bluuebunny/crossref_metadata_2025 huggingface dataset:
PKN2 Promotes Peripheral Nerve Repair by Regulating Autophagy via Activation of the AKT‐mTOR Pathway: An In Vitro Study
Authors: Wang Lin , Huang Yuan‐sheng
Published: November 2024

This study aims to explore the role of Protein Kinase N2 (PKN2) in peripheral nerve injury (PNI) and evaluate its potential as a therapeutic target. The study employed a PC12 cell model to assess the effects of PKN2 overexpression on cell proliferation, migration, synaptic growth, and autophagic activity, with a focus on the regulatory role of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. The results demonstrated that PKN2 overexpression significantly promoted PC12 cell proliferation and cell migration, while also enhancing synaptic growth. Additionally, a significant suppression of autophagy was observed. Mechanistic analysis revealed that PKN2 inhibited autophagic activity through the activation of the AKT/mTOR pathway. In summary, PKN2 plays a significant role in peripheral nerve repair by promoting cell proliferation, migration, and synaptic growth, while inhibiting autophagy through the AKT/mTOR pathway. These findings suggest that targeting PKN2 may represent an effective therapeutic strategy for the treatment of PNI.
CEO Inside Debt and Insider Trading
Authors: Brisker Eric R. , Outlaw Dominique , Smith Aimee Hoffmann
Published: November 2024

We examine insider trading to test existing theory about how insiders perceive CEO pensions and deferred compensation (inside debt). Managerial compensation theory posits that debt‐type compensation is an important component of optimal contracting because it reduces shareholder–debtholder agency costs, suggesting that shareholders may react positively to increases in CEO inside debt. Consistent with this conjecture, we document a positive association between CEO inside debt and net purchasing by well‐informed insiders. We alleviate endogeneity concerns using 2SLS instrumental variables estimation. Further supporting theoretical predictions, we obtain stronger results when focusing on opportunistic trades, directors’ and officers’ trades, and financially distressed firms.
Shared Traumatic Reality During the Continuous War in Ukraine and the Protective Role of Transgenerational Transfer: Voices of Mental Health Professionals
Authors: Leshem Becky , Zasiekina Larysa , Guterman Neil B. , Pat‐Horenczyk Ruth
Published: November 2024

Shared traumatic reality has nagative professional effects on mental health providers. The study explores the professional effects of prolonged shared traumatic reality, and the protective role of intergenerational transfer, among Ukrainian psychotherapists during the war with Russia, in the context of their national history of traumatic events. We conducted focus group interviews with 20 Ukrainian therapists who lived and worked in Ukrainian war zones. The recorded transcriptions were analyzed, applying two stages of inductive thematic analysis, and identifying common themes and sub‐themes. The main reported negative effect was compassion fatigue, with secondary traumatization and lack of interpersonal and professional support reported as the dominant risk factors. Positive effects included compassion satisfaction and professional growth. The leading protective factors included active coping and social support, while transgenerational transfer of empowering messages increased coping resources. We concluded that intergenerational transfer could promote coping and positive professional effects, especially in the context of chronic shared traumatic reality, suggested as a new construct. Further studies are suggested.
Examination of Gait Characteristics Related to Sarcopenia in Community‐Dwelling Older Adults: A Study Focusing on Plantar Pressure
Authors: Yamagiwa Daiki , Makino Keitaro , Katayama Osamu , Yamaguchi Ryo , Georg von Fingerhut , Yamashiro Yukari , Sudo Motoki , Shimada Hiroyuki
Published: November 2024

Background

Sarcopenia is a condition characterized by a decrease in skeletal muscle mass and strength with age, which results in a lower gait speed. Decreased gait speed in older individuals with sarcopenia can lead to adverse events such as falls and mortality. It is a major health issue; several studies have investigated gait speed in sarcopenia. However, plantar pressure has not been sufficiently evaluated. Plantar pressure facilitates gait analysis, including gait speed, and plays an important role in preventing adverse events such as falls and mortality. Therefore, the current study aimed to validate gait characteristics, including plantar pressure in community‐dwelling older adults with sarcopenia.

Methods

The current study included community‐dwelling Japanese adults aged ≥60 years who participated in health checkups between 2013 and 2018. Sarcopenia was diagnosed by measuring muscle mass and strength based on clinical definition (nonsarcopenia: n = 7662; probable sarcopenia: n = 1208; and sarcopenia: n = 477). Gait parameters (including gait speed, relative plantar pressure, cadence, stride length, step length, step width and foot angle) were measured at a comfortable speed using a computerized electronic walkway. Gait parameters between groups were compared via an analysis of covariance adjusted for age and BMI. In addition, post hoc analyses were performed with Bonferroni correction.

Results

The sarcopenia and probable sarcopenia groups had a significantly lower gait speed than the nonsarcopenia group (p < 0.01). Further, the sarcopenia and probable sarcopenia groups had a significantly lower forefoot plantar pressure, stride length and cadence than the nonsarcopenia group (all p < 0.01). When comparing, the sarcopenia group had a greater medial plantar pressure, step length, and foot angle and a lower lateral plantar pressure, cadence, and step width than the probable sarcopenia group (all p < 0.01).

