bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to improve sustainability: an analysis of 120 microenterprises in an emerging economy
Authors: Pardo Martínez Clara Inés , Cotte Poveda Alexander 
Published: February 2022

Non-technical summarySmall and medium enterprises generate an elevated environmental footprint, which requires green transformation to achieve sustainable development. The purpose of this study is to describe the intervention process in 120 microenterprises with the aim of improving environmental and sustainability performance in four categories: sustainability, water, energy and solid waste management to determine the importance to promote the sustainability process in this sector as a key factor to contribute to the inclusion and sustainable development.Technical summaryGlobal small and medium enterprises (SMEs) represent 90% of global business, creating and maintaining 50% of employment, and in emerging economies, formal SMEs provide 40% of the national gross domestic product and the gap of productivity is approximately 7% of global gross domestic product with respect to large firms. This study analyses the strategies and possibilities to improve sustainability in 120 microenterprises. The project included five stages: the postulation, selection and enrolment; sustainability diagnosis; action plan formulation; the results of implementation and evaluation and the feedback on results. This study demonstrated the importance of integrating sustainability into the business to improve productivity, competitiveness and access to new markets; in many cases, the microentrepreneur is unaware of all possibilities offered by having environmentally friendly processes, which was shown with evidence throughout the study. Approximately 242 action plans were implemented, achieving multiple results that involved knowledge of processes and equipment of microenterprises to measure and improve their environmental performance. The findings of this study demonstrated that microenterprises require adequate support and financial programmes that should be designed and implemented by policymakers with the aim of strengthening this sector, decreasing poverty and promoting sustainable economic growth, environmentally friendly processes and development in developing countries.Social media summaryMicroenterprises have an important role in the economy and have the potential to achieve sustainability processes.
Quantifying the Fractal Dimension and Morphology of Individual Atmospheric Soot Aggregates
Authors: Pang Yuner , Wang Yuanyuan , Wang Zhicheng , Zhang Yinxiao , Liu Lei , Kong Shaofei , Liu Fengshan , Shi Zongbo , Li Weijun 
Published: February 2022

AbstractThe complex morphology of soot aggregates is a major source of uncertainty in evaluating their warming effects in the atmosphere. Fractal dimension (Df) is a key parameter in quantifying the morphology of soot particles. Previous studies are mostly based on manual identification of soot monomers in electron microscopic images and are hard to provide comparable results in determination of Df. Here we develop a novel image recognition technique to automatically determine the Df of individual soot aggregates from electron microscopy images. The novel method has been shown to be able to trace the small change of the soot Df from an urban tunnel (1.61 ± 0.19) to its exit (1.70 ± 0.15). By applying this new method, we show a substantial difference in average Df of soot particles emitted from vehicles (1.66 ± 0.17) than from biomass burning (1.75 ± 0.18) and coal burning (1.76 ± 0.18). Average Df of soot from an urban atmosphere (1.77 ± 0.18) is close to that from biomass and coal combustion but much lower than that from a rural atmosphere (1.85 ± 0.13). In summary, the new technique provides an automatic, accurate and reliable quantification of soot morphology Df, enabling an improved understanding of soot aging processes and a more accurate modeling of soot impact on their climate.
Subcutaneous adipose tissue expansion mechanisms are similar in early and late onset overweight/obesity
Authors: Arner Peter , Andersson Daniel P. , Arner Erik , Rydén Mikael , Kerr Alastair G. 
Published: February 2022

Abstract
Background/objective
The development of overweight/obesity associates with alterations in white adipose tissue (WAT) cellularity (fat cell size/number) and lipid metabolism, in particular lipolysis. If these changes differ between early/juvenile (EOO < 18 years of age) or late onset overweight/obesity (LOO) is unknown and was presently examined.

Subjects/methods
We included 439 subjects with validated information on body mass index (BMI) at 18 years of age. Using this information and current BMI, subjects were divided into never overweight/obese (BMI < 25 kg/m2), EOO and LOO. Adipocyte size, number, morphology (size in relation to body fat) and lipolysis were determined in subcutaneous abdominal WAT. Body composition and WAT distribution was assessed by dual-X-ray absorptiometry.

