bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of metal accumulation and Phytochelatin Synthase (PCS) gene expression in Saccharum spontaneum L. as regards its function for remediation of lead (Pb) contamination
Authors: Rini D S , Hidayati N
Published: November 2021

Pollution caused by heavy metals, has become a serious problem. Adverse effects arising from the increased use of heavy metals in a variety of human activities lead to any environmental degradation. Lead (Pb) is one of most common contaminants in the environment and highly toxic. Pb is less mobile, so its compound tends to accumulate in soil and sediments. Definitely, efforts are needed to remove this contaminant in the environment. Saccharum spontaneum L. is a perennial grass which has potential to be used as an accumulator plant to clean up pollutants. The ability of this plant as metal accumulator was tested in this study. S.pontaneum plants were treated using Pb in the concentrations of 0 ppm (control), 100 ppm, 200 ppm, and 300 ppm for 8 weeks. The results showed that there was an increase in the percentage of relative accumulation of Pb in the treated plants. This also indicated that plant roots accumulated more Pb than shoots. Meanwhile, expression of Phytochelatin synthase (PCS) gene increased 1.3-to-3.5-fold inductions in roots by increasing concentration of Pb treatments for 24 h. PCS gene expression showed the higher induction in the roots than in the shoots of S.spontaneum plant under Pb treatments.
The effect of climate change damages on agriculture, forestry and fisheries in ASEAN countries
Authors: Indriawati R M , Prasetyani D
Published: November 2021

Countries in ASEAN region have a significant potential for the impact of climate change disruption and disasters such as El Nino, La Nina, earthquakes, tsunamis, volcanic eruptions, hurricanes, floods, tropical storms, landslides, and CO2 emissions. The ASEAN Secretariat recorded a progressive increase in CO2 emission levels of around 61% from 2014 to 2025, more than 90% of transboundary haze from the expansion of large-scale commercial plantations, accumulation of plastic waste and household waste that cannot be properly recycled. The contribution of agriculture, forestry and fisheries is also relatively varied. Geographical conditions, policy orientations of each government, structure of production inputs including human resource competence and technology are thought to determine the adverse effects of climate change on the agriculture, forestry, and fisheries sectors. This study focuses on the impact of climate change on the agriculture, fisheries, and forestry sectors in the ASEAN region. The analytical framework is adapted to the ASEAN Vision 2020 and ASEAN Vision 2021. In addition, a deeper analysis of several climate change impact control instruments such as polluter pays, agricultural insurance, agri-environment climate schemes and payments for environmental services will also be studied. These instruments are directed to achieve environmental sustainability in the ASEAN region.
The effect of biofilm biofertilizer formula and organic fertilizer dosage to phosphorus uptake and yield of shallot on Vertisols
Authors: Sudadi  , Setyawan C Y
Published: November 2021

The research aims to find the effect of biofilm biofertilizer formula and dose of organic fertilizer on phosphorus uptake and yield of shallot on Vertisols. The research was arranged in a completely randomized block design with two factors: dosage of organic fertilizer (0, 10, 20-ton ha-1) and the formula of biofilm biofertilizer (without BiO2, BiO2 1, BiO2 2, BiO2 3). Variables observed are available-P, P-uptake, bulb number, and bulb weight. Data were analyzed using F test followed by DMRT at α = 0.05. The result shows that 20-ton ha-1 organic fertilizer decomposed with biofilm biofertilizer yield highest P-uptake and plant dry weight which increases 322 and 216 % to control treatment (0.50 and 1.26 g plant-1). The use of 10-ton ha-1 of organic fertilizer yield highest bulb number and weight i.e 5.58 bulbs plant-1 and 116 g plant-1 increase 27 and 172% compared to the control. The BiO2 formula only affected to the plant height, and the use of formula 1 able to increase the plant height about 13.5% compared to control treatment.
Evaluation of implementation about Covid-19 medical waste management policies in health care facilities
Authors: Al-Fikri F F , Nugroho R A , Sudarmo
Published: November 2021

This paper evaluates policy implementation that discusses the management of medical waste in health care facilities. The government establishes a waste management policy with the Decree of the Minister of Health concerning Guidelines for the Management of Medical Waste for Health Service Facilities and Waste from Isolation Activities or Independent Quarantine in the Community in Handling (Covid-19) to prevent transmission and controlling the spread of Covid-19 and protecting health workers, non-health workers, and the public from the impact of waste in handling Covid-19. Although regulations related to the management of Covid-19 waste have been set, there are still problems in some areas in their implementation. The literature study was conducted to evaluate the implementation of medical waste management policies in health care facilities. Evaluation is seen based on socialization, implementation, and policy results. Based on the results of the literature study, it was found that the socialization of the policy had done well, evidenced by the implementation of socialization about medical waste in health care facilities. The implementation encountered several obstacles, such as limited shelters, shortage of waste destruction equipment, and medical waste transportation and processing services that had not yet reached all areas in Indonesia.
Batik stamp canting made of waste paper material as a frugal innovation in batik
Authors: Hidayat S R , Affanti T B , Josef A I , Nurcahyanti D
Published: November 2021

