Impact of severe acute kidney injury on short-term mortality in urosepsis.

PURPOSE: To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis. METHODS: This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development. RESULTS: The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development. CONCLUSIONS: Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids.

Realizing the full potential of organoids and assembloids to model neural development and disease will require improved methods for long-term, minimally invasive recording of electrical activity. Current technologies, such as patch clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not allow chronic recording of organoids in suspension, which is necessary to preserve architecture. Inspired by kirigami art, we developed flexible electronics that transition from a two-dimensional to a three-dimensional basket-like configuration with either spiral or honeycomb patterns to accommodate the long-term culture of organoids in suspension. Here we show that this platform, named kirigami electronics (KiriE), integrates with and enables chronic recording of cortical organoids for up to 120 days while preserving their morphology, cytoarchitecture and cell composition. We demonstrate integration of KiriE with optogenetic and pharmacological manipulation and modeling phenotypes related to a genetic disease. Moreover, KiriE can capture corticostriatal connectivity in assembloids following optogenetic stimulation. Thus, KiriE will enable investigation of disease and activity patterns underlying nervous system assembly.

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids.

Organoids and assembloids have emerged as a promising platform to model aspects of nervous system development. Longterm, minimally-invasive recordings in these multi-cellular systems are essential for developing disease models. Current technologies, such as patch-clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not, however, allow chronic recording of organoids in suspension, which is necessary to preserve their architecture. Inspired by the art of kirigami, we developed flexible electronics that transition from a 2D pattern to a 3D basketlike configuration to accommodate the long-term culture of organoids in suspension. This platform, named kirigami electronics (KiriE), integrates with and enables chronic recording of cortical organoids while preserving morphology, cytoarchitecture, and cell composition. KiriE can be integrated with optogenetic and pharmacological stimulation and model disease. Moreover, KiriE can capture activity in cortico-striatal assembloids. Moving forward, KiriE could reveal disease phenotypes and activity patterns underlying the assembly of the nervous system.

Consciousness influences the enhancement of visual statistical learning in Zipfian distributions.

It has been reported that visual statistical learning (VSL) is facilitated in skewed distributions. However, it remains unclear whether enhancement of VSL in Zipfian distributions is due to consciousness of the regularities presented at high frequency. This study addressed this issue. We measured participants' subjective confidence in regularities and awareness of regularities during familiarization by combining a previously reported procedure for VSL with a postdecision wagering task and posttest questionnaire. The results demonstrated that Zipfian distribution enhanced not only VSL but also metacognitive sensitivity, particularly for high-frequency regularities, as the effects of consciousness on VSL were limited to high-frequency regularities. Moreover, the results indicated that awareness during familiarization mediated VSL enhancement in the Zipfian distribution. These results suggest that VSL for events with high-frequency regularities plays an important role in the cognition of events with low-frequency regularities via awareness. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Generating human neural diversity with a multiplexed morphogen screen in organoids.

Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells toward particular neural cell fates in vitro often relies upon combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and knowledge of the general principles of regional specification remain in-complete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Leveraging advances in multiplexed RNA sequencing technology and annotated single cell references of the human fetal brain we discovered that this screening approach generated considerable regional and cell type diversity across the neural axis. By deconvoluting morphogen-cell type relationships, we extracted design principles of brain region specification, including critical morphogen timing windows and combinatorics yielding an array of neurons with distinct neuro-transmitter identities. Tuning GABAergic neural subtype diversity unexpectedly led to the derivation of primate-specific interneurons. Taken together, this serves as a platform towards an in vitro morphogen atlas of human neural cell differentiation that will bring insights into human development, evolution, and disease.

Film measurement and analytical approach for assessing treatment accuracy and latency in a magnetic resonance-guided radiotherapy system.

