Miracle-dz/UniFAR-FTUs huggingface dataset:
Sepsis Among Medicare Beneficiaries: 1. The Burdens of Sepsis, 2012–2018*

Supplemental Digital Content is available in the text. Objectives: To provide contemporary estimates of the burdens (costs and mortality) associated with acute inpatient Medicare beneficiary admissions for sepsis. Design: Analysis of paid Medicare claims via the Centers for Medicare & Medicaid Services DataLink Project. Setting: All U.S. acute care hospitals, excluding federally operated hospitals (Veterans Administration and Defense Health Agency). Patients: All Medicare beneficiaries, 2012–2018, with an inpatient admission including one or more explicit sepsis codes. Interventions: None. Measurements and Main Results: Total inpatient hospital and skilled nursing facility admission counts, costs, and mortality over time. From calendar year (CY)2012–CY2018, the total number of Medicare Part A/B (fee-for-service) beneficiaries with an inpatient hospital admission associated with an explicit sepsis code rose from 811,644 to 1,136,889. The total cost of inpatient hospital admission including an explicit sepsis code for those beneficiaries in those calendar years rose from $17,792,657,303 to $22,439,794,212. The total cost of skilled nursing facility care in the 90 days subsequent to an inpatient hospital discharge that included an explicit sepsis code for Medicare Part A/B rose from $3,931,616,160 to $5,623,862,486 over that same interval. Precise costs are not available for Medicare Part C (Medicare Advantage) patients. Using available federal data sources, we estimated the aggregate cost of inpatient admissions and skilled nursing facility admissions for Medicare Advantage patients to have risen from $6.0 to $13.4 billion over the CY2012–CY2018 interval. Combining data for fee-for-service beneficiaries and estimates for Medicare Advantage beneficiaries, we estimate the total inpatient admission sepsis cost and any subsequent skilled nursing facility admission for all (fee-for-service and Medicare Advantage) Medicare patients to have risen from $27.7 to $41.5 billion. Contemporary 6-month mortality rates for Medicare fee-for-service beneficiaries with a sepsis inpatient admission remain high: for septic shock, approximately 60%; for severe sepsis, approximately 36%; for sepsis attributed to a specific organism, approximately 31%; and for unspecified sepsis, approximately 27%. Conclusion: Sepsis remains common, costly to treat, and presages significant mortality for Medicare beneficiaries.
Hydroacoustic System in a Biomimetic Underwater Vehicle to Avoid Collision with Vessels with Low-Speed Propellers in a Controlled Environment

In this paper, a hydroacoustic system designed for a biomimetic underwater vehicle (BUV) is presented. The Biomimetic Underwater Vehicle No. 2 (BUV2) is a next-generation BUV built within the ambit of SABUVIS, a European Defense Agency project (category B). Our main efforts were devoted to designing the system so that it will avoid collisions with vessels with low-speed propellers, e.g., submarines. Verification measurements were taken in a lake using a propeller-driven pontoon with a spectrum similar to that produced by a submarine propulsion system. Here, we describe the hydroacoustic signal used, with careful consideration of the filter and method of estimation for the bearings of the moving obstacle. Two algorithms for passive obstacle detection were used, and the results are discussed herein.
Sepsis Among Medicare Beneficiaries: 2. The Trajectories of Sepsis, 2012–2018*

