Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical features and corneal optical anisotropies in a rabbit model of limbal stem cell deficiency.

PURPOSES To investigate the intra-laboratory reproducibility of clinical features and to evaluate corneal optical anisotropies in a rabbit model of limbal stem cell deficiency. METHODS Limbal injury was induced in the right eye of 23 adult New Zealand White rabbits using a highly aggressive protocol that combined 360 degrees limbal peritomy, keratolimbectomy, alkaline chemical burn, and mechanical removal of the epithelium. Clinical evaluation of the injured eyes was performed for 28 days and included corneal impression cytology. Corneas with a severe clinical outcome set typical of limbal stem cell deficiency were then collected, subjected to a histopathological examination, and examined for optical anisotropies. Corneas from healthy rabbit eyes were used as controls. Differences in optical path due to stromal collagen birefringence, as well as linear dichroism related to the expression and spatial orientation of glycosaminoglycan chains from proteoglycans, were measured from cross-sections under a quantitative polarized light microscope. RESULTS One eye showed signs of hypopyon and was excluded. Signs of ocular inflammation were observed in all eyes studied (n=22). Corneal impression cytology did not detect goblet cells. Twelve of the 22 corneas presented a clinical outcome set typical of limbal stem cell deficiency, which is characterized by the presence of epithelial defects, inflammatory cells, moderate-to-severe opacity, and neovascularization. Microscopic studies under polarized light revealed that relative to controls, limbal stem cell deficiency caused a 24.4% increase in corneal optical path differences. Further, corneas with limbal stem cell deficiency were less dichroic than controls. CONCLUSIONS These results suggest that rabbit models of limbal stem cell deficiency must be rigorously screened for use in preclinical studies to ensure experimental homogeneity because protocols used to create limbal stem cell deficiency could be not associated with good intra-laboratory reproducibility of clinical features. Limbal stem cell deficiency, as induced herein, altered the optical anisotropic properties of the corneal stroma. Such alterations are indicative of changes in collagen packing and the spatial orientation of glycosaminoglycan chains from proteoglycans. Knowledge of these changes is important to potentiate strategies aimed at restoring the morphofunctional integrity of the corneal stroma affected by limbal stem cell deficiency.
Significantly higher pathologic complete response (pCR) after the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy for HER2-positive breast cancer: Evidence from a meta-analysis of randomized controlled trials

Objectives: To investigate the effect of the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer in terms of pCR and cardiotoxicity. Methods: We systematically searched Pubmed, Embase, Cochrane and SinoMed databases from inception until 1 July 2017 for relevant articles of randomized controlled studies. After identified all relevant studies that reported the concurrent use of trastuzumab and anthracycline-based NAC for HER2-positive locally advanced breast cancer, five eligible randomized studies were extracted relevant data and assessed for design and quality, and the meta-analysis was conducted to evaluate the risk ratio (RR) of pCR and other interesting outcomes, such as left ventricular ejection fraction (LVEF) decrease more than 10%, responses, recurrence free survival (RFS) and overall survival (OS). Results: A total of five randomized controlled studies were included in the meta-analysis, including 232 HER2-positive locally advanced breast cancer patients received the concurrent use of trastuzumab and anthracycline-based NAC. The results showed that the pCR rate was significantly higher in the group received the concurrent use of trastuzumab and anthracycline-based NAC (48%) than that in the non-concurrent use of trastuzumab and anthracycline-based NAC group (26%) (RR: 1.76, 95%CI: 1.37-2.26, p<0.0001). Besides, higher rate of RFS (RR: 1.14, 95%CI: 1.03-1.26, p=0.009) was observed in the concurrent use of trastuzumab and anthracycline-based NAC group. No significant differences in LVEF decreased more than 10% (p=0.50) between both groups. Conclusions: Our meta-analysis of randomized controlled studies showed that pCR rates are significantly higher in the concurrent use of trastuzumab and anthracycline-based NAC compared with the non-concurrent use of trastuzumab and anthracycline-based NAC for certain HER2-positive breast cancer, meanwhile without significant increase of the cardiotoxicity.
Soluble Aβ42 Acts as Allosteric Activator of the Core Cholinergic Enzyme Choline Acetyltransferase

