Search Results (79)

Approximately 15% of total knee arthroplasty (TKA) patients remain dissatisfied after surgery, with joint line obliquity (JLO) potentially affecting patient outcomes. This study investigated whether JLO restoration influenced lower extremity frontal plane joint moments during stair negotiation by TKA patients. Thirty unrestored and twenty-two restored JLO patients participated in this study and were asked to perform five trials on each limb for stair negotiation while three-dimensional kinematics and ground reaction forces were recorded. Frontal plane moments at the ankle, knee and hip were calculated using Visual 3D. The restoration of JLO did not alter frontal plane joint moments during stair negotiation. Both groups showed symmetrical moment profiles, indicating no significant biomechanical differences between the restored and unrestored JLO groups. Restoring JLO did not affect frontal plane joint moments during stair negotiation, suggesting it may not contribute to patient satisfaction disparities post-TKA. Further research should explore other factors, such as surgical technique and implant design, that might influence recovery. Full article

Breast cancer remains one of the most prevalent malignancies worldwide, and radiation therapy is a central component of its management. However, intrinsic or acquired resistance to radiation significantly compromises therapeutic efficacy. This systematic review aimed to identify and evaluate molecular mechanisms and interventions that influence radiation sensitivity in breast cancer models. A comprehensive PubMed search was conducted using the terms “breast cancer” and “radiation resistance” for studies published between 2002 and 2024. Seventy-nine eligible studies were included. The most frequently investigated mechanisms included the dysregulation of the PI3K/AKT/mTOR and MAPK signaling pathways, enhanced DNA damage repair via non-homologous end joining (NHEJ), and the overexpression of cancer stem cell markers such as CD44⁺/CD24⁻/low and ALDH1. Several studies highlighted the role of non-coding RNAs, particularly the lncRNA DUXAP8 and microRNAs such as miR-21, miR-144, miR-33a, and miR-634, in modulating radiation response. Components of the tumor microenvironment, including cancer-associated fibroblasts and immune regulators, also contributed to radiation resistance. By synthesizing current evidence, this review provides a consolidated resource to guide future mechanistic studies and therapeutic development. This review highlights promising molecular targets and emerging strategies to enhance radiosensitivity and offers a foundation for translational research aimed at improving outcomes in radiation-refractory breast cancer. Full article

Background: Patients with proximal junctional kyphosis (PJK) or failure (PJF) may demonstrate disparate outcomes and recovery when fused to the upper (UT) versus lower (LT) thoracic spine. Few studies have distinguished the reoperation and recovery abilities of patients with PJK or PJF when fused to the upper (UT) versus lower (LT) thoracic spine. Methods: Adult spine deformity patients ≥ 18 yrs with preoperative and 5-year (5Y) data fused to the sacrum/pelvis were included. The rates of PJK, PJK revision, and radiographic PJF were compared between patients with upper instrumented vertebra (UIV) in the upper thoracic spine (UT; T1-T7) and lower thoracic spine (LT; T8-L1). Mean differences were assessed via analyses of covariance, factoring in any differences between cohorts at baseline and any use of PJF prophylaxis. Backstep logistic regressions assessed predictors of achieving Smith et al.’s Best Clinical Outcomes (BCOs) and complications, controlling for similar covariates. Results: A total of 232 ASD patients were included (64.2 ± 10.2 years, 78% female); 36.3% were UT and 63.7% were LT. Postoperatively, the rates of PJK for UT were lower than LT at 1Y (34.6 vs. 50.4%, p = 0.024), 2Y (29.5 vs. 49.6% (p = 0.003), and 5Y (48.7 vs. 62.8%, p = 0.048), with comparable rates of PJF. In total, 4.0% of UT patients underwent subsequent reoperation, compared to 13.0% of LT patients (p = 0.025). A total of 6.0% of patients had recurrent PJK, and 3.9% had recurrent PJF (both p > 0.05). After reoperation, UT patients reported higher rates of improvement in the minimum clinically important difference for ODI by 2Y (p = 0.007) and last follow-up (p < 0.001). While adjusted regression revealed that, for UT patients, the minimization of construct extension was predictive of achieving BCOs by last follow-up (model p < 0.001), no such relationship was identified in LT patients. Conclusions: Patients initially fused to the lower thoracic spine demonstrate an increased incidence of PJK and lower rates of disability improvement, but are at a lessened risk of neurologic complications if reoperation is required. Full article

