bluuebunny/crossref_metadata_2025 huggingface dataset:
Rock Falls Impacting Railway Tracks: Detection Analysis through an Artificial Intelligence Camera Prototype
Authors: Fantini Andrea , Fiorucci Matteo , Martino Salvatore
Published: October 2017

During the last few years, several approaches have been proposed to improve early warning systems for managing geological risk due to landslides, where important infrastructures (such as railways, highways, pipelines, and aqueducts) are exposed elements. In this regard, an Artificial intelligence Camera Prototype (AiCP) for real-time monitoring has been integrated in a multisensor monitoring system devoted to rock fall detection. An abandoned limestone quarry was chosen at Acuto (central Italy) as test-site for verifying the reliability of the integrated monitoring system. A portion of jointed rock mass, with dimensions suitable for optical monitoring, was instrumented by extensometers. One meter of railway track was used as a target for fallen blocks and a weather station was installed nearby. Main goals of the test were (i) evaluating the reliability of the AiCP and (ii) detecting rock blocks that reach the railway track by the AiCP. At this aim, several experiments were carried out by throwing rock blocks over the railway track. During these experiments, the AiCP detected the blocks and automatically transmitted an alarm signal.
Synchronous HPV-Related Cancer of Bilateral Tonsils Detected Using Transoral Endoscopic Examination with Narrow-Band Imaging
Authors: Shimizu Fukuko , Okami Kenji , Ebisumoto Koji , Maki Daisuke , Sakai Akihiro , Ogura Go , Nakamura Naoya , Iida Masahiro
Published: October 2017

Background. The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy. Methods and Results. We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy. Conclusion. To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.
Histone Acetyltransferase KAT6A Upregulates PI3K/AKT Signaling through TRIM24 Binding
Authors: Lv Deguan , Jia Feng , Hou Yanli , Sang Youzhou , Alvarez Angel A. , Zhang Weiwei , Gao Wei-Qiang , Hu Bo , Cheng Shi-Yuan , Ge Jianwei , Li Yanxin , Feng Haizhong
Published: October 2017

Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here, we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM), where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation, and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis. Overexpressing activated AKT or PIK3CA rescued the growth inhibition due to KAT6A silencing. Conversely, the pan-PI3K inhibitor LY294002 abrogated the growth-promoting effect of KAT6A. Overexpression of KAT6A or TRIM24, but not KAT6A acetyltransferase activity–deficient mutants or TRIM24 mutants lacking H3K23ac-binding sites, promoted PIK3CA expression, AKT phosphorylation, and cell proliferation. Taken together, our results define an essential role of KAT6A in glioma formation, rationalizing its candidacy as a therapeutic target for GBM treatment. Cancer Res; 77(22); 6190–201. ©2017 AACR.
PKCϵ Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly
Authors: Martini Silvia , Soliman Tanya , Gobbi Giuliana , Mirandola Prisco , Carubbi Cecilia , Masselli Elena , Pozzi Giulia , Parker Peter J. , Vitale Marco
Published: October 2017

To form a proper mitotic spindle, centrosomes must be duplicated and driven poleward in a timely and controlled fashion. Improper timing of centrosome separation and errors in mitotic spindle assembly may lead to chromosome instability, a hallmark of cancer. Protein kinase C epsilon (PKCϵ) has recently emerged as a regulator of several cell-cycle processes associated with the resolution of mitotic catenation during the metaphase–anaphase transition and in regulating the abscission checkpoint. However, an engagement of PKCϵ in earlier (pre)mitotic events has not been addressed. Here, we now establish that PKCϵ controls prophase-to-metaphase progression by coordinating centrosome migration and mitotic spindle assembly in transformed cells. This control is exerted through cytoplasmic dynein function. Importantly, it is also demonstrated that the PKCϵ dependency of mitotic spindle organization is correlated with the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a characteristic of many transformed cells. Thus, PKCϵ appears to become specifically engaged in a programme of controls that are required to support cell-cycle progression in transformed cells, advocating for PKCϵ as a potential cancer therapeutic target.

Implications: The close relationship between PKCϵ dependency for mitotic spindle organization and the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a hallmark of transformed cells, strongly suggests PKCϵ as a therapeutic target in cancer. Mol Cancer Res; 16(1); 3–15. ©2017 AACR.
Differentialdiagnostik bei Martorell-Ulkus und PAVK: Gemeinsamer Therapieansatz
Authors: Stücker Markus
Published: October 2017

Das Martorell-Syndrom ist eine äußerst schmerzhafte Form von Unterschenkelulzera. Oft tritt eine einzelne Läsion an der Außenseite der Unterschenkel auf, die im Zusammenhang mit schlecht kontrolliertem Bluthochdruck und Diabetes steht. Die Behandlung des Ulkus erfordert besondere Aufmerksamkeit und eine frühe korrekte Diagnose sowie ein adäquates Management des Blutdrucks, der Infektion und der Wundbehandlung. Wir beschreiben den Fall einer 77-jährigen Patientin mit Bluthochdruck und Diabetes, die sich mit unerträglichen Schmerzen im rechten lateralen Unterschenkel vorstellte, die zu einem nekrotischen Geschwür führten. Reihenaufnahmen von der Entwicklung der Läsion bis hin zur Heilung des Ulkus werden dargestellt.
Allergene Lipide und ihre Bedeutung für die Allergiediagnostik
Authors: Traidl-Hoffmann Claudia
Published: October 2017

