bluuebunny/crossref_metadata_2025 huggingface dataset:
“Mom-and-Pop” Landlords and Regulatory Backlash: A Seattle Case Study
Authors: Reosti Anna , Hess Chris , Allen Courtney , Crowder Kyle
Published: November 2024

Against the backdrop of an acute rental affordability crisis and a resurgent tenant’s rights movement, rental industry groups have frequently argued that tenant protection laws disproportionately harm “mom-and-pop” landlords and, by extension, the disadvantaged tenants they serve. The authors leverage a changing regulatory environment in Seattle to provide a rare empirical interrogation of these claims. This analysis of a novel set of consumer data linked with parcel records provides no evidence that tenant protection laws drove “mom-and-pop” landlords out of the rental market. Moreover, an analysis of a survey of almost 4,000 Seattle landlords suggests that “mom-and-pop” landlords use management practices that are largely similar to those used by landlords with larger rental portfolios. These findings run counter to pervasive political narratives regarding the detrimental effects of tenant protection regulations on the small-scale rental sector and bring needed attention to the repercussions of claims-making for stratification in the housing context.
Theorizing Digital Dialogic Comprehension Pedagogy With Rural Primary Teachers: A Relational Praxis of Knowledge, Space, and Time
Authors: Outlaw Janet K. , Grifenhagen Jill F.
Published: November 2024

This grounded theory study explored how primary-grade teachers perceive and enact dialogic English Language Arts (ELA) comprehension pedagogy in the novel context of pandemic-induced digital learning. The study involved nine diverse rural primary teachers teaching digitally during the coronavirus disease pandemic. The researchers followed a constructivist, postmodern orientation to co-construct substantive theory with the knowledge of participating teachers. The researchers conducted two rounds of virtual interviews and collected digital artifacts of ELA comprehension instruction. Qualitative data were analyzed using constant comparative analysis to address teacher perceptions and enactments of digital dialogic comprehension instruction. The emergent substantive theory represents connected, iterative processes of teachers perceiving and enacting dialogic, digital instruction. First, teachers espoused a dialogic stance toward ELA instruction based on their beliefs in various comprehension paradigms, diverse funds of knowledge, and multiplicity of voices in discourse. Relatedly, teachers responded to particularities of virtual contexts, digital discourses, and pandemic times to enact dialogic ELA comprehension instruction through a reconstruction of literacy pedagogies. Implications for research and practice are discussed, including the need for ongoing negotiation of dialogic pedagogy in diverse instructional contexts, to cultivate teachers’ dialogic literacy practices in locally and culturally responsive ways.
Optimizing Rehabilitation Outcomes Through Rehabilitative Ultrasonography: Applications in Musculoskeletal Care
Authors: Alghamdi Nabeel Hamdan , Malliaropoulos Nikos , Daoukas Stavros
Published: November 2024

Rehabilitative ultrasonography (RUS) has significantly enhanced musculoskeletal care by providing real-time, detailed visualizations of muscle, tendon, and soft tissue structures. This symposium explores the diverse applications of RUS, highlighting its advantages over traditional imaging methods. In muscle rehabilitation, RUS is pivotal for assessing muscle morphology, activation patterns, and providing biofeedback, thereby optimizing personalized rehabilitation programs. For tendon injuries, RUS facilitates precise evaluation of tendon integrity, enabling accurate diagnosis, monitoring, and guiding therapeutic interventions. Beyond muscles and tendons, RUS is invaluable in diagnosing and managing soft tissue pathologies, such as ligament and fascia injuries, allowing for targeted treatment strategies. By offering superior precision, safety, and cost-effectiveness, RUS sets a new benchmark in rehabilitation practices, leading to improved patient outcomes and a deeper understanding of musculoskeletal conditions. The integration of RUS into rehabilitation medicine represents a transformative advancement in patient care and treatment efficacy.
Methylation sequencing enhances interpretation of clonal hematopoiesis dynamics
Authors: Parker Alyssa C. , Van Amburg Joseph C. , Heimlich J. Brett , Pershad Yash , Mickels Nicole A. , Mack Taralynn M. , Ferrell P. Brent , Savona Michael R. , Jones Angela L. , Bick Alexander G.
Published: November 2024

We have developed a cost-effective DNA methylation sequencing assay to improve monitoring of clonal hematopoiesis. By inferring cell-type proportions, this method enhances interpretation of clonal trajectories compared with interpretation based on variant allele fraction only.
Mucus plugging, disease severity, and sputum myeloperoxidase concentration in bronchiectasis
Authors: Kim Sun-Hyung , Man Lee Ki , Yoo Jin Young , Chae Kum Ju , Kim Geun-Hyeong , Cho Jun Yeun , The Nguyen Minh , Kim Eung-Gook , Choi Joong-Kook , Choe Kang Hyeon , Lee Hyun , Yang Bumhee
Published: November 2024

Background

Bronchiectasis is characterized by impaired mucociliary clearance, leading to persistent mucus accumulation, known as mucus plugging (MP). Myeloperoxidase (MPO) is a key molecule that activates neutrophilic inflammation during bronchiectasis, leading to disease progression. However, whether sputum MPO concentration is an independent factor associated with MP remains unclear.

