Replication study identified EFEMP1 association with varicose vein predisposition among Indians.

BACKGROUND: Varicose vein is a chronic condition that affects the lower extremities of the human body. Several factors have been implicated in the development of this disease, viz age, gender, weight, height and prolonged standing. Recently, genome-wide studies have identified genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where the prevalence of varicose veins is high, and it is important to replicate these variants in the stated population. The study aimed to replicate the association of genetic variants associated with varicose veins in this target population, which were found to be associated with the other ethnic groups. METHODOLOGY: The studied cohort is of the Indian population comprising unrelated 104 varicose veins cases and 448 non-varicose vein controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. The allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p-value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians. RESULT: Variant rs3791679 of EFEMP1 was found to be associated with varicose veins in Indians. After observing the association of the EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1 to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEMP1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect ranges from 0.37-1.58. CONCLUSION: This study identifies EFEMP1 as a potential gene related to the risk of varicose veins in Indians. It also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins.

The False-Positive Rate of Synovial Fluid Culture at a Single Clinical Laboratory Using Culture Bottles.

Introduction Synovial fluid (SF) cultures can yield false-positive or negative results when diagnosing periprosthetic joint infection (PJI). False-positives may arise during sample collection or from laboratory contamination. Understanding false-positive SF culture rates is crucial for interpreting PJI laboratory data, yet clinical laboratories rarely report these rates. This study aimed to define the false-positive SF culture rate at a major specialized clinical laboratory. Methods This study retrospectively analyzed prospectively collected data at a single clinical laboratory that receives SF for clinical testing for PJI. A total of 180,317 periprosthetic SF samples from the hip, knee, and shoulder were identified from January 2016 to December 2023, which met the inclusion criteria for this study. Samples were classified by both a modified 2018 International Consensus Meeting (ICM) score and an inflammation score that combined the SF-C-reactive protein, alpha-defensin, SF-white blood cell count, and SF-polymorphonuclear% into one standardized metric. Logistic regression was utilized to evaluate the impact of various collection-based characteristics on culture positivity, including inflammation biomarkers, the source joint, quality control metrics, and days of specimen transport to the laboratory. SF culture false-positivity was calculated based on the ICM category of "not-infected" or low inflammation score. Results Overall, 13.3% (23,974/180,317) of the samples were associated with a positive culture result: 12.5% for knee samples, 20.3% for hip samples, and 14.7% for shoulder samples. The false-positive SF culture rate among 131,949 samples classified as "not-infected" by the modified 2018 ICM definition was 0.47% (95%CI: 0.43 to 0.51%). Stratification by joint revealed a false-positive rate of 0.34% (95%CI: 0.31 to 0.38%) for knee samples, 1.24% (95%CI: 1.05 to 1.45%) for hip samples, and 3.02% (95%CI: 2.40 to 3.80%) for shoulder samples, with p < 0.0001 for all comparisons. The false-positive SF culture rate among 90,156 samples, representing half of all samples with the lowest standardized inflammation scores, was 0.47% (95%CI: 0.43 to 0.52%). Stratification by joint revealed a false-positive rate of 0.33% (95%CI: 0.29 to 0.37%) for knee samples, 1.45% (95%CI: 1.19 to 1.77%) for hip samples, and 3.09% (95%CI: 2.41 to 3.95%) for shoulder samples, with p<0.0001 for all comparisons. Multivariate logistic regression demonstrated the joint source (hip, shoulder) and poor sample quality as collection-based factors associated with a false-positive culture. Evaluation of a cohort of samples selected to minimize collection-based causes of false-positive culture demonstrated a false-positive rate of 0.30%, representing the ceiling limit for laboratory-based SF culture false-positivity. Conclusions This study utilizes two methods to estimate the false-positive SF culture rate at a single specialized clinical laboratory, demonstrating an overall false-positive rate of approximately 0.5%. Stratification of samples by source joint demonstrated that periprosthetic SF from the shoulder and hip have a substantially higher false-positive culture rate than that of the knee. The lowest false-positive SF culture rate (0.30%) was observed among samples from the knee-passing quality control. Culture positivity due to contamination at this specific laboratory is less than 0.30% because all specimens undergo identical processing.

Exploring the determinants of internet addiction among Peri-urban adolescents (aged 13-18) in Delhi-NCR, India: an ordered logit model analysis.

