bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients
Authors: Zhang Jin-Lan , Li Yu-Huan , Wang Lu-Lu , Liu Hong-Qi , Lu Shuai-Yao , Liu Yong , Li Ke , Liu Bin , Li Su-Yun , Shao Feng-Min , Wang Kun , Sheng Ning , Li Rui , Cui Jin-Jin , Sun Pei-Chun , Ma Chun-Xia , Zhu Bo , Wang Zhe , Wan Yuan-Hao , Yu Shi-Shan , Che Yongsheng , Wang Chao-Yang , Wang Chen , Zhang Qiangqian , Zhao Li-Min , Peng Xiao-Zhong , Cheng Zhenshun , Chang Jun-Biao , Jiang Jian-Dong 
Published: December 2021

AbstractAzvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.
Virtual reality: a powerful technology to provide novel insight into treatment mechanisms of addiction
Authors: Mazza Massimiliano , Kammler-Sücker Kornelius , Leménager Tagrid , Kiefer Falk , Lenz Bernd 
Published: December 2021

AbstractDue to its high ecological validity, virtual reality (VR) technology has emerged as a powerful tool for mental health research. Despite the wide use of VR simulations in research on mental illnesses, the study of addictive processes through the use of VR environments is still at its dawn. In a systematic literature search, we identified 38 reports of research projects using highly immersive head-mounted displays, goggles, or CAVE technologies to provide insight into treatment mechanisms of addictive behaviors. So far, VR research has mainly addressed the roles of craving, psychophysiology, affective states, cognition, and brain activity in addiction. The computer-generated VR environments offer very realistic, dynamic, interactive, and complex real-life simulations requesting active participation. They create a high sense of immersion in users by combining stereoscopic three-dimensional visual, auditory, olfactory, and tactile perceptions, tracking systems responding to user movements, and social interactions. VR is an emerging tool to study how proximal multi-sensorial cues, contextual environmental cues, as well as their interaction (complex cues) modulate addictive behaviors. VR allows for experimental designs under highly standardized, strictly controlled, predictable, and repeatable conditions. Moreover, VR simulations can be personalized. They are currently refined for psychotherapeutic interventions. Embodiment, eye-tracking, and neurobiological factors represent novel future directions. The progress of VR applications has bred auspicious ways to advance the understanding of treatment mechanisms underlying addictions, which researchers have only recently begun to exploit. VR methods promise to yield significant achievements to the addiction field. These are necessary to develop more efficacious and efficient preventive and therapeutic strategies.
Less entanglement exhibiting more nonlocality with noisy measurements
Authors: Zhu Gaoyan , Dilley Daniel , Wang Kunkun , Xiao Lei , Chitambar Eric , Xue Peng 
Published: December 2021

AbstractThe Clauser–Horne–Shimony–Holt (CHSH) inequality test is widely used as a mean of invalidating the local deterministic theories. Most attempts to experimentally test nonlocality have presumed unphysical idealizations that do not hold in real experiments, namely, noiseless measurements. We demonstrate an experimental violation of the CHSH inequality that is free of idealization and rules out local models with high confidence. We show that the CHSH inequality can always be violated for any nonzero noise parameter of the measurement. Intriguingly, less entanglement exhibits more nonlocality in the CHSH test with noisy measurements. Furthermore, we theoretically propose and experimentally demonstrate how the CHSH test with noisy measurements can be used to detect weak entanglement on two-qubit states. Our results offer a deeper insight into the relation between entanglement and nonlocality.
Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer
Authors: Nadesh Ragima , Menon Krishnakumar N. , Biswas Lalitha , Mony Ullas , Subramania Iyer K. , Vijayaraghavan Sundeep , Nambiar Ajit , Nair Shantikumar 
Published: December 2021

AbstractIn the present study, a protocol was developed for processing of human adipose derived mesenchymal stem cell secretome formulation of varying concentration. Its molecular composition was evaluated, and its effectiveness in vitro using breast cancer cell lines, and in vivo in a nude mice breast cancer model was studied to determine its role in suppressing triple negative breast cancer in a dose dependent manner. Because the secretome could have value as an add-on therapy along with a current drug, the effectiveness of the secretome both in monotherapy and in combination therapy along with paclitaxel was evaluated. The results showed significant cell kill when exposed to the secretome above 20 mg/ml at which concentration there was no toxicity to normal cells. 70 mg/ml of SF showed 90 ± 10% apoptosis and significant decrease in CD44+/CD24−, MDR1+ and PDL-1+ cancer cells. In vivo, the tumor showed no growth after daily intra tumor injections at 50 mg/ml and 100 mg/ml doses whereas substantial tumor growth occurred after saline intra tumor injection. The study concludes that SF is a potential biotherapeutic for breast cancer and could be used initially as an add-on therapy to other standard of care to provide improved efficacy without other adverse effects.
The effect of paclitaxel on apoptosis, autophagy and mitotic catastrophe in AGS cells
Authors: Khing Tin Myo , Choi Won Seok , Kim Dong Min , Po Wah Wah , Thein Wynn , Shin Chang Yell , Sohn Uy Dong 
Published: December 2021

