bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic amendments for crop production, phosphorus bioavailability and heavy metal immobilisation: a review
Authors: Mamun Shamim Al , Saha Shatabdi , Ferdush Jannatara , Tusher Tanmoy Roy , Islam Md. Saiful
Published: May 2022

Repeated and excessive use of inorganic phosphorus fertilisers adversely affects soil fertility, reduces plant phosphorus (P)-use efficiency, increases soil heavy metal concentrations and poses human health risks via food chain interaction. Organic amendments (OAs) are considered as cost-effective and environment-friendly supplement to inorganic P fertilisers that are produced from scarce phosphate rocks. Numerous studies have reported the synergistic and antagonistic effects of OAs on crop production, P solubility and availability, and immobilisation of heavy metals. However, the results of these studies are found to be variable and demand a critical review. This article summarises the environmental and health implications of continuous inorganic P fertilisers application along with a detailed overview of commonly available OAs and their efficacy to stimulate plant growth and yield. Moreover, this review describes the potentiality of OAs to increase the bioavailability of P in soil, discusses how and to what extent these soil amendments can immobilise heavy metals and reduce plant uptake, and finally provides future research directions for organic farming and sustainable agricultural practices.
Marine anoxia linked to abrupt global warming during Earth’s penultimate icehouse
Authors: Chen Jitao , Montañez Isabel P. , Zhang Shuang , Isson Terry T. , Macarewich Sophia I. , Planavsky Noah J. , Zhang Feifei , Rauzi Sofia , Daviau Kierstin , Yao Le , Qi Yu-ping , Wang Yue , Fan Jun-xuan , Poulsen Christopher J. , Anbar Ariel D. , Shen Shu-zhong , Wang Xiang-dong
Published: May 2022

Significance

Massive carbon (C) release with abrupt warming has occurred repeatedly during greenhouse states, and these events have driven episodes of ocean deoxygenation and extinction. Records from these paleo events, coupled with biogeochemical modeling, provide clear evidence that with continued warming, the modern oceans will experience substantial deoxygenation. There are, however, few constraints from the geologic record on the effects of rapid warming under icehouse conditions. We document a C-cycle perturbation that occurred under an Earth system state experiencing recurrent glaciation. A suite of proxies suggests increased seafloor anoxia during this event in step with abrupt increase in CO2partial pressure and a biodiversity nadir. Warming-mediated increases in marine anoxia may be more pronounced in a glaciated versus unglaciated climate state.
US foreign aid restrictions and maternal and children’s health: Evidence from the “Mexico City Policy”
Authors: Kavakli Kerim Can , Rotondi Valentina
Published: May 2022

Significance

Although family planning services are crucial for global health and achievement of the Sustainable Development Goals, their funding remains controversial. We document the health consequences of the “Mexico City Policy” (MCP), which restricts US funding for abortion-related activities worldwide. Since its enactment in 1985, the MCP has been enforced only under Republican administrations and quickly rescinded when a Democrat wins the presidency. Our analysis shows that the MCP makes it harder for women to get information on and support for reproductive health and is associated with higher maternal and child mortality rates and HIV rates worldwide. We estimate that reinstating the MCP between 2017 and 2021 resulted in approximately 108,000 maternal and child deaths and 360,000 new HIV infections.
Mapped coral mortality and refugia in an archipelago-scale marine heat wave
Authors: Asner Gregory P. , Vaughn Nicholas R. , Martin Roberta E. , Foo Shawna A. , Heckler Joseph , Neilson Brian J. , Gove Jamison M.
Published: May 2022

Corals are a major habitat-building life-form on tropical reefs that support a quarter of all species in the ocean and provide ecosystem services to millions of people. Marine heat waves continue to threaten and shape reef ecosystems by killing individual coral colonies and reducing their diversity. However, marine heat waves are spatially and temporally heterogeneous, and so too are the environmental and biological factors mediating coral resilience during and following thermal events. This combination results in highly variable outcomes at both the coral bleaching and mortality stages of every event. This, in turn, impedes the assessment of changing reef-scale patterns of thermal tolerance or places of resistance known as reef refugia. We developed a large-scale, high-resolution coral mortality monitoring capability based on airborne imaging spectroscopy and applied it to a major marine heat wave in the Hawaiian Islands. While water depth and thermal stress strongly mediated coral mortality, relative coral loss was also inversely correlated with preheat-wave coral cover, suggesting the existence of coral refugia. Subsequent mapping analyses indicated that potential reef refugia underwent up to 40% lower coral mortality compared with neighboring reefs, despite similar thermal stress. A combination of human and environmental factors, particularly coastal development and sedimentation levels, differentiated resilient reefs from other more vulnerable reefs. Our findings highlight the role that coral mortality mapping, rather than bleaching monitoring, can play for targeted conservation that protects more surviving corals in our changing climate.
A corpus-pragmatics approach to evaluation in professor reviews
Authors: Ho Mei-ching
Published: May 2022

