bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interactive Role of Sleep and Circadian Rhythms in Episodic Memory in Older Adults
Authors: Carlson Elyse J , Wilckens Kristine A , Wheeler Mark E
Published: May 2023

Adequate sleep is essential for healthy physical, emotional, and cognitive functioning, including memory. However, sleep ability worsens with increasing age. Older adults on average have shorter sleep durations and more disrupted sleep compared with younger adults. Age-related sleep changes are thought to contribute to age-related deficits in episodic memory. Nonetheless, the nature of the relationship between sleep and episodic memory deficits in older adults is still unclear. Further complicating this relationship are age-related changes in circadian rhythms such as the shift in chronotype toward morningness and decreased circadian stability, which may influence memory abilities as well. Most sleep and cognitive aging studies do not account for circadian factors, making it unclear whether age-related and sleep-related episodic memory deficits are partly driven by interactions with circadian rhythms. This review will focus on age-related changes in sleep and circadian rhythms and evidence that these factors interact to affect episodic memory, specifically encoding and retrieval. Open questions, methodological considerations, and clinical implications for diagnosis and monitoring of age-related memory impairments are discussed.
Cyclical Migration in Alaska Native Elders and Its Impact on Elders’ Identity and Later Life Well-Being
Authors: Lewis Jordan P , Kim Steffi M , Asquith-Heinz Zayla , Thompson Lena
Published: May 2023

Objectives

This paper outlines the unique culturally driven cyclical migration of Alaska Native (AN) Elders, distinct from previously described migration patterns in that Elders spend extended time in more than one community. We describe this Indigenous cyclical migration of AN Elders and its influence on their identity and later life health and well-being.

Methods

Interviews with 124 AN Elders were conducted across 5 regions of Alaska: Bristol Bay, Interior, Norton Sound, Aleutian Pribilof Islands, and Southcentral. Within this sample, 87 participants engaged in cyclical migration. Thematic analysis was employed to identify themes related to Elders’ cyclical migration between rural and urban communities and the impact on their identity and later life health and well-being.

Results

We identified 2 distinct patterns of Indigenous cyclical migration—Elders living primarily in rural communities migrating to urban communities and Elders living primarily in urban communities migrating to rural communities. Elders engaged in these 2 patterns of cyclical migration to maintain cultural practices, access social, and health care services to maintain their physical health and well-being, and continue their community roles contributing to their AN Elder identity.

Discussion

This study builds upon existing migration theories by introducing a cyclical pattern uniquely driven by AN identity, culture, and traditional practices. Findings illustrate how AN communities can support Elders who experience cyclical migration patterns to ensure they age successfully in both locations. Future research should explore cyclical migration patterns among other Indigenous populations with migration histories.
T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases
Authors: Høye Eirik , Dagenborg Vegar J , Torgunrud Annette , Lund-Andersen Christin , Fretland Åsmund A , Lorenz Susanne , Edwin Bjørn , Hovig Eivind , Fromm Bastian , Inderberg Else M , Greiff Victor , Ree Anne H , Flatmark Kjersti
Published: May 2023

Background

Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T-cell infiltration in CLM using T-cell receptor (TCR) repertoire sequencing. Eighty-five resected CLMs from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T-cell fractions were calculated, repertoire clonality was analyzed based on Hill evenness curves, and TCR sequence convergence was assessed using network analysis.

Results

Increased T-cell fractions (10.6% vs. 6.3%) were detected in CLMs exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT-exposed tumors independently of the timing of NACT administration and surgery. While private clones made up >90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence.

Conclusions

TCR repertoire sequencing can be used to quantify T-cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T-cell clonal expansion in CLM in a clinical context.
An Animal Model of Neonatal Intensive Care Unit Exposure to Light and Sound in the Preterm Infant
Authors: Gay Jennifer D , Dangcil Evelynne , Nacipucha Jacqueline , Botrous Jonathon E , Suresh Nikhil , Tucker Aaron , Carayannopoulos Nicolas L , Khan Muhammad R , Meng Raphael , Yao Justin D , Wackym P Ashley , Mowery Todd M
Published: May 2023

