bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Empiric Coverage of Previously Cultured Multidrug Resistant Organisms in Critically Ill Patients Admitted for Sepsis
Authors: Padgett Cassidy H. , King G. Shawn , Hughes R. Ethan , Hull Megan N. , Colon Eliseo A.
Published: June 2024

Purpose: Multidrug-resistant organisms (MDROs) are associated with an increased length of stay and a higher risk of mortality in hospitalized patients. A lack of literature exists that evaluates the need to empirically cover patients for historic MDROs upon readmission. Methods: A retrospective, single-center, cohort study was conducted to evaluate the impact of empiric MDRO antibiotic coverage in patients with a history of MDROs. Differences in length of stay were assessed between two groups of patients: those empirically treated for their historic MDRO and those not. Secondary outcomes included in-hospital mortality, ICU length of stay, need for antibiotic escalation, need for antibiotic de-escalation, and antibiotic duration. Results: Seventy-two patients with historic MDRO(s) were readmitted to the hospital and met inclusion criteria for this study. Hospital length of stay was similar between those empirically covered and those not (11 days vs 15.1 days; P = 0.149). When analyzed in a population only including Gram-negative MDROs, hospital length of stay was shorter in those who received empiric coverage (10.7 days vs 17.2 days; P = 0.032). Conclusion: In the total study population, empiric coverage of historic MDROs failed to significantly reduce hospital length of stay. When analyzed in a population of only Gram-negative MDROs, empiric coverage of historic organisms reduced hospital length of stay by 6.5 days. This suggests that in patients readmitted to the ICU for sepsis, empiric coverage of historic Gram-negative MDROs may be beneficial.
Flight parameter prediction for high-dynamic Hypersonic vehicle system based on pre-training machine learning model
Authors: Zhou Dengji , Huang Dawen , Zhang Xing , Tie Ming , Wang Yulin , Shen Yaoxin
Published: June 2024

Given the harsh operating circumstances, hypersonic vehicles operating at high Mach number demand accurate advanced information of the flight and health state. Flight parameter prediction is a crucial foundation for achieving this requirement. This work addressed the trade-off between prediction accuracy and efficiency by proposing a flight parameter prediction model with the model pre-training and online parameter updating. To create training data, a mechanism model is established. Then, we construct and evaluate three distinct prediction models to increase prediction accuracy. Finally, we conducted comparative validation experiments to compare the prediction performance of the three models. The findings demonstrate that the suggested model greatly raises prediction accuracy without raising model complexity, better balancing prediction accuracy and efficiency. The prediction accuracy of the suggested model has increased by 81.9% when compared to the traditional model.
High-performance finite elements with MFEM
Authors: Andrej Julian , Atallah Nabil , Bäcker Jan-Phillip , Camier Jean-Sylvain , Copeland Dylan , Dobrev Veselin , Dudouit Yohann , Duswald Tobias , Keith Brendan , Kim Dohyun , Kolev Tzanio , Lazarov Boyan , Mittal Ketan , Pazner Will , Petrides Socratis , Shiraiwa Syun’ichi , Stowell Mark , Tomov Vladimir
Published: June 2024

The MFEM (Modular Finite Element Methods) library is a high-performance C++ library for finite element discretizations. MFEM supports numerous types of finite element methods and is the discretization engine powering many computational physics and engineering applications across a number of domains. This paper describes some of the recent research and development in MFEM, focusing on performance portability across leadership-class supercomputing facilities, including exascale supercomputers, as well as new capabilities and functionality, enabling a wider range of applications. Much of this work was undertaken as part of the Department of Energy’s Exascale Computing Project (ECP) in collaboration with the Center for Efficient Exascale Discretizations (CEED).
Prognostic Factors for Recurrent Glioma: A Population-Based Analysis
Authors: Fu Pengfei , Shen Jingjing , Song Kun , Xu Ming , Zhou Zhirui , Xu Hongzhi
Published: June 2024

Background:

The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients.

Methods:

We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves.

Results:

According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS ( P < .001).

