bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrological constraints on the potential of enhanced geothermal systems in the ductile crust
Authors: Scott Samuel , Yapparova Alina , Weis Philipp , Houde Matthew
Published: March 2024

Continental crust at temperatures > 400 °C and depths > 10–20 km normally deforms in a ductile manner, but can become brittle and permeable in response to changes in temperature or stress state induced by fluid injection. In this study, we quantify the theoretical power generation potential of an enhanced geothermal system (EGS) at 15–17 km depth using a numerical model considering the dynamic response of the rock to injection-induced pressurization and cooling. Our simulations suggest that an EGS circulating 80 kg s−1 of water through initially 425 ℃ hot rock can produce thermal energy at a rate of ~ 120 MWth (~ 20 MWe) for up to two decades. As the fluid temperature decreases (less than 400 ℃﻿), the corresponding thermal energy output decreases to around 40 MWth after a century of fluid circulation. However, exploiting these resources requires that temporal embrittlement of nominally ductile rock achieves bulk permeability values of ~ 10–15–10–14 m2 in a volume of rock with dimensions ~ 0.1 km3, as lower permeabilities result in unreasonably high injection pressures and higher permeabilities accelerate thermal drawdown. After cooling of the reservoir, the model assumes that the rock behaves in a brittle manner, which may lead to decreased fluid pressures due to a lowering of thresholds for failure in a critically stressed crust. However, such an evolution may also increase the risk for short-circuiting of fluid pathways, as in regular EGS systems. Although our theoretical investigation sheds light on the roles of geologic and operational parameters, realizing the potential of the ductile crust as an energy source requires cost-effective deep drilling technology as well as further research describing rock behavior at elevated temperatures and pressures.
Deformation characteristics and instability mechanism of large-scale anti-dip rock slides
Authors: Wang Xuebing , Zhang Nan , Zhang Zhihua , Wang Luqi , Yu Shu , Zhao Peng , Yan Guoqiang
Published: March 2024

The anti-dip bedding rock slopes have threatened global infrastructure construction and urban expansion seriously. Taking the Guang'an Village rockslide as an example, this paper firstly studied the deformation characteristics of the rockslide with anti-dip bedding structure based on in-situ investigation and monitoring, and then the relevant influencing factors were summarized. On this basis, a new evolution model of continuous-pushing-section pressing locked-section and the instability mechanism of the rock slope were proposed. Finally, the applicability of the model and the deformation tendency of the rock slope were further discussed. A catastrophic sliding event has once occurred in the Guang'an Village rockslide in 2017, after which the deformation of the potential source area III (PSA-III) was accelerating. The presence of the sliding-prone geological structure provides the basic conditions for the deformation of the rock slope and the development of the sliding zone. Rainfall is the major external trigger that promotes the deformation. As the sliding zone extends forward, the overlying deformation body will keep on pushing against the preceding rock mass, which will contribute to the forward extension of the sliding zone as well. When the final locked section is crushed, the rock slope will lose balance. According to the observation in the field, the PSA-III is in the late stage of the deformation-increasing phase currently. This study can provide a reference for the analysis of failure mechanism and the design of monitoring and mitigation of other large anti-dip bedding rock slides.
ProjectDRIVE: study protocol for a randomized controlled trial to improve driving practices of high-risk teen drivers with a traffic violation
Authors: Yang Jingzhen , Peek-Asa Corinne , Zhang Ying , Hamann Cara , Zhu Motao , Wang Yang , Kaur Archana , Recker Robyn , Rose Dominique , Roth Lisa
Published: March 2024

Background

Teen drivers with a traffic violation are at increased risk for crashes and crash-related injuries; however, most parent-focused interventions target teen drivers with supervised learner’s permits. Very few interventions are implemented at the probationary driver's license stage or target high-risk teen drivers, such as those with traffic violations. This paper describes the protocol of ProjectDRIVE, A Randomized Controlled Trial to Improve Driving Practices of High-Risk Teen Drivers with a Traffic Violation, which targets improving parent-teen communication about safe driving practices to reduce unsafe driving behaviors and traffic violation recidivism of teen drivers cited for traffic violation.

Methods

Teen drivers (ages 16 or 17) cited for a moving violation and the parent/legal guardian most involved with the teen’s driving are recruited from juvenile traffic courts following their required court hearing. After completing informed consent/assent, enrolled dyads are randomized into one of three groups using stratified block randomization: control, device feedback only, or device feedback plus parent communication training. Participating dyads are followed for 6 months with 3 months of active intervention. Using in-vehicle device and smartphone application technology, the study provides real-time and cumulative driving feedback to intervention teens and collects continually recorded, objectively measured driving outcome data throughout the teen’s study participation. Primary outcomes include rates of risky driving events and unsafe driving behaviors per 1000 miles driven. Secondary outcomes include traffic violation recidivism up to 12 months following study completion and frequency and quality of parent-teen communication about safe driving practices.

Discussion

Through partnership with the local juvenile traffic courts, this study integrates recruitment and randomization into existing court practices. Successfully completing this study will significantly impact juvenile traffic court’s practices and policies by informing judges’ decisions regarding the driving safety programs they refer to teens to prevent motor vehicle crashes and crash-related injuries and deaths.

