bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep molecular dreaming: inverse machine learning for de-novo molecular design and interpretability with surjective representations
Authors: Shen Cynthia , Krenn Mario , Eppel Sagi , Aspuru-Guzik Alán 
Published: June 2021

Abstract
Computer-based de-novo design of functional molecules is one of the most prominent challenges in cheminformatics today. As a result, generative and evolutionary inverse designs from the field of artificial intelligence have emerged at a rapid pace, with aims to optimize molecules for a particular chemical property. These models ‘indirectly’ explore the chemical space; by learning latent spaces, policies, and distributions, or by applying mutations on populations of molecules. However, the recent development of the SELFIES (Krenn 2020 Mach. Learn.: Sci. Technol.
1 045024) string representation of molecules, a surjective alternative to SMILES, have made possible other potential techniques. Based on SELFIES, we therefore propose PASITHEA, a direct gradient-based molecule optimization that applies inceptionism (Mordvintsev 2015) techniques from computer vision. PASITHEA exploits the use of gradients by directly reversing the learning process of a neural network, which is trained to predict real-valued chemical properties. Effectively, this forms an inverse regression model, which is capable of generating molecular variants optimized for a certain property. Although our results are preliminary, we observe a shift in distribution of a chosen property during inverse-training, a clear indication of PASITHEA’s viability. A striking property of inceptionism is that we can directly probe the model’s understanding of the chemical space on which it is trained. We expect that extending PASITHEA to larger datasets, molecules and more complex properties will lead to advances in the design of new functional molecules as well as the interpretation and explanation of machine learning models.
Hospital variation in sphincter-preservation rates in rectal cancer treatment: results of a population-based study in the Netherlands
Authors: Koëter T , de Nes L C F , Wasowicz D K , Zimmerman D D E , Verhoeven R H A , Elferink M A , de Wilt J H W 
Published: June 2021

Abstract

Background
This study aimed to examine the sphincter-preservation rate variations in rectal cancer surgery. The influence of hospital volume on sphincter-preservation rates and short-term outcomes (anastomotic leakage (AL), positive circumferential resection margin (CRM), 30- and 90-day mortality rates) were also analysed.

Methods
Non-metastasized rectal cancer patients treated between 2009 and 2016 were selected from the Netherlands Cancer Registry. Surgical procedures were divided into sphincter-preserving surgery and an end colostomy group. Multivariable logistic regression models were generated to estimate the probability of undergoing sphincter-preserving surgery according to the hospital of surgery and tumour height (low, 5 cm or less, mid, more than 5 cm to 10 cm, and high, more than 10 cm). The influence of annual hospital volume (less than 20, 20–39, more than 40 resections) on sphincter-preservation rate and short-term outcomes was also examined.

Results
A total of 20 959 patients were included (11 611 sphincter preservation and 8079 end colostomy) and the observed median sphincter-preservation rate in low, mid and high rectal cancer was 29.3, 75.6 and 87.9 per cent respectively. After case-mix adjustment, hospital of surgery was a significant factor for patients’ likelihood for sphincter preservation in all three subgroups (P &lt; 0.001). In mid rectal cancer, borderline higher rates of sphincter preservation were associated with low-volume hospitals (odds ratio 1.20, 95 per cent c.i. 1.01 to 1.43). No significant association between annual hospital volume and sphincter-preservation rate in low and high rectal cancer nor short-term outcomes (AL, positive CRM rate and 30- and 90-day mortality rates) was identified.

Conclusion
This population-based study showed a significant hospital variation in sphincter-preservation rates in rectal surgery. The annual hospital volume, however, was not associated with sphincter-preservation rates in low, and high rectal cancer nor with other short-term outcomes.
Determination of Phthalate Esters in Cosmetics and Baby Care Products by a Biosorbent Based on Lawsone Capped Chitosan and Followed by Liquid Chromatography
Authors: Samadi Fatemeh , Es’haghi Zarrin 
Published: June 2021

