bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial respiratory chain deficiency correlates with the severity of neuropathology in sporadic Creutzfeldt-Jakob disease
Authors: Flønes Irene H. , Ricken Gerda , Klotz Sigrid , Lang Alexandra , Ströbel Thomas , Dölle Christian , Kovacs Gabor G. , Tzoulis Charalampos 
Published: April 2020

AbstractMitochondrial dysfunction has been implicated in multiple neurodegenerative diseases but remains largely unexplored in Creutzfeldt-Jakob disease. Here, we characterize the mitochondrial respiratory chain at the individual neuron level in the MM1 and VV2 common molecular subtypes of sporadic Creutzfeldt-Jakob disease. Moreover, we investigate the associations between the mitochondrial respiratory chain and neuropathological markers of the disease.Brain tissue from individuals with sporadic Creutzfeldt-Jakob disease and age-matched controls were obtained from the brain collection of the Austrian Creutzfeldt-Jakob Surveillance. The mitochondrial respiratory chain was studied through a dichotomous approach of immunoreactivities in the temporal cortex and the hippocampal subregions of CA4 and CA3.We show that profound deficiency of all mitochondrial respiratory complexes (I-V) occurs in neurons of the severely affected temporal cortex of patients with Creutzfeldt-Jakob disease. This deficiency correlates strongly with the severity of neuropathological changes, including vacuolation of the neuropil, gliosis and disease associated prion protein load. Respiratory chain deficiency is less pronounced in hippocampal CA4 and CA3 regions compared to the temporal cortex. In both areas respiratory chain deficiency shows a predilection for the MM1 molecular subtype of Creutzfeldt-Jakob disease.Our findings indicate that aberrant mitochondrial respiration could be involved early in the pathogenesis of sporadic Creutzfeldt-Jakob disease and contributes to neuronal death, most likely via ATP depletion. Based on these results, we propose that the restricted MRI diffusion profile seen in the brain of patients with sporadic Creutzfeldt-Jakob disease might reflect cytotoxic changes due to neuronal respiratory chain failure and ATP loss.
Increasing high school teachers self-efficacy for integrated STEM instruction through a collaborative community of practice
Authors: Kelley Todd R. , Knowles J. Geoffery , Holland Jeffrey D. , Han Jung 
Published: April 2020

AbstractBackgroundTeachers can have a significant impact on student interest and learning in science, technology, engineering, and math (STEM) subjects and careers. Teacher self-efficacy can also significantly affect student learning. Researchers investigated the effects of teacher professional development and integrated STEM curriculum development on teacher self-efficacy. Participants in the study included high school science and engineering technology teachers enrolled in a National Science Foundation–ITEST project called Teachers and Researchers Advancing Integrated Lessons in STEM (TRAILS). The TRAILS program sought to prepare teachers to integrate STEM content using engineering design, biomimicry, science inquiry, and 3D printing as pedagogical approaches. Teachers learned within a community of practice working alongside industry partners and college faculty. The purpose of the study was to investigate the impact of the 70 h of professional development to train three cohorts of teachers over 3 years on teacher self-efficacy. The research design utilized a quasi-experimental nonequivalent control group approach, including an experimental group and an untreated control group.ResultsMeasurements on beliefs about teacher self-efficacy were collected on pretest, posttest, and delayed posttest survey assessments. Researchers analyzed the T-STEM survey results for teaching self-efficacy using the Wilcoxson signed-rank test for detecting significant differences. Science teachers showed a significant increase in teacher self-efficacy comparing the pretest and delayed posttest scores after TRAILS professional development and STEM lesson implementation (p=.001, effect size = .95). Additionally, significant differences between groups (science experimental vs science control group teachers) using the Wilcoxon rank-sum test were detected from pretest to posttest (p= .033, effect size = .46), posttest to delayed posttest (p= .029, effect size = .47), and pretest to delayed posttest (p= .005, effect size = .64). There were no significant differences detected in the control group. Engineering technology teachers showed no significant differences between the pretest, posttest, and delayed posttest self-efficacy scores.ConclusionsThe results indicate the science teachers’ self-efficacy increased after professional development and after lesson implementation. Potential implications from this research suggest that the science teacher participants benefited greatly from learning within a community of practice, engaging in science practices, and using science knowledge to solve a real-world problem (engineering design).
Liver resection for a congenital intrahepatic portosystemic shunt in a child with hyperammonemia and hypermanganesemia: a case report
Authors: Takama Yuichi , Nakamura Tetsuro , Santo Kenji , Yoneda Akihiro 
Published: April 2020

Abstract
Background
Congenital portosystemic shunt (CPSS) is a rare malformation that leads to hyperammonemia, hypermanganesemia, and various symptoms. CPSSs are divided into intrahepatic and extrahepatic shunts. In patients with persistent CPSS including an intrahepatic portosystemic shunt (IPSS), early intervention to occlude the shunt reverses the associated complications.

