bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients
Authors: Yadav Madhav Prasad , Ballal Sanjana , Bal Chandrashekhar , Sahoo Ranjit Kumar , Damle Nishikant Avinash , Tripathi Madhavi , Seth Amlesh 
Published: November 2019

Purpose
The aim of this study was to evaluate the efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC).

Methods
In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic 68Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent 177Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients.

Results
The median age of patients was 66.5 years (range, 30–88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects.

Conclusions

177Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.
Detection of Unusual Peritoneal Metastases of Prostate Cancer With 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Simsek Duygu Has , Sanli Yasemin 
Published: November 2019

Abstract
Peritoneal metastasis of prostate cancer (PC) is unusual site of metastatic disease; only limited case reports are published in literature. 68Ga–prostate-specific membrane antigen (PSMA) PET/CT is recently used for detection of PC metastasis with high accuracy rates. We present a case of a 68-year-old man with disseminated peritoneal metastases and abdominal metastatic lymph nodes of PC, demonstrated in 68Ga-PSMA PET/CT with intense PSMA uptake.
FDG PET Findings of Hyperprogression During Immunotherapy in a Patient With Hepatocellular Carcinoma
Authors: Wang Jingnan , Wang Xuezhu , Yang Xu , Zhao Haitao , Huo Li 
Published: November 2019

Abstract
Although immunotherapy is a successful approach in oncology, it might be detrimental to some patients. In the condition of hyperprogression, patients experience accelerated progression after immunotherapy, resulting in a worse outcome. Hyperprogression may be difficult to be identified in the early stage. Once the diagnosis is confirmed in the follow-up evaluation, the immunotherapy should be stopped immediately. In this case, we report a hyperprogression patient during combined immunotherapy toward metastatic hepatocellular carcinoma observed by serial 18F-FDG PET.
Retroperitoneal Liposarcoma on 99mTc-DTPA Renal Scintigraphy
Authors: Chen Haotian , Wei Jing , Wang Rang , Xiang Yongzhao , Fan Chengzhong 
Published: November 2019

Abstract
Retroperitoneal liposarcoma is usually large and can press on other organs. We report a case of a 66-year-old woman with a history of retroperitoneal liposarcoma resection who presented to the emergency department with abdominal pain. Ultrasonography revealed a large abdominal mass with renal displacement. Dynamic renal scintigraphy with 99mTc-DTPA was conducted to evaluate renal function. However, severe impairment of the right kidney function and abnormal tracer accumulation were observed during the examination. SPECT/CT was performed; 2 kidneys were successfully localized, and the recurrence of tumor was correctly detected.
Cerebellar ataxias: an update
Authors: Manto Mario , Gandini Jordi , Feil Katharina , Strupp Michael 
Published: November 2019

Purpose of review
Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum.

Recent findings
Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias.

Summary
Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.
Spaceflight associated neuro-ocular syndrome
Authors: Wojcik Peter , Kini Ashwini , Al Othman Bayan , Galdamez Laura A. , Lee Andrew G. 
Published: November 2019

Purpose of review
Several decades of long duration space flight missions by the National Aeronautics and Space Administration has revealed an interesting and unique constellation of neuro-ophthalmic findings now called spaceflight associated neuro-ocular syndrome (SANS). The unique space environment of microgravity produces novel physiological changes and derangements that present a challenge to astronauts in current and future long duration space missions. Although the precise mechanism of SANS is not fully understood, in this review, we examine recent developments that may to help explain possible causes and potential countermeasures.

Recent findings
The cause of SANS is still largely unknown. A growing body of evidence implicates multiple factors that contribute to the development of SANS including cephalad fluid shifts, increased intracranial pressure, venous/lymphatic stasis, inflammation, metabolism, axoplasmic stasis and radiation exposure.

Summary
The pathologic mechanism behind SANS may be multifactorial and may be amenable to different countermeasures for prevention and management of SANS.
A Pilot Study Comparing Effects of Bifrontal Versus Bitemporal Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Mild Alzheimer Disease
Authors: Liu Celina S. , Herrmann Nathan , Gallagher Damien , Rajji Tarek K. , Kiss Alex , Vieira Danielle , Lanctôt Krista L. 
Published: November 2019

Objective
While transcranial direct current stimulation (tDCS) can enhance aspects of memory in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), there has been wide variability in both the placement of tDCS electrodes and treatment response. This study compared the effects of bifrontal (anodal stimulation over the dorsolateral prefrontal cortices), bitemporal (anodal stimulation over the temporal cortices), and sham tDCS on cognitive performance in MCI and AD.