This study takes a corpus pragmatics approach to investigate the use of evaluative language in professor reviews, focusing on how review writers express evaluation through recurrent four-word sequences and the pragmatic functions of these sequences in positive and negative reviews on the website,RateMyProfessors.com. Based on an analysis of a 2.9-million-word corpus of free text comments, the findings indicate that positive reviews used more 4-grams, and more varied types, than negative ones. The 4-word sequences were found to carry out four pragmatic functions: attitudinal evaluation, reader engagement, referential expression, and discourse organization. While a similar distribution of the main functional categories was observed among the top 100 4-grams in both review types, with evaluative clusters being most predominant, distinctive intra-genre variations were found in the ways review writers employed different functional sub-categories. For example, positive reviews relied heavily on hedged suggestion 4-grams to engage readers, whereas negative reviews used directive 4-grams for the same purpose. These findings suggest the important role of multi-word sequences in the understanding of evaluative resources in professor reviews of different valence types.
The constructionalization of antonymous compounds
Authors: Lu Xiaolong
Published: May 2022

In modern Chinese, the adverbchi-zaois regarded as an adjective-adjective compound, with morphemeschi‘late’ andzao‘early’ as extreme poles in a gradable temporality. The formation ofchi-zaoas an antonymous compound has not received much attention from a diachronic construction grammar perspective. This study reports on the historical change ofchi-zaoas evidence showing the interplay of antonymous compounds and constructionalization in modern Chinese. Based on corpus analysis, I found that the formation ofchi-zaoas a lexical construction inherits from previous changes but emerges instantaneously in Pre-Modern Chinese, where its form has been condensed and its meaning has been bleached to indicate subjectivity. Three arguments shed light on the model of constructionalization: (1) constructionalization at the compound level can be associated with three motivations: subjectivity, frequency, and metaphor; and (2) the operation of constructionalization is at work not only at the sentential and phrasal level but also at the morphological level of compound word formation in Chinese; (3) rhetoric as an output of language use plays a part in the development of constructionalization in relation to antonymous compounds.
Fluidity of casting Al–Si series alloys for automotive light-weighting: A systematic review
Authors: Niu Guodong , Wang Yu , Zhu Langjie , Ye Jinwen , Mao Jian
Published: May 2022

With the increasing demand requirements of lightweight automobiles, foundry industries are facing urgent requests from the demanders to manufacture increasingly lighter castings with thin walls and complex shapes. Fluidity is the essential parameter to evaluate the filling ability of casting alloys. Many factors are affecting the fluidity of casting Al–Si series alloys. In this review, the current understanding of the various factors influencing the fluidity of casting Al–Si series alloys was systematically summarised. Moreover, the solidification mechanism of hypoeutectic Al–Si alloys under the high-pressure die casting (HPDC) process is also discussed. HPDC process is not inversely proportional to the solidification interval, but the fluidity length increases with decreasing solidus temperature of the hypoeutectic Al–Si alloys.
Internet use and Uptake of a Web-Based Prevention and Risk Reduction Intervention for Persons who use Drugs in New York City – Webhealth4Us Study (2013–2016)
Authors: Lewis Crystal Fuller , Williams Sharifa Z. , Tofighi Babak , Lekas Helen-Maria , Joseph Adriana , Rivera Alexis , Amesty Silvia C.
Published: May 2022

Background: Data on Internet utilization is needed, particularly during a time when in-person services are limited or only available virtually. The purpose of this study was to identify characteristics of Internet use among persons who use drugs and assess adoption of an interactive, risk reduction informational website – WebHealth4Us. Methods: Participant recruitment occurred in pharmacies participating in the New York State pharmacy syringe access program ( n = 209). ACASI surveys were conducted on-site to ascertain Internet use and related sociodemographics and risk behaviors. Internet users (use ≥ once/month) were shown a website WebHealth4Us highlighting social services and risk reduction information on four topic areas: mental health, HIV, HCV, and other STI; users could also sign-up for weekly text messages for any topic area. Follow-up ACASI occurred at four weeks to assess user experiences and website adoption. Results: Study sample ( n = 196) was mostly male (60%), average age 46, black/Latinx (76%), had a history of incarceration (79%), and reported past/current injection (53%) or non-injection (51%) drug use. Internet use was high (79%), accessed >4 times/week (60%) most commonly for: housing (61%), health issues (54%), and drug treatment (45%). Over one-third accessed WebHealth4Us during follow-up, and 35% of those opted for weekly text messages (mental health most common topic selected). After adjustment, younger age (AOR = 0.96) and alcohol use (AOR = 2.26) predicted WebHealth4Us access. Conclusion: Internet use was high with considerable WebHealth4Us access, and specifically for mental health needs. Web-based interventions warrant large-scale investigation in high-risk communities, prioritizing social determinants and behavioral health.
Association of Substance use Characteristics and Future Homelessness among Emergency Department Patients with Drug use or Unhealthy Alcohol Use: Results from a Linked Data Longitudinal Cohort Analysis
Authors: Yoo Ruth , Krawczyk Noa , Johns Eileen , McCormack Ryan P. , Rotrosen John , Mijanovich Tod , Gelberg Lillian , Doran Kelly M.
Published: May 2022