OBJECTIVES: In recent years, there has been phenomenal growth in internet usage worldwide, with a substantial proportion of children and adolescents actively engaging with online platforms. While the internet presents numerous opportunities for children and adolescents, the lack of digital literacy and adequate online safety measures exposes them to various cybercrimes, including cyberbullying, cyberstalking, identity theft, and sexual predation. Moreover, there is growing concern regarding internet addiction among this population. METHODS: To investigate the determinants of internet addiction among adolescents, we conducted a cross-sectional study in peri-urban Delhi-NCR, India. We used a self-administered questionnaire to gather information on internet usage, and 630 adolescents aged 13-18 participated in the study, also completing an Internet Addiction Test. RESULTS: The findings indicate that 415 adolescents (65.9 %) exhibited no signs of internet addiction, suggesting a healthy relationship with the internet. However, 215 adolescents (33.1 %) displayed symptoms of internet addiction. Among those exhibiting internet addictions, 159 (74.0 %) were classified as mild internet addicts, indicating moderate levels of internet usage. Furthermore, 56 (26.0 %) adolescents were classified as moderate internet addicts, reflecting a higher level of internet addiction. CONCLUSIONS: Our study highlights the significant influence of various factors, including family dynamics, environmental factors, and personal experiences, on internet addiction among adolescents. Based on these findings, we propose implementing measures at different levels to foster responsible internet use among adolescents, thereby substantially reducing internet addiction.

Down-conversion luminescence nanocomposites based on nitrogen-doped carbon quantum dots@bioplastic for applications in optical displays, LEDs and UVC tubes.

Carbon quantum dots (CQDs)-based composites as luminous down-conversion materials are becoming more popular due to several advantages such as steady fluorescence, ease of functionalization, tailoring of emission in the visible range, and so on. We report an inexpensive and environmentally sustainable synthesis of fluorescent nitrogen doped-CQDs produced from Cissus quadrangularis, a low-cost plant precursor with therapeutic value. The morphological, structural, and physicochemical features of the material were carefully investigated. Under UV stimulation (365 nm), almost spherical shaped N-CQDs with an average diameter of 5.1 nm were discovered to generate yellow-green fluorescence, have excellent photostability, and strong water solubility, with a quantum yield of up to 5 %. Furthermore, as a solid-phase dispersion matrix for CQDs, ecologically friendly and biodegradable bioplastic is appealing. The down-conversion of solid-state fluorescence of LEDs and UVC tubes was demonstrated by creating a nanocomposite by inserting N-CQDs into the solid matrix of a wheat starch-based bioplastic. Furthermore, employing constructed quantum dot-based optical displays, down-converted LEDs, and UVC tubes, the impacts of varied CQD concentrations and pH sensitivity were examined.

Bibliometric Analysis-Based Review of Fused Deposition Modeling 3D Printing Method (1994-2020).

This study aimed at the detailed bibliometric analysis (BA) of fused deposition modeling (FDM) to understand the trend and research area. Web of Science database was used for extracting data using keywords, and 2793 documents were analyzed. From the analysis, the most influential and productive authors, countries, sources, and so on were identified and corresponding interrelations were represented by a three-field plot. Lotka's law was derived for author productivity and its reliability was verified by the Kolmogorov-Smirnov (K-S) test. Bradford's law was used for identifying the core sources contributing to the field of FDM. From the trend topic analysis, it was found that initially the research was focused upon removing error related to deposition as well as part orientation, but with the course of time, it diversified to include topics such as optimization of printing parameters, materials, and applications. Based on the inferences from BA, the article also discusses on current research trend and highlights certain future areas for research work.

Shape Memory Effect of Four-Dimensional Printed Polylactic Acid-Based Scaffold with Nature-Inspired Structure.

The four-dimensional (4D) printing is an evolving technology that has immense scope in various fields of science and technology owing to ever-challenging needs of human. It is an innovative upgradation of 3D printing procedure, which instills smart capabilities into materials such that they respond to external stimulus. This article aims to investigate the feasibility of 4D printing of polylactic acid (PLA)-based composite scaffolds fabricated by incorporating four different nature-inspired architectures (honeycomb, giant water lily, spiderweb, and nautilus shell). The composites were developed by adding 1, 3, and 5 wt.% of Calcium Phosphate (CaP) into PLA. Various thermomechanical tests were accomplished to evaluate the properties of developed material. Furthermore, the shape memory characteristics of these scaffolds were examined using thermally controlled conditions. The characterization tests displayed favorable outcomes in terms of thermal stability and hydrophilic nature of the PLA and PLA/CaP composite materials. It was found that the honeycomb structure showed the best shape memory and mechanical behavior among the four designs. Furthermore, the introduction of CaP was found to enhance mechanical strength and shape memory property, whereas the surface integrity was adversely affected. This study can play a vital role in developing self-fitting high-shape recovery biomedical scaffolds for bone-repair applications.

