bluuebunny/crossref_metadata_2025 huggingface dataset:
The value of single-molecule real-time technology in the diagnosis of rare thalassemia variants and analysis of phenotype–genotype correlation
Authors: Luo Shiqiang , Chen Xingyuan , Zeng Dingyuan , Tang Ning , Yuan Dejian , Zhong Qingyan , Mao Aiping , Xu Ruofan , Yan Tizhen
Published: October 2021

To compare single-molecule real-time technology (SMRT) and conventional genetic diagnostic technology of rare types of thalassemia mutations, and to analyze the molecular characteristics and phenotypes of rare thalassemia gene variants, we used 434 cases with positive hematology screening as the cohort, then used SMRT technology and conventional gene diagnosis technology [(Gap-PCR, multiple ligation probe amplification technology (MLPA), PCR-reverse dot blot (RDB)] for thalassemia gene screening. Among the 434 enrolled cases, conventional technology identified 318 patients with variants (73.27%) and 116 patients without variants (26.73%), SMRT identified 361 patients with variants (83.18%), and 73 patients without variants (16.82%). The positive detection rate of SMRT was 9.91% higher than conventional technology. Combination of the two methods identified 485 positive alleles among 49 types of variant. The genotypes of 354 cases were concordant between the two methods, while 80 cases were discordant. Among the 80 cases, 76 cases had variants only identified in SMRT method, 3 cases had variants only identified in conventional method, and 1 false positive result by the traditional PCR detection technology. Except the three variants in HS40 and HBG1-HBG2 loci, which was beyond the design of SMRT method in this study, all the other discordant variants identified by SMRT were validated by further Sanger sequencing or MLPA. The hematological phenotypic parameters of 80 discordant cases were also analyzed. SMRT technology increased the positive detection rate of thalassemia genes, and detected rare thalassemia cases with variable phenotypes, which had great significance for clinical thalassemia gene screening.
Lnc-PFAR facilitates autophagy and exacerbates pancreatic fibrosis by reducing pre-miR-141 maturation in chronic pancreatitis
Authors: Zhang Tao , Zhang Guangquan , Yang Wenbo , Chen Hongze , Hu Jisheng , Zhao Zhongjie , Cheng Chundong , Li Guanqun , Xie Yu , Li Yilong , Kong Rui , Wang Yongwei , Wang Gang , Chen Hua , Bai Xue-Wei , Pan Shangha , Sun Bei , Li Le
Published: October 2021

Chronic pancreatitis (CP) is described as progressive inflammatory fibrosis of pancreas, accompanied with irreversible impaired endocrine and exocrine insufficiency. Pancreatic stellate cells (PSCs) are widely distributed in the stroma of the pancreas and PSCs activation has been shown as one of the leading causes for pancreatic fibrosis. Our previous study has revealed that autophagy is dramatically activated in CP tissues, which facilitates PSCs activation and pancreatic fibrosis. Long non-coding RNAs (LncRNAs) have been recognized as crucial regulators for fibrosis-related diseases. LncRNAs interact with RNA binding protein or construct competitive endogenous RNA (ceRNA) hypothesis which elicited the fibrotic processes. Until now, the effects of lncRNAs on PSCs activation and pancreatic fibrosis have not been clearly explored. In this study, a novel lncRNA named Lnc-PFAR was found highly expressed in mouse and human CP tissues. Our data revealed that Lnc-PFAR facilitates PSCs activation and pancreatic fibrosis via RB1CC1-induced autophagy. Lnc-PFAR reduces miR-141 expression by suppressing pre-miR-141 maturation, which eventually upregulates the RB1CC1 and fibrosis-related indicators expression. Meanwhile, Lnc-PFAR enhanced PSCs activation and pancreatic fibrosis through trigging autophagy. Our study interrogates a novel lncRNA-induced mechanism in promoting the development of pancreatic fibrosis, and Lnc-PFAR is suggested to be a prospective therapeutic target in clinical scenarios.
MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α
Authors: Tang Jianing , Luo Yongwen , Long Guo , Zhou Ledu
Published: October 2021

Breast cancer is the most commonly diagnosed malignant tumor among females. Estrogen receptor α (ERα) is initially expressed in 70% of breast cancers and is a well-known target of endocrine therapy for ERα-positive breast cancer. In the present study, we identified MINDY1, a member belongs to the motif interacting with Ubcontaining novel DUB family (MINDY), as a potential deubiquitylase of ERα in breast cancer. There was a positive correlation between ERα and MINDY1 protein levels in human breast cancer tissues. We found that high expression of MINDY1 was associated with poor prognosis. MINDY1 interacted with ERα, thereby mediating the deubiquitination of ERα and increased its stability in a deubiquitylation activity-dependent manner. MINDY1 depletion significantly decreased the ERα protein level and ERα signaling activity in breast cancer cells. Specifically, MINDY1 associated with the N-terminal of ERα via its catalytic domain, thus inhibiting K48-specific poly-ubiquitination process on ERα protein. In addition, MINDY1 depletion led to growth inhibition and cell cycle arrest of ERα-positive breast cancer cells. Finally, overexpression of ERα could rescue the MINDY1 depletion-induced growth inhibition both in vitro and in vivo, suggesting that MINDY1 promotes breast carcinogenesis through increasing ERα stability. Overall, our study proposed a novel post-translational mechanism of ERα in supporting breast cancer progression. Targeting the MINDY1 may prove to be a promising strategy for patients with ERα-positive breast cancer.
ZBTB38 suppresses prostate cancer cell proliferation and migration via directly promoting DKK1 expression
Authors: Ding Guanxiong , Lu Wei , Zhang Qing , Li Kai , Zhou Huihui , Wang Fei , Zhao Chunchun , Fan Caibin , Wang Jianqing
Published: October 2021