Background: Homelessness and substance use are intricately related, and both are prevalent among emergency department (ED) patients. This study examined the longitudinal association of substance use characteristics with future homeless shelter entry among ED patients with any drug use or unhealthy alcohol use. Methods: We present results from a longitudinal cohort study of public hospital ED patients who screened positive for drug use or unhealthy alcohol use and who were not homeless at their baseline (index) ED visit. The primary outcome was homeless shelter entry within 12 months of baseline, ascertained in city homeless shelter administrative data. Primary independent variables of interest were alcohol use severity (AUDIT), drug use severity (DAST-10), and types of drugs used, as reported on baseline survey questionnaires. Results:Analyses included 1,210 ED patients. By 12 months following the baseline ED visit, 114 (9.4%) had entered a homeless shelter. Among patients with the most severe problems related to drug use (DAST-10 score 9–10), 40.9% entered a shelter within 12 months. Past shelter use was the strongest predictor of future shelter entry; once adjusting for historic shelter use the relationship of AUDIT and DAST-10 scores with future shelter entry was no longer statistically significant in multivariable models. Conclusions: ED patients with past year drug use or unhealthy alcohol use had relatively high likelihood of future shelter entry. Risk for homelessness should be addressed in future interventions with this population. Findings illustrate the complexity of relationships between substance use and homelessness.
Targeted metabolomics analyses for brain tumor margin assessment during surgery
Authors: Cakmakci Doruk , Kaynar Gun , Bund Caroline , Piotto Martial , Proust Francois , Namer Izzie Jacques , Cicek A Ercument
Published: May 2022

Motivation

Identification and removal of micro-scale residual tumor tissue during brain tumor surgery are key for survival in glioma patients. For this goal, High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) spectroscopy-based assessment of tumor margins during surgery has been an effective method. However, the time required for metabolite quantification and the need for human experts such as a pathologist to be present during surgery are major bottlenecks of this technique. While machine learning techniques that analyze the NMR spectrum in an untargeted manner (i.e. using the full raw signal) have been shown to effectively automate this feedback mechanism, high dimensional and noisy structure of the NMR signal limits the attained performance.

Results

In this study, we show that identifying informative regions in the HRMAS NMR spectrum and using them for tumor margin assessment improves the prediction power. We use the spectra normalized with the ERETIC (electronic reference to access in vivo concentrations) method which uses an external reference signal to calibrate the HRMAS NMR spectrum. We train models to predict quantities of metabolites from annotated regions of this spectrum. Using these predictions for tumor margin assessment provides performance improvements up to 4.6% the Area Under the ROC Curve (AUC-ROC) and 2.8% the Area Under the Precision-Recall Curve (AUC-PR). We validate the importance of various tumor biomarkers and identify a novel region between 7.97 ppm and 8.09 ppm as a new candidate for a glioma biomarker.

Availability and implementation

The code is released at https://github.com/ciceklab/targeted_brain_tumor_margin_assessment. The data underlying this article are available in Zenodo, at https://doi.org/10.5281/zenodo.5781769.

Supplementary information

Supplementary data are available at Bioinformatics online.
A new approach to testing mediation of the microbiome at both the community and individual taxon levels
Authors: Yue Ye , Hu Yi-Juan
Published: May 2022

Motivation

Understanding whether and which microbes played a mediating role between an exposure and a disease outcome are essential for researchers to develop clinical interventions to treat the disease by modulating the microbes. Existing methods for mediation analysis of the microbiome are often limited to a global test of community-level mediation or selection of mediating microbes without control of the false discovery rate (FDR). Further, while the null hypothesis of no mediation at each microbe is a composite null that consists of three types of null, most existing methods treat the microbes as if they were all under the same type of null, leading to excessive false positive results.

Results

We propose a new approach based on inverse regression that regresses the microbiome data at each taxon on the exposure and the exposure-adjusted outcome. Then, the P-values for testing the coefficients are used to test mediation at both the community and individual taxon levels. This approach fits nicely into our Linear Decomposition Model (LDM) framework, so our new method LDM-med, implemented in the LDM framework, enjoys all the features of the LDM, e.g. allowing an arbitrary number of taxa to be tested simultaneously, supporting continuous, discrete, or multivariate exposures and outcomes (including survival outcomes), and so on. Using extensive simulations, we showed that LDM-med always preserved the FDR of testing individual taxa and had adequate sensitivity; LDM-med always controlled the type I error of the global test and had compelling power over existing methods. The flexibility of LDM-med for a variety of mediation analyses is illustrated by an application to a murine microbiome dataset, which identified several plausible mediating taxa.

Availability and implementation

Our new method has been added to our R package LDM, which is available on GitHub at https://github.com/yijuanhu/LDM.

Supplementary information

Supplementary data are available at Bioinformatics online.
Minimax designs for causal effects in temporal experiments with treatment habituation
Authors: Basse Guillaume W , Ding Yi , Toulis Panos
Published: May 2022

In many modern settings, such as an online marketplace, randomized experiments need to be executed over multiple time periods. In such temporal experiments, it has been observed that the effects of an intervention on an experimental unit may be large when the unit is first exposed to it, but then it attenuates after repeated exposures. This is typically due to units’ habituation to the intervention, or some other form of learning, such as when users gradually start to ignore repeated mails sent by a promotional campaign. This paper proposes randomized designs for estimating causal effects in temporal experiments when habituation is present. We show that our designs are minimax optimal in a large class of practical designs. Our analysis is based on the randomization framework of causal inference, and imposes no parametric modelling assumptions on the outcomes.
Systematic literature review of topical local anaesthesia or analgesia to donor site wounds
Authors: McBride Craig A , Wong Marilyn , Patel Bhaveshkumar
Published: May 2022

Background

Topical local analgesic and anaesthetic agents have been used both pre- and immediately post-harvest on split-thickness skin graft (STSG) donor site wounds (DSW). There is no systematic review of their effectiveness in providing post-harvest analgesia, or of the possible toxic effects of systemic absorption. This study is designed to address the question of which agent, if any, is favoured over the others and whether there are any safety data regarding their use.