Results
Compared with never overweight/obese, EOO and LOO displayed larger WAT amounts in all examined depots, which in subcutaneous WAT was explained by a combination of increased size and number of fat cells in EOO and LOO. EOO had 40% larger subcutaneous fat mass than LOO (p < 0.0001). Visceral WAT mass, WAT morphology and lipolysis did not differ between EOO and LOO except for minor differences in men between the two obesity groups. On average, the increase in BMI per year was 57% higher in subjects with EOO compared to LOO (p < 0.0001).

Conclusion
Early onset overweight/obesity causes a more rapid and pronounced accumulation of subcutaneous WAT than adult onset. However, fat mass expansion measures including WAT cellularity, morphology and fat cell lipolysis do not differ in an important way suggesting that similar mechanisms of WAT growth operate in EOO and LOO.
Association of perinatal sentinel events, placental pathology and cerebral MRI in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia
Authors: Hellwig Lia , Brada Muriel , Held Ulrike , Hagmann Cornelia , Bode Peter , Frontzek Karl , Frey Bernhard , Brotschi Barbara , Grass Beate 
Published: February 2022

AbstractObjectivePlacental pathology might provide information on the etiology of hypoxic-ischemic encephalopathy (HIE). To evaluate the association of perinatal sentinel events (PSE), placental pathology and cerebral MRI in cooled neonates with moderate/severe HIE.Study designRetrospective analysis of 52 neonates with HIE registered in the Swiss National Asphyxia and Cooling Register 2011–2019. PSE and Non-PSE groups were tested for association with placental pathology. Placental pathology categories were correlated with MRI scores.ResultsIn total, 14/52 neonates (27%) had a PSE, 38 neonates (73%) did not have a PSE. There was no evidence for an association of occurrence of PSE and placental pathologies (p = 0.364). Neonates with high MRI scores tended to have more often chronic pathologies in their placentas than acute pathologies or normal placentas (p = 0.067).ConclusionIndependent of the occurrence of PSE, chronic placental pathologies might be associated with more severe brain injury and needs further study.
Biomarkers of response to PD-1 pathway blockade
Authors: Li Hanxiao , van der Merwe P. Anton , Sivakumar Shivan 
Published: February 2022

AbstractThe binding of T cell immune checkpoint proteins programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to their ligands allows immune evasion by tumours. The development of therapeutic antibodies, termed checkpoint inhibitors, that bind these molecules or their ligands, has provided a means to release this brake on the host anti-tumour immune response. However, these drugs are costly, are associated with potentially severe side effects, and only benefit a small subset of patients. It is therefore important to identify biomarkers that discriminate between responders and non-responders. This review discusses the determinants for a successful response to antibodies that bind PD-1 or its ligand PD-L1, dividing them into markers found in the tumour biopsy and those in non-tumour samples. It provides an update on the established predictive biomarkers (tumour PD-L1 expression, tumour mismatch repair deficiency and tumour mutational burden) and assesses the evidence for new potential biomarkers.
Ultrafast infrared nano-imaging of far-from-equilibrium carrier and vibrational dynamics
Authors: Nishida Jun , Johnson Samuel C. , Chang Peter T. S. , Wharton Dylan M. , Dönges Sven A. , Khatib Omar , Raschke Markus B. 
Published: February 2022

AbstractUltrafast infrared nano-imaging has demonstrated access to ultrafast carrier dynamics on the nanoscale in semiconductor, correlated-electron, or polaritonic materials. However, mostly limited to short-lived transient states, the contrast obtained has remained insufficient to probe important long-lived excitations, which arise from many-body interactions induced by strong perturbation among carriers, lattice phonons, or molecular vibrations. Here, we demonstrate ultrafast infrared nano-imaging based on excitation modulation and sideband detection to characterize electron and vibration dynamics with nano- to micro-second lifetimes. As an exemplary application to quantum materials, in phase-resolved ultrafast nano-imaging of the photoinduced insulator-to-metal transition in vanadium dioxide, a distinct transient nano-domain behavior is quantified. In another application to lead halide perovskites, transient vibrational nano-FTIR spatially resolves the excited-state polaron-cation coupling underlying the photovoltaic response. These examples show how heterodyne pump-probe nano-spectroscopy with low-repetition excitation extends ultrafast infrared nano-imaging to probe elementary processes in quantum and molecular materials in space and time.
Bacterial N4-methylcytosine as an epigenetic mark in eukaryotic DNA
Authors: Rodriguez Fernando , Yushenova Irina A. , DiCorpo Daniel , Arkhipova Irina R. 
Published: February 2022

