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We demonstrate an approach to two-dimensional electronic spectroscopy (2DES) that combines the benefits of shot-to-shot detection at high-repetition rates with the simplicity of a broadband white light continuum input and conventional optical elements to generate phase-locked pump pulse pairs. We demonstrate this through mutual synchronization between the laser repetition rate, the acousto-optical deflector, the pump delay stage, and the CCD line camera, which allows for rapid scanning of pump optical delay synchronously with the laser repetition rate, while the delay stage is moved at a constant velocity. The resulting shot-to-shot detection scheme is repetition rate scalable and only limited by the CCD line rate and the maximum stage velocity. Using this approach, we demonstrate the measurement of an averaged 2DES absorptive spectrum in as much as 1.2 s of continuous sample exposure per 2D spectrum. We achieve a signal-to-noise ratio of 6.8 for optical densities down to 0.05 with 11.6 s of averaging at 100 kHz laser repetition rate. Combining rapid scanning of mechanical delay lines with shot-to-shot detection as demonstrated here provides a viable alternative to acousto-optic pulse shaping approaches that is repetition-rate scalable, has comparable throughput and sensitivity, and minimizes sample exposure per 2D spectrum with promising micro-spectroscopy applications. [ABSTRACT FROM AUTHOR]

Several damaging tropical cyclones (TCs) have occurred recently over the South Indian Ocean (SIO) region, causing enormous social and economic losses. Yet, while many studies have examined SIO TC characteristics using observations and reanalysis, only a few have assessed these characteristics specifically for this region in climate models, and fewer have investigated their projections under climate change. Here we do this for a historical (1980–2010) and future (2020–2050) period, using multimodel simulations from the High Resolution Model Intercomparison Project, as well as examine biases in the historical period relative to a reanalysis (ERA5). The models have horizontal resolutions of 25–50 km, which has enabled an improved ability to represent tropical cyclones globally in previous studies. TempestExtremes software is employed to detect tropical storm and cyclone tracks. In cases where TempestExtremes cannot be applied due to a lack of requisite variables in a dataset, we instead examine extreme wind speeds in that dataset. For the historical period, we find considerable variation in model biases compared to ERA5, which itself exhibits realistic spatial patterns of tracks and their monthly distribution. Models do at least agree on positive biases in track frequency east of Madagascar and somewhat in the Mozambique Channel. However, the models and ERA5 only produce Category 3 tropical cyclones at best. Wind speeds for 25 km resolution models have much larger positive biases than for 50 km ones, suggesting the former can simulate even higher‐category tropical cyclones. Considerable intermodel variation is also found in track changes between the future and historical periods. No systematic intercategory pattern of change exists, and low signal‐to‐noise may obscure any such patterns in the limited timespan of available data. Thus, no meaningful conclusions can be drawn regarding changes in track intensity. Nevertheless, track frequency broadly decreases across models for the region, as does accumulated cyclone energy. An east‐to‐west shift in track location from east of Madagascar toward the Mozambique Channel is also implied by track frequency and wind speed changes. Our findings provide information to potentially improve storm resiliency in this vulnerable region. [ABSTRACT FROM AUTHOR]

Background: Normal tissue sparing from radiation damage upon ultra-high dose rate irradiation, known as the FLASH effect with an equivalent tumor response, has been widely reported in murine skin models, and translation of this type of radiotherapy to humans has already begun, with skin sparing being a primary outcome expected. Methods: This study reviews the status of the field, focusing on the proposed mechanisms and skin response assays, outlining what has become known in terms of input parameters that might control the magnitude of the FLASH effect. Results: Murine studies have largely focused on acute damage responses, developing over 3–8 weeks, to single doses of FLASH versus conventional dose rate (CDR), suggesting that at dose rates above tens of Gray per second, with a total dose of more than 20 Gy, the FLASH effect is induced. Fractionated delivery appears to be possible, although fraction sizes >17 Gy appear to be needed for sparing efficacy. The interplay between the dose rate and total dose per fraction remains to be fully elucidated. Oxygen is a modulator of efficacy, with both hypoxia and hyperoxia diminishing the effect of FLASH. Measurement of transient changes in oxygen levels is possible and may be a marker of treatment efficacy. Conclusion: Taken together, murine skin data provide important information for translational studies, despite the associated limitations. Studies of later-term sparing effects, as well as studies on pig skin, are needed to take the next step in assessing translational FLASH efficacy. The control of biological factors, such as tissue oxygenation, may be required to understand and control the response. [ABSTRACT FROM AUTHOR]

Despite a high level of interest and investment in "gold standard" evaluations of interventions in education, the gap between teaching practice and the latest research on learning appears wider than ever; likewise, persistent attainment gaps between certain groups remain. This report summarizes the presentations and discussion from a roundtable event that brought together representatives from educational practice, research, and policy to explore challenges and solutions in relation to establishing "what works" in different educational contexts. The commentary addresses issues surrounding (a) who is involved and when, (b) a need for methodological innovation, (c) communication, and (d) understanding and use of evidence by educators and policymakers. Suggestions for best practice in relation to addressing these issues using national and international examples are presented. Identified recommendations related to facilitating a research culture within the teaching profession, the promotion of data sharing and communication, and conducting realistic evaluations. Outstanding questions are highlighted. This report summarizes the presentations and discussion from a roundtable event that discussed challenges and solutions in relation to establishing what works in different contexts, including (a) who is involved and when, (b) a need for methodological innovation, (c) communication issues, and (d) understanding and use of evidence by educators and policymakers. We highlight best practice in relation to addressing these issues using national and international examples. Recommendations related to facilitating a research culture within the teaching profession, the promotion of data sharing and communication, and conducting realistic evaluations. Outstanding questions are highlighted. [ABSTRACT FROM AUTHOR]