Mechanical bowel preparation (MBP) is essential for visualisation of the colon during colonoscopy. Previous studies have identified changes in gut microbiota composition after MBP and colonoscopy. Considering the gut microbiota is increasingly implicated in psychiatry, we explored the potential impact of this intervention on mood and the microbiota–gut–brain axis. We conducted a pre–post intervention study in adults, with timepoints of one week before and one month after MBP and colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores. We examined changes in average anxiety, stress, and quality of life scores and gut microbiota composition using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and gut microbiota and conducted post hoc analyses to explore potential effect modifiers. Average depressive symptom scores decreased one month post-procedure compared to baseline (n = 59; adjusted β = −0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (β = 1.78; 95%CI: 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Reduced alpha diversity, modest effects on beta-diversity, and increases in health-associated genera were observed one month post-procedure. Increases in the CLR-transformed abundances of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. There is preliminary evidence of a potential mental health effect of MBP and colonoscopy, particularly for those with IBS, which may be associated with changes to the gut microbiota. Further research is required to confirm these findings and their clinical relevance. Full article

This paper proposes a novel model-agnostic method for weighting the outputs of base classifiers in machine learning (ML) ensembles. Our approach uses class-based weight coefficients assigned to every output class in each learner in the ensemble. This is particularly useful when the base classifiers have highly variable performance across classes. Our method generates a dense set of coefficients for the models in our ensemble by considering the model performance on each class. We compare our novel method to the commonly used ensemble approaches like voting and weighted averages. In addition, we compare our approach to class-specific soft voting (CSSV), which was also designed to address variable performance but generates a sparse set of weights by solving a linear system. We choose to illustrate the power of this approach by applying it to an ensemble of extreme learning machines (ELMs), which are well suited for this approach due to their stochastic, highly varying performance across classes. We illustrate the superiority of our approach by comparing its performance to that of simple majority voting, weighted majority voting, and class-specific soft voting using ten popular open-source multiclass classification datasets. Full article

Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas with additional immunomodulatory properties. Previously, we published that REG3A expression in ischemic stroke patient systemic blood, during mechanical thrombectomy (MT), is significantly associated with inflammatory cytokines and patient function on admission. This paper, however, did not investigate post-acute death rates. Therefore, we investigated plasma REG3A protein expression, during MT, in patients (n = 141) that survived or died within the end of the follow-up after MT. Subjects who died had significantly higher systemic plasma REG3A levels at the time of MT compared to survivors (p = 0.001). Age, sex, time from last known normal, and admission NIHSS were included as predictors to control for confounding variables and were all examined to determine their association in patient mortality. Logistic regression was used to demonstrate that higher odds of death were associated with increased REG3A levels (p = 0.002). REG3A demonstrated acceptable discrimination (AUC (95% CI): 0.669 (0.566–0.772) in predicting mortality. The overall model with age, sex, time from last known normal, and admission NIHSS discriminated well between survivors and those who died (AUC (95% CI): 0.784 (0.703–0.864)). In conclusion, REG3A could be promising as a biomarker to prognosticate stroke outcomes and stratify high-risk groups following acute ischemic stroke. Full article

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n = 59) exploring re-establishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n = 45) and without (n = 13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential re-establishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house. Full article

Recently, studies suggest that the protective effects of Lactobacillus within the female reproductive tract may be partly due to their ability to form biofilms. This study aims to explore the possibility that Lactobacillus can produce key mediators to further bolster the survival of biofilms in human vaginal microbiomes. Three bacterial species, namely, Lactobacillus gasseri, L. crispatus, and L. jensenii, sourced from human female subjects were used to carry out experiments examining the growth of biofilms using a microfermenter system. The bacteria were used to inoculate a glass rod spatula which was subsequently transferred to the microfermenter system. The resulting biofilm growing on the glass spatula was harvested in media and stored in a −80 °C freezer for gas chromatography–mass spectroscopy analysis. We found that quorum sensing compounds, acyl homoserine lactones (AHLs), were detected in the biofilm of L. crispatus and L. jensenii, but none were detected in L. gasseri. The biofilm produced by L. crispatus and L. jensenii was much higher in quantity than the biofilm produced by L. gasseri. Aside from oligopeptides quorum sensing, lactobacilli were found to also have AHL compounds that may help them produce more biofilms and improve the survival and growth of their bacterial communities in the female genital area. Full article

Due to limitations in current motion tracking technologies and increasing interest in alternative sensors for motion tracking both inside and outside the MRI system, in this study we share our preliminary experience with three alternative sensors utilizing diverse technologies and interactions with tissue to monitor motion of the body surface, respiratory-related motion of major organs, and non-respiratory motion of deep-seated organs. These consist of (1) a Pilot-Tone RF transmitter combined with deep learning algorithms for tracking liver motion, (2) a single-channel ultrasound transducer with deep learning for monitoring bladder motion, and (3) a 3D Time-of-Flight camera for observing the motion of the anterior torso surface. Additionally, we demonstrate the capability of these sensors to simultaneously capture motion data outside the MRI environment, which is particularly relevant for procedures like radiation therapy, where motion status could be related to previously characterized cyclical anatomical data. Our findings indicate that the ultrasound sensor can track motion in deep-seated organs (bladder) as well as respiratory-related motion. The Time-of-Flight camera offers ease of interpretation and performs well in detecting surface motion (respiration). The Pilot-Tone demonstrates efficacy in tracking bulk respiratory motion and motion of major organs (liver). Simultaneous use of all three sensors could provide complementary motion information outside the MRI bore, providing potential value for motion tracking during position-sensitive treatments such as radiation therapy. Full article

Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS infection of primary keratinocytes increased fatty acids that were associated with enhanced PPARβ/δ activity. Fatty acids caused PPARβ/δ-dependent increases in chromatin occupancy and the expression of angiopoietin-like protein 4 (Angptl4) mRNA. Analyses demonstrated that stearoyl Co-A desaturase 1 (Scd1) mediates an increase in intracellular monounsaturated fatty acids in keratinocytes that act as PPARβ/δ ligands. The activation of PPARβ/δ with palmitoleic or oleic acid causes arrest at the G2/M phase of the cell cycle of HRAS-expressing keratinocytes that is not found in similarly treated HRAS-expressing Pparb/d-null keratinocytes. HRAS-expressing Scd1-null mouse keratinocytes exhibit enhanced cell proliferation, an effect that is mitigated by treatment with palmitoleic or oleic acid. Consistent with these findings, the ligand activation of PPARβ/δ with GW0742 or oleic acid prevented UVB-induced non-melanoma skin carcinogenesis, an effect that required PPARβ/δ. The results from these studies demonstrate that PPARβ/δ has endogenous roles in keratinocytes and can be activated by lipids found in diet and cellular components. Full article

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO₂ integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed. Full article

Background: The objective of this study was to evaluate if imbalance influences complication rates, radiological outcomes, and patient-reported outcomes (PROMs) following adult spinal deformity (ASD) surgery. Methods: ASD patients with baseline and 2-year radiographic and PROMs were included. Patients were grouped according to whether they answered yes or no to a recent history of pre-operative loss of balance. The groups were propensity-matched by age, pelvic incidence–lumbar lordosis (PI-LL), and surgical invasiveness score. Results: In total, 212 patients were examined (106 in each group). Patients with gait imbalance had worse baseline PROM measures, including Oswestry disability index (45.2 vs. 36.6), SF-36 mental component score (44 vs. 51.8), and SF-36 physical component score (p < 0.001 for all). After 2 years, patients with gait imbalance had less pelvic tilt correction (−1.2 vs. −3.6°, p = 0.039) for a comparable PI-LL correction (−11.9 vs. −15.1°, p = 0.144). Gait imbalance patients had higher rates of radiographic proximal junctional kyphosis (PJK) (26.4% vs. 14.2%) and implant-related complications (47.2% vs. 34.0%). After controlling for age, baseline sagittal parameters, PI-LL correction, and comorbidities, patients with imbalance had 2.2-times-increased odds of PJK after 2 years. Conclusions: Patients with a self-reported loss of balance/unsteady gait have significantly worse PROMs and higher risk of PJK. Full article

Mercury (Hg) is a toxic metal that is easily released into the atmosphere as a gas or a particulate. Since Hg has serious health impacts based on human exposure, it is a major concern where it accumulates. Southern Florida is a region of high Hg deposition in the United States. It has entered the southern Florida environment for over 56 MY. For the past 3000 to 8000 years, Hg has accumulated in the Everglades peatlands, where approximately 42.3 metric tons of Hg was deposited. The pre-industrial source of mercury that was deposited into the Everglades was from the atmosphere, consisting of combined Saharan dust and marine evasion. Drainage and the development of the Everglades for agriculture, and other mixed land uses have caused a 65.7% reduction in the quantity of peat, therefore releasing approximately 28 metric tons of Hg into the southern Florida environment over a period of approximately 133 years. Both natural and man-made fires have facilitated the Hg release. The current range in mercury release into the southern Florida environment lies between 994.9 and 1249 kg/yr. The largest source of Hg currently entering the Florida environment is from combined atmospheric sources, including Saharan dust, aerosols, sea spray, and ocean flux/evasion at 257.1–514.2 kg/yr. The remobilization of Hg from the Everglades peatlands and fires is approximately 215 kg/yr. Other large contributors include waste to energy incinerators (204.1 kg/yr), medical waste and crematory incinerators (159.7+ kg/yr), and cement plant stack discharge (150.6 kg/yr). Minor emissions include fuel emissions from motorized vehicles, gas emissions from landfills, asphalt plants, and possible others. No data are available on controlled fires in the Everglades in sugar farming, which is lumped with the overall peatland loss of Hg to the environment. Hg has impacted wildlife in southern Florida with recorded excess concentrations in fish, birds, and apex predators. This bioaccumulation of Hg in animals led to the adoption of regulations (total maximum loads) to reduce the impacts on wildlife and warnings were given to consumers to avoid the consumption of fish that are considered to be contaminated. The deposition of atmospheric Hg in southern Florida has not been studied sufficiently to ascertain where it has had the greatest impacts. Hg has been found to accumulate on willow tree leaves in a natural environment in one recent study. No significant studies of the potential impacts on human health have been conducted in southern Florida, which should be started based on the high rates of Hg fallout in rainfall and known recycling for organic sediments containing high concentrations of Hg. Full article