Two major questions in the field of Alzheimer-type dementia remain elusive. One is the native function of amyloid-β (Aβ) peptides and the other is an early deficit in the central cholinergic network. Nevertheless, recent evidence suggests that Aβ peptides are involved in the regulation of acetylcholine (ACh) homeostasis either by allosteric activation of ACh-degrading cholinesterases or by inhibiting the high-affinity choline uptake transporter. In the current study, we report that Aβ peptides, in particular Aβ42, allosterically enhances the catalytic rate of the core-cholinergic enzyme choline acetyltransferase (ChAT), responsible for biosynthesis of ACh. Detailed in vitro enzyme kinetic analysis indicated that both soluble Aβ40 and Aβ42 enhanced the catalytic efficiency of ChAT by ∼21% and 26% at physiological concentration ranges found in human cerebrospinal fluid (CSF). Further analyses indicated that activation of ChAT by Aβ was highly specific. Intriguingly, Aβ42 exhibited an EC50 of activation potency at 10-fold lower concentrations compared to Aβ40. The activation was persistent even in the presence of a physiological Aβ 40/42 mixture ratio, expected in human CSF. In conclusion, we report for the first time that Aβ42 peptide acts as allosteric enhancers of ACh-biosynthesizing enzyme ChAT. Together with two previous observations, this points to a complex molecular cross-talk between Aβ and the enzymatic machinery involved in maintaining cellular, synaptic and extra-synaptic ACh homeostasis, warranting further investigation.
Pediatric and Adolescent T-type Distal Humerus Fractures

Although fractures of the elbow are extremely common in pediatric patients, the T-type distal humerus fracture is rare and offers unique challenges. The mechanism of injury may be similar to the adult counterpart and is usually caused by a fall onto a flexed elbow or from a direct blow. Diagnosing these injuries may be difficult. They often resemble extension-type supracondylar fractures, yet the treatment algorithm is quite different. In younger patients, percutaneous pinning remains a viable option, but for older adolescents, open reduction and internal fixation provides stable fixation at the elbow and the most reliable restoration of the articular surface. Appropriate imaging, careful radiographic diagnosis, and choice of surgical technique are of paramount importance when treating young patients with this injury. Most pediatric and adolescent patients with T-type distal humerus fractures have results better than those of adults but often worse than other elbow fractures in this age group.
Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus

Men are generally superior to women in remembering spatial relationships, whereas the reverse holds for semantic information, but the neurobiological bases for these differences are not understood. Here we describe striking sexual dimorphism in synaptic mechanisms of memory encoding in hippocampal field CA1, a region critical for spatial learning. Studies of acute hippocampal slices from adult rats and mice show that for excitatory Schaffer–commissural projections, the memory-related long-term potentiation (LTP) effect depends upon endogenous estrogen and membrane estrogen receptor α (ERα) in females but not in males; there was no evident involvement of nuclear ERα in females, or of ERβ or GPER1 (G-protein-coupled estrogen receptor 1) in either sex. Quantitative immunofluorescence showed that stimulation-induced activation of two LTP-related kinases (Src, ERK1/2), and of postsynaptic TrkB, required ERα in females only, and that postsynaptic ERα levels are higher in females than in males. Several downstream signaling events involved in LTP were comparable between the sexes. In contrast to endogenous estrogen effects, infused estradiol facilitated LTP and synaptic signaling in females via both ERα and ERβ. The estrogen dependence of LTP in females was associated with a higher threshold for both inducing potentiation and acquiring spatial information. These results indicate that the observed sexual dimorphism in hippocampal LTP reflects differences in synaptic kinase activation, including both a weaker association with NMDA receptors and a greater ERα-mediated kinase activation in response to locally produced estrogen in females. We propose that male/female differences in mechanisms and threshold for field CA1 LTP contribute to differences in encoding specific types of memories. SIGNIFICANCE STATEMENT There is good evidence for male/female differences in memory-related cognitive function, but the neurobiological basis for this sexual dimorphism is not understood. Here we describe sex differences in synaptic function in a brain area that is critical for learning spatial cues. Our results show that female rodents have higher synaptic levels of estrogen receptor α (ERα) and, in contrast to males, require membrane ERα for the activation of signaling kinases that support long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning. The additional requirement of estrogen signaling in females resulted in a higher threshold for both LTP and hippocampal field CA1-dependent spatial learning. These results describe a synaptic basis for sexual dimorphism in encoding spatial information.
An investigation into setting the blood flow restriction pressure based on perception of tightness

Objective: To determine whether the perceived tightness scale could be used to set sub-occlusive blood flow restriction pressures. A secondary aim was to determine variables that may impact individual ratings. Approach: One hundred and twenty participants completed three separate conditions in one limb within the upper and lower body. Participants were asked to rate their perceived tightness for two of the three conditions, regarded as moderate pressure without pain (7/10) and intense pressure with pain (10/10). A third condition, arterial occlusion pressure, was completed that required no rating from participants. Order of conditions and limb assignment were randomized for each participant. Measurements for muscle and fat thickness along with limb circumference were completed on the tested limbs. Main results: Order of conditions did not affect results in the upper or lower body. A condition effect was found for the upper body with the 7/10 rating lower than the arterial occlusion pressure [7/10: 132 (38) mmHg < Arterial Occlusion: 162 (24) mmHg < 10/10: 202 (46) mmHg]. A condition effect was also found for the lower body with 7/10 condition [120 (33) mmHg] rating lower than arterial occlusion pressure [171 (28) mmHg] and 10/10 condition [178 (49) mmHg]. However, there was a non-significant difference between the arterial occlusion pressure and the 10/10 condition (difference of 7(−3, 18) mmHg, (P = 0.159). Significance: Participants appear adept in their ability to rate sub-occlusive pressure based upon perceived tightness. Findings from this study provide some support for the utility of this method as a means for completion of practical blood flow restriction, whereby individuals tighten the cuff based upon their relative perceptual response.
A balance of deubiquitinating enzymes controls cell cycle entry