In this article, we give an overview of translational educational neuroscience (mind, brain, and education) in the United Kingdom. We consider the state of translation, describing respectively the state of the dialogue between researchers and educators, the state of evaluation of approaches to improve educational outcomes, and the state of innovation in research translation. We consider the teacher perspective. What do UK teachers think about educational neuroscience and its potential for informing classroom practice, and how do ideas about pedagogical approaches feature among their everyday concerns? We describe the results of a recent survey from a representative sample of over 1,000 UK teachers, and a case study of a UK high school teacher who employs educational neuroscience in his practice and what this entails. Lastly, we consider the policy perspective and assess the recent move by the UK government to introduce knowledge of cognitive science into initial and early‐career teacher training. In this article, we give an overview of translational educational neuroscience (mind, brain, and education) in the United Kingdom. We consider the state of translation, including the dialogue between researchers and educators, approaches to evaluation, and innovation in translating research into practice. We consider the teacher perspective, including the results of a survey of over 1,000 UK teachers on their views on educational neuroscience and how it relates to their classroom practice. And we consider the policy perspective, including the recent move by the UK government to introduce knowledge of cognitive science into initial and early‐career teacher training. [ABSTRACT FROM AUTHOR]

In pragmatic clinical trials (PCTs), the intervention is carried out by participating sites instead of research staff. In this paper, we evaluate study sites' implementation adherence during a pilot PCT of home-delivered meals for older adults with dementia. Participants at three home-delivered meal programs were randomized to receive either (1) meals delivered daily or (2) frozen meals mailed every two weeks; participants' outcomes were tracked for six months. Using the adherence domains from the Framework for Implementation Fidelity, we identified six metrics to assess adherence, with a total possible adherence score ranging from 6 (low adherence) to 18 (high adherence); all three sites scored within the top quartile of adherence. Despite challenges to meal delivery during the COVID-19 pandemic, sites successfully implemented the intervention, justifying a follow-on PCT to test the comparative effectiveness of models of meal delivery on the time to nursing home placement for people living with dementia. [ABSTRACT FROM AUTHOR]

High-throughput transcriptomics (HTTr) uses gene expression profiling to characterize the biological activity of chemicals in in vitro cell-based test systems. As an extension of a previous study testing 44 chemicals, HTTr was used to screen an additional 1,751 unique chemicals from the EPA's ToxCast collection in MCF7 cells using 8 concentrations and an exposure duration of 6 h. We hypothesized that concentration-response modeling of signature scores could be used to identify putative molecular targets and cluster chemicals with similar bioactivity. Clustering and enrichment analyses were conducted based on signature catalog annotations and ToxPrint chemotypes to facilitate molecular target prediction and grouping of chemicals with similar bioactivity profiles. Enrichment analysis based on signature catalog annotation identified known mechanisms of action (MeOAs) associated with well-studied chemicals and generated putative MeOAs for other active chemicals. Chemicals with predicted MeOAs included those targeting estrogen receptor (ER), glucocorticoid receptor (GR), retinoic acid receptor (RAR), the NRF2/KEAP/ARE pathway, AP-1 activation, and others. Using reference chemicals for ER modulation, the study demonstrated that HTTr in MCF7 cells was able to stratify chemicals in terms of agonist potency, distinguish ER agonists from antagonists, and cluster chemicals with similar activities as predicted by the ToxCast ER Pathway model. Uniform manifold approximation and projection (UMAP) embedding of signature-level results identified novel ER modulators with no ToxCast ER Pathway model predictions. Finally, UMAP combined with ToxPrint chemotype enrichment was used to explore the biological activity of structurally related chemicals. The study demonstrates that HTTr can be used to inform chemical risk assessment by determining in vitro points of departure, predicting chemicals' MeOA and grouping chemicals with similar bioactivity profiles. [ABSTRACT FROM AUTHOR]

Longitudinal research can assess how diverging development of multiple cognitive skills during infancy, as well as familial background, are related to the emergence of neurodevelopmental conditions. Sensorimotor and effortful control difficulties are seen in infants later diagnosed with autism; this study explored the relationships between these skills and autism characteristics in 340 infants (240 with elevated familial autism likelihood) assessed at 4–7, 8–10, 12–15, 24, and 36 months. We tested: (1) the relationship between parent‐reported effortful control (Rothbart's temperament questionnaires) and sensorimotor skills (Mullen Scales of Early Learning), using random intercept cross‐lagged panel modelling; (2) whether household income and maternal education predicted stable individual differences in cognition; (3) sensorimotor and effortful control skills as individual and interactive predictors of parent‐reported autism characteristics (Social Responsiveness Scale) at 3 years, using multiple regression; and (4) moderation of interactions by familial likelihood. Sensorimotor skills were longitudinally associated with effortful control at the subsequent measurement point from 12–15 months. Socioeconomic status indicators did not predict stable between‐infant differences in sensorimotor or effortful control skills. Effortful control skills were longitudinally related to 3‐year autism characteristics from the first year of life, with evidence for an interaction with sensorimotor skills at 24 months. Effects of effortful control increased with age and were particularly important for infants with family histories of autism. Results are discussed in relation to different theoretical frameworks: Developmental Cascades and Anterior Modifiers in the Emergence of Neurodevelopmental Disorders. We suggest a role for 24‐month effortful control in explaining the emergent autism phenotype. Research Highlights: Sensorimotor skills longitudinally predicted effortful control from 12–15 months onward but effortful control did not longitudinally predict sensorimotor skills during infancy.Measures of effortful control skills taken before the age of 1 predicted continuous variation in autism characteristics at 36 months, with associations increasing in strength with age.Effortful control (measured at 12–15 and 24 months) was a stronger predictor of 36‐month autism characteristics in infants with elevated familial likelihood for autism.The relationship between 24‐month sensorimotor skills and 36‐month autism characteristics was stronger in infants with weaker effortful control skills. [ABSTRACT FROM AUTHOR]