Trial registration The study was registered on ClinicalTrials.gov Registry (NCT04317664) on March 19, 2020, https://clinicaltrials.gov/study/NCT04317664 and updated on April 27, 2021. This protocol was developed per the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Checklist.
A brief review of single silicate crystal paleointensity: rock-magnetic characteristics, mineralogical backgrounds, methods and applications
Authors: Kato Chie , Usui Yoichi , Sato Masahiko
Published: March 2024

Single silicate crystals hosting tiny magnetic inclusions are remarkable targets to study the paleointensities of the Earth and extraterrestrial samples. Since the pioneering work done in late 1990s, paleointensity studies using various silicate minerals such as feldspar, quartz, zircon, pyroxene, and olivine with magnetic inclusions trapped during grain growth or exsolved from the host phase have been reported. It has been shown that some single crystals have the ability to record paleomagnetic information as reliable or more reliable than the whole rock, by direct comparison of the obtained paleointensity estimate from single crystal and the whole-rock sample or the magnetic observatory data. Various rock-magnetic studies also support the fidelity of these crystals. Here, we provide a brief review of the rock-magnetic characteristics of the single crystals, the mineralogical background of the hosting silicates, and experimental procedures developed to obtain reliable data from magnetically weak samples with distinctive rock-magnetic features. We also overview the studies on paleointensity and related topics on various terrestrial and extraterrestrial samples published mainly after the comprehensive reviews in late 2000s. The present review covers the advantages as well as the limitations and caveats of paleointensity studies using single crystal samples and will help readers who wish to utilize this technique in their research.

Graphical Abstract
Early Jurassic extrinsic solar system dynamics versus intrinsic Earth processes: Toarcian sedimentation and benthic life in deep-sea contourite drift facies, Cardigan Bay Basin, UK
Authors: Pieńkowski Grzegorz , Uchman Alfred , Ninard Krzysztof , Page Kevin N. , Hesselbo Stephen P.
Published: March 2024

The Cardigan Bay Basin (UK) may have functioned as a deep and narrow strait, and thereby influenced Early Jurassic oceanic circulation through the northern and southern Laurasian Seaway, and between Boreal and Peri-Tethys domains. Toarcian hemipelagic deposits of the basin in the Mochras borehole show strongly bioturbated contourite facies. Trace fossils are strongly dominated by Phycosiphon incertum (represented by four morphotypes), which was produced by opportunistic colonizers. Thalassinoides, Schaubcylindrichnus and Trichichnus are common (the latter is a deep-tier trace fossil produced by filamentous sulfide-oxidizing bacteria with a high tolerance for dysoxia), accompanied by less common Zoophycos, Planolites, Palaeophycus, Teichichnus, Rhizocorallium, Chondrites, and dwelling and resting structures, such as cf. Polykladichnus, Siphonichnus, Skolithos, Arenicolites, Monocraterion and Lockeia. Ichnological and lithological signals suggest repetitive fluctuations in benthic conditions attributed to a hierarchy of orbital cycles (precession and obliquity [4th order], short eccentricity [3rd order], long eccentricity [2nd order] and Earth–Mars secular resonance [1st order]). The Pliensbachian–Toarcian transition appears to be a significant palaeoceanographic turning point in the Cardigan Bay Basin, starting a CaCO3 decline, and with the most severe oxygen crisis of the Tenuicostatum Zone (here dysoxic but not anoxic) ending at the onset, in the early Serpentinum Zone (Exaratum Subzone), of the Toarcian negative carbon isotope excursion (To-CIE—linked with the Toarcian Oceanic Anoxic Event occurring in the lower part in the Serpentinum Zone). This trend contrasts with the prevalence of anoxia synchronous with the To-CIE in many other settings. Minor dysoxia returned to the Mochras setting in the latest Thouarsense to Dispansum zone interval. Extreme climate warming during the To-CIE may have enhanced and caused a reversal in the direction of deep marine circulation, improving oxygenation of the sea floor. Spectral analysis of binary data on ichnotaxa appearances gives high confidence in orbital signals and allows refined estimation of ammonite zones and the duration of the Toarcian (minimum ~ 9.4 Myr).
Immune cells: potential carriers or agents for drug delivery to the central nervous system
Authors: Zhang Shan-Shan , Li Ruo-Qi , Chen Zhong , Wang Xiao-Ying , Dumont Aaron S. , Fan Xiang
Published: March 2024

Drug delivery systems (DDS) have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery. However, the access of nanoparticles/drugs to the central nervous system (CNS) remains a challenge mainly due to the obstruction from brain barriers. Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery. Herein, we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier. We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS, as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases. Finally, we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
Mesenteric root pseudocyst: finding in an asymptomatic patient—a case report
Authors: Suldrup F. , Uad P. , Vaccaro A. , Mazza M. , Santino J. , Mazza O.
Published: March 2024

Background

Mesenteric cysts are one of the rarest abdominal tumor masses, representing a little-studied pathology. In turn, the variability and non-specificity of clinical manifestations make diagnosis difficult, as it can be reached by imaging findings due to another cause or by non-specific abdominal pain.

Case presentation

This article describes the case report of an asymptomatic 28-year-old patient who presented a 6-cm abdominal cystic mass with mixed density, which was found incidentally by computed tomography. Exploratory laparoscopy was performed followed by conversion to conventional surgery to extract the tumor mass. The anatomical pathology diagnosis was pseudocyst of the mesentery root. Mesenteric cysts are one of the rarest abdominal tumor masses, representing a little-studied pathology. In turn, the variability and non-specificity of clinical manifestations make diagnosis difficult, as it can be reached by imaging findings due to another cause or by non-specific abdominal pain.

Conclusions

Mesenteric cysts are rare, and their nonspecific symptoms often lead to diagnosis based on imaging findings. Complete laparoscopic enucleation is the standard treatment.
In vivo evaluation of tumor uptake and bio-distribution of 99mTc-labeled 1-thio-β-D-glucose and 5-thio-D-glucose in mice model
Authors: Muehlberg Fabian , Mohnike Konrad , Grosser Oliver S. , Pech Maciej , Goldschmidt Juergen , Smalla Karl-Heinz , Seidensticker Ricarda , Ümütlü Muzaffer Reha , Deniz Sinan , Ricke Jens , Steffen Ingo G. , Öcal Osman , Seidensticker Max
Published: March 2024

Background

To investigate the capacity of 99mTc-labeled 1-thio-β-D-glucose (1-TG) and 5-thio-D-glucose (5-TG) to act as a marker for glucose consumption in tumor cells in vivo as well as to evaluate the biodistribution of 1-TG and 5-TG. We investigated the biodistribution, including tumor uptake, of 1-TG and 5-TG at various time points after injection (0.5, 2 and 4 h) in human colorectal carcinoma (HCT-116) and human lung adenocarcinoma (A549) xenograft bearing nude mice (N = 4 per tracer and time point).

