bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal loss without amyloid‐β deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys
Authors: Ouyang Fubing , Chen Xinran , Chen Yonghong , Liang Jiahui , Chen Yicong , Lu Tao , Huang Weixian , Zeng Jinsheng 
Published: July 2019

AbstractConflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid‐β (Aβ) deposition, as observed in Alzheimer's disease. In this study, we aimed to evaluate the presence of Aβ deposits in the ipsilateral thalamus and hippocampus 12 months post‐stroke in non‐human primates, whose brains are structurally and functionally similar to that of humans. Four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (MCAO), and another four sham‐operated monkeys served as controls. All monkeys underwent magnetic resonance imaging examination on post‐operative day 7 to assess the location and size of the infarction. The numbers of neurons, astrocytes, microglia and the Aβ load in the non‐affected thalamus and hippocampus ipsilaterally remote from infarct foci were examined immunohistochemically at sacrifice 12 months after operation. Thioflavin S and Congo Red stainings were used to identify amyloid deposits. Multiple Aβ antibodies recognizing both the N‐terminal and C‐terminal epitopes of Aβ peptides were used to avoid antibody cross‐reactivity. Aβ levels in cerebrospinal fluid (CSF) and plasma were examined using enzyme‐linked immunosorbent assay. The initial infarct was restricted to the left temporal, parietal, insular cortex and the subcortical white matter, while the thalamus and hippocampus remained intact. Of note, there were fewer neurons and more glia in the ipsilateral thalamus and hippocampus in the MCAO group at 12 months post‐stroke compared to the control group (all P < 0.05). However, there was no sign of extracellular Aβ plaques in the thalamus or hippocampus. No statistically significant difference was found in CSF or plasma levels of Aβ40, Aβ42 or the Aβ40/Aβ42 ratio between the two groups (P > 0.05). These results suggest that significant secondary neuronal loss and reactive gliosis occur in the non‐affected thalamus and hippocampus without Aβ deposits in the late period after MCAO in non‐human primates.
Effects of metformin and phenformin on apoptosis and epithelial‐mesenchymal transition in chemoresistant rectal cancer
Authors: Park Ji‐Hye , Kim Young‐heon , Park Eun Hyeh , Lee Sun‐Joo , Kim Hyewon , Kim Areumnuri , Lee Seung Bum , Shim Sehwan , Jang Hyosun , Myung Jae Kyung , Park Sunhoo , Lee Su‐Jae , Kim Min Jung 
Published: July 2019

AbstractRecurrence and chemoresistance in colorectal cancer remain important issues for patients treated with conventional therapeutics. Metformin and phenformin, previously used in the treatment of diabetes, have been shown to have anticancer effects in various cancers, including breast, lung and prostate cancers. However, their molecular mechanisms are still unclear. In this study, we examined the effects of these drugs in chemoresistant rectal cancer cell lines. We found that SW837 and SW1463 rectal cancer cells were more resistant to ionizing radiation and 5‐fluorouracil than HCT116 and LS513 colon cancer cells. In addition, metformin and phenformin increased the sensitivity of these cell lines by inhibiting cell proliferation, suppressing clonogenic ability and increasing apoptotic cell death in rectal cancer cells. Signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling pathways were more activated in rectal cancer cells, and inhibition of signal transducer and activator of transcription 3 expression using an inhibitor or siRNA sensitized rectal cancer cells to chemoresistant by inhibition of the expression of antiapoptotic proteins, such as X‐linked inhibitor of apoptosis, survivin and cellular inhibitor of apoptosis protein 1. Moreover, metformin and phenformin inhibited cell migration and invasion by suppression of transforming growth factor β receptor 2‐mediated Snail and Twist expression in rectal cancer cells. Therefore, metformin and phenformin may represent a novel strategy for the treatment of chemoresistant rectal cancer by targeting signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling.
Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer
Authors: Wu Yingjie , Jamal Muhammad , Xie Tian , Sun Jiaxing , Song Tianbao , Yin Qian , Li Jingyuan , Pan Shan , Zeng Xingruo , Xie Songping , Zhang Qiuping 
Published: July 2019