Methods

We retrospectively evaluated 78 patients with bronchiectasis at Chungbuk National University Hospital between June 2022 and April 2023. According to the extent of MP in computed tomography of the chest, participants were divided into high MP (MP in ≥ 10 bronchopulmonary segments) and low MP (MP in ≤ 9 bronchopulmonary segments) groups. We evaluated whether sputum MPO concentration is independently associated with MP using multivariable adjusted logistic regression analyses.

Results

There were 59 (75.6%) and 19 (24.4%) participants in the low and high MP groups, respectively. Compared with the low MP group, the high MP group had significantly higher disease severity, as measured by the modified Reiff score (p<0.001) and FACED score (p=0.003). Sputum MPO concentration was significantly correlated with the extent of MP (r=0.313, p=0.009). In addition, sputum MPO concentration (adjusted odds ratio=1.60, 95% confidence interval: 1.06–2.42) was independently associated with a high extent of MP even after adjusting for potential confounders.

Conclusions

Sputum MPO concentration was associated with a high degree of MP, suggesting a potential role of MPO in the pathogenesis of mucus plugging.
Elabela alleviates cuproptosis and vascular calcification in vitaminD3- overloaded mice via regulation of the PPAR-γ /FDX1 signaling
Authors: Qi Rui-Qiang , Chen Yu-Fei , Cheng Jing , Song Jia-Wei , Chen Yi-Hang , Wang Si-Yuan , Liu Ying , Yan Kai-Xin , Liu Xiao-Yan , Li Jing , Zhong Jiu-Chang
Published: November 2024

Background

Vascular calcification is a crucial pathophysiological process associated with age-related cardiovascular diseases. Elabela, a recently identified peptide, has emerged as a significant player in the regulation of cardiovascular function and homeostasis. However, the effects and underlying mechanisms of Elabela on age-related vascular calcification remain largely unexplored.

Methods

In-vivo vascular calcifications of C57BL/6J mice (8-week-old) and young (8-week-old) or aged (72-week-old) SD rats were injected with vitamin D3 (VitD3) or saline, respectively. Furthermore, the VitD3-overloaded mice received Elabela (1 mg/kg/d), peroxisome proliferators-activated receptor-γ (PPAR-γ) activator Rosiglitazone (5 mg/kg/d) or copper-ionophore Elesclomol (20 mg/kg/d), respectively. As for in-vitro studies, primary rat vascular smooth muscle cells (VSMCs) were isolated from aortas and cultured for explore the role and underlying mechanism of Elabela in vascular calcification.

Results

There were marked increases in FDX1 and Slc31a1 levels in both aortas and VSMCs during vascular calcification, coinciding with a rise in copper levels and a decrease in Elabela levels. Alizarin red and von-Kossa staining indicated that the administration of Elabela effectively hindered the progression of vascular cuproptosis and arterial calcification in VitD3-overloaded mice and rat arterial rings models. Moreover, Elabela significantly suppressed osteogenic differentiation and calcium deposition in VSMCs and strikingly reversed high phosphate-induced augmentation of FDX1 expression, DLAT aggregation as well as intracellular copper ion levels. More importantly, Elabela exhibited remarkable abilities to prevent mitochondrial dysfunctions in primary rat VSMCs by maintaining mitochondrial membrane potential, inhibiting mitochondrial division, reducing mitochondrial ROS production and increasing ATP levels. Interestingly, Elabela mitigated cellular senescence and production of pro-inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-18 and TNF-α, respectively. Furthermore, Elabela upregulated the protein levels of PPAR-γ in VitD3-overloaded mice. Administrating PPAR-γ inhibitor GW9662 or blocking the efflux of intracellular copper abolished the protective effect of Elabela on vascular calcification by enhancing levels of FDX1, Slc31a1, Runx2, and BMP2.

Conclusion

Elabela plays a crucial role in protecting against vascular cuproptosis and arterial calcification by activating the PPAR-γ /FDX1 signaling. Elabela supplementation and cuproptosis suppression serve as effective therapeutic approaches for managing vascular calcification and related cardiovascular disorders.
Calculating the effect of intensive use of urban organic waste on soil concentrations of potentially toxic elements in a peri-urban agriculture context in Norway
Authors: Løes Anne-Kristin , Eiter Sebastian , Rittl Tatiana
Published: November 2024

Background

Recycling nutrients and organic matter available as waste in urban areas may close nutrient gaps and improve soil quality, but the concentrations of potentially toxic elements (PTEs) are commonly higher than in mineral fertilisers. How quickly may the limits for soil quality be exceeded, and for which elements, if such materials are applied intensively? For a rough answer to this question, we used soil data from ten case farms near Oslo and Bergen (Norway) to estimate how PTE concentrations increased when the demand for nitrogen (N), phosphorus (P) and potassium (K) in a theoretical carrot crop produced every year was covered by compost or digestate from source-separated food waste, or composted garden waste, compared with manure from horses and poultry which are often kept in peri-urban areas.

