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Objective: A prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets. Methods: In vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2–0.5 ​MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data. Results: Amide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 ​MPa seem to provide the best sparse IR spectra for cylindrical (d ​= ​3 ​mm) probe tips. Conclusion: Laser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of −8.35, −9.67 and −8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski’s rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

BackgroundMechanical power (MP) refers to the energy transmitted over time to the respiratory system and serves as a unifying determinant of ventilator-induced lung injury. MP normalization is required to account for developmental changes in children. We sought to examine the relationship between mechanical energy (MEBW), MP normalized to body weight (MPBW), and MP normalized to respiratory compliance (MPCRS) concerning the severity and outcomes of pediatric acute respiratory distress syndrome (pARDS).MethodIn this retrospective study, children aged 1 month to 18 years diagnosed with pARDS who underwent pressure-control ventilation for at least 24 h between January 2017 and September 2020 were enrolled. We calculated MP using Becher's equation. Multivariable logistic regression analysis adjusted for age, pediatric organ dysfunction score, and oxygenation index (OI) was performed to determine the independent association of MP and its derivatives 24 h after diagnosing pARDS with 28-day mortality. The association was also studied for 28 ventilator-free days (VFD-28) and the severity of pARDS in terms of OI.ResultsOut of 246 admitted with pARDS, 185 were eligible, with an overall mortality of 43.7%. Non-survivors exhibited higher severity of illness, as evidenced by higher values of MP, MPBW, and MEBW. Multivariable logistic regression analysis showed that only MEBW but not MP, MPBW, or MPCRS at 24 h was independently associated with mortality [adjusted OR: 1.072 (1.002–1.147), p = 0.044]. However, after adjusting for the type of pARDS, MEBW was not independently associated with mortality [adjusted OR: 1.061 (0.992–1.136), p = 0.085]. After adjusting for malnutrition, only MP at 24 h was found to be independently associated. Only MPCRS at 1–4 and 24 h but not MP, MPBW, or MEBW at 24 h of diagnosing pARDS was significantly correlated with VFD-28.ConclusionsNormalization of MP is better related to outcomes and severity of pARDS than non-normalized MP. Malnutrition can be a significant confounding factor in resource-limited settings.

Electronic absorption spectrums of methylene blue (MB) in the concentration range wherein monomer–dimer equilibria exist have been systematically investigated in aqueous solutions of polyethylene glycols (PEG's) having molar mass 400, 1000 and 4000 g∙mol–1, at 298 K. The data on the absorption spectrums (550–700 nm) of MB are resolved to obtain monomer and dimer spectrums as well the geometrical details of the species (such as oscillatory strength, dipole moment etc.) are calculated. The molar absorption extinction coefficients for monomer and dimer cations of MB, the dimer dissociation constant values are calculated as a function of PEG concentrations. It has been noted that, absorption maximum occurs at 664 ± 1 and 605 ± 1 nm, respectively, for monomer and dimers which do not get affected much by presence of polymeric molecules and the data show perfect obedience of Beer–Lambert's law. The changes in dimer geometry from sandwich type to end–on–end type have been studied by applying exciton theory of Kasha et al. The dimer dissociation constant values at finite as well for infinitely dilute concentration of PEG's exhibit orderly amendment with respect to molar mass of PEG's and alteration in chain length of molecules. We report the free energy changes of transfer of dimeric cations of different concentrations from water to aqueous solutions of PEG's of fixed concentration, that is, to probe the interactions of water and PEG molecules with a hope of getting information about salting–in/salting–out effects, as well of binding of dye molecules with PEG's. We have suggested complexation of end hydroxylic groups of PEG's with dimer cations. The results are further interpreted as salting–in of PEG complex with MB–dimers only in the limit of infinite dilution (solute–solvent interactions) while salting–out of these complexed species is observed as a function of MB–dimer concentration.

Studies have shown that the airway pressures displayed on the screen of the ventilator monitor do not correlate with the actual alveolar distending pressures known as transpulmonary pressure or stress. The change in tidal volume (Vt) on top of the available functional residual capacity (FRC), also known as strain, is an essential factor directly related to stress. Even the correlation of driving pressure (DP) with ventilator-induced lung injury (VILI) needs to be interpreted in the background of what Vt, respiratory compliance (Crs) and at what positive end-expiratory pressure (PEEP) is that DP calculated and at what was the chest wall compliance, and the flow rate at that time. Stress and strain are related to all these factors, either directly or indirectly. The impact of stress and strain should be interpreted in “dynamic terms” over time rather than at one point. Hence, VILI is minimized by optimizing the Strain (using appropriate PEEP and Vt against available FRC) and stress (transpulmonary inspiratory and expiratory pressures), applied at an optimal respiratory rate and flow. In the pediatric age group, pulmonary mechanics also change as age changes. Moreover, children respond differently to lung injury than adults, adding another layer of complexity to the concept of stress and strain in the pediatric population. Despite this, most knowledge about stress and strain has come from studies in the adult population. Therefore, more extensive studies focussing on pediatric age groups are needed to improve our understanding of stress and strain in pediatric ventilated patients.

