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Abstract Dynamic tracking of spinal instrumentation could facilitate real-time evaluation of hardware integrity and in so doing alert patients/clinicians of potential failure(s). Critically, no method yet exists to continually monitor the integrity of spinal hardware and by proxy the process of spinal arthrodesis; as such hardware failures are often not appreciated until clinical symptoms manifest. Accordingly, herein, we report on the development and engineering of a bio-adhesive metal detector array (BioMDA), a potential wearable solution for real-time, non-invasive positional analyses of osseous implants within the spine. The electromagnetic coupling mechanism and intimate interfacial adhesion enable the precise sensing of the metallic implants position without the use of radiation. The customized decoupling models developed facilitate the precise determination of the horizontal and vertical positions of the implants with incredible levels of accuracy (e.g.,

Abstract Autologous chimeric antigen receptor (CAR) T‐cell therapy has demonstrated remarkable response rates, yet its widespread implementation is hindered by logistical, financial, and physical constraints. Additionally, challenges such as poor persistence and allorejection are associated with allogeneic cell therapies. An innovative approach involves in vivo transduction of endogenous T‐cells through the administration of CAR mRNA encapsulated in polymeric nanoparticles (NPs), resulting in transient CAR surface expression on circulating T‐cells. This method presents a promising alternative, although the dose–exposure–response relationship of in vivo CAR‐Ts remains poorly elucidated. The transient nature of CAR expression may necessitate repeated dosing, potentially introducing additional hurdles like cost and patient compliance. To address this issue, we have devised a translational pharmacokinetic–pharmacodynamic (PK–PD) model that characterizes the transient surface CAR expression following mRNA‐encapsulated NP administration, leveraging in vitro and in vivo data alongside critical binding kinetic parameters sourced from literature. Our model adequately captures the transient surface CAR expression in both settings, while incorporating known physiological parameter values and exhibiting precise estimation of unknown parameters (coefficient of variation

Abstract Maintaining driving independence is important for older adults. However, cognitive decline, a common issue in older populations, can impair older adults’ driving abilities and overall safety on the roads. This study explores how cognitive impairment influences driving patterns and driving choices among older adults. We analyzed real-world driving patterns of 246 older adults using GPS dataloggers. Our sample included 230 cognitively normal older adults (CN; Clinical Dementia Rating $$^R$$ R [CDR] = 0) and 16 older adults with incident cognitive impairment (ICI; CDR = 0.5). The CN group had an average age of 68.2 years, with 46% females and an average of 16.5 years of education, while the ICI group’s average age was 69.2 years, with 36% females and an average of 16.0 years of education. We employed spatial clustering and hashing algorithms to evaluate driving behaviours. Significant differences emerged: The ICI group used fewer distinct routes to their most common destination. These differences can be leveraged to develop driving as a digital biomarker for the early detection and continuous monitoring of cognitive impairment.

Abstract Chimeric antigen receptor (CAR) T‐cell subsets and immunophenotypic composition of the pre‐infusion product, as well as their longitudinal changes following infusion, are expected to affect CAR T‐cell expansion, persistence, and clinical outcomes. Herein, we sequentially evolved our previously described cellular kinetic‐pharmacodynamic (CK‐PD) model to incorporate CAR T‐cell product‐associated attributes by utilizing published preclinical and clinical datasets from two affinity variants (FMC63 and CAT19 scFv) anti‐CD19 CAR T‐cells. In step 1, a unified cell‐level PD model was used to simultaneously characterize the in vitro killing datasets of two CAR T‐cells against CD19+ cell lines at varying effector:target ratios. In step 2, an augmented CK‐PD model for anti‐CD19 CAR T‐cells was developed, by integrating CK dataset(s) from two bioanalytical measurements (quantitative polymerase chain reaction and flow cytometry) in patients with cancer. The model described the differential in vivo expansion properties of CAR T‐cell subsets. The estimated expansion rate constant was ~1.12‐fold higher for CAR+CD8+ cells in comparison to CAR+CD4+ T‐cells. In step 3, the model was extended to characterize the disposition of four immunophenotypic populations of CAR T‐cells, including stem‐cell memory, central memory, effector memory, and effector cells. The model adequately characterized the longitudinal changes in immunophenotypes post anti‐CD19 CAR T‐cell infusion in pediatric patients with acute lymphocytic leukemia. Polyclonality in the pre‐infusion product was identified as a categorical covariate influencing differentiation of immunophenotypes. In the future, this model could be leveraged a priori toward optimizing the composition of CAR T‐cell infusion product, and further understand the CK‐PD relationship in patients.

Abstract INTRODUCTION This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study. METHODS Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood‐based biomarker collection, optional one‐time magnetic resonance imaging (MRI) scan, and community workshop. RESULTS Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective. DISCUSSION The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease‐modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation. Highlights Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers. Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement. Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation. Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants.

