Miracle-dz/UniFAR-FTUs huggingface dataset:
Editorial: Opposites Attract at CORR®-Machine Learning and Qualitative Research.

While most research published in orthopaedic surgery journals derives from one of several familiar study designs—case series, historically controlled studies, randomized trials, and variations on the systematic review theme—much of the fun (and a considerable portion of the benefit) we get from reading journals happens when clinician scientists tackle old, resistant problems in new ways. Clinical Orthopaedics and Related Research is on the vanguard of publishing innovative approaches in musculoskeletal science. Indeed, CORR leads the way both in terms of establishing editorial standards that ensure the consistent, clear reporting of a wide range of newer study designs [7, 11, 13, 19, 20], as well as providing tools for reviewers and readers [2, 17] to help them get the most out of the discoveries that we publish. We also take special pleasure in developing new article types that help surgeons do their jobs better; the mostrecent example has been our CORR Synthesis series [14-16], a reboot of the review-article format, but one that delivers robust approaches to screening, selection, and presentation that mitigate the sources of bias that otherwise are so deeply embedded in articles of this type [18]. CORR’s enthusiasm for two seemingly dissimilar article types, machine learning models and qualitative research, is just another example of our journal’s openness to new approaches to solving problems. We believe these article types deserve the enthusiasm of readers, as well.
Reporter Phage-Based Detection of Bacterial Pathogens: Design Guidelines and Recent Developments

Fast and reliable detection of bacterial pathogens in clinical samples, contaminated food products, and water supplies can drastically improve clinical outcomes and reduce the socio-economic impact of disease. As natural predators of bacteria, bacteriophages (phages) have evolved to bind their hosts with unparalleled specificity and to rapidly deliver and replicate their viral genome. Not surprisingly, phages and phage-encoded proteins have been used to develop a vast repertoire of diagnostic assays, many of which outperform conventional culture-based and molecular detection methods. While intact phages or phage-encoded affinity proteins can be used to capture bacteria, most phage-inspired detection systems harness viral genome delivery and amplification: to this end, suitable phages are genetically reprogrammed to deliver heterologous reporter genes, whose activity is typically detected through enzymatic substrate conversion to indicate the presence of a viable host cell. Infection with such engineered reporter phages typically leads to a rapid burst of reporter protein production that enables highly sensitive detection. In this review, we highlight recent advances in infection-based detection methods, present guidelines for reporter phage construction, outline technical aspects of reporter phage engineering, and discuss some of the advantages and pitfalls of phage-based pathogen detection. Recent improvements in reporter phage construction and engineering further substantiate the potential of these highly evolved nanomachines as rapid and inexpensive detection systems to replace or complement traditional diagnostic approaches.
Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease: In Vivo Neuroimaging Study of 11C-DTBZ PET Combined with Correlational Tractography

Previous histopathologic and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. 11C-dihydrotetrabenazine (11C-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion MRI can incorporate ligand-specific information provided by 11C-DTBZ PET into the fiber-tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on 11C-DTBZ PET. Methods: The study involved 30 subjects with mild to moderate PD (23 men and 7 women; mean age, 66 ± 6.2 y; disease duration, 6.4 ± 4.0 y; Hoehn and Yahr stage, 2.1 ± 0.6; Movement Disorder Society [MDS]–revised Unified Parkinson Disease Rating Scale [UPDRS] [I–III] total score, 43.4 ± 17.8) and 30 control subjects (18 men and 12 women; mean age, 62 ± 10.3 y). 11C-DTBZ PET was performed using standard synthesis and acquisition protocols. Correlational tractography was performed to assess quantitative anisotropy (QA; a measure of tract integrity) of white matter fibers correlating with information derived from striatal 11C-DTBZ data using the DSI Studio toolbox. Scans were realigned according to least and most clinically affected cerebral hemispheres. Results: Nigrostriatal tracts were identified in both hemispheres of PD patients. Higher mean QA values along the identified tracts were significantly associated with higher striatal 11C-DTBZ distribution volume ratios (least affected: r = 0.57, P = 0.001; most affected: r = 0.44, P = 0.02). Lower mean QA values of the identified tract in the LA hemisphere associated with increased severity of bradykinesia sub-score derived from MDS-UPDRS part III (r = −0.42; P = 0.02). Cross-validation revealed the generalizability of these results. Conclusion: These findings suggest that impaired integrity of dopaminergic nigrostriatal nerve terminals is associated with nigrostriatal axonal dysfunction in mild to moderate PD. Assessment of nigrostriatal tract integrity may be suitable as a biomarker of early- or even prodromal-stage PD.
Real-time CGM Is Superior to Flash Glucose Monitoring for Glucose Control in Type 1 Diabetes: The CORRIDA Randomized Controlled Trial

