bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer
Authors: Junttila Anna , Helminen Olli , Väyrynen Juha P. , Ahtiainen Maarit , Kenessey Istvan , Jalkanen Sirpa , Mecklin Jukka-Pekka , Kellokumpu Ilmo , Kuopio Teijo , Böhm Jan , Mrena Johanna 
Published: September 2020

Abstract
Background
Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1).

Methods
After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival.

Results
The 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26–0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis.

Conclusions
High ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.
SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury
Authors: Wang Zhi-Meng , Liu Cong , Wang Ying-Ying , Deng Yu-Sen , He Xuan-Cheng , Du Hong-Zhen , Liu Chang-Mei , Teng Zhao-Qian 
Published: September 2020

AbstractTraumatic brain injury is a global leading cause of disability and death, which puts patients at high risk for developing dementia. Early intervention is believed as the key to minimize the development of brain damages that could aggravate the symptoms. Here, we report that the serine protease inhibitor SerpinA3N is upregulated in hippocampal neurons in the early stage of hippocampal stab injury (HSI), while its deficiency causes a greater degree of neuronal apoptosis and severer impairments of spatial learning and memory in mice after HSI. We further show that MMP2 is a key substrate of SerpinA3N, and MMP2 specific inhibitor (ARP100) can protect against neuronal apoptosis and cognitive dysfunction in mice after HSI. These findings demonstrate a critical role for SerpinA3N in neuroprotection, suggesting that SerpinA3N and MMP2 inhibitors might be a novel therapeutic agents for neurotrauma.
Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins
Authors: Lindenboim Liora , Grozki Dan , Amsalem-Zafran Ayelet R. , Peña-Blanco Aida , Gundersen Gregg G. , Borner Christoph , Hodzic Didier , Garcia-Sáez Ana J. , Worman Howard J. , Stein Reuven 
Published: September 2020

AbstractThe canonical function of Bcl-2 family proteins is to regulate mitochondrial membrane integrity. In response to apoptotic signals the multi-domain pro-apoptotic proteins Bax and Bak are activated and perforate the mitochondrial outer membrane by a mechanism which is inhibited by their interaction with pro-survival members of the family. However, other studies have shown that Bax and Bak may have additional, non-canonical functions, which include stress-induced nuclear envelope rupture and discharge of nuclear proteins into the cytosol. We show here that the apoptotic stimuli cisplatin and staurosporine induce a Bax/Bak-dependent degradation and subcellular redistribution of nesprin-1 and nesprin-2 but not nesprin-3, of the linker of nucleoskeleton and cytoskeleton (LINC) complex. The degradation and redistribution were caspase-independent and did not occur in Bax/Bak double knockout (DKO) mouse embryo fibroblasts (MEFs). Re-expression of Bax in Bax/Bak DKO MEFs restored stress-induced redistribution of nesprin-2 by a mechanism which requires Bax membrane localization and integrity of the α helices 5/6, and the Bcl-2 homology 3 (BH3) domain. We found that nesprin-2 interacts with Bax in close proximity to perinuclear mitochondria in mouse and human cells. This interaction requires the mitochondrial targeting and N-terminal region but not the BH3 domain of Bax. Our results identify nesprin-2 as a Bax binding partner and also a new function of Bax in impairing the integrity of the LINC complex.
Nonsense variants of STAG2 result in distinct congenital anomalies
Authors: Aoi Hiromi , Lei Ming , Mizuguchi Takeshi , Nishioka Nobuko , Goto Tomohide , Miyama Sahoko , Suzuki Toshifumi , Iwama Kazuhiro , Uchiyama Yuri , Mitsuhashi Satomi , Itakura Atsuo , Takeda Satoru , Matsumoto Naomichi 
Published: September 2020

AbstractHerein, we report two female cases with novel nonsense mutations of STAG2 at Xq25, encoding stromal antigen 2, a component of the cohesion complex. Exome analysis identified c.3097 C>T, p.(Arg1033*) in Case 1 (a fetus with multiple congenital anomalies) and c.2229 G>A, p.(Trp743*) in Case 2 (a 7-year-old girl with white matter hypoplasia and cleft palate). X inactivation was highly skewed in both cases.
An integrated personal and population-based Egyptian genome reference
Authors: Wohlers Inken , Künstner Axel , Munz Matthias , Olbrich Michael , Fähnrich Anke , Calonga-Solís Verónica , Ma Caixia , Hirose Misa , El-Mosallamy Shaaban , Salama Mohamed , Busch Hauke , Ibrahim Saleh 
Published: September 2020

