bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Community in Response to COVID-19: Improving Student Interaction and Engagement in an Online Program
Authors: Currier Connie , Clements John , Shah Robey B. , Bennett Alec
Published: January 2024

This study investigated how student perceptions of interaction and engagement in fully online courses changed when synchronous discussions were built into the curriculum after the COVID-19 pandemic began. Moore’s Model of Interaction provided the analytical framework for assessing student-student and student-content interactions. Participants were Master of Public Health students from a large public university in the midwestern United States. Summary quantitative and qualitative data from student course evaluations are presented that assessed student interaction, connection, and learning. Results showed that synchronous discussions enabled students to “develop a sense of community” with other students and the content, while increasing their engagement and comprehension and integration of course concepts. Lessons learned for successful implementation of synchronous discussions in online courses are discussed to increase overall student satisfaction with engagement and improve learning outcomes.
Risk of stroke in patients with prior VKA or DOAC: A population-based real-world registry analysis
Authors: Mayer-Suess Lukas , Rinner Heinrich , Lang Wilfried , Greisenegger Stefan , Mikšová Dominika , Gattringer Thomas , Enzigner Christian , Sykora Marek , Vosko Milan , Mutzenbach Johannes S , Ferrari Julia , Kiechl Stefan , Knoflach Michael ,   for the Tyrolean Stroke Pathway group and the Austrian Stroke Unit Registry Collaborators
Published: January 2024

Introduction:

To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation.

Patients and methods:

Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists.

Results:

In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p = 0.003).

Discussion and conclusions:

One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential.
Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study
Authors: Wistinghausen Birte , Toner Keri , Barkauskas Donald A. , Jerkins Lauren P , Kinoshita Hannah , Chansky Pamela , Pezzella Gloria , Saguilig Lauren , Hayashi Robert J. , Abhyankar Harshal , Scull Brooks , Karri Vivekanudeep , Tanna Jay , Hanley Patrick , Hermiston Michelle L. , Allen Carl E. , Bollard Catherine M.
Published: January 2024

Posttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus–infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein–specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vβT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.
Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential
Authors: Wurtzel Jeremy G. T. , Lazar Sophia , Askari Shayan , Zhao Xuefei , Severa Jenna , Ayombil Francis , Michael James V. , Camire Rodney M. , McKenzie Steven E. , Stalker Timothy J. , Ma Peisong , Goldfinger Lawrence E.
Published: January 2024

Mechanisms of proteostasis in anucleate circulating platelets are unknown and may regulate platelet function. We investigated the hypothesis that plasma–borne growth factors/hormones (GFHs) maintain constitutive translation in circulating platelets to facilitate reactivity. Bio-orthogonal noncanonical amino acid tagging (BONCAT) coupled with liquid chromatography–tandem mass spectrometry analysis revealed constitutive translation of a broad-spectrum translatome in human platelets dependent upon plasma or GFH exposure, and in murine circulation. Freshly isolated platelets from plasma showed homeostatic activation of translation-initiation signaling pathways: phosphorylation of p38/ERK upstream kinases, essential intermediate MNK1/2, and effectors eIF4E/4E-BP1. Plasma starvation led to loss of pathway phosphorylation, but it was fully restored with 5-minute stimulation by plasma or GFHs. Cycloheximide or puromycin infusion suppressed ex vivo platelet GpIIb/IIIa activation and P-selectin exposure with low thrombin concentrations and low-to-saturating concentrations of adenosine 5′-diphosphate (ADP) or thromboxane analog but not convulxin. ADP–induced thromboxane generation was blunted by translation inhibition, and secondary-wave aggregation was inhibited in a thromboxane-dependent manner. Intravenously administered puromycin reduced injury-induced clot size in cremaster muscle arterioles, and delayed primary hemostasis after tail tip amputation but did not delay neither final hemostasis after subsequent rebleeds, nor final hemostasis after jugular vein puncture. In contrast, these mice were protected from injury-induced arterial thrombosis and thrombin-induced pulmonary thromboembolism (PE), and adoptive transfer of translation-inhibited platelets into untreated mice inhibited arterial thrombosis and PE. Thus, constitutive plasma GFH-driven translation regulates platelet G protein–coupled receptor reactivity to balance hemostasis and thrombotic potential.
Three cases of recalcitrant Paecilomyces keratitis in Southern California within a short period
Authors: Kim Christine K. , Mekhail Joseph T. , Morcos David M. , Yang Christopher D. , Kedhar Sanjay R. , Kim Cinthia , Del Valle Estopinal Maria , Lee Olivia L.
Published: January 2024

