Subsequent Closure Research Articles

Kir4.1 and Aqp4 Contribution to Schisis Cystic Water Accumulation and Clearance in the Rs1 Exon-1 Del XLRS Rat Model

Background/Objective: The Rs1 exon-1-del rat (Rs1KO) XLRS model shows normal retinal development until postnatal day 12 (P12) when small cystic spaces start to form in the inner nuclear layer. These spaces enlarge rapidly, peak at P15, and then collapse by P19. Methods: We explored the possible involvement of Kir4.1 and Aqp4, the principal retina channels for water movement and homeostasis, along with Muller glia cells (MGCs), using semi-quantitative fluorescent immunohistochemistry at P7, P9, P12, and P30, in Rs1KO and WT littermates. Results: Kir4.1 expression was reduced in Rs1KO retinas at all the early time points—P7, P9, and P12—as the schisis cavities began to form; downregulation would reduce water egress from the retina. Aqp4 was upregulated at P30 in Rs1KO retinas during schisis cavity closure but not as cavities formed at P12. When examined by GFAP expression, MGCs were not activated at the preschisis P12 age but showed considerable GFAP expression at P30 following retinal cystic structural damage at P15, indicating that MGCs were activated during the period of retina water removal and cavity closure. Conclusions: The study results implicate the downregulation of Kir4.1 in schisis formation and a role for both Kir4.1 and Aqp4 upregulation in subsequent schisis closure.

Insights into the structure and polymerization mechanisms of CO molecules under pressure

High pressure technique can greatly enrich the chemistry research by innovating the traditional research paradigm. Recently, tremendous attentions have been paid to the high-pressure behavior of low-Z molecules, such as CO, CO2, N2, O2 and mixtures. These molecules tend to polymerize into extended solids at the pressure of 1−100 GPa, but the structures and polymerization mechanisms are still poorly understood. Herein, as a research model, high pressure polymerization process of carbon monoxide (CO) is studied in detail both experimentally and theoretically. The in-situ Raman spectra and angle- resolved X-ray diffraction experiments prove the successful synthesis of p-CO and its amorphous structure. The theoretical simulations reveal that two CO molecules dimerize into the ethylenedione (OCCO) diradical with spin-polarized singlet state firstly, then the OCCO diradical induces the subsequent chain elongation, ring closure and chain crosslinking reactions, leading to formation of the amorphous 3D network. The multiple basic units, hybrid coordination of C/O atoms and complex connecting styles in p-CO are revealed. Based on the polymerization mechanisms, the fundamental principles governing the character (amorphous or crystalline) of extended solids under high pressure are elucidated. Due to the small dipole moment and the head-to-tail disorder of CO molecules, it is reasonable to speculate that crystalline p-CO may exist under more rigorous conditions than 110 GPa and 2000 K, at which the isoelectronic nitrogen (N2) molecules polymerize into a single-bonded cubic form of nitrogen. Our study provides a profound insight into the polymerization mechanism and structures of low-Z CO molecules under compression, contributes to the diversified chemical researches and has a generally scientific implications for the interior dynamics of planets.

Association of cytochrome P450 CYP2C9 (rs1057910) gene polymorphism and ibuprofen response in preterm neonates diagnosed with patent ductus arteriosus