Synopsis

According to the World Health Organization, ∼15 million children are born prematurely each year. Many of these infants end up spending days to weeks in a neonatal intensive care unit (NICU). Infants who are born prematurely are often exposed to noise and light levels that affect their auditory and visual development. Children often have long-term impairments in cognition, visuospatial processing, hearing, and language. We have developed a rodent model of NICU exposure to light and sound using the Mongolian gerbil (Meriones unguiculatus), which has a low-frequency human-like audiogram and is altricial. To simulate preterm infancy, the eyes and ears were opened prematurely, and animals were exposed to the NICU-like sensory environment throughout the gerbil’s cortical critical period of auditory development. After the animals matured into adults, auditory perceptual testing was carried out followed by auditory brainstem response recordings and then histology to assess the white matter morphology of various brain regions. Compared to normal hearing control animals, NICU sensory-exposed animals had significant impairments in learning at later stages of training, increased auditory thresholds reflecting hearing loss, and smaller cerebellar white matter volumes. These have all been reported in longitudinal studies of preterm infants. These preliminary results suggest that this animal model could provide researchers with an ethical way to explore the effects of the sensory environment in the NICU on the preterm infant’s brain development.
Child marriage as a risk factor for non-communicable diseases among women in India
Authors: Vikram Kriti , Visaria Abhijit , Ganguly Dibyasree
Published: May 2023

Background

Child marriage, defined as marriage under the age of 18 years, remains pervasive in India. Global evidence documents a negative association between child marriage and women's reproductive and sexual health outcomes; however, its relationship with non-communicable diseases (NCDs) remains underexplored.

Methods

We utilize biomarkers and self-reported data from the nationally representative National Family and Health Survey 4 (2015–2016) to examine the associations between child marriage and hypertension, diabetes, heart disease, asthma and thyroid disorder among currently married women (N = 421 107). We use regression models adjusted for a range of demographic and socio-economic controls to assess the association between child marriage and NCDs among women in India. We further assess whether and to what extent these relationships are mediated by early motherhood using the Karlson, Holm and Breen method of decomposition.

Results

Child marriage was associated with hypertension [adjusted odds ratio 1.20 (95% CI: 1.17–1.24)], diabetes [1.29 (1.22–1.37)], heart disease [1.27 (1.18–1.36)], asthma [1.19 (1.11–1.28)] and thyroid disorder [1.10 (1.02–1.18)]. Early motherhood also increased the risk of NCDs among women. Furthermore, it emerged as a pathway linking child marriage with hypertension, diabetes and heart disease; however, it provided a partial explanation for the disadvantage associated with child marriages.

Conclusions

Child marriage emerges as a risk factor for NCDs among women in India. Health systems need to recognize the enduring influence of child marriages on women’s health and ensure early detection and effective treatment of NCDs for this vulnerable group.
Influence of liquid column impact wall on liquid film thickness fluctuation outside the horizontal tube
Authors: Chen Lele , Qiu Qinggang , Zhang Xiaocui , Zhang Kun
Published: May 2023

A 3D falling film flow model outside the horizontal tube is established to study the influence of the liquid column impact the wall on the liquid film thickness distribution. It is found that the liquid film thickness fluctuates significantly at 0°–60° in single liquid column, and the minimum thickness appears. In the jet flow, there is a critical value of 70° due to the liquid film fluctuation. The liquid film thickness change before 70° was negatively correlated with Reynolds number and positively correlated after 70°. And the fluctuation amplitude negatively correlates with the Reynolds number.
Decoupling analysis of economic growth, energy consumption and CO2 emissions in the industrial sector of Guangdong Province
Authors: Guo Qing , You Wenlan
Published: May 2023

Industrial carbon emissions are the main part of China’s carbon emissions, so industrial carbon emission reduction is an important tool to achieve the ‘double carbon’ target. This paper constructs a Tapio model to decompose the total decoupling indicators into energy-saving decoupling indicators and emission-reduction decoupling indicators, with a view to revealing more deeply the reasons and mechanisms for the changes in the decoupling indicators between economic growth and CO2 emissions in the industrial sector of each prefecture-level city in Guangdong Province, as well as using cluster analysis to further explore the changes in the effect of energy saving and emission reduction in the industrial sector over the three five-year plans. The conclusions showed that: ( 1) the overall efficiency of energy saving and emission reduction in the industrial sector of Guangdong Province has improved, but there are large differences in efficiency between different cities and ( 2) the energy structure of the industrial sector in Guangdong Province has changed little due to immature technology. Based on the aforementioned findings, this paper puts forward corresponding policy recommendations.
Forum: Russia's Invasion of Ukraine: What Did We Miss?
Authors: Mahon Anastassiya , Pearce James C , Korobkov Andrei , Gabdulhakov Rashid , Gozalishvili Nino , Topuria Revaz , Stercul Natalia , Vacarelu Marius
Published: May 2023

