bluuebunny/crossref_metadata_2025 huggingface dataset:
A VAMS‐based LC–MS/MS method for precise cenobamate quantification in epilepsy (patients)
Authors: Pigliasco Federica , Cafaro Alessia , Barco Sebastiano , Biondi Margherita , Stella Manuela , Mattioli Francesca , Riva Antonella , de Grazia Ugo , Molteni Linda , Micalizzi Elisa , Villani Flavio , Striano Pasquale , Bandettini Roberto , Cangemi Giuliana
Published: September 2024

Objective

Cenobamate (CNB), a recently approved antiseizure medication by the European Medicines Agency (EMA), serves as an adjunctive therapy for focal‐onset seizures in adult patients unresponsive to at least two other treatments. Administered in polytherapy, CNB can potentially interact with co‐administered drugs in epilepsy patients, necessitating dose adjustments and the need for effective therapeutic drug monitoring (TDM).

Methods

In this study, we introduce a novel LC–MS/MS method for precise CNB quantification using Volumetric Absorptive Microsampling (VAMS), following validation according to ICH guidelines M10. VAMS samples are efficiently extracted with 200 μL of methanol, with chromatographic separation achieved using an Acquity UPLC HSS PFP column. The method's efficacy was confirmed through its application to real samples from adult CNB‐treated patients.

Results

Our results demonstrate that the method exhibits linearity within the range of 0.05–30 mg/L, with intra‐ and inter‐run precision ranging from 1% to 8% and accuracy from 1% to 10% based on 30 μL of sample. Furthermore, CNB stability in VAMS is confirmed for up to 15 days at 25°C and −20°C. Importantly, no significant difference was observed between CNB concentrations in VAMS samples and those in plasma obtained from venous blood.

Significance

This VAMS‐based LC–MS/MS method presents a robust alternative for TDM in CNB‐treated patients. Future investigations should explore CNB concentrations in capillary blood and assess their correlation with plasma levels to further enhance its clinical utility.

Plain Language Summary

Cenobamate is an antiepileptic drug and used for treatment of focal‐onset seizures in adult patients (≥18 age). TDM can prevent drug interactions and minimize drug toxicity. The aim of this work is to evaluate volumetric absorptive microsampling (VAMS) from capillary blood as an alternative strategy for TDM in patients treated with the newly antiepileptic drug. Our method is suitable for TDM, and this study suggests that VAMS allows monitoring of cenobamate concentration and can offer valuable support for personalized therapy in refractory epilepsy.
Structural and in vitro anticancer properties of the kaempferol–lactoferrin complex
Authors: Xue Peiyu , Zhao Hongmei , You Xinyong , Yue Weiming
Published: September 2024

Lactoferrin and polyphenols are common natural functional compounds. Their interactions and the consequential alterations in functional activity have received widespread attention. The work aimed to investigate the interaction between lactoferrin and kaempferol, as well as evaluate the in vitro anticancer properties of the lactoferrin–kaempferol complex. The results of the spectra experiments revealed that lactoferrin and kaempferol are capable of forming complexes to quench the endogenous fluorescence of lactoferrin. Further insight into the binding mechanism was gained through molecular docking and molecular dynamics simulations. These analyses suggest that both hydrophobic interactions and hydrogen bonding are essential factors in the interaction between lactoferrin and kaempferol. Furthermore, the MTT assay and apoptosis by flow cytometry were conducted, revealing a synergistic effect of kaempferol and lactoferrin on the inhibition of HeLa cell proliferation. The findings from this investigation could improve our understanding of lactoferrin's interaction with polyphenols and the role of the lactoferrin–kaempferol complex in inhibiting cancer cell proliferation.
Adherence to the Mediterranean diet in patients with psoriasis and its relationship with the severity of the disease: A case‐control study
Authors: Aryanian Zeinab , Asghari Mohsen , Zanousi Parisa Pasha , Ghadimi Reza , Kebria Azar Shirzadian , Hatami Parvaneh
Published: September 2024

Background and Aim

Psoriasis is a prevalent chronic inflammatory skin condition, and the Mediterranean diet is often recommended for its health benefits, particularly its ability to mitigate chronic inflammation. This study sought to examine the extent to which psoriasis patients adhere to the Mediterranean diet and to explore its correlation with the severity of their condition

Methods

Seventy‐one psoriasis patients and 71 age‐ and sex‐matched healthy controls were enrolled the study and filled a standard questionnaire of adherence to the Mediterranean diet. The relationship between disease severity and adherence to the diet was also dealt with.

Results

The Mediterranean diet adherence score in the psoriasis group (5.25 ± 1.64) was significantly lower than the control group (6.28 ± 2.10) (p = 0.004). In addition, the consumption of fruit and fish in psoriasis patients was significantly lower than the control group and the consumption of red meat was significantly higher in the patient group. No significant relationship was found between the severity of the disease and the score of adherence to the Mediterranean diet (p = 0.42).

