Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

In Vivo Reprogramming Using Yamanaka Factors in the CNS: A Scoping Review.

Central nervous system diseases, particularly neurodegenerative disorders, pose significant challenges in medicine. These conditions, characterized by progressive neuronal loss, have remained largely incurable, exacting a heavy toll on individuals and society. In recent years, in vivo reprogramming using Yamanaka factors has emerged as a promising approach for central nervous system regeneration. This technique involves introducing transcription factors, such as Oct4, Sox2, Klf4, and c-Myc, into adult cells to induce their conversion into neurons. This review summarizes the current state of in vivo reprogramming research in the central nervous system, focusing on the use of Yamanaka factors. In vivo reprogramming using Yamanaka factors has shown promising results in several animal models of central nervous system diseases. Studies have demonstrated that this approach can promote the generation of new neurons, improve functional outcomes, and reduce scar formation. However, there are still several challenges that need to be addressed before this approach can be translated into clinical practice. These challenges include optimizing the efficiency of reprogramming, understanding the cell of origin for each transcription factor, and developing methods for reprogramming in non-subventricular zone areas. Further research is needed to overcome the remaining challenges, but this approach has the potential to revolutionize the way we treat central nervous system disorders.

Deep learning models to predict the editing efficiencies and outcomes of diverse base editors.

Applications of base editing are frequently restricted by the requirement for a protospacer adjacent motif (PAM), and selecting the optimal base editor (BE) and single-guide RNA pair (sgRNA) for a given target can be difficult. To select for BEs and sgRNAs without extensive experimental work, we systematically compared the editing windows, outcomes and preferred motifs for seven BEs, including two cytosine BEs, two adenine BEs and three C•G to G•C BEs at thousands of target sequences. We also evaluated nine Cas9 variants that recognize different PAM sequences and developed a deep learning model, DeepCas9variants, for predicting which variants function most efficiently at sites with a given target sequence. We then develop a computational model, DeepBE, that predicts editing efficiencies and outcomes of 63 BEs that were generated by incorporating nine Cas9 variants as nickase domains into the seven BE variants. The predicted median efficiencies of BEs with DeepBE-based design were 2.9- to 20-fold higher than those of rationally designed SpCas9-containing BEs.

γ-Ray Irradiation Enables Annealing- and Light-Soaking-Free Solution Processable SnO2 Electron Transport Layer for Inverted Organic Solar Cells.

The electrode buffer layer is crucial for high-performance and stable OSCs, optimizing charge transport and energy level alignment at the interface between the polymer active layer and electrode. Recently, SnO2 has emerged as a promising material for the cathode buffer layer due to its desirable properties, such as high electron mobility, transparency, and stability. Typically, SnO2 nanoparticle layers require a postannealing treatment above 150°C in an air environment to remove the surfactant ligands and obtain high-quality thin films. However, this poses challenges for flexible electronics as flexible substrates can't tolerate temperatures exceeding 100°C. This study presents solution-processable and annealing-free SnO2 nanoparticles by employing y-ray irradiation to disrupt the bonding between surfactant ligands and SnO2 nanoparticles. The SnO2 layer treated with y-ray irradiation is used as an electron transport layer in OSCs based on PTB7-Th:IEICO-4F. Compared to the conventional SnO2 nanoparticles that required high-temperature annealing, the y-SnO2 nanoparticle-based devices exhibit an 11% comparable efficiency without postannealing at a high temperature. Additionally, y-ray treatment has been observed to eliminate the light-soaking effect of SnO2 . By eliminating the high-temperature postannealing and light-soaking effect, y-SnO2 nanoparticles offer a promising, cost-effective solution for future flexible solar cells fabricated using roll-to-roll mass processing.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Asymmetric TMO-Metal-TMO Structure for Enhanced Efficiency and Long-Term Stability of Si-Based Heterojunction Solar Cells.

In this study, we fabricated Si-based heterojunction solar cells (HSCs) with an asymmetric TMO-metal-TMO (TMT) structure using both MoO3 and V2O5 as the hole-selective contacts. Our HSCs offer enhanced long-term stability and effective passivation for crystal defects on the Si sur-face. We analyzed the oxygen vacancy state and surface morphology of the MoO3- and V2O5-TMO thin films using X-ray photoelectron spectroscopy and atomic force microscopy to investigate their passivation characteristics for Si surface defects. From the measured minority carrier lifetime, V2O5 revealed a highly improved lifetime (590 µs) compared to that of MoO3 (122.3 µs). In addition, we evaluated the long-term stability of each TMO thin film to improve the operation stability of the HSCs. We deposited different types of TMOs as the top- and bottom-TMO layers and assessed the effect of the thickness of each TMO layer. The fabricated asymmetric TMT/Si HSCs showed noticeable improvements in efficiency (7.57%) compared to 6.29% for the conventional symmetric structure which used the same TMO material for both the top and bottom layers. Furthermore, in terms of long-term stability, the asymmetric TMT/Si HSCs demonstrated an efficiency that was 250% higher than that of symmetric TMT/Si HSCs, as determined via power conversion efficiency degradation over 2000 h which is mainly attributed by the lower oxygen vacancy of the top-TMO, V2O5. These results suggest that the asymmetric TMT structure is a promising approach for the fabrication of low-cost and high-efficiency Si-based HSCs with enhanced long-term stability.

