bluuebunny/crossref_metadata_2025 huggingface dataset:
Loneliness Trajectories in U.S. Military Veterans: A 3-Year Longitudinal Study of Risk and Protective Factors
Authors: Ong Anthony D , Cintron Dakota W , Rottenberg Jonathan , Panaite Vanessa , Fischer Ian C , Na Peter J , Jeste Dilip V , Pietrzak Robert H
Published: October 2024

Objectives

Loneliness is a significant public health concern associated with adverse mental and physical health outcomes in older adults. This study examined the nature and correlates of predominant loneliness trajectories in a nationally representative sample of older U.S. military veterans.

Methods

Participants included 2,441 veterans (mean age = 63, 8% female, 80% White) from the National Health and Resilience in Veterans Study, a 3-year longitudinal cohort study. Growth mixture modeling (GMM) was used to identify distinct trajectory classes of loneliness based on self-reported ratings. Multinomial logistic 3-step regression analyses examined potential psychosocial risk and protective factors associated with loneliness trajectories.

Results

GMM revealed 3 distinct loneliness trajectories: low-decreasing loneliness (61.2%), moderate-increasing loneliness (31.6%), and high-increasing loneliness (7.2%). Being married/partnered and perceiving a greater purpose in life emerged as protective factors against elevated levels of loneliness. Worse cognitive functioning was a risk factor for the moderate-increasing loneliness trajectory, while greater psychological distress and more adverse childhood experiences were risk factors for the high-increasing loneliness trajectory.

Discussion

Nearly 40% of older U.S. veterans exhibited trajectories characterized by moderate to high levels of loneliness, with both groups showing increases over time. Targeted interventions that promote social connectedness, enhance purpose in life, and address mental health concerns and early life adversities may help mitigate the negative health consequences associated with chronic loneliness in this vulnerable population.
Gender Selectively Mediates the Association Between Sex and Memory in Cognitively Normal Older Adults
Authors: Bohn Linzy , Han Astrid Y , McFall G Peggy , Drouin Shannon M , Pettersen Jacqueline A , Rajah M Natasha , Einstein Gillian , Anstey Kaarin J , Dixon Roger A
Published: October 2024

Background and Objectives

Sex and gender are important topics of increasing interest in aging and dementia research. Few studies have jointly examined sex (as a biological attribute) and gender (as a sociocultural and behavioral characteristic) within a single study. We explored a novel data mining approach to include both sex and gender as potentially related influences in memory aging research.

Research Design and Methods

Participants were 746 cognitively normal older adults from the Victoria Longitudinal Study. First, we adapted the Gender Outcomes INternational Group: To Further Well-being Development (GOING-FWD) framework—which is informed by gender dimensions of the Women’s Health Research Network—to identify, extract, and operationalize gender-related variables in the database. Second, we applied principal component analysis (PCA) to a pool of potential gender variables for creating empirically derived gender-related components. Third, we verified the expected pattern of sex differences in memory performance and evaluated each gender-related component as a potential mediator of the observed sex–memory association.

Results

Systematic data mining produced a roster of potential gender-related variables, 56 of which corresponded to gender dimensions represented in the GOING-FWD framework. The PCA revealed 6 gender-related components (n indicators = 37): Manual Non-Routine Household Tasks, Subjective Memory Beliefs, Leisure Free Time, Social and Routine Household Management, Health Perceptions and Practices, and Brain Games. We observed sex differences in latent memory performance whereby females outperformed males. Sex differences in memory performance were mediated by Manual Non-Routine Household Tasks, Social and Routine Household Management, and Brain Games. Follow-up analyses showed that education also mediated the sex–memory association.

Discussion and Implications

We show that (i) data mining can identify and operationalize gender-related variables in archival aging and dementia databases, (ii) these variables can be examined for associations with sex, and (iii) sex differences in memory performance are mediated by selected facets of gender.
What Characteristics Modify the Relation of Neighborhood Walkability and Walking Behavior in Older Adults?
Authors: Rosso Andrea L , Moored Kyle D , Harding Alyson B , Studenski Stephanie , Bear Todd , Acharya Geeta , Rosano Caterina
Published: October 2024

Background and Objectives

Neighborhood walkability can influence walking behaviors in older adults. However, its associations of walkability with walking may differ by demographic, socioeconomic, health, social, and residential characteristics due to factors such as increased vulnerability to environmental factors or increased resilience.

Research Design and Methods

In a sample of older adults (n = 493, median age = 82 [range 78–89], 56% female, 31% Black), a walkability index was derived from audits of Google Street View images of participants’ immediate neighborhoods. Walking was self-reported in the past week. Effect modifiers by demographic (age, race, gender, marital status), socioeconomic (education, income), health (gait speed, falls, knee pain, depressive symptoms, cognitive status, perceived energy), social (driving status, social engagement), and residential/neighborhood (residence type, neighborhood socioeconomic status [SES], population density) characteristics were assessed by interaction terms in logistic regression models, adjusted for gender, race, gait speed, prior falls, high depressive symptoms, currently driving, and cognitive status. When effect modification was suggested (p for interaction <.1), adjusted analyses of walkability with walking stratified on the effect modifier were conducted.