AbstractDNA modifications are used to regulate gene expression and defend against invading genetic elements. In eukaryotes, modifications predominantly involve C5-methylcytosine (5mC) and occasionally N6-methyladenine (6mA), while bacteria frequently use N4-methylcytosine (4mC) in addition to 5mC and 6mA. Here we report that 4mC can serve as an epigenetic mark in eukaryotes. Bdelloid rotifers, tiny freshwater invertebrates with transposon-poor genomes rich in foreign genes, lack canonical eukaryotic C5-methyltransferases for 5mC addition, but encode an amino-methyltransferase, N4CMT, captured from bacteria >60 Mya. N4CMT deposits 4mC at active transposons and certain tandem repeats, and fusion to a chromodomain shapes its “histone-read-DNA-write” architecture recognizing silent chromatin marks. Furthermore, amplification of SETDB1 H3K9me3 histone methyltransferases yields variants preferentially binding 4mC-DNA, suggesting “DNA-read-histone-write” partnership to maintain chromatin-based silencing. Our results show how non-native DNA methyl groups can reshape epigenetic systems to silence transposons and demonstrate the potential of horizontal gene transfer to drive regulatory innovation in eukaryotes.
Atomic structure evolution related to the Invar effect in Fe-based bulk metallic glasses
Authors: Firlus Alexander , Stoica Mihai , Michalik Stefan , Schäublin Robin E. , Löffler Jörg F. 
Published: February 2022

AbstractThe Invar effect is universally observed in Fe-based bulk metallic glasses. However, there is limited understanding on how this effect manifests at the atomic scale. Here, we use in-situ synchrotron-based high-energy X-ray diffraction to study the structural transformations of (Fe71.2B24Y4.8)96Nb4 and (Fe73.2B22Y4.8)95Mo5 bulk metallic glasses around the Curie temperature to understand the Invar effect they exhibit. The first two diffraction peaks shift in accordance with the macroscopically measured thermal expansion, which reveals the Invar effect. Additionally, the nearest-neighbor Fe–Fe pair distance correlates well with the macroscopic thermal expansion. In-situ X-ray diffraction is thus able to elucidate the Invar effect in Fe-based metallic glasses at the atomic scale. Here, we find that the Invar effect is not just a macroscopic effect but has a clear atomistic equivalent in the average Fe–Fe pair distance and also shows itself in higher-order atomic shells composed of multiple atom species.
Leveraging the multivalent p53 peptide-MdmX interaction to guide the improvement of small molecule inhibitors
Authors: Cheng Xiyao , Chen Rong , Zhou Ting , Zhang Bailing , Li Zichun , Gao Meng , Huang Yongqi , Liu Huili , Su Zhengding 
Published: February 2022

AbstractOverexpressed Mdm2 and its 7homolog MdmX impair p53 activity in many cancers. Small molecules mimicking a p53 peptide can effectively inhibit Mdm2 but not MdmX. Here, we show a strategy for improving lead compounds for Mdm2 and MdmX inhibition based on the multivalency of the p53 peptide. Crystal structures of MdmX complexed with nutlin-3a, a strong Mdm2 inhibitor but a weak one for MdmX, reveal that nutlin-3a fits into the ligand binding pocket of MdmX mimicking the p53 peptide. However, due to distinct flexibility around the MdmX ligand binding pocket, the structures are missing many important intermolecular interactions that exist in the MdmX/p53 peptide and Mdm2/nultin-3a complexes. By targeting these flexible regions, we identify allosteric and additive fragments that enhance the binding affinity of nutlin-3a for MdmX, leading to potent Mdm2/MdmX inhibitors with anticancer activity. Our work provides a practical approach to drug design for signal transduction therapy.
Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma
Authors: Lee Karla A. , Thomas Andrew Maltez , Bolte Laura A. , Björk Johannes R. , de Ruijter Laura Kist , Armanini Federica , Asnicar Francesco , Blanco-Miguez Aitor , Board Ruth , Calbet-Llopart Neus , Derosa Lisa , Dhomen Nathalie , Brooks Kelly , Harland Mark , Harries Mark , Leeming Emily R. , Lorigan Paul , Manghi Paolo , Marais Richard , Newton-Bishop Julia , Nezi Luigi , Pinto Federica , Potrony Miriam , Puig Susana , Serra-Bellver Patricio , Shaw Heather M. , Tamburini Sabrina , Valpione Sara , Vijay Amrita , Waldron Levi , Zitvogel Laurence , Zolfo Moreno , de Vries Elisabeth G. E. , Nathan Paul , Fehrmann Rudolf S. N. , Bataille Véronique , Hospers Geke A. P. , Spector Tim D. , Weersma Rinse K. , Segata Nicola 
Published: February 2022

