Miracle-dz/UniFAR-FTUs huggingface dataset:
Asymptomatic ACDF Non-unions Underestimate the True Prevalence of Radiographic Pseudarthrosis.

STUDY DESIGN Secondary analysis of subjects in the control Anterior Cervical Discectomy and Fusion (ACDF) arm of Medtronic Investigational Device Exemption (IDE) trials for cervical disc arthroplasty (CDA) OBJECTIVES. : To compare Patient Reported Outcomes (PROs) in patients with radiographic nonunion to patients with a solid fusion. SUMMARY OF BACKGROUND DATA The true prevalence of nonunion after ACDF is unknown. Nonunion may be under-reported, as some patients are not symptomatic enough to justify radiographic evaluation. METHODS 345 subjects enrolled in the control arm of IDE trials for CDA who had single-level ACDF with allograft and plate with 24 month data formed the study cohort. Using the 24-month post-op evaluation, subjects were divided into those who had radiographic fusion and those who did not using strict study criteria. SF-36, NDI, Neck and Arm pain NRS scores were reported at 12, 24, 36, 60 and 84 months post-op. For subjects who had secondary surgery failures, the last observations before the secondary surgery were carried forward to future visits for the analysis. RESULTS 44 (13%) patients had radiographic non-union and 301 (87%) were fused at 24 months post-op. At 24 months, PROs were similar between the two groups. Seven patients in the Nonunion group (16%) and 10 (3%) in the Fused group had additional surgery at the index level prior to the 24 -follow-up (p = 0.003). Over the 84-month follow-up a total of 9 patients in the Nonunion group (21%) and 22 (7%) in the Fused group had additional surgery at the index level (p = 0.009). CONCLUSION While the radiographic non-union rate at 24 months was 13%, PROs show that many of the radiographic non-unions were asymptomatic. Although the majority of patients with radiographic non-union did not undergo additional surgery, the rate of secondary surgeries at the index level was significantly higher in the radiographic non-union group. LEVEL OF EVIDENCE 2.
Trehalose limits opportunistic mycobacterial survival during HIV co-infection by reversing HIV-mediated autophagy block

ABSTRACT Opportunistic bacterial infections amongst HIV–infected individuals contribute significantly to HIV-associated mortality. The role of HIV-mediated modulation of innate mechanisms like autophagy in promoting opportunistic infections, however, remains obscure. Here we show, HIV reactivation in or infection of macrophages inhibits autophagy and helps the survival of pathogenic Mycobacterium tuberculosis (Mtb) and nonpathogenic non-tuberculous mycobacterial strains (NTMs). The HIV-mediated impairment of xenophagy flux facilitated bacterial survival. Activation of autophagy by trehalose could induce xenophagy flux and kill intracellular Mtb or NTMs either during single or co-infections. Trehalose, we delineate, activates PIKFYVE leading to TFEB nuclear translocation in MCOLN1-dependent manner to induce autophagy. Remarkably, trehalose significantly reduced HIV-p24 levels in ex–vivo-infected PBMCs or PBMCs from treatment-naive HIV patients and also controlled mycobacterial survival within Mtb-infected animals. To conclude, we report leveraging of HIV-mediated perturbed host innate-immunity by opportunistic bacterial pathogens and show an attractive therapeutic strategy for HIV and associated co-morbidities. Abbreviations: AIDS: acquired immune deficiency syndrome; AMPK: AMP-activated protein kinase; ATG5: autophagy related 5; BafA1: bafilomycin A1; CFU: colony forming unit; CTSD: cathepsin D; CD63: CD63 molecule; EGFP: enhanced green fluorescent protein; FRET: Förster resonance energy transfer; GABARAP: gamma-aminobutyric acid receptor-associated protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GLUT: glucose transporter; HIV: human immunodeficiency virus; hMDMs: human monocyte derived macrophages; IL2: interleukin 2; LAMP1: lysosomal-associated membrane protein 1; LC3B-II: lipidated microtubule-associated proteins 1A/1B light chain 3B; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin; mRFP: monomeric red fluorescent protein; M6PR: mannose-6-phosphate receptor; NAC: N- acetyl- L –cysteine; NTM’s: non-tuberculous mycobacteria; PBMC: Peripheral Blood Mononuclear cells; PIKFYVE: phosphoinositide kinase; FYVE-Type Zinc Finger; PHA: phytohemagglutinin; PMA: phorbol 12-myristate 13-acetate; PtdIns(3,5)P2: Phosphatidylinositol 3,5-bisphosphate; ptfLC3: pEGFP-mRFP-LC3; ROS: reactive oxygen species; SQSTM1: sequestosome1; TFEB: transcription factor EB; MCOLN1/TRPML1: mucolipin 1; PIP4P1/TMEM55B: Human trans-membrane Protein 55B; UVRAG: UV Radiation Resistance Associate; VPS35: vacuolar protein sorting associated protein 35; WDR45: WD repeat domain 45; YCAM: Yellow Chameleon.
Salpingectomy at the Time of Cesarean Delivery: A Systematic Review and Meta-analysis.