OBJECTIVE The aim of this trial was to compare the efficacy of real-time and intermittently scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control. RESEARCH DESIGN AND METHODS In this randomized study, adults with type 1 diabetes (T1D) and normal hypoglycemia awareness (Gold score <4) used rtCGM (Guardian Connect Mobile) or isCGM (FreeStyle Libre) during 4 days of physical activity (exercise phase) and in the subsequent 4 weeks at home (home phase). Primary end points were time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) and time in range (3.9–10.0 mmol/L [70–180 mg/dL]). The isCGM group wore an additional masked Enlite sensor (iPro2) for 6 days to check for bias between the different sensors used by the rtCGM and isCGM systems. RESULTS Sixty adults with T1D (mean age 38 ± 13 years; A1C 62 ± 12 mmol/mol [7.8 ± 1.1%]) were randomized to rtCGM (n = 30) or isCGM (n = 30). All participants completed the study. Percentage of time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) was lower among rtCGM versus isCGM participants in the exercise phase (6.8 ± 5.5% vs. 11.4 ± 8.6%, respectively; P = 0.018) and during the home phase (5.3 ± 2.5% vs. 7.3 ± 4.4%, respectively; P = 0.035). Hypoglycemia differences were significant and most notable during the night. rtCGM participants spent more time in range (3.9–10 mmol/L [70–180 mg/dL]) than isCGM participants throughout both the exercise (78.5 ± 10.2% vs. 69.7 ± 16%, respectively; P = 0.0149) and home (75.6 ± 9.7% vs. 67.4 ± 17.8%, respectively; P = 0.0339) phases. The results were robust to the insignificant bias between rtCGM and isCGM sensors that masked CGM found in the isCGM arm. CONCLUSIONS rtCGM was superior to isCGM in reducing hypoglycemia and improving time in range in adults with T1D with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management.
Antagonistic Functions of Connexin 43 during the Development of Primary or Secondary Bone Tumors

Despite research and clinical advances during recent decades, bone cancers remain a leading cause of death worldwide. There is a low survival rate for patients with primary bone tumors such as osteosarcoma and Ewing’s sarcoma or secondary bone tumors such as bone metastases from prostate carcinoma. Gap junctions are specialized plasma membrane structures consisting of transmembrane channels that directly link the cytoplasm of adjacent cells, thereby enabling the direct exchange of small signaling molecules between cells. Discoveries of human genetic disorders due to genetic mutations in gap junction proteins (connexins) and experimental data using connexin knockout mice have provided significant evidence that gap-junctional intercellular communication (Gj) is crucial for tissue function. Thus, the dysfunction of Gj may be responsible for the development of some diseases. Gj is thus a main mechanism for tumor cells to communicate with other tumor cells and their surrounding microenvironment to survive and proliferate. If it is well accepted that a low level of connexin expression favors cancer cell proliferation and therefore primary tumor development, more evidence is suggesting that a high level of connexin expression stimulates various cellular process such as intravasation, extravasation, or migration of metastatic cells. If so, connexin expression would facilitate secondary tumor dissemination. This paper discusses evidence that suggests that connexin 43 plays an antagonistic role in the development of primary bone tumors as a tumor suppressor and secondary bone tumors as a tumor promoter.
Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus aureus Osteomyelitis.