Conclusion:

WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment.
Food sharing in tourism: A comparative analysis of U.S. and Chinese perspectives
Authors: Mohamed Mohamed E. , Lehto Xinran Y. , Behnke Carl , Byrd Karen
Published: June 2024

Destinations are constantly searching for ways to improve tourists’ dining experiences. However, the impact of dining styles on tourists' social and wellness needs has received limited attention. This study explores the influence of dining styles on the outcomes of tourists' food experiences. Two empirical experiments investigated how sharing meals impacts tourists' perceptions of intimacy, authenticity, and overall subjective wellbeing. The findings demonstrate that when tourists share food, it positively affects their interpersonal connections, their perception of authenticity, and their subjective wellbeing. The study compares two culturally distinct groups: U.S. and Chinese tourists, revealing that U.S. tourists perceive food sharing to have higher impact on authenticity and wellbeing compared to their Chinese counterparts. This study represents the first effort to unveil how tourists assess the act of sharing food while traveling. These results contribute to our theoretical understanding of convivial dining outcomes and social dynamics during travel. Furthermore, they offer insights to destinations on how to design and provide food-sharing experiences that cater to tourists' social and wellness needs while leveraging the unique aspects of their food-sharing cultures.
Hybridisation of adult education policy in peripheral countries: A system theory analysis of EU–Serbia relations
Authors: Popović Katarina , Maksimović Maja , Djerasimović Sanja
Published: June 2024

This article applies system theory to the analysis of the relationship between the EU and candidate country Serbia, with a focus on adult education policy. The study explores how the peripheral status of Serbia with its hybrid political regime combining autocratic and democratic features leads to the hybridisation of its adult education system, and how the EU’s policies, institutions, and funding mechanisms shape this relationship. The study draws on system theory and the results of our recent study of EU support for adult education in Serbia and applies qualitative content analysis to EU and Serbian adult education policy documents, to examine the consequences of interactions between system components on Serbian adult education policy. It posits that EU’s norm-setting on one side and the allocation of funding and control mechanisms on the other facilitate the neo-colonial position of Serbia as the periphery and perpetuate a power dynamic that allows hybrid regimes to flourish and prioritise their own interests over those of their citizens or civil society. The study further opens up the possibility that these dynamics may produce ‘glitches’ in the system and corruption of the system as a whole, and invites further research and theorisation that would illuminate similar patterns and relationships across other European (national) subsystems.
Comparing the Efficacy of Acupressure and Foot Reflexology on Sleep Quality in Patients With Leukemia: A Comparative Clinical Trial
Authors: Parizad Naser , Hassanpour Amireh , Goli Rasoul , Khalkhali Hamidreza , Nozad Aysan
Published: June 2024

Background:

Among leukemia patients, sleep disruptions are prevalent and can profoundly affect their overall quality of life. Acupressure and foot reflexology, modalities rooted in traditional Chinese medicine, have garnered attention for their potential to address sleep disturbances and mitigate associated symptoms.

Methods:

This research utilized a randomized controlled trial with a pretest-posttest design involving 102 leukemia patients admitted to Imam Khomeini Hospital in Urmia. Participants were randomly allocated to 3 groups: acupressure (n = 34), reflexology (n = 34), or control (n = 34). Prior to the intervention, patients completed a demographic survey and the Pittsburgh Sleep Quality Index (PSQI) for baseline assessments. Acupressure involved stimulation of the SP6 point twice daily for 10 minutes over 4 weeks, while reflexology entailed daily 10-minute sessions with sweet almond oil on the soles for the same duration. The control group received standard care without additional interventions. Following the 4-week intervention period, post-intervention evaluations were conducted using identical measurement tools.

Results:

The findings underscored the efficacy of both acupressure and foot reflexology in significantly improving sleep quality within the intervention groups ( P < .001). Initially, there were no notable differences in sleep quality among the 3 groups ( P > .05). Subsequently, pairwise comparisons adjusted with Bonferroni corrections revealed significant disparities in sleep quality between the acupressure and reflexology groups compared to the control group ( P < .001). However, post-intervention analysis indicated no statistically significant variance in enhancing sleep quality between the acupressure and foot reflexology groups ( P < .05).

Conclusion:

This study demonstrates that acupressure and foot reflexology interventions can enhance sleep quality in individuals with leukemia. These findings support the effectiveness of these complementary modalities, offering targeted relief and relaxation. While these non-invasive therapies show promise in improving well-being, further research is needed to confirm and expand upon these results due to study limitations.
Actual and Imagined Music-Cued Gait Training in People with Multiple Sclerosis: A Double-Blind Randomized Parallel Multicenter Trial
Authors: Seebacher Barbara , Helmlinger Birgit , Pinter Daniela , Heschl Bettina , Ehling Rainer , Hechenberger Stefanie , Reindl Markus , Khalil Michael , Enzinger Christian , Deisenhammer Florian , Brenneis MD Christian
Published: June 2024

Background

Actual and imagined cued gait trainings have not been compared in people with multiple sclerosis (MS).