Results

In this sample, 59% walked in the past week and greater walkability was associated with greater odds of walking (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.01–1.34). This association (p for interaction range 0.002–0.07) was present for those who were not currently married (OR = 1.35, 95% CI: 1.17–1.56), who reported knee pain (OR = 1.40, 95% CI: 1.14–1.72) or high depressive symptoms (OR = 1.30, 95% CI: 1.06–1.60), or who had declining cognitive function (OR = 1.30, 95% CI: 1.09–1.55).

Discussion and Implications

High walkability may influence physical activity, particularly for those with vulnerabilities related to social, pain, and brain health characteristics. These results should inform neighborhood planning and targeted interventions for vulnerable older adults.
Home Health Care and Place of Death in Medicare Beneficiaries With and Without Dementia
Authors: Kim Hyosin (Dawn) , Duberstein Paul R , Zafar Anum , Wu Bei , Lin Haiqun , Jarrín Olga F
Published: October 2024

Background and Objectives

Home health care supports patient goals for aging in place. Our objective was to determine if home health care use in the last 3 years of life reduces the risk of inpatient death without hospice.

Research Design and Methods

We analyzed the characteristics of 2,065,300 Medicare beneficiaries who died in 2019 and conducted multinomial logistic regression analyses to evaluate the association between the use and timing of home health care, dementia diagnosis, and place of death.

Results

Receiving any home health care in the last 3 years of life was associated with a lower probability of inpatient death without hospice (Pr 23.3% vs 31.5%, p < .001), and this effect was stronger when home health care began prior to versus during the last year of life (Pr 22.5% vs 24.3%, p < .001). Among all decedents, the probability of death at home with hospice compared to inpatient death with hospice was greater when any home health care was used (Pr 46.0% vs 36.5%, p < .001), and this association was strongest among beneficiaries with dementia who started home health care at least 1 year prior to death (Pr 55.6%, p < .001).

Discussion and Implications

Use of home health care during the last 3 years of life was associated with reduced rates of inpatient death without hospice, and increased rates of home death with hospice. Increasing affordable access to home health care can positively affect end-of-life care outcomes for older Americans and their family caregivers, especially those with dementia.
Deepdefense: annotation of immune systems in prokaryotes using deep learning
Authors: Hauns Sven , Alkhnbashi Omer S , Backofen Rolf
Published: October 2024

Background

Due to a constant evolutionary arms race, archaea and bacteria have evolved an abundance and diversity of immune responses to protect themselves against phages. Since the discovery and application of CRISPR-Cas adaptive immune systems, numerous novel candidates for immune systems have been identified. Previous approaches to identifying these new immune systems rely on hidden Markov model (HMM)–based homolog searches or use labor-intensive and costly wet-lab experiments. To aid in finding and classifying immune systems genomes, we use machine learning to classify already known immune system proteins and discover potential candidates in the genome. Neural networks have shown promising results in classifying and predicting protein functionality in recent years. However, these methods often operate under the closed-world assumption, where it is presumed that all potential outcomes or classes are already known and included in the training dataset. This assumption does not always hold true in real-world scenarios, such as in genomics, where new samples can emerge that were not previously accounted for in the training phase.

Results

In this work, we explore neural networks for immune protein classification, deal with different methods for rejecting unrelated proteins in a genome-wide search, and establish a benchmark. Then, we optimize our approach for accuracy. Based on this, we develop an algorithm called Deepdefense to predict immune cassette classes based on a genome. This design facilitates the differentiation between immune system–related and unrelated proteins by analyzing variations in model-predicted confidence values, aiding in the identification of both known and potentially novel immune system proteins. Finally, we test our approach for detecting immune systems in the genome against an HMM-based method.

Conclusions

Deepdefense can automatically detect genes and define cassette annotations and classifications using 2 model classifications. This is achieved by creating an optimized deep learning model to annotate immune systems, in combination with calibration methods, and a second model to enable the scanning of an entire genome.
Regional Approach to Boosting Local Pharmaceutical Manufacturing Capacity: A Critique of the East African Community Pharmaceutical Manufacturing Plan of Action
Authors: Olatunji Olugbenga Ajani
Published: October 2024

The East African Community (EAC) has had a chequered history, evidenced by multiple changes of names and objectives, and a hiatus lasting more than two decades following a collapse in 1977. It was resuscitated in 1999 by its founding members (Uganda, Tanzania, and Kenya). That four other partner states have since joined is a clear testament to the effectiveness of its overhaul. The community is regulated by the EAC Treaty which promotes collective actions in several areas of mutual interests. Plagued by an ongoing access-to-medicines conundrum, EAC governments have considered collective action as recommended by the Treaty. This effort began around the 2010s when policy measures aimed at exploring collective solutions were adopted with a view to replacing reliance on importation and external drug donation with a gradually developed regional pharmaceutical production capacity. EAC policies such as the Policy/Protocol on TRIPS Flexibilities, the Medicines Registration Harmonisation Initiative, the Draft Anti-Counterfeit Policy, and a Pharmaceutical Manufacturing Plan of Action (EAC PMP) have since been developed to achieve this ambitious goal. Using both doctrinal and empirical (semi-structured interviews) methods, this paper examines the EAC PMP – the ‘be all’ of the policies. The priority actions outlined under the plan’s six pillars and presented as a bankable pathway to self-sufficiency in pharmaceutical production are critiqued. The paper finds considerable implementation of the drug harmonisation theme, while the others (leveraging TRIPS flexibilities, ensuring coherence, and boosting research and development and technology transfer) remain largely unimplemented.
Collective Bargaining for the ‘New’ Working Class: Putting ‘Personal Work Relations’ to Work for Street Vendors
Authors: Von Broembsen Marlese
Published: October 2024

