bluuebunny/crossref_metadata_2025 huggingface dataset:
Terahertz metalens of hyper-dispersion
Authors: Zhao Fen , Li Ziping , Li Sheng , Dai Xuemei , Zhou Yi , Liao Xiaoyu , Cao J. C. , Liang Gaofeng , Shang Zhengguo , Zhang Zhihai , Wen Zhongquan , Li Hua , Chen Gang
Published: February 2022

Chromatic optical lenses have promising applications in three-dimensional imaging, which allows fast spectral tomography without mechanical moving parts. The scanning range of current chromatic optical lenses is limited by their dispersion ability. The recent development in metasurfaces provides ideal blocks for optical wavefront manipulation and dispersion engineering of artificial materials at sub-wavelength scales. Hyper-dispersive metalenses can be realized by utilizing dispersive meta-atoms, which have enhanced dispersion compared to regular diffractive lenses. This is critical for increasing the imaging depth of fast spectral tomography. In this work, a hyper-dispersive metalens is realized with a chromatic dispersion 1.76 times greater than that of a regular diffractive metalens in the THz frequency range of 2.40–2.61 THz by simultaneously controlling the frequency-dependent phase, group delay (GD), and GD dispersion of the metalens. This approach can also be extended to other optical spectra and improve the performance of spectral tomography.
Octave-spanning microcomb generation in 4H-silicon-carbide-on-insulator photonics platform
Authors: Cai Lutong , Li Jingwei , Wang Ruixuan , Li Qing
Published: February 2022

Silicon carbide has recently emerged as a promising photonics material due to its unique properties, including possessing strong second- and third-order nonlinear coefficients and hosting various color centers that can be utilized for a wealth of quantum applications. Here, we report the design and demonstration of octave-spanning microcombs in a 4H-silicon-carbide-on-insulator platform for the first time, to our knowledge. Such broadband operation is enabled by optimized nanofabrication achieving

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million intrinsic quality factors in a 36-μm-radius microring resonator, and careful dispersion engineering by investigating the dispersion properties of different mode families. For example, for the fundamental transverse-electric mode whose dispersion can be tailored by simply varying the microring waveguide width, we realized a microcomb spectrum covering the wavelength range from 1100 nm to 2400 nm with an on-chip power near 120 mW. While the observed comb state is verified to be chaotic and not soliton, attaining such a large bandwidth is a crucial step towards realizing

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self-referencing. In addition, we also observed a coherent soliton-crystal state for the fundamental transverse-magnetic mode, which exhibits stronger dispersion than the fundamental transverse-electric mode and hence a narrower bandwidth.
Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens
Authors: Naung Myo T. , Martin Elijah , Munro Jacob , Mehra Somya , Guy Andrew J. , Laman Moses , Harrison G. L. Abby , Tavul Livingstone , Hetzel Manuel , Kwiatkowski Dominic , Mueller Ivo , Bahlo Melanie , Barry Alyssa E.
Published: February 2022

Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite,Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens ofP.falciparumusing the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene ‘haplotypes’ from the global dataset and a new R-package namedVaxPackwas used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens includingcsp,trap,eba175,ama1,rh5, andCelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity ofP.falciparumantigens to be considered in the design of the next generation of malaria vaccines.
RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins
Authors: Sanchez-Burgos Ignacio , Espinosa Jorge R. , Joseph Jerelle A. , Collepardo-Guevara Rosana
Published: February 2022

Biomolecular condensates formed via liquid–liquid phase separation (LLPS) play a crucial role in the spatiotemporal organization of the cell material. Nucleic acids can act as critical modulators in the stability of these protein condensates. To unveil the role of RNA length in regulating the stability of RNA binding protein (RBP) condensates, we present a multiscale computational strategy that exploits the advantages of a sequence-dependent coarse-grained representation of proteins and a minimal coarse-grained model wherein proteins are described as patchy colloids. We find that for a constant nucleotide/protein ratio, the protein fused in sarcoma (FUS), which can phase separate on its own—i.e., via homotypic interactions—only exhibits a mild dependency on the RNA strand length. In contrast, the 25-repeat proline-arginine peptide (PR25), which does not undergo LLPS on its own at physiological conditions but instead exhibits complex coacervation with RNA—i.e., via heterotypic interactions—shows a strong dependence on the length of the RNA strands. Our minimal patchy particle simulations suggest that the strikingly different effect of RNA length on homotypic LLPS versus RBP–RNA complex coacervation is general. Phase separation is RNA-length dependent whenever the relative contribution of heterotypic interactions sustaining LLPS is comparable or higher than those stemming from protein homotypic interactions. Taken together, our results contribute to illuminate the intricate physicochemical mechanisms that influence the stability of RBP condensates through RNA inclusion.
Flux balance analysis of the ammonia-oxidizing bacterium Nitrosomonas europaea ATCC19718 unravels specific metabolic activities while degrading toxic compounds
Authors: Canto-Encalada Gabriela , Tec-Campos Diego , Tibocha-Bonilla Juan D. , Zengler Karsten , Zepeda Alejandro , Zuñiga Cristal
Published: February 2022

