bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly sensitive pre-column derivatization method for fluorescence detection of tobramycin using 2-naphthalenesulfonyl chloride as a derivatizing agent
Authors: Mabrouk Mokhtar M. , Soliman Suzan M. , El-Agizy Heba M. , Mansour Fotouh R. 
Published: December 2022

AbstractA new, simple, rapid and highly sensitive high performance liquid chromatographic method was developed for the determination of tobramycin (TOB) in ophthalmic solutions. The developed method was based on derivatizing this non-chromophoric drug with 2-naphthalenesulfonyl chloride (NSCl), at 80 ºC for 40 min, and measuring the fluorescent product. Elution from the column was isocratic, using a mobile phase consisting of acetonitrile –1% phosphoric acid in water, (90:10, v/v), with a flow rate of 2 mL/min, at 40 ºC. Determination was developed using fluorescence detection at an excitation wavelength of 300 nm and an emission wavelength of 380 nm. The chromatographic separation was achieved on Knauer-Eurospher 100–5 C18 silica column (300 mm × 4 mm i.d, 5 μm). Different approaches were used to optimize the conditions of the method and to reach the maximum yield. The linear regression data for the calibration plot showed acceptable correlation coefficient (r2 = 0.9998) at the concentration ranges of 2.5–1000 ng/mL for TOB. The method was successfully validated according to the guidelines of the International Council on Harmonization, and was found suitable for pharmaceutical applications. The method was new, simple and precise for analysis of TOB and applicable for routine analysis in quality control laboratories.
Periodic Dynamics of a Class of Non-autonomous Contact Hamiltonian Systems
Authors: Li Zhanyong , Tang Yaozong , Sha Bier A. Mina , Ye Jianguo 
Published: December 2022

AbstractIn this paper, we investigate the existence, number and stability of periodic orbits for the following contact Hamiltonian system $$H(p,q,s,t)=\frac{p^{2}}{2m}+G(t,q,m)-mdq+cs(c>0)$$

H

(
p
,
q
,
s
,
t
)

=

p
2

2
m

+
G

(
t
,
q
,
m
)

-
m
d
q
+
c
s

(
c
>
0
)

. At the same time, unbounded conditions of each solution are also given. The contact Hamiltonian system actually represents a kind of physical phenomenon with non-conservation of energy, but the contact Hamiltonian system studied in this paper represents a one-dimensional damped oscillator system with constant variable sign damping coefficient under certain conditions. Therefore, it is of great physical significance to study the periodic dynamic properties of such system.
Fast Three‐Dimensional Search Algorithm to Improve the Carrier Tracking Performance During the Entry, Descent, and Landing (EDL) Phase of Mars Probes
Authors: Deng Tao , Ma Maoli , Liu Qinghui 
Published: December 2022

AbstractCarrier tracking for highly dynamic and extremely weak signals is challenging, including during the entry, descent, and landing phase of Mars rovers and the soft landing of lunar probes. In this study, a novel frequency detector is designed based on the frequency maximum likelihood estimator, and a frequency‐locked loop algorithm is constructed. The frequency‐locked loop is suitable for tracking Doppler shifts with large first and second derivatives. Compared with the Jet Propulsion Laboratory frequency maximum likelihood estimator, the computation time is significantly reduced. The simulation results illustrate the effectiveness of the proposed algorithm. This method provides a good method for Doppler frequency measurement in deep space exploration, especially when tracking highly dynamic and extremely weak signals.
Carbonates in the Critical Zone
Authors: Covington M. D. , Martin J. B. , Toran L. E. , Macalady J. L. , Sekhon N. , Sullivan P. L. , García Á. A. , Heffernan J. B. , Graham W. D. 
Published: December 2022