Objective

To analyze the effects of cued motor imagery (CMI), cued gait training (CGT), and combined CMI and cued gait training (CMI-CGT) on motor, cognitive, and emotional functioning, and health-related quality of life in people with MS.

Methods

In this double-blind randomized parallel-group multicenter trial, people with MS were randomized (1:1:1) to CMI, CMI-CGT, or CGT for 30 minutes, 4×/week for 4 weeks. Patients practiced at home, using recorded instructions, and supported by ≥6 phone calls. Data were collected at weeks 0, 4, and 13. Co-primary outcomes were walking speed and distance, analyzed by intention-to-treat. Secondary outcomes were global cognitive impairment, anxiety, depression, suicidality, fatigue, HRQoL, motor imagery ability, music-induced motivation, pleasure and arousal, self-efficacy, and cognitive function. Adverse events and falls were continuously monitored.

Results

Of 1559 screened patients, 132 were randomized: 44 to CMI, 44 to CMI-CGT, and 44 to CGT. None of the interventions demonstrated superiority in influencing walking speed or distance, with negligible effects on walking speed (η2 = 0.019) and distance (η2 = 0.005) observed in the between-group comparison. Improvements in walking speed and walking distance over time corresponded to large effects for CMI, CMI-CGT, and CGT (η2 = 0.348 and η2 = 0.454 respectively). No severe study-related adverse events were reported.

Conclusions

CMI-GT did not lead to improved walking speed and distance compared with CMI and CGT alone in people with MS. Lack of a true control group represents a study limitation.

Trial registration

German Clinical Trials Register, DRKS00023978.
Deterministic and stochastic model predictive energy management of hybrid electric vehicles using two improved speed predictors
Authors: Gao Jingzhou , Xu Kai , Li Ke , Du Wei , Zheng Zhenhao , Zhao Shengdun , Yan Lijun
Published: June 2024

The performance of model predictive control strategies for hybrid electric vehicles (HEVs) highly depends on the accuracy of future speed predictions. This paper proposes improved prediction models for deterministic model predictive control (DMPC) and stochastic model predictive control (SMPC), respectively. For DMPC, the neural network-based predictor is first introduced and taken as the benchmark predictor. A novel deterministic predictor considering historical prediction errors is proposed, which relies on the assumption that the offset between the prediction and measurement at current instant is a good estimate of the offset in the short future. Based on the proposed deterministic predictor, a stochastic predictor that considers the distribution law of historical data at different locations is further proposed for SMPC. Simulation results show that the controller using the proposed deterministic prediction model improves fuel economy by 2.89%, and the controller using the proposed stochastic prediction model improves fuel economy by 4.5% compared with the benchmark.
School Copaganda in the US South: Tinsel, twinkle, and police-youth programming
Authors: Baggett Hannah Carson , Selman Kaitlyn J.
Published: June 2024

Told in schools across the US for decades, Officer Friendly is a story about policing. Through the literal reading of books like Miss Frances’ 1953 Your Friend the Policeman, visits from McGruff the Crime Dog, and even the ever-expanding TikTok world of dancing SROs, the story remains the same: police keep us safe from the bad guys. In this paper, we draw on data from school and police social media accounts in a community in Alabama to expose the bad faith underpinnings of this story, and how it functions through ‘friendly’ police-youth programming in schools. This story relies on at least three narrative devices to move the plot forward: humanising the violent equipment/tools that police use to harass, maim, and wage death; legitimising the authority of the police through mentorship and education; and naturalising surveillance and suspicion by deputising a naughty pair of Elves on a Shelf. We conclude by proposing that the ultimate function of what we’ve detailed here – the rationale behind deploying these three narrative devices – is to construct a story through which, by the end, we’ve all been recruited into the ‘pig majority’.
Examining Organizational Commitment to Environmental Performances Among Hotel Employees: The Role of Ethical Leadership, Psychological Ownership and Psychological Empowerment
Authors: Chao Han , Fanbo Meng , Patwary Ataul Karim
Published: June 2024

