Miracle-dz/UniFAR-FTUs huggingface dataset:
Perfectionism, Academic Motivation, and Psychological Adjustment: An Integrative Model

The purpose of this article was to propose and test an integrative model on the role of perfectionism, academic motivation, and psychological adjustment difficulties in undergraduate students. The model posits that self-oriented perfectionism facilitates self-determined academic motivation, whereas socially prescribed perfectionism enhances non-self-determined academic motivation. In turn, self-determined and non-self-determined academic motivations, respectively, lead to lower and higher levels of psychological adjustment difficulties. Results from two studies using structural equation modeling analyses provided support for the model.
Safety of Continuous Intrathecal Midazolam Infusion in the Sheep Model

We investigated the safety of midazolam administered by continuous intrathecal infusion in relevant animal models. Preservative-free midazolam was delivered to sheep and pigs by using implanted infusion systems (SynchroMed® pumps plus silicone catheters). Sheep received midazolam 5 mg/d (n= 4) or 15 mg/d (n= 7) or saline (n= 2) for 43 days at 125 μL/h. One sheep received 10 mg/d. Infusion concentrations ranged from 1.7 to 2.5 mg/mL (5 mg/d) and from 2.5 to 5.0 mg/mL (15 mg/d). Pigs were evaluated for toxicity only and received 15 mg/d (n= 2) or saline (n= 1) for 43 days at 125 μL/h. Behavior, neurologic function, and vital signs were documented. Serum and cerebrospinal fluid chemistry and cytology were evaluated, and histology was performed on spinal cord tissue. Behavior and neurologic function remained normal in all subjects. Gross and microscopic evaluation of spinal tissue revealed mild inflammation surrounding the catheter tract in both the midazolam-treated and the saline-treated groups. This inflammation was likely attributable to the mechanical presence of the catheter. These data demonstrate that continuous intrathecal infusion of preservative-free midazolam at doses up to 15 mg/d were well tolerated.
Biodegradation of lindane, methyl parathion and carbofuran by various enriched bacterial isolates

In the present study, lindane (1,2,3,4,5,6-hexachlorocyclohexane), methyl parathion (O-dimethylO-(4-nitro-phenyl) phosphorothioate) and carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate) degradation potential of different enriched bacterial cultures were evaluated under various environmental conditions. Enriched cultures behaved differently with different pesticides. Degradation was more in a facultative anaerobic condition as compared to that in aerobic condition. A specific pesticide enriched culture showed maximum degradation of that pesticide irrespective of pesticides and environmental conditions. Lindane and endosulfan enriched cultures behaved almost similarly. Degradation of lindane by lindane enriched cultures was 75 ± 3% in aerobic co-metabolic process whereas 78 ± 5% of lindane degradation occurred in anaerobic co-metabolic process. Degradation of methyl parathion by methyl parathion enriched culture was 87 ± 1% in facultative anaerobic condition. In almost all the cases, many intermediate metabolites were observed. However, many of these metabolites disappeared after 4–6 weeks of incubation. Mixed pesticide-enriched culture degraded all the three pesticides more effectively as compared to specific pesticide- enriched cultures. It can be inferred from the results that a bacterial consortium enriched with a mixture of all the possible pesticides that are present in the site seems to be a better option for the effective bioremediation of multi-pesticide contaminated site.
Case‐Control Association Tests Correcting for Population Stratification

In case‐control association studies unobserved population stratification may act as a confounder, leading to an increased number of false positive results. Methods accounting for population structure by using additional genetic markers broadly follow one of two concepts: Genomic Control (GC) and Structured Association (SA). While extending existing methods of Structured Association we show that it is necessary to incorporate phenotypic information when inferring population structure, otherwise a systematic bias is introduced. Moreover, for moderate population stratification a Wald test statistic should be preferred as a Structured Association test statistic in comparison to a likelihood ratio test. The introduced extensions are compared to existing methods of Structured Association, as well as to Genomic Control, in a simulation study which is based on realistic situations of large case‐control studies with moderate population stratification. A disadvantage of Genomic Control turns out to be the large variation in estimating the variance inflation factor, as well as the power loss if population structure increases. We come to the overall conclusion that Structured Association, if applied correctly, is superior to Genomic Control, at least in the case of simple population structure as simulated here.
Squamous intraepithelial cervical lesions in human immunodeficiency virus-seropositive women.