Aim: To describe real-world biomarker testing, treatment and survival in stage IA–IIIC non-small cell lung cancer (NSCLC). Methods: Electronic records of USA-based patients in the CancerLinQ Discovery® database with stage IA–IIIC NSCLC (diagnosed between 2014 and 2018) were screened; a curated cohort of 14,452 records was identified for further analysis. Results: Of 3121 (21.6%) patients who had EGFR testing, 493 (15.8%) were EGFR-mutation positive. Of 974 patients who underwent surgical resection, 513 (52.7%) received adjuvant therapy. A quarter of patients with EGFR-mutation positive NSCLC received targeted adjuvant therapy. Conclusion: Approximately a fifth of patients underwent EGFR testing; biomarker testing is important to ensure optimal outcomes for patients with stage I–III NSCLC. Plain Language Summary A study investigating how many patients with early-stage non-small cell lung cancer (NSCLC) had mutations in a protein called EGFR and which treatments they received in routine clinical practice: The treatment recommended by medical experts for stage IA–IIIA non-small cell lung cancer (NSCLC) is surgical removal of the growth (tumor). Patients with stage II or III, and some with stage IB disease, are recommended to receive treatment with medications such as chemotherapy or oral cancer treatments after surgery (adjuvant treatment). In some lung cancers, there are mutations in a protein called EGFR. Osimertinib, a drug that blocks the activity of mutated EGFR on cancer cells, reducing their growth and spread, is recommended as an adjuvant treatment for patients with EGFR-mutated, stage IB–IIIA NSCLC. This study aimed to understand how many patients with stage I–III NSCLC have tumors with EGFR mutations, and which treatments patients received in everyday clinical practice, before new medicines such as osimertinib (that treat EGFR-mutated NSCLC) were recommended. We looked at anonymous data from 14,452 patients with stage I–III NSCLC treated at cancer clinics in the USA between 2014 and 2018. We found that 3121 (21.6%) patients had an EGFR mutation test and 493 (15.8%) had EGFR-mutation positive NSCLC. Of patients who had surgery to remove the tumor, 55% received adjuvant therapy (treatment after surgery). It is important to perform EGFR mutation testing in patients with stage IB–IIIA NSCLC so that patients with EGFR-mutation positive NSCLC can receive appropriate treatment. Article Highlights Stage I–IIIA non-small cell lung cancer (NSCLC) is typically treated surgically; adjuvant chemotherapy is recommended in patients with stage II/III, and select stage IB disease. Osimertinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, is now approved for adjuvant treatment of resected EGFR-mutation positive stage IB–IIIA NSCLC. Immunotherapies have also been recently approved as neoadjuvant or adjuvant treatment in resectable NSCLC. Given these recent advancements, we assessed real-world biomarker testing patterns, and treatment and survival of patients with stage I–III NSCLC using data from the CancerLinQ Discovery® database, a health information platform that collects real-world data from oncology clinics in the USA. A cohort of 14,452 adults patients diagnosed with stage IA–IIIC NSCLC between January 2014 and December 2018 was identified. Of this cohort, 21.6% had at least one EGFR mutation test between the index date (date of diagnosis) and end of follow-up, with around two-thirds of these tests performed in the first 60 days following NSCLC diagnosis. Frequency of EGFR testing increased with increasing severity of NSCLC disease stage; female and Asian patients were more likely to receive an EGFR test. Of those with an EGFR test, 15.8% had EGFR-mutation positive (EGFRm) NSCLC; EGFRm NSCLC was more common in females, non-smokers and Asian patients. Surgical resection was the most common treatment for stage I and II NSCLC, while systemic therapy and/or radiotherapy without surgery was most common in stage III disease. Among patients who had resection, almost half did not receive a neoadjuvant or adjuvant treatment. Survival decreased with increasing disease stage; among patients with known EGFR status, median overall survival was longer in patients with EGFRm NSCLC than those with EGFRwt NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: The maintenance of intestinal homeostasis depends on a complex interaction between the immune system, intestinal epithelial barrier, and microbiota. Alteration in one of these components could lead to the development of inflammatory bowel diseases (IBD). Variants within the autophagy gene ATG16L1 have been implicated in susceptibility and severity of Crohn's disease (CD). Individuals carrying the risk ATG16L1 T300A variant have higher caspase 3-dependent degradation of ATG16L1 resulting in impaired autophagy and increased cellular stress. ATG16L1-deficiency induces enhanced IL-1β secretion in dendritic cells in response to bacterial infection. Infection of ATG16L1-deficient mice with a persistent strain of murine norovirus renders these mice highly susceptible to dextran sulfate sodium colitis. Moreover, persistent norovirus infection leads to intestinal virus specific CD8+ T cells responses. Both Toll-like receptor 7 (TLR7), which recognizes single-stranded RNA viruses, and ATG16L1, which facilitates the delivery of viral nucleic acids to the autolysosome endosome, are required for anti-viral immune responses. Results and discussion: However, the role of the enteric virome in IBD is still poorly understood. Here, we investigate the role of TLR7 and ATG16L1 in intestinal homeostasis and inflammation. At steady state, Tlr7-/- mice have a significant increase in large intestinal lamina propria (LP) granzyme B+ tissue-resident memory CD8+ T (TRM) cells compared to WT mice, reminiscent of persistent norovirus infection. Deletion of Atg16l1 in myeloid (Atg16l1ΔLyz2) or dendritic cells (Atg16l1ΔCd11c) leads to a similar increase of LP TRM. Furthermore, Tlr7-/- and Atg16l1ΔCd11c mice were more susceptible to dextran sulfate sodium colitis with an increase in disease activity index, histoscore, and increased secretion of IFN-γ and TNF-α. Treatment of Atg16l1ΔCd11c mice with the TLR7 agonist Imiquimod attenuated colonic inflammation in these mice. Our data demonstrate that ATG16L1-deficiency in myeloid and dendritic cells leads to an increase in LP TRM and consequently to increased susceptibility to colitis by impairing the recognition of enteric viruses by TLR7. Conclusion: In conclusion, the convergence of ATG16L1 and TLR7 signaling pathways plays an important role in the immune response to intestinal viruses. Our data suggest that activation of the TLR7 signaling pathway could be an attractive therapeutic target for CD patients with ATG16L1 risk variants. [ABSTRACT FROM AUTHOR]