During a few extremely distressing earthquakes in India, R.C.C. elevated water tanks suffered significant damage or collapsed. This may have been brought on by incorrect staging geometry as well as ignorance of how the tank's supporting system should behave in the event of an earthquake. The elevated water tank is made up of structural components such as footings, beams, columns, and slabs. Subjected loads are passed between these components and ultimately to the soil's sub-grade. When an overhead tank is advantageously analysed, the elevated water tank behaves differently for distinct types of loadings (Dead, Live, and Seismic). Various combinations of loads that support the possibility of occurrence are indicated by the codes for Indian standards. The primary goal of this research is to improve performance during earthquakes and complement conventional staging by better understanding the behaviour of various bracing systems. Equivalent static analysis of various bracing system types applied to the elevated circular water tank staging in the seismic zone are carried out using STAAD Pro. The axial force and maximum bending moment of the circular water tank are examined in the X, Y, and Z axes. Several models are used to calculate the axial force and maximum bending moment for staging with cross bracing, diagonal bracing, and alternating diagonal bracing.

Abstract Our objective was to identify functional brain changes that associate with driving behaviors in older adults. Within a cohort of 64 cognitively normal adults (age 60+), we compared naturalistic driving behavior with resting state functional connectivity using machine learning. Functional networks associated with the ability to interpret and respond to external sensory stimuli and the ability to multi-task were associated with measures of route selection. Maintenance of these networks may be important for continued preservation of driving abilities.

Dynamic compartmentalized data (DCD) and compartmentalized differential equations (CDEs) are key instruments for modeling transmission of pathogens such as the SARS-CoV-2 virus. We describe an effi-cient nowcasting algorithm for modeling transmission of SARS-CoV-2 with uncertainty quantification for the COVID-19 impact. A key concern for transmission of SARS-CoV-2 is under-reporting of cases, and this is addressed in our data-driven model by providing an estimate for the detection rate. Our novel top-down model is based on CDEs with stochastic constitutive parameters obtained from the DCD using Bayesian inference. We demonstrate the robustness of our algorithm for simulation studies using synthetic DCD, and nowcasting COVID-19 using real DCD from several regions across five continents.

Life skills, also known as psychosocial and non-cognitive skills, are critical to children’s development and well-being as they progress through early life courses but difficult to measure. The present study aims at validating a culturally adapted version of the Multidimensional Scale of Life Skills in Late Childhood in the context of primary school of rural Afghanistan and Pakistan. The instrument was face validated by six of the authors. The scale was found accessible to students’ grades three to five despite its original target of late childhood. Content validation was also carried out by the authors to evaluate the representativeness of the scale items for the various dimensions of life skills. The items were found relevant for the seven dimensions of life skills considered. The scale also showed overall good internal consistency, acceptable test retest and inter rate consistence and high responsiveness. Exploratory factorial analysis showed that 4 and 3 factors explained 40% and 37% of the total variance respectively in Pakistan and Afghanistan.

Summary: Background: Multidimensional poverty is associated with dementia, but no evidence is available for countries in conflict. Methods: A cross-sectional study was conducted in two provinces of Afghanistan between February 15th 2022 and April 20th 2022 among adults age 50 and older. Multidimensional poverty included six dimensions of well-being and 16 indicators of deprivation. The Rowland Universal Dementia Assessment Scale measured dementia. Poverty between adults with and without dementia was examined, adjusting for sex. Associations between dementia and poverty were investigated using multivariate regression model. Findings: Of the 478 adults included, 89 (52.7%) had mild, and 25 (14.8%) had moderate to severe dementia. More women than men had mild (52.7% vs 33.3%) and moderate-to-severe dementia (14.8% vs 5.8%). Approximately 33.9% adults with mild and 51.2% adults with moderate-to-severe dementia were found to be deprived in four or more dimensions compared to 21.8% without dementia. The difference in four dimensions of multidimensional poverty between adults with mild and moderate-to-severe dementia and adults without dementia was respectively 59.5% and 152.88%. Education, employment, health, and living conditions were the main contributors to the adjusted poverty head count ratio. Multidimensional poverty in four or five dimensions was strongly associated with dementia among older adults particularly over 70 years old (odds ratio [OR], 17.38; 95% CI, 2.22–135.63), with greater odds for older women overall (OR, 2.69; 95% CI, 1.76–4.11). Interpretation: Our findings suggest that early improvement in social determinants of health through targeted structural policies may lower dementia risk later in life. Specifically, better access to free, quality education, healthcare, and basic living standard together with employment opportunities could reduce risk of dementia. Funding: The present study was funded by a grant from the Alzheimer Association (AARG-NTF-21-851241).