Protein degradation during the cell cycle is controlled by the opposing activities of ubiquitin ligases and deubiquitinating enzymes (DUBs). Although the functions of ubiquitin ligases in the cell cycle have been studied extensively, the roles of DUBs in this process are less well understood. Here, we used an overexpression screen to examine the specificities of each of the 21 DUBs in budding yeast for 37 cell cycle–regulated proteins. We find that DUBs up-regulate specific subsets of proteins, with five DUBs regulating the greatest number of targets. Overexpression of Ubp10 had the largest effect, stabilizing 15 targets and delaying cells in mitosis. Importantly, UBP10 deletion decreased the stability of the cell cycle regulator Dbf4, delayed the G1/S transition, and slowed proliferation. Remarkably, deletion of UBP10 together with deletion of four additional DUBs restored proliferation to near–wild-type levels. Among this group, deletion of the proteasome-associated DUB Ubp6 alone reversed the G1/S delay and restored the stability of Ubp10 targets in ubp10Δ cells. Similarly, deletion of UBP14, another DUB that promotes proteasomal activity, rescued the proliferation defect in ubp10Δ cells. Our results suggest that DUBs function through a complex genetic network in which their activities are coordinated to facilitate accurate cell cycle progression.
Mode Division Multiplexing Based on Ring Core Optical Fibers

The unique modal characteristics of ring core fibers (RCFs) potentially enable the implementation of mode-division multiplexing (MDM) schemes that can increase optical data transmission capacity with either low-complexity modular multi-input multi-output (MIMO) equalization or no MIMO equalization. This paper attempts to present a comprehensive review of recent research on the key aspects of RCF-based MDM transmission. Starting from fundamental fiber modal structures, a theoretical comparison between RCFs and conventional step-index and graded-index multi-mode fibers in terms of their MDM capacity and the associated MIMO complexity is given first as the underlining rationale behind RCF-MDM. This is followed by a discussion of RCF design considerations for achieving high-mode channel count and low crosstalk performances in either MIMO-free or modular MIMO transmission schemes. The principles and implementations of RCF mode (de-)multiplexing devices are discussed in detail, followed by RCF-based optical amplifiers culminating in MIMO-free or modular-MIMO RCF-MDM data transmission schemes. A discussion on further research directions is also given.
Morphosyntax Production of Preschool Children With Hearing Loss: An Evaluation of the Extended Optional Infinitive and Surface Accounts.

Purpose The first aim of this study was to explore differences in profiles of morphosyntax production of preschool children with hearing loss (CHL) relative to age- and language-matched comparison groups. The second aim was to explore the potential of extending 2 long-standing theoretical accounts of morphosyntax weakness in children with specific language impairment to preschool CHL. Method This study examined conversational language samples to describe the accuracy and type of inaccurate productions of Brown's grammatical morphemes in 18 preschool CHL as compared with an age-matched group (±3 months, n = 18) and a language-matched group (±1 raw score point on an expressive language subtest, n = 18). Age ranged from 45 to 62 months. Performance across groups was compared. In addition, production accuracy of CHL on morphemes that varied by tense and duration was compared to assess the validity of extending theoretical accounts of children with specific language impairment to CHL. Results CHL exhibited particular difficulty with morphosyntax relative to other aspects of language. In addition, differences across groups on accuracy and type of inaccurate productions were observed. Finally, a unified approach to explaining morphosyntax weakness in CHL was more appropriate than a linguistic- or perceptual-only approach. Conclusions Taken together, the findings of this study support a unified theoretical account of morphosyntax weakness in CHL in which both tense and duration of morphemes play a role in morphosyntax production accuracy, with a more robust role for tense than duration.
Analysis of Publication Trends for the 2011-2015 American Orthopaedic Society for Sports Medicine Annual Meeting Abstracts

