Miracle-dz/UniFAR-FTUs huggingface dataset:
An Evaluation of Frozen Section and Lymph Node Dissection Results for Mucinous Ovarian Tumors

Objectives Intraoperative frozen section has greater than 90% accuracy for ovarian tumors; however, mucinous histology has been shown to be associated with increased frozen section inaccuracy. Recent data demonstrate that primary ovarian mucinous carcinomas have no lymph node involvement, even when extraovarian disease is present, and therefore may not require lymph node dissection. Our primary objective is to evaluate the accuracy of identifying mucinous histology on frozen section. Methods/Materials A cross-sectional review of mucinous ovarian tumors in surgical patients at one institution from 2006 to 2016 was performed. Cases reporting a mucinous ovarian tumor on frozen section or final pathology were identified. Frozen section results were compared with final diagnosis to calculate concordance rates. Analyses with χ2 and t tests were performed to identify variables associated with pathology discordance. Results A total of 126 mucinous ovarian tumors were identified. Of these, 106 were reported as mucinous on frozen section and 103 (97.2%) were concordant on final pathology. Discordant cases included 2 serous and 1 clear cell tumor. Among the 103 mucinous tumors, classification as malignant, borderline, or benign was concordant in 74 (71.8%) of 103 cases, whereas 22 (21.4%) of 103 were discordant and 7 (6.8%) were deferred to final pathology. Lymph node dissection was performed in 33 cases; the only case with lymph node metastasis was a gastrointestinal mucinous adenocarcinoma. Discordance between frozen section and final pathology was associated with larger tumor size and diagnosis other than benign: discordant cases had a mean tumor size of 21.7 cm compared with 14.4 cm for concordant cases (P < 0.001), and 93.5% of discordant cases were borderline or malignant, compared with 30.5% of concordant cases (P < 0.001). Conclusions Intraoperative identification of mucinous histology by frozen section is reliable with a concordance rate to final pathology of 97.2%. No lymph node metastases were present in any malignant or borderline primary ovarian cases.
Reconfiguration of Intrinsic Functional Coupling Patterns Following Circumscribed Network Lesions

&NA; Communication between cortical regions is necessary for optimal cognitive processing. Functional relationships between cortical regions can be inferred through measurements of temporal synchrony in spontaneous activity patterns. These relationships can be further elaborated by surveying effects of cortical lesions upon inter‐regional connectivity. Lesions to cortical hubs and heteromodal association regions are expected to induce distributed connectivity changes and higher‐order cognitive deficits, yet their functional consequences remain relatively unexplored. Here, we used resting‐state fMRI to investigate intrinsic functional connectivity (FC) and graph theoretical metrics in 12 patients with circumscribed lesions of the medial prefrontal cortex (mPFC) portion of the Default Network (DN), and compared these metrics with those observed in healthy matched comparison participants and a sample of 1139 healthy individuals. Despite significant mPFC destruction, patients did not demonstrate weakened intrinsic FC among undamaged DN nodes. Instead, network‐specific changes were manifested as weaker negative correlations between the DN and attentional and somatomotor networks. These findings conflict with the DN being a homogenous system functionally anchored at mPFC. Rather, they implicate a role for mPFC in mediating cross‐network functional interactions. More broadly, our data suggest that lesions to association cortical hubs might induce clinical deficits by disrupting communication between interacting large‐scale systems.
Bone tissue engineering using mesenchymal stem cells

