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As personalized medicine rapidly evolves, there is a critical demand for advanced biocompatible materials surpassing current additive manufacturing capabilities. This study presents a novel printable bioresin engineered with tunable mechanical, thermal, and biocompatibility properties through strategic molecular modifications. The study introduces a new bioresin comprising methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and a photoinitiator, which is further enhanced by incorporating high molecular weight polymethyl methacrylate (PMMA) to improve biostability and mechanical performance. The integration of printable PMMA presents several synthesis and processing challenges, necessitating substantial modifications to the 3D printing process. Additionally, the bioresin is functionalized with antibacterial silver oxide and bone-growth-promoting hydroxyapatite at various weight ratios to extend its application further. The results demonstrate the agile printability of the novel bioresin and its potential for transformative impact in biomedical applications, offering a versatile material platform for additive manufacturing-enabled personalized medicine. This work highlights the adaptability of the novel printable bioresin for real-life applications and its capacity for multiscale structural tailoring, potentially achieving properties comparable to native tissues and extending beyond conventional additive manufacturing techniques., (© 2024 Wiley‐VCH GmbH.)

Purpose: Maternal perinatal social support is theorised to promote offspring social-emotional development, yet few studies have prospectively examined this relationship. Findings may inform preventative intervention efforts, to support a healthy start to emotional life., Methods: This study examined whether maternal social support perinatally predicts infant social-emotional development at 12 months of age in two longitudinal cohort studies: The Australian Temperament Project (ATP) (n = 1,052 mother-infant dyads [653 mothers, M age_at_birth = 32.03, 88% Australian-born; 1,052 infants, 52% girls]) and The Triple B Pregnancy Cohort Study (Triple B) (n = 1,537 dyads [1,498 mothers, M age_at_birth = 32.53, 56% Australian-born; 1,537 infants, 49% girls]). Social support was assessed at pregnancy (third trimester) and eight-weeks post-birth. Infant social-emotional competencies (ATP: Brief Infant and Toddler Social and Emotional Assessment (BITSEA), Competencies Scale; Triple B: Bayley Scales of Infant and Toddler Development-Social Emotional Scale) and problems (ATP: BITSEA, Problems Scale; Triple B: Ages and Stages Questionnaires: Social-Emotional Scale), were assessed at 12-months of age., Results: In ATP, social support was associated with lower offspring problems (pregnancy: β = -0.15; post-birth: β = -0.12) and greater competencies (pregnancy: β = 0.12; post-birth: β = 0.16) at 12 months. In Triple B, social support also predicted lower offspring problems (pregnancy: β = -0.11; post-birth: β = -0.07) and greater competencies (pregnancy: β = 0.07) at 12 months. Findings did not indicate an association between support at eight-weeks post-birth and subsequent competencies (β = 0.06)., Conclusions: Evidence suggests that perinatal social support promotes healthy infant social and emotional development. These results underscore the critical importance of social support for mothers transitioning into parenthood., Competing Interests: Declarations. Conflict of interest: The authors declare that there are no conflicts of interest. Ethical approval: This research was approved by Human Research Ethics Committees affiliated with Royal Prince Alfred Hospital (Sydney), Royal Women’s Hospital (Sydney), Liverpool Hospital (Sydney), King Edward Memorial Hospital (Perth), University of New South Wales (Sydney), Curtin University (Perth), Deakin University (Melbourne), University of Sydney (Sydney), University of Queensland (Queensland), University of Melbourne (Melbourne), and Murdoch Children’s Research Institute (Melbourne). Written parental consent was obtained for the collection and reporting of parent and child data, and only deidentified group-level findings are reported., (© 2024. Crown.)

Purpose: Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival., Methods: We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients., Results: We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420)., Conclusions: These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients., (© 2024. The Author(s).)

This study investigates the differences in mechanical properties between acrylonitrile butadiene styrene (ABS) samples produced using fused deposition modeling (FDM) and stereolithography (SLA) using ABS filaments and ABS-like resin, respectively. The central question is to determine how these distinct printing techniques affect the properties of ABS and ABS-like resin and which method delivers superior performance for specific applications, particularly in dental treatments. The evaluation methods used in this study included Shore D hardness, accelerated aging, tensile testing, Izod impact testing, flexural resistance measured by a 3-point bending test, and compression testing. Poisson's ratio was also assessed, along with microstructure characterization, density measurement, confocal microscopy, dilatometry, wettability, Fourier-transform infrared spectroscopy (FTIR), and nanoindentation. It was concluded that ABS has the same hardness in both manufacturing methods; however, the FDM process results in significantly superior mechanical properties compared to SLA. Microscopy demonstrates a more accurate sample geometry when fabricated with SLA. It is also concluded that printable ABS is suitable for applications in dentistry to fabricate models and surgical guides using the SLA and FDM methods, as well as facial protectors for sports using the FDM method.

The 2016 and 2021 World Health Organization 2021 Classification of central nervous system tumors have resulted in a major improvement in the classification of isocitrate dehydrogenase (IDH)-mutant gliomas. With more effective treatments many patients experience prolonged survival. However, treatment guidelines are often still based on information from historical series comprising both patients with IDH wild-type and IDH-mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological, and molecular factors associated with the outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with IDH-mutant grades 2 and 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize the overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received., Methods: We assembled a cohort of patients with a histopathologically diagnosed glioma from The Cancer Genome Atlas, Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women's Hospital. This incorporated retrospective clinical, histological, and molecular data alongside prospective assessment of patient survival., Results: 4,400 gliomas were identified: 2,195 glioblastoma, 1,198 IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma respectively (all p<0.01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received., Conclusions: By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objective: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis., Design: We generated 312 intestinal epithelial organoids (IEOs) from mucosal biopsies of 168 patients with CD (n=72), UC (n=23) and healthy controls (n=73). We performed genome-wide molecular profiling including DNAm, bulk as well as single-cell RNA sequencing. Organoids were subjected to gene editing and the functional consequences of DNAm changes evaluated using an organoid-lymphocyte coculture and a nucleotide-binding oligomerisation domain, leucine-rich repeat and CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model., Results: We identified highly stable, CD-associated loss of DNAm at major histocompatibility complex (MHC) class 1 loci including NLRC5 and cognate gene upregulation. Single-cell RNA sequencing of primary mucosal tissue and IEOs confirmed the role of NLRC5 as transcriptional transactivator in the intestinal epithelium. Increased mucosal MHC-I and NLRC5 expression in adult and paediatric patients with CD was validated in additional cohorts and the functional role of MHC-I highlighted by demonstrating a relative protection from DSS-mediated mucosal inflammation in NLRC5-deficient mice. MHC-I DNAm in IEOs showed a significant correlation with CD disease phenotype and outcomes. Application of machine learning approaches enabled the development of a disease prognostic epigenetic molecular signature., Conclusions: Our study has identified epigenetically regulated intestinal epithelial MHC-I as a novel mechanism in CD pathogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this research, an experimental biomechanics construct was developed to reveal the mechanics of distal tibial fracture by submitting synthetic tibiae to cyclic loading, resulting in a combined stress state due to axial compression and bending loads. The synthetic tibia was fixed at the knee but allowed to rotate in the coronal and sagittal planes at the ankle. The first three loading regimes lasted for 4000 cycles/each, and the final until ultimate failure. After 12k±80 cycles, the observed failure patterns closely resembled distal tibial fractures. The collected data during cyclic loading were fitted into a phenomenological model to deduce the time-dependent response of the synthetic tibiae. Images were also collected and analyzed using digital image correlation to deduce the full-field state of strain. The latter revealed that longitudinal strain contours extended in the proximal-distal direction. The transverse strain contours exemplified a medial-to-lateral distribution, attributed to the combined contributions of the Poisson's effect and the flexural deformation from axial and bending components of the applied load, respectively. The experimental construct, full-field characterization, and data analysis approaches can be extended to elucidate the effect of different fixation devices on the overall mechanical behavior of the bone and validate computational models in future research., (Copyright © 2024 by ASME.)

