bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous Uptake of 18F-FDG and 68Ga-PSMA-11 in Hepatocellular Carcinoma
Authors: Perez Paola M. , Flavell Robert R. , Kelley Robin K. , Umetsu Sarah , Behr Spencer C. 
Published: January 2019

Abstract
We present the case of an 87-year-old man with a history of melanoma metastatic to the lungs found to have an FDG-negative liver lesion that was initially thought to be benign. Follow-up CT revealed growth of the liver lesion despite excellent response to nivolumab therapy of the pulmonary melanoma metastases. Biopsy of the lesion confirmed primary hepatocellular carcinoma. Follow-up 18F-FDG PET/CT showed minimal FDG uptake, slightly above liver background, and subsequent 68Ga-PSMA-11 PET/MR showed focal, intense uptake of radiotracer in a different region of the tumor. These imaging findings support intratumor metabolic heterogeneity with radiotracer uptake in different tumor locations.
68Ga-DOTATATE in Benign Prostate Hyperplasia
Authors: Wang Jiaqiong 
Published: January 2019

Abstract
A 79-year-old man had carcinoid syndrome and bilateral pulmonary nodules, which were biopsy confirmed as well-differentiated neuroendocrine tumor. PET/CT with 68Ga-[DOTA-Tyr3]-octreotate (68Ga-DOTATATE) showed multiple 68Ga-DOTATATE–avid bilateral pulmonary nodules, left hilar lymph node, as well as diffuse increased 68Ga-DOTATATE uptake in the prostate. A review of the history revealed that this patient had elevated prostate-specific antigen level. The prostate biopsy did not reveal evidence of prostate cancer but showed benign prostate hyperplasia.
Combination of Sonographic Morphology Score and Tumor Markers for Detecting Postoperative Recurrent Pelvic Ovarian Carcinoma
Authors: Shen Zhi Yong , Shen Ai Jun , Yang Shao Ling , Wu Ming Feng 
Published: January 2019

Abstract
To assess the efficacy of the combination of sonographic morphology score (SMS) with CA125 and HE4 for detecting recurrent pelvic ovarian carcinoma (OC). Data of 58 OC patients treated in our hospital between 2014 and 2016 were analyzed. After cytoreductive surgery and routine chemotherapy, all patients were followed up by transvaginal ultrasound examination (SMS for pelvic masses based on volume and structure scores) and tumor marker (serum CA125 and HE4) detection. Clinical diagnosis of recurrent OC was based on physical examination, magnetic resonance imaging, and punctured pathology for pelvic masses. Receiver operating characteristic (ROC) curves of SMS and the tumor markers were generated, and areas under the curve (AUC) values were assessed. There were 26 patients with tumor recurrence and 32 cases with no recurrence. Magnetic resonance imaging had 100% sensitivity and specificity. The areas under the ROC curves of SMS, CA125, HE4, and SMS-CA125-HE4 were 0.816, 0.825, 0.737, and 0.903, respectively. There was no significant difference in AUC values between SMS and CA125 or HE4. There were significant differences in AUC values between SMS-CA125-HE4 and SMS (Z = 2.48, P = 0.042), CA125 (Z = 2.38, P = 0.046), and HE4 (Z = 6.48, P = 0.016), respectively. With a cutoff value of SMS, 5; CA125, 35 U/mL; HE4, 105 pmol/L, the sensitivity, specificity, positive prognostic value, and negative prognostic value of SMS-CA125-HE4 for recurrent OC assessment were 0.9231, 0.8438, 0.8276, and 0.931, respectively. SMS-CA125-HE4 was correlated with recurrent OC (χ2 = 30.7428, P < 0.0001). Ultrasound combined with tumor markers may improve the diagnostic efficiency of recurrent OC.
Nuck Canal Hernias, Typical and Unusual Ultrasound Findings
Authors: Jedrzejewski Grzegorz , Osemlak Pawel , Wieczorek Andrzej Pawel , Nachulewicz Pawel 
Published: January 2019

Abstract

Background
Inguinal hernia in girls is a very rare condition. The cause of this pathology is incomplete closure of the processus vaginalis of the peritoneum, in girls named the canal of Nuck. Failed obliteration of this canal could result in hernia or hydrocele. Also less frequent findings, such as uterus herniated to the canal, were observed.

Objective
The purpose of this study was to describe the possible findings in female inguinal hernias and its ultrasound appearance.

Methods
Thirty-five patients with surgically confirmed hernias of the canal of Nuck were identified at our institution between January 2007 and November 2015. All the patients underwent ultrasonography before surgery.