OBJECTIVE To compare the differences in operative time and surgical outcomes between salpingectomy and standard tubal interruption at the time of cesarean delivery. DATA SOURCES PubMed, Medline, Google Scholar, Cochrane, and ClinicalTrials.gov were searched from inception until July 2019 for articles reporting outcomes for women undergoing salpingectomy during cesarean delivery compared with women undergoing standard sterilization methods. METHODS OF STUDY SELECTION Studies were selected if they included the main outcome of operative time or additional outcomes, which included infection, transfusion, readmission, change in hematocrit, and estimated blood loss. The Newcastle-Ottawa Quality Assessment scale or Cochrane Handbook were used to assess quality of cohort and randomized controlled trials (RCTs), respectively. A random-effects model was employed to calculate pooled relative risk or weighted mean difference for each outcome with their 95% CI. Heterogeneity was assessed using the I statistic, and L'Abbé plots were inspected visually to assess for homogeneity. TABULATION, INTEGRATION, AND RESULTS We identified 11 studies comprising 320,443 women undergoing total salpingectomy or standard sterilization methods at the time of cesarean delivery. Three RCTs and eight retrospective cohort studies were investigated separately by meta-analysis. When compared with standard sterilization methods, total operative time for patients receiving salpingectomy was significantly longer (6.3 minutes, 95% CI 3.5-9.1, seven studies, 7,303 patients) for cohort studies. With the three RCTs of 163 patients, total operative time was not significantly increased in women receiving salpingectomy (8.1 minutes, 95% CI -4.4 to 20.7). The salpingectomy group did not have an increased risk of wound infection, transfusion, readmission, reoperation, internal organ damage, blood loss, change in hemoglobin, or length of stay when compared with standard sterilization methods. CONCLUSION Salpingectomy at the time of cesarean delivery was associated with a small increase in operative time; however, it was not associated with an increased rate of surgical complications. This option should be considered for patients desiring sterilization during cesarean delivery. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42019145247.
Embryonic and early larval development of two marine angelfish, Centropyge bicolor and Centropyge bispinosa

Summary Marine angelfish (family: Pomacanthidae) are among the most sought-after fish species in the saltwater aquarium trade. However, there is a lack of information in the literature on their early ontogeny. The objective of this study was to describe the embryonic and early larval development of two dwarf angelfish, the bicolour angelfish, Centropyge bicolor and the coral beauty angelfish, Centropyge bispinosa. The eggs of these two species were obtained from spontaneous spawning of the broodstock fish in captivity and incubated at 26.0 ± 0.2°C throughout the study. Fertilized eggs (n = 15) of both species are transparent, pelagic and spherical; the mean diameters of the eggs were measured at 703.6 ± 7.8 μm for C. bicolor and 627.6 ± 7.8 μm for C. bispinosa. The eggs of both species possessed a narrow perivitelline space, smooth and thin chorion, a homogenous and non-segmented yolk as well as a single oil globule. Overall, the observed embryonic development pattern of C. bicolor and C. bispinosa was very similar, and the main difference was the embryonic pigmentation pattern, which only became evident close to hatching. Larvae of both species started hatching at 13 h 30 min after fertilization, and the larval characteristics of both species also showed high levels of similarities. However, the mouth opening time for C. bicolor was 72 h after hatching (AH) and 96 AH for C. bispinosa. In general, the observed early ontogeny of C. bicolor and C. bispinosa also resembled that of other Centropyge species documented in the literature.
Estrogen-related receptors are targetable ROS sensors