Results

With the intensive fertilisation assumed here, the Norwegian soil quality limits for PTEs were reached within 20–85 years, and faster for soil with more organic matter since regulatory limits set by weight discriminate soils with low bulk density. The limits were reached first for Cu and Zn, which are both essential micronutrients for crop plants. The concentrations of macronutrients in the urban waste-based fertilisers were not well balanced. Rates covering the K demand would lead to high surpluses of P and N. In peri-urban vegetable growing, high applications of compost are not unusual, but more balanced fertilisation is required.

Conclusions

The Norwegian regulations for PTEs in organic soil amendments and agricultural soil are stricter than in the EU, and do not support recycling of organic matter and nutrients from urban waste. Many materials which can only be applied with restricted amounts to Norwegian agricultural soil, may be applied according to crop demand in the EU. Growers utilising urban waste-based fertilisers intensively should monitor the soil regularly, including PTE analyses. Soil sampling should occur on fixed sampling points to reveal changes in concentrations over time. Norwegian authorities should consider a revision of the organic fertiliser regulation to support recycling of valuable organic materials. There is a need for more data on the PTE concentrations in agricultural soil and organic fertiliser materials.
Scoping review and thematic analysis of informed consent in humanitarian emergencies
Authors: Thomson Benjamin , Mehta S. , Robinson C.
Published: November 2024

Background

To identify and to summarize challenges related to the informed consent process for research completed during humanitarian emergencies.

Methods

Using relevant search terms, a search of 5 databases was completed, without language, date, or study type restriction. Studies were screened for inclusion, with eligible studies being those that were relevant to the informed consent process for research studies completed in humanitarian emergencies. A Grounded Theory Analysis was completed to identify themes and subthemes.

Results

Review identified 30 relevant studies. We identified 11 challenges (lack of trust, therapeutic misconception, reduced capacity, security and privacy concerns, harmful research, power differential, literacy, language/local and cultural context, researcher burden and re-evaluation of ongoing trials) and 7 strategies (engage local research communities, use alternative to standard written consent process, modify traditional process of research ethics board review, dynamic consent, training of research staff, mandating transparency of commercial interests, and mandating reporting of informed consent process in all publications) to confront the challenges. These challenges and strategies were unique to the informed consent process in research conducted during humanitarian emergencies.

Conclusions

This scoping review identified an evidence-based guide for researchers and research ethics boards to perform ethical informed consent procedures in humanitarian emergencies.

Trial Registration

This trial was not registered as scoping reviews can not be registered as per updated PROSPERO guidelines.
Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice
Authors: Michenthaler Helene , Duszka Kalina , Reinisch Isabel , Galhuber Markus , Moyschewitz Elisabeth , Stryeck Sarah , Madl Tobias , Prokesch Andreas , Krstic Jelena
Published: November 2024

Background

Dietary restriction (DR) has multiple beneficial effects on health and longevity and can also improve the efficacy of certain therapies. Diets used to instigate DR are diverse and the corresponding response is not uniformly measured. We compared the systemic and liver-specific transcriptional response to intermittent fasting (IF) and commercially available fasting-mimicking diet (FMD) after short- and long-term use in C57BL/6 J mice.

Results

We show that neither DR regimen causes observable adverse effects in mice. The weight loss was limited to 20% and was quickly compensated during refeeding days. The slightly higher weight loss upon FMD versus IF correlated with stronger fasting response assessed by lower glucose levels and higher ketone body, free fatty acids and especially FGF21 concentrations in blood. RNA sequencing demonstrated similar transcriptional programs in the liver after both regimens, with PPARα signalling as top enriched pathway, while on individual gene level FMD more potently increased gluconeogenesis-related, and PPARα and p53 target gene expression compared to IF. Repeated IF induced similar transcriptional responses as acute IF. However, repeated cycles of FMD resulted in blunted expression of genes involved in ketogenesis and fatty acid oxidation.

Conclusions

Short-term FMD causes more pronounced changes in blood parameters and slightly higher weight loss than IF, while both activate similar pathways (particularly PPARα signalling) in the liver. On individual gene level FMD induces a stronger transcriptional response, whereas cyclic application blunts transcriptional upregulation of fatty acid oxidation and ketogenesis only in FMD. Hence, our comparative characterization of IF and FMD protocols renders both as effective DR regimens and serves as resource in the fasting research field.
The embedded research model: an answer to the research and evaluation needs of community service organizations?
Authors: Kavanagh Bianca E. , Versace Vincent L. , Mc Namara Kevin P.
Published: November 2024

There is an increasing need to provide evidence of outcomes within the community services sector. However, funding challenges, workforce pressures, and the complex social contexts in which community service organizations operate limit their potential for organizational capacity building. This has flow on effects on the ability to conduct impactful and strategic research. The embedded research model (i.e., when a researcher is embedded into a “host” organisation) may aid in building research and evaluation capacity. This may be particularly useful for the purposes of routine outcome monitoring and continuous quality improvement, which may in turn lead to opportunities for local research and evaluation through the embedded research model. Previous research on the embedded research model across various settings has suggested a number of lessons for implementation. However, to date, nil research has focused on community service organizations. Additional considerations need to be made within this context due to resource limitations, ethical issues, and diverse reporting requirements. Such considerations include the need to take a ‘slow science’ approach to research and evaluation outputs, consideration of the organisation’s readiness for change, and the need to report activities in a transparent, thorough, and consistent manner. The endorsement of embedded research in community service organisations may aid in providing evidence of outcomes for clients, and simultaneously, increase the ability for policymakers to evidence-informed decisions on how to improve outcomes for the local population.
A patient stratification signature mirrors the immunogenic potential of high grade serous ovarian cancers
Authors: Berry Laurel K. , Pullikuth Ashok K. , Stearns Kristen L. , Wang Yuezhu , Wagner Calvin J. , Chou Jeff W. , Darby Janelle P. , Kelly Michael G. , Mall Raghvendra , Leung Ming , Chifman Julia , Miller Lance D.
Published: November 2024