Background and Objectives: The timing of the reinstitution of warfarin after cesarean section (CS) delivery was not adequately addressed in the literature. This study aims to evaluate the risks of early versus late initiation of warfarin post-CS in patients with mechanical heart valves., Methods: This randomized, open-label cohort study included 114 pregnant women with mechanical heart valves planned to be delivered by CS at or after 28 weeks of gestation. Patients were randomly divided into two groups: Day-2-group, where warfarin was started on day 2, and Day-5-group, where warfarin was started on day 5 after CS. Maternal postoperative bleeding complications, mechanical valve thrombosis, need for blood transfusion or reoperation, and maternal mortality were identified., Results: Ten women (8.8%) had 11 bleeding complications, of whom 2 patients (20%) had intraperitoneal hemorrhage (none in Day-2-group and 2 in Day-5-group), 3 patients (30%) had subcutaneous hematoma (none in Day-2-group and 3 in Day-5-group), and 6 patients (60%) had sub-rectus hematoma (3 in Day-2-group and 3 in Day-5-group). No mechanical valve thrombosis, other thromboembolic events, or in-hospital maternal mortality were reported., Conclusion: Despite the small number of events, the bleeding risk was lower in the group with early post-CS warfarin introduction than in the group with late warfarin introduction in patients with prosthetic heart valves., Trial Registration: ClinicalTrials.gov Identifier: NCT04855110., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Head impacts are a major concern in contact sports and sports with high-speed mobility due to the prevalence of head trauma events and their dire consequences. Surrogates of human heads are required in laboratory testing to safely explore the efficacy of impact-mitigating mechanisms. This work proposes using polymer additive manufacturing technologies to obtain a substitute for the human skull to be filled with a silicone-based brain surrogate. This assembly was instrumentalized with an Inertial Measurement Unit. Its performance was compared to a standard Hybrid III head form in validation tests using commercial headgear. The tests involved impact velocities in a range centered around 5 m/s. The results show a reasonable homology between the head substitutes, with a disparity in the impact response within 20% between the proposed surrogate and the standard head form. The head surrogate herein developed can be easily adapted to other morphologies and will significantly decrease the cost of the laboratory testing of head protection equipment, all while ensuring the safety of the testing process.

Background: Worsening renal function is a frequent finding in patients with acute decompensated heart failure (ADHF) and is a powerful independent prognostic factor for adverse outcomes. The link between abdominal congestion and worsening renal function in such patients is not yet fully addressed., Objective: To evaluate the role of abdominal congestion in the early prediction of worsening renal function in hospitalized patients with acute decompensated heart failure., Methods: This was a prospective study that enrolled 100 patients with a diagnosis of ADHF and received intravenous diuretic therapy. Intra-abdominal pressure (IAP), splenic Doppler impedance indices and serum prouroguanylin were measured on admission, 24 h after admission and on discharge. Patients were then divided into 2 groups: those who developed WRF (WRF group), and those who did not (non-WRF group). Worsening renal function was defined as an increase in serum creatinine level ≥0.3 mg/dL above baseline admission value. Intrabdominal pressure was measured transvesically using standard Foley catheter. Splenic Doppler impedance indices (resistivity and pulsatility indices) were measured using splenic Doppler ultrasound., Results: Among recruited patients (age: 54.73 ± 13.1 years, 72% are male), there was a significant decline in IAP (6.67 mmHg vs 8.36 mmHg, p = 0.001) and significant rise in splenic resistivity index (0.69 vs 0.67, p = 0.002) before discharge compared to admission values. The median level of serum prouroguanylin before discharge showed significant decline compared to admission level (29.2 vs 34.6 ng/l, p = 0.006). WRF developed in 37 (37%) patients. Independent predictors of WRF during hospitalization were high splenic arterial resistivity index 24 h after admission, high intra-abdominal pressure (≥8 mmHg) 24 h after admission, and low LVEF on admission., Conclusion: In ADHF patients receiving diuretic therapy, transvesical measurement of intra-abdominal pressure and splenic resistivity index by splenic Doppler early after admission can help to identify patients at increased risk of WRF near discharge., Competing Interests: Conflicts of interest: None declared., (© 2024 Saudi Heart Association.)

Purpose: Earlier pubertal timing is an important predictor of emotional and behavioral problems during adolescence. The current study undertook a comprehensive investigation of whether the social environment can buffer or amplify the associations between pubertal timing and emotional and behavioral problems., Methods: Research questions were examined in the Adolescent Brain Cognitive Development (ABCD) Study, a large population representative sample in the United States. We examined interactions between pubertal timing and the shared effects of a range of proximal and distal social environmental influences (i.e., parents, peers, schools, neighborhoods, socioeconomic status) in 10- to 13-year-olds., Results: Results revealed significant interaction between timing and proximal social influences (i.e., the "microsystem") in predicting emotional and behavioral problems. In general, adolescents with earlier pubertal timing and unfavorable (high levels of negative and low levels of positive) influences in the microsystem exhibited greater problems. Both males and females exhibited such associations for rule-breaking problems, while females alone exhibited associations for depressive problems. Results also illustrate the relative strength of each social context at moderating risk for emotional and behavioral problems in earlier versus later pubertal maturers., Discussion: These findings highlight the importance of proximal social influences in buffering vulnerability for emotional and behavioral problems related to earlier puberty. Findings also illustrate the broad implications of latent environmental factors, reflecting common variance of multiple social influences that typically covary with one another., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Adverse clinical events cause significant morbidity in patients with GBM (GBM). We examined whether genomic alterations were associated with AE (AE) in patients with GBM., Experimental Design: We identified adults with histologically confirmed IDH-wild-type GBM with targeted next-generation sequencing (OncoPanel) at Dana Farber Cancer Institute from 2013 to 2019. Seizure at presentation, lymphopenia, thromboembolic events, pseudoprogression, and early progression (within 6 months of diagnosis) were identified as AE. The biologic function of genetic variants was categorized as loss-of-function (LoF), no change in function, or gain-of-function (GoF) using a somatic tumor mutation knowledge base (OncoKB) and consensus protein function predictions. Associations between functional genomic alterations and AE were examined using univariate logistic regressions and multivariable regressions adjusted for additional clinical predictors., Results: Our study included 470 patients diagnosed with GBM who met the study criteria. We focused on 105 genes that had sequencing data available for ≥ 90% of the patients and were altered in ≥10% of the cohort. Following false-discovery rate (FDR) correction and multivariable adjustment, the TP53, RB1, IGF1R, and DIS3 LoF alterations were associated with lower odds of seizures, while EGFR, SMARCA4, GNA11, BRD4, and TCF3 GoF and SETD2 LoF alterations were associated with higher odds of seizures. For all other AE of interest, no significant associations were found with genomic alterations following FDR correction., Conclusions: Genomic biomarkers based on functional variant analysis of a routine clinical panel may help identify AE in GBM, particularly seizures. Identifying these risk factors could improve the management of patients through better supportive care and consideration of prophylactic therapies., (©2024 American Association for Cancer Research.)