In this study Vernier et al. demonstrate a direct molecular link between the activity of two estrogen-related receptor (ERR) isoforms and the control of glutamine utilization and glutathione antioxidant production. Their findings highlight the ERRs as novel redox sensors and effectors of a ROS defense program and highlight the potential therapeutic advantage of exploiting ERRγ inhibitors for the treatment of BCa and other diseases in which oxidative stress plays a central role.
Anogenital distance as a measure of male competitive ability in Rwenzori Angolan colobus

Anogenital distance (AGD) is positively correlated to fetal androgen exposure and developmental masculinization in mammals. Independent of overall body size, AGD shows a strong positive correlation with male fertility and in rodents, AGD is a good indicator of male competitive ability and is associated with female choice. We hypothesized that AGD will also predict male competitive ability in non‐human primates. To test this, we measured AGD noninvasively with a parallel laser in a wild population of Angolan colobus monkeys (Colobus angolensis ruwenzorii) in Uganda and correlated to it to their social structure. C. angolensis ruwenzorii form a multilevel society with both one‐male/multifemale units (OMUs) and multimale/multifemale units (MMUs). We compared AGD in males from five OMUs and six MMUs and related it to their fecal androgen metabolite concentrations, dominance rank and body size, and to the number of females in their unit. Males in OMUs had greater access to females, so were predicted to have longer AGDs, but this was not found. AGD also did not correlate overall with mean fecal androgen metabolites in MMUs. However, AGD was correlated with dominance rank in MMUs, demonstrating that higher‐ranking males in these multimale units had longer AGDs. Body size did not show the same relationship with dominance rank, suggesting that male rank was not just a reflection of absolute male size. Our findings indicate that AGD predicts male competitive ability in this species and that it may be a useful correlate throughout the non‐human primates. These results also support the idea that prenatal androgen exposure increases the likelihood of the expression of behaviors that maintain high dominance rank.
Autophagy interferes with human cytomegalovirus genome replication, morphogenesis, and progeny release

ABSTRACT Viral infections are often accompanied by the induction of autophagy as an intrinsic cellular defense mechanism. Herpesviruses have developed strategies to evade autophagic degradation and to manipulate autophagy of the host cells to their benefit. Here we addressed the role of macroautophagy/autophagy in human cytomegalovirus replication and for particle morphogenesis. We found that proteins of the autophagy machinery localize to cytoplasmic viral assembly compartments and enveloped virions in the cytoplasm. Surprisingly, the autophagy receptor SQSTM1/p62 was also found to colocalize with HCMV capsids in the nucleus of infected cells. This finding indicates that the autophagy machinery interacts with HCMV already at the early nuclear stages of particle morphogenesis. The membrane-bound form of LC3 and several autophagy receptors were packaged into extracellular HCMV virions. This suggested that autophagic membranes were included during secondary envelopment of HCMV virions. To further address the importance of autophagy in HCMV infection, we generated an HCMV mutant that expressed a dominant-negative version of the protease ATG4B (BAD-ATG4BC74A). The proteolytic activity of ATG4B is required for LC3 cleavage, priming it for membrane conjugation. Surprisingly, both genome replication and virus release were enhanced in cells infected with BAD-ATG4BC74A, compared to control strains. These results show that autophagy operates as an antiviral process during HCMV infection but is dispensable for secondary HCMV particle envelopment. Abbreviations: ATG: autophagy-related; BAC: bacterial artificial chromosome; BECN1: beclin 1; CPE: cytopathic effect; cVACs: cytoplasmic viral assembly compartments; d.p.i. : days post-infection; DB: dense body; EBV: Epstein-Barr virus; galK: galactokinase; HCMV: human cytomegalovirus; HFF: human foreskin fibroblasts; IE: immediate-early; IRS: internal repeat short; LC3: MAP1LC3A/B; m.o. i. ; multiplicity of infection; MCP: major capsid protein; Pp: phosphoprotein; sCP/UL48a: smallest capsid protein; TRS: terminal repeat short; UL: unique long; US: unique short
Rapid sex-specific adaptation to high temperature in Drosophila