In most cases, society and particular organizations need leaders who will set moral standards for their members and work to eliminate the corresponding environmental problems. In business, the environmental issues have been rising, recent decades have seen a growing consensus among theorists that ethics is crucial in shaping good character among individuals to ensure the success of societies and their members. The purpose of this research is to examine how ethical leadership contributes to psychological ownership, psychological empowerment and organizational commitment to environmental performances among hotel employees in China. Focusing on China, this article examines the mediating function of psychological ownership and psychological empowerment in the link between ethical leadership and organizational commitment to environmental performances. We used quantitative approach and applied PLS-SEM which is the appropriate tool to test theory and path analysis. The researcher decided to distribute 2,000 questionnaires among hotel employees in China and 860 responses with complete data and outliers were considered valid for testing the hypotheses. The study found positive relationships among proposed hypotheses and provided significant theoretical and practical implications. Theoretically, the findings of this study would contribute to the Social learning theory and its future implications.
Zimbabwean Women’s Attitudes Toward Wife-Beating and Associated Factors: A Latent Class Analysis
Authors: Vimbai Bengesai Annah , Mutereko Sybert
Published: June 2024

This paper sought to identify distinct classes of women who endorse wife-beating and the determinants of such justification to broaden current knowledge of the correlates of intimate partner violence in Zimbabwe. We drew on survey data from the 2015 Zimbabwe Demographic and Health Survey (ZDHS) and restricted our analytical sample to 2,966 currently partnered women. To classify women’s responses into patterns of tolerant attitudes, we used latent class analysis, an unsupervised classification method that helps identify heterogeneity in a population using observable variables. The data supported a three-class solution characterized by the following probabilities: class 1, high tolerance (6%); class 2, moderate tolerance (26%); and class 3, low tolerance (66%). The results from the regression analysis suggest that older age, reading a newspaper frequently, and having more than primary education were negatively associated with membership in the moderate and high tolerance classes. Women who made joint decisions or had no say in their healthcare issues were more likely to belong to the moderate and high tolerance classes. In other words, tolerant attitudes toward wife-beating were negatively associated with personal empowerment. Therefore, interventions that increase personal empowerment in the form of education and access to media might be needed to redress the endemic acceptance of wife-beating in Zimbabwe. At the same time, gender role transformative interventions are required to challenge patriarchal thinking, which denies women decision-making autonomy and perpetuates attitudes that encourage marital violence.
An Advantage for Survival Between Altruism and Envy with Strategic Interactions
Authors: Park Sung-Hoon
Published: June 2024

We examined the evolutionary stability of preferences (altruism and envy) in an evolutionary game that infinitely repeats a stage game. In the stage game, players who survived the previous game compete for survival in pairs. By solving the evolutionary game, we show that the survival advantage between altruism and envy depends on whether players’ efforts in the stage game are strategic complements or substitutes. With strategic complements, altruistic players have an advantage in survival. With strategic substitutes, envious players have advantages.
Is Workload Associated With Oblique Injuries in Professional Baseball Players?
Authors: Chalmers Peter N. , Mcelheny Kathryn , D’Angelo John , Ma Kevin , Rowe Dana , Erickson Brandon J.
Published: June 2024

Background:

Oblique strains have become a common injury among professional baseball players. The influence of player workload on oblique strains remains unknown.

Purpose/Hypothesis:

To determine whether workload is a risk factor for oblique strains in professional baseball players. We hypothesized that fewer days of rest, more innings pitched/fielded per game, and more batters faced/plate appearances per game would significantly increase a player's risk of sustaining an oblique strain.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

All professional baseball players who sustained an oblique strain between 2011 and 2017 were identified using the Major League Baseball Health and Injury Tracking System. A separate dataset of player usage—days of rest per game, innings pitched or fielded per game, and batters faced or plate appearances per game—was used to determine the workload. We compared these usage variables between player games ≤2, ≤6, ≤12, and >12 weeks before a documented oblique strain with player games from a control group of players with no oblique strains. In a paired analysis, we compared acute (player games ≤2, ≤6, and ≤12 weeks preinjury) versus chronic (player games >12 weeks preinjury) workloads.

Results:

There were 311 oblique strains in pitchers and 392 oblique strains in position players during the study period. In pitchers, more innings pitched and more batters faced were associated with a subsequent oblique strain ( P < .001 for all). In position players, fewer days of rest, more innings fielded, and more plate appearances were associated with a subsequent oblique strain ( P < .001 for all). Pitchers who pitched ≥7 innings per game had a 2.4-fold (95% CI, 1.4-4.9) increased risk of subsequent oblique strain compared with those who pitched 1 inning per game. The percentage of position players with a subsequent oblique strain increased by 2.1-fold (95% CI, 1.3-3.5) with >4 plate appearances compared with 1 plate appearance per game.