Abstract Optical imaging through diffuse media is a challenging issue and has attracted applications in many fields such as biomedical imaging, non-destructive testing, and computer-assisted surgery. However, light interaction with diffuse media leads to multiple scattering of the photons in the angular and spatial domain, severely degrading the image reconstruction process. In this article, a novel method to image through diffuse media using multiple modes of vortex beams and a new deep learning network named “LGDiffNet” is derived. A proof-of-concept numerical simulation is conducted using this method, and the results are experimentally verified. In this technique, the multiple modes of Gaussian and Laguerre-Gaussian beams illuminate the displayed digits dataset number, and the beams are then propagated through the diffuser before being captured on the beam profiler. Furthermore, we investigated whether imaging through diffuse media using multiple modes of vortex beams instead of Gaussian beams improves the imaging system's imaging capability and enhances the network's reconstruction ability. Our results show that illuminating the diffuser using vortex beams and employing the “LGDiffNet” network provides enhanced image reconstruction compared to existing modalities. An enhancement of ~ 1 dB, in terms of PSNR, is achieved using this method when a highly scattering diffuser of grit 220 and width 2 mm (7.11 times the mean free path) is used. No additional optimizations or reference beams were used in the imaging system, revealing the robustness of the “LGDiffNet” network and the adaptability of the imaging system for practical applications in medical imaging.

Introduction: Chronic Suppurative Otitis Media (CSOM) is chronic inflammation of epithelial lining of the middle ear cleft. Ossicular discontinuity and/or erosion is known in CSOM with cholesteatoma but at times it can be associated with tubotympanic CSOM which surprises the operating surgeon. This study to determine the relationship between preoperative and otoendoscopic findings in cases of CSOM was undertaken to facilitate the surgeon in planning about dealing the disease before rather than having surprise at exploration. Aim: To study predictors of ossicular dysfunction in cases of mucosal CSOM. Materials and Methods: This prospective cohort study of 64 cases was undertaken at Krishna Institute of Medical Sciences, Karad, Maharashtra, India, from November 2018 to April 2020. All cases were subjected to detailed clinical, otoscopic, and microscopic examination to assess the size of perforation, granulation tissue, tympanosclerosis, exposure of incudostapedeal joint, and condition of middle ear mucosa. A pure tone audiogram was also done. All cases underwent tympanoplasty with or without cortical mastoidectomy and the intraoperative findings of ossicular erosion were noted. All cases with granulation or polypoidal mucosa on otoscopic examination as well as mastoid exploration were subjected to histopathological examination for confirmation of disease pathology. Using Chi-square test with Yates continuity correction the variables data was processed and results were analysed. Results: Out of the 64 cases, 15 (23.4%) had ossicular erosion. Bivariate analysis showed a positive association for middle age group between 31-40 years (p-value 40 dB (p-value

Abstract Introduction Health disparities arise from biological‐environmental interactions. Neuroimaging cohorts are reaching sufficiently large sample sizes such that analyses could evaluate how the environment affects the brain. We present a practical guide for applying geospatial methods to a neuroimaging cohort. Methods We estimated brain age gap (BAG) from structural magnetic resonance imaging (MRI) from 239 city‐dwelling participants in St. Louis, Missouri. We compared these participants to population‐level estimates from the American Community Survey (ACS). We used geospatial analysis to identify neighborhoods associated with patterns of altered brain structure. We also evaluated the relationship between Area Deprivation Index (ADI) and BAG. Results We identify areas in St. Louis, Missouri that were significantly associated with higher BAG from a spatially representative cohort. We provide replication code. Conclusion We observe a relationship between neighborhoods and brain health, which suggests that neighborhood‐based interventions could be appropriate. We encourage other studies to geocode participant information to evaluate biological‐environmental interaction.

Daily driving is a multi-faceted, real-world, behavioral measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this instrumental activity of daily living. As the global population of older adult continues to grow, motor vehicle crashes become more frequent among this demographic. Cognitive reserve (CR) is the brain’s adaptability or functional robustness despite damage, while brain reserve (BR) refers the structural, neuroanatomical resources. This study examined whether CR and BR predicted changes in adverse driving behaviors in cognitively normal older adults. Cognitively normal older adults (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer’s Disease Research Center at Washington University. Participants (n = 186) were ≥65 years of age, required to have Magnetic Resonance Imaging (MRI) data, neuropsychological testing data, and at least one full year of naturalistic driving data prior to the beginning of COVID-19 lockdown in the United States (March 2020) as measured by Driving Real World In-vehicle Evaluation System (DRIVES). Findings suggest numerous changes in driving behaviors over time were predicted by increased hippocampal and whole brain atrophy, as well as lower CR scores as proxied by the Wide Range Achievement Test 4. These changes indicate that those with lower BR and CR are more likely to reduce their driving exposure and limit trips as they age and may be more likely to avoid highways where speeding and aggressive maneuvers frequently occur.

