bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractCNS 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractPhloretin (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

Abstract
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.