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Background/Objectives: Restorative proctocolectomy with ileo-anal pouch anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC). However, complications like pouchitis can occur. This study aimed to describe patients who underwent IPAA for inflammatory bowel disease (IBD) at Padua Hospital from 2005 to 2023 and identify risk factors for pouchitis. Secondary objectives included evaluating the effectiveness of biological therapy in chronic antibiotic-refractory pouchitis (CARP), Crohn’s disease of the pouch (CDP), and Crohn’s-like inflammation of the pouch (CDLPI), and assessing risk factors for pouch failure. Methods: This retrospective, observational study included 109 patients whose data were collected from medical records. Univariate logistic regression was used to analyze associations between preoperative and postoperative factors and outcomes such as acute pouchitis and pouch failure. The effectiveness of biological therapy was assessed by measuring changes in the Pouchitis Disease Activity Index (PDAI) and the Modified Pouchitis Disease Activity Index (mPDAI) over a 12-month treatment period. Results: Univariate logistic regression revealed significant associations between preoperative extraintestinal manifestations (OR 3.569, 95% CI 1.240–10.720), previous diagnosis of Crohn’s disease (OR 10.675, 95% CI 1.265–90.089), and transmural inflammation at cross-sectional imaging before surgery (OR 3.453, 95% CI 1.193–9.991) with an acute pouchitis risk. Pouch failure was significantly associated with a previous diagnosis of Crohn’s disease (OR 9.500, 95% CI 1.821–49.571) and post-surgical fistulas (OR 41.597, 95% CI 4.022–430.172). Biological therapy led to a significant reduction in the PDAI score in patients with CARP, decreasing from a median of 10 to 4 (p = 0.006). Similarly, in patients with CDP or CDLPI, the mPDAI score was significantly reduced from a median of 9 to 1 (p = 0.034), with remission achieved in 5/6 (83.3%) of these patients. Conclusions: This study provides valuable insights into the management of IPAA patients and highlights the importance of early identification and treatment of risk factors for pouchitis and failure. Biological therapy demonstrated significant effectiveness in reducing disease activity in patients with CARP, CDP, and CDLPI, suggesting its role as a crucial component in managing these complications.

Background: Regular physical activity (PA) is desirable, regardless of age, even in patients with chronic conditions such as inflammatory bowel disease (IBD). Aims: This study aims to assess PA levels and related barriers/facilitators in IBD patients, stratifying them into age groups (with a threshold of 50 years). Methods: The International PA Questionnaire (IPAQ) assessed PA levels regarding resting metabolic rate (Met) in minutes per week (min/wk). Patient-reported outcomes 2 (PRO-2) evaluated disease activity. Results: Among the 237 enrolled patients, PA rates were found to differ significantly in terms of patients being sufficiently active (55% vs. 39.8%), inactive (39.6% vs. 59.1%), and engaging in health-enhancing PA (5.4% vs. 1.1%) between patients under and at least 50 years old, respectively (p < 0.001). Overall, PA levels followed this trend, being higher in younger patients [892 (446.5–1439) vs. 545.25 (257–1210.47) Met min/wk, p = 0.007]. Individuals aged at least 50 years tend to have lower PA at regression analysis (OR: 3.302, p = 0.018). Patients aged at least 50 years perceived IBD as more of a barrier to PA (p = 0.04). Bowel urgency is a significant barrier, especially in older patients (p = 0.022). Conclusions: Age is an unmodifiable factor impacting and influencing PA levels. Strategies to recover exercise levels in older IBD patients should be encouraged.

The esophagus, traditionally viewed as a sterile conduit, is now recognized as a dynamic habitat for diverse microbial communities. The emerging evidence suggests that the esophageal microbiota plays an important role in maintaining esophageal health and contributing to disease. The aim of this systematic review was to synthesize the current knowledge on the esophageal microbiota composition, its variation between healthy individuals and those with esophageal diseases, and the potential mechanisms through which these microorganisms influence esophageal pathology. A systematic literature search was conducted using multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published up to July 2024. The inclusion criteria encompassed original research articles that used molecular techniques to characterize the esophageal microbiota in human subjects, comparing healthy individuals with patients affected by esophageal conditions such as gastroesophageal reflux disease (GERD), Barrett’s esophagus, eosinophilic esophagitis, and esophageal cancer. The primary outcomes were the composition and diversity of the esophageal microbiota, and the secondary outcomes included the correlations between microbial profiles and disease states. The esophageal microbiota of healthy individuals was dominated by Gram-positive bacteria, particularly Streptococcus. Conversely, the esophageal microbiota is considerably altered in disease states, with decreased microbial diversity and specific microbial signatures associated with these conditions, which may serve as biomarkers for disease progression and as targets for therapeutic intervention. However, the heterogeneous study designs, populations, and analytical methods underscore the need for standardized approaches in future research. Understanding the esophageal microbiota’s role in health and disease could guide microbiota-based diagnostics and treatments, offering novel avenues for managing esophageal conditions.