Methods

Systematic literature review of randomised controlled trials of topical agents applied to STSG DSWs, with a view to providing analgesia. Studies identified via search of Cochrane and EBSCO databases. No restrictions on language or publication year. Primary outcomes: pain at the time of (awake) STSG, and post-harvest pain (up to first dressing change). Secondary outcome was serum medication levels relative to published data on toxic doses. Cochrane risk of bias assessment tool utilised in assessment of included studies. At least 2 reviewers screened and reviewed included studies. A narrative review is presented.

Results

There were 11 studies meeting inclusion criteria. Overall methodological quality and patient numbers were low. Topical eutectic mixture of lidocaine and prilocaine pre-harvest affords good local anaesthesia in awake STSG harvesting. Topical bupivacaine (5 studies) or lidocaine (1 study) gave significantly better post-harvest anaesthesia/analgesia than placebo. Topical morphine performs no better than placebo. Topical local anaesthetic agents at reported doses were all well below toxic serum levels.

Conclusions

Topical local anaesthetics (lidocaine or bupivacaine) provide good analgesia, both during and after STSG harvest, at well below toxic serum levels, but there are no good data determining the best local anaesthetic agent to use. There is no evidence morphine performs better than placebo.
Association Between Inflammatory Bowel Disease and Spondyloarthritis: Findings from a Nationwide Study in Sweden
Authors: Shrestha Sarita , Brand Judith S , Järås Jacob , Schoultz Ida , Montgomery Scott , Askling Johan , Ludvigsson Jonas F , Olen Ola , Halfvarson Jonas ,   SWIBREG Study Group, Olsson Malin , Hjortswang Henrik , Myrelid Par , Bengtsson Jonas , Strid Hans , Andersson Marie , Jäghult Susanna , Eberhardson Michael , Nordenvall Caroline , Fagerberg Ulrika L , Rejler Martin , Grip Olof , Karling Pontus
Published: May 2022

Background and Aims

Inflammatory bowel disease [IBD] has been associated with spondyloarthritis [SpA], but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD with the general population, overall and by IBD subtype and age.

Methods

We used a nationwide register-based cohort study of 39 203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390 490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios [ORs] for a prior [prevalent] SpA diagnosis and conditional Cox regression to calculate hazard ratios [HRs] for a subsequent [incident] SpA diagnosis in IBD patients.

Results

IBD patients were more likely to have prevalent SpA at IBD diagnosis [2.5%] compared with reference individuals [0.7%] with an OR of 3.48 [95% CI: 3.23, 3.75]. They also more often received an incident diagnosis of SpA; during 23 341 934 person-years of follow-up in IBD patients, there were 1030 SpA events [5.0/1000 person-years] compared with 1524 SpA events in the reference group [0.72/1000 person-years], corresponding to an HR of 7.15 [95% CI: 6.60, 7.75]. In subgroup analyses, associations were most pronounced among patients with Crohn’s disease ([OR = 5.20; 95% CI: 4.59, 5.89], and [HR = 10.55; 95% CI: 9.16, 12.15]) and paediatric onset IBD ([OR = 3.63; 95% CI: 2.35, 5.59] and [HR = 15.03; 95% CI: 11.01, 20.53]).

Conclusions

IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared with the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity, across IBD subtypes and age groups, calls for targeted approaches to facilitate timely diagnosis and intervention.
Discovery of spirooxindole-pyrrolidine heterocyclic hybrids with potent antifungal activity against fungal pathogens
Authors: Dowdy Hannah , Kumar Raju Suresh , Almansour Abdulrahman I , Arumugam Natarajan , Ibrahim Alaqeel Shatha , Thangamani Shankar
Published: May 2022

Fungal pathogens mainly Candida and Cryptococcus species causes serious life-threating infections to humans, especially in individuals who are immunocompromised. Increasing frequency of antifungal drug resistance along with paucity of FDA-approved drugs suggest a dire need for new antifungal drugs. Our screening of newly synthesized spirooxindole heterocyclic hybrid compounds revealed that the novel small molecule, DPA-3, has potent antifungal activity without inducing mammalian cell cytotoxicity. Furthermore, DPA-3 significantly reduced hyphal and biofilm formation of Candida albicans ATCC 10231 strain, out-competing two FDA approved antifungal drugs. The results of our study conclude that DPA-3 is a compelling candidate for further development as an antifungal drug.
Divergent Genital Morphologies and Female–Male Covariation in Watersnakes
Authors: Greenwood J F , Lara Granados G , Secor S M , Todd B D , Showalter I , Hedrick B P , Brennan P L R
Published: May 2022

