bluuebunny/crossref_metadata_2025_split huggingface dataset:
The AMPK-Related Kinases SIK1 and SIK3 Mediate Key Tumor-Suppressive Effects of LKB1 in NSCLC
Authors: Hollstein Pablo E. , Eichner Lillian J. , Brun Sonja N. , Kamireddy Anwesh , Svensson Robert U. , Vera Liliana I. , Ross Debbie S. , Rymoff T.J. , Hutchins Amanda , Galvez Hector M. , Williams April E. , Shokhirev Maxim N. , Screaton Robert A. , Berdeaux Rebecca , Shaw Reuben J. 
Published: July 2019

Abstract

Mutations in the LKB1 (also known as STK11) tumor suppressor are the third most frequent genetic alteration in non–small cell lung cancer (NSCLC). LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates 14 AMPK family kinases (“AMPKRs”). The function of many of the AMPKRs remains obscure, and which are most critical to the tumor-suppressive function of LKB1 remains unknown. Here, we combine CRISPR and genetic analysis of the AMPKR family in NSCLC cell lines and mouse models, revealing a surprising critical role for the SIK subfamily. Conditional genetic loss of Sik1 revealed increased tumor growth in mouse models of Kras-dependent lung cancer, which was further enhanced by loss of the related kinase Sik3. As most known substrates of the SIKs control transcription, gene-expression analysis was performed, revealing upregulation of AP1 and IL6 signaling in common between LKB1- and SIK1/3-deficient tumors. The SIK substrate CRTC2 was required for this effect, as well as for proliferation benefits from SIK loss.

Significance:
The tumor suppressor LKB1/STK11 encodes a serine/threonine kinase frequently inactivated in NSCLC. LKB1 activates 14 downstream kinases in the AMPK family controlling growth and metabolism, although which kinases are critical for LKB1 tumor-suppressor function has remained an enigma. Here we unexpectedly found that two understudied kinases, SIK1 and SIK3, are critical targets in lung cancer.
This article is highlighted in the In This Issue feature, p. 1469
Distribution and habitats of Paphiopedilum Pfitzer (Orchidaceae) known to occur in Bhutan
Authors: Gurung Dhan Bahadur , Gyeltshen Nima , Tobgay Kezang , Dalström Stig , Wangdi Jangchuk , Ghalley Bhakta Bahadur , Chaida Lekey , Phuntsho Phuntsho , Gyeltshen Ngawang , Dawa Kelzang , Wangchuk Tandin , Pradhan Rebecca , Hoijer Thomas Axel Ivan , Gyeltshen Choki 
Published: July 2019

Paphiopedilum fairrieanum, P. spicerianum, and P. venustum (Orchidaceae: Cypripedioideae) are reported to occur in Bhutan, of which the former is known to be Critically Endangered and the latter two are Endangered. Based on numerous field trips conducted over the last decade, populations of P. fairrieanum and P. venustum were located in Bhutan. No individual of P. spicerianum, however, was found despite many search attempts. Its occurrence in Bhutan may have been originally erroneous. Based on the accessibility of the habitats, six 10m × 10m quadrats were defined to enumerate the plant species found in the Paphiopedilum habitats. Vegetation analyses and cluster dendrograms of the plant species composition indicated the presence of three forest types with distinct species compositions. Paphiopedilum fairrieanum was found growing mainly as a lithophyte on seasonally dry limestone cliffs or on limestone outcrops with a comparatively open forest canopy. These populations were mostly located on southwest- or northwest-facing slopes with soil pH ranging from 7.1 to 7.8. Paphiopedilum venustum, in contrast, was a ground-dwelling species restricted to relatively dense forests with soil pH ranging from 7.1 to 7.5.
Status of water birds in Haripura-Baur Reservoir, western Terai-Arc landscape, Uttarakhand, India
Authors: Ahmed Tanveer , Bargali Harendra Singh , Bisht Deepa , Mehra Gajendra Singh , Khan Afifullah 
Published: July 2019