Results

Ex vivo biodistribution studies revealed a moderate uptake with a maximum tumor-to-muscle ratio of 4.22 ± 2.7 and 2.2 ± 1.3 (HCT-116) and of 3.2 ± 1.1 and 4.1 ± 1.3 (A549) for 1-TG and 5-TG, respectively, with a peak at 4 h for 1-TG and 5-TG. Biodistribution revealed a significantly higher uptake compared to blood in kidneys (12.18 ± 8.77 and 12.69 ± 8.93%ID/g at 30 min) and liver (2.6 ± 2.8%ID/g) for 1-TG and in the lung (7.24 ± 4.1%ID/g), liver (6.38 ± 2.94%ID/g), and kidneys (4.71 ± 1.97 and 4.81 ± 1.91%ID/g) for 5-TG.

Conclusions

1-TG and 5-TG showed an insufficient tumor uptake with a moderate tumor-to-muscle ratio, not reaching the levels of commonly used tracer, for diagnostic use in human colorectal carcinoma and human lung adenocarcinoma xenograft model.
Predictors of serious infections in rheumatoid arthritis—a prospective Brazilian cohort
Authors: de Almeida Ana Luisa Bagno , Guimarães Maria Fernanda B. Resende , da Costa Pinto Maria Raquel , Pereira Leticia Rocha , Reis Ana Paula Monteiro Gomides , Bonfiglioli Karina Rossi , Louzada-Junior Paulo , Giorgi Rina Dalva Neubarth , de Castro Gláucio Ricardo Werner , Radominski Sebastião Cezar , Brenol Claiton Viegas , Pugliesi Alisson , da Mota Licia Maria Henrique , da Rocha Castelar-Pinheiro Geraldo
Published: March 2024

Background

Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients.

Objective

To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions.

Methods

We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment.

Results

841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5–6.9), 3.6 times (95% CI: 1.2–10.4) and 2.4 times (95% CI: 1.2–5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3–12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20–120%).

Conclusion

The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.
Effects of intra-articular injection of platelet-rich plasma on the inflammatory process and histopathological characteristics of cartilage and synovium in animals with osteoarthritis: a systematic review with meta-analysis
Authors: Garcia-Motta Homero , Carvalho Cristiano , Guilherme Evelyn Maria , de Oliveira Marcos Paulo Braz , Rossi Karina Nogueira Zambone Pinto
Published: March 2024

Background

Osteoarthritis (OA) affects the entire joint, causing structural changes in articular cartilage, subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles that afflicts millions of people globally, leading to persistent pain and diminished quality of life. The intra-articular use of platelet-rich plasma (PRP) is gaining recognition as a secure therapeutic approach due to its potential regenerative capabilities. However, there is controversial clinical data regarding efficacy of PRP for OA treatment. In this context, gathering scientific evidence on the effects of PRP in treating OA in animal models could provide valuable insights into understanding its impact on aspects like cartilage health, synovial tissue integrity, and the inflammatory process in affected joints. Thus, the objective of this study was to assess the effects of PRP injections on inflammation and histopathological aspects of cartilage and synovium in animal models of OA through a comprehensive systematic review with meta-analysis.

Methods

A electronic search was conducted on Medline, Embase, Web of Science, The Cochrane Library, LILACS, and SciELO databases for relevant articles published until June 2022. A random-effects meta-analysis was employed to synthesize evidence on the histological characteristics of cartilage and synovium, as well as the inflammatory process. The GRADE approach was utilized to categorize the quality of evidence, and methodological quality was assessed using SYRCLE’s RoB tool.

Results

Twenty-one studies were included in the review, with twelve of them incorporated into the meta-analysis. PRP treatment demonstrated superior outcomes compared to the control group in terms of cartilage histology (very low quality; p = 0.0002), synovium histology (very low quality; p < 0.0001), and reductions in proinflammatory markers, including IL-1 (low quality; p = 0.002), IL-6 (very low quality; p < 0.00001), and TNF-α (very low; p < 0.00001). However, PRP treatment did not yield a significant impact on PDGF-A levels (very low quality; p = 0.81).

Conclusion

PRP appears capable of reducing proinflammatory markers (IL-1, IL-6, TNF-α) and mitigating cartilage and synovium damage in animals with OA. However, the levels of evidence of these findings are low to very low. Therefore, more rigorous studies with larger samples are needed to improve the quality of evidence.

PROSPERO registration

CRD42022250314
Inflammatory myofibroblastic tumor in pediatric patients: challenges in diagnosis, multidisciplinary management, and surgical strategies
Authors: García Izchel Valdez , Gutierrez Alejandro Solano , Guzmán Sofia Brenes , Viveros Brenda Aguilar
Published: March 2024

Background

Inflammatory myofibroblastic tumor is a rare yet profoundly impactful condition, particularly within the pediatric population. This case report illuminates the intricate challenges of diagnosing and managing inflammatory myofibroblastic tumors in children, underscoring the importance of interdisciplinary collaboration in formulating effective treatment strategies. Notably, the choice of surgical approach holds a paramount influence on the risk of recurrence and metastasis, with wide resection with bronchotomy, lobectomy, and pneumonectomy demonstrating significantly diminished recurrence rates compared to wedge resection in bronchoscopic removal.

Case presentation

We present the case of a 3-year-old girl with a progressive, nonproductive cough, occasionally accompanied by episodes of hemoptysis and pneumonia for a year, secondary to an inflammatory myofibroblastic tumor that was removed by bronchotomy with excellent results.