Background

The aim of this report is to describe the risk factors, clinical course, and characteristics of three cases of Paecilomyces keratitis presenting concurrently within three months in the same location. We used in vivo confocal microscopy and histopathology to corroborate our clinical findings.

Observations

Three eyes of three elderly patients with culture-proven Paecilomyces keratitis were included in this series. These patients resided within a 15-mile radius and presented to a tertiary care eye institute in Southern California between February and April 2022. All three eyes experienced a prolonged, recalcitrant course with recurrence of keratitis in donor corneal tissue despite antifungal therapy and multiple therapeutic penetrating keratoplasties. In vivo confocal microscopy, histopathology, and microbiologic findings corroborated the diagnosis of fungal keratitis with Paecilomyces. With surgical intervention and extensive medical therapy, all three cases resolved after the addition of oral Posaconazole.

Conclusions

Paecilomyces is a rare cause of infectious keratitis. Herein we report three similar cases in elderly patients. All had prolonged, recalcitrant infections that required multiple treatment modalities. Our cases, which were supported by in vivo confocal microscopy and histopathology, highlight the importance of timely and aggressive therapy to prevent recurrence.
Analysis of the differentially expressed genes in the combs and testes of Qingyuan partridge roosters at different developmental stages
Authors: Qi Hao , Deng Zhidan , Ye Fei , Gou Junwei , Huang Miaoxin , Xiang Hai , Li Hua
Published: January 2024

Background

The sexual maturity of chickens is an important economic trait, and the breeding of precocious and delayed puberty roosters is an important selection strategy for broilers. The comb serves as an important secondary sexual characteristic of roosters and determines their sexual precocity. Moreover, comb development is closely associated with gonad development in roosters. However, the underlying molecular mechanism regulating the sexual maturity of roosters has not yet been fully explored.

Results

In order to identify the genes related to precocious puberty in Qingyuan partridge roosters, and based on the synchrony of testis and combs development, combined with histological observation and RNA-seq method, the developmental status and gene expression profile of combs and testis were obtained. The results showed that during the early growth and development period (77 days of age), the development of combs and testis was significant in the high comb (H) group versus the low comb (L) group (p < 0.05); however, the morphological characteristic of the comb and testicular tissues converged during the late growth and development period (112 days of age) in the H and L groups. Based on these results, RNA-sequencing analysis was performed on the comb and testis tissues of the 77 and 112 days old Qingyuan Partridge roosters with different comb height traits. GO and KEGG analysis enrichment analysis showed that the differentially expressed genes were primarily enriched in MAPK signaling, VEGF signaling, and retinol metabolism pathways. Moreover, weighted correlation network analysis and module co-expression network analysis identified WNT6, AMH, IHH, STT3A, PEX16, KPNA7, CATHL2, ROR2, PAMR1, WISP2, IL17REL, NDRG4, CYP26B1, and CRHBP as the key genes associated with the regulation of precocity and delayed puberty in Qingyuan Partridge roosters.

Conclusions

In summary, we identified the key regulatory genes of sexual precocity in roosters, which provide a theoretical basis for understanding the developmental differences between precocious and delayed puberty in roosters.
Unveiling the fructose metabolism system in Staphylococcus aureus: insights into the regulatory role of FruR and the FruRKT operon in bacterial fitness
Authors: Ge Yan , Li Daiyu , Wang Ning , Shi Yun , Guo Gang , Fang Liyuan , Zou Quanming , Liu Qiang
Published: January 2024

Background

The utilization of fructose as a carbon source and energy provider plays a crucial role in bacterial metabolism. Additionally, fructose metabolism directly impacts the pathogenicity and virulence of certain pathogenic microorganisms.