Results
In 14 cases, there was hydrocele of the canal of Nuck. In 9 cases, intestinal hernia was found. In 10 patients, the hernia content appeared as mass-containing cysts and was confirmed at surgery as ovary. In 1 patient, the ovary was herniated together with uterus. In 1 patient, atypical hypoechoic lesion was found, which turned out to be angiofibrolipoma. In all patients, ultrasound diagnosis was confirmed by surgery.

Conclusions
Ultrasound examination performed with high-frequency transducer is an examination of choice in female patients with pathological mass in inguinal region.
Radiologist's Guide to Diagnosis of Fetal Cardiac Anomalies on Prenatal Ultrasound Imaging
Authors: Revels Jonathan Wesley , Wang Sherry S. , Itani Malak , Nasrullah Ayesha , Katz Douglas , Dubinsky Theodore J. , Moshiri Mariam 
Published: January 2019

Abstract
Congenital cardiac anomalies are a common finding during prenatal anatomical survey ultrasound examination. Cardiac anomalies are a major cause of prenatal and neonatal mortality and morbidity. If the anomaly is not lethal, most would require surgical correction. Therefore, early recognition of these abnormalities is essential for parental counseling and delivery planning, as well as analysis of neonatal treatment options. Although prenatal ultrasound plays an important role in identification of such anomalies, diagnosis and interpretation of imaging findings require familiarity and knowledge of the common imaging features. In this article, we provide a comprehensive review of ultrasound appearance of common fetal cardiac anomalies.
Main Duct Dilatation Is the Best Predictor of High-grade Dysplasia or Invasion in Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Del Chiaro Marco , Beckman Ross , Ateeb Zeeshan , Orsini Nicola , Rezaee Neda , Manos Lindsey , Valente Roberto , Yuan Chunhui , Ding Ding , Margonis Georgios A. , Yin Lingdi , Cameron John L. , Makary Martin A. , Burkhart Richard A. , Weiss Matthew J. , He Jin , Arnelo Urban , Yu Jun , Wolfgang Christopher L. 
Published: January 2019

Objective:
The purpose of this study is to determine preoperative factors that are predictive of malignancy in patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms (IPMN).

Summary Background Data:
IPMN of the pancreas may be precursor lesions to pancreatic cancer (PC) and represent a target for early diagnosis or prevention. While there has been much effort to define preoperative risk factors for malignant pathology, guidelines are ever-changing and controversy remains surrounding which patients would benefit most from resection.

Methods:
We performed a retrospective analysis of 901 consecutive patients obtained from two tertiary referral centers who underwent pancreatic resection for histologically proven IPMN between 2004 and 2017. Collected data included patient demographic characteristics, preoperative symptoms, radiological findings, and laboratory data.

Results:
Main pancreatic duct (MPD) dilatation was the only variable that was significantly associated with increased probability of malignancy (defined high-dysplasia or invasion) on both univariate and multivariate analysis. Even middle-range MPD dilatation from 5 mm to 9.9 mm (n = 286) was associated with increased odds of HG-IPMN (OR = 2.74; 95% CI = 1.80–4.16) and invasion (OR = 4.42; 95% CI = 2.55–7.66). MPD dilatation >10 mm (n = 150) had even greater odds of HG-IPMN (OR = 6.57; 95% CI = 3.94–10.98) and invasion (OR = 15.07; 95% CI = 8.21–27.65). A cutoff of 5 to 7 mm MPD diameter was determined to be the best predictor to discriminate between malignant and benign lesions.

Conclusions:
In agreement with current IPMN management guidelines, we found MPD dilatation, even low levels from 5 mm to 9.9 mm, to be the single best predictor of HG-IPMN or invasion, highlighting the critical role that MPD plays in the selection of surgical candidates.
Practice Patterns and Perioperative Outcomes of Laparoscopic Pancreaticoduodenectomy in China
Authors: Wang Min , Peng Bing , Liu Jianhua , Yin Xinmin , Tan Zhijian , Liu Rong , Hong Defei , Zhao Wenxing , Wu Heshui , Chen Rufu , Li Dewei , Huang Heguang , Miao Yi , Liu Yahui , Liang Tingbo , Wang Wei , Cai Yunqiang , Xing Zhongqiang , Cheng Wei , Zhong Xiaosheng , Zhao Zhiming , Zhang Jungang , Yang Zhiyong , Li Guolin , Shao Yue , Lin Guirong , Jiang Kuirong , Wu Pengfei , Jia Baoxing , Ma Tao , Jiang Chongyi , Peng Shuyou , Qin Renyi 
Published: January 2019

Objective:
The aim of the study was to analyze the outcomes of patients who have undergone laparoscopic pancreaticoduodenectomy (LPD) in China.

