bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allele-Specific Silencing Ameliorates Restrictive Cardiomyopathy Attributable to a Human Myosin Regulatory Light Chain Mutation
Authors: Zaleta-Rivera Kathia , Dainis Alexandra , Ribeiro Alexandre J.S. , Cordero Pablo , Rubio Gabriel , Shang Ching , Liu Jing , Finsterbach Thomas , Parikh Victoria N. , Sutton Shirley , Seo Kinya , Sinha Nikita , Jain Nikhil , Huang Yong , Hajjar Roger J. , Kay Mark A. , Szczesna-Cordary Danuta , Pruitt Beth L. , Wheeler Matthew T. , Ashley Euan A. 
Published: July 2019

Background:

Restrictive cardiomyopathy is a rare heart disease associated with mutations in sarcomeric genes and with phenotypic overlap with hypertrophic cardiomyopathy. There is no approved therapy directed at the underlying cause. Here, we explore the potential of an interfering RNA (RNAi) therapeutic for a human sarcomeric mutation in
MYL2
causative of restrictive cardiomyopathy in a mouse model.

Methods:
A short hairpin RNA (M7.8L) was selected from a pool for specificity and efficacy. Two groups of myosin regulatory light chain N47K transgenic mice were injected with M7.8L packaged in adeno-associated virus 9 at 3 days of age and 60 days of age. Mice were subjected to treadmill exercise and echocardiography after treatment to determine maximal oxygen uptake and left ventricular mass. At the end of treatment, heart, lung, liver, and kidney tissue was harvested to determine viral tropism and for transcriptomic and proteomic analysis. Cardiomyocytes were isolated for single-cell studies.

Results:

A one-time injection of AAV9-M7.8L RNAi in 3-day-old humanized regulatory light chain mutant transgenic mice silenced the mutated allele (RLC-47K) with minimal effects on the normal allele (RLC-47N) assayed at 16 weeks postinjection. AAV9-M7.8L RNAi suppressed the expression of hypertrophic biomarkers, reduced heart weight, and attenuated a pathological increase in left ventricular mass. Single adult cardiac myocytes from mice treated with AAV9-M7.8L showed partial restoration of contraction, relaxation, and calcium kinetics. In addition, cardiac stress protein biomarkers, such as calmodulin-dependent protein kinase II and the transcription activator Brg1 were reduced, suggesting recovery toward a healthy myocardium. Transcriptome analyses further revealed no significant changes of argonaute (
AGO1
,
AGO2
) and endoribonuclease dicer (
DICER1
) transcripts, and endogenous microRNAs were preserved, suggesting that the RNAi pathway was not saturated.

Conclusions:
Our results show the feasibility, efficacy, and safety of RNAi therapeutics directed towards human restrictive cardiomyopathy. This is a promising step toward targeted therapy for a prevalent human disease.
Ischemic Stroke in Adults With Congenital Heart Disease: A Population‐Based Cohort Study
Authors: Pedersen Mette Glavind Bülow , Olsen Morten S. , Schmidt Morten , Johnsen Søren P. , Learn Christopher , Laursen Henning B. , Madsen Nicolas L. 
Published: July 2019

Background

Congenital heart disease (
CHD
) is associated with risk factors for ischemic stroke including cardiac arrhythmias and heart failure. However, few long‐term follow‐up data exist on ischemic stroke risk and associated mortality in adults with
CHD
.

Methods and Results

Using Danish nationwide registries, we identified individuals aged ≥18 years diagnosed with
CHD
, at any age, from 1963 to 2017 and a sex and birth year‐matched (1:10) general population comparison cohort. We computed risks, as well as sex and birth year‐adjusted hazard ratios (
aHR
s) for ischemic stroke and 30‐day post‐stroke mortality in
CHD
adults compared with the general population. Analyses were stratified according to age <60 years (young) and ≥60 years (older). We identified 16 836 adults with
CHD
. The risk of ischemic stroke at age 60 years was 7.4% in the
CHD
cohort and 2.9% in the general population cohort. The adjusted hazard ratios for ischemic stroke compared with the general population was 3.8 (95%
CI
: 3.3–4.3) in young
CHD
adults and 1.6 (95%
CI
: 1.4–1.9) in older
CHD
adults. The adjusted hazard ratios for post‐stroke mortality compared with the general population was 2.3 (95%
CI
: 1.2–4.4) in young
CHD
adults and 1.3 (95%
CI
: 0.9–1.9) in older
CHD
adults.