Results

In this study, we report the discovery of a fructose phosphotransferase system (PTS) in S. aureus. This system comprises three genes, namely fruR, fruK, and fruT, which are co-located in an operon that is indispensable for fructose utilization in S. aureus. Our findings confirm that these three genes are transcribed from a single promoter located upstream of the fruRKT operon. The fruR gene encodes a DeoR-type transcriptional regulator, designated as FruR, which represses the expression of the fruRKT operon by direct binding to its promoter region. Significantly, our experimental data demonstrate that the fruRKT operon can be induced by fructose, suggesting a potential regulatory mechanism involving intracellular fructose-1-phosphate as a direct inducer. Furthermore, we conducted RNA-seq analysis to investigate the specificity of FruR regulation in S. aureus, revealing that the fruRKT operon is predominantly regulated by FruR.

Conclusions

In summary, this study has uncovered a fructose phosphotransferase system (PTS) in S. aureus, highlighting the essential role of the fruR, fruK, and fruT genes in fructose utilization. We confirmed their co-location within an operon and established FruR as a key regulator by binding to the operon’s promoter. Importantly, we demonstrated that fructose can induce this operon, possibly through intracellular fructose-1-phosphate. Our identification of this PTS system represents the initial characterization of a fructose metabolism system in S. aureus.
An educative nutritional intervention supporting older hospital patients to eat sufficiently using eHealth: a mixed methods feasibility and pilot study
Authors: Terp Rikke , Kayser Lars , Lindhardt Tove
Published: January 2024

Background

Insufficient food intake is common in older hospital patients and increases the risk of readmission, mortality, and decline in functional status. To improve food intake in older patients, an eHealth solution (Food’n’Go) enabling them to participate in their own nutritional care was implemented in a hospital unit. We developed an educative nutritional intervention (ENI) to support hospitalized older adults (aged ≥ 65 years) to participate in their own nutritional care using Food’n’Go. In this study, we evaluate the feasibility of the ENI and its potential to improve nutritional intake.

Methods

Feasibility was evaluated using process evaluation, and nutritional intake was examined by using a pre- and post-test design. Assessment of feasibility: Contextual factors (availability of Food’n’Go and prevalence of counseling by a dietitian); Intervention fidelity (whether patients were informed of nutrition and Food’n’Go, and whether their needs for support were assessed); and Mechanism of impact (patients’ knowledge and skills related to nutrition and the use of Food’n’Go and their acceptance of the ENI). Assessment of nutritional intake: Patients’ intake of protein and energy based on one-day observations before implementation of the ENI (pre-test; n = 65) and after a three-month intervention (post-test; n = 65).

Results

Feasibility: Food’n’Go was available for more patients after the intervention (85 vs. 64%, p = .004). Most patients managed the use of Food’n’Go and were involved in ordering their food, but only a few monitored their food intake. Information on nutrition was not provided sufficiently to all patients. In general, the ENI had high acceptability among the patients. Nutritional intake: Compared to patients in the pre-test, patients in the post-test had a higher daily mean intake of energy (kJ) (6712 (SD: 2964) vs. 5660 (SD: 2432); difference 1052 (95% CI 111–1993)), and of protein (g) (60 (SD: 28) vs. 43 (SD: 19); difference 17 (95% CI 9–26)). Likewise, there was an increase in the mean attainment of protein requirements: 73% (SD: 34) vs. 59% (SD: 29) (p = .013).

Conclusion

The ENI is feasible for supporting hospitalized older adults to participate in their own nutrition using eHealth and preliminary results indicate that it may lead to an increasing energy and protein intake.
Spatial distribution and temporal trends of tuberculosis case notifications, Uganda: a ten-year retrospective analysis (2013–2022)
Authors: Aceng Freda Loy , Kabwama Steven Ndugwa , Ario Alex Riolexus , Etwom Alfred , Turyahabwe Stavia , Mugabe Frank Rwabinumi
Published: January 2024

Background

Uganda has a high incidence and prevalence of tuberculosis (TB). Analysis of spatial and temporal distribution of TB is an important tool for supporting spatial decision-making, planning, and policy formulations; however, this information is not readily available in Uganda. We determined the spatial distribution and temporal trends of tuberculosis notifications in Uganda, 2013–2022.

