bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal fertility, acrosome formation, IFT20 expression and localization in conditional Gmap210 knockout mice
Authors: Wang Zhenyu , Shi Yuqin , Ma Suheng , Huang Qian , Yap Yi Tian , Shi Lin , Zhang Shiyang , Zhou Ting , Li Wei , Hu Bo , Zhang Ling , Krawetz Stephen A. , Pazour Gregory J. , Hess Rex A. , Zhang Zhibing
Published: October 2019

GMAP210 (TRIP11) is a cis-Golgi network-associated protein and a Golgi membrane receptor for IFT20, an intraflagellar transport component essential for male fertility and spermiogenesis in mice. To investigate the role of GMAP210 in male fertility and spermatogenesis, floxed Gmap210 mice were bred with Stra8-iCre mice so that the Gmap210 gene is disrupted in spermatocytes and spermatids in this study. The Gmap210flox/flox: Stra8-iCre mutant mice showed no gross abnormalities and survived to adulthood. In adult males, testis and body weights showed no difference between controls and mutant mice. Low-magnification histological examination of the testes revealed normal seminiferous tubule structure, but sperm counts and fertility were significantly reduced in mutant mice compared with controls. Higher resolution examination of the mutant seminiferous epithelium showed that nearly all sperm had more oblong, abnormally shaped heads, while the sperm tails appeared to have normal morphology. Electron microscopy also revealed abnormally shaped sperm heads but normal axoneme core structure; some sperm showed membrane defects in the midpiece. In mutant mice, expression levels of IFT20 and other selective acrosomal proteins were significantly reduced, and their localization was also affected. Peanut-lectin, an acrosome maker, was almost absent in the spermatids and epididymal sperm. Mitochondrion staining was highly concentrated in the heads of sperm, suggesting that the midpieces were coiling around or aggregating near the heads. Defects in acrosome biogenesis were further confirmed by electron microscopy. Collectively, our findings suggest that GMAP210 is essential for acrosome biogenesis, normal mitochondrial sheath formation, and male fertility, and it determines expression levels and acrosomal localization of IFT20 and other acrosomal proteins.
Multiple roles of macrophage migration inhibitory factor in pulmonary hypertension
Authors: Jalce Gael , Guignabert Christophe
Published: October 2019

Pulmonary hypertension (PH) is a life-threatening condition arising from the loss and obstructive remodeling of the pulmonary arteries, leading to the sustained elevation of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) and subsequently right ventricular (RV) failure and death. PH encompasses a group of multifactorial diseases, such as pulmonary arterial hypertension (PAH) and chronic thromboembolic PH, for which there is no treatment that can stop or reverse the progression of remodeling of the pulmonary vasculature. The identification of new molecular targets for the development of more effective drugs is thus urgently needed. In this context, macrophage migration inhibitory factor (MIF), a pleiotropic upstream proinflammatory mediator, is emerging as a promising molecular target, as it contributes to perivascular inflammation and pulmonary arterial remodeling, two key hallmarks of PAH that are not specifically targeted by currently approved therapies. The objective of this review is to summarize the scientific evidence on the pathogenic roles of MIF and its potential as a biomarker and therapeutic target in PH/PAH.
Fritz Rohrer (1888–1926), a pioneer in pulmonary mechanics whose work was inexplicably ignored for about 30 years
Authors: West John B.
Published: October 2019

Fritz Rohrer (1888–1926) has a special place in the history of respiratory physiology for two reasons. The first is that he laid the foundations of modern pulmonary mechanics in the early 1900s. For example, his seminal paper on pulmonary dynamics, that is, the pressure-flow relationships in the airways, was published in 1915 in one of the top journals in the field. It included extensive measurements of airway dimensions in postmortem human lungs and a sophisticated analysis of the modes of airflow. This was closely followed by a very original analysis of lung statics, which included studies of airway pressures at normal, maximal, and minimal lung volumes in relaxed normal volunteers, and was published in 1916. Remarkably, both papers were essentially ignored at the time. Fortunately, in 1925 he was able to summarize his major findings in a chapter in an important handbook of physiology. However, he tragically died from pulmonary tuberculosis in the following year at the early age of 37. The second reason for his importance in the history of pulmonary mechanics is that inexplicably his very innovative research was essentially ignored for about 30 years. It was not until the 1940s that his work was rediscovered, although not in time to save investigators from duplicating his very original studies. Possible reasons why his work was ignored for so long are discussed. Even today it is not easy to recover some important features of his career, and some aspects of his very original research are still almost unknown.
Nutraceuticals as a potential adjunct therapy toward improving vascular health in CKD
Authors: Kruse Nicholas T.
Published: October 2019