InZnTiON Channel Layer for Highly Stable Thin-Film Transistors and Light-Emitting Transistors.

In this study, we incorporated TiN as a carrier suppressor into an amorphous InZnO channel to achieve stable channels for thin-film transistors (TFTs) and light-emitting transistors (LETs). The low electronegativity and standard electrode potential of the Ti dopant led to a reduction in the number of oxygen vacancies in the InZnO channel. Moreover, the substitution of nitrogen into the oxygen sites of InZnO effectively decreased the excess electrons. As a result, the cosputtering of the TiN dopant resulted in a decrease in the carrier concentration of the InZnO channel, serving as an effective carrier suppressor. Due to the distinct structures of TiN and InZnO, the TiN-doped InZnO channel exhibited a completely amorphous structure and a featureless surface morphology. The presence of oxygen vacancies in the InZnO channel creates trap states for electrons and holes. Consequently, the TFT with the InZnTiON channel demonstrated an improved subthreshold swing and enhanced stability during the gate bias stress test. Furthermore, the threshold voltage shift (ΔVth) changed from 3.29 to 0.86 V in the positive bias stress test and from -0.92 to -0.09 V in the negative bias stress test. Additionally, we employed an InZnTiON channel in LETs as a substitute for organic semiconductors. The reduction in the number of oxygen vacancies effectively prevented exciton quenching caused by hole traps within the vacancies. Consequently, appropriate TiN doping in the InZnO channel enhanced the intensity of the LET devices.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Massively parallel evaluation and computational prediction of the activities and specificities of 17 small Cas9s.

Recently, various small Cas9 orthologs and variants have been reported for use in in vivo delivery applications. Although small Cas9s are particularly suited for this purpose, selecting the most optimal small Cas9 for use at a specific target sequence continues to be challenging. Here, to this end, we have systematically compared the activities of 17 small Cas9s for thousands of target sequences. For each small Cas9, we have characterized the protospacer adjacent motif and determined optimal single guide RNA expression formats and scaffold sequence. High-throughput comparative analyses revealed distinct high- and low-activity groups of small Cas9s. We also developed DeepSmallCas9, a set of computational models predicting the activities of the small Cas9s at matched and mismatched target sequences. Together, this analysis and these computational models provide a useful guide for researchers to select the most suitable small Cas9 for specific applications.

Discovery of a Small-Molecule Inhibitor Targeting the Androgen Receptor N-Terminal Domain for Castration-Resistant Prostate Cancer.

The current mainstay therapeutic strategy for advanced prostate cancer is to suppress androgen receptor (AR) signaling. However, castration-resistant prostate cancer (CRPC) invariably arises with restored AR signaling activity. To date, the AR ligand-binding domain (LBD) is the only targeted region for all clinically available AR signaling antagonists, such as enzalutamide (ENZ). Major resistance mechanisms have been uncovered to sustain the AR signaling in CRPC despite these treatments, including AR amplification, AR LBD mutants, and the emergence of AR splice variants (AR-Vs) such as AR-V7. AR-V7 is a constitutively active truncated form of AR that lacks the LBD; thus, it can not be inhibited by AR LBD-targeting drugs. Therefore, an approach to inhibit AR through the regions outside of LBD is urgently needed. In this study, we have discovered a novel small molecule SC428, which directly binds to the AR N-terminal domain (NTD) and exhibits pan-AR inhibitory effect. SC428 potently decreased the transactivation of AR-V7, ARv567es, as well as full-length AR (AR-FL) and its LBD mutants. SC428 substantially suppressed androgen-stimulated AR-FL nuclear translocation, chromatin binding, and AR-regulated gene transcription. Moreover, SC428 also significantly attenuated AR-V7-mediated AR signaling that does not rely on androgen, hampered AR-V7 nuclear localization, and disrupted AR-V7 homodimerization. SC428 inhibited in vitro proliferation and in vivo tumor growth of cells that expressed a high level of AR-V7 and were unresponsive to ENZ treatment. Together, these results indicated the potential therapeutic benefits of AR-NTD targeting for overcoming drug resistance in CRPC.

DNA double-strand break-free CRISPR interference delays Huntington's disease progression in mice.

Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. CRISPR-Cas9 nuclease causes double-strand breaks (DSBs) in the targeted DNA that induces toxicity, whereas CRISPR interference (CRISPRi) using dead Cas9 (dCas9) suppresses the target gene expression without DSBs. Delivery of dCas9-sgRNA targeting CAG repeat region does not damage the targeted DNA in HEK293T cells containing CAG repeats. When this study investigates whether CRISPRi can suppress mutant HTT (mHTT), CRISPRi results in reduced expression of mHTT with relative preservation of the wild-type HTT in human HD fibroblasts. Although both dCas9 and Cas9 treatments reduce mHTT by sgRNA targeting the CAG repeat region, CRISPRi delays behavioral deterioration and protects striatal neurons against cell death in HD mice. Collectively, CRISPRi can delay disease progression by suppressing mHtt, suggesting DNA DSB-free CRISPRi is a potential therapy for HD that can compensate for the shortcoming of CRISPR-Cas9 nuclease.

Stoichiometry and Morphology Analysis of Thermally Deposited V2O5-x Thin Films for Si/V2O5-x Heterojunction Solar Cell Applications.

In recent decades, dopant-free Si-based solar cells with a transition metal oxide layer have gained noticeable research interest as promising candidates for next-generation solar cells with both low manufacturing cost and high power conversion efficiency. Here, we report the effect of the substrate temperature for the deposition of vanadium oxide (V2O5-x, 0 ≤ X ≤ 5) thin films (TFs) for enhanced Si surface passivation. The effectiveness of SiOx formation at the Si/V2O5-x interface for Si surface passivation was investigated by comparing the results of minority carrier lifetime measurements, X-ray photoelectron spectroscopy, and atomic force microscopy. We successfully demonstrated that the deposition temperature of V2O5-x has a decisive effect on the surface passivation performance. The results confirmed that the aspect ratio of the V2O5-x islands that are initially deposited is a crucial factor to facilitate the transport of oxygen atoms originating from the V2O5-x being deposited to the Si surface. In addition, the stoichiometry of V2O5-x TFs can be notably altered by substrate temperature during deposition. As a result, experimentation with the fabricated Si/V2O5-x heterojunction solar cells confirmed that the power conversion efficiency is the highest at a V2O5-x deposition temperature of 75 °C.

The Rab GTPase activating protein TBC-2 regulates endosomal localization of DAF-16 FOXO and lifespan.

FOXO transcription factors have been shown to regulate longevity in model organisms and are associated with longevity in humans. To gain insight into how FOXO functions to increase lifespan, we examined the subcellular localization of DAF-16 in C. elegans. We show that DAF-16 is localized to endosomes and that this endosomal localization is increased by the insulin-IGF signaling (IIS) pathway. Endosomal localization of DAF-16 is modulated by endosomal trafficking proteins. Disruption of the Rab GTPase activating protein TBC-2 increases endosomal localization of DAF-16, while inhibition of TBC-2 targets, RAB-5 or RAB-7 GTPases, decreases endosomal localization of DAF-16. Importantly, the amount of DAF-16 that is localized to endosomes has functional consequences as increasing endosomal localization through mutations in tbc-2 reduced the lifespan of long-lived daf-2 IGFR mutants, depleted their fat stores, and DAF-16 target gene expression. Overall, this work identifies endosomal localization as a mechanism regulating DAF-16 FOXO, which is important for its functions in metabolism and aging.

Photovoltaic Device Application of a Hydroquinone-Modified Conductive Polymer and Dual-Functional Molecular Si Surface Passivation Technology.

In the last decades, the conductive polymer PEDOT:PSS has been introduced in Si-based hybrid solar cells, gaining noticeable research interest and being considered a promising candidate for next generation solar cells which can achieve both of low manufacturing cost and high power conversion efficiency. This study succeeded in improving the electrical conductivity of PEDOT:PSS to 937 S/cm through a simple process of adding hydroquinone (HQ) to the pristine PEDOT:PSS solution. The results also showed that the addition of HQ to PEDOT:PSS(HQ-PEDOT:PSS) could not only dramatically improve the conductivity but also well-sustain the work function characteristics of PEDOT:PSS by promoting the formation of more continuous conductive-PEDOT channels without removing the insulating PSS. In this report, we reveal that the application of the HQ-PEDOT:PSS to the Si/PEDOT:PSS HSC could significantly improve the short-circuit current and open-circuit voltage characteristics to increase the power conversion efficiency of the HSCs compared to the conventional approaches. Moreover, we also treated the Si surface with the organic monomer, benzoquinone (BQ) to (1) passivate the excess Si surface defect states and (2) to improve the properties of the Si/PEDOT:PSS interface. We show that BQ treatment is able to dramatically increase the minority carrier lifetime induced by effective chemical and field-effect passivation in addition to enhancing the wettability of the Si surface with the PEDOT:PSS solution. As a result, the power conversion efficiency was increased by 10.6% by introducing HQ and BQ into the fabrication process of the Si/PEDOT:PSS HSC.