The ammonia-oxidizing bacteriumNitrosomonas europaeahas been widely recognized as an important player in the nitrogen cycle as well as one of the most abundant members in microbial communities for the treatment of industrial or sewage wastewater. Its natural metabolic versatility and extraordinary ability to degrade environmental pollutants (e.g., aromatic hydrocarbons such as benzene and toluene) enable it to thrive under various harsh environmental conditions. Constraint-based metabolic models constructed from genome sequences enable quantitative insight into the central and specialized metabolism within a target organism. These genome-scale models have been utilized to understand, optimize, and design new strategies for improved bioprocesses. Reduced modeling approaches have been used to elucidateNitrosomonas europaeametabolism at a pathway level. However, genome-scale knowledge about the simultaneous oxidation of ammonia and pollutant metabolism ofN.europaearemains limited. Here, we describe the reconstruction, manual curation, and validation of the genome-scale metabolic model forN.europaea,iGC535. This reconstruction is the most accurate metabolic model for a nitrifying organism to date, reaching an average prediction accuracy of over 90% under several growth conditions. The manually curated model can predict phenotypes under chemolithotrophic and chemolithoorganotrophic conditions while oxidating methane and wastewater pollutants. Calculated flux distributions under different trophic conditions show that several key pathways are affected by the type of carbon source available, including central carbon metabolism and energy production.
Identification of potential functional variants and genes at 18q21.1 associated with the carcinogenesis of colorectal cancer
Authors: Cheng Xiaoqing , Zhang Fenglan , Gong Jingwen , Li Yige , Zhou Dan , Wang Jing , Vong Eu Gene , Yuan Ying , Lai Maode , Zhang Dandan
Published: February 2022

Genome-wide association studies (GWAS) have identified more than 160 susceptibility loci for colorectal cancer (CRC). The effects of these variants, particularly their mechanisms, however, remain unclear. In this study, a comprehensive functional annotation of CRC-related GWAS signals was firstly conducted to identify the potential causal variants. We found that the SNP rs7229639 in intron 3 of SMAD7 at 18q21.1 might serve as a putative functional variant in CRC. The SNP rs7229639 is located in a region with evidence of regulatory potential. Dual-luciferase reporter assays revealed that three other SNPs (rs77544449, rs60385309 and rs72917785), in strong linkage disequilibrium (LD) with rs7229639, exhibited allele-specific enhancer activity, of which one of the target genes may conceivably be LIPG, as suggested by eQTL association data and Hi-C data. We also verified that LIPG promoted malignancy of CRC cells in vitro, with supporting clinical data indicating that LIPG is upregulated and correlated with a poor prognosis in CRC. Finally, pitavastatin was observed to exhibit an anti-CRC activity and modest inhibition of LIPG mRNA levels. Collectively, our data suggest that these functional variants at 18q21.1 are involved in the pathogenesis of CRC by modulating enhancer activity, and possibly LIPG expression, thus indicating a promising therapeutic target for CRC. The results of functional annotation in our investigation could also serve as an inventory for CRC susceptibility SNPs and offer guides for post-GWAS downstream functional studies.
Seroepidemiologic evidence of Q fever and associated factors among workers in veterinary service laboratory in South Korea
Authors: Acharya Dilaram , Park Ji-Hyuk , Chun Jeong-Hoon , Kim Mi Yeon , Yoo Seok-Ju , Lewin Antoine , Lee Kwan
Published: February 2022