Conclusion

A significant difference between the two groups of psoriasis and the control group following the Mediterranean diet might be indicative of the relationship between diet and psoriasis and the potential benefits of this type of diet due to its anti‐inflammatory properties.
The effect of an educational video on the immediate insertion of postpartum contraceptive implants: A randomized controlled trial
Authors: Boontor Nutruja , Kaewrudee Srinaree , Sothornwit Jen
Published: September 2024

Objective

To assess the impact of an educational video on immediate postpartum contraceptive implant utilization.

Methods

This was a randomized controlled study conducted in a university hospital. Postpartum women aged over 18 years were recruited and divided into two groups: the intervention group, which viewed a 7‐min educational video about contraceptive implants; and the control group, which did not. We evaluated the uptake of contraceptive implants immediately and during a 12‐week period postpartum, in addition to the reasons for not selecting this method.

Results

A total of 202 participants were included in the study, 101 in each group. Viewing the educational video was associated with higher immediate postpartum contraceptive implant usage (22.77% vs 10.89%; relative risk [RR] 2.09, 95% confidence interval [CI] 1.08–4.06). However, no significant difference was observed at the postpartum follow‐up visit (29.9% vs 25.74%; RR 1.61, 95% CI 0.74–1.82). The primary reasons for not selecting contraceptive implants were concerns about potential side effects and discomfort associated with the insertion procedure.

Conclusion

The inclusion of an animated educational video significantly improved immediate postpartum contraceptive implant uptake, making it a potentially viable strategy in settings with high rates of loss to follow‐up. However, further research into how to address patients' fears regarding the implant is required.
Introduction of advanced maternal age based on mortality‐specific severe morbidity
Authors: Masjedi Aaron D. , Anderson Zachary S. , Pon Fay F. , Matsuzaki Shinya , Mandelbaum Rachel S. , Ouzounian Joseph G. , Matsuo Koji
Published: September 2024

Synopsis

Re‐defining advanced maternal age based on the risk of severe maternal morbidity at delivery may be of value in obstetric medicine.
Differences in the physiology of Pichia pastoris grown on glycerol/glucose using polyurethane foam slabs as solid support
Authors: Zárate‐Bonilla Josué , Rodríguez‐Gómez Divanery , Viniegra‐González Gustavo , López‐Pérez Marcos
Published: September 2024

BACKGROUND

Growth physiology and metabolic flux of Pichia pastoris were analyzed using glass columns containing slabs of polyurethane foam as a solid support and culture medium with glycerol or glucose as a carbon source.

RESULTS

Media with glycerol produced an average of 30.91% more biomass than media where glucose was used. However, the specific growth rate registered higher values for media with glucose than those with glycerol at low substrate concentrations: 0.46 versus 0.22 h−1. Media with glycerol produced a large amount of d‐arabitol, whereas ethanol and citrate were the predominant metabolites in media with glucose. Both types of culture systems generated biphasic curves in terms of the respiratory quotient value, whose inflection point coincided with the transition from aerobic metabolism to a mixed one.

CONCLUSION

Adequate oxygen transfer occurred in both culture systems; therefore, the differences found in growth physiology can be explained by the transport mechanism that internalizes glycerol, the access point to primary metabolism, and the degree of glycerol oxidation. The arrangement of cells in the polyurethane matrix allowed an attenuation of the repression phenomenon due to excess substrate for both carbon sources. This is the first work to study metabolic flux comparisons using this system. © 2024 Society of Chemical Industry (SCI).
The application value of prenatal ultrasound in conjoined twins
Authors: Xiao Juhua , Liao Kun , Tan Zhiwen , Xie Jiping , Lai Hua , Zhang Shouhua , Luo Ye
Published: September 2024

Objective

To evaluate the application and effectiveness of prenatal ultrasound in diagnosing and managing conjoined twins.

Methods

A retrospective analysis was conducted on 20 cases of conjoined twins diagnosed at our hospital between January 2016 and December 2022. The types of conjoined twins, ultrasonographic characteristics, and associated anomalies were assessed.

Results

The gestational age at diagnosis ranged from 10 to 35 weeks, with an average of 14.21 ± 5.69 weeks. Thirteen cases were detected in the first trimester, five in the early second trimester, one at 23 + 2 weeks, and one at 35 weeks. Thoracopagus was the most common type (11 cases, 55%), followed by omphalopagus (4 cases, 20%), cephalopagus (4 cases, 20%), and parapagus dicephalus (1 case, 5%). In the first trimester, the most common abnormalities observed included increased nuchal translucency (NT), cystic hygroma, hydrops fetalis, and generalized edema. Major birth defects identified in conjoined twins were omphalocele (3 cases), congenital heart malformations (3 cases), neural tube defects (2 cases), urachal cyst (1 case), and umbilical cyst (1 case). Pregnancy was terminated in 18 cases, one case resulted in spontaneous abortion during the second trimester, and one case was delivered by cesarean section at 37 weeks, with successful separation and recovery.