Prostate cancer is still one of the most common malignancies in men all around the world. The mechanism of how prostate cancer initiates and develops is still not clear. Here in this study, we show that tumor suppressorZBTB38could suppress the migration and proliferation of prostate cancer cells. We find lowerZBTB38expression in prostate cancer tissues, which also strongly predicts a poorer prognosis of prostate cancer.ZBTB38bindsDKK1(DickkopfWNTsignaling pathway inhibitor 1) locus and promotesDKK1expression in prostate cancer cell lines. Consistently, reduction ofDKK1expression significantly restoresZBTB38-mediated suppression of migration and proliferation of prostate cancer cell lines. Mechanistically, we find thatZBTB38primarily binds the promoters of target genes, and differentially regulates the expression of 1818 genes. We also identifyPRKDC(protein kinase, DNA-activated, catalytic subunit) as aZBTB38-interacting protein that could repress the function ofZBTB38in suppressing migration and proliferation of prostate cancer cells. Taken together, our results indicate thatZBTB38could repress cell migration and proliferation in prostate cancer via promotingDKK1expression, and also provide evidence supportingZBTB38as a potential prognosis marker for prostate cancer.
Impact of intracellular innate immune receptors on immunometabolism
Authors: Chou Wei-Chun , Rampanelli Elena , Li Xin , Ting Jenny P.-Y.
Published: October 2021

Immunometabolism, which is the metabolic reprogramming of anaerobic glycolysis, oxidative phosphorylation, and metabolite synthesis upon immune cell activation, has gained importance as a regulator of the homeostasis, activation, proliferation, and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity. Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection, inflammation, cancer, autoimmune diseases, and metabolic disorders. The crosstalk between the PI3K–AKT–mTOR and LKB1–AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism. The bidirectional interaction between immune cells and metabolism is a topic of intense study. Toll-like receptors (TLRs), cytokine receptors, and T and B cell receptors have been shown to activate multiple downstream metabolic pathways. However, how intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood. The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors, such as nucleotide-binding and leucine-rich repeat-containing receptors (NLRs, or NOD-like receptors), absent in melanoma 2 (AIM2)-like receptors (ALRs), and the cyclic dinucleotide receptor stimulator of interferon genes (STING). We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways. Whenever appropriate, this review will provide a brief contextual connection to pathogenic infections, autoimmune diseases, cancers, metabolic disorders, and/or inflammatory bowel diseases.
Lessons learned from unsolicited findings in clinical exome sequencing of 16,482 individuals
Authors: van der Schoot Vyne , Haer-Wigman Lonneke , Feenstra Ilse , Tammer Femke , Oerlemans Anke J. M. , van Koolwijk Martine P. A. , van Agt Frans , Arens Yvonne H. J. M. , Brunner Han G. , Vissers Lisenka E. L. M. , Yntema Helger G.
Published: October 2021

Unsolicited findings (UFs) are uncovered unintentionally and predispose to a disease unrelated to the clinical question. The frequency and nature of UFs uncovered in clinical practice remain largely unexplored. We here evaluated UFs identified during a 5-year period in which 16,482 index patients received clinical whole-exome sequencing (WES). UFs were identified in 0.58% (95/16,482) of index patients, indicating that the overall frequency of UFs in clinical WES is low. Fewer UFs were identified using restricted disease-gene panels (0.03%) than when using whole-exome/Mendeliome analysis (1.03%). The UF was disclosed to 86 of 95 individuals, for reasons of medical actionability. Only 61% of these UFs reside in a gene that is listed on the “ACMG59”-list, representing a list of 59 genes for which the American College of Medical Genetics recommends UF disclosure. The remaining 39% were grouped into four categories: disorders similar to “ACMG59”-listed disorders (25%); disorders for which disease manifestation could be influenced (7%); UFs providing reproductive options (2%); and UFs with pharmacogenetic implications (5%). Hence, our experience shows that UFs predisposing to medically actionable disorders affect a broader range of genes than listed on the “ACMG59”, advocating that a pre-defined gene list is too restrictive, and that UFs may require ad hoc evaluation of medical actionability. While both the identification and disclosure of UFs depend on local policy, our lessons learned provide general essential insight into the nature and odds of UFs in clinical exome sequencing.
Elimination of oxygen sensitivity in α-titanium by substitutional alloying with Al
Authors: Chong Yan , Zhang Ruopeng , Hooshmand Mohammad S. , Zhao Shiteng , Chrzan Daryl C. , Asta Mark , Morris J. W. , Minor Andrew M.
Published: October 2021