The pervasive occurrence of sexual dimorphism demonstrates different adaptive strategies of males and females. While different reproductive strategies of the two sexes are well-characterized, very little is known about differential functional requirements of males and females in their natural habitats. Here, we study the impact environmental change on the selection response in both sexes. Exposing replicated Drosophila populations to a novel temperature regime, we demonstrate sex-specific changes in gene expression, metabolic and behavioral phenotypes in less than 100 generations. This indicates not only different functional requirements of both sexes in the new environment but also rapid sex-specific adaptation. Supported by computer simulations we propose that altered sex-biased gene regulation from standing genetic variation, rather than new mutations, is the driver of rapid sex-specific adaptation. Our discovery of environmentally driven divergent functional requirements of males and females has important implications-possibly even for gender aware medical treatments.
Immune priming: the secret weapon of the insect world

ABSTRACT Insects are a highly successful group of animals that inhabit almost every habitat and environment on Earth. Part of their success is due to a rapid and highly effective immune response that identifies, inactivates, and eliminates pathogens. Insects possess an immune system that shows many similarities to the innate immune system of vertebrates, but they do not possess an equivalent system to the antibody-mediated adaptive immune response of vertebrates. However, some insect do display a process known as immune priming in which prior exposure to a sublethal dose of a pathogen, or pathogen-derived material, leads to an elevation in the immune response rendering the insect resistant to a subsequent lethal infection a short time later. This process is mediated by an increase in the density of circulating hemocytes and increased production of antimicrobial peptides. Immune priming is an important survival strategy for certain insects while other insects that do not show this response may have colony-level behaviors that may serve to limit the success of pathogens. Insects are now widely used as in vivo models for studying microbial pathogens of humans and for assessing the in vivo efficacy of antimicrobial agents. Knowledge of the process of immune priming in insects is essential in these applications as it may operate and augment the perceived in vivo antimicrobial activity of novel compounds. Abbreviations: 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate; SBC3: antimicrobial peptides; AMPs: dorsal-related immunity factor; DIF: Down syndrome cell adhesion molecule; Dscam: Lipopolysaccharide; LPS: Pathogen-associated molecular patterns; PAMPS: Patterns recognition receptors; PRR: Prophenoloxidase; PO: Toll-like receptors; TLRs: Toll/IL-1R; TIR, Transgenerational Immune Priming; TgIP: Tumor necrosis factor-α; TNF-α.
Causes of mortality in northern elephant seal pups on San Miguel Island, California

In February 2015, we conducted a field study of causes of mortality of northern elephant seal (Mirounga angustirostris) pups on San Miguel Island, California. Autopsies were performed on 18 freshly dead pups. Ages of pups ranged from stillborn to 6–8 wk. Gross and histologic lesions included trauma (9 of 18 pups), multifocal necrotizing myopathy (8 of 18), starvation with emaciation (7 of 18), congenital anomalies (3 of 18), bacterial infections (3 of 18), and perinatal mortality (stillbirths and neonates; 2 of 18). Trauma and emaciation or starvation were the most significant contributors to death. Bacterial infections included hemolytic Escherichia coli isolated from the lungs of 2 pups with pneumonia. Additionally, non-hemolytic Streptococcus sp. and hemolytic E. coli were isolated from the liver of an emaciated pup that had mild multifocal suppurative hepatitis. Other lesions, including a previously described necrotizing myopathy, congenital anomalies, and bacterial infections, were detected concurrently in cases with starvation and/or emaciation or trauma.
Cold Atmospheric Plasma and Gold Quantum Dots Exert Dual Cytotoxicity Mediated by the Cell Receptor-Activated Apoptotic Pathway in Glioblastoma Cells

Brain cancer malignancies represent an immense challenge for research and clinical oncology. Glioblastoma is the most lethal form of primary malignant brain cancer and is one of the most aggressive forms commonly associated with adverse prognosis and fatal outcome. Currently, combinations of inorganic and organic nanomaterials have been shown to improve survival rates through targeted drug delivery systems. In this study, we developed a dual treatment approach using cold atmospheric plasma (CAP) and gold quantum dots (AuQDs) for brain cancer. Our results showed that CAP and AuQDs induced dual cytotoxicity in brain cancer cells via Fas/TRAIL-mediated cell death receptor pathways. Moreover, combination treatment with CAP and AuQDs suppressed the motility and sphere-formation of brain cancer cells, which are recognized indicators of cancer aggressiveness. Taken together, the application of AuQDs can improve the efficiency of CAP against brain cancer cells, posing an excellent opportunity for advancing the treatment of aggressive glioblastomas.
The mediating role of inflammation in the association between cigarette smoking and intima-media thickness