Background: Increased cardiovascular risk following preeclampsia is well established and there are signs of early cardiovascular aging 6 months postpartum. This study assessed whether blood pressure (BP) and other cardiovascular measures are abnormal 2 years postpartum in the same cohort to determine ongoing risk markers., Methods: Six months and 2 years postpartum, BP was measured using sphygmomanometry, 24-hour ambulatory BP monitoring, and noninvasive central BP. Anthropometric measures, blood, and urine biochemistry were performed. Cross-sectional comparisons between preeclampsia and normotensive pregnancy (NP) groups and longitudinal comparisons within each group were made at 6 months and 2 years., Results: Two years postpartum, 129 NP, and 52 preeclampsia women were studied who also had 6 months measures. At both time points, preeclampsia group had significantly higher BP (office BP 2 years, 112±12/72±8 versus 104±9/67±7 mm Hg NP; [ P <0.001]; mean ambulatory BP monitoring 116±9/73±8 versus 106±8/67±6 mm Hg NP; [ P <0.001]). No significant BP changes noted 6 months to 2 years within either group. Office BP thresholds of 140 mm Hg systolic and 90 mm Hg diastolic classified 2% preeclampsia and 0% NP at 2 years. American Heart Association 2017 criteria (above normal, >120/80 mm Hg) classified 25% versus 8% ( P <0.002), as did our reference range threshold of 122/79 mm Hg. American Heart Association criteria classified 60% post-preeclampsia versus 16% after NP with above-normal ambulatory BP monitoring ( P <0.001). Other cardiovascular risk markers more common 2 years post-preeclampsia included higher body mass index (median 26.6 versus 23.1, P =0.003) and insulin resistance., Conclusions: After preeclampsia, women have significantly higher BP 6 months and 2 years postpartum, and have higher body mass index and insulin-resistance scores, increasing their future cardiovascular risk. Regular cardiovascular risk screening should be implemented for all who have experienced preeclampsia., Competing Interests: None.

Aromatic polyurea has garnered assiduous research due to its excellent impact, shock, abrasion, moisture, and chemical resistance properties. Polyurea can be used in protective coating and impact mitigation applications but is inevitably exposed to harsh deployment conditions such as extended ultraviolet (UV) radiation. Fourier Transform Infrared (FTIR) spectroscopy, Terahertz-time domain spectroscopy (THz-TDS), and Excitation-Emission Matrix spectroscopy (EEMS) deciphered the effects of UV radiation on radiated polyurea samples under ambient and nitrogen-rich conditions. Samples were radiated continuously for up to 15 weeks in increments of 3 weeks. Comprehensive FTIR analyses revealed a monotonic increase in disordered hydrogen bonding as a function of exposure duration in an ambient environment. Otherwise, marginal changes were observed in UV-radiated samples under nitrogen. The hydrogen bond length exhibited significant variations in the former compared to their nitrogen atmosphere counterparts. The results infer the nitrogen shielding effect, protecting polyurea from the photodegradation and photo-oxidation observed in samples radiated under the ambient atmosphere. THz-TDS spectra affirmed the FTIR results by probing changes in the complex refractive index. Terahertz spectral peaks associated with torsional vibrations of intermolecular hydrogen bonds in polyurea were notably correlated with increased exposure duration in the ambient atmosphere. Changes in the complex index as a function of exposure duration under nitrogen are minimal. The excitation-emission spectra of polyurea samples reveal a strong fluorescent behavior in 9-week and 12-week ambient-exposed polyurea due to cluster-triggered emission mechanisms. The results synthesized based on three different spectroscopy techniques paint a holistic portrait of the adverse effects of extended ultraviolet radiation of macromolecules deployed in harsh environmental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and a reduced sense of accomplishment, which commonly arises from chronic workplace stress in the medical field. Given the higher risk of burnout in younger age groups reported in some studies, the Society for Neuro-Oncology (SNO) Young Investigator (YI) and Wellness Committees combined efforts to examine burnout in the SNO YI membership to better understand and address their needs., Methods: We distributed an anonymous online survey to SNO members in 2019. Only those meeting the definition of a YI were asked to complete the survey. The survey consisted of questions about personal and professional characteristics as well as the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) questionnaire. Statistical analyses included descriptive statistics, univariate and multivariate analyses, and incorporation of previously defined burnout profiles., Results: Data were analyzed for 173 participants who self-identified as YI. Measures of burnout showed that YI members scored higher on emotional exhaustion and depersonalization compared to normative population but similar to those in a prior SNO general membership survey. With respect to burnout profiles, 30% of YI respondents classified as overextended and 15% as burnout. Organizational challenges were the most common contributors to stress., Conclusions: Similar to results from a previous survey completed by general SNO membership, the prevalence of burnout among neuro-oncology clinical and research YI is high, and is mainly characterized by overextension, warranting interventions at institutional and organizational levels., Competing Interests: The authors do not have any conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To evaluate the benefit of anatomical muscle dissection repair for velopharyngeal insufficiency (VPI) in patients with submucous cleft palate (SMCP) with 22q11.2 deletion syndrome., Design: Retrospective blinded randomised analysis of a surgeon's management over 10 years., Setting: The study was performed at a specialised Paediatric hospital in the United Kingdom., Patients: Children with SMCP and 22q11.2 deletion syndrome., Interventions: All participants underwent radical muscle dissection veloplasty., Outcomes Measured: Pre- and post- operative measurements included severity of anatomical defect, speech samples and lateral images which were digitised, randomised then externally and blindly analysed using validated techniques. Stata software was used to perform statistical analysis., Results: 57 children with 22q11.2 deletion syndrome were included in this analysis. Intra-operatively, the majority of cases were identified as SMCP Grade I anomalies. Post-operatively, a statistically significant improvement in hypernasality, resting palate length, palate length at maximum closure, palate excursion and gap size at maximum closure was observed. Secondary surgery was performed for 59% of patients by ten years., Conclusion: Muscle dissection repair improves hypernasality, palate closure function and the closure gap in patients with 22q11.2 deletion syndrome. Although over 50% of patients may require further surgery, muscle dissection repair should be a first step due to its utility at a younger age, when invasive investigations are impossible, its lower morbidity, speech and language benefits or altering the plans for less obstructive secondary surgery when it lead to reduced velo-pharyngeal gap and improved palate mobility even when adequate velo-pharyngeal closure was not achieved., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: The response assessment in Neuro-Oncology (RANO) criteria and its versions were developed by expert opinion consensus to standardize response evaluation in glioma clinical trials. New patient-based data informed the development of updated response assessment criteria, RANO 2.0., Recent Findings: In a recent study of patients with glioblastoma, the post-radiation brain MRI was a superior baseline MRI compared to the pretreatment MRI, and confirmation scans were only beneficial within the first 12 weeks of completion of radiation in newly diagnosed disease. Nonenhancing disease evaluation did not improve the correlation between progression-free survival and overall survival in newly diagnosed and recurrent settings. RANO 2.0 recommends a single common response criteria for high- and low-grade gliomas, regardless of the treatment modality being evaluated. It also provides guidance on the evaluation of nonenhancing tumors and tumors with both enhancing and nonenhancing components., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions., Methods: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day)., Results: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30)., Conclusion: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria., Methods: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0)., Results: We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment., Conclusion: The revised RANO 2.0 criteria refine response assessment in gliomas.