Chronic kidney disease (CKD) is a major public health epidemic and increases risk for developing cardiovascular disease (CVD). Vascular dysfunction is a major independent risk factor toward increased risk for CVD in CKD. Several mechanisms have been postulated to result in vascular dysfunction in CKD, including oxidative stress-mediated inflammation by redox imbalance and reduced nitric oxide (NO) bioavailability and synthesis. Therefore, strategies that decrease oxidative stress and/or increase NO bioactivity may have major clinical implications toward improving vascular health and reducing the burden of CVD in CKD. Nutraceutical therapy in the form of polyphenols, dietary nitrates, or selective mitochondria-targeting therapies has recently been shown to improve vascular function by reducing oxidative stress and/or increasing NO bioavailability and synthesis. This review, therefore, highlights these three emerging nutraceuticals recently implicated in pathophysiological improvement of vascular function in CKD. This review also describes those pathophysiological mechanisms thought to be responsible for the beneficial effects on the vasculature and possible experimental considerations that may exist within human CKD populations. It is clear throughout this review that human-based mechanistic preclinical and health-related clinical studies are lacking regarding whether nutraceuticals do indeed improve vascular function in patients with CKD. As such, a comprehensive, detailed, and fully integrated understanding of nutraceuticals and vasculature function is necessary in patients with CKD. Many opportunities exist for original mechanistic and therapeutic discoveries and investigations on select nutraceuticals and their impact on vascular outcomes in patients with CKD, and these will remain exciting avenues of research in the future.
Platelet Biogenesis in the Lung Circulation
Authors: Lefrançais Emma , Looney Mark R.
Published: October 2019

Megakaryocytes are normal cellular components of the blood returning to the heart and entering the lungs, and historical data has pointed to a role of the lungs in platelet production. Recent studies using intravital microscopy have demonstrated that platelet release occurs in the lung from bone marrow megakaryocytes that embolize into the lung circulation.
Comparison of Preoperative Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Bladder Cancer Patients Undergoing Radical Cystectomy
Authors: Wang Ruiliang , Yan Yang , Liu Shenghua , Yao Xudong
Published: October 2019

Introduction. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proven to be significant prognostic factors in many cancers. We aimed to retrospectively investigate the prognostic value of NLR and PLR in patients with bladder cancer undergoing radical cystectomy. Materials and Methods. The study comprised patients from 2010 to 2018 who were diagnosed with bladder cancer and received radical cystectomy. Clinical and pathological parameters were collected. Receiver operating characteristic curves of NLR and PLR were plotted for overall survival (OS) and cancer-specific survival (CSS). The best cutoff value of NLR and PLR were determined using X-tile software. The prognostic value of NLR and PLR for OS and CSS was analyzed using the Kaplan–Meier method and Cox regression models. Results. A total of 223 patients were enrolled with a medium follow-up period of 57 months. Receiver operating characteristic curves showed that PLR was superior to NLR as a prognostic factor in patients with bladder cancer undergoing radical cystectomy. Univariate analysis revealed that NLR (p=0.032 and p=0.041) and PLR (p=0.003 and p=0.003) were significantly associated with both OS and CSS, respectively. Multivariate analysis identified only PLR as independent prognostic factors for OS (p=0.046) and CSS (p=0.039), respectively. Conclusions. The present findings suggested that compared with NLR, PLR was a superior prognostic factor of OS and CSS in bladder cancer patients indicated to radical cystectomy.
Exome-First Approach in Fetal Akinesia Reveals Chromosome 1p36 Deletion Syndrome
Authors: Toshimitsu Masatake , Nagaoka Shinichi , Kobori Shuusaku , Ogawa Maki , Suzuki Fumihiko , Kato Takema , Miyai Shunsuke , Kawamura Rie , Inagaki Hidehito , Kurahashi Hiroki , Murotsuki Jun
Published: October 2019

Background. Fetal akinesia refers to a broad spectrum of disorders with reduced or absent fetal movements. There is no established approach for prenatal diagnosis of the cause of fetal akinesia. Chromosome 1p36 deletion syndrome is the most common subtelomeric terminal deletion syndrome, recognized postnatally from typical craniofacial features. However, the influence of chromosome 1p36 deletion on fetal movements remains unknown. Case Report. A 32-week-old fetus with akinesia showed multiple abnormalities, including fetal growth restriction, congenital cardiac defects, and ventriculomegaly. G-banding analysis using cultured amniocytes revealed 46,XY,22pstk+. Postnatal whole exome sequencing and subsequent chromosomal microarray identified a 3 Mb deletion of chromosomal region 1p36.33–p36.32. These results of molecular cytogenetic analyses were consistent with the fetal sonographic findings. Conclusion. Using the exome-first approach, we identified a case with fetal akinesia associated with chromosome 1p36 deletion. Chromosome 1p36 deletion syndrome may be considered for differential diagnosis in cases of fetal akinesia with multiple abnormalities.
2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90
Authors: Kamm Anna , Przychodzeń Paulina , Kuban–Jankowska Alicja , Marino Gammazza Antonella , Cappello Francesco , Daca Agnieszka , Żmijewski Michał A. , Woźniak Michał , Górska–Ponikowska Magdalena
Published: October 2019

Melanoma is an aggressive type of skin cancer with one of the highest mortality rates. Notably, its incidence in the last few decades has increased faster than any other cancer. Therefore, searching for novel anticancer therapies is of great clinical importance. In the present study, we investigated the anticancer potential of 2-methoxyestradiol, potent chemotherapeutic, in the A375 melanoma cellular model. In order to furthermore evaluate the anticancer efficacy of 2-methoxyestradiol, we have additionally combined the treatment with a naturally occurring polyphenol, ferulic acid. The results were obtained using the melanoma A375 cellular model. In the study, we used MTT assay, flow cytometry, and western blot techniques. Herein, we have evidenced that the molecular mechanism of action of 2-methoxyestradiol and ferulic acid is partly related to the reduction of Hsp60 and Hsp90 levels and the induction of nitric oxide in the A375 melanoma cell model, while no changes were observed in Hsp70 expression after 2-methoxyestradiol and ferulic acid treatment separately or in combination. This is especially important in case of chemoresistance mechanisms because the accumulation of Hsp70 reduces induction of cancer cell death, thus decreasing antitumour efficacy.
Estrategias de prevención de infecciones tardías en unidades de cuidados intensivos neonatales
Authors: Toso Milos Alberto Antonio , Urzúa Baquedano María Soledad
Published: October 2019

