bluuebunny/crossref_metadata_2025 huggingface dataset:
Linkage disequilibrium between rare mutations
Authors: Good Benjamin H
Published: January 2022

The statistical associations between mutations, collectively known as linkage disequilibrium, encode important information about the evolutionary forces acting within a population. Yet in contrast to single-site analogues like the site frequency spectrum, our theoretical understanding of linkage disequilibrium remains limited. In particular, little is currently known about how mutations with different ages and fitness costs contribute to expected patterns of linkage disequilibrium, even in simple settings where recombination and genetic drift are the major evolutionary forces. Here, I introduce a forward-time framework for predicting linkage disequilibrium between pairs of neutral and deleterious mutations as a function of their present-day frequencies. I show that the dynamics of linkage disequilibrium become much simpler in the limit that mutations are rare, where they admit a simple heuristic picture based on the trajectories of the underlying lineages. I use this approach to derive analytical expressions for a family of frequency-weighted linkage disequilibrium statistics as a function of the recombination rate, the frequency scale, and the additive and epistatic fitness costs of the mutations. I find that the frequency scale can have a dramatic impact on the shapes of the resulting linkage disequilibrium curves, reflecting the broad range of time scales over which these correlations arise. I also show that the differences between neutral and deleterious linkage disequilibrium are not purely driven by differences in their mutation frequencies and can instead display qualitative features that are reminiscent of epistasis. I conclude by discussing the implications of these results for recent linkage disequilibrium measurements in bacteria. This forward-time approach may provide a useful framework for predicting linkage disequilibrium across a range of evolutionary scenarios.
Early-Life Factors as Predictors of Age-Associated Deficit Accumulation Across 17 Years From Midlife Into Old Age
Authors: Haapanen Markus J , Jylhävä Juulia , Kortelainen Lauri , Mikkola Tuija M , Salonen Minna , Wasenius Niko S , Kajantie Eero , Eriksson Johan G , von Bonsdorff Mikaela B
Published: January 2022

Background

Early-life exposures have been associated with the risk of frailty in old age. We investigated whether early-life exposures predict the level and rate of change in a frailty index (FI) from midlife into old age.

Methods

A linear mixed model analysis was performed using data from 3 measurement occasions over 17 years in participants from the Helsinki Birth Cohort Study (n = 2 000) aged 57–84 years. A 41-item FI was calculated on each occasion. Information on birth size, maternal body mass index (BMI), growth in infancy and childhood, childhood socioeconomic status (SES), and early-life stress (wartime separation from both parents) was obtained from registers and health care records.

Results

At age 57 years the mean FI level was 0.186 and the FI levels increased by 0.34%/year from midlife into old age. Larger body size at birth associated with a slower increase in FI levels from midlife into old age. Per 1 kg greater birth weight the increase in FI levels per year was −0.087 percentage points slower (95% confidence interval = −0.163, −0.011; p = 0.026). Higher maternal BMI was associated with a higher offspring FI level in midlife and a slower increase in FI levels into old age. Larger size, faster growth from infancy to childhood, and low SES in childhood were all associated with a lower FI level in midlife but not with its rate of change.

Conclusions

Early-life factors seem to contribute to disparities in frailty from midlife into old age. Early-life factors may identify groups that could benefit from frailty prevention, optimally initiated early in life.
Serum levels of C-Terminal Telopeptide (CTX) are Associated with Muscle Function in Community-Dwelling Older Adults
Authors: Kirk Ben , Lieu Nicky , Vogrin Sara , Sales Myrla , Pasco Julie A , Duque Gustavo
Published: January 2022

Background

Markers of bone metabolism have been associated with muscle mass and function. Whether serum cross-linked C-terminal telopeptides of type I collagen (CTX) is also associated with these measures in older adults remains unknown.

Methods

In community-dwelling older adults at high risk of falls and fractures, serum CTX (biochemical immunoassays) was used as the exposure, while appendicular lean mass (dual-energy x-ray absorptiometry) and muscle function (grip strength [hydraulic dynamometer], short physical performance battery [SPPB], gait speed, sit-to-stand, balance, Timed Up and Go [TUG]) were used as outcomes. Potential covariates including demographic, lifestyle, and clinical factors were considered in statistical models. Areas under the receiver operating characteristic (ROC) curves were calculated for significant outcomes.

Results

Two hundred and ninety-nine older adults (median age: 79 years, interquartile range: 73, 84; 75.6% women) were included. In multivariable models, CTX was negatively associated with SPPB (β = 0.95, 95% confidence interval [CI]: 0.92, 0.98) and balance (β = 0.92, 0.86, 0.99) scores, and positively associated with sit-to-stand (β = 1.02, 95% CI: 1.00, 1.05) and TUG (β = 1.03, 95% CI: 1.00, 1.05). Trend line for gait speed (β = 0.99, 95% CI: 0.98, 1.01) was in the hypothesized direction but did not reach significance. Area under the ROC curves showed low diagnostic power (<0.7) of CTX in identifying poor muscle function (SPPB: 0.63; sit-to-stand: 0.64; TUG: 0.61).