Finding a suitable material to be used in bone transplantations is a general objective in reconstructive surgery. Currently, autologous bone transplants are favored by most surgeons due to their reliability, however availability and donor morbidity are considerable drawbacks of this treatment. Tissue engineering has developed into a promising alternative, because the variety of biomaterials and the expertise in stem cell research are both rapidly increasing. The ideal tissue-engineered bone graft provides biocompatibility, bone-like mechanical stability, osseointegration and formation of new bone tissue. The goal of this study was to examine scaffolds of poly D,L-lactic acid (PDLLA), polyetherketoneketone (PEKK), and (hydroxyapatite-modified) silk from silk worm Bombyx mori in combination with mesenchymal stem cells (MSC) to be used for the purpose of a tissue-engineered bone graft. The chosen materials offer individual advantages such as degradability, cost-efficient production, radiolucency and biocompatibility. MSC are adult multipotent stem cells which are capable of differentiating into osteoblasts upon stimulation. Therefore, MSC are a frequently applied cell type in bone tissue engineering. The results of the In vitro tests showed that all scaffolds supported the attachment and osteogenic differentiation of both human and ovine (sheep origin) MSC. In subsequent in vivo experiments, scaffolds were implanted either cell-free, seeded with autologous ovine MSC, or seeded with osteogenically pre-differentiated autologous ovine MSC, into sheep calvarial defects of 10 mm diameter. After three months, the implants were examined for the volume and quality of newly formed bone. Surprisingly, the MSC seeding did not result in an enhanced bone formation in comparison to the cell-free samples. We hypothezise that the absence of the presumed enhancing effect of MSC was due to a fibrous capsule, which had formed around the scaffolds. Nevertheless, PEKK and hydroxyapatite-modified silk scaffolds supported new bone formation, either with or without MSC seeding and are thus potential scaffolds for bone tissue engineering. More basic research is needed however, to identify relevant factors for improved tissue integration of transplants, while at the same time avoiding fibrous capsule formation.
Neural Plasticity with Age: Unilateral Maximal Strength Training Augments Efferent Neural Drive to the Contralateral Limb in Older Adults

Efferent neural drive during strong muscle contractions is attenuated with age, even after life-long strength training. However, it is unknown if this deterioration may impede contralateral neural plasticity, and limit the clinical value of unilateral strength training. We assessed muscle force-generating capacity, evoked potentials recordings (V-wave and H-reflex normalized to M-wave; V/M-ratio and H/M-ratio) and voluntary activation (VA) in the plantar flexors of the contralateral limb following unilateral maximal strength training (MST) with the dominant limb for 3 weeks (nine sessions). Twenty-three 73 ± 4(SD) year old males were randomized to a MST group (N = 11), exercising with an intensity of ~90% of maximal strength, or a control group (CG, N = 12). MST improved contralateral maximal strength (107.6 ± 27.0 to 119.1 ± 34.8 Nm; 10%) and rate of force development (197.3 ± 54.1 to 232.8 ± 77.7 Nm s-1; 18%) (both p < .05). These strength gains were associated with (r = 0.465-0.608) an enhanced soleus V/M-ratio (0.12 ± 0.09 to 0.21 ± 0.17) and VA (79.5 ± 5.1 to 83.3 ± 5.2%) (all p < .05). H/M-ratio (10% maximal strength) remained unaltered after MST, and no changes were apparent in the CG. In conclusion, cross-limb effects in older adults are regulated by efferent neural drive enhancement, and advocate the clinical relevance of MST to improve neuromuscular function in individuals with conditions that results in unilateral strength reductions.
Quantitative analysis of protein interaction network dynamics in yeast

Many cellular functions are mediated by protein–protein interaction networks, which are environment dependent. However, systematic measurement of interactions in diverse environments is required to better understand the relative importance of different mechanisms underlying network dynamics. To investigate environment‐dependent protein complex dynamics, we used a DNA‐barcode‐based multiplexed protein interaction assay in Saccharomyces cerevisiae to measure in vivo abundance of 1,379 binary protein complexes under 14 environments. Many binary complexes (55%) were environment dependent, especially those involving transmembrane transporters. We observed many concerted changes around highly connected proteins, and overall network dynamics suggested that “concerted” protein‐centered changes are prevalent. Under a diauxic shift in carbon source from glucose to ethanol, a mass‐action‐based model using relative mRNA levels explained an estimated 47% of the observed variance in binary complex abundance and predicted the direction of concerted binary complex changes with 88% accuracy. Thus, we provide a resource of yeast protein interaction measurements across diverse environments and illustrate the value of this resource in revealing mechanisms of network dynamics.
Development and evaluation of 3D knitted fabrics to protect against mechanical risk

