bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Volcanic Geothermal Systems Based on Integrated Study of Volcanostratigraphy, Structural Geology, and Fluid Geochemistry in Southern Ngada Field, Indonesia
Authors: Pradipta Devito , Suryantini  , Rudyawan Alfend , Kusnadi Dedi , Permana Lano Adhitya
Published: March 2023

Southern Ngada is one of the areas that shows occurrence of volcanic geothermal potential in East Nusa Tenggara. The spreading volcanoes in the study area raised a hypothesis that the Southern Ngada Geothermal Field consists of several geothermal systems. The spreading volcanoes showed the presence of at least three volcanoes and manifestation clusters, which are Nage, Keli-Bena, and Wolo Puti Clusters. This research aimed to identify the number, type, and characteristics of geothermal systems in Southern Ngada Geothermal Field. The identification is conducted through the integration of geomorphology, volcanostratigraphy, structural geology, and geochemistry of fluid manifestation. The determination of geothermal system in Southern Ngada Geothermal Field is important to identify the field characteristics and reduce exploration risks. The Southern Ngada Field constitutes of the pre-caldera, post-caldera, and recent volcanism products. The study area is intensively deformed through strike slip faults and resembled Riedel Shear patterns. Fluid manifestation geochemistry in the study area showed various type of waters, which consists of Cl-SO4, SO4, and SO4-HCO3 waters with meteoric water mixing. The solfatara is associated with active magmatic gases due to boiling of reservoir beneath cinder cones. The fluid mixing processes are explained furthermore in Schoeller diagram plot. The integration of analyses showed the presence of Nage, Keli-Bena, and Wolo Puti Geothermal Systems with each different volcanostratigraphy, structural setting, and fluid mixing processes. The Nage System is associated with inferred heat source beneath the Nage Caldera and eastern part master and antithetic fault. The Keli-Bena System is associated with inferred heat source beneath Bena Crater and western antithetic fault. The Wolo Puti System is associated with inferred heat source beneath cinder cone volcanoes and northern extensional structures.
Water-Rock Interactions in the Metamorphic Complex of Geothermal Field: Case Study in Wahlua Complex, Buru Island
Authors: Gati Rai , Suryantini  , Sibarani Betseba
Published: March 2023

In Indonesia, surface thermal manifestation is commonly found in a volcanic geological setting. However, hot springs and alteration minerals in study area occur on metamorphic rock. In order to study its correlation with the emergence of the thermal fluid, the objective of this study is to characterize each metamorphic zone based on rock chemistry and the appearance of index minerals. Consequently, the correlation with thermal fluid chemistry can be observed. Data for this study are surface rock samples and thermal manifestation data. Metamorphic zones were determined by integrating geomorphology, petrography, and X-Ray Fluorescence (XRF) analyses. Three metamorphic zones were identified, namely, Garnet Zone, Biotite Zone, and Chlorite Zone. Garnet Zone is characterized by high concentrations of CaO and Al2O3 due to the presence of garnet. The abundance of biotite and muscovite in Biotite Zone may contribute to the highest concentration of K2O than the other two zones. Meanwhile, Chlorite Zone is characterized by the concentrations of SiO2, Fe2O3, and MgO. However, the composition of MgO might be influenced by mineral-fluid reaction. There are two clusters of thermal manifestation, which are western and eastern cluster manifestations. Western cluster manifestations are in the Biotite Zone. Meanwhile, the eastern cluster manifestation is in the Chlorite Zone. However, both clusters’ fluid chemistry shows significant differences in some elements such as SiO2, Na, K, Fe, and Mg concentration. It might suggest that the enrichment and depletion of these constituents in thermal fluid might correlate with each metamorphic zone’s characteristics. An inconsistent pattern between thermal fluid composition and rock chemistry was found in Mg concentration. It is most likely that the Mg concentration was influenced by groundwater dilution rather than the mineral-fluid interaction. The study concludes that the appearance of index minerals shows consistencies with composition variation of some elements in the manifestation fluid, such as SiO2, Na, K, and Fe.
Advances of typical mesoporous materials and the application in drug delivery
Authors: He Suna , Pan Haofeng , Zhang Junyang
Published: March 2023

For the excellent drug delivery systems, advanced functional materials are indispensable. In recent years, mesoporous materials have shown a promising prospect and attracted much attention in the field of drug delivery. The research of mesoporous materials as drug carriers becomes to be a hot-spots. As a drug vehicle, it is favored by scientists due to the advantages in increasing drug dissolution and bioavailability, improving drug stability, sustained and controlled drug release, reducing drug side effects, good biocompatibility, targeting and so on. The anticipated in vivo performance for the mesoporous materials based drug delivery systems can be improved through optimizing the synthesis conditions or modifying the materials. In the paper, mesoporous silica nanoparticles (MSNs), mesoporous carbon nanoparticles (MCNs), organic frameworks (OFs), mesoporous hydroxyapatite (mHAp) are selected as the representative mesoporous materials. The structural characteristics, preparation methods, application in the field of drug delivery of above materials are reviewed, and the future research is prospected.
Two-dimensional C6X (X = P2, N2, NP) with ultra-wide bandgap and high carrier mobility
Authors: Chen Xiaowei , Li Renqun , Lin Jiahe , Lin Qiubao , He Hongsheng
Published: March 2023