Previous studies have emphasized culturally sensitive curricula in the context of enhancing minoritized students' education. We examined the relationship between second-year higher education students' perceptions of the cultural sensitivity of their curriculum and both majoritized and minoritized students' interest in their course. A total of 286 (228 F) students rated the cultural sensitivity of their curriculum on six scales using a revised version of the Culturally Sensitive Curricula Scales (CSCS-R), the perceived quality of their relationships with teachers, and their interest. The CSCS-R widened the construct with two new scales and showed better reliability. Ethnic minority students (n = 99) perceived their curriculum as less culturally sensitive than White students (n = 182), corroborating previous findings. Black students perceived their curriculum as less culturally sensitive than Asian students. There were no significant differences between ethnic minority and White students on interest or perceived quality of relationships with teachers. Five dimensions of cultural sensitivity (Diversity Represented, Positive Depictions, Challenge Power, Inclusive Classroom Interactions, Culturally Sensitive Assessments) and perceived quality of relationships with teachers predicted interest. Ethnicity did not. Ensuring curricula and assessments represent diversity positively, challenge power and are inclusive may support students' interest while reflecting an increasingly diverse society. [ABSTRACT FROM AUTHOR]

Background: International students account for a significant proportion of medical graduates Australia‐wide, and most opting to remain in Australia for their first year of practice (Internship). Hence, understanding this particular demographic's perspectives is crucial for curriculum and workforce planning. Despite this, very few studies have addressed this demographic, and none have explored the impact of the COVID‐19 pandemic on international medical students specifically. Aim: A qualitative design was used to explore the perspectives of final‐year international medical students at an Australian medical school as they prepared for transition to internship during the COVID‐19 pandemic. Methods: Participants engaged in a semi‐structured interview about the pandemic's personal and professional implications. The data were analysed using inductive thematic analysis. Results: Seven out of 34 final‐year international medical students at the University of Adelaide participated. The main themes identified were that isolation was magnified, institutional support was lacking and that uncertainty was challenging. The pandemic did not deter participants from pursuing an Australian internship, as Australia was considered a desirable place for internship compared to their home countries. Conclusions: While the COVID‐19 pandemic exacerbated the situation, many of the challenges identified by international students already existed. Issues such as social isolation, racial discrimination, financial hardship and lack of institutional support have been prevalent for decades. Insights from this study reveal a need to improve the medical school experience. Australian Universities have a responsibility to ensure fair treatment of international students by training faculty, implementing support programmes and ensuring an inclusive and culturally safe learning environment. [ABSTRACT FROM AUTHOR]

Understanding the apical pressure and irrigant flow patterns in root canals is crucial for safe and effective irrigation. Therefore, this study aimed to assess the flow characteristics of irrigants in root canal models with varying tapers during final irrigation by employing various needle designs, including a back-to-back double-side-vented needle, through computational fluid dynamics. The root canal model was configured as a closed geometrical cone with a simulated apical zone (size 30) and features tapers of 4%, 6%, and 8%. Three needle types—open-ended needle (OEN), single side-vented needle (SSVN), and double side-vented needle (DSVN)—were investigated. The results indicated that for the 4% taper models, the open-ended needle generated the maximum apical pressure, followed by the double side-vented needle and the single side-vented needle. However, in the 6% and 8% tapering root canal models, the double-side-vented needle applied the lowest maximum apical pressure. Consequently, the DSVN can pose a risk for irrigant extrusion in minimally prepared canals due to heightened apical pressure. In wider canals, the DSVN exhibited lower apical pressure. The maximum irrigant replacement was observed with OEN compared to that of the closed-ended group for both flow rates. Additionally, compared with OENs, closed-ended needles exhibited nonuniform and lower shear wall stress. [ABSTRACT FROM AUTHOR]

Understanding the interplay between genotype and fitness is a core question in evolutionary biology. Here, we address this challenge in the context of microbial adaptation to environmental stressors. This study explores the role of epistasis in bacterial adaptation by examining genetic and phenotypic changes in silver-adapted Escherichia coli populations, focusing on the role of beneficial mutations in two-component response systems (TCRS). To do this, we measured 24-hour growth assays and conducted whole-genome DNA and RNA sequencing on E. coli mutants that confer resistance to ionic silver. We showed recently that the R15L cusS mutation is central to silver resistance, primarily through upregulation of the cus efflux system. However, here we show that this mutation's effectiveness is significantly enhanced by epistatic interactions with additional mutations in regulatory genes such as ompR, rho, and fur. These interactions reconfigure global stress response networks, resulting in robust and varied resistance strategies across different populations. This study underscores the critical role of epistasis in bacterial adaptation, illustrating how interactions between multiple mutations and how genetic backgrounds shape the resistance phenotypes of E. coli populations. This work also allowed for refinement of our model describing the role TCRS genes play in bacterial adaptation by now emphasizing that adaptation to environmental stressors is a complex, context-dependent process, driven by the dynamic interplay between genetic and environmental factors. These findings have broader implications for understanding microbial evolution and developing strategies to combat antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The use of diagenetic alterations in bone microstructure ('histotaphonomy') as indicators of funerary treatment in the past and for post-mortem interval calculations in forensic cases has received increasing attention in the last decade. Studies have used histological changes to conclude in-situ decomposition, mummification, infanticide and post-mortem interval. There has been very little attempt to experimentally validate the links between decomposition, depositional conditions, time-since-death and microscopic changes in human bone so that meaningful interpretations of archaeological and forensic observations can be made. Here, we address this problem experimentally using the largest sample of human remains from anatomical donors and the longest-term deposition framework to date. This study tests one key assumption of histotaphonomy; that putrefaction during the early stages of decay is reflected in bone microanatomy and composition. Seventeen human donors and six pigs were deposited on the surface in a known Australian environment and left to decompose between 463 and 1238 days. All remains underwent all stages of decomposition reaching skeletonisation. Rib and femur samples were analysed using conventional histological methods and scanning electron microscopy, by applying the Oxford Histological Index, and examining collagen birefringence, microcracking and re- and de mineralisation. Biomolecular changes of the femoral samples were analysed using Fourier-transform infrared (FTIR) spectroscopy. The results indicate that bioerosion in human bone does not occur due to putrefaction. There were no correlations between bone histology and the following variables: human vs pigs, season, primary vs secondary deposition, position, fresh vs frozen and time-since-deposition. Furthermore, no trends were observed between biomolecular changes and time-since-deposition. The study also shows that pigs cannot be used as substitutes for human remains for bone biodegradation research. This is the first, controlled, larger scale study of human remains providing a lack of support for a long-assumed relationship between putrefaction and bone histology bioerosion. Using bone degradation as an argument to prove putrefaction, in-situ decomposition and early taphonomic processes cannot be supported based on the experimental human data presented. [ABSTRACT FROM AUTHOR]

