Patients with ulcerative colitis who have normalized histology are clinically stable after de-escalation of therapy

We have previously demonstrated that histological normalization in ulcerative colitis (UC) is associated with superior maintenance of remission outcomes. This single-center, retrospective case-control study assessed outcomes after the therapeutic de-escalation in UC patients who have achieved histologic normalization. A total of 111 patients were included, of which 24 underwent de-escalation, and 87 patients without therapeutic changes. The most commonly withdrawn therapy was aminosalicylates (50%), followed by immunomodulators (37.5%), and biologics (12.5%). Fourteen patients remained on therapies after de-escalation, including aminosalicylate (9/14), immunomodulators (3/14), and biologics (3/14), while 10 patients were not on any therapy immediately after withdrawal. Median follow-up was 43 months in the de-escalation group and 47 months in the control. The rates of clinical, endoscopic, and histologic recurrence were not significantly different between the two groups, nor was the proportion of patients who subsequently required additional therapies after withdrawal (P = 0.133). Clinical and endo-histologic recurrence rates were the lowest in patients who withdrew immunomodulators (0% and 14.3%, respectively). We demonstrate the clinical stability of therapeutic withdrawal in UC patients with histologic normalization

Trastuzumab-Based Combination Chemotherapy in Patients with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. Case Report 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. Case Report 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. Conclusion: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy

Ultraflexible Wireless Imager Integrated with Organic Circuits for Broadband Infrared Thermal Analysis

Kawabata R., Li K., Araki T., et al. Ultraflexible Wireless Imager Integrated with Organic Circuits for Broadband Infrared Thermal Analysis. Advanced Materials 36, 2309864 (2024); https://doi.org/10.1002/adma.202309864.Flexible imagers are currently under intensive development as versatile optical sensor arrays, designed to capture images of surfaces and internals, irrespective of their shape. A significant challenge in developing flexible imagers is extending their detection capabilities to encompass a broad spectrum of infrared light, particularly terahertz (THz) light at room temperature. This advancement is crucial for thermal and biochemical applications. In this study, a flexible infrared imager is designed using uncooled carbon nanotube (CNT) sensors and organic circuits. The CNT sensors, fabricated on ultrathin 2.4 µm substrates, demonstrate enhanced sensitivity across a wide infrared range, spanning from near-infrared to THz wavelengths. Moreover, they retain their characteristics under bending and crumpling. The design incorporates light-shielded organic transistors and circuits, functioning reliably under light irradiation, and amplifies THz detection signals by a factor of 10. The integration of both CNT sensors and shielded organic transistors into an 8 × 8 active-sensor matrix within the imager enables sequential infrared imaging and nondestructive assessment for heat sources and in-liquid chemicals through wireless communication systems. The proposed imager, offering unique functionality, shows promise for applications in biochemical analysis and soft robotics

Identification of mTEC precursor cells

Medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (Aire) are critical for preventing the onset of autoimmunity. However, the differentiation program of Aire-expressing mTECs (Aire+ mTECs) is unclear. Here, we describe novel embryonic precursors of Aire+ mTECs. We found the candidate precursors of Aire+ mTECs (pMECs) by monitoring the expression of receptor activator of nuclear factor-κB (RANK), which is required for Aire+ mTEC differentiation. pMECs unexpectedly expressed cortical TEC molecules in addition to the mTEC markers UEA-1 ligand and RANK and differentiated into mTECs in reaggregation thymic organ culture. Introduction of pMECs in the embryonic thymus permitted long-term maintenance of Aire+ mTECs and efficiently suppressed the onset of autoimmunity induced by Aire+ mTEC deficiency. Mechanistically, pMECs differentiated into Aire+ mTECs by tumor necrosis factor receptor-associated factor 6-dependent RANK signaling. Moreover, nonclassical nuclear factor-κB activation triggered by RANK and lymphotoxin-β receptor signaling promoted pMEC induction from progenitors exhibiting lower RANK expression and higher CD24 expression. Thus, our findings identified two novel stages in the differentiation program of Aire+ mTECs

Risk prediction models for dementia constructed by supervised principal component analysis using miRNA expression data

Alzheimer’s disease (AD) is the most common subtype of dementia, followed by Vascular Dementia (VaD), and Dementia with Lewy Bodies (DLB). Recently, microRNAs (miRNAs) have received a lot of attention as the novel biomarkers for dementia. Here, using serum miRNA expression of 1,601 Japanese individuals, we investigated potential miRNA biomarkers and constructed risk prediction models, based on a supervised principal component analysis (PCA) logistic regression method, according to the subtype of dementia. The final risk prediction model achieved a high accuracy of 0.873 on a validation cohort in AD, when using 78 miRNAs: Accuracy = 0.836 with 86 miRNAs in VaD; Accuracy = 0.825 with 110 miRNAs in DLB. To our knowledge, this is the first report applying miRNA-based risk prediction models to a dementia prospective cohort. Our study demonstrates our models to be effective in prospective disease risk prediction, and with further improvement may contribute to practical clinical use in dementia

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity

The eye is protected by the ocular immunosurveillance system. We show that tear duct–associated lymphoid tissue (TALT) is located in the mouse lacrimal sac and shares immunological characteristics with mucosa-associated lymphoid tissues (MALTs), including the presence of M cells and immunocompetent cells for antigen uptake and subsequent generation of mucosal immune responses against ocularly encountered antigens and bacteria such as Pseudomonas aeruginosa. Initiation of TALT genesis began postnatally; it occurred even in germ-free conditions and was independent of signaling through organogenesis regulators, including inhibitor of DNA binding/differentiation 2, retinoic acid–related orphan receptor γt, lymphotoxin (LT) α1β2–LTβR, and lymphoid chemokines (CCL19, CCL21, and CXCL13). Thus, TALT shares immunological features with MALT but has a distinct tissue genesis mechanism and plays a key role in ocular immunity