We surveyed water birds in Haripura-Baur Reservoir using total count method between 2013 and 2015. A total of 65 species were recorded representing eight orders and 14 families. Numerically Anatidae was the dominant family followed by Ardeidae and Scolopacidae. Common Coot Fulica atra, Red-crested Pochard Netta rufina, Common Pochard Aythya ferina, Gadwall Anas strepera, and Tufted Pochard Aythya fuligula were dominant species in the reservoir. The Shannon diversity of water birds was more or less consistent over the years and ranged between 2.56 (2013–14) and 2.23 (2015–16). The reservoir supports water birds having declining population trends globally (41% of species), including three Vulnerable (Asian Woollyneck Ciconia episcopus, Lesser Adjutant Leptoptilos javanicus, and Sarus Crane Grus antigone and four Near Threatened species (Oriental Darter Anhinga melanogaster, Painted Stork Mycteria leucocephala, Black-necked Stork Ephippiorhynchus asiaticus, and River Lapwing Vanellus duvaucelii). Bird species belong to four feeding guilds with the domination of the carnivore group. The current information is expected to serve as preliminary database of water birds for further research and monitoring.
Pollination ecology of Brownlowia tersa (Malvaceae), a Near Threatened non-viviparous true mangrove shrub
Authors: Raju Aluri Jacob Solomon 
Published: July 2019

Brownlowia tersa is a low-ground semi-evergreen shrub species. The phenological events occur sequentially—leaf fall, leaf flushing, flowering and fruiting from April to November. It is hermaphroditic, protandrous, self-compatible, facultative xenogamous, and melittophilous involving worker honey bees, small male and female carpenter bees and male and female cuckoo bees. Of these, worker honey bees and female carpenter bees forage for both pollen and nectar while male carpenter bees and both sexes of cuckoo bees forage exclusively for nectar. Cuckoo bees are very important for cross-pollination because they are swift fliers and visit many flowers from different plants in the shortest time. Carpenter bees and honey bees are largely important for self-pollination as they are not fast fliers and tend to spend more time at each flower for forage collection. The flowers have a specialized pollination mechanism to resort to autonomous autogamy if not pollinated but this mode of pollination is subject to the availability of pollen in its own anthers. Fruit is a 1-seeded follicle produced from a single carpel of the flower. It is indehiscent and floats in tidal water when detached from the plant. When settled in muddy substratum, it breaks open to expose the seed which germinates and produces a new plant in quick succession. The study reports that the plant is highly threatened due to different human economic activities taking place in the area and hence immediate in situ conservation measures are required for its protection and propagation.
Comparison Between Contact Force Monitoring and Unipolar Signal Modification as a Guide for Catheter Ablation of Atrial Fibrillation
Authors: Ejima Koichiro , Kato Ken , Okada Ayako , Wakisaka Osamu , Kimura Ryusuke , Ishizawa Makoto , Imai Taku , Toyama Yuko , Shoda Morio , Hagiwara Nobuhisa 
Published: July 2019

Background:
Both contact force monitoring (CFM) and unipolar signal modification (USM) are guides for ablation, which improve the efficacy of pulmonary vein isolation of atrial fibrillation. We sought to compare the outcomes of atrial fibrillation ablation guided by CFM or USM.

Methods:
A total of 136 patients with paroxysmal atrial fibrillation underwent a circumferential pulmonary vein isolation using CF sensing ablation catheters and were randomly assigned to undergo catheter ablation guided by either CFM (CFM-guided group: n=70) or USM (USM-guided group: n=66). In the USM-guided group, each radiofrequency application lasted until the development of completely positive unipolar electrograms. In the CFM-guided group, a CF of 20 g (range, 10–30 g) and minimum force-time integral of 400 g were the targets for each radiofrequency application. The primary end point was freedom from any atrial tachyarrhythmia recurrence without antiarrhythmic drugs at 12-months of follow-up.

Results:

The cumulative freedom from recurrences at 12-months was 85% in the USM-guided group and 70% in the CFM-guided group (
P
=0.031). The incidence of time-dependent and ATP-provoked early electrical reconnections between the left atrium and PVs, procedural time, fluoroscopic time, and average force-time integral, did not significantly differ between the 2 groups. The radiofrequency time for the pulmonary vein isolation was shorter in the USM-guided group than CFM-guided group but was not statistically significant (
P
=0.077).

