Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Human CD4 D1D2 Domain in HIV-1 Infection

Broadly neutralizing antibodies and appropriate immunogens are critical for preexposure prophylaxis and therapeutic HIV vaccines. In this study, we aimed to explore effective antibodies against the genetically diverse HIV-1 strains by investigating the roles of human CD4 D1D2 domain and nonvariable immugens. The human CD4 D1D2 domain and the chimeric protein of mouse D1 domain/human D2 domain were expressed in Sf9 insect cells and purified by gel-filtration chromatography. The human CD4 D1D2 domain potently inhibited the infection of 77.8% HIV-1 pseudoviruses, including the clades AE, B’ and BC, with less than 20 μg/mL of IC50. pcDNA3.1-mhD1D2m and pcDNA3.1-mhD2m plasmids were used for the production of mouse anti-human CD4 polyclonal antibodies. The neutralizing activities of the polyclonal antibodies were determined by using pseudotyped HIV-1 viruses. The antibodies induced by plasmids containing human CD4 D1D2 domain were able to potently inhibit all pseudotyped HIV-1 strains. The antibodies from mhD1D2m-immunized mice also showed strong binding capacity to CD4 expressed on the surface of TZM-bl cells. The potent and broad inhibitory activity of antibodies against the human CD4 D1D2 domain may be used to develop effective passive immunization agent to control the spread of HIV infection.
Stages of estrous mediate the stress‐induced impairment of associative learning in the female rat

EXPOSURE to a stressful event facilitates classical eyeblink conditioning in male rats and impairs conditioning in females. The contribution of stages of estrous to the stress-induced impairment of eyeblink conditioning was evaluated. Females in proestrus, estrus and diestrus were either exposed to an acute stressor of intermittent tailshocks or swim stress and compared to unstressed females in the three stages. Females in proestrus, when estrogen levels are high, acquired the conditioned response at a facilitated rate relative to females in other stages. However, exposure to a stressor of either intermittent tailshocks or inescapable swim stress severely impaired acquisition in females during proestrus. These results suggest that the enhancing effect of estrogen on procedural memory formation is disrupted by previous exposure to a stressful event.
Surface protein‐CAT reporter fusions demonstrate differential gene expression in the wr regulon of Streptococcus pyogenes

Streptococcus pyogenes expresses at least two virulence factors, the anti‐phagocytic M protein and an inhibitor of chemotaxis, the C5a peptidase (ScpA), under control of the virR locus. To facilitate studies of this regulatory unit, we constructed a new shuttle vector with a staphylococcal chloramphenicol acetyl transferase (CAT) reporter box which replicates in S. pyogenes. We cloned polymerase chain reaction (PCR)‐derived potential promoter regions of the virR, M protein (emm12), and ScpA (scpA) genes from an M type 12 5. pyogenes, strain CS24. Promoter activity was assessed by measurements of specific mRNAs, transacetylase activity, and minimum inhibitory concentrations (MICs) for chloramphenicol resistance. We demonstrated that VirR is a necessary but not always sufficient positive trans‐acting regulator of emm12 and scpA expression; however, virR is not autoregulated. A potential virR‐bindlng consensus sequence is postulated for emm12, scpA and other M‐like protein genes. Promoter activity of the structural genes was found to be dramatically influenced by growth conditions such as anaerobiosis. Levels of control, over and above the requirement for virR, are realized. The virR and scpA promoters were mapped for the first time using primer extension analysis. The observed mRNA start sites did not completely agree within the sequence predicted start sites. Data suggest that scpA could be subject to transcription attenuation.
Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of cultured hippocampal neurons

The mitochondria in the axons and dendrites of neurons are highly motile, but the mechanism of these movements is not well understood. It has been thought that the transport of membrane‐bounded organelles in axons, and perhaps also in dendrites, depends on molecular motors of the kinesin and dynein families. However, recent evidence has suggested that some organelle transport, including that of mitochondria, may proceed along actin filaments as well. The present study sought to determine the extent to which mitochondrial movements in neurons depend on microtubule‐based and actin‐based transport systems. The mitochondria in cultured hippocampal neurons were labeled with a fluorescent dye and the cells were treated with either nocodazole, a drug that disrupts the microtubule network or cytochalasin D or latrunculin B, drugs which disrupt the actin network. The movement of the mitochondria in the axons and dendrites of neurons after each of these drug treatments was then examined with time‐lapse microscopy. Treatment with nocodazole, which depolymerizes microtubules, stopped most mitochondrial movements in both axons and dendrites. Treatment with cytochalasin D, which aggregates actin filaments, also inhibited most movements of mitochondria, but latrunculin B, which depolymerizes actin filaments, had virtually no effect. Together, these data suggest that most of the mitochondrial movements in both axons and dendrites are microtubule‐based, but in each domain there may also be some movement along actin filaments. J. Comp. Neurol. 427:351–361, 2000. © 2000 Wiley‐Liss, Inc.
Content and Rationale of Junior and Senior Preceptors Responding to Residents' Educational Needs Revisited

