Miracle-dz/UniFAR-FTUs huggingface dataset:
The expression and tyrosine phosphorylation of E‐cadherin/catenin adhesion complex, and focal adhesion kinase in invasive cervical carcinomas

The present study aimed to confirm the hypothesis that the expression and phosphorylation status of the E-cadherin/catenin adhesion complex is related to cervical carcinogenesis and cervical cancer invasion, and to investigate the expression and the tyrosine phosphorylation of focal adhesion kinase (FAK) and its relation with E-cadherin/catenin adhesion complex. The expression of E-cadherin, α- and β-catenin, and FAK were studied by a western blot analysis with 26 cervical carcinomas, nine normal cervices, and five carcinomas in situ of cervix. The tyrosine phosphorylation of α- and β-catenin and FAK were examined by an immunoprecipitation. The expressions of α- and β-catenin and E-cadherin were reduced in cervical carcinoma, and the tyrosine phosphorylation of α- and β-catenin in cervical carcinoma was higher than in normal cervix and carcinoma in situ of cervix. Tyrosine phosphorylation of FAK was elevated in cervical carcinoma although the expression of FAK was not significantly different. Moreover, α- and β-catenin were coimmunoprecipitated with FAK. We conclude that the loss of E-cadherin/catenin proteins and the tyrosine phosphorylation of E-cadherin/catenin are involved in cervical carcinogenesis and cancer invasion. Tyrosine phosphorylation of focal adhesion kinase is also related to the cervical cancer invasion. The E-cadherin/catenin complex and FAK may be related functionally and structurally.
Histoplasmosis: a Clinical and Laboratory Update

SUMMARY Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.
Experiences of factors contributing to women's ability to make informed decisions about the process of rehabilitation and return to work: a focus group study.

OBJECTIVE Functional, interactive and critical skills to use and act on health information, i.e. health literacy, are central preconditions for decision-making. To construct a decision aid that strengthens women's abilities to make decisions during sick leave, knowledge is needed about factors that increase health literacy. The aim of this study was for that reason to explore and describe women's experiences of factors that contribute to their ability to make informed decisions about the process of rehabilitation and return to work. PARTICIPANTS Nineteen women with a period of sick leave during the previous 12 months participated. METHODS A qualitative design with a focus group methodology was used. The qualitative data analysis was based on five focus group discussions. RESULTS A number of factors emerged that were experienced as supporting. They were distributed over five qualitative categories. Trusting in, valuing and using one's own resources, taking the initiative and obtaining information were described as crucial to making well-founded decisions. Being coached by a professional or being supported by significant others were other factors that contributed to decision-making. The women also experienced that a trustful, transparent, continuous relationship with the professionals involved in the rehabilitation process contributed to well-founded decisions. CONCLUSIONS The factors experienced as contributing to sick-listed women's ability to make informed decisions were both personal and environmental. Some have a connection with theories that conceptualize intentional relationships and self-efficacy. The factors may be useful as an initial source for the development of a decision aid for women.
Preoperative predictors of returning to work following primary total knee arthroplasty.