AbstractLung cancer has the highest morbidity and mortality among all cancers. Discovery of early diagnostic and prognostic biomarkers of lung cancer can greatly facilitate the survival rate and reduce its mortality. In our study, by analyzing Gene Expression Omnibus and Oncomine databases, we found a novel potential oncogene uridine‐cytidine kinase 2 (UCK2), which was overexpressed in lung tumor tissues compared to adjacent nontumor tissues or normal lung. Then we confirmed this finding in clinical samples. Specifically, UCK2 was identified as highly expressed in stage IA lung cancer with a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). We also found that high UCK2 expression was related to poorer clinicopathological features, such as higher T stage and N stage and higher probability of early recurrence. Furthermore, we found that patients with high UCK2 expression had poorer first progression survival and overall survival than patients with low UCK2 expression. Univariate and multivariate Cox regression analyses showed that UCK2 was an independent risk factor related with worse DFS and OS. By gene set enrichment analysis, tumor‐associated biological processes and signaling pathways were enriched in the UCK2 overexpression group, which indicated that UCK2 might play a vital role in lung cancer. Furthermore, in cytology experiments, we found that knockdown of UCK2 could suppress the proliferation and migration of lung cancer cells. In conclusion, our study indicated that UCK2 might be a potential early diagnostic and prognostic biomarker for lung cancer.
Childhood adiposity and adolescent sex steroids in the Exploring Perinatal Outcomes among Children study
Authors: Kim Catherine , Harrall Kylie K. , Glueck Deborah H. , Shumer Daniel , Dabelea Dana 
Published: July 2019

AbstractObjectiveIt is unclear how childhood adipose tissue deposition influences sex hormone profiles in later adolescence.DesignProspective cohort study.ParticipantsChildren (n = 418) with a mean age of 10.5 (1.5) years at visit 1 and 16.7 (1.2) at visit 2 in the Exploring Perinatal Outcomes among Children (EPOCH) Study.MeasurementsWe used reverse‐scale Cox proportional hazard models to assess associations between pubertal dehydroepiandrosterone (DHEA), testosterone (T), and oestradiol (E2) and childhood‐to‐puberty rate of change in visceral (VAT) and subcutaneous adipose tissue (SAT). Models stratified by sex and adjusted for childhood adiposity, maternal factors, birthweight and pubertal onset, and then further adjusted for insulin, luteinizing hormone (LH), leptin and hepatic fat fraction.ResultsAmong boys, more rapid accumulation of either VAT or SAT was associated with lower testosterone at visit 2 (HR 0.86, and .96, respectively, both P < .0001), independently of race/ethnicity, LH, leptin and hepatic fat fraction. Among boys, more childhood VAT was associated with lower testosterone in adolescence (HR 0.98, P = .003), but this association did not persist after adjustment for leptin or insulin. No associations were observed between either fat measure and oestradiol or DHEA in boys. In girls, no associations between childhood fat or fat accumulation and sex hormones were observed.ConclusionsMore rapid accumulation of fat is associated with lower testosterone in boys. These associations suggest that fat growth influences androgen profiles in adolescent boys. Since fat accumulation is a modifiable risk factor, the study results provide a possible intervention target and time period for improving adult health.
Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition
Authors: Gambale Antonella , Russo Roberta , Andolfo Immacolata , Quaglietta Lucia , De Rosa Gianluca , Contestabile Valentina , De Martino Lucia , Genesio Rita , Pignataro Piero , Giglio Sabrina , Capasso Mario , Parasole Rosanna , Pasini Barbara , Iolascon Achille 
Published: July 2019