Robert Hale’s famous proposition is that the propertyless man needs to eat and in order to eat, he exchanges his labour for access to property. Indeed, labour law is constituted by these property relations. Historically, most of the workforce (in the global North) has accessed property for livelihood purposes through an employment contract. However, in developing countries, most of the workforce is structurally unable to access property for livelihood purposes by means of an employment contract. These worker-citizens nevertheless need access to property to eat; street vendors need access to public space to trade. The question is whether the scope of labour law, particularly the institution of collective bargaining, can expand to include informal self-employed workers? The article discusses the capability, regulatory, human rights and personal work relations theories; it shows that Freedland and Kountouris’ theory of ‘labour law as personal work relations’ could incorporate informal self-employed workers and illustrates how it might be operationalized to realise collective bargaining laws for street vendors. Informal self-employed workers challenge labour law to examine its assumptions of how property relations are constituted; and to re-theorise property relations to account for workers accessing property by means of an employment contract as well as accessing property based on worker-citizens making rights-based claims.
Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia
Authors: Williams Derek J , Gautam Shruti , Creech C Buddy , Jimenez Natalia , Anderson Evan J , Bosinger Steven E , Grimes Tyler , Arnold Sandra R , McCullers Jonathan A , Goll Johannes , Edwards Kathryn M , Ramilo Octavio ,   for the 16-0036 Study Team, Anderson Julie , Johnson Gayle , Phillips Shanda , Sokolow Katherine , Yoder Sandra , Myers Deborah , Adkisson Robert , Jain Seema , Ampofo Krow , Pavia Andy , Cockcroft Jody , Kleinhenz Dean , Huston Hannah , Rouphael Nadine , McCullough Michele Paine
Published: October 2024

Background

Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches.

Methods

Using whole blood RNA sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed (DE) genes that best identified children according to detected microbial pathogens (viral only vs bacterial only and typical vs atypical bacterial [with or without [±] viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe).

Results

Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial detections (± viral co-detections), and 26 (12%) had atypical bacterial detections (± viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (± viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including 4 genes also identified in the viral-only versus bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and 4 genes from the typical versus atypical bacterial model (PRSS23, IFI27, OLFM4, ABO).

Conclusions

We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.
Causal Evidence for Theories of Contagious Civil Unrest
Authors: Fyfe Rebekah , Desmarais Bruce
Published: October 2024

Many types of civil unrest, including protest, violent conflict, and rebellion, have been found to be subject to both inter- and intra-state contagion. These spillover effects are conventionally tested through the application of parametric structural models that are estimated using observational data. Drawing on research in methods for network analysis, we note important challenges in conducting causal inference on contagion effects in observational data. We review a recently developed non-parametric test—the “split-halves test”—that is robust to confounding and apply the test to replication data from several recent studies in which researchers tested for contagion in civil unrest. We find that about half the time findings in the published literature fail to replicate with the split-halves test. Across ten total replications, we do not see strong patterns in terms of which results do and do not replicate. We do, however, find evidence for general contagion in six of the replications, indicating that contagion is a prevalent phenomenon in civil unrest. As such, we recommend that researchers (1) use the split-halves test as a general-purpose robustness check for parametric models of contagion in the study of civil unrest, and (2) consider modeling contagion in research on civil unrest.
Preferential Trade Agreements and Leaders’ Business Experience
Authors: Nones Nicola
Published: October 2024

Many theories attempt to explain the determinants of preferential trade agreements (PTAs) and their design. Existing accounts, however, focus almost exclusively on structural or domestic factors and ignore individual leaders. In this paper, I develop and test novel theoretical claims regarding executive leaders’ prior career in business and their trade cooperation policy once in office. I construct a new dataset on the heads of the executive’s business managerial experience and test my main claims in a time-series-cross-sectional setting covering 185 countries from 1948 to 2009. To establish causality, I rely on an instrumental variable strategy and leverage exogenous transitions due to sudden deaths or terminal illness in office. The results show that businesspersons-turned-politicians are more likely to enter PTAs and are more likely to sign deeper PTAs. The relationship is further investigated in an illustrative case study of the 1988—Canada trade deal. The substantive effect of business experience is comparable to that of established factors in the literature, such as regime type, and is robust to numerous tests, specifications, subsamples, and measurements of business experience.
Overall status of carbapenem resistance among clinical isolates of Acinetobacter baumannii: a systematic review and meta-analysis
Authors: Ghahramani Ali , Naghadian Moghaddam Mohammad Mahdi , Kianparsa Joben , Ahmadi Mohammad Hossein
Published: October 2024

Background

Resistance to carbapenems, the first-line treatment for infections caused by Acinetobacter baumannii, is increasing throughout the world. The aim of the present study was to determine the global status of resistance to carbapenems in clinical isolates of this pathogen, worldwide.