Two-dimensional (2D) materials with ultra-wide bandgap and high carrier mobility are highly promising for electronic applications. We predicted 2D C3P, C3N and C6NP monolayers through density-functional-theory calculations. The phonon spectra and Ab initio molecular dynamics simulation confirm that the three 2D materials exhibit good phase stability. The C3P monolayer shows excellent mechanical flexibility with a critical strain of 27%. The C3P and C6NP monolayers are ultra-wide bandgap semiconductors based on Heyd-Scuseria-Ernzerhof hybrid functional (HSE06) calculation. The C3P monolayer has a direct bandgap of 4.42 eV, and the C6NP and C3N monolayer have indirect bandgaps of 3.94 and 3.35 eV, respectively. The C3P monolayer exhibits a high hole mobility of 9.06 × 104 cm2V−1s−1, and the C3N monolayer shows a high electron mobility of 4.52 × 104 cm2V−1s−1. Hence, the C3P, C3N, and C6NP monolayers are promising materials for various electronic devices.
Comparison of intra- and inter-patient intensity standardization methods for multi-parametric whole-body MRI
Authors: Ceranka Jakub , Lecouvet Frédéric , Michoux Nicolas , de Mey Johan , Raeymaekers Hubert , Metens Thierry , Vandemeulebroucke Jef
Published: March 2023

Objective. To test and compare different intensity standardization approaches for whole-body multi-parametric MR images, aiming to compensate voxel intensity differences between scans. These differences, common for magnetic resonance imaging, pose problems in image quantification, assessment of changes between a baseline and follow-up scan, and hinder performance of image processing and machine learning algorithms. Approach. In this work, we present a comparison on the accuracy of intensity standardization approaches with increasing complexity, for intra- and inter-patient multi-parametric whole-body MRI. Several approaches were used: z-scoring of the intensities, piecewise linear mapping and deformable mapping of intensity distributions into established reference intensity space. For each method, the impact on standardization algorithm on the use of single image or average population distribution reference; as well as, whole image and region of interest were additionally investigated. All methods were validated on a data set of 18 whole-body anatomical and diffusion-weighted MR scans consisting of baseline and follow-up examinations acquired from advanced prostate cancer patients and healthy volunteers. Main results. The piecewise linear intensity standardisation approach provided the best compromise between standardization accuracy and method stability, with average deviations in intensity profile of 0.011-0.027 and mean absolute difference of 0.29-0.37 standard score (intra-patient) and 0.014-0.056 (inter-patient), depending on the type of used MR modality. Significance. Linear piecewise approaches showed the overall best performance across multiple validation metrics, mostly because of its robustness. The inter-patient standardization proved to perform better when using population average reference image; in contrary to intra-patient approach, where the best results were achieved by standardizing towards a reference image taken as the baseline scan.
Omicron BA.4/5 Neutralization and T-Cell Responses in Organ Transplant Recipients After Booster Messenger RNA Vaccine: A Multicenter Cohort Study
Authors: Ferreira Victor H , Ierullo Matthew , Mavandadnejad Faranak , Kurtesi Alexandra , Hu Queenie , Hardy W Rod , Hall Victoria G , Pinzon Natalia , Yotis Demitra , Gingras Anne-Claude , Belga Sara , Shalhoub Sarah , Hébert Marie-Josée , Humar Atul , Kabbani Dima , Kumar Deepali
Published: March 2023

Background

In solid organ transplant (SOT) recipients, the primary vaccination series against Coronavirus Disease 2019 is 3 doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies (nAbs) and T cells in a large multicenter cohort study.

Methods

Serum was collected 4–6 weeks post-third and post-fourth doses of messenger RNA vaccine in 222 SOT recipients. nAbs were measured using a pseudovirus neutralization assay that targeted the Omicron BA.4/5 spike protein. A subset underwent T-cell testing.

Results

The median age of the cohort was 63 years (interquartile range [IQR], 50–68) with 61.7% men. BA.4/5 nAb detection increased from 26.6% (59 of 222) post-third dose to 53.6% (119 of 222) post-fourth dose (P < .0001). In patients with breakthrough infection prior to the fourth dose (n = 27), nAbs were detected in 77.8% and median nAb titers were significantly higher compared with those with 4 vaccine doses alone (P < .0001). Factors associated with a low BA.4/5 neutralization response after the fourth dose were older age (odds ratio [OR], 0.96; 95% confidence interval [CI], .94–.99), mycophenolate use (OR, 0.39; 95% CI, .20–.77) and prednisone use (OR, 0.34; 95% CI, .18–.63), and vaccine type (OR, 0.72; 95% CI, .51–.99), while breakthrough infection prior to the fourth dose (OR, 3.6; 95% CI, 1.3–9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T cells significantly increased after 4 doses and were identified in 76.9% of patients at a median frequency of 213/106 cells (IQR, 98–650).