Case presentation
The patient was a 1-year-and-7-month-old girl. She presented with hypergalactosemia and elevation of blood ammonia level (75 μg/dL) and total bile acid levels (68.2 μmol/L) during the neonatal period. Two IPSSs were detected using ultrasound and enhanced computerized tomography. Magnetic resonance imaging (MRI) at 1 year and 3 months of age showed abnormally high signal intensity in the pallidum of her brain. Spontaneous closure was not observed. We performed a right hepatectomy at 1 year and 7 months of age. The portal vein pressure was 16 mmHg after temporary occlusion of the right portal vein. Blood ammonia and serum manganese levels decreased immediately after the operation. The abnormal signal on brain MRI disappeared. She had a favorable course with no sign of recurrence of IPSS 5 years postoperatively.

Conclusion
Liver resection for an IPSS to control the symptoms of a portosystemic shunt is reasonable in a child for whom interventional radiological treatment is not indicated.
Between funder requirements and ‘jobbing scientists’: the evolution of patient and public involvement in a mental health biomedical research centre - a qualitative study
Authors: Evans Joanne , Papoulias Stan (Constantina) 
Published: April 2020

AbstractBackgroundIn the UK, there has been a strong drive towards patient and public involvement (PPI) in health research. Its benefits include improvements in the quality, relevance and acceptability of research, and empowerment, self-respect and value for service users. Organisational context can significantly influence the operationalisation of PPI. Research has highlighted power asymmetries between clinicians, researchers and service users. A resistance to power sharing, tokenism and assimilation into the existing culture suggest that a consultative, technocratic form of PPI is operating within health research settings. The aim of the study was to explore the development of PPI within a London based mental health biomedical research centre (BRC) over a period of 10 years from its inception.MethodsThis qualitative study compared data from 52 organisational documents and 16 semi-structured interviews with staff and service users associated with PPI within the Maudsley BRC. The data were analysed using inductive thematic analysis. Study design, data collection, analysis and write up were conducted by service user researchers.ResultsOur analysis showed a picture of increasing activity and acceptance of PPI, its alignment with the broader BRC research agenda, progressive involvement of service users in governance, and the development of a collaborative culture in research processes. The presence of salaried service user researchers in the organisation was key to this progress. However, PPI remained localised and under resourced and there was a reluctance to change working practices which resulted in perceptions of tokenism. Service users faced conflicting expectations and were expected to assimilate rather than challenge the organisation’s ‘biomedical agenda’.ConclusionsService user researchers may play a key role in establishing PPI in a scientific, hierarchical research environment. Adoption of a more democratic approach to involvement would build on the good work already being done and help to transform the culture and research processes. However, such an adoption requires considerable changes to the funding and policy environment orienting health research.
The metaphyseal sleeve: an unexplored option in the treatment of complex primary knee osteoarthritis
Authors: Wong W. K. , Chua H. S. 
Published: April 2020

Abstract
Background
In an ever-aging society that as a whole has become more affluent, significant emphasis has been accorded to an improved quality of life. Knee osteoarthritis is ever-increasingly treated with total knee arthroplasty. The benefits and satisfaction experienced by those who have undergone total knee replacements (TKR) are well documented in the literature. The issue arises when osteoarthritis of the affected knee is more complex than simple osteoarthritis, i.e. the patient has complex primary osteoarthritis. This collective term encompasses conditions such as massive bone loss, ligamentous laxity, coronal defects and those with contractures. There are various classifications to describe massive bone loss but we utilized the Anderson Orthopaedic Research Institute (AORI) classification. Numerous treatment options are available and we report the use of metaphyseal sleeves as a highly successful treatment option.

Methods
We retrospectively reviewed all the patients at our centre who underwent primary TKR using the metaphyseal sleeves. Patients were assessed on symptoms and functional status, and radiographs were also taken to assess for osseointegration. Only patients who completed 2 years of follow up were included in our study.

Results
The updated (2011) Knee Society Score (KSS) was used in conjunction with radiological assessments at each follow up. Mean KSS scores improved from 53.83 preoperatively to 193.39 postoperatively. All patients demonstrated increasing osseointegration throughout follow up.