AbstractEarth's Critical Zone (CZ), the near‐surface layer where rock is weathered and landscapes co‐evolve with life, is profoundly influenced by the type of underlying bedrock. Previous studies employing the CZ framework have focused primarily on landscapes dominated by silicate rocks. However, carbonate rocks crop out on approximately 15% of Earth's ice‐free continental surface and provide important water resources and ecosystem services to ∼1.2 billion people. Unlike silicates, carbonate minerals weather congruently and have high solubilities and rapid dissolution kinetics, enabling the development of large, interconnected pore spaces and preferential flow paths that restructure the CZ. Here we review the state of knowledge of the carbonate CZ, exploring parameters that produce contrasts in the CZ in different carbonate settings and identifying important open questions about carbonate CZ processes. We introduce the concept of a carbonate‐silicate CZ spectrum and examine whether current conceptual models of the CZ, such as the conveyor model, can be applied to carbonate landscapes. We argue that, to advance beyond site‐specific understanding and develop a more general conceptual framework for the role of carbonates in the CZ, we need integrative studies spanning both the carbonate‐silicate spectrum and a range of carbonate settings.
2021 February Texas Ice Storm Induced Spring GPP Reduction Compensated by the Higher Precipitation
Authors: Yang Linqing , Liu Meng 
Published: December 2022

AbstractClimate extremes are more frequent and affect the carbon cycle. On 10–20 February, an exceptional winter storm in Texas brought severe ecological and economic effects. However, its impacts on vegetation activities and the carbon cycle are unclear. This study evaluated the early 2021 ice storm effects on spring phenology and the carbon cycle. The results showed that the ice storm led to a significant later vegetation spring phenology and a reduction of 42.32 Tg C in gross primary production (GPP) and a reduction of 34. 47 Tg C net ecosystem production (NEP) in spring. In the 2021 spring, Texas became a carbon source from the carbon sink. More precipitation in late spring and summer precipitation recharged the rootzone soil moisture, which enhanced summer vegetation GPP and NEP and compensated for the effects of the ice storm on spring carbon uptake. The summer GPP enhancement offset all the spring GPP reduction, and thus GPP was increased by 4.97% during 2021. 91.47% of the spring NEP reduction was compensated by summer NEP enhancement due to higher root zone soil moisture. Due to the NEP enhancement during autumn, NEP did not decrease as well and increased by 10.88% during 2021. This observation‐based research highlights the seasonal compensation effects on the interactions between extreme climate events and the biosphere.
A Subjective Bayesian Framework for Synthesizing Deep Uncertainties in Climate Risk Management
Authors: Doss‐Gollin James , Keller Klaus 
Published: December 2022

AbstractProjections of nonstationary climate risks can vary considerably from one source to another, posing considerable communication and decision‐analytical challenges. One such challenge is how to present trade‐offs under deep uncertainty in a salient and interpretable manner. Some common approaches include analyzing a small subset of projections or treating all considered projections as equally likely. These approaches can underestimate risks, hide deep uncertainties, and are mostly silent on which assumptions drive decision‐relevant outcomes. Here we introduce and demonstrate a transparent Bayesian framework for synthesizing deep uncertainties to inform climate risk management. The first step of this workflow is to generate an ensemble of simulations representing possible futures and analyze them through standard exploratory modeling techniques. Next, a small set of probability distributions representing subjective beliefs about the likelihood of possible futures is used to weight the scenarios. Finally, these weights are used to compute and characterize trade‐offs, conduct robustness checks, and reveal implicit assumptions. We demonstrate the framework through a didactic case study analyzing how high to elevate a house to manage coastal flood risks.
Projection of Hourly Extreme Precipitation Using the WRF Model Over Eastern China
Authors: Tang Jianping , Lu Yun , Wang Shuguang , Guo Ziyue , Lu Yutong , Fang Juan 
Published: December 2022