Background Patent ductus arteriosus (PDA) closure is one of the most significant changes necessary to transition to extrauterine life. The failure of closure in preterm infants has been associated with a variety of complications. Aim and objectives This study aim to investigate the correlation between cytochrome P450 CYP2C9 gene polymorphism and the response to ibuprofen treatment in preterm neonates with PDA. Subjects and methods This prospective study was conducted on 64 preterm neonates with patent ductus arteriosus (hsPDA). The neonates were treated with ibuprofen and diagnosed using clinical and echocardiographic examinations. The study was carried out at the Neonatal Intensive Care Unit (NICU), Pediatric Department, Kasr Alainy and ElMounira Pediatric Hospitals, Cairo University, in June 2018. Results A statistically significant difference in respiratory rate was observed between both groups ( p = 0.047). Additionally, there was a significant difference in the duration of treatment with ibuprofen ( p = 0.021). Treatment with ibuprofen had no impact on renal function parameters. The platelet count decreased after treatment with no statistical difference. Conclusion Use of Oral ibuprofen is a highly effective treatment for HsPDA in preterm neonates, demonstrating a remarkable success rate of 92.2% and fewer adverse effects. Whilst no correlation between the CYP2C9 (rs1057910) gene polymorphism and the efficacy of oral ibuprofen response, Other factors affecting the response of oral ibuprofen and subsequent PDA closure include gestational age, birth weight, Apgar score at 5 min, ductal diameter, RDS, and sepsis.

Transcranial Doppler as a Primary Screening Tool for Detecting Right-to-Left Shunt in Cryptogenic Stroke Patients?

Cryptogenic stroke (CS), a subtype of ischemic stroke with undetermined etiology, accounts for approximately 25% of the cases. Patent foramen ovale (PFO) is an important potential cause of CS via paradoxical embolism. While transesophageal echocardiography (TEE) is the current gold standard for PFO detection, transcranial Doppler (TCD) ultrasound offers a noninvasive alternative with potential advantages in sensitivity for right-to-left shunt (RLS) detection. This study's main goal is to evaluate the diagnostic performance of TCD compared to TEE for PFO detection in CS patients. We prospectively enrolled 110 patients aged 18-65years with confirmed CS from 2020 to 2024. All underwent TCD screening for RLS using a standardized protocol. Subsequently, they were categorized based on a simplified version of the Spencer Logarithmic Scale, followed by confirmatory TEE. Clinical characteristics, imaging findings, TCD results, and indications for PFO closure were analyzed. The mean age of the cohort was 45years, with 58.2% being males. TEE identified PFO in 44.5% (49/110) of subjects. TCD accurately detected RLS in 42 of the 49 PFO cases (85.7%) confirmed by TEE. For PFO detection, TCD demonstrated a sensitivity of 85.4%, specificity of 88.5%, PPV of 85.4%, and Youden's index of 0.73. Notably, of the seven PFO cases missed by TCD, none received percutaneous closure based on clinical criteria. TCD exhibited high diagnostic accuracy for detecting high-risk PFO in patients with CS when compared to the gold-standard TEE. As a noninvasive modality, TCD may serve as an effective screening tool to identify CS patients who could potentially benefit from confirmatory TEE and subsequent PFO closure intervention. The findings support the use of TCD as a screening tool to triage CS patients for confirmatory TEE and potential PFO closure.

Synthesis of Perfluoroalkylated Pyrazoles from α-Perfluoroalkenylated Aldehydes.

Within this study, we report a simple two-step process for the synthesis of perfluoroalkylated pyrazoles from aliphatic aldehydes. In the photocatalytic first step, the aldehydes are transformed into the corresponding perfluoroalkylated enals, which then undergo nucleophilic attack by hydrazine and subsequent ring closure, providing the fluorinated 3,4-substituted pyrazole products in a 64-84% yield. Using triphenylphosphine and imidazolidinone as organocatalysts, the method is operationally simple and omits heavy metal-containing waste.

Ablation Strategies for Repeat Procedures in Atrial Fibrillation Recurrences Despite Durable Pulmonary Vein Isolation: The Prospective Randomized ASTRO AF Multicenter Trial.