IntroductionPrenatal alcohol exposure (PAE) causes neuroinflammation that may contribute to the pathophysiology underlying Fetal Alcohol Spectrum Disorder. Supplementation with omega-3 polyunsaturated fatty acids (PUFAs) has shown success in mitigating effects of PAE in animal models, however, the underlying mechanisms are unknown. Some PUFA metabolites, specialized pro-resolving mediators (SPMs), play a role in the resolution phase of inflammation, and receptors for these are in the brain.MethodsTo test the hypothesis that the SPM receptors FPR2 and ChemR23 play a role in PAE-induced behavioral deficits, we exposed pregnant wild-type (WT) and knockout (KO) mice to alcohol in late gestation and behaviorally tested male and female offspring as adolescents and young adults.ResultsMaternal and fetal outcomes were not different among genotypes, however, growth and behavioral phenotypes in the offspring did differ and the effects of PAE were unique to each line. In the absence of PAE, ChemR23 KO animals showed decreased anxiety-like behavior on the elevated plus maze and FPR2 KO had poor grip strength and low activity compared to age-matched WT mice. WT mice showed improved performance on fear conditioning between adolescence and young adulthood, this was not seen in either KO.DiscussionThis PAE model has subtle effects on WT behavior with lower activity levels in young adults, decreased grip strength in males between test ages, and decreased response to the fear cue indicating an effect of alcohol exposure on learning. The PAE-mediated decreased response to the fear cue was also seen in ChemR23 KO but not FPR2 KO mice, and PAE worsened performance of adolescent FPR2 KO mice on grip strength and activity. Collectively, these findings provide mechanistic insight into how PUFAs could act to attenuate cognitive impairments caused by PAE.

Excess internal pressure of solution and excess partial molar volume of solute data embedded in the parameter reversible isothermal work (W) have been used to calculate the ion–ion pair correlation functions (gij(r), r being distance) and the thermodynamic properties of aqueous solutions of decyltrimethylammonium bromide (C10TAB) in concentration range 0.01 – 0.14 mol∙kg–1. It is observed that gij(r) exhibits a peak at critical micelle concentration (cmc), while the virial coefficient term (gij(r) – 1) also goes through a maximum. Using Friedman's methodology and McMillan–Mayer theory of solutions, these results have been examined. With the help of concept of Gurney cosphere around the ions, the overlap of solvation shells (water molecules) as the concentration of ions increases have been used to probe water– structure effects as water–structure making/breaking. Coefficients Aij are estimated (Coulombic term, a core repulsive term, a cavity formation term and overlap of cosphere term) at various concentrations of ionic surfactant and at a radial distance of 20 Å for a micellar entity. Further analysis indicates that gij parameter (that is, representing cation–cation interaction g++) dominate over g+– (representing ion–solvent interaction) in solution phase. Thus for a self–assembly process (formation of micelle with aggregation number) in a solution phase is being characterized by a peak in gij(r) function at cmc and aggregation number of ≈ 38, area under the peak, while the virial coefficient variation indicates a dominance of cation–cation interaction and cosphere water–structural effects. It is emphasized that the approach adopted by us to use excess PV work to estimate gij(r) is better to understand the thermodynamic process involved in self–assemblies and micelle formation.

A widely used approach to analyze single particles in electron microscopy data is 2D classification. This process is very computationally expensive, especially when large data sets are analyzed. In this paper we present GPU ISAC, a newly developed, GPU-accelerated version of the established Iterative Stable Alignment and Clustering (ISAC) algorithm for 2D images and generating class averages. While the previously existing implementation of ISAC relied on a computer cluster, GPU ISAC enables users to produce high quality 2D class averages from large-scale data sets on a single desktop machine equipped with affordable, consumer-grade GPUs such as Nvidia GeForce GTX 1080 TI cards. With only two such cards GPU ISAC matches the performance of twelve high end cluster nodes and, using high performance GPUs, is able to produce class averages from a million particles in between six to thirteen hours, depending on data set quality and box size. We also show GPU ISAC to scale linearly in all input dimensions, and thereby capable of scaling well with the increasing data load demand of future data sets. Further user experience improvements integrate GPU ISAC seamlessly into the existing SPHIRE GUI, as well as the TranSPHIRE on-the-fly processing pipeline. It is open source and can be downloaded at https://gitlab.gwdg.de/mpi-dortmund/sphire/cuISAC/