Conclusions

In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients who are older and on mycophenolate and prednisone need additional preventative strategies.
New Integral Distinguishers On Permutation Of Whirlpool
Authors: Wang Bolin , Wu Wenling , Zhang Yuhan , Zhang Li
Published: March 2023

Whirlpool is a hash function that has been standardized by ISO/IEC. In this paper, we develop a new type of distinguishing property for its underlying permutation $ W $. Division property proposed by Todo at EUROCRYPT 2015 was initially used in the integral cryptanalysis of symmetric-key algorithms. This work for the first time utilizes the MILP method to search for the integral distinguishers of $ W $ in both the forward and backward directions while concentrating on word-based division property. Under the known-key model, the fact that the permutation used in the hash function does not depend on any secret parameters allows the previous properties to be exploited from the middle, i.e. from an intermediate internal state. Therefore, we apply the inside-out strategy which is the essential step in the zero-sum property to connect the trails in opposite directions. Consequently, we obtain new distinguishers up to full rounds for the $ W $. To further reduce the complexity of the integral distinguishers, we add one round in the middle with the help of subspace trails. Finally, we succeed in extending the length and improving the complexity of the integral distinguishers. To the best of our knowledge, all the results in this paper are competitive with the previous work in both computational cost and memory complexity. It is worth mentioning that the methods presented in this paper are applicable to a broad class of hash functions.
Common congenital heart problems in acute and intensive care
Authors: Buber Jonathan , Valle Christopher , Valente Anne Marie
Published: March 2023

Over the past five decades, there have been multiple advances in the treatment of congenital heart defects, resulting in an increasing population of adults living with congenital heart disease (CHD). Despite improved survival, CHD patients often have residual haemodynamic sequelae and limited physiologic reserve and are at increased risk for acute decompensation with occurrence of arrhythmias, heart failure, and other medical conditions. Comorbidities occur more frequently and at an earlier age in CHD patients than in the general population. The management of the critically ill CHD patient requires an understanding of the unique aspects of congenital cardiac physiology as well as the recognition of other organ systems that may be involved. Certain patients may be candidates for mechanical circulatory support, and goals of care should be established with advanced care planning.
Annotated genome sequence of a fast-growing diploid clone of red alder (Alnus rubra Bong.)
Authors: Hixson Kim K , Fajardo Diego A , Devitt Nicholas P , Sena Johnny A , Costa Michael A , Meng Qingyan , Boschiero Clarissa , Zhao Patrick Xuechun , Baack Eric J , Paurus Vanessa L , Davin Laurence B , Lewis Norman G , Bell Callum J
Published: March 2023

Red alder (Alnus rubra Bong.) is an ecologically significant and important fast-growing commercial tree species native to western coastal and riparian regions of North America, having highly desirable wood, pigment, and medicinal properties. We have sequenced the genome of a rapidly growing clone. The assembly is nearly complete, containing the full complement of expected genes. This supports our objectives of identifying and studying genes and pathways involved in nitrogen-fixing symbiosis and those related to secondary metabolites that underlie red alder's many interesting defense, pigmentation, and wood quality traits. We established that this clone is most likely diploid and identified a set of SNPs that will have utility in future breeding and selection endeavors, as well as in ongoing population studies. We have added a well-characterized genome to others from the order Fagales. In particular, it improves significantly upon the only other published alder genome sequence, that of Alnus glutinosa. Our work initiated a detailed comparative analysis of members of the order Fagales and established some similarities with previous reports in this clade, suggesting a biased retention of certain gene functions in the vestiges of an ancient genome duplication when compared with more recent tandem duplications.
Numerical modeling of caldera formation using Smoothed Particle Hydrodynamics (SPH)
Authors: Mullet B , Segall P , Fávero Neto A H
Published: March 2023

Calderas are kilometer-scale basins formed when magma is rapidly removed from shallow magma storage zones. Despite extensive previous research, many questions remain about how host rock material properties influence the development of caldera structures. We employ a mesh-free, continuum numerical method, Smoothed Particle Hydrodynamics (SPH) to study caldera formation, with a focus on the role of host rock material properties. SPH provides several advantages over previous numerical approaches (finite element or discrete element methods), naturally accommodating strain localization and large deformations while employing well-known constitutive models. A continuum elastoplastic constitutive model with a simple Drucker–Prager yield condition can explain many observations from analogue sandbox models of caldera development. For this loading configuration, shear band orientation is primarily controlled by the angle of dilation. Evolving shear band orientation, as commonly observed in analogue experiments, requires a constitutive model where frictional strength and dilatancy decrease with strain, approaching a state of zero volumetric strain rate. This constitutive model also explains recorded loads on the down-going trapdoor in analogue experiments. Our results, combined with theoretical scaling arguments, raise questions about the use of analogue models to study caldera formation. Finally, we apply the model to the 2018 caldera collapse at Kīlauea volcano and conclude that the host rock at Kīlauea must exhibit relatively low dilatancy to explain the inferred near-vertical ring faults.
Theta oscillations in anterior cingulate cortex and orbitofrontal cortex differentially modulate accuracy and speed in flexible reward learning
Authors: Ye Tony , Romero-Sosa Juan Luis , Rickard Anne , Aguirre Claudia G , Wikenheiser Andrew M , Blair Hugh T , Izquierdo Alicia
Published: March 2023

