Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting self-intercepted medication ordering errors using machine learning

Current approaches to understanding medication ordering errors rely on relatively small manually captured error samples. These approaches are resource-intensive, do not scale for computerized provider order entry (CPOE) systems, and are likely to miss important risk factors associated with medication ordering errors. Previously, we described a dataset of CPOE-based medication voiding accompanied by univariable and multivariable regression analyses. However, these traditional techniques require expert guidance and may perform poorly compared to newer approaches. In this paper, we update that analysis using machine learning (ML) models to predict erroneous medication orders and identify its contributing factors. We retrieved patient demographics (race/ethnicity, sex, age), clinician characteristics, type of medication order (inpatient, prescription, home medication by history), and order content. We compared logistic regression, random forest, boosted decision trees, and artificial neural network models. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). The dataset included 5,804,192 medication orders, of which 28,695 (0.5%) were voided. ML correctly classified voids at reasonable accuracy; with a positive predictive value of 10%, ~20% of errors were included. Gradient boosted decision trees achieved the highest AUROC (0.7968) and AUPRC (0.0647) among all models. Logistic regression had the poorest performance. Models identified predictive factors with high face validity (e.g., student orders), and a decision tree revealed interacting contexts with high rates of errors not identified by previous regression models. Prediction models using order-entry information offers promise for error surveillance, patient safety improvements, and targeted clinical review. The improved performance of models with complex interactions points to the importance of contextual medication ordering information for understanding contributors to medication errors.
Sarcopenia is associated with 3-month and 1-year mortality in geriatric rehabilitation inpatients: RESORT

Abstract Background Sarcopenia is highly prevalent in geriatric rehabilitation patients and can worsen prognosis. This study aimed to investigate the association of sarcopenia and components of sarcopenia with 3-month and 1-year post-discharge mortality in geriatric rehabilitation inpatients. Methods REStORing health of acutely unwell adulTs (RESORT) is an observational, prospective longitudinal cohort of geriatric rehabilitation inpatients. Sex-stratified Cox proportional-hazards analyses were used to associate sarcopenia (and its components) at admission, by the European Working Group on Sarcopenia in Older People (EWGSOP, EWGSOP2) and the Asian Working Group for Sarcopenia 2019 (AWGS 2019), with 3-month and 1-year post-discharge all-cause mortality. Results Patients (n = 1,406) had a median interquartile ranges [IQR] age of 83.0 [77.4–88.2] years (58% females). Sarcopenia was significantly associated with 3-month and 1-year mortality in females (EWGSOP, EWGSOP2 and AWGS 2019) and males (EWGSOP2, AWGS 2019). In females, low muscle mass (EWGSOP, EWGSOP2 and AWGS 2019) was significantly associated with 3-month and 1-year mortality; low muscle strength (EWGSOP, EWGSOP2 and AWGS 2019) was significantly associated with 1-year mortality. For males, low muscle mass (EWGSOP2, AWGS 2019) was significantly associated with 3-month and 1-year mortality; low muscle strength (EWGSOP2, AWGS 2019) was significantly associated with 3-month mortality. The association between physical performance with mortality was not analysed due to less than five events (death) in patients with normal physical performance. Conclusions Sarcopenia, low muscle mass and low muscle strength at admission are associated with a significantly higher risk of mortality post-discharge from geriatric rehabilitation, highlighting the need to measure muscle mass and strength in clinical practice.
Surgical Site Infection After Autologous Cranioplasty for Decompressive Craniectomy in Traumatic Brain Injury: A Retrospective Review of Two Level 1 Trauma Centers

Supplemental Digital Content is available in the text Object: Surgical site infection (SSI) after cranioplasty can result in unnecessary morbidity. This analysis was designed to determine the risk factors of SSI after cranioplasty in patients who received a decompressive craniectomy with the autologous bone for traumatic brain injury (TBI). Methods: A retrospective review was performed at two level 1 academic trauma centers for adult patients who underwent autologous cranioplasty after prior decompressive craniectomy for TBI. Demographic and procedural variables were collected and analyzed for associations with an increased incidence of surgical site infection with two-sample independent t tests and Mann Whitney U tests, and with a Bonferroni correction applied in cases of multiple comparisons. Statistical significance was reported with a P value of < 0.05. Results: A total of 71 patients were identified. The mean interval from craniectomy to cranioplasty was 99 days (7–283), and 3 patients developed SSIs after cranioplasty (4.2%). Postoperative drain placement (P > 0.08) and administration of intrawound vancomycin powder (P = 0.99) were not predictive of infection risk. However, a trend was observed suggesting that administration of prophylactic preoperative IV vancomycin is associated with a reduced infection rate. Conclusions: The SSI rate after autologous cranioplasty in TBI patients is lower than previously reported for heterogeneous groups and indications, and the infection risk is comparable to other elective neurosurgical procedures. As such, the authors recommend attempting to preserve native skull and perform autologous cranioplasty in this population whenever possible.
G-Protein-Gated Inwardly Rectifying Potassium (Kir3/GIRK) Channels Govern Synaptic Plasticity That Supports Hippocampal-Dependent Cognitive Functions in Male Mice