Conclusion

Given the extraordinary rarity of this disease in pediatric patients, ongoing research endeavors and the accumulation of collective expertise are paramount.
The role of pelvic floor ultrasound correlated with pelvic organ prolapse quantification in the assessment of anterior and apical compartments of pelvic organ prolapse
Authors: El-Gohary Toqa , Hamed Soha T. , El-Azizi Hatem Mohamed , Haggag Hisham Mamdouh , Azzam Heba
Published: March 2024

Background

Pelvic organ prolapse (POP) is a gynecological disease significantly associated with older age. A higher prevalence of women with symptomatic POP showed physical and emotional distress, negatively affecting their quality of life (QoL). The most widespread tool used is the prolapse quantification system (POP-Q) of the International Continence Society (ICS). The aim of this study was to evaluate the role of ultrasound (U/S) compared to POP-Q for the detection and quantification of POP in the anterior (urinary bladder) and apical (cervix/vaginal vault) compartments of the pelvic floor in Egyptian women.

Results

The current study revealed that among 83 women, 53 had POP with a mean age of 50.83 years, 96.2% had anterior compartment prolapse (either alone or with apical compartment prolapse), 52% had apical compartment prolapse (either alone or with anterior compartment prolapse), 47.2% had anterior compartment prolapse only, and 3.7% had apical compartment prolapse only. There was a strong agreement (almost linear) between (POP-Q) and U/S in detecting significant pelvic organ prolapse in the anterior compartment (Kappa value 0.925, P < 0.001) and the apical compartment (Kappa value 0.945 and P < 0.001). With higher value of sensitivity and specificity, our study assigned significant anterior compartment prolapse using a cutoff value of 0 for point Ba of POP-Q and −11.5 for bladder neck descent at valsalva using U/S.

Conclusions

Pelvic floor ultrasound provides general and detailed anatomical overview of the pelvic floor as well as detection and assessment of the POP in anterior and middle compartments.
An automated fluorescent immunoassay for on-site screening of AFM1 in raw milk at the ppt level
Authors: Kou Jiaqian , Dou Leina , Mari Ghulam Mujtaba , Wu Weilin , Zhang Yingjie , Li Peipei , Wang Xiaonan , Zhang Suxia , Wen Kai , Chen Yiping , Yu Wenbo
Published: March 2024

In the dairy industry, the quality of raw milk as it is collected from dairy farmers must be strictly ensured. Therefore, when on-site screening of typical carcinogens in raw milk, this technology must simultaneously be convenient to operate and highly sensitive. Here, an automated and fluorescent immunoassay system for screening trace amounts of aflatoxin M1 (AFM1) in raw milk was developed. The whole immunoassay procedure can be processed in a true “sample-to-results” paradigm, avoiding the tedious manual operation of the traditional indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) method. In addition, we designed an integrated fluorescent spectrometer that can quantitatively measure fluorescent signals with high sensitivity. The automated and fluorescent immunoassay system can screen AFM1 in raw milk samples with an ultra low limit of detection (4.7 pg/mL in raw milk). The half maximal inhibitory concentration (IC50) was 8.3 pg/mL, which is approximately 4-fold lower than that of traditional ic-ELISA. When the system was applied to screen actual raw milk samples, the recovery rates ranged from 79.4% to 104.6%, with a coefficient of variation ranging from 8.9% to 15.2%. Overall, we believe that the automated and fluorescent immunoassay system can provide a one-stop solution that is user-friendly and highly sensitive for screening trace AFM1 contaminants in raw milk.
Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study
Authors: Kittai Adam S. , Bond David , Huang Ying , Bhat Seema A. , Blyth Emily , Byrd John C. , Chavez Julio C. , Davids Matthew S. , Dela Cruz Jamie P. , Dowling Mark R. , Duffy Caitlyn , Ho Carrie , Jacobson Caron , Jaglowski Samantha , Jain Nitin , Lin Kevin H. , Miller Cecelia , McCarthy Christine , Omer Zulfa , Parry Erin , Rai Manoj , Rogers Kerry A. , Saha Aditi , Schachter Levanto , Scott Hamish , Senapati Jayastu , Shadman Mazyar , Siddiqi Tanya , Stephens Deborah M. , Vanguru Vinay , Wierda William , Woyach Jennifer A. , Thompson Philip A.
Published: March 2024

PURPOSE

Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established.

METHODS

We performed an international multicenter retrospective study of patients with RT who received CAR-T. Patient, disease, and treatment characteristics were summarized using descriptive statistics, and modeling analyses were used to determine association with progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated from the date of CAR-T infusion.

RESULTS

Sixty-nine patients were identified. The median age at CAR-T infusion was 64 years (range, 27-80). Patients had a median of four (range, 1-15) previous lines of therapy for CLL and/or RT, including previous Bruton tyrosine kinase inhibitor and/or BCL2 inhibitor therapy in 58 (84%) patients. The CAR-T product administered was axicabtagene ciloleucel in 44 patients (64%), tisagenlecleucel in 17 patients (25%), lisocabtagene maraleucel in seven patients (10%), and brexucabtagene autoleucel in one patient (1%). Eleven patients (16%) and 25 patients (37%) experienced grade ≥3 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, respectively. The overall response rate was 63%, with 46% attaining a complete response (CR). After a median follow-up of 24 months, the median PFS was 4.7 months (95% CI, 2.0 to 6.9); the 2-year PFS was 29% (95% CI, 18 to 41). The median OS was 8.5 months (95% CI, 5.1 to 25.4); the 2-year OS was 38% (95% CI, 26 to 50). The median duration of response was 27.6 months (95% CI, 14.5 to not reached) for patients achieving CR.