OBJECTIVE To evaluate the relationship between human immunodeficiency virus (HIV) infection, CD4 serum level, cervical squamous intraepithelial lesions (SILs) and risk factors for human papillomavirus (HPV)-related dysplasia in HIV-positive women. STUDY DESIGN All 51 eligible patients who were seen at the Colposcopic Outpatient Service, Aviano Cancer Center, Aviano, Italy, from July 1, 1993, to June 30, 1994, were studied for risk factors for HPV and HIV infection and had cervical cytologic smears, colposcopy with cervical biopsy and a serum CD4 count. RESULTS Thirty of 51 patients (59%) had cytohistologically confirmed SIL. The prevalence of SIL was higher in HIV Centers for Disease Control stage IV disease than stages II and III (22/29 vs. 8/22 P < .05). There was no significant difference in the CD4 count between women with or without SIL (321 +/- 310 vs. 401 +/- 295/mm3 [mean +/- SD]). No relationship was found between CD4 count and severity of SIL (low grade SIL, 210 +/- 203/mm3; high grade SIL, 580 +/- 357/mm3). CONCLUSION In our series there was no relationship between CD4 count and cervical SIL, suggesting that the expression of HPV-related dysplasia is a complex process in which risk factors for genital SIL play an important role, while the role of HIV must be defined again.
HCV‐specific T cells in HCV/HIV co‐infection show elevated frequencies of dual Tim‐3/PD‐1 expression that correlate with liver disease progression

Co‐infection of HCV with HIV has been associated with more rapid progression of HCV‐related disease. HCV‐specific T‐cell immune responses, which are essential for disease control, are attenuated in co‐infection with HIV. T‐cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death‐1 (PD‐1) and T‐cell immunoglobulin and mucin domain‐containing molecule‐3 (Tim‐3) expression in T‐cell exhaustion during HCV/HIV co‐infection. We show that in HCV/HIV co‐infection, both total and HCV‐specific T cells co‐express Tim‐3 and PD‐1 in significantly higher frequencies, compared with HCV mono‐infection. Co‐expression of these two markers on HCV‐specific CD8+ T cells positively correlated with a clinical parameter of liver disease progression. HCV‐specific CD8+ T cells showed greater frequencies of Tim‐3/PD‐1 co‐expression than HIV‐specific CD8+ T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim‐3 or PD‐1 pathways restored both HIV‐ and HCV‐specific CD8+ T‐cell expansion in the blood of co‐infected individuals. These data demonstrate that co‐expression of Tim‐3 and PD‐1 may play a significant role in HCV‐specific T‐cell dysfunction, especially in the setting of HIV co‐infection.
Growth and nutrient intake in three- to twelve-month-old infants fed human milk or formulas with varying protein concentrations.

BACKGROUND Results on growth and nutrient intake in infants in the second half of infancy fed human milk or formulas with varying protein concentrations in combination with supplementary foods have not previously been reported. METHODS Seventy-one healthy infants were studied from 3 to 12 months of age. They were exclusively breast-fed until 3 months and were then randomly assigned to one of three feeding groups, F13, F15, or F18, indicating formulas with 13, 15 or 18 g/l of protein, respectively. Formula was gradually introduced when breast-feeding was terminated. Infants fed breast milk only were included in the breast-fed group, and those with breast milk and formula were included in the mixed-fed group. The same supplementary foods were provided to all infants. RESULTS There were no differences in growth between the feeding groups. Total protein intake exceeded minimum recommendations in all groups at all ages and was higher at 6 months in F18 than in F13 (2.3 vs. 1.9 g/kg per day; p < 0.01), whereas formula protein intake was higher at all ages in F18 compared with F13. Intake of protein from supplementary foods increased, but that from formula decreased between 6 and 12 months in all groups. CONCLUSIONS Intake of breast milk or infant formula with 13 g/l of protein along with high-protein supplementary foods provided enough protein with no adverse effect on growth. Infants fed formulas with higher protein concentrations had similar growth, despite higher intakes of formula protein.
Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta‐analysis