The incidence of Q fever has rapidly increased in South Korea since 2015. This study was undertaken to investigate the seroprevalence and seroreactivity of Q fever and the risk factors associated with its seroprevalence among workers in the veterinary service laboratory (VSL) in South Korea. This seroepidemiologic study was conducted in a total of 661 human subjects out of 1,328 subjects working in 50 VSL existing in South Korea between July 15 and July 29, 2019. Data were collected by administering survey questionnaires and by analyzing collected blood samples to determine the presence of antibodies against Coxiella burnetii. The seroprevalence and seroreactivity of C. burnetii infection were determined based on serum titers as (phase II IgG ≥1:256 and/or IgM ≥1:16) and (phase II IgG ≥1:16 and/or IgM ≥1:16) as determined by indirect immunofluorescent assay. Work, work environment, behavioral risk and protective factors associated with seroprevalence of Q fever were assessed by employing multivariable logistic regression analysis. Among the 661, the seroprevalence and seroreactivity of C. burnetii infection were 7.9% and 16.0%, respectively. Multivariate logistic regression analysis showed the risk factors significantly associated with seroprevalence were the antemortem inspection of cattle, goats, or sheep (APR (adjusted prevalence ratio), 2.52; 95% CI, 1.23–4.70)), animal blood splashed into or around eyes (APR, 2.24; 95% CI, 1.04–4.41), and contact with animals having Q fever (APR, 6.58; 95% CI, 3.39–10.85) during the previous year. This study suggests the need for precautions when contact with cattle, goats, or sheep is expected, especially during the antemortem inspection, when dealing with C. burnetii infected animals, or when there is a risk of ocular contact with animal derivatives. Therefore, we recommend the consistent use of appropriate personal protective equipment and other protective measures including PPE treatment and washing of body surfaces after work to prevent C. burnetii infections among VSL staff in South Korea.
Quantifying the inhibitory impact of soluble phenolics on anaerobic carbon mineralization in a thawing permafrost peatland
Authors: Cory Alexandra B. , Chanton Jeffrey P. , Spencer Robert G. M. , Ogles Olivia C. , Rich Virginia I. , McCalley Carmody K. ,   IsoGenie Project Coordinators,   EMERGE 2021 Field Team, Wilson Rachel M.
Published: February 2022

The mechanisms controlling the extraordinarily slow carbon (C) mineralization rates characteristic ofSphagnum-rich peatlands (“bogs”) are not fully understood, despite decades of research on this topic. Soluble phenolic compounds have been invoked as potentially significant contributors to bog peat recalcitrance due to their affinity to slow microbial metabolism and cell growth. Despite this potentially significant role, the effects of soluble phenolic compounds on bog peat C mineralization remain unclear. We analyzed this effect by manipulating the concentration of free soluble phenolics in anaerobic bog and fen peat incubations using water-soluble polyvinylpyrrolidone (“PVP”), a compound that binds with and inactivates phenolics, preventing phenolic-enzyme interactions. CO2and CH4production rates (end-products of anaerobic C mineralization) generally correlated positively with PVP concentration following Michaelis-Menten (M.M.) saturation functions. Using M.M. parameters, we estimated that the extent to which phenolics inhibit anaerobic CO2production was significantly higher in the bog—62 ± 16%—than the fen—14 ± 4%. This difference was found to be more substantial with regards to methane production—wherein phenolic inhibition for the bog was estimated at 54 ± 19%, while the fen demonstrated no apparent inhibition. Consistent with this habitat difference, we observed significantly higher soluble phenolic content in bog vs. fen pore-water. Together, these findings suggest that soluble phenolics could contribute to bogs’ extraordinary recalcitrance and high (relative to other peatland habitats) CO2:CH4production ratios.
High temporal resolution measurements of movement reveal novel early-life physiological decline in C. elegans
Authors: Sinha Drew Benjamin , Pincus Zachary Scott
Published: February 2022

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, many studies of movement vs. age generally focus on three distinct phases: sustained, youthful movement; onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is a sustained “healthy” level of high function followed by a discrete “movement catastrophe”—or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed isolated individuals throughout life with a previously unachieved combination of duration and temporal resolution. By tracking individuals across the first six days of adulthood, we observed declines in movement starting as early as the first two days of adult life, as well as high interindividual variability in total daily movement. These findings suggest that movement is a highly dynamic behavior early in life, and that factors driving movement decline may begin acting as early as the first day of adulthood. Using simulation studies based on acquired data, we suggest that too-infrequent sampling in common movement assays limits observation of early-adult changes in motility, and we propose feasible strategies and a framework for designing assays with increased sensitivity for early movement declines.
Prevalence of neural tube defects at Debre Berhan Referral Hospital, North Shewa, Ethiopia. A hospital based retrospective cross-section study
Authors: Kindie Zerihun , Mulu Abay
Published: February 2022

Background

Neural tube defect (NTD) is a structural defect of the central nervous system of the developing embryo during the first month of developmental process. Most congenital malformations are potentially preventable cause of perinatal morbidity and mortality. Worldwide, around 10% of infant mortalities are due to nervous system defects. In Ethiopia there are limited published data regarding the prevalence and established preventive strategy of NTDs. The purpose of this study was to assess the prevalence of NTDs among pregnancy outcomes in Debre Berhan Referral Hospital (DBRH), Ethiopia.

Methods

Hospital based retrospective cross sectional, descriptive study was conducted on registration of all pregnancy outcomes from August 30, 2017 to August 30, 2019 at DBRH, Ethiopia. The collected data were checked for completeness and consistencies, and cleaned, coded and entered using Epi data version 4.2 and exported to Statistical Package for Social Sciences (SPSS) software version 20 for analysis. Variables were interpreted per 1000 pregnancies and those variables having p<0.05 was considered as statistically significant.