Theory: Feedback and debriefing, as portrayed in expertise development and self-assessment, play critical roles in providing residents with useful information to foster their progress. Hypotheses: Prior work has shown that clinical preceptors' use of conceptual frameworks (CFs; ways of thinking based on theories, best practices, or models) while giving feedback to residents was positively associated with a greater diversity of responses. Also, senior preceptors produced more responses, used more CFs, and asked more probing-challenging questions than junior preceptors. The purpose was to confirm the generalization of these initial findings with a broader and better defined sample of preceptors. Method: We conducted a mixed-method study with 20 junior and 20 senior preceptors in a controlled environment to analyze their responses and rationales to residents' educational needs as portrayed in 6 written vignettes. The preceptors were recruited from 3 primary care specialties preceptors (family medicine, internal medicine, pediatrics) of the 3 French-speaking faculties of medicine in Québec, Canada. Results: The preceptors increased the 2012 list of response topics (96 to 126) and doubled the number of distinct CFs (16 to 32). The junior and senior preceptors expressed the same number and diversity of CFs. On average, senior preceptors asked more clarification questions and reflected more than juniors on the learning process that occurs during case discussions. Preceptor specialty and prior training in medical education did not influence the number and diversity of responses and CFs, except that preceptors with prior training generated more responses per vignette and were more reflective. Senior preceptors had a stronger positive relationship between the number of total and distinct CFs and the number of responses than the juniors. Conclusions: Although senior preceptors did not give more responses or use more CFs compared to the prior study, they continue to probe residents more and reflected more. The positive relationship between responses and CFs has important implications for faculty development and calls for more research to better understand the specific contribution of CFs to feedback.
Methotrexate Treatment of Unruptured Ectopic Pregnancy: A Report of 100 Cases

In an ongoing clinical trial, 100 patients with an unruptured ectopic pregnancy of 3.5 cm or less in greatest dimension were treated with an outpatient protocol of methotrexate and citrovorum factor chemotherapy. Methotrexate and citrovorum were given on alternating days until the hCG titer had decreased by 15% on 2 consecutive days. The patients ranged in age from 16-40 years, gravidity from 1-8, and parity from 0-5. Twenty-three patients had a previous ectopic pregnancy. Of the 100 patients, 96 (96%) received methotrexate/citrovorum as primary therapy and four (4%) were treated for persistent hCG titers after a conservative surgical procedure. The tubal pregnancies of patient nos. 1-50 were confirmed by laparoscopy, whereas patient nos. 51-100 were diagnosed according to a nonlaparoscopic algorithm. Four patients of 100 failed medical therapy and required surgery. Of these, one had an ectopic pregnancy with cardiac activity, one ruptured after intercourse, and the remaining two cases had no specific identifiable risk factors. Of the ectopic pregnancies with cardiac activity, 80% were successfully treated. Five patients (5%) had methotrexaterelated side effects, all after the fourth dose, but none required treatment for these side effects. Hysterosalpingograms done on 58 patients subsequently demonstrated tubal patency in 84.5% on the involved side. To date, 37 pregnancies have occurred in this group, of which 31 (89.2%) were intrauterine and four (10.8%) were recurrent ectopic pregnancies. We conclude that methotrexate/citrovorum is safe, effective, and helps to preserve reproductive performance when used as primary therapy for unruptured ectopic pregnancy and for treatment of persistent disease following a conservative surgical procedure.
Factors associated with suicide attempts by depressed older adults: a prospective study.