Introducción: la sepsis tardía (ST) sigue siendo un problema relevante en las unidades de cuidados intensivos de neonatología (UCIN), especialmente en recién nacidos (RN) menores de 1500 g o RN de muy bajo peso al nacer (RNMBPN). Método: se realizó una búsqueda de la mejor evidencia disponible respecto a las estrategias de prevención de infecciones en unidades de cuidados intensivos neonatales. Resultados: se han descrito diversas estrategias para intentar disminuir su incidencia, entre estas se incluye el uso de vacunas en el embarazo, profilaxis con fluconazol y uso de probióticos. Han demostrado utilidad otras medidas destinadas a reducir y racionalizar el uso de antibióticos, la creación de equipos especializados y la incorporación de bundles a la práctica clínica. Conclusiones: Este artículo resume la evidencia actualmente disponible y proporciona herramientas que pueden ser utilizadas en la práctica cotidiana dentro de las UCIN.
MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers
Authors: Seo Jimyung , Kim Min Hwan , Hong Hyowon , Cho Hyunsoo , Park Seongyeol , Kim Sang Kyum , Kim Joon
Published: October 2019

Transcriptional regulator YAP is activated in multiple human cancers and plays critical roles in tumor initiation, progression, metastasis, and drug resistance. However, therapeutic targeting of the Hippo–YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulation in cancer. Here we present a functional screen and identify a novel therapeutic target for YAP-driven tumorigenesis. RNAi screening using an oncogenic YAP activation model identified the serine/threonine kinase MK5 as a positive regulator of YAP. MK5 physically interacted with YAP and counteracted CK1δ/ϵ-mediated YAP ubiquitination and degradation independent of LATS1/2. MK5 kinase activity was essential for protecting YAP from ubiquitin-mediated degradation and cytoplasmic retention. Downregulating MK5 expression inhibited the survival of YAP-activated cancer cell lines and mouse xenograft models. MK5 upregulation was associated with high levels of YAP expression and poor prognosis in clinical tumor samples, confirming its important role for YAP activity in human cancer. These results uncover MK5 as a novel factor that regulates YAP stability, and targeting the YAP degradation pathway controlled by MK5 is a potential strategy for suppressing YAP activity in cancer.

Significance:

These findings reveal MK5 is a novel kinase that regulates YAP in a LATS-independent manner and can be targeted for cancer therapy.
Decreased NOTCH1 Activation Correlates with Response to Ibrutinib in Chronic Lymphocytic Leukemia
Authors: Del Papa Beatrice , Baldoni Stefano , Dorillo Erica , De Falco Filomena , Rompietti Chiara , Cecchini Debora , Cantelmi Maria Grazia , Sorcini Daniele , Nogarotto Manuel , Adamo Francesco Maria , Mezzasoma Federica , Silva Barcelos Estevão Carlos , Albi Elisa , Iacucci Ostini Roberta , Di Tommaso Ambra , Marra Andrea , Montanaro Guido , Martelli Maria Paola , Falzetti Franca , Di Ianni Mauro , Rosati Emanuela , Sportoletti Paolo
Published: October 2019

Purpose:

Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), has improved the outcomes of chronic lymphocytic leukemia (CLL), but primary resistance or relapse are issues of increasing significance. While the predominant mechanism of action of BTKi is the B-cell receptor (BCR) blockade, many off-target effects are unknown. We investigated potential interactions between BCR pathway and NOTCH1 activity in ibrutinib-treated CLL to identify new mechanisms of therapy resistance and markers to monitor disease response.

Experimental Design:

NOTCH activations was evaluated either in vitro and ex vivo in CLL samples after ibrutinib treatment by Western blotting. Confocal proximity ligation assay (PLA) experiments and analyses of down-targets of NOTCH1 by qRT-PCR were used to investigate the cross-talk between BTK and NOTCH1.

Results:

In vitro ibrutinib treatment of CLL significantly reduced activated NOTCH1/2 and induced dephosphorylation of eIF4E, a NOTCH target in CLL. BCR stimulation increased the expression of activated NOTCH1 that accumulated in the nucleus leading to HES1, DTX1, and c-MYC transcription. Results of in situ PLA experiments revealed the presence of NOTCH1-ICD/BTK complexes, whose number was reduced after ibrutinib treatment. In ibrutinib-treated CLL patients, leukemic cells showed NOTCH1 activity downregulation that deepened over time. The NOTCH1 signaling was restored at relapse and remained activated in ibrutinib-resistant CLL cells.