This forum focuses on the overlooked areas of the moment surrounding the nature and progression of Russia's invasion of Ukraine in 2022. It brings together scholars of different disciplines, backgrounds, and locations to provide analyses of the Russian aggression from varying perspectives such as history, law, military studies, politics, and media and communications, to name a few, encouraging the authors to focus on intricacies to deliver a deeper analysis of the invasion. Each author offers a unique take on the analyses of the past and present. The forum has two aims. First, the collection raises the question “What did we miss?” and it aims to highlight the lack of attention by Western scholars to Russian perceptions of Western threats and the concerns of former Soviet countries regarding Russia's aggressive foreign policy. Second, the forum intends to start a conversation on different non-Western perspectives of thinking about the Russian invasion. The forum covers the events of the period from the beginning of the invasion up to July 2022, with some post-revision comments in the introduction and conclusion mentioning the events up to February 2023.
Knowledgebase strategies to aid interpretation of clinical correlation research
Authors: Stead William W , Lewis Adam , Giuse Nunzia B , Koonce Taneya Y , Bastarache Lisa
Published: May 2023

Objective

Knowledgebases are needed to clarify correlations observed in real-world electronic health record (EHR) data. We posit design principles, present a unifying framework, and report a test of concept.

Materials and Methods

We structured a knowledge framework along 3 axes: condition of interest, knowledge source, and taxonomy. In our test of concept, we used hypertension as our condition of interest, literature and VanderbiltDDx knowledgebase as sources, and phecodes as our taxonomy. In a cohort of 832 566 deidentified EHRs, we modeled blood pressure and heart rate by sex and age, classified individuals by hypertensive status, and ran a Phenome-wide Association Study (PheWAS) for hypertension. We compared the correlations from PheWAS to the associations in our knowledgebase.

Results

We produced PhecodeKbHtn: a knowledgebase comprising 167 hypertension-associated diseases, 15 of which were also negatively associated with blood pressure (pos+neg). Our hypertension PheWAS included 1914 phecodes, 129 of which were in the PhecodeKbHtn. Among the PheWAS association results, phecodes that were in PhecodeKbHtn had larger effect sizes compared with those phecodes not in the knowledgebase.

Discussion

Each source contributed unique and additive associations. Models of blood pressure and heart rate by age and sex were consistent with prior cohort studies. All but 4 PheWAS positive and negative correlations for phecodes in PhecodeKbHtn may be explained by knowledgebase associations, hypertensive cardiac complications, or causes of hypertension independently associated with hypotension.

Conclusion

It is feasible to assemble a knowledgebase that is compatible with EHR data to aid interpretation of clinical correlation research.
Developing, pilot testing, and refining requirements for 3 EHR-integrated interventions to improve diagnostic safety in acute care: a user-centered approach
Authors: Garber Alison , Garabedian Pamela , Wu Lindsey , Lam Alyssa , Malik Maria , Fraser Hannah , Bersani Kerrin , Piniella Nicholas , Motta-Calderon Daniel , Rozenblum Ronen , Schnock Kumiko , Griffin Jacqueline , Schnipper Jeffrey L , Bates David W , Dalal Anuj K
Published: May 2023

Objective

To describe a user-centered approach to develop, pilot test, and refine requirements for 3 electronic health record (EHR)-integrated interventions that target key diagnostic process failures in hospitalized patients.

Materials and Methods

Three interventions were prioritized for development: a Diagnostic Safety Column (DSC) within an EHR-integrated dashboard to identify at-risk patients; a Diagnostic Time-Out (DTO) for clinicians to reassess the working diagnosis; and a Patient Diagnosis Questionnaire (PDQ) to gather patient concerns about the diagnostic process. Initial requirements were refined from analysis of test cases with elevated risk predicted by DSC logic compared to risk perceived by a clinician working group; DTO testing sessions with clinicians; PDQ responses from patients; and focus groups with clinicians and patient advisors using storyboarding to model the integrated interventions. Mixed methods analysis of participant responses was used to identify final requirements and potential implementation barriers.

Results

Final requirements from analysis of 10 test cases predicted by the DSC, 18 clinician DTO participants, and 39 PDQ responses included the following: DSC configurable parameters (variables, weights) to adjust baseline risk estimates in real-time based on new clinical data collected during hospitalization; more concise DTO wording and flexibility for clinicians to conduct the DTO with or without the patient present; and integration of PDQ responses into the DSC to ensure closed-looped communication with clinicians. Analysis of focus groups confirmed that tight integration of the interventions with the EHR would be necessary to prompt clinicians to reconsider the working diagnosis in cases with elevated diagnostic error (DE) risk or uncertainty. Potential implementation barriers included alert fatigue and distrust of the risk algorithm (DSC); time constraints, redundancies, and concerns about disclosing uncertainty to patients (DTO); and patient disagreement with the care team’s diagnosis (PDQ).

