Miracle-dz/UniFAR-FTUs huggingface dataset:
Axonal sensory motor neuropathy in copper‐deficient Wilson's disease

Copper deficiency may cause myeloneuropathy or progressive limb weakness. By contrast, Wilson's disease (WD) is characterized by progressive copper accumulation with hepatic and neurological impairment and requires life‐long treatment with zinc and/or chelator agents. We report a WD patient who developed axonal sensory motor neuropathy in the context of copper deficiency due to his treatment with zinc and chelators. Exhaustive testing for other etiologies was negative. After treatment adjustment, only mild clinical improvement was noted during long‐term follow‐up. Muscle Nerve 40: 294–296, 2009
Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial

This trial was designed to compare the efficacy and safety between epirubicin (E) and carboplatin (C) in combination with paclitaxel (P) and trastuzumab (H) in neoadjuvant setting. In 13 Chinese cancer centers, 100 patients with HER2-positive, locally advanced breast cancer were 1:1 randomized to receive medication as follows: trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group, or epirubicin every 3 weeks for PEH group. Patients were given 4 to 6 cycles of chemotherapy. The primary endpoint was pathologic complete response (pCR) rate, which was no significant difference in PCH and PEH regimen (39.1% vs. 48.8%; p=0.365). However, PEH regimen achieved higher pCR in luminal-B (HER2-poitive) subgroup (55.0% vs. 24.0%; p = 0.033), but not in ERBB2+ subgroup (42.9% vs. 57.1%; p = 0.355). PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup (69.2% vs.23.5%, p=0.012). No significant difference was observed in the subgroup analysis of TP53 mutation status, PTEN expression, FCGR2A SNP and FCGR3A SNP. Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety. PEH might improve pCR rate, especially in the luminal-B subtype and PIK3CA mutation subtype. PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH.
Characterization of a pH-dependent chromophore from nutritionally variant streptococci

Strains of nutritionally variant streptococci and Streptococcus mitis produce a chromophore when they are heated at acid pH. No other strains of streptococci elaborated this chromophore. Furthermore, the nutritionally variant streptococci produced approximately twice the amount of chromophore as the S. mitis strains. The chromophore was localized in the cell wall of these streptococcal strains and appeared to be resistant to trypsin treatment. Hydrolysis apparently is required because elevated temperatures at pH 2 are necessary for demonstration of the chromophore. The chromophore has a maximal absorbance at 504 nm with a pKa of 3.6. The chromophore absorbance spectrum showed an isosbestic point at 400 nm. This is the first example of a pH-dependent chromophore to be found in streptococci and serves as a positive characteristic for the description of nutritionally variant streptococci as well as S. mitis.
Comparative study of multiple dosage of quercetin against cisplatin- induced nephrotoxicity and oxidative stress in rat kidneys

Quercetin, a typical bioflavonoid ubiquitously present in fruits and vegetables, is considered to be helpful for human health. Cisplatin (cDDP) is one of the most active cytotoxic agents in the treatment of a wide range of solid tumors. The aim of this study was to investigate the possible effect of quercetin, a bioflavonoid with antioxidant potential, on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Gavage administrations of water, propylene glycol and quercetin (50 mg/kg) were made 24 and 1 h before saline or cDDP (5 mg/kg) ip injections and were repeated daily for 2, 5 or 20 subsequent days. Rats were killed 2, 5 and 20 days after ip injections, and blood and urine samples were collected to determine plasma creatinine, urine volume and osmolality. The kidneys were removed to determine the levels of thiobarbituric acid-reactive substances (TBARS) and for histological studies. Cisplatin increased lipid peroxidation, urine volume and plasma creatinine levels and decreased urine osmolality. Treatment with quercetin attenuated these alterations. These results demonstrate the role of oxidative stress and suggest a protective effect of quercetin on cisplatin-induced nephrotoxicity in adult Wistar rats.
COLEC10 is mutated in 3MC patients and regulates early craniofacial development

3MC syndrome is an autosomal recessive heterogeneous disorder with features linked to developmental abnormalities. The main features include facial dysmorphism, craniosynostosis and cleft lip/palate; skeletal structures derived from cranial neural crest cells (cNCC). We previously reported that lectin complement pathway genes COLEC11 and MASP1/3 are mutated in 3MC syndrome patients. Here we define a new gene, COLEC10, also mutated in 3MC families and present novel mutations in COLEC11 and MASP1/3 genes in a further five families. The protein products of COLEC11 and COLEC10, CL-K1 and CL-L1 respectively, form heteromeric complexes. We show COLEC10 is expressed in the base membrane of the palate during murine embryo development. We demonstrate how mutations in COLEC10 (c.25C>T; p.Arg9Ter, c.226delA; p.Gly77Glufs*66 and c.528C>G p.Cys176Trp) impair the expression and/or secretion of CL-L1 highlighting their pathogenicity. Together, these findings provide further evidence linking the lectin complement pathway and complement factors COLEC11 and COLEC10 to morphogenesis of craniofacial structures and 3MC etiology.
The schizophrenias, the neuroses and the covered wagon; a critical review