Background: Historical data on smoking can enhance our comprehension of the effectiveness of past tobacco control policies and play a key role in developing targeted public health interventions. This study was undertaken to assess trends in smoking initiation and cessation in Australia for the period 1910–2005. Methods: Rates of smoking initiation and cessation were calculated for participants in two population-based cohorts, the Busselton Health Study and the Tasmanian Longitudinal Health Study. The effects of time trends, gender and age group were evaluated. Results: Of the 29,971 participants, 56.8% ever smoked. In males, over the period 1910–1999, the rate of smoking initiation in young adolescents remained high with a peak in the 1970s; in older adolescents it peaked in the 1940s and then declined; in young adults it showed a steady decline. In females, the rate of smoking initiation in young adolescents rose sharply in the 1960s and peaked in the 1970s, in older adolescents it increased throughout the period, and in young adults it declined after 1970. In the period 1930–2005, 27.3% of 9,605 people aged 36–50 years who smoked ceased smoking. Rates of cessation in this age group increased throughout but decreased in males after 1990 and plateaued around 2000 in females. Conclusion: Our findings show substantial variation in the efficacy of tobacco control policies across age groups, with a notable lack of success among the younger population. [ABSTRACT FROM AUTHOR]

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Identifying the effects of pain catastrophizing on movement patterns in people with chronic low back pain (CLBP) has important clinical implications for treatment approaches. Prior research has shown people with CLBP have decreased lumbar-hip ratios during trunk flexion movements, indicating a decrease in the contribution of lumbar flexion relative to hip flexion during trunk flexion. In this study, we aim to explore the relationship between pain catastrophizing and movement patterns during trunk flexion in a CLBP population. Participants with CLBP (N = 98, male = 59, age = 39.1 ± 13.0) completed a virtual reality standardized reaching task that necessitated a progressively larger amount of trunk flexion. Specifically, participants reached for four virtual targets to elicit 15°, 30°, 45°, and 60° trunk flexion in the mid-sagittal plane. Lumbar flexion was derived from the motion data. Self-report measures of numerical pain ratings, kinesiophobia, and pain catastrophizing were obtained. Pain catastrophizing leads to decreased lumbar flexion angles during forward reaching. This effect is greater in females than males. [ABSTRACT FROM AUTHOR]

Rechargeable aqueous zinc/sulfur (Zn/S) batteries are promising candidates for large-scale energy storage applications owing to their high specific capacity and energy density with additional advantages of zinc and sulfur being abundant and cost-effective. However, practical application is impeded by the poor reversibility of the sulfur cathode and parasitic reactions at the Zn anode, limiting their capacity and cycling life. To address these challenges, an aqueous hybrid electrolyte comprising dimethylacetamide (DMA) as a high-donor number organic cosolvent and ZnI2 as an additive was developed. The designed hybrid electrolyte helps in facile sulfur conversion and efficiently suppresses the HER and corrosion by reconstructing the solvation shell of zinc ions, thereby facilitating uniform Zn deposition. The designed Zn/S battery exhibits improved electrode reversibility with a specific capacity of 1453 mA h g−1 at 0.1 A g−1 and 72% capacity retention at 5 A g−1 over 300 cycles. The DMA-modified electrolyte presents a novel approach for utilizing high donor-number solvents to mitigate water-induced side reactions in other aqueous metal–sulfur batteries. [ABSTRACT FROM AUTHOR]

Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's a = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations. [ABSTRACT FROM AUTHOR]

Background and Objectives A better understanding of factors associated with assisted living admission and discharge practices can help identify communities that are more likely to allow residents to age in place. This study examined how state regulations and assisted living organizational characteristics related to community admission and discharge practices for bathing, getting out of bed, and feeding. Research Design and Methods Using data from a representative sample of 250 assisted living communities in seven states and a database of assisted living state regulations, we employed multilevel logistic regression models to examine regulatory and organizational correlates of assisted living community admission and discharge practices for 3 activities of daily living (bathing, getting out of bed, and feeding). Results States' regulations were not associated with assisted living community admission and discharge practices. However, assisted living communities above the median in the number of personal care staff members per resident were 17% (95% confidence interval [CI]: 6.5%, 27.1%) more likely to admit residents who needed assistance with feeding and 25.4% (95% CI: −37.7, −13.2) less likely to discharge these residents. For-profit communities were more likely to admit residents with bathing and feeding limitations. Discussion and Implications Organizational characteristics (e.g. for-profit affiliation, staffing levels) may, in part, drive admission and discharge practices, especially related to different care needs. The ability to house residents with advanced care needs may be influenced more by the organizational resources available to care for these residents than by states' admission and discharge regulations. [ABSTRACT FROM AUTHOR]

We determine the efficacy of tumor necrosis factor-α (TNF) inhibitors in establishing scleritis quiescence. We conducted a multicenter retrospective chart review of patients with non-infectious scleritis treated with a TNF inhibitor for at least 6 months. The primary endpoint was scleritis quiescence at 6 months. Secondary endpoints included scleritis quiescence at 12 months, TNF inhibitor effects on concurrent doses of systemic corticosteroids and visual acuity outcomes at 6 and 12 months. At 6 months, 82.2% (37/45) of subjects obtained scleritis quiescence with TNF inhibition. At 12 months, 76.2% (32/42) of subjects remained quiescent. Baseline daily corticosteroid use (21.5 ± 21.6 mg) decreased to 5.4 ± 8.3 mg by 6 months (p < 0.0001) and 2.8 ± 6.1 mg by 12 months (p < 0.001). There was no significant difference between the baseline and 6-month BCVA (p = 0.52). TNF inhibitors are an effective scleritis therapy with significant systemic corticosteroid sparing effect. [ABSTRACT FROM AUTHOR]

