Search

Abstract Background The proximal femur is a common site of bone metastasis. The Mirels’ score is a frequently utilized system to identify patients at risk for pathologic fracture and while it has consistently demonstrated strong sensitivity, specificity has been relatively poor. Our group previously developed a Modified Mirels’ scoring system which demonstrated improved ability to predict cases at risk of fracture in this patient population through modification of the Mirels’ location score. The purpose of the present study is to internally validate this newly developed scoring system on an independent patient series. Methods Retrospective review was performed to identify patients who were evaluated for proximal femoral bone lesions. Patients were stratified into one of two groups: 1) those who went on to fracture within 4 months after initial evaluation (Fracture Group) and 2) those who did not fracture within 4 months of initial evaluation (No Fracture Group). Retrospective chart review was performed to assign an Original Mirels’ (OM) Score and Modified Mirels’ (MM) score to each patient at the time of initial evaluation. Descriptive statistics, logistic regression, receiver operating curve, and net benefit analyses were performed to determine the predictability of fractures when utilizing both scoring systems. Results The use of the MM scoring improved fracture prediction over OM scoring for patients observed over a 4 month follow up based on logistic regression. Decision curve analysis showed that there was a net benefit using the MM score over the OM scoring for a full range of fracture threshold probabilities. Fracture prevalence was similar for current internal validation dataset when compared to the dataset of our index study with a comparable reduction in misclassification of fracture prediction when utilizing the modified scoring system versus the original. Conclusions Use of MM scoring was found to improve fracture prediction over OM scoring when tested on an internal validation set of patients with disseminated metastatic lesions to the proximal femur. The improvement in fracture prediction demonstrated in the present study mirrored the results of our index study during which the MM system was developed.

Abstract The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.

Study objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. Design/setting/participants/interventions/outcome measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20–3/24/21) and 26,459 patients were admitted in the year prior (2/16/19–2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p

We present a high-level architecture for how artificial intelligences might advance and accumulate scientific and technological knowledge, inspired by emerging perspectives on how human intelligences advance and accumulate such knowledge. Agents advance knowledge by exercising a technoscientific method—an interacting combination of scientific and engineering methods. The technoscientific method maximizes a quantity we call “useful learning” via more-creative implausible utility (including the “aha!” moments of discovery), as well as via less-creative plausible utility. Society accumulates the knowledge advanced by agents so that other agents can incorporate and build on to make further advances. The proposed architecture is challenging but potentially complete: its execution might in principle enable artificial intelligences to advance and accumulate an equivalent of the full range of human scientific and technological knowledge.

IntroductionAdvanced heart failure (HF) is an epidemic that affects multiple organ systems with high morbidity and mortality rates despite optimal medical therapy (OMT) and remains the leading cause of hospitalizations in type 2 diabetes-related cardiovascular disease. The addition of sodium-glucose co-transporter inhibitors (SGLT2i) in treating these patients has seen improved mortality and hospital admission rates. As such, we felt it was important to investigate whether the use of SGLT2i improved functional capacity in patients with HF when compared to OMT by evaluating maximum oxygen consumption (peak VO2) using cardiopulmonary exercise testing (CPET).MethodsWe found 94 heart failure patients between August 2020 and August 2021 who underwent CPET before and after treatment at Mayo Clinic in Florida. 50 patients received OMT and 44 received OMT and SGLT2i therapy. CPET results before and after were compared for each group.ResultsThe baseline ejection fraction was not significantly different between groups, with the OMT group at 38% and the SGLT2i group at 33%, p = 0.10. OMT patients were found to have a significantly lower hemoglobin A1c of 5.7 (5.4–6.1) compared to those with SGLT2i therapy of 6.4 (5.8–7.1), p = 0.01. The baseline peak VO2 was 17.3 ml/kg/min (13.3–21.6) in the OMT group and 17.3 ml/kg/min (14.4–18.9) in the SGLT2i group, p = 0.18, not significantly different. The interesting finding is that the follow-up peak VO2 at one year for the OMT group was 17 ml/kg/min (13.3–21.6), which was not significantly different from the SGLT2i group peak VO2 of 17 ml/kg/min (14.6–19.6), p = 0.19. Our study is the first to compare before and after peak VO2 values of the OMT+SGLT2i group to the patient's own baseline and we found no significant improvement.ConclusionOur single-center data shows no improvement in functional capacity after the addition of SGLT2i therapy to OMT in patients with advanced heart failure. Improved hospitalization and symptoms may be attributed to other numerous effects of SGLT2i such as volume management.

Background Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Methods and Results We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON‐HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM‐HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity–Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (β‐2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein–outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), or high‐sensitivity cardiac troponin. Conclusions Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON‐HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. Registration URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

We described an exploration of the impact of India's state Gujarat Government's Employability enhancement drive, 'Finishing School' (FS) training on the graduate level tribal college students in Gujarat, India. A literature review on employment skills (ES), vision, mission, and ES set module of FS was used to formulate the tool–Employability Enhancement Measuring Scale (EEMS). Data generation methods include pre and post-tests by EEMS survey questionnaire. SPSS 24 statistical package program was used for data analysis. The values before and after the training were compared using the Paired and Independent samples t-test and descriptive statistics. Results indicated a significant positive effect on tribal students' employability skills. The tool traced what students became by improving upon the ES sets by the end of the 'FS' training. The study's significance lies in the focus on tribal groups, aligning with the state's long-term vision for holistic growth. With a majority of students from the underprivileged Dang Forest area, the research suggested that FS training promoted inclusive growth, contributing to New India @ 75, and supporting Sustainable Development Goals (SDGs) 4, 8, 10, and 16. It could be inferred that the experimental group in this study constituted 93% tribal students, many of whom were first-generation learners, making the Gujarat experiment a valuable model for potential adoption in diverse regions globally.