Flexible reward learning relies on frontal cortex, with substantial evidence indicating that anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) subregions play important roles. Recent studies in both rat and macaque suggest theta oscillations (5–10 Hz) may be a spectral signature that coordinates this learning. However, network-level interactions between ACC and OFC in flexible learning remain unclear. We investigated the learning of stimulus–reward associations using a combination of simultaneous in vivo electrophysiology in dorsal ACC and ventral OFC, partnered with bilateral inhibitory DREADDs in ACC. In freely behaving male and female rats and using a within-subject design, we examined accuracy and speed of response across distinct and precisely defined trial epochs during initial visual discrimination learning and subsequent reversal of stimulus–reward contingencies. Following ACC inhibition, there was a propensity for random responding in early reversal learning, with correct vs. incorrect trials distinguished only from OFC, not ACC, theta power differences in the reversal phase. ACC inhibition also hastened incorrect choices during reversal. This same pattern of change in accuracy and speed was not observed in viral control animals. Thus, characteristics of impaired reversal learning following ACC inhibition are poor deliberation and weak theta signaling of accuracy in this region. The present results also point to OFC theta oscillations as a prominent feature of reversal learning, unperturbed by ACC inhibition.
Cementing CO2 into C-S-H: A step toward concrete carbon neutrality
Authors: Stefaniuk Damian , Hajduczek Marcin , Weaver James C , Ulm Franz J , Masic Admir
Published: March 2023

Addressing the existing gap between currently available mitigation strategies for greenhouse gas emissions associated with ordinary Portland cement production and the 2050 carbon neutrality goal represents a significant challenge. In order to bridge this gap, one potential option is the direct gaseous sequestration and storage of anthropogenic CO2 in concrete through forced carbonate mineralization in both the cementing minerals and their aggregates. To better clarify the potential strategic benefits of these processes, here, we apply an integrated correlative time- and space-resolved Raman microscopy and indentation approach to investigate the underlying mechanisms and chemomechanics of cement carbonation over time scales ranging from the first few hours to several days using bicarbonate-substituted alite as a model system. In these reactions, the carbonation of transient disordered calcium hydroxide particles at the hydration site leads to the formation of a series of calcium carbonate polymorphs including disordered calcium carbonate, ikaite, vaterite, and calcite, which serve as nucleation sites for the formation of a calcium carbonate/calcium-silicate-hydrate (C-S-H) composite, and the subsequent acceleration of the curing process. The results from these studies reveal that in contrast to late-stage cement carbonation processes, these early stage (precure) out-of-equilibrium carbonation reactions do not compromise the material's structural integrity, while allowing significant quantities of CO2 (up to 15 w%) to be incorporated into the cementing matrix. The out-of-equilibrium carbonation of hydrating clinker thus provides an avenue for reducing the environmental footprint of cementitious materials via the uptake and long-term storage of anthropogenic CO2.
Occurrence, Characteristics, and qPCR-Based Identification of Pectobacterium versatile Causing Soft Rot of Chinese Cabbage in China
Authors: Su Yanyan , Li Xiaoying , Li Lei , Lukianova Anna , Tokmakova Anna , Chen Changlong , Fu Lu , Tian Yu , Shi Yanxia , Xie Jianbo , Miroshnikov Konstantin A. , Yang Jungang , Xie Hua
Published: March 2023