Luisa Bertin,1 Martina Crepaldi,1 Miriana Zanconato,1 Greta Lorenzon,1 Daria Maniero,1 Caterina De Barba,1 Erica Bonazzi,1 Sonia Facchin,1 Marco Scarpa,2 Cesare Ruffolo,2 Imerio Angriman,2 Andrea Buda,3 Fabiana Zingone,1 Edoardo Vincenzo Savarino,1 Brigida Barberio1 1Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; 2Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Padua, Italy; 3Gastroenterology Unit, Department of Oncological Gastrointestinal Surgery, Feltre, ItalyCorrespondence: Edoardo Vincenzo Savarino, Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy, Tel +39-049-8217749, Fax +39-049-8760820, Email edoardo.savarino@unipd.itAbstract: Crohn’s disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients’ quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD. Keywords: refractory Crohn’s disease, mesenchymal stem cell therapy, medical therapy, combination therapy, fecal microbiota transplantation, biologic drugs, perianal Crohn’s disease, small molecules, hyperbaric oxygen therapy

Crohn’s disease (CD) is a chronic, complex inflammatory disorder of the gastrointestinal tract that presents significant therapeutic challenges. Despite the availability of a wide range of treatments, many patients experience primary non-response, secondary loss of response, or adverse events, limiting the overall effectiveness of current therapies. Clinical trials often report response rates below 60%, partly due to stringent inclusion criteria. Emerging therapies that target novel pathways offer promise in overcoming these limitations. This review explores the latest investigational drugs in phases I, II, and III clinical trials for treating both luminal and perianal CD. We highlight promising therapies that target known mechanisms, including selective Janus kinase inhibitors, anti-adhesion molecules, tumor necrosis factor inhibitors, and IL-23 selective inhibitors. In addition, we delve into novel therapeutic strategies such as sphingosine-1-phosphate receptor modulators, miR-124 upregulators, anti-fractalkine (CX3CL1), anti-TL1A, peroxisome proliferator-activated receptor gamma agonists, TGFBRI/ALK5 inhibitors, anti-CCR9 agents, and other innovative small molecules, as well as combination therapies. These emerging approaches, by addressing new pathways and mechanisms of action, have the potential to surpass the limitations of existing treatments and significantly improve CD management. However, the path to developing new therapies for inflammatory bowel disease (IBD) is fraught with challenges, including complex trial designs, ethical concerns regarding placebo use, recruitment difficulties, and escalating costs. The landscape of IBD clinical trials is shifting toward greater inclusivity, improved patient diversity, and innovative trial designs, such as adaptive and Bayesian approaches, to address these challenges. By overcoming these obstacles, the drug development pipeline can advance more effective, accessible, and timely treatments for CD.

Pouchitis is an idiopathic inflammatory disease that may occur in ileal pouches, and it can lead to ileal pouch failure. This was a single-center, randomized, double-blinded, placebo-controlled trial that assessed the effect of Lactobacillus casei (L. casei) DG®, a probiotic strain, on the ileal pouch mucosa to determine the crosstalk between microbiota and mucosal immune system. Fifty-two patients undergoing restorative proctocolectomy were recruited and randomly assigned to receive a daily oral supplementation of L. casei DG® (n = 26) or placebo (n = 26) for 8 weeks from the ileostomy closure (T0) to a pouch endoscopy after 8 weeks (T1) and 1 year (T2). Ileal pouch mucosa samples were collected at T0, T1, and T2. At T1, the L. casei DG®-supplemented group showed a significant reduction of inflammatory cytokines levels compared to T0 baseline levels in the pouch mucosa, whereas in the placebo group cytokines levels resulted stable. In conclusion, probiotic manipulation of mucosal microbiota by L. casei DG®-supplementation after stoma closure in patients who underwent restorative proctocolectomy has a beneficial impact on the ileal pouch microenvironment. Registration number: NCT03136419 (http://www.clinicaltrials.gov).