Abstract Aims Red cell distribution width (RDW) is a strong prognostic marker in patients with heart failure (HF) and reduced ejection fraction and other conditions. However, very little is known about its prognostic significance in HF with preserved ejection fraction. We examined the relationship between RDW and outcomes and the effect of sacubitril/valsartan, compared with valsartan, on RDW and clinical outcomes in PARAGON‐HF. Methods and results PARAGON‐HF enrolled patients with a left ventricular ejection fraction of ≥45%, structural heart disease, and elevated N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). The primary endpoint was a composite of total HF hospitalizations and cardiovascular deaths. Median RDW at randomization was 14.1% (interquartile range 13.5–15.0%). Patients with higher RDW levels were more often men and had more comorbidity, a higher heart rate and NT‐proBNP concentration, more advanced New York Heart Association class, and worse Kansas City Cardiomyopathy Questionnaire scores. There was a graded relationship between quartiles of RDW at randomization and the primary endpoint, with a significantly higher risk associated with increasing RDW, even after adjustment for NT‐proBNP and other prognostic variables {Quartile 1, reference; Quartile 2, rate ratio 1.03 [95% confidence interval (CI) 0.83 to 1.28]; Quartile 3, 1.25 [1.01 to 1.54]; Quartile 4, 1.70 [1.39 to 2.08]}. This association was seen for each of the secondary outcomes, including cardiovascular and all‐cause death. Compared with valsartan, sacubitril/valsartan reduced RDW at 48 weeks [mean change −0.09 (95% CI −0.15 to −0.02)]. The effect of sacubitril/valsartan vs. valsartan was not significantly modified by RDW levels at randomization. Conclusions RDW, a routinely available and inexpensive biomarker, provides incremental prognostic information when added to established predictors. Compared with valsartan, sacubitril/valsartan led to a small reduction in RDW.

Artificial intelligence and cyber-physical systems (CPS) are two of the key technologies of the future that are enabling major global shifts. However, most of the current implementations of AI in CPS are not explainable, which creates serious problems in ethical, legal, regulatory, and other domains. Therefore, it is necessary for explainable artificial intelligence (XAI) to be integrated with cyber-physical systems to meet the vital needs for control, fairness, accountability, safety, cyber-resilience, and cybersecurity. The goal of this review is to demonstrate the need, benefits, challenges, and implementation of XAI for CPS. We review the existing literature about XAI and CPS, discuss the current state of the art, examine applications in different domains, and make recommendations for future research directions. To the best of our knowledge, this is the first peer-reviewed academic article to provide a comprehensive review of general XAI for CPS. We also contribute new research ideas including development of multisensory explanations and outputs for these systems, application of XAI to CPS to decrease occupational burnout and increase employee engagement, and enumeration of the multidisciplinary goals and benefits of XAI as applied to cyber-physical systems.

AbstractErythrina stricta Roxb., an underutilized legume species native to the Indian subcontinent, is traditionally employed in various medicinal applications. This study systematically examines the nutritional quality, encompassing proximate and mineral composition of E. stricta seeds, with a focus on characterizing the seed oil. The seeds exhibit commendable proximate composition, with 26.81% protein and 18.71% fibre. Noteworthy mineral elements include 5.0 mg/g DW of calcium and 787.0, 32.7, 36.8 and 497.0 µg/g of iron, copper, boron and zinc, respectively. The seeds yield 13.43% oil, with oleic, palmitic, linoleic and stearic acids as prominent fatty acids, constituting 48.82%, 20.63%, 20.27% and 6.47%, respectively. Antinutrients such as oxalate and phytate are present in concentrations of 26.85 and 16.04 mg/g FW, respectively. In conclusion, this study underscores E. stricta seeds as a robust source of both nutrients and oil, warranting further exploration and consideration for potential applications.

Background: Patients undergoing evaluation for advanced heart failure therapies (AHT) are at a critical juncture of their illness. Guidelines recommend shared decision-making with patients and caregivers; however, the approach and content of these discussions are unknown. Methods: Patients referred to a specialty palliative care service during AHT evaluation between October 2018 and September 2022 were identified from electronic health care records. Goals of care conversations documented in an advance care planning module were analyzed for participants, content, and timing before the transplant selection committee meeting. Primary outcomes included the prevalence of documented hopes, worries, shared prognostic communication, illness understanding, treatment expectations, and information preferences. Patients were followed for a minimum of 6 months to evaluate secondary processes and clinical outcomes. Results: Ninety-four patients (mean age 52.8 years, 76.6% male) met the criteria. Most patients (97.9%, n = 92) had illness understanding documented. In initial discussions, 76.3% (n = 71) hoped to “live longer” and 67.7% (n = 63) to “be independent”; thematic analysis supported these hopes with 91.0% of patients expecting “better functionality.” Most patients preferred multimodal information and communication. During follow-up, 27.7% (n = 26) had treatment decisions deferred at the initial committee presentation, and 43.6% (n = 41) were reviewed at multiple selection committee meetings. By the end of the study period, 53.2% (n = 50) underwent one or more AHT and 24.5% (n = 23) had died. Conclusions: Patients undergoing the AHT evaluation process face considerable uncertainty. A standardized approach by a specialty palliative care service elicits patients’ illness understanding, hopes, worries, treatment expectations, and information preferences to promote shared decision-making at this critical time.

ABSTRACTInflammatory bowel disease (IBD) is a group of inflammatory conditions of the gastrointestinal tract. The etiology of IBD remains elusive, but the disease is suggested to arise from the interaction of environmental and genetic factors that trigger inadequate immune responses and inflammation in the intestine. The gut microbiome majorly contributes to disease as an environmental variable, and although some causative bacteria are identified, little is known about which specific members of the microbiome aid in the intestinal epithelial barrier function to protect from disease. While chemically inducing colitis in mice from two distinct animal facilities, we serendipitously found that mice in one facility showed remarkable resistance to disease development, which was associated with increased markers of epithelial barrier integrity. Importantly, we show that Akkermansia muciniphila and Parabacteroides distasonis were significantly increased in the microbiota of resistant mice. To causally connect these microbes to protection against disease, we colonized susceptible mice with the two bacterial species. Our results demonstrate that A. muciniphila and P. distasonis synergistically drive a protective effect in both acute and chronic models of colitis by boosting the frequency of type 3 innate lymphoid cells in the colon and by improving gut epithelial integrity. Altogether, our work reveals a combined effort of commensal microbes in offering protection against severe intestinal inflammation by shaping gut immunity and by enhancing intestinal epithelial barrier stability. Our study highlights the beneficial role of gut bacteria in dictating intestinal homeostasis, which is an important step toward employing microbiome-driven therapeutic approaches for IBD clinical management.IMPORTANCEThe contribution of the gut microbiome to the balance between homeostasis and inflammation is widely known. Nevertheless, the etiology of inflammatory bowel disease, which is known to be influenced by genetics, immune response, and environmental cues, remains unclear. Unlocking novel players involved in the dictation of a protective gut, namely, in the microbiota component, is therefore crucial to develop novel strategies to tackle IBD. Herein, we revealed a synergistic interaction between two commensal bacterial strains, Akkermansia muciniphila and Parabacteroides distasonis, which induce protection against both acute and chronic models of colitis induction, by enhancing epithelial barrier integrity and promoting group 3 innate lymphoid cells in the colonic mucosa. This study provides a novel insight on how commensal bacteria can beneficially act to promote intestinal homeostasis, which may open new avenues toward the use of microbiome-derived strategies to tackle IBD.