Conclusion

The sarcopenia, probable sarcopenia and nonsarcopenia groups differed concerning gait characteristics, including plantar pressure. It is thought that exercise instruction that takes into account walking characteristics is important for probable sarcopenia and sarcopenia.
Early‐Stage Melanoma Cancer Diagnosis Framework for Imbalanced Data From Dermoscopic Images
Authors: Khan Amjad Rehman , Mujahid Muhammad , Alamri Faten S. , Saba Tanzila , Ayesha Noor
Published: November 2024

Skin problems are a serious condition that affects people all over the world. Prolonged exposure to ultraviolet rays' damages melanocyte cells, leading to the uncontrolled proliferation of melanoma, a form of skin cancer. However, the dearth of qualified expertise increases the processing time and cost of diagnosis. Early detection of melanoma in dermoscopy images significantly enhances its chance of survival. Pathologists benefit substantially from the precise and efficient melanoma cancer diagnosis using automated methods. Nevertheless, the diagnosis of melanoma has consistently been a challenging procedure due to the imbalance images and limited data. Our objective was to employ a novel deep method to diagnose melanoma from dermoscopic images automatically. The research has proposed a novel framework for detecting skin malignancies. The proposed plan, which includes CNN, DenseNet, a batch normalization layer, maxpooling, and a ReLU layer activation function, solves the overfitting problem well. Furthermore, we used a large number of samples for testing and effectively employed data augmentation to prevent any issues related to class imbalance. The Adam optimizer is the most efficient deep learning optimizer for addressing challenges associated with large datasets, such as lengthy processing times. This is due to its specifically designed algorithm. Experiments ensure that the proposed framework achieved 95.70% micro average accuracy on the ISIC‐2019 dataset and 93.24% accuracy on the HAM‐10000 dataset. Comprehensive evaluation and analysis were used to evaluate our framework's performance. The results show that the proposed approach performs better with cross‐validation by 94.8% accuracy than the most sophisticated deep learning‐based technique. During studies, medical professionals will employ the proposed model to identify skin cancer in its early stages.
Anteroposterior axis of the tibia for kinematic aligned total knee arthroplasty
Authors: Toyooka Seikai , Arai Noriaki , Masuda Hironari , Kawano Hirotaka , Nakagawa Takumi
Published: November 2024

Purpose

It is not known where the anatomical axis of rotation on the tibial side will be in kinematic alignment (KA), a rapidly expanding area of total knee arthroplasty (TKA) alignment technique today. The purpose of this study was to define the tibial axis for KA‐TKA.

Methods

Fifty patients who underwent computed tomography (CT) examination of the lower extremities at a single institution were included. The posterior condylar axis (PCA) and surgical epicondylar axis (SEA) were identified in the CT axial view and projected onto the tibial slice. The respective perpendicular lines that pass through was attachment of the posterior cruciate ligament (PCL) were identified as the anatomic axis of rotation of the tibia relative to the PCA and SEA, and the position of each axis of rotation. Furthermore, the relationship of these perpendicular lines with the Akagi line was evaluated.

Results

The axis of tibial rotation to the SEA was similar to that of the Akagi line; the axis of tibial rotation to the PCA was located approximately 2.9° medial to the Akagi line, and when the origin of the tibial axis was set at the PCL attachment site, the intersection point of the tibial axis was approximately 2.5 mm medial to the medial border of the tibial tuberosity. The distribution of tibial axis had a wide range.

Conclusion

Although there is a large individual variation, the average tibial axis for KA‐TKA is 2.9° more internally rotated than the Akagi line.

Level of Evidence

Level IV.
From Egg to Adult: A Developmental Table of the Ant Monomorium pharaonis
Authors: Rajakumar Arjuna , Pontieri Luigi , Li Ruyan , Larsen Rasmus Stenbak , Vásquez‐Correa Angelly , Frandsen Johanne K. L. , Rafiqi Ab Matteen , Zhang Guojie , Abouheif Ehab
Published: November 2024

Ants are one of the most ecologically and evolutionarily successful groups of animals and exhibit a remarkable degree of phenotypic diversity. This success is largely attributed to the fact that all ants are eusocial and live in colonies with a reproductive division of labor between morphologically distinct queen and worker castes. Yet, despite over a century of studies on caste determination and evolution in ants, we lack a complete ontogenetic series from egg to adult for any ant species. We, therefore, present a developmental table for the Pharaoh ant Monomorium pharaonis, a species whose colonies simultaneously produce reproductive queens and completely sterile workers. In total, M. pharaonis embryonic, larval, and pupal development lasts 45 days. During embryogenesis, the majority of developmental events are conserved between M. pharaonis and the fruit fly Drosophila melanogaster. We discovered, however, two types of same‐stage embryos before gastrulation: (1) embryos with internalized germ cells; and (2) embryos with germ cells outside of the blastoderm at the posterior pole. Moreover, we also found two‐types of embryos following germ band extension: (1) embryos with primordial germ cells that will develop into reproductive queens; and (2) embryos with no germ cells that will develop into completely sterile workers. Together, these data show that queen and worker castes are already determined and differentiated by early embryogenesis. During larval development, we confirmed that reproductive and worker larvae proceed through three larval instars. Using anatomical and developmental markers, we can further discern the development of gyne (unmated queen) larvae, male larvae, and worker larvae as early as the 1st instar. Overall, we hope that the ontogenetic series we present here will serve as a blueprint for the generation of future ant developmental tables.
Updated guidelines on HIV post‐exposure prophylaxis: continued efforts towards increased accessibility
Authors: Allan‐Blitz Lao‐Tzu , Mayer Kenneth H.
Published: November 2024

Introduction

HIV transmission is ongoing in both high‐ and low‐resource settings. Post‐exposure prophylaxis (PEP) remains an important tool in preventing HIV; however, PEP is significantly underutilized. The multitude of barriers to PEP implementation include low patient and provider awareness and acceptability, limited access to treatment and prevention services, and high rates of stigma. The World Health Organization (WHO) recently released updated guidance on the delivery of HIV PEP. This commentary aims to highlight the salient changes, evaluate how such recommendations can overcome the existing barriers to PEP implementation and discuss strategies needed to put the updated guidance into practice.

