bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 Since its enactment in 1985, the MCP has been enforced only under Republican administrations and quickly rescinded when a Democrat wins the presidency.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.
A corpus-pragmatics approach to evaluation in professor reviews
Authors: Ho Mei-ching 
Published: May 2022

AbstractThis 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

AbstractIn 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.
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

AbstractMotivationIdentification 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.ResultsIn 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 implementationThe 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 informationSupplementary 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

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

Summary
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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract

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 &lt; 0.001) a day after surgery, 11.40 [7.85, 22.65] U/ml (P &lt; 0.001) 14 days after surgery and 7.60 [4.80, 17.60] U/ml (P &lt; 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 &lt; 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

Abstract
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

Abstract

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

Abstract
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.