AbstractThe Weather Research and Forecasting (WRF) model was applied to simulate the current and future climates over eastern China at a convection‐permitting resolution (∼4 km). A continuous 10‐year (1998–2007) simulation was performed for the historical climate, and three pseudo‐global warming (PGW) experiments driven by climate perturbations during 2070–2099 were conducted under the RCP2.6, RCP4.5, and RCP8.5 scenarios. After validation against reanalysis and observational data, the historical simulation was found capable of reasonably reproducing the characteristics of mean precipitation, extreme hourly precipitation, and large‐scale circulation. The PGW experiments projected an increase in precipitation intensity over most regions, especially North China under the RCP8.5 scenario (up to 30%). However, the precipitation frequency was projected to decrease, especially over the Yangtze River Basin in summer. A wetting (drying) trend was observed over North China (South China) in summer (winter), due to the increase (decrease) in precipitation intensity (frequency). The intensity and frequency of extreme events were projected to increase over most areas of eastern China, and the increase was the most dramatic under the RCP8.5 scenario, indicating a greater flood risk under stronger global warming. The relationship between extreme precipitation and temperature (EP–T) displayed a hook‐shape structure in both the present and future climates. The extreme precipitation intensity increased with temperature at a super Clausius–Clapeyron (C–C) scaling rate (>7%/K) until reaching a peak at temperatures of around 25–29°C, and then decreased at higher temperatures. The decreases were mainly attributed to moisture limitation at high temperatures. In the future, the EP–T relationship is expected to change mostly following the C–C law, with greater precipitation peaks under scenarios with higher carbon emissions, indicating that warmer climates contribute to further enhancement of extreme precipitation.
Mixed heavy metal stress induces global iron starvation response
Authors: Goff Jennifer L , Chen Yan , Thorgersen Michael P , Hoang Linh T , Poole Farris L , Szink Elizabeth G , Siuzdak Gary , Petzold Christopher J , Adams Michael W W 
Published: December 2022

Abstract
Multiple heavy metal contamination is an increasingly common global problem. Heavy metals have the potential to disrupt microbially mediated biogeochemical cycling. However, systems-level studies on the effects of combinations of heavy metals on bacteria are lacking. For this study, we focused on the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) subsurface which is contaminated with several heavy metals and high concentrations of nitrate. Using a native Bacillus cereus isolate that represents a dominant species at this site, we assessed the combined impact of eight metal contaminants, all at site-relevant concentrations, on cell processes through an integrated multi-omics approach that included discovery proteomics, targeted metabolomics, and targeted gene-expression profiling. The combination of eight metals impacted cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Exposure to the metal mixture elicited a global iron starvation response not observed during individual metal exposures. This disruption of iron homeostasis resulted in decreased activity of the iron-cofactor-containing nitrate and nitrite reductases, both of which are important in biological nitrate removal at the site. We propose that the combinatorial effects of simultaneous exposure to multiple heavy metals is an underappreciated yet significant form of cell stress in the environment with the potential to disrupt global nutrient cycles and to impede bioremediation efforts at mixed waste sites. Our work underscores the need to shift from single- to multi-metal studies for assessing and predicting the impacts of complex contaminants on microbial systems.
Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre
Authors: Scheiter Alexander , Hierl Frederik , Lüke Florian , Keil Felix , Heudobler Daniel , Einhell Sabine , Klier-Richter Margit , Konstandin Nikola P. , Weber Florian , Scheiter Andrea , Kandulski Arne , Schlosser Sophie , Cosma Lidia-Sabina , Tews Hauke , Weiss Andreas R. R. , Grube Matthias , Bumes Elisabeth , Hau Peter , Proescholdt Martin , Steger Felix , Troeger Anja , Haferkamp Sebastian , Reibenspies Lucas E. , Schnabel Marco J. , Schulz Christian , Drexler Konstantin , Hatzipanagiotou Maria E. , Seitz Stephan , Klinkhammer-Schalke Monika , Unberath Philipp , Calvisi Diego F. , Pukrop Tobias , Dietmaier Wolfgang , Evert Matthias , Utpatel Kirsten 
Published: December 2022

Abstract
Background
Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021.

Methods and results
In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278).