AbstractCancer predisposition syndromes (CPS) result from germline pathogenic variants, and they are increasingly recognized in the etiology of many pediatric cancers. Herein, we report the genetic/genomic analysis of 40 pediatric patients enrolled from 2016 to 2018. Our diagnostic workflow was successful in 50% of screened cases. Overall, the proportion of CPS in our case series is 10.9% (20/184) of enrolled patients. Interestingly, 12.5% of patients achieved a conclusive diagnosis through the analysis of chromosomal imbalance. Indeed, we observed germline microdeletions/duplications of regions encompassing cancer‐related genes in 50% of patients undergoing array‐CGH: EIF3H duplication in a patient with infantile desmoplastic astrocytoma and low‐grade Glioma; SLFN11 deletion, SOX4 duplication, and PARK2 partial deletion in three neuroblastoma patients; a PTPRD partial deletion in a child diagnosed with glioblastoma multiforme. Finally, we identified two cases due to DICER1 germline mutations.
Biallelic mutations in Sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella (MMAF) phenotype
Authors: Sha Yanwei , Liu Wensheng , Wei Xiaoli , Zhu Xingshen , Luo Xiangmin , Liang Lei , Guo Tonghang 
Published: July 2019

AbstractMale patients with multiple morphological abnormalities of the sperm flagella (MMAF) are infertile and exhibit absent, short, coiled, bent and/or irregular sperm flagella. Mutations in the SPEF2 gene reduce sperm motility and cause sperm tail defects in animal models and humans. In the present study, we performed a genetic analysis on an MMAF patient and identified novel biallelic mutations in the SPEF2 gene. The biallelic mutations were confirmed by Sanger sequencing and in silico analysis revealed that, these variations were deleterious. The expression of truncated SPEF2 protein was reduced significantly in the patient's spermatozoa. The spermatozoa harbored biallelic mutations and showed severe ultrastructural defects in the axoneme and mitochondrial sheath. Our data suggest that biallelic mutations in SPEF2 can cause severe sperm flagellum defects, thus providing a novel candidate genetic pathogen for the human MMAF phenotype.
Immediate versus early loading protocols of titanium—zirconium narrow‐diameter implants for mandibular overdentures in edentulous patients: 1‐year results from a randomized controlled trial
Authors: Reis Rita , Nicolau Pedro , Calha Nuno , Messias Ana , Guerra Fernando 
Published: July 2019

AbstractObjectivesThe purpose of this randomized clinical trial was to compare immediate and early loading protocols for mandibular overdentures with two‐splinted narrow‐diameter implants in thin, non‐augmented residual ridge situations.Material and methodsEach edentulous patient received two implants in the interforaminal region. If primary stability after implant placement was achieved, patients were randomized either to the immediate (48 hr post‐surgery) or the early (2 weeks after surgery) loading group. In prosthetic rehabilitation, a bar prosthetic system with a titanium bar was used. Implant survival, success rates, and radiographic changes at the crestal bone level were evaluated after 1 year, and patient satisfaction was recorded at 1 and 6 months post‐surgery.ResultsTwenty‐four patients with a mean age of 67 ± 9 years were included. One patient passed away after 11 months due to treatment‐independent reasons. In the 24 implants of the immediate loading group, the mean bone level change from surgery/loading to the first‐year evaluation was 0.32 ± 0.80 mm (p = .066). Regarding the early group (22 implants), the mean bone level change from loading to 1 year was 0.34 ± 0.69 mm (p = .048). After 1 year, no differences could be detected between groups (p = .91) with a mean difference of 0.02 mm (95% CI: [−0.42, 0.47]). The mean implant survival and success rates were 100% for both groups.Patient satisfaction was high; however, at 6 months, there was a difference between groups regarding the ability to chew.ConclusionsBoth loading protocols for mandibular overdentures supported by two‐splinted narrow‐diameter implants were successful at the 1‐year follow‐up.
Progressive brain atrophy in Parkinson's disease patients who convert to mild cognitive impairment
Authors: Zhou Cheng , Guan Xiao‐Jun , Guo Tao , Zeng Qiao‐Ling , Gao Ting , Huang Pei‐Yu , Xuan Min , Gu Quan‐Quan , Xu Xiao‐Jun , Zhang Min‐Ming 
Published: July 2019