Background: Perioperative management of esophageal replacement is challenging due to significant disturbance in internal milieu of the body. To mitigate mediastinal dissection induced systemic inflammatory response, there is an unmet need to design and test a goal directed, resource conscious protocol for enhanced recovery, which will serve as a template to reduce morbid surgical complications and length of hospital stay. Methods: A retrospective cohort study was designed by convenience sampling method to group patients to compare outcomes of pediatric esophageal replacement using conventional protocol vs enhanced recovery after surgery novel protocol. Primary outcome measure was post-operative total length of stay in hospital. Secondary outcome measures were frequency of cardio-pulmonary complications, anastomotic leaks, infections, mortality, and initiation of early enteral jejunostomy feeding. Results: A total of 116 children with corrosive esophageal injury [n = 21(19%)] and esophageal atresia [n = 95(81 %)] were analyzed in this study. Novel protocol group(n = 62) when compared to conventional protocol group (n = 54) had lower mean total length of stay days (13.05 ± 7.92 days vs.21.96 ± 6.5 days p < 0.0001), shorter mean ICU days (5.74 ± 4.16 days vs 7.13 ± 3.16 days; p ≤ 0.048) and Novel protocol group had lower cardiac [3/62 (5 %) vs 12/54(22 %) p = 0.012]; and pulmonary [4/62 (6.5 %) vs 13/54(24 %) p = 0.007] complications. Novel protocol group had lower mean days to initiation of enteral feeding (3.13 ± 0.71 vs 5.45 ± 0.75 days; p < 0.0001) and lower rates of post-operative infections [5/62(8 %) vs 18/54 (33 %); p = 0.001]. Conclusions: Enhanced recovery after surgery novel protocol has the potential to change clinical practice due to mitigation of major complications.

Summary: To better understand the function of cholinergic projection neurons in the ventral pallidum (VP), we examined behavioral responses to appetitive (APP) and aversive (AV) odors that elicited approach or avoidance, respectively. Exposure to each odor increased cFos expression and calcium signaling in VP cholinergic neurons. Activity and Cre-dependent viral vectors selectively labeled VP cholinergic neurons that were activated and reactivated in response to either APP or AV odors, but not both, identifying two non-overlapping populations of VP cholinergic neurons differentially activated by the valence of olfactory stimuli. These two subpopulations showed differences in electrophysiological properties, morphology, and projections to the basolateral amygdala. Although VP neurons are engaged in both approach and avoidance behavioral responses, cholinergic signaling is only required for approach behavior. Thus, two distinct subpopulations of VP cholinergic neurons differentially encode valence of olfactory stimuli and play distinct roles in approach and avoidance behaviors.

Abstract Background The purpose of this study is to provide a systematic review of the literature pertaining to Patient-Reported Outcome Measurement Information System (PROMIS) validation and utilization as an outcomes metric in total knee arthroplasty (TKA) patients. This is the first systematic review on PROMIS use in total knee arthroplasty patients. Methods A systematic search of the Pubmed/MEDLINE and Embase databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study characteristics, patient demographics, psychometric properties (Pearson and Spearman correlation) with legacy patient-reported outcome measurement (PROM) instruments, floor and ceiling effects, responsiveness, and minimum clinically important difference (MCID) and PROMIS outcomes were recorded and analyzed. Results Fifteen studies investigating PROMIS in 11,140 patients were included. The weighted-average Pearson correlation coefficient comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.62 [standard error (SE) = 0.06] and the weighted-average Spearman correlation comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.59 (SE = 0.06), demonstrating moderate-to-strong correlation and validity. There were no differences in weighted average floor [0.03% (SE = 3.1) versus 0% (SE = 0.1) versus 0.01% (SE = 1.1); p = 0.25] or ceiling effects [0.01% (SE = 0.7) versus 0.02% (SE = 1.4) versus 0.04% (SE = 3.5); p = 0.36] between PROMIS and legacy instruments. The weighted average for percentage of patients achieving MCID was 59.1% for global physical health (GPH), 26.0% for global mental health (GMH), 52.7% for physical function (PF), 67.2% for pain interference (PI), and 37.2% for depression. Conclusion Notably, PROMIS global physical health, physical function, and pain interference were found to be significantly responsive, with PROMIS pain interference most effectively capturing clinical improvement as evidenced by the achievement of MCID.

Objective: To evaluate the impact of age and COVID-19 variant time period on morbidity and mortality among those hospitalized with COVID-19. Patients and Methods: Patients from the American Heart Association’s Get With The Guidelines COVID-19 cardiovascular disease registry (January 20, 2020-February 14, 2022) were divided into groups based on whether they presented during periods of wild type/alpha, delta, or omicron predominance. They were further subdivided by age (young: 18-40 years; older: more than 40 years), and characteristics and outcomes were compared. Results: The cohort consisted of 45,421 hospitalized COVID-19 patients (wild type/alpha period: 41,426, delta period: 3349, and omicron period: 646). Among young patients (18-40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.6; 95% CI, 1.3-2.1), major adverse cardiovascular events (MACE) (OR, 1.8; 95% CI, 1.3-2.5), and in-hospital mortality (OR, 2.2; 95% CI, 1.5-3.3) when compared with presentation during wild type/alpha. Among older patients (more than 40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.2; 95% CI, 1.1-1.3), MACE (OR, 1.5; 95% CI, 1.4-1.7), and in-hospital mortality (OR, 1.4; 95% CI, 1.3-1.6) when compared with wild type/alpha. Among older patients (more than 40 years), presentation during omicron associated with decreased odds of severe COVID-19 (OR, 0.7; 95% CI, 0.5-0.9) and in-hospital mortality (OR, 0.6; 95% CI, 0.5-0.9) when compared with wild type/alpha. Conclusion: Among hospitalized adults with COVID-19, presentation during a time of delta predominance was associated with increased odds of severe COVID-19, MACE, and in-hospital mortality compared with presentation during wild type/alpha. Among older patients (aged more than 40 years), presentation during omicron was associated with decreased odds of severe COVID-19 and in-hospital mortality compared with wild type/alpha.