Conclusions:

We demonstrated a strong clinical activity of ibrutinib in a real-life context. The ibrutinib clinical efficacy was associated with NOTCH1 activity downregulation that deepened over time. Our data point to NOTCH1 as a new molecular partner in BCR signaling with potential to further improve CLL-targeted treatments.
Genetic and Epigenetic Characterization of Growth Hormone–Secreting Pituitary Tumors
Authors: Välimäki Niko , Schalin-Jäntti Camilla , Karppinen Atte , Paetau Anders , Kivipelto Leena , Aaltonen Lauri A. , Karhu Auli
Published: October 2019

Somatic driver mechanisms of pituitary adenoma pathogenesis have remained incompletely characterized; apart from mutations in the stimulatory Gα protein (Gαs encoded by GNAS) causing activated cAMP synthesis, pathogenic variants are rarely found in growth hormone–secreting pituitary tumors (somatotropinomas). The purpose of the current work was to clarify how genetic and epigenetic alterations contribute to the development of somatotropinomas by conducting an integrated copy number alteration, whole-genome and bisulfite sequencing, and transcriptome analysis of 21 tumors. Somatic mutation burden was low, but somatotropinomas formed two subtypes associated with distinct aneuploidy rates and unique transcription profiles. Tumors with recurrent chromosome aneuploidy (CA) were GNAS mutation negative (Gsp−). The chromosome stable (CS) –group contained Gsp+ somatotropinomas and two totally aneuploidy-free Gsp− tumors. Genes related to the mitotic G1–S-checkpoint transition were differentially expressed in CA- and CS-tumors, indicating difference in mitotic progression. Also, pituitary tumor transforming gene 1 (PTTG1), a regulator of sister chromatid segregation, showed abundant expression in CA-tumors. Moreover, somatotropinomas displayed distinct Gsp genotype–specific methylation profiles and expression quantitative methylation (eQTM) analysis revealed that inhibitory Gα (Gαi) signaling is activated in Gsp+ tumors. These findings suggest that aneuploidy through modulated driver pathways may be a causative mechanism for tumorigenesis in Gsp− somatotropinomas, whereas Gsp+ tumors with constitutively activated cAMP synthesis seem to be characterized by DNA methylation activated Gαi signaling.

Implications:

These findings provide valuable new information about subtype-specific pituitary tumorigenesis and may help to elucidate the mechanisms of aneuploidy also in other tumor types.
The Challenge of Defining and Investigating the Causes of Idiopathic Short Stature and Finding an Effective Therapy
Authors: Inzaghi Elena , Reiter Edward , Cianfarani Stefano
Published: October 2019

Idiopathic short stature (ISS) comprises a wide range of conditions associated with short stature that elude the conventional diagnostic work-up and are often caused by still largely unknown genetic variants. In the last decade, the improvement of diagnostic techniques has led to the discovery of causal mutations in genes involved in the function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis as well as in growth plate physiology. However, many cases of ISS remain idiopathic. In the future, the more frequent identification of the underlying causes will allow a better stratification of subjects and offer a tailored management. GH therapy has been proposed and approved in some countries for the treatment of children with ISS. To improve the efficacy of GH therapy, trials with GH combined with GnRH agonists, aromatase inhibitors, and even IGF-I have been conducted. This review aims to revise the current definition of ISS and discuss the management of children with ISS on the basis of the most recent evidence.
Unusual Segregation of APP Mutations in Monogenic Alzheimer Disease
Authors: Mastromoro Gioia , Gambardella Stefano , Marchionni Enrica , Campopiano Rosa , Traversa Alice , Di Bonaventura Carlo , Pizzuti Antonio
Published: October 2019

APP gene mutations causing Alzheimer disease (AD) segregate in an autosomal dominant pattern. We report on a 40-year-old woman with a severe cognitive decline starting at 36 years, while her affected relatives presented symptoms onset in the 6th decade. The proband carried an APP missense variant in homozygous state (NM_000484.4: c.2032G>A; NP_000475.1: p.Asp678Asn; rs63750064) and showed a more severe clinical picture than the other AD relatives, as regards the age of onset and the rate of disease progression. This mutation behaves as a semi-dominant trait. The very rare chance of studying APP mutations in the homozygous state demonstrates they are not always dominant and other segregation models are possible.
Vascular Access Type Was Not Associated with Mortality and the Predictors for Cardiovascular Death in Elderly Chinese Patients on Hemodialysis
Authors: Yu Yang , Xiong Yuqin , Zhang Chunle , Fu Martina , Li Yi , Fu Ping
Published: October 2019