Discussion

A user-centered approach led to evolution of requirements for 3 interventions targeting key diagnostic process failures in hospitalized patients at risk for DE.

Conclusions

We identify challenges and offer lessons from our user-centered design process.
A metadata framework for computational phenotypes
Authors: Spotnitz Matthew , Acharya Nripendra , Cimino James J , Murphy Shawn , Namjou Bahram , Crimmins Nancy , Walunas Theresa , Liu Cong , Crosslin David , Benoit Barbara , Rosenthal Elisabeth , Pacheco Jennifer A , Ostropolets Anna , Reyes Nieva Harry , Patterson Jason S , Richter Lauren R , Callahan Tiffany J , Elhussein Ahmed , Pang Chao , Kiryluk Krzysztof , Nestor Jordan , Khan Atlas , Mohan Sumit , Minty Evan , Chung Wendy , Wei Wei-Qi , Natarajan Karthik , Weng Chunhua
Published: May 2023

With the burgeoning development of computational phenotypes, it is increasingly difficult to identify the right phenotype for the right tasks. This study uses a mixed-methods approach to develop and evaluate a novel metadata framework for retrieval of and reusing computational phenotypes. Twenty active phenotyping researchers from 2 large research networks, Electronic Medical Records and Genomics and Observational Health Data Sciences and Informatics, were recruited to suggest metadata elements. Once consensus was reached on 39 metadata elements, 47 new researchers were surveyed to evaluate the utility of the metadata framework. The survey consisted of 5-Likert multiple-choice questions and open-ended questions. Two more researchers were asked to use the metadata framework to annotate 8 type-2 diabetes mellitus phenotypes. More than 90% of the survey respondents rated metadata elements regarding phenotype definition and validation methods and metrics positively with a score of 4 or 5. Both researchers completed annotation of each phenotype within 60 min. Our thematic analysis of the narrative feedback indicates that the metadata framework was effective in capturing rich and explicit descriptions and enabling the search for phenotypes, compliance with data standards, and comprehensive validation metrics. Current limitations were its complexity for data collection and the entailed human costs.
Validation of a Rapid Microbiological Method for the Detection and Quantification of the Burkholderia cepacia Complex in an Antacid Oral Suspension
Authors: Prada-Ramírez Harold A , Celeita Sandra , Fonseca Juan Camilo
Published: May 2023

Background

Despite the broad adoption of Soleris® technology in the food industry as semiquantitative method, it is almost completely unexplored in the pharmaceutical industry as a quantitative method for quantification of Burkholderia cepacia complex (Bcc).

Objective

The efficacy of an automated growth-based system for a quantitative determination of the Bcc in an antacid oral suspension was studied. The main purpose of this validation study was to prove that the alternative method’s entire performance is not inferior to the conventional method for a quantitative determination of Bcc.

Method

The antacid oral suspension’s preservatives were neutralized, leading to the Burkholderia complex’s recovery by means of the alternative method and the reference method. A calibration curve was generated for each strain by plotting DTs relative to the corresponding log CFU values. An equivalence of results was done through the construction of calibration curves that allowed the establishment of numerically equivalent results between the enumeration data from the reference method and the alternative method.

Results

Thus following the guidelines of USP, essential validation parameters were shown, such as equivalence of results (CC >0.95), linearity (R2 >0.9025), accuracy (% recovery >70%), operating range, precision and ruggedness (DS <5 and CV <35%), specificity (inclusivity and exclusivity), limit of detection (LOD), and limit of quantification (LOQ).

Conclusions

It was shown that all the test results obtained from the alternative method were in statistical agreement with the standard method. Thus this new technology was found to meet all the validation criteria needed to be considered as an alternative method for the quantification of the Burkholderia complex in the antacid oral suspension tested.

Highlights

As outlined in USP chapter <1223> and demonstrated in this research the implementation of alternative methods can offer benefits in execution and automation while improving accuracy, sensitivity, and precision and can reduce the microbiological process time compared to the traditional ones.
Endocrine changes during the peripartal period related to colostrogenesis in mammalian species
Authors: Bigler Naomi A , Gross Josef J , Baumrucker Craig R , Bruckmaier Rupert M
Published: May 2023