Conclusions:
USM was superior to CFM as an end point for radiofrequency energy deliveries during the pulmonary vein isolation in patients with paroxysmal atrial fibrillation in terms of the 12-month recurrence-free rate.

Clinical Trial Registration:

URL:
https://www.umin.ac.jp/ctr/index.htm
. Unique identifier: UMIN000021127.
Acute Aspirin Plus Cilostazol Dual Therapy for Noncardioembolic Stroke Patients Within 48 Hours of Symptom Onset
Authors: Aoki Junya , Iguchi Yasuyuki , Urabe Takao , Yamagami Hiroshi , Todo Kenichi , Fujimoto Shigeru , Idomari Koji , Kaneko Nobuyuki , Iwanaga Takeshi , Terasaki Tadashi , Tanaka Ryota , Yamamoto Nobuaki , Tsujino Akira , Nomura Koichi , Abe Koji , Uno Masaaki , Okada Yasushi , Matsuoka Hideki , Yamagata Sen , Yamamoto Yasumasa , Yonehara Toshiro , Inoue Takeshi , Yagita Yoshiki , Kimura Kazumi , Mitsumura Hidetaka , Ueno Yuji , Watanabe Masao , Sakamoto Yuki , Arakawa Shuji , Nagakane Yoshinari , Ishibashi Ryota , Terasawa Yuka , Fujita Koji , Kashihara Kenichi , Mitomi Mutsumi , Nakano Tatsu , Shibazaki Kensaku , Takao Yoshiki , Tateishi Yohei , Goto Seiji , Manabe Yasuhiro , Kanda Naoaki , Ohashi Toshihiko , Itabashi Ryo , Furui Eisuke , Takizawa Takaaki , Minami Masahiro , Noguchi Yasuhiro , Kondo Yoshiyuki , Izumi Tesseki , Sakima Hirokuni , Ueno Yasushi , Kasuya Junji , Oba Naoki 
Published: July 2019

Background
The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset.

Methods and Results

The
ADS
(Acute Aspirin Plus Cilostazol Dual Therapy for Non‐Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator‐initiated, prospective, multicenter (34 hospitals in Japan), randomized, open‐label, and aspirin‐controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61–77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1–4) in both groups (
P
=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (
P
=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (
P
=0.624).

Conclusions
Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short‐term neurological worsening.

Clinical Trial Registration

URL
: umin.ac.jp/ctr/index/htm. Unique identifier:
UMIN
000004950.
Soluble Neprilysin in the General Population: Clinical Determinants and Its Relationship to Cardiovascular Disease
Authors: Reddy Yogesh N. V. , Iyer Seethalakshmi R. , Scott Christopher G. , Rodeheffer Richard J. , Bailey Kent , Jenkins Gregory , Batzler Anthony , Redfield Margaret M. , Burnett John C. , Pereira Naveen L. 
Published: July 2019

Background
Neprilysin is a metalloprotease involved in proteolysis of numerous peptides, including natriuretic peptides, and is of prognostic and therapeutic importance in heart failure with reduced ejection fraction. No studies have investigated circulating neprilysin in the community, its clinical correlates, or its relationship to cardiovascular disease in the general population.

Methods and Results

Plasma neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a commercially available sandwich
ELISA
assay. Clinical and echocardiographic correlates and subsequent outcomes were determined. Soluble neprilysin is non‐normally distributed in the community (median: 3.9 ng/mL; interquartile range: 1.0–43.0 ng/mL). There was no relationship between plasma neprilysin and age (Spearman correlation: −0.04,
P
=0.16); body mass index (Spearman correlation: −0.04,
P
=0.16); glomerular filtration rate (Spearman correlation: −0.007,
P
=0.8); or A‐, B‐, or C‐type natriuretic peptides (Spearman correlation: 0.03,
P
=0.22; −0.001,
P
=0.96; 0.01,
P
=0.67, respectively). Among tertiles of neprilysin, the lowest tertile group had the highest prevalence of smokers (
P
<0.001), hypertension (
P
=0.04), dyslipidemia (
P
=0.03), and diastolic dysfunction (
P
=0.02). Soluble neprilysin was not prospectively associated with death or heart failure over a median of 10.7 years.