This article discusses the innovation of batik stamp canting equipment using waste paper material. The first focus is on the emergence and the background of the innovation of batik stamp canting made of waste paper material. The second is on the elaboration of concept of stamp batik canting innovation made of waste paper material. The method applied in this study was qualitative approach with case studies by employing informants’ data sources, artifacts, events and documents. The results indicate that the innovation of stamp canting using paper material has occurred since 2014, and it began to be widely used in batik production process in 2016. The background of stamp canting innovation made of waste paper was triggered by the high price of stamp canting from copper which is commonly used in the production process of stamped batik. The concept applied to develop this stamp canting is frugal innovation. The value of knowledge gained is that innovation is not always carried out to improve the quality of processes or products. Innovation is more significantly needed to solve the problems related to the context.
Nano Silica application for inducing rice resistance and the possibility for Ytterbium Rare Earth Elements green mining
Authors: Candra S D , Musriati T
Published: November 2021

There is a growing interest and recognition of Silicon (Si) in plants to increase growth, productivity, and plant resistance. This research examines the role of Nano Silica to increase yield and resistance. This study set out to assess the effect of hydrophilic fumed Nano Silica application with the frequency of 1×, 2×, 3×, and 4× applications respectively with three replications using RCBD as well as SEM-EDX and XRF analysis. Nano Silica frequencies showed a distinctive decrease of damage intensity at the 3× and 4× applications. The rice husk increases of metal-like surface appearance as more Nano Silica frequency was applied. It is proposed that Nano Si induced plant resistance through the modification of surface layer and stronger plant tolerance against environmental stress. The most unexpected observation to emerge was the Ytterbium (Yb) concentration known as a Rare Earth Elements at the 3× and 4× Nano Si applications. This indicates that Nano Silica application provides insights and opportunities to Nano Si application on Rice for the purpose of acquiring Ytterbium from farmland. Nano Silica can play an important role as a new method in addressing the Ytterbium green mining.
Socio-economic study on empowering women farmers to support the SDGs
Authors: Abidin A Z , Prasetyani D
Published: November 2021

SDGs number 5 is a goal for women to increase their participation in the country’s economic development. There are many sectors where women can develop and have an impact on a country’s development. Among the many existing development sectors, agriculture is one of the sectors with the most contribution to Indonesia’s GDP. It is from the fact that Indonesia is a country that is rich in natural resources. However, there are still many Indonesian farmers, especially women, who live in poverty. Therefore, empowerment is an alternative to improve their standard of living. This study will examine the empowerment model among women farmers, at least in the agricultural sector in the area where they live. The research method used is a literature study. The results will show the pattern of empowerment formed among groups of women farmers in several regions in Indonesia. This pattern will explain how empowerment developed so that the participation of women farmers in economic development can increase in the future.
Electricity machinery, renewable energy and green economy
Authors: Agustin V S , Restikadewi A , Trinarningsih W , Hartomo D D
Published: November 2021

The increase in industrial activities is followed by an increase in complex environmental problems, such as air pollution due to factory exhaust fumes, which are mostly produced in industrial areas such as in Surabaya, Indonesia. Based on data from iqair.com, three industrial areas in Surabaya fall into the category of moderate to unhealthy sensitive groups. The Tandes industrial area is in the unhealthy category for sensitive groups with an AQI index of US 104. Meanwhile, Kertajaya and Benowo are in the moderate category with US AQI indexes of 61 and 86 respectively. It is necessary to implement a green economy program. The existing renewable energy power plants in Indonesia will support the industry to switch to the use of electricity-based machines from renewable energy which will reduce air pollution that causes greenhouse gas emissions. The purpose of this study is to analyze the factory environment and application of a green economy through the use of electricity-based machines. Qualitative method is employed in this study. The results showed that the application of electricity-based machines can reduce the level of air pollution in Surabaya and potentially increase renewable energy in Indonesia.
Flower and plant variants as abstraction in Javanese batik motifs from classical to contemporary era
Authors: Budi S , Widiastuti T , Ardianto D T , Mataram S
Published: November 2021

Batik is one of the artworks of old Javanese society which has continued to exist and develop until the present day. In the 18th century, batik was a special type of clothing worn by the nobility, and there were even prohibitions for using batik clothing with certain types of motifs. Its basic substance is the ornamental images made on the fabric. A piece of cloth can change its position and value only because of a difference in decoration. As a visual aesthetic, batik is the work of Javanese artists, created by abstracting the surrounding natural environment, especially various flora, and fauna. Up to 1912, there were more than 100 names of flowers, leaves, and plants that were abstracted to become classical motifs. In the contemporary era, where batik has become more acceptable as clothing for the public, flora-based motifs are no longer the result of abstraction of particular flowers or plants but are considered more for their ornamental aesthetic. The aesthetic value of contemporary batik motifs is no longer determined by the type of flowers or plants abstracted, but by how they are represented for the beauty of clothing.
Religiosity, Psychological Distress, and Well-Being: Evaluating Familial Confounding With Multicohort Sibling Data
Authors: Jokela Markus
Published: November 2021

