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Objective To evaluate preoperative disability’s influence on patient-reported outcomes (PROs) following surgery for degenerative spondylolisthesis (DS). Methods DS patients who underwent surgical intervention were retrospectively identified from a single-surgeon spine registry. Cohorts based on Oswestry Disability Index (ODI) < 41 (milder disability) and ≥ 41 (severe disability) were created. Demographic differences were accounted for with 1:1 propensity score matching. For the matched sample, perioperative and PRO data were additionally collected. PROs assessed included mental health, physical function, pain, and disability. Pre- and up to 2-year postoperative PROs were utilized. Average time to final follow-up was 15.7 ± 8.8 months. Improvements in PROs and minimal clinically important difference (MCID) rates were calculated. Continuous variables were compared through Student t-test and categorical variables were compared through chi-square tests. Results Altogether, 214 patients were included with 77 in the milder disability group. The severe disability group had worse postoperative day (POD) 1 pain scores and longer hospital stays (p ≤ 0.038, both). The severe disability group reported worse outcomes pre- and postoperatively (p < 0.011, all), but had greater average improvement in 12-item Short Form health survey mental composite score (SF-12 MCS), 9-Item Patient Health Questionnaire (PHQ-9), visual analogue scale (VAS)-back, and ODI by 6 weeks (p ≤ 0.037, all) and PHQ-9, VAS-back and ODI by final follow-up (p ≤ 0.015, all). The severe disability cohort was more likely to achieve MCID for SF-12 MCS, PHQ-9, and ODI (p ≤ 0.003, all). Conclusion Patients with greater baseline disability report higher POD 1 pain and discharge later than patients with milder disability. While these patients report inferior physical/mental health before and after surgery, they report greater improvements in mental health and disability postoperatively.

Objective To evaluate the effect of Veterans RAND 12-item health survey mental composite score (VR-12 MCS) on postoperative patient-reported outcome measures (PROMs) after undergoing lateral lumbar interbody fusion. Methods Retrospective data from a single-surgeon database created 2 cohorts: patients with VR-12 MCS ≥ 50 or VR-12 MCS < 50. Preoperative, 6-week, and final follow-up (FF)- PROMs including VR-12 MCS/physical composite score (PCS), 12-item Short Form health survey (SF-12) MCS/PCS, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), Patient Health Questionnaire-9 (PHQ-9), visual analogue scale (VAS)-back/leg pain (VAS-BP/LP), and Oswestry Disability Index (ODI) were collected. ∆6-week and ∆FF-PROMs were calculated. Minimal clinically important difference (MCID) achievement rates were determined from established cutoffs from the literature. For intercohort comparison, chi-square analysis was used for categorical variables, and Student t-test for continuous variables. Results Seventy-nine patients were included; 25 were in VR-12 MCS < 50. Mean postoperative follow-up time was 17.12 ± 8.43 months. The VR-12 MCS < 50 cohort had worse VR-12 PCS, SF-12 MCS, PROMIS-PF, PHQ-9, VAS-BP, and ODI scores preoperatively (p ≤ 0.014, all), worse VR-12 MCS/PCS, SF-12 MCS, PROMIS-PF, PHQ-9, and ODI scores at 6-week postoperatively (p ≤ 0.039, all), and worse VR-12 MCS, SF-12 MCS, PROMIS-PF, PHQ-9, VAS-BP, VAS-LP, and ODI scores at FF (p ≤ 0.046, all). The VR-12 MCS < 50 cohort showed greater improvement in VR-12 MCS and SF-12 MCS scores at 6 weeks and FF (p ≤ 0.005, all). The VR-12 MCS < 50 cohort experienced greater MCID achievement for VR-12 MCS, SF-12 MCS, and PHQ-9 (p ≤ 0.006, all). Conclusion VR-12 MCS < 50 yielded worse mental health, physical function, pain and disability postoperatively, yet reported greater improvements in magnitude and MCID achievement for mental health.