Hintergrund: Die allergische Sensibilisierung wird möglicherweise durch Lipide beeinflusst, die in den Allergenen enthalten sind. Dies lässt sich an der Reaktion natürlicher Killer-T-Zellen (NKT-Zellen) mit Antigen-präsentierenden Zellen (antigen-presenting cells, APC) erkennen. Das Ziel dieser Studie war die Untersuchung der Auswirkungen von Olivenpollenlipiden auf humane APC einschließlich Monozyten sowie aus Monozyten hervorgegangene Makrophagen (Mϕ) und dendritische Zellen (DZ). Methoden: Aus Pollenstaub des Olivenbaums (Olea europea) wurden Lipide extrahiert. Invariante NKT-Zellen (iNKT-Zellen), Monozyten, Mϕ und DZ wurden aus dem Buffy Coat von Blutspenden gesunder Spender gewonnen, und der Zell-Phänotyp wurde mit Hilfe der Durchflusszytometrie bestimmt. Die Beurteilung der Zytotoxizität von iNKT-Zellen erfolgte durch ein Laktatdehydrogenase-Assay. Die Genexpression von CD1A und CD1D wurde mittels RT-PCR bestimmt. Die Produktion der Zytokine IL-6, IL-10, IL-12 und TNF-α durch Monozyten, Mϕ, und DZ wurde unter Verwendung des Enzyme-linked Immunosorbent Assay (ELISA) gemessen. Ergebnisse: Unsere Ergebnisse belegen, dass Monozyten und Mϕ nach Behandlung mit Olivenpollenlipiden in hohem Maße iNKT-Zellen aktivieren. Wir beobachteten mehrere Veränderungen im Phänotyp der APC nach Exposition gegenüber den Pollenlipiden. Sowohl bei den Mϕ als auch bei den Monozyten stieg nach der Behandlung mit den Olivenpollenlipiden die CD1D-Genexpression, während eine Hochregulierung des CD1d-Zelloberflächenproteins nur bei den Mϕ eintrat. Auch im Humanserum differenzierte DZ steigerten ihre CD1d-Oberflächenexpression nach Exposition gegenüber Olivenpollenlipiden. Außerdem vermochten Olivenpollenlipide die IL-6-Produktion zu stimulieren, die Produktion von Lipopolysaccharid-induziertem IL-10 durch Mϕ hingegen wurde herunterreguliert. Schlussfolgerungen: Olivenpollenlipide bewirken Veränderungen im Phänotyp von Monozyten, Mϕ und DZ, die zur Aktivierung von NKT-Zellen führen, was wiederum potenziell die allergische Immunreaktion beeinflussen kann.
Visusverlust durch Adalimumab-Therapie bei Plaque-Psoriasis
Authors: Saffra Norman A. , Astafurov Konstantin
Published: October 2017

Bei einem 61-jährigen Patienten kaukasischer Abstammung mit schwerer Plaque-Psoriasis ohne Gelenkbeteiligung wurde eine Behandlung mit Adalimumab eingeleitet. Kurz darauf stellte er sich aufgrund akuter Sehverschlechterung im rechten Auge in der Notaufnahme vor. Eine umfassende systemische Untersuchung wurde durchgeführt, einschließlich Magnetresonanztomographie (MRT)-Aufnahmen des Gehirns und der Orbitae mit und ohne Gadoliniumverstärkung. Der MRT-Befund war vereinbar mit ZNS-Demyelinisierung und Retrobulbärneuritis. Adalimumab wurde sofort abgesetzt und keine weitere systemische Therapie eingeleitet. 6 Wochen später war das Sehvermögen des Patienten vollständig wiederhergestellt. Weitere Psoriasis- oder neurologische Behandlungsmaßnahmen erfolgten nicht. Der Patient ist seit 14 Monaten stabil. Übersetzung aus Case Reports in Dermatology 2017;9:60-64 (DOI:10.1159/000461572)
Psoriasiformer Ausschlag durch Propranolol: Wie häufig ist eine Ausnahme?
Authors: Fölster-Holst Regina
Published: October 2017

Propanolol, ein nichtselektiver Blocker β-adrenerger Rezeptoren, ist heute die erste Wahl zur Behandlung des komplizierten infantilen Hämangioms. Die Anwendung in der pädiatrischen Patientenpopulation hat in den letzten Jahren dementsprechend zugenommen. Bei Erwachsenen wurde festgestellt, dass β-Blocker die häufigsten Auslöser für arzneimittelinduzierte Psoriasis sind. Bei Säuglingen mit infantilem Hämangiom, die mit Propanolol behandelt werden, wurde bisher nicht über psoriasiformen Windelausschlag berichtet. Wir berichten hier über den unseres Wissens ersten Fall eines potenziell durch oral verabreichtes Propranolol induzierten psoriasiformen Windelausschlags bei einem 18 Monate alten Mädchen ohne Psoriasis in der Familienanamnese.
Eye Size, Fovea, and Foraging Ecology in Accipitriform Raptors
Authors: Potier Simon , Mitkus Mindaugas , Bonadonna Francesco , Duriez Olivier , Isard Pierre-François , Dulaurent Thomas , Mentek Marielle , Kelber Almut
Published: October 2017