AbstractPaclitaxel is an anti-microtubule agent that has been shown to induce cell death in gastric cancer. However, the detailed mechanism of action is unclear. In this study, we reveal that the paclitaxel-induced cell death mechanism involves mitotic catastrophe, autophagy and apoptosis in AGS cells. Paclitaxel induced intrinsic apoptosis by activating caspase-3, caspase-9 and PARP. In addition, the significant increase in autophagy marker LC3B-II, together with Atg5, class III PI3K and Beclin-1, and the down-regulation of p62 following paclitaxel treatment verified that paclitaxel induced autophagy. Further experiments showed that paclitaxel caused mitotic catastrophe, cell cycle arrest of the accumulated multinucleated giant cells at the G2/M phase and induction of cell death in 24 h. Within 48 h, the arrested multinucleated cells escaped mitosis by decreasing cell division regulatory proteins and triggered cell death. Cells treated with paclitaxel for 48 h were grown in fresh medium for 24 h and checked for CDC2, CDC25C and lamin B1 protein expressions. These proteins had decreased significantly, indicating that the remaining cells became senescent. In conclusion, it is suggested that paclitaxel-induced mitotic catastrophe is an integral part of the cell death mechanism, in addition to apoptosis and autophagy, in AGS cells.
Understanding host-microbiota interactions in the commercial piglet around weaning
Authors: Saladrigas-García M. , D’Angelo M. , Ko H. L. , Nolis P. , Ramayo-Caldas Y. , Folch J. M. , Llonch P. , Solà-Oriol D. , Pérez J. F. , Martín-Orúe S. M. 
Published: December 2021

AbstractWeaning is a critical period in the life of pigs with repercussions on their health and welfare and on the economy of the swine industry. This study aimed to assess the effect of the commercial early weaning on gut microbiota, intestinal gene expression and serum metabolomic response via an integrated-omic approach combining 16S rRNA gene sequencing, the OpenArray gene expression technology and 1H-NMR spectroscopy. Fourteen piglets from different litters were sampled for blood, jejunum tissue and caecal content two days before (− 2d), and three days after (+ 3d) weaning. A clearly differential ordination of caecal microbiota was observed. Higher abundances of Roseburia, Ruminococcus, Coprococcus, Dorea and Lachnospira genera in weaned piglets compared to prior to weaning showed the quick microbial changes of the piglets’ gut microbiota. Downregulation of OCLN, CLDN4, MUC2, MUC13, SLC15A1 and SLC13A1 genes, also evidenced the negative impact of weaning on gut barrier and digestive functions. Metabolomic approach pinpointed significant decreases in choline, LDL, triglycerides, fatty acids, alanine and isoleucine and increases in 3-hydroxybutyrate after weaning. Moreover, the correlation between microbiota and metabolome datasets revealed the existence of metabolic clusters interrelated to different bacterial clusters. Our results demonstrate the impact of weaning stress on the piglet and give insights regarding the associations between gut microbiota and the animal gene activity and metabolic response.
A free-geometry geodynamic modelling of surface gravity changes using Growth-dg software
Authors: Camacho Antonio G. , Vajda Peter , Miller Craig A. , Fernández José 
Published: December 2021

AbstractGlobally there is abundant terrestrial surface gravity data used to study the time variation of gravity related to subsurface mass and density changes in different geological, geodynamical and geotechnical environments. We present here a tool for analysing existing and newly acquired, 4D gravity data, which creates new findings from its reuse. Our method calculates in an almost automatic way the possible sources of density change responsible for the observed gravity variations. The specifics of the new methodology are: use of a low number of observation points, relatively small source structures, low signal/noise ratio in the data, and a free 3D source geometry without initial hypothesis. The process is based on the non-linear adjustment of structures defined by aggregation of small cells corresponding to a 3D section of the sub-floor volume. This methodology is implemented in a software tool, named GROWTH-dg, which can be freely downloaded for immediate use, together with a user manual and application examples.
Combined detection of lymphocyte clonality and MALT1 translocations in bronchoalveolar lavage fluid for diagnosing pulmonary lymphomas
Authors: Kido Takashi , Ishimoto Hiroshi , Ishii Hiroshi , Hara Kanako , Ozasa Mutsumi , Kawabata Hiroki , Kawanami Toshinori , Suzuki Yu , Yoshikawa Hiroki , Hara Atsuko , Sakamoto Noriho , Matsumoto Nobuhiro , Yoshii Chiharu , Fukuoka Junya , Fujita Masaki , Nakazato Masamitsu , Kadota Junichi , Mukae Hiroshi , Yatera Kazuhiro 
Published: December 2021

AbstractDiagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. We previously showed that pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma can be diagnosed by detecting MALT lymphoma translocation gene 1 (MALT1) translocations in bronchoalveolar lavage fluid (BALF) cells. Analysis of B-cell clonality based on immunoglobulin heavy chain (IGH) gene rearrangements was also reportedly useful for diagnosing pulmonary lymphoma. The aim of this prospective multicenter study was to evaluate the yet unknown diagnostic potential of combined detection of MALT1 translocations and clonality using BALF. We analyzed B- and T-cell clonality based on IGH and T-cell receptor (TCR) rearrangements together with MALT1 translocations using BALF of patients with clinically suspected pulmonary lymphomas. In total, 39 patients were evaluated and categorized into three groups: B-cell lymphoma, lymphoproliferative disorders, and other diseases. IGH rearrangement detection for B-cell lymphoma diagnosis exhibited sensitivity and specificity of 88.9% and 90.0%, respectively. TCR rearrangements were not observed in patients with B-cell lymphomas. The presence of IGH rearrangements together with the absence of TCR rearrangements indicated 96.0% specificity for the diagnosis of B-cell lymphoma. The sensitivity and specificity of MALT1 translocations for diagnosing MALT lymphoma were 28.6% and 100%, respectively. The combined detection of lymphocyte clonality and MALT1 translocations using BALF is suitable for screening and diagnosis of B-cell lymphomas. Analysis of specific genes such as MALT1 should improve the precision of B-cell lymphoma diagnosis.
A nomogram for predicting probability of low risk of MammaPrint results in women with clinically high-risk breast cancer
Authors: Lee Young Joo , Hwang Young Sol , Kim Junetae , Ahn Sei-Hyun , Son Byung Ho , Kim Hee Jeong , Ko Beom Seok , Kim Jisun , Chung Il Yong , Lee Jong Won , Lee Sae Byul 
Published: December 2021

AbstractWe aimed to develop a prediction MammaPrint (MMP) genomic risk assessment nomogram model for hormone-receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2–) breast cancer and minimal axillary burden (N0-1) tumors using clinicopathological factors of patients who underwent an MMP test for decision making regarding adjuvant chemotherapy. A total of 409 T1-3 N0-1 M0 HR + and HER2– breast cancer patients whose MMP genomic risk results and clinicopathological factors were available from 2017 to 2020 were analyzed. With randomly selected 306 patients, we developed a nomogram for predicting a low-risk subgroup of MMP results and externally validated with remaining patients (n = 103). Multivariate analysis revealed that the age at diagnosis, progesterone receptor (PR) score, nuclear grade, and Ki-67 were significantly associated with MMP risk results. We developed an MMP low-risk predictive nomogram. With a cut off value at 5% and 95% probability of low-risk MMP, the nomogram accurately predicted the results with 100% positive predictive value (PPV) and negative predictive value respectively. When applied to cut-off value at 35%, the specificity and PPV was 95% and 86% respectively. The area under the receiver operating characteristic curve was 0.82 (95% confidence interval [CI] 0.77 to 0.87). When applied to the validation group, the nomogram was accurate with an area under the curve of 0.77 (95% CI 0.68 to 0.86). Our nomogram, which incorporates four traditional prognostic factors, i.e., age, PR, nuclear grade, and Ki-67, could predict the probability of obtaining a low MMP risk in a cohort of high clinical risk patients. This nomogram can aid the prompt selection of patients who does not need additional MMP testing.
Nationwide registry of glecaprevir plus pibrentasvir in the treatment of HCV in Taiwan
Authors: Huang Chung-Feng , Kuo Hsing-Tao , Chang Te-Sheng , Lo Ching-Chu , Hung Chao-Hung , Huang Chien-Wei , Chong Lee-Won , Cheng Pin-Nan , Yeh Ming-Lun , Peng Cheng-Yuan , Cheng Chien-Yu , Huang Jee-Fu , Bair Ming-Jong , Lin Chih-Lang , Yang Chi-Chieh , Wang Szu-Jen , Hsieh Tsai-Yuan , Lee Tzong-Hsi , Lee Pei-Lun , Wu Wen-Chih , Lin Chih-Lin , Su Wei-Wen , Yang Sheng-Shun , Wang Chia-Chi , Hu Jui-Ting , Mo Lein-Ray , Chen Chun-Ting , Huang Yi-Hsiang , Chang Chun-Chao , Huang Chia-Sheng , Chen Guei-Ying , Kao Chien-Neng , Tai Chi-Ming , Liu Chun-Jen , Lee Mei-Hsuan , Tsai Pei-Chien , Dai Chia-Yen , Kao Jia-Horng , Lin Han-Chieh , Chuang Wang-Long , Chen Chi-Yi , Tseng Kuo-Chih , Yu Ming-Lung 
Published: December 2021