AbstractThe composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course.
The microstructure and the origin of the Venus from Willendorf
Authors: Weber Gerhard W. , Lukeneder Alexander , Harzhauser Mathias , Mitteroecker Philipp , Wurm Lisa , Hollaus Lisa-Maria , Kainz Sarah , Haack Fabian , Antl-Weiser Walpurga , Kern Anton 
Published: February 2022

AbstractThe origin and key details of the making of the ~ 30,000 year old Venus from Willendorf remained a secret since its discovery for more than a hundred years. Based on new micro-computed tomography scans with a resolution of 11.5 µm, our analyses can explain the origin as well as the choice of material and particular surface features. It allowed the identification of internal structure properties and a chronological assignment of the Venus oolite to the Mesozoic. Sampling numerous oolite occurrences ranging ~ 2500 km from France to the Ukraine, we found a strikingly close match for grain size distribution near Lake Garda in the Southern Alps (Italy). This might indicate considerable mobility of Gravettian people and long-time transport of artefacts from South to North by modern human groups before the Last Glacial Maximum.
Large university with high COVID-19 incidence is not associated with excess cases in non-student population
Authors: Bharti Nita , Lambert Brian , Exten Cara , Faust Christina , Ferrari Matthew , Robinson Anthony 
Published: February 2022

AbstractLarge US colleges and universities that re-opened campuses in the fall of 2020 and the spring of 2021 experienced high per capita rates of COVID-19. Returns to campus were controversial because they posed a potential risk to surrounding communities. A large university in Pennsylvania that returned to in-person instruction for Fall 2020 and Spring 2021 semesters reported high incidence of COVID-19 among students. However, the co-located non-student resident population in the county experienced fewer COVID-19 cases per capita than reported in neighboring counties. Activity patterns from mobile devices indicate that the non-student resident population near the university restricted their movements during the pandemic more than residents of neighboring counties. Respiratory virus prevention and management in student and non-student populations requires different, specifically targeted strategies.
External quality assessment of HIV-1 DNA quantification assays used in the clinical setting in Italy
Authors: Vicenti Ilaria , Dragoni Filippo , Giannini Alessia , Casabianca Anna , Lombardi Francesca , Di Sante Laura , Turriziani Ombretta , Racca Sara , Paolucci Stefania , Lai Alessia , Bon Isabella , Abbate Isabella , Rozera Gabriella , Belmonti Simone , Scutari Rossana , Alteri Claudia , Saladini Francesco , Zazzi Maurizio ,   Italian HIV DNA Network, Orlandi Chiara , Magnani Mauro , Di Giambenedetto Simona , Longo Roberta , Menzo Stefano , Di Carlo Daniele , Mazzuti Laura , Ardemagni Anna , Clementi Massimo , Baldanti Fausto , Giardina Federica , Bergna Annalisa , Balotta Claudia , Bertoldi Alessia , Capobianchi Maria Rosaria , Ceccherini-Silberstein Francesca , Antonello Maria , Perno Carlo Federico , Andreoni Massimo 
Published: February 2022