Conclusion

Prenatal ultrasound is the primary diagnostic tool for conjoined twins. It effectively assesses the extent of twin fusion, provides critical information for clinical decision‐making, and aids in the management of obstetric care.
Finite element analysis part 1 of 2: Influence of short stem implant polyethylene configuration on glenohumeral joint biomechanics
Authors: Nourissat Geoffroy , Housset Victor , Daudet Jean‐Marie , Fradet Léo , Bianco Rohan‐Jean , Srikumaran Uma
Published: September 2024

Purpose

Stress shielding in short‐stem arthroplasty can cause critical metaphyseal bone loss. If the size and shape of the humeral shaft are important factors, it is unknown whether the shape of the polyethylene component in reverse shoulder arthroplasty (RSA) affects bone stress around or within the stem. We explored the impact of polyethylene shape on humeral and scapular stress distribution using a finite element model.

Methods

We developed a shoulder‐specific finite element model. A defined set of muscle forces was applied to simulate movements. An intact rotator cuff state and a superior deficient rotator cuff state were modelled. We used the FX V135 short stem in three conditions: total shoulder arthroplasty (TSA), and RSA with symmetrical and asymmetrical polyethylene (145°/135°). We measured biomechanical markers related to bone stress for different implant sizes. Joint kinematics and the mechanical behaviour of the implant were compared.

Results

Rupture of the supraspinatus muscle produced a functionally limited shoulder. The placement of an anatomic TSA with an intact rotator cuff restored function similar to that of a healthy shoulder. RSA in the rotator cuff‐deficient shoulder restored function regardless of stem size and polyethylene shape. While stem size had an impact on the stress distribution in the bone and implant, it did not show significant potential for increasing or decreasing overall stress. For the same stem, stress distribution at the humerus is different between TSA and RSA. Polyethylene shape did not alter the transmission of stress to the bone in RSA. Asymmetric polyethylene produced a greater abduction range of motion.

Conclusions

In terms of bone stress distribution, smaller stems seemed more appropriate for TSA, while larger stems may be more appropriate for RSA. Polyethylene shape resulted in different ranges of motion but did not influence bone stress.

Level of Evidence

Diagnostic Tests or Criteria; Level IV.
A qualitative descriptive study examining the impact of child‐raising experience on Japanese family doctors
Authors: Fujihara Manabu , Watanabe Satoko , Kodama Kuniko , Nakamura Koki , Stanyon Maham , Kanke Satoshi , Kassai Ryuki
Published: September 2024

Background

The Patient‐Centered Clinical Method (PCCM) plays an important role in family doctors' ability to communicate effectively with patients. Although the parenting experiences of healthcare providers can be utilized to communicate with patients, it is unclear how they contribute to family doctors' practice.

Methods

A qualitative descriptive study focusing on the parenting experiences of Japanese family doctors and their perceptions of how these experiences interfaced with their clinical practice of the PCCM was conducted. Participants were selected using snowball sampling, and the data were collected via semi‐structured interviews while recording online, which were transcribed verbatim and analyzed using qualitative descriptive analysis, with data‐derived codes being systematically applied and reflexively interpreted. The categories were refined concurrently with the interviews. Once it was established that no additional categories were required, the recruitment and analysis process was concluded.

Results

The eight participants were recruited, and the following themes were extracted; these were “Developing patience and new perspectives through raising children,” “Empathizing with the experiences of others,” “Building awareness of social factors and home context,” “Reflecting on one's own words and behavior,” “Forming partnerships with patients through shared parenting experiences,” and “Facilitating interpersonal growth.”

Conclusion

The communication skills that have been refined through personal experiences of raising children are transferable between professional and family situations. This research shows that such skills are not mutually exclusive to professional or family settings and can be used effectively to improve clinical practice as part of the PCCM model of consulting.
d $d$‐connectivity of the random graph with restricted budget
Authors: Lichev Lyuben
Published: September 2024

In this short note, we consider a graph process recently introduced by Frieze, Krivelevich and Michaeli. In their model, the edges of the complete graph are ordered uniformly at random and are then revealed consecutively to a player called Builder. At every round, Builder must decide if they accept the edge proposed at this round or not. We prove that, for every , Builder can construct a spanning ‐connected graph after rounds by accepting edges with probability converging to 1 as . This settles a conjecture of Frieze, Krivelevich and Michaeli.
A Top Solvent‐Additive‐Ionization Technique Combination for Pesticides Direct Infusion MS Analysis
Authors: Anđelković Darko , Branković Milica
Published: September 2024

