Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterizing the impact of pressure on virus filtration processes and establishing design spaces to ensure effective parvovirus removal

Virus filtration provides robust removal of potential viral contaminants and is a critical step during the manufacture of biotherapeutic products. However, recent studies have shown that small virus removal can be impacted by low operating pressure and depressurization. To better understand the impact of these conditions and to define robust virus filtration design spaces, we conducted multivariate analyses to evaluate parvovirus removal over wide ranges of operating pressure, solution pH, and conductivity for three mAb products on Planova™ BioEX and 20N filters. Pressure ranges from 0.69 to 3.43 bar (10.0–49.7 psi) for Planova BioEX filters and from 0.50 to 1.10 bar (7.3 to 16.0 psi) for Planova 20N filters were identified as ranges over which effective removal of parvovirus is achieved for different products over wide ranges of pH and conductivity. Viral clearance at operating pressure below the robust pressure range suggests that effective parvovirus removal can be achieved at low pressure but that Minute virus of mice (MVM) logarithmic reduction value (LRV) results may be impacted by product and solution conditions. These results establish robust design spaces for Planova BioEX and 20N filters where high parvovirus clearance can be expected for most antibody products and provide further understanding of viral clearance mechanisms. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog. , 33:1294–1302, 2017
Prevalence and determinants of high-risk human papillomavirus (HPV) infection and cervical cytological abnormalities in imprisoned women

SUMMARY The aim of the study was to estimate the prevalence and risk factors associated with infection by high-risk human papillomavirus (HR-HPV) in cervix and squamous intra-epithelial lesions (SIL) in imprisoned women. This was done by a cross-sectional study of imprisoned women attending the gynaecological clinic in Foncalent prison in Alicante, Spain. The study period was from May 2003 to December 2005. HR-HPV infection was determined through Digene HPV Test, Hybrid Capture II (HC-II). HPV typing was determined by multiplex nested PCR assay combining degenerate E6/E7 consensus primers. Multiple logistic regression modelling was used for the analysis of associations between variables where some were considered possible confounders after checking for interactions. A total of 219 women were studied. HR-HPV prevalence was 27·4% and prevalence of SIL was 13·3%. HIV prevalence was 18%, higher in Spaniards than in migrant women (24·6% vs. 14·3%, P<0·05). In multivariate analyses, risk factors for HPV infection were younger age (P for trend=0·001) and tobacco use (OR 2·62, 95% CI 1·01–6·73). HPV infection (OR 4·8, 95% CI 1·7–13·8) and HIV infection were associated with SIL (OR 4·8, 95% CI 1·6–14·1). The commonest HPV types were HPV16 (29·4%), HPV18 (17·6%), HPV39 (17·6%) and HPV68 (17·6%). The prevalence of both HR-HPV infection and SIL in imprisoned women found in this study is high. Determinants for each of the outcomes studied were different. HPV infection is the most important determinant for SIL. A strong effect of HIV co-infection on the prevalence of SIL has been detected. Our findings reinforce the need to support gynaecological clinics in the prison setting.
The Effects of Biosynthetic Insulin-Like Growth Factor-1 Supplementation on Somatic Growth, Maturation, and Erythropoiesis on the Neonatal Rat

ABSTRACT: Somatomedins are anabolic hormones that may stimulate growth during the perinatal period. To test this hypothesis, neonatal rats were injected with a biosynthetic somatomedin, insulin-like growth factor 1 (IGF-1) twice daily for the first 2 wk of life. Two biosynthetic IGF-1 preparations of different potency were tested as well as a preparation of human growth hormone in five litters of rats. When compared to saline-injected rats, IGF-1 injected rats had increased body weight and tail length as well as specific increases in weights of liver, brain, heart, and testes. In addition, significant increases in bone marrow erythropoietic cell precursors were apparent after IGF-1 injection. IGF-1-treated neonatal rats also exhibited precocious eye opening as a sign of epithelial cell differentiation. Five additional litters of rats received similar injections but were exposed to postnatal nutritional deprivation via artificially increasing litter size. Although IGF-1 caused stimulation of bone marrow erythropoiesis and precocious eye opening, no effects of IGF-1 on somatic or organ growth could be documented. This represents the first demonstration in vivo of the anabolic effects of IGF-1 in rapidly growing neonatal rats but suggests that nutritional sufficiency may also be necessary for the full expression of somatomedin effects.
Main Effect and Interactions of Brain Regions and Gender in the Calculation of Volumetric Asymmetry Indices in Healthy Human Brains: Ancova Analyses of In Vivo 3T MRI Data

