Miracle-dz/UniFAR-FTUs huggingface dataset:
Groundwater promotes emergence of asporogenic mutants of emetic Bacillus cereus.

Bacillus cereus is a ubiquitous endospore-forming bacterium, which mainly affects humans as a food-borne pathogen. B. cereus can contaminate groundwater used to irrigate food crops. Here, we examined the ability of the emetic strain B. cereus F4810/72 to survive abiotic conditions encountered in groundwater. Our results showed that vegetative B. cereus cells rapidly evolved in a mixed population composed of endospores and asporogenic variants bearing spo0A mutations. One asporogenic variant, VAR-F48, was isolated and characterized. VAR-F48 can survive in sterilized groundwater over a long period in a vegetative form, and has a competitive advantage compared to its parental strain. Proteomics analysis allowed us to quantify changes to cellular and exoproteins after 24 and 72 h incubation in groundwater, for VAR-F48 compared to its parental strain. The results revealed a significant rerouting of the metabolism in the absence of Spo0A. We concluded that VAR-F48 maximizes its energy use to deal with oligotrophy, and the emergence of spo0A-mutated variants may contribute to the persistence of emetic B. cereus in natural oligotrophic environments. This article is protected by copyright. All rights reserved.
Synthesis of Carboxylic Acid and Dimer Ester Surrogates to Constrain the Abundance and Distribution of Molecular Products in α-Pinene and β-Pinene Secondary Organic Aerosol.

Liquid chromatography/negative electrospray ionization mass spectrometry [LC/(-)ESI-MS] is routinely employed to characterize the identity and abundance of molecular products in secondary organic aerosol (SOA) derived from monoterpene oxidation. Due to a lack of authentic standards, however, commercial terpenoic acids (e.g., cis-pinonic acid) are typically used as surrogates to quantify both monomeric and dimeric SOA constituents. Here, we synthesize a series of enantiopure, pinene-derived carboxylic acid and dimer ester homologues. We find that the (-)ESI efficiencies of the dimer esters are 19-36 times higher than that of cis-pinonic acid, demonstrating that the mass contribution of dimers to monoterpene SOA has been significantly overestimated in past studies. Using the measured (-)ESI efficiencies of the carboxylic acids and dimer esters as more representative surrogates, we determine that molecular products measureable by LC/(-)ESI-MS account for only 21.8 ± 2.6% and 18.9 ± 3.2% of the mass of SOA formed from ozonolysis of α-pinene and β-pinene, respectively. The 28-36 identified monomers (C7-10H10-18O3-6) constitute 15.6-20.5% of total SOA mass, whereas only 1.3-3.3% of the SOA mass is attributable to the 46-62 identified dimers (C15-19H24-32O4-11). The distribution of identified α-pinene and β-pinene SOA molecular products is examined as a function of carbon number (nC), average carbon oxidation state (OSC), and volatility (C*). The observed order-of-magnitude difference in (-)ESI efficiency between monomers and dimers is expected to be broadly applicable to other biogenic and anthropogenic SOA systems analyzed via (-) or (+) LC/ESI-MS under various LC conditions, and demonstrates that the use of unrepresentative surrogates can lead to substantial systematic errors in quantitative LC/ESI-MS analyses of SOA.
Exploring mechanisms of action in clinical trials of complex surgical interventions using mediation analysis