A facile NMR method is reported for analysis of ammonia from the electrochemical reduction of nitrogen, which compares a calibrated colorimetric method, a calibrated 1H NMR method and two 1H NMR direct measurements using external reference materials. Unlike spectrophotometric methods, 1H NMR requires less bench time and does not require separation of ammonia from the electrolyte. A novel approach to the problem of radiation damping in NMR measurements considered the specific role of hardware tuning. Radiation damping is suppressed improving signal‐to‐noise ratio and detection limit (1.5 µg L−1). The method is demonstrated to be effective for the analysis of ammonia from direct electrochemical nitrogen reduction in KOH, and from lithium‐mediated nitrogen reduction in a non‐aqueous solution. An uncertainty budget is prepared for the measurement of ammonia. [ABSTRACT FROM AUTHOR]

Background: Residential care/assisted living (RC/AL) is an increasingly common place of end‐of‐life care for persons with Alzheimer's disease and related dementia (ADRD), who have unique care needs as their health declines. Approximately 22% of RC/ALs provide specialized memory care (memory‐care RC/AL). Understanding how end‐of‐life outcomes differ by memory care among residents with ADRD could facilitate aging/dying in place for this population. The objective of this paper is to examine if end‐of‐life outcomes (i.e., mortality, hospice use, and number of days receiving hospice in the last month of life) differ between residents with ADRD who moved to memory‐care RC/AL, compared with residents with ADRD who moved to RC/AL without memory care (general RC/AL). Methods: Prospective cohort of 15,152 fee‐for‐service Medicare beneficiaries with ADRD who moved to large RC/AL (> = 25 beds) between 2016 and 2018. We used inverse probability treatment weighting to account for observable differences between memory‐care and general RC/AL residents. Two‐part models estimated the difference by memory care in the number of days receiving hospice care in the last months of life among RC/AL decedents. Results: The unadjusted mortality rates were 13.4% in general RC/AL and 15.8% in memory‐care RC/AL with an adjusted difference of 1.3 percentage points higher mortality among memory‐care RC/AL residents (p = 0.04). Hospice use was 8% and 10.6% among general and memory‐care RC/AL residents, respectively, with an adjusted difference of 1.4 percentage points (p = 0.01) higher in memory care. Two‐part models showed that decedents in memory‐care RC/AL spent about 1.4 more days receiving hospice care in the last month of life (p = 0.02). Conclusion: We find a higher mortality rate and higher rate of hospice use among memory‐care RC/AL residents. These findings suggest that memory care may attract residents closer to the end of life and/or promote hospice use at the end of life. [ABSTRACT FROM AUTHOR]

Objectives To introduce quantum computing technologies as a tool for biomedical research and highlight future applications within healthcare, focusing on its capabilities, benefits, and limitations. Target Audience Investigators seeking to explore quantum computing and create quantum-based applications for healthcare and biomedical research. Scope Quantum computing requires specialized hardware, known as quantum processing units, that use quantum bits (qubits) instead of classical bits to perform computations. This article will cover (1) proposed applications where quantum computing offers advantages to classical computing in biomedicine; (2) an introduction to how quantum computers operate, tailored for biomedical researchers; (3) recent progress that has expanded access to quantum computing; and (4) challenges, opportunities, and proposed solutions to integrate quantum computing in biomedical applications. [ABSTRACT FROM AUTHOR]

Short interfering RNA (siRNA) therapeutics have soared in popularity due to their highly selective and potent targeting of faulty genes, providing a non‐palliative approach to address diseases. Despite their potential, effective transfection of siRNA into cells requires the assistance of an accompanying vector. Vectors constructed from non‐viral materials, while offering safer and non‐cytotoxic profiles, often grapple with lackluster loading and delivery efficiencies, necessitating substantial milligram quantities of expensive siRNA to confer the desired downstream effects. We detail the recombinant synthesis of a diverse series of coiled‐coil supercharged protein (CSP) biomaterials systematically designed to investigate the impact of two arginine point mutations (Q39R and N61R) and decahistidine tags on liposomal siRNA delivery. The most efficacious variant, N8, exhibits a twofold increase in its affinity to siRNA and achieves a twofold enhancement in transfection activity with minimal cytotoxicity in vitro. Subsequent analysis unveils the destabilizing effect of the Q39R and N61R supercharging mutations and the incorporation of C‐terminal decahistidine tags on α‐helical secondary structure. Cross‐correlational regression analyses reveal that the amount of helical character in these mutants is key in N8's enhanced siRNA complexation and downstream delivery efficiency. [ABSTRACT FROM AUTHOR]

Global fertilizer production and mismanagement significantly contribute to many harmful environmental impacts, revealing the need for a greater understanding of crop growth and nutrient uptake, which can be used to optimize fertilizer management. This study experimentally adapts first-principles microbial modeling techniques to the hydroponic cultivation of Bibb lettuce (Lactuca sativa) under nitrogen-limited conditions. Monod and Michaelis–Menten's approaches are applied to predict biomass productivity and nutrient uptake and to evaluate the feasibility of reclaimed wastewater as a nutrient source of nitrogen. Experimental and modeling results reveal significantly different kinetic saturation constants ( K s = 1.331 and K m = 17.887 mg L−1) and a corresponding cell yield strongly dependent on nutrient concentration, producing visually and compositionally distinct tissue between treatments receiving ≤ 26.2 and ≥ 41.7 m g N L−1. The resulting Monod model overestimates dry mass predictions during low nutrient conditions, and the collective results support the development of a dynamic Monod curve that is temporally dependent during the plants' lifecycle. Despite this shortcoming, these results support the feasibility of reclaiming nitrogen from wastewater in hydroponic agriculture, expecting to produce lesser biomass lettuce exhibiting healthy tissue. Furthermore, this study provides a mathematical foundation for agricultural simulations and nutrient management. [ABSTRACT FROM AUTHOR]