Conclusions

Both younger and older
CHD
adults have an increased risk of ischemic stroke and by 60 years of age 7.4% of
CHD
adults will have had an ischemic stroke. Post‐stroke mortality was also increased in
CHD
adults compared with the general population.
Racial Disparities in the Utilization and Outcomes of Structural Heart Disease Interventions in the United States
Authors: Alkhouli Mohamad , Alqahtani Fahad , Holmes David R. , Berzingi Chalak 
Published: July 2019

Background
Data on race‐ and ethnicity‐based disparities in the utilization and outcomes of structural heart disease interventions in the United States are scarce.

Methods and Results

We used the National Inpatient Sample (2011‐2016) to examine racial and ethnic differences in the utilization, in‐hospital outcomes, and cost of structural heart disease interventions among patients ≥65 years of age. A total of 106 119 weighted hospitalizations for transcatheter aortic valve replacement, transcatheter mitral valve repair, and left atrial appendage occlusion were included. The utilization rates (defined as the number of procedures performed per 100 000
US
people >65 years of age) were higher in whites compared with blacks and Hispanics for transcatheter aortic valve replacement (43.1 versus 18.0 versus 21.1), transcatheter mitral valve repair (5.0 versus 3.2 versus 3.2), and left atrial appendage occlusion (6.6 versus 2.1 versus 3.5), respectively (
P
<0.001). Black and Hispanic patients had distinctive socioeconomic and clinical risk profiles compared with white patients. There were no significant differences in the adjusted in‐hospital mortality or key complications between patients of white race, black race, and Hispanic ethnicity following transcatheter aortic valve replacement, transcatheter mitral valve repair, or left atrial appendage occlusion. No difference in cost was observed between white and black patients following any of the 3 procedures. However, Hispanic patients incurred modestly higher cost with transcatheter mitral valve repair and left atrial appendage occlusion compared with white patients.

Conclusions
Racial and ethnic disparities exist in the utilization of structural heart disease interventions in the United States. Nonetheless, adjusted in‐hospital outcomes were comparable among white, black, and Hispanic patients. Further studies are needed to understand the reasons for these utilization disparities.
Ficophagus curtipes n. sp. (Nematoda: Aphelenchoididae), an associate of Ficus curtipes in China
Authors: Zhang Dayuan , Zeng Wensheng , Huang Jianfeng , Zeng Yongsan , Peng Yanqiong , Ye Weimin , Huang Jianghua , Giblin-Davis Robin M. 
Published: July 2019

Summary
A new nematode species was recovered from the syconia of Ficus curtipes from Xishuangbanna Tropical Botanical Garden, Yunnan, China. It is described herein as Ficophagus curtipes n. sp. and is differentiated from all currently described species in the genus by the possession of a spicule with a ventrally recurved tip (terminal barb). It is further characterised by possessing a short post-uterine sac, an ovoid spermatheca, presence of crustaformeria, excretory pore located near the head, amoeboid sperm, three pairs of subventral papillae on the male tail, rounded male tail tip without mucron, rose-thorn-shaped spicules without cucullus and absence of gubernaculum (= apophysis). Ficophagus curtipes n. sp. was differentiated from other sequenced species by the partial small subunit rRNA gene and D2-D3 expansion segments of the large subunit rRNA gene. Phylogenetic analyses suggested that F. curtipes n. sp. has a closer relationship with F. benjamina and F. microcarpus in the same highly supported monophyletic clade than to the other sequenced Ficophagus and Schistonchus s.l. species.
Molecular characterisation of some stubby root nematodes (Nematoda: Trichodoridae) from the USA and other countries
Authors: Subbotin Sergei A. , Cid Del Prado Vera Ignacio , Inserra Renato N. , Chizhov Vladimir N. , Decraemer Wilfrida 
Published: July 2019

