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Mesoporous ceramic materials used in applications such as catalysis, filtration, or sensing, are usually hierarchically structured. Thereby, their structural hierarchy is often inherently related to the manufacturing methods and cannot be independently locally designed along all length scales. This study combines light‐based additive manufacturing and bottom‐up light‐induced self‐assembly (LISA) sol‐gel chemistry to engineer hierarchically structured porous silica from the nanoscale to the macroscopic object geometry. A LISA‐based printing solution that enables printing of ordered mesoporous silica with geometrically complex shapes by using a commercially available digital light processing (DLP)‐based 3D printer is presented. This approach exploits the self‐assembly process of block copolymer mesopore templates, such as Pluronic P123, and hydrolysis and condensation of silica precursors upon irradiation in the 3D printer to shape mesoporous silica objects. Furthermore, different resins are added to the LISA solution to print 3D silica‐resin objects. Mesoporous silica objects up to 10 mm in size, consisting of ordered mesopores with diameters around 5 nm and having high specific surface areas of ≈400 m2 g−1 are successfully printed with a fast and easy post‐processing. [ABSTRACT FROM AUTHOR]

Background: Risk-reducing gynecological surgery (RRGS) is a prophylactic procedure that may be offered to BRCA1, BRCA2, and Lynch syndrome (LS) mutation carriers to reduce the risk of developing gynecological cancer. This study was conducted to better understand patients' information needs and evaluate how patients weigh different sources of information in their decision-making process surrounding RRGS. Methods: This study used a qualitative approach to understanding women's perspectives towards RRGS. Semi-structured interviews were conducted virtually with 8 women. Women offered RRGS between 35 and 70 years of age who are English-speaking and have an identifiable BRCA or LS mutation were included. Data from interviews was coded with constant comparative analysis to develop themes. Results: Of the eight women, six had selected to undergo either prophylactic hysterectomy or oophorectomy: 5 decided yes to RRGS; 1 decided no; 2 were undecided. Thematic analysis found that the key factors affecting women's decisions around prophylactic surgery were cancer risk, surgical menopause, and psychological readiness. To make an informed decision, women relied most heavily on information provided by healthcare professionals (e.g. doctors, genetic counselors) and family members with prior cancer experience. However, some women reported that they did not feel adequately informed enough to make a decision and identified COVID-19 as a significant barrier affecting access to information. Conclusion: This qualitative study revealed the key sources of information influencing attitudes regarding RRGS and how women consulted different sources of information to reach a decision. Results underscore the need for greater attention to women's information needs in the context of psychological readiness, particularly amidst the pandemic. Research involving a larger sample size may help to better inform how support can be provided to individuals with BRCA and LS mutations considering RRGS. [ABSTRACT FROM AUTHOR]

Introduction: On June 24, 2022, the U.S. Supreme Court's decision in Dobbs v. Jackson reversed the precedent set forth by Roe v. Wade, empowering individual states to regulate abortion care. This aftermath of this ruling has given rise to widespread bans, limiting the accessibility of abortion services for patients and impeding providers' ability to deliver a comprehensive spectrum of reproductive health services. Of particular concern is the disproportionate impact on medically underserved groups, further heightening existing social and structural disparities in reproductive health. Methods: We conducted a scoping review to broadly evaluate the clinical and public health impact of Dobbs on patients' access to abortion care and related reproductive health services, in addition to the training and clinical practice of healthcare providers. We searched eight bibliographic databases (PubMed, Scopus, Embase, PsycINFO, Google Scholar, Science Direct, JSTOR, and Web of Science) and three preprint servers (medRxiv, bioRxiv, and Europe PMC) using various combinations of keywords related to 'abortion', 'Dobbs', and 'Roe' on March 22, 2023. Four reviewers independently screened the studies based on pre-specified eligibility criteria and one reviewer performed data extraction for pre-identified themes. The search was conducted based on PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guidelines. Results: Eighteen studies, comprising 12 peer-reviewed articles and 6 study abstracts, met the inclusion criteria. The studies demonstrated that Dobbs increased demand for contraception, magnified existing travel- and cost-related barriers to access, further polarized views on abortion and complex family planning on social media (e.g., Twitter), and evoked substantial concerns among medical trainees regarding their scope of practice and potential legal repercussions for providing abortion care. Conclusion: In the wake of Dobbs v. Jackson, further public health and clinical interventions are urgently needed to bridge disparities in abortion care and reproductive health, mitigating the deleterious consequences of this emerging public health crisis. [ABSTRACT FROM AUTHOR]