Supplemental Digital Content is available in the text. Objectives: To distinguish characteristics of Medicare beneficiaries who will have an acute inpatient admission for sepsis from those who have an inpatient admission without sepsis, and to describe their further trajectories during and subsequent to those inpatient admissions. Design: Analysis of paid Medicare claims via the Centers for Medicare and Medicaid Services DataLink Project. Setting: All U.S. acute care hospitals, excepting federal hospitals (Veterans Administration and Defense Health Agency). Patients: Medicare beneficiaries, 2012–2018, with an inpatient hospital admission including one or more explicit sepsis codes. Interventions: None. Measurements and Main Results: Prevalent diagnoses in the year prior to the inpatient admission; healthcare contacts in the week prior to the inpatient admission; discharges, transfers, readmissions, and deaths (trajectories) for 6 months following discharge from the inpatient admission. Beneficiaries with no sepsis inpatient hospital admission for a year prior to an index hospital admission for sepsis were nearly indistinguishable by accumulated diagnostic codes from beneficiaries who had an index hospital admission without sepsis. Although the timing of healthcare services in the week prior to inpatient hospital admission was similar among beneficiaries who would be admitted for sepsis versus those whose inpatient admission did not include a sepsis code, the setting differed: beneficiaries destined for a sepsis admission were more likely to have received skilled nursing or unskilled nursing (e.g., nursing aide for activities of daily living) care. In contrast, comparing beneficiaries who had been free of any inpatient admission for an entire year and then required an inpatient admission, acute inpatient stays that included a sepsis code led to more than three times as many deaths within 1 week of discharge, with more admissions to skilled nursing facilities and fewer discharges to home. Comparing all beneficiaries who were admitted to a skilled nursing facility after an inpatient hospital admission, those who had sepsis coded during the index admission were more likely to die in the skilled nursing facility; more likely to be readmitted to an acute inpatient hospital and subsequently die in that setting; or if they survive to discharge from the skilled nursing facility, they are more likely to go next to a custodial nursing home. Conclusions: Although Medicare beneficiaries destined for an inpatient hospital admission with a sepsis code are nearly indistinguishable by other diagnostic codes from those whose admissions will not have a sepsis code, their healthcare trajectories following the admission are worse. This suggests that an inpatient stay that included a sepsis code not only identifies beneficiaries who were less resilient to infection but also signals increased risk for worsening health, for mortality, and for increased use of advanced healthcare services during and postdischarge along with an increased likelihood of an inpatient hospital readmission.
Radiomics in predicting mutation status for thyroid cancer: A preliminary study using radiomics features for predicting BRAFV600E mutations in papillary thyroid carcinoma

Purpose To evaluate whether if ultrasonography (US)-based radiomics enables prediction of the presence of BRAFV600E mutations among patients diagnosed as papillary thyroid carcninoma (PTC). Methods From December 2015 to May 2017, 527 patients who had been treated surgically for PTC were included (training: 387, validation: 140). All patients had BRAFV600E mutation analysis performed on surgical specimen. Feature extraction was performed using preoperative US images of the 527 patients (mean size of PTC: 16.4mm±7.9, range, 10–85 mm). A Radiomics Score was generated by using the least absolute shrinkage and selection operator (LASSO) regression model. Univariable/multivariable logistic regression analysis was performed to evaluate the factors including Radiomics Score in predicting BRAFV600E mutation. Subgroup analysis including conventional PTC <20-mm (n = 389) was performed (training: 280, validation: 109). Results Of the 527 patients diagnosed with PTC, 428 (81.2%) were positive and 99 (18.8%) were negative for BRAFV600E mutation. In both total 527 cancers and 389 conventional PTC<20-mm, Radiomics Score was the single factor showing significant association to the presence of BRAFV600E mutation on multivariable analysis (all P<0.05). C-statistics for the validation set in the total cancers and the conventional PTCs<20-mm were lower than that of the training set: 0.629 (95% CI: 0.516–0.742) to 0.718 (95% CI: 0.650–0.786), and 0.567 (95% CI: 0.434–0.699) to 0.729 (95% CI: 0.632–0.826), respectively. Conclusion Radiomics features extracted from US has limited value as a non-invasive biomarker for predicting the presence of BRAFV600E mutation status of PTC regardless of size.
The Bacillus Subtilis K-State Promotes Stationary-Phase Mutagenesis via Oxidative Damage