This review discusses endocrine and functional changes during the transition from late gestation to lactation that are related to the production of colostrum in different mammalian species. Species covered in this article include ungulate species (cattle, sheep, goats, pigs, horses), rodents (rat, mouse), rabbits, and carnivores (cats, dogs), as well as humans. An immediate availability of high quality colostrum for the newborn after birth is crucial in species where a transfer of immunoglobulins (Ig) does not or only partially occur via the placenta during pregnancy. Declining activity of gestagens, in most species progesterone (P4), is crucial at the end of pregnancy to allow for the characteristic endocrine changes to initiate parturition and lactation, but the endocrine regulation of colostrogenesis is negligible. Both, the functional pathways and the timing of gestagen withdrawal differ considerably among mammalian species. In species with a sustaining corpus luteum throughout the entire pregnancy (cattle, goat, pig, cat, dog, rabbit, mouse, and rat), a prostaglandin F2α (PGF2α)-induced luteolysis shortly before parturition is assumed to be the key event to initiate parturition as well as lactogenesis. In species where the gestagen production is taken over by the placenta during the course of gestation (e.g., sheep, horse, and human), the reduction of gestagen activity is more complex, as PGF2α does not affect placental gestagen production. In sheep the steroid hormone synthesis is directed away from P4 towards estradiol-17β (E2) to achieve a low gestagen activity at high E2 concentrations. In humans the uterus becomes insensitive to P4, as parturition occurs despite still high P4 concentrations. However, lactogenesis is not completed as long as P4 concentration is high. Early colostrum and thus Ig intake for immune protection is not needed for the human newborn which allows a delayed onset of copious milk secretion for days until the placenta expulsion causes the P4 drop. Like humans, horses do not need low gestagen concentrations for successful parturition. However, newborn foals need immediate immune protection through Ig intake with colostrum. This requires the start of lactogenesis before parturition which is not fully clarified. The knowledge of the endocrine changes and related pathways to control the key events integrating the processes of colostrogenesis, parturition, and start of lactation are incomplete in many species.
Genetic parameters for mouth size and their influence on growth traits in pasture-raised Nelore cattle
Authors: Dominguez-Castaño Pablo , Marchi Maiorano Amanda , Silva Lopes Jose Eduardo , Vargas de Oliveira Matheus Henrique , Michel Castilhos Andre , Vasconcelos Silva Josineudson Augusto Ii
Published: May 2023

Evaluating traits that allow breeders to increase production efficiency in beef production systems is important. The mouth size (MS) score is a trait easily measured and implemented by breeders. Bite size is related to MS in beef cattle and is a determinant of daily feed intake of pasture-raised animals, influencing their growth. The aim of this study was to estimate genetic parameters for MS, weaning weight (WW) and postweaning weight gain (PWG) of Nelore cattle and to evaluate the influence of the interaction between MS and WW on PWG. Phenotypic records of 134,282 Nelore animals born between 1995 and 2019 were used. Variance components were estimated using multitrait animal model with the Bayesian method. The model included the contemporary group as fixed effect, age at measurement of the trait as linear covariate, and direct additive genetic and residual effects as random effects. For WW, random maternal and maternal permanent environmental effects were added to the model. A Bayesian approach was used to analyze the interaction between WW clusters and MS. The heritability estimates were 0.24, 0.15, and 0.23 for MS, WW, and PWG, respectively. The genetic correlation between variables studied ranged from 0.24 to 0.46. The results suggest that animals with a larger mouth tend to have greater PWG, demonstrating the positive influence of MS score on the postweaning performance of cattle. The direct heritability estimates confirm the possibility of selecting animals for the traits studied.
Lone star ticks (Acari: Ixodidae) infected with Bourbon virus in New Jersey, USA
Authors: Egizi Andrea , Wagner Nicole E , Jordan Robert A , Price Dana C
Published: May 2023

Lone star ticks (Amblyomma americanum L.) are expanding within the northeast United States, a region historically focused on Ixodes scapularis-transmitted diseases. In Monmouth County, NJ, the shift has been dramatic, and lone star ticks now vastly outnumber blacklegged ticks. As a result, there is an enhanced need to focus on the potential health risks of A. americanum-transmitted pathogens, such as the emerging Heartland (HRTV) and Bourbon (BRBV) viruses. We screened 1,205 nymphal lone star ticks for HRTV and BRBV using RT-qPCR assays and detected BRBV in 3 ticks collected in Monmouth County, NJ, in 2021. Additionally, we sequenced a complete BRBV genome from a single infected specimen, finding 99.4% identity with human pathogenic isolates from the eastern-central United States. Our results have important public health implications for a region only recently becoming aware of public health risks posed by lone star ticks. Of note, we report successful detection of viral RNA in samples that were stored and intended for DNA preservation, for example, kept in ethanol at room temperature, which may reduce barriers for public health agencies seeking to expand their tick testing to include viruses.
Copy number aberrations in circulating tumor DNA enables prognosis prediction and molecular characterization of breast cancer
Authors: Kim Min Hwan , Kim Gun Min , Ahn Jin Mo , Ryu Won-Ji , Kim Seul-Gi , Kim Jee Hung , Kim Tae Yeong , Han Hyun Ju , Kim Jee Ye , Park Hyung Seok , Park Seho , Park Byeong Woo , Kim Seung Il , Jeong Joon , Lee Jieun , Paik Soonmyung , Kim Sangwoo , Jung Kyung Hae , Cho Eun Hae , Sohn Joohyuk
Published: May 2023

Background

Low-pass whole-genome sequencing (LP-WGS)–based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer.