Cancer stem cells (CSCs) undergo epithelial-mesenchymal transition (EMT) to drive metastatic dissemination in experimental cancer models. However, tumour cells undergoing EMT have not been observed disseminating into the tissue surrounding human tumour specimens, leaving the relevance to human cancer uncertain. We have previously identified both EpCAM and CD24 as CSC markers that, alongside the mesenchymal marker Vimentin, identify EMT CSCs in human oral cancer cell lines. This afforded the opportunity to investigate whether the combination of these three markers can identify disseminating EMT CSCs in actual human tumours. Examining disseminating tumour cells in over 12,000 imaging fields from 74 human oral tumours, we see a significant enrichment of EpCAM, CD24 and Vimentin co-stained cells disseminating beyond the tumour body in metastatic specimens. Through training an artificial neural network, these predict metastasis with high accuracy (cross-validated accuracy of 87-89%). In this study, we have observed single disseminating EMT CSCs in human oral cancer specimens, and these are highly predictive of metastatic disease., Competing Interests: GY, LG, LA, SL, AS, HC, KP, IM, MP, AB No competing interests declared, (© 2023, Youssef et al.)

Introduction and Background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence., Materials and Methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included. Tumor, treatment and clinical data were collected. Logistic and Cox regression analysis were used for statistical analysis., Results: One hundred and seventeen recurrent glioblastoma patients were identified, receiving 129 courses of re-irradiation. In 66 % (85/129) of cases, patients had prior BEV. In the 80 patients (62 %) with available re-irradiation plans, 20 (25 %) had all T2/FLAIR abnormality included in the gross tumor volume (GTV). Median overall survival (OS) for the cohort was 7.3 months, and median progression-free survival (PFS) was 3.6 months. Acute CTCAE grade ≥ 3 toxicity occurred in 8 % of cases. Concurrent use of TMZ or ICI was not associated with improved OS nor PFS. On multivariable analysis, higher KPS was significantly associated with longer OS (p < 0.01). On subgroup analysis, patients with prior BEV had significantly more marginal recurrences than those without (26 % vs. 13 %, p < 0.01)., Conclusion: Re-irradiation can be safely employed in recurrent glioblastoma patients. Marginal recurrence was more frequent in patients with prior BEV, suggesting a need to consider more inclusive treatment volumes incorporating T2/FLAIR abnormality., Competing Interests: CH has received research support through the “Filling the Gap” Program of the University of Zurich. CH has received honoraria from Vifor. DAR has received research support through DFCI from Acerta Phamaceuticals; Agenus; Bristol-Myers Squibb; Celldex; EMD Serono; Enterome; Epitopoietic Research Corporation; Incyte; Inovio; Insightec; Merck; Novartis; Omniox; Tragara. DAR has received advisory fees from Agios; AnHeart Therapeutics; Avita Biomedical, Inc., Bristol Myers Squibb; Boston Biomedical; CureVac AG; Del Mar Pharma; DNAtrix; Hoffman-LaRoche, Ltd; Imvax; Janssen; Kiyatec; Medicenna Therapeutics; Neuvogen; Novartis; Novocure; Pyramid; Sumitomo Dainippon Pharma; Vivacitas Oncology, Inc Y-mabs Therapeutics. DAR has received Honoraria from Abbvie; Advantagene; Agenus; Agios; Amgen; Avita Biomedical, Inc., Bayer; Boston Biomedical; Boehringer Ingelheim; Bristol-Myers Squibb; Celldex; Deciphera; DelMar; Ellipses Pharma; EMD Serono; Genenta; Genentech/Roche; Imvax; Inovio; Kintara; Kiyatec; Medicenna Biopharma, Inc.; Merck; Merck KGaA; Monteris; Neuvogen; Novartis; Novocure; Oncorus; Oxigene; Regeneron; Stemline; Sumitono Dainippon Pharma; Taiho Oncology, Inc. NA reports personal fees from AstraZeneca; Debiopharm; ViewRay; BrainLab. NA received research grants from ViewRay. MG has received research support from ViewRay; AstraZeneca. MG is the current President-elect of ESTRO. MW has received research grants from Versameb; Quercis. MW has received consulting fees from Bayer; Curevac; Medac; Novocure; Philogen; Roche; Sandoz. MW has received honoraria from Novartis. MV holds a board role at Orbus. PY has received research grants from Astra Zeneca/Medimmune; Black Diamond; Beigene; Celgene; Chimerix; Eli Lily; Erasca; Genentech/Roche; Kazia; MediciNova; Merck; Novartis; Nuvation Bio; Puma, Servier; Vascular Biogenics; VBI Vaccines. PY has received consulting fees from Astra Zeneca, Bayer; Black Diamond; Boehringer Ingelheim; Boston Pharmaceuticals; Celularity; Chimerix; Day One Bio; Genenta; Glaxo Smith Kline; Karyopharm; Merck, Mundipharma; Novartis; Novocure; Nuvation Bio; Prelude Therapeutics; Sapience; Servier; Sagimet; Vascular Biogenics; VBI Vaccines. PY holds board positions at Novocure; Day One Bio.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Unintended pregnancies are linked to adverse parental mental health, yet little attention has been given to this relationship in fathers specifically. We aimed to meta-analyse associations between unintended pregnancies and mental health problems in fathers with children aged ≤36 months., Methods: We conducted keyword searches of Medline, CINAHL, Academic Search Complete, PsycInfo and Embase to February 2, 2022, and hand searched included reference lists., Results: Of 2826 records identified, 23 studies (N = 8085 fathers), reporting 29 effects, were eligible for meta-analysis. Included studies assessed depression, anxiety, stress, parenting stress, post-traumatic stress disorder (PTSD), alcohol misuse and psychological distress. Pooled estimates, from random effects meta-analyses, for all mental health outcomes (k = 29; OR = 2.28) and depression only (k = 19; OR = 2.36), showed that the odds of reporting mental health difficulties were >2-fold higher in men reporting unintended births compared with those reporting intended births. However, there was no evidence of association with anxiety (k = 2) or stress (k = 2). Overall, mental health problems were greater in low-income countries. No differences were found across parity, timepoint of mental health assessment, or instruments used to measure mental health symptoms., Limitations: Analyses were limited by the use of retrospective assessment of pregnancy intention, and heterogeneity of measures used. Further, assessment of fathers' mental health was restricted to the first year postpartum. This review was limited to English language studies., Conclusions: Unintended pregnancies present an identifiable risk for postpartum mental health problems in fathers., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Attention deficit hyperactivity disorder (ADHD) and irritability commonly co-occur, and follow similar developmental trajectories from childhood to adolescence. Understanding of the developmental relationship between these co-occurrences is limited. This study provides a longitudinal assessment of how ADHD diagnostic status and symptom patterns predict change in irritability., Methods: A community sample of 337 participants (45.2% ADHD), recruited for the Childhood Attention Project, completed the Affective Reactivity Index (ARI) to measure irritability at baseline (mean age 10.5 years) and follow-up after 18-months. Latent change score models were used to assess how (a) baseline ADHD vs. control group status, (b) baseline symptom domain (inattention, hyperactivity-impulsivity) and (c) longitudinal change in ADHD symptom severity predicted change in irritability., Results: Irritability was significantly higher among the ADHD group than controls; however, change in irritability over time did not differ between groups. When assessed across the entire cohort, change in irritability was predicted by higher symptom count in the hyperactive-impulsive domain, but not the inattentive domain. Greater declines in ADHD symptoms over time significantly predicted greater declines in irritability. Baseline ADHD symptom severity was found to significantly predict change in irritability; however, baseline irritability did not significantly predict change in ADHD symptoms., Conclusions: ADHD symptoms-particularly hyperactive-impulsive symptoms-predict the degree and trajectory of irritability during childhood and adolescence, even when symptoms are below diagnostic thresholds. The use of longitudinal, dimensional and symptom domain-specific measures provides additional insight into this relationship., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date., Methods: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies., Results: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes., Conclusions: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01920048., Competing Interests: Disclosures None.