Methods

We conducted a retrospective analysis of routinely-generated program data reported through the National TB and Leprosy Programme (NTLP) surveillance system. We abstracted data on all TB cases diagnosed from 2013 to 2022 by district and region. We drew choropleth maps for Uganda showing the TB case notification rates (CNR) per 100,000 and calculated the CNR using the cases per district as the numerator and individual district populations as the denominators. Population estimates were obtained from the 2014 National Population and Housing Census, and a national growth rate of 3% was used to estimate the annual population increase.

Results

Over the entire study period, 568,957 cases of TB were reported in Uganda. There was a 6% annual increase in TB CNR reported from 2013 (134/100,000) to 2022 (213/100,000) (p-value for trend p < 0.00001). Cases were reported from all 12 Ministry of Health regions during the entire period. The distribution of CNR was heterogeneous throughout the country and over time. Moroto, Napak and Kampala districts had consistently high CNR throughout the ten years. Kalangala district had lower CNR from 2013 to 2018 but high CNR from 2019 to 2022. Moroto region, in the northeast, had consistently high CNR while Mbale and Soroti regions in Eastern Uganda had the lowest CNR throughout the ten years.

Conclusion

There was an overall increasing trend in TB CNR from 2013 to 2022. We recommend that the National TB program institutes intensified measures aided by more funding to mitigate and reverse the negative impacts of the COVID-19 pandemic on TB.
Factors associated with blood mercury concentrations and their interactions with three glutathione S-transferase genes (GSTT1, GSTM1, and GSTP1): an exposure assessment study of typically developing Jamaican children
Authors: Zaman Sheikh Farzana , Samms-Vaughan Maureen , Saroukhani Sepideh , Bressler Jan , Hessabi Manouchehr , Grove Megan L. , Pellington Sydonnie Shakespeare , Loveland Katherine A. , Rahbar Mohammad H.
Published: January 2024

Background

Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

Methods

In this exposure assessment study we used data from 375 typically developing (TD) 2–8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general linear models (GLMs).

Results

We identified the child’s age, consumption of saltwater fish, canned fish (sardine, mackerel), string beans, grain, and starches (pasta, macaroni, noodles) as the environmental factors significantly associated with BHgCs (all P < 0.05). A significant interaction between consumption of canned fish (sardine, mackerel) and GSTP1 in relation to BHgC using either a co-dominant or recessive genetic model (overall interaction P = 0.01 and P < 0.01, respectively) indicated that consumption of canned fish (sardine, mackerel) was significantly associated with higher mean BHgC only among children with the GSTP1 Ile105Val, Ile/Ile [Ratio of mean Hg (95% CI) = 1.59 (1.09, 2.32), P = 0.02] and Ile/Val [Ratio of mean Hg (95% CI) = 1.46 (1.12, 1.91), P = 0.01] genotypes.

Conclusions

Since this is the first study from Jamaica to report these findings, replication in other populations is recommended.
Indian fathers are involved in nurturing healthy behaviours in adolescents: A qualitative inquiry
Authors: Rathi Neha , Kansal Sangeeta , Worsley Anthony
Published: January 2024

Background

Indian adolescents exhibit unhealthy food behaviours and inactive lifestyles which increase their risk of developing obesity and associated negative health consequences. The family food environment represents a vital setting to nurture healthy lifestyle behaviours in adolescents, with parents influencing their adolescents’ dietary and physical activity behaviours. Yet, much of the existing evidence exploring parental influences predominantly focuses on mothers while fathers’ engagement in instilling healthy dietary and physical activity behaviours is understudied, more so in the context of developing economies like India. Therefore, this qualitative study was designed to understand Indian fathers’ views on instilling healthy behaviours in their children.

Methods

Convenience sampling along with snowball sampling techniques were employed to recruit fathers of adolescents aged 10–19 years from Kolkata city, India. Informed by the research aim and review of literature, an interview guide was developed and pre-tested. Interviews were carried out either in person or virtually (Zoom/telephone) in English/Hindi/Bengali as per the preference of the participants. All interactions were audio recorded, transcribed verbatim, and translated to English for the purpose of data analysis. The transcripts were analysed thematically using NVivo software program. Themes were identified using both inductive and deductive approaches.