Background: Surgical interventions allow for tailoring of treatment to individual patients and implementation may vary with surgeon and healthcare provider. In addition, in clinical trials assessing two competing surgical interventions, the treatments may be accompanied by co-interventions. Aims: This study explores the use of causal mediation analysis to (1) delineate the treatment effect that results directly from the surgical intervention under study and the indirect effect acting through a co-intervention and (2) to evaluate the benefit of the surgical intervention if either everybody in the trial population received the co-intervention or nobody received it. Methods: Within a counterfactual framework, relevant direct and indirect effects of a surgical intervention are estimated and adjusted for confounding via parametric regression models, for the situation where both mediator and outcome are binary, with baseline stratification factors included as fixed effects and surgeons as random intercepts. The causal difference in probability of a successful outcome (estimand of interest) is calculated using Monte Carlo simulation with bootstrapping for confidence intervals. Packages for estimation within standard statistical software are reviewed briefly. A step by step application of methods is illustrated using the Amaze randomised trial of ablation as an adjunct to cardiac surgery in patients with irregular heart rhythm, with a co-intervention (removal of the left atrial appendage) administered to a subset of participants at the surgeon’s discretion. The primary outcome was return to normal heart rhythm at one year post surgery. Results: In Amaze, 17% (95% confidence interval: 6%, 28%) more patients in the active arm had a successful outcome, but there was a large difference between active and control arms in the proportion of patients who received the co-intervention (55% and 30%, respectively). Causal mediation analysis suggested that around 1% of the treatment effect was attributable to the co-intervention (16% natural direct effect). The controlled direct effect ranged from 18% (6%, 30%) if the co-intervention were mandated, to 14% (2%, 25%) if it were prohibited. Including age as a moderator of the mediation effects showed that the natural direct effect of ablation appeared to decrease with age. Conclusions: Causal mediation analysis is a useful quantitative tool to explore mediating effects of co-interventions in surgical trials. In Amaze, investigators could be reassured that the effect of the active treatment, not explainable by differential use of the co-intervention, was significant across analyses.
Characteristics of temporal dynamics of intrinsic brain activity in unmedicated bipolar disorder with suicidality

Background: Bipolar disorder is associated with a high risk of suicide. Routine neuroimaging examination exhibited that bipolar disorder with suicidality was associated with brain structural and functional changes. However, the alterations of brain dynamics have still remained elusive. Purpose: To investigate the alterations of brain dynamics in unmedicated bipolar disorder II depression with suicidality and predict the severity of suicidality. Materials and Methods: This prospective study included 106 bipolar disorder II participants (20 with suicidal attempt, 35 with suicidal ideation, 51 without suicidal ideation) and 50 healthy controls who underwent resting-state functional magnetic resonance imaging between February 2016 and December 2017. We first used sliding window analysis to evaluate the dynamic amplitude of low-frequency fluctuations. Then, we predicted the severity of suicidality using a multivariate regression model. Results: One-way analysis of covariance revealed that the dynamic amplitude of low-frequency fluctuations in the right temporal pole, inferior temporal gyrus, superior temporal gyrus and the bilateral precuneus/posterior cingulate cortex was significantly different among the four groups. Post hoc pairwise comparisons revealed that dynamic amplitude of low-frequency fluctuations was remarkably decreased in the bilateral precuneus/posterior cingulate cortex in the three bipolar disorder II groups compared with that in healthy controls group. Increased dynamic amplitude of low-frequency fluctuations was found in the right superior temporal gyrus and inferior temporal gyrus in the suicidal attempt group compared with that in the other groups, and in the right temporal pole in the suicidal attempt group compared with that in the suicidal ideation and healthy controls groups. Importantly, these temporal variabilities could be used to predict the severity of suicidality (r = 0.330, p = 0.036), whereas static amplitude of low-frequency fluctuations couldn’t (r = –0.050, p = 0.532). Conclusion: Our findings indicated that alterations of temporal variability in the precuneus/posterior cingulate cortex are such a common feature of bipolar disorder patients. Besides, the severity of suicidality could be predicted by the dynamic amplitude of low-frequency fluctuations abnormalities rather than static amplitude of low-frequency fluctuations abnormalities, which is the first evidence of dynamic brain alterations in bipolar disorder patients with suicidality. The proposed predictive model may be advantageous for clinical applications.
Minimal Clinically Important Difference, Substantial Clinical Benefit, and Patient Acceptable Symptomatic State After Arthroscopic Rotator Cuff Repair