Background

While high-grade serous ovarian cancer (HGSC) has proven largely resistant to immunotherapy, sporadic incidents of partial and complete response have been observed in clinical trials and case reports. These observations suggest that a molecular basis for effective immunity may exist within a subpopulation of HGSC. Herein, we developed an algorithm, CONSTRU (Computing Prognostic Marker Dependencies by Successive Testing of Gene-Stratified Subgroups), to facilitate the discovery and characterization of molecular backgrounds of HGSC that confer resistance or susceptibility to protective anti-tumor immunity.

Methods

We used CONSTRU to identify genes from tumor expression profiles that influence the prognostic power of an established immune cytolytic activity signature (CYTscore). From the identified genes, we developed a stratification signature (STRATsig) that partitioned patient populations into tertiles that varied markedly by CYTscore prognostic power. The tertile groups were then analyzed for distinguishing biological, clinical and immunological properties using integrative bioinformatics approaches.

Results

Patient survival and molecular measures of immune suppression, evasion and dysfunction varied significantly across STRATsig tertiles in validation cohorts. Tumors comprising STRATsig tertile 1 (S-T1) showed no immune-survival benefit and displayed a hyper-immune suppressed state marked by activation of TGF-β, Wnt/β-catenin and adenosine-mediated immunosuppressive pathways, with concurrent T cell dysfunction, reduced potential for antigen presentation, and enrichment of cancer-associated fibroblasts. By contrast, S-T3 tumors exhibited diminished immunosuppressive signaling, heightened antigen presentation machinery, lowered T cell dysfunction, and a significant CYTscore-survival benefit that correlated with mutational burden in a manner consistent with anti-tumor immunoediting. These tumors also showed elevated activity of DNA damage/repair, cell cycle/proliferation and oxidative phosphorylation, and displayed greater proportions of Th1 CD4 + T cells. In these patients, but not those of S-T1 or S-T2, validated predictors of immunotherapy response were prognostic of longer patient survival. Further analyses showed that STRATsig tertile properties were not explained by known HGSC molecular or clinical subtypes or singular immune mechanisms.

Conclusions

STRATsig is a composite of parallel immunoregulatory pathways that mirrors tumor immunogenic potential. Approximately one-third of HGSC cases classify as S-T3 and display a hypo-immunosuppressed and antigenic molecular composition that favors immunologic tumor control. These patients may show heightened responsiveness to current immunotherapies.
Risdiplam: therapeutic effects and tolerability in a small cohort of 6 adult type 2 and type 3 SMA patients
Authors: Severa Gianmarco , Alfaro Maria del Carmen , Alimi Ichola Christophe , Shoaito Hussein , Souvannanorath Sarah , Authier François-Jerôme , Malfatti Edoardo
Published: November 2024

Background

Risdiplam is a validated treatment for adult SMA patients, but clear guidelines concerning functional assessment at baseline and during the follow-up are still limited, especially in terms of sensible and validated outcome measures able to capture minimal changes in motor performances induced by therapy. The aim of this work is to describe the effect of Risdiplam on a cohort of 6 adult type 2 and type 3 SMA patients, using Motor Function Measure (MFM32) as a standardized scaleto quantify the motor improvements induced by therapy.

Results

Risdiplam at the dose of 5 mg/daily was administered to a population of 6 (4 F;2 M) type 2 (N = 4) and type 3 (N = 2), adult SMA patients. Two patients were previously treated by Nusinersen, later suspended due to side effects. At baseline, all patients received a neuromuscular evaluation and a MFM32 assessment. After the beginning of treatment, we evaluated MFM32, patient reported outcomes (PROs), and adverse events over 7–27 months of follow-up. The MFM32 showed an increased score ranging from + 2.16% to + 7.29% in 4 patients. The improvement was maintained overtime, with two patients presenting the longest follow-up period of 24 and 27 months respectively. Subdomain D3 was ameliorated in 66.6% of patients. Two patients previously treated with Nusinersen maintained the pre-Risdiplam scores. The HFMSE was also performed and failed to show significant improvements after treatment. All patients reported subjective ameliorations. The commonest PROs were improvements in breath fatigue, voice’s intelligibility, hand strength and dexterity. Adverse effects were mild and decreased over time.