Background: Academic conferences are sources of novel research that can influence clinical decision making. Orthopaedic surgery maintains a relatively high rate of publication compared with other surgical subspecialties, and sports medicine conferences hold an even higher rate within the subspecialty. The American Orthopaedic Society for Sports Medicine (AOSSM) annual meetings have been shown to have among the highest rates of publication for accepted abstracts. Purpose: To determine differences between 2-year publication rates of poster and podium abstracts accepted into the AOSSM annual meetings and identify factors associated with publication. Study Design: Cross-sectional study. Methods: The AOSSM archives were queried for all accepted poster and podium presentations for annual meetings from 2011 through 2015. Google Scholar and MEDLINE databases were used to determine which abstracts transitioned into journal articles. Publication rates were compared based on publication 2 years following presentation. Logistic regression was performed to demonstrate which variables were most correlated with successful publication. Data on publication impact factor and number of citations were collected by use of the InCites database. Results: Of 628 abstracts accepted during this period, 265 were poster presentations and 363 were podium presentations. Overall, 44.7% of abstracts presented were accepted into peer-reviewed journals within 2 years of presentation. No statistical difference was found between poster and podium presentations for journal publication (P = .328). Poster presentations were published in journals with statistically lower impact factor (P = .005) and had a statistically lower number of citations (P < .001) compared with podium presentations. Multivariate logistic regression analysis demonstrated that only number of authors was correlated with publication (P = .003). Conclusion: Podium and poster presentations accepted into AOSSM conferences had equal rates of publication within 2 years and should influence decision making equally. The relative impact of podium presentations appeared to be greater, which suggests that the AOSSM selects podium presentations that will have greater clinical impact. Increasing number of coauthors was the only factor found to be correlated with publication.
Interlaminar Shear Behavior of Laminated Carbon Fiber Reinforced Plastic from Microscale Strain Distributions Measured by Sampling Moiré Technique

In this article, the interlaminar shear behavior of a [±45°]4s laminated carbon fiber reinforced plastic (CFRP) specimen is investigated, by utilizing microscale strain mapping in a wide field of view. A three-point bending device is developed under a laser scanning microscope, and the full-field strain distributions, including normal, shear and principal strains on the cross section of CFRP, in a three-point bending test, are measured using a developed sampling Moiré technique. The microscale shear strain concentrations at interfaces between each two adjacent layers were successfully detected and found to be positive-negative alternately distributed before damage occurrence. The 45° layers slipped to the right relative to the −45° layers, visualized from the revised Moiré phases, and shear strain distributions of the angle-ply CFRP under different loads. The absolute values of the shear strain at interfaces gradually rose with the increase of the bending load, and the sudden decrease of the shear strain peak value implied the occurrence of interlaminar damage. The evolution of the shear strain concentrations is useful in the quantitative evaluation of the potential interlaminar shear failure.
Discovering Topical Interactions in Text-Based Cascades Using Hidden Markov Hawkes Processes

Social media conversations unfold based on complex interactions between users, topics and time. While recent models have been proposed to capture network strengths between users, users' topical preferences and temporal patterns between posting and response times, interaction patterns between topics has not been studied. We propose the Hidden Markov Hawkes Process (HMHP) that incorporates topical Markov Chains within Hawkes processes to jointly model topical interactions along with user-user and user-topic patterns. We propose a Gibbs sampling algorithm for HMHP that jointly infers the network strengths, diffusion paths, the topics of the posts as well as the topic-topic interactions. We show using experiments on real and semi-synthetic data that HMHP is able to generalize better and recover the network strengths, topics and diffusion paths more accurately than state-of-the-art baselines. More interestingly, HMHP finds insightful interactions between topics in real tweets which no existing model is able to do.
Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke

Although epidemiological evidence suggests significant sex and gender-based differences in stroke risk and recovery, females have been widely under-represented in preclinical stroke research. The neurovascular sequelae of brain ischemia in females, in particular, are largely uncertain. We set out to address this gap by a multimodal in vivo study of neurovascular recovery from endothelin-1 model of cortical focal-stroke in sham vs. ovariectomized female rats. Three weeks post ischemic insult, sham operated females recapitulated the phenotype previously reported in male rats in this model, of normalized resting perfusion but sustained peri-lesional cerebrovascular hyperreactivity. In contrast, ovariectomized (Ovx) females showed reduced peri-lesional resting blood flow, and elevated cerebrovascular responsivity to hypercapnia in the peri-lesional and contra-lateral cortices. Electrophysiological recordings showed an attenuation of theta to low-gamma phase-amplitude coupling in the peri-lesional tissue of Ovx animals, despite relative preservation of neuronal power. Further, this chronic stage neuronal network dysfunction was inversely correlated with serum estradiol concentration. Our pioneering data demonstrate dramatic differences in spontaneous recovery in the neurovascular unit between Ovx and Sham females in the chronic stage of stroke, underscoring the importance of considering hormonal-dependent aspects of the ischemic sequelae in the development of novel therapeutic approaches and patient recruitment in clinical trials.