This review focuses on the physiology of glymphatic solute transport and waste clearance, using evidence from experimental animal models as well as from human studies. Specific topics addressed include the biophysical characteristics of fluid and solute transport in the central nervous system, glymphaticlymphatic coupling, as well as the role of cerebrospinal fluid movement for brain waste clearance. We also discuss the current understanding of mechanisms underlying increased waste clearance during sleep. [ABSTRACT FROM AUTHOR]

Multistimuli-responsive, in-situ functionalized mesoporous silica films were fabricated by evaporation-induced self-assembly through physical entrapment of the functional template poly(ethylene oxide)- b -poly(2-nitrobenzyl acrylate) (PEO- b -PNBA). The light-cleavable and pH-responsive block copolymer PEO- b -PNBA simultaneously serves as structure-directing agent and for in-situ polymer functionalization of the generated mesopore space. The use of different PEO- b -PNBA compositions results in highly filled hybrid mesoporous silica films with different pore sizes, porosity, and polymer chain sequence within the mesopores. Based on these structural variations and the polymer chain sequence the ionic permselectivity of the silica-polymer hybrid thin films is adjusted. The side chains of the template PNBA block can be deprotected upon irradiation, hereby releasing pH-responsive carboxylic acid groups. The irradiation energy and irradiation time-dependent deprotection allows gradually controlled charge regulation in mesopores. This approach of in-situ functionalization using multistimuli-responsive PEO- b -PNBA block copolymers facilitates the fabrication of multi-responsive hybrid mesoporous silica films and bears high potential for the production of complex, hierarchical, multifunctional mesoporous materials. This fabrication method including direct functionalization of mesoporous structures is of high interest for many applications based on controlled molecular transport in nanoscale pores, such as sensing, separation, or catalysis. [Display omitted] • In-situ functionalization of mesoporous silica films by using PEO- b -PNBA in EISA. • Light- and pH-controlled charge regulation in in-situ functionalized mesopores. • Structure property relation: mesopore order, irradiation, ionic pore accessibility. [ABSTRACT FROM AUTHOR]

Prosody has often been considered a universal cue of prominence across languages. This paper presents the results of a study that aimed to provide congruent data on the question of universality vs. cross-linguistic variability of pragmatic–prosodic mappings (prosodic variation as a cue to pragmatic interpretation) in a specific linguistic construction, namely, [I + verb] belief constructs before an opinion. Specifically, this study presents a perception test implemented to investigate the phenomenon of cross-linguistic pragmatic-prosodic mapping in [I + verb] belief constructs. Since opinions carry inherent notions of speaker belief, these constructions may initially appear superfluous. However, [I + verb] forms may actually fulfill various pragmatic functions depending on prosodic variation. Usage of various pragmatic functions of this construct was analyzed and compared between native Mandarin and English speakers using the most common belief verb, “think” (‘juede’ in Mandarin). Results illustrated that confidence rating of prosodic–syntactic [I + verb] variations were linked to pragmatic implicatures generated via alternative semantics theory. Furthermore, the same confidence rating trends appeared across both Mandarin and English, exhibiting a similar pragmatic-prosodic mapping for [I + verb] across these typologically different languages. This study thereby provides validity of prosody as a cross-linguistic pragmatic tool to express speaker attitude. [ABSTRACT FROM AUTHOR]