Objective In order to compare their validity, this review applies scientific standards for sustaining the neuroses, the schizophrenias and bipolar disorders as separate “bona-fide” psychiatric diseases. The standards for disease validation demand specific and unique symptoms. Method We review a wide variety of clinical and basic science comparisons between schizophrenia and psychotic bipolar in a select English-language literature. Results Like covered wagons, the neuroses once served us well but became obsolete and were discarded or reorganized based on what was known about commonalities of symptoms, causation and pharmacological responsivity. Bipolar patients meet unique and specific diagnostic criteria and demonstrate consistent results across a variety of scientific disciplines. Neither the neuroses nor the schizophrenias have such unique or disease specific diagnostic criteria. Psychotic mood disorders account for the DSM diagnostic criteria for schizophrenia. A recent, selected but diverse basic science literature demonstrates surprising similarities between schizophrenia and psychotic bipolar which should not exist if these disorders are distinct. Conclusions Like the neuroses, there is stigma, confusion and misunderstanding about the condition called schizophrenia, resulting in substantial negative impact on bipolar patients misdiagnosed as having schizophrenia. The psychoses, including the schizophrenias, likely are explained by a single disease, psychotic bipolar disorder, that has demonstrated a wide spectrum of severity of symptoms and chronicity of course, not traditionally recognized.
Novel PtdIns(3)P-binding protein Etf1 functions as an effector of the Vps34 PtdIns 3-kinase in autophagy

Autophagy is the process whereby cytoplasmic cargo (e.g., protein and organelles) are sequestered within a double membrane–enclosed transport vesicle and degraded after vesicle fusion with the vacuole/lysosome. Current evidence suggests that the Vps34 phosphatidylinositol 3-kinase is essential for macroautophagy, a starvation-induced autophagy pathway (Kihara et al., 2001). Here, we characterize a requirement for Vps34 in constitutive autophagy by the cytoplasm-to-vacuole targeting (Cvt) pathway. First, we show that transient disruption of phosphatidylinositol (PtdIns) 3-phosphate (PtdIns[3]P) synthesis through inactivation of temperature-sensitive Vps34 or its upstream activator, Vps15, blocks the Cvt and macroautophagy pathways. Yet, PtdIns(3)P-binding FYVE domain-containing proteins, which mediate carboxypeptidase Y (CPY) transport to the vacuole by the CPY pathway, do not account for the requirement of Vps34 in autophagy. Using a genetic selection designed to isolate PtdIns(3)P-binding effectors of Vps34, we identify Etf1, an uncharacterized type II transmembrane protein. Although Etf1 does not contain a known 3-phosphoinositide–binding domain (i.e., FYVE or Phox), we find that Etf1 interacts with PtdIns(3)P and that this interaction requires a basic amino acid motif (KKPAKK) within the cytosolic region of the protein. Moreover, deletion of ETF1 or mutation of the KKPAKK motif results in strong sorting defects in the Cvt pathway but not in macroautophagy or in CPY sorting. We propose that Vps34 regulates the CPY, Cvt, and macroautophagy pathways through distinct sets of PtdIns(3)P-binding effectors and that Vps34 promotes protein trafficking in the Cvt pathway through activation/localization of the effector protein Etf1.
Weighted Krippendorff’s alpha is a more reliable metrics for multi-coders ordinal annotations: experimental studies on emotion, opinion and coreference annotation

The question of data reliability is of first importance to assess the quality of manually annotated corpora. Although Cohen ' s κ is the prevailing reliability measure used in NLP, alternative statistics have been proposed. This paper presents an experimental study with four measures (Cohen's κ, Scott's π, binary and weighted Krippendorff ' s α) on three tasks: emotion, opinion and coreference annotation. The reported studies investigate the factors of influence (annotator bias, category prevalence, number of coders, number of categories) that should affect reliability estimation. Results show that the use of a weighted measure re- stricts this influence on ordinal annotations. They suggest that weighted α is the most reliable metrics for such an annotation scheme.
On the asymptotic behavior of the spectral density of autoregressive estimates

The problem of estimating discrete time stochastic processes by autoregressive (AR) models is encountered in many applications. The present paper explores the asymptotic behavior of the spectral density of such approximations. It is shown that under certain assumptions on the spectral density and the covariance sequence of the original process, the spectral density of the approximating autoregressive sequence converges at the origin. Under additional mild conditions it is also shown that the spectral density of the autoregressive approximation converges in L2 as the order of approximation increases.
The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis.