Abstract
This research presents a green synthetic pathway for the preparation of a new biosorbent and eco-friendly extraction process of three phthalate esters: dimethyl phthalate, di-butyl phthalate and benzyl butyl phthalate, from cosmetics and baby care products. Dispersive solid-phase extraction was used based on a new core-shell biomass/sorbent; chitosan-loaded lawsone. The proposed method provides fortunate trapping of phthalate esters in a one-step extraction. Under the optimized extraction conditions, the current work was presented low detection limits (0.03–0.15 ng. g−1), limits of quantification (0.1–0.5 ng·g−1) and reasonable linearity (0.1–10 000 ng. g−1). The applicability of the method was estimated by recovery experiments at different spiking levels (n = 5) for phthalate esters in the real samples.
Unraveling the acetals as ageing markers of Chinese Highland Qingke Baijiu using comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry combined with metabolomics approach
Authors: Wang Xinlei , Song Xuebo , Zhu Lin , Geng Xiaojie , Zheng Fuping , Zhao Qiangzhong , Sun Xiaotao , Zhao Dongrui , Feng Shengbao , Zhao Mouming , Sun Baoguo 
Published: June 2021

Abstract

Objectives
The ageing process has a significant impact on the aroma of Chinese Baijiu, which could strengthen the desirable flavor characteristics and reduce the undesirable ones. The aim of this study was to observe the initiation of meaningful changes in volatile fraction and locate the ageing markers during ageing storage of Chinese Highland Qingke Baijiu.

Materials and Methods
Samples of Chinese Qingke Baijiu were aged for 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 months before analysis. The samples were isolated by liquid–liquid extraction and then analyzed by comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry. The acquired data were processed by untargeted and targeted metabolomics approach to locate the ageing markers.

Results
The untargeted metabolomics analysis (hierarchical clustering analysis, HCA) shows that the chemical composition of Qingke Baijiu presents a statistically significant deviation from the reference scenario after 5 months. Subsequently, supervised statistics analysis (orthogonal partial least squares discrimination analysis) was performed to locate the markers, which changed significantly during ageing. Fifteen markers were located, and seven of them were acetals. Notably, 1,1-diethoxy-propane, 1,1-diethoxy-butane, and 1,1-diethoxy-3-methyl-butane are important contributors to the flavor of Chinese Baijiu. The identified markers were applied for the untargeted metabolomics (HCA), and the results revealed that these markers could divide the Qingke Baijiu into two ageing stages, 0–5 months and 6–11 months.

Conclusion
The results suggest that it is a valuable tool for monitoring the changes of volatile compounds and locating the age markers in Chinese Baijiu.
A novel mitigator of enzymatic browning—hawthorn leaf extract and its application in the preservation of fresh-cut potatoes
Authors: Qiao Liping , Wang Hailin , Shao Jinsheng , Lu Laifeng , Tian Jinhu , Liu Xia 
Published: June 2021

Abstract

Objectives
The purpose of this study was to evaluate the antibrowning functions of hawthorn leaf extract on fresh-cut potato and its possible mechanism.

Materials and Methods
Fresh-cut potatoes were treated with different concentrations (0.01%, 0.05%, and 0.1%) of hawthorn leaf extract and preserved at 4 ℃ for 8 days. The appearance and colour of potato slices were evaluated, along with the content of the phenol, malondialdehyde (MDA), and hydrogen peroxide (H2O2) during cold storage. Meanwhile, the activities of polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia-lyase (PAL), lipoxygenase (LOX), catalase (CAT), superoxide dismutase (SOD), and the antioxidant capacity were determined. Furthermore, the composition of hawthorn leaf extract was analyzed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS).

Results
The addition of hawthorn leaf extract effectively delayed the browning process. It not only enhanced the CAT activity and antioxidant capacity but also reduced the LOX activity and accumulation of MDA and H2O2. Meanwhile, the activities of PPO, POD, and PAL as well as the content of phenol were controlled. Additionally, 25 phenols, 34 flavonoids, and 5 proanthocyanidins were identified through high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), including caffeic acid, quercetin and catechol.

Conclusion
Hawthorn leaf extract significantly alleviated the browning of fresh-cut potato. It could serve as a natural antibrowning alternative by stabilizing the membrane and modulating reactive oxygen species and redox reactions.
Immunomodulatory Effect of Serum Exosomes From Crohn Disease on Macrophages via Let-7b-5p/TLR4 Signaling
Authors: Gong Lingqi , Xiao Jintao , Yi Jun , Xiao Junbo , Lu Fanggen , Liu Xiaowei 
Published: June 2021

Abstract

Background
Exosomes are extensively reported to be strongly associated with many immunologic diseases, including Crohn disease (CD). Meanwhile, the dysfunction of macrophage activation has been proposed to be critical for the pathogenesis of CD. However, it is an unsettled issue whether serum exosomes from CD could activate macrophages and participate in its pathogenesis. Our study intended to clarify the role of CD-derived exosomes on macrophages to elucidate a novel mechanism and possible diagnostic and therapeutic strategies.