Discussion

The 2024 WHO PEP guidelines continue a trend towards increasing access to PEP. Most notably, the WHO now provides strong recommendations that: (1) PEP be delivered in community settings (e.g. pharmacies, police stations and online platforms), and (2) PEP delivery and monitoring be done via task sharing involving non‐specialist health workers (e.g. pharmacists or community health workers). The guidelines also emphasize that the PEP encounter is an important educable moment whereby a transition to pre‐exposure prophylaxis among individuals at continued risk for HIV infection should be discussed. The decentralization of PEP delivery has the potential to overcome numerous barriers to PEP implementation, reduce time to initiation and support adherence with the 28‐day course. To translate the recommendations into delivery programmes, however, much more work is needed. Detailed templates can help overcome the heterogeneity of both the community settings in which PEP can now be provided and the populations (e.g. survivors of sexual assault, healthcare workers, sex workers, etc.) among whom PEP may be indicated. Training of the workforce will be essential, which should include, as emphasized by the WHO, training in trauma‐based care. Novel formulations of and delivery mechanisms for PEP are also emerging, and how such iterations can synergize with decentralized PEP delivery programmes remains to be seen.

Conclusions

The updated WHO PEP guidelines make major strides towards increasing access to PEP. Realization of such aims will require ongoing evaluation and support given the heterogeneity in who benefits most from PEP.
Increasing event‐driven HIV pre‐exposure prophylaxis use among gay, bisexual and other men who have sex with men in Australia: results from behavioural surveillance 2019–2023
Authors: Chan Curtis , Holt Martin , Smith Anthony K. J. , Broady Timothy R. , MacGibbon James , Mao Limin , Wilcock Ben , Rule John , Bavinton Benjamin R.
Published: November 2024

Introduction

HIV pre‐exposure prophylaxis (PrEP) has been publicly available since 2018 in Australia as a daily regimen. In 2019, clinical guidelines were updated to support guidance on event‐driven PrEP (ED‐PrEP) use. We assessed trends in the PrEP dosing regimen by comparing daily PrEP use to ED‐PrEP among cisgender gay, bisexual and other men who have sex with men (GBMSM).

Methods

Data from repeated, cross‐sectional, national behavioural surveillance surveys were analysed from 2019 to 2023 among participants not living with HIV. Logistic regression models were conducted to assess trends and compared ED‐PrEP users to non‐PrEP users and daily PrEP.

Results

Among 38,880 participants, overall PrEP use with any regimen increased from 27.6% in 2019 to 42.7% in 2023 (OR = 1.16, 95% CI = 1.15−1.18, p < 0.001). Among 12,922 participants who reported PrEP use in the last 6 months, the proportion reporting ED‐PrEP use increased from 7.6% in 2019 to 27.8% in 2023 (OR = 1.41, 95% CI = 1.37−1.46, p < 0.001) with those who reported daily PrEP decreasing from 92.4% to 63.3% (OR = 0.64, 95% CI = 0.62−0.66, p < 0.001). In a cross‐sectional sub‐sample in 2022–2023 (n = 8840), compared to ED‐PrEP users, non‐PrEP users were less likely to have received three or more HIV tests in the last 12 months (aRRR = 0.26, 95% CI = 0.22−0.31, p < 0.001), have 2−10 male sexual partners in the last 6 months (aRRR = 0.24, 95% CI = 0.14−0.41, p < 0.001) or 11 or more (aRRR = 0.26, 95% CI = 0.15−0.45, p < 0.001) compared to none, or to report condomless anal intercourse with casual partners (aRRR = 0.38, 95% CI = 0.32−0.46, p < 0.001). Compared to ED‐PrEP users, daily PrEP users were more likely to have received three of more HIV tests in the last year (aRRR = 3.73, 95% CI = 3.15−4.40, p < 0.001) and less likely to be born overseas and lived in Australia for less than 5 years compared to being born in Australia (aRRR = 0.64, 95% CI = 0.49−0.83, p = 0.001).

Conclusions

While daily PrEP remains the most common PrEP dosing regimen among GBMSM in Australia, there has been a steep increase in the proportion of PrEP users who are taking ED‐PrEP. Monitoring of PrEP use should continue to adapt to new dosing methods and future PrEP options. As ED‐PrEP use increases, further work is needed to ensure those taking ED‐PrEP are taking it effectively to prevent HIV.
Comparison of technological and physical properties of matcha powders of different geographical origins
Authors: Stępień Anna , Liszka‐Skoczylas Marta , Gwóźdź Gabriela
Published: November 2024

Background

The sorption characteristics and glass transition temperature are important attributes that determine the shelf life of foods, particularly in powder form, whereas color is a key factor influencing consumer acceptance. As the popularity of matcha green tea powder is increasing, this study investigated whether the country of origin of examples of matcha products available on the Polish market influenced the sorption properties, glass transition temperature, and color.

Results

All matcha powders exhibited sigmoidal water adsorption isotherms at 25 °C. The monolayer moisture content corresponding to the point of maximum stability ranged from 0.045 to 0.053 g water per g of sample. The glass transition temperature of anhydrous matcha powders varied between 106.3 and 139.0 °C. Based on the sorption and glass transition results, the matcha from Brazil should be the most stable during storage. The same sample showed the highest water solubility index values at temperatures above 80 °C and the lowest bulk density. The color parameters (L*, a*, b*, C*, and h) depended on the matcha powder variant.