Objectives: Current studies suggest arteriovenous fistula (AVF) and arteriovenous graft as superior vascular access (VA) types for elderly hemodialysis (HD) patients due to better outcomes. This study aimed to examine the impact of VA type on cardiovascular and all-cause mortality as well as the predictors for outcome in elderly Chinese patients. Methods: Patients who initiated HD aged ≥70 years and received a primary VA creation at the West China Hospital were enrolled in this retrospective study. Clinical characteristics, maturation, utilization, conversion of VA, and outcomes were collected. The observational period for each patient was from the point of the first permanent VA creation to the last time of follow-up. Kaplan-Meier and multivariate regression analysis were employed. Results:A total of 358 elderly Chinese HD patients with a median age of 74 (72–78) years were analyzed. During the study period of 25.8 (12–43) months, 54 (15.1%) and 113 patients (15.1%) died of cardiovascular events and all-cause, respectively. With regard to VA type, the modality of AVF, tunneled cuffed central venous catheter (tcCVC), or AVF and tcCVC was not associated with mortality. Furthermore, diastolic blood pressure (DBP) and congestive heart failure (CHF) were the independent predictors for cardiovascular mortality. Conclusions: The modality of VA types showed an insignificant effect on mortality in elderly Chinese population, while preoperative DBP and the presence of CHF might be used for the risk assessment of cardiovascular death. Disparities among nations in the areas of VA and HD necessitate additional studies.
Cognitive Impairment Is Associated with Absolute Intraoperative Frontal α-Band Power but Not with Baseline α-Band Power: A Pilot Study
Authors: Koch Susanne , Feinkohl Insa , Chakravarty Sourish , Windmann Victoria , Lichtner Gregor , Pischon Tobias , Brown Emery N. , Spies Claudia ,   BioCog Study Group
Published: October 2019

Background: Cognitive abilities decline with aging, leading to a higher risk for the development of postoperative delirium or postoperative neurocognitive disorders after general anesthesia. Since frontal α-band power is known to be highly correlated with cognitive function in general, we hypothesized that preoperative cognitive impairment is associated with lower baseline and intraoperative frontal α-band power in older adults. Methods: Patients aged ≥65 years undergoing elective surgery were included in this prospective observational study. Cognitive function was assessed on the day before surgery using six age-sensitive cognitive tests. Scores on those tests were entered into a principal component analysis to calculate a composite “g score” of global cognitive ability. Patient groups were dichotomized into a lower cognitive group (LC) reaching the lower 1/3 of “g scores” and a normal cognitive group (NC) consisting of the upper 2/3 of “g scores.” Continuous pre- and intraoperative frontal electroencephalograms (EEGs) were recorded. EEG spectra were analyzed at baseline, before start of anesthesia medication, and during a stable intraoperative period. Significant differences in band power between the NC and LC groups were computed by using a frequency domain (δ 0.5–3 Hz, θ 4–7 Hz, α 8–12 Hz, β 13–30 Hz)-based bootstrapping algorithm. Results: Of 38 included patients (mean age 72 years), 24 patients were in the NC group, and 14 patients had lower cognitive abilities (LC). Intraoperative α-band power was significantly reduced in the LC group compared to the NC group (NC –1.6 [–4.48/1.17] dB vs. LC –6.0 [–9.02/–2.64] dB), and intraoperative α-band power was positively correlated with “g score” (Spearman correlation: r = 0.381; p = 0.018). Baseline EEG power did not show any associations with “g.” Conclusions: Preoperative cognitive impairment in older adults is associated with intraoperative absolute frontal α-band power, but not baseline α-band power.
Association between p.R4810K Variant and Postoperative Collateral Formation in Patients with Moyamoya Disease
Authors: Ge Peicong , Ye Xun , Liu Xingju , Deng Xiaofeng , Wang Jia , Wang Rong , Zhang Yan , Zhang Dong , Zhang Qian , Zhao Jizong
Published: October 2019

Object: To investigate the association between p.R4810K variant and postoperative collateral formation (PCF) in patients with moyamoya disease. Methods: The p.R4810K variant was detected in 254 Chinese moyamoya patients. Surgically treated 273 hemispheres with preoperative and postoperative digital subtraction angiography were included. PCF was evaluated on lateral and anteroposterior views using angiography. Univariate and multivariate logistic regression analyses were performed to determine the influence factors for PCF. Results: Among 254 patients, 191 (75.2%) patients carried wild-type p.R4810K variant (GG) and 63 patients (24.8%) carried the heterozygous p.R4810K variant (GA). PCF was better in patients with GA than in patients with GG both on lateral views and anteroposterior views (p < 0.001 and p < 0.001). Over the median 7 months follow-up after discharge, good PCF was observed in 201 hemispheres (73.6%), and poor PCF was observed in 72 hemispheres (26.4%). The univariable logistic regression showed that patients with GA (OR 4.681; 95% CI 1.925–11.383; p = 0.001) was associated with good PCF. On the other hand, the increasing age (OR 0.971; 95% CI 0.952–0.989; p = 0.002) and the presence of hemorrhage (OR 0.189; 95% CI 0.096–0.374; p = 0.000) were associated with poor PCF. Multivariate logistic regression analyses of p.R4810K variant and clinical variables showed that GA (OR 3.671; 95% CI 1.452–9.283; p = 0.006) was associated with a good PCF, while the presence of hemorrhage (OR 0.258; 95% CI 0.065–0.362; p = 0.000) was identified as a predictor of poor PCF. Conclusions: The heterozygous p.R4810K variant was associated with better PCF.
Outpatient Kidney Biopsy: A Single Center Experience and Review of Literature
Authors: Aaltonen Sari , Finne Patrik , Honkanen Eero
Published: October 2019