Conclusions
In a large community‐based cohort, for the first time, we described the distribution of circulating neprilysin in the general community. We observed that neprilysin does not correlate with natriuretic peptide levels and is not independently associated with adverse outcomes. The novel associations observed between low soluble neprilysin levels and an adverse cardiometabolic and smoking profile requires further investigation.
Penetration of Fire into Iron
Authors: Biriukov Dmitry 
Published: July 2019

Abstract
I consider the ways whereby the Stoic natural philosophical paradigm of total blending, through the example of penetration of fire into iron, was naturalized by the Early Christian and Byzantine theologians who intended to display the penetration of the divine into the created and the conjunction of the created with the divine, with the condition that the created does not dissolve in divine but remains within its own nature being penetrated by the properties of deity.
Studies into the Folk Hagiography of the Russian North: Judas Koneschelsky
Authors: Moroz Andrey B. , Pigin Alexander V. 
Published: July 2019

Abstract
The article deals with the problems of studying folk hagiography, a complex of peasants’ written and oral texts, which contain information about saints or revered non-canonized devotees and express the very specifics of the popular understanding of holiness. The first half of the article discusses the phenomenon of folk hagiography, defines the range of folklore genres, reflecting folk beliefs about saints, and investigates the mechanisms of interaction between the written and oral traditions. The second half analyzes texts and religious practices related to the folk worship of the non-canonized elder Judas Koneschelsky (Archangelsk North). There are following sources for the study of this cult: judicial documents of the turn of the 19th and the 20th centuries, a peasant’s diary of the turn of the 19th and the 20th centuries, local priests’ notes from that time, and field data, collected by folklorists at the beginning of the 21th century. On the basis of these sources, the authors, considering a specific case, make an attempt to study the mechanisms of functioning of folk hagiography. A large time span between the early and late data records and various texts about Judas make it possible to trace evolution of this cult.
ʿAbdīšōʿ of Gāzartā, Patriarch of the Chaldean Church as a Scribe
Authors: Pritula Anton 
Published: July 2019

Abstract
ʿAbdīšōʿ of Gāzartā, the second patriarch (1555-1570) of the East Syriac Uniate (Chaldean) Church, is known as a founder of its literary tradition, and an author of numerous liturgical and non-liturgical poems. He was also active as a scribe, of whose production several manuscripts survive that were never studied before. The present paper discusses them, in particular the historical and autobiographical information that is found in the scribe’s colophons and notes. This information is of a large importance for the history of the Christian communities in early Ottoman time.
Systematic Comparison of Convection-Allowing Models during the 2017 NOAA HWT Spring Forecasting Experiment
Authors: Potvin Corey K. , Carley Jacob R. , Clark Adam J. , Wicker Louis J. , Skinner Patrick S. , Reinhart Anthony E. , Gallo Burkely T. , Kain John S. , Romine Glen S. , Aligo Eric A. , Brewster Keith A. , Dowell David C. , Harris Lucas M. , Jirak Israel L. , Kong Fanyou , Supinie Timothy A. , Thomas Kevin W. , Wang Xuguang , Wang Yongming , Xue Ming 
Published: July 2019

Abstract
The 2016–18 NOAA Hazardous Weather Testbed (HWT) Spring Forecasting Experiments (SFE) featured the Community Leveraged Unified Ensemble (CLUE), a coordinated convection-allowing model (CAM) ensemble framework designed to provide empirical guidance for development of operational CAM systems. The 2017 CLUE included 81 members that all used 3-km horizontal grid spacing over the CONUS, enabling direct comparison of forecasts generated using different dynamical cores, physics schemes, and initialization procedures. This study uses forecasts from several of the 2017 CLUE members and one operational model to evaluate and compare CAM representation and next-day prediction of thunderstorms. The analysis utilizes existing techniques and novel, object-based techniques that distill important information about modeled and observed storms from many cases. The National Severe Storms Laboratory Multi-Radar Multi-Sensor product suite is used to verify model forecasts and climatologies of observed variables. Unobserved model fields are also examined to further illuminate important intermodel differences in storms and near-storm environments. No single model performed better than the others in all respects. However, there were many systematic intermodel and intercore differences in specific forecast metrics and model fields. Some of these differences can be confidently attributed to particular differences in model design. Model intercomparison studies similar to the one presented here are important to better understand the impacts of model and ensemble configurations on storm forecasts and to help optimize future operational CAM systems.
Is there a role for antibodies targeting muscarinic acetylcholine receptors in the pathogenesis of schizophrenia?
Authors: Ryan Alexander E , Mowry Bryan J , Kesby James P , Scott James G , Greer Judith M 
Published: July 2019