With notable and growing exceptions, there is a dearth of research on mechanisms by which youth in foster care build resilience and achieve positive outcomes. We report on data from an interview study with young adults exiting or recently exited foster care in Maryland (N=15) designed to understand what facilitates their engagement with courts. Our findings indicate that despite challenges of ?being in foster care?, youth found ways to pursue their goals and make their voices heard through developing stable relationships with supportive adults (including judges, caseworkers, or lawyers) and demanding that child welfare professionals ?speak to me not at me.? Youth indicated that their needs, capabilities, and goals changed as they matured and as their circumstances changed. Such changes helped them find their voices but also created tensions within their child welfare system interactions. This led us to develop the theory of adaptive responsivity, according to which child welfare stakeholders should respond appropriately to developmental and circumstantial changes to help child-welfare involved youth face difficult circumstances and thrive. Such responses include providing developmentally and situationally appropriate information and decision-making power to youth in their own cases as well as opportunities to weigh in on systems change. [ABSTRACT FROM AUTHOR]

The current study tests the Interface Hypothesis through forward and backward anaphora in complex sentences with temporal subordinate clauses in highly proficient English-speaking learners’ second-language (L2) Chinese. Forward anaphora is involved when the overt pronoun ta ‘he/she’ or a null element appears in the subject position of the main clause, whereas backward anaphora is involved when it is in the subject position of the temporal clause, because the main clause always follows the temporal clause in Chinese. Specifically, the article tests the syntactic and discourse constraints in the interpretation and representation of ta and the null element in complex sentences. Ta is constrained by the syntactic cyclic-c-command condition. Thus it is possible for ta to refer to the other sentential subject in forward anaphora, but not in backward anaphora in Chinese. Unlike English, Chinese allows a null element in subject positions of finite subordinate and main clauses. It is proposed in the article that the null element in these positions is a Øtopic, a syntax–discourse interface category. Results from an acceptability judgement task and a picture judgment task indicate that Øtopic at the external interface has been acquired, whereas the cyclic-c-command condition within narrow syntax is fossilized in L2 Chinese. [ABSTRACT FROM PUBLISHER]

This article considers the decision of the Court of Appeal in R v Clinton where Lord Judge CJ speaking for the Court of Appeal held that sexual infidelity could be considered under the third prong of the new partial defence of loss of control, even though it is expressly exclude under the second prong. We argue that sexual infidelity is excluded from being considered under all the prongs of the new defence. It is expressly excluded as a form of qualifying provocation, which means it cannot be considered as a 'circumstance' that might prevent a person of D's sex and age with a normal degree of tolerance and self-restraint from killing. The objective tests in the new defence overlap, because the jury already has objective self-restraint in mind when it is considering the objectiveness of the provocation. When the jury is considering whether a normal person would have been provoked by the victim's conduct, it is also considering whether a normal person would have exercised self-restraint. Conceptually,these are two aspects of a single broader question: Was it reasonable for the defendant to lose control? Therefore, the jury cannot consider whether sexual infidelity prevented a person of a normal degree of tolerance from exercising control, even if it is a circumstance that relates to some other qualifying trigger. Where sexual infidelity is a (major)contributory trigger for the loss of control, it should not be considered under any of the prongs of the defence. If D has been taunted about has impotence in circumstances where he is enraged by his wife's sexual infidelity, the defence will only be made out if the jury accepts that the taunts about the impotence constituted objective provocation on their own, and that the taunts about the impotence per se might have prevented a person of normal control and tolerance from exercising self-restraint.The sexual infidelity would have to be compartmentalised, so that the jury would not be influenced by it. [ABSTRACT FROM AUTHOR]

It has been proposed that external interfaces are vulnerable to residue optionality, whereas pure syntax and internal interfaces are acquirable in second language (L2) acquisition (Sorace, 2005, 2011; Sorace and Filiaci, 2006). The proposal was tested in this article through the interpretation of overt and null embedded arguments in L2 Chinese grammars. The article identifies two types of null elements in Chinese: Øziji and Øtopic. Øziji is a purely syntactic category, whereas Øtopic is a syntax–discourse interface category. Being a D-pronoun, ta ‘he/him’ can refer to either the matrix subject or a discourse entity in the embedded argument position. Its interpretation involves lexicon–syntax and syntax–semantics internal interfaces. Results from a picture judgment task showed that external interfaces were acquired as well as pure syntax and internal interfaces, which supports the claims of Ivanov, 2009; Iverson et al., 2008; Kraš, 2008; Rothman, 2007, 2009; Slabakova and Ivanov, 2011. In addition, Øtopic was acquired at different states in different sentence positions. This supports the claim that interface categories should not be considered holistically (Yuan, 2010). The article further speculates that cross-linguistic influence and the nature of the possible positive evidence may have contributed to the difference here in terms of representation and/or processing. [ABSTRACT FROM AUTHOR]

