Rapid point-of-care breath test predicts breast cancer and abnormal mammograms in symptomatic women.

Previous studies have reported volatile organic compounds (VOCs) in the breath as biomarkers of breast cancer. These biomarkers may be derived from cancer-associated fibroblasts, in which oxidative stress degrades polyunsaturated fatty acids to volatile alkanes and methylated alkane derivatives that are excreted in the breath. We evaluated a rapid point-of-care test for breath VOC biomarkers as predictors of breast cancer and abnormal mammograms. We studied 593 women aged⩾18 yr referred to three sites for mammography for a symptomatic breast-related concern (e.g. breast mass, nipple discharge). A rapid point-of-care breath testing system collected and concentrated alveolar breath VOCs on a sorbent trap and analyzed them with gas chromatography and surface acoustic wave detection in <6 min. Breath VOC chromatograms were randomly assigned to a training set or to a validation set. Monte Carlo analysis identified significant breath VOC biomarkers of breast cancer and abnormal mammograms in the training set, and these biomarkers were incorporated into a multivariate algorithm to predict disease in the validation set.Prediction of breast cancer:50 women had biopsy-proven breast cancer (invasive cancer 41, ductal non-invasive cancer 9)Unsplit data set:breath VOCs identified breast cancer with 83% accuracy (area under curve of receiver operating characteristic), 82% sensitivity and 77.1% specificity.Split data sets:training set breath VOCs identified breast cancer with 80.3% accuracy, 84% sensitivity and 74.3% specificity. Corresponding values in the validation set were 68%% accuracy, 72.4% sensitivity and 61.5% specificity.Prediction of BIRADS 4 and 5 mammograms (versus BIRADS 1, 2 and 3): unsplit data set:breath VOCs identified abnormal mammograms with 76.2% accuracy.Split data sets:breath VOCs identified abnormal mammograms with 74.2% accuracy, 73.3% sensitivity and 60% specificity. Corresponding values in the validation set were 60.5% accuracy, 64.2% sensitivity and 51% specificity. A rapid point-of-care test for breath VOC biomarkers predicted risk of breast cancer and abnormal mammograms in women with breast-related symptoms.

Beyond monopole electrostatics in regulating conformations of intrinsically disordered proteins.

Conformations and dynamics of an intrinsically disordered protein (IDP) depend on its composition of charged and uncharged amino acids, and their specific placement in the protein sequence. In general, the charge (positive or negative) on an amino acid residue in the protein is not a fixed quantity. Each of the ionizable groups can exist in an equilibrated distribution of fully ionized state (monopole) and an ion-pair (dipole) state formed between the ionizing group and its counterion from the background electrolyte solution. The dipole formation (counterion condensation) depends on the protein conformation, which in turn depends on the distribution of charges and dipoles on the molecule. Consequently, effective charges of ionizable groups in the IDP backbone may differ from their chemical charges in isolation-a phenomenon termed charge-regulation. Accounting for the inevitable dipolar interactions, that have so far been ignored, and using a self-consistent procedure, we present a theory of charge-regulation as a function of sequence, temperature, and ionic strength. The theory quantitatively agrees with both charge reduction and salt-dependent conformation data of Prothymosin-alpha and makes several testable predictions. We predict charged groups are less ionized in sequences where opposite charges are well mixed compared to sequences where they are strongly segregated. Emergence of dipolar interactions from charge-regulation allows spontaneous coexistence of two phases having different conformations and charge states, sensitively depending on the charge patterning. These findings highlight sequence dependent charge-regulation and its potential exploitation by biological regulators such as phosphorylation and mutations in controlling protein conformation and function.

A novel copy number variant in the murine Cdh23 gene gives rise to profound deafness and vestibular dysfunction.