Methods

We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated.

Results

We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response.

Conclusions

These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients.
Outcomes of a Comprehensive Forest Landowner Extension Program
Authors: Guynn Susan T , Hiesl Patrick , Bible Joe , Steele Janet
Published: May 2023

Forestry in South Carolina has an annual economic impact of $23 billion and provides over 100,000 jobs statewide. Approximately 87% of forest lands in South Carolina is privately owned and faces shifts in ownership and management practices that may impact forest health. We conducted a bus tour that demonstrated the entire life cycle of a loblolly pine (Pinus taeda) forest from final harvest through forest maturity. The bus tour was aimed at increasing landowner knowledge and influencing the likelihood that they will implement forest management practices. An evaluation using multiple methods was conducted to determine whether the bus tour achieved its objectives. Qualitative and quantitative data converged to show that the forest management bus tour appeared to have been effective in increasing forest landowner knowledge and intent to implement forest management practices, thus potentially increasing forest health across the state.
Fatigue, Stress Appraisal, and Emotional Functioning Among Youth With Sickle Cell Disease: A Daily Diary Study
Authors: Reinman Laura , Schatz Jeffrey , Johnston Julia , Bills Sarah
Published: May 2023

Objective

The aim of this study was to assess how fatigue is related to mood among youth with sickle cell disease (SCD) by evaluating if the cognitive appraisal of stress moderates the impact of fatigue on emotional functioning consistent with the Risk-and-Resistance Model of Chronic Illness.

Methods

Daily diaries assessing fatigue (Numerical Rating Scale), pain intensity (Numerical Rating Scale), mood (Positive and Negative Affect Schedule for Children), and cognitive appraisal of stress (Stress Appraisal Measure for Adolescents) were collected from 25 youth with SCD (ages 11–18 years) for 8 consecutive weeks resulting in 644 daily diaries for analyses.

Results

When measured concurrently, higher fatigue was associated with higher negative mood controlling for pain and prior-night sleep quality. Fatigue predicted next-day negative mood through its interaction with primary and secondary appraisal of stress, consistent with stress appraisal as a protective factor. A similar pattern was observed for pain, which, like fatigue, is a common SCD-related stressor.

Conclusion

Fatigue and negative mood are inter-related when concurrently assessed, but their temporal association in SCD suggests that mood changes are not an inevitable sequalae of increased fatigue; fatigue influenced subsequent levels of negative mood, but only in the presence of less adaptive cognitions about stress; specifically, a higher perceived threat from stress and a lower belief in the ability to manage stress. The results suggest specific cognitive targets for reducing the negative impact of fatigue on mood in SCD.
Combination of metabolomics and network pharmacology analysis to decipher the mechanisms of total flavonoids of Litchi seed against prostate cancer
Authors: Cui Dianxin , Luo Zhuo , Liu Xi , Chen Xin , Zhang Qiuping , Yang Xin , Lu Qinpei , Su Zhiheng , Guo Hongwei
Published: May 2023

Objectives

To explore the underlying mechanism of total flavonoids of Litchi seed (TFLS) in treating prostate cancer (PCa).

Methods

Cell Counting Kit-8 (CCK-8), EdU incorporation assay, trypan blue dye assay and colony formation assay were employed to evaluate the effect of TFLS on PCa in vitro. The xenograft mouse model was established to explore the anti-tumour effect of TFLS in vivo. Alterations in the metabolic profiles of the PC3 cells and mouse serum were obtained by untargeted metabolomics. Combination with metabolomics analysis and network pharmacology strategies, the potential targets were predicted and further validated by RT-qPCR.

Key findings

TFLS attenuated PCa progression both in vitro and in vivo. Metabolomics results yielded from cells and serum indicated that the anti-cancer effect of TFLS was correlated with synergistic modulation of five common metabolic pathways including glycerophospholipid metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, tryptophan metabolism and steroid biosynthesis. Using in silico prediction and RT-qPCR analysis, we further revealed that TFLS exerted anti-PCa activities via regulating the expressions of nine genes, including MAOA, ACHE, ALDH2, AMD1, ARG1, PLA2G10, PLA2G1B, FDFT1 and SQLE.