Individually, increasing the concentration of either oxygen or aluminum has a deleterious effect on the ductility of titanium alloys. For example, extremely small amounts of interstitial oxygen can severely deteriorate the tensile ductility of titanium, particularly at cryogenic temperatures. Likewise, substitutional aluminum will decrease the ductility of titanium at low-oxygen concentrations. Here, we demonstrate that, counter-intuitively, significant additions of both Al and O substantially improves both strength and ductility, with a 6-fold increase in ductility for a Ti-6Al-0.3 O alloy as compared to a Ti-0.3 O alloy. The Al and O solutes act together to increase and sustain a high strain-hardening rate by modifying the planar slip that predominates into a delocalized, three-dimensional dislocation pattern. The mechanism can be attributed to decreasing stacking fault energy by Al, modification of the “shuffle” mechanism of oxygen-dislocation interaction by the repulsive Al-O interaction in Ti, and micro-segregation of Al and O by the same cause.
Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo
Authors: Jann Johann-Christoph , Mossner Maximilian , Riabov Vladimir , Altrock Eva , Schmitt Nanni , Flach Johanna , Xu Qingyu , Nowak Verena , Obländer Julia , Palme Iris , Weimer Nadine , Streuer Alexander , Jawhar Ahmed , Darwich Ali , Jawhar Mohammad , Metzgeroth Georgia , Nolte Florian , Hofmann Wolf-Karsten , Nowak Daniel
Published: October 2021

The bone marrow (BM) stroma in myeloid neoplasms is altered and it is hypothesized that this cell compartment may also harbor clonal somatically acquired mutations. By exome sequencing of in vitro expanded mesenchymal stromal cells (MSCs) from n = 98 patients with myelodysplastic syndrome (MDS) and n = 28 healthy controls we show that these cells accumulate recurrent mutations in genes such as ZFX (n = 8/98), RANK (n = 5/98), and others. MDS derived MSCs display higher mutational burdens, increased replicative stress, senescence, inflammatory gene expression, and distinct mutational signatures as compared to healthy MSCs. However, validation experiments in serial culture passages, chronological BM aspirations and backtracking of high confidence mutations by re-sequencing primary sorted MDS MSCs indicate that the discovered mutations are secondary to in vitro expansion but not present in primary BM. Thus, we here report that there is no evidence for clonal mutations in the BM stroma of MDS patients.
Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave
Authors: Davis Jessica T. , Chinazzi Matteo , Perra Nicola , Mu Kunpeng , Pastore y Piontti Ana , Ajelli Marco , Dean Natalie E. , Gioannini Corrado , Litvinova Maria , Merler Stefano , Rossi Luca , Sun Kaiyuan , Xiong Xinyue , Longini Ira M. , Halloran M. Elizabeth , Viboud Cécile , Vespignani Alessandro
Published: October 2021

Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally1–7. Although a limited number of SARS-CoV-2 introductions were reported in January and February 2020 (refs.8,9), the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening10, left many countries vulnerable to unmitigated, cryptic transmission. Here we use a global metapopulation epidemic model to provide a mechanistic understanding of the early dispersal of infections and the temporal windows of the introduction of SARS-CoV-2 and onset of local transmission in Europe and the USA. We find that community transmission of SARS-CoV-2 was likely to have been present in several areas of Europe and the USA by January 2020, and estimate that by early March, only 1 to 4 in 100 SARS-CoV-2 infections were detected by surveillance systems. The modelling results highlight international travel as the key driver of the introduction of SARS-CoV-2, with possible introductions and transmission events as early as December 2019 to January 2020. We find a heterogeneous geographic distribution of cumulative infection attack rates by 4 July 2020, ranging from 0.78% to 15.2% across US states and 0.19% to 13.2% in European countries. Our approach complements phylogenetic analyses and other surveillance approaches and provides insights that can be used to design innovative, model-driven surveillance systems that guide enhanced testing and response strategies.
HIV-2 Vpx neutralizes host restriction factor SAMHD1 to promote viral pathogenesis
Authors: Mohamed Ahlam , Bakir Talal , Al-Hawel Huda , Al-Sharif Ibtihaj , Bakheet Razan , Kouser Lubna , Murugaiah Valarmathy , Al-Mozaini Maha
Published: October 2021

SAMHD1, a human host factor found in myeloid cells which restricts HIV-1 replication. It depletes the dNTPs pool for viral cDNA syntheses, thus preventing the viral replication in the cells. The viral accessory protein, Vpx, exists only in SIVmac/HIV-2 particles. Vpx in SIVmac can induce proteosomal degradation of SAMHD1, which then leads to a decrease in the cytoplasmic dNTP pool. The protein–protein interaction between Vpx and SAMHD1 and its consequences are still unclear. Methods: In this study, we cloned, for the first time, Vpx gene from a HIV-2 infected patient and found up to 30% sequence variation compared to known HIV-2 strains. We then analyzed the role of SAMHD1 protein expression in transfected THP-1 and U937 cells by transfecting with the Vpx gene derived from SIVmac, HIV-2 from the NIH sample as well as HIV-2 from a Saudi patient. We found that Vpx gene expression led to reduced levels of intracellular SAMHD1. When the supernatants of the transfected cell lines were examined for secreted cytokines, chemokines and growth factors, Vpx expression seemed to be suppressive of pro-inflammatory response, and skewed the immune response towards an anti-inflammatory response. These results suggest that Vpx can act at two levels: clearance of intracellular restriction factor and suppression of cytokine storm: both aimed at long-term latency and host–pathogen stand-off, suggesting that Vpx is likely to be a potential therapeutic target.
Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS
Authors: Goon Danial Efendy , Ab-Rahim Sharaniza , Mohd Sakri Amir Hakimi , Mazlan Musalmah , Tan Jen Kit , Abdul Aziz Mardiana , Mohd Noor Norizal , Ibrahim Effendi , Sheikh Abdul Kadir Siti Hamimah
Published: October 2021

Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.
Optimal virtual water flows for improved food security in water-scarce countries
Authors: Maroufpoor Saman , Bozorg-Haddad Omid , Maroufpoor Eisa , Gerbens-Leenes P. Winnie , Loáiciga Hugo A. , Savic Dragan , Singh Vijay P.
Published: October 2021