The G-protein-gated inwardly rectifying potassium (Kir3/GIRK) channel is the effector of many G-protein-coupled receptors (GPCRs). Its dysfunction has been linked to the pathophysiology of Down syndrome, Alzheimer's and Parkinson's diseases, psychiatric disorders, epilepsy, drug addiction, or alcoholism. In the hippocampus, GIRK channels decrease excitability of the cells and contribute to resting membrane potential and inhibitory neurotransmission. Here, to elucidate the role of GIRK channels activity in the maintenance of hippocampal-dependent cognitive functions, their involvement in controlling neuronal excitability at different levels of complexity was examined in C57BL/6 male mice. For that purpose, GIRK activity in the dorsal hippocampus CA3−CA1 synapse was pharmacologically modulated by two drugs: ML297, a GIRK channel opener, and Tertiapin-Q (TQ), a GIRK channel blocker. Ex vivo, using dorsal hippocampal slices, we studied the effect of pharmacological GIRK modulation on synaptic plasticity processes induced in CA1 by Schaffer collateral stimulation. In vivo, we performed acute intracerebroventricular (i.c.v.) injections of the two GIRK modulators to study their contribution to electrophysiological properties and synaptic plasticity of dorsal hippocampal CA3−CA1 synapse, and to learning and memory capabilities during hippocampal-dependent tasks. We found that pharmacological disruption of GIRK channel activity by i.c. v. injections, causing either function gain or function loss, induced learning and memory deficits by a mechanism involving neural excitability impairments and alterations in the induction and maintenance of long-term synaptic plasticity processes. These results support the contention that an accurate control of GIRK activity must take place in the hippocampus to sustain cognitive functions. SIGNIFICANCE STATEMENT Cognitive processes of learning and memory that rely on hippocampal synaptic plasticity processes are critically ruled by a finely tuned neural excitability. G-protein-gated inwardly rectifying K+ (GIRK) channels play a key role in maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Here, we demonstrate that modulation of GIRK channels activity, causing either function gain or function loss, transforms high-frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD), inducing deficits in hippocampal-dependent learning and memory. Together, our data show a crucial GIRK-activity-mediated mechanism that governs synaptic plasticity direction and modulates subsequent hippocampal-dependent cognitive functions.
Smoking and Incidence of Colorectal Cancer Subclassified by Tumor-Associated Macrophage Infiltrates.

BACKGROUND Biological evidence indicates that smoking can influence macrophage functions and polarization, thereby promoting tumor evolution. We hypothesized that the association of smoking with colorectal cancer incidence might differ by macrophage infiltrates. METHODS Utilizing the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of smoking with incidence of colorectal cancer subclassified by macrophage counts. Multiplexed immunofluorescence [for CD68, CD86, IRF5, MAF, and MRC1 (CD206)] combined with digital image analysis and machine learning was used to identify overall, M1-polarized, and M2-polarized macrophages in tumor. We used inverse-probability-weighted multivariable Cox proportional hazards regression models to control for potential confounders and selection bias due to tissue data availability. All statistical tests were 2-sided. RESULTS During follow-up of 131,144 participants (3,648,370 person-years), we documented 3,092 incident colorectal cancer cases including 871 cases with available macrophage data. The association of pack-years smoked with colorectal cancer incidence differed by stromal macrophage densities (Pheterogeneity=.003). Compared to never smoking, multivariable-adjusted hazard ratios (95% confidence interval) for tumors with low macrophage densities were 1.32 (0.97 to 1.79) for 1-19 pack-years, 1.31 (0.92 to 1.85) for 20-39 pack-years, and 1.74 (1.26 to 2.41) for ≥40 pack-years (Ptrend=.004). In contrast, pack-years smoked were not statistically significantly associated with the incidence of tumors having intermediate or high macrophage densities (Ptrend>.009, with the α level of 0.005). No statistically significant differential association was found for colorectal cancer subclassified by M1-like or M2-like macrophages. CONCLUSIONS The association of smoking with colorectal cancer incidence is stronger for tumors with lower stromal macrophage counts. Our findings suggest an interplay of smoking and macrophages in colorectal carcinogenesis.
Characterization of calcium-silicate-hydrate and calcium-alumino-silicate-hydrate