Conclusions

In older adults, higher CTX levels were associated with poorer lower-limb muscle function (but showed poor diagnostic power for these measures). These clinical data build on the biomedical link between bone and muscle.
Hormonal interactions underlying parthenocarpic fruit formation in horticultural crops
Authors: Sharif Rahat , Su Li , Chen Xuehao , Qi Xiaohua
Published: January 2022

In some horticultural crops, such as Cucurbitaceae, Solanaceae, and Rosaceae species, fruit set and development can occur without the fertilization of ovules, a process known as parthenocarpy. Parthenocarpy is an important agricultural trait that can not only mitigate fruit yield losses caused by environmental stresses but can also induce the development of seedless fruit, which is a desirable trait for consumers. In the present review, the induction of parthenocarpic fruit by the application of hormones such as auxins (2,4 dichlorophenoxyacetic acid; naphthaleneacetic acid), cytokinins (forchlorfenuron; 6-benzylaminopurine), gibberellic acids, and brassinosteroids is first presented. Then, the molecular mechanisms of parthenocarpic fruit formation, mainly related to plant hormones, are presented. Auxins, gibberellic acids, and cytokinins are categorized as primary players in initiating fruit set. Other hormones, such as ethylene, brassinosteroids, and melatonin, also participate in parthenocarpic fruit formation. Additionally, synergistic and antagonistic crosstalk between these hormones is crucial for deciding the fate of fruit set. Finally, we highlight knowledge gaps and suggest future directions of research on parthenocarpic fruit formation in horticultural crops.
Transcriptomic and physiological analysis identifies a gene network module highly associated with brassinosteroid regulation in hybrid sweetgum tissues differing in the capability of somatic embryogenesis
Authors: Zhao Ruirui , Qi Shuaizheng , Cui Ying , Gao Ying , Jiang Shuaifei , Zhao Jian , Zhang Jinfeng , Kong Lisheng
Published: January 2022

Somatic embryogenesis is a preferred method for large-scale production of forest trees due to its high propagation efficiency. In this study, hybrid sweetgum leaves with phase changes from mature to embryogenic state were selected as experimental material to study somatic embryo initiation. Embryogenicity ranged from high to low, i.e. from 45%, 25%, and 12.5% to 0, with the samples of embryogenic callus (EC), whiten leaf edge (WLI), whiten leaf (WLII), and green leaf (GL) respectively. High correlations existed between embryogenicity and endogenous brassinosteroids (BRs) (r = 0.95, p < 0.05). Similarly, concentrations of endogenous BRs of the sample set correlated positively (r = 0.93, 0.99, 0.87, 0.99, 0.96 respectively, P < 0.05) to expression of somatic embryo (SE)-related genes, i.e. BBM, LEC2, ABI3, PLT2, and WOX2. Hierarchical cluster and weighted gene coexpression network analysis identified modules of coexpressed genes and network in 4820 differentially expressed genes (DEGs) from All-BR-Regulated Genes (ABRG). Moreover, exogenously-supplemented epiBR, together with 2,4-D and 6-BA, increased embryogenicity of GL-sourced callus, and expression of SE- and auxin-related genes, while brassinazole (BRZ), a BR biosynthesis inhibitor, reduced embryogenicity. Evidences obtained in this study revealed that BRs involved in phase change of leaf explants and may function in regulating gene expression and enhancing auxin effects. This study successfully established protocols for inducing somatic embryogenesis from leaf explants in hybrid sweetgum, which could facilitate the propagation process greatly, and provide theoretical basis for manipulating SE competence of explants in ornamental woody plants.
Between mobile corridors and immobilizing borders: race, fixity and friction in Palestine/Israel
Authors: Manchanda Nivi , Plonski Sharri
Published: January 2022

This article wrestles with the question of ‘national’ borders in racial capitalism. We do so through an examination of border and capitalist corridors. We focus particularly on the Israeli border, branded and then sold to the rest of the world by the epistemic community of border-makers and interlocutors. In tracking the Israeli border and showing the implication of the experts and their markets, we ask how the border reflects and is refracted through a global order organized by the twin dictates of racism and capitalism. We are especially interested in how racialized processes of bordering, ostensibly governed by national exigencies, are transplanted on to other contexts. Two points emerge from this: in the first instance, we ask who and what enables this movement of the border. And in the second, we interrogate which logics and practices are transplanted with the border, as it is reproduced and seemingly fixed in a new place. We examine the violent ontologies that give shape and reputation to Israel's high-tech border industry, which has become a model for the ever-growing global homeland security industry. We ask: has Israel's border become an exportable commodity and who are the actors who have enabled this ‘achievement’? Related to this, what sort of occlusions and structural violence does the fetishization of the Israeli border rely on?
Researching climate justice: a decolonial approach to global climate governance
Authors: Wilkens Jan , Datchoua-Tirvaudey Alvine R C
Published: January 2022

This article addresses the broader question of the special issue by reflecting on the coloniality of knowledge production in a context of global climate governance. Drawing on the rationale of the special issue, we highlight key dynamics in which knowledge shape climate policies and propose a decolonial approach at the nexus of academic knowledge production and policy formation by accounting for diverse ways of knowing climate justice. To this end, the article asks how to develop a decolonial approach to researching climate justice in order to identify the meaning-in-use of climate justice by affected people in what we describe as sensitive regions of the Arctic and the Mediterranean. To this end, the article develops a research design that accounts for diverse ways of knowing. The article proceeds as follows: first, we will discuss how diverse ways of knowing are related to global climate governance and climate justice; second, we outline our practice-based research framework that addresses research ethics, decolonial approaches and norm contestation; and third, we discuss how our approach can inform not only the co-production of research in climate governance, but also current debates on climate justice.
Women and the Afghan peace and reintegration process
Authors: Rivas Althea-Maria , Safi Mariam
Published: January 2022