Pectobacterium is one of the most important genera of phytopathogenic bacteria. It can cause soft-rot diseases on a wide range of plant species across the world. In this study, three Pectobacterium strains (KC01, KC02, and KC03) were isolated from soft-rotted Chinese cabbage in Beijing, China. These three strains were identified as Pectobacterium versatile based on phylogenetic analysis of Pectobacterium 16S ribosomal RNA, pmrA, and 504 Pectobacterium core genes, as well as a genomic average nucleotide identity analysis. Their biochemical characteristics were found to be similar to the P. versatile type strain ICMP9168T but differed in response to citric acid, stachyose, D-glucuronic acid, dextrin, and N-acetyl-β-D-mannosamine. All of the tested P. versatile strains showed different carbohydrate utilization abilities compared with P. carotovorum and P. odoriferum, particularly in their ability to utilize D-arabitol, L-rhamnose, and L-serine. Under laboratory conditions, the maceration ability of P. versatile on Chinese cabbage was the highest at 28°C, compared with those at 13, 28, 23, and 33°C. Additionally, P. versatile could infect all of the 17 known Pectobacterium host plants, except for Welsh onion (Allium fistulosum). A SYBR Green quantitative PCR (qPCR) detection system was developed to distinguish P. versatile from other soft-rot bacteria based on the combined performance of melting curve (with a single melting peak at around 85°C) and fluorescence curve (with cycle threshold <30) when the bacterial genomic DNA concentration was in the range of 10 pg/µl to 10 ng/µl. This study is the first to report the presence of P. versatile on Chinese cabbage in China, as well as a specific and sensitive qPCR assay that can be used to quickly identify P. versatile. The work contributes to a better understanding of P. versatile and will facilitate the effective diagnosis of soft-rot disease, ultimately benefitting commercial crop production.
Mpox (monkeypox)
Authors: Jarrell Lynda , Perryman Kashiris
Published: March 2023

Mpox (formerly “monkeypox”) is a viral zoonosis that presents similarly to smallpox but is less contagious and causes less severe disease. Mpox may be transmitted from infected animals to humans through direct contact or a scratch or bite. Human-to-human transmission occurs through direct contact, respiratory droplets, and fomites. Two vaccines, JYNNEOS® and ACAM2000®, are currently available for postexposure prophylaxis as well as for prevention in certain populations at high risk for mpox. Most cases of mpox are self-limited; however, tecovirimat, brincidofovir, and cidofovir are available as treatments for at-risk populations.
Hybrid magnetic resonance and PET imaging for prostate cancer recurrence
Authors: Rednam Nikita , Kundra Vikas
Published: March 2023

Purpose of review

Recurrence post definitive local therapy by prostatectomy or radiation therapy is often detected via rise in serum prostate-specific antigen (PSA) levels; however, PSA rise does not localize the disease. Distinguishing local versus distant recurrence guides whether to choose subsequent local versus systemic therapy. The purpose of this article is to review imaging for prostate cancer recurrence post local therapy.

Recent findings

Among imaging modalities, multiparametric MRI (mpMRI) is commonly used to assess for local recurrence. New radiopharmaceuticals target prostate cancer cells and enable whole-body imaging. These tend to be more sensitive for lymph node metastases than MRI or computed tomography (CT) and for bone lesions than bone scan at lower PSA levels but can be limited for local prostate cancer recurrence. Given greater soft tissue contrast, similar criteria for lymph nodes, and greater sensitivity for prostate bone metastases, MRI is advantageous to CT. MRI of the whole body and mpMRI are now feasible within a reasonable time frame and complementary to PET imaging, enabling whole-body and pelvis-focused PET-MRI, which should be advantageous in the setting of recurrent prostate cancer.

Hybrid PET-MRI with prostate cancer targeted radiopharmaceuticals and whole body with local multiparametric MRI can be complementary for detecting local and distant recurrence to guide treatment planning.
Window-of-opportunity clinical trials for biomarker discovery in head and neck squamous cell carcinoma
Authors: Marret Grégoire , Borcoman Edith , Le Tourneau Christophe
Published: March 2023

Purpose of review

We review the window-of-opportunity clinical trials that have been reported in head and neck squamous cell carcinoma (HNSCC), and discuss their challenges.

Recent findings

Limited treatment options exist in HNSCC. Cetuximab, an mAb targeting epidermal growth factor receptor, and the PD-1 inhibitors nivolumab and pembrolizumab, are the only drugs that improved overall survival in the recurrent and/or metastatic setting. Both cetuximab and nivolumab improve overall survival by less than 3 months, potentially because of the lack of predictive biomarkers. The only validated predictive biomarker to date is protein ligand PD-L1 expression that predicts the efficacy of pembrolizumab in first-line, nonplatinum refractory recurrent and/or metastatic HNSCC. The identification of biomarkers of efficacy of new drugs is key to avoid administering toxic drugs to patients who will not benefit from them, and to expect increased drug efficacy in the biomarker-positive group of patients. One way of identifying such biomarkers are the window-of-opportunity trials in which drugs are given for a short period of time before the definitive treatment, with the aim to collect samples for translational research. These trials differ from neoadjuvant strategies where efficacy is the primary endpoint.

We show that these trials were safe and successful in identifying biomarkers.
Stereotactic body irradiation for metastasis from renal carcinoma: A retrospective study
Authors: Rida Hanan , Zaine Hind , Jouhadi Hassan , Benider Abdellatif , Samlali Hamza , Samlali Redouane
Published: March 2023

Background

Renal cell carcinoma (RCC) has traditionally been considered to be radioresistant. Response rates are believed to be improved by a high dose of stereotactic body radiotherapy (SBRT). A retrospective analysis was conducted of patients treated with SBRT for metastatic disease from RCC.