BACKGROUND AND OBJECTIVE ABO blood types are determined by antigen modifications on glycoproteins and glycolipids and associated with altered plasma levels of inflammatory and endothelial injury markers implicated in AKI pathogenesis. We sought to determine the association of ABO blood types with AKI risk in critically ill patients with trauma or sepsis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted two prospective cohort studies at an urban, academic, level I trauma center and tertiary referral center; 497 patients with trauma admitted to the surgical intensive care unit between 2005 and 2010 with an injury severity score >15 and 759 patients with severe sepsis admitted to the medical intensive care unit between 2008 and 2013 were followed for 6 days for the development of incident AKI. AKI was defined by Acute Kidney Injury Network creatinine and dialysis criteria. RESULTS Of 497 patients with trauma, 134 developed AKI (27%). In multivariable analysis, blood type A was associated with higher AKI risk relative to type O among patients of European descent (n=229; adjusted risk, 0.28 versus 0.14; risk difference, 0.14; 95% confidence interval, 0.03 to 0.24; P=0.02). Of 759 patients with sepsis, AKI developed in 326 (43%). Blood type A again conferred higher AKI risk relative to type O among patients of European descent (n=437; adjusted risk, 0.53 versus 0.40; risk difference, 0.14; 95% confidence interval, 0.04 to 0.23; P=0.01). Findings were similar when analysis was restricted to those patients who did not develop acute respiratory distress syndrome or were not transfused. We did not detect a significant association between blood type and AKI risk among individuals of African descent in either cohort. CONCLUSIONS Blood type A is independently associated with AKI risk in critically ill patients with trauma or severe sepsis of European descent, suggesting a role for ABO glycans in AKI susceptibility.
Novel asymmetrically engineered antibody Fc variant with superior FcγR binding affinity and specificity compared with afucosylated Fc variant

Fc engineering is a promising approach to enhance the antitumor efficacy of monoclonal antibodies (mAbs) through antibody-dependent cell-mediated cytotoxicity (ADCC). Glyco- and protein-Fc engineering have been employed to enhance FcγR binding and ADCC activity of mAbs; the drawbacks of previous approaches lie in their binding affinity to both FcγRIIIa allotypes, the ratio of activating FcγR binding to inhibitory FcγR binding (A/I ratio) or the melting temperature (TM) of the CH2 domain. To date, no engineered Fc variant has been reported that satisfies all these points. Herein, we present a novel Fc engineering approach that introduces different substitutions in each Fc domain asymmetrically, conferring optimal binding affinity to FcγR and specificity to the activating FcγR without impairing the stability. We successfully designed an asymmetric Fc variant with the highest binding affinity for both FcγRIIIa allotypes and the highest A/I ratio compared with previously reported symmetrically engineered Fc variants, and superior or at least comparable in vitro ADCC activity compared with afucosylated Fc variants. In addition, the asymmetric Fc engineering approach offered higher stability by minimizing the use of substitutions that reduce the TM of the CH2 domain compared with the symmetric approach. These results demonstrate that the asymmetric Fc engineering platform provides best-in-class effector function for therapeutic antibodies against tumor antigens.
16.3 BASELINE CLIMATOLOGY OF SOUNDING DERIVED PARAMETERS ASSOCIATED WITH DEEP, MOIST CONVECTION

A baseline climatology of several parameters commonly used to forecast deep, moist convection is developed using an extensive sample of upper-air observations. Previous climatologies often contain a limited number of cases or do not include null cases, which limit their forecast utility. Three years of evening (0000 UTC) rawinsonde data (approximately 60,000 soundings) from the lower 48 United States are evaluated. Cloud-to-ground lightning data and severe weather reports from Storm Data are used to categorize soundings as representative of conditions for no thunder, general thunder, severe, significant hail / wind, or significant tornado. Among the detailed calculations are comparisons between both convective available potential energy (CAPE) and lifted condensation level (LCL) using a most unstable parcel versus a mean lifted 100-hPa parcel. Lapse rates for several different layers are inspected to determine the utility of using static stability versus CAPE to forecast storm severity. Lastly, low-level shear is studied in an attempt to distinguish between severe and significant tornado episodes. One of the major findings is a considerable difference between 0-1 km above ground level (AGL) magnitude of vector difference of wind for significant tornado episodes versus the other five categories. Statistically significant differences are also noted between LCL / mean lifted LCL (MLLCL) heights AGL for significant tornado events and the other convective categories. In addition, much less seasonal variation is found for 0-1 km shear, 0-6 km shear, and MLLCL heights AGL for significant tornado events compared with the remainder of the data set.
U.S. Army Physical Demands Study: Reliability of Simulations of Physically Demanding Tasks Performed by Combat Arms Soldiers