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes.

Introduction Despite international efforts, the number of individuals struggling with obesity is still increasing. An important aspect of obesity prevention relates to identifying individuals at risk at early stage, allowing for timely risk stratification and initiation of countermeasures. However, obesity is complex and multifactorial by nature, and one isolated (bio)marker is unlikely to enable an optimal risk stratification and prognosis for the individual; rather, a combined set is required. Such a multicomponent interpretation would integrate biomarkers from various domains, such as classical markers (eg, anthropometrics, blood lipids), multiomics (eg, genetics, proteomics, metabolomics), lifestyle and behavioural attributes (eg, diet, physical activity, sleep patterns), psychological traits (mental health status such as depression) and additional host factors (eg, gut microbiota diversity), also by means of advanced interpretation tools such as machine learning. In this paper, we will present a protocol that will be employed for a scoping review that attempts to summarise and map the state-of-the-art in the area of multicomponent (bio)markers related to obesity, focusing on the usability and effectiveness of such biomarkers.Methods and analysis PubMed, Scopus, CINAHL and Embase databases will be searched using predefined key terms to identify peer-reviewed articles published in English until January 2024. Once downloaded into EndNote for deduplication, CADIMA will be employed to review and select abstracts and full-text articles in a two-step procedure, by two independent reviewers. Data extraction will then be carried out by several independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Peer Review of Electronic Search Strategies guidelines will be followed. Combinations employing at least two biomarkers from different domains will be mapped and discussed.Ethics and dissemination Ethical approval is not required; data will rely on published articles. Findings will be published open access in an international peer-reviewed journal. This review will allow guiding future directions for research and public health strategies on obesity prevention, paving the way towards multicomponent interventions.

Background The sodium glucose cotransporter‐2 inhibitors are guideline‐recommended to treat heart failure across the spectrum of left ventricular ejection fraction; however, economic evaluations of adding sodium glucose cotransporter‐2 inhibitors to standard of care in chronic heart failure across a broad left ventricular ejection fraction range are lacking. Methods and Results We conducted a US‐based cost‐effectiveness analysis of dapagliflozin added to standard of care in a chronic heart failure population using pooled, participant data from the DAPA‐HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. The 3‐state Markov model used estimates of transitional probabilities, effectiveness of dapagliflozin, and utilities from the pooled trials. Costs estimates were obtained from published sources, including published rebates in dapagliflozin cost. Adding dapagliflozin to standard of care was estimated to produce an additional 0.53 quality‐adjusted life years (QALYs) compared with standard of care alone. Incremental cost effectiveness ratios were $85 554/QALY when using the publicly reported full (undiscounted) Medicare cost ($515/month) and $40 081/QALY, at a published nearly 50% rebate ($263/month). The addition of dapagliflozin to standard of care would be of at least intermediate value (

Neurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA). Using a genetically encoded acetylcholine (ACh) sensor in mice, we demonstrate that BLA-projecting cholinergic neurons can ‘learn’ the association between a naive tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24 hr later (recall). In the NBM/SIp cholinergic neurons express the immediate early gene, Fos following both training and memory recall. Cholinergic neurons that express Fos following memory recall display increased intrinsic excitability. Chemogenetic silencing of these learning-activated cholinergic neurons prevents expression of the defensive behavior to the tone. In contrast, we show that NBM/SIp cholinergic neurons are not activated by an innately threatening stimulus (predator odor). Instead, VP/SIa cholinergic neurons are activated and contribute to defensive behaviors in response to predator odor, an innately threatening stimulus. Taken together, we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli, demonstrating functionally refined organization of specific types of memory within the cholinergic basal forebrain of mice.

Objective: To assess the perceptions and intentions of pregnant women regarding COVID-19 vaccination and to explore the reasons for vaccine hesitancy as well as acceptance. Methods: This prospective cross-sectional study was conducted in tertiary care hospital in Karnataka. Around 811 pregnant women attending the antenatal clinic were recruited into the study. Data were collected using a face-to-face, anonymous questionnaire written in local language. Results: Eighty six point two percent participants were aged 20 to 30 years and 64.6% had completed their schooling. 94.3% of them were homemakers and 58 % of the participants were in their third trimester. 65.5% of study group members lived in a COVID-supportive environment. Participants with COVID-19 vaccination awareness accounted for 87.4% and 65.4% were willing to receive the same whole heartedly. Our study found that 65.4% of participants were willing to receive covid-19 vaccine. The reasons for refusal were Lack of sufficient information regarding the vaccine, may be harmful to foetus and mother and lack of data proving its quality and efficiency. Conclusion: Pregnant women in the North Karnataka region were highly receptive to COVID-19 immunization. Although a high level of awareness was apparent, the lack of data and fear of side effects were two major concerns for refusal. Confidence in the government and the availability of free vaccines for all have demonstrated a massive impact on vaccination. Keywords: antenatal, covid-19, pregnancy, vaccination. Abstrak Tujuan: Menilai persepsi dan keinginan perempuan hamil terkait vaksin COVID-19 dan alasan terkait penerimaan dan juga keraguan terhadap vaksin. Metode: Penelitian ini merupakan penelitian potong lintang dengan pendekatan prospektif yang dilakukan di Rumah Sakit Karnataka. Perempuan hamil sebanyak 811 menjadi subjek penelitian. Data dikumpulkan menggunakan kuesioner yang dituliskan dalam Bahasa lokal dan pengumpulan data dilakukan secara tatap muka. Hasil: Sebanyak 86,2 % sampel penelitian berusia 20 hingga 30 tahun dan 64,6% telah lulus sekolah. Sebanyak 94,3% sampel adalah ibu rumah tangga dan 58% dari sampel dengan usia kehamilan pada trimester ketiga. Sebanyak 65,5% grup tinggal pada kondisi. Sebanyak 87,4% sampel sadar akan keutamaan vaksin dan 65,4% bersedia mendapatkan vaksin. Alasan penolakan terhadap vaksin adalah kurangnya pengetahun mengenai vaksin dan ketakutan akan efek sampingnya. Kesimpulan: Perempuan hamil di Karnatakan Utara terbuka terhadap imunisasi COVID-19. Disamping tingginya angka kesadaran akan imunisasi COVID-19, penolakan umumnya didominasi akibat kurangnya pengetahuan dan ketakutan akan efek samping. Keyakinan pada pemerintah dan ketersediaan vaksin secara gratis sangat berpengaruh pada vaksinasi. Kata kunci: antenatal. covid-19, kehamilan, vaksinasi.