Methods
Serum exosomes were isolated and identified. Functional assays in vitro were performed on Raw264.7 macrophages, followed by exosomal microRNA (miRNA) profiling and bioinformatics analyses via high-throughput sequencing. In animal experiments, exosomes were intraperitoneally injected into dextran sulfate sodium–induced colitis.

Results
In vitro CD-derived exosomes induced proinflammatory cytokine expression and increased macrophage counts. Meanwhile, the intervention of exosomes from CD with epithelial cells led to increased permeability of the intestinal epithelial barrier. In vivo, CD-derived exosomes could circulate into the intestinal mucosa and significantly aggravate colitis. Furthermore, CD changed the miRNA profile of exosomes and further analysis revealed a differential expression of let-7b-5p. Mechanistically, the let-7b-5p/TLR4 pathway was recognized as a potential contributor to macrophage activation and inflammatory response. Furthermore, serum exosome–mediated let-7b-5p mimic delivery alleviated colitis significantly.

Conclusions
Our study indicated that serum exosomes can circulate into the intestinal mucosa to aggravate colitis by regulating macrophage activation and epithelial barrier function. In addition, CD showed altered exosomal miRNA profiles. Furthermore, serum exosome–mediated let-7b-5p-mimic delivery may significantly alleviate colitis, providing potential novel insight into an exosome-based strategy for the diagnosis and treatment of CD.
Overview of the United States’ Immunization Program
Authors: Roper Lauren , Hall Mary Ann Kirkconnell , Cohn Amanda 
Published: June 2021

Abstract
This manuscript describes the history, background, and current structure of the United States Immunization Program, founded upon public- and private-sector partnerships that include federal agencies, state and local health departments, tribal nations and organizations, healthcare providers, vaccine manufacturers, pharmacies, and a multitude of additional stakeholders. The Centers for Disease Control and Prevention sets the U.S. adult and childhood immunization schedules based on recommendations from the Advisory Committee on Immunization Practices. We review the current immunization schedules; describe the set of surveillance and other systems used to monitor the health impact, coverage levels, and safety of recommended vaccines; and note significant challenges. Vaccines have reduced the incidence of many diseases to historic lows in the US, and have potential to further reduce the burden of respiratory and other infectious diseases in the United States. Though the United States vaccination program has had notable successes in reducing morbidity and mortality from infectious disease, challenges—including disparities in access and vaccine hesitancy—remain. Supporting access to and confidence in vaccines as an essential public health intervention will not only protect individuals from vaccine-preventable diseases; it will also ensure the country is prepared for the next pandemic.
Nasal Lavage Fluid as a Biomedical Sample for Verification of Chlorine Exposure
Authors: Lindén Pernilla , Jonasson Sofia , Hemström Petrus , Ålander Lovisa , Larsson Andreas , Ågren Lina , Elfsmark Linda , Åstot Crister 
Published: June 2021

