BACKGROUND & AIMS Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 μg/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.
Rapid and reliable identification of multivariate geochemical anomalies is critical for delineating prospective mineralized zones and reducing uncertainty in mineral exploration targeting. Extended isolation forest (EIF) is a powerful unsupervised ensemble learning algorithm that efficiently isolates anomalies from high-dimensional geochemical datasets using randomly oriented hyperplane partitions. Previous studies have demonstrated the effectiveness of EIF in multivariate geochemical anomaly detection and mineral potential modeling. However, its performance can be significantly affected by stochastic variability arising from random partitioning and random subsampling during isolation tree construction, which may result in unstable anomaly patterns and inconsistent exploration targets in complex geological environments. To mitigate this limitation, we developed a robust unsupervised framework for the identification of multivariate geochemical anomalies associated with gold mineralization in the Southwestern Yilgarn Craton, Australia. The proposed framework integrates robust factor analysis (RFA), a Jaccard-based stability index and EIF to enhance the reliability and reproducibility of anomaly detection. RFA was first applied to compositional soil geochemical data to identify the most significant pathfinder elements associated with gold mineralization, which were subsequently used as input variables for the EIF model. The model was then optimized using a Jaccard-based stability criterion to ensure consistent anomaly detection across repeated independent runs. Model performance was assessed using area under the receiver operating characteristic curve (AUC). The obtained AUC value of 0.82 indicates strong predictive capacity, confirming that the generated anomaly map effectively delineates mineralization-related geochemical patterns and provides a reliable proxy for mineral prospectivity mapping. Overall, the proposed framework offers a robust and reproducible unsupervised approach for multivariate geochemical anomaly detection with strong applicability in both greenfield and brownfield mineral exploration settings.
Background /Aims: Few studies have explored how family history of colorectal cancer (CRC) affects CRC incidence in inflammatory bowel disease (IBD). We estimated CRC incidence rates (IRs) and IR differences, by family history of CRC, and the interaction between IBD and family history. Methods Nationwide, register-based cohort study 1996-2023, including patients with IBD and matched (age, sex, parish, year) comparators from the general population. The exposure was family history, defined as the number of first-degree relatives (parent, sibling, or child) and their age at CRC diagnosis (<50 or ≥50 years). Results During a median follow-up of 11 years, 1,882 CRC events occurred in 124,387 patients with IBD (IR 1.17[95%CI:1.12-1.23]/1,000 person-years) and 14,177 CRC events in 1,213,641 comparators (IR 0.88[95%CI:0.86-0.89]/1,000 person-years). In IBD, the greatest CRC risk increase was seen in those with ≥2 affected relatives: 2.69(95%CI:0.60-4.78) additional cases per 1,000 person-years versus no family history, while risk increase with early-onset CRC heredity was modest: 0.42(95%CI: -0.47-1.31)/1,000 person-years. The IRs were comparable between patients and matched comparators with the same family history, except among those without family history of CRC, where the CRC incidence was higher in IBD. The relative effect of family history was weaker in IBD, where the baseline CRC risk was already elevated. Conclusion On the absolute scale, family history of CRC increased CRC incidence similarly in IBD and matched comparators, with the greatest increase in individuals with multiple affected relatives. Guidelines advise special attention to patients with family history of early-onset CRC; our findings raise the question if surveillance strategies should instead prioritize patients with multiple affected relatives.
Background & Aims In the duodenum of patients with irritable bowel syndrome (IBS), acute food-induced mucosal reactions have been visualized using confocal laser endomicroscopy (CLE). In uncontrolled studies, a diet excluding trigger foods led to symptomatic improvement. Here, we aim to assess the association of food-induced alterations identified using CLE and the efficacy of a targeted diet in a controlled study. Methods Double-blind, controlled, crossover study in patients with IBS. Following CLE, patients excluded up to two foods that did (= real diet) and up to two foods that did not (= sham diet) cause alterations in a randomized order. Diets were followed for four weeks each. Clinical response was defined as improving ≥50 points on the IBS symptom severity score (IBS-SSS). Healthy controls underwent the same CLE protocol as patients with IBS. Results Altered mucosa was visualized in all patients either before (11%) or after food administration. Clinical response rates were not different between real and sham diet (42% vs 36%, OR = 1.33, p = 0.6). Symptoms improved both on the real and the sham diet (-30 vs -20; p = 0.7). Also, in 15 healthy volunteers, altered mucosa was visualized in 100% of the exams either at baseline (13%) or after food administration. Conclusions Acute alterations visualized using CLE have poor sensitivity and specificity for dietary responses in IBS patients. Moreover, altered mucosa was present in 100% of healthy volunteers and likely represents a non-specific mucosal reaction to food exposure rather than pathology, challenging the use of CLE in clinical practice to identify culprit foods. (clinicaltrials.gov: NCT05097872)
Obesity remains one of the most prevalent costly diseases in the US and across the world. New therapies are available to treat obesity, and more therapies are in the pipeline. While lifestyle therapy by itself achieves only modest weight loss, the new generation anti-obesity medications, endoscopic bariatric and metabolic therapies and bariatric surgeries are highly effective at treating obesity. Despite these therapies, the rate of obesity in the US has remained stable. Multiple factors likely contribute to inadequate obesity treatment in the US including cost and insufficient insurance coverage, but lack of access to care due to insufficient numbers of providers prescribing anti-obesity medications or performing endoscopic or surgical procedures would remain a problem even with improved insurance coverage. Although most gastroenterologists do not have specific obesity training, they are in a unique position to help fill this void as the most effective obesity therapies are gut or gut hormone directed. This manuscript outlines the current obesity treatments, future therapies on the horizon, and clinical pearls for managing patients with obesity management medications, endoscopic bariatric and metabolic therapies, and bariatric and metabolic surgery.