Point-of-care diagnosis of tissue fibrosis: a review of advances in vibrational spectroscopy with machine learning.

Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources. Vibrational spectroscopy is a novel technique that offers an alternative atraumatic approach, with short scan times, while providing metabolic and morphological data. This review evaluates vibrational spectroscopy for the assessment of fibrosis, with a focus on point-of-care capabilities. OVID Medline, Embase and Cochrane databases were systematically searched using PRISMA guidelines for search terms including vibrational spectroscopy, human tissue and fibrosis. Studies were stratified based on imaging modality and tissue type. Outcomes recorded included tissue type, machine learning technique, metrics for accuracy and author conclusions. Systematic review yielded 420 articles, of which 14 were relevant. Ten of these articles considered mid-infrared spectroscopy, three dealt with Raman spectroscopy and one with near-infrared spectroscopy. The metrics for detecting fibrosis were Pearson correlation coefficients ranging from 0.65-0.98; sensitivity from 76-100%; specificity from 90-99%; area under receiver operator curves from 0.83-0.98; and accuracy of 86-99%. Vibrational spectroscopy identified fibrosis in myeloproliferative neoplasms in bone, cirrhotic and hepatocellular carcinoma in liver, end-stage heart failure in cardiac tissue and following laser ablation for acne in skin. It also identified interstitial fibrosis as a predictor of early renal transplant rejection in renal tissue. Vibrational spectroscopic techniques can therefore accurately identify fibrosis in a range of human tissues. Emerging data show that it can be used to quantify, classify and provide data about the nature of fibrosis with a high degree of accuracy with potential scope for point-of-care use.

Assessment of Different Indices as Predictors of Difficult Airway in Obese Patients.

Introduction Difficulties with tracheal intubation contribute to the morbidity and mortality associated with anesthesia. Suggested predictors for difficult airway include, history of obstructive sleep apnea, high Mallampati score, elderly, male, short neck, and high Wilson score. However, none of these has high diagnostic accuracy particularly in obese population. Parameters used to quantify obesity such as Body Mass Index(BMI), mid arm circumference, skin fold thickness, etc. have not been used as independent predictors of difficult airway. This study has been designed to evaluate the accuracy of commonly used tools to assess difficult airway and to test other obesity markers as scale for assessing difficult airway i.e. Bag mask ventilation grade ≥3 or Cormack-Lehane Grade≥3 on Direct Laryngoscopy or number of intubation attempts ≥3. Aim To assess BMI, Mallampati grading, Neck circumference and Thyromental distance as predictors of difficult airway in obese patients and to validate neck circumference to thyromental distance ratio and skin fold thickness as a tool for assessment of difficult airway (Bag mask ventilation grade ≥3 or Cormack-Lehane Grade≥3 on Direct Laryngoscopy or number of intubation attempts ≥3.) in obese patients. Methods This prospective observational study was carried out on 51 obese patients (as per BMI) of ASA grade II, either sex, aged 23 to 57 years posted for elective surgery under general anesthesia with endotracheal intubation. After subjective assessment of difficult airway following data sets and variables were obtained - sex, weight, height, body mass index (BMI), Modified Mallampati class (MPG), Cormack-Lehane (CL) grade, adequacy of bag mask ventilation (BMV), number of endotracheal intubation attempts, patient's neck circumference (NC), thyromental distance (TMD), waist-hip ratio (WHR) and Skin fold thickness. The observations made during the study were statistically analyzed and correlated as predictors for difficult airway. Result Correlation of MPG to CL-grade (r-0.41, p-0.003), BMV (r-0.31, p-0.028) & No. of intubation attempts (r-0.37, p-0.007) was mild & statistically significant. Correlation of Neck Circumference with CL-grade (r-0.57, p-0.000), & No. of intubation attempts (r-0.62, p-0.000), found moderate & statistically significant, & with BMV was mild and statistically significant (r-0.48, p-0.000). Correlation of Thyromental Distance to CL-grade (r-0.65, p-0.000), BMV (r-0.70, p-0.000) & No. of intubation attempts (r-0.61, p-0.000) was moderate & statistically significant. Correlation of BMI to CL-grade (r-0.11, p-0.428), BMV (r-0.04, p-0.757) & No. of intubation attempts (r-0.16, p-0.257) was weak & not significant. Skin Fold Thickness showed no significant association with Difficult airway i.e., CL Grade (p-0.478), BMV (p-0.101), and No. of intubation attempts (p-0.143). Correlation of NC/TMD ratio with BMV (r-0.74, p-0.000), CL-grade (r-0.76, p-0.000), & No. of intubation attempts (r-0.77, p-0.000) was moderate & statistically significant. Conclusion NC, TMD and NC/TMD Ratio depicted a close association with airway difficulty in obese patients. Obesity grade is a risk factor for difficult airway but predictors of obesity including Skin Fold Thickness, individually did not show association with difficult airway (small sample size may be a limiting factor). None of the commonly performed tests alone has proven to be adequate in predicting difficult intubation in the obese population.