The worsening water scarcity has imposed a significant stress on food production in many parts of the world. This stress becomes more critical when countries seek self-sufficiency. A literature review shows that food self-sufficiency has not been assessed as the main factor in determining the optimal cultivation patterns. However, food self-sufficiency is one of the main policies of these countries and requires the most attention and concentration. Previous works have focused on the virtual water trade to meet regional food demand and to calculate trade flows. The potential of the trade network can be exploited to improve the cropping pattern to ensure food and water security. To this end, and based on the research gaps mentioned, this study develops a method to link intra-country trade networks, food security, and total water footprints (WFs) to improve food security. The method is applied in Iran, a water-scarce country. The study shows that 781 × 106 m3 of water could be saved by creating a trade network. Results of the balanced trade network are input to a multi-objective optimization model to improve cropping patterns based on the objectives of achieving food security and preventing water crises. The method provides 400 management scenarios to improve cropping patterns considering 51 main crops in Iran. Results show a range of improvements in food security (19–45%) and a decrease in WFs (2–3%). The selected scenario for Iran would reduce the blue water footprint by 1207 × 106 m3, and reduce the cropland area by 19 × 103 ha. This methodology allows decision makers to develop policies that achieve food security under limited water resources in arid and semi-arid regions.
Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature
Authors: Brydges Christopher R. , Fiehn Oliver , Mayberg Helen S. , Schreiber Henry , Dehkordi Siamak Mahmoudian , Bhattacharyya Sudeepa , Cha Jungho , Choi Ki Sueng , Craighead W. Edward , Krishnan Ranga R. , Rush A. John , Dunlop Boadie W. , Kaddurah-Daouk Rima ,   the Mood Disorders Precision Medicine Consortium, Penninx Brenda , Binder Elizabeth , Kastenmüller Gabi , Arnold Matthias , Nevado-Helgado Alejo , Blach Colette , Milaneschi Yuri , Knauer-Arloth Janine , Jansen Rich , Mook-Kanamori Dennis , Han Xianlin , Baillie Rebecca , Rinaldo Piero
Published: October 2021

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite’s effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies.

Clinical trial NCT00360399 “Predictors of Antidepressant Treatment Response: The Emory CIDAR” https://clinicaltrials.gov/ct2/show/NCT00360399.
Excited-state structural dynamics of nickel complexes probed by optical and X-ray transient absorption spectroscopies: insights and implications
Authors: Phelan Brian T. , Mara Michael W. , Chen Lin X.
Published: October 2021

Excited states of nickel complexes undergo a variety of photochemical processes relevant to solar energy conversion and photocatalysis. Here we outline the role of optical and X-ray transient absorption spectroscopies for advancing these fields.
Modulation of H+/H− exchange in iridium-hydride 2-hydroxypyridine complexes by remote Lewis acids
Authors: Shanahan J. P. , Moore C. M. , Kampf Jeff W. , Szymczak N. K.
Published: October 2021

We disclose a unique series of iridium hydride complexes where rapid H+/H− exchange is modulated by a remote binding site.
Calix[n]triazolium based turn-on fluorescent sensing ensemble for selective adenosine monophosphate (AMP) detection
Authors: Cho Jihee , Shin Jinwoo , Kang Minjung , Verwilst Peter , Lim Changhyun , Yoo Hanbin , Kim Jeung Gon , Zhang Xingcai , Hong Chang Seop , Kim Jong Seung , Kim Sanghee
Published: October 2021

We report a series of calix[n]triazoliums showing excellent selectivity for AMP. The unique supramolecular ensemble exhibits a selective turn-on fluorescence response towards AMP over various anions, including adenosine polyphosphates.
Red circularly polarized luminescence from intramolecular excimers restricted by chiral aromatic foldamers
Authors: Zheng Dan , Guo Shengzhu , Zheng Lu , Xu Qi , Wang Ying , Jiang Hua
Published: October 2021

The absolute handed aromatic oligoamide foldamers containing restricted pyrene units at its same side exhibiting red excimer CPL.
Kinetics of the parallel-consecutive bimolecular reaction: a solution to the inverse problem involving the Lambert-W function
Authors: Pitt Phillip , Harwood Laurence M.
Published: October 2021

Parallel-consecutive bimolecular reactions: a solution to the inverse kinetic problem and a characteristic equation involving the Lambert W function.
A protein scaffold enables hydrogen evolution for a Ni-bisdiphosphine complex
Authors: Laureanti Joseph A. , Su Qiwen , Shaw Wendy J.
Published: October 2021

An artificial metalloenzyme acting as a functional biomimic of hydrogenase enzymes was activated by assemblyviacovalent attachment of the molecular complex, [Ni(PNglycineP)2]2−, within a structured protein scaffold.
Divergent Ritter-type amination via photoredox catalytic four-component radical-polar crossover reactions
Authors: Guo Sheng-Qiang , Yang Hui-Qing , Wang Ai-Lian , Jiang Yu-Zhen , Xu Guo-Qiang , Luo Yong-Chun , Chen Zhao-Xu , Xu Peng-Fei
Published: October 2021

Divergent Ritter-type amination via photoredox catalytic four-component radical-polar crossover reactions with high atom-, step- and redox economy.
Facile and efficient recovery of lithium from spent LiFePO4 batteries via air oxidation–water leaching at room temperature
Authors: Jin Hao , Zhang Jialiang , Wang Duoduo , Jing Qiankun , Chen Yongqiang , Wang Chengyan
Published: October 2021