Abstract Inflammatory bowels diseases (IBD) are high risk conditions for colorectal cancer (CRC). The discovery of IBD and CRC noninvasive protein/peptide biomarkers using saliva and feces was the aim of this study involving 20 controls, 25 IBD (12 Crohn’s Disease-CD), 37 CRC. By untargeted proteomic (LTQ-Orbitrap/MS), a total of 152 proteins were identified in saliva. Absent in controls, 73 proteins were present in both IBD and CRC, being mainly related to cell-adhesion, cadherin-binding and enzyme activity regulation (g-Profiler). Among the remaining 79 proteins, 14 were highly expressed in CD and 11 in CRC. These proteins clustered in DNA replication/expression and innate/adaptive immunity. In stool, endogenous peptides from 30 different proteins were identified, two being salivary and CD-associated: Basic Proline-rich Protein 1 (PRBs) and Acidic Proline-rich Phosphoprotein. Biological effects of the PRBs-related peptides GQ-15 and GG-17 found in CD stool were evaluated using CRC cell lines. These peptides induced cell proliferation and activated Erk1/2, Akt and p38 pathways. In conclusion, the salivary proteome unveiled DNA stability and immunity clusters shared between IBD and CRC. Salivary PRB-derived peptides, enriched in CD stool, stimulate CRC cell proliferation and the pro-oncogenic RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways suggesting a potential involvement of PRBs in IBD and cancer pathogenesis.

Dopamine (DA) acts in various key neurological and physiological processes as both a neurotransmitter and circulating hormone. Over the past several decades, the DA signaling network has been shown to regulate the progression of several types of solid tumors, and considerable evidence has shown it is a druggable pathway in the cancer cell context. However, the specific activity and effect of these pathway components appears to be tissue‐type and cell‐context‐dependent. In the present study, expression and methylation of dopamine receptor D1 (DRD1) were measured using RNA sequencing (RNAseq) and reverse transcription polymerase chain reaction (RT‐PCR) in non‐small cell lung cancer (NSCLC) samples, and validated using publicly available datasets, including The Cancer Genome Atlas (TCGA). In vitro and in vivo functional experiments were performed for cell proliferation and tumor growth, respectively. Mechanistic analyses of the transcriptome and kinome in DRD1‐modulated cells informed further experiments, which characterized the effects on the epidermal growth factor receptor (EGFR) pathway and programmed cell death 1 ligand 1 (PD‐L1) proteins. Through these experiments, we identified the DRD1 gene as a negative regulator of disease progression in NSCLC. We show that DRD1, as well as other DA pathway components, are expressed in normal human lung tissue, and that loss of DRD1 expression through promoter hypermethylation is a common feature in NSCLC patients and is associated with worse survival. At the cellular level, DRD1 affects proliferation by inhibiting the activation of EGFR and mitogen‐activated protein kinase 1/2 (ERK1/2). Interestingly, we also found that DRD1 regulates the expression of PD‐L1 in lung cancer cells. Taken together, these results suggest that DRD1 methylation may constitute a biomarker of poor prognosis in NSCLC patients while other components of this pathway could be targeted to improve response to EGFR‐ and PD‐L1‐targeted therapies.

Objective. Ulcerative colitis and Crohn’s disease are chronic inflammatory diseases and represent the two most important types of inflammatory bowel diseases (IBD), while spondyloarthritis (SpA) comprises a heterogeneous group of systemic inflammatory chronic rheumatic diseases, including peripheral SpA and axial SpA. Joint manifestations are the most commonly observed extraintestinal manifestations, and they can precede or not the diagnosis of IBD. Notably, in women, misdiagnoses of IBD as irritable bowel syndrome and SpA as fibromyalgia are common, leading to delayed diagnoses, increased disease burden, and poorer prognoses. This narrative review emphasizes the critical role of diagnostic tools in facilitating early referrals of IBD patients with suspected SpA and vice versa to rheumatologists and gastroenterologists, respectively. Special attention is given to the multidisciplinary approach for more effective management of these conditions, particularly in female patients. Methods. In this narrative review, we critically evaluated the literature on this topic, focusing on papers written in English that address female issues in IBD and SpA. Results. IBD and SpA are chronic inflammatory disorders often occurring in the same patients. Female patients are often misdiagnosed, and this delay in diagnosis is associated with a higher disease burden and a poorer prognosis. Conclusions. A multidisciplinary approach is needed to enable early referral between gastroenterologists and rheumatologists, as this means a better prognosis for patients with a reduction in the economic and social burden associated with IBD and SpA.