PurposeImmune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).MethodsThe analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively. We evaluated the association between treatment efficacy and development of imAEs using univariate and multivariate survival analyses. Using machine learning, we built a predictive model utilizing baseline clinical and laboratory features to identify patients at risk of developing imAEs and further evaluated patient survival based on a threshold index extracted from the model.ResultsPatients who developed any grade of imAE had improved overall survival versus patients without (hazard ratio [HR] 0.51; 95% confidence interval [CI]: 0.41–0.62). imAE development was associated with improved overall survival (HR 0.54; 95% CI 0.44–0.66) in a multivariate Cox proportional hazard model considering patient demographic features and baseline characteristics. Higher odds of imAE development were observed (odds ratio 3.023; 95% CI: 1.56–5.83) in responders versus non-responders in patients treated with immunotherapy. Based on baseline characteristics, the random forest classification algorithm was used to formulate a predictive model to identify patients at increased risk of developing imAEs during treatment.ConclusionPost-hoc exploratory analysis found that the efficacy of immunotherapy was improved in patients who developed on-treatment imAEs. This was independent of severity of imAEs or the need for steroid treatment, which is important in allowing patients to remain on treatment and derive optimal clinical benefit. Further research is warranted to establish the correlation between incidence of imAEs and efficacy in this patient population.

Abstract Background Alzheimer disease (AD) is the most common cause of dementia. Preclinical AD is the period during which early AD brain changes are present but cognitive symptoms have not yet manifest. The presence of AD brain changes can be ascertained by molecular biomarkers obtained via imaging and lumbar puncture. However, the use of these methods is limited by cost, acceptability, and availability. The preclinical stage of AD may have a subtle functional signature, which can impact complex behaviours such as driving. The objective of the present study was to evaluate the ability of in-vehicle GPS data loggers to distinguish cognitively normal older drivers with preclinical AD from those without preclinical AD using machine learning methods. Methods We followed naturalistic driving in cognitively normal older drivers for 1 year with a commercial in-vehicle GPS data logger. The cohort included n = 64 individuals with and n = 75 without preclinical AD, as determined by cerebrospinal fluid biomarkers. Four Random Forest (RF) models were trained to detect preclinical AD. RF Gini index was used to identify the strongest predictors of preclinical AD. Results The F1 score of the RF models for identifying preclinical AD was 0.85 using APOE ε4 status and age only, 0.82 using GPS-based driving indicators only, 0.88 using age and driving indicators, and 0.91 using age, APOE ε4 status, and driving. The area under the receiver operating curve for the final model was 0.96. Conclusion The findings suggest that GPS driving may serve as an effective and accurate digital biomarker for identifying preclinical AD among older adults.

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross-cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.

Abstract Background Genomic studies of high-grade/progressive meningiomas have reported a heterogeneous mutation spectrum, identifying few recurrently mutated genes. Most studies have been underpowered to detect genomic subclasses of aggressive meningiomas due to relatively small number of available samples. Here, we present a genomic survey of one of the largest multi-institutional cohorts of high-grade/progressive meningiomas to date. Methods 850 high-grade/progressive meningiomas, including 441 WHO grade 2 and 176 WHO grade 3 meningiomas and 220 progressive WHO grade 1 meningiomas, were tested as part of a clinical testing program by hybridization capture of 406 cancer-related genes to detect base substitutions, indels, amplifications, deletions, and rearrangements. Information from pathology reports, histopathology review, and patient clinical data was assessed. Results Genomic analyses converged to identify at least three distinct patterns of biologically-aggressive meningiomas. The first and most common contained NF2-mutant tumors (n = 426, 50%), was associated with male sex (64.4% %, p = 0.0001) and often harbored additional mutations in CDKN2A/B (24%), and the chromatin regulators ARID1A (9%), and KDM6A (6%). A second group (NF2-agnostic) featured TERT promoter (TERTp; n = 56) or TP53 mutations (n = 25) and were either NF2-mutant or wild-type, and displayed no association with either sex (p = 0.39). The remaining group generally lacked NF2 mutations, and accounted for 40% of the cases—with three subgroups. One consistent primarily of grade 3 lesions harboring alterations in chromatin regulators BAP1 (n = 22) or PBRM1 (n = 16). A second subgroup contained AKT1 (n = 26), PIK3CA (n = 14) and SMO (n = 7) mutant skull-based meningiomas, and a third mixed subgroup included 237 meningiomas with a heterogeneous spectrum of low frequency and non-recurrent alterations. Conclusions Our findings indicate that the patterns of genomic alterations in high-grade/progressive meningiomas commonly group into three different categories. The most common NF2-associated canonical group frequently harbored CDKN2A/B alterations, which is potentially amenable to targeted therapies. An NF2-agnostic group harbored frequent TERTp and TP53 mutations. The final subclass, distinct from the canonical NF2 mutant associated pathway, was partly characterized by BAP1/PBRM1 alterations (rhabdoid/papillary histology) or skull-base disease. Overall, these data increase our understanding of the pathobiology of high-grade/progressive meningiomas and can guide the design of clinical trials. IRB approval status Reviewed and approved by Western IRB; Protocol No. 20152817.