Several studies have associated religiosity with better mental health, but these studies have only partially addressed the problem of confounding. The present study pooled data from multiple cohort studies with siblings to examine whether associations between religiosity and mental health are confounded by familial factors (i.e., shared family background and siblings’ shared genetics). Data were collected between 1982 and 2017. Mental health was assessed with self-reported psychological distress (including depressive symptoms) and psychological well-being. Religious attendance was associated with lower psychological distress (standard-deviation difference between weekly vs. never attendance, B = −0.14, confidence interval (CI): −0.19, −0.09; n = 24,598 pairs), and this was attenuated by almost half in the sibling analysis (B = −0.08, CI: = −0.13, −0.04). Religious attendance was also related to higher well-being (B = 0.29, CI: = 0.14, 0.45; n = 3,728 pairs), and this estimate remained unchanged in sibling analysis. Results were similar for religiousness. The findings suggest that previous longitudinal studies may have overestimated the association between religiosity and psychological distress, as the sibling estimate was only one-third of the previously reported meta-analytical association (standardized correlation −0.03 vs. −0.08).
Kelsen, Kletzer, and the Differentiation of Law
Authors: Schauer Frederick
Published: November 2021

The differentiation of law is a pervasive and crucially important topic. Although H.L.A. Hart and others have stressed how law resembles games and other institutions, Hans Kelsen’s focus on law as a “specific” social technique represents a needed focus on what makes law different, or special. Christoph Kletzer admirably follows Kelsen in focusing and what makes law unique, and Kletzer’s claim that law is unique in ordering the use of force is also a valuable contribution to the project of recognizing how force, sanctions, and coercion remain important features of law. Kletzer may go too far, however, in believing that an account of law must show how law is sharply demarcated from other social institutions. A more fruitful and more descriptively and conceptually plausible project would give up the search for rigid demarcation and explore those features of law that may not be unique to law but are concentrated in law. And thus we might think of law not as something that exists or not, but that different institutions might have differing degrees of what we can call “lawness.”
Moonlight influence on quality of nestlings of scops owls depends on paternal coloration
Authors: Avilés Jesús M , Cruz-Miralles Ángel , Parejo Deseada
Published: November 2021

Lunar phases might favor the maintenance of color polymorphism via disruptive selection if the different color variants performed differently in terms of prey capture under different moonlight levels. Moonlight, however, may affect prey capture as a side effect of its influence on prey behavior. Here we combine data of parental provisioning and quality of owlets with one ex-situ study of grasshopper activity to test whether Eurasian scops owls (Otus scops) with different plumage color and their prey are differently affected by moonlight. Food provisioning increased from new- to full-moon. However, the effect of moonlight on owlet mass gain and immune response depended on paternal coloration. On the one hand, body mass gain of nestlings of the greyest fathers increased from nights with new- to full-moon, whereas it did not change with moonlight for the brownest fathers. On the other hand, PHA response of nestlings of the brownest fathers increased with high moonlight levels during the first week of life, whereas it did not change with moonlight levels for the greyest fathers. Grasshoppers were more active at new moon than at full or waning moon. Our study provides supporting evidence that moonlight influences the behavior of both scops owls and its prey and suggests that fluctuations in environmental conditions can modulate the advantages of morphs. These results are important because they provide a general insight into a little appreciated mechanism for the maintenance of color polymorphism in natural populations based on the interactive effect of different environmental factors.
A novel fast multiple nucleotide sequence alignment method based on FM-index
Authors: Liu Huan , Zou Quan , Xu Yun
Published: November 2021

Multiple sequence alignment (MSA) is fundamental to many biological applications. But most classical MSA algorithms are difficult to handle large-scale multiple sequences, especially long sequences. Therefore, some recent aligners adopt an efficient divide-and-conquer strategy to divide long sequences into several short sub-sequences. Selecting the common segments (i.e. anchors) for division of sequences is very critical as it directly affects the accuracy and time cost. So, we proposed a novel algorithm, FMAlign, to improve the performance of multiple nucleotide sequence alignment. We use FM-index to extract long common segments at a low cost rather than using a space-consuming hash table. Moreover, after finding the longer optimal common segments, the sequences are divided by the longer common segments. FMAlign has been tested on virus and bacteria genome and human mitochondrial genome datasets, and compared with existing MSA methods such as MAFFT, HAlign and FAME. The experiments show that our method outperforms the existing methods in terms of running time, and has a high accuracy on long sequence sets. All the results demonstrate that our method is applicable to the large-scale nucleotide sequences in terms of sequence length and sequence number. The source code and related data are accessible in https://github.com/iliuh/FMAlign.
An integrated brain-specific network identifies genes associated with neuropathologic and clinical traits of Alzheimer’s disease
Authors: Lin Cui-Xiang , Li Hong-Dong , Deng Chao , Liu Weisheng , Erhardt Shannon , Wu Fang-Xiang , Zhao Xing-Ming , Guan Yuanfang , Wang Jun , Wang Daifeng , Hu Bin , Wang Jianxin
Published: November 2021