Birds with larger eyes are predicted to have higher spatial resolution because of their larger retinal image. Raptors are well known for their acute vision, mediated by their deep central fovea. Because foraging strategies may demand specific visual adaptations, eye size and fovea may differ between species with different foraging ecology. We tested whether predators (actively hunting mobile prey) and carrion eaters (eating dead prey) from the order Accipitriformes differ in eye size, foveal depth, and retinal thickness using spectral domain optical coherence tomography and comparative phylogenetic methods. We found that (1) all studied predators (except one) had a central and a temporal fovea, but all carrion eaters had only the central fovea; (2) eye size scaled with body mass both in predators and carrion eaters; (3) predators had larger eyes relative to body mass and a thicker retina at the edge of the fovea than carrion eaters, but there was no difference in the depth of the central fovea between the groups. Finally, we found that (4) larger eyes generally had a deeper central fovea. These results suggest that the visual system of raptors within the order Accipitriformes may be highly adapted to the foraging strategy, except for the foveal depth, which seems mostly dependent upon the eye size.
Transversal Width of Mandibular Bone and Neurosensory Disturbance after Bilateral Sagittal Splitting Ramus Osteotomy
Authors: Takaku Yuichiro , Takano Masayuki , Yamashita Shuichiro , Fukuda Kenichi
Published: October 2017

Objective: This study evaluated the condition of mandibular cancellous and cortical bone on computed tomography (CT) images in order to investigate its relationship with the incidence of neurosensory disturbances (NSD) in the mental nerve region after bilateral sagittal splitting ramus osteotomy (BSSRO). Methods: BSSRO was performed on 58 lateral mandibles in 29 patients. From preoperative CT images, the width endpoints of the transversal bone were measured in region I immediately inferior to the mandibular foramen, region II in the mandibular angle region, and region III distal to the lower second molar. The incidence of NSD immediately after surgery and the residual NSD rate at 1, 3, and 6 months after surgery were investigated. The correlation between incidence of NSD in the mental nerve region and each transversal bone width endpoint immediately after and at 6 months after surgery was also comparatively evaluated. Results: The overall incidence of NSD immediately after surgery was 67.2% (39/58 sides) and the overall residual NSD rate at 1, 3, and 6 months after surgery was 53.4% (31/58 sides), 31.0% (18/58 sides), and 17.2% (10/58 sides), respectively. No significant differences were observed for any width endpoints of the transversal bone measured at regions I or III, but the transversal width of the entire mandible was significantly different in region II between patients with and without NSD at 6 months after surgery (p < 0.05). Conclusion: These findings demonstrate that the transversal width of the entire mandible may be an important factor in predicting NSD incidence.
Venous Thromboembolism and the Risk of Death and Graft Loss in Kidney Transplant Recipients
Authors: Lam Ngan N. , Garg Amit X. , Knoll Greg A. , Kim S. Joseph , Lentine Krista L. , McArthur Eric , Naylor Kyla L. , Bota Sarah E. , Sood Manish M.
Published: October 2017

Background: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described. Methods: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant. Results: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE. Conclusions: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss.
Efficacy of Endoscopic Retrograde Cholangiopancreatography in the Treatment of Biliary Complications following Liver Transplant: 10 Years of a Single-Centre Experience
Authors: Alves Ana Rita , Gomes Dário , Furtado Emanuel , Tomé Luís
Published: October 2017

Background and Aims: Biliary tract complications following liver transplant remain an important source of morbidity and mortality. Endoscopic retrograde cholangiopancreatography (ERCP) has become a common therapeutic option before other invasive procedures. The aim of this study was to evaluate ERCP efficacy in managing this type of complications. Methods: Retrospective study of all patients who underwent therapeutic ERCP due to post-liver transplant biliary complications between September 2005 and September 2015, at a deceased donor liver transplantation centre. Results: Therapeutic ERCP was performed in 120 patients (64% men; mean age 46 ± 14 years). Biliary complications were anastomotic strictures (AS) in 70%, non-anastomotic strictures (NAS) in 14%, bile leaks (BL) in 5.8%, and bile duct stones (BDS) in 32%. The mean time between liver transplant and first ERCP was: 19 ± 30 months in AS, 17 ± 30 months in NAS, 61 ± 28 months in BDS, and 0.7 ± 0.6 months in BL (p < 0.001). The number of ERCP performed per patient was: 3.8 ± 2.4 in AS, 3.8 ± 2.1 in NAS, 1.9 ± 1 in BDS, and 1.9 ± 0.5 in BL (p = 0.003). The duration of the treatment was: 18 ± 19 months in AS, 21 ± 17 months in NAS, 10 ± 10 months in BDS, and 4 ± 3 months in BL (p = 0.064). Overall, biliary complications were successfully managed by ERCP in 46% of cases, either as an isolated procedure (43%) or rendez-vous ERCP (3%). Per complication, ERCP was effective in 39% of AS, in 12% of NAS, in 91% of BDS, and in 86% of BL. Globally, the mean follow-up of the successful cases was 43 ± 31 months. Percutaneous transhepatic cholangiography and/or surgery were performed in 48% of patients in whom ERCP was unsuccessful. The odds ratio for effective endoscopic treatment was 0.2 for NAS (0.057-0.815), 12.4 for BDS (1.535-100.9), and 6.9 for BL (0.798-58.95). No statistical significance was found for AS (p = 0.247). Conclusions: ERCP allowed the treatment of biliary complication in about half of patients, avoiding a more invasive procedure. Endoscopic treatment was more effective for BDS and BL.
Endoscopic Ultrasound-Guided Choledochoduodenostomy as Palliative Treatment: A Challenging Case Report
Authors: Ribeiro Helena , Azevedo Richard , Caldeira Ana , Sousa Rui , Pereira Eduardo , Banhudo António
Published: October 2017