Near-infrared spectroscopy as a novel method of ex vivo bladder cancer tissue characterisation.

OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.

Genome-wide SNP discovery and genotyping delineates potential QTLs underlying major yield-attributing traits in buckwheat.

Buckwheat (Fagopyrum spp.) is an important nutritional and nutraceutical-rich pseudo-cereal crop. Despite its obvious potential as a functional food, buckwheat has not been fully harnessed due to its low yield, self-incompatibility, increased seed cracking, limited seed set, lodging, and frost susceptibility. The inadequate availability of genomics resources in buckwheat is one of the major reasons for this. In the present study, genome-wide association mapping (GWAS) was conducted to identify loci associated with various morphological and yield-related traits in buckwheat. High throughput genotyping by sequencing led to the identification of 34,978 single nucleotide polymorphisms that were distributed across eight chromosomes. Population structure analysis grouped the genotypes into three sub-populations. The genotypes were also characterized for various qualitative and quantitative traits at two diverse locations, the analysis of which revealed a significant difference in the mean values. The association analysis revealed a total of 71 significant marker-trait associations across eight chromosomes. The candidate genes were identified near 100 Kb of quantitative trait loci (QTLs), providing insights into several metabolic and biosynthetic pathways. The integration of phenology and GWAS in the present study is useful to uncover the consistent genomic regions, related markers associated with various yield-related traits, and potential candidate genes having implications for being utilized in molecular breeding for the improvement of economically important traits in buckwheat. Moreover, the identified QTLs will assist in tracking the desirable alleles of target genes within the buckwheat breeding populations/germplasm.

Accelerometer-derived sleep metrics in mild and difficult-to-treat asthma.

INTRODUCTION: Poor sleep health is associated with increased asthma morbidity and mortality. Accelerometers have been validated to assess sleep parameters though studies using this method in patients with asthma are sparse and none have compared mild to difficult-to-treat asthma populations. METHODS: We performed a retrospective analysis from two recent in-house trials comparing sleep metrics between patients with mild and difficult-to-treat asthma. Participants wore accelerometers for 24-hours/day for seven days. RESULTS: Of 124 participants (44 mild, 80 difficult-to-treat), no between-group differences were observed in sleep-window, sleep-time, sleep efficiency or wake time. Sleep-onset time was ~ 40 min later in the difficult-to-treat group (p = 0.019). DISCUSSION: Broadly, we observed no difference in accelerometer-derived sleep-metrics between mild and difficult-to-treat asthma. This is the largest analysis of accelerometer-derived sleep parameters in asthma and the first comparing groups by asthma severity. Sleep-onset initiation may be delayed in difficult-to-treat asthma but a dedicated study is needed to confirm.

Achieving an improved performance in double-sided friction stir weld joints by adjusting the welding conditions during the passes of AA6061-T6 aluminium alloy.

The present study aims at investigating the effect of interaction between the process parameters of each weld pass (1st pass and 2nd pass) to improve the joint performance during the double-sided friction stir welded joints of AA6061-T6 aluminium alloy. Experimental designs were conducted following a design matrix developed using response surface methodology to investigate the impact on the microstructural changes and tensile properties. Pronounced interaction between the process parameters of each weld pass of the joint was observed and indicated a strong interdependency between them. The detailed microstructural study conducted through EBSD insights into the extent of homogenization, and abnormal grain refinement and reflects a vast transformation of low-angle grain boundaries into high-angle grain boundaries within the stir zone. The profound examination through scanning electron microscopy and transmission electron microscopy analysis validated the uniform homogeneous distribution of Al-Fe and Al-Si-rich precipitates. The significant improvement in the grain refinement and distribution of the strengthening precipitates within the stir zone led to a substantial enhancement in the microhardness, along with achieving a maximum ultimate tensile strength of 223 MPa and a percentage elongation of 14%. A study of the fracture morphology ensures the ductile fracture behavior of the tensile fracture specimen by observing the presence of numerous dimples within a well-bonded joint.