AbstractAimsCognitive impairment is a common symptom in the trajectory of Parkinson's disease (PD). However, the pathological underpinning is not fully known. We aimed to explore the critical structural alterations in the process of cognitive decline and its relationships with the dopaminergic deficit and the level of related cerebrospinal fluid (CSF) proteins.MethodsNinety‐four patients with PD and 32 controls were included in this study. Neuropsychological tests were performed at baseline and after 28 months to identify which patients had normal cognition and which ones developed PD‐MCI after follow‐up (“converters”). Gray matter atrophy was assessed in cross‐sectional and longitudinal analyses, respectively. The associations between altered GMV with dopamine transporter (DAT) results and the level of CSF proteins were assessed.ResultsAmong the 94 patients with normal cognition at baseline, 24 (mean age, 63.1 years) developed PD‐MCI after 28 months of follow‐up, and 70 (mean age, 62.3 years) remained nonconverters. The converters showed significant right temporal atrophy at baseline and extensive atrophy in temporal lobe at follow‐up. Progressive bilateral frontal lobe atrophy was found in the converters. Baseline right temporal atrophy was correlated with the striatal dopaminergic degeneration in the converters. No correlation was found between the right temporal atrophy and the alterations of CSF proteins.ConclusionEarly atrophy in temporal lobes and progressive atrophy in frontal lobes might be a biomarker for developing multidomain impairment of cognition and converting to PD‐MCI. Furthermore, cognition‐related temporal atrophy might be associated with dopaminergic deficit reflected by DAT scan but independent of CSF proteins in patients with PD who convert to PD‐MCI.
A systematic review of studies investigating the effects of controlled whole‐body vibration intervention on peripheral circulation
Authors: Mahbub MH , Hiroshige Keiichi , Yamaguchi Natsu , Hase Ryosuke , Harada Noriaki , Tanabe Tsuyoshi 
Published: July 2019

SummaryThe findings of the published studies investigating the changes in peripheral circulation induced by exposure to whole‐body vibration (WBV) are not consensual or conclusive. Also, those studies did not consider the role of vibration magnitude on the peripheral circulatory responses making the interpretation of the observed findings difficult. We aimed to review the published literature investigating the effects of controlled WBV intervention on peripheral circulation by characterizing the relevant exposure conditions including vibration magnitudes, and ascertain the specific patterns of responses in peripheral circulation of the lower extremity from such exposure. A computerized search was performed in PubMed and Scopus using selected key search terms, and the relevant data were extracted. The vibration magnitude in the included studies frequently exceeded the limit specified in the International Standard ISO 2631‐1 (1997) for such exposure. As observed, exposure to WBV with frequencies ≤30 Hz caused an improvement in peripheral blood flow (BF) and/or skin temperature (ST) of the lower extremity. In contrast, the responses in BF and ST from exposure to WBV of higher frequencies (31 Hz–50 Hz) produced conflicting results. The findings of this review indicate that WBV exposure with relatively lower frequency and magnitude can be safely and effectively used to induce improvements in peripheral circulation. For this purpose, the limits recommended by the ISO 2631‐1 (1997) should be considered till safe and effective vibration‐related parameters are established.
The Abdominal Transplant Surgery Workforce: Current state and future trends
Authors: Kaldas Fady M. , Rocca Juan P. , Bhati Chandra S. , Duan Ning , Evenson Amy R. , Tan Henkie P. , Redfield Robert R. , di Sabato Diego M. , Yoshida Atsushi , Abt Peter L. , Geevarghese Sunil K. 
Published: July 2019

AbstractTransplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy‐one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5‐8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up‐to‐date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.
Does duration of donor brain injury impact heart transplantation outcomes?
Authors: Kogan Alexander , Ram Eilon , Nachum Eyal , Kassif Yigal , Lavee Jacob , Peled Yael 
Published: July 2019