Objective: To evaluate the feasibility of Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy to detect cartilage degradation due to osteoarthritis and to validate the methodology with osteochondral human cartilage samples for future development towards clinical use. Design: Cylindrical (d ​= ​4 ​mm) osteochondral samples (n ​= ​349) were prepared from nine human cadavers and measured with FTIR-ATR spectroscopy. Afterwards, the samples were assessed with Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system and divided into two groups: 1) healthy (OARSI 0–2) and 2) osteoarthritic (OARSI 2.5–6). The classification was done with partial least squares discriminant analysis model utilizing cross-model validation. Receiver operating characteristics curve analysis was performed and the area under curve (AUC) was calculated. Results: For all samples combined, classification accuracy was 73% with AUC of 0.79. Femoral samples had accuracy of 74% and AUC of 0.77, while tibial samples had accuracy of 66%, and AUC of 0.74. Patellar samples had accuracy of 84% and AUC of 0.91. Conclusions: The results indicate that FTIR-ATR spectroscopy can differentiate between healthy and osteoarthritic femoral, tibial and patellar human tissue. If combined with a fiber optic probe, FTIR-ATR spectroscopy could provide additional objective intraoperative information during arthroscopic surgeries, which could improve clinical outcomes.

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available.The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP.In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies).The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes.In light of the large number of people exposed to TRAP – both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers.

Exposure to respirable air particulate matter (PM2.5) in ambient air is associated with morbidity and premature deaths. A major source of PM2.5 is the photooxidation of volatile plant-produced organic compounds such as isoprene. Photochemical oxidation of isoprene leads to the formation of hydroperoxides, environmental oxidants that lead to inflammatory (IL-8) and adaptive (HMOX1) gene expression in human airway epithelial cells (HAEC). To examine the mechanism through which these oxidants alter intracellular redox balance, we used live-cell imaging to monitor the effects of isoprene hydroxyhydroperoxides (ISOPOOH) in HAEC expressing roGFP2, a sensor of the glutathione redox potential (EGSH). Non-cytotoxic exposure of HAEC to ISOPOOH resulted in a rapid and robust increase in EGSH that was independent of the generation of intracellular or extracellular hydrogen peroxide. Our results point to oxidation of GSH through the redox relay initiated by glutathione peroxidase 4, directly by ISOPOOH or indirectly by ISOPOOH-generated lipid hydroperoxides. We did not find evidence for involvement of peroxiredoxin 6. Supplementation of HAEC with polyunsaturated fatty acids enhanced ISOPOOH-induced glutathione oxidation, providing additional evidence that ISOPOOH initiates lipid peroxidation of cellular membranes. These findings demonstrate that ISOPOOH is a potent environmental airborne hydroperoxide with the potential to contribute to oxidative burden of human airway posed by inhalation of secondary organic aerosols.

Glaucoma is an optic neuropathy in which progressive degeneration of retinal ganglion cells and the optic nerve leads to irreversible visual loss. Glaucoma is one of the leading causes of blindness. The pathogenesis of glaucoma is determined by different pathogenetic mechanisms, including increased intraocular pressure, mechanical stress, excitotoxicity, resistance to aqueous drainage and oxidative stress. Topical formulations are often used in glaucoma treatment, whereas surgical measures are used in acute glaucoma cases. For most patients, long-term glaucoma treatments are given. Poor patient compliance and low bioavailability are often associated with topical therapy, which suggests that sustained-release, long-acting drug delivery systems could be beneficial in managing glaucoma. This review summarizes the eye's physiology, the pathogenesis of glaucoma, current treatments, including both pharmacological and nonpharmacological interventions, and recent advances in long-acting drug delivery systems for the treatment of glaucoma., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All the authors agree to publish this article in Drug Delivery and Translational Research. Competing interests: The authors declare that they have no conflicts of interest., (© 2024. The Author(s).)