Conclusions

TFLS suppressed tumour proliferation in PCa, which may be associated with regulating lipid and amino acid metabolisms.
Euterpe oleracea Mart. (Açai) seed extract improves physical performance in old rats by restoring vascular function and oxidative status and activating mitochondrial muscle biogenesis
Authors: de Andrade Soares Ricardo , Cardoso de Oliveira Beatriz , dos Santos Ferreira Flávia , Pontes de Menezes Matheus , Henrique Romão Matheus , Freitas de Bem Graziele , Nascimento Ana Lúcia Rosa , José de Carvalho Jorge , Aguiar da Costa Cristiane , Teixeira Ognibene Dayane , Soares de Moura Roberto , Castro Resende Angela
Published: May 2023

Objectives

Alterations in cardiovascular and skeletal muscle function are hallmarks of ageing that lead to exercise intolerance. We aimed to examine whether the treatment with Euterpe oleracea Mart. seed extract (ASE) associated with exercise training improves aerobic exercise performance by promoting healthy ageing in the elderly.

Methods

Male Wistar rats were divided into five groups: Young (3 months), Old (18 months), Old+ASE (ASE 200 mg/kg/day), Old+Training (exercise training 30 min/day; 5 days/week) and Old+Training+ASE, for 4 weeks.

Key findings

ASE treatment increased the exercise time and the running distance concerning the initial maximal treadmill stress test (MTST) in the Old+Training+ASE group. Exercise training or ASE treatment restored the aorta oxidative damage and antioxidant defence. It reduced the acetylcholine (ACh)-induced vasodilation in the aorta of old animals to the same values as the young and improved hypertension. Only the association of both strategies restored the ACh-induced vasodilation in mesentery arteries. Remarkably, exercise training associated with ASE increased the antioxidant defence, nitrite levels and expression of the mitochondrial SIRT-1, PGC1α in soleus muscle homogenates.

Conclusions

ASE treatment associated with exercise training contributes to better exercise performance and tolerance in ageing by improving vascular function, oxidative stress and activating the muscle SIRT-1/PGC-1α pathway.
Chrysin prevents inflammation-coinciding liver steatosis via AMPK signalling
Authors: Gao Chuanyue , Zhang Huan , Nie Lulin , He Kaiwu , Li Peimao , Wang Xingxing , Zhang Zaijun , Xie Yongmei , Li Shupeng , Liu Gongping , Huang Xinfeng , Deng Huiping , Liu Jianjun , Yang Xifei
Published: May 2023

Objectives

We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism.

Methods

To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin’s therapeutic effects further.

Key findings

CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression.

Conclusions

In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.
Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway
Authors: Yin Qin , Wang Sen , Yang Jie , Fan Cunyu , Yu Yihan , Li Juan , Mei Feng , Zhang Shiwei , Xi Rengang , Zhang Xiuyun
Published: May 2023

Objectives

Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms.

Methods

The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8.

Key findings

Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs.

Conclusion

Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.
Diagnosed Behavioral Health Disorders, Related Duty Limitations, and Return to Duty Time in the U.S. Army: Population-based Data, from 2017 to 2019
Authors: Carreno-Davidson Jamie T , Faller Theresa N , Richardson Melissa , Roy Tanja C
Published: May 2023

Introduction

Less than half of service members with a behavioral health (BH) problem seek care. Soldiers may avoid seeking needed care because of concerns related to being placed on a duty-limiting profile and the related medical disclosures that follow.

Materials and Methods

This study used a retrospective population-based design to identify all new BH diagnoses across the U.S. Army. The relationship between diagnostic category, risk of being issued a duty limitation (profile), and time until return to full duty was also examined. Data were collected from a comprehensive data repository that includes medical and administrative records. Soldiers with a new BH diagnosis were identified from 2017 to 2018. All duty limitation profiles within 12 months of initial diagnosis were identified.

Results

Records for 614,107 unique service members were reviewed. This cohort was mostly male, enlisted, unmarried, and White. The mean age was 27.13 years (SD = 8.05). Soldiers with a new BH diagnosis accounted for 16.7% (n = 102,440) of the population. The most common diagnostic category was adjustment disorder (55.7%). About a quarter (23.6%) of soldiers with a new diagnosis were issued a related profile. The mean length of these profiles was 98.55 days (SD = 56.91). Of those with a new diagnosis, sex and race failed to have an effect on the odds of being placed on a profile. Overall, enlisted, unmarried, or younger soldiers had greater odds of being placed on a profile.