Conclusion
The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly.
Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis
Authors: Guo Jiawei , Song Zihao , Yu Jie , Li Chengyi , Jin Chenchen , Duan Wei , Liu Xiu , Liu Yingying , Huang Shuai , Tuo Yonghua , Pei Fei , Jian Zhengyang , Zhou Pengyu , Zheng Shaoyi , Zou Zhaowei , Zhang Feng , Gong Quan , Liang Sijia 
Published: December 2022

AbstractIschemia/reperfusion (I/R)-induced liver injury with severe cell death is a major complication of liver transplantation. Transmembrane member 16A (TMEM16A), a component of hepatocyte Ca2+-activated chloride channel, has been implicated in a variety of liver diseases. However, its role in hepatic I/R injury remains unknown. Here, mice with hepatocyte-specific TMEM16A knockout or overexpression were generated to examine the effect of TMEM16A on hepatic I/R injury. TMEM16A expression increased in liver samples from patients and mice with I/R injury, which was correlated with liver damage progression. Hepatocyte-specific TMEM16A knockout alleviated I/R-induced liver damage in mice, ameliorating inflammation and ferroptotic cell death. However, mice with hepatic TMEM16A overexpression showed the opposite phenotype. In addition, TMEM16A ablation decreased inflammatory responses and ferroptosis in hepatocytes upon hypoxia/reoxygenation insult in vitro, whereas TMEM16A overexpression promoted the opposite effects. The ameliorating effects of TMEM16A knockout on hepatocyte inflammation and cell death were abolished by chemically induced ferroptosis, whereas chemical inhibition of ferroptosis reversed the potentiated role of TMEM16A in hepatocyte injury. Mechanistically, TMEM16A interacted with glutathione peroxidase 4 (GPX4) to induce its ubiquitination and degradation, thereby enhancing ferroptosis. Disruption of TMEM16A–GPX4 interaction abrogated the effects of TMEM16A on GPX4 ubiquitination, ferroptosis, and hepatic I/R injury. Our results demonstrate that TMEM16A exacerbates hepatic I/R injury by promoting GPX4-dependent ferroptosis. TMEM16A–GPX4 interaction and GPX4 ubiquitination are therefore indispensable for TMEM16A-regulated hepatic I/R injury, suggesting that blockades of TMEM16A–GPX4 interaction or TMEM16A inhibition in hepatocytes may represent promising therapeutic strategies for acute liver injury.
Transglutaminase type 2-dependent crosslinking of IRF3 in dying melanoma cells
Authors: Occhigrossi Luca , D’Eletto Manuela , Vecchio Alessio , Piacentini Mauro , Rossin Federica 
Published: December 2022

AbstractcGAS/STING axis is the major executor of cytosolic dsDNA sensing that leads to the production of type I interferon (IFNI) not only upon bacterial infection, but also in cancer cells, upon DNA damage. In fact, DNA damage caused by ionizing radiations and/or topoisomerase inhibitors leads to a release of free DNA into the cytosol, which activates the cGAS/STING pathway and the induction of IFNI expression. Doxorubicin-induced apoptotic cancer cells release damage-associated molecular patterns (DAMPs), including IFNI, which are able to stimulate the immune system. Our results indicate that Transglutaminase type 2 (TG2) is directly involved in the formation of a covalent cross-linked IRF3 (Interferon regulatory factor 3) dimers, thereby limiting the production of IFNI. Indeed, we demonstrated that upon doxorubicin treatment TG2 translocates into the nucleus of apoptotic melanoma cells interacting with IRF3 dimers. Interestingly, we show that both the knockdown of the enzyme as well as the inhibition of its transamidating activity lead to a decrease in the dimerization of IRF3 correlated with an increase in the IFNI mRNA levels. Taken together, these data demonstrate that TG2 negatively regulates the IRF3 pathway in human melanoma cells suggesting a so far unknown TG2-dependent mechanism by which cancer cells reduce the IFNI production after DNA damage to limit the immune system response.
Real world outcomes of photodynamic therapy for chronic central serous chorioretinopathy
Authors: Khandhadia Samir , Thulasidharan Suresh , Hoang Nguyen Thuy Vy , Ibrahim Sameh Alkhalili , Ouyang Yanling , Lotery Andrew 
Published: December 2022

Abstract
Objectives
We describe the real-world outcomes of photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR) in a single centre over nine years.