Introduction: Macroanatomical right‐left hemispheric differences in the brain are termed asymmetries, although there is no clear information on the global influence of gender and brain‐regions. The aim of this study was to evaluate the main effects and interactions of these variables on the measurement of volumetric asymmetry indices (VAIs). Materials and methods: Forty‐seven healthy young‐adult volunteers (23 males, 24 females) agreed to undergo brain magnetic resonance imaging in a 3T scanner. Image post processing using voxel‐based volumetry allowed the calculation of 54 VAIs from the frontal, temporal, parietal and occipital lobes, limbic system, basal ganglia, and cerebellum for each cerebral hemisphere. Multivariate ANCOVA analysis calculated the main effects and interactions on VAIs of gender and brain regions controlling the effect of age. Results: The only significant finding was the main effect of brain regions (F (6, 9373.605) 44.369, P < . 001; partial η2 = . 101, and power of 1.0), with no significant interaction between gender and brain regions (F (6, 50.517) . 239, P = . 964). Conclusion: Volumetric asymmetries are present across all brain regions, with larger values found in the limbic system and parietal lobe. The absence of a significant influence of gender and age in the evaluation of the numerous measurements generated by multivariate analyses in this study should not discourage researchers to report and interpret similar results, as this topic still deserves further assessment. Anat Rec, 296:1913–1922, 2013. © 2013 Wiley Periodicals, Inc.
A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome

Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by diverse cell populations. Studies in mice suggest that the cellular source of IL-10 is a key determinant in various disease pathologies, yet little is known regarding the control of tissue-specific human IL-10 expression. To assess cell type-specific human IL-10 regulation, we created a human IL-10 transgenic mouse with a bacterial artificial chromosome (hIL10BAC) in which the IL10 gene is positioned centrally. Since human IL-10 is biologically active in the mouse, we could examine the in vivo capacity of tissue-specific human IL-10 expression to recapitulate IL-10-dependent phenotypes by reconstituting Il10−/− mice (Il10−/−/hIL10BAC). In response to LPS, Il10−/−/hIL10BAC mice proficiently regulate IL-10-target genes and normalize sensitivity to LPS toxicity via faithful human IL-10 expression from macrophages and dendritic cells. However, in the Leishmania donovani model of pathogen persistence, Il10−/−/hIL10BAC mice did not develop the characteristic IL-10+IFN-γ+CD4 T cell subset thought to mediate persistence and, like Il10−/− mice, cleared the parasites. Furthermore, the IL-10-promoting cytokine IL-27 failed to regulate transgenic human IL-10 production in CD4+ T cells in vitro which together suggests that the hIL10BAC encodes for weak T cell-specific IL-10 expression. Thus, the hIL10BAC mouse is a model of human gene structure and function revealing tissue-specific regulatory requirements for IL-10 expression which impacts disease outcomes.
Bimodal hearing and speech perception with a competing talker.

PURPOSE The objective of the study was to investigate the influence of bimodal stimulation upon hearing ability for speech recognition in the presence of a single competing talker. METHOD Speech recognition was measured in 3 listening conditions: hearing aid (HA) alone, cochlear implant (CI) alone, and both devices together (CI + HA). To examine the use of low-frequency cues, the competing masker voice was manipulated with respect to fundamental frequency (F0) and formant frequencies. Twelve implanted adults were included in the study. RESULTS Group results revealed only a relatively small benefit of CI + HA compared with the CI alone. A detailed analysis of errors, which was assumed to be an indicator for the release from masking, revealed that this benefit was not attributed to improved target-masker segregation. The variable determined to be responsible for segregating target and masker talkers was a large difference in F0 of the voices. This held true for all CI alone, HA alone, and CI + HA listening conditions. CONCLUSIONS Bimodal hearing improved overall speech recognition of both the target and the masker. No evidence for better target-masker separation with bimodal fitting could be found.
Involvement of Caspase-9 in the Inhibition of Necrosis of RAW 264 Cells Infected with Mycobacterium tuberculosis

