bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Outcomes of 125 Patients With Metastatic Pheochromocytoma or Paraganglioma Treated With 131-I MIBG
Authors: Thorpe Matthew P , Kane Ari , Zhu Jason , Morse Michael A , Wong Terence , Borges-Neto Salvador 
Published: October 2019

Abstract

Context
Prognosis of metastatic pheochromocytoma/paraganglioma following 131-Iodine metaiodobenzylguanidine (MIBG) is incompletely characterized due to small samples and shorter follow-up in these rare, often indolent tumors.

Objective
To describe long-term survival, frequency, and prognostic impact of imaging, biochemical, and symptomatic response to 131-I MIBG.

Design
Retrospective chart and imaging review at a tertiary referral center.

Patients
Six hundred sixty-eight person-years of follow-up in 125 patients with metastatic pheochromocytoma/paraganglioma with progression through prior multimodal treatment.

Intervention
Median 18 800 MBq 131-I MIBG.

Main Outcome Measures
Overall survival, Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) imaging response, symptomatic response per chart review, and biochemical response (20% change over 2 consecutive assays of catecholamines, vanillylmandelic acid, metanephrines, or chromogranin A).

Results
Median survival standard deviation [SD] from diagnosis was 11.5 years [2.4]; following metastasis, 6.5 years [0.8]; post treatment, 4.3 years [0.7]. Among 88 participants with follow-up imaging, 1% experienced complete response, 33% partial response, 53% stability, and 13% progression. Fifty-one percent showed subsequent progression, median progression-free survival [SD] of 2.0 years [0.6]. Stability/response vs progression at first imaging follow-up (3–6 months) predicted improved survival, 6.3 vs 2.4 years (P = 0.021). Fifty-nine percent of 54 patients demonstrated biochemical response. Fifty percent of these relapsed, with median time to laboratory progression [SD] of 2.8 years [0.7]. Biochemical response did not predict extended survival. Seventy-five percent of 83 patients reported improvement in pretreatment symptoms, consisting primarily of pain (42%), fatigue (27%), and hypertension (14%). Sixty-one percent of these patients experienced subsequent symptomatic progression at median [SD] 1.8 years [0.4]. Symptomatic response did not predict extended survival.

Conclusions
Imaging, symptomatic, and laboratory response to multimodal treatment including high-dose 131-I MIBG were achieved on long-term follow-up in metastatic pheochromocytoma or paraganglioma. Imaging response at 3 to 6 months was prognostic.
Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome
Authors: Wiwatpanit Teerawat , Murphy Alina R , Lu Zhenxiao , Urbanek Margrit , Burdette Joanna E , Woodruff Teresa K , Kim J Julie 
Published: October 2019

AbstractContextPolycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer.ObjectiveTo study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established.DesignHuman endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues. Organoids were treated for 14 days with physiologic levels of estradiol and testosterone to mimic a normal follicular phase or PCOS hormone profiles. Organoids were harvested for immunostaining and ribonucleic acid sequencing.SettingAcademic institution.PatientsEndometrial tissues from 10 premenopausal women undergoing hysterectomy for benign pathologies were obtained following written consent.Main Outcome MeasuresOrganoid architecture, cell specific markers, functional markers, proliferation, and gene expression were measured.ResultsA method to generate scaffold-free endometrial organoids containing epithelial and stromal cells was established. These organoids exhibited distinct organization with epithelial cells lining the outer surface and stromal cells in the center of the organoids. Epithelial cells were polarized, organoids expressed cell type specific and functional markers, as well as androgen, estrogen, and progesterone receptors. Treatment with PCOS hormones increased cell proliferation and dysregulated genes in endometrial organoids.ConclusionsA new multicellular, scaffold-free endometrial organoid system was established that resembled physiology of the native endometrium. Excess androgens in PCOS promoted cell proliferation in endometrial organoids, revealing new mechanisms of PCOS-associated with risk of endometrial neoplasia.
MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the primary cilium
Authors: Xie Shuwei , Farmer Trey , Naslavsky Naava , Caplan Steve 
Published: October 2019