Abstract
Chlorine is a toxic chemical that has been used as a chemical warfare agent in recent armed conflicts. There is an urgent need for methods to verify alleged uses of chlorine, and phospholipid chlorohydrins (PL-HOCl) derived from the pulmonary surfactant of exposed victims have previously been proposed as biomarkers of chlorine exposure. Here, we describe an improved protocol for the chemical analysis of these biomarkers and its applicability to biomedical samples from chlorine-exposed animals. By the use of a polymeric solid-phase-supported transesterification of PL-HOCl using ethanolamine, a common biomarker, oleoyl ethanolamide chlorohydrin (OEA-HOCl), was derived from all the diverse oleoyl PL-HOCl that may be formed by chlorine exposure. Compared to native lipid biomarkers, OEA-HOCl represents a larger biomarker pool and is better suited for nano-liquid chromatography--tandem mass spectrometry (nLC–MS-MS analysis), generating 3 amol Limit of Detection (LOD) and a reduced sample carry-over. With the improved protocol, significantly elevated levels of OEA-HOCl were identified in bronchoalveolar lavage fluid (BALF) of chlorine-exposed rats, 2–48 hours after exposure. The difficulty of BALF sampling from humans limits the methods usefulness as a verification tool of chlorine exposure. Conversely, nasal lavage fluid (NLF) is readily collected without advanced equipment. In NLF from chlorine-exposed rats, PL-HOCl were identified and significantly elevated levels of the OEA-HOCl biomarker were detected 2–24 hours after exposure. In order to test the potential of NLF as a biomedical sample for verification of human exposure to chlorine, in-vitro chlorination of human NLF samples was performed. All human in-vitro chlorinated NLF samples exhibited elevated OEA-HOCl biomarker levels, following sample derivatization. These data indicate the potential of human NLF as a biomedical sample for the verification of chlorine exposure, but further work is required to develop and validate the method for the use on real-world samples.
Physical and Psychological Recovery Following Toxic Epidermal Necrolysis: A Patient Survey
Authors: DeNiro Katherine L , Honari Shari , Hippe Dan S , Dai Andrea , Pham Tam N , Caceres Maria , Mandell Samuel P , Duong Phi Q , McMullen Kara A , Gibran Nicole S 
Published: June 2021

Abstract
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute, life-threatening diseases that cause sloughing of the skin and mucous membranes. Despite improved survival rates, few studies focus on long-term outcomes. We conducted a single-center review of all patients with SJS/TEN admitted from January 2008 to 2014. SJS/TEN survivors were invited to participate in the validated Veterans RAND 12-Item Health Survey (VR-12) to assess health-related quality of life using a mental health composite score and physical health component score (PCS). The sample was compared to U.S. norms using one-sample two-tailed t tests. A second questionnaire addressed potential long-term medical complications related to SJS/TEN. Of 81 treated subjects, 24 (30%) long-term survivors responded. Participants identified cutaneous sequelae most frequently (79%), followed by nail problems (70%), oral (62%), and ocular (58%) sequalae. Thirty-eight percent rated their quality of life to be “unchanged” to “much better” since their episode of SJS/TEN. The average PCS was lower than U.S. population norms (mean: 36 vs 50, P = .006), indicating persistent physical sequelae from SJS/TEN. These results suggest that SJS/TEN survivors continue to suffer from long-term complications that impair their quality of life and warrant ongoing follow-up by a multidisciplinary care team.
Molecular Monitoring of Knockdown Resistance in Head Louse (Phthiraptera: Pediculidae) Populations in Iran
Authors: Ghahvechi Khaligh Fereshteh , Djadid Navid Dinparast , Farmani Mostafa , Asadi Saatlou Zahra , Frooziyan Samira , Abedi Astaneh Fatemeh , Farnoosh Fariba , Sofizadeh Aioub , Naseri Firoozeh , Adib Delnia , Taheri Mohammad , Lalehzari Emran , Pashaei Shabnam , Soltanbeiglou Shadiyeh , Soltani Aboozar , Khooban Hassan , Abbasi Ebrahim , Aivazi Ali-Ashraf , Saeedi Samrand , Taghilou Behrooz , Jafari Abbas , Dashti Khavidak Kamal , Toloza Ariel C , Gholizadeh Saber 
Published: June 2021

Abstract
Knockdown resistance (kdr) is a common mechanism of insecticide resistance in head lice to the conventionally used pyrethroid pediculosis and can be the result of various amino acid substitutions within the voltage-sensitive sodium channel (VSSC). In this study, 54 sequences from varied specimens were investigated to monitor well-known resistance mutations and probable new mutations. The Pediculus humanus capitis de Geer specimens were collected from 13 provinces in Iran. The specimens were stored in 70% ethanol until DNA extraction and PCR amplification of ~900-bp fragment of VSSC. The sequences were analyzed using different bioinformatics software for the detection of well-known kdr substitutions and additional mutations potentially associated with kdr resistance in head lice. There were six new and an old (haplotype I) kdr haplotypes within the Iranian head louse population. K794E, F815I, and N818D amino acid substitutions were reported for the first time. The P813H mutation was the most prevalent amino acid substitution in eight provinces. Among 53 sequences, 26 (49%) were homozygous susceptible, and 27 (51%) were heterozygotes. Thus, 51% of the head lice collected in Iran harbored only the P813H allele. The exact test for the Hardy–Weinberg (H–W) equilibrium showed that genotype frequencies differed significantly from the expectation in East-Azerbaijan and Tehran provinces. Moreover, these populations had an inbreeding coefficient (Fis) &lt;0, indicating the excess of heterozygotes. This observation suggests that the populations of head lice from Iran are currently under active selective pressure. For the rest of the populations, H–W equilibrium and the expectations were significantly in harmony. The results of the current study highlight molecular techniques in the accurate detection of resistance genotypes before their establishment within the head louse population. Accurate detection of resistant genotypes seems to be helpful in decision-making on lice control programs and resistance monitoring and management.
Dominant roles but distinct effects of groundwater depth on regulating leaf and fine-root N, P and N:P ratios of plant communities
Authors: Wang Yin , Wang Jianming , Wang Xiaolin , He Yicheng , Li Guanjun , Li Jingwen 
Published: June 2021