OBJECTIVE This study sought to ascertain demographic, clinical, and interpersonal factors prospectively associated with suicide attempts by older adults with major depressive disorder. METHOD Elderly inpatients diagnosed as having major depressive disorder according to the Research Diagnostic Criteria were administered a structured diagnostic interview and then followed up for 1 year. Factors bearing on the interpersonal context of depression, including the emotional adjustment of patients' spouses and adult children, interpersonal strains, and relatives' concerns related to the care of their depressed family members, were also ascertained at the time of the patients' hospital admission. The elderly patients who attempted suicide during the follow-up period were compared with the nonattempters across demographic, clinical, and interpersonal factors assessed during the initial interviews. RESULTS A suicide attempt was made by 8.7% (N = 11) of the 126 elderly depressed patients within 1 year after hospital admission. Compared with the nonattempters, the attempters were of a higher socioeconomic status, evidenced more past suicide attempts and current suicidal behavior, and constituted a disproportionately large percentage of those patients who had never had a remission of their index depressive episodes. Notably, the spouses and adult children of patients who later attempted suicide evidenced more psychiatric symptoms, more strain in the relative-patient relationship, and more difficulties in caring for the patient than the relatives of nonattempters. CONCLUSIONS The findings emphasize the need for careful attention to both clinical and interpersonal factors in the assessment of suicide risk in the elderly.
Bronchiolitis: Analysis of 10 consecutive epidemic seasons

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non‐peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, “Sapienza” University of Rome over the period 2004–2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co‐infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December–January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non‐peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330–1335. © 2016 Wiley Periodicals, Inc.
Metabolic Consequences of Sustained Suppression of Free Fatty Acids by Acipimox in Patients With NIDDM

To examine whether overnight suppression of free fatty acid levels reduces hepatic glucose production, 20 NIDDM patients were given a slow-release formulation of the antilipolytic agent acipimox, in a double-blind crossover manner at bedtime for 4 wk. During acipimox treatment, serum free fatty acid concentrations were suppressed between 2400 and 0600 by 64% (P < 0.001), but no reduction in hepatic glucose production was observed (2.16 ± 0.16 vs. 2.23 ± 0.16 mg · kg−1 · min−1, acipimox vs. placebo). In contrast, from 0800 to 2000 a sustained 50% rise occurred in serum free fatty acids (P < 0.001). As a consequence, the 24-h area under the free fatty acid curve was similar during both treatment periods. In the morning, the rise in free fatty acid concentration occurred despite identical serum acipimox concentrations as those measured at midnight, when free fatty acid levels were suppressed. Although energy expenditure was higher (P < 0.05) during periods of elevated free fatty acid levels, the sums of energy expenditure measured in the morning and in the evening were similar during the acipimox and placebo periods. To exclude that the free fatty acid rise was caused by administration of acipimox only once at bedtime, additional experiments were performed administering acipimox every 2 h for 4 days. Despite similar acipimox concentration on day 1 and day 4 of this frequent dosing regimen, the free fatty acid concentrations were significantly higher on day 4 compared with day 1 (P < 0.01). In conclusion, under these circumstances overnight lowering of serum free fatty acid by antilipolytic treatment does not reduce hepatic glucose production in patients with NIDDM. Instead, it results in a sustained daytime rise in free fatty acid, leading to unchanged 24-h free fatty acid levels. This compensatory free fatty acid rise may be necessary to maintain energy production unchanged. Long-term studies are required to answer the question whether it is possible to inhibit the appearance of a major energy substrate as free fatty acid during chronic therapy in patients with NIDDM.
Predictors of the failure of treatment with chloroquine plus chlorpheniramine, in children with acute, uncomplicated, Plasmodium falciparum malaria

Abstract Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro and in vivo, by chlorpheniramine, a histamine H1 receptor antagonist. This reversal raises the possibility of using chlorpheniramine to prolong the clinical usefulness of chloroquine in resource-poor communities. The factors that identify children at risk of treatment failure after being given chloroquine plus chlorpheniramine have now been evaluated in 281 children with uncomplicated, P. falciparum malaria. The children, who had taken part in six trials of antimalarial drugs between February 1996 and September 1999, in a hyper-endemic area of south-western Nigeria, were enrolled prospectively for the present study. Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of ≤3 years (adjusted odds ratio=11.1; 95% confidence interval=2.2−55.3; P=0.003) and a parasitaemia that took >3 days to clear (adjusted odds ratio=7.9; 95% confidence interval= 1.3−49.4; P=0.027) were found to be independent predictors of treatment failure. In addition, compared with the children who had a lower axillary temperature then, the children who had an axillary temperature of ≥38°C 2 days after commencing treatment were significantly more likely to be treatment failures. In resource-poor communities using chloroquine plus chlorpheniramine, the easily identifiable predictors of treatment failure might be used to identify children requiring alternative antimalarial drugs.
Parental Influences on Students' Self-Concept, Task Value Beliefs, and Achievement in Science