Conclusion

The results indicate that the optimal storage conditions for tea powders do not depend directly on the country of origin. Further research should therefore focus on analyzing the impact of climate or fertilization. © 2024 Society of Chemical Industry.
The use of heat‐treated whey protein isolate as a natural emulsifier in fat‐filled whey powder with a pre‐emulsification process
Authors: Li Hongjuan , Li Ke , Zhang Leilei , Wu Zhengyan , Yu Hongmei , Li Hongbo , Lv Jiaping , Zhang Shuwen , Yu Jinghua
Published: November 2024

BACKGROUND

Fat‐filled whey powder is a type of whey powder that has been developed in recent years and is widely applied in the dry processing of infant formula milk powder. The addition of sodium caseinate, dextrin, or modified starch as emulsifiers can also improve the stability of fat‐filled whey powders. However, regulations forbid the use of these substances as raw materials in powdered infant formulas. The development of new natural emulsifiers is therefore essential.

RESULTS

A pre‐emulsification process (P‐EP) with heat‐treated whey protein (HWP) increased the solubility of fat‐filled whey powders, reduced the Turbiscan stability index value, and reduced surface fat content. Microstructural analysis showed that the fat‐filled whey powder in the experimental group (≤35 wt% fat in dry matter) exhibited a more uniform particle distribution in comparison with a control group.

CONCLUSION

The P‐EP with HWP as a natural emulsifier can improve the stability and emulsifying effect in fat‐filled whey powders. The use of P‐EP with HWP was a promising method for producing fat‐filled whey powder without artificial additives, relying solely on milk‐derived ingredients for a clean label. © 2024 Society of Chemical Industry.
Recurrence Timing and Risk Following Curative Resection of Colorectal Liver Metastases: Insights From a Hazard Function Analysis
Authors: Kawashima Jun , Akabane Miho , Endo Yutaka , Woldesenbet Selamawit , Altaf Abdullah , Ruzzenente Andrea , Popescu Irinel , Kitago Minoru , Poultsides George , Sasaki Kazunari , Aucejo Federico , Sahara Kota , Endo Itaru , Pawlik Timothy M.
Published: November 2024

Introduction

There is no consensus on the optimal surveillance interval for patients undergoing resection of colorectal liver metastases (CRLM). We sought to assess the timing and intensity of recurrence following curative‐intent resection of CRLM utilizing a recurrence‐free survival (RFS) hazard function analysis.

Methods

Patients with CRLM who underwent curative‐intent resection were identified from a multi‐institutional database. The RFS hazard function was used to plot hazard rates and identify the peak of recurrence over time.

Results

Among 1804 patients, the median RFS was 19.9 months. In the analytic cohort, the RFS hazard curve peaked at 5.9 months (peak hazard rate: 0.054) and gradually declined, indicative of early recurrence. In subgroup analyses, patients with high and medium tumor burden scores (TBS) had RFS hazard peaks at 4.9 months (peak hazard rate: 0.060) and 5.8 months (peak hazard rate: 0.054), respectively. In contrast, patients with low TBS had a later peak at 7.5 months, with the lowest peak hazard rate of 0.047.

Conclusions

The recurrence peak for CRLM patients occurred approximately 6 months postsurgery, highlighting the need for intensified early postoperative surveillance. Patients with high TBS experienced earlier recurrence, underscoring the importance of close monitoring, particularly during the first 6 months after surgery.
Drive Them to Rail—How Can Tourist Destinations Increase the Market Share of Rail Travel? A Discrete Choice Experiment
Authors: Bursa Bartosz , Tappeiner Gottfried , Vicoli Sebastian , Mölk Felix , Mailer Markus
Published: November 2024

Mobility accounts for the largest share of CO2 emissions generated by tourism industry. The extent of CO2 resulting from tourists' long‐distance travel depends strongly on the transport mode used. To reduce these emissions, destinations should engage in promoting a shift from flying and driving to traveling on rail. This study hypothesizes that the entire mobility chain, that is, long‐distance travel and mobility at destination, represents an interconnected bundle of services. Using data from a Discrete Choice Experiment conducted with visitors to a tourist destination in Austrian Alps, we estimated the effects of attributes of long‐distance travel by personal vehicle and rail (travel time, travel costs, number of transfers) and effects of attributes of local mobility services offered at the destination (transit frequency, carsharing, mobility hub). The outcomes indicate that local mobility services are highly relevant for transport mode choice of tourists and can increase the market share of rail significantly.
Collaborating for growth: Insights from Publisherspeak UK 2024, a scholarly publishing community gathering – part 1
Authors: Venkataramani Ravi , Mahadevan Sowmya , Ramkumar Arun , De Boer Jason , Krishnan Janani , Russell Louise , Anderton Sophia , Burley Caroline , Cockburn Emily , Kelly Joe
Published: November 2024

Key points

Publisherspeak UK 2024, sponsored by Kriyadocs, facilitated breakout sessions to tackle key challenges in scholarly publishing.

Themes explored included research integrity, interoperability, environmental sustainability, and research communities.

Solutions focused on enhancing collaboration, standardizing industry guidelines, and improving efficiency across publishing workflows.