Methods

Electronic databases were searched using the appropriate keywords, including: ‘Acinetobacter’ ‘baumannii’, ‘Acinetobacter baumannii’ and ‘A. baumannii’, ‘resistance’, ‘antibiotic resistance’, ‘antibiotic susceptibility’, ‘antimicrobial resistance’, ‘antimicrobial susceptibility’, ‘carbapenem’, ‘carbapenems’, ‘imipenem’, ‘meropenem’ and ‘doripenem’. Finally, following some exclusions, 177 studies from various countries were included in this study. The data were then subjected to a meta-analysis.

Results

The average resistance rate of A. baumannii to imipenem, meropenem and doripenem was 44.7%, 59.4% and 72.7%, respectively. A high level of heterogeneity (I2 > 50%, P value < 0.05) was detected in the studies representing resistance to imipenem, meropenem and doripenem in A. baumannii isolates. Begg’s and Egger’s tests did not indicate publication bias (P value > 0.05).

Conclusions

The findings of the current study indicate that the overall resistance to carbapenems in clinical isolates of A. baumannii is relatively high and prevalent throughout the world. Moreover, time trend analysis showed that the resistance has increased from the year 2000 to 2023. This emphasizes the importance of conducting routine antimicrobial susceptibility testing before selecting a course of treatment, as well as monitoring and controlling antibiotic resistance patterns in A. baumannii strains, and seeking novel treatment options to lessen the emergence and spread of resistant strains and to reduce the treatment failure.
Long-term monitoring of the hypogeal Etruscan Tomba degli Scudi, Tarquinia, Italy. Early detection of black spots, investigation of fungal community, and evaluation of their biodeterioration potential
Authors: Kratter Matilde , Beccaccioli Marzia , Vassallo Ylenia , Benedetti Francesca , La Penna Giancarlo , Proietti Anacleto , Zanellato Gianluca , Faino Luigi , Cirigliano Angela , Neisje de Kruif Fiona , Tomassetti Maria Cristina , Rossi Marco , Reverberi Massimo , Quagliariello Andrea , Rinaldi Teresa
Published: October 2024

Aims

Hypogeal environments with cultural heritage interest pose a real challenge for their preservation and conservation. The ancient Etruscan Necropolis of Tarquinia, Italy, consists of 200 tombs decorated with extraordinary mural paintings, of great artistic and historical value. Since the beginning of the restoration campaign in 2016, a regular microbiological survey has been performed in the Tomba degli Scudi. The aim of this study was to investigate the nature of an expansion of black spots on the pictorial layers recently observed.

Methods and results

To determine the origin of the black spots in the atrium chamber of the Tomba degli Scudi, the fungal community was sampled using various techniques: cellulose discs, swabs, and nylon membranes and investigated by a multi-analytical approach. The obtained results suggest that the identified fungal strains (e.g. Gliomastix murorum and Pseudogymnoascus pannorum) are common to many subterranean environments around the world, such as Lascaux cave.

Conclusions

The continuous and long-term monitoring made it possible to detect alterations at an early stage and assess the harmfulness of different fungal strains. This work is a demonstration of the effectiveness of prevention and monitoring actions within these fragile and valuable environments.
Specific Determination of (-)- and (+)-Gossypol in Vegetable Oil by Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry with Chiral Pre-Column Derivatization
Authors: Guo Mimi , Wang Yameng , Xue Yalin , Duan Zhangqun , Chang Qiaoying
Published: October 2024

Background

As the unique ingredient of cottonseed oil, gossypol is toxic and there are differences between the enantiomers. Although the determination of (-)- and (+)-gossypol in cotton plants or cottonseed has been performed, the detection of the gossypol enantiomers in vegetable oil has rarely been reported.

Objective

To develop a specific inspection method for (-)- and (+)-gossypol in vegetable oil by ultra-performance liquid chromatography (UPLC)–tandem mass spectrometry with chiral pre-column derivatization.

Methods

(-)- and (+)-Gossypol were separated on an ACQUITY C18 reverse-phase column (100 mm × 2.1 mm, 1.7 μm) maintained at 40°C on an UPLC system with gradient elution. The mobile phases were composed of methanol (solvent A) and water containing 0.1% formic acid (solvent B). Analytes were detected using an electrospray ionization (ESI) source in positive mode. The contents of (-)- and (+)-gossypol standard derivatives were quantified by multiple reaction monitoring (MRM) with the transitions of m/z 633/483 for quantitative ion pairs and m/z 633/558 for qualitative ion pairs.