AbstractA small number of de novo assembled human genomes have been reported to date, and few have been complemented with population-based genetic variation, which is particularly important for North Africa, a region underrepresented in current genome-wide references. Here, we combine long- and short-read whole-genome sequencing data with recent assembly approaches into a de novo assembly of an Egyptian genome. The assembly demonstrates well-balanced quality metrics and is complemented with variant phasing via linked reads into haploblocks, which we associate with gene expression changes in blood. To construct an Egyptian genome reference, we identify genome-wide genetic variation within a cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genome references. Thus, the Egyptian genome reference will be a valuable resource for precision medicine.
DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice
Authors: Li Xiaozhou , Pan Jian , Li Huiling , Li Guangdi , Liu Xiangfeng , Liu Bohao , He Zhibiao , Peng Zhengyu , Zhang Hongliang , Li Yijian , Xiang Xudong , Chai Xiangping , Yuan Yunchang , Zheng Peilin , Liu Feng , Zhang Dongshan 
Published: September 2020

AbstractRecent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.
Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
Authors: Nabet Behnam , Ferguson Fleur M. , Seong Bo Kyung A. , Kuljanin Miljan , Leggett Alan L. , Mohardt Mikaela L. , Robichaud Amanda , Conway Amy S. , Buckley Dennis L. , Mancias Joseph D. , Bradner James E. , Stegmaier Kimberly , Gray Nathanael S. 
Published: September 2020

AbstractChemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAGV-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12F36V-tagged proteins. dTAGV-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.
Multiplex flow magnetic tweezers reveal rare enzymatic events with single molecule precision
Authors: Agarwal Rohit , Duderstadt Karl E. 
Published: September 2020

AbstractThe application of forces and torques on the single molecule level has transformed our understanding of the dynamic properties of biomolecules, but rare intermediates have remained difficult to characterize due to limited throughput. Here, we describe a method that provides a 100-fold improvement in the throughput of force spectroscopy measurements with topological control, which enables routine imaging of 50,000 single molecules and a 100 million reaction cycles in parallel. This improvement enables detection of rare events in the life cycle of the cell. As a demonstration, we characterize the supercoiling dynamics and drug-induced DNA break intermediates of topoisomerases. To rapidly quantify distinct classes of dynamic behaviors and rare events, we developed a software platform with an automated feature classification pipeline. The method and software can be readily adapted for studies of a broad range of complex, multistep enzymatic pathways in which rare intermediates have escaped classification due to limited throughput.
Controlling in-gap end states by linking nonmagnetic atoms and artificially-constructed spin chains on superconductors
Authors: Schneider Lucas , Brinker Sascha , Steinbrecher Manuel , Hermenau Jan , Posske Thore , dos Santos Dias Manuel , Lounis Samir , Wiesendanger Roland , Wiebe Jens 
Published: September 2020

AbstractChains of magnetic atoms with either strong spin-orbit coupling or spiral magnetic order which are proximity-coupled to superconducting substrates can host topologically non-trivial Majorana bound states. The experimental signature of these states consists of spectral weight at the Fermi energy which is spatially localized near the ends of the chain. However, topologically trivial Yu-Shiba-Rusinov in-gap states localized near the ends of the chain can lead to similar spectra. Here, we explore a protocol to disentangle these contributions by artificially augmenting a candidate Majorana spin chain with orbitally-compatible nonmagnetic atoms. Combining scanning tunneling spectroscopy with ab-initio and tight-binding calculations, we realize a sharp spatial transition between the proximity-coupled spiral magnetic order and the non-magnetic superconducting wire termination, with persistent zero-energy spectral weight localized at either end of the magnetic spiral. Our findings open a new path towards the control of the spatial position of in-gap end states, trivial or Majorana, via different chain terminations, and the realization of designer Majorana chain networks for demonstrating topological quantum computation.
Electron hydrodynamics in anisotropic materials
Authors: Varnavides Georgios , Jermyn Adam S. , Anikeeva Polina , Felser Claudia , Narang Prineha 
Published: September 2020