Delegates developed strategies to address the diffusion of responsibility in research integrity and foster interoperability.
Adaptive Mesh Refinement Based on Finite Analytical Method for Two‐Dimensional Flow in Heterogeneous Porous Media
Authors: Xiao Chang‐Hao , Yu Jin‐Biao , Cao Wei‐Dong , Wang Yong , Wang Xiao‐Hong , Liu Zhi‐Feng , Wang Min
Published: November 2024

In this work, we improve the traditional adaptive mesh refinement (AMR) by combining it with the finite analytical method (FAM) to solve the multiphase flow in heterogeneous porous media numerically. The FAM can provide rather accurate internodal transmissibility, and it is employed to improve the accuracy of coarsening and refining processes in AMR. The high performance of the proposed AMR‐FAM is indicated through numerical tests for solving the two‐phase flow in 2D heterogeneous media. The numerical simulation results indicate that the proposed AMR‐FAM is more accurate than the traditional AMR‐FAM. Compared with the simulation in the original fine grids, the proposed AMR‐FAM can provide nearly the same results. Moreover, the computational cost in the AMR grids is only approximately one‐third of the cost in the original fine grids according to our numerical tests.
Impact of Overactive Bladder and Dry Mouth on Subjective and Comprehensive Sleep Quality in Older Adults With Nocturia
Authors: Natsume Osamu , Shimizu Takuto , Fujimoto Kiyohide
Published: November 2024

Background

Nocturia is among the most common and bothersome urinary tract symptoms in older adults. While sleep quality is key to nocturia management, there is little information on the impact of nocturia itself on sleep quality. We investigated the impacts of nocturia on sleep quality and quality of life and explored factors contributing to reduced sleep quality.

Methods

A total of 186 men, aged 42–88 years (patients with nocturia and a control group), were evaluated using the Pittsburgh Sleep Quality Index, the Nocturia Quality‐of‐Life questionnaire, a visual analog scale measurement of dry mouth, and the Overactive Bladder Symptom Score, among other tools. Patients were graded into four categories of nocturia severity based on 3‐day frequency volume charts. Factors associated with reduced subjective and comprehensive sleep quality were investigated using multiple regression analysis.

Results

Initial undisturbed sleep duration was negatively associated with nocturia frequency. Subjective and comprehensive sleep quality, overactive bladder scores, sleep efficiency and oral dryness were significantly associated with nocturia‐related quality of life, when controlled for both age and nocturia severity. Sleep efficiency was a major predictor of reduced subjective and comprehensive sleep quality; overactive bladder scores and oral dryness were also independently significantly associated with reduced subjective and comprehensive sleep quality on multiple regression analysis, although nocturia frequency and initial undisturbed sleep duration were not.

Conclusions

It may be beneficial to conduct a comprehensive assessment for overactive bladder and dry mouth when managing nocturia in older adults with poor sleep quality.
Prevalence of Pain and Associated Clinical Characteristics in 10‐Year Survivors of Head and Neck Cancer
Authors: Howren M. Bryant , Pagedar Nitin A.
Published: November 2024

Objective

Pain prevalence in long‐term head and neck cancer (HNC) survivors is important but understudied to date. The present investigation examined pain prevalence, associated clinical characteristics, and disease‐specific health‐related quality of life (HRQOL) in a cohort of survivors 10 years postdiagnosis (N = 187).

Study Design

Retrospective cohort study.

Setting

Single‐institution tertiary care center.

Methods

Pain was assessed using a single‐item numeric rating scale. Clinical characteristics were abstracted from the patient medical record and HNC‐specific HRQOL scores were measured using the Head and Neck Cancer Inventory (HNCI) and are presented by the pain subgroup.

Results

At 10 years postdiagnosis, 56.7% reported no pain, 20.3% reported mild pain, 16.0% reported moderate pain, and 7.0% reported severe pain. Most patients with moderate or severe pain at the 10‐year follow‐up assessment also had advanced‐stage disease at diagnosis. Multiple linear regression analyses indicated that advanced‐stage disease at diagnosis was a significant predictor of pain at 10 years postdiagnosis controlling for age, sex, and comorbidity status (β = .184, t = 2.193, P = .030, sr2 = 0.025). Across all HNC‐specific HRQOL domains, those reporting moderate/severe pain at 10 years postdiagnosis failed to reach a score of 70 which is indicative of high functioning on the HNCI in the areas of aesthetics, eating, speech, and social disruption.

Conclusion

Pain is a significant issue in long‐term HNC survivors up to 10 years postdiagnosis. More research is needed to understand the correlates and types of long‐term pain exhibited after treatment, including the implementation of screening and intervention into clinical workflow to improve outcomes and optimize HNC survivorship care.
Management of Ganglioneuroma and Ganglioneuroblastoma Intermixed: A United Kingdom Children's Cancer and Leukaemia Group (UK CCLG) Nationwide Study Report
Authors: Burnand Katherine M. , Neville Jonathan , Budzanowski Annita , Okoye Bruce O. , Cross Kate , Wheeler Kate , Gray Juliet , Hall Nigel , Ramanujakar Ramya , Reddy Snigdha , Pachl Max , Kierulff Carla , Herd Fiona , Makin Guy , Howell Lisa , Pizer Barry , Rogers Timothy , Al‐Khafaji Nadeem , Tweddle Deborah , Carruthers Vicky‐Anne , Barone Giuseppe , Anderson John , Vaidya Sucheta , George Sally , Braungart Sarah , Kwok Chun , Jacovides Michael , Burke Amos , Yeomanson Dan , Murphy Dermot , Losty Paul D. , Angelini Paola , Gabra Hany
Published: November 2024

Background

Ganglioneuroblastoma intermixed (GNBi) and ganglioneuroma (GN) represent benign variants of peripheral neuroblastic tumours. While historically surgical resection was recommended, watchful active observation has become the accepted management for a subset of patients.