The primary objectives of this thesis were to synthesize calcium silicate hydrate (C-S-H) and calcium aluminosilicate hydrate (C-AS -H) and characterize their structures with varying Ca/Si ratios and aluminum content. As a secondary objective, carbonation behavior in synthesized C-S-H was studied. C-S-H was synthesized in the lab using two different methods: the double decomposition of calcium nitrate and sodium silicate solutions, and the direct reaction between calcium oxide and fumed silica in water. In C-AS -H the source of aluminum was sodium aluminate or aluminum nitrate. A variety of phases were present depending on the degree of carbonation of the were all observed throughout the course of study. X-ray diffraction (XRD) was the technique used to identify these phases. XRD was also used to explore the changes in crystal structure with varying Ca/Si ratios and aluminum content. No significant changes to the crystal structure were found. The effect of Ca/Si ratio, aluminum content, and synthesis method were studied on the molecular scale using 29 Si and 27 Al nuclear magnetic resonance spectroscopy (NMR). An increasing Ca/Si ratio has the effect of a shorter alumino-silicate chain length and an increase in aluminum content increases the alumino-silicate chain length. Aluminum substitution occurred primarily in the bridging tetrahedron position, but also in the pairing tetrahedron position. Aluminum uptake was also examined with respect with Ca/Si ratio and was found to decrease with increasing Ca/Si ratio. The changes in chemical environment of the iii aluminum ion with varying Ca/(Si+Al) ratios was also observed by 27 Al NMR. It was found that as the Ca/(Si+Al) ratio increased, the amount of chemical shielding of the 27 Al nuclei decreased. Carbonation of C-S-H was also examined and it was found that the double decomposition synthesis method allows for more rapid carbonation of the C-S-H. The source of increased carbonation rate is the high pH of the solutions. iv ACKNOWLEDGEMENTS I would like to first, and foremost, thank my advisor, Professor Leslie Struble, for her guidance and support throughout this research project. Her dedication to her research and students is unparalleled and I am grateful I had the opportunity to work with her. Considerable thanks go to Dr. Jennifer Rapp as well for her invaluable help with nuclear magnetic resonance spectroscopy. Without her constant support this project would not have been possible. Professor Paramita Mondal has also contributed through her helpful discussions and I look forward to my …
Taste receptors in aquatic mammals: Potential role of solitary chemosensory cells in immune responses

The sense of taste is associated with the evaluation of food and other environmental parameters such as salinity. In aquatic mammals, anatomic and behavioral evidence of the use of taste varies by species and genomic analysis of taste receptors indicates an overall reduction and, in some cases, complete loss of intact bitter and sweet taste receptors. However, the receptors used by taste buds in the oral cavity are found on cells in other areas of the body and play an important role in immune responses. In the respiratory tract, an example of such cells is solitary chemosensory cells (SCCs) which have bitter and sweet taste receptors. The bitter receptors detect chemicals given off by pathogens and initiate an innate immune response. Although many aquatic mammals may not have a role for taste in the assessment of food, they likely would benefit from the added protection that SCCs provide, especially considering respiratory diseases are a problem for many aquatic mammals. While evidence indicates that some species do not possess functional bitter receptors for taste, many do have intact bitter receptor genes and it is important for researchers to be aware of all roles for these receptors in homeostasis. Through a better understanding of the anatomy and physiology of aquatic mammal's respiratory systems, better treatment and management is possible.
Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1

PURPOSE CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1–specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti–programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma. PATIENTS AND METHODS Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed. RESULTS A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1–specific T cells (P = .01) and NY-ESO-1–specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02). CONCLUSION Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti–programmed death ligand-1 therapies merits further evaluation in other clinical contexts.
2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde

According to the updated International Myeloma Working Group criteria, smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by an M-component >3 g/dL, bone marrow plasma cell infiltration >10% and <60%, and absence of any myeloma-defining event. Active multiple myeloma is preceded by SMM, with a median time to progression of approximately 5 years. Cases of SMM range from the extremes of “monoclonal gammopathy of undetermined significance-like”, in which patients never progress during their lifetimes, to “early multiple myeloma”, in which transformation into symptomatic disease, based on genomic evolution, may be rapid and devastating. Such a “split personality” makes the prognosis and management of individual patients challenging, particularly with regard to the identification and possible early treatment of high-risk SMM. Outside of clinical trials, the conventional approach to SMM generally remains close observation until progression to active multiple myeloma. However, two prospective, randomized trials have recently demonstrated a significant clinical benefit in terms of time to progression, and of overall survival in one of the two studies, for some patients with higher-risk SMM treated with lenalidomide ± dexamethasone, raising the question of whether such an approach should be considered a new standard of care. In this paper, experts from the European Myeloma Network describe current biological and clinical knowledge on SMM, focusing on novel insights into its molecular pathogenesis, new prognostic scoring systems proposed to identify SMM patients at higher risk of early transformation, and updated results of completed or ongoing clinical trials. Finally, some practical recommendations for the real-life management of these patients, based on Delphi consensus methodology, are provided.
Investigation of multi-level safety culture in the Indian construction industry: a multi-level employees’ perception-based approach

Inadequate compliance with safety practices is a major hurdle in the construction industry, and a single-level source of input to assess safety culture is a major limitation of the literature. Therefore, this study aimed to capture multi-level employees’ (top management, middle management and workers) perceptions to assess multi-level safety culture (organizational level, project level and personnel level) in the construction industry. This study considered the Indian construction industry as the study area and used a questionnaire survey and interview technique as research instruments. In total, 184 responses were collected from multi-level employees. Data analysis was performed using a descriptive statistical method and hypothesis testing using the Mann–Whitney U test followed by the Kruskal–Wallis and post hoc tests. Findings highlighted inadequate safety compliances and significant (p < 0.05) perception differences among multi-level employees. Further, root cause analysis for observed perception differences was performed, and managerial implications were discussed from implementation perspectives.
The mechanism of gap creation by a multifunctional nuclease during base excision repair

ExoIII tightly anchors itself at the AP site, cuts the backbone, and processively digests the downstream DNA without dissociation. During base excision repair, a transient single-stranded DNA (ssDNA) gap is produced at the apurinic/apyrimidinic (AP) site. Exonuclease III, capable of performing both AP endonuclease and exonuclease activity, are responsible for gap creation in bacteria. We used single-molecule fluorescence resonance energy transfer to examine the mechanism of gap creation. We found an AP site anchor-based mechanism by which the intrinsically distributive enzyme binds strongly to the AP site and becomes a processive enzyme, rapidly creating a gap and an associated transient ssDNA loop. The gap size is determined by the rigidity of the ssDNA loop and the duplex stability of the DNA and is limited to a few nucleotides to maintain genomic stability. When the 3′ end is released from the AP endonuclease, polymerase I quickly initiates DNA synthesis and fills the gap. Our work provides previously unidentified insights into how a signal of DNA damage changes the enzymatic functions.
Safety and effectiveness of SARS‐CoV‐2 vaccines: A systematic review and meta‐analysis

Objective: To systematically evaluate the effectiveness and safety of the SARS‐CoV‐2 vaccines currently undergoing clinical trials. Methods: PubMed, EMBASE, and Cochrane Library databases were searched to collect open human COVID‐19 vaccines randomized controlled trials, without limiting the search time and language. The research papers collected in the above‐mentioned databases were initially screened according to the title and abstract content and merged, and the repeated ones were removed. After reading the full text of the remaining research, the studies that did not meet the inclusion criteria were excluded, and finally, nine studies were obtained. After extracting the statistical data of adverse events in the study, load them into Review Manager for heterogeneity analysis. Results: The incidence of adverse reactions of inactivated virus vaccines, RNA vaccines, and adenovirus vector vaccines was higher than that of placebo. Common adverse reactions included pain, swelling, and fever at the injection site. Conclusion: From the perspective of effectiveness, RNA vaccine > adenovirus vector vaccine > inactivated virus vaccine. From the perspective of safety, the incidence of adverse reactions of the three vaccines is higher than that of a placebo, and the incidence of adverse reactions of the adenovirus vector vaccine is higher.
High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder

Key Points Question Is high-dose (>12 mg) buprenorphine induction safe and well tolerated in patients with untreated opioid use disorder who present to the emergency department? Findings In this case series of 579 cases, 54 clinicians followed a high-dose buprenorphine (monoproduct) protocol. There were no documented episodes of respiratory depression or excessive sedation, and precipitated withdrawal was rare (0.8% of cases) and was not associated with dosing. Meaning These findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site, urban emergency department, was safe and well tolerated in patients with untreated opioid use disorder.