Results

The results indicated that the quantitative analysis could be accomplished within 12.5 min and the LODs of (-)- and (+)-gossypol were 25.55 and 14.67 μg/kg, respectively. When this method was applied to olive oil spiked with gossypol standards, good recoveries [95.37–105.84% for (-)-gossypol and 98.96–105.14% for (+)-gossypol] and RSDs [3.41–6.02% for (-)-gossypol and 4.50–6.94% for (+)-gossypol)] were achieved.

Conclusion

The present study confirms the feasibility of determining gossypol enantiomers and achieves trace determination of (-)- and (+)-gossypol in vegetable oil. These results make this method more suitable for the qualitative identification of whether the vegetable oil has been mixed with cottonseed oil.

Highlights

The trace determination of (-)- and (+)-gossypol in vegetable oils has been achieved. This method provides technical support for further identification of whether commercially available vegetable oil has been mixed with cottonseed oil.
Transplantation of fecal microbiota from different breeds improved intestinal barrier condition and modulated ileal microflora of recipient pigs
Authors: Yang Tong , Liu Yang , Yin Jie , Yv Tian , Zhou Feng , Li Yinghui , Yang Lingyuan , Han Li , Huang Xingguo
Published: October 2024

In this study, we investigated the effects of transplanting Ningxiang pig fecal bacteria on the ileum microflora and intestinal barrier of Duroc × Landrace × Large White (DLY) pigs. Thirty-two DLY pigs at 90-d-old were equally assigned to either control groups (fed the basal diet) or test groups (fed the basal diet + 10 mL fecal microbiota suspension from Ningxiang pig). Results showed that fecal microbiota transplantation (FMT) did not influence the growth performance, but increased the number of ileum goblet cells and the expression level of mucin-2. Additionally, the mucosal levels of anti-inﬂammatory cytokines interlukin-4 and interlukin-10 were upregulated, but the level of pro-inﬂammatory cytokine interferon-γ was downregulated by FMT. Moreover, FMT increased the expression level of porcine β defensin-114 in ileum mucus. 16S rRNA gene sequencing of ileal digesta showed that FMT modulated the diversity and composition of ileal microbiota of DLY pigs by increasing the relative abundances of beneﬁcial bacteria, while decreasing the abundance of the pathogenic bacterium Streptococcus. Taken together, the study showed that FMT of Ningxiang pigs could improve the intestinal barrier condition of DLY pigs by improving intestinal microflora and promoting intestinal health.
Maternal loss of 24-hydroxylase causes increased intestinal calcium absorption and hypercalcemia during pregnancy but reduced skeletal resorption during lactation in mice
Authors: Maekawa Alexandre S , Bennin David , Hartery Sarah A , Kirby Beth J , Poulton Ingrid J , St-Arnaud René , Sims Natalie A , Kovacs Christopher S
Published: October 2024

Inactivation of 24-hydroxylase (CYP24A1) causes mild hypercalcemia in humans that becomes severe and life-threatening during pregnancy through unclear mechanisms. We studied Cyp24a1 null mice during pregnancy, lactation, and post-weaning. We hypothesized that Cyp24a1 nulls have a much greater increase in calcitriol during pregnancy and lactation, leading to markedly increased intestinal calcium absorption and reduced lactational bone loss. WT and Cyp24a1 null sisters were mated to Cyp24a1+/- males. Timepoints included baseline (BL), late pregnancy (LP), mid-lactation (ML), late lactation (LL), and weekly x4 weeks of post-weaning recovery (R1-4). Assessments included intestinal calcium absorption (IntCaAbs) by gavage of 45Ca, BMC by DXA, microCT of femurs, 3-point bending tests of tibias, serum hormones, serum and urine minerals, milk analysis, and intestinal gene expression. At LP, whole body BMC increased equally by ~12% in null and WT. Calcitriol was 2.5-fold higher in nulls vs WT, accompanied by 3-fold increased IntCaAbs, hypercalcemia, hypercalciuria, and 6.5-fold higher FGF23. PTH was suppressed in both. Twenty percent of null dams died during delivery but their serum calcium at LP did not differ from Cyp24a1 nulls that survived. At ML, calcitriol, IntCaAbs, and FGF23 declined in both genotypes but remained higher than BL values in Cyp24a1 nulls. By LL, nulls were still hypercalcemic vs WT, and had lost less mean whole body BMC (11% vs. 21%, p<0.02), but by micro-CT there were no differences from WT in cortical or trabecular bone mass. Lactational losses in BMC, cortical thickness, and trabecular number were restored by R4 in both genotypes. In summary, ablation of Cyp24a1 increased IntCaAbs and caused hypercalcemia during pregnancy and lactation, late gestational mortality in some nulls, and reduced lactational BMC loss. Treating women with gestational hypercalcemia from CYP24A1 mutations should focus on reducing calcitriol or IntCaAbs, since increased bone resorption is not the cause.
Significance of honeybee pollination in increasing seed yield of Trifolium alexandrinum (Fabales: Fabaceae) and its impact on economic sustainability of smallholder farmers
Authors: Tufail Muhammad Shoaib , Krebs Gaye L , Southwell Alison , Piltz John W , Wynn Peter C , Cook David F
Published: October 2024