Summary
The stubby root nematodes are world-wide distributed polyphagous root ectoparasites and can cause damage to a wide range of crops and natural vegetation. In this study, 22 valid and putative species of stubby root nematodes were identified in 37 samples collected in Malaysia, Mexico, Russia, and the USA (California, Florida, Minnesota and Nevada). The analysis of 58 new sequences of the D2-D3 expansion fragments of 28S rRNA gene revealed the following species: Nanidorus minor from California, Florida and Mexico, N. renifer from Florida, two unidentified Nanidorus species from California and Malaysia, respectively, Paratrichodorus allius from Florida and Minnesota, P. pachydermus and Paratrichodorus sp. from Russia, Trichodorus californicus, T. intermedius, and T. obscurus from California, T. obtusus from Florida, eight unidentified Trichodorus species from California, one unidentified Trichodorus species from Nevada, and two unidentified species of stubby root nematodes, one of Trichodorus and another undetermined species from Mexico. Molecular characterisation of T. californicus, T. intermedius and T. obscurus is given for the first time. The phylogenetic tree reconstructed from the analysis of 108 D2-D3 of 28S rRNA gene sequences of 58 valid and putative species of the stubby root nematodes contained five major clades: i) Trichodorus from Europe, Asia and North America; ii) Nanidorus and Trichodorus from Asia; iii) Trichodorus from California; iv) Paratrichodorus from several distant geographical regions; and v) Monotrichodorus from Central and South America. It has been hypothesised that the California Floristic Province is one of the centres of origin and diversification of stubby root nematodes. There is no information on the economic importance of the stubby root nematode species found in California and Mexico. The confirmation of the occurrence of N. renifer and P. allius in Florida should be of concern for the blueberry and potato industries in the state.
Malignant Peritoneal Mesothelioma
Authors: de Pangher Manzini Vincenzo 
Published: July 2019

Background The clinical characteristics of malignant peritoneal mesothelioma are not fully known, and it appears as a variable entity with different types of clinical presentation and with a difficult diagnosis. Patients Fifteen patients with malignant peritoneal mesothelioma were analyzed for asbestos exposure, clinical presentation, thrombocytosis, X-rays and echotomographic findings, peritoneal fluid cytology, surgical investigations, diagnosis in vita, therapy, cause of death, diagnosis time, and survival time. Results Asbestos exposure was present in 12 men. Abdominal pain, ascites, abdominal mass, weight loss and fever were the most common presentation symptoms. In 5 patients, the disease presented as a surgical emergency. Assembling the presenting symptoms, malignant peritoneal mesothelioma was subdivided in 3 types: classical (6 cases), surgical (5 cases) and medical (4 cases). Thrombocytosis was present in 11 cases. Peritoneal fluid cytology was positive for neoplastic mesothelial cells in 8 of 10 cases. Laparotomy (5 patients) and laparoscopy (7 cases) were diagnostic in all cases. Diagnosis in vita was malignant peritoneal mesothelioma for 13 patients, peritoneal carcinomatosis for 1, with only 1 autopsy diagnosis. Seven patients were treated with chemotherapy, showing a progression of the disease. Mean symptoms-to-diagnosis time was 122 days (4-410), and mean symptoms-to-survival time was 345 days (45-1510). Conclusions Malignant peritoneal mesothelioma is a very unusual disease characterized by a difficult diagnosis, a rapid evolution, a poor response to therapy, and a very high prevalence of thrombocytosis. A new clinical classification into three types (classical, surgical and medical) may be useful for a correct diagnosis. The early diagnosis of malignant peritoneal mesothelioma remains an important open question.
Primary Pulmonary Lymphoma: Diagnosis and Follow-Up of 6 Cases and Review of an Uncommon Entity
Authors: Varona Jose Felipe , Guerra Juan Manuel , Grande Carlos , Villena Victoria , González-Lois Carmen , Martinez Miguel Angel 
Published: July 2019

Aims and background Primary pulmonary lymphoma is an uncommon disease with a poorly defined management. We reviewed and followed the cases of primary pulmonary lymphoma in our institution to gather an estimation of this entity in our population. Design and methods We reviewed the records of all patients with biopsy-proven lymphoma of the lung. The main diagnostic criterion for primary pulmonary lymphoma was the absence of extrapulmonary involvement. Results We identified 6 cases of primary pulmonary lymphoma among 33 patients with biopsy-proven lymphoma of the lung evaluated in our center in a 12-year period. A radiological abnormality in an asymptomatic patient was the most common clinical presentation. Four cases were low-grade and two cases high-grade non-Hodgkin PPL. Histopathologic analyses of lung specimens obtained by transbronchial biopsy were sufficient for a diagnosis in 5 of the 6 cases and avoided invasive surgical maneuvers. Most patients followed an indolent course, but with a tendency to relapse. Conclusions Although clinical management of this entity is undefined, we feel bronchoscopic study, which is less aggressive than surgery, may be an adequate procedure for a diagnosis. Mono-chemotherapy using alkylating agents and careful clinical observation may be the best therapeutic approach for these patients, since most of them have favorable outcomes, whatever the treatment modalities.
Prognostic Factors in Early Glottic Carcinoma Implications for Treatment
Authors: Nur Demiral Ayse , Oguz Cetinayak , Kemal Erdag Taner , Ferhat Eyiler , Sülen Sarıoglu , Emel Ada , Munir Kınay , Ann Cooper Sen Rachel , Mehmet Sen 
Published: July 2019