A facile, economical and environmentally friendly method was proposed to selectively extract lithium from the spent LFP cathode material via air oxidation–water leaching.
“Left-hand strategy” for the design, synthesis and discovery of novel triazole–mercaptobenzothiazole hybrid compounds as potent quorum sensing inhibitors and anti-biofilm formation ofPseudomonas aeruginosa
Authors: Tung Truong Thanh , Xuan Huy Luong
Published: October 2021

Triazole–benzothiazole hybrids as potent quorum sensing inhibitors and antibiofilm formation of Gram-negative bacteria.
Three-dimensional carbon foam-metal oxide-based asymmetric electrodes for high-performance solid-state micro-supercapacitors
Authors: Kumar Sumana , Misra Abha
Published: October 2021

An asymmetric solid-state micro-supercapacitor is fabricated by employing a simple and scalable spray printing method using a custom-made mask that can be integrated on a large scale.
Deep generative design with 3D pharmacophoric constraints
Authors: Imrie Fergus , Hadfield Thomas E. , Bradley Anthony R. , Deane Charlotte M.
Published: October 2021

A novel deep generative model combines convolution and graph neural networks to allow 3D-aware molecular design. We show how 3D pharmacophoric information can be incorporated into generative models and apply our model to both linker and R-group design.
Flow profiles near receding three-phase contact lines: influence of surfactants
Authors: Straub Benedikt B. , Schmidt Henrik , Rostami Peyman , Henrich Franziska , Rossi Massimiliano , Kähler Christian J. , Butt Hans-Jürgen , Auernhammer Günter K.
Published: October 2021

The dynamics of dewetting is largely determined by the velocity field near the contact lines. Surfactant laden drops show a strong coupling of the internal hydrodynamic flow and the surfactant dynamics at the liquid–gas interface.
A conserved NAG motif is critical to the catalytic activity of galactinol synthase, a key regulatory enzyme of RFO biosynthesis
Authors: Salvi Prafull , Kumar Bhavnesh , Kamble Nitin Uttam , Hazra Abhijit , Majee Manoj
Published: October 2021

Galactinol synthase (GolS) catalyzes the key regulatory step in the biosynthesis of Raffinose Family Oligosaccharides (RFOs). Even though the physiological role and regulation of this enzyme has been well studied, little is known about active site amino acids and the structure-function relationship with substrates of this enzyme. In the present study, we investigate the active site amino acid and structure-function relationship for this enzyme. Using a combination of three-dimensional homology modeling, molecular docking along with a series of deletion, site-directed mutagenesis followed by in vitro biochemical and in vivo functional analysis; we have studied active site amino acids and their interaction with the substrate of chickpea and Arabidopsis GolS enzyme. Our study reveals that the GolS protein possesses GT8 family-specific several conserved motifs in which NAG motif plays a crucial role in substrate binding and catalytic activity of this enzyme. Deletion of entire NAG motif or deletion or the substitution (with alanine) of any residues of this motif results in complete loss of catalytic activity in in vitro condition. Furthermore, disruption of NAG motif of CaGolS1 enzyme disrupts it's in vivo cellular function in yeast as well as in planta. Together, our study offers a new insight into the active site amino acids and their substrate interaction for the catalytic activity of GolS enzyme. We demonstrate that NAG motif plays a vital role in substrate binding for the catalytic activity of galactinol synthase that affects overall RFO synthesis.
Effect of Capsaicin Atomization–Induced Cough on Sputum Excretion in Tracheotomized Patients After Hemorrhagic Stroke: A Randomized Controlled Trial
Authors: Wu Chao , Zhang Yijie , Yang Li , Shen Fang , Ma Chen , Shen Meifen
Published: October 2021

Background

Timely and effective removal of respiratory secretions is of great significance for tracheotomized patients. The purpose of this study is to investigate the effectiveness of capsaicin nebulization to stimulate cough to promote early clearance of respiratory secretions in tracheotomized patients after hemorrhagic stroke.

Method

This study implemented a randomized controlled design. Sixty-three patients who were tracheotomized following a hemorrhagic stroke completed this randomized controlled trial. In the control group, 33 cases were given a routine care after tracheotomy. In the intervention group, 30 cases were given a capsaicin solution nebulization in addition to the routine care. The daily sputum output and the number of sputum suctioning were observed. The differences in sputum viscosity, cough function, and Clinical Pulmonary Infection Score (CPIS) were compared between the two groups before and after the intervention. Vital sign changes during capsaicin nebulization and suctioning were compared between the two groups in a pilot study.

Results

The daily sputum output of the capsaicin intervention group was significantly higher than that of the control group (
p
< .05). The number of sputum suctioning of capsaicin group was less than that of the control group after intervention (
p
< .05). The CPIS score of the capsaicin group was lower than that of the control group (
p
< .05) after a 1-week intervention. Patients' heart rate, respiratory rate, and oxygen saturation during capsaicin nebulization were not statistically different from those during routine sputum suctioning (
p
> .05).

Conclusions

Capsaicin atomization–induced cough can effectively promote sputum excretion of hemorrhagic stroke patients undergoing tracheotomy and has a good safety profile. The Clinical Trial registration number of this study is ChiCTR2000037772 (
http://www.chictr.org.cns
).

