treadmill walking, as well as periodic γ-band changes within each stride (across multiple walking speeds). Additionally, these changes appeared to be of motor, rather than sensory, origin. However, M1 activity during walking shared few features with M1 activity during individual leg muscle movements, and was not highly correlated with lower limb trajectories on a single channel basis. These findings suggest that M1 primarily encodes high-level gait motor control (i.e., walking duration and speed) instead of the low-level patterns of leg muscle activation or movement trajectories. Therefore, M1 likely interacts with subcortical/spinal networks, which are responsible for low-level motor control, to produce normal human walking.

Bi-directional brain-computer interfaces (BCIs) require simultaneous stimulation and recording to achieve closed-loop operation. It is therefore important that the interface be able to distinguish between neural signals of interest and stimulation artifacts. Current bi-directional BCIs address this problem by temporally multiplexing stimulation and recording. This approach, however, is suboptimal in many BCI applications. Alternative artifact mitigation methods can be devised by investigating the mechanics of artifact propagation. To characterize stimulation artifact behaviors, we collected and analyzed electrocorticography (ECoG) data from eloquent cortex mapping. Ratcheting and phase-locking of stimulation artifacts were observed, as well as dipole-like properties. Artifacts as large as ±1,100 μV appeared as far as 15-37 mm away from the stimulating channel when stimulating at 10 mA. Analysis also showed that the majority of the artifact power was concentrated at the stimulation pulse train frequency (50 Hz) and its super-harmonics (100, 150, 200 Hz). Lower frequencies (0-32 Hz) experienced minimal artifact contamination. These findings could inform the design of future bi-directional ECoG-based BCIs.

ObjectiveTo observe the duration of anesthesia in C57BL/6J mice anesthetized using different doses of Zoletil combined with serazine hydrochloride to provide an effective reference for all types of mouse surgery and related experimental design.MethodsOne hundred C57BL/6J mice (half male and female) were randomly divided into five groups, with 20 mice (half male and female) in each group. The mice in the four groups were intraperitoneally injected with 55 mg/kg Zoletil and 13.75 mg/kg serazine hydrochloride, 65 mg/kg Zoletil and 16.25 mg/kg serazine hydrochloride, 75 mg/kg Zoletil and 18.75 mg/kg serazine hydrochloride, or 85 mg/kg Zoletil and 21.25 mg/kg serazine hydrochloride, respectively. After the righting reflex stopped, one drop (about 20 µL) was injected into each eye, and the mice were placed on a heat preservation pad. Mice in the control group were intraperitoneally injected with 200 μL normal saline. Differences in the anesthesia induction time, maintenance time, and awakening time were observed and compared. The mice were fed for one day after anesthesia; serum was collected, and liver and kidney function indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA) were determined using Hitachi 7080 automatic biochemical analyzer.ResultsThe success rate of anesthesia in C57BL/6J mice treated with Zoletil combined with serazine hydrochloride was 100%. When the anesthetic dose was 55-75 mg/kg, the anesthesia was induced quickly and safely, and the anesthetic effect was good. The duration of anesthesia was proportional to the injection dose of Zoletil (r2 = 0.827 in male mice, r2 =0.841 in female mice, both P < 0.01), and the induction time was inversely proportional to the injection dose (r2 =0.432 in male mice, r2=0.410 in female mice, both P < 0.05). However, there was no significant difference in liver and kidney function between the groups and the control group (P＞0.05).ConclusionAnesthetizing C57BL/6J mice with Zoletil combined with serazine hydrochloride is a reliable and stable method, and the duration of anesthesia can be controlled by adjusting the dosage.