Alzheimer’s disease (AD) has a strong genetic predisposition. However, its risk genes remain incompletely identified. We developed an Alzheimer’s brain gene network-based approach to predict AD-associated genes by leveraging the functional pattern of known AD-associated genes. Our constructed network outperformed existing networks in predicting AD genes. We then systematically validated the predictions using independent genetic, transcriptomic, proteomic data, neuropathological and clinical data. First, top-ranked genes were enriched in AD-associated pathways. Second, using external gene expression data from the Mount Sinai Brain Bank study, we found that the top-ranked genes were significantly associated with neuropathological and clinical traits, including the Consortium to Establish a Registry for Alzheimer’s Disease score, Braak stage score and clinical dementia rating. The analysis of Alzheimer’s brain single-cell RNA-seq data revealed cell-type-specific association of predicted genes with early pathology of AD. Third, by interrogating proteomic data in the Religious Orders Study and Memory and Aging Project and Baltimore Longitudinal Study of Aging studies, we observed a significant association of protein expression level with cognitive function and AD clinical severity. The network, method and predictions could become a valuable resource to advance the identification of risk genes for AD.
TP53_PROF: a machine learning model to predict impact of missense mutations in TP53
Authors: Ben-Cohen Gil , Doffe Flora , Devir Michal , Leroy Bernard , Soussi Thierry , Rosenberg Shai
Published: November 2021

Correctly identifying the true driver mutations in a patient’s tumor is a major challenge in precision oncology. Most efforts address frequent mutations, leaving medium- and low-frequency variants mostly unaddressed. For TP53, this identification is crucial for both somatic and germline mutations, with the latter associated with the Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition. We present TP53_PROF (prediction of functionality), a gene specific machine learning model to predict the functional consequences of every possible missense mutation in TP53, integrating human cell- and yeast-based functional assays scores along with computational scores. Variants were labeled for the training set using well-defined criteria of prevalence in four cancer genomics databases. The model’s predictions provided accuracy of 96.5%. They were validated experimentally, and were compared to population data, LFS datasets, ClinVar annotations and to TCGA survival data. Very high accuracy was shown through all methods of validation. TP53_PROF allows accurate classification of TP53 missense mutations applicable for clinical practice. Our gene specific approach integrated machine learning, highly reliable features and biological knowledge, to create an unprecedented, thoroughly validated and clinically oriented classification model. This approach currently addresses TP53 mutations and will be applied in the future to other important cancer genes.
A deep learning method for repurposing antiviral drugs against new viruses via multi-view nonnegative matrix factorization and its application to SARS-CoV-2
Authors: Su Xiaorui , Hu Lun , You Zhuhong , Hu Pengwei , Wang Lei , Zhao Bowei
Published: November 2021

The outbreak of COVID-19 caused by SARS-coronavirus (CoV)-2 has made millions of deaths since 2019. Although a variety of computational methods have been proposed to repurpose drugs for treating SARS-CoV-2 infections, it is still a challenging task for new viruses, as there are no verified virus-drug associations (VDAs) between them and existing drugs. To efficiently solve the cold-start problem posed by new viruses, a novel constrained multi-view nonnegative matrix factorization (CMNMF) model is designed by jointly utilizing multiple sources of biological information. With the CMNMF model, the similarities of drugs and viruses can be preserved from their own perspectives when they are projected onto a unified latent feature space. Based on the CMNMF model, we propose a deep learning method, namely VDA-DLCMNMF, for repurposing drugs against new viruses. VDA-DLCMNMF first initializes the node representations of drugs and viruses with their corresponding latent feature vectors to avoid a random initialization and then applies graph convolutional network to optimize their representations. Given an arbitrary drug, its probability of being associated with a new virus is computed according to their representations. To evaluate the performance of VDA-DLCMNMF, we have conducted a series of experiments on three VDA datasets created for SARS-CoV-2. Experimental results demonstrate that the promising prediction accuracy of VDA-DLCMNMF. Moreover, incorporating the CMNMF model into deep learning gains new insight into the drug repurposing for SARS-CoV-2, as the results of molecular docking experiments reveal that four antiviral drugs identified by VDA-DLCMNMF have the potential ability to treat SARS-CoV-2 infections.
The brain activation-based sexual image classifier (BASIC): a sensitive and specific fMRI activity pattern for sexual image processing
Authors: van ’t Hof Sophie R , Van Oudenhove Lukas , Janssen Erick , Klein Sanja , Reddan Marianne C , Kragel Philip A , Stark Rudolf , Wager Tor D
Published: November 2021