In 2010, as the Afghan government announced its intention to begin a formal peace process, there were numerous calls for women to have a seat at the table. Both mainstream and critical discourse on women and the peace process in Afghanistan, however, relied on the production of essentialized subjectivities which failed to recognize the political and social complexity of women's lives, diminished their intellectual contributions and silenced their voices. This article challenges the simultaneous hyper-visualization and silencing of Afghan women by both Afghan and international actors. Drawing on feminist and decolonial theory, we examine the ways in which the colonial mechanisms of intervention, patriarchy and the global hierarchies of knowledge production worked in tandem to marginalize Afghan women while upholding them as agents of peace. The article brings together findings from three participatory research projects on women and peace, which took place from 2010 to 2014 across eight provinces in Afghanistan. A prismed view of the participants' intersectional realities is constructed, which highlights diverse positionalities and articulations of peace, the social and political cleavages, and differentiated obstacles to their involvement in the peace and reintegration process. The concluding remarks emphasize the relevance of these findings for Afghanistan at the time of publication.
100 years of International Affairs
Authors: Dorman Andrew M
Published: January 2022

2022 marks International Affairs' 100th year. This editorial reflects on the journal's history and outlines plans and goals for its second century, not least ensuring that International Affairs becomes a truly global and inclusive journal.
Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer
Authors: Cushing Kelly C , Du Xiaomeng , Chen Yanhua , Stetson L C , Kuppa Annapurna , Chen Vincent L , Kahlenberg J Michelle , Gudjonsson Johann E , Vanderwerff Brett , Higgins Peter D R , Speliotes Elizabeth K
Published: January 2022

Background

Inflammatory bowel disease is associated with an increased risk of skin cancer. The aims of this study were to determine whether IBD susceptibility variants are also associated with skin cancer susceptibility and if such risk is augmented by use of immune-suppressive therapy.

Methods

The discovery cohort included participants in the UK Biobank. The validation cohort included participants in the Michigan Genomics Initiative. The primary outcome of interest was skin cancer, subgrouped into nonmelanoma skin cancers (NMSC) and melanoma skin cancers (MSC). Multivariable logistic regression with matched controls (3 controls:1 case) was performed to identify genomic predictors of skin malignancy in the discovery cohort. Variants with P < .05 were tested for replication in the validation cohort. Validated Single nucleotide polymorphisms were then evaluated for effect modification by immune-suppressive medications.

Results

The discovery cohort included 10,247 cases of NMSC and 1883 cases of MSC. The validation cohort included 7334 cases of NMSC and 3304 cases of MSC. Twenty-nine variants were associated with risk of NMSC in the discovery cohort, of which 5 replicated in the validation cohort (increased risk, rs7773324-A [DUSP22; IRF4], rs2476601-G [PTPN22], rs1847472-C [BACH2], rs72810983-A [CPEB4]; decreased risk, rs6088765-G [PROCR; MMP24]). Twelve variants were associated with risk of MSC in the discovery cohort, of which 4 were replicated in the validation cohort (increased risk, rs61839660-T [IL2RA]; decreased risk, rs17391694-C [GIPC2; MGC27382], rs6088765-G [PROCR; MMP24], and rs1728785-C [ZFP90]). No effect modification was observed.

Conclusions

The results of this study highlight shared genetic susceptibility across IBD and skin cancer, with increased risk of NMSC in those who carry risk variants in IRF4, PTPN22, CPEB4, and BACH2 and increased risk of MSC in those who carry a risk variant in IL2RA.
Caveolin-1 Alleviates Crohn’s Disease–induced Intestinal Fibrosis by Inhibiting Fibroblasts Autophagy Through Modulating Sequestosome 1
Authors: Yu Mengli , Zhu Wei , Wang Jinhai , Chen Xueyang , He Xinjue , Lin Bingru , Cen Li , Zhou Tianyu , Lu Chao , Yu Chaohui , Sun Jing
Published: January 2022

Background

Intestinal fibrosis is a common complication of Crohn’s disease (CD) and is characterized by the excessive accumulation of extracellular matrix produced by activated myofibroblasts. Caveolin-1 (CAV1) inhibits fibrosis. However, limited data show that CAV1 affects intestinal fibrosis.

Methods

Human CD tissue samples were gained from patients with CD who underwent surgical resection of the intestine and were defined as stenotic or nonstenotic areas. A dextran sodium sulfate–induced mouse model of intestinal fibrosis was established. For in vitro experiments, we purchased CCD-18Co intestinal fibrosis cells and isolated and cultured human primary colonic fibroblasts. These fibroblasts were activated by transforming growth factor β administration for 48 hours. In the functional experiments, a specific small interfering RNA or overexpression plasmid was transfected into fibroblasts. The messenger RNA levels of fibrosis markers, such as α-smooth muscle actin, fibronectin, connective tissue growth factor, and collagen I1α, were determined using quantitative polymerase chain reaction. Western blot analysis was applied to detect the expression of CAV1, SQSTM1/p62 (sequestosome 1), and other fibrosis markers.

Results

In human CD samples and the dextran sodium sulfate–induced mouse model of intestinal fibrosis, we observed a downregulation of CAV1 in fibrosis-activated areas. Mechanistically, CAV1 knockdown in both human primary colonic fibroblasts and CCD-18Co cells promoted fibroblast activation, while CAV1 overexpression inhibited fibroblast activation in vitro. We found that SQSTM1/p62 positively correlated with CAV1 expression levels in patients with CD and that it was indirectly modulated by CAV1 expression. Rescue experiments showed that CAV1 decreased primary human intestinal fibroblast activation by inhibiting fibroblast autophagy through the modulation of SQSTM1/p62.