Results

The total prevalence of NTDs was 10.9 (95% CI 8.9 to 13.3) per 1000 pregnancies and the prevalence of each NTD type was anencephaly 5.6 (95% CI 4.2 to 7.4) per 1000 pregnancies, spina bifida 3.5 (95% CI 2.4 to 4.9) per 1000 pregnancies, encephalocele 1.1 (95% CI 0.6 to 2.0) per 1000 pregnancies, and both spina bifida and anencephaly 0.7(95% CI 0.3 to 1.4) per 1000 pregnancies. Among livebirths, aborted, stillbirths and medically terminated pregnancies (n = 8862), there were 50 anencephaly cases, 31 spina bifida cases, 10 encephalocele cases, and 6 cases affected by both spina bifida and anencephaly.

Conclusion

The prevalence of NTDs in this study was among the highest globally reported. The total prevalence was 10.9 per 1000 pregnancies. Increased periconceptional folic acid use, counseling for women with certain medical illnesses at higher risk for NTDs, and early maternal screening for genetic factors are possible approaches to reduce in NTDs in the population.
mRNA Covid-19 vaccines in pregnancy: A systematic review
Authors: Pratama Nando Reza , Wafa Ifan Ali , Budi David Setyo , Putra Manesha , Wardhana Manggala Pasca , Wungu Citrawati Dyah Kencono
Published: February 2022

Objective

Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses.

Methods

Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20–22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described.

Results

There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer–BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio.

Conclusions

The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed.

Systematic review registration

PROSPERO (CRD42021261684).
Predictors of lower limb fractures in general Japanese: NIPPON DATA90
Authors: Saito Yoshino , Miura Katsuyuki , Arima Hisatomi , Hayakawa Takehito , Takashima Naoyuki , Kita Yoshikuni , Okuda Nagako , Fujiyoshi Akira , Iwahori Toshiyuki , Miyagawa Naoko , Kondo Keiko , Torii Sayuki , Kadota Aya , Ohkubo Takayoshi , Okayama Akira , Okamura Tomonori , Ueshima Hirotsugu ,   for the NIPPON DATA90 Research Group
Published: February 2022

Objective

This study aimed to investigate the incidence rates and predictors of lower limb fractures in a general Japanese population.

Methods

NIPPON DATA is a nationwide, long-term, prospective cohort study of individuals who participated in the National Cardiovascular Survey Japan and the National Nutrition Survey in 1990. Overall, 3,134 individuals (1,827 women, 1,307 men) who participated in follow-up assessments in 1995, 2000, and/or 2006 were included in the present analysis. The outcomes of this study were lower limb fractures (including proximal femur fractures).

Results

The mean age at baseline was 63.8 years in women and 63.1 years in men. The average body mass index (BMI) was 23.3 kg/m2 in women and 22.9 kg/m2 in men. During a mean follow-up of 12.1 years, 271 total lower limb fractures were observed. In women, older age, lower BMI, and less intake of vegetables were associated with increased risks of proximal femur fractures. With regard to the outcome of total lower limb fractures, less intake of vegetables and regular exercise were significant predictors in women. Calcium intake was not significantly associated with proximal femur or total lower limb fractures. There were no significant predictors of proximal femur or total lower limb fractures in men, except for age.

Conclusions

Aging was a significant risk factor for proximal femur and total lower limb fractures in both men and women. With regard to modifiable risk factors, low BMI and low intake of vegetables were associated with increased risks of proximal femur and/or total lower limb fractures in the general population of Japanese women.
Impact of Education 4.0 among engineering students for learning English language
Authors: Srivani V. , Hariharasudan A. , Nawaz Nishad , Ratajczak Sabina
Published: February 2022

Education 4.0 is considered a significant technology for teaching and learning. The present study aims to explore the impact and the importance of Education 4.0 for improving English language learning in the perception of students in India, especially Hyderabad City. Moreover, Education 4.0 has bloomed as an important need to move along with the fast-growing education system of the world. But, it is a fact that many Indian students have complications and difficulties in learning English due to many reasons. The traditional methods of teaching are one of those reasons. Students learn only through the conventional methods, and they may find it boring and not effective. The education and mode of teaching have changed a lot, and it has attained a newer form of using the technology. Moreover, in the current era, where work from home and online teaching has become a new normal throughout the world, the technology used for teaching is inseparable. Hence, the authors are motivated to study the impact of Education 4.0 on improving English learning from Hyderabad, India. The methodology of the study has applied quantitative research. The study has employed pre-tested, close-ended questionnaires and post-assessment to gather data from the respondents to understand students’ performance in English language learning after implying Education 4.0. The five-point Likert scale has been used to analyse the collected data and to get mean values of responses. The total number of respondents is 145 students who pursue their engineering degrees in the select region. Among the collected data, most of them were from urban. The data obtained from the respondents proved that there is a direct correlation between the students’ perception and implementation of Education 4.0 in learning the English language. This study indicated that the respondents upheld Education 4.0 to improve English language learning in Hyderabad, India.
Breaking the bonds of reinforcement: Effects of trial outcome, rule consistency and rule complexity against exploitable and unexploitable opponents
Authors: Sundvall Jukka , Dyson Benjamin James
Published: February 2022