Abstract Cigarette smoking is associated with thicker carotid intima-media thickness (IMT), probably partly through inflammatory pathways. However, to what extent does inflammation mediate the smoking-carotid atherosclerosis association is unclear. We investigated the mediating effect of inflammation on the association between cigarette smoking and carotid IMT, and quantified the respective contributions of inflammatory markers to this association. A total of 1752 participants from Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort (GBCS-CVD) were included. Using causal mediation analysis under the counterfactual framework, we decomposed total effects of cigarette smoking on IMT into indirect effects (through inflammatory response) and direct effects (not through inflammatory response). After adjusting for traditional risk factors, the indirect effects of per 109/L increment in leukocyte and granulocyte, per mg/L increment in high-sensitivity C-reactive protein (hs-CRP), and per mg/dL increment in fibrinogen on carotid IMT was 0.0028 mm (95% confidence interval [CI], 0.0011–0.0047), 0.0019 mm (95% CI, 0.0006–0.0034), 0.0017 mm (95% CI, 0.0006–0.003), and 0.001 mm (95% CI, 0.0001–0.0021), respectively. No evidence for a mediating role of lymphocyte was found. The proportion of the smoking-IMT association mediated by leukocyte, granulocyte, hs-CRP, and fibrinogen was 12.57% (95% CI, 8.50%–22.11%), 8.50% (95% CI, 5.76%–15.09%), 7.64% (95% CI, 5.20%–13.79%), and 4.48% (95% CI, 3.04%–8.03%), respectively. Restricting data analysis to men showed similar results. The effects of cigarette smoking on IMT were partly mediated by leukocyte, hs-CRP, and fibrinogen. The mediating role of leukocyte was likely mainly driven by higher granulocyte.
Food Safety Trust, Risk Perception, and Consumers’ Response to Company Trust Repair Actions in Food Recall Crises

Food recalls have severe impacts on the operation, reputation, and even the survival of a recalling company involved in a crisis, with consumer trust violation being the immediate threat to the recalling firm. The involved firms adopt trust repair strategies and release messages relevant to these actions to the public. In this research, we developed a conceptual model to analyze consumers’ general responses to the food recall, and we then compared the effect of two types of consumer trust repair strategies, i.e., self-sanction and information-sharing. The results show that consumer food safety trust has negative impacts on consumers’ protective behavioral intention during a food recall crisis. In the scientific-evidence sharing group, consumers have a higher risk perception, coping appraisal efficacy, information-seeking tendency, and protection behavioral intention. However, consumers’ food safety trust fails to predict protection behavioral intention because scientific-evidence actions can either be regarded as an explanation and self-serving, or as useful facts and solutions. Self-sanction actions overcome the disadvantages of information-sharing actions, but consumers still require information on facts of and solutions to the crisis. Therefore, it is recommended that recalling firms combine these two strategies in the case of consumer trust repair in food recall crises. Furthermore, the involved firms are encouraged to employ a third party to release the scientific evidence.
Estrogen activates pyruvate kinase M2 and increases the growth of TSC2-deficient cells

Lymphangioleiomyomatosis (LAM) is a devastating lung disease caused by inactivating gene mutations in either TSC1 or TSC2 that result in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). As LAM occurs predominantly in women during their reproductive age and is exacerbated by pregnancy, the female hormonal environment, and in particular estrogen, is implicated in LAM pathogenesis and progression. However, detailed underlying molecular mechanisms are not well understood. In this study, utilizing human pulmonary LAM specimens and cell culture models of TSC2-deficient LAM patient-derived and rat uterine leiomyoma-derived cells, we tested the hypothesis that estrogen promotes the growth of mTORC1-hyperactive cells through pyruvate kinase M2 (PKM2). Estrogen increased the phosphorylation of PKM2 at Ser37 and induced the nuclear translocation of phospho-PKM2. The estrogen receptor antagonist Faslodex reversed these effects. Restoration of TSC2 inhibited the phosphorylation of PKM2 in an mTORC1 inhibitor-insensitive manner. Finally, accumulation of phosphorylated PKM2 was evident in pulmonary nodule from LAM patients. Together, our data suggest that female predominance of LAM might be at least in part attributed to estrogen stimulation of PKM2-mediated cellular metabolic alterations. Targeting metabolic regulators of PKM2 might have therapeutic benefits for women with LAM and other female-specific neoplasms.