We conducted a meta‐analysis of randomized trials in which the effects of treatment with antidepressant medication were compared to the effects of combined pharmacotherapy and psychotherapy in adults with a diagnosed depressive or anxiety disorder. A total of 52 studies (with 3,623 patients) met inclusion criteria, 32 on depressive disorders and 21 on anxiety disorders (one on both depressive and anxiety disorders). The overall difference between pharmacotherapy and combined treatment was Hedges' g = 0.43 (95% CI: 0.31‐0.56), indicating a moderately large effect and clinically meaningful difference in favor of combined treatment, which corresponds to a number needed to treat (NNT) of 4.20. There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive‐compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment. We conclude that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression, panic disorder, and OCD. These effects remain strong and significant up to two years after treatment. Monotherapy with psychotropic medication may not constitute optimal care for common mental disorders.
Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile

To verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre‐existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congénitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre‐fortification periods (1982–1989 and 1990–2000), and from one fortified period (2001–2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre‐fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre‐fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends. © 2005 Wiley‐Liss, Inc.
Darlington Statement: Joint consensus statement from the intersex community retreat in Darlington, March 2017

More than 20 intersex advocates from Australian and Aotearoa/New Zealand intersex organisations, along with other independent activists came together at a two-day retreat in Darlington, Sydney, on 2-3 March. A year in the making, the collaborative event also led to the issuing of the "Darlington Statement”, outlining key priorities including legal reform to recognise our bodily autonomy, effective rights-based oversight of clinical decisions, alongside access to affirmative health care and the importance of peer support.
Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment

Abstract Objective: The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy. Research design and methods: A total of 493 patients of the Austrian TIGER study receiving adjuvant tamoxifen therapy were studied for this pharmacogenetic interaction. All women with estrogen receptor positive tumors and tamoxifen therapy longer than 6 months were genotyped for CYP2D6*4 using TaqMan technology. Time to tumor progression, defined as local, regional, distant recurrence or contralateral breast cancer and progression free survival, was analyzed. Results: No significant difference in time to tumor progression or progression free survival between the CYP2D6*4 genotype groups in the overall study cohort was found. In a subgroup of patients treated with chemotherapy the CYP2D6*4 poor metabolizers had a tendency towards a shorter mean time to progression. In this group the mean time to tumor progression and the progression free survival were 1.0 years in the CYP2D6*4/*4 group, 6.3 years in the *1/*4 group and 4.97 years in the *1/*1 group (Wilcoxon p = 0.104). Conclusion: While earlier data on CYP2D6 and tamoxifen excluded women with prior chemotherapy, the present analysis suggests that CYP2D6*4 genotype might be particularly crucial in this group of high-risk patients. Key limitations are restriction to the CYP2D6*4 allele and missing data of comedication.
HIV-1 amino acid changes among participants with virologic failure: associations with first-line efavirenz or atazanavir plus ritonavir and disease status.

BACKGROUND Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes. METHODS In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences. RESULTS Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes. CONCLUSIONS Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non-drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count. CLINICAL TRIALS REGISTRATION NCT00118898.
Neuroanatomy of the Human Hypothalamic Kisspeptin System

Hypothalamic kisspeptin (KP) neurons are key players in the neuronal network that regulates the onset of puberty and the pulsatile secretion of gonadotropin-releasing hormone (GnRH). In various mammalian species, the majority of KP-synthesizing neurons are concentrated in two distinct cell populations in the preoptic region and the arcuate nucleus (ARC). While studies of female rodents have provided evidence that preoptic KP neurons play a critical sex-specific role in positive estrogen feedback, KP neurons of the ARC have been implicated in negative sex steroid feedback and they have also been hypothesized to contribute to the pulse generator network which regulates episodic GnRH secretion in both females and males. Except for relatively few morphological studies available in monkeys and humans, our neuroanatomical knowledge of the hypothalamic KP systems is predominantly based on observations of laboratory species which are phylogenetically distant from the human. This review article discusses the currently available literature on the topographic distribution, network connectivity, neurochemistry, sexual dimorphism, and aging-dependent morphological plasticity of the human hypothalamic KP neuronal system.
The Transmembrane Domain of Hepatitis C Virus Glycoprotein E1 Is a Signal for Static Retention in the Endoplasmic Reticulum