Conclusions

Our data demonstrate that CAV1 deficiency induces fibroblast activation by indirectly regulating SQSTM1/p62 to promote fibroblast autophagy. CAV1 or SQSTM1/p62 may be potential therapeutic targets for intestinal fibrosis.
Preoperative monocyte count is a predictor of recurrence after Stage I lung adenocarcinoma resection
Authors: Yoshida Chihiro , Kadota Kyuichi , Ishikawa Ryo , Go Tetsuhiko , Haba Reiji , Yokomise Hiroyasu
Published: January 2022

OBJECTIVES

High-grade tumours are observed even in Stage I lung adenocarcinomas. Tumour spread through air spaces (STAS) is a risk factor for recurrence after resection. However, there is no ideal predictive biomarker for STAS in high-grade Stage I lung adenocarcinoma. This study assessed the prognostic impact of the preoperative peripheral monocyte count in lung adenocarcinoma.

METHODS

We retrospectively analysed the data of 444 patients with resected Stage I lung adenocarcinoma during 2006–2016. Univariable and multivariable Cox proportional analyses of recurrence-free probability (RFP) and overall survival (OS) were used to analyze preoperative complete peripheral blood cell count data. Since monocyte count was associated with poor prognosis, the relationship between preoperative peripheral monocyte count and clinicopathological factors, including STAS, was assessed. In addition, immunohistochemical CD68 staining was performed to evaluate tumour-associated macrophages (TAMs).

RESULTS

A higher preoperative peripheral monocyte count was a predictor of lower RFP (P = 0.004) and lower OS (P < 0.001). In multivariable analysis, a higher peripheral monocyte count was an independent prognostic factor for RFP and OS (hazard ratio: 1.88, 95% confidence interval: 1.07–3.31, P = 0.029; hazard ratio: 2.13, 95% confidence interval: 1.22–3.75, P = 0.008, respectively). A higher peripheral monocyte count was associated with a higher frequency of STAS (P = 0.017) and higher number of CD68+ TAMs (P = 0.013).

CONCLUSIONS

A higher preoperative peripheral monocyte count was an independent marker for a poor prognosis in Stage I lung adenocarcinoma and was associated with a higher frequency of STAS.
Understanding the Potential Drivers for Respiratory Syncytial Virus Rebound During the Coronavirus Disease 2019 Pandemic
Authors: Li You , Wang Xin , Cong Bingbing , Deng Shuyu , Feikin Daniel R , Nair Harish
Published: January 2022

Nonpharmaceutical interventions (NPIs) were widely introduced to combat the coronavirus disease 2019 (COVID-19) pandemic. These interventions also likely led to substantially reduced activity of respiratory syncytial virus (RSV). From late 2020, some countries observed out-of-season RSV epidemics. Here, we analyzed the role of NPIs, population mobility, climate, and severe acute respiratory syndrome coronavirus 2 circulation in RSV rebound through a time-to-event analysis across 18 countries. Full (re)opening of schools was associated with an increased risk for RSV rebound (hazard ratio [HR], 23.29 [95% confidence interval {CI}, 1.09–495.84]); every 5°C increase in temperature was associated with a decreased risk (HR, 0.63 [95% CI, .40–.99]). There was an increasing trend in the risk for RSV rebound over time, highlighting the role of increased population susceptibility. No other factors were found to be statistically significant. Further analysis suggests that increasing population susceptibility and full (re)opening of schools could both override the countereffect of high temperatures, which explains the out-of-season RSV epidemics during the COVID-19 pandemic.
New Dimensions of Global Feminist Influence: Tracking Feminist Mobilization Worldwide, 1975–2015
Authors: Forester Summer , Kelly-Thompson Kaitlin , Lusvardi Amber , Weldon S Laurel
Published: January 2022

Feminist mobilization, crucial for advancing women's human rights, has increased in all world regions since 1975. However, we do not know enough about the global impact of this mobilization because we lack adequate databases to explore the ways that feminist mobilization interacts with other factors that enhance and limit women's rights, such as democracy, intergovernmental processes, and transnational, regional organizing. Our ability to explore these questions is obstructed by a lack of data on the global south and measures that focus on formal organizations. This project remedies these gaps, developing an improved measure of feminist mobilization that encompasses autonomous, domestic feminist mobilization in 126 countries, 1975–2015, enabling us to track global and regional trends. Using regional comparisons and statistical analysis, we use this new measure to reveal new patterns and complexities in feminist mobilization. We discern distinct regional patterns in such organizing that defy facile predictions of global convergence and suggest a central role for UN processes advancing women's rights. Our analysis also points to the importance of transnational feminist networks and democratization as factors enabling and strengthening feminist mobilization. We conclude by suggesting some fruitful avenues for exploring relationships between feminist movements, international institutions, and democracy.
The impact of the COVID-19 pandemic on antimicrobial prescribing at a specialist paediatric hospital: an observational study
Authors: Vestesson Emma , Booth John , Hatcher James , McGarrity Orlagh , Sebire Neil J. , Steventon Adam , Suarez Alonso Carlos , Tomlin Stephen , Standing Joseph F.
Published: January 2022

Background

The COVID-19 pandemic has severely impacted healthcare delivery and there are growing concerns that the pandemic will accelerate antimicrobial resistance.

Objectives

To evaluate the impact of the COVID-19 pandemic on antibiotic prescribing in a tertiary paediatric hospital in London, UK.