Objective: The management of chronic prostatitis/chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III. Materials and methods: From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC. Results: A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/mL, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 mL and the median peak flow was 16.3 mL/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS. Conclusions: In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.

Background: Inflammatory bowel diseases (IBDs) have a peak incidence between the second and fourth decades of life and can affect women’s reproductive life. Objectives: Our study aimed to assess the impact of IBD on the reproductive life of female patients with this condition. Design: Cross-sectional study. Methods: Women with IBD followed at our IBD Unit and a group of healthy controls were enrolled. Data on reproductive life were collected using a dedicated questionnaire. Results: The study included 457 women, of whom 228 had IBD, and 229 age-matched healthy controls. No differences were found in the use of contraceptives, infertility, and endometriosis. The risk of spontaneous and voluntary abortions was significantly higher in IBD patients than in healthy controls [odds ratio (OR) 2 and 3.62, respectively]. The risk of obstetrical complications in the IBD population was more than six times higher in patients who experienced disease reactivations during pregnancy than in those with persistent remission [OR 6.9, 95% confidence interval (CI) 1.51–31.28]. Finally, we found that the chances of breastfeeding were 66% lower in patients with IBD than in controls (OR 0.44, 95% CI 0.22–0.91). Conclusion: Our study underlines the negative impact of IBD on women’s reproductive life, supporting the need for proactive preconception counseling.

MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating gene expression. Many studies, mostly conducted on pediatric patients, suggested that oxidative stress and several miRNAs may play an important role in coeliac disease (CeD) pathogenesis. However, the interplay between oxidative stress and miRNA regulatory functions in CeD remains to be clarified. In this review, we aimed to perform a literature review on the role of miRNAs and oxidative stress in adult CeD patients and to analyze their potential interactions. In this direction, we also reported the preliminary results of a pilot study we recently performed.

Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments for anti-TNF drugs. However, several challenges currently impede the widespread adoption of TDM in clinical practice, particularly addressing the delay between sample collection and result availability. To overcome this limitation, the use of point-of-care technology tests (POCTs) is a potential solution. Point-of-care technology tests are medical diagnostic tests performed at the site of patient care to provide immediate results, allowing for quicker decision-making and treatment. The current standard of care (SOC) for drug level measurement relies on the enzyme-linked immunosorbent assay (ELISA), a method that is time-consuming and requires specialized personnel. This study aims to evaluate a novel, user-friendly, and efficient POCT method (ProciseDx Inc.) and compare its performance with the SOC ELISA in assessing infliximab and adalimumab levels in blood samples from IBD patients. Methods: In this prospective, single-center study, we collected blood samples from IBD patients, both CD and UC, receiving infliximab (87 IBD patients; 50% UC and 50% CD) or adalimumab (60 patients; 14% UC and 48% CD) and we analyzed the blood’s drugs levels using both the ProciseDx Analyzer POC and the SOC ELISA. We examined the correlation between the two methods using statistical analyses, including the Deming regression test. Additionally, we assessed the ease of use, turnaround time, and overall practicality of the POCT in a clinical setting. Results: The ProciseDx test demonstrated a strong correlation with the SOC ELISA for measuring both infliximab and adalimumab levels. In particular, the overall correlation between the ProciseDx POCT and the ELISA assessments showed an r coefficient of 0.83 with an R squared value of 0.691 (95% CI 0.717–0.902) for IFX measurements, and an r coefficient of 0.85 with an R squared value of 0.739 (95% CI 0.720–0.930). Conclusions: the ProciseDx POC test offers significantly faster turnaround times and is more straightforward to use, making it a viable alternative for routine clinical monitoring. Despite its promising potential, further refinement and validation of the ProciseDx test are necessary to ensure its effectiveness across diverse patient populations and clinical settings. Future research should focus on optimizing the POC tests’ performance and evaluating its long-term impact on IBD management.