Results

A total 36 fathers participated in the interviews. Seven main themes were identified: (i) Involvement of fathers in adolescent upbringing (i.e. engagement in meal preparation, food shopping, educational activities, physical activity); (ii) Family food environment (i.e. setting food rules, having meals with children, making food available); (iii) Challenges to instilling healthy behaviours in adolescents (i.e. adolescents’ sedentary lifestyle and liking for unhealthy foods); (iv) Barriers to routine involvement in adolescent upbringing (i.e. time constraints due to paid employment, poor socio-economic status); (v) Adolescent nutrition education: (vi) Dual burden of malnutrition (i.e. awareness of malnutrition, no knowledge about government-led health programs for adolescents); (vii) Paternal knowledge.

Conclusions

The emerging themes reveal that Indian fathers played a crucial role in instilling healthy dietary and physical activity behaviour in their adolescents through various parenting practices such as purchasing nutritious food, enforcing food rules, disseminating nutrition-related knowledge, and encouraging adolescents to participate in moderate-to-vigorous intensity outdoor sports. This provides strong support for the inclusion of fathers in sustainable family-focused lifestyle interventions to maximise the nurturing care required by adolescents as well as assist in normalising the representation of fathers in health and welfare policies designed for adolescents.
Characterizing food environments of hospitals and long-term care facilities in the Netherlands: a mixed methods approach
Authors: Wierda Joline J. , de Vet Emely , Troost Ellemijn , Poelman Maartje P.
Published: January 2024

Background

Hospitals and long-term care facilities, which are key institutions to serve health and well-being, have an important exemplary role in providing supportive food environments to encourage healthy and sustainable food choices. The objective of this study is to characterize the physical, socio-cultural, political and economic dimensions of the food environment for health care receivers, health workforce and visitors in healthcare settings, and make comparisons between the food environment of hospitals and long-term care facilities.

Methods

To characterize the food environment in healthcare settings, two sub-studies were conducted. In sub-study 1, semi-structured interviews were held with staff members (n = 46) representing 11 hospitals and 26 long-term care facilities (rehabilitation centres, nursing homes, institutions for people with intellectual disabilities and mental healthcare institutions). In sub-study 2, staff members audited the food environment in hospitals (n = 28) and long-term care facilities (n = 36) using a predefined checklist.

Results

The food environment in Dutch healthcare settings varies substantially between locations although noticeable differences between hospitals and long-term care facilities were identified. Hospitals and larger long-term care facilities featured more often restaurants and utilized central spaces for preparation of meals, while smaller long-term care facilities often operated as household-like settings. Type of healthcare shaped the socio-cultural food environment, with hospitals primarily emphasizing nutrition for fast recovery, while long-term care facilities more often as an instrument (i.e., to structure the day). Participants highlighted the importance of food policies and broad organizational support for realizing and regulating improvement of the food environment. Yet, long-term care facilities were less familiar with national guidelines for food environments compared to hospitals. Several economical aspects, like profit motives, strict budgets and contracts with external parties affected and shaped the food available within all healthcare settings.

Conclusions

This study characterized the food environment in Dutch healthcare settings. Disclosed differences between hospitals and long-term care facilities should be incorporated in strategies for a transition of the food environment. Future research should investigate the underlying mechanisms of the healthcare food environment attaining all healthcare stakeholders - health care receivers, staff and visitors - while prioritizing sustainability alongside healthiness.
Age-dependent inflammatory response is altered in an ex vivo model of bacterial pneumonia
Authors: Sommer Charline , Reamon-Buettner Stella Marie , Niehof Monika , Hildebrand Christina Beatrix , Braun Armin , Sewald Katherina , Dehmel Susann , Brandenberger Christina
Published: January 2024

Background

Aging is associated with an increased incidence and mortality of Pseudomonas aeruginosa-induced pneumonias. This might be partly due to age-dependent increases in inflammatory mediators, referred to as inflamm-aging and a decline in immune functions, known as immunosenescence. Still, the impact of dysregulated immune responses on lung infection during aging is poorly understood. Here, we aimed to mimic inflamm-aging using ex vivo precision-cut lung slices (PCLS) and neutrophils – as important effector cells of innate immunity – from young and old mice and investigated the influence of aging on inflammation upon infection with P. aeruginosa bacteria.