Aim In this study we aimed to determine the prognostic factors affecting local control (LC) in limited glottic carcinoma treated with definitive radiotherapy (RT). Material and methods Between June 1991 and December 2001, 114 patients with early squamous-cell carcinoma of the glottis were treated with definitive RT at our institution. Only four (3.5%) patients were women. The median age was 60 (27-79). Fifteen percent, 72% and 13% of the patients had Tis, T1 and T2 tumors, respectively. Forty-three (37.7%) patients had anterior commissure invasion. Prior to RT 35 (31%) patients had undergone vocal cord stripping and two (2%) cordectomy. A median dose of 66 Gy (50-70.2) was given over a median period of 46 days (20-60). Univariate and multivariate analyses were performed for LC. The prognostic parameters analyzed for LC were T classification, anterior commissure involvement, total RT dose, and overall treatment time. Results Five-year local and regional control rates were 84.2% and 97.7%. RTOG grade 3-4 late side effects were observed only in one (0.9%) patient. In 15 patients with local failure, salvage treatment consisted of partial laryngectomy in eight patients and total laryngectomy in five. One of the remaining two patients was medically inoperable, and the other refused salvage surgery. In one of the three patients with regional failure, salvage surgery was applied and the other two were given palliative chemotherapy because of unresectable disease. Following salvage treatments, the ultimate five-year LC rate was 96.9% and the five-year larynx preservation rate was 91.1%. Second primary cancer was diagnosed in 17 (14.9%) patients. Only one patient developed distant metastases and two patients died of laryngeal cancer. While T2 disease and anterior commissure involvement were found to be unfavorable prognostic factors significantly influencing LC in univariate analyses, only T2 disease remained independent in multivariate analysis. Conclusion In patients with early glottic carcinoma, T classification proved to be the only independent prognostic factor affecting LC after primary radiotherapy according to the results of this study.
Expression of P53 Protein and Dna Flow Cytometry in Gastric Adenocarcinoma: Implications in Patients Treated with Adjuvant Etoposide, Adriamycin and Cisplatin
Authors: Büyükçelik Abdullah , Onur Handan , Akbulut Hakan , Yalçin Bülent , Ensari Arzu , Utkan Güngör , Önal Binnur Sönmez , İçli Fikri 
Published: July 2019

Aims and background We evaluated the prognostic value of p53 protein, DNA content and S-phase fraction in patients with adenocarcinoma of the stomach or the gastroesophageal junction treated with adjuvant etoposide, doxorubicin and cisplatin. Methods and study design Thirty-five consecutive patients with stage II or III gastric or gastroesophagial junction adenocarcinoma treated with at least two cycles of adjuvant etoposide, doxorubicin and cisplatin after curative gastric resection were included. The expression of p53 protein was determined by immunohistochemistry and DNA content by flow cytometry. The presence of p53 expression and DNA content was compared with clinicopathological features. Results Median age was 54 years (range, 31–71). P53 expression was detected in 42.9% (15 of 35) of gastric cancer tissues of the patients. Aneuploidy was observed in 31.4% of patients, and S-phase fraction was more than 10% in 22.9%. P53 immunoreactivity (33.3% vs 47.8%) was more common in advanced disease. There was no association among p53 immunoreactivity, DNA content and S-phase fraction. We also found no significant relationship between p53 immunoreactivity, DNA content, S-phase fraction or other clinicopathological parameters. In univariate analysis, the involvement of lymph nodes was a significant predictor of a poor outcome (P = 0.001). Also, p53-positive patients had a poor survival close to the level of significance (P = 0.051). Likewise, p53 immunoreactivity (P = 0.0071), in addition to lymph node involvement (P = 0.0016), were the independent prognostic factors in multivariate analysis. Conclusions This trial supports the results of previous reports that p53 immunoreactivity is a prognostic factor for patients with adenocarcinoma of stomach or gastroesophageal junction treated with adjuvant chemotherapy.
Usefulness of Ultrasound-Guided Fine-Needle Aspiration Cytology in the Diagnosis of Non-Palpable Small Thyroid Nodules
Authors: Accurso Antonello , Rocco Nicola , Palumbo Alessio , Leone Francesco 
Published: July 2019