ABSTRACT In order to know how caspases contribute to the intracellular fate of Mycobacterium tuberculosis and host cell death in the infected macrophages, we examined the effect of benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethane (z-VAD-fmk), a broad-spectrum caspase inhibitor, on the growth of M. tuberculosis H37Rv in RAW 264 cells. In the cells treated with z-VAD-fmk, activation of caspase-8, caspase-3/7, and caspase-9 was clearly suppressed, and DNA fragmentation of the infected cells was also reduced. Under this experimental condition, it was found that the treatment markedly inhibited bacterial growth inside macrophages. The infected cells appeared to undergo cell death of the necrosis type in the presence of z-VAD-fmk. We further found that z-VAD-fmk treatment resulted in the generation of intracellular reactive oxygen species (ROS) in the infected cells. By addition of a scavenger of ROS, the host cell necrosis was inhibited and the intracellular growth of H37Rv was significantly restored. Among inhibitors specific for each caspase, only the caspase-9-specific inhibitor enhanced the generation of ROS and induced necrosis of the infected cells. Furthermore, we found that severe necrosis was induced by infection with H37Rv but not H37Ra in the presence of z-VAD-fmk. Caspase-9 activation was also detected in H37Rv-infected cells, but H37Ra never induced such caspase-9 activation. These results indicated that caspase-9, which was activated by infection with virulent M. tuberculosis, contributed to the inhibition of necrosis of the infected host cells, presumably through suppression of intracellular ROS generation.
Conjugate ocular oscillations during shifts of the direction and depth of visual fixation.

PURPOSE To characterize dynamic properties of combined saccade-vergence eye movements that occur as the point of visual fixation is shifted between objects lying in different directions and at different depths. METHODS Using the scleral search-coil technique, eye movements were measured in 10 normal subjects as they made voluntary, disjunctive gaze shifts comprising a range of saccades and vergence movements. RESULTS By analyzing eye acceleration records, the authors identified small-amplitude (0.2-0.7 degrees), high-frequency (23-33 Hz), conjugate horizontal oscillations of the eyes during the vergence movement that followed the initial saccade. When the shift of the fixation point required a large vergence component (17 degrees , every subject showed these oscillations; they were present in approximately a third of responses. Approximately 5% of responses showed oscillations that had horizontal and vertical components. Oscillations were less prominent with shifts that had smaller vergence components and were absent after saccades made between targets located at optical infinity. CONCLUSIONS These findings suggest that a common mechanism gates both the saccadic and vergence components of disjunctive gaze shifts, a likely candidate being the pontine omnipause neurons. When a saccade is immediately followed by a prolonged vergence movement, the omnipause neurons remain silent, leading to small-amplitude saccadic oscillations. Shifts in the point of visual fixation that require a large vergence movement may be a useful experimental strategy to induce saccadic oscillations.
Asymmetric Dimethyloarginin (ADMA) Concentration in the Aqueous Humor of Patients with Exfoliation Syndrome or Exfoliative Glaucoma

Abstract Background: Asymmetric dimethyloarginin or dimethylarginin (ADMA) is a marker and maker of oxidative stress. It is elevated in several pathological conditions, such as hyperhomocysteinemia and endothelial dysfunction, which have also been reported in patients with exfoliation syndrome (XFS), or exfoliative glaucoma (XFG). We evaluated ADMA levels in the aqueous humor of XFS and XFG patients. Methods: This study included 48 aqueous samples; 16 from cataract patients with XFS, 16 from cataract patients with XFG and 16 from age-matched cataract control patients. ADMA levels were determined employing a commercial ELISA kit. Results: ADMA concentration was significantly greater in XFG patients (0.398 ± 0.026 μM) compared to either XFS (0.168 ± 0.028 μM; p < 0.0001) or normal cataract controls (0.245 ± 0.025 μM; p = 0.0002). In contrast, no significant difference was detected for ADMA levels in the aqueous of XFS patients as compared to normal controls (p = 0.0477). Conclusions: Aqueous humor ADMA concentration is significantly elevated in XFG patients supporting the view that oxidative stress plays a key role in XFG pathobiology. The lower level of this marker in XFS suggests that the development of XFG is a prerequisite for ADMA elevation.
Does Psychological Safety Impact the Clinical Learning Environment for Resident Physicians? Results From the VA's Learners' Perceptions Survey.

BACKGROUND Psychological safety (PS) is the perception that it is safe to take interpersonal risks in the work environment. In teaching hospitals, PS may influence the clinical learning environment for trainees. OBJECTIVE We assessed whether resident physicians believe they are psychologically safe, and if PS is associated with how they rate satisfaction with their clinical learning experience. METHODS Data were extracted from the Learners' Perceptions Survey (LPS) of residents who rotated through a Department of Veterans Affairs health care facility for academic years 2011-2014. Predictors of PS and its association with resident satisfaction were adjusted to account for confounding and response rate biases using generalized linear models. RESULTS The 13 044 respondents who completed the LPS (30% response rate) were comparable to nonpediatric, non-obstetrics-gynecology residents enrolled in US residency programs. Among respondents, 11 599 (89%) agreed that ". members of the clinical team of which I was part are able to bring up problems and tough issues. " Residents were more likely to report PS if they were male, were in a less complex clinical facility, in an other medicine or psychiatry specialty, or cared for patients who were aged, had multiple illnesses, or had social supports. Nonpsychiatric residents felt safer when treating patients with no concurrent mental health diagnoses. PS was strongly associated with how residents rated their satisfaction across 4 domains of their clinical learning experience (P < .001). CONCLUSIONS PS appears to be an important factor in resident satisfaction across 4 domains that evaluators of graduate medical education programs should consider when assessing clinical learning experiences.
Apparently "low" serum asymmetric dimethylarginine is associated with fasting glucose and tends toward association with type-2 diabetes.