Objective Conventional techniques for atlantoaxial fixation and fusion typically pass cables or wires underneath C1 lamina to secure the bone graft between the posterior elements of C1–2, which leads to complications such as cerebrospinal fluid (CSF) leak and neurological injury. With the evolution of fixation hardware, we propose a novel C1–2 fixation technique that avoids the morbidity and complications associated with sublaminar cables and wires. Methods This technique entails wedging and anchoring a structural iliac crest graft between C1 and C2 for interlaminar arthrodesis and securing it using a 0-Prolene suture at the time of C1 lateral mass and C2 pars interarticularis screw fixation. Results We identified 32 patients who underwent surgery for atlantoaxial with our technique. A 60% improvement in pain-related disability from preoperative baseline was demonstrated by Neck Disability Index (p

Plasmacytoma is a monoclonal neoplasm derived from progenitor B lymphocyte. Extra-medullary plasmacytoma is proliferation of malignant plasma cells involving the soft tissues with the absence of malignant plasma cells in the bone marrow and with normal gammaglobulin in serum, which is a rarely occurring variant of solitary plasmacytoma (3-4% of all solitary plasmacytoma). Seventy two years old man, suffered from right side nasal blockage for last 6 months. Nasal endoscopy revealed ipsilateral complete choanal occlusion by an endophytic mass having smooth surface arising from the lateral wall of the nasopharynx with an extension to the same side of oropharynx. On computed tomography of paranasal sinus an endophytic homogenous enhancing soft tissue shadow arising predominantly from right postero-lateral nasopharyngeal wall with an extension to oropharynx and without any surrounding bony erosion. The lesion was completely excised endoscopically. Histopathology as well as immunohistochemistry confirmed plasmacytoma. Extra medullary plasmacytoma was diagnosed as per International Myeloma Working Group (IMWG) criteria. Patient was treated with radiotherapy in a total dose of 50Gy in 25 cycles. Follow up at 5 and 10 months showed no evidence of recurrence or progression to multiple myeloma. A rare tumourextra medullary plasmacytoma of naso-oropharynx has very good prognosis. The radiotherapy remains mainstay of treatment in extra-medullary plasmacytoma. The complete endoscopic excision before radiotherapy improves outcome of treatment as in this case

Objective Lumbar fusion with implantation of interbody cage is a common procedure for treatment of lumbar degenerative disease. This study aims to compare the fusion and subsidence rates of titanium (Ti) versus polyetheretherketone (PEEK) interbody cages after posterior lumbar interbody fusion and investigate the effect of clinical and radiological outcomes following fusion on patient-reported outcomes. Methods A systematic search strategy of 4 electronic databases (MEDLINE, Embase, Web of Science, and Cochrane) was conducted using different MeSH (medical subject headings) terms until January 2020. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using fixed and random-effect models based upon the heterogeneity (I2) to estimate the association between interbody cages and the measured outcomes. Results A total of 1,094 patients from 11 studies were reviewed. The final analysis included 421 patients (38.5%) who had lumbar surgery using a Ti and/or a Ti-coated interbody cage and 673 patient (61.5%) who had lumbar surgery using a PEEK cage. Overall, PEEK interbody devices were associated with a significantly lower fusion rate compared with Ti interbody devices (OR, 0.62; 95% CI, 0.41–0.93; p = 0.02). There was no difference in subsidence rates between Ti and PEEK groups (OR, 0.91; 95% CI, 0.54–1.52; p = 0.71). Also, there were no statistically significant differences in visual analogue scale (VAS)-low back pain (p = 0.14) and Japanese Orthopedic Association scale (p = 0.86) between the 2 groups. However, the PEEK group had lower odds of leg pain after surgery compared to the Ti group (OR [VAS-leg], 0.61; 95% CI, 0.28–0.94; p = 0.003). Conclusion Ti and Ti-coated PEEK cages used for posterior lumbar interbody fusion are associated with similar rates of subsidence, but a higher rate of fusion compared to PEEK interbody cages. Randomized controlled trials are needed to better assess the effect of cage materials and potential factors that could influence the outcomes of interbody lumbar fusion.

Introduction Forward head posture (FHP) is the most common postural deviation of the upper back. It is believed to be one of the predisposing factors for the development of mechanical neck pain (MNP). We propose doing a systematic review to find the effectiveness of interventions targeted on FHP with MNP and assess implementation fidelity associated with these interventions.Methods and analysis Medline (PubMed), Web of Science (Social Science Citation Index), EMBASE, Scopus, PEDro and CINAHL databases will be searched for studies published in English from their inception. Forward and backward citations of the included studies will be investigated for identifying additional records. We will include randomised controlled trials and non/quasi-experimental studies with two groups assessing the effectiveness of interventions targeted on FHP with MNP. Observational studies, non-randomised studies with single group and reviews will be excluded. We will consider the following outcome measures: postural variables of FHP, neck pain, performance-based functional disability scores of the neck, quality of life, basic activities of daily living and work-related outcomes. The unique citations will be screened by titles/abstracts and full texts, independently. The Cochrane Risk of Bias 2 tool will be used to critically appraise the included studies. The risk of bias and data abstraction of included studies will be undertaken independently. A qualitative synthesis will be conducted and, if sufficient studies with comparable outcome measures are available, we will statistically pool the result.Ethics and dissemination We will undertake a systematic review of primary studies, and will not directly recruit participants hence, ethical clearance is not applicable. We will aim to present the findings of the completed systematic review at an international conference and subsequently submit the manuscript in a peer-reviewed journal for publication.PROSPERO registration number CRD42021250310.