ABSTRACT
The endocytic protein EHD1 plays an important role in ciliogenesis by facilitating fusion of the ciliary vesicle and removal of CP110 (also known as CCP110) from the mother centriole, as well as removal of Cep215 (also known as CDK5RAP2) from centrioles to permit disengagement and duplication. However, the mechanism of its centrosomal recruitment remains unknown. Here, we address the role of the EHD1 interaction partner MICAL-L1 in ciliogenesis. MICAL-L1 knockdown impairs ciliogenesis in a similar manner to EHD1 knockdown, and MICAL-L1 localizes to cilia and centrosomes in both ciliated and non-ciliated cells. Consistent with EHD1 function, MICAL-L1-depletion prevents CP110 removal from the mother centriole. Moreover, upon MICAL-L1-depletion, EHD1 fails to localize to basal bodies. Since MICAL-L1 localizes to the centrosome even in non-ciliated cells, we hypothesized that it might be anchored to the centrosome via an interaction with centrosomal proteins. By performing mass spectrometry, we identified several tubulins as potential MICAL-L1 interaction partners, and found a direct interaction between MICAL-L1 and both α-tubulin–β-tubulin heterodimers and γ-tubulin. Our data support the notion that a pool of centriolar γ-tubulin and/or α-tubulin–β-tubulin heterodimers anchor MICAL-L1 to the centriole, where it might recruit EHD1 to promote ciliogenesis.
Tumor-derived extracellular vesicles: molecular parcels that enable regulation of the immune response in cancer
Authors: Sheehan Colin , D'Souza-Schorey Crislyn 
Published: October 2019

ABSTRACT
Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound vesicles released by cells that contain bioactive cargoes including proteins, lipids and nucleic acids. Multiple subpopulations of EVs have now been recognized and these include exosomes and microvesicles. EVs have been thought to facilitate intercellular and distal communication to bring about various processes that enable tumor progression and metastases. Here, we describe the current knowledge of the functional cargo contained within EVs, with a focus on tumor microvesicles, and review the emerging theory of how EVs support immune suppression in cancer.
Expanding our horizons: central pattern generation in the context of complex activity sequences
Authors: Berkowitz Ari 
Published: October 2019

ABSTRACT
Central pattern generators (CPGs) are central nervous system (CNS) networks that can generate coordinated output in the absence of patterned sensory input. For decades, this concept was applied almost exclusively to simple, innate, rhythmic movements with essentially identical cycles that repeat continually (e.g. respiration) or episodically (e.g. locomotion). But many natural movement sequences are not simple rhythms, as they include different elements in a complex order, and some involve learning. The concepts and experimental approaches of CPG research have also been applied to the neural control of complex movement sequences, such as birdsong, though this is not widely appreciated. Experimental approaches to the investigation of CPG networks, both for simple rhythms and for complex activity sequences, have shown that: (1) brief activation of the CPG elicits a long-lasting naturalistic activity sequence; (2) electrical stimulation of CPG elements alters the timing of subsequent cycles or sequence elements; and (3) warming or cooling CPG elements respectively speeds up or slows down the rhythm or sequence rate. The CPG concept has also been applied to the activity rhythms of populations of mammalian cortical neurons. CPG concepts and methods might further be applied to a variety of fixed action patterns typically used in courtship, rivalry, nest building and prey capture. These complex movements could be generated by CPGs within CPGs (‘nested’ CPGs). Stereotypical, non-motor, non-rhythmic neuronal activity sequences may also be generated by CPGs. My goal here is to highlight previous applications of the CPG concept to complex but stereotypical activity sequences and to suggest additional possible applications, which might provoke new hypotheses and experiments.
Bioactive compounds in wines produced in a new area for vitiviniculture in Brazil
Authors: Vilas Boas Ana Carolina , Resende Nassur Rita de Cássia Mirela , De Castro Henrique Paôla , Pereira Giuliano Elias , Lima Luiz Carlos Oliveira de 
Published: October 2019

