Young Invincibles

Introduction: To describe the first case, to the authors' knowledge, of KeraKlear artificial corneal implant, assisted by a Carl Zeiss femtosecond laser, in iridocorneal endothelial (ICE) syndrome with secondary glaucoma. Patient and Clinical Findings: A 66-year-old woman with known ICE syndrome and secondary glaucoma in her right eye, using long-term glaucoma eyedrops (Xalacom, Simbrinza), presented with a 3-year history of progressive blurred vision in the right eye associated with a slowly enlarging whitish subepithelial fibrotic membrane from the temporal cornea, with corrected distance visual acuity deteriorating from 0.8 to 0.1 (Snellen). The fibrotic membrane is a subepithelial scar secondary to chronic corneal edema involving the temporal and central cornea. Diagnosis, Intervention, and Outcomes: A femtosecond laser-assisted KeraKlear artificial cornea implantation was performed in the patient's right eye. After 3 months, the KeraKlear prosthetic cornea remained stable with no signs of extrusion or periprosthetic corneal thinning. Corrected distance visual acuity was improved to 0.3 (Snellen), and the endothelial cell counts remained stable at around 2700 cell/mm 2 (vs 2800 in the left eye). Conclusions: Penetrating and endothelial keratoplasties carry a high risk for failure in ICE syndrome, especially in the setting of glaucoma. The KeraKlear was a useful alternative to keratoplasty in this setting, and unlike keratoplasty has not been shown to worsen glaucoma.

Gastric tube cancers are rare but clinically challenging entities that may arise years after esophageal or gastric surgery. Due to anatomical alteration and subtle mucosal changes, early detection remains difficult, particularly for signet-ring cell carcinoma (SRCC), which often progresses unnoticed. We report a rare case of micro SRCC arising in a reconstructed gastric tube, which was detected early and curatively resected by endoscopic submucosal dissection (ESD). The patient was initially diagnosed with adenocarcinoma of the esophagogastric junction during a routine esophagogastroduodenoscopy (EGD) performed as part of a medical check-up at a local clinic. He underwent ESD, but the pathological evaluation revealed a positive vertical margin, and he was subsequently referred to a tertiary center. Curative resection was achieved through open proximal gastrectomy combined with robot-assisted thoracoscopic esophagectomy of the middle and lower esophagus. Two years postoperatively, a follow-up EGD revealed a small, flat, whitish lesion measuring 5 mm on the lesser curvature of the gastric angle in the reconstructed gastric tube. Biopsy results revealed undifferentiated-type gastric cancer, predominantly composed of SRCC. Given the lesion’s clearly shallow invasion and very small size on endoscopic examination, ESD was performed. Pathological findings confirmed a 4 × 4 mm SRCC limited to the mucosal layer, with negative horizontal and vertical margins, and no lymphovascular invasion, consistent with curative resection. This case highlights the importance of vigilant long-term endoscopic follow-up after upper gastrointestinal surgery and demonstrates that even micro SRCCs in reconstructed gastric tubes can be successfully detected and treated at an early stage by ESD.

This study aims to analyze modal strategies in police press releases in two languages — Russian and English — with the aim of identifying the frequency and typology of modal meanings which are expressed in this type of texts. The object of the study is official police announcements (specifically, Russian-language and English-language press releases) as a genre of official business and public communication. The subject of the study is imperative and deontological modal constructions, that is, linguistic means of expressing obligation, permission, and prohibition. The material for the study was a corpus of 60 press releases, of which 30 were in Russian (from the Russian Ministry of Internal Affairs and regional departments), and 30 were in English (from the Metropolitan Police of London, the Los Angeles Police Department (LAPD), and others). The research methodology included discourse analysis, corpus analysis, comparative analysis, elements of pragmatic analysis, and an analysis of the functional semantics of the utterance. The analysis revealed that the most frequent sub-meanings are those of necessity conditioned by external circumstances (social, official, legal) and the influence of institutional will. Law enforcement press releases in both Russian and English predominantly feature indirect imperatives, represented by deontological constructions. Russian texts predominantly employ institutional-normative structures emphasizing the legal legitimacy of orders, while English texts favor performative and advisory forms reflecting a partnership strategy. The novelty of the research lies in identifying and systematizing linguistic strategies for expressing obligation, permission, and prohibition, as well as methods for softening and strengthening the direct nature characteristic of Russian-language and English-language police reports. This contributes to a comparative typology of modal meanings and their expressions. The research findings can be applied in training law enforcement specialists, press officers, and in teaching the translation of official institutional discourse. The findings can serve as the basis for developing methodological recommendations for law enforcement press officers.

Healthcare and social workers (HSWs) often face demanding psychosocial work environments, which may lead to hypnotic use. This study investigates the associations between psychosocial work conditions, mental distress, burnout, and hypnotic use among HSWs compared to general employees. Data from the 2022 Survey of Perceptions of Safety and Health in Work Environment in Taiwan included 202 HSWs and 808 matched general employees. Regression analyses examined relationships between psychosocial factors (e.g., job demands, job control, workplace violence) and mental health outcomes. HSWs reported higher job demands, workplace violence, burnout, and hypnotic use than general employees. Adverse psychosocial factors were linked to mental distress for both groups, with HSWs showing significantly higher odds of hypnotic use (OR, 2.47; 95% CI, 1.21-5.03). Targeted interventions are essential to enhance workplace conditions and mental health for HSWs.