AbstractAimWe aimed to study the implications of pre‐transplantation time intervals on HT outcomes.MethodsBrain injury time (BIT) was defined as the period from the donor brain injury to brain death declaration. Brain death interval (BDI) was defined as the period from brain death to application of an aortic cross‐clamp during donor heart procurement. Allograft ischemia was defined as the time from donor aortic cross‐clamp to aortic unclamping. End points included mortality and rejections.ResultsBetween 1997 and 2017, we assessed 173 patients. Kaplan‐Meier analyses showed that prolonged donor BIT, BDI, allograft ischemia, and total injury time had no significant effect on mortality and rejections. Patients were subdivided into short BIT (<97 hours, n = 87) and long BIT (≥97 hours, n = 86) groups. No differences in rejection scores nor in time to first rejection were noted. Kaplan‐Meier analysis showed a similar long‐term survival in the two groups. Sub‐analysis of both groups according to their median BDI (12 hours) revealed no differences in mortality or time to rejection.ConclusionsPre‐transplantation time intervals do not affect mortality or rejection. Our findings have important clinical implications regarding HT allocation and organ availability.
A case of S‐100‐negative CD1a‐positive indeterminate cell histiocytosis
Authors: Amin Sima , Jamerson Jordan , Tee Ronald G. , Parekh Palak 
Published: July 2019

AbstractHistiocytoses are a group of rare disorders characterized by a proliferation of monocytes/macrophages and dendritic cells. We present a case of a 3‐year‐old girl with a diffuse papular eruption without systemic symptoms demonstrating a proliferation of strongly CD1a+ histiocytes, but negative for S‐100 and langerin on histopathology. Systemic work‐up including bone marrow biopsy was unremarkable, and the patient received a diagnosis of CD1a+ S− 100‐indeterminate cell histiocytosis.
Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation: A new variant
Authors: Mestre‐Alagarda Claudia , Nieto Gema , Terrádez Liria , Monteagudo Carlos 
Published: July 2019

AbstractIsolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87‐year‐old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle‐cell and epithelial‐like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with atypical mitotic figures. BER‐EP4 immunostaining was exclusively found in the nodular BCC component whereas the sarcomatoid component revealed immunostaining for α‐smooth muscle actin (SMA), muscle‐specific actin (MSA), calponin, and p63 in both epithelial‐like and spindle‐cell populations. Focal immunoreactivity was observed in the epithelial component for S100 and glial fibrillary acidic protein (GFAP). Furthermore, EWSR1‐PBX1 gene fusion was also detected. This is to our knowledge, the first fully documented case of biphasic sarcomatoid BCC with myoepithelial carcinoma differentiation.
Factors that influence the intended intensity of diabetes care in a person‐centred setting
Authors: van Vugt H. A. , Heijmans M. J. W. M. , de Koning E. J. P. , Rutten G. E. H. M. 
Published: July 2019

AbstractAimsTo assess the intended intensity of Type 2 diabetes care and the factors associated with that intensity of care after the annual monitoring visit in which a new person‐centred diabetes consultation model including shared decision making was used.MethodsWe conducted an observational study in 1284 people from 47 general practices and six hospital outpatient clinics. Intensity of care (more, no/minimal change, less) was based on monitoring frequency and referral to other care providers. We used multivariable analyses to determine the factors that were independently associated with intensity of care. Care providers also reported three factors which, in their opinion, determined the intensity of care.ResultsAfter the consultation, 22.8% of people chose more intensive care, 70.6% chose no/minimal change and 6.6% chose less intensive care. Whether care became more intensive vs not/minimally changed was associated with a high educational level (odds ratio 1.65, CI 1.07 to 2.53; P=0.023), concern about illness (odds ratio 1.08; CI 1.00 to 1.17; P=0.045), goal‐setting (odds ratio 6.53, CI 3.79 to 11.27; P<0.001), comorbidities (odds ratio 1.12, CI 1.00 to 1.24; P=0.041) and use of oral blood glucose lowering medication (odds ratio 0.59, CI 0.39 to 0.89; P=0.011). Less intensive care vs no/minimal change was associated with lower diabetes distress levels (odds ratio 0.87, CI 0.79 to 0.97; P=0.009). According to care providers, quality of life, lifestyle, person's preferences and motivation, glycaemic control, and self‐management possibilities most frequently determined the intended care.ConclusionsIn person‐centred diabetes care, the intended intensity of care was associated with both disease‐ and person‐related factors.