The leading type of ionization technique in mass spectrometry analyses is the ionization at atmospheric pressure. The aim of this study was to assess ESI and APCI ionization efficiency of pesticides introduced to the MS source in four organic phases, non‐doped and doped with formic acid and ammonium formate. Ionization efficiency in modified ESI and APCI, applying in‐source sample heating, was also assessed. The study was primarily designed to support non‐chromatography‐based mass spectrometry pesticides analysis by the direct infusion technique. Evaluation of analysis performances such as calibration performances, detectability, and sensitivity should indicate a top solvent‐additive‐source combination, leading to the highest ionization efficiency and lowest analytes detection limits.
Cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation in recalcitrant plantar warts: Analysis of 48 patients
Authors: Amo‐Navarrete Jéssica , García‐Oreja Sara , León‐Herce Diego , Navarro‐Pérez David , Lázaro‐Martínez José Luís , Álvaro‐Afonso Francisco Javier
Published: September 2024

A plantar wart is a benign hyperplasia that appears on the feet due to the human papillomavirus (HPV). One method used for the treatment of recalcitrant plantar warts, those lasting over 2 years or persisting after at least two treatment attempts, is the cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation, also known as the CPS formulation. Although this method is in use, there are few studies on it. This study's objective was to ascertain its cure rate. For this retrospective observational study, we reviewed the medical records of patients treated with the CPS formulation at a podiatric clinic specializing in plantar wart treatment. Our sample size was 48 subjects. The CPS formulation had a cure rate of 62.5%. Out of the cured patients, 86.67% (26/30) required one or two applications. There was no observable correlation (p > 0.05) between wart resolution and virus biotype, evolution time, patient's morphological and clinical attributes, location, number of warts, or preceding treatments. The CPS formulation presents a relatively high efficacy rate for treating recalcitrant HPV plantar warts. Still, additional studies are necessary to evaluate its safety and efficiency.
Metabolite variations in sulla shoots induced by drought stress
Authors: Troise Antonio Dario , De Pascale Sabrina , Piluzza Giovanna , Re Giovanni Antonio , Sanna Federico , Scaloni Andrea , Sulas Leonardo
Published: September 2024

BACKGROUND

Climate change results in an increased occurrence of drought periods, which affect the performance of Mediterranean legumes such as sulla. To evaluate the effects of drought stress on the antioxidant capacity and the accumulation of phytochemicals in sulla shoots, rainfed and drought‐stressed plants (RAI) and watered plants with timely vegetative regeneration (STI) were cultivated in parallel in a field experiment and sampled at four different times.

RESULTS

Drought stress strongly and positively affected the antioxidant capacity and the accumulation of polyphenols in sulla shoots, with key differences at wintertime. These findings were supported through untargeted and targeted metabolomics of RAI and STI samples, which detailed the accumulation of about 300 secondary metabolites in RAI, mostly polyphenols and saponins.

CONCLUSION

This study provided new insights into the changes in secondary metabolites in sulla due to drought stress, which can be used to produce forages or raw plant extracts with enhanced biological effects. © 2024 Society of Chemical Industry.
Limosilactobacillus reuteri RE225 alleviates gout by modulating the TLR4/MyD88/NF‐κB inflammatory pathway and the Nrf2/HO‐1 oxidative stress pathway, and by regulating gut microbiota
Authors: Qin Yang , Zhou Yucong , Xiong Jiayi , Lu Chenyang , Zhou Jun , Su Xiurong , Han Jiaojiao
Published: September 2024

BACKGROUND

Gout poses a significant health threat. The use of Lactobacillus from the gut microbiota is one potential remedy. However, the intricate molecular mechanisms governing the impact of Lactobacillus on gout remain largely uncharted. In this study, a strain of Limosilactobacillus reuteri RE225 was separated from the gut of mice and colitis was treated with polypeptide intervention.

RESULTS

Limosilactobacillus reuteri RE225 reduced foot tumefaction markedly in mice with gout and extended the pain threshold time in their feet. It also improved the health of gut microbiota. Intervention with L. reuteri RE225 also suppressed the TLR4/MyD88/NF‐κB and nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) pathways in the mice, reduced the levels of pro‐inflammatory cytokines – interleukin 1β (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) – and increased the level of the anti‐inflammatory cytokine interleukin 10 (IL‐10), thereby mitigating inflammation.

CONCLUSION

This study provides a theoretical basis for the comprehensive development of Limosilactobacillus reuteri and new ideas for the non‐pharmacological treatment of gout. © 2024 Society of Chemical Industry.
Robotic and Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Multicenter Study From Saudi Arabia
Authors: Alyami Mohammad , Abdulrahem Abdullah Muhammed , Alqannas Mashhour , AlHabes Hessa , Alyami Awad , Alshammari Sulaiman , Guiral Delia Cortes , Alzamanan Mahdi , Alzahrani Nayef , Bin Traiki Thamer
Published: September 2024

Background

Peritoneal metastasis (PM) is a common evolution of abdominal tumors. Without aggressive multimodal treatment, it is associated with a poor prognosis. The aim of this study is to present a multicenter results from Saudi Arabia on minimally invasive CRS and HIIPEC.