Supplemental Material

https://doi.org/10.23641/asha.16821352
A novel evolving framework for energy management in wind‐gas reinforced unit commitment with demand response
Authors: Safipour Hamed , Abdollahi Amir , Hajmohammadi Mohammad Sadegh , Alizadeh Mohammad Iman
Published: October 2021

This research work tries to investigate the provision of flexibility on both sides of production and demand security constraint unit commitment (SCUC) before the schedule is considered. To this end, a powerful heuristic technique based on modified firefly algorithm (FA) is devised to achieve the optimal solution. Moreover, fast‐starting gas units (FGUs) are considered as providers of lateral flexibility as a result of their quickness in starting work and high ramp capability. Considering the fact that the normal operation of units is subject to the supply of reliable gas through connected gas transmission lines, the uncertainty of gas supply in the suggested model is considered to imitate the effects of deviation in the volume of gas over pipelines. The application of the suggested model has been tested on IEEE‐118 bus.
Dynamic atmospheres and winds of cool luminous giants
Authors: Höfner S. , Bladh S. , Aringer B. , Eriksson K.
Published: October 2021

Context. The winds observed around asymptotic giant branch (AGB) stars are generally attributed to radiation pressure on dust formed in the extended dynamical atmospheres of these long-period variables. The composition of wind-driving grains is affected by a feedback between their optical properties and the resulting heating due to stellar radiation.

Aims. We explore the gradual Fe enrichment of wind-driving silicate grains in M-type AGB stars to derive typical values for Fe/Mg and to test the effects on wind properties and synthetic spectra.

Methods. We present new radiation-hydrodynamical DARWIN models that allow for the growth of silicate grains with a variable Fe/Mg ratio and predict mass-loss rates, wind velocities, and grain properties. Synthetic spectra and other observables are computed a posteriori with the COMA code.

Results. The self-regulating feedback between grain composition and radiative heating, in combination with quickly falling densities in the stellar wind, leads to low values of Fe/Mg, typically a few percent. Nevertheless, the new models show distinct silicate features around 10 and 18 microns. Fe enrichment affects visual and near-IR photometry moderately, and the new DARWIN models agree well with observations in (J − K) versus (V − K) and Spitzer color–color diagrams. The enrichment of the silicate dust with Fe is a secondary process, taking place in the stellar wind on the surface of large Fe-free grains that have initiated the outflow. Therefore, the mass-loss rates are basically unaffected, while the wind velocities tend to be slightly higher than in corresponding models with Fe-free silicate dust.

Conclusions. The gradual Fe enrichment of silicate grains in the inner wind region should produce signatures observable in mid-IR spectro-interferometrical measurements. Mass-loss rates derived from existing DARWIN models, based on Fe-free silicates, can be applied to stellar evolution models since the mass-loss rates are not significantly affected by the inclusion of Fe in the silicate grains.
Broad-band analysis of X-ray pulsar 2S 1845–024
Authors: Nabizadeh Armin , Tsygankov Sergey S. , Molkov Sergey V. , Karasev Dmitri I. , Ji Long , Lutovinov Alexander A. , Poutanen Juri
Published: October 2021

We present the results of a detailed investigation of the poorly studied X-ray pulsar 2S 1845−024 based on data obtained at the NuSTAR observatory during the type I outburst in 2017. Neither pulse phase-averaged nor phase-resolved spectra of the source show evidence for a cyclotron absorption feature. We also used data obtained from other X-ray observatories (Swift, XMM-Newton and Chandra) to study the spectral properties as a function of orbital phase. The analysis reveals a high hydrogen column density for the source reaching ∼1024 cm−2 around periastron. Using high-quality Chandra data we were able to obtain an accurate localization of 2S 1845−024 at RA = 18h48m16.s8 and Dec = −2°25′25.″1 (J2000), which allowed us to use infrared (IR) data to roughly classify the optical counterpart of the source as an OB supergiant at a distance of ≳15 kpc.
Topische Anwendung von Heilpflanzen zur Unterstützung der Wundheilung
Authors: Embacher Karin , Zilkowski Ilona , Turek Claudia , Stintzing Florian C
Published: October 2021

Die Wundheilung ist ein komplexer Prozess, der durch eine auf den jeweiligen Wundzustand abgestimmte Versorgung unterstützt werden kann. Der Artikel betrachtet bekannte (Arnika, Johanniskraut, Ringelblume/Calendula), aber auch in Vergessenheit geratene Heilpflanzen (Beinwell, Brennnessel, Deutsche Schwertlilie, Lebensbaum/Thuja, Waldbingelkraut, Wundklee) im Hinblick auf ihr wundheilungsförderndes und antimikrobielles Potenzial bei topischer Anwendung. Auf Grundlage aktueller Literaturdaten aus In-vitro- und In-vivo-Untersuchungen sowie klinischen Studien werden die Pflanzen und ihre Wirkmechanismen den Wundheilungsphasen zugeordnet. Besonderes Augenmerk wird zudem auf die Vorteile der Kombination von Heilpflanzen gelegt, um ein breiteres Wirkspektrum über verschiedene Phasen der Wundheilung hinweg zu erhalten und eine umfassende Unterstützung dieser anzustreben.
Völlig unterschiedlich oder doch recht ähnlich? Die
soziodemografische Struktur der AOK Niedersachsen im Vergleich zur
niedersächsischen und bundesweiten Allgemein- und
Erwerbsbevölkerung
Authors: Epping Jelena , Geyer Siegfried , Eberhard Sveja , Tetzlaff Juliane
Published: October 2021

Ziel der Studie Routinedaten von Krankenkassen sind als Datenquelle
mittlerweile gut etabliert. Hinsichtlich der Verallgemeinerbarkeit der
Ergebnisse bei Analysen mit Daten einer Krankenkasse treten Fragen der
Repräsentativität der Versichertenpopulation auf, insbesondere
da nicht alle Studien auf soziodemografische Merkmale adjustieren. Diese Arbeit
untersucht mittels deskriptiver Analyse, ob und inwieweit sich die
Sozialstruktur der Versichertenpopulation der AOK Niedersachsen von der
Sozialstruktur der Allgemeinbevölkerung und der
sozialversicherungspflichtig Beschäftigten in Niedersachsen (NDS) und in
der Bundesrepublik (BRD) unterscheiden.