PURPOSE: We measure the dose distribution of gated delivery for different target motions and estimate the gating latency in a magnetic resonance-guided radiotherapy (MRgRT) system. METHOD: The dose distribution accuracy of the gated MRgRT system (MRIdian, Viewray) was investigated using an in-house-developed phantom that was compatible with the magnetic field and gating method. This phantom contains a simulated tumor and a radiochromic film (EBT3, Ashland, Inc.). To investigate the effect of the number of beam switching and target velocity on the dose distribution, two types of target motions were applied. One is that the target was periodically moved at a constant velocity of 5 mm/s with different pause times (0, 1, 3, 10, and 20 s) between the motions. During different pause times, different numbers of beams were switched on/off. The other one is that the target was moved at velocities of 3, 5, 8, and 10 mm/s without any pause (i.e., continuous motion). The gated method was applied to these motions at MRIdian, and the dose distributions in each condition were measured using films. To investigate the relation between target motion and dose distribution in the gating method, we compared the results of the gamma analysis of the calculated and measured dose distributions. Moreover, we analytically estimated the gating latencies from the dose distributions measured using films and the gamma analysis results. RESULTS: The gamma pass rate linearly decreased with increasing beam switching and target velocity. The overall gating latencies of beam-hold and beam-on were 0.51 ± 0.17 and 0.35 ± 0.05 s, respectively. CONCLUSIONS: Film measurements highlighted the factors affecting the treatment accuracy of the gated MRgRT system. Our analytical approach, employing gamma analysis on films, can be used to estimate the overall latency of the gated MRgRT system.

Failure modes and effects analysis study for accelerator-based Boron Neutron Capture Therapy.

BACKGROUND: Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail. PURPOSE: The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system. METHODS: In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived. RESULTS: The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities. CONCLUSIONS: This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

Top-down effect of body representation on pain perception.

Many studies on body representation intend to change the perceived size, material, and structure of the body. However, whether the perception of a stimulus can be modified by manipulating body representation remains largely unexplored. Thus, the current study investigated the relationship between transparency of body representation and pain perception. Using augmented reality technology, we made the participants' limbs transparent and analyzed changes in body representation. Using a questionnaire, we confirmed that the participants perceived their limb as transparent. Simultaneously, their sense of ownership of the limb decreased, because they felt that it no longer belonged to their body. The participants were given an electrical stimulus to assess their subjective perception of pain intensity. An increase in limb opacity decreased the perception of pain, which, in turn, increased the feeling of transparency. These results suggested that the feeling of transparency in their limb favored the decrease in perceived pain. This effect was modified by body ownership, where high levels reinforced the analgesic effect. However, body ownership displayed a positive relationship with perceived pain. The study suggests that body transparency may constitute a strategy for decreasing refractory pain given that body ownership is retained at a high level.

Prognostic impact of eligibility for adjuvant immunotherapy in locally advanced urothelial cancer.

Objective: To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle-invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods: We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3-4 or pN+ without neoadjuvant chemotherapy and ypT2-4 or pN+ treated with neoadjuvant chemotherapy (trial-eligible group) or others (trial-ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease-free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results: The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty-two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI-positive status was significantly associated with poor prognosis among patients in the trial-eligible group. A very high risk (LVI+ or pN+ among the pT3-4 or ypT2-4) was significantly associated with poor prognosis. Conclusion: A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

Prognostic impact of proton pump inhibitors for immunotherapy in advanced urothelial carcinoma.

Objective: To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. Patients and methods: We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune-related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression-free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting-adjusted Cox regression analysis. Results: Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non-PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting-adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non-PPI users, whereas Abs use was not associated with poorer outcomes. Conclusion: The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.

ERK5 inhibitor BIX02189 attenuates methamphetamine-induced hyperactivity by modulating microglial activation in the striatum.

Extracellular signal-regulated protein kinase 5 (ERK5) has various physiological functions. However, the physiological role of ERK5 in the treatment of mice with an illicit drug such as methamphetamine (METH) remains unknown. We revealed that mice treated with METH showed hyperactivity, and increased p-ERK5 and Iba1 (a microglia marker) levels in the striatum. Additionally, these changes were inhibited by pretreatment with the ERK5 inhibitor BIX02189. The results suggest that METH-induced hyperactivity is associated with the activation of microglia via p-ERK5 in the striatum. Thus, the ERK5 pathway components in the central nervous system are potential therapeutic targets for preventing METH addiction.

Sulfobetaine polymers for effective permeability into multicellular tumor spheroids (MCTSs).