Conclusion

These data provide relevant information for both the service member who seeks care and command teams seeking readiness projections.
Historical Routes for Diversification of Domesticated Chickpea Inferred from Landrace Genomics
Authors: Igolkina Anna A , Noujdina Nina V , Vishnyakova Margarita , Longcore Travis , von Wettberg Eric , Nuzhdin Sergey V , Samsonova Maria G
Published: May 2023

According to archaeological records, chickpea (Cicer arietinum) was first domesticated in the Fertile Crescent about 10,000 years BP. Its subsequent diversification in Middle East, South Asia, Ethiopia, and the Western Mediterranean, however, remains obscure and cannot be resolved using only archeological and historical evidence. Moreover, chickpea has two market types: “desi” and “kabuli,” for which the geographic origin is a matter of debate.

To decipher chickpea history, we took the genetic data from 421 chickpea landraces unaffected by the green revolution and tested complex historical hypotheses of chickpea migration and admixture on two hierarchical spatial levels: within and between major regions of cultivation.

For chickpea migration within regions, we developed popdisp, a Bayesian model of population dispersal from a regional representative center toward the sampling sites that considers geographical proximities between sites. This method confirmed that chickpea spreads within each geographical region along optimal geographical routes rather than by simple diffusion and estimated representative allele frequencies for each region. For chickpea migration between regions, we developed another model, migadmi, that takes allele frequencies of populations and evaluates multiple and nested admixture events. Applying this model to desi populations, we found both Indian and Middle Eastern traces in Ethiopian chickpea, suggesting the presence of a seaway from South Asia to Ethiopia. As for the origin of kabuli chickpeas, we found significant evidence for its origin from Turkey rather than Central Asia.
GeneRanger and TargetRanger: processed gene and protein expression levels across cells and tissues for target discovery
Authors: Marino Giacomo B , Ngai Michael , Clarke Daniel J B , Fleishman Reid H , Deng Eden Z , Xie Zhuorui , Ahmed Nasheath , Ma’ayan Avi
Published: May 2023

Several atlasing efforts aim to profile human gene and protein expression across tissues, cell types and cell lines in normal physiology, development and disease. One utility of these resources is to examine the expression of a single gene across all cell types, tissues and cell lines in each atlas. However, there is currently no centralized place that integrates data from several atlases to provide this type of data in a uniform format for visualization, analysis and download, and via an application programming interface. To address this need, GeneRanger is a web server that provides access to processed data about gene and protein expression across normal human cell types, tissues and cell lines from several atlases. At the same time, TargetRanger is a related web server that takes as input RNA-seq data from profiled human cells and tissues, and then compares the uploaded input data to expression levels across the atlases to identify genes that are highly expressed in the input and lowly expressed across normal human cell types and tissues. Identified targets can be filtered by transmembrane or secreted proteins. The results from GeneRanger and TargetRanger are visualized as box and scatter plots, and as interactive tables. GeneRanger and TargetRanger are available from https://generanger.maayanlab.cloud and https://targetranger.maayanlab.cloud, respectively.
Role of diet quality in bone health in children and adolescents: a systematic review
Authors: Suhett Lara Gomes , Filgueiras Mariana De Santis , de Novaes Juliana Farias , Sukumar Deeptha
Published: May 2023

Context

Poor diet quality and unhealthy dietary patterns have been linked to poor bone health, yet few studies have investigated the role of diet quality in bone health in pediatric populations.

Objective

This systematic review aims to assess the available evidence on the association between diet quality and bone health markers in children and adolescents.

Data Sources

The PubMed, Scopus, and Virtual Health Library databases were searched electronically from October to November 2022, without any restrictions on date or language. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist was used to assess the quality of the studies.

Data Extraction

Published observational studies in children and adolescents (ages 2 to 19 years) that investigated the association between diet quality and bone health were eligible for inclusion. Two researchers independently analyzed and selected all articles using the Rayyan app. Initially, 965 papers were identified. A total of 12 observational studies qualified, including 8 cross-sectional and 4 longitudinal studies. The sample comprised 7130 individuals aged 3 to 17.9 years, representing both sexes. Bone health was evaluated by measures of bone mineral density and bone mineral content.

Data Analysis

Seven studies (58.3%) showed significant associations between diet quality and bone health markers, all of which evaluated diet quality by identifying dietary patterns. Diet quality as evaluated by all dietary indexes was not associated with bone health markers.

Conclusions

Adherence to a healthy diet may benefit bone health in children and adolescents. These findings emphasize the importance of developing effective public health policies that encourage healthy eating habits from childhood to preserve bone health. Longitudinal research using a specific tool to assess diet quality in relation to bone health is warranted. Future studies should also measure bone-regulating hormones and markers of bone turnover.

Systematic Review Registration

PROSPERO registration no. CRD42022368610.