Pharmacogenomic evaluation of CYP2C19 alleles linking low clopidogrel response and the risk of acute coronary syndrome in Indians.

BACKGROUND: Clopidogrel is an antiplatelet drug widely prescribed to prevent atherothrombotic events in coronary artery disease patients. However, there is evidence to suggest that the effectiveness of clopidogrel varies owing to genetic diversity in CYP2C19. This heterogeneity in South Asians, who are also known to have high risk of cardiac events than other population groups, highlights the importance of investigating CYP2C19 variants to estimate the risk proportion in the groups. METHODS: Given the high prevalence and genetic heterogeneity, the population-based case control was conducted in a cohort of 1191 subjects comprising 645 acute coronary syndrome (ACS) cases (unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) and 546 healthy controls of South Asian Indian origin. The metabolization status of CYP2C19 was assessed using *2, *3 and *17 variants in the stated cohorts to determine the prevalence of metabolization and its association with phenotypes. RESULTS: The results suggest a possible genetic association between studied CYP2C19 polymorphisms and ACS, since there was a higher proportion of intermediate and poor metabolizers present in the studied cohorts. The association analyses revealed that the *2 allele of CYP2C19 confers a significant risk for ACS, while the *17 allele provides protection. CONCLUSIONS: These findings contribute to the understanding of CYP2C19 genetic variants and their impact on clopidogrel response in South Asian Indians. Additionally, they underline the significance of assessing CYP2C19 variations in patients receiving clopidogrel therapy in order to improve therapeutic outcomes.

Metagenomics in the fight against zoonotic viral infections: A focus on SARS-CoV-2 analogues.

Zoonotic viral infections continue to pose significant threats to global public health, as highlighted by the COVID-19 pandemic caused by the SARS-CoV-2 virus. The emergence of SARS-CoV-2 served as a stark reminder of the potential for zoonotic transmission of viruses from animals to humans. Understanding the origins and dynamics of zoonotic viruses is critical for early detection, prevention, and effective management of future outbreaks. Metagenomics has emerged as a powerful tool for investigating the virome of diverse ecosystems, shedding light on the diversity of viral populations, their hosts, and potential zoonotic spillover events. We provide an in-depth examination of metagenomic approaches, including, NGS metagenomics, shotgun metagenomics, viral metagenomics, and single-virus metagenomics, highlighting their strengths and limitations in identifying and characterizing zoonotic viral pathogens. This review underscores the pivotal role of metagenomics in enhancing our ability to detect, monitor, and mitigate zoonotic viral infections, using SARS-CoV-2 analogues as a case study. We emphasize the need for continued interdisciplinary collaboration among virologists, ecologists, and bioinformaticians to harness the full potential of metagenomic approaches in safeguarding public health against emerging zoonotic threats.

Open arch-my way! Branch first continuous perfusion arch repair (BF-CPAR).

We herein describe our technique of "branch first continuous perfusion arch repair (BF-CPAR)" which does away with both cerebral circulatory arrest and the need for deep hypothermia. We use this technique for all aortic surgeries including for type A acute aortic dissections. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01535-2.

Revealing Structure and Localization of Steroid Regioisomers through Predictive Fragmentation Patterns in Mass Spectrometry Imaging.

Identifying and mapping steroids in tissues can provide opportunities for biomarker discovery, the interrogation of disease progression, and new therapeutics. Although separation coupled to mass spectrometry (MS) has emerged as a powerful tool for studying steroids, imaging and annotating steroid isomers remains challenging. Herein, we present a new method based on the fragmentation of silver-cationized steroids in tandem MS, which produces distinctive and consistent fragmentation patterns conferring confidence in steroid annotation at the regioisomeric level without using prior derivatization, separation, or instrumental modification. In addition to predicting the structure of the steroid with isomeric specificity, the method is simple, flexible, and inexpensive, suggesting that the wider community will easily adapt to it. We demonstrate the utility of our approach by visualizing steroids and steroid isomer distributions in mouse brain tissue using silver-doped pneumatically assisted nanospray desorption electrospray ionization mass spectrometry imaging.

