Pancreatic cancer is one of the most lethal malignancies, primarily due to late-stage diagnosis and limited therapeutic options. Cancer stem cells (CSCs) contribute to tumor heterogeneity, therapy resistance, and recurrence through activation of developmental pathways such as Hedgehog, Wnt, Notch, JAK-STAT, and Hippo. Identifying CSCs is therefore essential for understanding pancreatic ductal adenocarcinoma (PDAC) pathogenesis and advancing targeted therapies. This study compares the expression of key CSC-associated markers (CD44, CD117, OCT3/4, and c-Myc) in PDAC, fetal, and adult pancreas to elucidate CSC dynamics. Immunohistochemistry for CSC markers (CD44, CD117, OCT3/4, and c-Myc) was performed on PDAC tissues and control pancreatic samples (fetal pancreas 28–36 weeks and adult pancreas) to evaluate marker expression. Proliferative potential was assessed using CK7 and Ki-67 expression patterns. CD44 showed strong membranous and cytoplasmic expression in PDAC, moderate in fetal pancreas (epithelial/ductal regions), and minimal expression in adult tissue. CD117 was mainly restricted to stromal cells in PDAC, also present in fetal tissue but low in adults.c-Myc and Ki-67 were moderately expressed in PDAC, significantly higher than the control samples. CK7 demonstrated strong cytoplasmic staining in PDAC, moderate expression in adults, and weak expression in fetal samples. CD44 and c-Myc re-expression in PDAC supports their role as CSC-associated markers and potential drivers of tumor progression. CD117’s stromal localization suggests tumor–stroma interactions. These findings highlight developmental reactivation of CSC markers in PDAC, with implications for early detection and targeted therapy.

Purpose: To evaluate the safety and efficacy of ultrasound-guided retrograde internal jugular venous (IJV) puncture in neurointerventional procedures. Materials and Methods: This single-centre retrospective study evaluates data collected over 20 years. All punctures were performed under general anaesthesia using ultrasound guidance. The data were analyzed to assess patient demographics, indications and potential advantages, the technique of puncture, safety, outcomes, and complications associated with such punctures. Results: The study included 60 patients (males: n=38, 63%; females: n=22, 37%). The median age was 33 years (range 13–73 years). A total of 74 retrograde jugular punctures were performed. Isolated right-sided punctures were done in 31 patients (52%), isolated left-sided punctures in 18 (30%), and 11 patients (18%) underwent bilateral punctures. The preferred access needle was an 18G needle; however, micropuncture access was used in some patients. No inadvertent arterial punctures were encountered. The most common indication was mechanical thrombectomy for cerebral venous thrombosis (62%). Other indications included transvenous embolization of carotid-cavernous fistulae (16%), embolization of cerebral dural arteriovenous fistulae (8%), inferior petrosal sinus sampling (8%), and cerebral venous sinus angioplasty or stenting (6%). In all procedures, the expected technical outcome was achieved. Conclusion Ultrasound-guided retrograde IJV puncture is a safe and effective method for accessing neurovascular pathologies requiring a transvenous approach. Based on our experience, this access has been routinely used without any major complications. We foresee the technique being accepted on a larger scale in the future.

Cranial prostheses are frequently required for patients with cranial defects secondary to trauma, decompressive craniectomy, or other pathologies. When the resected or craniotomized bone cannot be reused, cranioplasty with artificial materials offers both aesthetic and protective benefits. However, high-end custom-made options, like polyether ether ketone or titanium prostheses, are expensive and not widely available. Heat-cured polymethyl methacrylate (PMMA) prostheses are generally preferred over their cold-cured counterparts. In-house dental laboratories can provide a cost-effective and practical solution by employing a lost-wax technique akin to denture fabrication, utilizing a three-dimensional printed custom open mold. Fabricating large heatcured PMMA cranioplasts presents certain challenges, such as the need for large flasks and potential porosity. These can be overcome by using a large stainless steel container (a tiffin box) and M-Seal epoxy to ensure an airtight curing process. This method can be easily adopted by standard dental laboratories. At our center, four patients have successfully fitted with cranioplasty prostheses produced using this technique. Even though the patients are outside of the scope of this technical note all of them indicated high satisfaction, and no complications were reported. This straightforward approach demonstrates that in-house, heat-cured PMMA cranioplasts can represent a viable, cost-effective option for cranial reconstruction.