In this research, eight different 3D weft-knitted fabrics were developed and evaluated. 3D fabrics have been knitted on circular weft-knitting machines with two different gauges: 20E gauge and 28E gauge. Three different raw materials were used for the fabric’s production: high molecular mass polyethylene (HPPE) yarn and 0.05 mm diameter steel wire in the outer layers (for the front and reverse) and polyamide yarn in the binding layer. The experiments were conducted on the developed 3D knitted fabrics to determine the fabric’s resistance to mechanical risks such as circular blade cut, puncture, abrasion, and also to evaluate the comfort parameter, such as air permeability. It was defined that 3D weft-knitted fabrics best results on tests: circular blade cut, puncture and abrasion resistant were achieved using HPPE yarn twisted with steel wire, higher mass per unit area with more significant amount of steel wire. According to the standard EN 388:2003, three samples of developed 3D weft-knitted fabrics had the highest 5th blade cut and the highest (4th) abrasion resistance level. All of them had the highest (4th) level of puncture resistance. 3D fabrics knitted on a circular weft-knitting machine of gauge 28E ensured 1.3–2.1 times greater blade cut and 4.9–12.1 times greater abrasion resistance result, than fabrics knitted on gauge 20E, due to a higher stitch density, higher mass per unit area, density and fabric’s thickness. But on the other hand, these parameters lowered air permeability by 20.2–43.0%.
The management of chronic non-arthritic scapholunate dissociation: a systematic review

A systematic review was conducted to identify the best management for chronic scapholunate dissociation. EMBASE, MEDLINE, and CENTRAL were searched from 1965–2016. A narrative synthesis was performed. One thousand, one hundred and ninety-one citations were identified, of which 17 had final analysis. In all interventions, the pain score at 2 years reduced from 6.0 to 2.8 with similar effect from capsulodesis and tenodesis techniques. Overall there was an 18% loss of flexion arc. Radial to ulnar arc improved in capsulodesis (+19%; n = 45) and worsened in tenodesis (−6%; n = 45). Grip strength was better in capsulodesis (+31%; n = 64 versus + 11%; n = 56). There was insufficient evidence to link radiological outcome with clinical outcome. Rates of complications (20%) and CRPS (3.8%) were high, with implications for patient consent. Due to heterogeneity in data collection, the lack of comparative studies and short-term follow-up, no conclusion regarding the superiority of a single technique was possible. Longer term comparative studies are required, as are natural history studies. A minimum data set has been advised. Level of evidence: II
Novel quantum phase transition from bounded to extensive entanglement

Significance One of the main quests of many-body physics and quantum information is to understand various quantum phases and in particular the entanglement present in them. In this work we have uncovered a unique, physically transparent quantum phase transition in a spin chain where entanglement entropy itself jumps from low scaling, most typical for gapped models and short-range correlations, to a critical phase where the scaling exhibits an extraordinary amount of entanglement. This discovery pushes the boundaries of a possible range of nonlocal quantum correlations displayed by local Hamiltonians and opens a door to fundamental and practical questions about the interplay of entanglement and locality in many-body systems. The nature of entanglement in many-body systems is a focus of intense research with the observation that entanglement holds interesting information about quantum correlations in large systems and their relation to phase transitions. In particular, it is well known that although generic, many-body states have large, extensive entropy, ground states of reasonable local Hamiltonians carry much smaller entropy, often associated with the boundary length through the so-called area law. Here we introduce a continuous family of frustration-free Hamiltonians with exactly solvable ground states and uncover a remarkable quantum phase transition whereby the entanglement scaling changes from area law into extensively large entropy. This transition shows that entanglement in many-body systems may be enhanced under special circumstances with a potential for generating “useful” entanglement for the purpose of quantum computing and that the full implications of locality and its restrictions on possible ground states may hold further surprises.
Standardizing Descemet Membrane Endothelial Keratoplasty Graft Preparation Method in the Eye Bank—Experience of 527 Descemet Membrane Endothelial Keratoplasty Tissues