Genital evolution can be driven by diverse selective pressures. Across taxa we see evidence of covariation between males and females, as well as divergent genital morphologies between closely related species. Quantitative analyses of morphological changes in coevolving male and female genitalia have not yet been shown in vertebrates. This study uses 2D and 3D geometric morphometrics to quantitatively compare the complex shapes of vaginal pouches and hemipenes across three species of watersnakes (the sister taxa Nerodia fasciata, N. sipedon, and a close relative N. rhombifer) to address the relationship between genital morphology and divergence time in a system where sexual conflict may have driven sexually antagonistic coevolution of genital traits. Our pairwise comparisons of shape differences across species show that the sister species have male and female genitalia that are significantly different from each other, but more similar to each other than to N. rhombifer. We also determine that the main axes of shape variation are the same for males and females, with changes that relate to deeper bilobation of the vaginal pouch and hemipenes. In males, the protrusion of the region of spines at the base of the hemipene trades off with the degree of bilobation, suggesting amelioration of sexual conflict, perhaps driven by changes in the relative size of the entrance of the vaginal pouch that could have made spines less effective.
Effects of cardiopulmonary bypass on immunoglobulin G antibody titres after SARS-CoV2 vaccination
Authors: Hayashi Ryosuke , Takami Yoshiyuki , Fujigaki Hidetsugu , Amano Kentaro , Sakurai Yusuke , Akita Kiyotoshi , Yamana Koji , Maekawa Atsuo , Saito Kuniaki , Takagi Yasushi
Published: May 2022

OBJECTIVES

Patients with cardiovascular disease are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Although SARS-CoV2 vaccination may be effective, its impact on surgical patients is not well studied. We investigated the effects of cardiovascular surgery, especially under cardiopulmonary bypass (CPB), on the antibody titres after SARS-CoV2 vaccination.

METHODS

A prospective observational study was designed for patients undergoing surgery between July and November 2021. The immunoglobulin G against the receptor-binding domain was measured and antibody preserved rate (APR) was calculated from perioperative titres comparison.

RESULTS

Enrolled 63 study patients were divided into 39 undergoing surgery with CPB (Group CPB) and 24 without CPB (Group None). Preoperative vaccines were BNT162b2 (Pfizer/BioNTech) (n = 58, 92%) and mRNA-1273 (Moderna) (n = 5, 8%). While immunoglobulin G against the receptor-binding domain titres did not significantly decrease after surgery in Group None, they decreased significantly in Group CPB from 21.80 [11.15, 37.85] to 11.95 [6.80, 18.18] U/ml (P < 0.001) a day after surgery, 11.40 [7.85, 22.65] U/ml (P < 0.001) 14 days after surgery and 7.60 [4.80, 17.60] U/ml (P < 0.001) a month after surgery. The APRs a day after the surgery were significantly lower in Group CPB (0.46 [0.41, 0.60]) than in Group None (0.80 [0.68, 0.87]) (P < 0.001).

CONCLUSIONS

The SARS-CoV2 antibody titres significantly decreased with lower APRs immediately after surgery under CPB. Based on our informative results, careful considerations of vaccination schedule might be required for surgery under CPB.
Commentary on the new English smoking cessation Advanced service: a sustainable gateway to care or will it disappear in a puff of smoke?
Authors: Latif Asam , Mandane Baguiasri , Qureshi Sadaf
Published: May 2022

Further to plans to make England ‘smoke-free’ by 2030, a new English community pharmacy smoking cessation service was launched in March 2022. The service includes offering people admitted to hospital an opportunity to enrol on a smoking cessation service that allows care to be maintained through their community pharmacy upon discharge. There is a high expectation for this service, which is expected to increase 1-year quit rates by 11% and in its first year, save the UK NHS £85 million in healthcare resources. The service also offers opportunities for pharmacists to assume a greater role in managing the long-term care of smokers. However, as with any new service, without careful monitoring of the implementation, there may be unforeseen and unintended consequences for what are otherwise well-intentioned actions. For instance, despite existing smoking cessation services being effective, historically there has always been poor smoker uptake, particularly people from less affluent backgrounds and from marginalised groups. Questions also arise about service adoption and implementation and how the risks associated with transitions between care providers will be managed. This timely commentary explores and examines these issues. Specifically, we add to the debate by focusing on the extent to which the new service caters or enables people from disadvantaged groups to participate fully. The challenges of adoption and implementation in pharmacies are discussed as well as the strategies to overcome foreseeable problems that might arise during transitions of care.
Dolutegravir Suppresses Thermogenesis via Disrupting Uncoupling Protein 1 Expression and Mitochondrial Function in Brown/Beige Adipocytes in Preclinical Models
Authors: Jung IkRak , Tu-Sekine Becky , Jin Sunghee , Anokye-Danso Frederick , Ahima Rexford S , Brown Todd T , Kim Sangwon F
Published: May 2022

Background

Antiretroviral therapy (ART) containing integrase strand transfer inhibitors (INSTIs) has been associated with weight gain in both ART initiation and switch studies, especially in women, but the underlying mechanisms are unclear.

Methods

The effects of dolutegravir (DTG) on food intake, energy expenditure, oxygen consumption in female mice, and gene expression from adipose tissues were assessed. Human and murine preadipocytes were treated with DTG either during differentiation into mature brown/beige adipocytes or postdifferentiation. Lipid accumulation, lipolysis, β-adrenergic response, adipogenic markers, mitochondrial respiration, and insulin response were analyzed.