This article reports an investigation of embedded null subjects in both L1 and L2 Chinese. Chinese null embedded subjects can refer either to a matrix subject or to a discourse entity. In the Government-Binding (GB) framework, these two possibilities resulted from the null subject being either pro or a variable. Neither pro nor a variable is compatible with the assumptions of the more recent Minimalist Program, however. This article proposes an alternative account for null embedded subjects in Chinese that is consistent with the Minimalist Program: deletion of the anaphor ziji and deletion of a topic under identity with appropriate antecedents. It then reports a study of knowledge of such deletion in the Chinese of L2 speakers. Although the existing literature has found that embedded null subjects are allowed by L2 learners of Chinese at early stages of development, no research has investigated whether they are interpreted in a target-like way by L2 speakers. A picture judgment task and a written interpretation task showed that English-speaking learners of high-intermediate proficiency in Chinese allow an embedded null subject to refer to the matrix subject, but not to a discourse entity. It is only at advanced proficiency that L2 speakers allow co-reference with both a matrix subject and a discourse entity. The implications of these results are discussed. [ABSTRACT FROM AUTHOR]

This paper evaluates fair labeling in the areas of criminalization and punishment in China. We consider the justice of criminal labeling from a comparative perspective by examining several core offenses and comparing how these offenses would be labeled and punished in China, the United States, and Britain. Our analysis shows that collectivist conceptualizations of responsibility, which are deeply rooted in Chinese thinking, are yielding to more individualistic conceptions of justice. Notwithstanding this phenomenon, themes of collectivism and deterrence continue to influence criminalization and punishment decisions in China, especially where individual acts of wrongdoing aggregate to form serious harm. Our analysis is doctrinal in that instead of conducting a large empirical study, we examine several high-profile cases and outline the general theoretical distinctions between them. Our analysis focuses on three core areas of wrongdoing: bribery offenses, manslaughter, and the criminalization of those who are remotely connected to a primary harm. We examine the way China handles corruption and corporate criminality when they result in human fatalities and ask whether its approach is reconcilable with Western notions of justice and fairness. Thereafter, we analyze and compare the use of the proportionality principle in Chinese and Western punishment. We conclude that Western definitions of harm and proportionate punishment are not universal, nor even consistently adhered to in Britain and the U.S. [ABSTRACT FROM AUTHOR]

Capsaicin (CAP), a member of the vanilloid family, is the main active component of chili peppers, which has been widely explored for its various pharmacological effects and influence on cell physiology, such as axonal growth and apoptosis of tumor cells. In particular, CAP plays a crucial role in determining the proliferation and fate specification of stem cells by modulating a variety of signaling pathways, such as PPARγ, C/EBPα and Notch signaling. Since CAP-mediated processes are complex and multifactorial, we hope to achieve a better understanding of these processes and their implications in clinical applications. This review aims to shed light on the influences and mechanisms of CAP on the actions of various stem cells in adults and discusses the role of CAP in the different process of stem cell behaviors, including proliferation and differentiation. Our purpose is to provide certain prospects for the application of CAP and stem cell therapy in treating diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition that occurs when the body produces a pro-inflammatory immune response to infection, leading to a decrease in blood flow that results in organ failure and death. Sepsis has the ability to kill within hours, and is responsible for 20% of deaths globally. However, current diagnostic techniques in the pre-hospital setting are limited by time and resources. It has recently been found that sepsis screening tools like qSOFA and lactate biomarkers used within the hospital could supplement diagnostic needs within the EMS setting. With research showing that lactate levels can be indirectly and instantaneously measured via capnography by EMS personnel, this technique may complement existing sepsis screening tools to achieve faster diagnosis. This article investigates the current flaws of sepsis diagnosis within the EMS setting and evaluates the benefits of the implementation of qSOFA and lactate technology. [ABSTRACT FROM AUTHOR]