Methodik Die Datengrundlage bilden pseudonymisierte Daten der AOK NDS, die
Beschäftigtenstatistik der Bundesagentur für Arbeit und der
Bevölkerungsstand in NDS und der BRD. Die Versichertenpopulation wird an
zwei Stichtagen 31.12.2012 und 31.12.2017 hinsichtlich der Geschlechter-und
Altersstruktur mit der Bevölkerung in NDS und der BRD verglichen.
Anschließend werden die Daten der sozialversicherungspflichtig
Beschäftigten in der AOK NDS und aus der Beschäftigtenstatistik
der Bundesagentur für Arbeit gegenübergestellt, um
Ausbildungsabschlüsse, Komplexität der ausgeübten
Tätigkeit und elf Berufsbereiche zu vergleichen.

Ergebnisse Die Geschlechterstruktur unterscheidet sich nicht zwischen den
drei Vergleichspopulationen. Verglichen mit der Bevölkerung in NDS und
der BRD ist der Anteil der unter 30-Jährigen in der AOK NDS
überdurchschnittlich, der Anteil der Personen zwischen 50 und 76 Jahren
etwas unterdurchschnittlich. Sozialversicherungspflichtig Beschäftigte
mit Hochschulabschluss und in Tätigkeiten mit höherer
Komplexität sind in der AOK NDS unterrepräsentiert. Die
Verteilung der sozialversicherungspflichtig Beschäftigten auf elf
Berufsbereiche unterscheidet sich ebenfalls.

Schlussfolgerung Die Studie zeigt, dass soziodemographische und
sozio-ökonomische Merkmale in Studien mit Krankenkassendaten wann immer
möglich berücksichtigt werden sollten. In Zukunft wird das
Informationssystem Versorgungsdaten krankenkassenübergreifende Analysen
mit Sekundärdaten ermöglichen. Fragestellungen der
gesundheitlichen Ungleichheit können damit jedoch aufgrund des Fehlens
von sozio-ökonomischen Merkmalen nicht beantwortet werden. Auch die
Identifikation von vulnerablen Gruppen, die gezielt geeigneten Maßnahmen
zugeführt werden könnten, ist ohne Berücksichtigung von
sozio-ökonomischen Merkmalen erschwert.
Analyse der Zeitangaben in Krankenhausabrechnungsdaten bei
ST-Streckenhebungs-Herzinfarkt und Linksherzkatheterintervention
Authors: Nimptsch Ulrike , Busse Reinhard
Published: October 2021

Hintergrund und Ziel Krankenhausabrechnungsdaten enthalten neben
demografischen, medizinischen und administrativen Informationen auch Zeitangaben
zum Behandlungsverlauf, beispielsweise den Zeitpunkt der Aufnahme oder den
Zeitpunkt der Durchführung einer Prozedur. Anhand dieser Datenfelder
könnten wesentliche Prozessindikatoren berechnet werden, mit denen die
Qualität der Versorgung beurteilt werden kann. Allerdings liegen zur
Plausibilität der Zeitangaben in den Abrechnungsdaten bislang kaum
Informationen vor. Ziel dieser Arbeit ist, die Zeitangaben in den Daten am
Beispiel von ST-Streckenhebungs-Herzinfarkt und Linksherzkatheterintervention zu
untersuchen, um damit einen ersten Anhaltspunkt für die Bewertung der
Plausibilität zu erhalten.

Methode Anhand der deutschlandweiten Krankenhausabrechnungsdaten
(DRG-Statistik) von 2014 bis 2017 wurden Behandlungsfälle mit akutem
ST-Streckenhebungs-Herzinfarkt im erstbehandelnden Krankenhaus identifiziert.
Gegenstand der explorativen Analyse waren der Zeitpunkt (Datum und Uhrzeit) der
Aufnahme, sowie der Zeitpunkt (Datum und Uhrzeit) der
Linksherzkatheterintervention. Aus der Differenz zwischen Aufnahmezeit und
Interventionszeit wurde das Zeitintervall berechnet und in Kategorien
eingeteilt.

Ergebnisse Die Analyse des Aufnahmezeitpunktes der
Behandlungsfälle mit ST-Streckenhebungs-Herzinfarkt
(N=254 719) nach Wochentag und Stunde zeigte ein Muster mit
Häufigkeitsgipfeln an Werktagen zwischen 9:00 und 13:00 Uhr. Die
Betrachtung der dokumentierten Zeiten der Linksherzkatheterintervention
(N=206 079) zeigte eine ähnliche Verteilung, die jedoch
an allen Wochentagen durch Häufigkeitsspitzen jeweils um 12:00 Uhr und
um 0:00 Uhr charakterisiert war. Der Anteil der Behandlungsfälle mit
unplausiblen Zeitintervallen sank von 9,5% im Jahr 2014 auf 7,8%
im Jahr 2017 und zeigte eine hohe Variation auf der Krankenhausebene.