Previous studies suggest there is a complex relationship between sexual and general affective stimulus processing, which varies across individuals and situations. We examined whether sexual and general affective processing can be distinguished at the brain level. In addition, we explored to what degree possible distinctions are generalizable across individuals and different types of sexual stimuli, and whether they are limited to the engagement of lower-level processes, such as the detection of visual features. Data on sexual images, nonsexual positive and negative images, and neutral images from Wehrum et al. (2013) (N = 100) were reanalyzed using multivariate support vector machine models to create the brain activation-based sexual image classifier (BASIC) model. This model was tested for sensitivity, specificity, and generalizability in cross-validation (N = 100) and an independent test cohort (N = 18; Kragel et al. 2019). The BASIC model showed highly accurate performance (94–100%) in classifying sexual versus neutral or nonsexual affective images in both datasets with forced choice tests. Virtual lesions and tests of individual large-scale networks (e.g., visual or attention networks) show that individual networks are neither necessary nor sufficient to classify sexual versus nonsexual stimulus processing. Thus, responses to sexual images are distributed across brain systems.
A nonlinear hidden layer enables actor–critic agents to learn multiple paired association navigation
Authors: Kumar M Ganesh , Tan Cheston , Libedinsky Camilo , Yen Shih-Cheng , Tan Andrew Y Y
Published: November 2021

Navigation to multiple cued reward locations has been increasingly used to study rodent learning. Though deep reinforcement learning agents have been shown to be able to learn the task, they are not biologically plausible. Biologically plausible classic actor–critic agents have been shown to learn to navigate to single reward locations, but which biologically plausible agents are able to learn multiple cue–reward location tasks has remained unclear. In this computational study, we show versions of classic agents that learn to navigate to a single reward location, and adapt to reward location displacement, but are not able to learn multiple paired association navigation. The limitation is overcome by an agent in which place cell and cue information are first processed by a feedforward nonlinear hidden layer with synapses to the actor and critic subject to temporal difference error-modulated plasticity. Faster learning is obtained when the feedforward layer is replaced by a recurrent reservoir network.
Genome sequencing and analysis of two early-flowering cherry (Cerasus × kanzakura) varieties, ‘Kawazu-zakura’ and ‘Atami-zakura’
Authors: Shirasawa Kenta , Itai Akihiro , Isobe Sachiko
Published: November 2021

To gain genetic insights into the early-flowering phenotype of ornamental cherry, also known as sakura, we determined the genome sequences of two early-flowering cherry (Cerasus × kanzakura) varieties, ‘Kawazu-zakura’ and ‘Atami-zakura’. Because the two varieties are interspecific hybrids, likely derived from crosses between Cerasus campanulata (early-flowering species) and Cerasus speciosa, we employed the haplotype-resolved sequence assembly strategy. Genome sequence reads obtained from each variety by single-molecule real-time sequencing (SMRT) were split into two subsets, based on the genome sequence information of the two probable ancestors, and assembled to obtain haplotype-phased genome sequences. The resultant genome assembly of ‘Kawazu-zakura’ spanned 519.8 Mb with 1,544 contigs and an N50 value of 1,220.5 kb, while that of ‘Atami-zakura’ totalled 509.6 Mb with 2,180 contigs and an N50 value of 709.1 kb. A total of 72,702 and 69,528 potential protein-coding genes were predicted in the genome assemblies of ‘Kawazu-zakura’ and ‘Atami-zakura’, respectively. Gene clustering analysis identified 2,634 clusters uniquely presented in the C. campanulata haplotype sequences, which might contribute to its early-flowering phenotype. Genome sequences determined in this study provide fundamental information for elucidating the molecular and genetic mechanisms underlying the early-flowering phenotype of ornamental cherry tree varieties and their relatives.
Coulomb threshold rate-and-state model for fault reactivation: application to induced seismicity at Groningen
Authors: Heimisson Elías R , Smith Jonathan D , Avouac Jean-Philippe , Bourne Stephen J
Published: November 2021

A number of recent modelling studies of induced seismicity have used the 1994 rate-and-state friction model of Dieterich 1994 to account for the fact that earthquake nucleation is not instantaneous. Notably, the model assumes a population of seismic sources accelerating towards instability with a distribution of initial slip speeds such that they would produce earthquakes steadily in the absence of any perturbation to the system. This assumption may not be valid in typical intraplate settings where most examples of induced seismicity occur, since these regions have low stressing rates and initially low seismic activity. The goal of this paper is twofold. First, to derive a revised Coulomb rate-and-state model, which takes into account that seismic sources can be initially far from instability. Second, to apply and test this new model, called the Threshold rate-and-state model, on the induced seismicity of the Groningen gas field in the Netherlands. Stress changes are calculated based on a model of reservoir compaction since the onset of gas production. We next compare the seismicity predicted by our threshold model and Dieterich’s model with the observations. The two models yields comparable spatial distributions of earthquakes in good agreement with the observations. We find however that the Threshold model provides a better fit to the observed time-varying seismicity rate than Dieterich’s model, and reproduces better the onset, peak and decline of the observed seismicity rate. We compute the maximum magnitude expected for each model given the Gutenberg–Richter distribution and compare to the observations. We find that the Threshold model both shows better agreement with the observed maximum magnitude and provides result consistent with lack of observed seismicity prior to 1993. We carry out analysis of the model fit using a Chi-squared reduced statistics and find that the model fit is dramatically improved by smoothing the seismicity rate. We interpret this finding as possibly suggesting an influence of source interactions, or clustering, on a long timescale of about 3–5 yr.
Informing decisions with disparate stakeholders: cross-sector evaluation of cash transfers in Malawi
Authors: Ramponi Francesco , Nkhoma Dominic , Griffin Susan
Published: November 2021