AbstractRotational invariance strongly constrains the viscosity tensor of classical fluids. When this symmetry is broken in anisotropic materials a wide array of novel phenomena become possible. We explore electron fluid behaviors arising from the most general viscosity tensors in two and three dimensions, constrained only thermodynamics and crystal symmetries. We find nontrivial behaviors in both two- and three-dimensional materials, including imprints of the crystal symmetry on the large-scale flow pattern. Breaking time-reversal symmetry introduces a non-dissipative Hall component to the viscosity tensor, and while this vanishes for 3D isotropic systems we show it need not for anisotropic materials. Further, for such systems we find that the electronic fluid stress can couple to the vorticity without breaking time-reversal symmetry. Our work demonstrates the anomalous landscape for electron hydrodynamics in systems beyond graphene, and presents experimental geometries to quantify the effects of electronic viscosity.
Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation
Authors: Chan Jason Yongsheng , Toh Ming Ren , Chong Siao Ting , Ishak Nur Diana Binte , Kolinjivadi Arun Mouli , Chan Sock Hoai , Lee Elizabeth , Boot Arnoud , Shao-Tzu Li , Chew Min-Hoe , Ngeow Joanne 
Published: September 2020

AbstractGitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole-exome sequencing confirmed germline compound heterozygous mutations of c.179C > T and c.1326C > G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A > G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome.
Variational fast forwarding for quantum simulation beyond the coherence time
Authors: Cîrstoiu Cristina , Holmes Zoë , Iosue Joseph , Cincio Lukasz , Coles Patrick J. , Sornborger Andrew 
Published: September 2020

AbstractTrotterization-based, iterative approaches to quantum simulation (QS) are restricted to simulation times less than the coherence time of the quantum computer (QC), which limits their utility in the near term. Here, we present a hybrid quantum-classical algorithm, called variational fast forwarding (VFF), for decreasing the quantum circuit depth of QSs. VFF seeks an approximate diagonalization of a short-time simulation to enable longer-time simulations using a constant number of gates. Our error analysis provides two results: (1) the simulation error of VFF scales at worst linearly in the fast-forwarded simulation time, and (2) our cost function’s operational meaning as an upper bound on average-case simulation error provides a natural termination condition for VFF. We implement VFF for the Hubbard, Ising, and Heisenberg models on a simulator. In addition, we implement VFF on Rigetti’s QC to demonstrate simulation beyond the coherence time. Finally, we show how to estimate energy eigenvalues using VFF.
Technological approaches to streamline vaccination schedules, progressing towards single-dose vaccines
Authors: Lofano Giuseppe , Mallett Corey P. , Bertholet Sylvie , O’Hagan Derek T. 
Published: September 2020

AbstractVaccines represent the most successful medical intervention in history, with billions of lives saved. Although multiple doses of the same vaccine are typically required to reach an adequate level of protection, it would be advantageous to develop vaccines that induce protective immunity with fewer doses, ideally just one. Single-dose vaccines would be ideal to maximize vaccination coverage, help stakeholders to greatly reduce the costs associated with vaccination, and improve patient convenience. Here we describe past attempts to develop potent single dose vaccines and explore the reasons they failed. Then, we review key immunological mechanisms of the vaccine-specific immune responses, and how innovative technologies and approaches are guiding the preclinical and clinical development of potent single-dose vaccines. By modulating the spatio-temporal delivery of the vaccine components, by providing the appropriate stimuli to the innate immunity, and by designing better antigens, the new technologies and approaches leverage our current knowledge of the immune system and may synergize to enable the rational design of next-generation vaccination strategies. This review provides a rational perspective on the possible development of future single-dose vaccines.
Light intensity regulates flower visitation in Neotropical nocturnal bees
Authors: Liporoni Rodolfo , Cordeiro Guaraci Duran , Prado Paulo Inácio , Schlindwein Clemens , Warrant Eric James , Alves-dos-Santos Isabel 
Published: September 2020