BACKGROUND Glucosaminidase (Gmd) is known to be a protective antigen in animal models of Staphylococcus aureus osteomyelitis. We compared the endogenous anti-Gmd antibody levels in sera of patients with culture-confirmed S. aureus bone infections to their sera at 1 year after operative treatment of the infection. METHODS A novel global biospecimen registry of 297 patients with deep-wound culture-confirmed S. aureus osteomyelitis was analyzed to assess relationships between baseline anti-Gmd serum titers (via custom Luminex assay), known host risk factors for infection, and 1-year postoperative clinical outcomes (e.g., infection control, inconclusive, refracture, persistent infection, septic nonunion, amputation, and septic death). RESULTS All patients had measurable humoral immunity against some S. aureus antigens, but only 20 patients (6.7%; p < 0.0001) had high levels of anti-Gmd antibodies (>10 ng/mL) in serum at baseline. A subset of 194 patients (65.3%) who completed 1 year of follow-up was divided into groups based on anti-Gmd level: low (<1 ng/mL, 54 patients; 27.8%), intermediate (<10 ng/mL, 122 patients; 62.9%), and high (>10 ng/mL, 18 patients; 9.3%), and infection control rates were 40.7%, 50.0%, and 66.7%, respectively. The incidence of adverse outcomes in these groups was 33.3%, 16.4%, and 11.1%, respectively. Assessing anti-Gmd level as a continuous variable showed a 60% reduction in adverse-event odds (p = 0.04) for every tenfold increase in concentration. No differences in patient demographics, body mass index of >40 kg/m, diabetes status, age of ≥70 years, male sex, Charlson Comorbidity Index of >1, or Cierny-Mader host type were observed between groups, and these risk factors were not associated with adverse events. Patients with low anti-Gmd titer demonstrated a significant 2.68-fold increased odds of adverse outcomes (p = 0.008). CONCLUSIONS Deficiency in circulating anti-Gmd antibodies was associated serious adverse outcomes following operative treatment of S. aureus osteomyelitis. At 1 year, high levels of anti-Gmd antibodies were associated with a nearly 3-fold increase in infection-control odds. Additional prospective studies clarifying Gmd immunization for osteomyelitis are needed. LEVEL OF EVIDENCE Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Sexual Reproduction of Centric Diatom Skeletonema costatum

The sexual reproduction and auxospore formation of Centrales had been misinterpreted for a long time. It was believed until recently that auxospore formation had no connection with sexual reproduction. More recently, however, STOSCH2) demonstrated oogamy clearly in Melosira varians for the first time, and since then STOSCH4-8) and GEITLER9, 10) studied the sexual reproduction in many marine Centrales. In this work, the author observed the sexual reproduction of Skeletonema costatum in axenic culture, and the following results were obtained. 1. When the narrow filamentous colonies of Skeletonema less than 5-6μ in breadth were cultured at the temperature of 17-23°C, formation of spermatogonia and oogonia was observed. 2. The spermatogonia are produced after 1 or 2 cell-divisions of vegetative cells, and four spermatozoa are formed in each spermatogonium. The spermatozoa are globular in shape, 3-3. 5μ in diameter, poor in plastids, and they each have one flagellum being 7-10μ in length. 3. The oogonia are produced from vegetative cells by extension of the cells, and one egg cell is formed in each oogonium. 4. After fertilization, a zygote develops into an auxospore without any resting stage. The fully grown auxospore is generally about three times as large in diameter as the mother cell. 5. The spermatogonia and oogonia are produced in the same clone, and accordingly this species is monoecious. 6. The auxospore formation is found more abundantly at the temperature of 20°C than 15 or 25°C. The sex determination in this species is influenced by light intensity. Clones of vegetative cells produce female cells under strong light, but they produce only male cells under weak light.
Mitochondrial DNA polymorphism in Candida albicans.

On decrit le polymorphisme des profils de restriction de C. albicans. Ce polymorphisme presente un grand interet en tant qu'outil epidemiologique. Cette etude a confirme l'origine endogene de l'infection a C. albicans chez les malades hospitalises etudies
Inhibition of the MYC-Regulated Glutaminase Metabolic Axis Is an Effective Synthetic Lethal Approach for Treating Chemoresistant Ovarian Cancers

Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics. Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. Significance: Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics. Graphical Abstract: http://cancerres.aacrjournals. org/content/canres/80/20/4514/F1.large. jpg. Graphical Abstract
Global gene expression patterns in Porites white patch syndrome: Disentangling symbiont loss from the thermal stress response in reef‐building coral

The mechanisms resulting in the breakdown of the coral symbiosis once the process of bleaching has been initiated remain unclear. Distinguishing the process of symbiont loss from the thermal stress response may shed light on the cellular and molecular pathways involved in each process. This study examined physiological changes and global gene expression patterns associated with white patch syndrome (WPS) in Porites lobata, which manifests in localized bleaching independent of thermal stress. In addition, a meta‐analysis of global gene expression studies in other corals and anemones was used to contrast differential regulation as a result of disease and thermal stress from patterns correlated with symbiotic state. Symbiont density, chlorophyll a content, holobiont productivity, instant calcification rate, and total host protein content were uniformly reduced in WPS relative to healthy tissue. While expression patterns associated with WPS were secondary to fixed effects of source colony, specific functional enrichments combined with a lack of immune regulation suggest that the viral infection putatively giving rise to this condition affects symbiont rather than host cells. Expression in response to WPS also clustered independently of patterns in white syndrome impacted A. hyacinthus, further supporting a distinct aetiology of this syndrome. Expression patterns in WPS‐affected tissues were significantly correlated with prior studies that examined short‐term thermal stress responses independent of symbiotic state, suggesting that the majority of expression changes reflect a nonspecific stress response. Across studies, the magnitude and direction of expression change among particular functional enrichments suggests unique responses to stressor duration and highlights distinct responses to bleaching in an anemone model.
Expression of IDE and PITRM1 genes in ERN1 knockdown U87 glioma cells: effect of hypoxia and glucose deprivation