BACKGROUND There is little in the literature to guide clinicians in advising patients regarding their return to work following a primary total knee arthroplasty. In this study, we aimed to identify which factors are important in estimating a patient's time to return to work following primary total knee arthroplasty, how long patients can anticipate being off from work, and the types of jobs to which patients are able to return following primary total knee arthroplasty. METHODS A prospective cohort study was performed in which patients scheduled for a primary total knee arthroplasty completed a validated questionnaire preoperatively and at four to six weeks, three months, and six months postoperatively. The questionnaire assessed the patient's occupational physical demands, ability to perform job responsibilities, physical status, and motivation to return to work as well as factors that may impact his or her recovery and other workplace characteristics. Two survival analysis models were constructed to evaluate the time to return to work either at least part-time or full-time. Acceleration factors were calculated to indicate the relative percentage of time until the patient returned to work. RESULTS The median time to return to work was 8.9 weeks. Patients who reported a sense of urgency about returning to work were found to return in half the time taken by other employees (acceleration factor = 0.468; p < 0.001). Other preoperative factors associated with a faster return to work included being female (acceleration factor = 0.783), self-employment (acceleration factor = 0.792), higher mental health scores (acceleration factor = 0.891), higher physical function scores (acceleration factor = 0.809), higher Functional Comorbidity Index scores (acceleration factor = 0.914), and a handicap accessible workplace (acceleration factor = 0.736). A slower return to work was associated with having less pain preoperatively (acceleration factor = 1.132), having a more physically demanding job (acceleration factor = 1.116), and receiving Workers' Compensation (acceleration factor = 4.360). CONCLUSIONS Although the physical demands of a patient's job have a moderate influence on the patient's ability to return to work following a primary total knee arthroplasty, the patient's characteristics, particularly motivation, play a more important role.
Monoclonal Antibodies against Epidermal Growth Factor Receptor Acquire an Ability To Kill Tumor Cells through Complement Activation by Mutations That Selectively Facilitate the Hexamerization of IgG on Opsonized Cells

Triggering of the complement cascade induces tumor cell lysis via complement-dependent cytotoxicity (CDC) and attracts and activates cytotoxic cells. It therefore represents an attractive mechanism for mAb in cancer immunotherapy development. The classical complement pathway is initiated by IgG molecules that have assembled into ordered hexamers after binding their Ag on the tumor cell surface. The requirements for CDC are further impacted by factors such as Ab epitope, valency, and affinity. Thus, mAb against well-validated solid tumor targets, such as the epidermal growth factor receptor (EGFR) that effectively induces complement activation and CDC, are highly sought after. The potency of complement activation by IgG Abs can be increased via several strategies. We identified single-point mutations in the Fc domain (e.g., E345K or E430G) enhancing Fc:Fc interactions, hexamer formation, and CDC after Ab binds cell-surface Ag. We show that EGFR Abs directed against clinically relevant epitopes can be converted into mAb with unprecedented CDC activity. Alternative strategies rely on increasing the affinity of monomeric IgG for C1q by introduction of a quadruple mutation at the C1q binding site or via generation of an IgG1/IgG3 chimera. In this study we show that selective enhancement of C1q binding via avidity modulation is superior to the unattended increase in C1q binding via affinity approaches, particularly for target cells with reduced EGFR expression levels. Improving Fc:Fc interactions of Ag-bound IgG therefore represents a highly promising and novel approach for potentiating the anti-tumor activity of therapeutic mAb against EGFR and potentially other tumor targets.
Liposome-encapsulated hemoglobin modulates lipopolysaccharide-induced tumor necrosis factor-alpha production in mice.