Conclusions

Risdiplam is a well-tolerated treatment in our cohort of adult type 2 and type 3 SMA patients and resulted in improvement or stabilization in motor functions. MFM32 proved to be sensitive to detect changes induced by therapy. Subjective meaningful improvements were sustained overtime especially in bulbar functions, breath fatigue and distal motor abilities.
Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications
Authors: Wireko Andrew Awuah , Ben-Jaafar Adam , Kong Jonathan Sing Huk , Mannan Krishitha Meenu , Sanker Vivek , Rosenke Sophie-Liliane , Boye Allswell Naa Adjeley , Nkrumah-Boateng Princess Afia , Poornaselvan Jeisun , Shah Muhammad Hamza , Abdul-Rahman Toufik , Atallah Oday
Published: November 2024

CNS tumours encompass a diverse group of neoplasms with significant morbidity and mortality. The SHH signalling pathway plays a critical role in the pathogenesis of several CNS tumours, including gliomas, medulloblastomas and others. By influencing cellular proliferation, differentiation and migration in CNS tumours, the SHH pathway has emerged as a promising target for therapeutic intervention. Current strategies such as vismodegib and sonidegib have shown efficacy in targeting SHH pathway activation. However, challenges such as resistance mechanisms and paradoxical effects observed in clinical settings underscore the complexity of effectively targeting this pathway. Advances in gene editing technologies, particularly CRISPR/Cas9, have provided valuable tools for studying SHH pathway biology, validating therapeutic targets and exploring novel treatment modalities. These innovations have paved the way for a better understanding of pathway dynamics and the development of more precise therapeutic interventions. In addition, the identification and validation of biomarkers of SHH pathway activation are critical to guide clinical decision making and improve patient outcomes. Molecular profiling and biomarker discovery efforts are critical steps towards personalised medicine approaches in the treatment of SHH pathway-associated CNS tumours. While significant progress has been made in understanding the role of the SHH pathway in CNS tumorigenesis, ongoing research is essential to overcome current therapeutic challenges and refine treatment strategies. The integration of molecular insights with advanced technologies and clinical expertise holds great promise for developing more effective and personalised therapies for patients with SHH pathway-driven CNS tumours.

Graphical Abstract
Integrating habit science and learning theory to promote maintenance of behavior change: does adding text messages to a habit-based sleep health intervention (HABITs) improve outcomes for eveningness chronotype young adults? Study protocol for a randomized controlled trial
Authors: Diaz Marlen , Ovalle Patino Estephania , Oliver Sophia , Tiab Sondra S. , Salazar Nena , Song Jiyoung , Dong Lu , Sarfan Laurel D. , Susman Eli S. , Agnew Emma R. , Gardner Benjamin , Harvey Allison G.
Published: November 2024

Background

Eveningness chronotype—the tendency for later sleep and wake times—arises from a confluence of psychosocial, behavioral, and biological factors. With the onset and progression of puberty, many young people develop an eveningness chronotype, which remains prevalent through the transition into adulthood. Eveningness has been associated with increased risk for poorer health. While eveningness is modifiable, maintaining the necessary behavior changes can be challenging. The science on habits demonstrates that habit formation is a key mechanism for maintaining behavior change over time. Learning theory offers schedules of reinforcement that also hold promise for enhancing the maintenance of behavior change. The present study will evaluate the Habit-based Sleep Health Intervention (HABITs)—which combines the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) with the science of habits—and a text message intervention informed by learning theory to attempt to sustainably modify the contributors to eveningness among young adults (18–30 years of age).

Methods

Participants (N = 160) will be randomly allocated to HABITs and HABITs + Texts. Both interventions include HABITs which involves three 50-min sessions followed by six 30-min sessions. Alongside the latter six sessions, HABITs + Texts will concurrently receive the text message intervention. Aims 1–3 will compare HABITs + Texts to HABITs on improvements in the outcomes of (1) utilization of sleep health behaviors and habit formation, (2) sleep and circadian functioning, and (3) functioning in five health-relevant domains, in the short (post-treatment) and longer (6-month and 12-month follow-up) term. Exploratory analysis will (1) compare HABITs and HABITs + Texts on (a) if sleep health behavior habit formation mediates the effects of intervention on improvement in outcomes and (b) if intervention effects are moderated by select variables, and (2) to evaluate if HABITs (regardless of the text message intervention) is associated with an improvement in outcomes in the short and longer term.

Discussion

This study has the potential to advance knowledge on (1) the value of leveraging the science of habits and learning theory in behavior change interventions, (2) the use of a low-cost and efficient intervention for habit formation and maintenance, (3) interventions that address eveningness chronotype, and (4) processes related to behavior change during emerging adulthood.

Trial registration

Clinicaltrials.gov NCT05167695. Registered on December 22, 2021.
Investigation of renal tubular function with newly diagnosed type 1 diabetes mellitus during diabetic ketoacidosis
Authors: Kumagai Naonori , Takao Hiroki , Sudo Yuta , Yoshikane Masatoshi , Kondoh Tomomi , Matsumoto Yuji , Mizuno Haruo , Abe Michiaki , Ikezumi Yohei
Published: November 2024

Background

Proximal renal tubular dysfunction occurs during diabetic ketoacidosis (DKA) in type 1 diabetes. However, only a few studies have reported on the multiple proximal renal tubular functions simultaneously. Moreover, to the best of our knowledge, distal renal tubular function has not yet been investigated.