Diffuse optical tomography (DOT) is a non-invasive method for detecting breast cancer; however, it struggles to produce high-quality images due to the complexity of scattered light and the limitations of traditional image reconstruction algorithms. These algorithms can be affected by boundary conditions and have a low imaging accuracy, a shallow imaging depth, a long computation time, and a high signal-to-noise ratio. However, machine learning can potentially improve the performance of DOT by being better equipped to solve inverse problems, perform regression, classify medical images, and reconstruct biomedical images. In this study, we utilized a machine learning model called “XGBoost” to detect tumors in inhomogeneous breasts and applied a post-processing technique based on genetic programming to improve accuracy. The proposed algorithm was tested using simulated DOT measurements from complex inhomogeneous breasts and evaluated using the cosine similarity metrics and root mean square error loss. The results showed that the use of XGBoost and genetic programming in DOT could lead to more accurate and non-invasive detection of tumors in inhomogeneous breasts compared to traditional methods, with the reconstructed breasts having an average cosine similarity of more than 0.97 ± 0.07 and average root mean square error of around 0.1270 ± 0.0031 compared to the ground truth.

Symptomatic cervical spinal stenosis and carotid artery stenosis are common neurosurgical diseases, but little is known about the management of their concurrent presentation. We present a 62 year-old woman with a precipitous decline in bilateral lower extremity strength, dexterity, and gait, and a 2-year history of amaurosis fugax. She was found to have cervical stenosis at C5-C7 with cord compression, lumbar stenosis at L3-L5 with a right L4-L5 synovial cyst, and moderate right internal carotid artery stenosis of 50–70%. The patient underwent a staged procedure. Stage 1 was a simultaneous right carotid endarterectomy and C6 corpectomy with C5-C7 anterior fusion. Stage 2 was a C3-T1 posterior decompression and fusion and L3-L5 decompression with synovial cyst removal. The presentation of concurrent cervical stenosis and CAS is likely underappreciated. Deciding between simultaneous or staged CEA and spinal decompression should be based on a careful risk-benefit assessment and tailored to the relative severity of symptoms, patient anatomy and comorbidities.

The potential of big data analytics to improve the quality of care for patients with spine tumors is significant. At this moment, the application of big data analytics to oncology and spine surgery is at a nascent stage. As such, efforts are underway to advance data-driven oncologic care, improve patient outcomes, and guide clinical decision making. This is both relevant and critical in the practice of spine oncology as clinical decision making is often made in isolation looking at select variables deemed relevant by the physician. With rapidly evolving therapeutics in surgery, radiation, interventional radiology, and oncology, there is a need to better develop decision-making algorithms utilizing the vast data available for each patient. The challenges and limitations inherent to big data analyses are presented with an eye towards future directions.

Background: Amongst the common problems faced globally, Allergic Rhinitis (AR) is very distressing at times. This is an inflammatory response to either known or unknown allergen. The symptomatic relief in AR using topical steroid Fluticasone propionate and antihistaminic Azelastine Hydrochloride in a combination has been studied. Very few studies showing comparison between these two drugs in a combination and steroid alone are available in the literature. Aim and Objectives: To study the effectiveness of topical treatment using corticosteroid Fluticasone propionate and antihistaminic in a combination versus Fluticasone propionate alone in patients of AR. Material and Methods: The cases presented with symptoms of allergic rhinitis were randomized in two groups at start of treatment. All cases of Group I were treated with Fluticasone propionate whereas of Group II with Fluticasone propionate and Azelastine hydrochloride combination. In each group, the individual symptom scores were recorded pre-treatment and post-treatment at the end of four weeks with the help of symptom evaluation scale. Based on these individual symptom scores, the Total Symptom Score (TSS) was calculated. The effectiveness of group specific drugs was evaluated by comparing individual and TSS. Results: After four weeks, both TSS and individual symptom score were reduced in either group (p

Antioxidant and antibacterial activities of natural anthraquinones namely chrysophanol (1) and emodin (2), and synthesized anthraquinones viz. 2-methylanthraquinone (3), anthraquinone (4), 2-bromoanthraquinone (5), rubiadin (6), chrysophanol diacetate (7), rubiadin diacetate (8) and 1,8-dimethoxy-3-methylanthraquinone (9) were investigated. Anthraquinones 9, 3, 6, 5 and 2 exhibited a high DPPH• radical scavenging capacity (IC50 =