Purpose: To share the experience and provide a standardized protocol for Descemet membrane endothelial keratoplasty (DMEK) graft preparation. Methods: A retrospective study based on 527 prestripped DMEK tissues that were prepared between 2014 and 2017. The experience of using different instruments and techniques has been described, and a standardized technique for preparing DMEK grafts has been identified. The tissues in general were prepared by superficially tapping the endothelial side with a Moria trephine (9.5 mm diameter). The plane of cleavage was identified using a cleavage hook, and the DMEK graft was deadhered from the trephined site throughout the circumference for ease of excising the graft. The DMEK graft was peeled using either one or multiple quadrant methods depending on the challenges faced during excision. The graft was finally marked with the letter “F” to identify the orientation during surgery. Data on endothelial cell loss (ECL) and challenging cases were observed, monitored, and recorded during this period. Results: Less than 1 percent trypan blue-positive cells with tissue wastage of <6% was observed during the study period. Our standardized stripping technique has resulted in an overall ECL of 4.6%. Marking Descemet membrane showed 0.5% cell mortality. Conclusions: Standardizing DMEK technique using specific tools and simple techniques would help new surgeons to decide the instruments and improve their tissue preparation skills also in challenging cases such as previous cataract incisions or horseshoe-shaped tears, further reducing ECL or tissue wastage.
Generation of Elf5‐Cre knockin mouse strain for trophoblast‐specific gene manipulation

Placental development is a complex and highly controlled process during which trophoblast stem cells differentiate to various trophoblast subtypes. The early embryonic death of systemic gene knockout models hampers the investigation of these genes that might play important roles during placentation. A trophoblast specific Cre mouse model would be of great help for dissecting out the potential roles of these genes during placental development. For this purpose, we generate a transgenic mouse with the Cre recombinase inserted into the endogenous locus of Elf5 gene that is expressed specifically in placental trophoblast cells. To analyze the specificity and efficiency of Cre recombinase activity in Elf5‐Cre mice, we mated Elf5‐Cre mice with Rosa26mT/mG reporter mice, and found that Elf5‐Cre transgene is expressed specifically in the trophoectoderm as early as embryonic day 4.5 (E4.5). By E12.5, the activity of Elf5‐Cre transgene was detected exclusively in all derivatives of trophoblast lineages, including spongiotrophoblast, giant cells, and labyrinth trophoblasts. In addition, Elf5‐Cre transgene was also active during spermatogenesis, from spermatids to mature sperms, which is consistent with the endogenous Elf5 expression in testis. Collectively, our results provide a unique tool to delete specific genes selectively and efficiently in trophoblast lineage during placentation.
Synergistic antibacterial effect of silver and ebselen against multidrug‐resistant Gram‐negative bacterial infections

Multidrug‐resistant (MDR) Gram‐negative bacteria account for a majority of fatal infections, and development of new antibiotic principles and drugs is therefore of outstanding importance. Here, we report that five most clinically difficult‐to‐treat MDR Gram‐negative bacteria are highly sensitive to a synergistic combination of silver and ebselen. In contrast, silver has no synergistic toxicity with ebselen on mammalian cells. The silver and ebselen combination causes a rapid depletion of glutathione and inhibition of the thioredoxin system in bacteria. Silver ions were identified as strong inhibitors of Escherichia coli thioredoxin and thioredoxin reductase, which are required for ribonucleotide reductase and DNA synthesis and defense against oxidative stress. The bactericidal efficacy of silver and ebselen was further verified in the treatment of mild and acute MDR E. coli peritonitis in mice. These results demonstrate that thiol‐dependent redox systems in bacteria can be targeted in the design of new antibacterial drugs. The silver and ebselen combination offers a proof of concept in targeting essential bacterial systems and might be developed for novel efficient treatments against MDR Gram‐negative bacterial infections.
Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1