Objectives

To review clinical features, biology, natural history and management of a retrospective UK CCLG study cohort of GN and GNBi, and compare outcomes of patients treated with surgical resection or watchful active observation.

Methods

Retrospective review of histologically confirmed non‐metastatic GN and GNBi diagnosed between 1990 and 2020.

Results

A total of 259 patients were identified (163 GN, 93 GNBi, median age 62 months). In all 201 (78%) had initial surgery and 58 (22%) were observed. Overall survival was 98%. Twenty‐one of 58 observed (36%) required subsequent surgery due to progressive tumour growth (52%). Gross total resection (GTR) was achieved in 79% of patients with a 19% complication rate. GTR was obtained in a similar proportion of patients having initial surgery (65%) and delayed surgery (76%). Patients obtaining GTR were more likely to have complete symptom(s) control (43% vs. 24%). In 45 cases (39%), surgical pathology was different from pathology at biopsy, and in 14 (12%) the pathology changed from GN/GNBi to neuroblastoma/GNB nodular.

Conclusion

Watchful active observation can be a safe approach, with surgical resection reserved for symptomatic patients. However, a small proportion of patients in the observation group had their diagnosis revised to malignant at surgery. Careful assessment of surgical risk and expected benefits, after considering an initial period of observation, will allow clinicians to make optimal decisions for patients and their families.
Pediatric Head and Neck Malignancies in the United States: A 20‐Year Population‐Based Study
Authors: Kraguljac Simo , Hajjar Fouad , Wong Richard , Shah Jatin , Lopez Joseph
Published: November 2024

Background

Epidemiologic data for pediatric head and neck (HN) cancers in the United States (US) have not been reported in many years. An update is essential to highlight trends to guide future treatment.

Methods

We analyzed the Surveillance Epidemiology and End Results database from 2000 to 2019. We included patients aged <1–21 years with a malignancy in the HN region. We also report trends in incidence rates over time.

Results

HN tumors encompassed 16.7% of all pediatric tumors with a mean age of 13.1 years. Females accounted for 59.0% of tumors. The female predominance is largely due to thyroid carcinoma; if thyroid malignancies are excluded male incidence is higher. The overall incidence (0–19 years) was found to be 3.29 malignancies per 100,000 person‐years. The incidence from 2000 to 2004 was 2.84 [95% CI, 2.77, 2.91] while from 2015 to 2019 was 3.65 [3.57, 3.73]. This increase of 28.5% was greater than overall pediatric cancer, which increased by 13.7%. Incidence varies significantly by age group with 4.56 [4.35, 4.78] at age <1, 2.45 [2.37, 2.53] from 1 to 4 years, 1.46 [1.40, 1.51] from 5 to 9 years, 2.27 [2.21, 2.34] from 10 to 14 years, 4.81 [4.71, 4.90] from 15 to 19 years, and 7.35 [7.17, 7.40] from 20 to 21 years. Thus, there is a bimodal rise at the extremes of the pediatric age group.

Conclusions

Pediatric HN tumors more commonly affect females. These tumors appear in a bimodal distribution; they most commonly present in very young patients and then during late adolescence The incidence has increased since 2000 and faster than overall incidence. Reporting of these data and trends will allow for advancement in treatment.
An Improved Synthesis of Compound 11, a Unique Bicyclic Melanocortin‐3 Antagonist
Authors: Joy Stephen T. , Dahir Naima S. , Cone Roger D. , Mapp Anna K.
Published: November 2024

The melanocortin‐3 receptor (MC3R) is a G‐protein coupled receptor that regulates appetite and is a potential therapeutic target for anorexia and weight loss treatments. The report of a highly selective synthetic antagonist of MC3R, Cpd11, represents a major advance toward therapeutic targeting of MC3R. However, Cpd11 is challenging to access synthetically, severely limiting its use and additional structural optimization. Here, we outline an improved synthesis of Cpd11 that addresses three major synthetic challenges, including the formation of Cpd11's structurally unique bicyclic core. With these changes, Cpd11 was readily produced (2.3 mg from a 0.05 mmol scale versus ≪ 0.1 mg using the original synthetic methodology) and utilized in MC3R studies in C57BL/6J male mice. Thus, this new approach will increase the accessibility of Cpd11 and is translatable to related bicyclic agonists and antagonists for other melanocortin receptors and may have general applicability toward the synthesis of other multicyclic poly‐cysteine peptides.
Comparing the Effects of Different Dielectric Materials on an Atmospheric Pressure Plasma Jet by Experiments and Simulations
Authors: Huang Po‐Chun , Weng Hao‐Hsiang , Hsueh Cheng‐Hsiao , Tsai Hsing‐Che , Cheng Yun‐Chien
Published: November 2024

This study investigates how quartz and alumina affect atmospheric pressure plasma jet (APPJ) stability using numerical simulations and experiments. Unlike previous research, it uses simulations and equivalent circuits to explore discharge characteristics. Experimental results show a temperature increase in quartz APPJ, leading to decreased gas voltage and enhanced plasma intensity, validated by equivalent circuit analysis. Alumina APPJ maintains more stable plasma intensity. Simulation reveals that higher dielectric coefficients enhance capacitance, leading to higher plasma parameters such as electron density, ion density, and electron temperature. This research clarifies quartz's voltage increase over time, which is crucial for biomedical plasma applications, aiding in selection of stable dielectric materials.
The Use of Textile Electrodes for Electrical Resistivity Tomography in Periglacial, Coarse Blocky Terrain: A Comparison With Conventional Steel Electrodes
Authors: Bast Alexander , Pavoni Mirko , Lichtenegger Matthias , Buckel Johannes , Boaga Jacopo
Published: November 2024