In two experiments, we used the simple zero-sum game Rock, Paper and Scissors to study the common reinforcement-based rules of repeating choices after winning (win-stay) and shifting from previous choice options after losing (lose-shift). Participants played the game against both computer opponents who could not be exploited and computer opponents who could be exploited by making choices that would at times conflict with reinforcement. Against unexploitable opponents, participants achieved an approximation of random behavior, contrary to previous research commonly finding reinforcement biases. Against exploitable opponents, the participants learned to exploit the opponent regardless of whether optimal choices conflicted with reinforcement or not. The data suggest that learning a rule that allows one to exploit was largely determined by the outcome of the previous trial.
Covid-19 and excess mortality in medicare beneficiaries
Authors: Greenwald Scott D. , Chamoun Nassib G. , Manberg Paul J. , Gray Josh , Clain David , Maheshwari Kamal , Sessler Daniel I.
Published: February 2022

We estimated excess mortality in Medicare recipients in the United States with probable and confirmed Covid-19 infections in the general community and amongst residents of long-term care (LTC) facilities. We considered 28,389,098 Medicare and dual-eligible recipients from one year before February 29, 2020 through September 30, 2020, with mortality followed through November 30th, 2020. Probable and confirmed Covid-19 diagnoses, presumably mostly symptomatic, were determined from ICD-10 codes. We developed a Risk Stratification Index (RSI) mortality model which was applied prospectively to establish baseline mortality risk. Excess deaths attributable to Covid-19 were estimated by comparing actual-to-expected deaths based on historical (2017–2019) comparisons and in closely matched concurrent (2020) cohorts with and without Covid-19. Overall, 677,100 (2.4%) beneficiaries had confirmed Covid-19 and 2,917,604 (10.3%) had probable Covid-19. A total of 472,329 confirmed cases were community living and 204,771 were in LTC. Mortality following a probable or confirmed diagnosis in the community increased from an expected incidence of about 4.0% to actual incidence of 7.5%. In long-term care facilities, the corresponding increase was from 20.3% to 24.6%. The absolute increase was therefore similar at 3–4% in the community and in LTC residents. The percentage increase was far greater in the community (89.5%) than among patients in chronic care facilities (21.1%) who had higher baseline risk of mortality. The LTC population without probable or confirmed Covid-19 diagnoses experienced 38,932 excess deaths (34.8%) compared to historical estimates. Limitations in access to Covid-19 testing and disease under-reporting in LTC patients probably were important factors, although social isolation and disruption in usual care presumably also contributed. Remarkably, there were 31,360 (5.4%) fewer deaths than expected in community dwellers without probable or confirmed Covid-19 diagnoses. Disruptions to the healthcare system and avoided medical care were thus apparently offset by other factors, representing overall benefit. The Covid-19 pandemic had marked effects on mortality, but the effects were highly context-dependent.
Aerobes and phototrophs as microbial organic fertilizers: Exploring mineralization, fertilization and plant protection features
Authors: Wambacq Eva , Alloul Abbas , Grunert Oliver , Carrette Jasper , Vermeir Pieter , Spanoghe Janne , Sakarika Myrsini , Vlaeminck Siegfried E. , Haesaert Geert
Published: February 2022