Hearing loss is the most common congenital sensory deficit worldwide and exhibits high genetic heterogeneity, making molecular diagnoses elusive for most individuals. Detecting novel mutations that contribute to hearing loss is crucial to providing accurate personalized diagnoses, tailored interventions, and improving prognosis. Copy number variants (CNVs) are structural mutations that are understudied, potential contributors to hearing loss. Here, we present the Abnormal Wobbly Gait (AWG) mouse, the first documented mutant exhibiting waltzer-like locomotor dysfunction, hyperactivity, circling behaviour, and profound deafness caused by a spontaneous CNV deletion in cadherin 23 (Cdh23). We were unable to identify the causative mutation through a conventional whole-genome sequencing (WGS) and variant detection pipeline, but instead found a linked variant in hexokinase 1 (Hk1) that was insufficient to recapitulate the AWG phenotype when introduced into C57BL/6J mice using CRISPR-Cas9. Investigating nearby deafness-associated genes revealed a pronounced downregulation of Cdh23 mRNA and a complete absence of full-length CDH23 protein, which is critical for the development and maintenance of inner ear hair cells, in whole head extracts from AWG neonates. Manual inspection of WGS read depth plots of the Cdh23 locus revealed a putative 10.4 kb genomic deletion of exons 11 and 12 that was validated by PCR and Sanger sequencing. This study underscores the imperative to refine variant detection strategies to permit identification of pathogenic CNVs easily missed by conventional variant calling to enhance diagnostic precision and ultimately improve clinical outcomes for individuals with genetically heterogenous disorders such as hearing loss.

Analysis of technical failure after 1,613 surgical microwave ablations: A propensity score-matched analysis.

BACKGROUND: Microwave ablation is becoming increasingly common for the treatment of liver tumors. Despite numerous studies aimed at identifying risk factors for local recurrence after microwave ablation, a consensus on modifiable risk factors for failure remains elusive, partly because of the limited statistical power of these studies. This study investigated the incidence of technical failure after microwave ablation, encompassing both incomplete ablation and local recurrence, and aimed to identify modifiable factors that reduce technical failure. METHODS: This retrospective review included patients who underwent surgical microwave ablation at a high-volume institution between October 2006 and March 2023. Univariate analysis, multivariate analysis, and propensity score matching were performed to identify risk factors for technical failure. RESULTS: A total of 1,613 surgical microwave ablations were performed on 3,035 tumors, with 226 instances (14% per procedure, 7.4% per tumor) of technical failure. Incomplete ablation occurred at a rate of 1.7% per tumor, whereas local recurrence was identified in 6.5% of ablations in per-tumor analysis. Body mass index >25 was significant for failure (odds ratio, 1.50; 95% confidence interval, 1.07-2.11; P < .05), suggesting that more difficult targeting may lead to increased technical failure rates. African American race (odds ratio, 1.62; 95% confidence interval, 1.16-2.27; P < .05), pre-microwave ablation transarterial chemoembolization (odds ratio, 1.54; 95% confidence interval, 1.08-2.21; P < .05), and previous ablation (odds ratio, 1.58; 95% confidence interval, 1.09-2.29; P < .05) were found to be statistically significant. CONCLUSION: On the basis of the largest microwave ablation database available to date, this study identified novel modifiable and nonmodifiable risk factors of microwave ablation failure. These results can lead to decreasing technical failure rates after microwave ablation.

Comparison of surgical or non-surgical management for non-acute anterior cruciate ligament injury: the ACL SNNAP RCT.

Background: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. Objective(s): To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). Design: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out. Setting: Twenty-nine NHS orthopaedic units in the United Kingdom. Participants: Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Interventions: Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. Main outcome measures: The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Results: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively. Limitations: Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. Conclusions: Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation. Future work: Confirmatory studies and those to explore the influence of fidelity and compliance will be useful. Trial registration: This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367. Funding: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.

