Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and genetic spectra of Charcot‐Marie‐Tooth disease in Chinese Han patients

Charcot‐Marie‐Tooth disease (CMT) is a common hereditary motor and sensory neuropathy. Epidemiological data for Chinese CMT patients are few. This study aimed to analyze the electrophysiological and genetic characteristics of Chinese Han patients. A total of 106 unrelated patients with the clinical diagnosis of CMT were included. Clinical examination, nerve conduction studies (NCS), next‐generation sequencing (NGS), and bioinformatic analyses were performed. Genetic testing was performed for 82 patients; 27 (33%) patients carried known CMT‐associated gene mutations. PMP22 duplication was detected in 10 (12%) patients and GJB1 mutations in 9 (11%) patients. The mutation rate was higher in patients with a positive family history than in the sporadic cases (50% vs. 27%, p < 0.05). Six novel CMT‐associated gene mutations including BSCL2 (c.461C>T), LITAF (c.32C>G), MFN2 (c.497C>T), GARS (c.794C>T), NEFL (c.280C>T), and MPZ (c.440T>C) were discovered. All except the LITAF (c.32C>G) mutation were identified as “disease causing” via bioinformatic analyses. In this Chinese Han population, the frequency of PMP22 gene duplication in those with CMT1 was slightly (50% vs. 70%–80%) less than in Western/Caucasian populations. The novel CMT‐associated gene mutations broaden the mutation diversity of CMT1. NGS should be considered for genetic analyses in CMT patients.
Critical Motor Involvement in Prediction of Human and Non-biological Motion Trajectories

Abstract Objectives: Adaptive interaction with the environment requires the ability to predict both human and non-biological motion trajectories. Prior accounts of the neurocognitive basis for prediction of these two motion classes may generally be divided into those that posit that non-biological motion trajectories are predicted using the same motor planning and/or simulation mechanisms used for human actions, and those that posit distinct mechanisms for each. Using brain lesion patients and healthy controls, this study examined critical neural substrates and behavioral correlates of human and non-biological motion prediction. Methods: Twenty-seven left hemisphere stroke patients and 13 neurologically intact controls performed a visual occlusion task requiring prediction of pantomimed tool use, real tool use, and non-biological motion videos. Patients were also assessed with measures of motor strength and speed, praxis, and action recognition. Results: Prediction impairment for both human and non-biological motion was associated with limb apraxia and, weakly, with the severity of motor production deficits, but not with action recognition ability. Furthermore, impairment for human and non-biological motion prediction was equivalently associated with lesions in the left inferior parietal cortex, left dorsal frontal cortex, and the left insula. Conclusions: These data suggest that motor planning mechanisms associated with specific loci in the sensorimotor network are critical for prediction of spatiotemporal trajectory information characteristic of both human and non-biological motions. (JINS, 2017, 23, 171–184)
Bloom DNA Helicase Facilitates Homologous Recombination between Diverged Homologous Sequences*

Bloom syndrome caused by inactivation of the Bloom DNA helicase (Blm) is characterized by increases in the level of sister chromatid exchange, homologous recombination (HR) associated with cross-over. It is therefore believed that Blm works as an anti-recombinase. Meanwhile, in Drosophila, DmBlm is required specifically to promote the synthesis-dependent strand anneal (SDSA), a type of HR not associating with cross-over. However, conservation of Blm function in SDSA through higher eukaryotes has been a matter of debate. Here, we demonstrate the function of Blm in SDSA type HR in chicken DT40 B lymphocyte line, where Ig gene conversion diversifies the immunoglobulin V gene through intragenic HR between diverged homologous segments. This reaction is initiated by the activation-induced cytidine deaminase enzyme-mediated uracil formation at the V gene, which in turn converts into abasic site, presumably leading to a single strand gap. Ig gene conversion frequency was drastically reduced in BLM−/− cells. In addition, BLM−/− cells used limited donor segments harboring higher identity compared with other segments in Ig gene conversion event, suggesting that Blm can promote HR between diverged sequences. To further understand the role of Blm in HR between diverged homologous sequences, we measured the frequency of gene targeting induced by an I-SceI-endonuclease-mediated double-strand break. BLM−/− cells showed a severer defect in the gene targeting frequency as the number of heterologous sequences increased at the double-strand break site. Conversely, the overexpression of Blm, even an ATPase-defective mutant, strongly stimulated gene targeting. In summary, Blm promotes HR between diverged sequences through a novel ATPase-independent mechanism.
Interexaminer Reliability of Meibography: Upper or Lower Eyelid?

