Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathology of hypersensitivity pneumonitis

Purpose of review Hypersensitity pneumonitis, caused by inhalation of various antigens, is characterized by interstitial mononuclear cell infiltration, nonnecrotizing granulomas, cellular bronchiolitis, and fibrosis. The pathological picture of chronic hypersensitivity pneumonitis is, however, complicated; it is sometimes difficult to differentiate chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia, nonspecific interstitial pneumonia, and connective-tissue-related lung disease. The clinical, radiological, and pathological features of chronic hypersensitivity pneumonitis have recently been described. This study reviews the previously reported information and provides new insights into the pathological features of chronic hypersensitivity pneumonitis. Recent findings The pathological features of chronic hypersensitivity pneumonitis comprise overlapping usual interstitial pneumonia-like pattern with subpleural patchy fibrosis, alternating normal alveoli and fibroblastic foci, a nonspecific interstitial pneumonia-like pattern, and centrilobular fibrosis. In contrast to pathological features of acute and subacute hypersensitivity pneumonitis, epithelioid cell granulomas are sparse or absent, but giant cells are seen in the interstitium. Bridging fibrosis between peribronchiolar area and perilobular areas is an outstanding feature of chronic hypersensitivity pneumonitis. Autopsy cases of chronic hypersensitivity pneumonitis have demonstrated not only upper lobe contraction but also lower lobe contraction, mimicking usual interstitial pneumonia pattern and diffuse alveolar damage. Summary The present review focuses on the pathological features of chronic hypersensitivity pneumonitis and presents that centrilobular fibrosis and bridging fibrosis are the important hallmarks of chronic hypersensitivity pneumonitis, even with a usual interstitial pneumonia-like pattern.
Mitochondrial Respiratory Function and Cell Death in Focal Cerebral Ischemia

Abstract : Pyruvate‐supported oxygen uptake was determined as a measure of the functional capacity of mitochondria obtained from rat brain during unilateral middle cerebral artery occlusion and reperfusion. During ischemia, substantial reductions developed in both ADP‐stimulated and uncoupled respiration in tissue from the focus of the affected area in the striatum and cortex. A similar pattern of change but with lesser reductions was seen in the adjacent perifocal tissue. Succinate‐supported respiration was more affected than that with pyruvate in perifocal tissue at 2 h of ischemia, suggesting additional alterations to mitochondrial components in this tissue. Mitochondrial respiratory activity recovered fully in samples from the cortex, but not the striatum, within the first hour of reperfusion following 2 h of ischemia and remained similar to control values at 3 h of reperfusion. In contrast, impairment of the functional capacity of mitochondria from all three regions was seen in the first 3 h of reperfusion following 3 h of ischemia. Extensive infarction generally affecting the cortical focal tissue with more variable involvement of the perifocal tissue developed following 2 h of focal ischemia. Thus, mitochondrial impairment during the first 3 h of reperfusion was apparently not essential for tissue infarction to develop. Nonetheless, the observed mitochondrial changes could contribute to the damage produced by permanent focal ischemia as well as the larger infarcts produced when reperfusion was initiated following 3 h of ischemia.
Structure–function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites

Summary. The Duffy antigen/receptor for chemokines (DARC), a seven‐transmembrane glycoprotein carrying the Duffy (Fy) blood group, acts as a widely expressed promiscuous chemokine receptor. In a structure–function study, we analysed the binding of chemokines and anti‐Fy monoclonal antibodies (mAbs) to K562 cells expressing 39 mutant forms of DARC with alanine substitutions spread out on the four extracellular domains (ECDs). Using synthetic peptides, we defined previously the Fy6 epitope (22‐FEDVW‐26), and we characterized the Fya epitope as the linear sequence 41‐YGANLE‐46. In agreement with these results, mutations of F22‐E23, V25 and Y41, G42, N44, L45 on ECD1 abolished the binding of anti‐Fy6 and anti‐Fya mAbs to K562 cells respectively, Anti‐Fy3 binding was abolished by D58–D59 (ECD1), R124 (ECD2), D263 and D283 (ECD4) substitutions. Mutations of C51 (ECD1), C129 (ECD2), C195 (ECD3) and C276 (ECD4 severely reduced anti‐Fy3 and CXC‐chemokine ligand 8 (CXCL‐8) binding. CXCL‐8 binding was also abrogated by mutations of F22–E23, P50 (ECD1) and D263, R267, D283 (ECD4). These results defined the Fya epitope and suggested that (1) two disulphide bridges are involved in the creation of an active chemokine binding pocket; (2) a limited number of amino acids in ECDs 1–4 participate in CXCL‐8 binding; and (3) Fy3 is a conformation‐dependent epitope involving all ECDs. We also showed that N‐glycosylation of DARC occurred on N16SS and did not influence antibody and chemokine binding.
Failure of nonoperative management of pediatric blunt liver and spleen injuries: A prospective Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium study

BACKGROUND Nonoperative management (NOM) is standard of care for most pediatric blunt liver and spleen injuries (BLSI); only 5% of patients fail NOM in retrospective reports. No prospective studies examine failure of NOM of BLSI in children. The aim of this study was to determine the frequency and clinical characteristics of failure of NOM in pediatric BLSI patients. METHODS A prospective observational study was conducted on patients 18 years or younger presenting to any of 10 Level I pediatric trauma centers April 2013 and January 2016 with BLSI on computed tomography. Management of BLSI was based on the Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium pediatric guideline. Failure of NOM was defined as needing laparoscopy or laparotomy. RESULTS A total of 1008 patients met inclusion; 499 (50%) had liver injury, 410 (41%) spleen injury, and 99 (10%) had both. Most patients were male (n = 624; 62%) with a median age of 10.3 years (interquartile range, 5.9, 14.2). A total of 69 (7%) underwent laparotomy or laparoscopy, but only 34 (3%) underwent surgery for spleen or liver bleeding. Other (nonexclusive) operations were for 21 intestinal injuries; 15 hematoma evacuations, washouts, or drain placements; 9 pancreatic injuries; 5 mesenteric injuries; 3 diaphragm injuries; and 2 bladder injuries. Patients who failed were more likely to receive blood (52 of 69 vs. 162 of 939; p < 0.001) and median time from injury to first blood transfusion was 2.3 hours for those who failed versus 5.9 hours for those who did not (p = 0.002). Overall mortality rate was 24% (8 of 34) in those who failed NOM due to bleeding. CONCLUSION NOM fails in 7% of children with BLSI, but only 3% of patients failed for bleeding due to liver or spleen injury. For children failing NOM due to bleeding, the mortality was 24%. LEVEL OF EVIDENCE Therapeutic study, level II.
Prognostic value of pretreatment 18F-FDG PET-CT for nasopharyngeal carcinoma patients

Background: Nasopharyngeal carcinoma (NPC) is a special subtype of head and neck cancer (HNC). At present, there are no highly specific prognostic markers to aid in tumor grading and guide patient treatment modalities for NPC. The prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-PET-CT) in NPC patients is controversial and no consensus exists as to its predictive capability. Methods: To analyze the predictive efficacy of 18F-PET-CT imaging in NPC patients, data from MEDLINE, EMBASE, the Cochrane library, CBM, CNKI, and VIP (inception to July 2016) were accessed. Results from prospective and retrospective observational studies that used 18F-FDG PET to predict disease prognosis in NPC patients were used for analysis. Two authors independently assessed study quality and extracted data. Event-free survival (EFS) was considered the primary endpoint and overall survival rate (OS) was considered the secondary endpoint. Results: Data from 14 studies and 1134 patients were included in our analysis. The hazard ratios (HRs) of maximum standardized uptake value of primary tumor (SUVmax-T), metabolic tumor volume of primary tumor (MTV-T), and total lesional glycolysis of primary tumor (TLG-T) for EFS were 1.31 (95% confidence interval [CI], 1.11–1.55, P = .001), 2.38 (95% CI 1.53–3.70, P < .001), and 1.65 (95% CI 0.76–3.59, P = .21), respectively. Among studies including TLG-T, those with a fixed SUV of 2.5 had an HR of 3.55 (95% CI, 1.42–8.84, P = .007). The HRs of SUVmax-T and MTV-T for OS were 2.19 (95% CI, 1.47–3.27, P < .001) and 2.69 (95% CI, 1.01–7.17, P = .05), respectively. Among studies including MTV-T, those with a fixed SUV of 2.5 had an HR of 4.07 (95% CI, 2.22–7.46, P < .001). Tests used for assessing predictive value of pretreatment SUVmax, MTV, and TLG of lymph nodes for EFS and OS showed that these parameters did not have significant predictive value (P>.05). Conclusion: Our results suggested that SUVmax, MTV, and TLG (with a fixed SUV of 2.5) of primary tumors before treatment initiation may be independent prognostic factors for NPC patients; however, SUVmax, MTV, and TLG of metastatic lymph nodes are not.
Clinicopathological and Immunohistochemical Characteristics in Male Breast Cancer: A Retrospective Case Series.