The study aimed to find out whether it is better to offer surgical reconstruction or rehabilitation first to patients with a more long-standing injury of their anterior cruciate ligament in their knee. This injury causes physical giving way of the knee and/or sensations of it being wobbly (instability). The instability can affect daily activities, work, sport and can lead to arthritis. There are two main treatment options for this problem: non-surgical rehabilitation (prescribed exercises and advice from physiotherapists) or an operation by a surgeon to replace the damaged ligament (anterior cruciate ligament reconstruction). Although studies have highlighted the best option for a recently injured knee, the best management was not known for patients with a long-standing injury, perhaps occurring several months previously. Because the surgery is expensive to the NHS (around £100 million per year), it was also important to look at the costs involved. We carried out a study recruiting 316 non-acute anterior cruciate ligament-injured patients from 29 different hospitals and allocated each patient to either surgery or rehabilitation as their treatment option. We measured how well they did with special function and activity scores, patient satisfaction and costs of treatment. Patients in both groups improved substantially. It was expected that some patients in the rehabilitation group would want surgery if non-surgical management was unsuccessful. Forty-one per cent of patients who initially underwent rehabilitation subsequently elected to have reconstructive surgery. Overall, the patients allocated to the surgical reconstruction group had better results in terms of knee function and stability, activity level and satisfaction with treatment than patients allocated to the non-operative rehabilitation group. There were few problems or complications with either treatment option. Although the surgery was a more expensive treatment option, it was found to be cost-effective in the UK setting. The evidence can be discussed in shared decision-making with anterior cruciate ligament-injured patients. Both strategies of management led to improvement. Although a rehabilitation strategy can be beneficial, especially for recently injured patients, it is advised that later-presenting non-acute and more long-standing anterior cruciate ligament-injured patients undergo surgical reconstruction without necessarily delaying for a period of rehabilitation.

Usability, Acceptability, and Implementation of Artificial Intelligence (AI) and Machine Learning (ML) Techniques in Surgical Coaching and Training: A Scoping Review.

OBJECTIVE: To define the current state of peer-reviewed literature demonstrating the usability, acceptability, and implementation of artificial intelligence (AI) and machine learning (ML) techniques in surgical coaching and training. DESIGN: We conducted a literature search with defined inclusion and exclusion criteria. We searched five scholarly databases: MEDLINE via PubMed, Embase via Elsevier, Scopus via Elsevier, Cochrane Central Register of Controlled Trials, and the Healthcare Administration Database via ProQuest. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. RESULTS: Only 4 articles met the inclusion criteria and used standardized methods for performance evaluation with expert observation. We found no literature examining the impact on performance, user acceptance, or implementation of AI/ML techniques used for surgical coaching and training. We highlight the need for qualitative and quantitative research demonstrating these techniques' effectiveness before broad implementation. CONCLUSION AND RELEVANCE: We emphasize the need for research to specifically evaluate performance, impact, user acceptance, and implementation of AI/ML techniques. Incorporating these facets of research when developing AI/ML techniques for surgical training is crucial to ensure emerging technology meets user needs without increasing cognitive burden or frustrating users.

Research in China about the biological mechanisms that potentially link socioenvironmental changes and mental health: a scoping review.

China's rapid socioeconomic development since 1990 makes it a fitting location to summarise research about how biological changes associated with socioenvironmental changes affect population mental health and, thus, lay the groundwork for subsequent, more focused studies. An initial search identified 308 review articles in the international literature about biomarkers associated with 12 common mental health disorders. We then searched for studies conducted in China that assessed the association of the identified mental health related-biomarkers with socioenvironmental factors in English-language and Chinese-language databases. We located 1330 articles published between 1 January 1990 and 1 August 2021 that reported a total of 3567 associations between 56 specific biomarkers and 11 socioenvironmental factors: 3156 (88·5%) about six types of environmental pollution, 381 (10·7%) about four health-related behaviours (diet, physical inactivity, internet misuse, and other lifestyle factors), and 30 (0·8%) about socioeconomic inequity. Only 245 (18·4%) of the papers simultaneously considered the possible effect of the biomarkers on mental health conditions; moreover, most of these studies assessed biomarkers in animal models of mental disorders, not human subjects. Among the 245 papers, mental health conditions were linked with biomarkers of environmental pollution in 188 (76·7%), with biomarkers of health-related behaviours in 48 (19·6%), and with biomarkers of socioeconomic inequality in 9 (3·7%). The 604 biomarker-mental health condition associations reported (107 in human subjects and 497 in animal models) included 379 (62·7%) about cognitive functioning, 117 (19·4%) about anxiety, 56 (9·3%) about depression, 21 (3·5%) about neurodevelopmental conditions, and 31 (5·1%) about neurobehavioural symptoms. Improved understanding of the biological mechanisms linking socioenvironmental changes to community mental health will require expanding the range of socioenvironmental factors considered, including mental health outcomes in more of the studies about the association of biomarkers with socioenvironmental factors, and increasing the proportion of studies that assess mental health outcomes in humans.