A major limitation to producing high seed yields in berseem clover (Trifolium alexandrinum L.) is failure to set seed, predominantly due to lack of pollination. Despite the importance of berseem clover as a leading forage legume, the contribution of pollinators to seed set is scarce. In Pakistan, the honeybee population is declining mainly because of the extensive use of neonicotinoid pesticides and habitat fragmentation. This, combined with the region’s harsh environment and the use of inferior, locally bred genotypes, has resulted in low seed yields. Insufficient seed availability leads to limited forage supply, resulting in poor livestock nutrition, which subsequently impacts livestock health and productivity, and reduces farmers’ income. The present study estimated the seed production of 3 berseem clover genotypes resulting from honeybees [Apis mellifera L. (Hymenoptera: Apidae)] pollination in 2 growing seasons (2012–2014) in the central Punjab region of Pakistan. Experiments had 2 pollination treatments (open pollination and honeybee inclusion) and 3 seed genotypes, viz. farmer own-saved, market, and the improved variety cultivars. For both growing seasons, honeybee pollination resulted in significant increases in seed yields ranging from 35% to 67%, regardless of seed genotype. With the exception of the number of seed heads/m2, all seed yield parameters also increased significantly in response to honeybee inclusion. The combination of improved variety and honeybee inclusion resulted in the production of a maximum number of seeds per head (45.3), 1,000-seed weight (3.7 g), and estimated seed yield (375.5 kg/ha). In addition, the increase in estimated net income of seed ranged from PKR 82,485 Rs/ha (US$844/ha) to PKR 168,975 Rs/ha (US$1728/ha) with the use of honeybees as an insect pollinator across all the seed genotypes. Honeybee pollination has broader implications for mixed farming systems by playing a key role in preserving biodiversity and promoting sustainable agriculture. It also enhances the quality and quantity of berseem crops by increasing the production of high-quality seeds and forage leading to improved livestock productivity and family food security which strengthens the economic resilience of rural communities.
Electroantennographic and behavioral responses of Bactrocera dorsalis (Diptera: Tephritidae) adults to the volatiles of plum fruits
Authors: Ling Jing , Li Yuan , Zheng Xia-Lin , Lu Wen , Wang Xiao-Yun
Published: October 2024

Fruit volatiles play a crucial role in the host localization by the oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae). This study focused on identifying the fruit volatiles from Sanyue plum and Sanhua plum (Prunus salicina Lindl.), which are 2 varieties of the same species, and examined their impact on the behavior of B. dorsalis by using a Y-olfactometer. A total of 35 and 54 volatiles from Sanyue plum and Sanhua plum were identified, respectively. Among these, 23 volatiles elicited electroantennographic (EAG) responses by B. dorsalis adults, showing concentration-dependent effects in males and females. Ethyl butyrate, butyl acetate, butyl hexanoate, ethyl caproate, ethyl hexanoate, and hexyl acetate significantly attracted B. dorsalis compared to liquid paraffin, while nonaldehyde was avoided. There was no significant difference in the behavioral responses of both sexes to sorbitol esters, hexyl isobutyrate, and 1-tetradecene compared with the control liquid paraffin group. Interestingly, (3Z)-C-3-hexenyl acetate significantly attracted females, but not males. The above findings suggest that plum fruit volatiles are likely to facilitate the localization of host fruit by B. dorsalis adults and may even aid in mate-finding. This study opens up new avenues for exploring novel plant-based attractants that might be of value for the integrated management of B. dorsalis.
False Narratives and Political Mobilization
Authors: Eliaz Kfir , Galperti Simone , Spiegler Ran
Published: October 2024

We present an equilibrium model of politics in which political platforms compete over public opinion. A platform consists of a policy, a coalition of social groups with diverse intrinsic attitudes to policies, and a narrative. We conceptualize narratives as subjective models that attribute a commonly valued outcome to (potentially spurious) postulated causes. When quantified against empirical observations, these models generate a shared belief among coalition members over the outcome as a function of its postulated causes. The intensity of this belief and the members’ intrinsic attitudes to the platform’s policy determine the extent to which the coalition is mobilized. Only platforms that generate maximal mobilization prevail in equilibrium. Our equilibrium characterization demonstrates how false narratives can be detrimental to the commonly valued outcome, and how political fragmentation leads to their proliferation. The false narratives that emerge in equilibrium have a flavor of “scapegoating:” They attribute good outcomes to the exclusion of social groups from ruling coalitions.
The miniaturized isolation of neutrophil granules (MING) method allowed a deep proteome mapping of human neutrophil granules
Authors: Alexandria Gabrielly , Valerio Hellen P , Massafera Mariana P , Reis Lorenna R , Coelho Fernando R , Di Mascio Paolo , Ronsein Graziella E
Published: October 2024