Results

Two-week administration of DTG to female mice reduced energy expenditure, which was accompanied by decreased uncoupling protein 1 (UCP1) expression in brown/beige adipose tissues. In vitro studies showed that DTG significantly reduced brown adipogenic markers, especially UCP1 in brown and beige adipocytes, whereas drugs from other classes did not. Furthermore, a loss of UCP1 by DTG led to a decrease in mitochondrial complex IV component, followed by a reduction in mitochondrial respiratory capacity and reduced insulin-stimulated glucose uptake.

Conclusions

Our findings show that DTG targets UCP1 and mitochondrial functions in brown and beige adipocytes and disrupts thermogenic functions in preclinical models, providing the potential mechanisms by which DTG suppresses energy expenditure leading to weight gain.
Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo
Authors: Pal Anasuya C , Renard Isaline , Singh Pallavi , Vydyam Pratap , Chiu Joy E , Pou Sovitj , Winter Rolf W , Dodean Rozalia , Frueh Lisa , Nilsen Aaron C , Riscoe Michael K , Doggett J Stone , Ben Mamoun Choukri
Published: May 2022

Human babesiosis is a malaria-like illness caused by tick-borne intraerythrocytic Babesia parasites of the Apicomplexa phylum. Whereas several species of Babesia can cause severe disease in humans, the ability to propagate Babesia duncani both in vitro in human erythrocytes and in mice makes it a unique pathogen to study Babesia biology and pathogenesis. Here we report an optimized B. duncani in culture–in mouse (ICIM) model that combines continuous in vitro culture of the parasite with a precise model of lethal infection in mice. We demonstrate that B. duncani–infected erythrocytes as well as free merozoites can cause lethal infection in C3H/HeJ mice. Highly reproducible parasitemia and survival outcomes could be established using specific parasite loads in different mouse genetic backgrounds. Using the ICIM model, we discovered 2 new endochin-like quinolone prodrugs (ELQ-331 and ELQ-468) that alone or in combination with atovaquone are highly efficacious against B. duncani and Babesia microti.
Simultaneous Determination of Adulterants in Dietary Food Supplements Using Multivariate Data Analysis after Preconcentration with Novel Nanosorbents and Chromatographic Measurement
Authors: Hosseini Ensie , Ghasemi Jahan B , Shekarchi Maryam
Published: May 2022

Background

The increasing popularity of dietary supplements and, consequently, related adulteration emphasizes the rising need to examine the association of food supplements with fraud. Intentional or unintentional fraud in food supplements by hazardous chemicals compounds is a problem that many countries are struggling with. Much effort have been made to effectively and reliably control the quality of food supplements.

Objective

Due to the importance of the subject, an analytical method for the simultaneous and reliable detection and quantitative determination of three key adulterants in dietary food supplements was developed. The proposed method benefits from analytical methods and multivariate calibration methods to progress the determination of adulterants in a complex matrix.

Methods

HPLC assisted by multivariate curve resolution-alternating least square (MCR-ALS) analysis was used to detect adulterants in real samples after separation and preconcentration using novel mesoporous carbon nanoparticles. Solid-phase extraction (SPE) optimization was accomplished by central composite design (CCD). In order to obtain the best results, the MCR-ALS model was compared with the parallel factor analysis 2 (PARAFAC2) model and validated by estimation of linearity, detection limits, and recovery.

Results

The detection limits and linear dynamics were calculated as 1.5, 4.27, and 4.77 µg/mL, and 1–50, 5–20, and 5–20 µg/mL for caffeine, ephedrine, and fluoxetine, respectively. Mean recovery for determination of caffeine, ephedrine, and fluoxetine using the developed method was reported as 101.75, 91.7, and 92.36, respectively.

Conclusion

The results showed that to avoid negative health outcomes associated with the excessive consumption of adulterated food supplements releasing such products should be carefully regulated. The developed method was validated using statistical factors and showed acceptable and reliable results.

Highlights

(1) The application of MCR-ALS coupled with HPLC-Diode-Array Detection data sets allowed the simultaneous identification and quantification of three key adulterants (caffeine, ephedrine, and fluoxetine) in dietary food supplements. (2) A small amount of the novel adsorbent was successfully used to preconcentrate the trace amounts of adulterants in samples. (3) This method benefits from the chemometrics tools and experimental design to significantly reduce the use of toxic solvents and complicated instruments to propose a less time-consuming method for quantification of multicomponents in the presence of uncalibrated interferents.
Speaker Responsibility for Synthetic Speech Derived from Neural Activity
Authors: Rainey Stephen
Published: May 2022

This article provides analysis of the mechanisms and outputs involved in language-use mediated by a neuroprosthetic device. It is motivated by the thought that users of speech neuroprostheses require sufficient control over what their devices externalize as synthetic speech if they are to be thought of as responsible for it, but that the nature of this control, and so the status of their responsibility, is not clear.
SN 2020acat: an energetic fast rising Type IIb supernova
Authors: Medler K , Mazzali P A , Teffs J , Ashall C , Anderson J P , Arcavi I , Benetti S , Bostroem K A , Burke J , Cai Y-Z , Charalampopoulos P , Elias-Rosa N , Ergon M , Galbany L , Gromadzki M , Hiramatsu D , Howell D A , Inserra C , Lundqvist P , McCully C , Müller-Bravo T , Newsome M , Nicholl M , Padilla Gonzalez E , Paraskeva E , Pastorello A , Pellegrino C , Pessi P J , Reguitti A , Reynolds T M , Roy R , Terreran G , Tomasella L , Young D R
Published: May 2022