Schlussfolgerung Eine Nutzung der Datenfelder für Zeitangaben in
Krankenhausabrechnungsdaten könnte wertvolle Informationen zur Bewertung
der Behandlungsprozesse liefern und klinisch tätiges Personal von
separaten Dokumentationsaufgaben entlasten. Die Ergebnisse dieser Analyse zeigen
jedoch, dass implausible Angaben und verschiedene Unsicherheiten die
Interpretierbarkeit stark einschränken. Um die Qualität der
Dokumentation von Zeitangaben zu verbessern, müssten Anreize für
eine korrekte Dokumentation geschaffen und konkrete Vorgaben (z. B. zur
Definition des Aufnahmezeitpunktes) gemacht werden.
The Impact of SARS-CoV-2 Infection on Blood Coagulation and Fibrinolytic Pathways: A Review of Prothrombotic Changes Caused by COVID-19
Authors: Bahraini Mehran , Dorgalaleh Akbar
Published: October 2021

The cardinal pathology of coronavirus disease 2019 (COVID-19) is a primary infection of pulmonary tract cells by severe acute respiratory syndrome coronavirus 2, provoking a local inflammatory response, often accompanied by cytokine storm and acute respiratory distress syndrome, especially in patients with severe disease. Systemic propagation of the disease may associate with thrombotic events, including deep vein thrombosis, pulmonary embolism, and thrombotic microangiopathy, which are important causes of morbidity and mortality in patients with COVID-19. This narrative review describes current knowledge of the pathophysiological mechanisms of COVID-19-associated coagulopathy, with focus on prothrombotic changes in hemostatic mediators, including plasma levels of clotting factors, natural anticoagulants, components of fibrinolytic system, and platelets. It will also highlight the central role of endothelial cells in COVID-19-associated coagulopathy. This narrative review discusses also potential therapeutic strategies for managing thrombotic complications. Awareness by medical experts of contributors to the pathogenesis of thrombotic events in COVID-19 is imperative to develop therapeutics not limited to regular anticoagulants. Instituting cooperation among medical personnel and researchers may lessen this novel virus' impact now, and in the event of recurrence.
Status of AI-Enabled Clinical Decision Support Systems Implementations in China
Authors: Ji Mengting , Chen Xiaoyun , Genchev Georgi Z. , Wei Mingyue , Yu Guangjun
Published: October 2021

Background AI-enabled Clinical Decision Support Systems (AI + CDSSs) were heralded to contribute greatly to the advancement of health care services. There is an increased availability of monetary funds and technical expertise invested in projects and proposals targeting the building and implementation of such systems. Therefore, understanding the actual system implementation status in clinical practice is imperative.

Objectives The aim of the study is to understand (1) the current situation of AI + CDSSs clinical implementations in Chinese hospitals and (2) concerns regarding AI + CDSSs current and future implementations.

Methods We investigated 160 tertiary hospitals from six provinces and province-level cities. Descriptive analysis, two-sided Fisher exact test, and Mann-Whitney U-test were utilized for analysis.

Results Thirty-eight of the surveyed hospitals (23.75%) had implemented AI + CDSSs. There were statistical differences on grade, scales, and medical volume between the two groups of hospitals (implemented vs. not-implemented AI + CDSSs, p <0.05). On the 5-point Likert scale, 81.58% (31/38) of respondents rated their overall satisfaction with the systems as “just neutral” to “satisfied.” The three most common concerns were system functions improvement and integration into the clinical process, data quality and availability, and methodological bias.

Conclusion While AI + CDSSs were not yet widespread in Chinese clinical settings, professionals recognize the potential benefits and challenges regarding in-hospital AI + CDSSs.
Advances in tuning hybrid organic-inorganic perovskites with pressure yield new material phases
Authors: Liebendorfer Adam
Published: October 2021

Findings point to new crystal structures not commonly found during synthesis and unique electronic, optical and magnetic properties when materials are under hydrostatic pressure.
Gold-tantalum alloy films deposited by high-density-plasma magnetron sputtering
Authors: Bae J. H. , Bayu Aji L. B. , Shin S. J. , Engwall A. M. , Nielsen M. H. , Baker A. A. , McCall S. K. , Moody J. D. , Kucheyev S. O.
Published: October 2021

Gold-tantalum alloy films are of interest for biomedical and magnetically-assisted inertial confinement fusion applications. Here, we systematically study the effects of substrate tilt (0°–80°) and negative substrate bias (0–100 V) on properties of ≲3-μm-thick films deposited by high-power impulse magnetron sputtering (HiPIMS) from a Au–Ta alloy target (with 80 at. % of Ta). Results reveal that, for all the substrate bias values studied, an increase in substrate tilt leads to a monotonic decrease in film thickness, density, residual compressive stress, and electrical conductivity. Larger substrate bias favors the formation of a body-centered cubic phase, with films exhibiting lower column tilt and higher density, electrical conductivity, and residual compressive stress. These changes are attributed to metal atom ionization effects, based on the lack of correlation with distributions of landing energies and incident angles of depositing species as calculated by Monte Carlo simulations of ballistic collisions and gas phase atomic transport. By varying substrate tilt and bias in HiPIMS deposition, properties of Au–Ta alloy films can be controlled in a very wide range, including residual stress from −2 to +0.5 GPa, density from 12 to 17 g/cm3, and the electrical resistivity from 50 to 4500 μΩ cm, enabling optimum deposition conditions to be selected for specific applications.