Objectives: To investigate the interexaminer reliability of meibography evaluation and the impact of eyelid selection for the procedure. Methods: Meibography images of 30 subjects' right eye, including both lids, were evaluated by three clinicians. Meibomian gland (MG) dropout was noted with respect to both percentage and grading (0–4). The examiners' (E1, E2, and E3) consistency was assessed by the intraclass correlation coefficient for MG loss percent and weighted kappa for grading. Correlations between the meibography findings and the fluorescein tear break-up time (FBUT), ocular surface disease index (OSDI) questionnaire, and noninvasive tear break-up time (NIBUT) data were also analyzed. Results: The patients' mean age was 49.2±13.4 years, and the male/female ratio distribution was 15/15. Mean FBUT was 9.6±3.1 sec. OSDI and NIBUT were not correlated with meibography findings. FBUT measurements were correlated with the MG loss assessments of all examiners for the upper lid (Spearman correlation test, E1: r=−0.617, P<0.001; E2: r=–0.428, P<0.018; E3: r=−0.429, P=0.018) but not for the lower lid. Weighted kappa statistics based on MG dropout grading revealed moderate-to-good agreement for the upper lid (E1–E2: &kgr;=0.516, P<0.001; E1−E3: &kgr;=0.621, P<0.001; E2−E3: &kgr;=0.650, P<0.001) and fair-to-moderate agreement for the lower lid (E1–E2: &kgr;=0.212; E1–E3: &kgr;=0.272; E2–E3: &kgr;=0.530). Conclusions: Meibography is an objective tool for the detection of MG loss. Because of the correlation with FBUT and better interexaminer agreement on dropout by grading, the upper lid might be the preferred lid to make an evaluation.
Modeling and rendering of quasi-homogeneous materials

Many translucent materials consist of evenly-distributed heterogeneous elements which produce a complex appearance under different lighting and viewing directions. For these quasi-homogeneous materials, existing techniques do not address how to acquire their material representations from physical samples in a way that allows arbitrary geometry models to be rendered with these materials. We propose a model for such materials that can be readily acquired from physical samples. This material model can be applied to geometric models of arbitrary shapes, and the resulting objects can be efficiently rendered without expensive subsurface light transport simulation. In developing a material model with these attributes, we capitalize on a key observation about the subsurface scattering characteristics of quasi-homogeneous materials at different scales. Locally, the non-uniformity of these materials leads to inhomogeneous subsurface scattering. For subsurface scattering on a global scale, we show that a lengthy photon path through an even distribution of heterogeneous elements statistically resembles scattering in a homogeneous medium. This observation allows us to represent and measure the global light transport within quasi-homogeneous materials as well as the transfer of light into and out of a material volume through surface mesostructures. We demonstrate our technique with results for several challenging materials that exhibit sophisticated appearance features such as transmission of back illumination through surface mesostructures.
Effects of external hard particles on brake friction characteristics during hard braking

The effects of external hard particles on the friction coefficients and its oscillation amplitudes during hard braking were investigated. Silica sands of the size between 180 to 355 μm were used during the experiments. The results were compared to the results obtained without the grit particles present in order to determine the change in friction coefficient and the fluctuation of frictional oscillation amplitude. Different sliding speeds were applied and external hard particle of different size is found to significantly affect the friction coefficient and standard deviation of friction oscillation amplitude values. The friction coefficients increase with hard particle due to the rapid changes of the effective contact area and the abrasion mode. Some embedded particles operating in two body abrasion mode help to increase the disc surface roughness and influence the stopping time of the disc. The standard deviation values of friction oscillation amplitude however were stable due to more wear debris produced and get compacted to form friction films assisting friction and they tend to reduce at medium speeds because many contact plateaus and effective contact area started to stabilize.
Primary Care Nurse Practitioner Practice Characteristics: Barriers and Opportunities for Interprofessional Teamwork

Developing team-based care models and expanding nurse practitioner (NP) workforce in primary care are recommended by policy makers to meet demand. Little is known how to promote interprofessional teamwork. Using a mixed-methods design, we analyzed qualitative interview and quantitative survey data from primary care NPs to explore practice characteristics important for teamwork. The Interprofessional Teamwork for Health and Social Care Framework guided the study. We identified NP-physician and NP-administration relationships; organizational support and governance; time and space for teamwork; and regulations and economic impact as important. Practice and policy change addressing these factors is needed for effective interprofessional teamwork.
Characterisation of Normalisation Properties for λμ using Strict Negated Intersection Types