Abstract Aims Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin–angiotensin–aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non‐absorbed intestinal potassium binder proven to lower serum potassium concentrations. Methods and results PRIORITIZE‐HF was an international, multicentre, parallel‐group, randomized, double‐blind, placebo‐controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID‐19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. Conclusions PRIORITIZE‐HF was terminated prematurely due to COVID‐19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium‐reducing agent SZC compared with placebo.

Background Frailty is common among patients with advanced heart failure (HF), and screening for frailty to guide care is recommended. Although multiple tools are available to screen for frailty, the feasibility of routinely incorporating frailty screening into daily clinical practice among hospitalised advanced HF patients has not been rigorously tested.Methods This was a prospective, single-centre, quality improvement study. Two brief frailty screening tools were incorporated into palliative care consultations for all patients ≥50 years from August 2021 to October 2022. In the first phase, the Clinical Frailty Scale (CFS) was implemented, followed by the Study of Osteoporotic Fracture (SOF) tool or a modified SOF (mSOF) version in the second phase. The primary outcome was feasibility (%) of performing frailty screenings for this high-risk population.Results A total of 212 patients (mean age 69±10 years, 69% male, 79% white, 30% with ischaemic HF) were referred for palliative care consultation during the study period. Overall, frailty screens were completed in 86% (n=183) of patients. CFS and mSOF reached >80% of adoption, while SOF adoption was 54%. Altogether, 52% of the population screened frail by use of CFS and 52% also by mSOF. All clinicians (n=6) participating in the study reported that frailty screening tools were useful and acceptable, and 83% reported plans for continued utilisation in future clinical practice.Conclusions Frailty screening with CFS or mSOF tools was feasible in hospitalised patients with advanced HF. Tools that require physical assessment were more challenging to implement. These data support the feasibility of incorporating questionnaire-based frailty screening in a busy hospital setting.

We present a joint cosmic shear analysis of the Dark Energy Survey (DES Y3) and the Kilo-Degree Survey (KiDS-1000) in a collaborative effort between the two survey teams. We find consistent cosmological parameter constraints between DES Y3 and KiDS-1000 which, when combined in a joint-survey analysis, constrain the parameter $S_8 = \sigma_8 \sqrt{\Omega_{\rm m}/0.3}$ with a mean value of $0.790^{+0.018}_{-0.014}$. The mean marginal is lower than the maximum a posteriori estimate, $S_8=0.801$, owing to skewness in the marginal distribution and projection effects in the multi-dimensional parameter space. Our results are consistent with $S_8$ constraints from observations of the cosmic microwave background by Planck, with agreement at the $1.7\sigma$ level. We use a Hybrid analysis pipeline, defined from a mock survey study quantifying the impact of the different analysis choices originally adopted by each survey team. We review intrinsic alignment models, baryon feedback mitigation strategies, priors, samplers and models of the non-linear matter power spectrum. Supplementary information: you can download the chains here or create your own chains with CosmoSIS here.

Drug induced cardiac arrhythmias are seen commonly in clinical practice. Amongst drugs, antibiotics have a specific predisposition, and amongst them, macrolides and fluoroquinolones are specifically seen to have such a tendency. However, amongst fluoroquinolones, the rate of incidence of quinolone induced cardiac arrhythmia is reported as 5.4 cases per 10 million prescriptions. Here, we report a rare case of a probable Adverse Drug Reaction (ADR) i.e., Left Ventricular inferoposterior surface bigeminy recorded 24 hours after initiation of levofloxacin which disappeared after 24 hours of its discontinuation.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin commonly occurring in pleura. It can occur at many extrapleural sites but is rare in orbit. Most cases are benign and recurrence is not unusual in the head and neck and orbit and is usually due to incomplete surgical excision. However, malignant transformation (MT) in orbital SFT is extremely unusual. We present a case of orbital SFT in adult male who developed recurrence with MT eight years after initial surgical excision. He underwent left orbital exenteration. The recurrent tumor revealed features of malignancy with areas exhibiting morphology typical of SFT. The immunochemistry confirmed the diagnosis of SFT with MT. The patient was given adjuvant radiation and was disease free for the last 18 months. Identification of malignancy in orbital SFT is important for the patient to receive appropriate postoperative treatment, as seen in the present case.

Metal corrosion is a significant and growing area of study in industrial problems, which has found productive research ground in the field of green chemistry. In the last 10 years, green chemistry has been highlighting the importance of safeguarding human as well as the environmental well-being, in an economically advantageous way aiming at keeping away from reducing waste hazardous toxins, and pollutants. The era of metal degradation, commonly faced due to the usage of hazardous chemicals became very relevant and useful in the research area of chemistry. Even though several experiments have been conducted and, several research articles were published on this topic of nature-friendly green and clean inhibitors still there are yet a lot of things to be explored in this field for sustainable eco-friendly existence of human and natural interconnected existence. The main aim of the study is to provide a summary and describe the past authentic research that accounted in the research literature to employ eco-friendly corrosion inhibitors, especially extraction from leaves, stems, seeds, and fruits of the plants for aluminum alloy in acid solutions in the past decade. Weight loss and electrochemical approaches are among the most often utilized methods to measure corrosion rate and to evaluate the effectiveness of green corrosion inhibitors. The relevance of the area prompted the further study, leading to a large number of substances being evaluated.