Methods
We carried out a retrospective analysis of patients with chronic CSCR who received half dose PDT in a single centre between 2011 and 2019. Visual acuity (VA) and retinal thickness (RT) was recorded between baseline visit and first recorded review visit.

Results
We included 125 eyes of 113 patients in this study. Mean age at treatment was 55.0 ± 12.1 years, with a higher male predominance (83 men, 30 women). Mean baseline VA was 0.40 ± 0.31 logMAR with a mean visual outcome gain post-PDT of 0.05 logMAR (p = 0.005). Mean baseline RT was 390 ± 82 microns with a mean reduction of RT post-PDT of 66 microns (p < 0.001). 17.6% of eyes were treated for recurrent CSCR.

Conclusion
We found overall a mean improvement in VA and structural outcomes after PDT. In the absence of randomised clinical trials this study supports the use of half dose PDT for treatment of chronic CSCR.
Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease
Authors: Lekka Evangelia , Kokanovic Aleksandra , Mosole Simone , Civenni Gianluca , Schmidli Sandro , Laski Artur , Ghidini Alice , Iyer Pavithra , Berk Christian , Behera Alok , Catapano Carlo V. , Hall Jonathan 
Published: December 2022

AbstractLin28 RNA-binding proteins are stem-cell factors that play key roles in development. Lin28 suppresses the biogenesis of let-7 microRNAs and regulates mRNA translation. Notably, let-7 inhibits Lin28, establishing a double-negative feedback loop. The Lin28/let-7 axis resides at the interface of metabolic reprogramming and oncogenesis and is therefore a potential target for several diseases. In this study, we use compound-C1632, a drug-like Lin28 inhibitor, and show that the Lin28/let-7 axis regulates the balance between ketogenesis and lipogenesis in liver cells. Hence, Lin28 inhibition activates synthesis and secretion of ketone bodies whilst suppressing lipogenesis. This occurs at least partly via let-7-mediated inhibition of nuclear receptor co-repressor 1, which releases ketogenesis gene expression mediated by peroxisome proliferator-activated receptor-alpha. In this way, small-molecule Lin28 inhibition protects against lipid accumulation in multiple cellular and male mouse models of hepatic steatosis. Overall, this study highlights Lin28 inhibitors as candidates for the treatment of hepatic disorders of abnormal lipid deposition.
Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex
Authors: Wilson Madison N. , Thunemann Martin , Liu Xin , Lu Yichen , Puppo Francesca , Adams Jason W. , Kim Jeong-Hoon , Ramezani Mehrdad , Pizzo Donald P. , Djurovic Srdjan , Andreassen Ole A. , Mansour Abed AlFatah , Gage Fred H. , Muotri Alysson R. , Devor Anna , Kuzum Duygu 
Published: December 2022

AbstractHuman cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in multi-unit activity (MUA) and gamma power and phase locking of stimulus-evoked MUA with slow oscillations indicate functional integration between the organoid and the host brain. Immunostaining confirms the presence of human-mouse synapses. Implantation of transparent microelectrodes with organoids serves as a versatile in vivo platform for comprehensive evaluation of the development, maturation, and functional integration of human neuronal networks within the mouse brain.
Single planar photonic chip with tailored angular transmission for multiple-order analog spatial differentiator
Authors: Liu Yang , Huang Mingchuan , Chen Qiankun , Zhang Douguo 
Published: December 2022

AbstractAnalog spatial differentiation is used to realize edge-based enhancement, which plays an important role in data compression, microscopy, and computer vision applications. Here, a planar chip made from dielectric multilayers is proposed to operate as both first- and second-order spatial differentiator without any need to change the structural parameters. Third- and fourth-order differentiations that have never been realized before, are also experimentally demonstrated with this chip. A theoretical analysis is proposed to explain the experimental results, which furtherly reveals that more differentiations can be achieved. Taking advantages of its differentiation capability, when this chip is incorporated into conventional imaging systems as a substrate, it enhances the edges of features in optical amplitude and phase images, thus expanding the functions of standard microscopes. This planar chip offers the advantages of a thin form factor and a multifunctional wave-based analogue computing ability, which will bring opportunities in optical imaging and computing.