Organic fertilizers and especially microbial biomass, also known as microbial fertilizer, can enable a paradigm shift to the conventional fertilizer-to-food chain, particularly when produced on secondary resources. Microbial fertilizers are already common practice (e.g. Bloom® and Synagro); yet microbial fertilizer blends to align the nutrient release profile to the plant’s needs are, thus far, unexplored. Moreover, most research only focuses on direct fertilization effects without considering added value properties, such as disease prevention. This study has explored three promising types of microbial fertilizers, namely dried biomass from a consortium of aerobic heterotrophic bacteria, a microalga (Arthrospira platensis) and a purple non-sulfur bacterium (Rhodobacter sphaeroides). Mineralization and nitrification experiments showed that the nitrogen mineralization profile can be tuned to the plant’s needs by blending microbial fertilizers, without having toxic ammonium peaks. In a pot trial with perennial ryegrass (Lolium perenne L.), the performance of microbial fertilizers was similar to the reference organic fertilizer, with cumulative dry matter yields of 5.6–6.7 g per pot. This was confirmed in a pot trial with tomato (Solanum lycopersicum L.), showing an average total plant length of 90–99 cm after a growing period of 62 days for the reference organic fertilizer and the microbial fertilizers. Moreover, tomato plants artificially infected with powdery mildew (Oidium neolycopersici), a devastating disease for the horticultural industry, showed reduced disease symptoms when A. platensis was present in the growing medium. These findings strengthen the application potential of this novel class of organic fertilizers in the bioeconomy, with a promising match between nutrient mineralization and plant requirements as well as added value in crop protection.
Hunting before herding: A zooarchaeological and stable isotopic study of suids (Sus sp.) at Hardinxveld-Giessendam, the Netherlands (5450–4250 cal BC)
Authors: Brusgaard Nathalie Ø. , Dee Michael W. , Dreshaj Merita , Erven Jolijn , van den Hurk Youri , Raemaekers Daan , Çakırlar Canan
Published: February 2022

Suids (Sus sp.) played a crucial role in the transition to farming in northern Europe and, like in many regions, in the Netherlands pig husbandry became an important subsistence activity at Neolithic sites. Yet little is known about wild boar palaeoecology and hunting in the Late Mesolithic Netherlands with which to contextualize this transition. This paper presents the first multi-proxy analysis of archaeological suid remains in the Netherlands. It explores human-suid interactions at the Swifterbant culture sites of Hardinxveld-Giessendam Polderweg and De Bruin (5450–4250 BC) through biometric analysis, estimation of age-at-death, and stable carbon and nitrogen isotope analysis. The results reveal targeted hunting of adult wild boar in the Late Mesolithic (5450–4850 BC), with a possible shift over time towards more juveniles. The wild boar in this period are demonstrated to be of comparably large size to contemporary northern European populations and exhibiting a wide range of dietary regimes. In the final occupational period (4450–4250 BC), small suids are present, possibly domestic pigs, but there is no evidence of pig management. This study demonstrates that the nature of human-suid interactions varied over time, which may have been connected to changing environmental conditions, human mobility, and wild boar behaviour. This study also contributes the first biometric and dietary baseline for mid-Holocene wild boar in the Netherlands.
Gut microbiota and butyrate contribute to nonalcoholic fatty liver disease in premenopause due to estrogen deficiency
Authors: Liu Limin , Fu Qingsong , Li Tiantian , Shao Kai , Zhu Xing , Cong Yingzi , Zhao Xiaoyun
Published: February 2022

The incidence of nonalcoholic fatty liver disease (NAFLD) in postmenopausal women has increased significantly. Estrogen plays a very important role in NAFLD, but whether NAFLD in premenopausal women was caused by estrogen deficiency was unknown. Thus, it is of great clinical significance to explore the mechanism of NAFLD in premenopausal women. Gut microbiota and its metabolites short chain fatty acids (SCFA) have been shown to play important roles in the development of NAFLD. In this study, we investigated the impact of gut microbiota and SCFA in NAFLD patients and mice caused by estrogen deficiency. We showed that premenopause NAFLD patients had much lower estrogen levels. Estrogen deficient mice, due to ovariectomy (OVX), suffered more severe liver steatosis with an elevated body weight, abdominal fat weight, serum triglycerides and deterioration in hepatic steatosis. Altered gut microbiota composition and decreased butyrate content were found in NAFLD patients and in OVX mice. Furthermore, fecal microbiota transplantation (FMT) or supplementing with butyrate alleviated NAFLD in OVX mice. The production of antimicrobial peptides (AMP) Reg3ɣ, β-defensins and the expression of intestinal epithelial tight junction, including ZO-1 and Occluding-5, were decreased in the OVX mice compared to control mice. Upregulation of PPAR-ɣ and VLDLR, downregulation of PPAR-ɑ indicated that OVX mice suffered from abnormal lipid metabolism. These data indicate that changes in the gut microbiota and SCFA caused by estrogen reduction, together with a disorder in AMP production and lipid metabolism, promote NAFLD, thus provide SCFAs derived from microbiota as new therapeutic targets for the clinical prevention and treatment of NAFLD.
Randomized controlled trial to test the efficacy of a brief, communication-based, substance use preventive intervention for parents of adolescents: Protocol for the SUPPER Project (Substance Use Prevention Promoted by Eating family meals Regularly)
Authors: Skeer Margie R. , Sabelli Rachael A. , Rancaño Katherine M. , Lee-Bravatti Michelle , Ryan Emma C. , Eliasziw Misha , Spirito Anthony
Published: February 2022

Background

Substance use among adolescents in the U.S. is associated with adverse physical and mental health outcomes in the long-term. Universal youth-focused substance use prevention programs have demonstrated effectiveness but are often not sustainable due to the significant amount of time, effort, and resources required. We describe a trial protocol for a brief, low-participant-burden intervention to improve substance use-specific parent-child communication through the promotion of family meals and increased parental engagement.