Herein, we review established clinical use cases for SARS-CoV-2 antibody measures, which include diagnosis of recent prior infection, isolating high titer convalescent plasma, diagnosing multisystem inflammatory syndrome in children (MIS-C), and booster dosing in the immunosuppressed and other populations. We then address whether an antibody correlate of protection (CoP) for SARS-CoV-2 has been successfully defined with the following considerations: Antibody responses in the immunocompetent, vaccine type, variants, use of binding antibody tests vs. neutralization tests, and endpoint measures. In the transition from the COVID-19 pandemic to endemic, there has been much interest in defining an antibody CoP. Due to the high mutability of respiratory viruses and our current knowledge of SARS-CoV-2 variants defining a CoP for prevention of infection is unrealistic. However, a CoP may be defined for prevention of severe disease requiring hospitalization and/or death. Most SARS-CoV-2 CoP research has focused on neutralization measurements. However, there can be significant differences in neutralization test methods, and disparate responses to new variants depending on format. Furthermore, neutralization assays are often impractical for high throughput applications (e.g., assessing humoral immune response in populations or large cohorts). Nevertheless, CoP studies using neutralization measures are reviewed to determine where there is consensus. Alternatively, binding antibody tests could be used to define a CoP. Binding antibody assays tend to be highly automatable, high throughput, and therefore practical for large population applications. Again, we review studies for consensus on binding antibody responses to vaccines, focusing on standardized results. Binding antibodies directed against the S1 receptor binding domain (S1-RBD) of the viral spike protein can provide a practical, indirect measure of neutralization. Initially, a response for S1-RBD antibodies may be selected that reflects the peak response in immunocompetent populations and may serve as a target for booster dosing in the immunocompromised. From existing studies reporting peak S1-RBD responses in standardized units, an approximate range of 1372–2744 BAU/mL for mRNA and recombinant protein vaccines was extracted that could serve as an initial CoP target. This target would need to be confirmed and potentially adjusted for updated vaccines, and almost certainly for other vaccine formats (i.e., viral vector). Alternatively, a threshold or response could be defined based on outcomes over time (i.e., prevention of severe disease). We also discuss the precedent for clinical measurement of antibodies for vaccine-preventable diseases (e.g., hepatitis B). Lastly, cellular immunity is briefly addressed for its importance in the nature and durability of protection. Full article

Many studies identified factors associated with vaccination intention and hesitancy, but factors associated with vaccination promptness and the effect of vaccination intention on vaccination promptness are unknown. This study identified factors associated with COVID-19 vaccination promptness and evaluated the role of vaccination intention on vaccination promptness in 1223 participants in a community-based longitudinal cohort study (June 2020 to December 2021). Participants answered questions regarding COVID-19 vaccination intention, vaccination status, and reasons for not receiving a vaccine. The association of baseline vaccine hesitancy with vaccination was assessed by the Kaplan–Meier survival analysis. Follow-up analyses tested the importance of other variables predicting vaccination using the Cox proportional hazards model. Older age was associated with shorter time to vaccination (HR = 1.76 [1.37–2.25] 85-year-old versus 65-year-old). Lower education levels (HR = 0.80 [0.69–0.92]), household incomes (HR = 0.84 [0.72–0.98]), and baseline vaccination intention of ‘No’ (HR = 0.16 [0.11–0.23]) were associated with longer times to vaccination. The most common reasons for not being vaccinated (N = 58) were vaccine safety concerns (n = 33), side effects (n = 28), and vaccine effectiveness (n = 25). Vaccination campaigns that target populations prone to hesitancy and address vaccine safety and effectiveness could be helpful in future vaccination rollouts. Full article