Chronic kidney disease (CKD) affects 8%-15% of the population globally and can cause renal failure, partly due to lack of effective treatments and drug targets. Three novel cembrane diterpenoids papyifurans A‒C (1-3), in particular of 1 with an unprecedented trioxatetracyclo[10.2.1.1^2,5.1^6,9]heptadecane polyether scaffold, derived from Boswellia papyrifera resin, were found to effectively protect against renal fibrosis in vitro and in vivo. Their structures were fully characterized using a combination of spectroscopic, computational, modified Mosher's, and X-ray crystallographic analysis. In particular, we performed chemical proteomic analyses and found that Elongation factor 2 (EEF2) is the key target of compound 1 for anti-renal fibrosis in vitro. Moreover, previous studies have linked EEF2 with lung fibrosis, while compound 1 was found to inhibit the hallmarks of organ fibrosis in vitro. Such effects were observed to decrease with the knock down of EEF2 in vitro, suggesting that EEF2 might be a universal drug target of organ fibrosis. Collectively, the present study demonstrated an example of identifying drug targets by using structurally novel natural products, which will be beneficial for developing therapeutic agents against organ fibrosis.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Cranial prostheses are frequently required for patients with cranial defects secondary to trauma, decompressive craniectomy, or other pathologies. When the resected or craniotomized bone cannot be reused, cranioplasty with artificial materials offers both aesthetic and protective benefits. However, high-end custom-made options, like polyether ether ketone or titanium prostheses, are expensive and not widely available. Heat-cured polymethyl methacrylate (PMMA) prostheses are generally preferred over their cold-cured counterparts. In-house dental laboratories can provide a cost-effective and practical solution by employing a lost-wax technique akin to denture fabrication, utilizing a three-dimensional printed custom open mold. Fabricating large heatcured PMMA cranioplasts presents certain challenges, such as the need for large flasks and potential porosity. These can be overcome by using a large stainless steel container (a tiffin box) and M-Seal epoxy to ensure an airtight curing process. This method can be easily adopted by standard dental laboratories. At our center, four patients have successfully fitted with cranioplasty prostheses produced using this technique. Even though the patients are outside of the scope of this technical note all of them indicated high satisfaction, and no complications were reported. This straightforward approach demonstrates that in-house, heat-cured PMMA cranioplasts can represent a viable, cost-effective option for cranial reconstruction.

Background/Aims: Self-expanding metallic stents (SEMS) are an alternative to emergency surgery (ES) for malignant colorectal obstruction. This study aimed to compare surgical outcomes between SEMS as a bridge to surgery (BTS) and ES in patients with malignant colorectal obstruction. Methods: A comprehensive database search was conducted until October 2023 to compare outcomes between SEMS as a BTS and ES. A subgroup analysis of results by malignancy site was performed. Results: We analyzed 57 studies, including 7,223 patients over a mean duration of 35.4 months. SEMS as a BTS showed clinical and technical success rates of 88.0% (95% confidence interval [CI], 86.1%–90.1%; I2=68%) and 91.6% (95% CI, 89.7%–93.7%; I2=66%), respectively. SEMS as a BTS revealed reduced postoperative adverse events (odds ratio [OR], 0.51; 95% CI, 0.41–0.63; I2=70%; p<0.001) and 30-day mortality (OR, 0.52; 95% CI, 0.37–0.72; I2=10%; p<0.001) compared to ES. Subgroup analysis showed postoperative mortality of 5% and 1.5% for left- and right-sided malignancies, respectively. Adverse events were 15% and 33% for the right and left colon, respectively. Conclusions SEMS as a BTS demonstrated a higher success rate, fewer postoperative adverse events, and a reduced 30-day mortality rate than ES, supporting its use as the preferred initial intervention for right- and left-sided obstructions and indicating broader clinical adoption.

Background/Aims: The irregular Z-line, defined as a segment of columnar mucosa less than 1 cm in the distal esophagus, is often biopsied despite guidelines advising against it due to a low risk of progression to esophageal adenocarcinoma (EAC). However, the clinical significance of an irregular Z-line remains unclear. This meta-analysis examines the prevalence of Barrett’s esophagus, dysplasia, and EAC in patients with an irregular Z-line. Methods: We searched Medline, Embase, and Scopus databases up to October 2023 for studies on the prevalence of Barrett’s esophagus, dysplasia, and EAC in these patients. A random-effects model was used for meta-analysis, and heterogeneity was assessed using I2 statistics. Results: Nine studies involving 17,637 patients were analyzed. Among those with an irregular Z-line, the prevalence of intestinal metaplasia was 29.4%. In patients with intestinal metaplasia, dysplasia was found in 6.2%, low-grade dysplasia in 5.9%, high-grade dysplasia in 1.6%, and EAC in 1.5%. These rates were higher compared to those without intestinal metaplasia. Conclusions Patients with an irregular Z-line and intestinal metaplasia may be at higher risk and could benefit from endoscopic surveillance. Further studies are needed to determine the necessity of biopsying irregular Z-lines.

Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.

INTRODUCTION: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. METHODS: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. RESULTS: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS ( P = 0.026) and OS ( P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. CONCLUSION Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Mouth Neoplasms/mortality* ; Mouth Mucosa/radiation effects* ; Treatment Outcome ; Aged ; Adult ; Radiation Dose Hypofractionation ; Disease-Free Survival ; India ; Kaplan-Meier Estimate ; Dose Fractionation, Radiation ; Aged, 80 and over