Bacterial cells develop mutations in the absence of cellular division through a process known as stationary-phase or stress-induced mutagenesis. This phenomenon has been studied in a few bacterial models, including Escherichia coli and Bacillus subtilis; however, the underlying mechanisms between these systems differ. For instance, RecA is not required for stationary-phase mutagenesis in B. subtilis like it is in E. coli. In B. subtilis, RecA is essential to the process of genetic transformation in the subpopulation of cells that become naturally competent in conditions of stress. Interestingly, the transcriptional regulator ComK, which controls the development of competence, does influence the accumulation of mutations in stationary phase in B. subtilis. Since recombination is not involved in this process even though ComK is, we investigated if the development of a subpopulation (K-cells) could be involved in stationary-phase mutagenesis. Using genetic knockout strains and a point-mutation reversion system, we investigated the effects of ComK, ComEA (a protein involved in DNA transport during transformation), and oxidative damage on stationary-phase mutagenesis. We found that stationary-phase revertants were more likely to have undergone the development of competence than the background of non-revertant cells, mutations accumulated independently of DNA uptake, and the presence of exogenous oxidants potentiated mutagenesis in K-cells. Therefore, the development of the K-state creates conditions favorable to an increase in the genetic diversity of the population not only through exogenous DNA uptake but also through stationary-phase mutagenesis.
NRF2 negatively regulates primary ciliogenesis and hedgehog signaling

Primary cilia are lost during cancer development, but the mechanism regulating cilia degeneration is not determined. While transcription factor nuclear factor-erythroid 2-like 2 (NRF2) protects cells from oxidative, proteotoxic, and metabolic stress in normal cells, hyperactivation of NRF2 is oncogenic, although the detailed molecular mechanisms by which uncontrolled NRF2 activation promotes cancer progression remain unclear. Here, we report that NRF2 suppresses hedgehog (Hh) signaling through Patched 1 (PTCH1) and primary ciliogenesis via p62/sequestosome 1 (SQSTM1). PTCH1, a negative regulator of Hh signaling, is an NRF2 target gene, and as such, hyperactivation of NRF2 impairs Hh signaling. NRF2 also suppresses primary cilia formation through p62-dependent inclusion body formation and blockage of Bardet–Biedl syndrome 4 (BBS4) entrance into cilia. Simultaneous ablation of PTCH1 and p62 completely abolishes NRF2-mediated inhibition of both primary ciliogenesis and Hh signaling. Our findings reveal a previously unidentified role of NRF2 in controlling a cellular organelle, the primary cilium, and its associated Hh signaling pathway and also uncover a mechanism by which NRF2 hyperactivation promotes tumor progression via primary cilia degeneration and aberrant Hh signaling. A better understanding of the crosstalk between NRF2 and primary cilia/Hh signaling could not only open new avenues for cancer therapeutic discovery but could also have significant implications regarding pathologies other than cancer, including developmental disorders, in which improper primary ciliogenesis and Hh signaling play a major role.
Primary blast wave protection in combat helmet design: A historical comparison between present day and World War I

Since World War I, helmets have been used to protect the head in warfare, designed primarily for protection against artillery shrapnel. More recently, helmet requirements have included ballistic and blunt trauma protection, but neurotrauma from primary blast has never been a key concern in helmet design. Only in recent years has the threat of direct blast wave impingement on the head–separate from penetrating trauma–been appreciated. This study compares the blast protective effect of historical (World War I) and current combat helmets, against each other and ‘no helmet’ or bare head, for realistic shock wave impingement on the helmet crown. Helmets included World War I variants from the United Kingdom/United States (Brodie), France (Adrian), Germany (Stahlhelm), and a current United States combat variant (Advanced Combat Helmet). Helmets were mounted on a dummy head and neck and aligned along the crown of the head with a cylindrical shock tube to simulate an overhead blast. Primary blast waves of different magnitudes were generated based on estimated blast conditions from historical shells. Peak reflected overpressure at the open end of the blast tube was compared to peak overpressure measured at several head locations. All helmets provided significant pressure attenuation compared to the no helmet case. The modern variant did not provide more pressure attenuation than the historical helmets, and some historical helmets performed better at certain measurement locations. The study demonstrates that both historical and current helmets have some primary blast protective capabilities, and that simple design features may improve these capabilities for future helmet systems.
Effect of γ-aminobutyric acid producing bacteria on in vitro rumen fermentation, growth performance, and meat quality of Hanwoo steers