Methods

This study is a parallel-group randomized controlled trial designed to assess the efficacy of a 13-week intervention. A total of 500 dyads of parents and their 5th-7th grade children are recruited from across Massachusetts. Dyads are randomized to the intervention or attention-control condition using block urn randomization, based on child grade, gender, and school. Parents/guardians in the substance use preventive intervention arm receive a short handbook, attend two meetings with an interventionist, and receive two SMS messages per week. Parents/guardians in the control arm receive the same dose but with content focused on nutrition, physical activity, and weight stigma. Participant dyads submit videos of family meals, audio recordings of prompted conversations, and quantitative surveys over an 18-month period (baseline, 3, 6, 12, 18 months post-intervention). The primary outcomes measure the quantity and quality of parent-child substance use conversations and proximal child indicators (i.e., substance use attitudes and expectancies, affiliation with substance-using peers, and intentions and willingness to use substances). The secondary outcome is child substance use initiation.

Discussion

This is a novel, brief, communication-focused intervention for parents/guardians that was designed to reduce participant burden. The intervention has the potential to improve parent-child engagement and communication and conversations about substance use specifically and decrease child substance use risk factors and substance use initiation.

Trial registration

ClinicalTrials.gov NCT03925220. Registered on 24 April 2019.
Visual aids in ambulatory clinical practice: Experiences, perceptions and needs of patients and healthcare professionals
Authors: Hafner Catherine , Schneider Julie , Schindler Mélinée , Braillard Olivia
Published: February 2022

This study aims to explore how visual aids (VA) are used in ambulatory medical practice. Our research group (two doctors, one graphic designer and one sociologist) have led a qualitative study based on Focus Groups. A semi-structured guide and examples of VA were used to stimulate discussions. Participants were healthcare professionals (HP) working in ambulatory practice in Geneva and French-speaking outpatients. After inductive thematic analysis, the coding process was analyzed and modified to eventually reach consensus. Six focus groups gathered twenty-one HP and fifteen patients. Our study underlines the variety of purposes of use of VA and the different contexts of use allowing the distinction between “stand-alone” VA used out of consultation by patients alone and “interactive” VA used during a consultation enriched by the interaction between HP and patients. HP described that VA can take the form of useful tools for education and communication during consultation. They have questioned the quality of available VA and complained about restricted access to them. Patients expressed concern about the impact of VA on the interaction with HP. Participants agreed on the beneficial role of VA to supplement verbal explanation and text. Our study emphasizes the need to classify available VA, guarantee their quality, facilitate their access and deliver pertinent instructions for use.
Study of thin layer film evolution near bacterial cellulose membrane by Ag|AgCl electrodes in chamber with lower concentration
Authors: Grzegorczyn Sławomir , Ślęzak Andrzej
Published: February 2022

We used the method of measuring potential difference between two Ag|AgCl electrodes immersed directly into electrolyte solution with lower concentration and at different distances from membrane. The bacterial cellulose membrane was placed in horizontal plane in the membrane system with configurations with higher NaCl concentration and density under (A) and over the membrane (B). In both configurations at the initial moment the voltage between electrodes amounted to zero. After turning off mechanical stirring of solutions, in configuration A we observed the monotonic increase and next stabilization of voltage while in configuration B after short time dependent on the initial quotient of NaCl concentrations on the membrane we observed appearance of pulsations of measured voltage and gradual decrease of mean voltage over time. Smooth changes of voltage are connected with diffusional reconstruction of Concentration Boundary Layers (CBLs) while fast increase and subsequent pulsations of voltage are connected with the appearance of hydrodynamic instabilities (gravitational convection) near membrane imposed on diffusive reconstruction of thin layer. The time needed for the appearance of hydrodynamic instabilities in CBL depended nonlinearly on the initial ratio of electrolyte concentrations on the membrane.
Comparing the impact of vaccination strategies on the spread of COVID-19, including a novel household-targeted vaccination strategy
Authors: Voigt André , Omholt Stig , Almaas Eivind
Published: February 2022