Functional nanopores play an essential role in many biotechnological applications such as sensing, or drug delivery. Prominent examples are polymer functionalized ceramic or solid state nanopores. Intensive research efforts led to a discovery of a plethora of polymer functionalized nanopores demonstrating gated molecular transport upon basically all common stimuli. Nevertheless, nature's biological pore transport precision is unreached. This can be, among others, ascribed to limits in design precision especially with respect to functionalization. Recent trends in polymer functionalized nanopores address the role of confinement and polymerization control, strategies toward more sustainable reaction conditions, such as visible light initiation and strategies toward nanoscale local placement of polymer functionalization. The resulting multi-stimuli responsive nanopore performance enables concerted release or transport, side selective separation and selective detection. [ABSTRACT FROM AUTHOR]

Background: Fragile X syndrome (FXS), the most prevalent inherited intellectual disability and one of the most common monogenic forms of autism, is caused by a loss of fragile X messenger ribonucleoprotein 1 (FMR1). We have previously shown that FMR1 represses the levels and activities of ubiquitin ligase MDM2 in young adult FMR1-deficient mice, and treatment by a MDM2 inhibitor Nutlin-3 rescues both hippocampal neurogenic and cognitive deficits in FMR1-deficient mice when analyzed shortly after the administration. However, it is unknown whether Nutlin-3 treatment can have long-lasting therapeutic effects.Methods: We treated 2-month-old young adult FMR1-deficient mice with Nutlin-3 for 10 days and then assessed the persistent effect of Nutlin-3 on both cognitive functions and adult neurogenesis when mice were 6-month-old mature adults. To investigate the mechanisms underlying the persistent effects of Nutlin-3, we analyzed the proliferation and differentiation of neural stem/progenitor cells isolated from these mice and assessed the transcriptome of the hippocampal tissues of treated mice.Results: We found that transient treatment with Nutlin-3 of 2-month-old young adult FMR1-deficient mice prevents the emergence of neurogenic and cognitive deficits in mature adult FXS mice at 6 months of age. We further found that the long-lasting restoration of neurogenesis and cognitive function might not be mediated by changing intrinsic properties of adult neural stem cells. Transcriptomic analysis of the hippocampal tissue demonstrated that transient Nultin-3 treatment leads to significant expression changes in genes related to the extracellular matrix, secreted factors, and cell membrane proteins in the FMR1-deficient hippocampus.Conclusions: Our data indicates that transient Nutlin-3 treatment in young adults leads to long-lasting neurogenic and behavioral changes likely through modulating adult neurogenic niche that impact adult neural stem cells. Our results demonstrate that cognitive impairments in FXS may be prevented by an early intervention through Nutlin-3 treatment. [ABSTRACT FROM AUTHOR]

Background: Hydrocephalus (increased ventricular size due to CSF accumulation) is a common finding in human ciliopathies and in mouse models with genetic depletion of the multiciliated cell (MCC) cilia machinery. However, the contribution of MCC to CSF dynamics and, the mechanism by which impaired MCC function leads to hydrocephalus remains poorly understood. The aim of our study was to examine if defects in MCC ciliogenesis and cilia-generated CSF flow impact central nervous system (CNS) fluid homeostasis including glymphatic transport and solute waste drainage. Methods: We used two distinct mouse models of MCC ciliopathy: MCC-specific CEP164 conditional knockout mice (FOXJ1-Cre;CEP164fl/fl (N = 10), 3-month-old) and p73 knock-out (p73−/− (N = 8), 5-month-old) mice. Age-matched, wild-type littermates for each of the mutants served as controls. Glymphatic transport and solute drainage was quantified using in vivo T1 mapping by magnetic resonance imaging (MRI) after CSF infusion of gadoteric acid. Brain morphometry and aquaporin 4 expression (AQP4) was also assessed. Intracranial pressure (ICP) was measured in separate cohorts. Results: In both of the two models of MCC ciliopathy we found the ventriculomegaly to be associated with normal ICP. We showed that FOXJ1-Cre;CEP164fl/fl mice with hydrocephalus still demonstrated sustained glymphatic transport and normal AQP4 expression along capillaries. In p73−/− mice glymphatic transport was even increased, and this was paralleled by an increase in AQP4 polarization around capillaries. Further, solute drainage via the cribriform plate to the nasal cavity was severely impaired in both ciliopathy models and associated with chronic rhinitis and olfactory bulb hypoplasia. Conclusions: The combination of sustained glymphatic transport, impaired solute drainage via the cribriform plate to the nasal cavity and hydrocephalus has not previously been reported in models of MCC ciliopathy. Our data enhance our understanding of how different types of ciliopathies contribute to disruption of CNS fluid homeostasis, manifested in pathologies such as hydrocephalus. [ABSTRACT FROM AUTHOR]