We report the case of an 88-year-old female with obstructive jaundice due to a periampullary tumor. The patient developed acute cholangitis and consequent clinical deterioration, so it was decided to perform palliative biliary drainage. Due to duodenal tumor invasion, it was not possible to perform endoscopic retrograde cholangiopancreatography. A different approach was attempted and it was decided to carry out an endoscopic ultrasound-guided choledochoduodenostomy. This procedure was performed with a linear echoendoscope, and using a duodenal bulbar approach, a fistula was created between the bulb and the common bile duct. A self-expandable fully covered metal biliary stent was placed in the common bile duct under endoscopic and fluoroscopic guidance, allowing biliary drainage. The patient presented clinical improvement. However, 3 weeks after being discharged, she was readmitted to our department with hematemesis associated with the migration of the biliary stent to the duodenal bulb. Endoscopic hemostasis was performed but the patient had multiple bleeding relapses that were controlled through arterial embolization. Despite the migration of the biliary stent, the fistula between the duodenum and the common bile duct remained patent, allowing a successful palliation of the obstructive jaundice. Therefore, despite the occurred complication, we admitted a technical and clinical success of the endoscopic ultrasound-guided choledochoduodenostomy. This is an emerging technique and a valuable alternative for palliative biliary drainage in cases of malignant distal obstruction. This clinical report supports this finding, reporting technical aspects of the procedure, associated complications and their management as well as the clinical outcomes.
Combination of Androgen Deprivation Therapy and Salvage Radiotherapy versus Salvage Radiotherapy Alone for Recurrent Prostate Cancer after Radical Prostatectomy
Authors: Yoo Sangjun , You Dalsan , Kim Young Seok , Hong Jun Hyuk , Ahn Hanjong , Kim Choung-Soo
Published: October 2017

Introduction: To assess the value of androgen deprivation therapy (ADT) on salvage radiotherapy (RT) in post-prostatectomy recurrent prostate cancer patients, we compared the oncologic outcomes between patients receiving RT + ADT and those receiving RT alone. Materials and Methods: We reviewed the records of patients diagnosed with prostate cancer between 1995 and 2011, including 93 patients who underwent salvage RT and 69 patients who underwent salvage RT + ADT. The ADT-free duration after withdrawal was calculated to verify testosterone recovery. Results: Presalvage prostate serum antigen (PSA) was the only significantly different characteristic between the 2 groups (p < 0.001). The ADT-free duration was greater than 6 months in >80% of patients. Presalvage PSA ≥0.6 ng/mL, pathologic stage ≥T3b, and RT + ADT were significantly associated with biochemical progression after salvage treatment. RT + ADT reduced biochemical progression in patients with seminal vesicle invasion or presalvage PSA ≥0.6 ng/mL (p = 0.001) compared to RT alone; biochemical progression-free probability was unchanged in seminal vesicle noninvasive prostate cancer patients with presalvage PSA <0.6 ng/mL (p = 0.541). Conclusions: RT + ADT reduced the risk of biochemical progression after salvage treatment in patients with seminal vesicle invasion or presalvage PSA ≥0.6 ng/mL, but had no effect in patients with seminal vesicle noninvasive disease and presalvage PSA <0.6 ng/mL.
Patiromer Lowers Serum Potassium When Taken without Food: Comparison to Dosing with Food from an Open-Label, Randomized, Parallel Group Hyperkalemia Study
Authors: Pergola Pablo E. , Spiegel David M. , Warren Suzette , Yuan Jinwei , Weir Matthew R.
Published: October 2017

Background: Patiromer is a sodium-free, nonabsorbed, potassium binder approved for treatment of hyperkalemia. This open-label study compares the efficacy and safety of patiromer administered without food versus with food. Methods: Adults with hyperkalemia (potassium ≥5.0 mEq/L) were randomized (1:1) to receive patiromer once daily without food or with food for 4 weeks. The dosage was adjusted (maximum: 25.2 g/day) using a prespecified titration schedule to achieve and maintain potassium within a target range (3.8-5.0 mEq/L). The primary efficacy endpoint was the proportion of patients with serum potassium in the target range at either week 3 or week 4. Safety was assessed by adverse events (AEs) and laboratory testing. Results: Efficacy was evaluated in 112 patients; 65.2% were ≥65 years of age, 75.9% had chronic kidney disease, and 82.1% had diabetes. Baseline mean serum potassium was similar in the without-food (5.44 mEq/L) and with-food (5.34 mEq/L) groups. The primary endpoint was achieved by 87.3% (95% CI 75.5-94.7) and 82.5% (95% CI 70.1-91.3) of patients in the with-food and without-food groups, respectively; least squares mean changes in serum potassium from baseline to week 4 were -0.65 and -0.62 mEq/L, respectively (p < 0.0001). The most common AEs were diarrhea and constipation. Serum K+ remained ≥3.5 mEq/L in all patients; 5 patients developed serum magnesium <1.4 mg/dL, including 4 whose baseline magnesium was below the lower limit of normal. Conclusion: Patiromer is equally effective and well tolerated when taken without food or with food, thereby offering the potential for dosing flexibility.
Unerwünschte Wirkungen von Biologika bei Psoriasis
Authors: Lockwood Stephen J. , Prens Lisette M. , Kimball Alexa B.
Published: October 2017