AbstractThe foraging activity of diurnal bees often relies on flower availability, light intensity and temperature. We do not know how nocturnal bees, which fly at night and twilight, cope with these factors, especially as light levels vary considerably from night to day and from night to night due to moon phase and cloud cover. Given that bee apposition compound eyes function at their limits in dim light, we expect a strong dependence of foraging activity on light intensity in nocturnal bees. Besides being limited by minimum light levels to forage, nocturnal bees should also avoid foraging at brighter intensities, which bring increased competition with other bees. We investigated how five factors (light intensity, flower availability, temperature, humidity, and wind) affect flower visitation by Neotropical nocturnal bees in cambuci (Campomanesia phaea, Myrtaceae). We counted visits per minute over 30 nights in 33 cambuci trees. Light intensity was the main variable explaining flower visitation of nocturnal bees, which peaked at intermediate light levels occurring 25 min before sunrise. The minimum light intensity threshold to visit flowers was 0.00024 cd/m2. Our results highlight the dependence of these nocturnal insects on adequate light levels to explore resources.
Wearing compression garments differently affects monopodal postural balance in high-level athletes
Authors: Baige Kévin , Noé Frédéric , Paillard Thierry 
Published: September 2020

AbstractThis study investigated the acute effects of compression garments (CG) on balance control in elite athletes. 15 male professional handball players were recruited. They had to stand as motionless as possible in a monopedal stance on a force plate with the eyes closed and on a wobble board with the eyes open, while wearing CG or not. Centre of foot pressure mean velocity and surface area were calculated. Statistics were first calculated with the data from the whole sample. A hierarchical cluster analysis was also performed in order to categorize the participants’ behaviours into subgroups with similar characteristics. The whole group analysis showed that there were no significant effects attributed to CG. The clustering analysis identified two distinct and homogeneous subgroups of participants. Only athletes with the best balance abilities at baseline could benefit from CG wearing to improve their balance control. These athletes, who swayed less and were more sensitive to somatosensory manipulation due to CG wearing, seem to control balance by adopting a support-dependent preferred sensorimotor tactic. Our findings suggest that amongst high-level athletes, the ability to benefit from CG wearing to improve balance control seems to depend on participants’ intrinsic balance skills and/or preferred sensorimotor tactics.
Increased extreme precipitation challenges nitrogen load management to the Gulf of Mexico
Authors: Lu Chaoqun , Zhang Jien , Tian Hanqin , Crumpton William G. , Helmers Mathew J. , Cai Wei-Jun , Hopkinson Charles S. , Lohrenz Steven E. 
Published: September 2020

AbstractAlthough the hypoxia formation in the Gulf of Mexico is predominantly driven by increased riverine nitrogen (N) export from the Mississippi-Atchafalaya River basin, it remains unclear how hydroclimate extremes affect downstream N loads. Using a process-based hydro-ecological model, we reveal that over 60% of the land area of the Basin has experienced increasing extreme precipitation since 2000, and this area yields over 80% of N leaching loss across the region. Despite occurring in ~9 days year−1, extreme precipitation events contribute ~1/3 of annual precipitation, and ~1/3 of total N yield on average. Both USGS monitoring and our modeling estimates demonstrate an approximately 30% higher annual N load in the years with extreme river flow than the long-term median. Our model suggests that N load could be reduced by up to 16% merely by modifying fertilizer application timing but increasing contribution of extreme precipitation is shown to diminish this potential.
Coincident locations of rupture nucleation during the 2019 Le Teil earthquake, France and maximum stress change from local cement quarrying
Authors: De Novellis Vincenzo , Convertito Vincenzo , Valkaniotis Sotiris , Casu Francesco , Lanari Riccardo , Monterroso Tobar Mario Fernando , Pino Nicola Alessandro 
Published: September 2020

AbstractEarthquake occurrence is ultimately controlled by tectonic stress load. Nevertheless, the 2019, Mw = 4.9, Le Teil earthquake in southern France occurred in an area where strain rates are relatively low. Human operations can produce increases in stress load and degradation of strength on nearby active faults, which raises the potential for failure. Here we present estimates of the rupture geometry and source directivity of the Le Teil earthquake based on differential synthetic aperture radar interferometry and seismic data. We find that almost two centuries of mass removal at a nearby cement quarry likely provided the required stress change to hasten the occurrence of the Le Teil earthquake by more than 18,000 years. We suggest that further mass removal in the area might lead to even stronger earthquakes, by activating deeper sectors of the same fault plane.