Methods

Data on patient characteristics and antimicrobial administration for inpatients treated between 29 April 2019 and Sunday 28 March 2021 were extracted from the electronic health record (EHR). Interrupted time series analysis was used to evaluate antibiotic days of therapy (DOT) and the proportion of prescribed antibiotics from the WHO ‘Access’ class.

Results

A total of 23 292 inpatient admissions were included. Prior to the pandemic there were an average 262 admissions per week compared with 212 during the pandemic period. Patient demographics were similar in the two periods but there was a shift in the specialities that patients had been admitted to. During the pandemic, there was a crude increase in antibiotic DOTs, from 801 weekly DOT before the pandemic to 846. The proportion of Access antibiotics decreased from 44% to 42%. However, after controlling for changes in patient characteristics, there was no evidence for the pandemic having an impact on antibiotic prescribing.

Conclusions

The patient population in a specialist children’s hospital was affected by the COVID-19 pandemic, but after adjusting for these changes there was no evidence that antibiotic prescribing was significantly affected by the pandemic. This highlights both the value of routine, high-quality EHR data and importance of appropriate statistical methods that can adjust for underlying changes to populations when evaluating impacts of the pandemic on healthcare.
The Challenge of Measuring Sweet Taste in Food Ingredients and Products for Regulatory Compliance: A Scientific Opinion
Authors: Starkey Dustin E , Wang Zhuzhu , Brunt Kommer , Dreyfuss Lise , Haselberger Philip A , Holroyd Stephen E , Janakiraman Kaushik , Kasturi Prabhakar , Konings Erik J M , Labbe David , Latulippe Marie E , Lavigne Xavier , McCleary Barry V , Parisi Salvatore , Shao Tony , Sullivan Darryl , Torres Marina , Yadlapalli Sudhakar , Vrasidas Ioannis
Published: January 2022

The Codex Alimentarius Commission, a central part of the joint Food and Agricultural Organization/World Health Organizations Food Standards Program, adopts internationally recognized standards, guidelines, and code of practices that help ensure safety, quality, and fairness of food trade globally. Although Codex standards are not regulations per se, regulatory authorities around the world may benchmark against these standards or introduce them into regulations within their countries. Recently, the Codex Committee on Nutrition and Foods for Special Dietary Uses (CCNFSDU) initiated a draft revision to the Codex standard for follow-up formula (FUF), a drink/product (with added nutrients) for young children, to include requirements for limiting or measuring the amount of sweet taste contributed by carbohydrates in a product. Stakeholders from multiple food and beverage manufacturers expressed concern about the subjectivity of sweetness and challenges with objective measurement for verifying regulatory compliance. It is a requirement that Codex standards include a reference to a suitable method of analysis for verifying compliance with the standard. In response, AOAC INTERNATIONAL formed the Ad Hoc Expert Panel on Sweetness in November 2020 to review human perception of sweet taste, assess the landscape of internationally recognized analytical and sensory methods for measuring sweet taste in food ingredients and products, deliver recommendations to Codex regarding verification of sweet taste requirements for FUF, and develop a scientific opinion on measuring sweet taste in food and beverage products beyond FUF. Findings showed an abundance of official analytical methods for determining quantities of carbohydrates and other sweet-tasting molecules in food products and beverages, but no analytical methods capable of determining sweet taste. Furthermore, sweet taste can be determined by standard sensory analysis methods. However, it is impossible to define a sensory intensity reference value for sweetness, making them unfit to verify regulatory compliance for the purpose of international food trade. Based on these findings and recommendations, the Codex Committee on Methods of Analysis and Sampling agreed during its 41st session in May 2021 to inform CCNFSDU that there are no known validated methods to measure sweetness of carbohydrate sources; therefore, no way to determine compliance for such a requirement for FUF.
Qualitative Screening of Amphetamine- and Ketamine-Type Abuse Drugs in Urine Employing Dual Mode Extraction Column by Liquid Chromatography–Tandem Mass Spectrometry (LC–MS-MS)
Authors: Wong George Fai , Lee Wing-Man , Li Chi-Keung
Published: January 2022

This manuscript reported a fast and rapid qualitative screening method for abuse drugs in urine by liquid chromatography–tandem mass spectrometry (LC–MS-MS). The scope of the abuse drugs under investigation included methamphetamine (MA), amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), paramethoxymethamphetamine (PMMA), ephedrine, pseudoephedrine, ketamine (KET), deschloroketamine (DCK), 2-fluorodeschloroketamine (2 F-DCK) and deschloro-N-ethylketamine (2-oxo-PCE). The method employed a dual mode extraction (DME) column as a novel clean-up method for the urine matrix. To an aliquot of 0.2 mL urine, internal standards (ISTDs) and 0.4 mL of acidified methanol were added. After vortex and centrifugation, the supernatant was passed through a DME column before LC–MS-MS analysis. Chromatographic separation was achieved with a C18 column by gradient elution. The limits of detection (LODs) for MA, AMP, MDMA, MDA and PMMA were 3 ng/mL, whereas those for ephedrine and pseudoephedrine were 10 ng/mL and those for KET, DCK, 2 F-DCK and 2-oxo-PCE were 1 ng/mL. The matrix effects ranged from −12% to 7% (%CV from 4% to 19%). This method is fit for the intended purpose for forensic toxicology, as well as for forensic analysis of drugs facilitating sexual assault and other criminal acts.
Age and Injury Size Influence the Magnitude of Fecal Dysbiosis in Adult Burn Patients
Authors: Dyamenahalli Kiran , Choy Kevin , Frank Daniel N , Najarro Kevin , Boe Devin , Colborn Kathryn L , Idrovo Juan-Pablo , Wagner Anne L , Wiktor Arek J , Afshar Majid , Burnham Ellen L , McMahan Rachel H , Kovacs Elizabeth J
Published: January 2022