BACKGROUND Due to its rarity, male breast cancer (mBC) remains an inadequately characterized disease, and current evidence for treatment derives from female breast cancer (FBC). METHODS We retrospectively analyzed the clinicopathological characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to 2013. RESULTS From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed. Median age was 65 years (range: 25-87 years). Estrogen receptors were positive in 88 patients (96.7%), and progesterone receptors were positive in 84 patients (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was 51.5 months (range: 0.5-219.3 months). Five-year progression-free survival (PFS) was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2 presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5-year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%) experienced recurrent disease and 16 of 91 patients (17.6%) developed a second neoplasia. CONCLUSION Male breast cancer shows different biological patterns compared with FBC, with higher positive hormone-receptor status and lower HER-2 overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS. IMPLICATIONS FOR PRACTICE There is little evidence that prognostic features established in female breast cancer, such as grading and Ki-67 labeling index, could be applied to male breast cancer as well. This study found that grade 3 was associated with shorter overall survival and a trend for Ki-67 >20%; this could help in choosing the best treatment option in the adjuvant setting. Many questions remain regarding the impact of HER-2 positivity on survival and treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast cancer, the results suggest that common regimens of chemo-, endocrine and immunotherapy used in female breast cancer are safe and effective for men. Male breast cancer patients show a higher incidence of second primary tumors, especially prostate and colon cancers and should therefore be carefully monitored.
Myelin proteomics: the past, the unexpected and the future

Myelin proteomics has been the subject of intense research over the last decade, and its profiling has achieved good results by both in-gel and mass spectrometry-based techniques. 1280 proteins have been identified, a number expected to increase. Some of the identified proteins are as yet not established as true components of myelin. There appears to be a limit in our ability to discover markers of myelin biogenesis, function and disease. Myelin can be easily isolated free of contaminants, thanks to its lipidic nature, which however necessitates pretreatment with detergents before mass spectrometry analysis. Here, the key issue of solubilization of myelin proteins for mass spectrometry measurements is addressed. An in-depth characterization of the myelin proteome would have a profound impact on our knowledge of its pathology and physiology. Future quantitative proteomic studies of the low-abundance myelin protein complement, likely representing key regulatory components, may in future provide molecular description of the dysmyelinating/demyelinating diseases.
Evidence for the expression of the EGF receptor on human monocytic cells.