Background: Minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) are emerging criteria for patient-based treatment assessments. However, few studies have investigated these measures after rotator cuff repair. Purpose: (1) To determine MCID, SCB, and PASS values for pain visual analog scale (pVAS), Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons (ASES) score, and University of California, Los Angeles (UCLA) score after arthroscopic rotator cuff repair. (2) To determine factors for achieving the MCID, SCB, and PASS. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: We analyzed prospectively collected data from a rotator cuff surgery registry between March 2018 and February 2019. Eighty-two patients were included, and anchor questions for deriving MCID, SCB, and PASS values were applied at 1-year follow-up after the surgery. The MCID and SCB for the pVAS, ASES, SANE, and UCLA scores were then derived via 2 methods: a sensitivity- and specificity-based approach, which was used alone to derive PASS values, and a between-patients approach. Additionally, univariable and multivariable logistic regression analyses were performed to determine factors for achieving the MCID, SCB, and PASS. Results: All 4 scores showed acceptable areas under the curve. MCID, SCB, and PASS values for the pVAS were 1.5, 2.5, and 1.7; for ASES scores, 21.0, 26.0, and 78.0; for SANE, 13.0, 20.0, and 71.0; and for UCLA scores, 6.0, 8.0, and 23.0, respectively. Poor preoperative scores demonstrated significantly higher odds ratios (ORs) for achieving the MCID and SCB and lower ORs for achieving the PASS. Retear, large to massive tear, and older age showed lower ORs for achieving the MCID or SCB. For PASS items, male sex and biceps tenodesis had higher ORs, and older age had lower ORs. MCID, SCB, and PASS values per the sensitivity- and specificity-based approach were applied in factor analyses. Conclusion: Reliable MCID, SCB, and PASS values were obtained from patient evaluations 1 year after arthroscopic rotator cuff surgery. Poor preoperative score (MCID and SCB), male sex, and biceps tenodesis showed higher ORs, whereas poor preoperative score (PASS), retear, large to massive tear, and older age demonstrated lower ORs.
Altered touch perception and associated risk factors in individuals with diabetes mellitus.

OBJECTIVE To evaluate the prevalence of altered touch perception in the feet of individuals with diabetes mellitus and the associated risk factors. METHOD Cross-sectional study with 224 individuals with diabetes mellitus conducted in an endocrinology clinic at a public hospital in Campina Grande, Paraíba. The evaluation used touch sensitivity and perception, and a descriptive and multivariate analysis with Poisson regression was performed. RESULTS We found the prevalence of altered touch perception to be 53.1%. The risk factors that had a significant and joint impact on its occurrence were: female gender; previous ulcer; diabetes mellitus type 2; burning sensation, cracks, fissures, calluses, and Charcot foot. CONCLUSIONS This study found a high prevalence of altered perception of touch, and this should support the planning of actions aimed at preventing the problem. The study showed the relevance of the phenomenon as a nursing diagnosis that could be included in NANDA-International.
Lamin A‐mediated nuclear lamina integrity is required for proper ciliogenesis

The primary cilium is a sensory organelle that receives specific signals from the extracellular environment important for vertebrate development and tissue homeostasis. Lamins, the major components of the nuclear lamina, are required to maintain the nuclear structure and are involved in most nuclear activities. In this study, we show that deficiency in lamin A/C causes defective ciliogenesis, accompanied by increased cytoplasmic accumulation of actin monomers and increased formation of actin filaments. Disruption of actin filaments by cytochalasin D rescues the defective ciliogenesis in lamin A/C‐depleted cells. Moreover, lamin A/C‐deficient cells display lower levels of nesprin 2 and defects in recruiting Arp2, myosin Va, and tau tubulin kinase 2 to the basal body during ciliogenesis. Collectively, our results uncover a functional link between nuclear lamina integrity and ciliogenesis and implicate the malfunction of primary cilia in the pathogenesis of laminopathy.
Quantitative Determination of Ethyl Glucuronide and Ethyl Sulfate in Postmortem and Antemortem Whole Blood Using Phospholipid Removal 96-Well Plate and UHPLC–MS-MS