Background: A kidney biopsy is an important tool in managing kidney diseases. Bleeding is the most significant complication. The biopsy can be performed as an inpatient or an outpatient procedure with a shorter post-biopsy bed rest and monitoring period. It is cost-effective, but raises some questions about patient safety. At Helsinki University Hospital, the majority of elective kidney biopsies have been performed as outpatient procedures since 2010. The aim of this study was to retrospectively evaluate the safety and risk factors of this protocol. Methods: We collected data from all patients undergoing an elective outpatient biopsy of a native or transplanted kidney following the outpatient protocol between January 2011 and February 2016. We recorded the data on the biopsy procedure and complications: bleeding (hematoma or macrohematuria), severe pain, death, or “other” (infection, accidental puncture of another organ). A complication was classified as major, if it required interventions such as transfusion or radiological or surgical intervention. Results: Over a 5-year period, 824 (448 native and 326 transplant kidney) patients were biopsied. In total, 94 (11.4%) had a complication, but only 4 patients (0.5%) had a major complication; no deaths were recorded. All major and 70 minor complications emerged during post-biopsy monitoring (4–6 h). Patients with complications were younger (p = 0.001), female (p < 0.001), and had lower hemoglobin (p = 0.001) than those without. Transplant biopsies were associated with fewer complications than native kidney biopsies (p= 0.002). Conclusions: In selected patients, an outpatient kidney biopsy is a relatively safe procedure.
A Case Report of Idiopathic Follicular Hyperkeratotic Spicules and Literature Review
Authors: Leerunyakul Kanchana , Chirasuthat Phatcharawat , Suchonwanit Poonkiat
Published: October 2019

Follicular hyperkeratotic spicules is a rare skin disorder that is usually associated with multiple myeloma. The condition typically presents with tiny hyperkeratotic spicules in follicular distribution and predominantly on the face. To our knowledge, there has been one reported case of this condition without underlying disease. We herein report the second case of idiopathic follicular hyperkeratotic spicules in a 54-year-old Thai woman presenting with multiple follicular horn-like spicules on her face and neck.
Consensus Meeting of Breast Imaging: BI-RADS® and Beyond
Authors: Müller-Schimpfle Markus , Bader Werner , Baltzer Pascal , Bernathova Maria , Fuchsjäger Michael , Golatta Michael , Helbich Thomas H. , Hellerhoff Karin , Heywang-Köbrunner Sylvia H. , Kurtz Claudia , Mundinger Alexander , Siegmann-Luz Katja C. , Skaane Per , Solbach Chistine , Weigel Stefanie
Published: October 2019

Organizers of medical educational courses are often confronted with questions that are clinically relevant yet trespassing the frontiers of scientifically proven, evidence-based medicine at the point of care. Therefore, since 2007 organizers of breast teaching courses in German language met biannually to find a consensus in clinically relevant questions that have not been definitely answered by science. The questions were prepared during the 3 months before the meeting according to a structured process and finally agreed upon the day before the consensus meeting. At the consensus meeting, the open questions concerning 2D/3D mammography, breast ultrasound, MR mammography, interventions as well as risk-based imaging of the breast were presented first for electronic anonymized voting, and then the results of the audience were separately displayed from the expert votes. Thereafter, an introductory statement of the moderator was followed by pros/cons of two experts, and subsequently the final voting was performed. With ≥75% of votes of the expert panel, an answer qualified as a consensus statement. Seventeen consensus statements were gained, addressing for instance the use of 2D/3D mammography, breast ultrasound in screening, MR mammography in women with intermediate breast cancer risk, markers for localization of pathologic axillary lymph nodes, and standards in risk-based imaging of the breast. After the evaluation, comments from the experts on each field were gathered supplementarily. Methodology, transparency, and soundness of statements achieve a unique yield for all course organizers and provide solid pathways for decision making in breast imaging.
Vancomycin Induced Thrombocytopenia – Protracted Course in a Hemodialysis Patient
Authors: Ajit Nisha Elizabeth , Devarashetty Sindhu Priya , Master Samip
Published: October 2019

Vancomycin induced thrombocytopenia (VIT) is an uncommon side effect of vancomycin which can manifest from mild petechiae to life-threatening bleed. Decreased renal clearance of vancomycin results in prolonged thrombocytopenia by antibody-mediated platelet destruction in the presence of vancomycin. Improvement in thrombocytopenia is achieved with the elimination of vancomycin. We describe a patient with end stage renal disease who experienced a protracted course of thrombocytopenia from vancomycin. We illustrate the mechanism of thrombocytopenia and the treatment modalities used by us and those described in literature. VIT is an important differential in patients with thrombocytopenia admitted to the hospital.
Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis
Authors: Bellos Ioannis , Kontzoglou Konstantinos , Psyrri Amanda , Pergialiotis Vasilios
Published: October 2019