Ablation strategies for patients with symptomatic atrial fibrillation and isolated pulmonary veins vary and their effects on arrhythmia recurrence remain unclear. A prospective randomized German multicenter trial sought to compare 2 ablation strategies in this patient cohort. Patients with atrial fibrillation despite durable pulmonary vein isolation were randomly assigned at 7 centers to undergo low-voltage area ablation using 3-dimensional mapping and irrigated radiofrequency current ablation (group A) or empirical left atrial appendage isolation (LAAI) using the cryoballoon followed by staged interventional left atrial appendage closure (group B). The primary end point was freedom from atrial tachyarrhythmias between 91 and 365 days after index ablation. The study was powered for superiority of LAAI compared with low-voltage area. Patients (40% women; mean age, 68.8±8 years) with paroxysmal (32%) or persistent atrial fibrillation (68%) were randomized to undergo low-voltage area ablation (n=79) or cryoballoon-guided LAAI (n=82). After a planned interim analysis, enrollment was halted for futility on January 10, 2023. In the LAAI group, 77 of 82 left atrial appendages were successfully isolated with subsequent left atrial appendage closure in 57 patients. Procedure-related complications occurred in 4 (5%) and 11 (13.5%) patients in group A and B, respectively (P=0.10). The median follow-up was 367 days (interquartile range, 359-378). The Kaplan-Meier point estimate for freedom from atrial tachyarrhythmias was 51.7% (CI, 40.9%-65.4%) for group A and 55.5% (CI, 44.4%-69.2%; P=0.8069) for group B. The current study did not detect superiority of cryoballoon-guided LAAI over low-voltage area ablation in patients with atrial fibrillation despite durable PVI. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04056390.

The role of vitreous cortex remnants in secondary macular hole formation and spontaneous closure following vitrectomy for rhegmatogenous retinal detachment

BackgroundMacular hole (MH) formation after rhegmatogenous retinal detachment (RRD) surgery is rare, and in most cases, additional surgical procedures are required to repair MH. Spontaneous closure of the MH is even rarer. In this study, we aimed to report a series of cases of spontaneous closure of the secondary MH and provide a review of the literature. MethodsWe retrospectively collected the cases of secondary MH formation following vitrectomy in RRD patients followed by spontaneous closure. Ophthalmological data at presentation and during follow-up were collected and analyzed. ResultsWe reported a total of three RRD patients aged 31,67,12 years, including two females and one male. The three patients underwent pars plana vitrectomy (PPV) with either silicone oil tamponade or air tamponade. Optical coherence tomography (OCT) revealed a second full-thickness MH formation with remnant vitreous cortex bridging in the macular region during early follow-up. Observations of the cases revealed subsequent remnant vitreous cortex traction remission and spontaneous closure of MH during follow-up, although with subsequent thin macular and abnormal macular structure. ConclusionThe progression of secondary MH formation in the cases may be related to vitreomacular traction (VMT) by the posterior vitreous cortex remnant after PPV, and the release of VMT may help the spontaneous closure of the MH after PPV for RRD.

Investigating colostomy-related morbidity in children following stoma formation and closure in a tertiary hospital, Abha, Saudi Arabia: a retrospective cohort study 2024

BackgroundOverall, stoma-related morbidity affects a reported 20–38% of pediatric patients. However, determining the true incidence of major stoma-related morbidity is challenging due to limited cohort sizes in existing studies. Thus, the aim of this study was to investigate colostomy related morbidity among children both after stoma formation and stoma closure.MethodologyThis is a retrospective cohort hospital-based study, conducted in an Abha maternity and children hospital, between August 1, 2018, and August 1, 2023, among 126 pediatric patients (aged 0–12 years) who underwent colostomy formation and subsequent closure during the study period. Data were collected from medical records. Data was analyzed using Statistical Package for Social Sciences (SPSS) v.26.ResultsThis study included a total of 126 children who underwent colostomy. (N = 37, 29.4%) of cases included in this study were emergency cases, while (N = 89, 70.6%) were elective. A variety of antibiotics were used for surgical prophylaxis, metronidazole (77%) and cefuroxime (62.7%) were the most prevalent. Oral feeding was started after 5–6 days in more than one third of cases (39.7%). Wound infection (N = 15, 11.9%) was the most reported post-operative complication, followed with bowel obstruction (N = 6, 4.8%). Emergency cases had a longer duration of hospital stay than elective cases; this difference was statistically significant (P = .04).ConclusionsMajority of patients reported no stoma related complications, while among those who reported complications, wound infection was the most reported complication, followed by bowel obstruction.

EP202 - Mesh-Mediated Fascial Traction (MMFT) and Negative Pressure Abdominal Dressing (ABTHERA): Useful in Difficult Open Abdomens?

Abstract Background Challenging abdominal surgical emergencies may require an 'Open Abdomen (OA)' as a life-saving procedure. OA has serious complications: wound infection, fluid and protein loss, catabolic state, loss of abdominal domain, and entero-atmospheric fistula. To assess the efficacy of mesh-mediated fascial traction (MMFT) & Abthera Dressing in achieving definitive abdominal closures. Patients and Method Retrospective analysis of prospectively collected data of 6 patients managed between August and November 23 in a large DGH. Following laparotomy and management of primary pathology, Abthera Dressing combined with bilateral continuous 2-0 PDS suture fixation at 0.5cm gap of macroporous Prolene (Merinium, Meril Life) meshes to each rectus sheath followed by sequential midline mesh traction closure over a time period that allowed subsequent definitive abdominal wound closure. Data collection included patient demographics (age, sex, BMI, ASA), intervention details for OA, wound characteristics, follow-up, and outcome. Results Six included M: F 4:2, age 61* (40-76 ) years, BMI 30* ( 24-35), ASA 3. Three were strangulated incisional hernia, 2 burst abdomens from faecal peritonitis, and 1 necrotizing fasciitis. Initial wound length 25*(20-32) cm, width 12.5* (4-17) cm after management of primary pathology reduced to width 4.5* (0-9) cm through MMFT and Abthera Dressing followed by definitive abdominal closure. Relook surgery required were 4* (1-9) with one full and 4 bridged mesh closures. Length of stay 39* (14-74) days. One death from respiratory failure. Conclusion The study highlights the benefit of MMFT & Abthera Dressing in achieving definitive abdominal closure for challenging OA where primary abdominal closure was not possible. * Median

50216 Topical Timolol for Improving the Appearance of Surgical Scars following Mohs Surgery with Subsequent Primary Linear Closure: Results from a Split-Scar Clinical Trial

50216 Topical Timolol for Improving the Appearance of Surgical Scars following Mohs Surgery with Subsequent Primary Linear Closure: Results from a Split-Scar Clinical Trial

Design of a Multicenter, Randomized Controlled Trial for the Treatment of Peripheral Neuropathic Pain (COMFORT Study) with a Micro-Implantable Pulse Generator.

Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone.

Synthesis of 1,3-benzotellurazole derivatives from phenyl ureas and tellurium tetrachloride

A method has been developed to prepare previously inaccessible substituted 1,3-benzotellurazoles following an efficient two-step process, consisting of the tellurination of electron rich phenyl ureas with tellurium tetrachloride and subsequent ring closure of the resulting aryl tellurium trichlorides. Tellurination occurs regiospecifically ortho to the urea moiety due to intramolecular Te–O coordination, producing highly crystalline solids that are readily isolated in yields up to 83 %. Subsequent ring closure, accomplished by heating with phosphorus trichloride and subsequent reduction with hydrazine hydrate, provides access to 1,3-benzotellurazole derivatives. Selected products were characterized by X-ray crystallography.

Opening and Closure of the Sulu Sea: Revealed by Its Peripheral Subduction and Collision Processes

The Sulu Sea is a small marginal sea in the western Pacific, but it is a very complex and tectonically active region, situated amidst the convergence of the Eurasian, Pacific, and India-Australian plates. Deciphering its geodynamic evolution is crucial, but our understanding of its opening, closure, and tectonic history remains inadequate. The main aim of this study was to systematically study the opening and subsequent closure of the Sulu Sea though discerning tectonic unconformities, structural features, and subduction-collision tectonic zones around margins of the sea. The interpreted sections and gravity anomaly data indicate that the NE Sulu Sea has undergone Neogene extension and contraction due to subduction and collision along the northern margins of the Sulu Sea, whereas the SE Sulu Sea gradually extended from northwest to southeast during the Middle Miocene and has subsequently subducted since the Middle Miocene along the southeastern margins of the Sulu Sea. Several subduction and collision boundaries with different characteristics were developed including continent-continent collision, arc-continent collision, and ocean-arc subduction. The different margins of the Sulu Sea showed distinct asynchronous subduction and collision processes. The northern margins of the Sulu Sea can be divided into three subduction-collision tectonic zones from west to east: the Sabah-Nansha block collision has occurred in NE Borneo since the Early Miocene, followed by the SW Palawan-Cagayan arc collision in SW Palawan Island since the Middle Miocene, and the NW Palawan-Mindoro arc collision since the Late Miocene with further oblique subduction of the Philippine Sea Plate. The southeastern margins can also be divided into two subduction tectonic zones from south to east: the SE Sulu Sea has subducted southward beneath the Celebes Sea since the Middle Miocene, followed by the southeastward subduction beneath the Philippine Sea Plate since the Pliocene. Since the Miocene, the interactions among the Australia-India, the Philippine Sea, and the Eurasian plates have formed the circum-Sulu Sea subduction-collisional margins characterized by microplate collisions, deep-sea trough development, and thick sediments filling in the orogenic foreland. This study is significant for gaining insights into the opening and closure of marginal seas and the dynamics of multiple microplates in Southeast Asia.

Evaluation of Point-of-Care-Directed Coagulation Management in Pediatric Cardiac Surgery.

Coagulatory alterations are common after pediatric cardiac surgery and can be addressed with point-of-care (POC) coagulation analysis. The aim of the present study is to evaluate a preventive POC-controlled coagulation algorithm in pediatric cardiac surgery. This single-center, retrospective data analysis included patients younger than 18 years who underwent cardiac surgery with cardiopulmonary bypass (CPB) and received a coagulation therapy according to a predefined POC-controlled coagulation algorithm. Patients were divided into two groups (<10 and >10 kg body weight) because of different CPB priming strategies. In total, 173 surgeries with the use of the POC-guided hemostatic therapy were analyzed. In 71% of cases, target parameters were achieved and only in one case primary sternal closure was not possible. Children with a body weight ≤10 kg underwent surgical re-evaluation in 13.2% (15/113), and respectively 6.7% (4/60) in patients >10 kg. Hemorrhage in children ≤10 kg was associated with cyanotic heart defects, deeper intraoperative hypothermia, longer duration of CPB, more complex procedures (RACHS-1 score), and with more intraoperative platelets, and respectively red blood cell concentrate transfusions (all p-values < 0.05). In children ≤10 kg, fibrinogen levels were significantly lower over the 12-hour postoperative period (without revision: 3.1 [2.9-3.3] vs. with revision 2.8 [2.3-3.4]). Hemorrhage in children >10 kg was associated with a longer duration of CPB (p = 0.042), lower preoperative platelets (p = 0.026), and over the 12-hour postoperative period lower platelets (p = 0.002) and fibrinogen (p = 0.05). The use of a preventive, algorithm-based coagulation therapy with factor concentrates after CPB followed by POC created intraoperative clinical stable coagulation status with a subsequent executable thorax closure, although the presented algorithm in its current form is not superior in the reduction of the re-exploration rate compared to equivalent collectives. Reduced fibrinogen concentrations 12 hours after surgery may be associated with an increased incidence of surgical revisions.

Local Control of Pyoderma Gangrenosum Using Human Amniotic Membrane and Transcriptome Analysis.

Pyoderma gangrenosum (PG) is a rare, chronic, ulcerative disease characterized by non-healing wounds that worsen with debridement, a phenomenon called pathergy. No consensus regarding pathogenesis, diagnosis, or treatment exists for PG. A previous pilot study using dehydrated human amniotic/chorionic membrane (dHACM), following excisional debridement, augmented PG wound healing and allowed for subsequent wound closure through split-thickness skin grafting (STSG). In this clinical trial (NCT05120726), four patients with an established PG diagnosis were enrolled to undergo treatment with dHACM and characterize the pre- and post-treatment transcriptome profiles. RNA sequencing was used to isolate the total RNA from specimens. Genes of particular interest were quantified through real-time quantitative reverse transcription polymerase chain reaction. We observed varied changes to the local expression of inflammatory response, positive regulators of cellular proliferation, and extracellular matrix disassembly cytokines. All PG wounds produced granulation tissue following treatment and were closed using split-thickness skin grafts.

A Technique for Peripheral Compartment First and Periportal Access for Hip Arthroscopy

Hip arthroscopy has become the preferred method for surgical management of numerous hip pathologies. Traditionally, arthroscopic access to the hip has mainly been performed by starting in the central compartment first, which commonly requires capsulotomy and subsequent closure to access the hip joint. This technique is both technically challenging and has been associated with iatrogenic damage to the hip cartilage, as well as the labrum, potentially compromising the integrity of the hip capsule. In this Technical Note, we present our approach to hip arthroscopy that accesses the hip through the peripheral compartment first, with minimal periportal capsulotomies, using a post-less traction bed. This technique can decrease the risk of iatrogenic damage, decrease surgical time, and improve visualization and accessibility for both novice and advanced hip arthroscopy surgeons.

Resilience, remoteness and war shape the land cover dynamics in one of the world's largest miombo woodlands

The highlands of southeast Angola are one of the world's largest intact formations of miombo woodland. Recent interest from conservation groups is increasing the possibility of a new protected area in this conflict-afflicted, remote region, contributing to the “30 × 30” target of the Global Biodiversity Framework. With the potential for a new protected area, it is important to quantify the extent and change of natural and anthropogenic land covers in the region, not least because of the close dependence of livelihoods on natural resources in the miombo. We developed a 1990–2020 land cover time series, analysing deforestation, canopy opening, canopy closure, and vegetation regrowth after disturbance. Regional woodland extent has remained roughly constant despite frequent transitions between dense and open woodlands. Canopy opening peaked post-civil war, potentially related to the resettlement of displaced people. Over 30 years, 61 % ± 2 % of canopy opening was offset by subsequent canopy closure, which peaked a decade after the war ended, indicating the resilience of miombo systems. A woodland resource-use frontier, consisting of deforestation and canopy opening, is evident in the north-west of the area, likely driven by urban demand for agricultural products, charcoal, timber and other wood-derived goods. A distinct “core” of dynamic woodland occupies 52 % of the study region, where there is no evidence that shifting cultivation and local livelihoods are a net cause of land cover change. We do not find evidence for extensive net woody encroachment, only 2 % of the study region is being encroached by woody vegetation. This canopy closure is associated with remoteness from anthropogenic pressures and biophysical drivers that facilitate woody vegetation growth. Policymakers and conservation managers can use these data to aid in locating and prioritising interventions to sustainably produce agricultural and wood fuel products to meet increasing urban demand. Additionally, supporting conditions for maintaining both biophysical processes and livelihoods in remote areas is crucial to achieving 30 × 30 equitably.

Theoretical investigation on diastereoselective [2+2] cycloaddition and Pd-catalyzed enantioselective [3+2] cycloaddition for synthesis of cis-β-lactam and exo-furobenzopyranone

The mechanism is investigated for Wolff rearrangement/Staudinger [2+2] cycloaddition cascade and Pd-catalyzed, decarboxylative, formal [3+2] cycloaddition. Wolff rearrangement of 3-diazotetramic acid is determined to be rate-limiting step generates cyclic acyl ketene. The interaction of ketene with imine firstly results in zwitterion followed by conrotatory cyclization giving major cis-β-lactam. For synthesis of s-VECs, the epoxidation−cyclization cascade and hydrolysis give precursor of better performing exocyclic derivative. The reaction with 3-cyanochromone includes decarboxylation, nucleophilic attack and subsequent ring closure yielding 5-exo-trig furobenzopyranone. Based on the comparison between possible paths, the diastereoselectivity of cis over trans and regio-divergence of 5-exo-trig over 7-endo-trig are both kinetically controlled for [2+2] and [3+2] cycloaddition in common. The positive solvation effect is suggested by decreased absolute and activation energies in chlorobenzene and chloroform solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.