Abstract Postmortem ethanol formation is a well-known problem in forensic toxicology. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are ethanol metabolites that can be used to distinguish antemortem alcohol intake from postmortem formation of ethanol and in addition can be a helpful tool in assessment of the hip-flask defense. To an aliquot of 100 µL whole blood, internal standard (IS) and water was added before protein precipitation treatment (PPT) with ice-cold acetonitrile (ACN). The supernatants were filtered through a 96-well phospholipid removal plate, evaporated to dryness and reconstituted in 150 µL water/ACN/formic acid (FA). Identification of compounds was performed using multiple reaction monitoring (MRM) in negative mode. Gradient elution was performed on a C18 column with methanol (MeOH) and 0.1% FA. The run time was 4.5 min, and 0.5 µL was injected on an ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS-MS) instrument. Linearity was achieved (coefficient of determination (R2) ≥ 0.999) for EtG in the range of 0.089 to 22 mg/L (0.40–100 µM) and EtS 0.025 to 6.3 mg/L (0.20–50 µM). The limit of quantification (LOQ) was 0.067 mg/L (0.30 µM) for EtG and 0.019 mg/L (0.15 µM) for EtS. Between assay accuracy was –15% to 8% and precision reported as relative standard deviation (RSD) was ≤ 4.5%. Precision, estimated as the RSD of the concentration difference between results from two independent analyses of authentic whole blood samples, was ≤ 6.7%. Recovery was ≥ 61% for EtG and ≥ 77% for EtS and matrix effects (ME) were 99% to 103%. Method comparison was carried out with a previously used UHPLC–MS-MS method, and satisfactory agreement was achieved, and external proficiency testing control samples had z-score < ± 1. The method has been used in routine work for more than 4 years analyzing about 6,000 antemortem and postmortem whole blood samples and has proven to be robust and reliable.
Prevalence, consequences and factors associated with drug use among individuals over 50 years of age in the family perspective

Abstract Objectives The aim of this study was to investigate the prevalence, consequences and factors associated with drug use among individuals over 50 years of age, from the perspective of their families, with particularly reference to cocaine use. Methods Cross-sectional study based on secondary data with 624 family members of substance users who sought family support in 14 units of the Recomeço Família Program in São Paulo, Brazil. Results The participants were predominately men, aged 50 to 59 years (68%); cocaine users (inhaled and/ or smoked); living alone; with a low level of education and were unemployed. They were likely to use family money to pay for their substance use, with a history of theft and aggression against strangers, and were not in treatment. Unlike other participants [≥ 60 years (31.1%)]; who were better educated and retired. In this latter group, 32.8% are alcohol users, 14.8% cocaine users (inhaled and smoked), 32.6% has physically assaulted their family, 39.7% had assaulted someone else and 18.3% had stolen objects or money from home. Conclusions The population has peculiar characteristics of vulnerability (cocaine use and violence) that remain under investigated; not only do routes into treatment for older adults (≥ 60) but appropriate treatment packages need to be developed too.
Sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) and microvascular infiltration: a systematic review and meta-analysis

Objective Microvascular invasion is shown to be an independent risk factor for liver cancer recurrence. Timely treatment may reduce the recurrence rate and prolong total survival time. The aim of this study was to investigate the effectiveness of sorafenib in treating patients with hepatocellular carcinoma (HCC) and microvascular invasion Methods A comprehensive literature search was conducted in PubMed, EMBASE, MEDLINE, web of science and Cochrane Library databases for articles published up to December 2019. Two researchers independently reviewed and cross-checked independent reports with sufficient information. A meta-analysis was conducted to assess the impact of sorafenib on mortality in patients with HCC and microvascular involvement. Results Four studies were included in the qualitative and quantitative analyses, comprising 955 cancer events and 505 cancer deaths. Meta-analyses showed that sorafenib treatment was associated with an improved survival rate versus no sorafenib treatment in patients with HCC and microvascular invasion (relative risk 1.369, 95% confidence interval 1.193, 1.570). Conclusions Sorafenib treatment may improve survival in patients with HCC and microvascular invasion. However, due to the potential for residual confounding, the results should be interpreted with caution.
African Immigrant Health: Prostate Cancer Attitudes, Perceptions, and Barriers