Clinical studies have demonstrated that age 50 years or older is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent postburn mortality are perplexing, changes in the intestinal microbiome, may contribute to the heightened, dysregulated systemic response seen in aging burn patients. The fecal microbiome from 22 patients admitted to a verified burn center from July 2018 to February 2019 was stratified based on the age of 50 years and total burn surface area (TBSA) size of ≥10%. Significant differences (P = .014) in overall microbiota community composition (ie, beta diversity) were measured across the four patient groups: young <10% TBSA, young ≥10% TBSA, older <10% TBSA, and older ≥10% TBSA. Differences in beta diversity were driven by %TBSA (P = .013) and trended with age (P = .087). Alpha diversity components, richness, evenness, and Shannon diversity were measured. We observed significant differences in bacterial species evenness (P = .0023) and Shannon diversity (P = .0033) between the groups. There were significant correlations between individual bacterial species and levels of short-chain fatty acids. Specifically, levels of fecal butyrate correlated with the presence of Enterobacteriaceae, an opportunistic gut pathogen, when elevated in burn patients lead to worsen outcomes. Overall, our findings reveal that age-specific changes in the fecal microbiome following burn injuries may contribute to immune system dysregulation in patients with varying TBSA burns and potentially lead to worsened clinical outcomes with heightened morbidity and mortality.
miR-31, miR-155, and miR-221 Expression Profiles and Their Association With Graft Skin Tolerance in a Syngeneic vs Allogeneic Murine Skin Transplantation Model
Authors: Mandujano-Tinoco Edna Ayerim , González-García Francisco , Salgado Rosa M , Abarca-Buis René Fernando , Sanchez-Lopez José Manuel , Carranza-Castro Pilar Hazel , Padilla Luis , Krötzsch Edgar
Published: January 2022

Grafting is the preferred treatment for severe skin burns. Frequently, allogeneic tissue is the only transient option for wound coverage, but their use risks damage to surrounding tissues. MicroRNAs have been associated with acute rejection of different tissues/organs. In this study, we analyzed the expression of miR-31, miR-155, and miR-221 and associate it with graft tolerance or rejection using a murine full-thickness skin transplantation model. Recipient animals for the syngeneic and allogeneic groups were BALB/c and C57BL/6 mice, respectively; donor tissues were obtained from BALB/c mice. After 7 days posttransplantation (DPT), the recipient skin and grafts in the syngeneic group maintained most of their structural characteristics and transforming growth factor (TGF)-β1 and TGF-β3 expression. Allografts were rejected early (Banff grades II and IV at 3 and 7 DPT, respectively), showing damage to the skin architecture and alteration of TGF-β3 distribution. miRNAs skin expression changed in both mouse strains; miR-31 expression increased in the recipient skin of syngeneic grafts relative to that of allogeneic grafts at 3 and 7 DPT (P < .05 and P < .01, respectively); miR-221 expression increased in the same grafts at 7 DPT (P < .05). The only significant difference between donor tissues was observed for miR-155 expression at 7 DPT which was associated with necrotic tissue. Only miR-31 and miR-221 levels were increased in the blood of BALB/c mice that received syngeneic grafts after 7 DPT. Our data suggest that local and systemic miR-31 and miR-221 overexpression are associated with graft tolerance.
Consumption of Supplemental Spring Protein Feeds by Western Honey Bee (Hymenoptera: Apidae) Colonies: Effects on Colony Growth and Pollination Potential
Authors: Hoover Shelley E , Ovinge Lynae P , Kearns Jeffery D
Published: January 2022

Adequate nutrition is required to support productive honey bee colonies, therefore beekeepers supplement colonies with additional protein at targeted time points. We tested the effects of commercially available protein feeds in spring, in advance of colonies being used for hybrid canola pollination. The feed treatments across the three-year study included the following patty types: Global 15% pollen, Global 0% pollen, Bee Pollen-Ate, FeedBee, and Healthy Bees, as well as an unsupplemented control in year two of the study only. The amount of feed consumed varied among colonies, treatments, date, and year. Similarly, there were also differences in feed efficiency (bees reared per gram of feed consumed), likely due to the relative availability of external forage sources to supplement the feed provided. Unsupplemented colonies were able to rear less brood, and subsequently had fewer adult bees than supplemented colonies, in an apiary where pollen was not abundant. Differences in consumption among treatments often failed to translate in to differences in amount of brood reared or subsequent adult population. All the protein feed treatments contained all ten amino acids essential to honey bees, however lysine and arginine were below the optimal proportion required for growth in all patties except the FeedBee patty. The amount of protein and amount and types of sugars and fats in the products also varied among product type and batch. The results of this study demonstrate a benefit to supplementary spring protein feeding to increase honey bee colony populations in advance of a summer pollination market.
Survey of malignant pleural mesothelioma treatment in Japan: Patterns of practice and clinical outcomes in tomotherapy facilities
Authors: Nakanishi-Imai Mikiko , Murai Taro , Onishi Masahiro , Mouri Atsuto , Komiyama Takafumi , Omura Motoko , Kudo Shigehiro , Miyamoto Akihiko , Hoshino Masaru , Ogawa Shinichi , Ohashi Shizuko , Koizumi Masahiko , Omagari Junichi , Mayahara Hiroshi , Karasawa Katsuyuki , Okumura Toshiyuki , Shibamoto Yuta
Published: January 2022