Alkaline exonucleases (AE) are present in several large DNA viruses including bacteriophage λ and herpesviruses, where they play roles in viral DNA processing during genome replication. Given the genetic conservation of AEs across viruses infecting different kingdoms of life, these enzymes likely assume central roles in the lifecycles of viruses where they have yet to be well characterized. Here, we applied a structure-guided functional analysis of the bifunctional AE in the oncogenic human gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), called SOX. In addition to identifying a preferred DNA substrate preference for SOX, we define key residues important for DNA binding and DNA processing, and how SOX activity on DNA partially overlaps with its functionally separable cleavage of mRNA. By engineering these SOX mutants into KSHV, we reveal roles for its DNase activity in viral gene expression and infectious virion production. Our results provide mechanistic insight into gammaherpesviral AE activity as well as areas of functional conservation between this mammalian virus AE and its distant relative in phage λ.

BackgroundSouth Asians, inclusive of individuals originating in India, Pakistan, Maldives, Bangladesh, Sri Lanka, Bhutan, and Nepal, comprise the largest diaspora in the world, with large South Asian communities residing in the Caribbean, Africa, Europe, and elsewhere. There is evidence that South Asian communities have disproportionately experienced COVID-19 infections and mortality. WhatsApp, a free messaging app, is widely used in transnational communication within the South Asian diaspora. Limited studies exist on COVID-19-related misinformation specific to the South Asian community on WhatsApp. Understanding communication on WhatsApp may improve public health messaging to address COVID-19 disparities among South Asian communities worldwide.ObjectiveWe developed the COVID-19-Associated misinfoRmation On Messaging apps (CAROM) study to identify messages containing misinformation about COVID-19 shared via WhatsApp.MethodsWe collected messages forwarded globally through WhatsApp from self-identified South Asian community members between March 23 and June 3, 2021. We excluded messages that were in languages other than English, did not contain misinformation, or were not relevant to COVID-19. We deidentified each message and coded them for one or more content categories, media types (eg, video, image, text, web link, or a combination of these elements), and tone (eg, fearful, well intentioned, or pleading). We then performed a qualitative content analysis to arrive at key themes of COVID-19 misinformation.ResultsWe received 108 messages; 55 messages met the inclusion criteria for the final analytic sample; 32 (58%) contained text, 15 (27%) contained images, and 13 (24%) contained video. Content analysis revealed the following themes: "community transmission" relating to misinformation on how COVID-19 spreads in the community; "prevention" and "treatment," including Ayurvedic and traditional remedies for how to prevent or treat COVID-19 infection; and messaging attempting to sell "products or services" to prevent or cure COVID-19. Messages varied in audience from the general public to South Asians specifically; the latter included messages alluding to South Asian pride and solidarity. Scientific jargon and references to major organizations and leaders in health care were included to provide credibility. Messages with a pleading tone encouraged users to forward them to friends or family.ConclusionsMisinformation in the South Asian community on WhatsApp spreads erroneous ideas regarding disease transmission, prevention, and treatment. Content evoking solidarity, "trustworthy" sources, and encouragement to forward messages may increase the spread of misinformation. Public health outlets and social media companies must actively combat misinformation to address health disparities among the South Asian diaspora during the COVID-19 pandemic and in future public health emergencies.

Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I-IV (now 1-4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility.

Behavioral and neuroanatomical studies show that reading comprehension is based on mental simulation, as modality-specific sensorimotor representations and processes related to the meaning of the text are activated during reading. Supporting this simulation view of reading comprehension, cognitive semantics analyses show that changes in lexico-grammatical features are accompanied by changes in mental simulation. We hypothesized that Academic Language (AL) texts with different linguistic structuring will alter students’ mental simulations, particularly their perspectives differently, which can be tracked through its effect on attention. We first changed the linguistic structuring of AL text – particularly nominalization – to change the encoded perspective. We then tracked the effect of this change on the global and local perspectives of student mental simulations, using the Navon task. Initial results show a trend where changes in the passage structure led to a local attention effect. We discuss the implications of this indicative result, and ongoing work to further examine this finding.