Background and Aims: Refractory ascites represents a significant complication of decompensated cirrhosis, associated with increased mortality rates. The aim of this meta-analysis was to evaluate whether response to treatment with tolvaptan is associated with improved overall survival in cirrhotic patients with refractory ascites. Methods: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception to April 11, 2019. All studies that assessed the overall survival of patients with ascites depending on their response to tolvaptan were held eligible. Results: Nine studies were included, with a total of 736 patients with cirrhosis and ascites. Response to tolvaptan was estimated to be linked to significantly improved overall survival (hazard ratio [HR] 0.42, 95% CI [0.31–0.58]). Subgroup analysis indicated that the same outcome was present when tolvaptan responsiveness was defined either as effective body weight loss (HR 0.44, 95% CI [0.30–0.63] or as effective sodium restoration (HR 0.35, 95% CI [0.20–0.61]. Sensitivity analysis suggested that the presence of hepatocellular carcinoma, the sample size, and the quality of the studies did not significantly affect the overall result of the meta-analysis. Conclusions: The outcomes of the meta-analysis support the prognostic role of tolvaptan response in patients with cirrhosis and refractory ascites, as it was shown to lead to significantly improved overall survival. These findings should be confirmed by future large-scale studies, while efficient biomarkers should be identified in order to accurately predict response to tolvaptan and discriminate patients that would benefit from its administration.
Reasons for Prehospital Delay in Acute Ischemic Stroke
Authors: Fladt Joachim , Meier Nicole , Thilemann Sebastian , Polymeris Alexandros , Traenka Christopher , Seiffge David J. , Sutter Raoul , Peters Nils , Gensicke Henrik , Flückiger Benjamin , de Hoogh Kees , Künzli Nino , Bringolf‐Isler Bettina , Bonati Leo H. , Engelter Stefan T. , Lyrer Philippe A. , De Marchis Gian Marco
Published: October 2019

Background

Prehospital delay reduces the proportion of patients with stroke treated with recanalization therapies. We aimed to identify novel and modifiable risk factors for prehospital delay.

Methods and Results

We included patients with an ischemic stroke confirmed by diffusion‐weighted magnetic resonance imaging, symptom onset within 24 hours and hospitalized in the Stroke Center of the University Hospital Basel, Switzerland. Trained study nurses interviewed patients and proxies along a standardized questionnaire. Prehospital delay was defined as >4.5 hours between stroke onset—or time point of wake‐up—and admission. Overall, 336 patients were enrolled. Prehospital delay was observed in 140 patients (42%). The first healthcare professionals to be alarmed were family doctors for 29% of patients (97/336), and a quarter of these patients had a baseline National Institute of Health Stroke Scale score of 4 or higher. The main modifiable risk factor for prehospital delay was a face‐to‐face visit to the family doctor (adjusted odds ratio, 4.19; 95%
CI
, 1.85–9.46). Despite transport by emergency medical services being associated with less prehospital delay (adjusted odds ratio, 0.41; 95%
CI
, 0.24–0.71), a minority of patients (39%) who first called their family doctor were transported by emergency medical services to the hospital. The second risk factor was lack of awareness of stroke symptoms (adjusted odds ratio, 4.14; 95%
CI
, 2.36–7.24).

Conclusions

Almost 1 in 3 patients with a diffusion‐weighted magnetic resonance imaging–confirmed ischemic stroke first called the family doctor practice. Face‐to‐face visits to the family doctor quadrupled the odds of prehospital delay. Efforts to reduce prehospital delay should address family doctors and their staffs as important partners in the prehospital pathway.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02798770.
People’s Intuitions About Innateness
Authors: Berent Iris , Platt Melanie , Sandoboe Gwendolyn M.
Published: October 2019

Few questions in science are as controversial as the origins of knowledge. Whether knowledge (e.g., “objects are cohesive”) is partly innate has been debated for centuries. Here, we ask whether our difficulties with innate knowledge could be grounded in human cognition itself. In eight experiments, we compared reasoning about the innateness of traits that capture knowledge (cognitive traits) with noncognitive (sensorimotor and emotive) traits. Experiments 1–4 examined adult and infant traits; Experiment 5 presented detailed descriptions of published infant experiments. Results showed that people viewed cognitive traits as less likely to be innate in humans—the stronger the association with “thinking,” the lower the rating for “innateness.” Experiments 6–8 explored human, bird, and alien traits that were presented as innate. Participants, however, still considered cognitive traits as less likely to emerge spontaneously (i.e., be innate). These results show that people are selectively biased in reasoning about the origins of knowledge.
Historiographical Approaches on Experience and Empiricism in the Early Nineteenth-Century: Degérando and Tennemann
Authors: Manzo Silvia
Published: October 2019

This paper examines the views of Joseph-Márie Degérando and Wilhelm Gottlieb Tennemann about empiricism, and the scope and limits of experience as well as its relation to reason and its role in the attainment of true knowledge. While Degérando adopted the “philosophy of experience” and Tennemann advocated Kant’s critical philosophy, both authors blamed each other for the same mistake: if Degérando considered that, despite all appearances to the contrary, critical philosophy fell into empiricism, Tennemann judged that the philosophy of experience was nothing but pure and simple empiricism. Degérando’s and Tennemann’s discrepancies involved not only a discussion of “nomenclatures” and of the role and limits of experience in knowing, but also an epistemological and ideological commitment to the pacification of the intellectual field in the aftermath of the French Revolution. In this line, Degérando’s alignment with the philosophy of experience attempted to distance himself from the politically dangerous sensualism attributed to the idéologie. But, unlike his countryman Charles Villers, he did not want to replace the sensualism by critical philosophy. His opposition to philosophical novelty (which he associated with political revolution) led him to praise only the “eclectic” spirit of Kant’s philosophy.
Experimental Method and the Spiritualist Soul: The Case of Victor Cousin
Authors: Antoine-Mahut Delphine
Published: October 2019