The ultraviolet (UV) and near-infrared (NIR) photometric and optical spectroscopic observations of SN 2020acat covering ∼250 d after explosion are presented here. Using the fast rising photometric observations, spanning from the UV to NIR wavelengths, a pseudo-bolometric light curve was constructed and compared to several other well-observed Type IIb supernovae (SNe IIb). SN 2020acat displayed a very short rise time reaching a peak luminosity of $\mathrm{{\rm Log}_{10}}(L) = 42.49 \pm 0.17 \, \mathrm{erg \, s^{-1}}$ in only ∼14.6 ± 0.3 d. From modelling of the pseudo-bolometric light curve, we estimated a total mass of 56Ni synthesized by SN 2020acat of MNi = 0.13 ± 0.03 M⊙, with an ejecta mass of Mej = 2.3 ± 0.4 M⊙ and a kinetic energy of Ek = 1.2 ± 0.3 × 1051 erg. The optical spectra of SN 2020acat display hydrogen signatures well into the transitional period (≳ 100 d), between the photospheric and the nebular phases. The spectra also display a strong feature around 4900  Å that cannot be solely accounted for by the presence of the Fe ii 5018 line. We suggest that the Fe ii feature was augmented by He i 5016 and possibly by the presence of N ii 5005. From both photometric and spectroscopic analysis, we inferred that the progenitor of SN 2020acat was an intermediate-mass compact star with an MZAMS of 15–20 M⊙.
Characterizing locus specific chromatin structure and dynamics with correlative conventional and super-resolution imaging in living cells
Authors: Mehra Dushyant , Adhikari Santosh , Banerjee Chiranjib , Puchner Elias M
Published: May 2022

The dynamic rearrangement of chromatin is critical for gene regulation, but mapping both the spatial organization of chromatin and its dynamics remains a challenge. Many structural conformations are too small to be resolved via conventional fluorescence microscopy and the long acquisition time of super-resolution photoactivated localization microscopy (PALM) precludes the structural characterization of chromatin below the optical diffraction limit in living cells due to chromatin motion. Here we develop a correlative conventional fluorescence and PALM imaging approach to quantitatively map time-averaged chromatin structure and dynamics below the optical diffraction limit in living cells. By assigning localizations to a locus as it moves, we reliably discriminate between bound and unbound dCas9 molecules, whose mobilities overlap. Our approach accounts for changes in DNA mobility and relates local chromatin motion to larger scale domain movement. In our experimental system, we show that compacted telomeres move faster and have a higher density of bound dCas9 molecules, but the relative motion of those molecules is more restricted than in less compacted telomeres. Correlative conventional and PALM imaging therefore improves the ability to analyze the mobility and time-averaged nanoscopic structural features of locus specific chromatin with single molecule sensitivity and yields unprecedented insights across length and time scales.
PiER: web-based facilities tailored for genetic target prioritisation harnessing human disease genetics, functional genomics and protein interactions
Authors: Fang Hai
Published: May 2022

Integrative prioritisation promotes translational use of disease genetic findings in target discovery. I report ‘PiER’ (http://www.genetictargets.com/PiER), web-based facilities that support ab initio and real-time genetic target prioritisation through integrative use of human disease genetics, functional genomics and protein interactions. By design, the PiER features two facilities: elementary and combinatory. The elementary facility is designed to perform specific tasks, including three online tools: eV2CG, utilising functional genomics to link disease-associated variants (particularly located at the non-coding genome) to core genes likely responsible for genetic associations in disease; eCG2PG, using knowledge of protein interactions to ‘network’ core genes and additional peripheral genes, producing a ranked list of core and peripheral genes; and eCrosstalk, exploiting the information of pathway-derived interactions to identify highly-ranked genes mediating crosstalk between molecular pathways. Each of elementary tasks giving results is sequentially piped to the next one. By chaining together elementary tasks, the combinatory facility automates genetics-led and network-based integrative prioritisation for genetic targets at the gene level (cTGene) and at the crosstalk level (cTCrosstalk). Together with a tutorial-like booklet describing instructions on how to use, the PiER facilities meet multi-tasking needs to accelerate computational translational medicine that leverages human disease genetics and genomics for early-stage target discovery and drug repurposing.
BioExcel Building Blocks Workflows (BioBB-Wfs), an integrated web-based platform for biomolecular simulations
Authors: Bayarri Genís , Andrio Pau , Hospital Adam , Orozco Modesto , Gelpí Josep Lluís
Published: May 2022