OBJECTIVE To investigate the effect of liposome-encapsulated hemoglobin, an experimental blood substitute, on the function of the mononuclear phagocytic system in normovolemic mic, in ex vivo murine splenocytes and in a transformed murine monocytic cell line, RAW 264.7. DESIGN Prospective, randomized trial. SETTING Center for Biomolecular Science and Engineering, Naval Research Laboratory, and the Thomas Jefferson University. SUBJECTS Female Balb/c mice (n = 27). INTERVENTIONS Mice were injected into the tail vein with liposome-encapsulated hemoglobin or liposome vehicle and were killed at varying time points for blood sampling and splenocyte isolation and culture. MEASUREMENTS AND MAIN RESULTS Injection of liposome-encapsulated hemoglobin in mice (2.2 of lipid/kg and 0.56 g of hemoglobin/kg, n = 9) did not increase serum tumor necrosis factor (TNF)-alpha concentrations at 2, 8, 15, and 24 hrs after administration. In the ex vivo procedure, lipopolysaccharide (1 microgram/mL)-induced TNF-alpha production by splenocytes from mice injected with liposome-encapsulated hemoglobin was attenuated at 2 and 4 hrs (73%, p = .002 at 2 hrs), compared with TNF-alpha production by splenocytes from sham animals challenged with the same concentration of lipopolysaccharide. In the in vitro procedure, simultaneous exposure of liposome-encapsulated hemoglobin (0.88 to 8.8 mg/mL) and lipopolysaccharide (0.125 to 1 microgram/mL) to the murine-derived, peritoneal monocytic RAW 264.7 cell line showed significantly reduced TNF-alpha peptide, but not messenger RNA, 1 to 4 hrs after exposure as compared with cells challenged with lipopolysaccharide alone. This effect correlated with the rapid phagocytosis (1 hr to 4 hrs) of liposome-encapsulated hemoglobin by RAW 264.7 cells. Phagocytic activity in RAW 264.7 cells exposed to both liposome-encapsulated hemoglobin and lipopolysaccharide showed reduced uptake compared with uptake of liposome-encapsulated hemoglobin. The liposome-induced reduction in TNF-alpha peptide production elicited by lipopolysaccharide was countered by extending the time period to an overnight delay between liposome-encapsulated hemoglobin exposure and lipopolysaccharide challenge. Liposome-encapsulated hemoglobin incubated with lipopolysaccharide in vitro, and subsequently washed to remove free lipopolysaccharide, stimulated TNF-alpha expressed by RAW 264.7 cells. Incubation with liposome-encapsulated hemoglobin alone did not evoke TNF-alpha production in these cells. CONCLUSIONS These data suggest that liposome-encapsulated hemoglobin modulates the response of the mononuclear phagocyte system to endotoxin, possibly through binding of lipopolysaccharide, presentation to macrophages with subsequent phagocytosis, and modulation of cytokine response by a posttranscriptional mechanism. This effect is attenuated by extending the period between exposure to liposome-encapsulated hemoglobin and endotoxin. The clinical relevance of these findings awaits further investigation.
The impact of mineral fertilization and atmospheric precipitation on yield of field crops on family farms

The field crop production, as the most important branch of plant production of the Republic of Serbia, in the period 2002-2011, was carried out on an average of over 2.7 million hectares, 82.7% of which took place on the individual farms/family holdings. Hence, the subject of research in this paper covers yields of major field crops realized on family farms in the region of Vojvodina in the period 1972-2011. The main objective of the research is to study the interdependence of utilization of mineral fertilizers and atmospheric precipitation during the vegetation period and realized yields of major field crops on family farms in the observed period. The regression analysis was applied in order to verify dependencies and determine the form of dependence of achieved yields from examined variables. The results showed that the main limiting factors for obtaining high and stable yields of field crops is inadequate use of fertilizers and the lack of precipitation during the vegetation period.
Plant Community Diversity, Herbivore Movement, and an Insect-Transmitted Disease of Maize.

Field experiments were carried out in Nicaragua to examine the influence of plant community diversity, plant density, and host plant quality on the spread of an insect-transmitted plant pathogen. Population levels of the corn leafhopper Dalbulus maidis, which transmits the corn stunt spiroplasma to maize, were monitored in four experimental communities; low-density maize monoculture, high-density maize monoculture, two-species (maize/bean) polyculture, and multispecies (maize/weeds) polyculture. Leafhopper abundance per plant and the incidence of corn stunt were lower in high-density maize monocultures than in low-density monocultures. Increasing plant diversity by intercropping with nonhost species such as beans or weeds also led to lower leafhooper abundance and decreased disease incidence, but the effect was not enhanced as additional nonhost species were added to the community. Manipulating host plant quality by increasing nitrogen fertilization resulted in higher leafhopper densities at higher nitrogen levels. To explore the role of vector movement in disease spread, leafhopper movement rates and emigration were estimated by observing changes in the spatial gradients of leafhopper densities over time. This method of movement analysis requires neither marking the insects nor releasing them at a single point, and thus reduces the extreme disturbance caused by traditional mark-release techniques. The analysis indicated that leafhopper movement rates were lowest in the polycultures. In particular, across-row movement was strikingly inhibited in the bean polyculture. This polyculture also had the highest rates of emigration. These results indicate that plant quality, density, and diversity significantly affect the spread of corn stunt through their effects on the abundance and movement behavior of the corn leafhopper. These factors could be manipulated in a program of cultural control for corn stunt in maize fields in tropical America.
Mediastinitis After Coronary Artery Bypass Graft Surgery: Risk Factors and Long‐Term Survival