ABSTRACT Positive-strand RNA viruses, including picornaviruses, utilize cellular machinery for genome replication. Previously, we reported that each of the 2B, 2BC, 2C, 3A, and 3AB proteins of Aichi virus (AiV), a picornavirus, forms a complex with the Golgi apparatus protein ACBD3 and phosphatidylinositol 4-kinase IIIβ (PI4KB) at viral RNA replication sites (replication organelles [ROs]), enhancing PI4KB-dependent phosphatidylinositol 4-phosphate (PI4P) production. Here, we demonstrate AiV hijacking of the cellular cholesterol transport system involving oxysterol-binding protein (OSBP), a PI4P-binding cholesterol transfer protein. AiV RNA replication was inhibited by silencing cellular proteins known to be components of this pathway, OSBP, the ER membrane proteins VAPA and VAPB (VAP-A/B), the PI4P-phosphatase SAC1, and PI-transfer protein β. OSBP, VAP-A/B, and SAC1 were present at RNA replication sites. We also found various previously unknown interactions among the AiV proteins (2B, 2BC, 2C, 3A, and 3AB), ACBD3, OSBP, VAP-A/B, and SAC1, and the interactions were suggested to be involved in recruiting the component proteins to AiV ROs. Importantly, the OSBP-2B interaction enabled PI4P-independent recruitment of OSBP to AiV ROs, indicating preferential recruitment of OSBP among PI4P-binding proteins. Protein-protein interaction-based OSBP recruitment has not been reported for other picornaviruses. Cholesterol was accumulated at AiV ROs, and inhibition of OSBP-mediated cholesterol transfer impaired cholesterol accumulation and AiV RNA replication. Electron microscopy showed that AiV-induced vesicle-like structures were close to ER membranes. Altogether, we conclude that AiV directly recruits the cholesterol transport machinery through protein-protein interactions, resulting in formation of membrane contact sites between the ER and AiV ROs and cholesterol supply to the ROs. IMPORTANCE Positive-strand RNA viruses utilize host pathways to modulate the lipid composition of viral RNA replication sites for replication. Previously, we demonstrated that Aichi virus (AiV), a picornavirus, forms a complex comprising certain proteins of AiV, the Golgi apparatus protein ACBD3, and the lipid kinase PI4KB to synthesize PI4P lipid at the sites for AiV RNA replication. Here, we confirmed cholesterol accumulation at the AiV RNA replication sites, which are established by hijacking the host cholesterol transfer machinery mediated by a PI4P-binding cholesterol transfer protein, OSBP. We showed that the component proteins of the machinery, OSBP, VAP, SAC1, and PITPNB, are all essential host factors for AiV replication. Importantly, the machinery is directly recruited to the RNA replication sites through previously unknown interactions of VAP/OSBP/SAC1 with the AiV proteins and with ACBD3. Consequently, we propose a specific strategy employed by AiV to efficiently accumulate cholesterol at the RNA replication sites via protein-protein interactions.
Exercise‐induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work

High work of breathing and exercise‐induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise‐induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole‐body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing‐related changes in quadriceps muscle fatigue.
The MUC1-C Oncoprotein Binds to the BH3 Domain of the Pro-apoptotic BAX Protein and Blocks BAX Function*

Background: The MUC1-C oncoprotein attenuates activation of the intrinsic apoptotic pathway by mechanisms that are not understood. Results: MUC1-C binds directly to the pro-apoptotic BAX protein at the critical BH3 domain. Conclusion: MUC1-C blocks BAX dimerization and BAX-mediated release of mitochondrial cytochrome c. Significance: MUC1-C is a novel inhibitor of BAX function. The pro-apoptotic BAX protein contains a BH3 domain that is necessary for its dimerization and for activation of the intrinsic apoptotic pathway. The MUC1 (mucin 1) heterodimeric protein is overexpressed in diverse human carcinomas and blocks apoptosis in the response to stress. In this study, we demonstrate that the oncogenic MUC1-C subunit associates with BAX in human cancer cells. MUC1-C·BAX complexes are detectable in the cytoplasm and mitochondria and are induced by genotoxic and oxidative stress. The association between MUC1-C and BAX is supported by the demonstration that the MUC1-C cytoplasmic domain is sufficient for the interaction with BAX. The results further show that the MUC1-C cytoplasmic domain CQC motif binds directly to the BAX BH3 domain at Cys-62. Consistent with binding to the BAX BH3 domain, MUC1-C blocked BAX dimerization in response to (i) truncated BID in vitro and (ii) treatment of cancer cells with DNA-damaging agents. In concert with these results, MUC1-C attenuated localization of BAX to mitochondria and the release of cytochrome c. These findings indicate that the MUC1-C oncoprotein binds directly to the BAX BH3 domain and thereby blocks BAX function in activating the mitochondrial death pathway.