Application of prime editing to the correction of mutations and phenotypes in adult mice with liver and eye diseases.

The use of prime editing-a gene-editing technique that induces small genetic changes without the need for donor DNA and without causing double strand breaks-to correct pathogenic mutations and phenotypes needs to be tested in animal models of human genetic diseases. Here we report the use of prime editors 2 and 3, delivered by hydrodynamic injection, in mice with the genetic liver disease hereditary tyrosinemia, and of prime editor 2, delivered by an adeno-associated virus vector, in mice with the genetic eye disease Leber congenital amaurosis. For each pathogenic mutation, we identified an optimal prime-editing guide RNA by using cells transduced with lentiviral libraries of guide-RNA-encoding sequences paired with the corresponding target sequences. The prime editors precisely corrected the disease-causing mutations and led to the amelioration of the disease phenotypes in the mice, without detectable off-target edits. Prime editing should be tested further in more animal models of genetic diseases.

In vivo gene editing via homology-independent targeted integration for adrenoleukodystrophy treatment.

Adrenoleukodystrophy (ALD) is caused by various pathogenic mutations in the X-linked ABCD1 gene, which lead to metabolically abnormal accumulations of very long-chain fatty acids in many organs. However, curative treatment of ALD has not yet been achieved. To treat ALD, we applied two different gene-editing strategies, base editing and homology-independent targeted integration (HITI), in ALD patient-derived fibroblasts. Next, we performed in vivo HITI-mediated gene editing using AAV9 vectors delivered via intravenous administration in the ALD model mice. We found that the ABCD1 mRNA level was significantly increased in HITI-treated mice, and the plasma levels of C24:0-LysoPC (lysophosphatidylcholine) and C26:0-LysoPC, sensitive diagnostic markers for ALD, were significantly reduced. These results suggest that HITI-mediated mutant gene rescue could be a promising therapeutic strategy for human ALD treatment.

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy.

Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalopathy is rarely considered. We report a case of co-occurring SPG4 and CADASIL. A 61-year-old male presented with sudden visual impairment after a headache. He showed a spastic gait and had a family history with similar symptoms. An SPG4 gene mutation and a pathogenic variant in the NOTCH3 gene were found. This case shows that the diverse and complex clinical manifestations of patients with extensive leukoencephalopathy are related to more than one gene mutation. We also suggest the necessity for relevant genetic tests in the diagnosis of adult-onset leukoencephalopathy.

Outcome in Patients Treated with Intra-arterial thrombectomy: The optiMAL Blood Pressure control (OPTIMAL-BP) Trial.

RATIONALE: Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain. AIM: We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment. SAMPLE-SIZE ESTIMATES: We aim to randomize 668 patients (334 per arm), 1:1. METHODS AND DESIGN: We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP < 140 mm Hg) group or the conventional BP-lowering (systolic BP, 140-180 mm Hg) group. STUDY OUTCOMES: The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0-2 vs. 3-6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months. DISCUSSION: The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP < 140 mmHg during 24 h in patients with successful recanalization after intra-arterial treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04205305.

Lithium Polystyrene Sulfonate as a Hole Transport Material in Inverted Perovskite Solar Cells.

Despite the exceptional efficiency of perovskite solar cells (PSCs), further improvements can be made to bring their power conversion efficiencies (PCE) closer to the Shockley-Queisser limit, while the development of cost-effective strategies to produce high-performance devices are needed for them to reach their potential as a widespread energy source. In this context, there is a need to improve existing charge transport layers (CTLs) or introduce new CTLs. In this contribution, we introduced a new polyelectrolyte (lithium poly(styrene sulfonate (PSS))) (Li:PSS) polyelectrolyte as an HTL in inverted PSCs, where Li+ can act as a counter ion for the PSS backbone. The negative charge on the PSS backbone can stabilize the presence of p-type carriers and p-doping at the anode. Simple Li:PSS performed poorly due to poor surface coverage and voids existence in perovskite film as well as low conductivity. PEDOT:PSS was added to increase the conductivity to the simple Li:PSS solution before its use which also resulted in lower performance. Furthermore, a bilayer of PEDOT:PSS and Li:PSS was employed, which outperformed simple PEDOT:PSS due to high quality of perovskite film with large grain size also the large electron injection barrier (ϕe ) impeded back diffusion of electrons towards anode. As a consequence, devices employing PEDOT:PSS / Li:PSS bilayers gave the highest PCE of 18.64%.