Electrical resistivity tomography (ERT) is widely used to map, characterize, and monitor the ground in alpine and periglacial environments, where coarse blocky surfaces are often ubiquitous. ERT measurements typically use conventional steel electrodes in combination with a water‐soaked sponge. However, ensuring an optimum contact resistance between the electrodes and the ground to obtain high‐quality data is often challenging and requires considerable logistical, physical, and time commitment. To overcome this, we tested a promising sand‐filled, fist‐sized conductive textile electrode. We conducted ERT measurements using both steel and textile electrodes at a landslide and two rock glaciers in the European Alps with coarse blocky surfaces and performed statistical analyses to test the accuracy and precision of the proposed textile electrodes. Our results show that the textile electrodes can be used as an alternative to the conventional steel electrodes without limitations, as they ensure good galvanic contact with the ground and accurate resistivity measurements. The use of textile electrodes also resulted in lower contact resistances, less time invested, physical and logistical advantages, and reduced risk of injury. In the future, this will enable applications such as enhanced ERT monitoring and/or faster (quasi‐3D) imaging of the interior of entire landforms.
Evaluating the Efficacy of Capacitive Resistive Monopolar Radiofrequency Combined With Proprioceptive Neuromuscular Facilitation in Managing Chronic Low Back Pain: A Randomised Controlled Trial
Authors: Jurak Ivan , Grabar Silvija , Žura Nikolino , Jakuš Lukrecija
Published: November 2024

Background and Purpose

This randomised controlled trial evaluates the effectiveness of capacitive resistive monopolar radiofrequency (CRMRF) combined with proprioceptive neuromuscular facilitation (PNF) training in managing chronic low back pain (CLBP). Given the multifactorial nature of CLBP, this study explores a multimodal treatment approach integrating CRMRF, known for its thermal effects and ability to alleviate pain through improved cell metabolism and microcirculation, with PNF training, which enhances muscle strength, flexibility, and proprioception.

Methods

This study was designed as a single‐blind, parallel, randomised controlled trial conducted in an outpatient clinical setting. Over the course of four months, 62 participants, suffering from chronic low back pain were randomly assigned to receive either the combined CRMRF and PNF treatment or PNF alone, with primary outcomes measured in terms of pain and functional disability using the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI). For secondary outcome of disability associated with pain, Quebec Pain Disability Scale (QPDS) and Roland‐Morris Disability Questionnaire (RMDQ) were used. The study's hypothesis was that the combined treatment would reduce pain and disability more effectively than PNF alone.

Results

Results indicated that the experimental group experienced greater improvements in pain and functional disability, surpassing the minimally clinically important difference (MCID) for the VAS, ODI, QPDS and RMDQ, suggesting the clinical relevance of the combined CRMRF and PNF approach.

Discussion

These findings are consistent with previous research highlighting the benefits of CRMRF in various musculoskeletal disorders and suggest that integrating CRMRF with PNF training offers a promising non‐invasive treatment option for CLBP sufferers. Overall, our study contributes to the growing evidence base supporting innovative, multimodal treatment strategies for managing CLBP, with the potential to enhance patients' quality of life.

Trial Registration: ClinicalTrials.gov identifier: NCT05682287
NMDA Receptor–Mediated Ca2+ Flux Attenuated by the NMDA Receptor/TRPM4 Interface Inhibitor Brophenexin
Authors: Casby Jordan , Gansemer Benjamin M. , Thayer Stanley A.
Published: November 2024

Transient receptor potential melastatin‐4 (TRPM4) forms a complex with N‐methyl‐D‐aspartate receptors (NMDARs) that facilitates NMDAR‐mediated neurotoxicity. Here we used pharmacological tools to determine how TRPM4 regulates NMDAR signaling. Brophenexin, a compound that binds to TRPM4 at the NMDAR binding interface, protected hippocampal neurons in culture from NMDA‐induced death, consistent with published work. Brophenexin (10 μM) reduced NMDA‐evoked whole‐cell currents recorded at 22°C by 87% ± 14% with intracellular Ca2+ chelated to prevent TRPM4 activation. Brophenexin inhibited NMDA‐evoked currents recorded in Na+‐free solution by 87% ± 13%, suggesting that brophenexin and TRPM4 modulate NMDAR function. Incubating cultures in Mg2+‐free buffer containing tetrodotoxin, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione, and bicuculline for 30 min inhibited NMDA‐evoked increases in intracellular Ca2+ concentration ([Ca2+]i) recorded at 22°C by 50% ± 18% and prevented inhibition by brophenexin. In the absence of these inhibitors, brophenexin inhibited the NMDA‐evoked response by 51% ± 16%. Treatment with the TRPM4 inhibitor 4‐chloro‐2‐(1‐naphthyloxyacetamido)benzoic acid (NBA; 10 μM) increased NMDA‐evoked Ca2+ influx by 90% ± 15%. Increasing extracellular NaCl to 237 mM, a treatment that activates TRPM4, inhibited the NMDA‐evoked increase in [Ca2+]i by a process that occluded the inhibition produced by brophenexin and was prevented by NBA. In recordings performed at 32°C–34°C, brophenexin inhibited the NMDA‐evoked [Ca2+]i response by 42% ± 10% but NBA was without effect. These results are consistent with a model in which TRPM4 interacts with NMDARs to potentiate Ca2+ flux through the NMDAR ion channel and thus provides a potential mechanism for the neuroprotection afforded by NMDAR/TRPM4 interface inhibitors such as brophenexin.
Clinical study design strategies to mitigate confounding effects of time‐dependent clearance on dose optimization of therapeutic antibodies
Authors: Proctor Jeffrey R. , Wong Harvey
Published: November 2024

