In Science Journals.

Highlights from the Science family of journals.

In Science Journals.

Highlights from the Science family of journals.

In Science Journals.

Highlights from the Science family of journals.

In Science Journals.

Highlights from the Science family of journals.

Seven tesla knee MRI T2*-mapping detects intrasubstance meniscus degeneration in patients with posterior root tears.

Background: Medial meniscus root tears often lead to knee osteoarthritis. The extent of meniscal tissue changes beyond the localized root tear is unknown. Purpose: To evaluate if 7 Tesla 3D T2*-mapping can detect intrasubstance meniscal degeneration in patients with arthroscopically verified medial meniscus posterior root tears (MMPRTs), and assess if tissue changes extend beyond the immediate site of the posterior root tear detected on surface examination by arthroscopy. Methods: In this prospective study we acquired 7 T knee MRIs from patients with MMPRTs and asymptomatic controls. Using a linear mixed model, we compared T2* values between patients and controls, and across different meniscal regions. Patients underwent arthroscopic assessment before MMPRT repair. Changes in pain levels before and after repair were calculated using Knee Injury & Osteoarthritis Outcome Score (KOOS). Pain changes and meniscal extrusion were correlated with T2* using Pearson correlation (r). Results: Twenty patients (mean age 53 ± 8; 16 females) demonstrated significantly higher T2* values across the medial meniscus (anterior horn, posterior body and posterior horn: all P < .001; anterior body: P = .007), and lateral meniscus anterior (P = .024) and posterior (P < .001) horns when compared to the corresponding regions in ten matched controls (mean age 53 ± 12; 8 females). Elevated T2* values were inversely correlated with the change in pain levels before and after repair. All patients had medial meniscal extrusion of ≥2 mm. Arthroscopy did not reveal surface abnormalities in 70% of patients (14 out of 20). Conclusions: Elevated T2* values across both medial and lateral menisci indicate that degenerative changes in patients with MMPRTs extend beyond the immediate vicinity of the posterior root tear. This suggests more widespread meniscal degeneration, often undetected by surface examinations in arthroscopy.

In Science Journals.

Highlights from the Science family of journals.

In Science Journals.

Highlights from the Science family of journals.

N-95/P2 respirator compliance with fit testing recommendations and respirator satisfaction amongst hospital staff.

BACKGROUND: Filtering Facepiece Respirators (FFRs) are an important and readily scalable infection control measure; however their effectiveness is ultimately determined by compliance. We aimed to examine staff compliance and satisfaction with wearing the N95/P2 FFRs assigned to them via the standardised fit testing protocol implemented in a single large healthcare network in Victoria, Australia. METHODS: In this cross-sectional survey, employees from five hospital campuses who participated in the health networks N95/P2 FFR fit testing process were invited in person to participate in the study. Data were analysed descriptively, after which chi-squared analysis was performed to determine differences between respirator types, gender, and age groups. RESULTS: Amongst the 258 staff members surveyed, 28% had either never or only sometimes worn an FFR to which they had been successfully fit tested, and 11% had experienced facial changes that potentially rendered their most recent fit test invalid. More than half (53%) of those surveyed had experienced side effects, the most common being skin irritation and pressure sores. A majority (87%) of staff felt that wearing an FFR had some impact on their ability to perform their duties. Pooled mean self-reported satisfaction ratings were highest for three-panel flat-fold and duckbill models. CONCLUSION: 28% of HCWs surveyed described not wearing N-95/P2 FFRs for which they had successfully been fit tested. Reasons for non-compliance remain unclear, but rates of side effects and interference with duties were high. Further research is required to determine and address potential causative factors and ascertain ongoing optimal organisation-level fit test strategies.

Re-Examining the Link Between Premarital Sex and Divorce.

Premarital sex predicts divorce, but we do not know why. Scholars have attributed the relationship to factors such as differences in beliefs and values, but these explanations have not been tested. It is further unclear how this relationship changes by number of sexual partners, or differs by gender. We re-examine this relationship with event history models using data from the National Longitudinal Study of Adolescent to Adult Health. Models include measures of adolescent beliefs and values, religious background, and personal characteristics, as well as approximate number of premarital sexual partners in young adulthood. We find the relationship between premarital sex and divorce is highly significant and robust even when accounting for early-life factors. Compared to people with no premarital partners other than eventual spouses, those with nine or more partners exhibit the highest divorce risk, followed by those with one to eight partners. There is no evidence of gender differences.