We present BioExcel Building Blocks Workflows, a web-based graphical user interface (GUI) offering access to a collection of transversal pre-configured biomolecular simulation workflows assembled with the BioExcel Building Blocks library. Available workflows include Molecular Dynamics setup, protein-ligand docking, trajectory analyses and small molecule parameterization. Workflows can be launched in the platform or downloaded to be run in the users’ own premises. Remote launching of long executions to user's available High-Performance computers is possible, only requiring configuration of the appropriate access credentials. The web-based graphical user interface offers a high level of interactivity, with integration with the NGL viewer to visualize and check 3D structures, MDsrv to visualize trajectories, and Plotly to explore 2D plots. The server requires no login but is recommended to store the users’ projects and manage sensitive information such as remote credentials. Private projects can be made public and shared with colleagues with a simple URL. The tool will help biomolecular simulation users with the most common and repetitive processes by means of a very intuitive and interactive graphical user interface. The server is accessible at https://mmb.irbbarcelona.org/biobb-wfs.
Sieving carbons promise practical anodes with extensible low-potential plateaus for sodium batteries
Authors: Li Qi , Liu Xiangsi , Tao Ying , Huang Jianxing , Zhang Jun , Yang Chunpeng , Zhang Yibo , Zhang Siwei , Jia Yiran , Lin Qiaowei , Xiang Yuxuan , Cheng Jun , Lv Wei , Kang Feiyu , Yang Yong , Yang Quan-Hong
Published: May 2022

Non-graphitic carbons are promising anode candidates for sodium-ion batteries, while their variable and complicated microstructure severely limits the rational design of high-energy carbon anodes that could accelerate the commercialization of sodium-ion batteries, as is the case for graphite in lithium-ion batteries. Here, we propose sieving carbons, featuring highly tunable nanopores with tightened pore entrances, as high-energy anodes with extensible and reversible low-potential plateaus (<0.1 V). It is shown that the tightened pore entrance blocks the formation of the solid electrolyte interphase inside the nanopores and enables sodium clustering to produce the plateau. Theoretical and spectroscopic studies also show that creating a larger area of sodiophilic pore surface leads to an almost linearly increased number of sodium clusters, and controlling the pore body diameter guarantees the reversibility of sodium cluster formation, producing a sieving carbon anode with a record-high plateau capacity of 400 mAh g–1. More excitingly, this approach to preparing sieving carbons has the potential to be scalable for modifying different commercial porous carbons.
Disciplining interdisciplinarity: Infrastructure, identity, and interdisciplinary practice in nanoELSI research
Authors: Ku Sharon Tsai-hsuan , Zehr Stephen
Published: May 2022

Large-scale interdisciplinary collaboration between natural and social sciences has been advocated by funding agencies for enhancing communication between science and society. However, the actual infrastructure design and operation remain challenging, particularly for social-science-led interdisciplinary centers, which normally do not have core scientific facilities or centralized laboratories to coordinate collaborations among disciplines. Drawing upon ethnographic and interview data, this paper examines how the notion of interdisciplinarity was practiced in two federally-funded Centers for Nanotechnology in Society. We show how federal policies, university cultures, and local organizational structures significantly impacted forms of interdisciplinary practice and identity. In addition, we show that individuals’ interdisciplinary rhetoric, epistemic claims, and daily operation of interdisciplinarity require strong infrastructural support in terms of spatial and human resource arrangements to nurture cross-disciplinary coordination and trust as well as softening collaborative tensions while developing complementary projects.
Krüppel-like Factor 4 Supports the Expansion of Leukemia Stem Cells in MLL-AF9-driven Acute Myeloid Leukemia
Authors: Lewis Andrew Henry , Bridges Cory Seth , Moorshead David Neal , Chen Taylor J , Du Wa , Zorman Barry , Sumazin Pavel , Puppi Monica , Lacorazza H Daniel
Published: May 2022

Acute myeloid leukemia (AML) is an aggressive malignancy of the bone marrow with 5-year overall survival of less than 10% in patients over the age of 65. Limited progress has been made in the patient outcome because of the inability to selectively eradicate the leukemic stem cells (LSC) driving the refractory and relapsed disease. Herein, we investigated the role of the reprogramming factor KLF4 in AML because of its critical role in the self-renewal and stemness of embryonic and cancer stem cells. Using a conditional Cre-lox Klf4 deletion system and the MLL-AF9 retroviral mouse model, we demonstrated that loss-of-KLF4 does not significantly affect the induction of leukemia but markedly decreased the frequency of LSCs evaluated in limiting-dose transplantation studies. Loss of KLF4 in leukemic granulocyte-macrophage progenitors (L-GMP), a population enriched for AML LSCs, showed lessened clonogenicity and percentage in the G2/M phase of the cell cycle. RNAseq analysis of purified L-GMPs revealed decreased expression of stemness genes and MLL-target genes and upregulation of the RNA sensing helicase DDX58. However, silencing of DDX58 in KLF4 knockout leukemia indicated that DDX58 is not mediating this phenotype. CRISPR/Cas9 deletion of KLF4 in MOLM13 cell line and AML patient-derived xenograft cells showed impaired expansion in vitro and in vivo associated with a defective G2/M checkpoint. Collectively, our data suggest a mechanism in which KLF4 promotes leukemia progression by establishing a gene expression profile in AML LSCs supporting cell division and stemness.
Change of generations in the Austrian private foundation
Authors: Müller Katharina , Melzer Martin
Published: May 2022

In the Austrian private foundation, the status of founder cannot be acquired after the establishment of the foundation. The founder's genuine rights, such as the right to amend the foundation deed and the right to revoke the private foundation, can neither be transferred inter vivos nor upon death. Therefore, founders must ensure during their lifetime that the foundation deed is also tailored to the needs of the subsequent generations.