Psoriasis ist eine chronische Autoimmunerkrankung, von der weltweit Millionen Menschen betroffen sind. Die Erkrankung ist nicht nur für sich selbst genommen sehr belastend und kann die Lebensqualität verringern, sondern sie stellt auch einen Risikofaktor für weitere systemische Erkrankungen dar, z.B. metabolisches Syndrom, kardiovaskuläre und maligne Erkrankungen. In der Behandlung der Psoriasis wurden im mittleren bis späten 20. Jahrhundert bahnbrechende Fortschritte erzielt, unter anderem durch die Entwicklung von topischen Kortikosteroiden und Vitamin-D-Analoga sowie Methotrexat, systemischen Retinoiden und Phototherapie. Doch erst 2004, mit dem Aufkommen der Biologika - neuartiger systemischer biologischer Arzneimittel, die sehr spezifisch gegen bestimmte Zielstrukturen des Immunsystems gerichtet sind -, wurde das Ansprechen laut PASI (Psoriasis Area and Severity Index) als Maßstab für das Hauptziel der Behandlung von einer Verbesserung um 50% (PASI 50) auf PASI 75, PASI 90 und sogar PASI 100, d.h. die vollständige Rückbildung der Hautläsionen, angehoben. Heute erreichen viele Patienten mit einer Biologika-Therapie routinemäßig eine Verringerung der kutanen Krankheitslast um 75% oder 90% und eine signifikante Verbesserung ihrer Lebensqualität insgesamt. Biologika sind im Allgemeinen gut verträglich und sicher, doch wie jedes Arzneimittel sind auch sie mit unerwünschten Wirkungen assoziiert. Einige dieser unerwünschten Wirkungen können anhand von Effekten der Immunmodulation, von Tiermodellen sowie von menschlichen Populationen mit bekannten Zytokindefizienzen vorhergesagt werden. Im nächsten Schritt ist es wichtig, sowohl in klinischen Studien als auch in Registern zur Anwendungsbeobachtung die Sicherheitsprofile dieser Wirkstoffe sorgfältig zu überwachen, um die Langzeitsicherheit zu bestätigen. Erfreulicherweise bescheinigen die großen Sicherheitsregister den neu hinzugekommenen bzw. hinzukommenden Biologika ein verbessertes Sicherheitsprofil. Übersetzter Auszug aus Curr Probl Dermatol. Basel, Karger, 2018, vol 53, pp 1-14 (DOI: 10.1159/000478072)
Oxaliplatin-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Pancreatic Cancer: A Case Report
Authors: Ogata Takatsugu , Satake Hironaga , Ogata Misato , Hatachi Yukimasa , Yasui Hisateru
Published: October 2017

Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX) chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m2) and oxaliplatin (100 mg/m2) on day 1, repeated every 2 weeks. The second cycle of GEMOX was administered as planned. However, he appeared to have difficulties with daily activities. Two days later, he visited the emergency room complaining of drowsiness. On examination, the patient had a Glasgow Coma Scale (GCS) score of 14 (E4V4M6), and asterixis was not present. Blood examination revealed a serum ammonia level of 202 µg/dL. The levels of serum hepatic enzymes were only mildly elevated, and the hemoglobin level was typical for this patient. Computed tomography, magnetic resonance imaging, lumbar puncture test, and blood culture showed no abnormality. Based on these results, he was diagnosed with oxaliplatin-induced hyperammonemia. One day after hospitalization, GCS score had significantly decreased to 6 (E1V1M4). His consciousness disorder improved after administration of a nutritional supplement containing a high concentration of branched-chain amino acids for 5 days, and the level of serum ammonia improved to 79 µg/dL. He stated that he could not remember the episode. The findings of this case suggest the importance of examining serum ammonia levels in patients receiving an oxaliplatin-containing regimen who develop disordered consciousness.
Effectiveness of IHD with Adsorptive PMMA Membrane in Myeloma Cast Nephropathy: A Cohort Study
Authors: Sens Florence , Chaintreuil Déborah , Jolivot Anne , Guebre-Egziabher Fitsum , Robinson Philip , Karlin Lionel , Bridoux Frank , Juillard Laurent
Published: October 2017

Background: In patients with cast nephropathy and acute kidney injury (AKI) requiring dialysis, the reduction of serum free light chains (FLC) using chemotherapy and intensive hemodialysis (IHD) with a high cut-off filter may improve renal and patient outcomes. We evaluated the effectiveness of a combination of chemotherapy and IHD with an adsorbent polymethylmethacrylate membrane (IHD-PMMA) on renal recovery and survival. Methods: A single-center retrospective cohort-study was conducted. Between 2007 and 2014, patients with dialysis-dependent acute cast nephropathy treated with chemotherapy and IHD-PMMA were included. Patients had six 6-h hemodialysis sessions a week, until predialysis serum FLC fell below 200 mg/L, for a maximum of 3 weeks. Primary outcomes were renal recovery, defined as dialysis independence, and survival. Results: Seventeen patients were included, all with stage 3 AKI. All received chemotherapy, mostly based on bortezomib and steroids (88%). Twelve patients (71%) achieved renal recovery, usually within 60 days (92%). At 3 months, the overall hematological response rate was 57%; hematological response was maintained for at least 2 years in 86% of responders. At 6, 12, and 24 months, 76, 75, and 62% of patients were alive, respectively. Higher reduction in involved FLC by day 12 (p = 0.022) and day 21 (p = 0.003) was associated with renal recovery. Patients with FLC reduction rate >50% by day 21 experienced a lower mortality (hazard ratio 0.10, 95% CI 0.02–0.63). Conclusion: In patients with dialysis-dependent myeloma cast nephropathy, early FLC removal by IHD-PMMA combined with chemotherapy was associated with high rates of renal recovery and survival.
Enhanced at Puberty-1 (Eap1) Expression Critically Regulates the Onset of Puberty Independent of Hypothalamic Kiss1 Expression
Authors: Li Chenxi , Li Pin 
Published: October 2017