Background: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the United States (US), Argentina, Chile, Mexico, and Peru. Methods: 1,608 (646 White, 852 Latino, 77 Black, 33 Asian; 72% female) individuals from the US and four Latin American countries aged ≥ 55 years completed an online survey regarding well-being and cognition during the pandemic between May and September 2020. Outcome variables (pandemic impact, discrimination, loneliness, purpose of life, subjective cognitive concerns) were compared across four US ethnoracial groups and older adults living in Argentina, Chile, Mexico, and Peru. Findings: Mean age for all participants was 66.7 (SD = 7.7) years and mean education was 15.4 (SD = 2.7) years. Compared to Whites, Latinos living in the US reported greater economic impact (p

Cognitive impairment is a significant risk factor for hazardous driving among older drivers with Alzheimer’s dementia, but little is known about how the driving behavior of mildly symptomatic compares with those in the preclinical, asymptomatic phase of Alzheimer’s disease (AD). This study utilized two in-car technologies to characterize driving behavior in symptomatic and preclinical AD. The goals of this pilot study were to (1) describe unsafe driving behaviors in individuals with symptomatic early AD using G-force triggered video capture and (2) compare the driving habits of these symptomatic AD drivers to two groups of cognitively normal drivers, those with and those without evidence of cerebral amyloidosis (CN/A+ and CN/A−) using a global positioning system (GPS) datalogger. Thirty-three drivers (aged 60+ years) were studied over 3 months. G-force triggered video events captured instances of near-misses/collisions, traffic violations, risky driver conduct, and driving fundamentals. GPS data were sampled every 30 s and all instances of speeding, hard braking, and sudden acceleration were recorded. For the early AD participants, video capture identified driving unbelted, late response, driving too fast for conditions, traffic violations, poor judgment, and not scanning intersections as the most frequently occurring safety errors. When evaluating driving using the GPS datalogger, hard breaking events occurred most frequently on a per trip basis across all three groups. The CN/A+ group had the lowest event rate across all three event types with lower instances of speeding. Slower psychomotor speed (Trail Making Part A) was associated with fewer speeding events, more hard acceleration events, and more overall events. GPS tracked instances of speeding were correlated with total number of video-captured near-collisions/collisions and driving fundamentals. Results demonstrate the utility of electronic monitoring to identify potentially unsafe driving events in symptomatic and preclinical AD. Results suggest that drivers with preclinical AD may compensate for early, subtle cognitive changes by driving more slowly and cautiously than healthy older drivers or those with cognitive impairment. Self-regulatory changes in driving behavior appear to occur in the preclinical phase of AD, but safety concerns may not arise until symptoms of cognitive impairment emerge and the ability to self-monitor declines.

Introduction: Safe driving requires integration of higher-order cognitive and motor functions, which are commonly compromised in patients with antibody-mediated encephalitis (AME) associated with N-methyl-D-aspartate receptors or leucine-rich glioma-inactivated 1 autoantibodies. How these deficits influence the return to safe driving is largely unknown. Recognizing this, we piloted non-invasive remote monitoring technology to longitudinally assess driving behaviors in recovering AME patients.Methods: Five recovering AME patients [median age, 52 years (range 29–67); two females] were recruited from tertiary care clinics at Washington University (St. Louis, MO). Trip data and aggressive actions (e.g., hard braking, sudden acceleration, speeding) were continuously recorded using a commercial Global Positioning System data logger when the patient's vehicle was driven by the designated driver. Longitudinal driving data were compared between AME patients and cognitively normal older adults (2:1 sex-matched) enrolled within parallel studies.Results: Driving behaviors were continuously monitored for a median of 29 months (range, 21–32). AME patients took fewer daily trips during the last vs. the first 6 months of observation, with a greater proportion of trips exceeding 10 miles. Compared to cognitively normal individuals, AME patients were more likely to experience hard braking events as recovery progressed. Despite this, no accidents were self-reported or captured by the data logger.Conclusion: Driving behaviors can be continuously monitored in AME patients using non-invasive means for protracted periods. Longitudinal changes in driving behavior may parallel functional recovery, warranting further study in expanded cohorts of recovering AME patients.

CONSTANS promotes flowering under long-day conditions in Arabidopsis but is rapidly degraded in short-day conditions. Here the authors show that the blue-light photoreceptor FKF1 can interact with the E3 ligase COP1 in a light-dependent manner and prevent degradation of CO in long-day conditions.