Wines are known for its high content of bioactive compounds that can be influenced by the region and climate where the grapes are produced. New regions of production are normally developed using techniques and standards for other traditional regions, but is important to characterize the wine profile, which is different according to the terroir, and can be important for future geographic indications. The aim of this study was to evaluate color, antioxidant activity, anthocyanin content and phenolic compounds profile in wines produced in Minas Gerais State, Brazil. Wines were produced in different wineries of the same region using the varieties Syrah, Merlot, Cabernet Sauvignon, Cabernet Franc (red), Chardonnay and Sauvignon Blanc (white) and Syrah (rose), from municipalities of Cordislândia, Boa Esperança and Três Corações, located in the south of Minas Gerais State, Brazil. Wines produced in Minas Gerais State presented contents of t-resveratrol, total phenolics, anthocyanins, flavonols, flavanols and phenolic acids consistent to the contents observed in wines from traditional regions of production. However, the terroir and the grape variety can result in a differentiation of compounds observed in wines. Syrah red wines produced in Boa Esperança stood out with higher amounts of anthocyanins (24.29 mg L-1), phenolic acids (123,19 mg L-1 ) and flavonols (35.55 mg L-1), when compared to wines from the same variety from other municipalities and other evaluated red wines. Sauvignon Blanc wines from Boa Esperança presented higher contents of phenolic acids and total flavonols, when compared to wines of the same variety produced in Cordislândia. Chardonay wines presented higher total phenolics content, when compared to ohther evaluated white wines. Rose wine produced in the South of Minas Gerais presented the phenolic acids content of 36,33 mg L-1 and total flavonols content of 29,7 mg L-1. The highest antioxidant activity using the DPPH method, (% of free radicals scavenging - FRS) was observed for Syrah wines from Três Corações, (75.37%), but not different from Cabernet Sauvignon wines from Cordislândia (72.50%), values that can be correlated with the largest content of phenolics observed in wines as phenolic compounds (3009 mg L-1). No differences were observed in the contents of the antioxidant activity of white wines. This results indicate that the studied wines present the necessary nutritional and beneficial characteristics to compete in the supply of bioactive compounds during consumption, when compared to wines produced in traditional and different regions in Brazil and other countries.
Protective properties of kefir on burn wounds of mice that were infected with S. aureus, P. auroginasa and E. coli
Authors: Cetik Yildiz Songul , Demir Cemil , Cengiz Mustafa , Ayhanci Adnan 
Published: October 2019

Burns and burn wounds are very sensitive to infections and cause a large amount of death worldwide. Although burn wound is sterile at the beginning, because of the risk factors such as prolonged hospital stay, immune suppression and burn affecting large surface area, colonisation with Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli occur. For the burn therapy, one of the most important ways is to control bacterial infections. A probiotic fermented milk product kefir has antioxidant, antimicrobial, antiinflammatory, anticancer and various health promoting features. This study aims to examine possible protective properties of kefir which was used on the burn wounds that were infected with S. aureus, P. auroginasa and E. coli. Swiss albino / Balb-c mice were seperated into four groups: (1) used as control group, (2) second-degree burn model+ burn wounds were infected with P.aeruginosa + S.aureus + E.coli, (3) second-burn wounds were treated with sterile pads dressed with kefir and (4) second-degree burn+burn wounds were infected with P. aeruginosa + S.aureus +E.coli before being treated with sterile pads dressed with kefir. The serum biochemical results verified the histopathological results and our findings showed that kefir is an effective product with cell-protecting properties.
Analgesic, anti-inflammatory and sedative/hypnotic effects of Icaritin, and its effect on chloride influx in mouse brain cortical cells
Authors: Huang Fengyu , Zhang Yaodong , Xu Yinfeng , Xiang Wei , Xie Chaofan 
Published: October 2019

Inflammation and insomnia are medical problems that may severely affect work and health, thereby necessitating strategies for their effective treatment. Icartin (ICT) is a major active monomeric component of icariin . Studies have revealed that ICT possesses several pharmacological properties such anti-inflammatory, anti-tumor, anti-fibrotic, anti-osteoporotic and neuroprotective effects. The present research was carried out to investigate the anti-inflammatory, analgesic and sedative/hypnotic effects of ICT. The results obtained revealed that ICT exerted a good anti-inflammatory effect related to the downregulations of inflammatory cytokines and the inhibition of COX-2 signaling pathway. Moreover, ICT enhanced Cl- influx in mouse cortical cells in a concentration-dependent manner. These data suggest that ICT exerts a hypnotic effect in mice through a mechanism associated with increased Cl- influx in cortical cells.
Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines
Authors: Tahtouh Roula , Wardi Layal , Sarkis Riad , Hachem Ray , Raad Issam , El Zein Nabil , Hilal George 
Published: October 2019