The aim of this study was twofold: firstly, to investigate the grade level (elementary and middle school) and gender effect on students' motivation in science (perceived academic science self-concept and task value) and perceived family involvement, and secondly to examine the relationship among family environment variables (fathers' educational level, mothers' educational level, and perceived family involvement), motivation, gender and science achievement in elementary and middle schools. Multivariate Analysis of Variance (MANOVA) showed that elementary school students have more positive science self-concept and task value beliefs compared to middle school students. Moreover, elementary school students appeared to perceive more family involvement in their schooling. Path analyses also suggested that family involvement was directly linked to elementary school students' task value and achievement. Also, in elementary school level, significant relationships were found among father educational level, science self-concept, task value and science achievement. On the other hand, in middle school level, family involvement, father educational level, and mother educational level were positively related to students' task value which is directly linked to students' science achievement. Moreover, mother educational level contributed to science achievement through its effect on self-concept. Este estudio tenía dos objetivos: en primer lugar, investigar el efecto del curso (educación primaria y secundaria) y del género en la motivación de los alumnos en ciencias (autoconcepto académico percibido en ciencias y valor de la tarea) y la implicación percibida de la familia; y en segundo lugar, examinar la relación entre las variables del entorno familiar (nivel de estudios del padre y de la madre, implicación percibida de la familia), motivación, género y logro en ciencias en la educación primaria y media). Análisis de varianza multivariada (MANOVA) mostró que los alumnos de primaria tienen un autoconcepto en ciencias y creencias acerca del valor de la tarea más positivos que los alumnos de educación media. Además, los alumnos de primaria parecían percibir más implicación de la familia en su educación. Análisis de ruta (path analysis) también sugirió que la implicación de la familia estaba directamente relacionada con el valor de la tarea y los logros de los alumnos de primaria. Además, en el nivel de primaria, se encontraron relaciones significativas entre el nivel de estudios del padre, el autoconcepto en ciencias, el valor de la tarea y el logro en ciencias. Por otro lado, en el nivel escolar medio, la implicación de la familia y el nivel de estudios del padre y de la madre se relacionaban positivamente con el valor de tarea del alumno, que está directamente relacionado con el logro en ciencias del estudiante. Además, el nivel de estudios de la madre contribuía al logro en ciencias a través de su efecto en el autoconcepto.
Quantitative analysis of permeability for glioma grading using dynamic contrast-enhanced magnetic resonance imaging

The objective of the present study was to quantitatively analyze the permeability of tumor entity and peritumor edema in glioma grading, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In the present retrospective study, 80 patients underwent T1-weighted DCE-MRI examination at 3.0 T and the pathological results (including astrocytoma and oligodendroglioma) were obtained between January 2012 and June 2015. All cases were surgically validated as grade I–IV gliomas. The original DCE-MRI data were analyzed using dual compartment modified Tofts model. The forward volume transfer constant (Ktrans), backflux rate (kep) and fractional volume (ve) were calculated with the region of interest selected on the highest permeability area of the tumor entity and peritumor edema. Analysis of variance with the Bonferroni correction was used to compare the values of Ktrans, kep, and ve of the tumor entity and peritumor edema in different glioma grades. The results of the present study revealed that the Ktrans, kep, and ve values in each stage were associated with the pathological grading (r=0.951, 0.804 and 0.766, respectively). There were significant differences identified between different tumor grades in Ktrans, kep, with the exception being between grades II and III in kep. In addition, there was a significant difference revealed between grade I/II and grade III/IV in ve. Receiver operator characteristics curve analysis was used to evaluate the diagnosis accuracies of permeability parameters. Ktrans was demonstrated to exhibit the highest sensitivity and specificity for evaluating the tumor grade. With the threshold values of 0.160, 0.420 and 0.935 in Ktrans on tumor, glioma grades I vs. II, II vs III and III vs. IV may be differentiated with sensitivities of 0.900, 0.950 and 0.950, and specificities of 0.950, 0.950 and 0.850, respectively. Furthermore, associations were observed between the Ktrans, kep and ve values of peritumor edema and the pathological grading in glioma (Ktrans r=0.438, P<0.001; Kep r=0.385, P<0.001; Ve r=0.397, P<0.001, respectively). Ktrans values in peritumoral edema revealed significant differences between low-grade and high-grade glioma. The sensitivity and specificity for Ktrans of peritumor edema were 0.975 and 0.950, with a threshold value of 0.007. Therefore, the DCE-MRI parameters of Ktrans of tumor entity and peritumor edema in gliomas may be used to accurately differentiate glioma grades.