Prostate cancer (PCa) is the second leading cause of cancer-related death among Black men who present with higher incidence, mortality, and survival compared to other racial groups. African immigrant men, however, are underrepresented in PCa research and thus this research sought to address that gap. This study applied a social determinants of health framework to understand the knowledge, perceptions, and behavioral tendencies regarding PCa in African immigrants. African immigrant men and women residing in different parts of the country (California, Texas, Colorado, Oklahoma, and Florida) from various faith-based organizations, African community groups, and social groups were recruited to participate in key informant interviews (n = 10) and two focus groups (n = 23). Four themes were identified in this study: (a) PCa knowledge and attitudes—while knowledge is very limited, perceptions about prostate health are very strong; (b) culture and gender identity strongly influence African health beliefs; (c) preservation of manhood; and (d) psychosocial stressors (e.g., financial, racial, immigration, lack of community, and negative perceptions of invasiveness of screening) are factors that play a major role in the overall health of African immigrant men. The results of this qualitative study unveiled perceptions, attitudes, beliefs, and knowledge of PCa among African immigrants that should inform the planning, development, and implementation of preventive programs to promote men’s health and PCa awareness.
The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia

Animal studies indicate that hypothalamic dysfunction plays a major role in type 2 diabetes mellitus (T2DM) development, and that insulin resistance and inflammation are important mechanisms involved in this disorder. However, it remains unclear how T2DM and antidiabetic treatments affect the human hypothalamus. Here, we characterized the proopiomelanocortin (POMC) immunoreactive (-ir) neurons, the neuropeptide-Y–ir (NPY-ir) neurons, the ionized calcium-binding adapter molecule 1–ir (iba1-ir) microglia, and the transmembrane protein 119–ir (TMEM119-ir) microglia in the infundibular nucleus (IFN) of human postmortem hypothalamus of 32 T2DM subjects with different antidiabetic treatments and 17 matched nondiabetic control subjects. Compared with matched control subjects, T2DM subjects showed a decrease in the number of POMC-ir neurons, but no changes in NPY-ir neurons or microglia. Interestingly, T2DM subjects treated with the antidiabetic drug metformin had fewer NPY-ir neurons and microglia than T2DM subjects not treated with metformin. We found that the number of microglia correlated with the number of NPY-ir neurons, but only in T2DM subjects. These results indicate that different changes in POMC and NPY neurons and microglial cells in the IFN accompany T2DM. In addition, T2DM treatment modality is associated with highly selective changes in hypothalamic neurons and microglial cells.
Otolaryngology Match 2020-21: Survey of Prospective Applicants in the Setting of COVID-19

Objectives: To capture the perspectives of candidates applying for otolaryngology residency positions in the 2020-21 cycle, in the context of disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. Subjects and methods: Candidates planning to apply to the otolaryngology 2020-21 match were invited to complete a cross-sectional online survey. Distribution was via otomatch.com and word of mouth. Descriptive statistics were performed. Results: Of 85 eligible responses (estimated 18.9% of all applicants), many have had at least one board examination (71.8%) disrupted. A majority (85.9%) believe evaluation of candidates will change due to the pandemic, and 54.1% report they were now less confident in matching. Female applicants (37.6% of respondents) were found to have significantly higher odds of decreased confidence in matching (OR 2.781 [95% CI 1.045-7.4044]; P = .041). Many report a move to virtual interviews would increase the number of applications submitted (45.9%) and the number of interviews attended (77.6%). Some applicants (36.5%) did not believe residency programs would gather sufficient information about their candidacy to make an informed decision, and most (62.4%) did not believe that they would gather sufficient information to inform their own rank list. Conclusions: We find that candidates believe their candidacy will be assessed differently in light of the COVID-19 pandemic, are largely less confident in successfully matching, and are planning to apply and interview more broadly. These data are relevant to otolaryngology residency leadership to inform clear dialogue and a smooth transition into an unprecedented application cycle.
Liver resection of hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guideline recommendations: Results from a high‐volume liver surgery center in East Asia

The Barcelona Clinic Liver Cancer (BCLC) guidelines were updated in 2012, and a single large hepatocellular carcinoma (HCC) more than 5 cm was regarded as BCLC stage A rather than B in the updated version. In this study, we sought to re‐evaluate the outcomes of patients with HCC who underwent liver resection (LR) within (stage 0 and A) and beyond (stage B and C) the BCLC guideline recommendations of the updated BCLC staging system.