Material and methods

We reviewed records from 20 patients who underwent SBRT for a total of 30 RCC metastases from 2015 to 2020. Patients were included who had a confirmed primary RCC and radiographic evidence of metastasis, either synchronous or metachronous. The most common SBRT fractionation was 30 Gy in 3 fractions.

Results

Median age was 60 years (range, 40–77 years) and 60% were male. After a median follow-up of 18 months (range, 3–36 months), overall survival was estimated to be 85% and 70%, at 1 and 2 years, respectively, and local control at 2 years was 83.33%. Only 5 patients had documented progression of disease, all of whom received biologically effective dose inferior to 100 Gy, and no patients treated with a higher biologically effective dose had disease, which progressed. The most common acute toxicity was grade 1 fatigue (20%). No grade 3 or higher acute toxicity occurred.

Conclusions

Treatment with SBRT in patients with RCC metastases yielded a high local control rate, promising survival rate, and low toxicity.
The spectrum and etiologies of lower urinary tract symptoms in postmenopausal women
Authors: Bharti Vishrut , Tiwari Rajesh K. , Gupta Sanjay , Upadhyay Rohit , Singh Manoj K. , Singh Deelip K.
Published: March 2023

Background

Although the prevalence of lower urinary tract symptoms (LUTS) is high in the female population, it is even higher in postmenopausal females. The frequency, severity, and etiology of LUTS vary among populations and individuals. This study aimed to define the characteristics of LUTS in postmenopausal women and their underlying etiologies.

Material and methods

Overall, 74 postmenopausal patients presenting with LUTS in the urological outpatient department were included in the study. A detailed evaluation of LUTS and their underlying etiologies was performed. Patients were divided into 2 groups based on age (<65 and ≥65 years), and the variation in different factors was compared across the groups. Variables were compared using the t test and 1-way analysis of variance.

Results

Nocturia was the most common symptom (89.2%) followed by frequency (83.8%). Among voiding LUTS, the most common was a weak stream (63.5%). Frequency, nocturia, urgency, urge urinary incontinence (UI), stress UI, and nocturnal enuresis were more common in patients older than 65 years. Urgency and urge UI were recognized to be the most bothersome symptoms by 37% of the study population followed by straining (32%). The mean storage scores, incontinence scores, and quality of life (QoL) scores for patients younger than 65 years and 65 years or older were 6.9 and 8.5 (p < 0.01), 1.8 and 4.1 (p ≤ 0.01), 4.9 and 6.1, respectively. The most common diagnosis was bladder outlet obstruction due to urethral/meatal stenosis (40.5%) followed by an overactive bladder (32.4%), urinary tract infection (10.8%), cystocele (8.1%), urethral prolapse (4.1%), and urethral caruncle (4.1%).

Conclusions

Storage LUTS were the most common and increased in both frequency and severity with age. The QoL was also more severely affected in older postmenopausal women. Bladder outlet obstruction due to meatal with or without distal urethral stenosis was the most common underlying cause of LUTS followed by an overactive bladder. Overactive bladder had the most severe impact on patients’ QoL among all the etiologies.
Sensitivity and Uncertainty Analysis for Two-stream Capture–Recapture Methods in Disease Surveillance
Authors: Zhang Yuzi , Chen Jiandong , Ge Lin , Williamson John M. , Waller Lance A. , Lyles Robert H.
Published: March 2023

Capture–recapture methods are widely applied in estimating the number (

) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are 2 data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically nonidentifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist’s understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of

. By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is a simulation-based approach designed to more realistically acknowledge variability in the estimated

associated with uncertainty in an expert’s opinion about the nonidentifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture–recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating

in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from >2 surveillance streams.
CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma
Authors: Asnagli Hélène , Minet Norbert , Pfeiffer Christina , Hoeben Eef , Lane Rebecca , Laughton David , Birch Louise , Jones Geraint , Novak Andrew , Parker Andrew E. , Ludwig Heinz , Fischer Alain , Latour Sylvain , Beer Philip A.
Published: March 2023

Lymphoma is the most common hematological malignancy and is among the 10 most prevalent cancers worldwide. Although survival has been improved by modern immunochemotherapeutic regimens, there remains a significant need for novel targeted agents to treat both B-cell and T-cell malignancies. Cytidine triphosphate synthase 1 (CTPS1), which catalyzes the rate-limiting step in pyrimidine synthesis, plays an essential and nonredundant role in B-cell and T-cell proliferation but is complemented by the homologous CTPS2 isoform outside the hemopoietic system. This report describes the identification and characterization of CTPS1 as a novel target in B- and T-cell cancers. A series of small molecules have been developed which show potent and highly selective inhibition of CTPS1. Site-directed mutagenesis studies identified the adenosine triphosphate pocket of CTPS1 as the binding site for this small molecule series. In preclinical studies, a potent and highly selective small molecule inhibitor of CTPS1 blocked the in vitro proliferation of human neoplastic cells, showing the highest potency against lymphoid neoplasms. Importantly, pharmacological CTPS1 inhibition induced cell death by apoptosis in the majority of lymphoid cell lines tested, thus demonstrating a cytotoxic mechanism of action. Selective CTPS1 inhibition also inhibited the growth of neoplastic human B- and T- cells in vivo. These findings identify CTPS1 as a novel therapeutic target in lymphoid malignancy. A compound from this series is in phase 1/2 clinical studies for the treatment of relapsed/refractory B- and T-cell lymphoma (NCT05463263).
Preoperative renal insufficiency predicts postoperative adverse outcomes in a mixed surgical population: a retrospective matched cohort study using the NSQIP database
Authors: Liao Yu-Chen , Chang Chuen-Chau , Chen Chien-Yu , Liu Chih-Chung , Liao Chien-Chang , Shih Yu-Ru Vernon , Lin Chao-Shun
Published: March 2023