Methods

Murine PCLS were infected with the P. aeruginosa standard lab strain PAO1 and a clinical P. aeruginosa isolate D61. After infection, whole-transcriptome analysis of the tissue as well as cytokine expression in supernatants and tissue lysates were performed. Responses of isolated neutrophils towards the bacteria were investigated by quantifying neutrophil extracellular trap (NET) formation, cytokine secretion, and analyzing expression of surface activation markers using flow cytometry.

Results

Inflamm-aging was observed by transcriptome analysis, showing an enrichment of biological processes related to inflammation, innate immune response, and chemotaxis in uninfected PCLS of old compared with young mice. Upon P. aeruginosa infection, the age-dependent pro-inflammatory response was even further promoted as shown by increased production of cytokines and chemokines such as IL-1β, IL-6, CXCL1, TNF-α, and IL-17A. In neutrophil cultures, aging did not influence NET formation or cytokine secretion during P. aeruginosa infection. However, expression of receptors associated with inflammatory responses such as complement, adhesion, phagocytosis, and degranulation was lower in neutrophils stimulated with bacteria from old mice as compared to young animals.

Conclusions

By using PCLS and neutrophils from young and old mice as immunocompetent ex vivo test systems, we could mimic dysregulated immune responses upon aging on levels of gene expression, cytokine production, and receptor expression. The results furthermore reflect the exacerbation of inflammation upon P. aeruginosa lung infection as a result of inflamm-aging in old age.
Perspectives of primary care physicians in Spain on malaria: a cross-sectional survey and retrospective review of cases
Authors: Linares-Rufo Manuel , Bermudez-Marval Harold , García-Bertolín Carlos , Santos-Galilea Joaquín , Balsa-Vázquez Javier , Pérez-Tanoira Ramón , Santos-Larrégola Laura , Cuadros-González Juan , Rojo-Marcos Gerardo , Ramos-Rincón José-Manuel
Published: January 2024

Background

In Spain, the risk of imported malaria has increased in recent years due to the rise in international travel and migration. Little is known about the knowledge, information sources, clinical practice, and specific needs of primary care physicians (PCPs) concerning malaria despite the pivotal role played by these professionals in managing the health of tourists. The objective of this study was to assess the knowledge, attitudes, and practices of PCPs in Spain regarding malaria.

Methods

This research analyses data from (1) a cross-sectional nationwide survey assessing the knowledge and attitudes of PCPs regarding malaria, and (2) a retrospective review of 373 malaria cases appearing in primary care medical records (PCMRs) in the Madrid area over the past 15 years to determine how cases were documented, managed, or characterized in the primary care setting.

Results

The survey findings reveal a modest level of self-perceived familiarity with malaria (221/360, 57.6%), even though 32.8% of the practitioners reported having delivered care for confirmed or suspected cases of the disease, these practitioners had greater knowledge of malaria (80.4%) compared to physicians who reported not having delivered care for malaria (19.6%, p < 0.001). Ten percent of the survey participants did not know the name of the mosquito that transmits malaria, and only 40.7% would promptly request malaria testing for a traveller with symptoms after a trip to an endemic area. Responses provided by younger PCPs varied to a greater extent than those of their more experienced colleagues regarding prevention practices and patient management.

A review of PCMRs showed that only 65% of all patients were recorded as such. Among those registered, only 40.3% had a documented malaria episode, and of those, only 16.6% received proper follow-up. Only 23.7% of the patients with a PCMR had a record that specifically indicated travel to an endemic country or travel classified as visiting friends and relatives (VFR).