Background: The Centers for Medicare & Medicaid Services (CMS) mandate that every US hospital provide public online pricing information for services rendered. This allows patients to compare prices across hospital systems before establishing care. The goal of this project was to evaluate hospital compliance and patient-level accessibility to price transparency for common breast cancer surgical procedures., Methods: A sample case of a 62-year-old female with a T2N0 breast cancer was chosen. The patient would have the option of undergoing a partial mastectomy or mastectomy, both with sentinel lymph node biopsy (SLNB). Eight Massachusetts academic medical centers were evaluated. Searches were performed by authors for each hospital system and procedure using the sample case., Results: Every hospital had a cost calculator on its website. The average success rate of establishing a cost for partial mastectomy, mastectomy, and SLNB was 58, 35, and 25%, respectively. The median time to reach the cost calculator tool was 32 s (range 25-37 s). In successful attempts, the median pre-insurance estimated cost of a partial mastectomy was $16,509 (range $11,776-22,169), compared with $24,541 (range $16,921-25,543) for mastectomy and $12,342 (range $4034-20,644) for SLNB. SLNB costs varied significantly across hospitals (p = 0.025), but no statistically significant difference was observed for partial mastectomy or mastectomy., Conclusion: Despite new regulatory requirements by CMS for increased price transparency for surgical procedures, our results demonstrate poor success rates in obtaining cost estimates and significant variability of reported hospital charges. Further efforts to improve the quality of hospital cost estimate calculators are necessary for informed decision-making for patients with breast cancer., (© 2023. Society of Surgical Oncology.)

Background and Aims: Alcohol is a major modifiable risk factor for female breast cancer, with breast cancer risk now associated with substantially lower consumption levels than those previously deemed safe. This study sought to measure risky drinking among women attending breast screening services in Australia according to new national alcohol guidelines and to compare daily, weekly and recent (past 12 months) consumption to Australian gender and age population norms., Design, Setting and Participants: This study was a retrospective analysis of cross-sectional data from the Lifepool Project (collected October 2011-January 2016) in Victoria, Australia, comprising a convenience sample of women attending breast screening services aged 40+ years., Measurements: Typical and heavy alcohol consumption patterns over the previous 12 months (frequency, quantity), socio-demographic (e.g. age, education) and health-related (e.g. menopause status, breast cancer history) characteristics. Primary outcomes were the proportion of women drinking at a level exceeding new guidelines for weekly and daily alcohol consumption., Findings: Of 49 240 women, mean age was 59.94 years (standard deviation = 7.14, range = 40-94 years). Most women had consumed alcohol during the past 12 months [41 628, 85.48%, 95% confidence interval (CI) = 85.16, 85.79]. One in five women (8464, 18.34%, 95% CI = 17.99, 18.69) were drinking at a level exceeding new national guidelines for weekly consumption (i.e. greater than 10 standard drinks per week), and one in six (7446, 15.60%, 95% CI = 15.28, 15.93) were exceeding new guidelines for consumption on a single day (i.e. greater than four standard drinks on any 1 day, more than once per month). The proportion of women in this sample drinking daily (4.21-11.19%), weekly (34.73-50.71%) and in the past 12 months (74.96-90.81%) was significantly greater among nearly all age groups (by decade), compared with Australian gender and age norms [drinking daily (3.4-9.1%), weekly (27.1-37.6%) and in the past 12 months (64.4-81.9%)]., Conclusions: There appears to be a high prevalence of risky alcohol consumption among a large convenience sample of breast screening service clients in Australia using new national alcohol guidelines introduced in December 2020., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Glioblastoma (GBM) patients are treated with radiation therapy, chemotherapy, and corticosteroids, which can cause myelosuppression. To understand the relative prognostic utility of blood-based biomarkers in GBM and its implications for clinical trial design, we examined the incidence, predictors, and prognostic value of lymphopenia, neutrophil-to-lymphocyte ratio (NLR), and platelet count during chemoradiation (CRT) and recurrence., Methods: This cohort study included 764 newly diagnosed glioblastoma patients treated from 2005 to 2019 with blood counts prior to surgery, within 6 weeks of CRT, and at first recurrence available for automatic extraction from the medical record. Logistic regression was used to evaluate exposures and Kaplan-Meier was used to evaluate outcomes., Results: Among the cohort, median age was 60.3 years; 87% had Karnofsky performance status ≥ 70, 37.5% had gross total resection, and 90% received temozolomide (TMZ). During CRT, 37.8% (248/656) of patients developed grade 3 or higher lymphopenia. On multivariable analysis (MVA), high NLR during CRT remained an independent predictor for inferior survival (Adjusted Hazard Ratio [AHR] = 1.57, 95% CI = 1.14-2.15) and shorter progression-free survival (AHR = 1.42, 95% CI = 1.05-1.90). Steroid use was associated with lymphopenia (OR = 2.66,1.20-6.00) and high NLR (OR = 3.54,2.08-6.11). Female sex was associated with lymphopenia (OR = 2.33,1.03-5.33). At first recurrence, 28% of patients exhibited grade 3 or higher lymphopenia. High NLR at recurrence was associated with worse subsequent survival on MVA (AHR = 1.69, 95% CI = 1.25-2.27)., Conclusions: High NLR is associated with worse outcomes in newly diagnosed and recurrent glioblastoma. Appropriate eligibility criteria and accounting and reporting of blood-based biomarkers are important in the design and interpretation of newly diagnosed and recurrent glioblastoma trials., Competing Interests: LN reports: Consulting for Ono, Brave Bio, Genmab. Advisory board for Ono, Kite/Gilead. Royalty from Wolters Kluwer (UpToDate). Clinical trial support from Merck, Astra Zeneca, Kazia, Ono, Bristol Myers Squibb. All other authors do not report relevant disclosures. RR reports research support from Project Data Sphere., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Ichthyosis defines a group of chronic conditions that manifest phenotypically as a thick layer of scales, often affecting the entire skin. While the gene mutations that lead to ichthyosis are well documented, the actual signalling mechanisms that lead to scaling are poorly characterized; however, recent publications suggest that common mechanisms are active in ichthyotic tissue and in analogous models of ichthyosis., Objectives: To determine common mechanisms of hyperkeratosis that may be easily targeted with small-molecule inhibitors., Methods: We combined gene expression analysis of gene-specific short hairpin RNA (shRNA) knockdowns in rat epidermal keratinocytes (REKs) of two genes mutated in autosomal recessive congenital ichthyosis (ARCI), Tgm1 and Alox12b, and proteomic analysis of skin scale from patients with ARCI, as well as RNA sequencing data from rat epidermal keratinocytes treated with the Toll-like receptor 2 (TLR2) agonist Pam3CSK4., Results: We identified common activation of the TLR2 pathway. Exogenous TLR2 activation led to increased expression of important cornified envelope genes and, in organotypic culture, caused hyperkeratosis. Conversely, blockade of TLR2 signalling in keratinocytes from patients with ichthyosis and our shRNA models reduced the expression of keratin 1, a structural protein overexpressed in ichthyosis scale. A time course of TLR2 activation in REKs revealed that although there was rapid initial activation of innate immune pathways, this was rapidly superseded by widespread upregulation of epidermal differentiation-related proteins. Both nuclear factor kappa B phosphorylation and GATA3 upregulation was associated with this switch, and GATA3 overexpression was sufficient to increase keratin 1 expression., Conclusions: Taken together, these data define a dual role for TLR2 activation during epidermal barrier repair that may be a useful therapeutic modality in treating diseases of epidermal barrier dysfunction., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