Several malignancies over-express the epidermal growth factor receptor, ligation of which results in cellular differentiation and multiplication. Mononuclear phagocytes secrete this cytokine and its receptor has been detected on microglial cells. This communication describes the expression (and its regulation) of epidermal growth factor receptor (EGFR) on U937 cells. We have shown that a few are EGFR-positive, with expression being up regulated by interleukin 6 (IL-6). Also, when cultured in the presence of serum with the monoclonal anti-EGFR, ICR62, U937s showed a reduced growth rate. By contrast, ICR9 caused a significant increase in cellular proliferation. Both antibodies induced cycle arrest in late G(1)/S phase. When the cells were cultured in the absence of serum, low antibody concentration (10 microg/ml) showed an early inhibitory effect on cell proliferation. By contrast, at high antibody concentrations (50 micro/ml), ICR62 significantly increased the proliferation of U937 cells. We suggest that these results provide indirect evidence for an autocrine action of EGF on U937 cells.
A Cross-Sectional Study of Empathy and Emotion Management: Key to a Work Environment for Humanized Care in Nursing

Introduction At the present time, technological advances have increased the technification of healthcare services, in which high priority is given to efficiency and results achieved, leading healthcare personnel to prioritize administrative and procedural aspects to the detriment of humanization of care and the work environment. Objective This study was intended to continue progress in research on the work environment based on the humanization construct by analyzing the explanatory value of emotional intelligence and empathy in nursing personnel. Materials and Methods The study was quantitative, observational, and cross-sectional. The sample was made up of 338 Spanish nurses with a mean age of 32.20 (SD = 7.54; range 22–56). The instruments employed for analysis were the Healthcare Professional Humanization Scale (HUMAS), Brief Emotional Intelligence Inventory for Adults, and Basic Empathy Scale (BES). Results Mood and stress management—both emotional intelligence components—and cognitive empathy explained over half (51%) of the variability found in humanization of care in a sample of nurses. Furthermore, the mediation models proposed emphasized the mediating role of cognitive empathy in stress management and improvement in mood and its relationship to humanization. Conclusion It is recommended that healthcare professionals reinforce their personal competencies in order to tend to the needs of their patients empathetically and improve emotional competencies for coping successfully with potentially stressful situations.
Evaluation of the anxiolytic-like effects of clomipramine in two rat strains with different anxiety vulnerability (Wistar and Wistar-Kyoto rats): participation of 5-HT1A receptors

The main aim of this study was to evaluate the anxiolytic-like effects of the serotonergic antidepressant, clomipramine (0.6–5.0 mg/kg), and the 5-HT1A agonist, (±)8-hydroxy-2-(di-n)-propil-aminotetraline hydrobromide (8-OH-DPAT; 0.01–0.5 mg/kg), in two strains of rat with different anxiety vulnerability: Wistar-Kyoto (WKY; with trait anxiety) and Wistar rats (control strain). The anxiety model used was the burying behavior test; decreases in burying, grooming of the snout, and freezing were interpreted as a reduction of anxiety-like levels. A second objective was to explore the participation of 5-HT1A receptors in the effects of clomipramine and 8-OH-DPAT. Behavior in the burying behavior test was strain dependent. In addition to the burying behavior, WKY rats showed high levels of freezing and grooming of the snout. Clomipramine and 8-OH-DPAT decreased the burying behavior in both strains of rats through a direct interaction with the 5-HT1A receptor. 8-OH-DPAT decreased freezing behavior in both strains through a mechanism that was not related to 5-HT1A receptors. Finally, clomipramine was able to block freezing and grooming behaviors only in WKY rats. In conclusion, strains with different anxiety vulnerability express different behavioral responses toward the same aversive stimulus, and the anxiolytic-like effects of clomipramine and 8-OH-DPAT are both behavior and strain dependent.
The impact of routine histopathological examination on cholecystectomy specimens from an Asian demographic.

INTRODUCTION Most gallbladder carcinoma cases are suspected pre-operatively or intra-operatively. In Malaysia histopathological examination of cholecystectomy specimens has become routine practice. The aim of this study was to assess the impact of routine histological examinations on cholecystectomy specimens from an Asian demographic, which may differ from a Caucasian demographic. METHODS A retrospective study was performed of all histopathology reports for cholecystectomies (laparoscopic and open) undertaken over a period of 12 years (1997-2008) in a single teaching hospital. RESULTS A total of 1,375 gallbladder specimens were sent for histopathological analysis, with 7 (0.5%) being reported as malignant while only three (0.2%) were found to contain primary gallbladder carcinoma. Other premalignant findings included two specimens with dysplastic changes of the mucosa and one tubulovillous adenoma with a dysplastic epithelium. From the ten malignant and premalignant specimens, seven were diagnosed pre-operatively, two were suspected intra-operatively and one was diagnosed with dysplastic changes on the histopathology report post-operatively. CONCLUSIONS This study supports earlier research carried out in the UK and the demographic difference does not affect the impact of the histology examination on cholecystectomy specimens in diagnosing this disease. A selective policy is recommended in Malaysia.
Discovery and Characterization of a New Cold-Active Protease From an Extremophilic Bacterium via Comparative Genome Analysis and in vitro Expression