Abstract Patient reported outcome measures (PROMs) are essential for clinical research and patient-centric care because they allow us to capture patient perspectives on their health condition. In knee arthroplasty, PROMs are frequently used to assess the risks and benefits of new interventions, surgical approaches, and other management strategies. A few examples of PROMs used in total knee arthroplasty (TKA) include the Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Forgotten Joint Score (FJS) (collectively referred to as “legacy” PROMs). More recently, attention has been brought to another PROM called the Patient-Reported Outcomes Measurement Information System (PROMIS). PROMIS was developed by the National Institute of Health (NIH) and has over 300 domains assessing various aspects of patient health, including pain, physical function, and mental health. With the use of PROMIS increasing in TKA literature, there is a need to review the advancements being made in understanding and applying PROMIS for this population. Thus, the purpose of this study is to provide insight on the utilization, advantages, and disadvantages of PROMIS within the field of knee arthroplasty and to provide a comparison to legacy PROMs.

This research underscores the profound impact of data cleansing, ensuring dataset integrity and providing a structured foundation for unraveling convoluted connections between diverse physical properties and cytotoxicity. As the scientific community delves deeper into this interplay, it becomes clear that precise data purification is a fundamental aspect of investigating parameters within datasets. The study presents the need for data filtration in the background of machine learning (ML) that has widened its horizon into the field of biological application through the amalgamation of predictive systems and algorithms that delve into the intricate characteristics of cytotoxicity of nanoparticles. The reliability and accuracy of models in the ML landscape hinge on the quality of input data, making data cleansing a critical component of the pre-processing pipeline. The main encounter faced here is the lengthy, broad and complex datasets that have to be toned down for further studies. Through a thorough data cleansing process, this study addresses the complexities arising from diverse sources, resulting in a refined dataset. The filtration process employs K-means clustering to derive centroids, revealing the correlation between the physical properties of nanoparticles, viz, concentration, zeta potential, hydrodynamic diameter, morphology, and absorbance wavelength, and cytotoxicity outcomes measured in terms of cell viability. The cell lines considered for determining the centroid values that predicts the cytotoxicity of silver nanoparticles are human and animal cell lines which were categorized as normal and carcinoma type. The objective of the study is to simplify the high-dimensional data for accurate analysis of the parameters that affect the cytotoxicity of silver NPs through centroids.

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1 σ . The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we “extended” each PTA’s data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA’s Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA.

We address the problem of optimally identifying all kilonovae detected via gravitational-wave emission in the upcoming LIGO/Virgo/KAGRA observing run, O4, which is expected to be sensitive to a factor of ∼7 more binary neutron star (BNS) alerts than previously. Electromagnetic follow-up of all but the brightest of these new events will require >1 m telescopes, for which limited time is available. We present an optimized observing strategy for the DECam during O4. We base our study on simulations of gravitational-wave events expected for O4 and wide-prior kilonova simulations. We derive the detectabilities of events for realistic observing conditions. We optimize our strategy for confirming a kilonova while minimizing telescope time. For a wide range of kilonova parameters, corresponding to a fainter kilonova compared to GW170817/AT 2017gfo, we find that, with this optimal strategy, the discovery probability for electromagnetic counterparts with the DECam is ∼80% at the nominal BNS gravitational-wave detection limit for O4 (190 Mpc), which corresponds to an ∼30% improvement compared to the strategy adopted during the previous observing run. For more distant events (∼330 Mpc), we reach an ∼60% probability of detection, a factor of ∼2 increase. For a brighter kilonova model dominated by the blue component that reproduces the observations of GW170817/AT 2017gfo, we find that we can reach ∼90% probability of detection out to 330 Mpc, representing an increase of ∼20%, while also reducing the total telescope time required to follow up events by ∼20%.

Abstract In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance toward commensals, yet the influence of maternal diet and microbial composition on offspring immune maturation remains poorly understood. We colonized germ‐free mice with a consortium of 14 strains, fed them a standard fiber‐rich chow or a fiber‐free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber‐rich diet, pups of fiber‐deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin‐foraging bacterium that can also use milk oligosaccharides. The pups of fiber‐deprived dams exhibited an enrichment of colonic transcripts corresponding to defense response pathways and a peak in Il22 expression at weaning. Removal of A. muciniphila from the community, but maintenance on the fiber‐rich diet, was associated with reduced proportions of RORγt‐positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune development.

A high yielding mid-late duration culture DPLN 2 was developed at the Department of Agriculture Botany, College of Agriculture, Dapoli and released as Dapoli 3 during 2020 at the state level and notified by the ministry of Agriculture and farmer welfare, Department of Agriculture and farmer welfare with notification number CG-DL-E-04012022- 232406 extraordinary part-II-section 3-subsection (ii) dated 24th Dec. 2021. Dapoli 3 has developed through pure line selection from local germplasm. Out of twenty one culture, the culture DPLN 2 was found promising in respect of yield over check Dapoli 1, Dapoli 2 and PR 202 in station, multilocation and adaptive research trials. It yields an average of 2405 kg/ha of grain under rainfed conditions. Besides high yield culture has semi compact earhead, uniform maturity, non-lodging, continuous spikelets, non-shattering with moderate protein (7.52 %) and calcium (264 ppm) content. The weight of earhead of culture is 8.9 g as compared to 7.2 g of Dapoli 1. The culture recorded a grain yield of 2405 kg/ ha which was 26.64 per cent increase over the check Dapoli 1 (1899 kg/ha) in station trails. It recorded a grain yield of 2014 kg/ha which was 13.78 per cent increase over the check Dapoli 1 (1770 kg/ ha) in multilocation trials conducted during Kharif 2016 and 2017 at 13 locations whereas the mean grain yield recorded by culture DPLN 2 (was 1518 kg/ ha) which was 12.19 per cent increase over check Dapoli 1(1353 kg/ha) in adaptive research trial conducted in Konkan and Goa region during Kharif 2019. It has given the mean yield of 3228 kg/ha which was 5.76 per cent increase over the national check GPU 45 (3052 kg/ha) and 12.98 per cent increase over the VL 376 (2857 kg/ha) in all India coordinated trails tested during kharif, 2019.