Mental health and psychosocial interventions to limit the adverse psychological effects of disasters and emergencies in China: a scoping review.

Exposure to disasters and public health emergencies negatively affects mental health. Research documenting the psychosocial responses to these calamities in China increased dramatically after the 2008 Wenchuan earthquake. However, there is no comprehensive assessment of the available literature on China's mental health and psychosocial support (MHPSS) responses to these events. This scoping review systematically maps existing published research and grey literature sources regarding MHPSS to disasters and emergencies in China. We examined relevant literature in English and Chinese from six databases and official websites from Jan 1, 2000, to Aug 13, 2021, and included 77 full-text records in this review. The main types of interventions reported included a) stepped care intervention models, b) individual structured psychotherapy and pharmacotherapy, c) mental health education, d) psychological counselling, and e) government-based policy interventions. Most interventions were evaluated using quantitative methods that assessed the treatment of common mental disorders. The review found that rapid national mobilization, emphasis on resilience-strengthening interventions, and the widespread use of step-care models were essential components of reducing the adverse psychosocial effects of disasters. The review also identified remaining gaps, including a) a lack of integration of disaster-related services with the pre-existing health care system, b) inadequate supervision of MHPSS providers, and c) limited monitoring and evaluation of the services provided. These results show where additional research is needed in China to improve mental health services. It also provides a framework that other countries can adapt when developing and evaluating MHPSS policies and plans in response to disasters.

Use of the Chinese version of the MATRICS Consensus Cognitive Battery to assess cognitive functioning in individuals with high risk for psychosis, first-episode schizophrenia and chronic schizophrenia: a systematic review and meta-analysis.

More than one hundred studies have used the mainland Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) to assess cognition in schizophrenia, but the results of these studies, the quality of the reports, and the strength of the evidence provided in the reports have not been systematically assessed. We identified 114 studies from English-language and Chinese-language databases that used the Chinese MCCB to assess cognition in combined samples of 7394 healthy controls (HC), 392 individuals with clinical high risk for psychosis (CHR-P), 4922 with first-episode schizophrenia (FES), 1549 with chronic schizophrenia (CS), and 2925 with schizophrenia of unspecified duration. The mean difference (MD) of the composite MCCB T-score (-13.72) and T-scores of each of the seven cognitive domains assessed by MCCB (-14.27 to -7.92) were significantly lower in individuals with schizophrenia than in controls. Meta-analysis identified significantly greater cognitive impairment in FES and CS than in CHR-P in six of the seven domains and significantly greater impairment in CS than FES in the reasoning and problem-solving domain (i.e., executive functioning). The only significant covariate of overall cognitive functioning in individuals with schizophrenia was a negative association with the severity of psychotic symptoms. These results confirm the construct validity of the mainland Chinese version of MCCB. However, there were significant limitations in the strength of the evidence provided about CHR-P (small pooled sample sizes) and the social cognition domain (inconsistency of results across studies), and the quality of many reports (particularly those published in Chinese) was rated 'poor' due to failure to report sample size calculations, matching procedures or methods of handling missing data. Moreover, almost all studies were cross-sectional studies limited to persons under 60 with at least nine years of education, so longitudinal studies of under-educated, older individuals with schizophrenia are needed.