Neutrophils are the innate immune system's first line of defense, and their storage organelles are essential to their function. The storage organelles are divided into 3 different granule types named azurophilic, specific, and gelatinase granules, besides a fourth component called secretory vesicles. The isolation of neutrophil's granules is challenging, and the existing procedures rely on large sample volumes, about 400 mL of peripheral blood, precluding the use of multiple biological and technical replicates. Therefore, the aim of this study was to develop a miniaturized isolation of neutrophil granules method, using biochemical assays, mass spectrometry–based proteomics and a machine learning approach to investigate the protein content of these organelles. Neutrophils were isolated from 40 mL of blood collected from 3 apparently healthy volunteers and disrupted using nitrogen cavitation; the organelles were fractionated with a discontinuous 3-layer Percoll density gradient. The method was proven successful and allowed for a reasonable separation and enrichment of neutrophil's storage organelles using a gradient approximately 37 times smaller than the methods described in the literature. Moreover, mass spectrometry–based proteomics identified 368 proteins in at least 3 of the 5 analyzed samples, and using a machine learning strategy aligned with markers from the literature, the localization of 50 proteins was predicted with confidence. When using markers determined within our dataset by a clusterization tool, the localization of 348 proteins was confidently determined. Importantly, this study was the first to investigate the proteome of neutrophil granules using technical and biological replicates, creating a reliable database for further studies.
Grade-stratified meningioma risk among individuals who are non-Hispanic Black and interactions with male sex
Authors: Walsh Kyle M , Price Mackenzie , Raleigh David R , Calabrese Evan , Kruchko Carol , Barnholtz-Sloan Jill S , Ostrom Quinn T
Published: October 2024

Background

Meningioma risk factors include older age, female sex, and being Black/African American. Limited data explore how meningioma risk in individuals who are Black varies across the lifespan, interacts with sex, and differs by tumor grade.

Methods

The Central Brain Tumor Registry of the United States is a population-based registry covering the entire US population. Meningioma diagnoses from 2004 to 2019 were used to calculate incidence rate ratios for non-Hispanic Black individuals compared with non-Hispanic White individuals across 10-year age intervals and stratified by sex and World Health Organization tumor grade in this retrospective study.

Results

A total of 53 890 non-Hispanic Black individuals and 322 373 non-Hispanic White individuals with an intracranial meningioma diagnosis were included in analyses. Beginning in young adulthood, the non-Hispanic Black to non-Hispanic White incidence rate ratio was elevated for grade 1 and grades 2-3 tumors. The incidence rate ratio peaked in the seventh decade of life regardless of grade and was higher for grades 2-3 tumors (incidence rate ratio  = 1.57, 95% confidence interval [CI] = 1.46 to 1.69) than grade 1 tumors (incidence rate ratio = 1.27, 95% CI = 1.25 to 1.30) in this age group. The non-Hispanic Black to non-Hispanic White incidence rate ratio was elevated in women (incidence rate ratio = 1.17, 95% CI = 1.16 to 1.18) and was further elevated in men (incidence rate ratio = 1.28, 95% CI = 1.26 to 1.30), revealing synergistic interaction between non-Hispanic Black race and ethnicity and male sex (Pinteraction = .001).

Conclusions

Relative to non-Hispanic White individuals, non-Hispanic Black individuals are at elevated risk of meningioma from young adulthood through old age. Non-Hispanic Black race and ethnicity conferred greater risk of meningioma among men than women and greater risk of grades 2-3 tumors. Population-level differences in meningioma incidence and tumor behavior suggest potential disparities in the geographic, socioeconomic, and racial distribution of meningioma risk factors within the United States.
Clinical guidelines for the management of mammographic density: a systematic review of breast screening guidelines worldwide
Authors: Isautier Jennifer Marie Jacqueline , Houssami Nehmat , Hadlow Claudia , Marinovich Michael Luke , Hope Serena , Zackrisson Sophia , Brennan Meagan Elizabeth , Nickel Brooke
Published: October 2024

Background

High breast density is an independent risk factor for breast cancer and decreases the sensitivity of mammography. This systematic review synthesizes the international clinical guidelines and the evidence base for screening and supplemental screening recommendations in women with dense breasts.

Methods

A systematic search of CINHAL, Embase, and Medline databases was performed in August 2023 and grey literature searched in January 2024. Two authors independently assessed study eligibility and quality (Appraisal of Guidelines for Research and Evaluation II instrument).

Results

Of 3809 articles, 23 guidelines published from 2014 to 2024 were included. The content and quality varied between the guidelines; the average AGREE II total score was 58% (range = 23%-87%). Most guidelines recommended annual or biennial screening mammography for women more than 40 years old with dense breasts (n = 16). Other guidelines recommended breast tomosynthesis (DBT, n = 6) or magnetic resonance imaging (MRI, n = 1) as the preferred screening modality. One third of the guidelines (n = 8) did not recommend supplemental screening for women with dense breasts. Of those that recommended supplemental screening (n = 14), ultrasound was the preferred modality (n = 7), with MRI (n = 3), DBT (n = 3), and contrast-enhanced mammography (n = 2) also recommended.