Water conservancy and hydropower projects enhance regional climate resilience and watershed water security yet inevitably trigger large-scale involuntary reservoir resettlement. As representative involuntarily displaced populations, reservoir resettlees' social identity directly impacts local social stability and regional sustainable socioeconomic development. Based on a ten-year longitudinal qualitative investigation including in-depth interviews and participant observation in Village Y of Wuxikou Reservoir, Jiangxi Province, this paper divides the entire resettlement process into three stages: relocation, stabilization and development. From the dual perspectives of host community identity and out-groups identity, this study explores the dynamic evolutionary rules of resettlees' social identity. The results indicate that resettlees sequentially develop alienated identity, superficial adaptive identity and segregated identity across different phases. On this basis, the core concept of differential identity is proposed, which features a dual structure of vertical temporal differentiation and horizontal spatial differentiation. This paper expands the applicable scope and explanatory power of the “differential mode of association” and social identity theory in involuntary resettlement contexts. Grounding on the differential identity framework, this paper puts forward targeted integrated governance solutions to break intergroup segregation, facilitate cross-group integration and build resilient resettlement communities consistent with Sustainable Development Goals (SDGs) 11 and 13.
The discrimination of ore deposit types is primarily based on geological, geochemical, and isotopic characteristics. Conventionally, these types are identified using specific element diagrams. However, traditional geochemical methods often fail to determine scheelite deposit types of the complex Xuefengshan Sb-Au-W metallogenic belt in China, where mineralization resulted from the superposition of multiphase geological events. Machine learning (ML) methods, have been increasingly applied to identify deposit genesis by establishing relationships between deposit characteristics and genetic types using extensive datasets. However, inaccurate data labels, the limitations of single models, and poor model interpretability lead to decreased accuracy. This study proposes a ML framework based on interpretable ensemble learning. We collects geochemical element data from typical orogenic and magmatic-hydrothermal scheelite deposits globally. Deep clustering is used to filter data and overcome the subjectivity of original data labels. An ensemble learning model is used to construct a classifier to improve the model's robustness and generalization ability. An interpretable model is introduced to analyze the contribution of individual feature elements, revealing the metallogenic genesis. This method demonstrates high accuracy on the test set. According to this method, the scheelite deposit type of the Xuefengshan metallogenic belt is primarily magmatic-hydrothermal in origin, with orogenic superposition. This helps resolve a long-standing controversy in the region and establishes a repeatable and interpretable new paradigm for ML-based discrimination of ore deposit genetic types.
Though volcanogenic massive sulfide (VMS) deposits are major global sources of indium (In), the physicochemical mechanisms and key factors controlling its significant enrichment remain poorly understood. To address the issue, this study investigates the Tiemurt VMS Pb-Zn-Cu deposit, utilizing detailed petrography, in-situ LA-ICP-MS analysis, and thermodynamic modeling to reveal the In enrichment mechanisms in VMS deposits. Petrographic observations identified two distinct generations of sphalerite corresponding to different mineralization stages. The early-stage sphalerite (Sp1) is euhedral-subhedral, associated with pyrite, and displays darker colors (red to brown), whereas the late-stage sphalerite (Sp2) is anhedral, intimately intergrown with chalcopyrite, and shows lighter colors (mainly yellow). The trace element results demonstrate that Sp1 has a significantly higher In content (average 317 ppm) than Sp2 (average 220 ppm). Additionally, In concentrations positively correlate with Fe contents. Because Fe is the primary chromophore that darkens sphalerite, this strong coupled enrichment mechanism allows macroscopic sphalerite color (red > brown > yellow) to serve as a reliable indicator for In concentration. Crystallization temperatures calculated using the GGIMFis thermometer range from 344 to 382 °C for Sp1 and 312 to 355 °C for Sp2, indicating a cooling trend during fluid evolution. Thermodynamic modeling data showed that in the early-stage hydrothermal fluids (≥360 °C), Zn2+ preferentially complexes with Cl−, leaving InCl2+ or In3+ as unstable species, and In efficiently precipitates into Sp1 under the environment of log fO2 = −32 to −26 and pH = 6–8. As the fluids cool at ~340 °C, weakened Zn2+ competition allows In3+ to form stable InCl3, and In precipitates into Sp2 under the conditions of log fO2 = −42 to −32 and pH = 5.5–11. We therefore conclude that the key factor controlling the difference in In content between Sp1 and Sp2 is the precipitation mechanism rather than migration capacity. This may be different from the In enrichment mechanism associated with magmatic hydrothermal systems, where In is mainly present as InCl3 complexes with strong migration capacity. These new findings enable us to understand how the physicochemical conditions of fluids control the enrichment of In in VMS deposits, and also highlight that the color of sphalerite can be used to target potential In resources in PbZn deposits.