ZnS quantum dots (QDs) were fabricated using the co-precipitation technique with no capping agent. The effects of different annealing temperatures (non-annealed, 240 °C and 340 °C for 2 h) on the structural and optical characteristics of ZnS QDs are reported. The samples were examined by XRD, TEM, PL, FTIR, and UV-Vis. An increase in annealing temperature led to an increase in the dot size and a lowering of the energy band gap (E G ). The average crystallite size, D of ZnS was between 4.4 and 5.6 nm. The ZnS QDs showed a band gap of 3.75, 3.74 and 3.72 eV for non-annealed, 240 °C, and 340 °C annealed samples. The reflection spectra increased in the visible light and decreased in UV region with an increase in annealing temperature. This work showed that the band gap and size of ZnS QDs could be tuned by varying the annealing temperature., (© 2023. The Author(s).)

Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update., Materials and Methods: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated., Results: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO., Conclusion: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.

Background: Glioblastomas comprise heterogeneous cell populations with dynamic, bidirectional plasticity between treatment-resistant stem-like and treatment-sensitive differentiated states, with treatment influencing this process. However, current treatment protocols do not account for this plasticity. Previously, we generated a mathematical model based on preclinical experiments to describe this process and optimize a radiation therapy fractionation schedule that substantially increased survival relative to standard fractionation in a murine glioblastoma model., Methods: We developed statistical models to predict the survival benefit of interventions to glioblastoma patients based on the corresponding survival benefit in the mouse model used in our preclinical study. We applied our mathematical model of glioblastoma radiation response to optimize a radiation therapy fractionation schedule for patients undergoing re-irradiation for glioblastoma and developed a first-in-human trial (NCT03557372) to assess the feasibility and safety of administering our schedule., Results: Our statistical modeling predicted that the hazard ratio when comparing our novel radiation schedule with a standard schedule would be 0.74. Our mathematical modeling suggested that a practical, near-optimal schedule for re-irradiation of recurrent glioblastoma patients was 3.96 Gy × 7 (1 fraction/day) followed by 1.0 Gy × 9 (3 fractions/day). Our optimized schedule was successfully administered to 14/14 (100%) patients., Conclusions: A novel radiation therapy schedule based on mathematical modeling of cell-state plasticity is feasible and safe to administer to glioblastoma patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single-arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1% [95% CI 4.23; 8.76%] for cytotoxic chemothera + pies (ORR = 7.59% for lomustine, 7.57% for temozolomide, 0.64% for irinotecan, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2= 0.4078, P < .0001), biologics (R2= 0.4003, P = .0003), and immunotherapy trials (R2= 0.8994, P < .0001), but not anti-angiogenic agents (R2= 0, P = .8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2= 0.3900, P < .0001; mOS [weeks] = 1.4xORR + 24.8). Assuming an ineffective cytotoxic (control) therapy has ORR = 7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR>25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P < .01) and adequate power (>80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR >25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Medicare reimbursement for plastic surgery procedures increased by 2% while inflation increased by 19% in the past decade. Given increasing national breast reduction case volume and the negative impact decreased reimbursements have on surgeon well-being, we sought to evaluate actual surgeon reimbursements for bilateral breast reduction over a decade., Methods: A retrospective review was performed including all identifiable breast reduction procedures (Current Procedure Terminology 19318) performed at a tertiary academic hospital between October 2011 and September 2021 (fiscal year 2012-2021). The annual number of patients undergoing breast reduction, the payor, and average yearly amounts reimbursed were evaluated and trended over time. Percent change from Medicare average yearly reimbursements was evaluated and trended over time. All values were adjusted to 2021 US dollars., Results: During our study period, there were 486 bilateral breast reduction procedures with 36 outlier payments; therefore, 450 reimbursements were included in the study. There were 5 payors, and the average adjusted reimbursement amount was $2418.74 ± $1123.83. All private payors had significantly higher average reimbursement than Medicare ( P < 0.0001), and Medicare was the only payor with significant decrease in reimbursement over time (-$58.58 per year, 95% confidence interval, -$110.80 to -$6.33, P = 0.033)., Conclusions: Our data demonstrate that a difference exists between public and private payors for bilateral breast reduction procedures. Private payor reimbursements outpaced inflation. Medicare is an unreliable benchmark that may indirectly lead to declining reimbursements over time., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors., Method: Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used., Results: All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN)., Conclusions: Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden.

Elastomers with segmental microstructure are a fascinating class of shock-tolerant and impact-resistant materials. However, their technological potential remains untapped due to a vague understanding of the molecular contributions to their superior mechanical behavior. Herein, in situ light-matter interactions, to reveal the extent of microstructural mobility by temporally exploiting molecular processes during creep response, are leveraged. The segmental microstructure comprises aromatic hard domains embedded within an aliphatic soft matrix. High-resolution digital image correlation reveals the development of strain striations, mild anisotropy, and the mechanisms responsible for domain mobility, where the rate of hard segment mobility is found to be 60% slower than that of the soft segment. Terahertz spectral analyses pinpoint the contributions of interchain hydrogen bonding of the hard segments and their significant conformational changes by observing spectral features at ≈1.2THz and ≈1.67THz. Moreover, the domain mobility is examined using experimental and computational light scattering approaches, uncovering dynamic scattering and elucidating the difference in the complex refractive index of the soft and hard segments. The study unlocks the pathway for quantitative measurements of elusive molecular mobility and conformational changes during mechanical loading and sheds light on the origin of the shock tolerance in some elastomeric polymers with segmental microstructure., (© 2023 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