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of [p21.sup.+] cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of [p21.sup.+] cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, [p21.sup.+] cell clearance did not alter bone loss due to aging; conversely, [p16.sup.+] cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, [p21.sup.+] neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while [p21.sup.+] OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was [p21.sup.+] and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of [p21.sup.+] versus [p16.sup.+] senescent/ senescent-like cells that may be leveraged for therapeutic opportunities., Introduction At the cellular level, aging is characterized by several hallmarks, including cellular senescence (1), which is driven by an increase in the cyclin-dependent kinase inhibitors Cdknla (p21) and/or Cdknla [...]

Abstract Devising an approach to deterministically position organisms can impact various fields such as bioimaging, cybernetics, cryopreservation, and organism‐integrated devices. This requires continuously assessing the locations of randomly distributed organisms to collect and transfer them to target spaces without harm. Here, an aspiration‐assisted adaptive printing system is developed that tracks, harvests, and relocates living and moving organisms on target spaces via a pick‐and‐place mechanism that continuously adapts to updated visual and spatial information about the organisms and target spaces. These adaptive printing strategies successfully positioned a single static organism, multiple organisms in droplets, and a single moving organism on target spaces. Their capabilities are exemplified by printing vitrification‐ready organisms in cryoprotectant droplets, sorting live organisms from dead ones, positioning organisms on curved surfaces, organizing organism‐powered displays, and integrating organisms with materials and devices in customizable shapes. These printing strategies can ultimately lead to autonomous biomanufacturing methods to evaluate and assemble organisms for a variety of single and multi‐organism‐based applications.

This study investigates the prevalence and dynamics of pomegranate wilt disease induced by Meloidogyne incognita across the Kullu, Mandi and Solan districts of Himachal Pradesh (India), revealed notable spatial and temporal variations in nematode populations and galling severity across the regions. The highest average nematode infestation of 9.25 % was observed at Nauni with highest counts of average second-stage juvenile (J2) larvae (449 larvae per 100 cc of soil) followed by Hurla (Kullu) with 7.42 % infestation. Correlation analysis reveals a strong positive relationship between larval population and galling severity suggesting a potential link between nematode levels and plant damage. Common disease symptoms were leaf size reduction, yellowing and gradual decline of pomegranate plants, often observed in patches within orchards. Microscopic identification revealed distinctive pear-shaped body of mature females while J2 larvae displayed vermiform shapes and the associated species of M. incognita was confirmed through examination of the perineal pattern. Pathogenicity test reveals initiation of leaf yellowing symptom after 45 days of inoculation of larval suspension and root galling was observed after 60 days onward followed by plant decline under greenhouse conditions. Results from pot and field experiments demonstrated the efficacy of Fluopyram and Fluensulfone in reducing nematode populations and galling severity. Treatment with drenching of Fluopyram at the rate of 2 ml/L reduced 98.56 % larvae under field and 99.00 % larvae/100 cc soil under pot conditions. Statistical analysis (paired t-test and MANOVA) confirms significant differences in galling severity and larval population before and after drenching. The study also underscores the importance of weed management in disease mitigation as several weed species (Chenopodium album and Solanum nigrum) were identified as potential reservoirs for M. incognita in infested pomegranate plant basin. This investigation contributes to the advancement of management practices for pomegranate cultivation that addresses both nematode and weed infestations ultimately enhancing crop resilience and productivity.