The Social Cash Transfer Programme (SCTP) in Malawi is a cross-sectoral policy with impacts on health, education, nutrition, agriculture and welfare. Implementation of the SCTP requires collaboration across sectors and across national and international stakeholders. Economic evaluation can inform investment by indicating whether benefits exceed costs, but economic evaluations that provide an overall benefit–cost ratio typically assume a common agreed objective and agreed set of value judgements. In reality, the various stakeholders involved in the delivery of the SCTP may have different remits and objectives and may differ in how they value the impacts of the programme. We use the SCTP as a case study to illustrate a cross-sectoral analytical framework that accounts for these differences. The stakeholders that contribute to the SCTP include the Ministry of Gender, Ministry of Finance, Ministry of Economic Planning and Development and Global Fund. We estimate how the SCTP changes outcomes in education, health, net production and poverty, and distinguish outcomes in three groups: SCTP recipients; population in Malawi not eligible for the SCTP and population in other countries. After estimating the direct effects and opportunity costs from investing in the SCTP, we summarize the results according to different perspectives. The SCTP is estimated to provide benefits in excess of costs from the perspective of national stakeholders. From the perspective of an international donor interested in health outcomes, its health benefits do not outweigh the opportunity costs unless health improvement in SCTP recipients is valued at 18 times that of other potential spending beneficiaries or the donor values broader outcomes than health alone. This work illustrates the potential of a cross-sectoral economic evaluation to guide debate about stakeholder contributions to the SCTP, and the value judgements required to favour the SCTP above other policy options.
An epileptic encephalopathy associatedGABRG2missense mutation leads to pre- and postsynaptic defects in zebrafish
Authors: Zhou Jing , Liang Wenpeng , Wang Jie , Chen Juan , Liu Dong , Wang Xin , Wu Youjia , Zhang Qi , Shen Dingding
Published: November 2021

Mutations in the γ-aminobutyric acid type A (GABAA) receptor γ2 subunit gene, GABRG2, have been associated with a variety of epilepsy syndromes. A de novo mutation (c.T1027C, p.F343L) in GABRG2 was identified in a patient with early onset epileptic encephalopathy. Zebrafish overexpressing mutant human GABRG2 (F343L) subunits displayed spontaneous seizure activity and convulsive behaviors. In this study, we demonstrated that Tg (hGABRG2F343L) zebrafish displayed hyperactivity during light phase with normal circadian rhythm, as well as increased drug-induced locomotor activity. Real-time quantitative PCR, whole mount in situ hybridization and western blotting showed that Tg(hGABRG2F343L) zebrafish had altered expression of GABAA receptor subunits. Furthermore, investigation of synaptic protein expression and synapse ultrastructure uncovered a robust synaptic phenotype that is causally linked to GABRG2(F343L) mutation. Strikingly, Tg(hGABRG2F343L) zebrafish not only had postsynaptic defects, but also displayed an unanticipated deficit at the presynaptic level. Overall, our Tg(hGABRG2F343L) overexpression zebrafish model has expanded the GABAergic paradigm in epileptic encephalopathy from channelopathy to synaptopathy.
Novel microarchitecture of human endometrial glands: implications in endometrial regeneration and pathologies
Authors: Tempest Nicola , Hill Christopher J , Maclean Alison , Marston Kathleen , Powell Simon G , Al-Lamee Hannan , Hapangama Dharani K
Published: November 2021

BACKGROUND

Human endometrium remains a poorly understood tissue of the female reproductive tract. The superficial endometrial functionalis, the site of embryo implantation, is repeatedly shed with menstruation, and the stem cell-rich deeper basalis is postulated to be responsible for the regeneration of the functionalis. Two recent manuscripts have demonstrated the 3D architecture of endometrial glands. These manuscripts have challenged and replaced the prevailing concept that these glands end in blind pouches in the basalis layer that contain stem cells in crypts, as in the intestinal mucosa, providing a new paradigm for endometrial glandular anatomy. This necessitates re-evaluation of the available evidence on human endometrial regeneration in both health and disease in the context of this previously unknown endometrial glandular arrangement.

OBJECTIVE AND RATIONALE

The aim of this review is to determine if the recently discovered glandular arrangement provides plausible explanations for previously unanswered questions related to human endometrial biology. Specifically, it will focus on re-appraising the theories related to endometrial regeneration, location of stem/progenitor cells and endometrial pathologies in the context of this recently unravelled endometrial glandular organization.