Conclusions

The findings of this study underscore the critical role of PCPs in the field of travel medicine, particularly given the increase in imported malaria cases. These results highlight the need for targeted training in travel medicine and the need to ensure optimal patient education in care settings.
Association of remnant cholesterol with decreased kidney function or albuminuria: a population-based study in the U.S.
Authors: He Xuan , Zou Renfang , Du Xiaoqiong , Li Kuo , Sha Dujuan
Published: January 2024

Background

Dyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S.

Method

Data were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model.

Results

A total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (β -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI).

Conclusion

A higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies.
Impact of feedback generation and presentation on self-monitoring behaviors, dietary intake, physical activity, and weight: a systematic review and meta-analysis
Authors: Krukowski Rebecca A. , Denton Andrea H. , König Laura M.
Published: January 2024

Self-monitoring of dietary intake, physical activity, and weight is a key strategy in behavioral interventions, and some interventions provide self-monitoring feedback to facilitate goal setting and promote engagement. This systematic review aimed to evaluate whether feedback increases intervention effectiveness, and which forms of feedback presentation (e.g., personalized vs. not personalized) and generation (i.e., human vs. algorithm-generated) are most effective. To achieve this aim, 5 electronic databases (PubMed/MEDLINE, Web of Science, CINAHL, PsycINFO, and Google Scholar) were searched in April 2022 and yielded 694 unique records, out of which 24 articles reporting on 19 studies were included (with a total of 3261 participants). Two reviewers independently screened titles and abstracts and then full texts and categorized articles as eligible or excluded according to the pre-registered criteria (i.e., availability of full text, peer reviewed manuscript in English; adult participants in a randomized controlled trial that included both self-monitoring and feedback; comparisons of different forms of feedback or comparisons of feedback vs. no feedback; primary outcomes of diet, physical activity, self-monitoring behavior, and/or weight). All included studies were assessed for methodological quality independently by two reviewers using the revised Cochrane risk-of-bias tool for randomized studies (version 2). Ten studies compared feedback to no feedback, 5 compared human- vs. algorithm-generated feedback, and the remaining 4 studies compared formats of feedback presentation (e.g., frequency, richness). A random effects meta-analysis indicated that physical activity interventions with feedback provision were more effective than physical activity interventions without feedback (d=0.29, 95% CI [0.16;0.43]). No meta-analysis could be conducted for other comparisons due to heterogeneity of study designs and outcomes. There were mixed results regarding which form of feedback generation and presentation is superior. Limitations of the evidence included in this review were: lack of details about feedback provided, the brevity of most interventions, the exclusion of studies that did not isolate feedback when testing intervention packages, and the high risk of bias in many studies. This systematic review underlines the importance of including feedback in behavioral interventions; however, more research is needed to identify most effective forms of feedback generation and presentation to maximize intervention effectiveness.

Trial registration (PROSPERO)

CRD42022316206.
TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma
Authors: Chen Yafan , Han Zhengyang , Zhang Le , Gao Caihong , Wei Jingyi , Yang Xuyuan , Han Yabing , Li Yunbo , Zhang Chunmei , Wei Yixin , Dong Jiaqi , Xun Wenxing , Sun Weifu , Zhang Taotao , Zhang Hui , Chen Jingtao , Yuan Peng
Published: January 2024

Background

Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations.

Methods

We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1).

Results

Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS.

Conclusion

TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.
ChemR23 signaling ameliorates brain injury via inhibiting NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke
Authors: Liu Lan , Zhang Jiawei , Lu Kaili , Zhang Yaxuan , Xu Xiaofeng , Deng Jiangshan , Zhang Xiaojie , Zhang Haibing , Zhao Yuwu , Wang Xiuzhe
Published: January 2024

Background

Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemia. ChemR23 signaling is involved in the pathophysiology of various inflammatory diseases. Nevertheless, the role of ChemR23 signaling in ischemic stroke remains largely unknown.

Methods

Permanent ischemic stroke mouse model was accomplished by middle cerebral artery occlusion (MCAO). Resolvin E1 (RvE1) or chemerin-9 (C-9), the agonists of ChemR23, were administered by intracerebroventricular (i.c.v) injection before MCAO induction. Then, analysis of neurobehavioral deficits and brain sampling were done at Day 1 after MCAO. The brain samples were further analyzed by histological staining, immunofluorescence, RNA sequencing, ELISA, transmission electron microscope, and western blots. Furthermore, oxygen–glucose deprivation (OGD) was employed in SH-SY5Y to mimic MCAO in vitro, and ChemR23 signaling pathway was further studied by overexpression of ChemR23 or administration of related agonists or antagonists. Analysis of cell death and related pathway markers were performed.