Introduction: Sensorineural Hearing Loss (SNHL) is potentially disabling and yet overlooked, while subjecting patients of head and neck cancer to conventional ionising radiation at most tertiary care centers. The demand for cancer care, along with the rising cost of therapy using newer treatment technologies such as intensity modulated radiotherapy is a concern to the health care system in India. Cochlea often remains in the field of radiation and hence need to be shielded to prevent development of SNHL. Aim: To assess role of radiotherapy causing sensorineural hearing loss in patients of head and neck cancer. Materials and Methods: A prospective study was initiated on 110 cases with normal hearing requiring Radiotherapy (RT), for biopsy proven tumours of head and neck in the Department of Otorhinolaryngology. All cases were treated with external beam conventional radiotherapy using telecobalt machine and a shielding collimator. Out of 110 cases treated by either curative or palliative dose of RT which was around 60 Gray (Gy) and 30 Gray (Gy) respectively, 16 did not come for follow-up. The study was concluded with remaining 94 cases who completed the follow-up. Hearing acuity was assessed using 500, 1000 and 2000 Hz frequency before start of radiotherapy, immediately following radiotherapy and at first follow-up after six months in all cases. Quantification of the degree of SNHL was done using one-way analysis of variance (ANOVA). During follow-up the hearing loss noted was graded into mild and moderate. Results: The ototoxic effect after RT was found amongst the cases who received curative dose of 60 Gy, while none in cases who received palliative dose of 30 Gy. Out of 188 ears in 94 cases, 59 ears (31.38%) had SNHL, including newly developed SNHL in 44 ears during the 6 month post-RT follow-up period. The number of ears having SNHL was 18 at immediate post-RT which further increased to 59 at 6 month follow-up as compared to pre-RT normal hearing levels. Conclusion: In cases of head and neck cancer treated by conventional radiotherapy using telecobalt machine and shielding, the risk of consequent sensorineural hearing loss -SNHL was about just less than one third (31.38%). The tolerance of cochlea to total dose of radiotherapy was less than 60 Gray in cases of head and neck cancer treated by conventional radiotherapy.

Over the past decades, Unmanned Aerial Vehicle (UAV) have been effectively adapted to perform disaster missions, agricultural and various societal applications. The path planning plays a crucial role in bringing autonomy to the UAVs to attain the designated tasks by avoiding collision in the obstacles prone regions. Optimal path planning of UAV is considered to be a challenging issue in real time navigation during obstacle prone environments. The present article focused on implementing a well-known A* and variant of A* namely MEA* algorithm to determine an optimal path in the varied obstacle regions for the UAV applications which is novel. Simulation is performed to investigate the performance of each algorithm with respect to comparing their execution time, total distance travelled and number of turns made to reach the source to target. Further, experimental flight trails are made to examine the performance of these algorithms using a UAV. The desired position, velocity and yaw of UAV is obtained based on the waypoints of optimal path planned data and effective navigation is performed. The simulation and experimental results are compared for confirming the effectiveness of these algorithms.

Between 2009 and 2018, the number of older adults (i [...]

There is a vast literature on stroke as a cardiovascular disease and driving outcomes, however little is known about other cardiovascular conditions and driving. The purpose of this review is to examine the literature for studies assessing the effect of non-stroke, vascular conditions on daily driving, reported crash risk and driving decline in older adult drivers as captured by naturalistic methodologies. A systematic review of Embase, Ovid and Scopus Plus examined articles on driving and vascular conditions among older adults. A search yielded 443 articles and, following two screenings, no articles remained that focused on non-stroke, vascular conditions and naturalistic driving. As a result, this review examined non-stroke, vascular conditions in nine driving studies of older adults that used road testing, driving simulators and self-report measures. These studies fell into three categories—heart failure, vascular dementia and white matter hyperintensities/leukoaraiosis. The combined findings of the studies suggest that heart failure, vascular dementia and white matter hyperintensities (WMH) negatively impact driving performance and contribute to driving cessation among older adults. Future research should examine cardiovascular risk factors like hypertension, hypercholesterolemia, myocardial infraction or atherosclerosis using naturalistic driving measurement, as well as traditional measures, in order to more fully characterize how these conditions impact older adult driving.

Maintenance of homeostasis of the endoplasmic reticulum (ER) ensures the balance between loading of nascent proteins and their secretion. Certain developmental conditions or environmental stressors affect protein folding causing ER stress. The resultant ER stress is mitigated by upregulating a set of stress-responsive genes in the nucleus modulating the mechanism of the unfolded protein response (UPR). In plants, the UPR is mediated by two major pathways; by the proteolytic processing of bZIP17/28 and by the IRE1-mediated splicing of bZIP60 mRNA. Recent studies have shown the involvement of plant-specific NAC transcription factors in UPR regulation. The molecular mechanisms activating plant-UPR transducers are only recently being unveiled. This review focuses on important structural features involved in the activation of the UPR transducers like bZIP17/28/60, IRE1, BAG7, and NAC017/062/089/103. Also, we discuss the activation of the UPR pathways, including BAG7-bZIP28 and IRE1-bZIP60, in detail, together with the NAC-TFs, which adds a new paradigm to the plant UPR.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.