Conclusion:

Our analysis demonstrated that workload was associated with an increased risk of sustaining an oblique injury in professional baseball players. High workload over time was more predictive of oblique strains compared to acute increases over chronic baseline workload.
High Anticholinergic Burden and Dental Caries: Findings from Northern Finland Birth Cohort 1966
Authors: Tiisanoja A. , Anttonen V. , Syrjälä A.-M. , Ylöstalo P.
Published: June 2024

Introduction:

Anticholinergic drugs propose a threat for oral health by causing dry mouth. The aim of this cross-sectional study was to investigate whether a high anticholinergic burden was associated with the presence of initial caries lesions, manifested caries lesions, dental fillings, or tooth loss among 46-y-old people.

Methods:

The study population consisted of 1,906 participants from the Northern Finland Birth Cohort 1966 who underwent an oral health examination in 2012–2013. Socioeconomic and medical data were collected from questionnaires, medical records, and national registers. Nine previously published anticholinergic scales were combined and used to measure the high anticholinergic burden from the participants’ medication data. Cariological status was determined according to the International Caries Detection and Assessment System, and the number of missing teeth (excluding third molars) was used as an indicator for tooth loss. The decayed, missing, and filled surfaces index was used to depict caries experience. Negative binominal regression models were used to estimate prevalence rate ratios (PRRs) and confidence intervals (CIs).

Results:

Fourteen percent of the participants (n = 276) used at least 1 anticholinergic drug and about 3% had a high anticholinergic burden (n = 61). After adjusting for confounding factors, participants with a high anticholinergic burden had a higher likelihood of having manifested carious lesions needing restorative treatment (PRR, 1.60; CI, 1.11–2.29) and more missing teeth (PRR, 1.59; CI, 1.13–2.24) when compared to participants without any or with a lower anticholinergic burden.

Conclusions:

High anticholinergic burden was associated with a present caries experience and with tooth loss among the general middle-aged population.

Knowledge Transfer Statement:

The findings of this study suggest that middle-aged patients with a high anticholinergic burden may have a heightened risk of dental caries. These patients may benefit from targeted caries preventive regimes.
Social Inequities in Access to Dental Care in Australian Adults over Time
Authors: Jamieson L.M. , Luzzi L. , Mejia G.C. , Chrisopoulos S. , Ju X.
Published: June 2024

Introduction:

Social inequities in dental caries are reflected by both inequities in the social structures that contribute to disease severity and inequities in the provision of dental care. This study aimed to describe social differentials in the dental caries experience among Australian adults across a 13-y period and to examine if the highest magnitude of oral health inequities persisted across dental caries prevalence (decayed teeth [DT]) or its management (missing teeth [MT], filled teeth [FT]).

Methods:

Data were from 2 population-based cross-sectional surveys of Australian adult oral health conducted in 2004–2006 (National Survey of Adult Oral Health–1 [NSAOH-1], n = 5,505) and 2017–2018 (NSAOH-2, n = 5,022). In each survey, representative samples of adults were obtained through a 3-stage, stratified sample design within metropolitan and regional areas in each state/territory. Clinical outcomes included the prevalence and mean of DT, MT, FT, and DMFT. Equivalized household income was grouped into approximately quartiles from low to high.

Results:

Across all income quartiles, the mean DT and % DT >0 was higher in NSAOH-2 than in NSAOH-1. The increase in prevalence was highest in the third highest income group (prevalence difference [PD] = 8.4, from 24.1 to 32.5). Similarly, % MT >0 was lower in NSAOH-2 than in NSAOH-1 across all income groups, with the decrease most marked for the lowest income group (PD = −6.5, from 74.1 to 67.8). Across all income quartiles, % FT >0 was lower in NSAOH-2 than in NSAOH-1. The decrease was the most marked for the lowest income group (PD = −8.9, from 81.1 to 72.2).

Conclusion:

The findings confirm that although oral health inequities decreased for the most extreme management outcome of dental caries (MT), inequities increased for experience of that disease (DT) and the more conservative management of dental caries (FT). For all D, M, and F components (DMFT), inequities between the lowest and highest household income groups increased from 2004–2006 to 2017–2018.