We conducted a nationwide survey of tomotherapy for malignant pleural mesothelioma (MPM) in Japan. Fifty-six facilities were surveyed and data on 31 patients treated curatively between 2008 and 2017 were collected from 14 facilities. Twenty patients received hemithorax irradiation after extrapleural pneumonectomy (EPP) (first group). Five patients received irradiation without EPP (second group), while six received salvage radiotherapy for local recurrence (salvage group). Among the seven patients not undergoing EPP, five (four in the second group and one in the salvage group) were treated with lung sparing pleural irradiation (LSPI) and two with irradiation to visible tumors. Two-year overall survival (OS) rates in the first and second groups were 33% and 60%, respectively (median, 13 vs 30 months, P = 0.82). In the first and second groups, 2-year local control (LC) rates were 53 and 67%, respectively (P = 0.54) and 2-year progression-free survival (PFS) rates were 16% and 60%, respectively (P = 0.07). Distant metastases occurred in 15 patients in the first group and three in the second group. In the salvage group, the median OS was 18 months. Recurrence was observed in the irradiated volume in four patients. The contralateral lung dose was higher in LSPI than in hemithorax irradiation plans (mean, 11.0 ± 2.2 vs 6.1 ± 3.1 Gy, P = 0.002). Grade 3 or 5 lung toxicity was observed in two patients receiving EPP and hemithorax irradiation, but not in those undergoing LSPI. In conclusion, outcomes of EPP and hemithorax irradiation were not satisfactory, whereas LSPI appeared promising and encouraging.
The Association Between Interpersonal Violence and Unstable Housing Among Veterans
Authors: Hargrave Anita S , Kimberg Leigh , Machtinger Edward L , Kushel Margot B , Cohen Beth E
Published: January 2022

Background

Despite programs to address housing for Veterans, they continue to be at high risk of unstable housing. Interpersonal violence is also highly prevalent among Veterans and may contribute to unstable housing. Our study aimed to determine whether interpersonal violence was associated with unstable housing among Veterans, and how this association was influenced by common co-occurring conditions such as substance use and mental illness.

Methods

Veterans in the Mind Your Heart Study (N = 741) completed survey data on history of interpersonal violence and access to housing in the prior year. Interpersonal violence was defined as experiencing sexual violence, physical violence, or mugging/physical attack using the Brief Trauma Questionnaire. Multivariable models examined associations between interpersonal violence and unstable housing. Primary models were adjusted for age and sex. Potential explanatory factors were added in subsequent models, including marital status, education, income, substance use disorder, PTSD, and other mental illness.

Results

Veterans who had experienced interpersonal violence had almost twice the odds of unstable housing after adjustment for age and sex (AOR 1.9, 95% CI 1.2–3.0). This association was attenuated in the fully adjusted model including substance use, PTSD, and other mental illness, illustrating the interdependence of these factors (AOR 1.5, 95% CI 0.91–2.5). Subtypes of interpersonal violence were individually associated with increased odds of unstable housing after adjustment for age and sex (physical abuse AOR 1.7, 95% CI 1.2–2.5; mugging/physical attack AOR 1.8, 95% CI 1.2–2.7; sexual violence AOR 1.4, 95% CI 0.89–2.2), but were no longer significant in the fully adjusted model.

Conclusions

Previous experiences of interpersonal violence were associated with unstable housing among Veterans. Substance use, PTSD, and other mental illness played an important role in this relationship—highlighting the potential to improve health outcomes through trauma informed approaches that address mental health, substance use, and housing concurrently.
Testing modified (Horndeski) gravity by combining intrinsic galaxy alignments with cosmic shear
Authors: Reischke Robert , Bosca Victor , Tugendhat Tim , Schäfer Björn Malte
Published: January 2022

We study the impact of modified gravity of the Horndeski class on intrinsic shape correlations in cosmic shear surveys. As these correlations intrinsic alignments are caused by tidal gravitational fields acting on galaxies as a collection of massive non-relativistic test particles, they are only sensitive to the gravitational potential, which forms in conjunction with the curvature perturbation. In contrast, the cosmic shear signal probes the sum of these two, i.e. both Bardeen potentials. Combining these probes therefore constitutes a test of gravity, derived from a single measurement. Focusing on linear scales and alignments of elliptical galaxies, we study the impact on inference of the braiding $\hat{\alpha }_{\rm B}$ and the time evolution of the Planck mass $\hat{\alpha }_{\rm M}$ by treating IAs as a genuine signal contributing to the overall ellipticity correlation. We find that for euclid, IAs can help to improve constraints on modified gravity of the Horndeski-class by 10 per cent if the alignment parameter needed for the linear alignment model is provided by simulations. If, however, the IA needs to be self-calibrated, all of the sensitivity is put into the inference of the alignment strength D since there is a very strong correlation with the evolution of the Planck mass. Thus, diminishing the benefit of IA for probing modified gravitational theories. While this paper shows results mainly for modified gravity parameters, similar deductions can be drawn for the investigation of anisotropic stresses, parametrized modifications to the Poisson equation, the phenomenology of gravitational slip and to breaking degeneracies in a standard cosmology.
Extremely massive disc galaxies in the nearby Universe form through gas-rich minor mergers
Authors: Jackson R A , Kaviraj S , Martin G , Devriendt J E G , Noakes-Kettel E A , Silk J , Ogle P , Dubois Y
Published: January 2022