ABSTRACT: Mammalian colostrum, known as “liquid gold,” is considered a valuable source of essential nutrients, growth factors, probiotics, prebiotics, antibodies, and other bioactive compounds. Precisely for this reason, bovine colostrum (BC) is an emerging ingredient for the feed, food, and pharmaceutical industries, being nowadays commercially available in a variety of forms in several countries. Moreover, quite a large number of functional foods and supplements for athletes, human medicines, pet nutrition plans, and complementary feed for some livestock categories, such as piglets and calves, contain BC. The amount of BC yielded by a cow after calving represents approximately 0.5% of the yearly output in dairy breeds. For its nutritional properties and low availability, BC is characterized by a greater market value and an increasing demand compared with other by-products of the dairy sector. However, information regarding the market size of BC for the food and pharmaceutical industries, as well as future developments and perspectives, is scarcely available in the scientific literature. This lack can be attributed to industrial secrecy as well as to the relatively small scale of the BC business when compared with other dairy products, which makes the BC market limited, specific, and intended for a restricted audience. From a legal perspective, regulations assign BC to the large family of milk-derived powders; thus, collecting specific production data, as well as import-export trend information, is not straightforward and can result in unprecise estimates. Given that the interest in BC is increasing in different fields, it is important to have an overview of the production steps and of pros and cons of this emerging ingredient. The present narrative review discloses why BC has started to be considered a product rather than a by-product of the dairy industry. Moreover, the present document aims to summarize the existing methodologies used to assess BC quality in terms of immunoglobulin concentration, the different applications of BC in the industry, and the BC processing technologies. Finally, a panoramic view of the current international market is provided for the first time for this dairy product.

Abstract Background In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. Methods Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. Results We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p

Refractory celiac disease (RCD) and enteropathy-associated T-cell lymphoma (EATL) are rare, yet severe complications of celiac disease (CD). Over the last decades, several studies have addressed the biology and clinical-pathological features of such conditions, highlighting unique disease patterns and recurrent genetic events. Current classification proposals identify two forms of RCD, namely: (i) type 1 RCD (RCD-I), characterized by phenotypically normal intra-epithelial lymphocytes (IELs); and (ii) type 2 RCD (RCD-II), featuring phenotypically aberrant IELs. While RCD-I likely represents a gluten-independent dysimmune reaction against small bowel epithelial cells, RCD-II is better considered an in situ aggressive T-cell lymphoma, with high rates of progression to overt EATL. The diagnosis of RCD and EATL is often challenging, due to misleading clinical-pathological features and to significant overlap with several CD-unrelated gastro-intestinal disorders. Similarly, the treatment of RCD and EATL is an unmet clinical need for both gastroenterologists and hematologists. Moving from such premises, this review aims to provide a comprehensive view of RCD and EATL, specifically considering their pathogenesis and the many still open issues concerning their diagnosis and clinical management.

Abstract Background Squamous cell carcinoma (SqCC) is a subtype of non-small cell lung cancer for which patient prognosis remains poor. The extracellular matrix (ECM) is critical in regulating cell behavior; however, its importance in tumor aggressiveness remains to be comprehensively characterized. Methods Multi-omics data of SqCC human tumor specimens was combined to characterize ECM features associated with initiation and recurrence. Penalized logistic regression was used to define a matrix risk signature for SqCC tumors and its performance across a panel of tumor types and in SqCC premalignant lesions was evaluated. Consensus clustering was used to define prognostic matreotypes for SqCC tumors. Matreotype-specific tumor biology was defined by integration of bulk RNAseq with scRNAseq data, cell type deconvolution, analysis of ligand-receptor interactions and enriched biological pathways, and through cross comparison of matreotype expression profiles with aging and idiopathic pulmonary fibrosis lung profiles. Results This analysis revealed subtype-specific ECM signatures associated with tumor initiation that were predictive of premalignant progression. We identified an ECM-enriched tumor subtype associated with the poorest prognosis. In silico analysis indicates that matrix remodeling programs differentially activate intracellular signaling in tumor and stromal cells to reinforce matrix remodeling associated with resistance and progression. The matrix subtype with the poorest prognosis resembles ECM remodeling in idiopathic pulmonary fibrosis and may represent a field of cancerization associated with elevated cancer risk. Conclusions Collectively, this analysis defines matrix-driven features of poor prognosis to inform precision medicine prevention and treatment strategies towards improving SqCC patient outcome.

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.

Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment.