This study from Duke University Medical Center addresses both the risk factors for the development of mediastinitis, as well as the long-term impact of mediastinal infection on survival in 6459 consecutive patients undergoing coronary artery bypass graft (CABG) surgery at that institution from 1987 to 1994. Data on 20 preoperative and intraoperative variables were collected prospectively and analyzed using univariate and multivariate analyses, with evaluation of long-term survival in the infected and uninfected groups. Eight-three patients (1.3%) developed mediastinitis, defined as deep sternal wound infection requiring extensive debridement and drainage. The mean postoperative hospital stay was prolonged in the mediastinitis group (25 versus 10 days, no statistical analysis provided). Variables associated with an increased incidence of mediastinitis by univariate analysis included obesity (P =.009), New York Heart Association congestive heart failure (NYHA CHF) class (P =.002), diabetes mellitus (P =.009), priorsternotomy (P =.009), duration of cardiopulmonary bypass (P =.02), presence of comorbid conditions (P =.03) and poor hemostasis at sternotomy closure (P =.09). Multivariate logistic regression analysis revealed four independent predictors of mediastinitis development: NYHA CHF class (P =.002), obesity (P =.0002), prior sternotomy (P =.008), and duration of cardiopulmonary bypass (P =.05). Variables without significant influence included age, number of internal mammary artery grafts utilized, duration of preoperative stay, and chronic obstructive pulmonary disease. The median duration of follow-up in the mediastinitis group was 1.5 years, with a follow-up of 3.4 years in the patients without mediastinitis. Interval and cumulative mortality rates were higher in the mediastinitis group up to 2 years following CABG surgery, a difference which persisted when controlled for variables associated with late postoperative mortality, including age, ejection fraction, cere-brovascular disease, and mitral insufficiency. Patients developing mediastinitis suffered a nearly fourfold increase in mortality in the 1–2 postoperative years (8.1% versus 2.3%). The authors provide a review of the literature addressing risk factors for mediastinitis development. In addition, they propose a model of preoperative risk assessment in individual patients, using NYHA CHF class III or IV, obesity, and prior heart surgery as variables. According to their data, patients possessing one factor have a threefold increased incidence of postoperative mediastinitis, and those possessing all three have a nearly 20-fold increased risk of this postoperative complication.
Thalamic Mechanisms of EEG Alpha Rhythms and Their Pathological Implications

During relaxed wakefulness, the human brain exhibits pronounced rhythmic electrical activity in the α frequency band (8-13 Hz). This activity consists of 3 main components: the classic occipital α rhythm, the Rolandic μ rhythm, and the so-called third rhythm. In recent years, the long-held belief that α rhythms are strongly influenced by the thalamus has been confirmed in several animal models and, in humans, is well supported by numerous noninvasive imaging studies. Of specific importance is the emergence of 2 key cellular thalamic mechanisms, which come together to generate locally synchronized α activity. First, a novel form of rhythmic burst firing, termed high-threshold (HT) bursting, which occurs in a specialized subset of thalamocortical (TC) neurons, and second, the interconnection of this subset via gap junctions (GJs). Because repetitive HT bursting in TC neurons occurs in the range of 2 to13 Hz, with the precise frequency increasing with increasing depolarization, the same cellular components that underlie thalamic α rhythms can also lead to θ (2-7 Hz) rhythms when the TC neuron population is less depolarized. As such, this scenario can explain both the deceleration of α rhythms that takes place during early sleep and the chronic slowing that characterizes a host of neurological and psychiatric disorders.
Oligodendrocyte-Specific FADD Deletion Protects Mice from Autoimmune-Mediated Demyelination