Aerobic glycolysis, known as the "Warburg effect”, is one of several hallmarks of cancer cells. The conversion of phosphoenolpyruvate (PEP) to pyruvate can be down regulated by the re-expression of the embryonic isoform 2 of pyruvate kinase (PKM2). This mechanism allows the accumulation of glycolytic intermediates for the biosynthesis of macromolecules, such as proteins, lipids and nucleic acids. PKM2 is favored by the well-known PI3K/Akt/mTOR proliferative pathway. This pathway is induced by high glucose levels, and the mTOR kinase is the central activator of the Warburg effect. In this study, we investigated the role of glucose restriction (GR) and mTOR inhibition in reversing the Warburg effect in MDA-MB 231 and MCF-7 breast cancer cell lines. PKM2 expression was measured by western blot. Lactate production by cells was determined by a colorimetric assay. The concentration of glucose in the supernatant of cells was measured using the Trinder method. ATP level was evaluated by using a Colorimetric/Fluorometric ATP Assay Kit. Our results showed that MDA-MB 231 cells increased glucose consumption when the glucose concentration was 0 g/L (P <0.01). In MCF-7 cells, glucose deprivation reduced lactate secretion by 80% (P =0.0001) but tripled glucose consumption (P = 0.0041). ATP concentration increased approximately when MCF-7 cells were deprived of glucose (P = 0.02). GSK1059615 does not significantly modulate lactate secretion and glucose uptake in both cell lines. Glucose restriction contribute to the reduction of the Warburg effect through mTOR inhibition and regulation of PKM2 kinases.
Sharp explicit oscillation conditions for difference equations with several delays
Authors: Chudinov Kirill M. 
Published: October 2019

Abstract
We consider explicit sufficient conditions for all solutions of a first-order linear difference equation with several variable delays and non-negative coefficients to be oscillatory.
The conditions have the form of inequalities bounding below the upper and lower limits of the sums of coefficients over a subset of the discrete semiaxis.
Our main results are oscillation tests based on a new principle for composing the estimated sums of coefficients.
We also give some results in the form of examples, including a counterexample to a wrong oscillation test cited in several recent papers.
Torsion elements of order 𝑝2 in the Nottingham group
Authors: Hui Chun Yin , Kishore Krishna 
Published: October 2019

Abstract
Let κ be a characteristic p finite field of q elements and

𝔑
κ

{\mathfrak{N}_{\kappa}}

the Nottingham group over κ.
Lubin associated to every conjugacy class of torsion element of

𝔑
κ

{\mathfrak{N}_{\kappa}}

a type.
We establish an upper bound

B
⁢

(
q
;
l
,
m
)

{B(q;l,m)}

on the number of conjugacy classes of order

p
2

{p^{2}}

torsion elements u of

𝔑
κ

{\mathfrak{N}_{\kappa}}

of type

〈
l
,
m
〉

{\langle l,m\rangle}

.
In the case where

l
<
p

{l<p}

, the bound

B
⁢

(
q
;
l
,
m
)

{B(q;l,m)}

is the exact number of conjugacy classes.
Moreover, we give a criterion on when u and

u
n

{u^{n}}

are conjugate.
Behavior and hippocampal Epac signaling to nicotine CPP in mice
Authors: Liu Jing , Tao Xinrong , Liu Fei , Hu Yuting , Xue Song , Wang Qi , Li Bing , Zhang Rongbo 
Published: October 2019

Abstract
Tobacco use is a major challenge to public health in the United States and across the world. Many studies have demonstrated that adult men and women differ in their responses to tobacco smoking, however neurobiological studies about the effect of smoking on males and females were limited. Exchange protein directly activated by cAMP (Epac) signaling participates in drug addictive behaviors. In this study, we examined the hippocampal Epac signaling in nicotine-induced place conditioning mice. Nicotine at 0.2 mg/kg and 0.4 mg/kg induced a conditioned place preference (CPP) in male and female mice, respectively. After CPP, male mice presented less anxiety-like behavior as demonstrated by an open-field test. The hippocampal Epac2 protein was elevated in both male and female nicotine place conditioning mice. However, Rap1 protein was elevated and CREB phosphorylation was reduced in female nicotine place conditioning mice. Our data provide direct evidence that hippocampal Epac signaling is altered in nicotine-induced CPP mice. Pharmacology manipulation Epac signaling may open a new avenue for the treatment of nicotine abuse and dependence.
Nahal Yarmuth 38: a new and unique Pre-Pottery Neolithic B site in central Israel
Authors: Gopher Avi , Eirikh-Rose Anna , Ashkenazi Hai , Marco Eyal , May Hila , Makoviychuk Yulia , Sapir-Hen Lidar , Galmor Shirad , Schechter Heeli C. , Ackerfeld Dana , Haklay Gil , Zutovski Katia 
Published: October 2019