Objective: Muscarinic receptor dysfunction has been suggested to play an important role in the pathophysiology of schizophrenia. Recently, it has also become clear that immune reactivity directed against neurotransmitter receptors may play a pathogenic role in some cases of schizophrenia. The aim of this review is to summarize the case for muscarinic receptor dysfunction in schizophrenia and the evidence supporting the hypothesis that this dysfunction is related to the development of muscarinic receptor–targeting antibodies. Method: The article reviews studies of muscarinic receptors and the presence and potential role(s) of anti-muscarinic acetylcholine receptor antibodies in people with schizophrenia. Results: There is accumulating evidence that altered or deficient muscarinic signalling underlies some of the key clinical features of schizophrenia. Although the number of studies investigating anti-muscarinic acetylcholine receptor antibodies in schizophrenia is relatively small, they consistently demonstrate that such antibodies are present in a proportion of patients. This evidence suggests that these antibodies could have pathogenic effects or exist as a biomarker to an unknown pathophysiological process in schizophrenia. Conclusion: The presence of elevated levels of anti-muscarinic acetylcholine receptor antibodies may identify a subgroup of people with schizophrenia, potentially informing aetiopathogenesis, clinical presentation and treatment. To date, all studies have examined antibodies in participants with chronic schizophrenia, who have likely received antipsychotic medication for many years. As these medications modulate immune functions and regulate receptor densities, it is recommended that future studies screen for the presence of anti-muscarinic antibodies in people experiencing their first episode of psychosis.
Spuriously raised serum amylase in a five-year-old girl: a note of caution in paediatric blood sampling
Authors: Cull Frith , Cullis Paul S , Bradnock Timothy J , Sabharwal Atul J 
Published: July 2019

Introduction Capillary (finger prick) blood sampling is commonplace in paediatric practice but this method is prone to produce spurious laboratory results. Case presentation A five-year-old girl presented with abdominal pain, epigastric tenderness, tachycardia and reduced oxygen saturation. A venous blood sample haemolysed, and serum amylase on a finger prick sample was reported as 2831 units/L. The working diagnosis was acute pancreatitis and respiratory tract infection. A repeat amylase 9 h later was within the normal range. The patient was known to bite her fingers and the possibility of salivary contamination was considered. Serum isoenzyme analysis confirmed presence of high salivary amylase levels with no pancreatic amylase detected. A viral respiratory tract infection and buried gastrostomy bumper were eventually thought to account for the patient’s presentation. Conclusion Increased awareness of the potential for salivary contamination of serum amylase in finger prick samples may prevent misdiagnoses of pancreatitis.
Tracking snacking in real time: Time to look at individualised patterns of behaviour
Authors: Allan Julia , McMinn David , Powell Daniel 
Published: July 2019

Background: Identifying when and where people overeat is important for intervention design, yet little is known about how unhealthy behaviours unfold in real life. Aim: To track the activities, social contexts and locations that co-occur with unhealthy snacking. Methods: Sixty-four adults (49F, mean age = 38.6 years) used electronic diaries to record snacking, location, social context and current activity every waking hour over 7 days. The proportion of snacking episodes that co-occurred with each location/activity/context was calculated by group and individual. Results: Over the group, snacking was most frequent whilst socialising (19.9% of hours spent socialising) or using the TV/computer (19.7%), when with friends (16.7%) and when at home (15.3%). All intra-class correlation statistics for cued behaviour were low, indicating the importance of within-person variability. There were marked individual differences between people in what constituted a ‘typical’ context for snacking. Conclusions: People show substantial differences in the contexts in which they snack. Tailoring interventions to these individual patterns of behaviour may improve intervention efficacy.