In situ measurements of particulate inherent optical properties (IOPs) – absorption (ap(λ)), scattering (bp(λ)), and beam attenuation (cp(λ)) – are crucial for development of optical algorithms that retrieve biogeochemical quantities such as Chlorophyll a , particulate organic carbon (POC) and total suspended matter (TSM). Here we present a compilation of particulate absorption-attenuation spectrophotometric data measured underway on nine Atlantic Meridional Transect (AMT) cruises between 50° north to 50° south from 2009–2019. The compilation includes co-incident high performance liquid chromatography (HPLC) phytoplankton pigment concentrations, which are used to calibrate transects of Total Chlorophyll a (Tot_Chl_a) concentrations derived from the ap(λ) line-height method. The IOP data are processed using a consistent methodology, and include propagated uncertainties for each IOP variable, uncertainty quantification for the Tot_Chl_a concentrations based on HPLC match-ups, application of consistent set of quality-control filters, and standardisation of output data fields and formats. The total IOP dataset consists of ~310,000 measurements at a 1 minute binning (~270,000 hyper-spectral) and > 700 co-incident HPLC pigment surface samples (~600 of which are coincident with hyper-spectral IOPs). We present geographic variation in the IOPs, HPLC phytoplankton pigments, and the ap -derived Tot_Chl_a concentrations, which are shown to have uncertainties between 8–20 %. Additionally, to stimulate further investigation of accessory pigment extraction from ap(λ) , we quantify pigment correlation matrices and identify spectral characteristics of end-member ap(λ) spectra where accessory pigment groupings are present in higher concentrations relative to Tot_Chl_a. All data are made publicly available in SeaBASS and NetCDF formats via the following links: https://seabass.gsfc.nasa.gov/archive/PML/AMT , and https://doi.org/10.5281/zenodo.12527954. [ABSTRACT FROM AUTHOR]

Government policy in England aims for the elimination of bovine tuberculosis (bTB). This policy includes culling of European badger (Meles meles) to reduce cattle TB incidence. The rationale is based on a field trial, the Randomised Badger Culling Trial (RBCT) 1998–2005, which reported a substantial decrease in bTB herd incidence where badger culling had been implemented, in comparison to untreated control areas. The RBCT was undertaken because previous studies of reductions in badgers by culling, reported a possible association between bTB in badger and cattle, but none could directly show causation. The effect of intensive widespread (proactive) culling in the RBCT was reported in 2006 in the journal Nature. Analysis of an extensive badger removal programme in England since 2013 has raised concerns that culling has not reduced bTB herd incidence. The present study re-examined RBCT data using a range of statistical models. Most analytical options showed no evidence to support an effect of badger culling on bTB herd incidence ‘confirmed’ by visible lesions and/or bacterial culture post mortem following a comparative intradermal skin test (SICCT). However, the statistical model chosen by the RBCT study was one of the few models that showed an effect. Various criteria suggest that this was not an optimal model, compared to other analytical options available. The most likely explanation is that the RBCT proactive cull analysis over-fitted the data with a non-standard method to control for exposure giving it a poor predictive value. Fresh appraisal shows that there was insufficient evidence to conclude RBCT proactive badger culling affected bTB breakdown incidence. The RBCT found no evidence of an effect of culling on ‘total’ herd incidence rates. Total herd incidences include those confirmed as bTB at necropsy and those herds where there was at least one animal animal positive to the comparative intradermal skin test, the standard diagnostic test used for routine surveillance, but not confirmed at necropsy. This was also the case using the more suitable statistical models. Use only of ‘confirmed’ herd incidence data, together with a more recent (2013) published perception that RBCT data presented ‘a strong evidence base….with appropriate detailed statistical or other quantitative analysis’ should be reconsidered. The results of the present report are consistent with other analyses that were unable to detect any disease control benefits from badger culling in England (2013–2019). This study demonstrates one form of potential driver to the reproducibility crisis, in this case with disease control management in an increasingly intensified livestock industry. [ABSTRACT FROM AUTHOR]

The objective of this study is to analyze the association between surgical day of the week and distance traveled with prolonged length of stay (LOS) following robotic-assisted partial nephrectomy (RAPN). 563 consecutive RAPN performed by a single surgeon were evaluated. Early week RAPN was considered Monday through Wednesday, while late-week RAPN was defined as surgery performed Thursday through Friday. Distance traveled for RAPN was evaluated as greater than or less than 60 miles. The respective groups were compared to see if the surgical day of the week or distance traveled influenced the hospital stay or prolonged hospital stay (defined as hospital length of stay equal or greater than 3 days). Overall, 213 patients (38.0%) undergoing RAPN experienced a prolonged LOS. A total of 380 patients underwent early week RAPN compared to 183 late-week RAPN. Patients undergoing late-week RAPN were more likely to have a prolonged LOS compared to early week RAPN (n = 81, 44% vs. n = 133, 35%, respectively; p = 0.004). 229 patients traveled less than 60 miles, while 332 patients traveled more than 60 miles to receive RAPN. 135 patients (40.7%) traveling more than 60 miles experienced a prolonged stay compared to 78 patients (34.1%) traveling less than 60 miles, although this difference was not statistically significant (p = 0.128). Patients who underwent RAPN at the end of the week were more likely to have a prolonged LOS, while distance traveled for RAPN did not appear to affect likelihood of prolonged LOS. [ABSTRACT FROM AUTHOR]

Background and Objectives Approximately 60% of people living with dementia at home are unable to routinely participate in mealtime activities (e.g. eating, safe food preparation), warranting assistance to ensure people with dementia meet their health and nutritional needs. The purpose of this study was to characterize these barriers to mealtime participation and identify potential caregiver-led strategies to enhance mealtime activities. Research Design and Methods We used a qualitative descriptive approach and obtained semistructured interview data from (a) allied health professionals and (b) community-based nutrition program providers who frequently serve people with dementia. Interview data were examined by means of directed content analysis and framework methodology until data saturation was reached. Codes from our analysis were categorized according to constructs drawn from the Socio-Ecological Model for Developing and Implementing Comprehensive Dementia Care. Results Data were obtained from 20 participants who attributed common mealtime participation barriers to: impairments in functional status, cognitive status deficits, a lack of caregiver knowledge and skills, and unsafe living conditions. Caregiver-led strategies to overcome these barriers included: reducing auditory and visual distractions, providing written cues to perform mealtime activities, eliminating clutter and fall risk hazards, and leveraging community-based nutrition program providers (e.g. home-delivered meal providers). Discussion and Implications People with dementia face several eating and mealtime participation obstacles. Caregiver-led strategies implemented by family, friends, or community-based nutrition program providers may enhance mealtime activities at home. Findings point to opportunities to develop decision-making tools and resources for caregivers to optimize the health and nutrition of people with dementia. [ABSTRACT FROM AUTHOR]