Methods

A retrospective analysis of a prospective maintained multicenter database was queried for all patients treated with laparoscopic or robotic CRS and HIPEC between 2019 and 2024 in Saudi Arabia. Surgical and oncological outcome was analyzed.

Results

Eleven consecutive patients underwent minimally invasive CRS and HIPEC between 2019 and 2024. Eight patients (72.7%) were operated by laparoscopy, one of them by single port access and three patients (27.3%) were operated robotically. Six patients (54.5%) were female. Median age was 42 (29–64). Primary tumor was PMP from the appendix, colon, and MCM in 6 (54.5%), 4 (36.4%), and 1 (9.1%) respectively. The median duration to complete the surgical procedure for all patients was 330 (230–580) min and for robotic CRS the median docking time was 570 (330–580) min. Median PCI was 2 (1–7) and completeness Cytoreduction (CC score 0) was achieved in the all patients (100%). Median hospital stay was 8 days (3–20). Four patients had one night postoperative ICU stay. Major morbidity (CTCAE) 3 and 4 occurred in three patients (27.3%) (Port site hernia, bleeding, and wound infection). No readmission to the hospital and no 90 days mortalities.

Conclusion

The minimally invasive approach by laparoscopy or robot is a feasible and promising option for CRS and HIPEC. It reduces the hospital stay, early return to intended oncological treatment (RIOT). Further prospective clinical studies are needed to evaluate this approach.
Recent advances in liquid chromatography‐tandem mass spectrometry for the detection of thyroid hormones and thyroglobulin in clinical samples: A review
Authors: Jin Yuting , Zhai Taiyu , Wang Ying , Li Jiuyan , Wang Tingting , Huang Jing
Published: September 2024

Thyroid hormones (THs), including triiodothyronine (T3), thyroxine (T4), and their metabolites, are essential for regulating development, growth, and energy metabolism. Thyroglobulin (Tg) produced by thyroid follicular cells acts as an essential substrate for TH synthesis. The combination of THs with Tg is a widely used serological laboratory test for thyroid function assessment. Early detection and timely intervention are significant for preventing and managing thyroid disease. In recent years, liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) has emerged as a powerful tool for the precise detection of small molecular analytes and steroid hormones in clinical practice as a result of its high sensitivity and specificity. While LC‐MS/MS has been increasingly used for detecting THs and Tg recently, its application in clinical practice is still in its early stages. Recent advances in the assessment of thyroid metabolism using LC‐MS/MS in clinical samples published during 2004–2023 were reviewed, with a special focus on the use of this technique for quantifying molecules involved in thyroid diseases.
Good rate of satisfaction but suboptimal clinical outcome at long‐term follow‐up in a large series of patients who had operative stabilization of the deltoid ligament of the ankle
Authors: Krogsgaard Michael Rindom , Palm Henrik , Obionu Kenneth , Astrup Yvette , Lange Naja Bjørslev , Haak Tobias , Dippmann Christian
Published: September 2024

Purpose

To report results following deltoid ligament reconstruction in a large series of patients.

Methods

For consecutive patients who had a medial ankle ligament stabilization 2010–2018 information from their medical files was registered, and they were invited for follow‐up in 2021–2022. They answered questions about satisfaction with the treatment and current symptoms, and they completed the Foot and Ankle Measurement (FAAM) questionnaire.

Results

Of the 503 patients, 342 (68%) had a history of trauma to the ankle and 114 (23%) had previous ankle surgery. 67% had other procedures (besides synovectomy) simultaneous to medial ligament reconstruction. 269 patients (54%) responded to the invitation for follow‐up. For 182 (71%) of the responders, the operation solved their ankle problems. 163 (63%) were satisfied with the surgery. 192 (71%) would repeat the operation. 173 (67%) had pain in the ankle during the past week, and 86 (50%) of these were not able to run. FAAM ADL‐scores were significantly higher than in a mixed group of ankle/foot patients but not normal.

Conclusion

The relatively high degree of satisfaction despite suboptimal clinical results may reflect the complex nature of the deltoid ligament insufficient ankle. It is concluded that repair or reconstruction of the deltoid ligament is only performed in patients reporting ankle instability and with peroperatively demonstrated medial instability and pathology to the ligament.