We show characterisation results for normalisation, head-normalisation, and strong normalisation for λ μ using intersection types. We reach these results for a strict notion of type assignment for λ μ that is the natural restriction of the domain-based system of van Bakel et al. (2011) for λ μ by limiting the type inclusion relation to just intersection elimination. We show that this system respects β μ-equality, by showing both soundness and completeness results. We then define a notion of reduction on derivations that corresponds to cut-elimination, and show that this is strongly normalisable. We use this strong normalisation result to show an approximation result, and through that a characterisation of head-normalisation. Using the approximation result, we show that there is a very strong relation between the system of van Bakel et al. (2011) and ours. We then introduce a notion of type assignment that eliminates ω as an assignable type, and show, using the strong normalisation result for derivation reduction, that all terms typeable in this system are strongly normalisable as well, and show that all strongly normalisable terms are typeable. We conclude by adding type variables to our system, and show that system essentially is that of van Bakel (2010b).
Clinical relevance of a p value: Does tranexamic acid save lives after trauma or postpartum hemorrhage?

[Extract] Tranexamic acid (TXA), an antifibrinolytic agent, has been widely publicized as saving lives after traumatic hemorrhage in the CRASH-2, MSATTERs, and PER-TRAX trials (2-5) and more recently after postpartum hemorrhage (PPH) in the World Maternal Antifibrinolytic (WOMAN) trial (6). Prophylactic administration of TXA is also increasingly used in major elective and emergency surgery to reduce excessive bleeding, transfusion requirements, and possible reexploration. (7)
Assessment of the Related Factors of Blood Loss and Blood Ingredients Among Patients Under Hypotensive Anesthesia in Orthognathic Surgery

Objective: The objective of the study was to understand the factors associated with presurgical and postsurgical blood loss and blood ingredients among patients in the treatment of mandibular prognathism by intraoral vertical ramus osteotomy combined genioplasty. Methods: Preoperative and postoperative values of blood loss and blood ingredients were collected from 30 mandibular prognathic patients who underwent orthognathic surgery. The linear regression models and correlation coefficients were used to identify factors with respect to patients' blood loss level and 3 types of blood ingredients (ie, red blood cells, hemoglobin, and hematocrit). Results: The mean blood loss and operation time were 179.2 mL and 311.7 minutes, respectively. No blood transfusion was received by our patients. After adjusting for potential factors, the regression models showed that no significant factor was found to be associated with blood loss and reduce blood ingredients. Moreover, female patients were found to be more likely to have a low level of presurgical blood ingredients (&bgr; = −0.293 to −3.551; P < 0.05), whereas female sex (&bgr; = −1.606 to −4.008; P < 0.001), a high blood loss level (&bgr; = −0.003 to −0.009; P < 0.05), and long operation time (&bgr; = −0.005 to −0.018; P < 0.05) were associated with a low level of postsurgical blood ingredients (ie, hemoglobin and hematocrit). Conclusions: No significant factor was associated with blood loss and reduced blood ingredients among patients in orthognathic surgery with hypotenstive anesthesia. Improvements in anesthesia provided surgeons with more time to promote hemostasis during surgery. Hypotensive anesthesia was a well-accepted method to reduce blood loss during orthognathic surgery.
Comprehensive assessment of the arginine pathway and its relationship to inflammation in HIV

Background:Nitric oxide helps maintain vascular function and is generated through the oxidation of arginine. Whether altered arginine metabolism may lead to elevated levels of inflammation in HIV is unclear. Methods:We performed a cross-sectional analysis of HIV-infected adults on stable antiretroviral therapy with HIV-1 RNA less than 50 copies/ml and HIV-uninfected controls. We measured biomarkers in the arginine pathway, markers of systemic inflammation, and monocyte activation. T-tests, &khgr;2 tests, and propensity score matching analyses were used to compare markers by HIV status, and multiple linear regressions were used to assess associations of arginine metabolites with markers of inflammation. Results:Overall, 131 participants were enrolled (93 HIV-infected and 38 HIV-uninfected controls); 70% were men; 58% African-Americans; median age was 51 years, median absolute CD4+ was 735 cell/mm3. Lysine, arginine, citrulline, global arginine bioavailability ratio, and symmetrical dimethylarginine were different between HIV-infected and HIV-uninfected adults (P = ⩽0.02), but asymmetric dimethylarginine was not (P ≥ 0.13). Arginine biomarkers in HIV-infected, but not in HIV-uninfected controls, were associated with all measured markers of inflammation, endothelial activation, and coagulation (P ⩽ 0.05). Conclusion:HIV-infected participants on antiretroviral therapy with virologic suppression have altered plasma levels of biomarkers in the arginine pathway compared with controls. These biomarkers are independently associated with markers of inflammation and monocyte activation in HIV.
Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently‐proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA‐assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre‐central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default‐mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole‐brain scale, with ultra‐high field fMRI.
Holder-Pasteurized Human Donor Milk: How Long Can It Be Preserved?