Methods

Patients with newly diagnosed type 1 diabetes mellitus were classified into those with DKA and those without DKA, and their proximal and distal renal tubular functions were investigated. The diagnostic criteria for DKA were blood glucose > 200 mg/dL, blood pH < 7.3 or HCO3– < 15 mEq/L, and urine ketone body positivity.

Results

Six patients with DKA and five patients without DKA were included. In patients with DKA, urinary β2-microglobulin levels were significantly higher, while blood pH, HCO3–, and tubular reabsorption of phosphorus were significantly lower than in those without DKA. There were no significant differences in blood glucose, HbA1c, serum phosphorus, urinary N-acetyl-beta-glucosaminidase, and urinary amino acid excretion between patients with and without DKA. Elevated NH3 levels and impaired urinary acidification were not observed in patients with and without DKA.

Conclusions

In patients with newly diagnosed type 1 diabetes mellitus complicated with DKA, multiple proximal renal tubular dysfunctions occur simultaneously, suggesting transient Fanconi syndrome. Distal renal tubular acidosis was unlikely. The diagnostic criteria for DKA are appropriate also in the view of proximal renal tubular dysfunction and are considered suggestive of pathophysiological factors that may cause proximal renal tubular dysfunction.
Cancer-associated fibroblasts reveal aberrant DNA methylation across different types of cancer
Authors: Schmidt Marco , Maié Tiago , Cramer Thorsten , Costa Ivan G. , Wagner Wolfgang
Published: November 2024

Background

Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment and play a critical role in cancer progression. Numerous studies have identified significant molecular differences between CAFs and normal tissue-associated fibroblasts (NAFs). In this study, we isolated CAFs and NAFs from liver tumors and conducted a comprehensive analysis of their DNA methylation profiles, integrating our finding with data from studies on other cancer types.

Results

Our analysis revealed that several CAF samples exhibited aberrant DNA methylation patterns, which corresponded with altered gene expression levels. Notably, DNA methylation at liver CAF-specific CpG sites was linked to survival outcomes in liver cancer datasets. An integrative analysis using publicly available datasets from various cancer types, including lung, prostate, esophageal, and gastric cancers, uncovered common epigenetic abnormalities across these cancers. Among the consistently altered CpGs were cg09809672 (EDARADD), cg07134930 (HDAC4), and cg05935904 (intergenic). These methylation changes were associated with prognosis across multiple cancer types.

Conclusion

The activation of CAFs by the tumor microenvironment seems to be associated with distinct epigenetic modifications. Remarkably, similar genomic regions tend to undergo hypomethylation in CAFs across different studies and cancer types. Our findings suggest that CAF-associated DNA methylation changes hold potential as prognostic biomarkers. However, further research and validation are necessary to develop and apply such signatures in a clinical setting.
Microbial community analysis of mildewed cigar tobacco leaves from high-throughput sequencing data
Authors: Wei Min , Shi Youzhi , Song Xuyan , Rong Lin , Li Ziwei , Li Jing , Wang Bo , Chen Bifeng
Published: November 2024

Background

Cigar tobacco leaves contain abundant bacteria and fungi that are vital for their quality. In this study, the microbial communities were analyzed in the artificial mildewed cigar tobacco leaves of different mildew stages (healthy control, early stage, middle stage and late stage).

Results

For cigar wrapper tobacco leaves, there was an increased bacterial genera abundance of Terribacillus, Bacillus and Micrococcus, while there was an increased fungal genera abundance of Aspergillus, Penicillium and Mucor. For cigar filler tobacco leaves, there was an increased bacterial genera abundance of Staphylococcus, while there was an increased fungal genera abundance of Aspergillus and Trichomonascus. Microbial communities (bacterial and fungal) showed significantly different compositions in both cigar wrapper and filler tobacco leaves from different mildew stages. The top important microbial communities (bacterial and fungal) in cigar wrapper and filler tobacco were Sphingomonas, Aerococcus, Wallemia and Trichomonascus, respectively.

Conclusion

This study provided evidence for the great changes in microbial communities during the mildew process of cigar wrapper and filler tobacco. The effects of the dominant bacterial genera and fungal genera on tobacco mildew should be explored in depth, whose findings may be applied to develop strategies for controlling tobacco mildew.
Weight-adjusted waist index and cardiovascular disease: a population-based study in Ravansar, Iran
Authors: Sadafi Sepehr , Azizi Ali , Shakiba Ebrahim , Pasdar Yahya
Published: November 2024

Background

The weight-adjusted-waist index (WWI) is a relatively new index to obesity. This study aimed to explore the reationship between WWI and cardiovascular disease (CVD).

Methods

This cross-sectional study included 8,899 participants aged 35 to 65 from the Ravansar non-communicable diseases (RaNCD) cohort study in Ravansar, Iran. The WWI was calculated by dividing waist circumference (WC) by the square root of weight. The receiver operating characteristic (ROC) curve was utilized to assess the predictive performance of WWI in relation to CVD. The study applied multiple logistic regression to assess the association between WWI and CVD.