Knowledge Transfer Statement:

This study found that social inequities in oral health (experience of untreated dental caries and missing teeth) increased between the most socially advantaged and disadvantaged groups between 2004–2006 and 2017–2018. This suggests that models of dental service provision in Australia are increasingly benefitting those who can afford and access the care and who arguably need the services less than their less socially advantaged counterparts do.
Anti-BCMA–engineered exosomes for bortezomib-targeted delivery in multiple myeloma
Authors: Yuan Shushu , Li Qi , He Chuan , Bing Mengli , Zhang Xinyun , Xu Hao , Wang Zhiming , Zhao Meifang , Zhang Yucheng , Chai Yali , Li Bingzong , Zhuang Wenzhuo
Published: June 2024

Exosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared with conventional drug delivery systems. In this study, we developed a delivery platform using exosomes derived from monocytes, specifically designed for targeted delivery of bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B-cell maturation antigen (anti-BCMA), because BCMA selectively expresses on myeloma cells. This modified anti-BCMA was then efficiently incorporated into the monocyte-derived exosomes. These adapted exosomes effectively encapsulated Btz, leading to enhanced drug accessibility within MM cells and sustained intracellular accumulation over an extended period. Remarkably, our results demonstrated that anti-BCMA–modified exosome-loaded Btz (anti-BCMA-Exo-Btz) outperformed free Btz in vitro, exhibiting a more potent myeloma-suppressive effect. In orthotopic MM xenograft models, anti-BCMA-Exo-Btz exhibited a significant antitumor effect compared with free Btz. Furthermore, it demonstrated remarkable specificity in targeting Btz to myeloma cells in vivo. Importantly, we observed no significant histological damage in mice treated with anti-BCMA-Exo-Btz and a slight effect on peripheral blood mononuclear cells. In addition, our study highlighted the multifunctional potential of monocyte exosomes, which induced cell apoptosis, mediated immune responses, and enhanced the osteogenic potential of mesenchymal stromal cells. In conclusion, our study suggests that exosomes modified with targeting ligands hold therapeutic promise for delivering Btz to myelomas, offering substantial potential for clinical applications.
The implication of serum HLA-G in angiogenesis of multiple myeloma
Authors: Wang Chi , Su Nai-Wen , Hsu Kate , Kao Chen-Wei , Chang Ming-Chih , Chang Yi-Fang , Lim Ken-Hong , Chiang Yi-Hao , Chang Yu-Cheng , Sung Meng-Ta , Wu Hsueh-Hsia , Chen Caleb G.
Published: June 2024

Background

Despite the advances of therapies, multiple myeloma (MM) remains an incurable hematological cancer that most patients experience relapse. Tumor angiogenesis is strongly correlated with cancer relapse. Human leukocyte antigen G (HLA-G) has been known as a molecule to suppress angiogenesis. We aimed to investigate whether soluble HLA-G (sHLA-G) was involved in the relapse of MM.

Methods

We first investigated the dynamics of serum sHLA-G, vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in 57 successfully treated MM patients undergoing remission and relapse. The interactions among these angiogenesis-related targets (sHLA-G, VEGF and IL-6) were examined in vitro. Their expression at different oxygen concentrations was investigated using a xenograft animal model by intra-bone marrow and skin grafts with myeloma cells.

Results

We found that HLA-G protein degradation augmented angiogenesis. Soluble HLA-G directly inhibited vasculature formation in vitro. Mechanistically, HLA-G expression was regulated by hypoxia-inducible factor-1α (HIF-1α) in MM cells under hypoxia. We thus developed two mouse models of myeloma xenografts in intra-bone marrow (BM) and underneath the skin, and found a strong correlation between HLA-G and HIF-1α expressions in hypoxic BM, but not in oxygenated tissues. Yet when stimulated with IL-6, both HLA-G and HIF-1α could be targeted to ubiquitin-mediated degradation via PARKIN.

Conclusion

These results highlight the importance of sHLA-G in angiogenesis at different phases of multiple myeloma. The experimental evidence that sHLA-G as an angiogenesis suppressor in MM may be useful for future development of novel therapies to prevent relapse.
ACE2 mediates tryptophan alleviation on diarrhea by repairing intestine barrier involved mTOR pathway
Authors: Li Jinze , Yan Yingli , Fu Yang , Chen Zhe , Yang Yongjie , Li Yu , Pan Jie , Li Feiwu , Zha Cuifang , Miao Kai , Ben Lukuyu , Saleemi Muhammad Kashif , Zhu Yongwen , Ye Hui , Yang Lin , Wang Wence
Published: June 2024

The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.
Inflammation due to ocular surface homeostasis imbalance caused by pterygia: tear lymphotoxin-alpha study and a literature review
Authors: Fang Xie , Lan Guoli , Lin Yuan , Xie Zhiwen , Zhong Yanlin , Luo Shunrong , Xiao Xianwen , Luo Lianghuan , Zhang Yiqiu , Li Hanqiao , Wu Huping
Published: June 2024

Objective

To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test.