Conclusion
The metaphyseal sleeve is an excellent treatment option for complex primary osteoarthritic knees with good results objectively, functionally and radiologically and would be a great choice for all orthopaedic surgeons to include in their armamentarium.
Identification of validated substitute for Asoka (Saraca asoca (Roxb.) Willd.) by phytochemical and pharmacological evaluations
Authors: C. T. Sulaiman , C. K. Jyothi , G. Jinu Krishnan Unnithan , K.M. Prabhukumar , Balachandran Indira 
Published: April 2020

AbstractBackgroundAsokais an important drug used in many Ayurvedic formulations. The bark ofSaraca asoca(Roxb.) Willd. is the genuine source plant forAsoka. Due to diminishing availability and increasing requirement, the Ayurvedic industry is facing acute shortage of this crude drug. It is usual that traders try to deceive the consumers by tendering similar bark of other trees. The unscientific substitution may affect the quality of herbal preparations adversely. The aim of the present study is to identify a scientifically validated substitute forAsoka.ResultsPhytochemical and pharmacological evaluation has been carried out using plant parts of four medicinal plants viz,Saraca asoca(AB),Polyalthia longifolia(PB),Shorea robusta(SB), andTrema orientalis(TB). The results of the study showed that among the tested extracts, AB and SB showed significant dose-dependent protection against bilateral ovariectomy-induced changes in estrus cycle, uterus weights, and lipid profile. LC/MS analysis revealed the presence of active catechins in both AB and SB.Polyalthia longifolia, the common adulterant ofAsoka, showed entirely different chemical and biological properties.ConclusionThis study concluded the possibility of usingS.robustabark as substitute forAsoka.Graphical abstract
Serial RT-PCR detection of circulating tumour cells as a marker of disease progression in patients with malignant melanoma
Authors: Ascierto P. A. , Budroni M. , Cossu A. , Scala S. , Simeone E. , Giuliano P. , Satriano S. M. , Caracò C. , Casula M. , Palmieri G. 
Published: April 2020

18009 Background: Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods: One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results: Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusions: Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease. No significant financial relationships to disclose.
Correlation between hemodynamic parameters and response to high-dose interleukin-2 in metastatic melanoma
Authors: Dutcher J. P. , Dasanu C. , Codreanu I. , Yeddu M. , Muniswamy H. , Wiernik P. H. , Alexandrescu D. T. 
Published: April 2020

18012 Background: A direct correlation between the levels of hypotension during IL-2 treatment and response in melanoma has not yet been demonstrated, although both have been correlated with higher IL-2 doses and production of nitric oxide. Methods: A retrospective study analyzed the association between response to IL-2 and systolic, diastolic, mean blood pressure (BP), and heart rate (HR) at baseline and during treatment, by using the t-test. Further, same comparison was performed after BP was corrected for the amount of neosynephrine (neo) utilized during IL-2 treatment (subtracting the raise in BP produced by neo using individual patient coefficients). 22 patients (13 females, 9 males) with a median age of 54 years (range 36–71) received a total of 26 courses of IL-2 (between 2001–2005). Median number of prior treatments was 2.5 (range 0–5). Outcomes were divided in (A) responders (1CR, 3PRs and 4SDs), and (B) non-responders (18PD). Results: When adjusting for the effects of neo, the corrected mean BP during treatment was significantly lower in (A) compared to (B) (52.17 vs 64.34 mmHg, P = 0.018; mean difference −12.17, 95% CI −22.06 to −2.27). Similarly, the decrease in corrected mean blood pressure from baseline was greater in (A) (−34.89 vs −20.67 mmHg, P = 0.003; mean difference −14.22, 95% CI −23.09 to −5.37). A trend towards statistical significance was recorded for the variation in uncorrected mean BP (17.86 vs. 23.22 mmHg, P = 0.085; mean difference −5.36, 95% CI −11.53 to 0.80). Separate analysis demonstrated a significant drop in both systolic (−17.85 mmHg, P = 0.009; 95% −30.77 to −4.91) and diastolic (−12.05 mmHg, P = 0.01; 95% CI −21.02 to −3.07) corrected BP in (A) vs. (B), but no significant difference for either uncorrected parameters. No correlation between response and the HR, number of IL-2 doses or total quantity of neo was observed. Conclusions: Uncorrected variation in mean BP shows a trend towards significance in predicting response to IL-2. However, corrected mean, systolic and diastolic BP correlate closely with response to treatment. Implications of this association may reside in better outcomes for an intensive IL-2 treatment, with aggressive pressor support. A common pathogenetic basis for response to IL-2 and induction of hypotension is possible. No significant financial relationships to disclose.
A phase II trial of oxaliplatin in patients with advanced melanoma
Authors: Lutzky J. , Nunez Y. , Graham P. 
Published: April 2020