Enhancing Chemotherapy Response Prediction via Matched Colorectal Tumor-Organoid Gene Expression Analysis and Network-Based Biomarker Selection.

Colorectal cancer (CRC) poses significant challenges in chemotherapy response prediction due to its molecular heterogeneity. This study introduces an innovative methodology that leverages gene expression data generated from matched colorectal tumor and organoid samples to enhance prediction accuracy. By applying Consensus Weighted Gene Co-expression Network Analysis (WGCNA) across multiple datasets, we identify critical gene modules and hub genes that correlate with patient responses, particularly to 5-fluorouracil (5-FU). This integrative approach advances precision medicine by refining chemotherapy regimen selection based on individual tumor profiles. Our predictive model demonstrates superior accuracy over traditional methods on independent datasets, illustrating significant potential in addressing the complexities of high-dimensional genomic data for cancer biomarker research.

Retraction: Carbon content drives high temperature superconductivity in a carbonaceous sulfur hydride below 100 GPa.

Retraction of 'Carbon content drives high temperature superconductivity in a carbonaceous sulfur hydride below 100 GPa' by G. Alexander Smith et al., Chem. Commun., 2022, 58, 9064-9067, https://doi.org/10.1039/D2CC03170A.

Prognostic value of high-sensitivity cardiac troponin in non-cardiac surgical patients in intensive care units.

Type II myocardial injury following surgical procedures is associated with adverse outcomes. The prognostic value of high-sensitivity cardiac troponin (hs-cTn) due to type II myocardial injury in surgical patients admitted to intensive care unit (ICU) remains unclear. The aim of this study was to assess prognostic value of hs-cTn in type II acute myocardial injury in non-cardiac surgical patients requiring post-operative ICU admission. Retrospective analysis of patients admitted to two level III ICUs following surgery and had hs-cTn measured on the day of ICU admission. Patients who had type I acute myocardial infarction (AMI) during their admission were excluded from the study. The primary outcome was hospital mortality. Secondary outcomes included ICU mortality, ICU length of stay (LOS) and hospital LOS. A total of 420 patients were included. On univariable analysis, higher hs-cTn was associated with increased hospital mortality (14.6% vs 6.3%, p = 0.008), ICU LOS (41.1 h, vs 25 h, p = 0.004) and hospital LOS (253 h vs 193 h, p = 0.02). On multivariable analysis, hs-cTn was not independently associated with increased risk of hospital mortality. However, in patients who had elective surgery, hs-cTn was associated with increased risk (OR 1.048; 95% CI 1.004-1.094; p = 0.031) of hospital mortality with area under the receiver operating characteristic curve of 0.753 (95% CI 0.598-0.908). In elective surgical patients, hs-cTn was associated with increased risk of mortality. Larger multicentre studies are required to confirm this association that may assist in risk stratification of elective surgical patients requiring ICU admission.

Longitudinal clinical data improve survival prediction after hematopoietic cell transplantation using machine learning.

ABSTRACT: Serial prognostic evaluation after allogeneic hematopoietic cell transplantation (allo-HCT) might help identify patients at high risk of lethal organ dysfunction. Current prediction algorithms based on models that do not incorporate changes to patients' clinical condition after allo-HCT have limited predictive ability. We developed and validated a robust risk-prediction algorithm to predict short- and long-term survival after allo-HCT in pediatric patients that includes baseline biological variables and changes in the patients' clinical status after allo-HCT. The model was developed using clinical data from children and young adults treated at a single academic quaternary-care referral center. The model was created using a randomly split training data set (70% of the cohort), internally validated (remaining 30% of the cohort) and then externally validated on patient data from another tertiary-care referral center. Repeated clinical measurements performed from 30 days before allo-HCT to 30 days afterwards were extracted from the electronic medical record and incorporated into the model to predict survival at 100 days, 1 year, and 2 years after allo-HCT. Naïve-Bayes machine learning models incorporating longitudinal data were significantly better than models constructed from baseline variables alone at predicting whether patients would be alive or deceased at the given time points. This proof-of-concept study demonstrates that unlike traditional prognostic tools that use fixed variables for risk assessment, incorporating dynamic variability using clinical and laboratory data improves the prediction of mortality in patients undergoing allo-HCT.

The role of total neoadjuvant therapy in locally advanced rectal cancer: a survey of specialists attending the All-Ireland Colorectal Cancer Conference 2022 including lead investigators of OPRA, PRODIGE-23 and RAPIDO.