CONCLUSION

CAR-T demonstrates clinical efficacy for patients with RT.
Continuous Subcutaneous Delivery of rhPTH(1-84) and rhPTH(1-34) by Pump in Adults With Hypoparathyroidism
Authors: Charoenngam Nipith , Bove-Fenderson Erin , Wong Daniel , Cusano Natalie E , Mannstadt Michael
Published: March 2024

Context

Continuous subcutaneous infusion of recombinant parathyroid hormone (rhPTH) through a pump has been proposed as a therapeutic alternative for patients with chronic hypoparathyroidism who remain symptomatic or hypercalciuric on conventional treatment (calcium and active vitamin D) or daily injections of rhPTH(1-84) or rhPTH(1-34). However, the real-world evidence of the outcome of this novel therapy is limited.

Case Descriptions

We report the clinical and biochemical outcomes of 12 adults with hypoparathyroidism (11 women, age 30-70 years, and 1 man, age 30 years) from 3 different clinical sites in the United States who were transitioned from conventional therapy to daily injections of rhPTH(1-84) or rhPTH(1-34) and then switched to continuous administration of rhPTH(1-84)/rhPTH(1-34) via pump therapy. In most patients, mean serum calcium concentrations increased while on PTH pump therapy compared with both conventional therapy (in 11 patients) and single/multiple daily rhPTH injections (in 8 patients). Despite this, 10 patients had lower median 24-hour urinary calcium levels while on PTH pump therapy compared with prior therapy (mean ± SD difference: −130 ± 222 mg/24 hours). All patients reported a qualitative decrease in hypocalcemic symptoms while receiving pump therapy. Three patients had pod failure at least once, and 1 patient developed an infusion site reaction.

Conclusion

In this case series of 12 patients with chronic hypoparathyroidism treated with rhPTH(1-84)/rhPTH(1-34) administered via a pump, improvement in clinical and biochemical parameters were observed in the majority of the patients. Our observations indicate benefits of pump administration of rhPTH that warrant further investigation.
Not Only RET but NF1 and Chromosomal Instability Are Seen in Young Patients with Sporadic Medullary Thyroid Carcinoma
Authors: Castroneves Luciana Audi , Mangone Flavia Regina Rotea , Lerario Antonio Marcondes , da Cunha Mercante Ana Maria , Batista Rafael Loch , Barros Luciana Rodrigues Carvalho , Ferreira Carla Vaz , Farias Evelin Cavalcante , Vanderlei Felipe Augusto Brasileiro , Maia Ana Luiza , Nagai Maria Aparecida , Jorge Alexander Augusto Lima , Hoff Ana Oliveira
Published: March 2024

Context

Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in RET, RAS, and occasionally other genes. However, around 20% of patients with sporadic MTC lack a known genetic driver.

Objective

To uncover potential new somatic or germline drivers, we analyze a distinct cohort of patients with sporadic, very early–onset, and aggressive MTC.

Methods

Germline and somatic DNA exome sequencing was performed in 19 patients, previously tested negative for germline RET variants.

Results

Exome sequencing of 19 germline samples confirmed the absence of RET and identified an NF1 pathogenic variant in 1 patient. Somatic sequencing was successful in 15 tumors revealing RET variants in 80%, predominantly p.Met918Thr, which was associated with disease aggressiveness. In RET-negative tumors, pathogenic variants were found in HRAS and NF1. The NF1 germline and somatic variants were observed in a patient without a prior clinical diagnosis of neurofibromatosis type 1, demonstrating that the loss of heterozygosity of NF1 functions as a potential MTC driver. Somatic copy number alterations analysis revealed chromosomal alterations in 53.3% of tumors, predominantly in RET-positive cases, with losses in chromosomes 9 and 22 being the most prevalent.

Conclusion

This study reveals that within a cohort of early-onset nonhereditary MTC, RET remains the major driver gene. In RET-negative tumors, NF1 and RAS are drivers of sporadic MTC. In addition, in young patients without a RET germline mutation, a careful clinical evaluation with a consideration of germline NF1 gene analysis is ideal to exclude Neurofibromatosis type 1 (NF1).
Preoperative Mobile Health Data Improve Predictions of Recovery From Lumbar Spine Surgery
Authors: Greenberg Jacob K. , Frumkin Madelyn , Xu Ziqi , Zhang Jingwen , Javeed Saad , Zhang Justin K. , Benedict Braeden , Botterbush Kathleen , Yakdan Salim , Molina Camilo A. , Pennicooke Brenton H. , Hafez Daniel , Ogunlade John I. , Pallotta Nicholas , Gupta Munish C. , Buchowski Jacob M. , Neuman Brian , Steinmetz Michael , Ghogawala Zoher , Kelly Michael P. , Goodin Burel R. , Piccirillo Jay F. , Rodebaugh Thomas L. , Lu Chenyang , Ray Wilson Z.
Published: March 2024

BACKGROUND AND OBJECTIVES:

Neurosurgeons and hospitals devote tremendous resources to improving recovery from lumbar spine surgery. Current efforts to predict surgical recovery rely on one-time patient report and health record information. However, longitudinal mobile health (mHealth) assessments integrating symptom dynamics from ecological momentary assessment (EMA) and wearable biometric data may capture important influences on recovery. Our objective was to evaluate whether a preoperative mHealth assessment integrating EMA with Fitbit monitoring improved predictions of spine surgery recovery.

METHODS:

Patients age 21–85 years undergoing lumbar surgery for degenerative disease between 2021 and 2023 were recruited. For up to 3 weeks preoperatively, participants completed EMAs up to 5 times daily asking about momentary pain, disability, depression, and catastrophizing. At the same time, they were passively monitored using Fitbit trackers. Study outcomes were good/excellent recovery on the Quality of Recovery-15 (QOR-15) and a clinically important change in Patient-Reported Outcomes Measurement Information System Pain Interference 1 month postoperatively. After feature engineering, several machine learning prediction models were tested. Prediction performance was measured using the c-statistic.