Who eats last? Intra-household gender inequality in food allocation among children in educationally backward areas of India.

The practice of women eating after men is a common gender-inequitable food allocation mechanism among adults in Indian households and has been associated with poor health and nutritional outcomes for women. However, empirical evidence on whether a similar practice of girls eating after boys is prevalent among children is scarce. Using primary data from a household survey conducted in educationally backward areas of four Indian states, we provide new evidence of this practice among children. Almost 28 per cent of the sample households follow the mealtime custom of girls eating after boys. Scheduled Tribes and households with higher incomes are less likely to follow this practice. Other relevant factors include children's relative ages by sex and an interplay between family size and children's sex composition. While our findings may not be generalizable, they suggest an intersectionality between gender and other dimensions of inequality, namely social identity and economic class.

Valve-sparing aortic root replacement: Long-term variables significantly associated with mortality and morbidity.

OBJECTIVES: In aortic root surgery, valve-sparing aortic root replacement is an attractive alternative by mitigating the risks inherent to prosthetic valves; however, little is known about the variables that impact its durability. We review our mid- to long-term outcomes after valve-sparing aortic root replacement and describe factors that impact survival and valve reintervention and insufficiency. METHODS: A retrospective review of 284 consecutive patients undergoing valve-sparing aortic root replacement between November 1999 and January 2022 at Austin Health, Melbourne, Australia, was undertaken, with a median follow-up of 6.43 ± 4.83 years, but up to 22.0 years. Freedom from mortality, aortic reintervention, and insufficiency was analyzed using Kaplan-Meier methods, Cox proportional hazard models, and Fine-Gray analysis. RESULTS: The median age of patients at intervention was 60.0 years (interquartile range, 48.0-67.0), of whom 68 (23.9%) had bicuspid aortic valve disease, 27 (9.5%) had Marfan syndrome, 119 (41.9%) had severe aortic root dilation (>50 mm), and 155 had (54.6%) severe aortic insufficiency at the time of intervention. The 30-day mortality was 1.8%, with freedom from mortality of 96.0% (95% CI, 92.6-97.8) at 5 years and 88.2% (95% CI, 81.4-92.6) at 10 years. Freedom from aortic reintervention was 92.2% (95% CI, 87.7-95.2) at 5 years and 79.8% (95% CI, 71.8-85.8) at 10 years. Factors associated with reintervention were concomitant leaflet repair (hazard ratio, 8.13, 95% CI, 1.07-61.7) and bicuspid valvulopathy (hazard ratio, 2.23, 95% CI, 1.07-4.68), with reintervention in the bicuspid aortic valve being more likely due to aortic stenosis and in the tricuspid aortic valve due to aortic insufficiency (chi-square P = .05). The freedom from aortic insufficiency was 89.1% (95% CI, 83.5-92.9), 84.9% (95% CI, 77.8-89.9) at 5 and 10 years, respectively, and 80.7% (95% CI, 71.0-87.4). CONCLUSIONS: Valve-sparing aortic root replacement has excellent long-term outcomes, with low mortality and reintervention rates. Concomitant leaflet repair and bicuspid valve disease are the only long-term factors associated with reintervention.

Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results: Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20-60) and mature fibrosis of 30% (10%-50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%-15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial-least square regression machine learning, this study predicted the percentage of both immature (R 2 = 0.842) and mature (R 2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion: This study demonstrates that a point-of-care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Long-term history dependence of growth rates of E. coli after nutrient shifts.

According to a widely accepted paradigm of microbiology, steady-state growth rates are determined solely by current growth conditions1-3 and adaptations between growth states are rapid, as recently recapitulated by simple resource allocation models4. However, even in microbes overlapping regulatory networks can yield multi-stability or long-term cellular memory. Species like Listeria monocytogenes5 and Bacillus subtilis "distinguish" distinct histories for the commitment to sporulation6, but it is unclear if these states can persist over many generations. Remarkably, studying carbon co-utilization of Escherichia coli, we found that growth rates on combinations of carbon sources can depend critically on the previous growth condition. Growing in identical conditions, we observed differences in growth rates of up to 25% and we did not observe convergence of growth rates over 15 generations. We observed this phenomenon occurs across combinations of different phosphotransferase (PTS) substrates with various gluconeogenic carbon sources and found it to depend on the transcription factor Mlc.