Level of Evidence

Level III.
Design of a LiDAR ranging system based on dual‐frequency phase modulation
Authors: Mu Yuanhui , Feng Shanshan , Liu Ruzhang , Liu Luyin , Wang Shuying , Cai Enlin
Published: September 2024

Phase‐based light detection and ranging (LiDAR) technology is emerging in the fields of industrial mapping, autonomous driving, and robotics, but the traditional phase‐based ranging technology generally suffers from the problem that the ranging accuracy is inversely proportional to the measurement range under a single measurement frequency, the system structure is complicated, and the performance is unstable, and so forth. In this article, a new type of LiDAR system design based on phase ranging is proposed. The system adopts a 100 + 1 MHz double measuring ruler modulation light source, uses the laser to control the phase difference detection method of the same frequency reference, optimizes the structure of the transceiver optical system, and the design of AD8302 high‐resolution signal phase discriminator circuit, builds a high‐precision laser ranging system, and carries out the experiments on the measurement accuracy of the LiDAR ranging system. The experimental results show that the measurement accuracy of the system is millimeter level, which is simple, practical, and can meet the needs of a wide range of practical applications. This study provides a feasible and innovative solution for LiDAR technology in high‐precision distance measurement.
Scatterer spacing based on Gabor atoms matched from harmonic ultrasound echoes to improve assessment of microwave‐induced thermal lesions
Authors: Zeng Xiuhua , Zhang Yufeng , Li Zhiyao , Yang Jian , Gao Lian , Zhang Junhua
Published: September 2024

Background

Microwave ablation (MWA) is a minimally invasive alternative for the treatment of unresectable liver tumors. To verify the effectiveness and safety of MWA, it is critical to measure the temperature variation and assess the regions of the microwave‐induced thermal lesions.

Purpose

Recent studies have indicated that the locations of optimally matched Gabor atoms (LOMGA) from ultrasound radiofrequency (RF) echo signals allow accurate and stable scatterer spacing estimation. Herein, a harmonic‐based LOMGA method is proposed to estimate the scatterer spacing for improving the assessment of microwave‐induced thermal lesions.

Methods

The mean scatterer spacing (MSS) is estimated via the LOMGA method incorporating the selection of concise atoms from separated second‐harmonic RF echo signals with the pulse‐inversion algorithm for thermal lesion evaluation. In vitro experiments, 10 fresh porcine liver samples were ablated at different time nodes during the ablation period, and 200 sets of second‐harmonic and fundamental RF echo signals were randomly selected from the regions of interest in the coagulated liver samples for MSS estimation. The means and standard deviations of the MSSs, as well as the linear regression for the mean MSSs, were calculated from fundamental and second‐harmonic signals for comparison and evaluation, the receiver operating characteristic (ROC) curves for the 200 sets of fundamental‐based and harmonic‐based MSS estimates from the 10 liver samples at five pairs of adjacent time nodes were calculated, and one‐way analysis of variance (ANOVA) tests were performed for the five pairs of adjacent time nodes. The fundamental and harmonic‐based p‐values in the ANOVA tests and the areas under the ROC curves (AUCs) were calculated to statistically analyze the differences in the MSSs between adjacent time nodes.

Results

The harmonic‐based increments in the intensity variation and coherent components were larger than the fundamental‐based increments with the increasing ablation time. The harmonic‐based MSSs from the 10 liver samples at five pairs of adjacent time nodes were found to be highly statistically significant (p < 0.01). Thus, the harmonic‐based MSSs had greater variations. Compared with the fundamental‐based results, for the five preset ST values, the average increment in the harmonic‐based mean slopes was 69.22% and the average decrement in the mean standard deviations was 11.67% for the linear‐fitting MSS results, and the results were statistically significant (p < 0.05).

Conclusion

Harmonic‐based MSSs are more sensitive and robust to variations in coagulated tissues, which is advantageous for the assessment of microwave‐induced thermal lesions.
Access for ALL in ALS: A large‐scale, inclusive, collaborative consortium to unlock the molecular and genetic mechanisms of amyotrophic lateral sclerosis
Authors: Berry James D. , Paganoni Sabrina , Harms Matthew B. , Shneider Neil , Andrews Jinsy , Miller Timothy M. , Babu Suma , Sherman Alex V. , Harris Brent T. , Provenzano Frank A. , Phatnani Hemali P. , Shefner Jeremy , Garret Mark A. , Ladha Shaffeeq S. , Tsou Amy Y. , Mohan Praveena , Igne Courtney ,   The ALL ALS Consortium, Bowser Robert
Published: September 2024

Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi‐institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large‐scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open‐science dataset to help researchers answer important scientific questions of clinical relevance in ALS.
Self‐regulation and self‐efficacy of EFL learners in hybrid educational settings in Türkiye
Authors: Kaptanoğlu Mehmet Yağız , Kavanoz Suzan
Published: September 2024