BACKGROUND: The treatment of locally advanced rectal cancer (LARC) has evolved following recent landmark trials of total neoadjuvant therapy (TNT)-the delivery of preoperative chemotherapy sequenced with radiation. AIM: To assess the preferences of colorectal surgery (CRS), radiation oncology (RO) and medical oncology (MO) specialists attending the All-Ireland Colorectal Cancer Conference (AICCC) 2022 regarding the neoadjuvant management of LARC. METHODS: A live electronic survey explored the preferred treatment approach and TNT regimen for early-, intermediate-, bad-, and advanced-risk categories of rectal cancer according to the European Society of Medical Oncology (ESMO) guidelines. The survey was preceded by an update from lead investigators of TNT trials (OPRA, PRODIGE-23 and RAPIDO), who then participated in a multidisciplinary panel discussion. RESULTS: Ten CRS, 7 RO and 15 MO (32 of 45 specialists) participated fully in the survey resulting in a response rate of 71%. Ninety-four percent, 76% and 53% of specialists preferred a TNT approach for patients with advanced, bad, and intermediate-risk rectal cancer, respectively. A consolidation TNT regimen of long-course chemoradiotherapy followed by chemotherapy was the most preferred regimen. Upfront surgery was preferred by 77% for early-risk disease. CONCLUSION: This survey illustrated the general acceptance of TNT by rectal cancer specialists attending the AICCC as a valuable treatment strategy for higher-risk category LARC. Whilst the treatment of LARC changes, it remains best practice to individualize care, incorporating the selective use of TNT as discussed by an MDT and in keeping with the patient's goals of care.

Factors influencing parents' choice of palliative treatment goals for children with relapsed or refractory neuroblastoma: A multi-site longitudinal survey study.

BACKGROUND: Many parents of children with advanced cancer report curative goals and continue intensive therapies that can compound symptoms and suffering. Factors that influence parents to choose palliation as the primary treatment goal are not well understood. The objective of this study was to examine experiences impacting parents' report of palliative goals adjusted for time. The authors hypothesized that awareness of poor prognosis, recall of oncologists' prognostic disclosure, intensive treatments, and burdensome symptoms and suffering would influence palliative goal-setting. METHODS: The authors collected prospective, longitudinal surveys from parents of children with relapsed/refractory neuroblastoma at nine pediatric cancer centers across the United States, beginning at relapse and continuing every 3 months for 18 months or until death. Hypothesized covariates were examined for possible associations with parental report of palliative goals. Generalized linear mixed models were used to evaluate factors associated with parents' report of palliative goals at different time points. RESULTS: A total of 96 parents completed surveys. Parents were more likely to report a primary goal of palliation when they recalled communication about prognosis by their child's oncologist (odds ratio [OR], 52.48; p = .010). Treatment intensity and previous ineffective therapeutic regimens were not associated with parents' report of palliative goals adjusted for time. A parent who reported new suffering for their child was less likely to report palliative goals (OR, 0.13; p = .008). CONCLUSIONS: Parents of children with poor prognosis cancer may not report palliative goals spontaneously in the setting of treatment-related suffering. Prognostic communication, however, does influence palliative goal-setting. Evidence-based interventions are needed to encourage timely, person-centered prognostic disclosure in the setting of advanced pediatric cancer. PLAIN LANGUAGE SUMMARY: Many parents of children with poor-prognosis cancer continue to pursue curative treatments that may worsen symptoms and suffering. Little is known about which factors influence parents to choose palliative care as their child's main treatment goal. To explore this question, we asked parents of children with advanced neuroblastoma across the United States to complete multiple surveys over time. We found that the intensity of treatment, number of treatments, and suffering from treatment did not influence parents to choose palliative goals. However, when parents remembered their child's oncologist talking about prognosis, they were more likely to choose palliative goals of care.

Striving to be the fittest: quantitative P2/N95 respirator fit test results among hospital staff during the COVID-19 pandemic.