Density gradation of foam structures has been investigated and found to be a practical approach to improve the mechanical efficacy of protective padding in several applications based on nature-based evidence of effectiveness. This research aims to disclose a discrete gradation approach without adhesives by relying on the properties of the frothed foam slurry to bond and penetrate through previously cured foam sheets naturally. As confirmed by electron microscopy observations, bilayer- and trilayer-graded elastomeric polyurea foam sheets were fabricated, resulting in seamless interfaces. The mechanical performance of seamless, graded foam samples was compared with monolayer, mono-density benchmark foam, considered the industry standard for impact mitigation. All foam samples were submitted to compressive loading at a quasi-static rate, reporting key performance indicators (KPIs) such as specific energy absorption, efficiency, and ideality. Polyurea foams, irrespective of gradation and interface type, outperformed benchmark foam in several KPIs despite the drastic difference in the effective or average density. The average compressive stress-strain curves were fitted into empirical constitutive models to reveal critical insights into the elastic, plateau, and densification behaviors of the tested foam configuration. The novelty of these outcomes includes (1) a fabrication approach to adhesive-free density-graded foam structures, (2) implementation of a diverse set of KPIs to assess the mechanical efficacy of foams, and (3) elucidation of the superiority of polyurea foam-based lightweight protective paddings. Future research will focus on assessing the dynamic performance of these graded foam structures under impact loading conditions at a wide range of velocities., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Aims: This study examined the trajectory of alcohol use frequency among parents from April-2020 to May-2021 during the COVID-19 pandemic in the state of Victoria, Australia (who experienced one of the longest lockdowns in the world), compared to parents from the other states of Australia (who experienced relatively fewer restrictions). We further examined the extent to which baseline demographic factors were associated with changes in alcohol use trajectories among parents., Method: Data were from the COVID-19 Pandemic Adjustment Survey (2,261 parents of children 0-18 years). Alcohol use frequency was assessed over 13 waves. Baseline demographic predictors included parent gender, age, speaking a language other than English, number of children, partnership status, education, employment, and income., Results: Overall, alcohol trajectories declined over time. Victorian parents, in comparison to parents from other states, reported a smaller reduction in alcohol use frequency across 2020, with a more notable decline during 2021. Female/other gender, speaking a language other than English at home, unemployment, and lower income (Victoria only) were associated with alcohol trajectories of less frequent use, and older age was associated with a trajectory of more frequent use., Conclusions: Results suggest subtle difference in alcohol trajectories reflecting COVID-19 restrictions, when comparing Victoria and other states in Australia. Socioeconomically advantaged groups were most at risk for elevated trajectories of alcohol use frequency. Population level support may beneficial to reduce drinking behaviours., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Cardiovascular disease (CVD) is the most common cause of death in patients with renal diseases. Cardiac arrhythmia and sudden cardiac death are particularly important, and the burden is higher in patients on hemodialysis. The aim of this study is to compare specific ECG changes as markers of arrhythmias in patients with CKD and patients with end-stage renal disease (ESRD); all without clinically manifest heart disease, with normal control subjects., Results: Seventy-five ESRD patients on regular hemodialysis, 75 patients with stage 3-5 CKD and 40 healthy control subjects were included. All candidates were subjected to thorough clinical evaluation and laboratory tests including serum creatinine, glomerular filtration rate calculation, serum potassium, magnesium, calcium, phosphorus, iron, parathyroid hormone, and total iron binding capacity (TIBC). Resting twelve-lead ECG was done to calculate P wave dispersion (P-WD), corrected QT interval, QTc dispersion, Tpeak-Tend interval (Tp-e), and Tp-e/QT. Patients with ESRD had a significantly higher QTc dispersion (p < 0.001) and P-WD (p = 0.001) when compared to the other 2 groups. In the ESRD group, males had a significantly higher P-WD (p = 0.045), insignificantly higher QTc dispersion (p = 0.445), and insignificantly lower Tp-e/QT ratio (p = 0.252) as compared to females. Multivariate linear regression analysis for ESRD patients showed that serum creatinine (β = 0.279, p = 0.012) and transferrin saturation (β =  - 0.333, p = 0.003) were independent predictors of increased QTc dispersion while ejection fraction (β = 0.320, p = 0.002), hypertension (β =  - 0.319, p = 0.002), hemoglobin level (β =  - 0.345, p = 0.001), male gender (β =  - 0.274, p = 0.009) and TIBC (β =  - 0.220, p = 0.030) were independent predictors of increased P wave dispersion. In the CKD group, TIBC (β =  - 0.285, p = 0.013) was an independent predictor of QTc dispersion while serum calcium (β = 0.320, p = 0.002) and male gender (β =  - 0.274, p = 0.009) were independent predictors of Tp-e/QT ratio., Conclusions: Patients with stage 3-5 CKD and those with ESRD on regular hemodialysis exhibit significant ECG changes that are considered substrates for ventricular as well as supraventricular arrhythmias. Those changes were more evident in patients on hemodialysis., (© 2023. The Author(s).)

Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and CD8 + T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment that disrupts the blood-tumor barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a "hot" tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.

The COVID-19 pandemic presents significant risks to population mental health. Despite evidence of detrimental effects for adults, there has been limited examination of the impact of COVID-19 on parents and children specifically. We aim to examine patterns of parent and child (0-18 years) mental health, parent substance use, couple conflict, parenting practices, and family functioning during COVID-19, compared to pre-pandemic data, and to identify families most at risk of poor outcomes according to pre-existing demographic and individual factors, and COVID-19 stressors. Participants were Australian mothers (81%) and fathers aged 18 years and over who were parents of a child 0-18 years (N = 2365). Parents completed an online self-report survey during 'stage three' COVID-19 restrictions in April 2020. Data were compared to pre-pandemic data from four Australian population-based cohorts. Compared to pre-pandemic estimates, during the pandemic period parents reported higher rates of parent depression, anxiety, and stress (Cohen's d = 0.26-0.81, all p < 0.001), higher parenting irritability (d = 0.17-0.46, all p < 0.001), lower family positive expressiveness (d = - 0.18, p < 0.001), and higher alcohol consumption (22% vs 12% drinking four or more days per week, p < 0.001). In multivariable analyses, we consistently found that younger parent age, increased financial deprivation, pre-existing parent and child physical and mental health conditions, COVID-19 psychological and environmental stressors, and housing dissatisfaction were associated with worse parent and child functioning and more strained family relationships. Our data suggest wide-ranging, detrimental family impacts associated with the COVID-19 pandemic; and support policy actions to assist families with financial supports, leave entitlements, and social housing., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Despite the magnitude of alcohol use problems globally, treatment uptake remains low. This study sought to determine the proportion of people presenting to telephone-delivered alcohol treatment who are first-time help-seekers, and explored perceived barriers to help-seeking to understand the barriers this format of treatment may help to address., Methods: Secondary analysis of baseline data from a randomized controlled trial of a telephone-delivered intervention for alcohol use problems. Latent class analysis (LCA) identified participant profiles according to self-reported barriers to alcohol treatment., Results: Participants' (344) mean age was 39.86 years (SD = 11.36, 18-73 years); 51.45% were male. Despite high alcohol problem severity (Alcohol Use Disorder Identification Test: mean = 21.54, SD = 6.30; 63.37% probable dependence), multiple barriers to accessing treatment were endorsed (mean = 5.64, SD = 2.41), and fewer than one-third (29.36%) had previously accessed treatment. LCA revealed a two-class model: a 'low problem recognition' class (43.32%) endorsed readiness-for-change and attitudinal barriers; a 'complex barriers' class (56.68%) endorsed stigma, structural, attitudinal and readiness-to-change barriers, with complex barrier class membership predicted by female sex (adjusted OR = 0.45, 95% CI 0.28, 0.72) and higher psychological distress (adjusted OR = 1.13, 95% CI 1.08, 1.18)., Conclusion: The majority of people accessing this telephone-delivered intervention were new to treatment, yet had high alcohol problem severity. Two distinct profiles emerged, for which telephone interventions may overcome barriers to care and tailored approaches should be explored (e.g. increasing problem awareness, reducing psychological distress). Public health strategies to address stigma, and raise awareness about the low levels of drinking that constitute problem alcohol use, are needed to increase help-seeking., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press.)