18016 Background: Oxaliplatin is a platinum derivative without nephrotoxicity with in vitro activity against human melanoma cell lines. (Mohammed, MQ, 2000; Tashiro, T, 1989). A Phase I trial suggested activity in melanoma (Mathe, G, 1986) but Phase II data is lacking. A non-nephrotoxic platinum compound active in melanoma is of interest in the development of combination chemo-or chemoimmunotherapy. Methods: This was a Phase II prospective study of oxaliplatin in patients with previously treated or refractory advanced melanoma. The primary endpoint was to evaluate the response rate, survival, freedom from progression (FFP) and the tolerability of oxaliplatin in this patient population. Key inclusion criteria were: metastatic (stage IV) or unresectable malignant melanoma progressing following treatment with at least one and at most three chemotherapy regimens. ECOG PS 0–2, measurable disease and adequate organ and marrow function were required. Oxaliplatin 130 mg/m2 was given IV in 250–500 mL D5W over 120 minutes every 21 days for at least 2 cycles. Patients were evaluated for response every 2 cycles. Gehan’s two-stage design was utilized. Results: Ten patients were treated between March 2004 and March 2005. Three patients were female and 3 male with a median age of 62.5 years. All patients had PS 0–1. The median number of cycles was 2 (1–6). Three patients had disease stabilization (SD) for median of 3 months. No objective responses were seen; therefore, the study did not progress to the second stage.All patients have progressed and all have expired but one. Median survival from registration was 168 days (128–383). Toxicities included grade 2 fatigue (2 pts) and grade 2 neuropathy (3 pts); one patient had grade 3 diarrhea. Conclusions: Treatment with oxaliplatin in previously treated patients with melanoma is well tolerated at the dose and schedule studied but did not result in objective responses and further development in this population cannot be recommended. Incorporation into combination regimens in previously untreated patients may be of interest. No significant financial relationships to disclose.
NAD(P)H:quinone oxidoreductase 1 expression in human primary melanotic melanomas of the skin
Authors: Zappa F. , Cavalli F. 
Published: April 2020

18018 NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron reducing enzyme which is often over-expressed in cancers and can activate quinones to form cytotoxic species. This over-expression is used as target in the design of novel anti-cancer drugs. DTD is also expressed in normal tissues, but little is known about its “body mapping”. Because of the dearth of information on the cell-specific expression of DTD in pigment-producing cells of the skin, we analysed its expression in normal and tumoral samples. Twenty skin biopsies of primary malignant melanotic melanomas (ten with vertical invasion, ten with superficial spreading) were analysed by immunohistochemistry. In normal skin DTD expression was weak in all epidermal layers, including normal melanocytes. Malignant melanomas showed a very strong DTD expression in tumoral cells of all samples and in endothelial lining of peri-tumoral vessels. These results suggest that DT-diaphorase may be a new marker that could be useful in determining the extent of a malignant melanocytic lesion, and also tend to support the potential of malignant melanomas as target for DTD-directed antitumour agents. No significant financial relationships to disclose.
Do male partners of breast cancer patients perceive the quality of life of their mates?
Authors: Rabin E. G. , Ferreira Filho A. F. , Da Silva D. L. , De Almeida Fleck M. P. 
Published: April 2020

18502 Background: Scant scientific data exists regarding the quality of life (QOL) of female breast cancer patients as perceived by their male partners. Methods: We evaluated the QOL of 73 breast cancer patients and their partners perception using the abbreviated and Portuguese (from Brazil) validated questionnaires forms of the World Health Organization Quality of life (WHOQOL-bref) and WHOQOL-bref adapted for the third person, respectively. The breast cancer patients were also evaluated by the Beck Depression Scale (BDS) and were considered depressed if they had a score equal or greater than 10. The inclusion criteria for this study were: female breast cancer patients with stage I to III, cohabitation with a male partner for at least one year, age from 18 to 65 years old, being able to understand the questionnaires and sign an informed consent term. In order to compare the the scores of the WHOQOL-bref of breast cancer patients and the scores of the adapted WHOQOL-bref of their partners, we used the Pearson correlation index, Student’s t test and variation analysis. All statistical tests were two-sided, and P < .05 was used to indicate statistical significance. Results: In the analysis of all 73 patients, we found no difference between the perceptions of QOL and its domains between the breast cancer patients and their partners (see table ). However, in the subgroups of patients who had a mastectomy (n = 32) or were depressed (n = 35) as measured by the BDS scale, we found differences as their partners rated them higher on the physical domain and psychological domain (P = 0.003 and P = 0.009), respectively. Conclusions: Male partners of breast cancer patients have an accurate perception of their mates’ QOL. The only exceptions we found were in subgroup analysis of women who had a mastectomy and/or were depressed. Our findings suggest that the male partners of breast cancer patients can be seen as reliable surrogates of their QOL. [Table: see text] No significant financial relationships to disclose.