Background/Aims: Enhance at puberty-1 (Eap1) is an intronless gene that regulates the onset of puberty through a network of hypothalamic genes. However, precise mechanistic events essential for Eap1-regulation of puberty have not been fully elucidated. Eap1 is thought to promote the initiation of puberty through regulation of the hypothalamic metastasis-suppressor KiSS1. We aim to investigate this hypothesis by genetically perturbing Eap1 through RNA interference in vivo. Methods: We first engineered and optimized four sets of shRNAs that target rat Eap1 mRNA as well as one negative control shRNA. After generating lentiviral (LV) particles, we examined the suppression of Eap1 in NRK-54E cell line to select the most efficient one. Sequencelly, LV-Eap1-shRNA or controls including LV-eGFP and saline were intraventricular microinjected into 21-day-old rats. Rats were raised in appropriate conditions and we examined the time of vaginal opening, ovary physiology as well as hypothalamic puberty-regulatory genes at three developmental stages: juvenile (postnatal day PND25), early puberty (PND35), adult (PND42). Results: Hypothalamic suppression of Eap1 delayed the onset of rat vaginal opening. Hematoxylin and eosin (H&E) staining revealed a significant reduction of corpus luteum (CL) at PND35, but at PND42 CL levels were normal relative to control. In conjunction with differences in phenotype and ovary morphology, GnRH expression and transcripts were also reduced at PND25 and PND35, while their levels were similar to control at PND42. KiSS1 mRNA and protein levels were not significantly different at all three developmental stages. Conclusion: Eap1 expression critically regulates puberty as well as GnRH expression. However, Eap1-regulation of puberty may not necessitate KiSS1/GPR54 signaling.
Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats
Authors: Silva Renata A. C. , Gonçalves Andréa F. , dos Santos Priscila P. , Rafacho Bruna , Claro Renan F. T. , Minicucci Marcos F. , Azevedo Paula S. , Polegato Bertha F. , Zanati Silméia G. , Fernandes Ana Angélica , Paiva Sergio A. R. , Zornoff Leonardo A. M.
Published: October 2017

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.
Early Right Ventricular Assist Device Use in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Implantation
Authors: Kiernan Michael S. , Grandin E. Wilson , Brinkley Marshall , Kapur Navin K. , Pham Duc Thinh , Ruthazer Robin , Rame J. Eduardo , Atluri Pavan , Birati Edo Y. , Oliveira Guilherme H. , Pagani Francis D. , Kirklin James K. , Naftel David , Kormos Robert L. , Teuteberg Jeffrey J. , DeNofrio David
Published: October 2017

Background:

To investigate preimplant risk factors associated with early right ventricular assist device (RVAD) use in patients undergoing continuous-flow left ventricular assist device (LVAD) surgery.

Methods and Results:

Patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent primary continuous-flow–LVAD surgery were examined for concurrent or subsequent RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and the combined end point of RVAD or death within 14 days of LVAD were assessed with stepwise logistic regression. We compared survival between patients with and without RVAD using Kaplan–Meier method and Cox proportional hazards modeling. Of 9976 patients undergoing continuous-flow–LVAD implantation, 386 patients (3.9%) required an RVAD within 14 days of LVAD surgery. Preimplant characteristics associated with RVAD use included interagency registry for mechanically assisted circulatory support patient profiles 1 and 2, the need for preoperative extracorporeal membrane oxygenation or renal replacement therapy, severe preimplant tricuspid regurgitation, history of cardiac surgery, and concomitant procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic determinants included elevated right atrial pressure, reduced pulmonary artery pulse pressure, and reduced stroke volume. The final model demonstrated good performance for both RVAD implant (area under the curve, 0.78) and the combined end point of RVAD or death within 14 days (area under the curve, 0.73). Compared with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1- and 6-month survival: 78.1% versus 95.8% and 63.6% versus 87.9%, respectively (
P
<0.0001 for both).

Conclusions:

The need for RVAD implantation after LVAD is associated with indices of global illness severity, markers of end-organ dysfunction, and profiles of hemodynamic instability.
Preload Stress Echocardiography Predicts Outcomes in Patients With Preserved Ejection Fraction and Low-Gradient Aortic Stenosis
Authors: Kusunose Kenya , Yamada Hirotsugu , Nishio Susumu , Torii Yuta , Hirata Yukina , Seno Hiromitsu , Saijo Yoshihito , Ise Takayuki , Yamaguchi Koji , Yagi Shusuke , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: October 2017

Background—

The projected aortic valve area (AVA
proj
) at a normal transvalvular flow rate using dobutamine is helpful to determine the actual severity of aortic stenosis (AS) and to predict risk of adverse events in low-gradient AS cases with unclear surgical indication. Our study aimed to identify the independent and incremental value of preload stress echocardiography-derived AVA
proj
to predict outcomes in patients with preserved ejection fraction and low-gradient AS.