Methods
Seventeen patients diagnosed with MCI or mild AD received 3 sessions of anodal tDCS (bifrontal, bitemporal, 2 mA for 20 minutes; and sham) in random order. Sessions were separated by 1 week. The Alzheimer's Disease Assessment Scale–Cognitive Word Recognition Task, Alzheimer's Disease Assessment Scale–Cognitive Word Recall Task, 2-back, and Montreal Cognitive Assessment were used to assess cognition.

Results
There was a significant effect of stimulation condition on 2-back accuracy (F
2,28 = 5.28 P = 0.01, η2
p = 0.27), with greater improvements following bitemporal tDCS compared with both bifrontal and sham stimulations. There were no significant changes on other outcome measures following any stimulation. Adverse effects from stimulation were mild and temporary.

Conclusions
These findings demonstrate that improvements in specific memory tasks can be safely achieved after a single session of bitemporal tDCS in MCI and mild AD patients.
Role of the hippocampus during logical reasoning and belief bias in aging
Authors: Ziaei Maryam , Bonyadi Mohammad Reza , Reutens David C. 
Published: November 2019

AbstractReasoning requires initial encoding of the semantic association between premises or assumptions, retrieval of these semantic associations from memory, and recombination of information to draw a logical conclusion. Currently-held beliefs can interfere with the content of the assumptions if not congruent and inhibited. This study aimed to investigate the role of the hippocampus and hippocampal networks during logical reasoning tasks in which the congruence between currently-held beliefs and assumptions varies. Participants of younger and older age completed a series of syllogistic reasoning tasks in which two premises and one conclusion were presented and they were required to decide if the conclusion logically followed the premises. The belief load of premises was manipulated to be either congruent or incongruent with currently-held beliefs. Our whole-brain results showed that older adults recruited the hippocampus during the premise integration stage more than their younger counterparts. Functional connectivity using a hippocampal seed revealed that older, but not younger, adults recruited a hippocampal network that included anterior cingulate and inferior frontal regions when premises were believable. Importantly, this network contributed to better performance in believable inferences, only in older adults group. Further analyses suggested that, in older adults group, the integrity of the left cingulum bundle was associated with the higher correct rejection of believable premises more than unbelievable ones. Using multimodal imaging, this study highlights the importance of the hippocampus during premise integration and supports the compensatory role of the hippocampal network during a logical reasoning task among older adults.
Distinct transcriptional programs of SOX2 in different types of small cell lung cancers
Authors: Tenjin Yuki , Matsuura Kumi , Kudoh Shinji , Usuki Shingo , Yamada Tatsuya , Matsuo Akira , Sato Younosuke , Saito Haruki , Fujino Kosuke , Wakimoto Joeji , Ichimura Takaya , Kohrogi Hirotsugu , Sakagami Takuro , Niwa Hitoshi , Ito Takaaki 
Published: November 2019

AbstractSOX2is an oncogene in human small cell lung cancer (SCLC), an aggressive neuroendocrine (NE) tumor. However, the roles of SOX2 in SCLC remain unclear, and strategies to selectively target SOX2 in SCLC cells have not yet been established. We herein demonstrated that SOX2 is involved in NE differentiation and tumorigenesis in cooperation with ASCL1, a lineage-specific transcriptional factor, in the classical subtype of SCLC cell lines. ASCL1 recruits SOX2, which promotes INSM1 expression. Precursor SCLC lesions were established inTrp53(-/-);CCSPrtTA; tetOCre; floxedRb1; floxedHes1mice, and the NE neoplasms induced were positive for Ascl1, Sox2, and Insm1. In contrast to the ASCL1-SOX2 signaling axis to control the SCLC phenotype in classical subtype SCLC, SOX2 targeted distinct genes, such as those related to the Hippo pathway, in ASCL1-negative, variant subtype SCLC. The present results support the importance of the ASCL1-SOX2 axis as a main subtype of SCLC, and suggest the therapeutic potential of targeting the ASCL1-SOX2 signaling axis and the clinical utility of SOX2 as a biological marker in the classical subtype of SCLC.
Two-way migration ofLychnis wilfordiicaused by the circular landform of Japan-Korea-northeast China-Russian Far East region and its suggestion for conservation in northeast Asia
Authors: Tamura Saya , Kwak Myounghai , Kokubugata Goro , Park Chan-ho , Lee Byoung-Yoon , Fukuda Tomoko , Petrunenko Ekaterina , Koksheeva Inna , Pimenova Elena , Krestov Pavel , Bondarchuk Svetlana , Ma Jin-Shuang , Zhou Hai-Cheng , Tsuboi Hayato , Nishikawa Yoko , Shimamura Takashi , Fujita Hiroko , Nakamura Koh 
Published: November 2019