Time‐dependent pharmacokinetics (TDPK) is a frequent confounding factor that misleads exposure‐response (ER) analysis of therapeutic antibodies, where a decline in clearance results in increased drug exposure over time in patients who respond to therapy, causing a false‐positive ER finding. The object of our simulation study was to explore the influence of clinical trial designs on the frequency of false‐positive ER findings. Two previously published population PK models representative of slow‐ (pembrolizumab) and fast‐onset (rituximab) TDPK were used to simulate virtual patient cohorts with time‐dependent clearance and the frequency of false‐positive ER findings. The impact of varying the number of dose groups, dose range, and sample size was evaluated over time. Study designs with a single tested dose level showed a high probability of showing a false‐positive ER finding. When TDPK has a slow onset, use of exposure measures from early timepoints in ER analysis significantly reduces the risk of a false‐positive, while with fast onset it did not. Randomization of patients to two dose levels greatly reduced the risk, with a threefold or greater dose range offering the greatest benefit. The likelihood of false‐positive increases with a larger sample size, where greater care should be taken to identify confounding factors. Clinical trial simulation supports that appropriate clinical study design and analysis with adequate dose exploration can reduce but cannot entirely eliminate the risk of misleading ER findings.
Lattice Dynamics of LiNb1–xTaxO3 Solid Solutions: Theory and Experiment
Authors: Bernhardt Felix , Gharat Soham , Kapp Alexander , Pfeiffer Florian , Buschbeck Robin , Hempel Franz , Pashkin Oleksiy , Kehr Susanne C. , Rüsing Michael , Sanna Simone , Eng Lukas M.
Published: November 2024

Lithium niobate (LNO) and lithium tantalate (LTO) see widespread use in fundamental research and commercial technologies reaching from electronics over classical optics to integrated quantum communication. The mixed crystal system lithium niobate tantalate (LNT) allows for the dedicate engineering of material properties by combining the advantages of the two parental materials LNO and LTO. Vibrational spectroscopies such as Raman spectroscopy or (Fourier transform) infrared (IR) spectroscopy are vital techniques to provide detailed insight into the material properties, which is central to the analysis and optimization of devices. This work presents a joint experimental–theoretical approach allowing to unambiguously assign the spectral features in the LNT material family through both Raman and IR spectroscopy, as well as providing an in‐depth explanation for the observed scattering efficiencies based on first‐principles calculations. The phononic contribution to the static dielectric tensor is calculated from the experimental and theoretical data using the generalized Lyddane–Sachs–Teller relation and compared with the results of the first‐principles calculations.
Irradiated Coherent States in Magnetoresistance of 2D Electron Systems
Authors: Iñarrea Jesús , Platero Gloria
Published: November 2024

Herein, a novel theoretical approach on the microwave‐induced resistance oscillations based on the coherent states of the quantum harmonic oscillator is reported. Within the theoretical model of microwave‐induced electron orbits, the coherent state expression for the quantum harmonic oscillator under a time‐dependent force (radiation) is calculated. Thus, it is found that the principle of minimum uncertainty of coherent states, involving time and energy, is the main responsible of photo‐oscillations and zero‐resistance states. Thus, essential experimental results of this remarkable effect are shed light (and explained) on. The origin of photo‐oscillations, their position with respect to the magnetic field, and their periodicity can be distinguished.
Suffruticosol B from Paeonia lactiflora Ameliorates Alzheimer's Disease Pathology by Inhibiting MAO‐B Activity
Authors: Heo Jae‐Jun , Han Young‐Eun , Kim Min Soo , Cheong Eunji , Choi Chun Whan , Oh Soo‐Jin
Published: November 2024

Monoamine oxidase B (MAO‐B) has emerged as a therapeutic target for Alzheimer's disease (AD) due to its involvement in the synthesis of γ‐aminobutyric acid (GABA) in reactive astrocytes, which inhibits neuronal activity. Suffruticosol B (Suf‐B), isolated from Paeonia lactiflora, is one of the resveratrol oligomers. Although resveratrol oligomers have demonstrated neuroprotective effects, it remains unexplored whether Suf‐B exerts therapeutic effects on AD by targeting MAO‐B. In this study, we investigated whether Suf‐B alleviates AD pathology by mitigating reactive astrogliosis and inhibiting the overproduction of astrocytic GABA. After confirming the MAO‐B inhibitory effect of Suf‐B through MAO‐B enzyme assay, we administered Suf‐B to APP/PS1 AD model mice. To test the potential therapeutic action of Suf‐B in AD, a series of experiments were conducted, including behavioral tests such as the open field test, novel object recognition test, Barnes maze test, passive avoidance test, as well as immunohistochemistry and whole‐cell patch‐clamp recordings. We found that Suf‐B markedly inhibited MAO‐B activity without causing cytotoxicity. Immunohistochemistry and electrophysiology experiments demonstrated that Suf‐B significantly reduced astrocyte reactivity, as well as an aberrant increase in GABA production and tonic GABA release from astrocytes in AD. Behavior test results indicated that Suf‐B treatment restored cognitive function in APP/PS1 mice. In conclusion, Suf‐B effectively reduces excessive GABA production in reactive astrocytes by inhibiting MAO‐B, normalizing aberrant inhibition in hippocampal neurons in an AD mouse model. These results suggest that Suf‐B has potential as a treatment for AD and may be applicable to other brain diseases associated with reactive astrogliosis.