Measurement(s) Magnetic Resonance Imaging Technology Type(s) Magnetic Resonance Imaging of the Brain with and without Contrast Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment brain Sample Characteristic - Location United States of America

CONTEXT:. Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant Staphylococcus aureus (MRSA), there is a paucity of published Gram-positive pediatric sepsis models. Large animal models replicating sepsis-induced coagulopathy are needed to test new therapeutics before human clinical trials. HYPOTHESIS:. Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours. METHODS AND MODELS:. Ten 3 weeks old piglets, implanted with telemetry devices for continuous hemodynamic monitoring, were IV injected with MRSA (n = 6) (USA300, Texas Children’s Hospital 1516 strain) at 1 × 109 colony forming units/kg or saline (n = 4). Fluid resuscitation was given for heart rate greater than 50% or mean arterial blood pressure less than 30% from baseline. Acetaminophen and dextrose were provided as indicated. Point-of-care complete blood count, prothrombin time (PT), activated thromboplastin time, d-dimer, fibrinogen, and specialized coagulation assays were performed at pre- and post-injection, at 0, 24, 48, 60, and 70 hours. Piglets were euthanized and necropsies performed. RESULTS:. Compared with the saline treated piglets (control), the septic piglets within 24 hours had significantly lower neurologic and respiratory scores. Over time, PT, d-dimer, and fibrinogen increased, while platelet counts and activities of factors V, VII, protein C, antithrombin, and a disintegrin and metalloproteinase with thrombospondin-1 motifs (13th member of the family) (ADAMTS-13) decreased significantly in septic piglets compared with control. Histopathologic examination showed minor focal organ injuries including microvascular thrombi and necrosis in the kidney and liver of septic piglets. INTERPRETATIONS AND CONCLUSIONS:. We established a 70-hour swine model of MRSA sepsis-induced coagulopathy with signs of consumptive coagulopathy, disseminated microvascular thrombosis, and early organ injuries with histological minor focal organ injuries. This model is clinically relevant to pediatric sepsis and can be used to study dysregulated host immune response and coagulopathy to infection, identify potential early biomarkers, and to test new therapeutics.

In the industry, ball bearings are the most widely used machine element. The ball materials may differ in various bearing applications. Wear of the ball and recess after a period of use is the most common cause of ball bearing failure. The present study aims to develop the artificial neural network model for assessing the wear of different ball bearing materials. A wear test method has been followed as suggested by the ASTM-G99 standard. The pin on disc apparatus was selected to conduct numerous trials. L9 array was considered to design the experiments. The factors considered for this study were load, time, and sliding speed. Based on the results obtained, ANN code was proposed to evaluate wear using numerous test parameters. The results obtained from the proposed model are nearly similar to experimental results, which would be evidence for the correctness of the model. The proposed neural network model can be used in numerous applications with given parameters.

Abstract Multi-omic data, i.e., clinical measures, radiomic, and genetic data, capture multi-faceted tumor characteristics, contributing to a comprehensive patient risk assessment. Here, we investigate the additive value and independent reproducibility of integrated diagnostics in prediction of overall survival (OS) in isocitrate dehydrogenase (IDH)-wildtype GBM patients, by combining conventional and deep learning methods. Conventional radiomics and deep learning features were extracted from pre-operative multi-parametric MRI of 516 GBM patients. Support vector machine (SVM) classifiers were trained on the radiomic features in the discovery cohort (n = 404) to categorize patient groups of high-risk (OS

Dog vaccination is an effective rabies prevention measure, but widespread vaccination campaigns are challenging in settings like India with large free-roaming dog populations. Here, the authors describe a One Health campaign in Goa state which led to a large reduction of cases in dogs and elimination in humans.

Abstract Purpose Robotic‐assisted total knee arthroplasty typically necessitates use of tracking pins, which can vary in diameter. Complications such as infections and fractures at the pin‐site have been observed, but clarification of the effect of pin diameter on complication is needed. The aim of this study is to compare the pin‐related complication rates following robotic‐assisted total knee arthroplasty between 4.5 mm and 3.2 mm diameter pins. Methods In this retrospective cohort study, 90‐day pin‐site complication rates after robotic‐assisted total knee arthroplasty were compared between 4.5 mm diameter and 3.2 mm diameter groups. In total, 367 patients were included: 177 with large pin diameter and 190 with small pin diameter. All four pin sites were evaluated using postoperative radiographs. Cases without orthogonal views or visualization of all four pin tracts were noted. Multivariate logistic regression was used to control for age, which differed between the two cohorts. Results The rate of pin‐site complications was 5.6% in the large pin diameter cohort and 2.6% in the small pin diameter cohort, with no statistically significant difference between the groups. The adjusted odds ratio for complications in small compared to large diameter group was 0.48, with a p‐value of 0.18. The most common pin‐site complication was infection/persistent drainage, found in 1.9% of patients, followed by intraoperative fracture of the second cortex in 1.4%. Intraoperative fracture could not be ruled out in 96 cases due to inadequate radiographic visualization of all pin sites. There was one postoperative pin‐site fracture in the large diameter cohort, which required operative fixation. Conclusion This study demonstrates no statistically significant difference in pin‐site complication rates after robotic‐assisted total knee arthroplasty between 4.5 mm and 3.2 mm pin diameter cohorts, although there was a trend towards increased intraoperative and postoperative pin‐site fractures in the 4.5 mm group.

Abstract Background Anatomic total shoulder arthroplasty is typically performed through the deltopectoral approach followed by either a subscapularis tenotomy, tendon peel, or lesser tuberosity osteotomy to provide adequate exposure. These subscapularis-takedown methods have been associated with incomplete subscapularis healing, however, and as a result often lead to functional deficits and complications. Subscapularis-sparing approaches have been introduced to mitigate these complications, but thus far have either been limited to hemiarthroplasty or resulted in residual inferior humeral head osteophytes and humeral component size mismatch. The present technique demonstrates the possibility for surgeons to capitalize on the improved patient outcomes that are afforded by subscapularis-sparing approaches, while still utilizing the deltopectoral interval to perform a total glenohumeral joint arthroplasty. Methods This article describes in detail the placement of a stemless anatomic TSA with the use of angled glenoid instruments through a subscapularis-sparing deltopectoral approach. Postoperatively, patients are placed in a sling but are instructed to remove as tolerated, as early as the 1st postoperative week. Physical therapy is started at week 1 with a 4-phase progression. Conclusions This technique using a TSA system with a polyaxial glenoid reamer and angled pegs on the backside of the glenoid allows the potential for maintenance of the strong postoperative radiographic and patient-reported outcomes that are achieved using traditional TSA approaches, with the advantage of accelerated rehabilitation protocols and decreased risk of subscapularis insufficiency that result from the use of subscapularis-sparing approaches.