Methods and Results—

We prospectively performed echocardiographic studies in 79 patients with low-gradient AS (age, 77±7 years; 30% men) with preload stress echocardiography using leg positive pressure. AVA
proj
was calculated using AVA and transvalvular flow rate at baseline and during leg positive pressure. The primary end point was the decision for aortic valve surgery or cardiac death. During a median period of 19 months, 23 patients had the decision for aortic valve surgery, and none died during follow-up. In a stepwise multivariable analysis, indexed AVA
proj
(AVAi
proj
; hazard ratio, 2.00 per 0.1 cm
2
/m
2
decrease; 95% confidence interval, 1.36–2.96;
P
<0.001) was associated with the primary end point. Using a receiver operating characteristic curve analysis, the best cutoff value of AVAi
proj
for predicting cardiac events was <0.72 cm
2
/m
2
. By incorporating AVAi
proj
into AVAi at baseline, continuous net reclassification index for cardiac events was 0.48 (
P
=0.04).

Conclusions—

In patients with low-gradient AS, indexed AVA
proj
derived from preload stress echocardiography can be useful to predict risk of adverse events. The present article should be considered as a proof of concept study, and we think that larger multicenter studies are warranted.
Impact of Coronary Artery Disease on 30‐Day and 1‐Year Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: A Meta‐Analysis
Authors: Sankaramangalam Kesavan , Banerjee Kinjal , Kandregula Krishna , Mohananey Divyanshu , Parashar Akhil , Jones Brandon M. , Jobanputra Yash , Mick Stephanie , Krishnaswamy Amar , Svensson Lars G. , Kapadia Samir R.
Published: October 2017

Background

The impact of coronary artery disease (
CAD
) on outcomes after transcatheter aortic valve replacement (
TAVR
) is understudied. Literature on the prognostic role of
CAD
in the survival of patients undergoing
TAVR
shows conflicting results. This meta‐analysis aims to investigate how
CAD
impacts patient survival following
TAVR
.

Methods and Results

We completed a comprehensive literature search of Embase,
MEDLINE
, and the Cochrane Library, and included studies reporting outcome of
TAVR
based on
CAD
status of patients for the analysis. From the initial 1631 citations, 15 studies reporting on 8013 patients were analyzed using a random‐effects model. Of the 8013 patients undergoing
TAVR
, with a median age of 81.3 years (79–85.1 years), 46.6% (40–55.7) were men and 3899 (48.7%) had
CAD
(ranging from 30.8% to 78.2% in various studies). Overall, 3121
SAPIEN
/
SAPIEN XT
/
SAPIEN
3 (39.6%) and 4763 CoreValve (60.4%) prostheses were implanted, with transfemoral access being the most frequently used approach for the implantation (76.1%). Our analysis showed no significant difference between patients with and without
CAD
for all‐cause mortality at 30 days post
TAVR
, with a cumulative odds ratio of 1.07 (95% confidence interval, 0.82–1.40;
P=
0.62). However, there was a significant increase in all‐cause mortality at 1 year in the
CAD
group compared with patients without
CAD
, with a cumulative odds ratio of 1.21 (95% confidence interval, 1.07–1.36;
P
=0.002).

Conclusions

Even though coexisting
CAD
does not impact 30‐day mortality, it does have an impact on 1‐year mortality in patients undergoing
TAVR
. Our results highlight a need to revisit the revascularization strategies for concomitant
CAD
in patients with TAVR.
Association of Neighborhood Socioeconomic Context With Participation in Cardiac Rehabilitation
Authors: Bachmann Justin M. , Huang Shi , Gupta Deepak K. , Lipworth Loren , Mumma Michael T. , Blot William J. , Akwo Elvis A. , Kripalani Sunil , Whooley Mary A. , Wang Thomas J. , Freiberg Matthew S.
Published: October 2017

Background

Cardiac rehabilitation (CR) is underutilized in the United States, with fewer than 20% of eligible patients participating in CR programs. Individual socioeconomic status is associated with CR utilization, but data regarding neighborhood characteristics and CR are sparse. We investigated the association of neighborhood socioeconomic context with CR participation in the SCCS (Southern Community Cohort Study).

Methods and Results

The SCCS is a prospective cohort study of 84 569 adults in the southeastern United States from 2002 to 2009, 52 117 of whom have Medicare or Medicaid claims. Using these data, we identified participants with hospitalizations for myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery and ascertained their CR utilization. Neighborhood socioeconomic context was assessed using a neighborhood deprivation index derived from 11 census‐tract level variables. We analyzed the association of CR utilization with neighborhood deprivation after adjusting for individual socioeconomic status. A total of 4096 SCCS participants (55% female, 57% black) with claims data were eligible for CR. CR utilization was low, with 340 subjects (8%) participating in CR programs. Study participants residing in the most deprived communities (highest quintile of neighborhood deprivation) were less than half as likely to initiate CR (odds ratio 0.42, 95% confidence interval, 0.27–0.66,
P
<0.001) as those in the lowest quintile. CR participation was inversely associated with all‐cause mortality (hazard ratio 0.77, 95% confidence interval, 0.60–0.996,
P
<0.05).