Professional characteristics, numbers, distribution and training of China's mental health workforce from 2000 to 2020: a scoping review.

Over the last 20 years, the numbers, types, distribution, and qualifications of mental health professionals in China have changed dramatically. However, there has been no systematic attempt to collect information about this transformation in the human resources available to provide mental health services-information that needs to be regularly updated to improve the country's coordination of these services. This scoping review compiles current details about China's mental health workforce and identifies critical gaps in available research and reporting. We reviewed all relevant studies and reports published between 1 January 2000 and 30 June 2021 in two English-language and four Chinese-language databases, the website of China's National Health Commission, and national and provincial health services yearbooks. In addition to summarising data from government yearbooks, we integrated relevant results from 82 peer-reviewed publications and two government reports. From 2000 to 2020, the number of psychiatrists in the country increased by 139%, and the number of psychiatric nurses increased by 340%. However, the much higher ratio of mental health professionals per 100,000 population and the better quality of training of mental health professionals in urban, eastern provinces compared to rural, western provinces has not changed. Progress has been made in standardising the training of psychiatrists, but there are no standardised training programs for psychiatric nurses, clinical psychologists, or psychiatric social workers. Future research needs to address several issues that limit the effectiveness of policies aimed at increasing the size, quality and equitable distribution of China's mental health workforce: 1) limited data available about the numbers and characteristics of professionals who provide mental health services, 2) absence of nationally standardised training programs for non-psychiatric medical professionals and non-medical personnel who provide essential monitoring and supportive care to persons with mental illnesses, and 3) failure to scientifically assess the outcomes of currently available training programs.

The common p.Ile291Val variant of ERLIN1 enhances TM6SF2 function and is associated with protection against MASLD.

BACKGROUND: The ERLIN1 p.Ile291Val single-nucleotide polymorphism (rs2862954) is associated with protection from steatotic liver disease (SLD), but effects of this variant on metabolic phenotypes remain uncertain. METHODS: Metabolic phenotypes and outcomes associated with ERLIN1 p.Ile291Val were analyzed by using a genome-first approach in the UK Biobank (UKB), Penn Medicine BioBank (PMBB), and All of Us cohort. FINDINGS: ERLIN1 p.Ile291Val carriers exhibited significantly lower serum levels of alanine aminotransferase and aspartate aminotransferase as well as higher levels of triglycerides, low-density lipoprotein cholesterol, Apolipoprotein B, high-density lipoprotein cholesterol, and Apolipoprotein A1 in UKB, and these values were affected by ERLIN1 p.Ile291Val in an allele-dose-dependent manner. Homozygous ERLIN1 p.Ile291Val carriers had a significantly reduced risk of developing metabolic dysfunction-associated SLD (MASLD, adjusted odds ratio [aOR] = 0.92, 95% confidence interval [CI], 0.88-0.96). The protective effect of this variant was enhanced in patients with alcoholic liver disease. Our results were replicated in PMBB and the All of Us cohort. Strikingly, the protective effects of ERLIN1 p.Ile291Val were not apparent in individuals carrying the TM6SF2 p.Glu167Lys variant associated with increased risk of SLD. We analyzed the effects of predicted loss-of-function ERLIN1 variants and found that they had opposite effects, namely reduced plasma lipids, suggesting that ERLIN1 p.Ile291Val may be a gain-of-function variant. CONCLUSION: Our study contributes to a better understanding of ERLIN1 by investigating a coding variant that has emerged as a potential gain-of-function mutation with protective effects against MASLD development.

Neighborhood child opportunity is associated with hospital length of stay following pediatric burn injury.