Results

Participants had an average age of 47.52 ± 8.29 years, with 45.30% being men and 41.13% residing in rural areas. The prevalence of CVD was found to be 17.36%. A positive correlation between WWI and CVD was obseved, with individuals in the highest WWI quartile having a 36% (OR = 1.36, 95%CI: 1.11, 1.78) greater odds of CVD compared to those in the lowest quartile (OR = 1.03, 95%CI: 0.79, 1.33) (ptrend = 0.010). Subgroup analyses indicated stronger links between WWI and CVD among participants over 50, males, urban residents, those of high socioeconomic status (SES), and passive smokers (p < 0.001). The ROC analysis revealed that WWI is a greater ability in predicting CVD (AUC: 0.64, 95%CI: 0.61, 0.64) compared to body mass index (BMI) (AUC: 0.60, 95%CI: 0.58, 0.61) and WC (AUC: 0.61, 95%CI: 0.59, 0.62).

Conclusion

The increase in WWI elevates the odds of CVD, making the management of WWI crucial for CVD prevention.
Biosynthesis of phloretin and its C-glycosides through stepwise culture of Escherichia coli
Authors: Lee Shin-Won , Lee Garok , Jo Ji-Hyeon , Yang Youri , Ahn Joong-Hoon
Published: November 2024

Phloretin (PT) belongs to the dihydrochalcones (DHCs) family and is found in apple and rooibos tea. Its glycosides, including phlorizin (PT 2′-O-glucoside), trilobatin (PT 4′-O-glucoside), and nothofagin (NF, PT 3′-C-glucoside), are present in various plants. Phloretin and its related glycosides possess health benefits, including antioxidant, anti-inflammatory, and antibacterial activities. To biosynthesize PT and its glycosides, the relevant pathways in plants were studied and introduced into Escherichia coli. We reconstructed the biosynthetic pathways pertaining to PT and three PT C-glycosides (NF, PT 3′, 5′-di-C-glucoside [PDG], and PT 3′-C-arabinoside [PARA]) in E. coli. To prevent the undesirable synthesis of flavonoids instead of PT, we strategically divided the entire pathway into two parts: the first involved the synthesis of tyrosine to phloretic acid (PA), while the second involved the synthesis of PA to PT and its glycosides. The gene set pertaining to each part was incorporated into a different engineered microbe. We optimized phloretin microbial biosynthesis by improving enzyme affinity, identifying the gene that increased the output, refining the production design to a stepwise culture approach, and analyzing the culture conditions (substrate and yeast extract concentrations and pH) conducive to maximum output and the prevention of product degradation. Using the stepwise culture approach, 12.8 mg/L of PT, 26.1 mg/L of NF, 30.0 mg/L of PDG, and 18.1 mg/L of PARA were synthesized. This study provides valuable information for future approaches in the microbe-based synthesis of PT derivatives.
Role of social innovations in health in the prevention and control of infectious diseases: a scoping review
Authors: Khazaee-Pool Maryam , Pashaei Tahereh , Zarghani Maryam , Ponnet Koen
Published: November 2024

Background

The implementation of social innovations for addressing societal challenges, particularly in health, leverages community participation and technology to optimally meet social needs compared to traditional approaches. A key feature of these innovations is their ability to utilize existing capacities for contributing to resolving infectious disease outbreaks, which has attracted significant attention from health organizations. Given the potential of these innovations, this study has investigated social innovations in the prevention and control of infectious diseases as one of the major global challenges in the form of a comprehensive literature review.

Methods

This review study examined the relevant literature from January 1, 2010 to December 31, 2022. Based on inclusion and exclusion criteria, 50 documents were retained and fully examined. The documents were analyzed by applying a thematic analysis, and important content related to the application of social innovations for the prevention and control of pandemic infectious diseases was extracted using a data collection form.

Results

Five major themes concerning social innovation in the prevention and control of epidemic diseases were discerned as follows: new products, novel processes and policies, empowerment, innovative practices and behaviors, and community engagement. New products include technological products for control and management of epidemics, preventive products, diagnostic and therapeutic products. Novel processes and policies are related to reorienting and reorganizing care methods, control and monitoring policies, participatory and creative strategies. Empowerment is focused on enhancing the capabilities of health workers, community leaders, and communities. Innovative practices and behaviors involve technology-based participation and support mechanisms. Community engagement is related to awareness, consultation, community mobilization, and participation in production and support.

Conclusions

During the outbreak of infectious diseases, governments are faced with many challenges, including health, economic and social challenges. To answer these challenges, tools should be used that have the ability to answer the problem from several aspects. Social innovation as an appropriate process in response to health crises has led to new forms of relationships and empowered the communities. And to promote public health, it provides the opportunity for all members of the society to participate in crisis resolution and optimal use of resources.
FBXL16: a new regulator of neuroinflammation and cognition in Alzheimer’s disease through the ubiquitination-dependent degradation of amyloid precursor protein
Authors: Qu Liqun , Tang Yong , Wu Jianhui , Yun Xiaoyun , Lo Hang Hong , Song Linlin , Wang Xingxia , Wang Huimiao , Zhang Ruilong , Liu Menghan , Wang Cairen , Ng Jerome P. L. , Fu Xianjun , Wong Io Nam , Wong Vincent Kam Wai , Law Betty Yuen Kwan
Published: November 2024

Background

Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer’s disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system.