Multicellular tumor spheroids (MCTSs) are attractive for drug screening before animal tests because they emulate an in vivo microenvironment. The permeability of the MCTSs and tumor tissues towards the candidate drugs is not sufficient even though the drugs can penetrate monolayer cultured cells; therefore, nanocarriers are required to enhance permeability and deliver drugs. In this study, we prepared zwitterionic polymers of sulfobetaine methacrylates and (meth)acrylamides with or without hydroxy groups between the zwitterions to serve as highly permeable nanocarriers. In the sulfobetaine polymers, poly(2-hydroxy-3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate), P(OH-MAAmSB), the hydroxy group containing methacrylamide polymer exhibited little cytotoxicity and membrane translocation ability against monolayer cultured cells. Moreover, the excellent permeability of the hepatocyte MCTS enabled P(OH-MAAmSB) to permeate it and reach the center region (∼325 µm in diameter) at approximately 150 s, although poly(trimethyl-2-methacroyloxyethylammonium), a cationic polymer, penetrated just 1 to 2 layers from the periphery. The superior permeability of P(OH-MAAmSB) might be due to its good solubility and side chain conformation. P(OH-MAAmSB) is a promising nanocarrier with membrane translocation and permeability.

Engineering brain assembloids to interrogate human neural circuits.

The development of neural circuits involves wiring of neurons locally following their generation and migration, as well as establishing long-distance connections between brain regions. Studying these developmental processes in the human nervous system remains difficult because of limited access to tissue that can be maintained as functional over time in vitro. We have previously developed a method to convert human pluripotent stem cells into brain region-specific organoids that can be fused and integrated to form assembloids and study neuronal migration. In contrast to approaches that mix cell lineages in 2D cultures or engineer microchips, assembloids leverage self-organization to enable complex cell-cell interactions, circuit formation and maturation in long-term cultures. In this protocol, we describe approaches to model long-range neuronal connectivity in human brain assembloids. We present how to generate 3D spheroids resembling specific domains of the nervous system and then how to integrate them physically to allow axonal projections and synaptic assembly. In addition, we describe a series of assays including viral labeling and retrograde tracing, 3D live imaging of axon projection and optogenetics combined with calcium imaging and electrophysiological recordings to probe and manipulate the circuits in assembloids. The assays take 3-4 months to complete and require expertise in stem cell culture, imaging and electrophysiology. We anticipate that these approaches will be useful in deciphering human-specific aspects of neural circuit assembly and in modeling neurodevelopmental disorders with patient-derived cells.

Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: A multicenter analysis.

PURPOSE: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC). METHOD: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. RESULTS: The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR, 4.108; p = 0.0261) were independent factors associated with the OR of ATZ + BV treatment using RECIST. CONCLUSION: In real-world practice, ATZ + BV treatment might offer significant benefits in patients who meet B-IMbrave150 criteria or have low NLR.

Performance of a newly designed end-to-end phantom compatible with magnetic resonance-guided radiotherapy systems.

PURPOSE: In this study, we report on our proposed phantom based on the new end-to-end (E2E) methodology and its results. In addition, we verify whether the proposed phantom can replace conventional phantoms. METHODS: The hexagonal-shaped newly designed phantom has pockets on each side for a film dosimeter of size 80 × 90 mm2 , which is easily removable, considering the 60 Co penumbra. The new phantom comprises water, shell, and auxiliary shell phantoms. The shell and auxiliary shell materials are Solid Water HE. A mock tumor (aluminum oxide) was attached by a single prop in the water phantom and placed at the center of the new phantom. The results of a conventional E2E test were compared with those of the novel E2E test using the newly designed phantom. The irradiated film dosimeter in the novel E2E test was scanned in a flatbed scanner and analyzed using an in-house software developed with MATLAB. The irradiated field center, laser center, and mock tumor center were calculated. In the novel image-matching E2E (IM-E2E) test, image matching is performed by aligning the laser center with ruled lines. In the novel irradiation-field E2E (IF-E2E) test, the displacement of the irradiation-field center was defined as its distance from the laser center. In the composite E2E test, the overall displacement, which included the accuracy of the irradiated field and image matching, was defined as the distance between the irradiated field center and mock tumor center. In addition, using the newly designed phantom, the overall irradiation accuracy of the machine was evaluated by calculating the three-dimensional (3D) center of the irradiated field, phantom, and laser. The composite E2E test could be performed using the newly designed phantom only. RESULTS: In the IM-E2E test, the results of the conventional and novel IM-E2E tests were significantly different in each direction (left-right direction: p-value < < 0.05, anterior-posterior direction: p-value = 0.002, and superior-inferior direction: p-value = 0.002). The displacement directions were the same in both the conventional and novel IM-E2E tests. In the analysis of the IF-E2E test, no significant difference was evident between the results in each direction. Moreover, the displacement directions were the same in the conventional and novel IF-E2E tests, except for the left-right lateral direction of head three. In addition, the 3D analysis results of the novel IF-E2E test were less than 1 mm in all directions. In the analysis of the composite E2E test, the maximum displacement was 1.4 mm in all directions. In addition, almost all results of 3D analysis for the composite E2E test were less than 1 mm in all directions. CONCLUSION: The newly designed E2E phantom simplifies the E2E test for MRIdian, and is a possible alternative to the conventional E2E test. Furthermore, we can perform the previously unfeasible composite E2E tests that include the entire treatment process.