Design

Prospective, single-center study.

Participants

400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls.

Methods

The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group.

Result

Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency.

Conclusion

The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.
The chloroplast genome of Chrozophora sabulosa Kar. & Kir. and its exploration in the evolutionary position uncertainty of genus Chrozophora
Authors: Javaid Nida , Ramzan Musarrat , Jabeen Shagufta , Du Yanjun , Anwar Muhammad , Xiqiang Song
Published: June 2024

Chrozophora sabulosa Kar. & Kir. is a biennial herbaceous plant that belongs to the Euphorbiaceae family and has medicinal properties. This research aimed to identify the genetic characteristics and phylogenetic position of the Chrozophora genus within the Euphorbiaceae family. The evolutionary position of the Chrozophora genus was previously unknown due to insufficient research. Therefore, to determine the evolutionary link between C. sabulosa and other related species, we conducted a study using the NGS Illumina platform to sequence the C. sabulosa chloroplast (cp.) genome. The study results showed that the genome was 156,488 bp in length. It had a quadripartite structure consisting of two inverted repeats (IRb and IRa) of 24,649-bp, separated by an 87,696-bp LSC region and a 19,494-bp SSC region. The CP genome contained 113 unique genes, including four rRNA genes, 30 tRNA genes, and 79 CDS genes. In the second copy of the inverted repeat, there were 18 duplicated genes. The C. sabulosa lacks the petD, petB, rpl2, and rps16 intron. The analysis of simple sequence repeats (SSRs) revealed 93 SSR loci of 22 types and 78 oligonucleotide repeats of four kinds. The phylogenetic investigation showed that the Chrozophora genus evolved paraphyletically from other members of the Euphorbiaceae family. To support the phylogenetic findings, we selected species from the Euphorbiaceae and Phyllanthaceae families to compare with C. sabulosa for Ks and Ka substitution rates, InDels investigation, IR contraction and expansion, and SNPs analysis. The results of these comparative studies align with the phylogenetic findings. We identified six highly polymorphic regions shared by both families, which could be used as molecular identifiers for the Chrozophora genus (rpl33-rps18, rps18-rpl20, rps15-ycf1, ndhG-ndhI, psaI-ycf4, petA-psbJ). The cp. genome sequence of C. sabulosa reveals the evolution of plastid sequences in Chrozophora species. This is the first time the cp. genome of a Chrozophora genus has been sequenced, serving as a foundation for future sequencing of other species within the Chrozophoreae tribe and facilitating in-depth taxonomic research. The results of this research will also aid in identifying new Chrozophora species.
Analysis of a new phage, KZag1, infecting biofilm of Klebsiella pneumoniae: genome sequence and characterization
Authors: Saqr Ebtsam , Sadik Mahmoud W. , El-Didamony Gamal , Askora Ahmed
Published: June 2024

Background

This study investigates the effectiveness of the bacteriophage KZag1 against drug-resistant Klebsiella pneumoniae, aiming to assess its potential as a therapeutic agent. The novelty lies in the characterization of KZag1, a Myovirus with specific efficacy against multidrug-resistant K. pneumoniae strains. This highlights the significance of exploring alternative strategies, particularly phage therapy, in addressing biofilm-associated infections.

Methods

KZag1, characterized by a typical Myovirus structure with a 75 ± 5 nm diameter icosahedral head and a 15 ± 5 nm short tail, was evaluated in experimental trials against 15 strains of K. pneumoniae. The infection cycle duration was determined to be 50 min, resulting in an estimated burst size of approximately 83 plaque-forming units per colony-forming unit (PFU/CFU). Stability assessments were conducted within a pH range of 4 to 12 and temperatures ranging from 45°C to 60°C. Biofilm biomass reduction was observed, particularly at a multiplicity of infection (MOI) of 10.

Results

KZag1 demonstrated infection efficacy against 12 out of 15 tested K. pneumoniae strains. The phage exhibited stability across a broad pH range and at elevated temperatures. Notably, treatment with KZag1 significantly reduced K. pneumoniae biofilm biomass, emphasizing its potential in combating biofilm formation. Genomic analysis revealed a complete genome of 157,089 base pairs with a GC content of 46.38%, encompassing 203 open reading frames (ORFs) and a cysteine-specific tRNA sequence. Comparison with phage GP4 highlighted similarities, with KZag1 having a longer genome by approximately 4829 base pairs and a higher GC content by approximately 0.93%. Phylogenetic analysis classified KZag1 within the Myoviridae family.