Introduction: Post-operative complications related to hardware, particularly symptoms caused by it, such as implant impingement, wire breakage, and skin infection are frequently reported following surgical management of patellar fractures with stainless steel wires. As a potential solution, some researchers have advocated for the use of non-absorbable sutures for fracture fixation. This study aims to investigate the clinical and radiological outcomes of patients treated with fiber taping as an alternative technique., Materials and Methods: We conducted a retrospective evaluation of 20 patients diagnosed radiographically with displaced patellar fractures (including transverse, poles, and severely comminuted). These patients underwent tension band technique with the help of high strength polyethylene fiber tape. Clinical and radiological outcomes were meticulously assessed, with specific attention to union time, complications, and functional outcome assessed by the Lysoholm scoring system, all of which were carefully observed and documented., Results: The mean age of the patients was 42.5 ± 14.3 years, and the majority were male (70%). The mean operative time was 68.5 ± 22.4 min. All fractures achieved union without any reported cases of wound complications, infections, loss of reduction, or implant failure. The mean Lysholm Knee Score improved from 36.4 ± 8.2 at baseline to 92.1 ± 5.9 at 12-month post-surgery. The visual analogue scale for pain decreased from 7.8 ± 1.4 at baseline to 0.8 ± 0.6 at 12 months. The mean range of motion improved from 96.5° ± 12.8° of flexion and -5.2° ± 3.1° of extension at baseline to 134.2° ± 6.1° of flexion and 0.6° ± 0.7° of extension at 12 months., Conclusion: Our investigation into a modified tension band technique using fiber tape sutures revealed encouraging clinical outcomes, marked by minimal complications. The adoption of fiber tape as a substitute for metal wire counterparts in patellar fracture treatment shows potential for reducing hardware related symptoms and shows lesser morbidity., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature. In keeping with epigenetic alterations being a common driver of many childhood cancers, fragmentomics analysis of cfDNA identified tumour-specific epigenetic states and transcription factor binding sites accessible in chromatin. This study leverages a large and well-annotated genomic dataset of aggressive childhood malignancies, identifies genomic and epigenetic drivers of childhood cancer relapse, and highlights the power and practicality of cfDNA analysis to capture both intra-tumoural heterogeneity and the epigenetic state of cancer cells.

Purpose: we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT)., Experimental Design: 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA., Results: 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS>10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new "outlier" variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations., Conclusions: ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.