Aims and background Diverse and contradictory approaches have been suggested for the management of non-palpable thyroid nodules. The aim of our study was to evaluate the indications and limits of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in non-palpable infracentimetric thyroid nodules. Methods and study design From September 2003 to December 2004 we observed 325 patients with non-palpable thyroid nodules. We divided our series into three groups according to the diameter of the lesion in order to verify the effectiveness of US-FNAC for lesions of less than 1 cm. Results We assessed the cases with satisfactory and unsatisfactory results in the three groups into which the sample was divided (4 mm to 1 cm; 10.1 mm to 15 mm, and 15.1 mm to 25.5 mm). Our statistical analysis by means of the z-test showed there was no significant (5%) difference in the percentage distribution of the unsatisfactory results in the three groups. Conclusions Fine-needle cytology appears to be a useful diagnostic tool also for nodules of less than one cm because the percentage of unsatisfactory results is not related to the size of the nodule.
Recurrence of Pseudomyxoma Peritonei within the Inguinal Canal
Authors: Cabanas Jacobo , da Silva Rodrigo Gomes , Goldstein Paulo , Verghese Mohan , Sugarbaker Paul H. 
Published: July 2019

Aim and Background Tumor appearing in an inguinal hernia sac indicates widespread carcinomatosis with ascites. A new onset hernia is a common clinical presentation of pseudomyxoma peritonei syndrome arising in an appendiceal mucinous tumor. Recurrence of pseudomyxoma peritonei within the inguinal region was previously reported in only a single patient. We present five patients with a recurrence of pseudomyxoma peritonei tumor nodules in the inguinal region following cytoreductive surgery and attempt to understand the etiology of this treatment failure. Methods and Study Design From a database of 910 patients with mucinous appendiceal tumors with peritoneal dissemination who had definitive treatment, five patients who had disease recurrence within the inguinal region were identified. The clinical histories were studied and presented in order to make future recommendations regarding the management of these patients. Results Five patients with ages ranging 39 to 67 years had a mucinous tumor in the inguinal region as a recurrence after a previous cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. One of them had separate recurrence in both right and left inguinal regions. All these patients were made disease-free by the reoperative surgery with a sacrifice of the testicle in four. None have evidence of a recurrence of an inguinal hernia despite the lack of formal repair. Conclusion At the time of initial cytoreductive surgery the surgeon should be aware of the inguinal region as a possible site of relapse. This may be more problematic in patients who have had prior surgery with mucoid fluid in a hernia as the presenting sign of pseudomyxoma peritonei. Inguinal recurrences should be removed with clear margins even if orchiectomy is required.
Postoperative Chemoradiotherapy of Pancreatic Cancer: What is the Appropriate Target Volume of Radiation Therapy?
Authors: Kim Kyubo , Kim Suzy , Chie Eui Kyu , Kim Sun Whe , Bang Yung-Jue , Ha Sung W. 
Published: July 2019

Aims and Background To evaluate the influence of radiation therapy target volume on the treatment outcome of adjuvant chemoradiotherapy for pancreatic cancer after curative resection. Methods Between February 1987 and July 2001, 70 patients treated with curative resection and adjuvant chemoradiotherapy for pancreatic adenocarcinoma were analyzed. There were 49 males and 21 females, with a median age of 57 years. Whipple's operation was performed in 44 patients, pylorus-preserving pancreaticoduodenectomy in 14, distal pancreatectomy in 9, and subtotal pancreatectomy in 3. Postoperative adjuvant radiotherapy was given up to 40 Gy at 2 Gy per fraction with a two-week planned rest. Intravenous 5-fluorouracil (500 mg/m2/day) was given on days 1 to 3 of each split course of radiotherapy. Until 1991, whole pancreas or preoperative tumor volume and retroperitoneal lymph nodes were irradiated (extended field, n = 14). Thereafter, the target volume included the retroperitoneal lymph nodes and the involved pancreatic resection margin (limited field, n = 56). The median follow-up period of all the patients was 16 months (range, 2-99). Results The overall 2- and 5-year survival rate of all patients was 29.7% and 14.0%, respectively. According to the radiotherapy target volume, the median survival time was 14 months in the extended field group and 16 months in the limited field group ( P = 0.65). Conclusions From the viewpoint of the target volume of radiotherapy, a limited field did not worsen the treatment outcome, although the survival rate was poor in both groups.