Background: It is essential to identify the burden of poststroke cognitive impairment (PSCI) and to frame strategies for its prevention and progression in a developing country. Aim: The aim of the study was to estimate the prevalence and identify the risk factors of PSCI in older persons who survived an ischemic stroke. Materials and Methods: Patients with acute stroke satisfying the inclusion criteria were recruited. Clinical and demographic data, baseline functional capacity, and cognition as assessed by the Barthel index and the Informant Questionnaire on Cognitive Decline in the Elderly, respectively, were collected. The patients were then administered the Confusion Assessment Method, Mini-Cog, Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery within the 1st week of stroke and were reassessed at 1 month. The diagnosis of PSCI was done based on MoCA score within 1 week and at 1 month after stroke, and the analysis of risk factors for PSCI was done based on MoCA score at 1 month. Results: The prevalence of PSCI in this study was 63.8% within the 1st week and 71.8% at 1 month after the stroke. Lower educational and occupational status, higher Charlson Comorbidity Index, presence of delirium during the 1st week after stroke, poststroke depression, higher National Institutes of Health Stroke Scale score, and higher Modified Rankin Scale score were found to be risk factors for the development of PSCI on univariate analysis. Lower socioeconomic status was found to be a risk factor on both univariate and multivariate analyses. Conclusion: The prevalence of PSCI was 71.8% at 1 month after stroke. Lower socioeconomic status was found to be a risk factor for PSCI. Larger studies are needed to identify various modifiable risk factors, to improve the quality of life in older stroke survivors. [ABSTRACT FROM AUTHOR]

Rationale: The term "pre–chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score less than −1.264, corresponding to the lowest 10th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effects of performance-based feedback delivered via email on teacher candidates' implementation of a multiple stimulus without replacement (MSWO) preference assessment with an adult confederate. Six participants enrolled in a special education teacher preparation program were recruited to participate. After exposure to an introductory MSWO training video, participant fidelity of MSWO administration was measured. Following baseline, performance feedback was delivered via e-mail to each participant after the completion of each research session. Results indicate that performance feedback delivered via e-mail improved fidelity of implementation for all six participants. Implications and future directions are discussed. [ABSTRACT FROM AUTHOR]

Background: Two online behavioural interventions (one website for parents/carers of children with eczema; and one for young people with eczema) have been shown in randomised controlled trials to facilitate a sustained improvement in eczema severity. Aim: To describe intervention use and examine potential mediators of intervention outcomes and contextual factors that may influence intervention delivery and outcomes. Design and setting: Quantitative process evaluation in UK primary care. Method: Parents/carers and young people were recruited through primary care. Intervention use was recorded and summarised descriptively. Logistic regression explored sociodemographic and other factors associated with intervention engagement. Mediation analysis investigated whether patient enablement (ability to understand and cope with health issues), treatment use, and barriers to adherence were mediators of intervention effect. Subgroup analysis compared intervention effects among pre-specified participant subsets. Results: A total of 340 parents/carers and 337 young people were recruited. Most parents/carers (87%, n = 148/171) and young people (91%, n = 153/168) in the intervention group viewed the core introduction by 24 weeks. At 24 weeks, users had spent approximately 20 minutes on average on the interventions. Among parents/carers, greater intervention engagement was associated with higher education levels, uncertainty about carrying out treatments, and doubts about treatment efficacy at baseline. Among young people, higher intervention use was associated with higher baseline eczema severity. Patient enablement (the ability to understand and cope with health issues) accounted for approximately 30% of the intervention effect among parents/carers and 50% among young people. Conclusion: This study demonstrated that positive intervention outcomes depended on a modest time commitment from users. This provides further support that the wider implementation of Eczema Care Online is justified. [ABSTRACT FROM AUTHOR]

Simple Summary: This review article delves into the expanding role of 3D culture models in advancing breast cancer biology comprehension and enhancing drug response predictions, with an emphasis on triple-negative breast cancer (TNBC). It highlights the indispensable contribution of advanced technologies like patient-derived organoids and multi-omics analyses in unraveling tumor biology intricacies and drug sensitivity patterns, thereby fostering the creation of personalized therapeutic approaches. Additionally, it underscores the necessity of understanding the clinical translation for optimal model selection in TNBC therapy development, while acknowledging the impact of differences in cell culture models and culture conditions on drug response disparities. Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients' tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor's unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development. [ABSTRACT FROM AUTHOR]

Background and Objectives State-regulating agencies use 350 different licenses and certifications to govern assisted living (AL), resulting in significant variation in regulations governing health services, the scope of practice, and capacity. This lack of standardization makes it difficult to compare and contrast AL operations and residents' outcomes across similarly regulated communities. Research Design and Methods We used qualitative and quantitative methods to empirically develop and describe a typology of state AL regulations that captures inter- and intrastate variation. Based on the rules governing health services, we created regulatory specificity scores for 5 thematic dimensions: medication administration, third-party care, skilled nursing, medication review, and licensed nurse staffing. With these scores, we conducted a K -means cluster analysis to identify groups of AL license types. To differentiate the regulatory types, we calculated standardized mean differences across structure, process, outcome, and resident characteristics of the AL communities licensed under each type. Results We identified 6 types of AL differentiated by the regulatory provisions governing health services: Housing, Holistic, Hybrid, Hospitality, Healthcare, and Health Support. The types align with previous work and reflect tangible differences in resident characteristics, health service structures, processes, and outcomes. Discussion and Implications This typology effectively captures differences across regulated dimensions and can inform and support quality of care. Researchers, policy-makers, and consumers may benefit from using this typology and acknowledging these differences in AL licensure when designing research studies, developing policies, and selecting an AL community. [ABSTRACT FROM AUTHOR]