SEARCH METHODS

An extensive literature search was conducted from inception to April 2021 using multiple databases, including PubMed/Web of Science/EMBASE/Scopus, to select studies using keywords applied to endometrial glandular anatomy and regeneration, and the references included in selected publications were also screened. All relevant publications were included.

OUTCOMES

The human endometrial glands have a unique and complex architecture; branched basalis glands proceed in a horizontal course adjacent to the myometrium, as opposed to the non-branching, vertically coiled functionalis glands, which run parallel to each other as is observed in intestinal crypts. This complex network of mycelium-like, interconnected basalis glands is demonstrated to contain endometrial epithelial stem cells giving rise to single, non-branching functionalis glands. Several previous studies that have tried to confirm the existence of epithelial stem cells have used methodologies that prevent sampling of the stem cell-rich basalis. More recent findings have provided insight into the efficient regeneration of the human endometrium, which is preferentially evolved in humans and menstruating upper-order primates.

WIDER IMPLICATIONS

The unique physiological organization of the human endometrial glandular element, its relevance to stem cell activity and scarless endometrial regeneration will inform reproductive biologists and clinicians to direct their future research to determine disease-specific alterations in glandular anatomy in a variety of endometrial pathological conditions.
Selective Orexin Receptor Antagonists as Novel Augmentation Treatments for Major Depressive Disorder: Evidence for Safety and Efficacy From a Phase 2B Study of Seltorexant
Authors: Jha Manish Kumar
Published: November 2021

There is a large unmet need for effective treatment of major depressive disorder (MDD), an often chronic/recurrent disorder that affects 1 in 5 adults during their lifetime in the United States. Clinicians and individuals with MDD often rely on augmentation approaches given the low rate of remission with the initial antidepressant treatment. Therefore, the report by Savitz and colleagues on the safety and efficacy of seltorexant is of great interest because it provides initial evidence for the antidepressant potential of drugs targeting orexin neurotransmission. Findings of this study suggest that seltorexant 20 mg is more effective than placebo, especially in individuals with moderate or insomnia symptoms at baseline. Given that insomnia is a common feature of depression, orexin 2 receptor antagonists may serve as important new treatment alternatives for people with MDD.
Respiratory antibacterial prescribing in primary care and the COVID-19 pandemic in England, winter season 2020–21
Authors: Andrews Amelia , Bou-Antoun Sabine , Guy Rebecca , Brown Colin S , Hopkins Susan , Gerver Sarah
Published: November 2021

Background

Antibacterial prescribing for respiratory tract infections (RTIs) accounts for almost half of all prescribing in primary care. Nearly a quarter of antibacterial prescribing in primary care is estimated to be inappropriate, the greatest being for RTIs. The COVID-19 pandemic has changed the provision of healthcare services and impacted the levels of antibacterials prescribed.

Objectives

To describe the changes in community antibacterial prescribing for RTIs in winter 2020–21 in England.

Methods

RTI antibacterial prescribing was measured in prescription items/1000 population for primary care from January 2014 and in DDDs/1000 population/day for the totality of RTI prescribing [combined with Accident & Emergency (A&E) in secondary care], from January 2016 to February 2021. Trends were assessed using negative binomial regression and seasonally adjusted interrupted time-series analysis.

Results

Antibacterials prescribed for RTIs reduced by a further 12.4% per season compared with pre-COVID (P < 0.001). In winter 2020–21, RTI prescriptions almost halved compared with the previous winter in 2019–20 (P < 0.001). The trend observed for total RTI prescribing (primary care with A&E) was similar to that observed in the community alone.

Conclusions

During COVID-19, RTI prescribing reduced in the community and the expected rise in winter was not seen in 2020–21. We found no evidence that RTI prescribing shifted from primary care to A&E in secondary care. The most likely explanation is a decrease in RTIs and presentations to primary care associated with national prevention measures for COVID-19.
Lynn Welchman, AL-HAQ: A Global History of the First Palestinian Human Rights Organization
Authors: Oette Lutz
Published: November 2021

This review considers and reflects on Lynn Welchman’s Al-Haq: A Global History of the First Palestinian Human Rights Organization and explores the book’s key implications for human rights practitioners and their organizations.
Sex Specificity in Innate Immunity of Insect Larvae
Authors: Belousova Irina , Pavlushin Sergey , Subbotina Anna , Rudneva Natalya , Martemyanov Vyacheslav
Published: November 2021

The innate immunity of insects has been widely studied. Although the effect of sex on insect immunity has been extensively discussed, differences in immunity between the sexes of larvae insects remain largely unstudied. Studying larval sex differences in immunity may provide valuable information about the mechanisms underlying the insect immune system, which, in turn, can be valuable for the development and improvement of pest management. Here we compared the antibacterial activity in both the midgut tissue and cell-free hemolymph of Lymantria dispar L. (Lepidoptera: Erebidae) females and males at the larval stage without and after a challenge by entomopathogenic bacterium Bacillus thuringiensis Berliner. We also evaluated the sex-specific mortality of L. dispar induced by B. thuringiensis infection. We find that antibacterial activity in the midgut is activated by infection, but only in females. Thus, sex differences in immunity can have important effects even before sexual differentiation at adulthood.
Small molecules mediate cellular reprogramming across two kingdoms
Authors: Welsch Ralf , Touraev Alisher , Palme Klaus
Published: November 2021