(Abstracted from N Engl J Med 2024;391:526–537) Severe hemolytic disease of the fetus and newborn (HDFN) is the result of a transplacental transfer of maternal IgG alloantibodies, which can cause fetal anemia. Early-onset severe HDFN occurs at ≤24 weeks of gestation.

Unplanned hospital readmissions (UHRs) constitute a persistent health concern worldwide. A high level of UHRs imposes a burden on individuals, their families, and health care system budgets. This systematic review and meta-analysis aimed to evaluate the effectiveness of discharge interventions in the transition from hospital to home in the context of reducing UHRs. The study design was a meta-analysis of randomized and nonrandomized controlled trials. Eight databases were searched. The effect on UHR rates (odds ratio [OR]) of discharge interventions in the transition from hospital to home was calculated at a 95% confidence interval (95% CI) based on meta-regression and meta-analysis of random-effects models. Results showed that discharge interventions were effective in reducing rehospitalizations (effectiveness/OR =1.39; 95% CI, 1.24-1.55). It was furthermore determined that the studies showed heterogeneous characteristics ( P ≤ .001, Q = 50.083, I2 = 44.093; df = 28). According to Duval and Tweedie's trim and fill results, there was no publication bias. Interventions in which telephone communications and hospital visits (OR = 1.64; 95% CI, 1.25-2.16; P < .001) were applied together were effective among patients with cardiovascular diseases (OR = 1.54; 95% CI, 1.28-2.09; P < .001), and it was found that UHRs were reduced within a period of 90 days (OR = 1.68; 95% CI, 1.16-2.42; P < .001). It was also found that discharge interventions applied to transitions from hospital to home had a diminishing effect on UHRs as the publication dates of the reviewed studies advanced from the past to the present (OR = 0.015; 95% CI, 0.002-0.003; P < .001). Supporting and facilitating cooperation between health care professionals and families should be a key focus of discharge interventions.

(Abstracted from Lancet 2024;403:1341–1350) Prognosis for locally advanced cervical cancer is poor, with 5-year progression-free survival (PFS) and overall survival ranging from 47% to 80%. For the past several decades, treatment has included external beam radiotherapy with concurrent chemotherapy followed by brachytherapy, and novel therapeutic options are needed.

(Abstracted from Am J Obstet Gynecol 2024;230(2):109–117 The incidence rate for congenital cytomegalovirus (cCMV) infection ranges from 0.2% to 2.2%. CMV is the most common cause of congenital hearing loss and accounts for about a third of cases.

The robustness of large language models (LLMs) becomes increasingly important as their use rapidly grows in a wide range of domains. Retrieval-Augmented Generation (RAG) is considered as a means to improve the trustworthiness of text generation from LLMs. However, how the outputs from RAG-based LLMs are affected by slightly different inputs is not well studied. In this work, we find that the insertion of even a short prefix to the prompt leads to the generation of outputs far away from factually correct answers. We systematically evaluate the effect of such prefixes on RAG by introducing a novel optimization technique called Gradient Guided Prompt Perturbation (GGPP). GGPP achieves a high success rate in steering outputs of RAG-based LLMs to targeted wrong answers. It can also cope with instructions in the prompts requesting to ignore irrelevant context. We also exploit LLMs' neuron activation difference between prompts with and without GGPP perturbations to give a method that improves the robustness of RAG-based LLMs through a highly effective detector trained on neuron activation triggered by GGPP generated prompts. Our evaluation on open-sourced LLMs demonstrates the effectiveness of our methods.

BACKGROUND:Pulmonary hypertension (PH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and elevated mean pulmonary arterial pressure, resulting in right heart failure.METHODS:Here, we show that direct targeting of the endothelium to uncouple eNOS (endothelial nitric oxide synthase) with DAHP (2,4-diamino 6-hydroxypyrimidine; an inhibitor of GTP cyclohydrolase 1, the rate-limiting synthetic enzyme for the critical eNOS cofactor tetrahydrobiopterin) induces human-like, time-dependent progression of PH phenotypes in mice.RESULTS:Critical phenotypic features include progressive elevation in mean pulmonary arterial pressure, right ventricular systolic blood pressure, and right ventricle (RV)/left ventricle plus septum (LV+S) weight ratio; extensive vascular remodeling of pulmonary arterioles with increased medial thickness/perivascular collagen deposition and increased expression of PCNA (proliferative cell nuclear antigen) and alpha-actin; markedly increased total and mitochondrial superoxide production, substantially reduced tetrahydrobiopterin and nitric oxide bioavailabilities; and formation of an array of human-like vascular lesions. Intriguingly, novel in-house generated endothelial-specific dihydrofolate reductase (DHFR) transgenic mice (tg-EC-DHFR) were completely protected from the pathophysiological and molecular features of PH upon DAHP treatment or hypoxia exposure. Furthermore, DHFR overexpression with a pCMV-DHFR plasmid transfection in mice after initiation of DAHP treatment completely reversed PH phenotypes. DHFR knockout mice spontaneously developed PH at baseline and had no additional deterioration in response to hypoxia, indicating an intrinsic role of DHFR deficiency in causing PH. RNA-sequencing experiments indicated great similarity in gene regulation profiles between the DAHP model and human patients with PH.CONCLUSIONS:Taken together, these results establish a novel human-like murine model of PH that has long been lacking in the field, which can be broadly used for future mechanistic and translational studies. These data also indicate that targeting endothelial DHFR deficiency represents a novel and robust therapeutic strategy for the treatment of PH.