Conclusions

Lower neighborhood socioeconomic context was associated with decreased CR participation independent of individual socioeconomic status. These data invite research on interventions to increase CR access in deprived communities.
Cardiometabolic Risk Variables in Preadolescent Children: A Factor Analysis
Authors: Stoner Lee , Weatherall Mark , Skidmore Paula , Castro Nicholas , Lark Sally , Faulkner James , Williams Michelle A.
Published: October 2017

Background

Atherosclerosis begins during preadolescence and is occurring at an accelerated rate. This acceleration has been linked to poor lifestyle behaviors and subsequent cardiometabolic complications. Although the clustering of cardiometabolic risk factors has been recognized for over 2 decades, previous studies in children have predominantly examined the relationships between atherosclerosis and individual cardiometabolic risk factors or have grouped together preadolescent and adolescent children. Further, no known studies have included glycated hemoglobin or central hemodynamic measures such as central systolic blood pressure and augmentation index.

Methods and Results

Principal component analysis was performed on a cross‐sectional sample of 392 children (aged 9.5 years, 50% girls) from 3 representative sample sites across New Zealand. Four factors explained 60% of the variance in the measured variables. In order of variance explained, the factors were: blood pressure (central systolic blood pressure and peripheral systolic and diastolic blood pressure), adiposity (waist circumference, body mass index, and glycated hemoglobin), lipids (total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol), and vascular (augmentation index, heart rate, and fasting blood glucose).

Conclusions

In accordance with previous findings in adults and adolescents, one common factor is unlikely to define cardiometabolic health in preadolescent children. Each of the factors, except vascular, which was predominantly explained by augmentation index, are in agreement with previous findings in adolescents. An additional novel finding was that glycated hemoglobin and fasting blood glucose loaded onto different factors, supporting previous work suggesting that fasting blood glucose indicates short‐term glycemic control, whereas glycated hemoglobin reflects chronic glycemic control.

Clinical Trial Registration

URL
:
www.anzctr.org.au/
.
ID
:
ACTRN
12614000433606.
Production and Consumption of Staple Food Crops and the Separation of the Agricultural and Nonagricultural Sectors in China, 1952–2010: A Comparison with Japan, the United States, and South Korea (20世纪中期以来中国粮食生产、消费与产业分工关系解读：基于Agr与Nagr表达式的分析——兼与日美韩相比较)
Authors: Guo (郭爱民) Aimin
Published: October 2017

Correlative data from China, Japan, the United States, and South Korea show that since 1950, if the percentage of grain imported into a country is low, the growth of agricultural labor productivity is relatively high, which is the precondition for the separation (or further separation) between the agricultural and nonagricultural sectors. In China, agricultural labor productivity was low before the mid-1980s, a factor that contributed to rural poverty. Since the mid-1990s, however, the diet of the people of China has included a greater quantity of meat, eggs, and milk. At the same time, there has been a shortage of feed grain and the percentage of imported grain has begun to grow rapidly. If the proportion of imported grain continues to grow, the efficiency illusion that took place in Japan and South Korea will be repeated in China in the near future. Currently, China’s agriculture is faced with a series of imminent tasks that include promoting agricultural science and technology, accelerating the substitution of feed grains, and making sure that there will be no further loss of arable land.

20世纪中后期以来，中日美韩四国的数据表明，在粮食进口比重不大的情况下，农业劳动生产效率的大幅度提高是农业和非农产业分工（或分工进一步加强）的基础条件。在中国，1980年代中期之前，由于农业劳动生产效率较低，出现了长期的温饱问题和知青下乡问题。1990年代中期以来，在人们的饮食构成中，肉蛋奶数量趋高，饲料粮出现短缺，粮食进口比重快速增长。按照目前的趋势，如果粮食进口比重继续增长，在日韩出现的“效率假象”，将会在中国上演。进一步提高农业科技水平，加快饲料粮的替代，同时，确保18亿亩土地红线不被侵蚀，是中国农业面临的迫切任务。 (This article is in English.)
The Inverse Logics of Different Stages of Development under the Law of the Limit to Land Productivity (土地生产率极限法则下不同发展阶段的反向逻辑)
Authors: Pei (裴小林) Xiaolin
Published: October 2017

To remind China’s policy makers that seemingly correct theories in the West can become harmful in China, this article builds a dynamic land-use model, where the limit to land productivity causes the physical, economic, and institutional systems of land use to change inversely in the stages before, in, and after the population trap. The article uses historical data to test the inverse changes, and finds that the English agricultural revolution was a result of a shift of land use first from intensive to extensive and then back to intensive cultivation. In the process of returning to intensive cultivation, the Norfolk rotation system combined planting with livestock husbandry and raised agricultural output and labor productivity by increasing the number of draft animals and the acreage devoted to forage crops. But the revolution was possible precisely because land productivity was much lower in England than in China.

为提醒中国的政策制定者在西方似乎正确的理论在中国可能变得有害，本文建立了一个动态土地使用模型，在其中土地生产率极限使土地使用的物质、经济和制度系统在人口陷阱之前、之中和之后的三个不同发展阶段反向地变化。本文用历史数据检验了这些反向变化，发现英格兰的农业革命是土地使用从集约向粗放倒退然后再返回集约化的结果。在返回集约化的过程中，诺福克轮作制使种植业和畜牧业结合，通过大幅增加饲料作物和耕畜数量提高了农业总产值和劳动生产率。但这一革命能出现正是因为英格兰的土地生产率比中国低得多。 (This article is in English.)