Distance learning, online learning and hybrid learning models have been a part of language education for a long time. The adoption of these models and research focusing on related phenomena have become even more frequent since the breakout of the COVID‐19 pandemic in 2019. This mixed‐method study examines the relationship between online learning self‐efficacy and online self‐regulation of preparatory class English as a Foreign Language (EFL) learners to provide a picture of the learners' perspective regarding the online segment of the hybrid education system that was in effect during the mentioned era, to provide deeper insights regarding learner perceptions during such times of emergency. Turkish adaptations of the Online‐Learning Self‐Efficacy Scale and Online Self‐regulated Learning Questionnaire were utilized as data collection instruments. To validate and expand the content of quantitative findings, semi‐structured interviews were conducted with a selected group of participants. The findings reveal that preparatory year Turkish EFL learners perceive themselves to be self‐efficacious and self‐regulated at a satisfactory level in online learning environments. The study provides insight into the learners' perceptions during this period and contributes to filling a significant gap within the field as well as offering new perspectives in case we face similar conditions in the future.
A single‐center retrospective review of metastatic prostate cancer on PSMA position emission tomography/computed tomography: Beyond lymph nodes and bones
Authors: De Jesus Gabriela N. C. , Pereira Veronica , Karak Prasanta , Shearier Emily
Published: September 2024

Background

Prostate‐specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical‐pathologic correlates of extra‐nodal and extra‐osseous metastatic prostate cancer detected on PSMA PET/CT.

Methods

All available 650 PSMA PET/CT performed in patients with biopsy‐proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra‐nodal and extra‐osseous metastatic disease (M1C disease). Thirty‐four patients with M1C disease were identified.

Results

The most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate‐specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement.

Conclusions

Given the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement.
Deep PSA response and extended time‐to‐nadir as robust predictors of survival in Asian patients with de novo metastatic hormone‐sensitive prostate cancer receiving upfront intensified treatment
Authors: Wong Chris H.‐M. , Ko Ivan C.‐H. , Leung David K.‐W. , Siu Brian , Cheng Cheuk‐K. K. , Lim Yung‐Y. J. , Mok Hiu T. , Kwok Chun‐F. B. , Tang Cheuk Y. , Leung Steven C.‐H. , Chiu Peter K.‐F. , Teoh Jeremy Y.‐C. , Ng Chi F.
Published: September 2024

Introduction

In de novo metastatic hormone‐sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real‐world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes.

Methods

A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6‐months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders.

Findings

A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression‐free survival (HR = 0.56; 95%CI = 0.34–0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26–0.97; p = 0.036), and cancer‐specific survival (HR = 0.43; 95%CI = 0.19–0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis.

Conclusion

Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real‐world setting, providing valuable information for patient counselling and potentially guiding future trial design.
Population pharmacokinetic–pharmacodynamic model of elinzanetant based on integrated clinical phase I and II data
Authors: Willmann Stefan , Lloyd Adam , Austin Rupert , Joseph Shiju , Solms Alexander , Zhang Yang , Schneider Annika R. P. , Frechen Sebastian , Schultze‐Mosgau Marcus‐Hillert
Published: September 2024

Elinzanetant is a potent and selective dual neurokin‐1 (NK‐1) and ‐3 (NK‐3) receptor antagonist that is currently developed for the treatment of women with moderate‐to‐severe vasomotor symptoms (VMS) associated with menopause. Here, we report the development of a population pharmacokinetic (popPK) model for elinzanetant and its principal metabolites based on an integrated dataset from 366 subjects (including 197 women with VMS) collected in 10 phase I or II studies. The pharmacokinetics of elinzanetant and its metabolites could be well described by the popPK model. Within the investigated dose range of 40–160 mg, the oral bioavailability of elinzanetant was dose independent and estimated to be 36.7%. The clearance of elinzanetant was estimated to be 7.26 L/h and the central and peripheral distribution volume were 23.7 and 168 L. No intrinsic or extrinsic influencing factors have been identified in the investigated population other than the effect of a high‐fat breakfast on the oral absorption of elinzanetant. The popPK model was then coupled to a pharmacodynamic model to predict occupancies of the NK‐1 and NK‐3 receptors. After repeated once‐daily administration of the anticipated therapeutic dose of 120 mg elinzanetant, the model‐predicted median receptor occupancies are >99% for NK‐1 and >94.8% for NK‐3 during day and night‐time, indicating sustained and near‐complete inhibition of both target receptors during the dosing interval.
Procyanidin B1 Promotes PSMC3‐NRF2 Ubiquitination to Induce Ferroptosis in Glioblastoma
Authors: Gao Wei , Li Yuan , Lin Xiang , Deng Kun , Long Xinmiao , Li Danyang , Huang Meng , Wang Xiangyu , Xu Yucong , She Xiaoling , Wu Minghua
Published: September 2024