Same-day emergency care (SDEC) in unplanned and emergency care is an NHS England (NHSE) priority. Optimal use of these services requires rapid identification of suitable patients. NHSE suggests the use of one tool for this purpose. This systematic review compares studies that evaluate the performance of selection tools for SDEC pathways.Nine studies met the inclusion criteria. Three scores were evaluated: the Amb score (seven studies), Glasgow Admission Prediction Score (GAPS) (six studies) and Sydney Triage to Admission Risk Tool (START) (two studies). There was heterogeneity in the populations assessed, exclusion criteria used and definitions used for SDEC suitability, with proportions of patients deemed ‘suitable’ for SDEC ranging from 20 to 80%. Reported score sensitivity and specificity ranged between 18–99% and 10–89%. Score performance could not be compared due to heterogeneity between studies. No studies assessed clinical implementation.The current evidence to support the use of a specific tool for SDEC is limited and requires further evaluation.

The digitalization of agriculture is rapidly changing the way farmers do business. With the integration of advanced technology, farmers are now able to increase efficiency, productivity, and precision in their operations. Digitalization allows for real-time monitoring and management of crops, leading to improved yields and reduced waste. This paper presents a review of some of the use cases that digitalization has made an impact in the automation of open-field and closed-field cultivations by means of collecting data about soils, crop growth, and microclimate, or by contributing to more accurate decisions about water usage and fertilizer application. The objective was to address some of the most recent technological advances that are leading to increased efficiency and sustainability of crop production, reduction in the use of inputs and environmental impacts, and releasing manual workforces from repetitive field tasks. The short discussions included at the end of each case study attempt to highlight the limitations and technological challenges toward successful implementations, as well as to introduce alternative solutions and methods that are rapidly evolving to offer a vast array of benefits for farmers by influencing cost-saving measures. This review concludes that despite the many benefits of digitalization, there are still a number of challenges that need to be overcome, including high costs, reliability, and scalability. Most of the available setups that are currently used for this purpose have been custom designed for specific tasks and are still too expensive to be implemented on commercial scales, while others are still in their early stages of development, making them not reliable or scalable for widespread acceptance and adoption by farmers. By providing a comprehensive understanding of the current state of digitalization in agriculture and its impact on sustainable crop production and food security, this review provides insights for policy-makers, industry stakeholders, and researchers working in this field.

Particulate matter (PM) exposure is associated with adverse health outcomes, including respiratory illness. A large fraction of exposure to airborne contaminants occurs in the home. This study, conducted over 5 months in a community with high asthma rates (Chelsea, MA, USA), investigated the use of portable air cleaners (PACs) to reduce indoor PM. Seven asthma-affected households participated, receiving a PAC (Austin Air Health Mate HEPA filter), a QuantAQ sensor to measure PM 1 , PM 2.5 , PM 10 (µg/m 3 ), and a HOBO plug-load data logger to track PAC usage. Results describe hourly and daily PM concentrations and PAC usage for each household. Hourly average PM concentrations decreased when PACs were turned on (vs. when they were turned off) across households during the study period: PM 1 decreased by 0.46 µg/m 3 , PM 2.5 decreased by 0.69 µg/m 3 , and PM 10 decreased by 3.22 µg/m 3 . PAC usage varied for each household, including constant usage in one household and only usage at certain times of day in others. Higher filtration settings led to lower PM, with significant reductions in some, but not all, homes. Our findings highlight some difficulties in implementing household PAC interventions, yet also provide evidence to support household-level interventions to reduce PM and other indoor sources of air pollution. We also highlight academic-community partnerships as contributing to evidence-based solutions.

Brain metastases occur in almost one-third of adult patients with solid tumor malignancies and lead to considerable patient morbidity and mortality. The rising incidence of brain metastases has been ascribed to the development of better imaging and screening techniques and the formulation of better systemic therapies. Until recently, the multimodal management of brain metastases focused primarily on the utilization of neurosurgical techniques, with varying combinations of whole-brain radiation therapy and stereotactic radio-surgical procedures. Over the past 2 decades, in particular, the increment in knowledge pertaining to molecular genetics and the pathogenesis of brain metastases has led to significant developments in targeted therapies and immunotherapies. This review article highlights the recent updates in the management of brain metastases with an emphasis on novel systemic therapies.