Abstract Objective. The aim of the present investigation was to study the expression of genes encoding polyfunctional proteins insulinase (insulin degrading enzyme, IDE) and pitrilysin metallopeptidase 1 (PITRM1) in U87 glioma cells in response to inhibition of endoplasmic reticulum stress signaling mediated by ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) for evaluation of their possible significance in the control of metabolism through ERN1 signaling as well as hypoxia, glucose and glutamine deprivations. Methods. The expression level of IDE and PITRM1 genes was studied in control and ERN1 knockdown U87 glioma cells under glucose and glutamine deprivations as well as hypoxia by quantitative polymerase chain reaction. Results. It was found that the expression level of IDE and PITRM1 genes was down-regulated in ERN1 knockdown (without ERN1 protein kinase and endoribonuclease activity) glioma cells in comparison with the control glioma cells, being more significant for PITRM1 gene. We also found up-regulation of microRNA MIR7-2 and MIRLET7A2, which have specific binding sites in 3’-untranslated region of IDE and PITRM1 mRNAs, correspondingly, and can participate in posttranscriptional regulation of these mRNA expressions. Only inhibition of ERN1 endoribonuclease did not change significantly the expression of IDE and PITRM1 genes in glioma cells. The expression of IDE and PITRM1 genes is preferentially regulated by ERN1 protein kinase. We also showed that hypoxia down-regulated the expression of IDE and PITRM1 genes and that knockdown of ERN1 signaling enzyme function modified the response of these gene expressions to hypoxia. Glucose deprivation increased the expression level of IDE and PITRM1 genes, but ERN1 knockdown enhanced only the effect of glucose deprivation on PITRM1 gene expression. Glutamine deprivation did not affect the expression of IDE gene in both types of glioma cells, but up-regulated PITRM1 gene and this up-regulation was stronger in ERN1 knockdown cells. Conclusions. Results of this investigation demonstrate that ERN1 knockdown significantly decreases the expression of IDE and PITRM1 genes by ERN1 protein kinase mediated mechanism. The expression of both studied genes was sensitive to hypoxia as well as glucose deprivation and dependent on ERN1 signaling in gene-specific manner. It is possible that the level of these genes expression under hypoxia and glucose deprivation is a result of complex interaction of variable endoplasmic reticulum stress related and unrelated regulatory factors and contributed to the control of the cell metabolism.
Facile Construction of Copper-containing Covalent Bond for Peroxymonosulfate Activation: Efficient Redox Behavior of Copper Species via Electron Transfer Regulation.

Heterogeneous catalysis can be enhanced through the construction of effective atoms connection for rapid electron transport on the catalyst surface. Hence, this study proposed a new strategy for electron transfer regulation to facilitate redox cycle of Cu(II)/Cu(I). The objective was achieved by successful construction of copper-containing covalent bond through the in situ growth of porous g-C3N4 with oxygen dopants and nitrogen defects (O-CND) on CuAlxOy substrate (CuAl@O-CND). On the basis of X-ray absorption fine structure (XAFS) and other characterization results, the facilitated redox behavior of copper species by electron transfer regulation was ascribed to the formation of C-O-Cu bond on the porous-rich superficial of the catalyst, these covalent C-O-Cu bonds shortened the migration distance of electrons between Cu(II) and Cu(I) via Cu(I)-O-C-O-Cu(II) bridge. The construction of copper containing covalent bonds in the catalyst resulted in efficient PMS activation for rapid redox cycle of Cu(II)/Cu(I), triggering a series of reactions involving the continuous production of three highly active species (SO4•-, •OH and 1O2). The rapid diffusion and transportation of the generated active species from porous structures to directly attack typical pharmaceutically active compounds (PhACs), achieving superior catalytic performance. This study provides a new routine to construct C-O-Cu bond for PMS activation by regulating the electron transfer to accelerate the redox behavior of copper species for environmental remediation.