ABSTRACTIn northeast Asia, substantial portion of the floras, including endangered species, are shared among its component countries in the continental, peninsula, and island parts largely through Quaternary migration. To effectively conserve nationally endangered plants in Northeast Asia, transnational conservation studies are vitally needed.Lychnis wilfordii(Caryophyllaceae) has disjunct distribution in Russian Far East (Primorsky Krai), northeast China (Jilin), Korea (Gangwon-do) and Japan (Hokkaido, Aomori, Nagano), surrounding the sea, and this is designated as an endangered species in Japan and Korea. Population genetic and molecular dating analyses were conducted 1) to elucidate geographic genetic structure covering the species range, 2) to test possible scenarios of migration, and 3) to develop logical plans for effective conservation. Population genetic analyses indicated the continent and peninsula parts (north and south Primorsky Krai, Jilin, and Gangwon-do) had higher genetic diversity compared to those in the Japanese Archipelago (Hokkaido and Nagano). Five genetically distinct groups were recognized, namely, Nagano, Gangwon-do, Jilin, north and south Primorsky Krai plus Aomori, and Hokkaido. Genetic distance between Hokkaido and Nagano was larger than between Hokkaido and north Primorsky Krai, and between Nagano and Gangwon-do, crossing national borders and the natural barrier of the sea. Considering these results,L. wilfordiilikely migrated from the Asian continent to the Japanese Archipelago using two routes: north route from Russian Far East to Hokkaido and Aomori, and south route from the Korean Peninsula to Nagano. Based on molecular dating, migration from the continent to the islands likely occurred from the middle Pleistocene to the Holocene. For effective conservation ofL. wilfordii, Hokkaido and Nagano populations should be distinguished as different evolutionary significant units, although these two regions belong to the same country, because Hokkaido and Nagano populations are at the different ends of the two migratory routes based on the migration scenario.
Barking up the right tree: Univariate and multivariate fMRI analyses of homonym comprehension
Authors: Hoffman Paul , Tamm Andres 
Published: November 2019

AbstractHomonyms are a critical test case for investigating how the brain resolves ambiguity in language and, more generally, how context influences semantic processing. Previous neuroimaging studies have associated processing of homonyms with greater engagement of regions involved in executive control of semantic processing. However, the precise role of these areas and the involvement of semantic representational regions in homonym comprehension remain elusive. We addressed this by combining univariate and multivariate fMRI analyses of homonym processing. We tested whether multi-voxel activation patterns could discriminate between presentations of the same homonym in different contexts (e.g.,barkfollowingtreevs.barkfollowingdog). The ventral anterior temporal lobe, implicated in semantic representation but not previously in homonym comprehension, showed this meaning-specific coding, despite not showing increased mean activation for homonyms. Within inferior frontal gyrus (IFG), a key site for semantic control, there was a dissociation between pars orbitalis, which also showed meaning-specific coding, and pars triangularis, which discriminated more generally between semantically related and unrelated word pairs. IFG effects were goal-dependent, only occurring when the task required semantic decisions, in line with a top-down control function. Finally, posterior middle temporal cortex showed a hybrid pattern of responses, supporting the idea that it acts as an interface between semantic representations and the control system. The study provides new evidence for context-dependent coding in the semantic system and clarifies the role of control regions in processing ambiguity. It also highlights the importance of combining univariate and multivariate neuroimaging data to fully elucidate the role of a brain region in semantic cognition.
The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor positive metastatic breast cancer
Authors: Wander Seth A. , Cohen Ofir , Gong Xueqian , Johnson Gabriela N. , Buendia-Buendia Jorge , Lloyd Maxwell R. , Kim Dewey , Luo Flora , Mao Pingping , Helvie Karla , Kowalski Kailey J. , Nayar Utthara , Waks Adrienne G. , Parsons Stephen , Martinez Ricardo , Litchfield Lacey M. , Ye Xiang S. , Yu Chun Ping , Jansen Valerie M. , Stille John R. , Smith Patricia S. , Oakley Gerard J. , Chu Quincy , Batist Gerald , Hughes Melissa , Kremer Jill D. , Garraway Levi A. , Winer Eric P. , Tolaney Sara M. , Lin Nancy U. , Buchanan Sean , Wagle Nikhil 
Published: November 2019