Objective The present study aimed to evaluate the effects of γ-aminobutyric acid (GABA)-producing bacteria (GPB) on in vitro rumen fermentation and on the growth performance and meat quality of Hanwoo steers. Methods The effects of GPB (Lactobacillus brevis YM 3-30)-produced and commercially available GABA were investigated using in vitro rumen fermentation. Using soybean meal as a substrate, either GPB-produced or commercially available GABA were added to the in vitro rumen fermentation bottles, as follows: control, no additive; T1, 2 g/L GPB; T2, 5 g/L GPB; T3, 2 g/L autoclaved GPB; T4, 5 g/L autoclaved GPB; T5, 2 g/L GABA; and T6, 5 g/L GABA. In addition, 27 Hanwoo steers (602.06±10.13 kg) were subjected to a 129-day feeding trial, during which they were fed daily with a commercially available total mixed ration that was supplemented with different amounts of GPB-produced GABA (control, no additive; T1, 2 g/L GPB; T2, 5 g/L GPB). The degree of marbling was assessed using the nine-point beef marbling standard while endotoxin was analyzed using a Chromo-Limulus amebocyte lysate test. Results In regard to in vitro rumen fermentation, the addition of GPB-produced GABA failed to significantly affect pH or total gas production but did increase the ammonia nitrogen (NH3-N) concentration (p<0.05) and reduce total biogenic amines (p<0.05). Animals fed the GPB-produced GABA diet exhibited significantly lower levels of blood endotoxins than control animals and yielded comparable average daily gain, feed conversion ratio, and beef marbling scores. Conclusion The addition of GPB improved in vitro fermentation by reducing biogenic amine production and by increasing both antioxidant activity and NH3-N production. Moreover, it also reduced the blood endotoxin levels of Hanwoo steers.
Spondylodiscitis: experience of surgical management of complicated cases after failed antibiotic treatment

Introduction: The term Spondylodiscitis (SD) involves infection of the vertebra (Spondylitis), infection of the intervertebral disc (Discitis), or both (Spondylodiscitis). SD represents a diagnostic and therapeutic challenge to any spine surgeon. Any delay in its diagnosis or management may cause serious long-term morbidity or even lead to mortality. In this study, we report the experience of our Institution in the management of severe and complicated cases of SD. Methods: Over a period of 1 year, 39 patients with the diagnosis of SD were surgically treated in Assiut University Hospital, Assiut, Egypt. The management processes were tailored according to the clinical condition, radiological and lab studies of each case; and patients were then prospectively followed-up until they were cured (for a minimum of 6 months). The outcomes were analyzed, to be able to give recommendations while aiming to improve the overall outcome of such dangerous health issue. Results: In this series, patients were managed surgically by drainage and debridement of the infection site with/without instrumented fusion. Results included: satisfactory fusion was achieved in 97.3% of patients (confidence interval [CI] = 0.6856–1.3421). Neurological Improvement Rate (NIR) was 71.5% (Statistically significant improvement P-value = 0.014) and reoperation rate was 5% (CI = 0.00621–0.18525). Mortality rate was 7.7% (CI = 0.016–0.209). Several aspects were analyzed in each case. Conclusion: Surgical management of severe and complicated cases of SD allows for effective debridement and rapid cure of inflammation, earlier patient mobilization and significantly shorter duration of antibiotic usage.
Digital arterial pressure pulse wave analysis and cardiovascular events in the general population: the Prevention of Renal and Vascular End-stage Disease study.