Summary Background Data:
LPD is being increasingly used worldwide, but an extensive, detailed, systematic, multicenter analysis of the procedure has not been performed.

Methods:
We retrospectively reviewed 1029 consecutive patients who had undergone LPD between January 2010 and August 2016 in China. Univariate and multivariate analyses of patient demographics, changes in outcome over time, technical learning curves, and the relationship between hospital or surgeon volume and patient outcomes were performed.

Results:
Among the 1029 patients, 61 (5.93%) required conversion to laparotomy. The median operation time (OT) was 441.34 minutes, and the major complications occurred in 511 patients (49.66%). There were 21 deaths (2.43%) within 30 days, and a total of 61 (5.93%) within 90 days. Discounting the effects of the early learning phase, critical parameters improved significantly with surgeons’ experience with the procedure. Univariate and multivariate analyses revealed that the pancreatic anastomosis technique, preoperative biliary drainage method, and total bilirubin were linked to several outcome measures, including OT, estimated intraoperative blood loss, and mortality. Multicenter analyses of the learning curve revealed 3 phases, with proficiency thresholds at 40 and 104 cases. Higher hospital, department, and surgeon volume, as well as surgeon experience with minimally invasive surgery, were associated with a lower risk of surgical failure.

Conclusions:
LPD is technically safe and feasible, with acceptable rates of morbidity and mortality. Nonetheless, long learning curves, low-volume hospitals, and surgical inexperience are associated with higher rates of complications and mortality.
Liver Resection for Multiple Hepatocellular Carcinomas
Authors: Fukami Yasuyuki , Kaneoka Yuji , Maeda Atsuyuki , Kumada Takashi , Tanaka Junko , Akita Tomoyuki , Kubo Shoji , Izumi Namiki , Kadoya Masumi , Sakamoto Michiie , Nakashima Osamu , Matsuyama Yutaka , Kokudo Takashi , Hasegawa Kiyoshi , Yamashita Tatsuya , Kashiwabara Kosuke , Takayama Tadatoshi , Kokudo Norihiro , Kudo Masatoshi 
Published: January 2019

Objective:
The aim of the study was to evaluate the survival benefits of liver resection (LR) compared with transarterial chemoembolization (TACE) for patients with multiple hepatocellular carcinomas (HCCs).

Background:
Despite significant improvements in diagnostic imaging and the widespread application of screening programs, some patients with HCC continue to present with multiple tumors. The surgical indications for multiple HCCs remain controversial.

Methods:
Among 77,268 patients with HCC reported in a Japanese nationwide survey, 27,164 patients had multiple HCCs. The exclusion criteria were Child-Pugh B/C, treatment other than LR and TACE, >3 tumors, and insufficient available data. Ultimately, 3246 patients (LR: n = 1944, TACE: n = 1302) were included. The survival benefit of LR for patients multiple HCCs was evaluated by using propensity score matching analysis.

Results:
The study group of 2178 patients (LR: n = 1089, TACE: n = 1089) seemed to be well matched. The overall survival rate in the LR group was 60.0% at 5 years, which was higher than that in the TACE group (41.6%, P < 0.001). Among patients with a tumor size of 30 mm or more, LR showed a survival benefit over TACE at 5 years (53.0% vs 32.7%, P < 0.001). The multivariate analysis indicated that age, serum albumin level, serum alpha-fetoprotein (AFP) level, macrovascular invasion, tumor size, and TACE were independent predictors of poor prognosis in multiple HCCs.

Conclusions:
LR could offer better long-term survival than TACE for patients with multiple HCCs (up to 3 tumors). If patients have good liver function (Child-Pugh A), LR is recommended, even for those with multiple HCCs with tumor sizes of 30 mm or more.
Multicenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates
Authors: Haugen Christine E. , McAdams-DeMarco Mara , Holscher Courtenay M. , Ying Hao , Gurakar Ahmet O. , Garonzik-Wang Jacqueline , Cameron Andrew M. , Segev Dorry L. , Lai Jennifer C. 
Published: January 2019

Objective:
To determine if the association of frailty and waitlist mortality varies by candidate age.

Background:
Frailty, a construct developed in geriatrics, is a state of decreased physiologic reserve, and is associated with mortality while awaiting liver transplantation (LT). However, older candidates have high comorbidity burden and less physiologic reserve, so the relationship between frailty and waitlist mortality may vary by candidate age.