AbstractClinical resistance mechanisms to CDK4/6 inhibitors in HR+ breast cancer have not been clearly defined. Whole exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including RB1 loss, activating alterations in AKT1, RAS, AURKA, CCNE2, ERBB2, and FGFR2, and loss of ER expression. In vitro experiments confirmed that these alterations conferred CDK4/6i resistance. Cancer cells cultured to resistance with CDK4/6i also acquired RB1, KRAS, AURKA, or CCNE2 alterations, which conferred sensitivity to AURKA, ERK, or CHEK1 inhibition. Besides inactivation of RB1, which accounts for ∼5% of resistance, seven of these mechanisms have not been previously identified as clinical mediators of resistance to CDK4/6 inhibitors in patients. Three of these—RAS activation, AKT activation, and AURKA activation—have not to our knowledge been previously demonstrated preclinically. Together, these eight mechanisms were present in 80% of resistant tumors profiled and may define therapeutic opportunities in patients.SignificanceWe identified eight distinct mechanisms of resistance to CDK4/6 inhibitors present in 80% of resistant tumors profiled. Most of these have a therapeutic strategy to overcome or prevent resistance in these tumors. Taken together, these findings have critical implications related to the potential utility of precision-based approaches to overcome resistance in many patients with HR+ MBC.
Kinetic control of stationary flux ratios for a wide range of biochemical processes
Authors: Mallory Joel D. , Kolomeisky Anatoly B. , Igoshin Oleg A. 
Published: November 2019

ABSTRACTOne of the most intriguing features of biological systems is their ability to regulate the steady-state fluxes of the underlying biochemical reactions, however the regulatory mechanisms and their physicochemical properties are not fully understood. Fundamentally, flux regulation can be explained with a chemical kinetic formalism describing the transitions between discrete states with the reaction rates defined by an underlying free-energy landscape. Which features of the energy landscape affect the flux distribution? Here we prove that the ratios of the steady-state fluxes of quasi-first-order biochemical processes are invariant to energy perturbations of the discrete states and are only affected by the energy barriers. In other words, the non-equilibrium flux distribution is under kinetic and not thermodynamic control. We illustrate the generality of this result for three biological processes. For the network describing protein folding along competing pathways, the probabilities of proceeding via these pathways are shown to be invariant to the stability of the intermediates or to the presence of additional misfolded states. For the network describing protein synthesis, the error rate and the energy expenditure per peptide bond is proven to be independent of the stability of the intermediate states. For molecular motors such as myosin-V, the ratio of forward to backward steps and the number of ATP molecules hydrolyzed per step is demonstrated to be invariant to energy perturbations of the intermediate states. These findings place important constraints on the ability of mutations and drug perturbations to affect the steady-state flux distribution for a wide class of biological processes.
Enhancing stakeholder networks in wine tourism – evidence from Italian small municipalities
Authors: Festa Giuseppe , Shams S.M. Riad , Metallo Gerardino , Cuomo Maria Teresa 
Published: November 2019

Purpose
The purpose of this paper is to explore validity and reliability of a possible collaboration model for wine tourism with a “public” basis, i.e. from the point of view of the municipality engaged in promoting the wine tourism industry insisting on the territory.

Design/methodology/approach
The survey, proposing a theoretical/empirical framework, has investigated, through an electronic platform, the municipalities belonging to the National Association of “Wine Cities.”

Findings
The research has demonstrated a substantial trustworthiness of the model, with further evidence about the underestimation of stakeholder networks on behalf of Italian small municipalities. A clear difference of perception between non-small municipalities and small municipalities has emerged with regard to the perceived relevance of the collaboration with the territorial wine tourism players/stakeholders.

Practical implications
A recent legislation in Italy, just focused on small municipalities, might help overcome these gaps, between non-small municipalities and small municipalities, releasing in the territories new energies for the development of wine tourism, from both planning and financing points of view.

Originality/value
Italy as country is the largest producer of wine in the world. Similarly, wine tourism, as additional wine business opportunity, is a successful phenomenon in Italy, even though with great margins of development (especially with comparison to the New World of Wine). One of the main limits of this delay is the lack of public-private collaboration, at widespread level, among the players/stakeholders of the sector. The model that has been proposed in this research contributes scientifically and practically to fill this gaps.