Objective: To provide fit rates for specific P2/N95 respirators and compare these results by age, sex, clean-shaven status, and fit tester experience. Design: Exploratory audit involving secondary analysis of existing quantitative fit testing data. Setting: In response to the COVID-19 pandemic, healthcare services across Australia implemented respiratory protection protocols. This study details healthcare workers' (HCWs) fit testing results from a large Victorian public health service. Participants: Fit-tested employees of a large tertiary public health network. Methods: Fit rates for ten individual P2/N95 respirators were calculated, and the effect of age, sex, clean-shaven status, and fit tester experience was examined via logistic regression. Results: 4593 employees were included, with 97.98% successfully fitting at least one respirator. Males were found to have significantly increased odds of achieving fit success compared to females (OR 11.61 95%CI 1.60-84.10). Fit rates dropped by 4% with each 1-year age increase (OR 0.96 95%CI 0.94-0.98). Clean-shaven individuals were also more likely to achieve a fit compared to non-clean-shaved individuals (OR 79.23 95%CI 10.21-614.62). More experienced fit testers also yielded significantly higher fit rates (OR 3.95, 95%CI 2.34-6.67). Conclusions: 98% of staff achieved a successful fitting of at least one respirator, with three-panel flat fold models (Industree Trident, 3M Aura 9320A+, and 3M Aura 1870+) performing the most consistently. An individual's ability to achieve a successful fit was associated with; male sex, younger age, clean-shaven status, and fit tester experience.

Rewarded Maze Training Increases Approach Behavior in Rats Through Neurogenesis-Dependent Growth of Ventral Hippocampus-Prelimbic Circuits.

Background: Learning complex navigation routes increases hippocampal volume in humans, but it is not clear whether this growth impacts behaviors outside the learning situation or what cellular mechanisms are involved. Methods: We trained rats with pharmacogenetic suppression of adult neurogenesis and littermate controls in 3 mazes over 3 weeks and tested novelty approach behavior several days after maze exposure. We then measured hippocampus and prelimbic cortex volumes using magnetic resonance imaging and assessed neuronal and astrocyte morphology. Finally, we investigated the activation and behavioral role of the ventral CA1 (vCA1)-to-prelimbic pathway using immediate-early genes and DREADDs (designer receptors exclusively activated by designer drugs). Results: Maze training led to volume increase of both the vCA1 region of the hippocampus and the prelimbic region of the neocortex compared with rats that followed fixed paths. Growth was also apparent in individual neurons and astrocytes in these 2 regions, and behavioral testing showed increased novelty approach in maze-trained rats in 2 different tests. Suppressing adult neurogenesis prevented the effects on structure and approach behavior after maze training without affecting maze learning itself. The vCA1 neurons projecting to the prelimbic area were more activated by novelty in maze-trained animals, and suppression of this pathway decreased approach behavior. Conclusions: Rewarded navigational learning experiences induce volumetric and morphologic growth in the vCA1 and prelimbic cortex and enhance activation of the circuit connecting these 2 regions. Both the structural and behavioral effects of maze training require ongoing adult neurogenesis, suggesting a role for new neurons in experience-driven increases in novelty exploration.

Risk Factors and Outcomes of Delayed Presentation of Diabetic Retinopathy Patients to a County Hospital.

Purpose: To identify risk factors and evaluate outcomes of patients with delayed presentation and advanced diabetic retinopathy in our safety-net county hospital population. Methods: A retrospective study was performed on 562 patients who presented with a new diagnosis of diabetic retinopathy (DR). Delayed presentation was defined as moderate or severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) at the initial visit. Comparisons between patient groups were performed with chi-square or Fisher's exact test for categorical variables and multinomial logistic regression for multivariable analysis. Linear and logistic regression modeling with general estimating equations to account for patients having two eyes was used to compare eye-level outcomes. Results: Lack of a primary care provider (PCP) was highest in patients who presented initially with PDR (28.8%), compared to 14.3% in moderate/severe NPDR, 12.4% in mild NPDR, and 7.6% in no DR groups (P < 0.001). Only 69.4% of patients with a PCP had an ophthalmology screening referral. Highest lack of referral (47.2%) was seen in the PDR group (P = 0.002). Patients with PDR were more likely to be uninsured (19.2%) compared to no and mild DR groups, with rates of 7.6% and 9.0%, respectively (P = 0.001). The PDR group had worse initial and final visual acuities (P < 0.001). Conclusions: Several risk factors were noted for delayed DR presentation, including lack of PCP, lack of screening referral, and uninsured/underinsured status. Patients with advanced DR at presentation had worse final visual outcomes despite aggressive treatment. Translational Relevance: Screening programs targeting populations with identified risk factors are essential for improving outcomes.

Is Nonoperative Management of Rectal Cancer Feasible?

During the past decade, the treatment of locally advanced rectal cancer (LARC) has become more complex. Total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathologic complete response, resulting in improved long-term oncological outcomes. The feasibility to implement nonoperative management (NOM) depends on solving current challenges such as how to correctly identify the best candidates for a NOM without compromising oncologic safety. NOM should be part of the treatment discussion of LARC, considering increasing rates of clinical complete response, potential quality of life gains, avoidance of surgical morbidity, and patient preferences.