RESULTS:

A total of 133 participants were included, with a median (IQR) age of 62 (53, 68) years, and 56% were female. The median (IQR) number of preoperative EMAs completed was 78 (61, 95), and the median (IQR) number of days with usable Fitbit data was 17 (12, 21). 63 patients (48%) achieved a clinically meaningful improvement in Patient-Reported Outcomes Measurement Information System pain interference. Compared with traditional evaluations alone, mHealth evaluations led to a 34% improvement in predictions for pain interference (c = 0.82 vs c = 0.61). 49 patients (40%) had a good or excellent recovery based on the QOR-15. Including preoperative mHealth data led to a 30% improvement in predictions of QOR-15 (c = 0.70 vs c = 0.54).

CONCLUSION:

Multimodal mHealth evaluations improve predictions of lumbar surgery outcomes. These methods may be useful for informing patient selection and perioperative recovery strategies.
Preinjury Frailty Predicts 1-Year Mortality in Older Adults With Traumatic Spine Fractures
Authors: Fields Daryl P. , Varga Gregory , Alattar Ali , Shanahan Regan , Das Ashtah , Hamilton David K. , Okonkwo David O. , Kanter Adam S. , Forsythe Raquel M. , Weiner Debra K.
Published: March 2024

BACKGROUND AND OBJECTIVES:

Nearly 30% of older adults presenting with isolated spine fractures will die within 1 year. Attempts to ameliorate this alarming statistic are hindered by our inability to identify relevant risk factors. The primary objective of this study was to develop a prediction model that identifies feasible targets to limit 1-year mortality.

METHODS:

This retrospective cohort study included 703 older adults (65 years or older) admitted to a level I trauma center with isolated spine fractures, without neural deficit, from January 2013 to January 2018. Multivariable analysis was used to select for independently significant patient demographics, frailty variables, injury metrics, and management decisions to incorporate into distinct logistic regression models predicting 1-year mortality. Variables were considered significant, if P < .05.

RESULTS:

Of the 703 older adults, 199 (28.3%) died after hospital discharge, but within 1 year of index trauma. Risk Analysis Index (RAI; odds ratio [OR]: 1.116; 95% CI: 1.087-1.149; P < .001) and ambulation requiring a cane (OR: 2.601; 95% CI: 1.151-5.799; P = .02) or walker (OR: 4.942; 95% CI: 2.698-9.196; P < .001), ie, frailty variables, were associated with increased odds of 1-year mortality. Spine trauma scales were not associated with 1-year mortality. Longer hospital stays (OR: 1.112; 95% CI: 1.034-1.196; P = .004) and nursing home discharge (OR: 3.881; 95% CI: 2.070-7.378; P < .001) were associated with increased odds, while discharge to rehab (OR: 0.361; 95% CI: 0.155-0.799; P = .014) decreased 1-year mortality odds. A “preinjury” regression model incorporating Risk Analysis Index and ambulation status resulted in an area under receiver operating characteristic curve (AUROCC) of 0.914 (95% CI: 0.863-0.965). A “postinjury” model incorporating Glasgow Coma Scale, hospital stay duration, and discharge disposition resulted in AUROCC of 0.746 (95% CI: 0.642-0.849). Combining elements of the preinjury and postinjury models into an “integrated model” produced an AUROCC of 0.908 (95% CI: 0.852-0.965).

CONCLUSION:

Preinjury frailty measures are most strongly associated with 1-year mortality outcomes in older adults with isolated spine fractures. Incorporating injury metrics or management decisions did not enhance predictive accuracy. Further work is needed to understand how targeting frailty may reduce mortality.
Dynamism Diminished: The Role of Housing Markets and Credit Conditions
Authors: Davis Steven J. , Haltiwanger John
Published: March 2024

We estimate the effects of house price changes on young-firm employment shares and industry-level employment growth in local economies. A novel test shows that house price effects on local economies work through wealth, liquidity, and collateral effects on the propensity to start new firms and expand young ones. Aggregating local effects to the national level, our estimates imply that housing market ups and downs play a major role—as transmission channel and driving force—in medium-run fluctuations in young-firm employment shares in recent decades. We also find a distinct and smaller role for locally exogenous loan-supply shifts. (JEL D22, E24, E32, G21, L25, R11, R31)
Ambiguity Aversion and Heterogeneity in Households’ Beliefs
Authors: Michelacci Claudio , Paciello Luigi
Published: March 2024

UK households that wish for lower inflation and lower nominal interest rates have higher expected inflation. We interpret the evidence through the lens of a New Keynesian model where ambiguity-averse households differ in wealth, skill, labor market participation, and the receipt of government transfers and are subject to Knightian uncertainty. Households act based on beliefs that are negatively affected by their wishes, the more so the greater the amount of uncertainty. Using indirect inference, we find substantial output costs due to uncertainty. Monetary policy uncertainty contributes little to the costs because households generally dislike monetary expansions. (JEL D12, D81, D83, E12, E31, E43, E52)
Testing the Effectiveness of Unconventional Monetary Policy in Japan and the United States
Authors: Ikeda Daisuke , Li Shangshang , Mavroeidis Sophocles , Zanetti Francesco
Published: March 2024

Unconventional monetary policy (UMP) may make the effective lower bound (ELB) on the short-term interest rate irrelevant. We develop a theoretical model that underpins our empirical test of this “irrelevance hypothesis,” based on the simple idea that under the hypothesis, the short rate can be excluded in any empirical model that accounts for alternative measures of monetary policy. We test the hypothesis for Japan and the United States using a structural vector autoregressive model with the ELB. We firmly reject the hypothesis but find that UMP has had strong delayed effects. (JEL E12, E23, E31, E43, E52, E58)
Collective trauma as a means of shaping the society of Kalavryta
Authors: Γουσέτη Φωτεινή
Published: March 2024