Methods

Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16. Subsequent experiments demonstrated that FBXL16 promotes the proteasomal degradation of the APP protein, as evidenced by co-immunoprecipitation with MG132 and cycloheximide (CHX), immunohistochemistry (IHC) and immunocytochemistry (ICC). Memory and cognitive improvements were observed in 3×Tg AD mice through the use of a lentivirus-mediated approach to generate a brain-specific AD mouse model overexpressing FBXL16 via stereotaxic injection. Furthermore, a brain-specific conditional knockout (cko) FBXL16 mouse model was generated and employed to further confirm the functional role of FBXL 16 in AD via various behavioral tests including Morris water maze and Y-maze.

Results

The level of FBXL16 in the brains of transgenic APP/PSEN mice with AD decreased with age. Accelerated degradation of APP was observed when FBXL16 was overexpressed in the hippocampi of these AD mice via a lentivirus. This process led to notable improvements in cognitive impairments and reductions in neuroinflammation. Further studies using proteomics and bioinformatics techniques identified transcription factors and binding proteins associated with FBXL16, providing deeper insights into the potential role of FBXL16 in the regulation of AD. Finally, the in vivo effects of FBXL16 deficiency were further substantiated in cko mice, which overexpress Aβ but specifically lack FBXL16 in the brain region.

Conclusions

These findings suggest that FBXL16 could be a new regulator of AD. These findings provide a foundation for further research into drug development and potential therapeutic strategies to combat other related neurodegenerative proteinopathies.
High detection rate of circulating-tumor DNA from cerebrospinal fluid of children with central nervous system germ cell tumors
Authors: Nakano Yoshiko , Burns Ian , Nobre Liana , Siddaway Robert , Rana Mansuba , Nesvick Cody , Bondoc Andrew , Ku Michelle , Yuditskiy Richard , Ku Dennis T. L. , Shing Matthew M. K. , Cheng Kevin K. F. , Ng Ho-Keung , Das Anirban , Bennett Julie , Ramaswamy Vijay , Huang Annie , Malkin David , Ertl-Wagner Birgit , Dirks Peter , Bouffet Eric , Bartels Ute , Tabori Uri , Hawkins Cynthia , Liu Anthony P. Y.
Published: November 2024

Central nervous system germ cell tumors (CNS-GCT) are malignant neoplasms that arise predominantly during adolescence and young adulthood. These tumors are typically sensitive to treatment, but resulting long-term health deficits are common. Additional clinical challenges include surgical risks associated with tumor biopsy, and need to determine treatment response for adapting radiotherapy protocols. The aim of this study was to establish the detectability of circulating-tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of children with CNS-GCT as a potential biomarker. We obtained CSF from patients with CNS-GCT by lumbar puncture or intra-operatively. Cell-free DNA (cfDNA) was extracted and subjected to low-pass whole genome sequencing (LP-WGS). Copy-number alterations (CNAs) were inferred and served as a marker of measurable residual disease (MRD). Comparisons with imaging findings and tumor marker levels were made. A total of 29 CSF samples from 21 patients (16 with germinoma, 5 with non-germinomatous GCT) were sequenced. Twenty samples from 19 patients were collected at diagnosis, and 9 samples from 7 patients were collected during or after therapy. Among the diagnostic samples, CNAs were detected in samples from 17/19 patients (89%), which included 8 with marker-negative tumors. Specific clinical scenarios suggested that serial cfDNA analysis may carry utility in tracking treatment responses as well as clarifying indeterminate imaging findings. Our results provide evidence for the high-sensitivity in detecting ctDNA from CSF of CNS-GCT patients using LP-WGS, with potential utility for non-invasive diagnosis and disease monitoring in upcoming CNS-GCT studies.
A topic map based learning management system to facilitate meaningful grammar learning: the case of Japanese grammar learning
Authors: Wang Jingyun , Wynn Adam , Mendori Takahiko , Hwang Gwo-Jen
Published: November 2024

This study investigates the effect of studying with topic maps provided by a self-developed language learning support system on (a) learning perception, (b) learning achievement and (c) variation in learning attitude and motivation, from the perspective of prior learning attitude, motivation and learning style. An analysis was conducted on the learning data of 90 participants for examining pre-test and post-test scores, learning perception, learning style indicators, attitude and motivation rankings before and after the study of target Japanese grammar content with the support of the system. The findings suggest that learners with high attitude/motivation perceived greater development of the habit of “learning from the comparison of related knowledge” and felt more satisfied with the learning situation in the system environment. Furthermore, the learners' attitude towards Japanese grammar learning and their motivation toward Japanese language learning were significantly stronger after the learning activity. It is also observed that (a) learner attitude towards Japanese grammar after studying with the system only had a positive correlation to prior attitudes; and (b) learner motivation towards Japanese language after studying with the system correlated highly with prior motivation and perception of development of the habit of “learning from the comparison of related knowledge.” Finally, from a learning style perspective, the analysis result suggests that “Global learners” expressed a stronger feeling about the usefulness of the comparison function of the system and their increment in motivation after using the system was higher than for “Sequential learners.” Moreover, between learning style indicators in the Sequential/Global dimension and level of learner expertise in the reported mental load scale, a significant interaction effect was found.