Conclusions

Consensus on supplemental screening in women with dense breasts is lacking. The quality of the guidelines is variable, and recommendations are based largely on low-quality evidence. As evidence of the benefits versus harms of supplemental screening in women with dense breasts is evolving, it is imperative to improve the methodological quality of breast cancer screening and supplemental screening guidelines.
Rise in inappropriate antibiotic prescriptions for Streptococcal Pharyngitis in an era of antibiotic shortages
Authors: Bausley Lauryn , Wozniak Amy , Qureshi Nadia K
Published: October 2024

Background

Group A streptococcal (GAS) pharyngitis is the most common cause of bacterial pharyngitis. It accounts for about a quarter of pharyngitis cases seen in children. The American Academy of Pediatrics (AAP) and Infectious Disease Society of America (IDSA) have issued guidelines for the diagnosis and treatment of GAS pharyngitis. Penicillin is the antibiotic of choice for GAS infections along with Amoxicillin. Based on a previous study at Loyola University Medical Center (LUMC), over 1/3rd of all antibiotics prescribed in our sample of 7000 encounters were considered inappropriate. During our intervention period, there was an increased incidence in GAS infections along with multiple antibiotic shortages from Oct 2022. Our study aimed to 1) Do provider education on evaluation of streptococcal pharyngitis and treatment 2) Evaluation of adherence to the evidence-based protocol 3) Determine frequency of inappropriate testing and antibiotic management 4) Determine the antibiotic when treating GAS at LUMC.

Methods

A retrospective chart review of patients between the ages of 0-18 years presented at LUMC with the pharyngitis diagnoses codes between Jan 2022-Dec 2022 and post-education between Jan 2023-June 2023 was done. LUMC providers were educated via different forums and an evidence-based protocol was shared. Patient-level data extracted from the Electronic Health Record (EHR) included race, gender, age in years, insurance type, drug allergies and encounter type i.e., clinic visit, immediate care (IMC) or emergency department (ED). P-values were calculated with repeated patients’ statement and exchangeable correlation matrix.

Results

Individuals with allergies and individuals who received antibiotics due to secondary diagnoses were excluded. The baseline year of 2022 had a lower incidence of positive GAS cases (5.7%) compared to the 2023 Q1 (27.5%) and Q2 (22.9%). Overall inappropriate prescribing was 19.2% in 2022 and increased to 39.2% and 40.9% in Q1 and Q2 of 2023, respectively. While there was an increased use of Penicillin in post-education period, there was an increase in use of other broad-spectrum antibiotics as well.

Conclusion

This study showed despite provider education, due to a significant increase in GAS cases across the US and national antibiotic shortages (amoxicillin and then penicillin) during our post-education period, there was an increase in inappropriate management of GAS cases. With reduction in antibiotic shortages, and continued provider education, future clinical management for GAS pharyngitis will improve for pediatric patients.

Fig 1. Summary of incorrect prescribing: By Scenario

Fig 2. Trends over time (by month) with reference lines for antibiotic shortages

Table 1. Summary of Testing and Prescribing by Time
Leveraging thePlasmodium falciparum esterase repertoire to design parasite-specific prodrugs
Authors: Sundararaman Sesh A , Kasak Paulina , Daniels Abigail , John Audrey O
Published: October 2024

Background

Antimalarial drug resistance remains a constant threat, highlighting the need to identify new antimalarials with novel modes of action. Unfortunately, new drug development is often hampered by poor drug-like properties of lead compounds. Prodrugging temporarily masks undesirable compound features, improving bioavailability and target penetration. However, many prodrugs are activated by non-specific host enzymes, losing these beneficial features before they reach their target site. Designing prodrugs that are activated by enzymes specific to a target pathogen, “pathogen specific prodrugs,” would allow prodrugs to maintain their beneficial pharmacokinetic and pharmacodynamic effects until they reach their target. We have previously shown that lipophilic ester prodrug modifications substantially increase the potency of antimalarial phosphonates both in vitro and in vivo. However, ester prodrug activation in the malaria parasite, Plasmodium falciparum is poorly understood, as only a single P. falciparum esterase has been characterized.

Methods

In this study, we use a novel fluorogenic ester substrate library, to characterize the substrate specificity of the entire esterase repertoire of P. falciparum. We compare this substrate specificity to that of host erythrocytes, serum, liver and intestinal epithelium. We employ a combination of substrate activity profiling, enzymatic inhibition assays, and liquid chromatography mass spectrometry, to identify the activating enzyme of highly potent antimalarial phosphonate prodrugs.

Results

We find that structurally similar substrates exhibit varying degrees of activation by human and parasite esterases. We identify a group of long unbranched alkyl substrates that are specifically activated by P. falciparum esterases, suggesting an important structure activity relationship. We also identify an erythrocyte serine hydrolase (APEH), which is imported by the parasite and activates multiple antimalarial phosphonate prodrugs.

Conclusion

This study identifies ester prodrug modifications that are specifically activated by P. falciparum, and highlights candidate enzymes responsible for their activation. Our data reveals that an imported human esterase is involved in the activation of antimalarial phosphonate ester prodrugs. Our method can be applied to other organisms or genetic mutants to rapidly characterize esterase activity. Ongoing work will use recombinantly expressed enzymes to specifically characterize their substrate specificities, allowing for the identification of substrates and prodrugs targeted towards those enzymes.