Η διατριβή αυτή αφορά μία ανθρωπολογική έρευνα της μεταπολεμικής κοινωνίας των Καλαβρύτων. Συγκεκριμένα αναλύεται η τραυματική μνήμη αυτής της κοινωνίας μέσα από την υπάρχουσα, στο πεδίο, μνημειοποίηση. Επίσης παρουσιάζονται οι μνημονικές περιοχές από τις οποίες απορρέουν τα έργα τέχνης που έχω δημιουργήσει πάνω στην ίδια θεματική, συχνά μετατοπίζοντας το κέντρο βάρους της αφήγησης με γνώμονα έμφυλες, ταξικές, ή άλλες κοινωνικές διαφοροποιήσεις/ιεραρχίες. Τέλος, η παρούσα διατριβή αφορά μία πρόταση σύμπραξης τέχνης και ανθρωπολογίας βασισμένη στο παράδειγμα της σύγχρονης κοινωνίας των Καλαβρύτων.
Αιτιατά μοντέλα με εφαρμογές στις βιοεπιστήμες
Authors: Γανοπούλου Μαρία
Published: March 2024

Ο στόχος της παρούσας διδακτορικής διατριβής ήταν να διερευνήσει τη δυναμική της εφαρμογής των αιτιατών μοντέλων σε βιολογικά δεδομένα από διαφορετικά επιστημονικά πεδία. Τα τελευταία χρόνια έχουν αναπτυχθεί και συνεχίζουν να αναπτύσσονται συστηματικά μεγάλες βάσεις βιολογικών δεδομένων. Σε αυτό έχουν συνεισφέρει πολλοί παράγοντες όπως οι διεπιστημονικές ερευνητικές συνέργειες και οι ραγδαίες τεχνολογικές εξελίξεις. Η ύπαρξη τέτοιων βάσεων δημιουργεί την ανάγκη για σύγχρονες μεθόδους ανάλυσης, που θα μπορούν να ανταποκριθούν στις ιδιαίτερες απαιτήσεις που δημιουργούνται και να αξιοποιήσουν την πλούσια διαθέσιμη πληροφορία. Στην κατεύθυνση αυτή, τα αιτιατά μοντέλα προβάλλουν ως ένα εργαλείο με σημαντική και σε μεγάλο βαθμό ανεξερεύνητη δυναμική. Τα ανταγωνιστικά τους πλεονεκτήματα σε σχέση με συμβατικές μεθόδους ανάλυσης μπορούν να αποτελέσουν το εφαλτήριο για την ανάπτυξη καινοτόμων μεθοδολογικών προσεγγίσεων και εφαρμογών στις βιοεπιστήμες, ενισχύοντας την προσπάθεια για αξιοποίηση των δεδομένων και την εξαγωγή νέας γνώσης. Στο πλαίσιο της παρούσας διατριβής ερευνήθηκε: (α) η βελτιστοποίηση της επιλογής των προβλεπτικών παραγόντων και της τελικής πρόβλεψης της εξαρτημένης μεταβλητής με χρήση της τοπικής αιτιατής δομής, (β) ο εντοπισμός σημαντικών βιολογικών μηχανισμών αξιοποιώντας τα αιτιατά μοντέλα σε ομικά δεδομένα, (γ) η σύγκριση της αιτιατής δομής των ανεξάρτητων μεταβλητών μεταξύ των διαφορετικών κατηγοριών της εξαρτημένης μεταβλητής και η ανθεκτικότητα της αιτιατής δομής σε παρεμβάσεις στα δεδομένα.
Βιοχημική και κυτταρική in vitro και in vivo προσέγγιση της αντικαρκινικής δράσης του θειωμένου υαλουρονικού στον καρκίνο του μαστού
Authors: Κουτσάκης Χρήστος
Published: March 2024