This study examined whether positive development (PD) in adolescence and young adulthood predicts offspring behavior in two Australasian intergenerational cohorts. The Australian Temperament Project Generation 3 Study assessed PD at age 19-28 (years 2002-2010) and behavior in 1165 infants (12-18 months; 608 girls) of 694 Australian-born parents (age 29-35; 2012-2019; 399 mothers). The Dunedin Multidisciplinary Health and Development Parenting Study assessed PD at age 15-18 (years 1987-1991) and behavior in 695 preschoolers (3-5 years; 349 girls) and their New Zealand born parents (age 21-46; 1994-2018; 363 mothers; 89% European ethnicity). In both cohorts, PD before parenthood predicted more positive offspring behavior (β range  = .11-.16) and fewer behavior problems (β range  = -.09 to -.11). Promoting strengths may secure a healthy start to life., (© 2022 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Several occupational and leisure activities involve a high risk of head impacts, resulting in varying degrees of injuries with chronic consequences that adversely affect life quality. The design and manufacturing of effective head protections rely on proper head simulators to mimic the behavior to impact loading. 3D-printed human skulls are reported herein to address the need for reproducible, cost-effective, anatomically-correct surrogates. To demonstrate the viability of the investigated approach, surrogate bone sections and skulls were mechanically tested under quasi-static loading conditions. The 3D-printed bone sections were flexural tested, elucidating the effect of printing orientations and the sample geometry on their mechanical behavior. The printing orientation minimally influenced the results due to the high infill percentage, while the sample geometry played a major role in the flexural properties because of the change in the section properties. The surrogate skulls were submitted to lateral compression and frontal penetration tests to assess the impact of the sectioning strategy on the overall mechanical performance. Results indicate that PLA-based surrogates reasonably reproduce the behavior of skulls. In addition, the sectioning strategy elucidated the effect of skull sutures, while streamlining the additive manufacturing process. The outcomes lay the foundation for future research seeking a complete surrogate head.

The current study examined associations between preconception diagnoses of major depressive disorder (MDD) and anxiety disorders in adolescence and young adulthood and perinatal depression and anxiety symptoms in early fatherhood. In an Australian community cohort study of health and development, earlier history of MDD and anxiety disorders (extending back to adolescence) were assessed retrospectively in the third trimester of pregnancy via the Composite International Diagnostic Interview. Paternal perinatal depression and anxiety were then assessed prospectively over three timepoints (third trimester of pregnancy, 8 weeks and 12 months postpartum), using established cut-points on the Edinburgh Postnatal Depression Scale and the Depression Anxiety Stress Scales (anxiety subscale). Mixed-effects regression models examined risk associations between preconception diagnoses of MDD and anxiety disorders, and perinatal depression and anxiety symptoms at each timepoint, adjusting for socio-demographic factors and concurrent maternal mental health difficulties. The odds of clinically concerning levels of paternal perinatal depression and anxiety were 6-fold and 4-fold higher, respectively, in men with a preconception history of MDD. The odds of perinatal depression were 3-fold higher in men with a preconception history of an anxiety disorder. Less evidence was found for an association between preconception diagnoses of an anxiety disorder and perinatal anxiety in fathers. Interventions aimed at improving mental health in men during adolescence and young adulthood may promote continued psychological health in men during early fatherhood., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

The concept of density-graded foams has been proposed to simultaneously enhance strain energy dissipation and the load-bearing capacities at a reduced structural weight. From a practical perspective, the fabrication of density-graded foams is often achieved by stacking different foam densities. Under such conditions, the adhesive interlayer significantly affects the mechanical performance and failure modes of the structure. This work investigates the role of different adhesive layers on the mechanical and energy absorption behaviors of graded flexible foams with distinct density layers. Three adhesive candidates with different chemical, physical, and mechanical characteristics are used to assemble density-graded polyurea foam structures. The mechanical load-bearing and energy absorption performances of the structures are evaluated under quasi-static and dynamic loading conditions. Mechanical tests are accompanied by digital image correlation (DIC) analyses to study the local strain fields developed in the vicinity of the interface. Experimental measurements are also supplemented by model predictions that reveal the interplay between the mechanical properties of an adhesive interlayer and the macroscale mechanical performance of the graded foam structures. The results obtained herein demonstrate that the deformation patterns and macroscale properties of graded foam composites can be tuned by selecting different bonding agents. It is also shown that the proper selection of an adhesive can be a practical way to address the strength-energy dissipation dichotomy in graded structures., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: A growing body of evidence suggests that parenting behaviors may affect child mental health via altering brain development. There is a scarcity of research, however, that has investigated associations between parenting behavior and brain structure using longitudinal magnetic resonance imaging. This study aimed to investigate associations between parenting behaviors and structural brain development across the transition from childhood to adolescence., Methods: Participants were 246 children who provided 436 magnetic resonance imaging datasets covering the age range from 8 to 13 years. Parents (94% mothers) completed self-report measures of parenting behavior, and both children and parents reported on child mental health. Factor analysis was used to identify dimensions of parental behavior. Linear mixed-effects models investigated associations between parenting behaviors and age-related change in cortical thickness and surface area and subcortical volume. Mediation models tested whether brain changes mediated associations between parenting behaviors and changes in internalizing/externalizing symptoms., Results: Hypothesized associations between parenting and amygdala, hippocampal, and frontal trajectories were not supported. Rather, higher levels of parent harsh/inconsistent discipline were associated with decreases in surface area in medial parietal and temporal pole regions and reduced cortical thinning in medial parietal regions. Some effects were present in female but not male children. There were no associations between these neurodevelopmental alterations and symptoms., Conclusions: This study provides insight into the links between parenting behavior and child neurodevelopment. Given the functions of implicated regions, findings may suggest that parental harsh/inconsistent discipline affects the development of neural circuits subserving sensorimotor and social functioning in children., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Drug-Induced Liver Injury (DILI), despite its low occurrence rate, can cause severe side effects or even lead to death. Thus, it is one of the leading causes for terminating the development of new, and restricting the use of already-circulating, drugs. Moreover, its multifactorial nature, combined with a clinical presentation that often mimics other liver diseases, complicate the identification of DILI-related (or "positive") literature, which remains the main medium for sourcing results from the clinical practice and experimental studies. This work-contributing to the "Literature AI for DILI Challenge" of the Critical Assessment of Massive Data Analysis (CAMDA) 2021- presents an automated pipeline for distinguishing between DILI-positive and negative publications. We used Natural Language Processing (NLP) to filter out the uninformative parts of a text, and identify and extract mentions of chemicals and diseases. We combined that information with small-molecule and disease embeddings, which are capable of capturing chemical and disease similarities, to improve classification performance. The former were directly sourced from the Chemical Checker (CC). For the latter, we collected data that encode different aspects of disease similarity from the National Library of Medicine's (NLM) Medical Subject Headings (MeSH) thesaurus and the Comparative Toxicogenomics Database (CTD). Following a similar procedure as the one used in the CC, vector representations for diseases were learnt and evaluated. Two Neural Network (NN) classifiers were developed: a baseline model that accepts texts as input and an augmented, extended, model that also utilises chemical and disease embeddings. We trained, validated, and tested the classifiers through a Nested Cross-Validation (NCV) scheme with 10 outer and 5 inner folds. During this, the baseline and extended models performed virtually identically, with F 1 -scores of 95.04 ± 0.61% and 94.80 ± 0.41%, respectively. Upon validation on an external, withheld, dataset that is meant to assess classifier generalisability, the extended model achieved an F 1 -score of 91.14 ± 1.62%, outperforming its baseline counterpart which received a lower score of 88.30 ± 2.44%. We make further comparisons between the classifiers and discuss future improvements and directions, including utilising chemical and disease embeddings for visualisation and exploratory analysis of the DILI-positive literature., Competing Interests: AL is funded by GlaxoSmithKline (GSK). SR is funded by JW Pharmaceutical. MM is an employee of LifeArc. WH and NH are funded by LifeArc. NH is a co-founder of KURE.ai and CardiaTec Biosciences and an advisor at Biorelate, Promatix, Standigm, and VeraVerse. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Katritsis, Liu, Youssef, Rathee, MacMahon, Hwang, Wollman and Han.)