Objective: When own mother's milk falls short, pasteurized human donor milk is recommended as alternative feeding for preterm infants. Donor milk has to meet the highest safety standards, but its processing and storage is expensive. The recommended storage time of pasteurized donor milk is 3 months. The objective of the present study was to determine whether the frozen storage time of pasteurized donor milk can be extended beyond 3 months without compromising its safety and quality. Methods: For this prospective observational study breast milk samples of 34 unique women, collected between November 2014 and June 2015, were provided by the Dutch Human Milk Bank. Samples were Holder pasteurized within 3 months after expression and stored at −20°C. Analysis of both bacterial growth (by inoculation of milk on a blood and a cysteine-, lactose-, and electrolyte-deficient agar) and fat, crude protein, carbohydrate and energy content of milk (analyzed by infrared spectroscopy) was done monthly during the first 6 months and every 2 months thereafter, up to 1 year postpasteurization. Results: Thirty of 306 (9.8%) follow-up samples showed bacterial growth when cultured. None of the samples showed sequential contamination with the same strain up to 8 months of frozen storage. No significant decreases in macronutrients and energy content were observed over 8 months. Conclusion: Pasteurized human donor milk can be stored safely for 8 months at −20°C, without compromising its macronutrient and energy content. This longer storage time will reduce disposal of expired donor milk and subsequently reduce costs.
High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome

Objectives Habitual diet plays a major role in shaping the composition of the gut microbiota, and also determines the repertoire of microbial metabolites that can influence the host. The typical Western diet corresponds to that of an omnivore; however, the Mediterranean diet (MD), common in the Western Mediterranean culture, is to date a nutritionally recommended dietary pattern that includes high-level consumption of cereals, fruit, vegetables and legumes. To investigate the potential benefits of the MD in this cross-sectional survey, we assessed the gut microbiota and metabolome in a cohort of Italian individuals in relation to their habitual diets. Design and results We retrieved daily dietary information and assessed gut microbiota and metabolome in 153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD. We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota. We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, Prevotella and some fibre-degrading Firmicutes, whose role in human gut warrants further research. Conversely, we detected higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD. Conclusions High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet. Trial registration number This study was registered at clinical trials.gov as NCT02118857.
Magnetic Resonance–Guided High-Intensity Focused Ultrasound Treatment of Locally Advanced Pancreatic Adenocarcinoma: Preliminary Experience for Pain Palliation and Local Tumor Control

PurposeThe purpose of this study was to evaluate the feasibility of magnetic resonance–guided focused ultrasound (MRgFUS) ablation for pain palliation and local tumor control in selected patients with unresectable primary pancreatic adenocarcinoma. Materials and MethodsAfter providing dedicated informed consent, 7 patients with histologically proven unresectable pancreatic adenocarcinoma underwent MRgFUS treatment on a dedicated 3-T unit featuring a dedicated ablation system. All lesions were evaluated for device accessibility before the treatment. Procedures of MRgFUS were performed with the patients under general anesthesia with constant controlled respiration. Clinical assessment included evaluation of symptom severity using a visual analog scale before and after the treatment. Imaging follow-up, including both computed tomographic and magnetic resonance examinations, was performed immediately after the treatment and at 3 and 6 months to evaluate the effects of MRgFUS on the targeted tumor and the occurrence, if any, of procedure-related complications. ResultsThe MRgFUS ablation was successfully performed in 6 patients; no adverse events were observed during or after the procedure. In a single patient, lesion accessibility was limited at treatment time, and the procedure was suspended. The visual analog scale score decreased in all patients from a mean (SD) of 7 (1) to 3 (1) after the treatment. Follow-up imaging results revealed negligible (n = 1) or no (n = 5) tumor regrowth within the ablation area. One patient died because of a metastatic disease 13 months after the treatment, whereas the other 5 are nonprogressing survivors at 6 and 8 months after the treatment. ConclusionsOur preliminary clinical experience suggests that MRgFUS is a feasible and repeatable ablative technique in selected patients with unresectable and device-accessible pancreatic adenocarcinoma.