The fertilized egg is the single totipotent cell from which multicellular organisms arise through the processes of cell division and differentiation. While animals typically lose their capacity to redifferentiate cells that are already fully differentiated, plant cells are thought to remain totipotent (Su et al., 2020). Every gardener knows well that plants can regenerate a full array of plant tissues from already differentiated organs. This also seems to be true for single plant cells such as protoplasts, which, under proper in vitro culture conditions, served as the initial source for generation of transgenic plants (Skoog and Miller, 1957; Birnbaum and Sánchez Alvarado, 2008). However, the mechanisms behind the totipotency of plant cells remain elusive, with the exception of the knowledge that the developmental fate of regenerating tissues can be directed by the ratio of two plant hormones, auxin and cytokinin (Skoog and Miller, 1957).
Nii: a Bayesian orbit retrieval code applied to differential astrometry
Authors: Jin Sheng , Ding Xiaojian , Wang Su , Dong Yao , Ji Jianghui
Published: November 2021

Here, we present an open source python-based Bayesian orbit retrieval code (Nii) that implements an automatic parallel tempering Markov chain Monte Carlo (APT-MCMC) strategy. Nii provides a module to simulate the observations of a space-based astrometry mission in the search for exoplanets, a signal extraction process for differential astrometric measurements using multiple reference stars, and an orbital parameter retrieval framework using APT-MCMC. We further verify the orbit retrieval ability of the code through two examples corresponding to a single-planet system and a dual-planet system. In both cases, efficient convergence on the posterior probability distribution can be achieved. Although this code specifically focuses on the orbital parameter retrieval problem of differential astrometry, Nii can also be widely used in other Bayesian analysis applications.
Too dense to go through: the role of low-mass clusters in the pre-processing of satellite galaxies
Authors: Pallero Diego , Gómez Facundo A , Padilla Nelson D , Bahé Yannick M , Vega-Martínez Cristian A , Torres-Flores S
Published: November 2021

We study the evolution of satellite galaxies in clusters of the c-eagle simulations, a suite of 30 high-resolution cosmological hydrodynamical zoom-in simulations based on the eagle code. We find that the majority of galaxies that are quenched at z = 0 (≳80${{\ \rm per\ cent}}$) reached this state in a dense environment (log10M200[M⊙] ≥13.5). At low redshift, regardless of the final cluster mass, galaxies appear to reach their quenching state in low-mass clusters. Moreover, galaxies quenched inside the cluster that they reside in at z = 0 are the dominant population in low-mass clusters, while galaxies quenched in a different halo dominate in the most massive clusters. When looking at clusters at z > 0.5, their in situ quenched population dominates at all cluster masses. This suggests that galaxies are quenched inside the first cluster they fall into. After galaxies cross the cluster’s r200 they rapidly become quenched (≲1 Gyr). Just a small fraction of galaxies ($\lesssim 15{{\ \rm per\ cent}}$) is capable of retaining their gas for a longer period of time, but after 4 Gyr, almost all galaxies are quenched. This phenomenon is related to ram pressure stripping and is produced when the density of the intracluster medium reaches a threshold of $\rho _{\rm ICM}\, \sim 3 \times 10 ^{-5}$ nH (cm−3). These results suggest that galaxies start a rapid-quenching phase shortly after their first infall inside r200 and that, by the time they reach r500, most of them are already quenched.
Master lineage transcription factors anchor trans mega transcriptional complexes at highly accessible enhancer sites to promote long-range chromatin clustering and transcription of distal target genes
Authors: White Shannon M , Snyder Michael P , Yi Chunling
Published: November 2021

The term ‘super enhancers’ (SE) has been widely used to describe stretches of closely localized enhancers that are occupied collectively by large numbers of transcription factors (TFs) and co-factors, and control the transcription of highly-expressed genes. Through integrated analysis of >600 DNase-seq, ChIP-seq, GRO-seq, STARR-seq, RNA-seq, Hi-C and ChIA-PET data in five human cancer cell lines, we identified a new class of autonomous SEs (aSEs) that are excluded from classic SE calls by the widely used Rank Ordering of Super-Enhancers (ROSE) method. TF footprint analysis revealed that compared to classic SEs and regular enhancers, aSEs are tightly bound by a dense array of master lineage TFs, which serve as anchors to recruit additional TFs and co-factors in trans. In addition, aSEs are preferentially enriched for Cohesins, which likely involve in stabilizing long-distance interactions between aSEs and their distal target genes. Finally, we showed that aSEs can be reliably predicted using a single DNase-seq data or combined with Mediator and/or P300 ChIP-seq. Overall, our study demonstrates that aSEs represent a unique class of functionally important enhancer elements that distally regulate the transcription of highly expressed genes.