OBJECTIVE We investigated the association of serum asymmetric dimethylarginine (ADMA) with metabolic syndrome (MetS), type-2 diabetes and coronary heart disease (CHD) in the general population. METHODS Cross-sectional and, at 2000 person-years' follow-up, prospective analysis. Adults with measured serum ADMA level (n=848) were analyzed using tertiles or dichotomized values. ADMA concentrations were measured by a validated commercial ELISA kit. RESULTS Dichotomized subjects of combined sexes with low (≤0.68 µmol/L) ADMA values had significantly higher fasting glucose, total cholesterol, apolipoprotein B and lower diastolic blood pressure. In linear regression analyses comprising age, smoking, triglyceride, HDL-cholesterol, C-reactive protein and waist circumference as well, creatinine was significantly and independently associated with ADMA, further in women glucose (inversely). In logistic regression analyses uniformly adjusted for age, smoking status and waist girth, prevalent MetS tended to positive independent association with ADMA tertiles only in men. Combined prevalent and incident diabetes weakly tended to be associated with the lowest (vs mid- and highest) ADMA tertiles in combined gender; and prevalent and incident CHD was not associated with ADMA tertiles in either sex. CONCLUSION Apparently "low" circulating ADMA is independently associated with fasting glucose and tends to be so with type-2 diabetes. The lack of anticipated positive associations of ADMA with cardiometabolic disorders is likely due to autoimmune responses operating against serum ADMA under oxidative stress, rendering partial failure in immunoassay.
Psychophysiological Changes during Pure vs Guided Mirror Exposure Therapies in Women with High Body Dissatisfaction: What Are They Learning about Their Bodies?

This study aimed to examine the psychophysiological changes resulting from two mirror exposure treatments that are effective at reducing body dissatisfaction. Thirty-five university women with body dissatisfaction and subclinical eating disorders were randomly assigned to one of two groups: pure (n = 17) or guided exposure (n = 18). The participants received six sessions of treatment. Their thoughts, feelings and avoidance behaviours were assessed after each session. Their subjective discomfort, heart rate and skin conductance were assessed within the sessions. Both groups showed improvement in cognitive-affective and avoidance behaviour symptoms. Nevertheless, the pure exposure group showed faster habituation of subjective discomfort and a greater physiological response than the guided exposure group. These findings suggest that both procedures are effective interventions for improving body image disturbances, although psychophysiological changes observed within session suggest that each technique would act through different processes. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Somatization: a spectrum of severity.

OBJECTIVE The DSM-III-R diagnosis of somatization disorder requires that a patient have a specific number of medically unexplained somatic symptoms. This number of symptoms was developed by committee consensus, and it is not clear whether patients with this specific number of symptoms can be differentiated from patients with lower but still substantial numbers of somatic symptoms. METHOD Fifty-one percent of 767 high utilizers of two primary care clinics were identified as distressed by an elevated SCL anxiety, depression, or somatization scale score or by their primary care physician. The Diagnostic Interview Schedule (DIS) was completed on 119 distressed high utilizers who were randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The 119 distressed high utilizers were separated into four categories according to the number of unexplained somatic symptoms found on the DIS and were compared on demographic, psychiatric distress, disability, medical, and health utilization variables. RESULTS The data suggest that many clinical and behavioral features of somatization are significantly more common in patients with four to 12 medically unexplained somatic symptoms rather than changing dramatically at the diagnostic threshold for somatization disorder. The data also showed that patients who meet the DSM-III-R criteria for somatization disorder are severely ill and have a high burden of psychiatric illness and disability. CONCLUSIONS The results suggest that the DSM-IV somatoform disorders section should include somatization disorder, an abridged definition of somatization disorder often associated with anxiety and depression, as well as a type of somatization associated with an adjustment disorder.
V(D)J recombination: signal and coding joint resolution are uncoupled and depend on parallel synapsis of the sites

V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations.