Increase In Volume Research Articles

Novel Inlay Methodology with Thermoplastic and Heating System for Durable Road Markings

Road markings, such as lane dividers and pedestrian crossings, are integral in ensuring the safety of road users. However, traditional markings frequently exhibit limitations, including short lifespans, diminished visibility, and significant maintenance costs, particularly as traffic volumes increase. To address these persistent challenges, this study presents a thermoplastic road marking system that combines material innovation and advanced application techniques. Central to this approach is the portable heating system, equipped with ceramic heaters and precise temperature controls, which facilitates uniform heating while mitigating fire risks. The thermoplastic blend, processed into pre-formed sheets, was integrated with this heating technology. Together, these components enabled a two-phase process, engraving asphalt surfaces followed by sheet integration, that ensured robust adhesion and seamless bonding. Field trials conducted on various asphalt types validated the system’s reliability, demonstrating its durability under traffic loads and consistent visibility. By integrating durable materials with advanced application methods, this methodology significantly enhances the efficiency, longevity, and safety of road markings. It presents a practical and scalable solution for modern infrastructure needs. Future research will focus on evaluating the system’s long-term performance under extreme weather conditions to further optimize its applicability.

Volumetric response after closure of a spinal CSF leak in patients with spontaneous intracranial hypotension: a multicompartmental longitudinal study

BackgroundCerebrospinal fluid (CSF) loss in spontaneous intracranial hypotension (SIH) is accompanied by volume shifts between the intracranial compartments. This study investigated tricompartimental and longitudinal volume shifts after closure of a...

Melanocitoma epilbulbar em gato doméstico

Melanocytic lesions are the most common cause of ocular neoplasia seen in cats. Melanocytomas are melanocytic lesions with benign behavior. What differentiates lesions of high malignant potential from those of low potential is the histopathological analysis of the material, and it is not possible to define their potential based on the macroscopic view of the lesion. The aim of this study was to report a case of epibulbar melanocytoma in an adult, mixed breed, neutered cat, with an increase in volume in the epibulbar region in the upper eyelid of the left eye, with a blackish color. We opted for a surgical approach to the tumor, where we performed transconjunctival enucleation of the affected eye, which was submitted for histopathological analysis, where the diagnosis of melanocytoma was confirmed. Given the apparent similarity between malignant and benign ocular melanocytic lesions, we conclude that it is necessary to analyze enucleated material when an ocular melanocytic lesion is suspected, since the diagnosis can define post-operative management and prognosis.

Trends in the Application of Citizen Science in Waterbird Conservation: A Bibliometric Analysis

Waterbirds serve as indicator species for the quality and health of wetland ecosystems, and their conservation is of critical significance for global biodiversity. Citizen science has gradually emerged in recent years, playing an increasingly positive role in scientific research, particularly in ornithological studies. However, a systematic description of the application of citizen science data in waterbird conservation remains lacking. Bibliometrics is an effective method for analyzing the development of scientific disciplines, exploring trends, and examining thematic evolution. This paper utilizes bibliometric analysis of citation data from the Web of Science database, covering the period from 1970 to September 2024. The analysis reveals that this research field has undergone three distinct developmental phases, with a significant increase in annual publication volume during the third phase. Research focus has shifted from specific species and types of waterbirds to key hotspots and ecological phenomena. Future research hotspots are expected to include migratory birds, China, citizen science, and biodiversity. Influential papers within the field emphasize that the primary focus of waterbird conservation is habitat protection and the construction of habitat networks. As the discipline has developed, there is growing recognition that increasing public awareness of waterbird conservation, starting with student education, plays a crucial role in the accumulation of citizen science data and the advancement of waterbird conservation efforts.

O-02 A RARE COLLISION TUMOR OF THE PITUITARY: CO-EXISTENCE OF CRANIOPHARYNGIOMA AND PROLACTINOMA

Abstract Introduction Pituitary adenomas are the most common lesions of the sellar region. The most common (40%) functional pituitary adenomas are prolactinomas. Craniopharyngiomas are epithelial tumors of embryonal origin originating from Rathke's sac. Very few cases of collision tumors co-existing with pituitary adenoma and craniopharyngioma have been described in the literature. Clinical Case We present a case of histopathologically proven craniopharyngioma accompanying prolactinoma in a 63-year-old female patient diagnosed with prolactinoma 40 years ago. She was treated with bromocriptine after the diagnosis, and the treatment was switched to cabergoline four years later. Although the biochemical remission was achieved, there was no significant decrease in tumor size. She had not received any treatment during last 4 years before the administration. She was admitted to our clinic with a complaint of headache. Her serum prolactin level was 1550 ng/ml ((Reference:4,79-23 ng/ml). According to the pituitary Magnetic Resonans Imaging(MRI); reports were as follows in 2007; an isolated 8x6x13 mm adenoma was observed, and then in 2015; another cystic lesion (craniopharyngioma?) was detected adjacent to the infindibular stalk in addition to the defined pituitary adenoma (Figure 1a). In the last pituitary MRI (2022); a cystic lesion extending from the sellar cavity to the suprasellar cistern and a solid mass lesion located left to the cavernous sinus, was observed (Figure 1b). Upon a dramatic increase of the tumor volume on pituitary MRI, she underwent pituitary surgery. The histopathological diagnosis was adamantinomatous craniopharyngioma. Postoperative prolactin level decreased to 10 ng/ml. Since prolactin levels decreased after the diagnosis of craniopharyngioma, the surgical material was re-evaluated by the pathologist. No evidence of prolactinoma was found. Significant regression was observed in the patient's 1st month follow-up pituitary MRI compared to the preoperative MRI. Postoperatively, prolactin levels remained within the normal range for the first 6 months. After the 6th month, cabergoline treatment was started when prolactin levels increased to 497 ng/ml. Conclusion Pituitary adenoma and craniopharyngioma collision tumors are extremely rare. Only 6 patients with the coexistence of craniopharyngioma and prolactinoma have been reported in the literature, including our case. Histopathological diagnosis may be necessary to differentiate craniopharyngioma from cystic macroprolactinoma.Figure 1:Magnetic Resonans ImagingFigure 1: a. Post-contrast coronal pituitary MRI examination revealed a pituitary adenoma (thick arrow) located in the left cavernous sinus. aAnother cystic mass lesion (thin arrow) was detected adjacent to the infindibular stalk.; b. Coronal contrast-enhanced pituitary MRI image showed cystic (arrow) and

Storage and Query of Drug Knowledge Graphs Using Distributed Graph Databases: A Case Study

Background: Distributed graph databases are a promising method for storing and conducting complex pathway queries on large-scale drug knowledge graphs to support drug research. However, there is a research gap in evaluating drug knowledge graphs’ storage and query performance based on distributed graph databases. This study evaluates the feasibility and performance of distributed graph databases in managing large-scale drug knowledge graphs. Methods: First, a drug knowledge graph storage and query system is designed based on the Nebula Graph database. Second, the system’s writing and query performance is evaluated. Finally, two drug repurposing benchmarks are used to provide a more extensive and reliable assessment. Results: The performance of distributed graph databases surpasses that of single-machine databases, including data writing, regular queries, constrained queries, and concurrent queries. Additionally, the advantages of distributed graph databases in writing performance become more pronounced as the data volume increases. The query performance benefits of distributed graph databases also improve with the complexity of query tasks. The drug repurposing evaluation results show that 78.54% of the pathways are consistent with currently approved drug treatments according to repoDB. Additionally, 12 potential pathways for new drug indications are found to have literature support according to DrugRepoBank. Conclusions: The proposed system is able to construct, store, and query a large graph of multisource drug knowledge and provides reliable and explainable drug–disease paths for drug repurposing.

Compensatory mechanisms underlying arginine vasopressin regulation in transient polyuria during pregnancy.

Transient polyuria during pregnancy is reportedly caused by increased arginine vasopressin (AVP) degradation due to vasopressinase produced by the placenta. The mechanism underlying transient polyuria during pregnancy has not been established. In this study we measured urine volume, urine osmolality, and AVP transcriptional activity during pregnancy in wild-type and familial neurohypophysial diabetes insipidus (FNDI) mice. The FNDI mice were used as a partial AVP deficiency model. Vasopressinase was shown to be present in the placentas of pregnant mice. The Avp hnRNA level in the supraoptic nucleus, which is indicative of AVP transcriptional activity, was upregulated in wild-type and FNDI mice during late pregnancy. FNDI mice, but not wild-type mice, had a significant increase in urine volume and a decrease in urine osmolality during pregnancy. These data suggest that an increase in urine volume during pregnancy only occurs when the compensatory increase in AVP release is insufficient to counteract degradation by vasopressinase.

Bio-inspired preparation of Ag NPs, rGO, and Ag/rGO nanocomposites for acoustical, antioxidant, and plant growth regulatory studies

Acoustical properties are essential for understanding the molecular interactions in fluids, as they influence the physicochemical behavior of liquids and determine their suitability for diverse applications. This study investigated the acoustical parameters of silver nanoparticles (Ag NPs), reduced graphene oxide (rGO), and Ag/rGO nanocomposite nanofluids at varying concentrations. Ag NPs and Ag/rGO nanocomposites were synthesized via a Bos taurus indicus (BTI) metabolic waste-assisted method and characterized using advanced techniques, including XRD, TEM, Raman, DLS, zeta potential, and XPS. The synthesized nanocomposites were evaluated for their acoustical, antioxidant, and plant growth-regulatory properties. Acoustical analysis revealed a linear relationship between the nanofluid concentration and density, with key parameters such as adiabatic compressibility, apparent molar compressibility, and apparent molar volume increase at lower concentrations. Irregular changes in ultrasonic velocity and other parameters at 0.025 mol/dm3 suggest unique nanoparticle-solvent interactions. The Ag/rGO nanocomposites exhibited superior antioxidative potential compared to Ag NPs, with DPPH scavenging activity reaching 65.69% and ABTS scavenging activity reaching 65.01% at 100 µg/mL. Plant growth studies have demonstrated enhanced germination rates (100% in spinach and 40% in fenugreek) and improved root and shoot elongation at 0.0025–0.005 mol/dm3. This study bridges the gap in understanding the acoustical and multifunctional properties of nanocomposites for biomedical, agricultural, and environmental applications.

Cortical Lesion Expansion in Chronic Traumatic Brain Injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration and cognitive decline, yet the underlying pathophysiologic mechanisms are incompletely understood. This gap in knowledge is in part related to a lack of reliable and efficient methods for measuring cortical lesions in neuroimaging studies. The objective of this study was to develop a semi-automated lesion detection tool and apply it to an investigation of longitudinal changes in brain structure among individuals with chronic TBI. We identified 24 individuals with chronic moderate-to-severe TBI enrolled in the Late Effects of TBI (LETBI) study who had cortical lesions detected by T1-weighted MRI and underwent two MRI scans at least two years apart. Initial MRI scans were performed more than one year post-injury, and follow-up scans were performed 3.1 (IQR=1.7) years later. We leveraged FreeSurfer parcellations of T1-weighted MRI volumes and a recently developed super-resolution technique, SynthSR, to automate the identification of cortical lesions in this longitudinal dataset. Trained raters received the data in a randomized order and manually edited the automated lesion segmentations, yielding a final semi-automated lesion mask for each scan at each time point. Inter-rater variability was assessed in an independent cohort of 10 additional LETBI subjects with cortical lesions. The semi-automated lesion segmentations showed a high level of accuracy compared to "ground truth" lesion segmentations performed via manual segmentation by a separate blinded rater. In a longitudinal analysis of the semi-automated segmentations, lesion volume increased between the two time points with a median volume change of 4.91 (IQR=12.95) mL (p<0.0001). Lesion volume significantly expanded in 40 of 61 measured lesions (65.6%), as defined by a longitudinal volume increase that exceeded inter-rater variability. Longitudinal analyses showed similar changes in lesion volume using the ground-truth lesion segmentations. Inter-scan duration was not associated with the magnitude of lesion growth. Reliable and efficient semi-automated lesion segmentation is feasible in studies of chronic TBI, creating opportunities to elucidate mechanisms of post-traumatic neurodegeneration.

Projected increases in the prevalence of diabetes mellitus in Aotearoa New Zealand, 2020-2044.

The prevalence of diabetes has been increasing in Aotearoa New Zealand by approximately 7% per year, and is three times higher among Māori and Pacific peoples than in Europeans. The depth of the diabetes epidemic, and the expansive breadth of services required for its management, elevate the need for high-quality evidence on the projected future burden of this complex disease. In this manuscript we have projected the prevalence of diabetes (type 1 and type 2 combined) out to 2040-2044 using age-period-cohort modelling. National-level data from central government on diabetes prevalence (Virtual Diabetes Register) were used to describe recent diabetes prevalence trends (2006-2019) by age group, calendar period and birth cohort, with these trends used to project diabetes prevalence out from 2020 to 2044. Aotearoa New Zealand will experience a significant increase in the absolute volume of prevalent diabetes, rising by nearly 90% to more than 500,000 by 2044. The age-standardised prevalence of diabetes will increase from around 3.9% of the population (268,248) to 5.0% overall (502,358). The prevalence and volume of diabetes diagnoses will increase most drastically for Pacific peoples, most notably Pacific females for whom diabetes prevalence is projected to increase to 17% of the population by 2044. The increases in the future burden of diabetes mellitus projected here will heighten pressure on health services. Immediate action is required to reduce new cases of diabetes and other obesity-related illnesses. Fiscal policies to prevent these diseases, coupled with population-level interventions to more effectively manage and control diabetes, are effective tools for reducing disease burden.

Giant Mesenteric Cyst of The Large Bowel: Case Report

Introduction: Mesenteric cysts are rare, benign intra-abdominal cystic lesions that arise from the mesentery, the tissue fold attaching the intestines to the abdominal wall. They can develop from the duodenum to the rectum. Mesenteric cysts have various histological origins, with lymphangiomas being more common in children and mesothelial cysts in young to middle-aged women. While they can remain asymptomatic, they may also cause complications such as intestinal obstruction or perforation. Complete resection is the preferred treatment due to its lower recurrence rate. Case Presentation: A 48-year-old female with a medical history of systemic arterial hypertension, allergies, hysterectomy, appendectomy, cesarean section, right axillary lipoma resection, and a cyst in the left zygomatic region, presented in June 2021 with dull, constant pelvic pain. Over time, her symptoms progressed to include volume increase, fatigue upon sitting, constipation, and hand tremors. Imaging studies revealed a large cystic lesion extending from the left ovary. In January 2024, an abdominal ultrasound showed a complex ovarian cyst (O-RADS 4). Surgical exploration revealed a mesenteric cyst associated with the sigmoid colon, which was resected along with a distal segment of the descending and sigmoid colon, preserving the left colic artery. The patient recovered well postoperatively, with proper colostomy function. Discussion: Mesenteric cysts are benign tumors that can occur throughout the gastrointestinal tract, most commonly in the small bowel mesentery. Their clinical presentation can range from asymptomatic to acute abdominal pain secondary to complications such as intestinal obstruction or cyst rupture. Diagnostic imaging typically involves ultrasound, CT, and MRI. Surgical resection is the treatment of choice to prevent recurrence. The prognosis following complete cyst excision is favorable, with no reported recurrences. Conclusion: Mesenteric cysts present a diagnostic challenge due to their wide range of symptoms. The recommended treatment, as supported by literature, is complete resection to minimize recurrence. Our case followed this approach, and the patient showed a positive clinical outcome

An Event Frequency‐Inverse Session Frequency Based Weighting Mechanism for Data Embedding Methodologies

ABSTRACTContextWith the rapid increase in data complexity and volume, analyzing and understanding large‐scale datasets has become a critical challenge, especially in domains like e‐commerce. This paper addresses this challenge by introducing a novel business process that utilizes an event frequency‐inverse session frequency (EF‐ISF) based weighting mechanism for embedding user navigational behavior in e‐commerce websites.ObjectiveThe primary research problem tackled in this study is the detection of patterns and distributions within user behavior data, which is often complicated by dynamic page content and session sparsity. We aim to enhance the interpretability and accuracy of user behavior analysis by integrating EF‐ISF with various embedding techniques, including Word2Vec, Node2Vec, DeepWalk, Struc2Vec, and LSTM Autoencoder.MethodologyOur approach is particularly effective in datasets where page refreshes lead to event repetitions, where sequential events with temporal dependencies are prevalent, and where event distributions across sessions are sparse. By applying this methodology across multiple e‐commerce datasets, we observe consistent performance in clustering quality, successfully detecting underlying patterns and groups within the data.ResultsA prototype implementation demonstrates the practical utility of the proposed method, with evaluation metrics confirming that EF‐ISF weighting not only enhances the embeddings but also facilitates a more nuanced and significant segmentation of users' browsing behaviors.ConclusionThese findings provide a valuable contribution to the field of e‐commerce data analytics, offering businesses a refined approach to optimizing user experience and engagement through a deeper understanding of user behavior patterns. This methodology can significantly improve the quality of insights derived from user behavior data, ultimately leading to better decision‐making and enhanced user satisfaction.

Maxillomandibular Advancement with the Use of Virtual Surgical Planning and the CAD/CAM Technology in OSA Surgery: Volumetric Analysis of the Posterior Airway Space

Background and Objectives: Obstructive sleep apnea is an extremely diffuse pathology that, if left untreated, can lead to very serious cardiovascular consequences. The primary goal of treatment is to maintain airflow in the upper airway tract, which can be obtained thanks to orthognathic surgery such as maxillo-mandibular advancement (MMA). This procedure increases the volume of the posterior airway space (PAS)—a parameter considered fundamental in OSA physiology. However, the correlation between the degree of advancement, the volume increase, and the clinical improvement in OSA is not yet clear, even in patients who undergo virtual surgical planning. Aiming to test the correlation of these parameters and the role of PAS volume changes, we present our pre- and post-operative volumetric analysis of the PAS using cone beam computed tomography (CBCT) following CAD/CAM-assisted maxillomandibular advancement. Materials and Methods: We collected information from patients who underwent MMA for moderate or severe OSA, planned virtually with custom-made devices, between 2020 and 2022 at the Maxillofacial Surgery and Odontostomatology Unit of the Policlinico Hospital in Milan. The degree of mandibular advancement (pogonion antero-posterior advancement) was noted. All patients underwent pre- and post-operative CBCT and pre- and post-operative polysomnography to measure the Apnea–Hypopnea Index (AHI) parameters. Both exams were performed within six months before and after surgery. The surgeries were planned virtually along with the production of custom-made devices (cutting guides and mandibular osteosynthesis plates). Volumetric analysis of the PAS was performed pre- and post-CBCT images using medical segmentation software (Mimics, Materialise, Mimcs 26.0). Results: Ten patients (nine men and one woman) with a mean age of 51 years were included in this study. The mean pogonion advancement was 14.5 mm, ranging from 13.8 to 15.6. The mean pre-surgical AHI was 52.31 events/h, while the mean post-surgical AHI was 5.94 events/h (SD 5.34). The improvement in AHI was statistically significant (Wilcoxon matched-pairs signed-rank test, p value 0.004). The mean pre-surgical PAS volume was 8933 mm3, while the mean post-surgical volume was 10,609 mm3. In 8 out of 10 patients, the volume increased, with a mean increase of 2640 mm3 (max. 5183, min. 951), corresponding to a percentage increase variation ranging from 78% to 6%. In two patients, the volume decreased by 1591 (−16%) and 2767 mm3 (−31%), respectively. The difference between pre- and post-operative results was not statistically significant (paired t-test, p value 0.033). Conclusions: The results obtained confirm the efficacy of virtually planned MMA performed with custom-made devices in OSA therapy. However, they also show that PAS volume should not be used as a comprehensive parameter for OSA treatment evaluation because it does not always have a positive correlation with advancement and AHI.

Enhancement of Dough Processing and Steamed Bread Quality with Modified Soybean Residue Dietary Fiber

The effects of different modified soybean residues’ dietary fiber on the physicochemical properties of wheat dough and the quality of steamed bread were systematically analyzed in this study. The physical and chemical parameters of dough, such as texture characteristics, water distribution, secondary structure, and the specific volume, color, and sensory evaluation results of steamed bread products were analyzed in detail. The results showed that adding 6% modified soybean residue dietary fiber enhanced the gluten network, increasing the S–S bond content and improving gluten stability. Notably, the inclusion of 6% residue modified by the ultrasound combined with enzyme method (UEDF) led to a 2.55% increase in the β-fold content of gluten proteins and a 3.60% rise in disulfide bond content. These changes resulted in a reduction in dough relaxation time, promoting a more uniform and compact pore structure in the dough. Additionally, steamed bread made with 6% UEDF showed a 0.3 mL/g increase in specific volume, a 4.69 point rise in L* value, and improved sensory attributes such as taste, odor, and appearance. These research results provide valuable insights and guidance for the development of soybean residue dietary fiber foods.

Monitoring and optimization of the microenvironment in a gravity-driven microfluidic system placed on a slow-tilting table.

Gravity-driven microfluidic chips offer portability and flexibility in different settings because pumps and connecting tubes are unnecessary for driving fluid flow. In a previous study, human induced pluripotent stem cells were cultured using gravity-driven microfluidics, with the liquid flow rate regulated by a tilting table. However, instability in cell culture has been observed, occasionally leading to cell death owing to unknown causes. This study measured the ability of a gravity-driven microfluidic system to maintain essential microenvironments, specifically the flow rate, CO2 levels, temperature, and humidity. The incubation procedure was improved to stabilize the parameters at target values. Improvements in the incubation process reduced the time required to reach the stabilized value for CO2, temperature, and humidity by 85, 67, and 5%, respectively, compared to previous methods. The system demonstrated a precise flow rate, confirmed by a consistent increase in the downstream tank's medium volume after 4h of perfusion. In addition, the adjustment of the tilting table maintained a steady angle and effectively regulated the flow rate, with the measured flow rate consistent with the theoretical value. The gravity-driven microfluidic system effectively facilitated the culture and differentiation of human iPSCs into the mesodermal lineage after bone morphogenetic protein 4 induction, as indicated by positive SSEA1 immunostaining, demonstrating its potential for stem cell research. Gravity-driven microfluidic systems satisfy these requirements and are suitable for stem cell culture experiments.

Развитие сельскохозяйственного производства на сельских территориях

Agriculture is a key element of rural development, providing employment and income for the population. Transformations in agriculture affect social and political stability, which underlines the importance of this sector. The purpose of this study is a comprehensive analysis of the development of agricultural production in rural areas and the development of recommendations for optimizing production processes in the agricultural sector. The study is based on the analysis of scientific articles, reports of the Ministry of Agriculture and statistical data. The methods used include literature review, statistical analysis, and comparative analysis. The analysis showed an overall increase in the development of agricultural production in the country, which is confirmed by an increase in crop volumes and productivity. The agricultural sector shows significant progress in the development of production, but faces a number of problems that hinder its efficiency and strengthen market positions. To ensure the sustainable development of agricultural production, the author offers a number of practical recommendations. Conclusions. Agricultural production is a key element of rural development, which affects the food independence and economic well-being of the country. The recommendations proposed by the author will be useful for a wide range of individuals and organizations interested in developing agriculture and improving rural life.

How government procurement shapes corporate climate disclosures, commitments, and actions

Abstract This study examines how government procurement impacts firms’ environmental disclosures and whether they have tangible effects. Using a triple-difference research design that exploits the exogenous increase in federal funding allocations to counties based on population census revisions, we find that firms with high exposure to government contracts significantly increase climate disclosure following expanded procurement opportunities. We also document that enhanced disclosure is characterized by a positive tone that emphasizes firms’ green investment and commitment to climate adaptation. The effect is more pronounced in counties with a greater increase in procurement volume and when firms have lower ex ante sustainability performance. Finally, we find firms that increase climate disclosure are more likely to earn government contracts, and they undertake real actions by reducing toxic emissions and enhancing the development of green products. Overall our results suggest government procurement promotes corporate climate responsibility by incentivizing firms to undertake climate mitigation actions.

Molecular Understanding of CO2 Absorption by Choline Chloride/Urea Confined within Nanoslits.

Clarifying the potential relationship between the microstructure of nanoconfined choline chloride/urea (ChClU) and CO2 absorption performance is key to understanding the abnormal increase in CO2 under nanoconfinement. In this study, we used molecular dynamics simulations and grand canonical Monte Carlo (GCMC) to systematically study the mechanism underlying the absorption of CO2 by ChClU within nanoslits. According to the spatial distribution, ChClU can form two different laminar regions within nanoslits, namely, the interfacial region (region I) and beyond region I (region II). In region II, the interface induces rearrangement of ChClU, resulting in an increase in free volume and subsequent increase in CO2 solubility. In region I, changing the interface from hydrophobic to hydrophilic (e.g., S_I to S_IV) by setting the appropriate charge patterns, the urea molecules gradually change from "disordered" to "ordered standing" relative to the solid surface. The preferential orientation of the urea molecules causes competition between the ChClU's free volume and urea molecules, resulting in a non-monotonic change in CO2 solubility. Specifically, from S_I to S_III, the increase in urea molecules enhances the CO2 solubility. In S_IV, space for CO2 absorption is insufficient due to the accumulation of urea molecules, and thus CO2 solubility decreases.

Long-term hemodynamic responses and reverse remodeling after pharmacotherapy in HFpEF versus HFrEF: a systematic review and meta-analysis.

Aims: The acute response to therapeutic afterload reduction differs between heart failure with preserved (HFpEF) versus reduced ejection fraction (HFrEF), with larger left ventricular (LV) stroke work augmentation in HFrEF compared to HFpEF. This may (partially) explain the neutral effect of HFrEF-medication in HFpEF. It is unclear whether such differences in hemodynamic response persist and/or differentially trigger reverse remodeling in case of long-term afterload reduction. Methods and results: A systematic search was performed, identifying 21 clinical trials investigating renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers and sodium-glucose cotransport 2 inhibitors that report data on afterload reduction, stroke volume and reverse remodeling in HFpEF and/or HFrEF. In both HFpEF and HFrEF, meta-analyses revealed limited long-term change in systolic/diastolic blood pressure (-5.6/-3.2 and -4.6/-1.4 mmHg, respectively) and LV afterload reduction (arterial elastance: -0.039 and -0.055 mmHg/mL, respectively). Long-term treatment did not result in increase in stroke volume, with the exception of beta-blockers in HFrEF. Indexed LV mass decreased slightly in both HFpEF and HFrEF (-2.8 and -2.3 g/m2, respectively). In HFrEF, treatment reduced LV end-diastolic and end-systolic volume (-8 and -6 ml, respectively), whereas in HFpEF there was no relevant change. Conclusion: Contrary to acute heart failure studies, long-term afterload reduction had little effect on blood pressure and stroke volume augmentation in both HFpEF and HFrEF. On the other hand, reverse remodeling was clearly present in HFrEF, but was essentially absent in HFpEF.

Utilizing Patient-Derived Xenografts to Model Precision Oncology for Biliary Tract Cancer.

Biliary tract cancers, which are rare and aggressive malignancies, are rich in clinically actionable molecular alterations. A major challenge in the field is the paucity of clinically relevant biliary tract cancer models that recapitulate the diverse molecular profiles of these tumors. The purpose of this study was to curate a collection of patient-derived xenograft (PDX) models that reflect the spectrum of genomic alterations present in biliary tract cancers to create a resource for modeling precision oncology. PDXs were derived from biliary tract cancer samples collected from surgical resections or metastatic biopsies. Alterations present in the PDXs were identified by whole-exome sequencing and RNA sequencing. PDXs were treated with approved and investigational agents. Efficacy was assessed by change in tumor volume from baseline. Event-free survival was defined as the time to tumor doubling from baseline. Responses were categorized at day 21: >30% decrease in tumor volume = partial response, >20% increase in tumor volume = progressive disease, and any non-partial response/progressive disease was considered stable disease. Genomic sequencing demonstrated key actionable alterations across this cohort, including alterations in FGFR2, isocitrate dehydrogenase I, ERRB2, PIK3CA, PTEN, and KRAS. RNA sequencing demonstrated fusions and expression of antibody-drug conjugate targets, including TROP2, HER2, and Nectin4. Therapeutic matching revealed objective responses to approved and investigational agents that have been shown to have antitumor activity clinically. In this study, we developed a catalog of biliary tract cancer PDXs that underwent comprehensive molecular profiling and therapeutic modeling. To date, this is one of the largest collections of biliary tract cancer PDX models and will facilitate the development of personalized treatments for patients with these aggressive malignancies.