Results

ChemR23 expression was upregulated following MCAO. Under in vitro and in vivo ischemic conditions, ChemR23 deficiency or inhibition contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18, as well as enhanced cleavage of GSDMD-N and neuronal pyroptosis. These influences ultimately aggravated brain injury and neuronal damage. On the other hand, ChemR23 activation by RvE1 or C-9 mitigated the above pathophysiological abnormalities in vivo and in vitro, and overexpression of ChemR23 in SH-SY5Y cells also rescued OGD-induced neuronal pyroptosis. Blockade of NLRP3 mimics the protective effects of ChemR23 activation in vitro.

Conclusion

Our data indicated that ChemR23 modulates NLRP3 inflammasome-mediated neuronal pyroptosis in ischemic stroke. Activation of ChemR23 may serve as a promising potential target for neuroprotection in cerebral ischemia.
iPSC-derived PSEN2 (N141I) astrocytes and microglia exhibit a primed inflammatory phenotype
Authors: Sullivan Michael A. , Lane Samuel D. , McKenzie André D. J. , Ball Sarah R. , Sunde Margaret , Neely G. Gregory , Moreno Cesar L. , Maximova Alexandra , Werry Eryn L. , Kassiou Michael
Published: January 2024

Background

Widescale evidence points to the involvement of glia and immune pathways in the progression of Alzheimer’s disease (AD). AD-associated iPSC-derived glial cells show a diverse range of AD-related phenotypic states encompassing cytokine/chemokine release, phagocytosis and morphological profiles, but to date studies are limited to cells derived from PSEN1, APOE and APP mutations or sporadic patients. The aim of the current study was to successfully differentiate iPSC-derived microglia and astrocytes from patients harbouring an AD-causative PSEN2 (N141I) mutation and characterise the inflammatory and morphological profile of these cells.

Methods

iPSCs from three healthy control individuals and three familial AD patients harbouring a heterozygous PSEN2 (N141I) mutation were used to derive astrocytes and microglia-like cells and cell identity and morphology were characterised through immunofluorescent microscopy. Cellular characterisation involved the stimulation of these cells by LPS and Aβ42 and analysis of cytokine/chemokine release was conducted through ELISAs and multi-cytokine arrays. The phagocytic capacity of these cells was then indexed by the uptake of fluorescently-labelled fibrillar Aβ42.

Results

AD-derived astrocytes and microglia-like cells exhibited an atrophied and less complex morphological appearance than healthy controls. AD-derived astrocytes showed increased basal expression of GFAP, S100β and increased secretion and phagocytosis of Aβ42 while AD-derived microglia-like cells showed decreased IL-8 secretion compared to healthy controls. Upon immunological challenge AD-derived astrocytes and microglia-like cells showed exaggerated secretion of the pro-inflammatory IL-6, CXCL1, ICAM-1 and IL-8 from astrocytes and IL-18 and MIF from microglia.

Conclusion

Our study showed, for the first time, the differentiation and characterisation of iPSC-derived astrocytes and microglia-like cells harbouring a PSEN2 (N141I) mutation. PSEN2 (N141I)-mutant astrocytes and microglia-like cells presented with a ‘primed’ phenotype characterised by reduced morphological complexity, exaggerated pro-inflammatory cytokine secretion and altered Aβ42 production and phagocytosis.
Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
Authors: Olney Kimberly C. , de Ávila Camila , Todd Kennedi T. , Tallant Lauren E. , Barnett J. Hudson , Gibson Katelin A. , Hota Piyush , Pandiane Adithya Shyamala , Durgun Pinar Cay , Serhan Michael , Wang Ran , Lind Mary Laura , Forzani Erica , Gades Naomi M. , Thomas Leslie F. , Fryer John D.
Published: January 2024

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.