Apoptosis of oligodendrocytes (ODCs), the myelin-producing glial cells in the CNS, plays a central role in demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To investigate the mechanism behind ODC apoptosis in EAE, we made use of conditional knockout mice lacking the adaptor protein FADD specifically in ODCs (FADDODC-KO). FADD mediates apoptosis by coupling death receptors with downstream caspase activation. In line with this, ODCs from FADDODC-KO mice were completely resistant to death receptor-induced apoptosis in vitro. In the EAE model, FADDODC-KO mice followed an ameliorated clinical disease course in comparison with control littermates. Lymphocyte and macrophage infiltration into the spinal cord parenchyma was significantly reduced, as was the extent of demyelination and proinflammatory gene expression. Collectively, our data show that FADD is critical for ODC apoptosis and the development of autoimmune demyelinating disease.
Familial risks, early-onset breast cancer, and BRCA1 and BRCA2 germline mutations.

BACKGROUND Having a family history of breast cancer, particularly if it involves early-onset disease, is a risk factor for breast cancer, but little is known about specific causes of this association. Consequently, we studied mothers, sisters, and aunts of an age-stratified sample of 1567 unselected case patients diagnosed with breast cancer before age 60 years, recruited to a population-based, case-control-family study, in which case patients, control subjects, and their relatives were administered the same questionnaire. METHODS Extensive BRCA1 and BRCA2 mutation testing was carried out for 788 case patients diagnosed before age 40 years, including manual sequencing of DNA from 72 patients with two or more affected relatives. Standardized morbidity ratios, age-specific cumulative risks, and hazard ratios were calculated for groupings of relatives. RESULTS Cumulative risks of breast cancer to age 50 years in the sisters, mothers, and aunts of the case patients, respectively, were 6, 3, and 2 times the population risk if the case patient was younger than age 40 years at diagnosis but were considerably lower if the case patient was older at diagnosis. When relatives of the case patients with a BRCA1 or BRCA2 mutation were excluded, these risks fell by, at most, 20%. Sisters and aunts, but not mothers, who had an additional first-degree relative with breast cancer were at increased risk, and the risk was greater when that relative was younger at diagnosis. Hazard ratios were 10.7 (95% confidence interval [CI] = 4.2 to 26.8) for sisters and 4.2 (95% CI = 2.2 to 8.1) for aunts, if the relative was aged 40 years at diagnosis. Fewer than one-third of the excess of breast cancers in relatives of case patients diagnosed before age 40 years that are attributed to familial factors are BRCA1- or BRCA2-related. CONCLUSION Mutations in genes other than BRCA1 and BRCA2 may be associated with a high risk of breast cancer, especially in young women.
Addressing complex challenges using a co-innovation approach: Lessons from five case studies in the New Zealand primary sector

Co-innovation can be effective for complex challenges – involving interactions amongst multiple stakeholders, viewpoints, perceptions, practices and interests across programmes, sectors and national systems. Approaches to challenges in the primary sector have tended to be linear, where tools and outputs are developed by a few, mostly scientists/researchers, and then extended to stakeholders. A co-innovation approach first deciphers and delineates the biophysical, societal, regulatory, policy, economic and environmental drivers, constraints and controls influencing these challenges at multiple levels. Second, stakeholder interactions and perspectives can inform and change the focus as well as help in co-developing solutions to deliver agreed outcomes. However, there is limited systematic and comparative research on how co-innovation works out in different projects. Here we analyse the results of applying a co-innovation approach to five research projects in the New Zealand primary sector. The projects varied in depth and breadth of stakeholder engagement, availability of ready-made solutions and prevalence of interests and conflicts. The projects show how and why co-innovation approaches in some cases contributed to a shared understanding of complex problems. Our results confirm the context specificity of co-innovation practices.