INTRODUCTION: Pediatric burns are associated with socioeconomic disadvantage and lead to significant morbidity. The Child Opportunity Index (COI) is a well-validated measure of neighborhood characteristics associated with healthy child development. We sought to evaluate the relationship between COI and outcomes of burn injuries in children. METHODS: We performed a single-institution retrospective review of pediatric (<16 years) burn admissions between 2015 and 2019. Based on United States residential zip codes, patients were stratified into national COI quintiles. We performed a multivariate Poisson regression analysis to determine the association between COI and increased length of stay. RESULTS: 2095 pediatric burn admissions occurred over the study period. Most children admitted were from very low (n = 644, 33.2 %) and low (n = 566, 29.2 %) COI neighborhoods. The proportion of non-Hispanic Black patients was significantly higher in neighborhoods with very low (44.5 %) compared to others (low:28.8 % vs. moderate:11.9 % vs. high:10.5 % vs. very high:4.3 %) (p < 0.01). Hospital length of stay was significantly longer in patients from very low COI neighborhoods (3.6 ± 4.1 vs. 3.2 ± 4.9 vs. 3.3 ± 4.8 vs. 2.8 ± 3.5 vs. 3.2 ± 8.1) (p = 0.02). On multivariate regression analysis, living in very high COI neighborhoods was associated with significantly decreased hospital length of stay (IRR: 0.51; 95 % CI: 0.45-0.56). CONCLUSION: Children from neighborhoods with significant socioeconomic disadvantage, as measured by the Child Opportunity Index, had a significantly higher incidence of burn injuries resulting in hospital admissions and longer hospital length of stay. Public health interventions focused on neighborhood-level drivers of childhood development are needed to decrease the incidence and reduce hospital costs in pediatric burns. TYPE OF STUDY: Retrospective study LEVEL OF EVIDENCE: Level III.

Outcomes after Surgical Microwave Ablation for the Treatment of Colorectal Liver Metastasis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Of these, approximately 25% will have liver metastasis. We performed 394 microwave ablations (MWAs) and analyzed outcomes for survival and ablation failure. STUDY DESIGN: We conducted a retrospective review of patients who underwent a surgical MWA at a single-center high-volume institution from October 2006 to September 2022 using a prospectively maintained database. The primary outcome was overall survival. RESULTS: A total of 394 operations were performed on 328 patients with 842 tumors undergoing MWA. Median tumor size was 1.5 cm (range 0.4 to 7.0 cm), with the median number of tumors ablated per operation being 1 (range 1 to 11). A laparoscopic approach was used 77.9% of the time. Concomitant procedures were performed 63% of the time, most commonly hepatectomy (22.3%), cholecystectomy (17.5%), and colectomy (6.6%). Clavien-Dindo grade III or IV complication occurred in 12 patients (3.6%), and all of these patients had undergone concomitant procedures. Mortality within 30 days occurred in 4 patients (1.2%). The rate of incomplete ablation was 1.5% per tumor. Local recurrence occurred at a rate of 6.3% per tumor. Black patients were found to have a higher incidence of incomplete ablation and local recurrence. One-year survival probability was 91% (95% CI 87.9 to 94.3), with a mean overall survival of 57.6 months (95% CI 49.9 to 65.4 months). CONCLUSIONS: Surgical MWA offers a low-morbidity approach to treatment of colorectal liver metastasis, with low rate of failure. This large series reviews the outcomes of MWA as definitive treatment for colorectal liver metastasis.

Nonwoven Reinforced Photocurable Poly(glycerol sebacate)-Based Hydrogels.