Purpose: To determine the efficacy and safety of cryoablation in pediatric and young adult patients with desmoid tumors (DTs) retrospectively over a 10-year period., Materials and Methods: Twenty-one patients (age 2-22 years; median 14 years), with 21 desmoid tumors, underwent a total of 34 percutaneous cryoablation procedures between August 2013 and August 2023. All patients, excluding two, had surgical resection, chemotherapy, or a combination of these therapies with failed or suboptimal response. Clinical and imaging outcomes were analyzed for technical success, change in tumor volume, and recurrence of tumor, symptom improvement or recurrence, and procedure-related complications., Results: All procedures were technically successful. The median follow-up duration was 9 months (range, 3-32 months); total symptomatic improvement was achieved in 90% (19/21) patients, noticeable pain relief was seen in 100% (18/18) and 90% (9/10) patients had improved range of motion (ROM), discomfort resolved in 66.7% (2/3) patients. Of the treated tumors, 43% (9/21) showed greater than 75% tumor volume reduction of which 44% (4/9) had no evidence of viable residual tumor at follow-up, and 33% (7/21) had 50-75% volume reduction and 14% (3/21) had greater than 40-50% tumor volume reduction. According to modified response evaluation criteria in solid tumors (mRECIST), 71%( 15/21) had partial response (PR), 19% (4/21) had complete response (CR), and 10% (2/21) had stable disease. Four (12%) treatments were associated with minor complications, which self-resolved., Conclusion: In this, predominantly pediatric patient cohort, cryoablation was effective and safe for the local control of extra-abdominal desmoid tumors in short-term follow-up., Competing Interests: Declarations. Conflict of interest: None. Ethical Approval: For this type of study, formal consent is not required. Informed Consent: This study has obtained IRB approval and the need for informed consent was waived. Consent for Publication: For this type of study, consent for publication is not required., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Plasmodium vivax malaria poses a major global health challenge, fueled by the parasite's ability to establish chronic infections via dormant liver hypnozoites that enable immune evasion and show transmission resilience. A key virulence determinant of P. vivax blood-stage infection is the ligand-receptor interaction of infected erythrocytes mediated by the Duffy Binding Protein (PvDBP) ligand. Gene duplication events leading to increased PvDBP copy numbers have been documented in parasite populations in Cambodia, Brazil, and Sudan, but whether such changes exist in Indian isolates is not known. India shoulders a disproportionately high P. vivax burden in the world. DNA extracted from malaria-positive samples from a multisite survey was subjected to diagnostic PCR to evaluate PvDBP duplication. We identified PvDBP duplication at 18.6% frequency across various regions in India via diagnostic PCR. Both 'Cambodian-type' and 'Malagasy-type' duplication patterns were detected. PvDBP copy number variations associated with specific Duffy antigen receptor genotypes were correlated in the patient cohort. While PvDBP duplication was widespread, its geographic distribution varied, occurring most prevalently in northeastern regions of India. The presence of Duffy binding protein gene duplication in nearly one-fifth of P. vivax isolates in India may have significant epidemiological and clinical implications. This genetic variation could potentially impact, parasite fitness and invasion efficiency, possibly leading to higher parasitemia levels and immune evasion capabilities, which may affect the efficacy of natural immunity and vaccine development efforts and / or transmission dynamics if the duplication confers any advantage in mosquito stages. To fully understand these implications, we propose longitudinal studies tracking patients with and without PvDBP duplications, comparing clinical outcomes, parasitemia levels, and transmission rates. Additionally, spatial and temporal analyses of duplication frequency across India could reveal patterns of spread and potential selective pressures driving this genetic change., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vibrational spectroscopy methods such as mid-infrared (MIR), near-infrared (NIR), and Raman spectroscopies have been shown to have great potential for in vivo biomedical applications, such as arthroscopic evaluation of joint injuries and degeneration. Considering that these techniques provide complementary chemical information, in this study, we hypothesized that combining the MIR, NIR, and Raman data from human osteochondral samples can improve the detection of cartilage degradation. This study evaluated 272 osteochondral samples from 18 human knee joins, comprising both healthy and damaged tissue according to the reference Osteoarthritis Research Society International grading system. We established the one-block and multi-block classification models using partial least squares discriminant analysis (PLSDA), random forest, and support vector machine (SVM) algorithms. Feature modeling by principal component analysis was tested for the SVM (PCA-SVM) models. The best one-block models were built using MIR and Raman data, discriminating healthy cartilage from damaged with an accuracy of 77.5% for MIR and 77.8% for Raman using the PCA-SVM algorithm, whereas the NIR data did not perform as well achieving only 68.5% accuracy for the best model using PCA-SVM. The multi-block approach allowed an improvement with an accuracy of 81.4% for the best model by PCA-SVM. Fusing three blocks using MIR, NIR, and Raman by multi-block PLSDA significantly improved the performance of the single-block models to 79.1% correct classification. The significance was proven by statistical testing using analysis of variance. Thus, the study suggests the potential and the complementary value of the fusion of different spectroscopic techniques and provides valuable data analysis tools for the diagnostics of cartilage health., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture. Secondary aims were to assess the variation in the provision of chemical prophylaxis and risk factors for VTE., Methods: This was a multicentre, prospective national collaborative audit with data collection over nine months for all patients undergoing foot and ankle surgery in an operating theatre or TA rupture treatment, within participating UK hospitals. The association between VTE and thromboprophylaxis was assessed with a univariable logistic regression model. A multivariable logistic regression model was used to identify key predictors for the risk of VTE., Results: A total of 13,569 patients were included from 68 sites. Overall, 11,363 patients were available for analysis: 44.79% were elective (n = 5,090), 42.16% were trauma excluding TA ruptures (n = 4,791), 3.50% were acute diabetic procedures (n = 398), 2.44% were TA ruptures undergoing surgery (n = 277), and 7.10% were TA ruptures treated nonoperatively (n = 807). In total, 11 chemical anticoagulants were recorded, with the most common agent being low-molecular-weight heparin (n = 6,303; 56.79%). A total of 32.71% received no chemical prophylaxis. There were 99 cases of VTE (incidence 0.87% (95% CI 0.71 to 1.06)). VTE-related mortality was 0.03% (95% CI 0.005 to 0.080). Univariable analysis showed that increased age and American Society of Anesthesiologists (ASA) grade had higher odds of VTE, as did having previous cancer, stroke, or history of VTE. On multivariable analysis, the strongest predictors for VTE were the type of foot and ankle procedure and ASA grade., Conclusion: The 90-day incidence of symptomatic VTE and mortality related to VTE is low in foot and ankle surgery and TA management. There was notable variability in the chemical prophylaxis used. The significant risk factors associated with 90-day symptomatic VTE were TA rupture and high ASA grade., Competing Interests: J. Mangwani reports support from the Leicester Hospitals Charity, related to this study. J. Mangwani reports payment or honoraria for lectures, presentations, educational events from Orthosolutions, and royalties from Meshworks, unrelated to this study. K. Malhotra reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from NewClip Technics, unrelated to this study. L. W. Mason reports royalties or licenses, consulting fees, and patents planned, issued or pending from Orthosolutions, unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