Background: Low bioavailability steroids, including beclomethasone dipropionate (BDP) and budesonide MMX, have been developed to ensure colonic targeting and low systemic activity than systematic corticosteroids in treating patients with ulcerative colitis (UC). Objectives: This systematic review and meta-analysis evaluated the efficacy and safety of BDP and budesonide MMX® compared with 5-aminosalicylic acid (5-ASAs) or placebo, in patients with mild-to-moderate UC. Design: Systematic review and meta-analysis Methods: We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials from inception to December 2021. We included all available randomized controlled trials (RCTs) comparing oral BDP or budesonide MMX with 5-ASAs or with placebo in induction of remission of mild-to-moderate UC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: We identified two RCTs comparing BDP 5 mg with 5-ASA, one RCTs comparing BDP 10 mg with 5-ASA, two RCTs BDP 5 mg versus placebo, one RCT BDP 10 mg versus placebo, two RCTs budesonide MMX 9 mg versus 5-ASA, and six RCTs budesonide MMX 9 mg versus placebo. In terms of achieving clinical remission or improvement, BDP 5 mg, BDP 10 mg, and budesonide MMX 9 mg were more effective than placebo (OR 2.36, 95% CI 1.37–4.08; OR 2.23, 95% CI 1.02–4.87; and OR 2.03, 95% CI 1.45–2.85, respectively). The drugs were also more effective than placebo in achieving endoscopic remission. Regarding the comparisons with 5-ASA, we found no differences between 5-ASA and BDP 5 mg or BDP 10 mg or budesonide MMX 9 mg in achieving clinical remission or improvement (OR 0.90, 95% CI 0.51–1.57; OR 1.54, 95% CI 0.42–5.64; and OR 1.17, 95% CI 0.82–1.66). However, 5-ASA was more effective than budesonide MMX 9 mg in achieving histological remission (OR 0.33, 95% CI 0.16–0.70). Overall, all the drugs were safe and well tolerated. Conclusion: Low bioavailability steroids were more effective than placebo in achieving clinical remission, clinical and endoscopic remission, and histological remission. No differences were found between 5-ASA and BDP or budesonide MMX. Surely, more RCTs, also comparing BDP and budesonide MMX, are mandatory to confirm or not these results.

Abstract Diatoms’ bloom dynamics, with seasonal cycling of waxes and wanes of cell abundance, imply frequent bottleneck and expansion events that can leave signatures in the genetic structure and diversity of populations. We explored changes in genetic diversity and structure within multiple species of the planktonic marine diatom genus Pseudo‐nitzschia living in sympatry in the Gulf of Naples (Tyrrhenian Sea, Italy) over 48 sampling dates (from 2011 to 2013) by means of metabarcode data. The genus Pseudo‐nitzschia includes complexes of cryptic species along with morphologically distinguishable ones. We assessed the resolution power of the hypervariable V4 region of the 18S rDNA in delimiting species using different algorithms and a set of reference sequences. We measured intra‐specific genetic diversity and differentiation among species over three annual cycles. Between‐species divergence was higher in the P. pseudodelicatissima complex, while signs of incomplete lineage sorting and/or introgression were detected in the P. delicatissima complex. Most of the species showed significant population differentiation over time, due to changes in haplotypic composition over the three years. Some haplotypes were lost and new ones appeared, with high polymorphism in species of the P. delicatissima complex. We hypothesize that the observed temporal changes in genetic structure result from frequent founder events linked to a population dynamic characterized by cyclical alternation of clonal expansions and bottlenecks and discuss possible factors affecting the microevolutionary pathways in these planktonic diatoms.

Praziquantel (PZQ) is an antihelmintic drug used worldwide against Schistosomiasis, despite its low solubility, bioavailability and the disgusting taste. This research represents a preliminary screening of 6 selected sweeteners in terms of their aptitude to be ground with PZQ, towards the development of a patient-friendly dosage form, capable of overcoming both dissolution and taste drawbacks. A vibrational mill was used to process equimolar mixtures of PZQ and each sweetener, and the dispersions were characterized by means of Differential Scanning Calorimetry, Powder X-ray Diffraction, Fourier Transform-Infrared Spectrometry, water solubility and Intrinsic Dissolution Rate. Physical stability of the coground systems was checked over a period of 1 year. The grinding for a short period (such as 30 min) of PZQ and selected sweeteners led to several very interesting products, with prevalent amorphous character, enhanced solubility and Intrinsic Dissolution Rate comparing to the raw drug. Peculiar behavior was found in the case of xylitol:PZQ ground mixtures where the appearance of traces of PZQ anhydrous Form B was noticed. Therefore, this research highlights the possibility of using binary premixes of PZQ and sweeteners in order to obtain an increase in the biopharmaceutical and organoleptic properties of the anthelmintic drug, underlining also the need for a careful screening of sweetener to design a PZQ patient-friendly dosage form.

The genomic profiling of tumours has not been widely adopted in the clinic due to technical and practical hurdles. Here, the authors develop PGDx elio tissue complete, a scalable, standardised and FDA-cleared test comprising a targeted gene panel and automated machine-learning analysis, which detects clinically relevant sequence biomarkers in cancer samples.