Ο καρκίνος του μαστού αποτελεί μία από τις επικρατέστερες κακοήθειες παγκοσμίως, με την εξέλιξη της νόσου να εξαρτάται σε μεγάλο βαθμό από την έκφραση των οιστρογονοϋποδοχέων (ERs), ενώ σημαίνοντα ρόλο παίζει και η έκφραση μορίων του εξωκυττάριου χώρου (ECM). Το υαλουρονικό (ΗΑ) αποτελεί ένα κύριο συστατικό του ECM και εμπλέκεται σε πλήθος φυσιολογικών και παθολογικών διεργασιών. Σε αντίθεση με τις υπόλοιπες γλυκοζαμινογλυκάνες, το ΗΑ δε φέρει υποκαταστάσεις στη δομή του φυσικά. Εντούτοις, πρόσφατες μελέτες αναδεικνύουν τη χρήση χημικά τροποποιημένων παραγώγων του ΗΑ, όπως το θειωμένο υαλουρονικό (sHA), σε εφαρμογές όπως η κατασκευή βιο-ικριωμάτων, η επούλωση πληγών, η οστεογένεση, καθώς και στη στόχευση ασθενειών. Στην παρούσα διδακτορική διατριβή μελετήθηκε η δράση του sHA σε κύτταρα καρκίνου του μαστού διαφορετικής έκφρασης ERs. Για το σκοπό αυτό, συντέθηκε sΗΑ υψηλού βαθμού θείωσης και μελετήθηκε η in vitro δράση του στις καρκινικές σειρές MCF-7, MDA-MB-231, Hs578T, καθώς και στη σταθερά διαμολυσμένη σειρά shERβ MDA-MB-231. Παράλληλα, αναπτύχθηκαν τρισδιάστατα μοντέλα in vitro κυτταρικών καλλιεργειών και διερευνήθηκε η επίδραση του sHA σε καταστάσεις που προσομοιάζουν εγγύτερα το μικροπεριβάλλον του όγκου. Ακολούθως, μελετήθηκε η επίδραση του sHA in vivo σε μοντέλα ανοσοκατεσταλμένων μυών. Τέλος, διερευνήθηκε ο πιθανός μηχανισμός δράσης του sHA μέσω μελέτης σηματοδοτικών μονοπατιών και πραγματοποιήθηκαν in silico μελέτες μοριακής πρόσδεσης ώστε να προβλεφθούν οι πιθανές αλληλεπιδράσεις με υποδοχείς και ένζυμα αποικοδόμησης του ΗΑ. Σύμφωνα με τα αποτελέσματα, το sHA μειώνει τον πολλαπλασιασμό, τη μετανάστευση και τη διήθηση στα πιο επιθετικά καρκινικά κύτταρα μαστού, ενώ αυξάνει την κυτταρική προσκόλληση. Επιπλέον, με χρήση ηλεκτρονικής μικροσκοπίας σάρωσης παρατηρούνται αλλαγές στη μορφολογία των κυττάρων προς έναν πιο επιθηλιακό φαινότυπο. Οι αλλαγές αυτές επιβεβαιώνονται και από μεταβολές στην έκφραση σημαντικών μορίων του ECM καθώς και δεικτών προώθησης ή καταστολής του καρκίνου σε γονιδιακό και πρωτεϊνικό επίπεδο. Παράλληλα, το sHA μειώνει την ογκογενετική ικανότητα των καρκινικών κυττάρων μαστού σε ανοσοκατεσταλμένους μύες. Συνολικά, το sHA παρουσιάζει αντικαρκινική δράση ισχυρότερη του ΗΑ ίδιου μοριακού βάρους, τόσο σε συμβατικές όσο και σε τρισδιάστατες κυτταρικές καλλιέργειες, με τη δράση αυτή να μεσολαβείται μέσω του κύριου υποδοχέα του, CD44, και να οφείλεται εν μέρει σε ανταγωνισμό με το ενδογενώς παραγόμενο HA. Συμπερασματικά, η παρούσα διατριβή αναδεικνύει την κατασταλτική δράση του sHA στον καρκίνο του μαστού, ιδιαίτερα στις πιο επιθετικές μορφές όπως ο μη ορμονοεξαρτώμενος τριπλά αρνητικός καρκίνος του μαστού, και το καθιστά ένα πολλά υποσχόμενο βιομόριο στην ανάπτυξη καινοτόμων θεραπευτικών προσεγγίσεων.
An Approximation to the Invariant Measure of the Limiting Diffusion of G/Ph/n + GI Queues in the Halfin–Whitt Regime and Related Asymptotics
Authors: Jin Xinghu , Pang Guodong , Xu Lihu , Xu Xin
Published: March 2024

In this paper, we develop a stochastic algorithm based on the Euler–Maruyama scheme to approximate the invariant measure of the limiting multidimensional diffusion of [Formula: see text] queues in the Halfin–Whitt regime. Specifically, we prove a nonasymptotic error bound between the invariant measures of the approximate model from the algorithm and the limiting diffusion. To establish the error bound, we employ the recently developed Stein’s method for multidimensional diffusions, in which the regularity of Stein’s equation obtained by the partial differential equation (PDE) theory plays a crucial role. We further prove the central limit theorem (CLT) and the moderate deviation principle (MDP) for the occupation measures of the limiting diffusion of [Formula: see text] queues and its Euler–Maruyama scheme. In particular, the variances in the CLT and MDP associated with the limiting diffusion are determined by Stein’s equation and Malliavin calculus, in which properties of a mollified diffusion and an associated weighted occupation time play a crucial role.

Funding: X. Jin is supported in part by the Fundamental Research Funds for the Central Universities [Grants JZ2022HGQA0148 and JZ2023HGTA0170]. G. Pang is supported in part by the U.S. National Science Foundation [Grants DMS-1715875 and DMS-2216765]. L. Xu is supported in part by the National Nature Science Foundation of China [Grant 12071499], Macao Special Administrative Region [Grant FDCT 0090/2019/A2], and the University of Macau [Grant MYRG2018-00133-FST]. This work was supported by U.S. National Science Foundation [Grant DMS-2108683].
Taguchi and ANOVA-based Optimization of CNC Milling Parameters for Aluminium 7075 Alloy
Authors: T. Sathish
Published: March 2024

This study is aimed at optimizing the CNC milling parameters for Aluminium 7075 alloy, using Taguchi and Analysis of Variance (ANOVA) approaches. The high-strength alloy has applications in the automobile and aerospace industries. The cutting depth, speed of milling and rate of feed were adjusted to methodically enhance the machining performance and efficiency; surface roughness was studied in these metrics. Taguchi and ANOVA approaches were helpful in optimizing the parameters to lower cost, improve machining quality and enhance the productivity of Aluminium 7075 alloy.
The Combustion and Emission Characteristics of Corn Oil Biodiesel with Titanium Oxide (TiO2) Nano-additive
Authors: Surakasi Raviteja  , K. Ch. Sekhar  , Sundara Ramam Rapeta  , D. Bhanuchandra Rao  , B. Ushaswini
Published: March 2024

This experiment produced biodiesel from corn oil through transesterification. Fuel mixture proportions were changed to assess engine performance and reduce fossil fuel emissions. This study examined brake power, mean effective pressure, mechanical efficiency, brake thermal efficiency and indicated thermal efficiency, and emissions such as hydrocarbons, carbon monoxide and NOx. 20% of corn oil was blended with diesel to make biodiesel. The fuel characteristics of the corn oil methyl ester matched ASTM standards. Experimental results were obtained by operating a single-cylinder four-stroke diesel engine under various load conditions. Titanium oxide nanoparticles in the biodiesel reduced HC and CO engine emissions whereas, there was an increase in CO2 and NOx emissions. Combustion parameters such as cumulative net heat release rate and fuel line pressure decreased whereas, cylinder pressure and net heat release rate increased; the sample BD20 + 100 ppm TiO2 sample exhibited appreciable results.