The efficacy of dasatinib (DAS) in treating hepatocellular carcinoma (HCC) is hindered by its poor bioavailability, limiting its clinical potential. In this study, we explored the use of TPGS-Soluplus micelles as an innovative drug delivery platform to enhance DAS solubility, stability, and therapeutic impact. A series of TPGS-Soluplus copolymers were synthesized, varying the D-α-tocopheryl polyethylene glycol succinate (TPGS) forms (1000, 2000, and 3500) and adjusting the TPGS to Soluplus weight ratios (1:1, 1:2, and 1:3). Our goal was to identify the optimal formulation with the highest entrapment efficiency, smallest particle size, and enhanced drug loading. The TPGS1000-Soluplus copolymer, with a DAS-to-polymer ratio of 1:30 and a TPGS ratio of 1:2, demonstrated superior performance, achieving an entrapment efficiency of 64.479 ± 1.45 % and drug loading of 5.05 ± 1.01 %. The DAS-loaded micelles (DAS-PMs) exhibited a notably small particle size of 64.479 ± 1.45 nm and demonstrated controlled release kinetics, with 85.60 ± 5.4 % of the drug released over 72 h. Cellular uptake studies using Hep G2 cells revealed significantly enhanced absorption of DAS-PMs compared to free DAS, reflected in lower IC50 values in MTT assays at 24 and 48 h. Pharmacokinetic analysis further highlighted the benefits of the DAS-PMs, with an AUC0-∞ 2.16 times higher and mean residual time (MRT) 1.3 times longer than free DAS, a statistically significant improvement (p < 0.01). These findings suggest that TPGS-Soluplus micelles offer a promising strategy for improving the bioavailability and efficacy of DAS in HCC treatment, presenting a potential new therapeutic avenue for patients with limited options. This innovative formulation could significantly enhance DAS delivery, potentially leading to improved clinical outcomes in liver cancer therapy., Competing Interests: Authors declare there are no conflict of interest., (© 2024 The Authors.)

Background Effective gender-based violence (GBV) interventions depend on precise tools to assess healthcare providers' knowledge, attitudes, and practices (KAP). This study aimed to develop and validate a culturally appropriate GBV questionnaire on the KAP of healthcare workers in India using a modified e-Delphi method. Methodology The study used a modified e-Delphi approach, conducted online, to validate a GBV questionnaire. The process included the following three rounds: content validation, quantitative validation, and finalization. It began with a literature review and questionnaire drafting in May 2022, followed by validation from September 2022 to December 2023. The expert panel included healthcare professionals, public health experts, and researchers. The questionnaire included the following four sections: demographic information, knowledge of GBV, attitudes toward GBV, and GBV-related practices. Results In Round 1, significant revisions were made to enhance relevance and clarity, including the addition of a "Don't Know" option and revisions to questions on gender roles and societal expectations. The quantitative validation of Round 2 revealed high scores for Importance (4.980), Usefulness (4.965), Relevance (4.965), Clarity (4.955), Simplicity (4.980), and Ambiguity (4.815), with all items retained and no significant modifications. In Round 3, consensus was achieved, finalizing the questionnaire with expert validation certificates, demonstrating strong reliability and contextual appropriateness. Conclusions The validated KAP questionnaire is a reliable tool for assessing healthcare providers' capacity to manage GBV. It can be used to inform and enhance interventions aimed at improving GBV management in healthcare settings., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, KLE Jagadguru Gangadhar Mahaswamigalu Moorsavirmath Medical College issued approval JGMMMCIEC/058/2023. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The study “Catalyzing Change: Enhancing the Capacity of Healthcare Workers to Address Violence Against Women - An Interventional Study in the Field Practice Area of KLE’s JGMM Medical College, Hubballi, Karnataka” was funded by the Research and Development Cell, KAHER, Belagavi, Karnataka, India. Financial relationships: Dr. Namratha Kulkarni Dr. Rizwana B Shaikh declare(s) a grant from Research Cell, KLE Academy of Higher Education and Research. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kulkarni et al.)