In our hierarchical structure-formation paradigm, the observed morphological evolution of massive galaxies – from rotationally supported discs to dispersion-dominated spheroids – is largely explained via galaxy merging. However, since mergers are likely to destroy discs, and the most massive galaxies have the richest merger histories, it is surprising that any discs exist at all at the highest stellar masses. Recent theoretical work by our group has used a cosmological, hydrodynamical simulation to suggest that extremely massive (M* > 1011.4 M⊙) discs form primarily via minor mergers between spheroids and gas-rich satellites, which create new rotational stellar components and leave discs as remnants. Here, we use UV-optical and H i data of massive galaxies, from the Sloan Digital Sky Survey, Galaxy Evolution Explorer, Dark Energy Camera Legacy Survey (DECaLS), and Arecibo Legacy Fast ALFA surveys, to test these theoretical predictions. Observed massive discs account for ∼13 per cent of massive galaxies, in good agreement with theory (∼11 per cent). ∼64 per cent of the observed massive discs exhibit tidal features, which are likely to indicate recent minor mergers, in the deep DECaLS images (compared to ∼60 per cent in their simulated counterparts). The incidence of these features is at least four times higher than in low-mass discs, suggesting that, as predicted, minor mergers play a significant (and outsized) role in the formation of these systems. The empirical star formation rates agree well with theoretical predictions and, for a small galaxy sample with H i detections, the H i masses and fractions are consistent with the range predicted by the simulation. The good agreement between theory and observations indicates that extremely massive discs are indeed remnants of recent minor mergers between spheroids and gas-rich satellites.
Mechanisms of Cre recombinase synaptic complex assembly and activation illuminated by Cryo-EM
Authors: Stachowski Kye , Norris Andrew S , Potter Devante , Wysocki Vicki H , Foster Mark P
Published: January 2022

Cre recombinase selectively recognizes DNA and prevents non-specific DNA cleavage through an orchestrated series of assembly intermediates. Cre recombines two loxP DNA sequences featuring a pair of palindromic recombinase binding elements and an asymmetric spacer region, by assembly of a tetrameric synaptic complex, cleavage of an opposing pair of strands, and formation of a Holliday junction intermediate. We used Cre and loxP variants to isolate the monomeric Cre-loxP (54 kDa), dimeric Cre2-loxP (110 kDa), and tetrameric Cre4-loxP2 assembly intermediates, and determined their structures using cryo-EM to resolutions of 3.9, 4.5 and 3.2 Å, respectively. Progressive and asymmetric bending of the spacer region along the assembly pathway enables formation of increasingly intimate interfaces between Cre protomers and illuminates the structural bases of biased loxP strand cleavage order and half-the-sites activity. Application of 3D variability analysis to the tetramer data reveals constrained conformational sampling along the pathway between protomer activation and Holliday junction isomerization. These findings underscore the importance of protein and DNA flexibility in Cre-mediated site selection, controlled activation of alternating protomers, the basis for biased strand cleavage order, and recombination efficiency. Such considerations may advance development of site-specific recombinases for use in gene editing applications.
Monoclonal Antibody Therapy for COVID-19: A Public Health Perspective From Arkansas
Authors: Kothari Atul , Woodland Borella Elizabeth , Smith Michelle R
Published: January 2022

COVID-19 monoclonal antibodies revolutionized the treatment for eligible patients who have tested positive for SARS CoV-2 infection in an ambulatory setting. In this short report, we describe our experience assisting in the distribution of monoclonal antibodies in Arkansas during the summer surge of the delta variant.
A DE1 BINDING FACTOR 1–GLABRA2 module regulates rhamnogalacturonan I biosynthesis in Arabidopsis seed coat mucilage
Authors: Xu Yan , Wang Yiping , Du Jinge , Pei Shengqiang , Guo Shuaiqiang , Hao Ruili , Wang Dian , Zhou Gongke , Li Shengjun , O’Neill Malcolm , Hu Ruibo , Kong Yingzhen
Published: January 2022

The mucilage surrounding hydrated Arabidopsis thaliana seeds is a specialized extracellular matrix composed mainly of the pectic polysaccharide rhamnogalacturonan I (RG-I). Although, several genes responsible for RG-I biosynthesis have been identified, the transcriptional regulatory mechanisms controlling RG-I production remain largely unknown. Here we report that the trihelix transcription factor DE1 BINDING FACTOR 1 (DF1) is a key regulator of mucilage RG-I biosynthesis. RG-I biosynthesis is significantly reduced in loss-of-function mutants of DF1. DF1 physically interacts with GLABRA2 (GL2) and both proteins transcriptionally regulate the expression of the RG-I biosynthesis genes MUCILAGE MODIFIED 4 (MUM4) and GALACTURONOSYLTRANSFERASE-LIKE5 (GATL5). Through chromatin immunoprecipitation-quantitative PCR and transcriptional activation assays, we uncover a cooperative mechanism of the DF1–GL2 module in activating MUM4 and GATL5 expression, in which DF1 binds to the promoters of MUM4 and GATL5 through interacting with GL2 and facilitates the transcriptional activity of GL2. The expression of DF1 and GL2 is directly regulated by TRANSPARENT TESTA GLABRA2 (TTG2) and, in turn, DF1 directly represses the expression of TTG2. Taken together, our data reveal that the transcriptional regulation of mucilage RG-I biosynthesis involves a regulatory module, comprising DF1, GL2, and TTG2.