Conclusion

The efficacy of KZag1 against K. pneumoniae biofilm suggests its potential as a therapeutic candidate, especially for drug-resistant infections. Further clinical research is warranted to explore its synergy with other treatments, elucidate genomic traits, compare with Myoviridae phages, and understand its host interactions. These findings underscore the promising role of KZag1 in addressing drug-resistant bacterial infections.
Integrative omics analysis reveals insights into small colony variants of Staphylococcus aureus induced by sulfamethoxazole-trimethoprim
Authors: Zhou Jingwen , He Chunyan , Yang Han , Shu Wen , Liu Qingzhong
Published: June 2024

Background

Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation.

Methods

Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis.

Results

Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria.

Conclusion

This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.
Assessing the climate adaptive potential of imported Chili in comparison with local cultivars through germination performance analysis
Authors: Ahmad Farhan , Kusumiyati Kusumiyati , Soleh Mochamad Arief , Khan Muhammad Rabnawaz , Sundari Ristina Siti
Published: June 2024

Background

The study offers insightful information about the adaptability of local and imported Chili cultivars. This experiment examines how three different chili cultivars Tanjung, Unpad, and Osaka perform in the germination and early growth phases while considering a wide range of environmental conditions. Research conducted in Jatinangor, Sumedang Regency, Indonesia, highlights the differences between cultivars and the varied possibilities for adaptability each variation possesses.

Results

Among them, Tanjung stands out as the most promising cultivar; its robust performance is demonstrated by its high germination index 91.7. Notable features of Osaka include the highest biomass output (1.429 g), the best water usage efficiency (WUE) at 0.015 g/liter, and the best distribution uniformity (91.2%) and application efficiency (73.6%) under different irrigation conditions. Tanjung’s competitiveness is further evidenced by the fact that it trails Osaka closely on several metrics. Lower performance across criteria for Unpad suggests possible issues with flexibility.

Conclusion

The value of this information becomes apparent when it comes to well-informed breeding programs and cultivation techniques, especially considering uncertain climate patterns and global climate change. This research contributes significantly to the body of knowledge, enabling well-informed choices for environmentally dynamic, sustainable chili farming.
mHealth based intervention by social care professionals to support family caregivers to persons with dementia living at home in Sweden (Caregiver Connect): a randomized controlled trial
Authors: Kabir Zarina Nahar , Tyrrell Marie , Konradsen Hanne , Craftman Åsa , Joshi Nitin , Gupta Manoj Kumar , Sharma Suresh , Bhardwaj Pankaj
Published: June 2024

Background

The majority of persons with dementia in Sweden reside in their own homes with support from family members. Approximately, 12% of persons with dementia have immigrant background. Within the next 20 years, the number of persons with dementia who are non-ethnic Swedes is said to double. Family caregivers with immigrant backgrounds are noted to receive less support in the community than ethnic Swedes and rate their health status lower than ethnic Swedish peers. The Swedish National Board of Health and Welfare have highlighted the importance of follow-up support for family caregivers with immigrant backgrounds as there is a recognized gap in research and available information tailored to meet the needs of this group.

Purpose of the study

The purpose of the study is to test effectiveness of an mHealth based intervention through which community social workers can improve caregiving competence of non-European immigrant family caregivers of people with dementia living at home in Sweden. The overarching aim is to reduce caregiver burden and depressive symptoms, and improve quality of life.

Methods

A randomized controlled trial (RCT) including wait list control group will be performed consisting of an intervention group (A, n = 44) and a wait list control group (B, n = 44), totaling a sample size of 88. On completion of the 10-weeks long intervention in the intervention group, the intervention will be delivered to group B. Effect of the intervention will be analyzed between and within groups over time. The content of the educational component of the intervention is inspired by the iSupport manual developed by the World Health Organization. The contents, in the form of a booklet, aims to equip the family caregivers with structured information on understanding dementia as a condition and its management at home, including self-care guidance designed specifically for family caregivers themselves.

Discussion

Similar telephone-delivered intervention studies targeted for family caregivers to persons with dementia are ongoing in Malaysia and will start in India using the same booklet adapted to the local context. These studies will provide evidence on the effectiveness of using digital technologies to deliver support to those who may not be reached or adequately served by the traditional healthcare system.

Trial registration

ISRCTN registry, Registration number ISRCTN64235563.