Background: ACKR1 blood group genes exhibit a high degree of polymorphisms with varying allele distribution seen among different populations and ethnic groups. The study aimed to genotype ACKR1 antigens and to establish FY allele frequency among the individuals with the Bombay (Oh) blood group phenotype., Materials and Methods: ACKR1 phenotype and genotype frequencies were estimated on 160 individuals typed as Oh and were compared with 100 non-oh blood donors from Mumbai, India by molecularly genotyping via PCR-RFLP., Results: The allelic and genotypic frequency of T(-67)C polymorphism showed the dominance of T allele and TT genotype [OR= 3.26 (0.59-17.99)] in both the study groups. The ACKR1 null (Fya-b-) phenotype was not found in the tested group. While the genotypic combination among the Oh group individuals was FYA/FYB (45.3 %), FYA/FYA (42.7 %), and FYB/FYB (12 %), in the non-Oh group donors, it was observed as FYA/FYB (53.3 %), FYA/FYA (39.1 %), and FYB/FYB (7.6 %). The haplotype TGGGC occurred in 38.4 % of the Oh group, but in non-Oh donors, it was found to be 50.9 % [OR = 1.820 (1.196-2.771)], and the difference was statistically significant (p = 0.005). Similarly, the TGGGT haplotype was found at a frequency of 12.7 % in non-Oh donors and 27.1 % in Oh group [OR= 0.411 (0.234-0.722)] (p = 0.001)., Conclusions: This study shows the prevalence of ACKR1 gene polymorphisms, including weak ACKR1 antigens in Oh individuals with a high frequency of haplotype TGGGC. The present study demonstrated for the first time the genotypes FyBweak, FyAweak and Fy Aweak/FyBESon RBC membranes in Indian subjects with Oh phenotype., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective:  To describe our technique and share our experience with image-guided transrectal drainage (TRD) of pelvic abscesses in children., Materials and Methods:  Retrospective review and analysis of indications for image-guided TRD and examination of procedural outcomes in pediatric patients with pelvic abscesses over 8 years., Results:  A total of 69 patients (33 males and 36 females) with symptomatic pelvic abscesses underwent image-guided TRD. The median age and weight of the patients were 11.5 years (range, 3-18) and 46.8 kg (range, 15.1-118.0), respectively. The etiologies of the pelvic abscesses were perforated appendicitis (72.5%) and post-operative collections (27.5%). All patients presented with abdominal pain. Fever, emesis, and diarrhea were also common symptoms. The size of the pelvic abscesses ranged from 24.0 to 937.1 mL (median, 132.7). Technical success was achieved in 68 of 69 TRD procedures (98.6%). Clinical improvement was observed in all patients with technically successful TRD. The TRD catheter dwell time ranged from 0 to 10 days (median, 4.0). Most patients who underwent TRD for perforated appendicitis subsequently underwent elective appendectomy after the resolution of the pelvic abscess (84.0%). The median time from TRD to elective appendectomy was 2.8 months (range, 0.3-6.1). There were no procedure-related complications., Conclusion:  Image-guided TRD is a safe and effective procedure with high technical and clinical success rates for the treatment of pelvic abscesses in children., Competing Interests: None declared., (Thieme. All rights reserved.)

Competing Interests: Conflict of interestNone.

Throughout development, complex networks of cell signaling pathways drive cellular decision-making across different tissues and contexts. The transforming growth factor β (TGF-β) pathways, including the BMP/Smad pathway, play crucial roles in determining cellular responses. However, as the Smad pathway is used reiteratively throughout the life cycle of all animals, its systems-level behavior varies from one context to another, despite the pathway connectivity remaining nearly constant. For instance, some cellular systems require a rapid response, while others require high noise filtering. In this paper, we examine how the BMP-Smad pathway balances trade-offs among three such systems-level behaviors, or "Performance Objectives (POs)": response speed, noise amplification, and the sensitivity of pathway output to receptor input. Using a Smad pathway model fit to human cell data, we show that varying non-conserved parameters (NCPs) such as protein concentrations, the Smad pathway can be tuned to emphasize any of the three POs and that the concentration of nuclear phosphatase has the greatest effect on tuning the POs. However, due to competition among the POs, the pathway cannot simultaneously optimize all three, but at best must balance trade-offs among the POs. We applied the multi-objective optimization concept of the Pareto Front, a widely used concept in economics to identify optimal trade-offs among various requirements. We show that the BMP pathway efficiently balances competing POs across species and is largely Pareto optimal. Our findings reveal that varying the concentration of NCPs allows the Smad signaling pathway to generate a diverse range of POs. This insight identifies how signaling pathways can be optimally tuned for each context., (© 2024. The Author(s).)