The present investigation was undertaken to assess genetic diversity in seventy genotypes of kodo millet. The analysis of variance revealed the presence of significant variation among the genotypes for all 13 characters. Higher genotypic coefficient of variation (GCV), phenotypic coefficient of variation (PCV), heritability and genetic advance as per cent mean were recorded for thumb raceme length, number of productive tillers per plant, length of panicle, raceme length and grain yield per plant, indicating that simple selection could be practised for improving these traits. Seventy genotypes were grouped into seven different clusters on the basis of magnitude of D2 values by Mahalanobis D2 analysis. Cluster I had 51 genotypes followed by cluster II with 14 genotypes, while clusters III, IV, V, VI and VII were mono genotypic. The inter–cluster distance was high between clusters II and III and therefore it is suggested to use these genotypes as parents for hybridization to evolve potential segregants.

Abstract Home health monitoring has the potential to improve outpatient management of chronic cardiopulmonary diseases such as heart failure. However, it is often limited by the need for adherence to self-measurement, charging and self-application of wearables, or usage of apps. Here, we describe a non-contact, adherence-independent sensor, that when placed beneath the legs of a patient’s home bed, longitudinally monitors total body weight, detailed respiratory signals, and ballistocardiograms for months, without requiring any active patient participation. Accompanying algorithms separate weight and respiratory signals when the bed is shared by a partner or a pet. Validation studies demonstrate quantitative equivalence to commercial sensors during overnight sleep studies. The feasibility of detecting obstructive and central apneas, cardiopulmonary coupling, and the hemodynamic consequences of non-sustained ventricular tachycardia is also established. Real-world durability is demonstrated by 3 months of in-home monitoring in an example patient with heart failure and ischemic cardiomyopathy as he recovers from coronary artery bypass grafting surgery. BedScales is the first sensor to measure adherence-independent total body weight as well as longitudinal cardiopulmonary physiology. As such, it has the potential to create a multidimensional picture of chronic disease, learn signatures of impending hospitalization, and enable optimization of care in the home.

Chromosomal translocations are considered as one of the major causes of lymphoid cancers. RAG complex, which is responsible for V(D)J recombination, can also cleave non-B DNA structures and cryptic RSSs in the genome leading to chromosomal translocations. The mechanism and factors regulating the illegitimate function of RAGs resulting in oncogenesis are largely unknown. Upon in silico analysis of 3760 chromosomal translocations from lymphoid cancer patients, we find that 93% of the translocation breakpoints possess adjacent cryptic nonamers (RAG binding sequences), of which 77% had CpGs in proximity. As a proof of principle, we show that RAGs can efficiently bind to cryptic nonamers present at multiple fragile regions and cleave at adjacent mismatches generated to mimic the deamination of CpGs. ChIP studies reveal that RAGs can indeed recognize these fragile sites on a chromatin context inside the cell. Finally, we show that AID, the cytidine deaminase, plays a significant role during the generation of mismatches at CpGs and reconstitute the process of RAG-dependent generation of DNA breaks both in vitro and inside the cells. Thus, we propose a novel mechanism for generation of chromosomal translocation, where RAGs bind to the cryptic nonamer sequences and direct cleavage at adjacent mismatch generated due to deamination of meCpGs or cytosines.

Background Mammography has been established as the key modality in the detection and diagnosis of breast cancers. Digital breast tomosynthesis (DBT) has emerged as a mammographic technique which allows improved visualization of abnormalities by reducing the effect of overlapping breast tissue. Purpose This article is a pictorial essay which highlights the advantages of DBT with two-dimensional (2D) synthesized mammography (2DSM) images, its clinical applications, and its role in breast imaging. Materials and Methods Selenia Dimensions HD mammography machine performs DBT which acquires a series of low-dose digital mammographic images of the compressed breast followed by full-field digital mammography. Software using specialized algorithms helps to create a 2DSM image reconstructed from the DBT data set. The images are interpreted on a dedicated work station on high-resolution monitors by the radiologist. American College of Radiology Breast Imaging-Reporting and Data System (BI-RADS) lexicon is used for reporting. High-resolution breast ultrasound which includes evaluation of the axilla is done for all cases. Conclusion DBT improves detection and better characterization of lesions which thereby increases confidence of interpretation of mammograms and assigning BI-RADS categories for further management.

Background Lobular carcinoma in situ (LCIS) is a noninvasive neoplasm that is known to have an increased relative risk for developing subsequent invasive breast carcinoma. Pure LCIS is usually an incidental finding on histopathological examination (HPE) of tissue samples. However, in the recent years, there has been an increasing trend seen in the diagnosis of LCIS. Purpose This article aims to bring out the spectrum of appearances on breast imaging in confirmed cases of pure LCIS on HPE and immunohistochemical. Materials and Methods Cases that were confirmed as pure LCIS on HPE from core or excision biopsy were retrospectively analyzed for abnormalities on breast imaging. Digital breast tomosynthesis mammography was performed with high-resolution ultrasound with elastography for all cases. Magnetic resonance imaging (MRI) was performed in cases wherever indicated, with dynamic postcontrast imaging after injecting intravenous gadolinium. Conclusion LCIS is recognized as an intermediate risk factor for the development of breast cancer. Pure LCIS has varied histology and imaging patterns on mammography, high-resolution ultrasound, and MRI. It is important to recognize the imaging appearances of these lesions to enable the radiologist to detect LCIS early for proper management.

Abstract Glioblastoma (GBM) has high metabolic demands, which can lead to acidification of the tumor microenvironment. We hypothesize that a machine learning model built on temporal principal component analysis (PCA) of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI can be used to estimate tumor acidity in GBM, as estimated by pH-sensitive amine chemical exchange saturation transfer echo-planar imaging (CEST-EPI). We analyzed 78 MRI scans in 32 treatment naïve and post-treatment GBM patients. All patients were imaged with DSC-MRI, and pH-weighting that was quantified from CEST-EPI estimation of the magnetization transfer ratio asymmetry (MTRasym) at 3 ppm. Enhancing tumor (ET), non-enhancing core (NC), and peritumoral T2 hyperintensity (namely, edema, ED) were used to extract principal components (PCs) and to build support vector machines regression (SVR) models to predict MTRasym values using PCs. Our predicted map correlated with MTRasym values with Spearman’s r equal to 0.66, 0.47, 0.67, 0.71, in NC, ET, ED, and overall, respectively (p