Methods:
We studied adults listed for LT at 2 transplant centers. The liver frailty index (grip strength, chair stands, balance) was measured at evaluation, with frailty defined as liver frailty index  ≥ 4.5. We compared the prevalence of frailty in older (≥65 yr) and younger (18–64 yr) candidates. We studied the association between frailty, age, interaction between the 2, and waitlist mortality using competing risks regression adjusted for sex, BMI, and MELDNa.

Results:
Among 882 LT candidates, 16.6% were ≥ 65 years. Older candidates were more likely to be frail (33.3% vs 21.7%, P = 0.002). Older age [adjusted subhazard ratio (aSHR): 2.16, 95% CI: 1.51–3.09, P < 0.001] and frailty (aSHR: 1.92, 95% CI: 1.38–2.67, P < 0.001) were independently associated with higher risk of waitlist mortality. However, the association between waitlist mortality and frailty did not vary by candidate age (aSHR of frailty for younger patients: 1.90, 95% CI: 1.28–2.80, P = 0.001; aSHR of frailty for older patients: 1.98, 95% CI: 1.07–3.67, P = 0.03; P interaction = 0.9).

Conclusions:
Older candidates experienced higher rates of frailty than younger candidates. However, regardless of age, frailty was associated with nearly 2-fold increased risk of waitlist mortality. Our data support the applicability of the frailty concept to the whole LT population and can guide the development of prehabilitation programs targeting frailty in LT patients of all ages.
Colocalization of IQGAP1 with DLC-1 and PLC-δ1; Its potential role in coronary spasm
Authors: Tanaka Makoto , Osanai Tomohiro , Homma Yoshimi , Hanada Kenji , Okumura Ken , Tomita Hirofumi 
Published: January 2019

AbstractPhospholipase C (PLC)-δ1, activated by p122RhoGTPase-activating protein (GAP)/deleted in liver cancer-1 (p122RhoGAP/DLC-1), contributes to the coronary spastic angina (CSA) pathogenesis. The present study aims to further investigate the p122RhoGAP/DLC-1 protein. We examined molecules assisting this protein and identified a scaffold protein—IQ motif-containing GTPase-activating protein 1 (IQGAP1). IQGAP1-C binds to the steroidogenic acute regulatory-related lipid transfer (START) domain of p122RhoGAP/DLC-1, and PLC-δ1 binds to IQGAP1-N, forming a complex. In fluorescence microscopy, small dots of PLC-δ1 created fine linear arrays like microtubules, and IQGAP1 and p122RhoGAP/DLC-1 were colocated in the cytoplasm with PLC-δ1. Ionomycin induced the raft recruitment of the PLC-δ1, IQGAP1, and p122RhoGAP/DLC-1 complex by translocation to the plasma membrane (PM), indicating the movement of this complex is along microtubules with the motor protein kinesin. Moreover, the IQGAP1 protein was elevated in skin fibroblasts obtained from patients with CSA, and it enhanced the PLC activity and peak intracellular calcium concentration in response to acetylcholine. IQGAP1, a novel stimulating protein, forms a complex with p122RhoGAP/DLC-1 and PLC-δ1 that moves along microtubules and enhances the PLC activity.
The Vibrio cholerae MARTX toxin simultaneously induces actin collapse while silencing the inflammatory response to cytoskeletal damage
Authors: Woida Patrick J. , Satchell Karla J. F. 
Published: January 2019

AbstractMultifunctional autoprocessing repeats-in-toxin (MARTX) toxins are pore-forming toxins that translocate multiple functionally independent effector domains into a target eukaryotic cell. Vibrio cholerae colonizes intestinal epithelial cells (IECs) and utilizes a MARTX toxin with three effector domains — an actin cross-linking domain (ACD), a Rho inactivation domain (RID), and an α/β hydrolase domain (ABH) — to suppress innate immunity and enhance colonization. We investigated whether these multiple catalytic enzymes delivered from a single toxin function in a coordinated manner to regulate intestinal innate immunity. Using cultured IECs, we demonstrate that ACD-induced cytoskeletal collapse activated ERK, p38, and JNK mitogen-activated protein kinase (MAPK) signaling to elicit a robust proinflammatory response characterized by production of interleukin-8 (IL-8) and expression of CXCL8, TNF, and other proinflammatory genes. However, RID and ABH, which are naturally delivered along with ACD, blocked MAPK activation via Rac1 and thus prevented the ACD-induced inflammation. RID also abolished IL-8 secretion induced by heat-killed bacteria, tumor necrosis factor, and latrunculin A. Thus, MARTX toxins utilize enzymatic multifunctionality to silence the host response to bacterial factors and to the damage it causes. Further, these data show how V. cholerae MARTX toxin suppresses intestinal inflammation and contributes to cholera being classically defined as non-inflammatory diarrheal disease.
Temporal gating of synaptic competition in the lateral amygdala by cannabinoid receptor modulation of the thalamic input
Authors: Drumond Ana , Madeira Natália , Fonseca Rosalina 
Published: January 2019