With limited availability of vaccines, an efficient use of the limited supply of vaccines in order to achieve herd immunity will be an important tool to combat the wide-spread prevalence of COVID-19. Here, we compare a selection of strategies for vaccine distribution, including a novel targeted vaccination approach (EHR) that provides a noticeable increase in vaccine impact on disease spread compared to age-prioritized and random selection vaccination schemes. Using high-fidelity individual-based computer simulations with Oslo, Norway as an example, we find that for a community reproductive number in a setting where the base pre-vaccination reproduction number R = 2.1 without population immunity, the EHR method reaches herd immunity at 48% of the population vaccinated with 90% efficiency, whereas the common age-prioritized approach needs 89%, and a population-wide random selection approach requires 61%. We find that age-based strategies have a substantially weaker impact on epidemic spread and struggle to achieve herd immunity under the majority of conditions. Furthermore, the vaccination of minors is essential to achieving herd immunity, even for ideal vaccines providing 100% protection.
Biolayer interferometry for DNA-protein interactions
Authors: Barrows John K. , Van Dyke Michael W.
Published: February 2022

Biolayer interferometry (BLI) is a widely utilized technique for determining macromolecular interaction dynamics in real time. Using changes in the interference pattern of white light reflected off a biosensor tip, BLI can determine binding parameters for protein-protein (e.g., antibody-substrate kinetics) or protein-small molecule (e.g., drug discovery) interactions. However, a less-appreciated application for BLI analysis is DNA-protein interactions. DNA-binding proteins play an immense role in cellular biology, controlling critical processes including transcription, DNA replication, and DNA repair. Understanding how proteins interact with DNA often provides important insight into their biological function, and novel technologies to assay DNA-protein interactions are of broad interest. Currently, a detailed protocol utilizing BLI for DNA-protein interactions is lacking. In the following protocol, we describe the use of BLI and biotinylated-DNA probes to determine the binding kinetics of a transcription factor to a specific DNA sequence. The experimental steps include the generation of biotinylated-DNA probes, the execution of the BLI experiment, and data analysis by scientific graphing and statistical software (e.g., GraphPad Prism). Although the example experiment used throughout this protocol involves a prokaryotic transcription factor, this technique can be easily translated to any DNA-binding protein. Pitfalls and potential solutions for investigating DNA-binding proteins by BLI are also presented.
Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis
Authors: Sadleir Katherine R. , Popovic Jelena , Khatri Ammaarah , Vassar Robert
Published: February 2022

Dysregulation of calcium homeostasis has been hypothesized to play a role in Alzheimer’s disease (AD) pathogenesis. Increased calcium levels can impair axonal transport, disrupt synaptic transmission, and ultimately lead to cell death. Given the potential role of calcium dyshomeostasis in AD, there is interest in testing the ability of already approved drugs targeting various calcium channels to affect amyloid pathology and other aspects of disease. The objective of this study was to test the effects of FDA-approved L-type calcium channel antagonist nimodipine on amyloid accumulation and dystrophic neurite formation in 5XFAD mice, a mouse model of amyloid pathology. 5XFAD transgenic mice and non-transgenic littermates were treated with vehicle or nimodipine-containing chow from two to eight months of age, then brains were harvested and amyloid pathology assessed by immunoblot and immunofluorescence microscopy analyses. Nimodipine was well tolerated and crossed the blood brain barrier, as expected, but there was no effect on Aβ accumulation or on the relative amount of neuritic dystrophy, as assessed by either immunoblot, dot blot or immunofluorescence imaging of Aβ42 and dystrophic neurite marker LAMP1. While we conclude that nimodipine treatment is not likely to improve amyloid pathology or decrease neuritic dystrophy in AD, it is worth noting that nimodipine did not worsen the phenotype suggesting its use is safe in AD patients.
Dynamic oxygenator blood volume during prolonged extracorporeal life support
Authors: Hendrix Rik H. J. , Kurniawati Eva R. , Schins Sanne F. C. , Maessen Jos G. , Weerwind Patrick W.
Published: February 2022

Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and oxygen exchange performance, and assessment of clotting-related laboratory parameters. However, these observations do not provide a quantitative assessment of oxygenator clot formation. By measuring changes in the dynamic oxygenator blood volume this study aimed to evaluate the relation to oxygenator resistance and oxygen transfer performance. Sixty-seven oxygenators were studied during adult extracorporeal life support. Oxygenator blood volume, oxygenator resistance, and oxygen transfer efficiency were monitored. Oxygenator blood volume decreased with increasing runtime (r = -0.462; p <0.001). There was a statistically significant, fair negative correlation between oxygenator blood volume and oxygenator resistance (r = -0.476; p<0.001) in all oxygenators, which became stronger analyzing only exchanged oxygenators (r = -0.680; p<0.001) and oxygenators with an oxygenator blood volume <187 mL (r = 0.831; p<0.001). No relevant correlation between oxygenator blood volume and O2transfer was found. Oxygenator blood volume declined over time and was clearly associated with an increasing oxygenator resistance during prolonged extracorporeal life support, though O2transfer was less affected.