AbstractThe study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.
Diversification of ergot alkaloids and heritable fungal symbionts in morning glories
Authors: Beaulieu Wesley T. , Panaccione Daniel G. , Quach Quynh N. , Smoot Katy L. , Clay Keith 
Published: December 2021

AbstractHeritable microorganisms play critical roles in life cycles of many macro-organisms but their prevalence and functional roles are unknown for most plants. Bioactive ergot alkaloids produced by heritablePeriglandulafungi occur in some morning glories (Convolvulaceae), similar to ergot alkaloids in grasses infected with related fungi. Ergot alkaloids have been of longstanding interest given their toxic effects, psychoactive properties, and medical applications. Here we show that ergot alkaloids are concentrated in four morning glory clades exhibiting differences in alkaloid profiles and are more prevalent in species with larger seeds than those with smaller seeds. Further, we found a phylogenetically-independent, positive correlation between seed mass and alkaloid concentrations in symbiotic species. Our findings suggest that heritable symbiosis has diversified among particular clades by vertical transmission through seeds combined with host speciation, and that ergot alkaloids are particularly beneficial to species with larger seeds. Our results are consistent with the defensive symbiosis hypothesis where bioactive ergot alkaloids fromPeriglandulasymbionts protect seeds and seedlings from natural enemies, and provide a framework for exploring microbial chemistry in other plant-microbe interactions.
Electromagnetic response in spiral magnets and emergent inductance
Authors: Kurebayashi Daichi , Nagaosa Naoto 
Published: December 2021

AbstractEmergent electromagnetism in magnets originates from the strong coupling between conduction electron spins and those of noncollinear ordered moments and the consequent Berry phase. This offers possibilities to develop new functions of quantum transport and optical responses. The emergent inductance in spiral magnets is an example recently proposed and experimentally demonstrated, using the emergent electric field induced by alternating currents. However, the microscopic theory of this phenomenon is missing, which should reveal factors to determine the magnitude, sign, frequency dependence, and nonlinearity of the inductanceL. Here we theoretically study electromagnetic responses of spiral magnets by taking into account their collective modes. In sharp contrast to collinear spin-density wave, the system remains metallic even in one dimension, and the canonical conjugate relation of uniform magnetization and phason coordinate plays an essential role, determining the properties ofL. This result opens a way to design the emergent inductance of desired properties.
Rbec: a tool for analysis of amplicon sequencing data from synthetic microbial communities
Authors: Zhang Pengfan , Spaepen Stjin , Bai Yang , Hacquard Stephane , Garrido-Oter Ruben 
Published: December 2021

Abstract
Synthetic microbial communities (SynComs) constitute an emerging and powerful tool in biological, biomedical, and biotechnological research. Despite recent advances in algorithms for the analysis of culture-independent amplicon sequencing data from microbial communities, there is a lack of tools specifically designed for analyzing SynCom data, where reference sequences for each strain are available. Here we present Rbec, a tool designed for the analysis of SynCom data that accurately corrects PCR and sequencing errors in amplicon sequences and identifies intra-strain polymorphic variation. Extensive evaluation using mock bacterial and fungal communities show that our tool outperforms current methods for samples of varying complexity, diversity, and sequencing depth. Furthermore, Rbec also allows accurate detection of contaminants in SynCom experiments.
Adherence and sustainability of interventions informing optimal control against the COVID-19 pandemic
Authors: Di Domenico Laura , Sabbatini Chiara E. , Boëlle Pierre-Yves , Poletto Chiara , Crépey Pascal , Paireau Juliette , Cauchemez Simon , Beck François , Noel Harold , Lévy-Bruhl Daniel , Colizza Vittoria 
Published: December 2021

Abstract
Background
After one year of stop-and-go COVID-19 mitigation, in the spring of 2021 European countries still experienced sustained viral circulation due to the Alpha variant. As the prospect of entering a new pandemic phase through vaccination was drawing closer, a key challenge remained on how to balance the efficacy of long-lasting interventions and their impact on the quality of life.

Methods
Focusing on the third wave in France during spring 2021, we simulate intervention scenarios of varying intensity and duration, with potential waning of adherence over time, based on past mobility data and modeling estimates. We identify optimal strategies by balancing efficacy of interventions with a data-driven “distress” index, integrating intensity and duration of social distancing.

Results
We show that moderate interventions would require a much longer time to achieve the same result as high intensity lockdowns, with the additional risk of deteriorating control as adherence wanes. Shorter strict lockdowns are largely more effective than longer moderate lockdowns, for similar intermediate distress and infringement on individual freedom.

Conclusions
Our study shows that favoring milder interventions over more stringent short approaches on the basis of perceived acceptability could be detrimental in the long term, especially with waning adherence.