The Violation of the Law and Religious Freedom in the Context of the Case of the Russian Church in Sofia—A Real Legal, Political and Canonical Issue

For more than a century, in the center of Sofia, the capital of the Republic of Bulgaria, there is and functions the church of St. Nikolai Mirlikiyski the Wonderworker, known as the Russian church. The church was built at the beginning of the 20th century with the idea of being part of the complex of the Russian imperial diplomatic body in Sofia and to serve the Russian diplomats, their families and the Orthodox Russian citizens living permanently or temporarily in the Bulgarian capital. However, after its consecration in 1914, disputes began, both regarding the ownership of the church building and the canonical jurisdiction of the church—of the Metropolitan of Sofia or the Holy Synod of the Russian Orthodox Church in Moscow. This dispute culminated in September 2023, with the expulsion from Bulgaria of several Russian and Belarusian clergies serving in the Russian church on charges of espionage in favor of the Russian Federation. The subsequent closure of the church by the Russian ambassador Mitrofanova led to internal and external political tension and ecclesiological chaos in the country. The Russian side violated the Bulgarian Law on Religions, known as the Confessions Act 2002, and directly infringed the Statute of the Bulgarian Orthodox Church. This article provides expert answers to the public law, property rights and canonical issues concerning the case of the Russian church in Sofia, based on the relevant sources of law (ecclesiastical and civil).

Investigating the Effect of Liver Regeneration on Tumor Growth: Development of a Mouse Model with Orthotopic Implantation of Patient-derived HCC Organoids

Abstract Background Recurrence after hepatocellular carcinoma (HCC) treatment is a significant problem. It affects more than 70% of patients undergoing liver resection. Recurrence can arise from undetected micro metastasis or de novo cancer. Clinical and experimental studies suggest that liver regeneration ensuing surgical resection may activate occult micro-metastasis leading to regeneration induced tumor recurrence. However, in vivo patient-derived organoid (PDO) HCC models that are translatable to patient tumors are sparse. Aims Here, we aim to establish a new in vivo model to understand the impact of liver regeneration on HCC tumor growth. Methods PDOs were generated from HCC tissue obtained from patients undergoing liver resection at the Clarunis University Digestive Health and Care Center and transduced with firefly luciferase. Implantation was performed via laparotomy and orthotopic injection of the organoids in the right superior liver lobe. Tumor growth is monitored by in vivo bioluminescence imaging until the endpoint of the experiment. As a primary endpoint tumor growth two weeks after liver resection was defined. Experimental groups underwent either minor (30%) or major (65%) hepatectomy of tumor-free liver, whereas the control group received a re-laparotomy with subsequent closure of the abdomen. Normal liver and tumor tissue were characterized using immunohistochemistry. Results Two HCC-PDO lines were successfully implanted. Compared to the control, after minor and major liver resection the mean weight increased significantly to 0.82% (p &amp;lt; 0.0001) respectively 0.99% (p &amp;lt; 0.0001). Preliminary data about the tumor volume have yet to be concluded. Histology and immunohistochemistry staining for HCC confirmed the origin of the PDOs from the original patient tumor. Conclusion The establishment of an orthotopic xenograft mouse model for HCC PDO was successful. Through liver resection, a regenerative environment could be achieved, to investigate the molecular behavior of HCC recurrence after surgery. This offers the basis to study potential new targets and mechanisms to improve HCC-treatment.