AbstractTotal cell-associated HIV-1 DNA is a surrogate marker of the HIV-1 reservoir, however, certified systems for its quantification are not available. The Italian HIV DNA Network was launched to validate HIV-1 DNA quantification methods in use at University and Hospital labs. A quality control panel including HIV-1 DNA standards, reconstructed blood samples (RBSs) and DNA from different HIV-1 subtypes was blindly tested by 12 participating labs by quantitative real-time PCR (n = 6), droplet digital PCR (n = 3) or both (n = 3). The median 95% hit rate was 4.6 (3.7–5.5) copies per test and linearity in the tested range was excellent (R2 = 1.000 [1.000–1.000]). The median values obtained across labs were 3,370 (2,287–4,245), 445 (299–498), 59 (40–81) and 7 (6–11) HIV-1 DNA copies, for the 3,584, 448, 56 and 7-copy standards, respectively. With RBSs, measured values were within twofold with respect to the median in two thirds of cases. HIV-1 subtypes were missed (CRF01_AE by 3 labs) or underestimated by > 1 log (subtypes A, C, D, F by one lab; CRF01_AE by one lab; CRF02_AG by one lab). The overall performance was excellent with HIV-1 DNA standards, however detection of different HIV-1 subtypes must be improved.
Contrasting assembly mechanisms and drivers of soil rare and abundant bacterial communities in 22-year continuous and non-continuous cropping systems
Authors: Su Yan , Hu Yanxia , Zi Haiyun , Chen Yi , Deng Xiaopeng , Hu Binbin , Jiang Yonglei 
Published: February 2022

AbstractDespite many studies on the influence of cropping practices on soil microbial community structure, little is known about ecological patterns of rare and abundant microbial communities in response to different tobacco cropping systems. Here, using the high-throughput sequencing technique, we investigated the impacts of two different cropping systems on soil biochemical properties and the microbial community composition of abundant and rare taxa and its driving factors in continuous and rotational tobacco cropping systems in the mountain lands of Yunnan, China. Our results showed that distinct co-occurrence patterns and driving forces for abundant and rare taxa across the different cropping systems. The abundant taxa were mainly constrained by stochastic processes in both cropping systems. In contrast, rare taxa in continuous cropping fields were mainly influenced by environmental perturbation (cropping practice), while governed by deterministic processes under rotational cropping. The α-diversity indices of rare taxa tended to be higher than those of the abundant ones in the two cropping systems. Furthermore, the network topologies of rare taxa were more complex than those of the abundant taxa in the two cropping systems. These results highlight that rare taxa rather than abundant ones play important roles in maintaining ecosystem diversity and sustaining the stability of ecosystem functions, especially in continuous cropping systems.
Tumor RNA transfected DCs derived from iPS cells elicit cytotoxicity against cancer cells induced from colorectal cancer patients in vitro
Authors: Maruoka Shimpei , Ojima Toshiyasu , Iwamoto Hiromitsu , Kitadani Junya , Tabata Hirotaka , Tominaga Shinta , Katsuda Masahiro , Hayata Keiji , Takeuchi Akihiro , Yamaue Hiroki 
Published: February 2022

AbstractSignificant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC vaccine, we transfected patient-derived iPSDCs with in vitro transcriptional RNA (ivtRNA), which was obtained from tumors of three patients with colorectal cancer. We investigated iPSDCs-ivtRNA which were induced by transfecting ivtRNA obtained from tumors of three colorectal cancer patients, and examined its antitumor effect. Moreover, we analyzed neoantigens expressed in colorectal cancer cells and examined whether iPSDCs-ivtRNA induced cytotoxic T lymphocytes (CTLs) against the predicted neoantigens. CTLs activated by iPSDCs-ivtRNA exhibited cytotoxic activity against the tumor spheroids in all three patients with colorectal cancer. Whole-exome sequencing revealed 1251 nonsynonymous mutations and 2155 neoantigens (IC50 < 500 nM) were predicted. For IFN-γ ELISPOT assay, these candidate neoantigens were further prioritised and 12 candidates were synthesized. IFN-γ ELISPOT assay revealed that the CTLs induced by iPSDCs-ivtRNA responded to one of the candidate neoantigens. In vitro CTLs obtained by transfecting tumor-derived RNA into iPSDCs derived from three patients with colorectal cancer showed potent tumor-specific killing effect.