Background:

The incidence of chronic kidney disease is increasing, but most cases are not diagnosed until the accidental finding of abnormal laboratory data or the presentation of severe symptoms. Patients with chronic kidney disease are reported to have an increased risk of postoperative mortality and morbidities, but previous studies mainly targeted populations undergoing cardiovascular surgery. The authors aimed to evaluate the risk of postoperative mortality and complications in a surgical population with preoperative renal insufficiency (RI).

Materials and Methods:

This retrospective cohort study used data from the National Surgical Quality Improvement Program database between 2013 and 2018 to evaluate the risk of postoperative morbidity and mortality in the surgical population. Patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m2 were defined as the RI group. Propensity score matching methods and multivariate logistic regression were used to calculate the risk of postoperative morbidity and mortality.

Results:

After propensity score matching, 502 281 patients were included in the RI and non-RI groups. The RI group had a higher risk of 30-day in-hospital mortality (odds ratio: 1.54, 95% CI: 1.49–1.58) than the non-RI group. The RI group was associated with a higher risk of postoperative complications, including myocardial infarction, stroke, pneumonia, septic shock, and postoperative bleeding. The RI group was also associated with an increased risk of prolonged ventilator use for over 48 h, readmission, and reoperation.

Conclusion:

Patients with preoperative RI have an increased risk of postoperative 30-day mortality and complications. RI group patients with current dialysis, estimated glomerular filtration rate less than or equal to 30 ml/min/1.73 m2 or concomitant anemia had an elevated risk of postoperative mortality.
Association of severity in the grading of microvascular invasion with long-term oncological prognosis after liver resection for early-stage hepatocellular carcinoma: a multicenter retrospective cohort study from a hepatitis B virus-endemic area
Authors: Xu Xin-Fei , Diao Yong-Kang , Zeng Yong-Yi , Li Chao , Li Feng-Wei , Sun Li-Yang , Wu Han , Lin Kong-Ying , Yao Lan-Qing , Wang Ming-Da , Zhang Cheng-Wu , Lau Wan Yee , Shen Feng , Yang Tian
Published: March 2023

Background:

The presence of microvascular invasion (MVI) is a significant malignant pathological feature related to recurrence and survival after liver resection for hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the severity in the grading of MVI and long-term oncological outcomes in patients with early-stage HCC.

Methods:

A retrospective study was conducted on a prospectively maintained multicenter database on patients who underwent curative resection for Barcelona Clinic Liver Cancer stage 0/A HCC between 2017 and 2020. Patients were classified into three groups according to the severity in the grading of MVI: M0 (no MVI), M1 (1–5 sites of MVI occurring ≤1 cm away from the tumor), and M2 (>5 sites occurring ≤1 cm and/or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups.

Results:

Of 388 patients, M0, M1, and M2 of the MVI gradings were present in 223 (57.5%), 118 (30.4%), and 47 (12.1%) patients, respectively. The median OS and RFS in patients with M0, M1, and M2 were 61.1, 52.7, and 27.4 months; and 43.0, 29.1, and 13.1 months (both P<0.001), respectively. Multivariable analyses identified both M1 and M2 to be independent risk factors for OS [hazard ratio (HR): 1.682, P=0.003; and HR: 3.570, P<0.001] and RFS (HR: 1.550, P=0.037; and HR: 2.256, P<0.001).

Conclusion:

The severity in the grading of MVI was independently associated with recurrence and survival after HCC resection. Patients with the presence of MVI, especially those with a more severe MVI grading (M2), require more stringent recurrence surveillance and/or active adjuvant therapy against recurrence.
The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis
Authors: Chen Yuanzhuo , Peng Liao , Zhang Chi , Chen Jiawei , Chen Jiahui , Shen Hong , Luo Deyi
Published: March 2023

Background:

Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy.

Objective:

The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO.

Methods:

The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual.

Results:

A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and β3-adrenoceptor-agonists possessed good effectiveness and safety.