Objectives: Approximately 25-40% of endometrial cancers (EC) demonstrate deficient DNA mismatch repair (MMRd). MMRd ECs have distinct tumor characteristics compared to MMR intact (MMRi) cohort with higher grade propensity for lymphovascular invasion and frequent lymph node involvement. Despite the worse tumor characteristics, PORTEC-3 data and smaller in vitro studies suggest increased radiosensitivity in MMRd EC. The study aimed to compare the recurrence patterns between MMRd and MMRi EC and assess whether the use of radiation in recurrent settings leads to higher salvage in the MMRd group. Methods: Cases of newly diagnosed EC of all stages and histology were prospectively recruited from three cancer centers in Ontario, Canada, between 2015-2018. All cases were treated with surgery followed by adjuvant treatment. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinical-pathologic, survival, and recurrence details were compared between the MMRd and MMRi cases. Results: Of 666 with EC, there were 83 (12%) recurrences, with 26 (31%; n =83) in MMRd and 57 (69%; n =83) in MMRi cohort after a median follow-up of 26 (2-60) months. There were 503 endometrioid EC, with 148 (29%) MMRd and 355 (71%) MMRi. Restricting the analysis to endometrioid histology only, there were 50 (13%; n =377) recurrences, with 23 (46%; n =50) in MMRd and 27 (54%; n =50) in MMRi cohort. There were no differences in their original stage (p=0.264), grade distributions (p=1.000), rate of lymphovascular space invasion (p=1.000), or type of adjuvant therapy used (p=0.374). Isolated vaginal/pelvic recurrences were more common in the MMRd than MMRi cohort (65% vs 30%), whereas distant recurrences were more common in MMRi cohort (70% vs 35%) (p=0.022). Similar proportion received further treatment for the recurrences (87% vs 81%; p=0.711). Post-recurrence survival (PRS; overall survival after recurrence) was higher in MMRd cohort (median PRS: 43.8 [23.4-53.7] vs 20 [8.1-102.3]; log-rank p=0.306). Of those who had local vaginal/pelvic recurrences, RT with curative intent was used in the majority (9 of 15 in MMRd and 7 of 8 in MMRi) in both groups. All those with local recurrences with MMRd tumors salvaged with curative-intent RT are alive without disease (9 of 9), whereas only two with MMRi tumors are alive without disease (2 of 7). Conclusions: MMRd endometrioid ECs are more likely to recur isolated in the vagina or pelvis than MMRi ECs. Once locoregional recurrence occurs in either MMRd or MMRi EC, curative-intent RT is more likely to salvage the MMRd EC, possibly indicating the increased radiosensitivity in this cohort. [ABSTRACT FROM AUTHOR]

Abstract: Metabotropic glutamate receptor 2 (mGluR2) has been implicated in a variety of CNS disorders, including schizophrenia. Disclosed herein is the development of a new series of allosteric potentiators of mGluR2. Structure–activity relationship studies in conjunction with pharmacokinetic data led to the discovery of indole 5, which is active in an animal model for schizophrenia. [Copyright &y& Elsevier]

Abstract: A general method for the synthesis of benzimidazole-4-sulfonamides is described. This methodology employs commercially available benzothiadiazole-4-sulfonyl chloride as a benzimidazole equivalent. Reaction with a variety of amines followed by highly chemoselective reductive desulfurization gives intermediate 1,2-phenylenediamines, which may then react with aryl, heteroaryl, and alkyl aldehydes to provide substituted benzimidazole sulfonamides. [Copyright &y& Elsevier]