Implantable hydrogels should ideally possess mechanical properties matched to the surrounding tissues to enable adequate mechanical function while regeneration occurs. This can be challenging, especially when degradable systems with a high water content and hydrolysable chemical bonds are required in anatomical sites under constant mechanical stimulation, e.g., a foot ulcer cavity. In these circumstances, the design of hydrogel composites is a promising strategy for providing controlled structural features and macroscopic properties over time. To explore this strategy, the synthesis of a new photocurable elastomeric polymer, poly(glycerol-co-sebacic acid-co-lactic acid-co-polyethylene glycol) acrylate (PGSLPA), is investigated, along with its processing into UV-cured hydrogels, electrospun nonwovens and fibre-reinforced variants, without the need for a high temperature curing step or the use of hazardous solvents. The mechanical properties of bioresorbable PGSLPA hydrogels were studied with and without electrospun nonwoven reinforcement and with varied layered configurations, aiming to determine the effects of the microstructure on the bulk compressive strength and elasticity. The nonwoven reinforced PGSLPA hydrogels exhibited a 60% increase in compressive strength and an 80% increase in elastic moduli compared to the fibre-free PGSLPA samples. The mechanical properties of the fibre-reinforced hydrogels could also be modulated by altering the layering arrangement of the nonwoven and hydrogel phase. The nanofibre-reinforced PGSLPA hydrogels also exhibited good elastic recovery, as evidenced by the hysteresis in compression fatigue stress-strain evaluations showing a return to the original dimensions.

Key Performance Indicators: A Framework for Allied Healthcare Educational Institutions.

Background: Performance evaluation in the allied healthcare education sector is complex, making it essential for policymakers and managers to approach it comprehensively and thoughtfully to understand their performance. Hence, the development and monitoring of Key Performance Indicators (KPIs) in this domain must be considered one of the key priorities for the policymakers in AHIs. Aim: This study aims to develop a framework for the AHIs to extract and profile the indicators, measure, and report the results appropriately. Methods: The authors adopted a general review of the literature approach to study the primary goals of the institutional KPI framework, emphasizing the need for benchmarking while implementing KPIs and how to track performance using a KPI dashboard. Results: The study provides the scope, relevant KPI categories, and a list of KPIs for evaluating the effectiveness of allied healthcare programs. The study findings also emphasized the need for benchmarking the KPIs and establishing a KPI dashboard while measuring and monitoring performance. Conclusion: KPIs are considered an invaluable tool that contributes immensely to the performance monitoring process of AHIs, irrespective of the specialties. This helps to identify and guide AHIs for developing KPIs and the associated minimum data set to measure organizational performance and monitor the quality of teaching and learning. In addition, the KPI framework reported in this study is a tool to assist performance monitoring that can subsequently contribute to the overall quality of AHIs.

Mixed-mode size-exclusion silica resin for polishing human antibodies in flow-through mode.

The polishing step in the downstream processing of therapeutic antibodies removes residual impurities from Protein A eluates. Among the various classes of impurities, antibody fragments are especially challenging to remove due to the broad biomolecular diversity generated by a multitude of fragmentation patterns. The current approach to fragment removal relies on ion exchange or mixed-mode adsorbents operated in bind-and-gradient-elution mode. However, fragments that bear strong similarity to the intact product or whose biophysical features deviate from the ensemble average can elude these adsorbents, and the lack of a chromatographic technology enabling robust antibody polishing is recognized as a major gap in downstream bioprocessing. Responding to this challenge, this study introduces size-exclusion mixed-mode (SEMM) silica resins as a novel chromatographic adsorbent for the capture of antibody fragments irrespective of their biomolecular features. The pore diameter of the silica beads features a narrow distribution and is selected to exclude monomeric antibodies, while allowing their fragments to access the pores where they are captured by the mixed-mode ligands. The static and dynamic binding capacity of the adsorbent ranged respectively between 30-45 and 25-33 gs of antibody fragments per liter of resin. Selected SEMM-silica resins also demonstrated the ability to capture antibody aggregates, which adsorb on the outer layer of the beads. Optimization of the SEMM-silica design and operation conditions - namely, pore size (10 nm) and ligand composition (quaternary amine and alkyl chain) as well as the linear velocity (100 cm/h), ionic strength (5.7 mS/cm), and pH (7) of the mobile phase - afforded a significant reduction of both fragments and aggregates, resulting into a final antibody yield up to 80% and monomeric purity above 97%.