AbstractAimsAs the determinant of water availability in drylands, groundwater plays a fundamental role in regulating vegetation distribution and ecosystem processes. Although considerable progress has been made over the past years in the relationship between environment stress and plant community-level traits, the potential influence of water stress induced by groundwater changes on plant community-level stoichiometry remains largely unclear. Here, we examined whether belowground and aboveground community-level stoichiometry responded differently to groundwater changes.MethodsWe measured nitrogen (N) and phosphorus (P) concentrations in plant leaves and fine-roots of 110 plots under a broad range of groundwater depths in a typical arid inland river basin. We examined the spatial patterns and drivers of community-level N:P stoichiometry in leaves and fine-roots.Important FindingsCommunity-level leaf and fine-root N, P and N:P ratios were mainly determined by groundwater, vegetation types and species composition, among which groundwater played a dominant role. Groundwater indirectly regulated community-level N:P stoichiometry through affecting vegetation types and species composition. Vegetation types and species composition had significant direct influences on community-level N:P stoichiometry. Furthermore, groundwater depth had opposite influences on community-level leaf and fine-root N:P stoichiometry. Groundwater depth regulated vegetation types and further decreased leaf N, P but increased leaf N:P ratios and fine-root N. Groundwater depth had a positive indirect impact on fine-root P but a negative indirect impact on fine-root N:P ratios primarily by affecting species composition. Our findings indicate that groundwater rather than climate conditions effectively regulates community-level N:P stoichiometry, and below- and aboveground N:P stoichiometry has opposite responses to groundwater.
Empirical comparison of genotoxic potency estimations: the in vitro DNA-damage ToxTracker endpoints versus the in vivo micronucleus assay
Authors: Wills John W , Halkes-Wellstead Elias , Summers Huw D , Rees Paul , Johnson George E 
Published: June 2021

Abstract
Genetic toxicology is an essential component of compound safety assessment. In the face of a barrage of new compounds, higher throughput, less ethically divisive in vitro approaches capable of effective, human-relevant hazard identification and prioritisation are increasingly important. One such approach is the ToxTracker assay, which utilises murine stem cell lines equipped with green fluorescent protein (GFP)-reporter gene constructs that each inform on distinct aspects of cellular perturbation. Encouragingly, ToxTracker has shown improved sensitivity and specificity for the detection of known in vivo genotoxicants when compared to existing ‘standard battery’ in vitro tests. At the current time however, quantitative genotoxic potency correlations between ToxTracker and well-recognised in vivo tests are not yet available. Here we use dose–response data from the three DNA-damage-focused ToxTracker endpoints and from the in vivo micronucleus assay to carry out quantitative, genotoxic potency estimations for a range of aromatic amine and alkylating agents using the benchmark dose (BMD) approach. This strategy, using both the exponential and the Hill BMD model families, was found to produce robust, visually intuitive and similarly ordered genotoxic potency rankings for 17 compounds across the BSCL2-GFP, RTKN-GFP and BTG2-GFP ToxTracker endpoints. Eleven compounds were similarly assessed using data from the in vivo micronucleus assay. Cross-systems genotoxic potency correlations for the eight matched compounds demonstrated in vitro–in vivo correlation, albeit with marked scatter across compounds. No evidence for distinct differences in the sensitivity of the three ToxTracker endpoints was found. The presented analyses show that quantitative potency determinations from in vitro data enable more than just qualitative screening and hazard identification in genetic toxicology.