BACKGROUND: Arterial stiffness influences the contour of the digital pressure pulse wave. METHOD: Here, we investigated whether the digital pulse propagation index (DPPI), based on the digital pressure pulse wave, DPPI is associated with cardiovascular events, heart failure, and mortality in a large population-based cohort. Between 2001 and 2003, DPPI was measured with a PortaPres noninvasive hemodynamic monitoring device (FinaPres Medical Systems, Amsterdam, The Netherlands) in participants of the Prevention of Renal and Vascular End-stage Disease study, a community-based cohort. We assessed the main determinants of the DPPI and investigated associations of DPPI with cardiovascular events and mortality. RESULTS: The study included 5474 individuals. Mean age was 52.3 ± 11.8 years and 50.5% was male. Median baseline DPPI was 5.81 m/s (interquartile range 5.47-6.20). Higher age, mean arterial blood pressure, body height, heart rate, current smoking, and lower HDL cholesterol levels and waist circumference were independent determinants of the DPPI (r = 0.43). After adjustment for heart rate, highlogDPPI was associated with all-cause mortality [hazard ratio: 1.67, 95% confidence interval (1.55-1.81) per SD; P < 0.001], cardiovascular mortality [hazard ratio 1.95 (1.72-2.22); P < 0.001], and incident heart failure with reduced ejection fraction [hazard ratio 1.81 (1.60-2.06); P < 0.001]. These associations remained independent upon further adjustment for confounders. Optimal cutoff values for DPPI ranged between 6.1 and 6.3 m/s for all endpoints. After multivariable adjustment, DPPI was no longer associated with coronary artery disease events or cerebrovascular events. CONCLUSION: The DPPI is associated with an increased risk of development of new onset heart failure with reduced ejection fraction and all-cause and cardiovascular mortality, but not with coronary artery events or cerebrovascular events.
Rhizospheric soil fungal community patterns of Duchesnea indica in response to altitude gradient in Yunnan, southwest China.

The impact magnitude of altitude gradient on microbial community and diversity has been under study since last few decades whereas bacteria has been the focus of most studies with relatively less spot light on fungi. Being a vital part of macro and micro ecosystem, rhizosphere fungi plays a vital role in organic matter decomposition, relative abundance of plant species and impact on plant growth and development. We observed the rhizosphere soil fungal community patterns across the altitude gradient in 15 sites of Yunnan province by selecting Duchesnea indica as the host plant using Illumina MiSeq sequencing of the fungal ITS1 region. We determined the fungal community composition and structure. We surprisingly found that rhizosphere soil fungal diversity of D. indica increases across the altitude gradient. There was a slight diversity difference among high and medium site samples with medium sites being on the top. Furthermore the rhizosphere soil fungal community composition and structure kept changing along the altitudinal gradient. Taxonomic results showed that phylum diversity range was maximum at high altitude sites besides Ascomycota, Basidiomycota, Zygomycota and Glomeromycota as the most dominant fungal phyla.
Detection of Occult Metastases in Patients with T1 and T2 Stage Lower Lip Squamous Cell Carcinomas after Positive Lymphoscintigraphy

The aim of this study was to detect lower lip squamous cell carcinomas (SCC) that had metastasized to the lymph nodes and to evaluate if neck dissection was necessary for patients with T1 or T2-stage lip cancer after a sentinel lymph node biopsy (SLNB). The study was conducted as a prospective clinical study to detect occult neck metastases in patients with T1 or T2 stage SCC of the lower lip. Thirty-one patients were eligible and underwent echo-ultrasound, computer tomography, magnetic resonance and lymphoscintigraphy (LSG) as diagnostic procedures. LSG was performed on the same day as the surgical procedure, after intradermal injection of 37 Mbq Tc99m-Sn-colloid/mL at four peritumoral sites. In patients with positive LSG results, the sentinel lymph nodes were extracted surgically. The risk factors for cancer development were sun exposure and smoking. The highest accuracy for detecting lymph node enlargements was achieved with magnetic resonance imaging (MRI; 80.7%). LSG showed excellent sensitivity (100%) and negative predictive value (NPV; 100%). Overall, occult metastases were diagnosed with an SLNB in eight (25.8%) patients. According to the results, with great caution, we suggest that an SLNB is reasonable to initiate only for patients with positive sentinel nodes by positive LSG, to be used as a lower morbidity approach for selected patients with T1 and T2 stage cancers.