Abstract Foulis, SA, Redmond, JE, Frykman, PN, Warr, BJ, Zambraski, EJ, and Sharp, MA. U.S. Army physical demands study: reliability of simulations of physically demanding tasks performed by combat arms soldiers. J Strength Cond Res 31(12): 3245–3252, 2017—Recently, the U.S. Army has mandated that soldiers must successfully complete the physically demanding tasks of their job to graduate from their Initial Military Training. Evaluating individual soldiers in the field is difficult; however, simulations of these tasks may aid in the assessment of soldiers' abilities. The purpose of this study was to determine the reliability of simulated physical soldiering tasks relevant to combat arms soldiers. Three cohorts of ∼50 soldiers repeated a subset of 8 simulated tasks 4 times over 2 weeks. Simulations included: sandbag carry, casualty drag, and casualty evacuation from a vehicle turret, move under direct fire, stow ammunition on a tank, load the main gun of a tank, transferring ammunition with a field artillery supply vehicle, and a 4-mile foot march. Reliability was assessed using intraclass correlation coefficients (ICCs), standard errors of measurement (SEMs), and 95% limits of agreement. Performance of the casualty drag and foot march did not improve across trials (p > 0.05), whereas improvements, suggestive of learning effects, were observed on the remaining 6 tasks (p ⩽ 0.05). The ICCs ranged from 0.76 to 0.96, and the SEMs ranged from 3 to 16% of the mean. These 8 simulated tasks show high reliability. Given proper practice, they are suitable for evaluating the ability of Combat Arms Soldiers to complete the physical requirements of their jobs.
Endothelin Receptor Antagonists for Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Update

Background and Purpose— Endothelin is considered to be a key mediator of vasospasm after subarachnoid hemorrhage. A meta-analysis of randomized trials on the effectiveness of endothelin receptor antagonists in subarachnoid hemorrhage has been published previously, but since then new major trials have been published. We present the results of a systematic review and meta-analysis update. Methods— We searched the Cochrane Library, the Cochrane Central Register of Controlled Trials, and PubMed with the following terms: subarachnoid hemorrhage AND (endothelin receptor antagonist OR clazosentan OR TAK-044 OR bosentan). All randomized, placebo-controlled trials investigating the effect of any endothelin receptor antagonists in patients with subarachnoid hemorrhage were included. Primary outcome was poor functional outcome (defined as death or dependency). Secondary outcomes were vasospasm, cerebral infarction as defined by investigators, and case fatality during follow-up. Data were pooled and effect sizes were expressed as risk ratio (RR) estimates with 95% confidence intervals (CI). We also calculated RR for several common complications. Results— In 5 trials with 2601 patients, endothelin receptor antagonists tended to increase the risk of poor functional outcome (RR, 1.12; 95% CI, 0.97–1.28) despite a decreased incidence of angiographic vasospasm (RR, 0.58; 95% CI, 0.48–0.71). No effect was observed on vasospasm-related cerebral infarction (RR, 0.76; 95% CI, 0.53–1.11), any new cerebral infarction (RR, 1.04; 95% CI, 0.91–1.19), or case-fatality (RR, 1.04; 95% CI, 0.78–1.39). Endothelin receptor antagonists increased the risk of lung complications (RR, 1.79; 95% CI, 1.52–2.11), pulmonary edema (RR, 2.12; 95% CI, 1.32–3.39), hypotension (RR, 2.42; 95% CI, 1.78–3.29), and anemia (RR, 1.47; 95% CI,1.19–1.83). Conclusion— These results argue against the use of endothelin receptor antagonists in patients with subarachnoid hemorrhage.
Orientation of cultured arterial smooth muscle cells growing on cyclically stretched substrates.

Arterial smooth muscle cells from rabbit aortic media were grown in first subcultures on hydrophilized and collagen-coated silicone membranes which were then subjected to directional cyclic stretches and relaxations at a frequency of 50 times/min. The membranes were stretched 2, 5 and 10% beyond their resting length. Cells on unstretched and stationary membranes in the same chamber served as controls. The cells which were stretched with an amplitude of 2% remained in random orientation after 14 days of continuously performed cyclic stretching. The cells which were stretched 5% for 12 days orientated at an angle of 61 +/- 9 degrees to the direction of stretching, while the cells which were stretched with an amplitude of 10% for 6 days orientated at an angle of 76 +/- 5 degrees. The cells on the stationary and unstretched membranes remained in random orientation. We were able to confirm that the angle of orientation is reversible, i.e. preorientated cells changed their orientation during application of another stretching amplitude. The results suggest that stretching of the artery wall by blood pulsation may be a factor influencing the orientation of smooth muscle cells within the media of the artery wall and of those smooth muscle cells which proliferate into the subendothelial space after mechanical injury of the endothelium or electrical stimulation of the artery wall. An apparatus is presented which produces cyclic and directional mechanical stimuli similar to those which may occur in the artery wall.
Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia

Background Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors. Aims To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness. Method Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart. Results Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss. Conclusions Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.