Following a screening of Antarctic glacier forefield-bacteria for novel cold-active enzymes, a psychrophilic strain Psychrobacter sp. 94-6PB was selected for further characterization of enzymatic activities. The strain produced lipases and proteases in the temperature range of 4–18°C. The coding sequence of an extracellular serine-protease was then identified via comparative analysis across Psychrobacter sp. genomes, PCR-amplified in our strain 94-6PB and expressed in the heterologous host E. coli. The purified enzyme (80 kDa) resulted to be a cold-active alkaline protease, performing best at temperatures of 20–30°C and pH 7-9. It was stable in presence of common inhibitors [β-mercaptoethanol (β-ME), dithiothreitol (DTT), urea, phenylmethylsulfonyl fluoride (PMSF) and ethylenediaminetetraacetic acid (EDTA)] and compatible with detergents and surfactants (Tween 20, Tween 80, hydrogen peroxide and Triton X-100). Because of these properties, the P94-6PB protease may be suitable for use in a new generation of laundry products for cold washing. Furthermore, we assessed the microdiversity of this enzyme in Psychrobacter organisms from different cold habitats and found several gene clusters that correlated with specific ecological niches. We then discussed the role of habitat specialization in shaping the biodiversity of proteins and enzymes and anticipate far-reaching implications for the search of novel variants of biotechnological products.
Bidirectional Intimate Partner Violence and Drug Use Among Homeless Youth

Intimate partner violence (IPV) among homeless youth (HY) is common, yet it has continuously been understudied, especially in relation to substance use. As part of a longitudinal study of Los Angeles area HY, drop-in service seeking youth completed a self-administered questionnaire. The presented results are from the third panel of data collection (N = 238), and the Revised Conflict Tactics Scale (CTS2) was used to assess IPV behavior regarding the participant’s most recent intimate relationship. Approximately 38% of participants reported IPV behavior in their most recent relationship, and the majority of this behavior was bidirectional. It was unlikely that a HY was only a victim or only a perpetrator. Multivariable models revealed that bidirectional IPV was related to increased odds of recent methamphetamine; whereas sole perpetration was associated with an increased likelihood of ecstasy use. Specific substance use and IPV are closely related to risk behaviors for HY. Comprehensive interventions should be developed to address both these risk behaviors.
The association of p53 expression levels with clinicopathological features and prognosis of patients with colon cancer following surgery

The present study aimed to examine the association of p53 expression levels with clinicopathological features and prognosis of patients with colon cancer following surgery. The present study included 484 patients with colon cancer that underwent colon resection between December 2003 and December 2011. All follow-ups were censored in December 2013 with a median follow-up time of 43 months. Kaplan-Meier survival curves and Cox regression analysis were used to determine predictors for overall survival rate. p53 expression status (positive or negative) was significantly different between patient groups when categorized by age distribution, disease course, tumor location, maximum tumor diameter, depth of tumor invasion, Dukes' stage, distant metastasis and lymph node (LN) metastasis (P<0.05). Cox regression analysis revealed that age, surgery type, histological subtypes, tumor size, tumor location, LN metastasis, distant metastases, Dukes' stage and p53 expression status are independent factors influencing the survival rate of patients with colon cancer following surgery (P<0.05). Therefore, the present study revealed that the loss of p53 expression levels in tumors was associated with aggressive clinicopathological characteristics in patients with colon cancer.