ABSTRACTThe acquisition of fear memories involves plasticity of the thalamic and cortical pathways to the lateral amygdala (LA). The maintenance of synaptic plasticity requires the interplay between input-specific synaptic tags and the allocation of plasticity-related proteins (PRPs). Based on this interplay, weakly activated synapses can express long-lasting synaptic plasticity by cooperation with strongly activated ones. Increasing the number of activated synapses can shift cooperation to competition. Synaptic cooperation and competition can determine whether two events, separated in time, are linked or selected. The rules that determine whether synapses cooperate or compete are unknown. We found that synaptic cooperation and competition, in the LA, are determined by the temporal sequence of cortical and thalamic stimulation and that the strength of the synaptic tag is modulated by the endocannabinoid signalling. This modulation is particularly effective in thalamic synapses, suggesting a critical role of endocannabinoids in restricting thalamic plasticity. Also, we found that PRPs availability is modulated by the action-potential firing of neurons, shifting competition to cooperation. Our data present the first evidence that pre-synaptic modulation of synaptic activation, by the cannabinoid signalling, function as a temporal gating mechanism limiting synaptic cooperation and competition.
Placental effects on maternal brain revealed by disrupted placental gene expression in mouse hybrids
Authors: Arévalo Lena , Campbell Polly 
Published: January 2019

AbstractThe mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signaling on the maternal brain are understudied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behavior. Using a cross between the house mouse and the Algerian mouse in which hybrid placental development is abnormal, we sequenced late gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression ofFmn1, Drd3, Caln1andCtsrwas significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families andDrd3in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally-derived placental genome can influence the expression of maternal-fetal communication genes, including placental hormones, suggesting an effect of the offspring’s father on the mother’s brain.
The biofilm matrix scaffold of Pseudomonas species contains non-canonically base paired extracellular DNA and RNA
Authors: Seviour Thomas , Winnerdy Fernaldo Richtia , Wong Lan Li , Shi Xiangyan , Mugunthan Sudarsan , Castaing Remi , Adav Sunil S , Kohli Gurjeet Singh , Shewan Heather M , Stokes Jason R , Rice Scott A. , Phan Anh Tuân , Kjelleberg Staffan 
Published: January 2019

AbstractWhile extracellular DNA (eDNA) is recognized as a critical biofilm matrix component, it is not understood how it contributes to biofilm function. Here we isolate eDNA from Pseudomonas biofilms using ionic liquids, and discover that its key biophysical signatures, i.e. fluid viscoelasticity, nucleic acid conformation, and temperature and pH dependencies of gel to solution transitions, are maintained. Solid-state analysis of isolated eDNA, as a proxy for eDNA structure in biofilms, revealed non-canonical Hoogsteen base pairs, triads or tetrads involving guanine and thymine or uracil. These were less abundant in chromosomal DNA and undetected as eDNA underwent gel-sol transition. Purine-rich RNA was present in the eDNA network, which potentially enables eDNA to be the main cross-linking exopolymer in the matrix through non-canonical nucleobase interactions. Our study suggests that Pseudomonas assemble extracellular DNA and RNA into a network with viscoelastic properties, which underpin their persistence and spreading, and may aid the development of more effective controls for biofilm-associated infections.
C99 selectively accumulates in vulnerable neurons in Alzheimer’s disease
Authors: Pulina Maria V. , Hopkins Maya , Haroutunian Vahram , Greengard Paul , Bustos Victor 
Published: January 2019

ABSTRACTIntroductionThe levels and distribution of amyloid deposits in the brain does not correlate well with Alzheimer’s disease (AD) progression. Therefore, it is likely that Amyloid-precursor-protein proteolytic fragments other than beta-amyloid contribute to the onset of AD.MethodsWe developed a sensitive assay adapted to the detection of C99, the direct precursor of beta-amyloid. Three postmortem groups were studied: control with normal and stable cognition; subjects with moderate AD, and individuals with severe AD. The amount of C99 and beta-amyloid was quantified and correlated with the severity of AD.ResultsC99 accumulates in vulnerable neurons, and its levels correlate with the degree of cognitive impairment in patients suffering from AD. In contrast, beta-amyloid levels are increased in both vulnerable and resistant brain areas.DiscussionThese results raise the possibility that C99, rather than beta-amyloid plaques, is responsible for the death of nerve cells in Alzheimer’s disease.