Conclusion:

OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and β3-adrenoceptor-agonists have good effectiveness and safety.
Balloon-occluded retrograde transvenous obliteration for treatment of portal hypertensive related varices
Authors: Stoleru Gianna , Henry Zachary
Published: March 2023

Purpose of review

Balloon-occluded retrograde transvenous obliteration (BRTO) is becoming a more commonly used procedure to manage various complications of liver disease. It is important to understand the technique of the procedure, the indications for its use, and also potential associated complications.

Recent findings

BRTO is superior to endoscopic cyanoacrylate injection and transjugular intrahepatic portosystemic shunt for bleeding gastric varices associated with a portosystemic shunt and should be considered a first line therapy in these patients. In addition, it has been shown to be useful in controlling ectopic variceal bleeding, improving portosystemic encephalopathy, and also in modulating blood flow in the post liver transplant setting. Modified versions of BRTO, plug assisted retrograde transvenous obliteration and coil assisted retrograde transvenous obliteration, have been developed to reduce procedure time and improve complication rates.

As the use of BRTO expands in clinical practice it will be important for gastroenterologists and hepatologists to better understand the procedure. There are still many research questions left to answer regarding the use of BRTO in specific situations and for specific patient populations.
Unintentional overdoses: understanding the fentanyl landscape and reducing harm
Authors: Bell Lauren A. , Hadland Scott E.
Published: March 2023

Purpose of review

Adolescent and young adult overdoses and overdose fatalities continue to increase despite reductions in self-reported substance use. This review aims to explore factors contributing to this overdose epidemic, highlight signs of overdose and the role of the overdose reversal medication naloxone, and provide recommendations for practice change to support patients and decrease their risk of unintentional overdose.

Recent findings

The potent opioid fentanyl is a common contaminant in nonopioid substances, as well as in heroin and counterfeit pills, heightening risk of fatal overdose. Adolescents and young adults who die of overdose are rarely engaged in substance use disorder treatment. Medications for opioid use disorder are effective at reducing risk of fatal overdose but are underutilized, as is the opioid reversal medication naloxone.

Pediatric clinician engagement in harm reduction with adolescents and young adults, starting with screening through a confidential interview, may enhance pathways to care and reduce the risk of overdose.
How resources affect management of periprosthetic fractures of the distal femur: perspectives from Israel, South Sudan, and South Africa
Authors: Bernstein Brian P. , Rivkin Gurion , Weil Yoram A. , Greenberg Alexander , Madison Brian B. , Areu Mapour M. , Joda Omojowk B. , Berry Kirsty Leigh , Nortje Marc
Published: March 2023

Periprosthetic fractures of the distal femur have significant morbidity in both total hip and total knee arthroplasty (THA and TKA, respectively). The incidence of these fractures is growing, with the predominant mechanism of injury being a fall from a standing height and therefore considered fragility fractures. In many countries, improved public funding and a flourishing private health care sector, when coupled with increased life expectancy, translates to more older patients receiving both TKA and THA and therefore an increased prevalence of periprosthetic fractures and their associated complications. These fractures may occur below a long stem THA, above a TKA, or between the two (so-called “interprosthetic fracture”). We will outline fracture classification, risk factors, diagnosis, and treatment options, highlighting perspectives on treating these fractures in Israel, South Africa, and South Sudan. These countries represent differing access to resources, varied comorbidity factors, and differing health care systems. The points of difference and the points of similarity will be considered.
The Isolated Humeral Metastasis as the Initial Presentation of Renal Cell Carcinoma Revealed by 18F-FDG PET/CT
Authors: Hou Guozhu , Zhang Wenjie , Zheng Rong
Published: March 2023

Renal cell carcinoma (RCC) with isolated humeral metastasis as the initial presentation is rare. We reported FDG PET/CT findings of isolated humeral metastasis from RCC in a 63-year-old man with right upper arm pain as the initial presentation. The bone scanning in an outside hospital showed that the focus with increased uptake of the right humerus was possibly malignant. FDG PET/CT showed that the right humeral mass had intense activity, and there was an additional FDG lesion in the lower pole of the right kidney. The mass of the right humerus was later confirmed as humeral metastasis from RCC by pathological examination.
FDG PET/CT in a Case of Pure Ductal Adenocarcinoma of the Prostate With Osteolytic Metastases and Normal PSA Level
Authors: Dong Aisheng , Lin Xumiao , Bai Yushu , Yang Bo , Xu Shengming
Published: March 2023

Prostatic ductal adenocarcinoma is an uncommon aggressive subtype of prostate carcinoma. It is more likely to present with advanced stage and lower prostate-specific antigen. We describe FDG PET/CT findings in a case of pure prostatic ductal adenocarcinoma with lymph node, bone and lung metastases, normal serum prostate-specific antigen level, and elevated serum carbohydrate antigen 19-9 and carbohydrate antigen 724 levels. The primary tumor, and lymph node and bone metastases were hypermetabolic. All the bone metastases were osteolytic. The multiple lung metastases showed no significant FDG uptake, which may be due to small size.