The Corona Virus Disease (COVID-19) has a huge impact on all of humanity, and people's disregard for COVID-19 regulations has sped up the disease's spread. Our study uses a state-of-the-art object detection model like YOLOv4 (You Only Look Once, version 4), a very effective tool, on real-time 25fps, 1920 X 1080 video data streamed live by a camera-mounted Unmanned Aerial Vehicle (UAV) quad-copter to observe proper maintenance of social distance in an area of 35m range in this study. The model has demonstrated remarkable efficacy in identifying and quantifying instances of social distancing, with an accuracy of 82% and little latency. It has been able to work efficiently with real-time streaming at 25-30 ms. Our model is based on CSPDarkNet-53, which was trained on the MS COCO dataset for image classification. It includes additional layers to capture feature maps from different phases. Additionally, the model's neck is made up of PANet, which is used to aggregate the parameters from various CSPDarkNet-53 layers. The CSPDarkNet-53's 53 convolutional layers are followed by 53 more layers in the model head, for a total of 106 completely convolutional layers in the design. This architecture is further integrated with YOLOv3, resulting in the YOLOv4 model, which will be used by our detection model. Furthermore, to differentiate humans The aforementioned method was used to evaluate drone footage and count social distance violations in real time. Our findings show that our model was reliable and successful at detecting social distance violations in real-time with an average accuracy of 82%., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arifuzzaman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of mid-infrared (MIR) spectroscopy for detecting structural, compositional, and functional changes in AC resulting from two injury types. Three grooves (two in parallel in the palmar-dorsal direction and one in the mediolateral direction) were made via arthrotomy in the AC of the radial facet of the third carpal bone (middle carpal joint) and of the intermediate carpal bone (the radiocarpal joint) of nine healthy adult female Shetland ponies (age = 6.8 ± 2.6 years; range 4-13 years) using blunt and sharp tools. The defects were randomly assigned to each of the two joints. Ponies underwent a 3-week box rest followed by 8 weeks of treadmill training and 26 weeks of free pasture exercise before being euthanized for osteochondral sample collection. The osteochondral samples underwent biomechanical indentation testing, followed by MIR spectroscopic assessment. Digital densitometry was conducted afterward to estimate the tissue's proteoglycan (PG) content. Subsequently, machine learning models were developed to classify the samples to estimate their biomechanical properties and PG content based on the MIR spectra according to injury type. Results show that MIR is able to discriminate healthy from injured AC (91%) and between injury types (88%). The method can also estimate AC properties with relatively low error (thickness = 12.7% mm, equilibrium modulus = 10.7% MPa, instantaneous modulus = 11.8% MPa). These findings demonstrate the potential of MIR spectroscopy as a tool for assessment of AC integrity changes that result from injury., (© 2024. The Author(s).)

Systemic sclerosis (SSc) is a complex, autoimmune connective tissue disease that affects multiple organs in the body, culminating in a variance of severity and a reduced quality of life. Breast cancer (BC) also affects patients with SSc, and these two conditions affect a similar demographic. With this systematic review, we aim to characterize the links between SSc and BC. Characterizing possible links between SSc and breast malignancies is important for advancing the understanding of SSc management and comorbidities. In this systematic meta-analysis, a comprehensive literature search was conducted in PubMed using relevant keywords and MeSH terms. The inclusion criteria included an English-language retrospective analysis that characterized patients with SSc with or without BC. Two independent reviewers assessed the study's eligibility based on predetermined criteria. Data extraction included patient antibody measurements, demographics (age and gender), family history, social behaviors (alcohol use and smoking history), concurrent condition treatments, and adverse effects following treatment. Thirteen articles were identified in the literature with relevant data on SSc and BC patients. Studies encompassed research about SSc patients with or without BC and relevant risk factors being measured. SSc was found to have a link to antibodies widely associated with cancer. Adverse treatment outcomes and concurrent conditions of BC were found when patients had a family history of SSc, BC, or an alcohol or smoking history. Our results suggest that the presence of antinuclear antibodies, anti-centromere antibodies, or anti-topoisomerase antibodies in SSc patients is correlated with BC. Out of the three antibodies, ATA seemed to be found more commonly in patients with SSc and malignancy across the studies. This systematic review discusses the link between SSc and BC through patients with relevant clinical markers, medical histories, and treatments. However, further research is necessary to advance the linkage between SSc and BC and determine whether management of one condition may prevent or alleviate the other., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Dutt et al.)