Abstract
Threat Memory Reminder Under Matrix Metalloproteinase 9 Inhibitor Doxycycline Globally Reduces Subsequent Memory Plasticity
Authors: Bach Dominik R. , Näf Monika , Deutschmann Markus , Tyagarajan Shiva K. , Quednow Boris B. 
Published: October 2019

Associative memory can be rendered malleable by a reminder. Blocking the ensuing reconsolidation process is suggested as a therapeutic target for unwanted aversive memories. Matrix metalloproteinase-9 (MMP-9) is required for structural synapse remodeling involved in memory consolidation. Inhibiting MMP-9 with doxycycline is suggested to attenuate human threat conditioning. Here, we investigated whether MMP-9 inhibition also interferes with threat memory reconsolidation. Male and female human participants (N= 78) learned the association between two visual conditioned stimuli (CS+) and a 50% chance of an unconditioned nociceptive stimulus (US), and between CS−and the absence of US. On day 7, one CS+was reminded without reinforcement 3.5 h after ingesting either 200 mg of doxycycline or placebo. On day 14, retention of CS memory was assessed under extinction by fear-potentiated startle. Contrary to our expectations, we observed a greater CS+/CS−difference in participants who were reminded under doxycycline compared with placebo. Participants who were reminded under placebo showed extinction learning during the retention test, which was not observed in the doxycycline group. There was no difference between the reminded and the nonreminded CS+in either group. In contrast, during relearning after the retention test, the CS+/CS−difference was more pronounced in the placebo group than in the doxycycline group. To summarize, a single dose of doxycycline before threat memory reminder appeared to have no specific impact on reconsolidation, but to globally impair extinction learning, and threat relearning, beyond drug clearance.SIGNIFICANCE STATEMENTMatrix metalloproteinase-9 inhibition appears to attenuate memory consolidation. It could also be a target for blocking reconsolidation. Here, we test this hypothesis in human threat conditioning. We find that doxycycline has no specific impact on a reminded cue, but confers a global reduction in extinction learning and threat learning beyond the clearance of the drug. This may point toward a more long-lasting impact of doxycycline treatment on memory plasticity.
Long acting porcine sequence ACTH in the diagnosis of adrenal insufficiency
Authors: Nair Abilash , Jayakumari Chellamma , George Geena Susan , Jabbar Puthiyaveettil Khadar , Das Darvin V , Jessy S J , Aneesh T S 
Published: October 2019

Objectives
Injectable tetracosactide hexa-acetate, ACTH 1-24 (Synacthen), is not marketed in many countries including India, whereas Injectable long acting porcine sequence, ACTH 1-39 (Acton Prolongatum®) is easily available and much cheaper. This study aimed to find the diagnostic accuracy of ACTH stimulation test using i.m. Acton Prolongatum® (acton prolongatum stimulation test, APST) in comparison with Synacthen (short synacthen test, SST) for the diagnosis of glucocorticoid insufficiency.

Methods
Subjects with a suspicion of adrenal insufficiency based on clinical features underwent a SST with 250 µg Synacthen followed by APST using 30 units of Acton Prolongatum®. Serum cortisol levels were measured at 60 and 120 min following injection of Acton Prolongatum®. Stimulated peak cortisol of less than 18 µg/dL on SST was considered as adrenal insufficiency.

Results
Forty seven patients with mean age of 36.7 ± 14.4 years were enrolled for the study. Based on SST, twenty (n = 20) persons were classified as having adrenal insufficiency, whereas twenty-seven (n = 27) were found to be normal. Area under the curve of APST (at 120 min) was 0.986 when compared to SST, thus proving its high accuracy. A serum cortisol cut off value of 19.5 µg/dL at 120-min following stimulation with Acton Prolongatum® showed a sensitivity of 100% and specificity of 88%.

Conclusion
ACTH stimulation test using Acton Prolongatum® is an economical and accurate alternative to the short Synacthen test.