ABSTRACT Hepatitis C virus (HCV) glycoproteins E1 and E2 assemble to form a noncovalent heterodimer which, in the cell, accumulates in the endoplasmic reticulum (ER). Contrary to what is observed for proteins with a KDEL or a KKXX ER-targeting signal, the ER localization of the HCV glycoprotein complex is due to a static retention in this compartment rather than to its retrieval from the cis-Golgi region. A static retention in the ER is also observed when E2 is expressed in the absence of E1 or for a chimeric protein containing the ectodomain of CD4 in fusion with the transmembrane domain (TMD) of E2. Although they do not exclude the presence of an intracellular localization signal in E1, these data do suggest that the TMD of E2 is an ER retention signal for HCV glycoprotein complex. In this study chimeric proteins containing the ectodomain of CD4 or CD8 fused to the C-terminal hydrophobic sequence of E1 were shown to be localized in the ER, indicating that the TMD of E1 is also a signal for ER localization. In addition, these chimeric proteins were not processed by Golgi enzymes, indicating that the TMD of E1 is responsible for true retention in the ER, without recycling through the Golgi apparatus. Together, these data suggest that at least two signals (TMDs of E1 and E2) are involved in ER retention of the HCV glycoprotein complex.
Acute Invasive Fungal Rhinosinusitis

Objectives To describe a 15-year single-institution experience of 41 cases of acute invasive fungal sinusitis (AIFRS), identify clinical indicators predictive of AIFRS, and discuss our approach to these high-acuity patients. Study Design Case series with chart review. Setting Tertiary referral center; The Pennsylvania State University Hershey Medical Center. Subjects and Methods A retrospective review was performed for AIFRS consultations between September 1999 and March 2014. Variables reviewed included underlying condition, presenting symptoms, absolute neutrophil count, disease extent on examination, radiographic findings, medical treatment, biopsy results, surgical treatment, and outcomes. Univariate analysis was performed to determine variables significantly associated with AIFRS. Outcome measures were assessed and patient assessment algorithm developed. Results Of 131 patients evaluated, 41 were diagnosed with AIFRS; 92.7% had an underlying hematologic malignancy. Disease predictive variables included absolute neutrophil count <500/μL (P < .0001; sensitivity = 78%), mucosal abnormalities of middle turbinate (P < .0001; specificity = 88%) and septum (P < .0001; specificity = 97%), and specifically, necrosis of the middle turbinate (P < .0001; specificity = 97%). Twenty-five AIFRS patients (61%) survived until discharge; 25% (n = 10) expired secondary to AIFRS infection explicitly. Conclusion This series represents one of the largest single-institution experiences of AIFRS published to date. Timely diagnosis is necessary to improve patient outcomes and limit morbidity. Maintaining a high index of suspicion in at-risk patient populations, followed by prompt evaluation and management, is crucial in suspected AIFRS. The presence or absence of certain findings appear to correlate with biopsy results and may aid in appropriately gauging clinical suspicion for the presence of AIFRS.
Hemodynamic Directed Cardiopulmonary Resuscitation Improves Short-Term Survival From Ventricular Fibrillation Cardiac Arrest*

Objectives:During cardiopulmonary resuscitation, adequate coronary perfusion pressure is essential for establishing return of spontaneous circulation. Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Design:Randomized interventional study. Setting:Preclinical animal laboratory. Subjects:Twenty-four 3-month-old female swine. Interventions:After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Measurements and Main Results:Forty-five–minute survival was higher in the coronary perfusion pressure-20 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p < 0.01). Total epinephrine dosing and defibrillation attempts were not different. Conclusions:Hemodynamic directed resuscitation targeting coronary perfusion pressures greater than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival, when compared to resuscitation with depth of compressions guided to 33 mm or 51 mm and standard American Heart Association vasopressor dosing.