Gemella haemolysans inhibits the growth of the periodontal pathogen Porphyromonas gingivalis.

The oral microbiome plays an important role in the human microbial community and in maintaining the health of an individual. Imbalances in the oral microbiome may contribute to oral and systemic diseases. The progression of periodontal disease is closely related to the growth of bacteria, such as Porphyromonas gingivalis, in the oral cavity. However, the pathogen growth mechanism specific to periodontal disease remains unknown. This study aimed to identify bacteria associated with periodontal health by focusing on hemolytic bacteria. Unstimulated saliva samples were collected from ten periodontitis patients and five healthy subjects to detect and identify the presence of hemolytic bacteria. The saliva of healthy subjects contained a higher proportion of G. haemolysans than saliva samples from patients with periodontitis. Growth inhibition assays indicated that the protein components contained in the culture supernatant of G. haemolysans directly suppressed the growth of P. gingivalis. This study shows that the presence of G. haemolysans in saliva is associated with periodontal health and that it inhibits the growth of P. gingivalis in vitro.

Mapping human brain organoids on a spatial atlas.

Brain organoids are tridimensional, self-organizing cultures derived from pluripotent stem cells that recapitulate aspects of human neurodevelopment and can be applied toward investigating neural disease and evolution. In this issue of Cell Stem Cell, Fleck et al. (2021) describe a computational platform for mapping cell identity in organoids.

Cellulose Triacetate (CTA) Hollow-Fiber (HF) Membranes for Sustainable Seawater Desalination: A Review.

Cellulose triacetate (CTA)-based hollow fiber (HF) membrane is one of the commercially successful semipermeable membranes that has had a long progress since the time the excellent semi-permeable feature of cellulose-based polymers was found in 1957. Because of the reliable and excellent performances, especially for drinking water production from seawater, CTA-HFs have been widely used as reverse osmosis (RO) membranes, especially in arid regions. In this review, recent developments and research trends on CTA-HF membranes for seawater reverse osmosis (SWRO) plants were presented. A flux analytical model, an optimization strategy for chlorine injection without losing salt rejection performance, and a module of current high performance CTA RO membranes along with its plant operation data were updated in this paper. Furthermore, a newly developed CTA-HF membrane for brine concentration (BC) application (called BC membrane) was also addressed. Finally, RO/BC hybrid operation was introduced as an effective SWRO desalination technique that enables minimizing the volume of brine disposal from the RO plant by increasing the recovery ratio and the subsequent amount of produced freshwater, without an additional energy input.

Primate cell fusion disentangles gene regulatory divergence in neurodevelopment.

Among primates, humans display a unique trajectory of development that is responsible for the many traits specific to our species. However, the inaccessibility of primary human and chimpanzee tissues has limited our ability to study human evolution. Comparative in vitro approaches using primate-derived induced pluripotent stem cells have begun to reveal species differences on the cellular and molecular levels1,2. In particular, brain organoids have emerged as a promising platform to study primate neural development in vitro3-5, although cross-species comparisons of organoids are complicated by differences in developmental timing and variability of differentiation6,7. Here we develop a new platform to address these limitations by fusing human and chimpanzee induced pluripotent stem cells to generate a panel of tetraploid hybrid stem cells. We applied this approach to study species divergence in cerebral cortical development by differentiating these cells into neural organoids. We found that hybrid organoids provide a controlled system for disentangling cis- and trans-acting gene-expression divergence across cell types and developmental stages, revealing a signature of selection on astrocyte-related genes. In addition, we identified an upregulation of the human somatostatin receptor 2 gene (SSTR2), which regulates neuronal calcium signalling and is associated with neuropsychiatric disorders8,9. We reveal a human-specific response to modulation of SSTR2 function in cortical neurons, underscoring the potential of this platform for elucidating the molecular basis of human evolution.