NRF2 signaling is a crucial antioxidant defense mechanism against ferroptosis in tumors, and targeting NRF2 is essential for tumor therapy. However, the effectiveness of NRF2 inhibitors remains unexplored. The active ingredients of traditional Chinese medicine serve as important sources of NRF2 inhibitors. In this study, we established an intracranial glioblastoma (GBM) orthotopic model and observed the effects of procyanidin B1 on tumor growth and ferroptosis. Using protein‐small‐molecule docking, z‐stack assay of laser confocal imaging, surface plasmon resonance assay, immunoprecipitation, mass spectrometry, and western blotting, we detected the binding between procyanidin B1 and NRF2 and the effect of PSMC3 on the ubiquitin‐dependent degradation of NRF2 in GBM cells. Our results showed that procyanidin B1 acted as a novel NRF2 inhibitor to suppress GBM cell proliferation and prolonged the survival of GBM‐bearing mice; it also mediated the interaction between PSMC3 and NRF2 to promote ubiquitin‐dependent protein degradation of NRF2, which induced ferroptosis in GBM cells. In addition, we found that procyanidin B1 enhanced H₂O₂ accumulation by downregulating NRF2 during ferroptosis in GBM cells. The botanical agent procyanidin B1 induced ferroptosis and exerted anti‐tumor effects through PSMC3‐mediated ubiquitin‐dependent degradation of NRF2 proteins, providing a potential drug candidate for adjuvant therapy in patients with GBM.
Influence of Pumping Laser Intensity Uniformity on Hybrid Optically Pumped Comagnetometer in the SERF Regime
Authors: Ma Longyan , Liu Ye , Pang Haoying , Quan Jiale , Ge Xiaohan , Duan Lihong , Quan Wei
Published: September 2024

The effect of pumping laser intensity uniformity (PLIU) on the operation of a hybrid optically pumped comagnetometer operating in the spin‐exchange relaxation‐free regime (SERF) regime is investigated in this paper. First, an analytical steady‐state output model for the comagnetometer with two alkali‐metal atoms and one noble‐gas atom is presented. By varying the diameter of the pumping laser beam to control the PLIU, 3D distribution models of the electron spin and nuclear spin polarization under different PLIU conditions are obtained. In the experiment, the effects of PLIU on multi‐parameter, low‐frequency magnetic‐noise suppression capability, and long‐term stability of the SERF comagnetometer are studied. The results indicate that within a certain range, increasing the diameter of the pumping laser beam improves the polarization uniformity of the atomic ensemble and reduces the light shift of the comagnetometer. As a result, both the low‐frequency magnetic noise suppression capability and the long‐term stability of the system increase. However, further reduction of the pumping laser diameter leads to a reversal of the system performance metrics, suggesting the presence of a tipping point. The research presented in this article is critical for advancing the efficient polarization study and hyperpolarization of SERF comagnetometers.
Pulmonary Langerhans cell histiocytosis with multiple cavitary nodules after lung cancer surgery
Authors: Sugihara Minoru , Okamoto Sawako , Taniguchi Tetsuo
Published: September 2024

Pulmonary Langerhans cell histiocytosis (PLCH) is a subtype of Langerhans cell histiocytosis, a rare neoplastic disease characterized by lung involvement. Here, we present a case involving a patient with multiple cavitary nodules who was diagnosed with PLCH during surveillance after lung cancer surgery. A 74‐year‐old woman underwent right upper lobe resection surgery for right upper lobe lung adenocarcinoma, pStage IIA, 5 years ago. The patient underwent surveillance without adjuvant chemotherapy. During the fifth year of follow‐up, multiple nodules with cavitation were observed on computed tomography in both lung fields. Chemotherapy was considered to address the suspected recurrence of lung cancer; however, video‐assisted thoracoscopic surgery was performed due to the need for biomarker testing. Pathological examination led to the diagnosis of PLCH. This case emphasizes the importance of a proactive histological diagnosis to determine the appropriate treatment strategy, even in situations where lung cancer recurrence is clinically suspected.
Concurrent learning for adaptive pontryagin's maximum principle of nonlinear systems with inequality constraints
Authors: Zhang Bin , Zhang Yuqi , Jia Yingmin
Published: September 2024

In this article, a finite‐horizon adaptive Pontryagin's maximum principle is presented for nonlinear systems with state inequality constraints. Concurrent learning (CL) technique is adopted to identify the unknown parameters of the dynamic systems. Based on the identification model, a novel adaptive iterative algorithm under the Pontryagin's framework is introduced to learn the finite‐horizon optimal control solution. Convergence analysis of the algorithm is provided by showing that the cost function sequence is monotonically decreasing. Furthermore, we extend the adaptive iterative algorithm to time‐varying nonlinear systems. The new algorithm overcomes the technical obstacles of the existing adaptive/approximate dynamic programming (ADP) approaches to deal with the time‐varying characteristic of Hamilton–Jacobi–Bellman (HJB) partial differential equation (PDE), especially when state constraints exist. Simulation examples are carried out to validate the effectiveness of the theoretical results.