Spiritualism designates a philosophy that lays claim to the separation of mind and body and the ontological and epistemological primacy of the former. In France, it is associated with the names of Victor Cousin and René Descartes, or more precisely with what Cousin made of Descartes as the founding father of a brittle rational psychology, closed off from the positive sciences, and as a critic in respect to the empiricist legacy of the idéologues. Moreover, by considering merely the end result, severed from its polemical genesis, we are prevented from understanding how the category of experience constituted a crucial question for spiritualism itself. Through returning to the origin of these discussions in the 1826 preface to Cousin’s Fragments philosophiques, this essay pursues a threefold path: to show (1) that the public birth of Cousinian spiritualism coincides with the affirmation of applying the experimental method, issuing from Bacon, to the study of facts of consciousness; (2) that Cousin’s later evolution follows a process of radicalization—that is, in this context, of ontologization and of reduction; and (3) that by recovering this genesis, we can distinguish many forms of spiritualisms committed to the experimental method, both in alliance with the early Cousin and against the later Cousin. In this way, we can rediscover the interwoven philosophical links, lost in the process of institutionalization, between metaphysical demands and empiricist concerns, or between “French” philosophy and the legacy of Condillac.
“True Empiricism”: The Stakes of the Cousin-Schelling Controversy
Authors: Whistler Daniel
Published: October 2019

Between 1833 and 1835, Victor Cousin and F.W.J. Schelling engaged in an “amical but serious critique” of each other’s philosophies. I argue that, despite perceptions to the contrary, key to this exchange is a common vision of an atypical, speculative empiricism. That is, against the grain of most commentaries, I contend that there are significant similarities between Cousin’s and Schelling’s philosophies of the early 1830s—similarities that converge on the possibility of a post-Kantian speculative empiricism, which they respectively dub metaphysical psychology or a priori empiricism.
The Development of Armeno-Turkish (Hayatar T‘rk‘erēn) in the 19th Century Ottoman Empire
Authors: Der Matossian Bedross
Published: October 2019

Armeno-Turkish played an important role in the lives of Armenians in the Ottoman Empire. At a time in which more than half of the Armenians of the Empire did not speak Armenian, Armeno-Turkish came to fill an important gap. It led to the proliferation of literacy among Armenians and allowed them to mark and strengthen their ethno-religious boundaries vis-à-vis other ethno-religious groups in the Ottoman Empire, while simultaneously allowing for the crossing of these boundaries which, in general, were characterized by fluidity. The 19th century represents an important phase in the development of Armeno-Turkish. Its development cannot be attributed to one factor; rather to a host of factors that include the impact of the Armenian Zart‘ōnk‘ (awakening), the spread of Catholicism and Protestantism, the impact of the Tanzimat Reforms (1839–1876), the development of Armenian ethno-religious boundaries, and the role of print culture. Finally, Armeno-Turkish raises important questions regarding identity formation, belonging, and cross-cultural interaction.
Lithophyllum longense (Corallinales, Rhodophyta): a species with a widespread Indian Ocean distribution

Authors: MANEVELDT G.W. , GABRIELSON P.W. , TOWNSEND R.A. , KANGWE J.
Published: October 2019

Lithophyllum longense is characterized from Long Reef, Western Australia, Australia and from Chwaka Bay, Zanzibar Island, Tanzania.  Both plastid markers psbA and rbcL confirm that L. longense is a distinct species despite its being morpho-anatomically nearly indistinguishable from several other fruticose Lithophyllum species, differing in only one (from L. atlanticum, L. platyphyllum, L. sublicatum, L. yemenense) or two (from L. affine, L. incrustans, L. kotschyanum, L. neocongestum, L. kaiseri, L. pseudoplatyphyllum, L. subreduncum) character states.  This is only the second tropical Lithophyllum species and the fourth tropical species confirmed by DNA sequencing to be widely distributed in the Indo-West Pacific.
Unintended consequences in implementing public sector accounting reforms in emerging economies: evidence from Egypt, Nepal and Sri Lanka
Authors: Adhikari Pawan , Kuruppu Chamara , Ouda Hassan , Grossi Giuseppe , Ambalangodage Dayananda
Published: October 2019

This study investigates the implementation of public sector accounting reforms in Egypt, Nepal and Sri Lanka. Data for the article are derived through document analysis and semi-structured interviews with public administrators, government accountants and members of professional accountancy bodies. The article brings out the factors that have either individually or collectively stifled the diffusion trajectory of public sector accounting reforms in Egypt, Nepal and Sri Lanka at the implementation phase, including the bundling process, pro-innovation biases, informal and interpersonal networks, a boundary-spanning process, organisational communication, power disparity, and dominance. As a result, public sector accounting reforms have resulted in resistance, internal conflicts and unintended consequences, including the fabrication of results, in all three countries without any evidence of yielding better results for public sector governance and accountability.

Points for practitioners

Public sector accounting practitioners should realise the importance of considering the specific contexts of emerging economies, including the power structures, communication channels, informal networks and communication flows, prior to the diffusion of reforms. When such contextual elements are de-emphasised, reforms would tend to encounter delay and resistance, ongoing reforms in Egypt, Nepal and Sri Lanka serving as examples. Also, instead of delegating power to professional accountants and expert groups, they can be employed as boundary spanners to facilitate communication with government accountants about the technical complexities of public sector accounting reforms. This may help establish an efficient communication network and strengthen interpersonal and informal networks, enabling reforms to pass through the diffusion trajectory without being stifled at the implementation phase.