bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment‐related neuroendocrine prostate cancer with BRCA2 germline mutation treated with olaparib
Authors: Ikeda Riko , Matsuoka Yoh , Inoue Masaharu , Ishikawa Ayataka , Akagi Kiwamu , Kageyama Yukio
Published: December 2023

Introduction

The efficacy of olaparib for treatment‐related neuroendocrine prostate cancer is unknown. Here, we report a case of treatment‐related neuroendocrine prostate cancer with a BRCA2 mutation that was treated with olaparib with 1‐year efficacy.

Case presentation

A 75‐year‐old man initially diagnosed with prostate adenocarcinoma developed treatment‐related neuroendocrine prostate cancer after 10‐year androgen deprivation therapy. Despite the initial temporary effects of etoposide and carboplatin, the patient experienced prostate bed tumor recurrence 1 year after chemotherapy cessation. FoundationOne® detected a BRCA2 gene mutation, and olaparib was initiated after repeating one chemotherapy course using the same chemotherapeutic agents. The patient received olaparib with sustained tumor regression for 1 year without severe side effects.

Conclusion

Olaparib may be the treatment of choice for treatment‐related neuroendocrine prostate cancer in patients with BRCA mutations.
Measuring farmer time preferences: A systematic literature review for Europe and North America
Authors: Wuepper David , Henzmann Severin , Finger Robert
Published: December 2023

We present the first systematic review of the literature on farmer time preference measurements across Europe and North America. We synthesize methodological developments, summarize the empirical findings, and discuss challenges and potential areas for further research. The average reported discount rate of the farmers in Europe and North America is 23% per annum. Farmer time preferences are, however, highly heterogeneous within and across studies. Moreover, we identify methodological challenges and knowledge gaps to be addressed in future research. We draw conclusions for policymakers and researchers.
Improvement of access to mental health care through implementing telehealth services by clinical pharmacist practitioners
Authors: Goodman Courtney S. , Chiulli Dana L. , Seratt Kimberly G. , Smith Tammy J.
Published: December 2023

The nationwide shortage of psychiatric providers delays patients from receiving vital mental health (MH) treatments. Mental Health clinical pharmacist practitioners (CPPs) are qualified to provide comprehensive medication management (CMM) services and expand care; however, many MH interdisciplinary teams have not incorporated MH CPPs or have not optimized their role. The purpose of this paper is to highlight how MH CPPs leveraged telemedicine to provide CMM to outpatient MH clinics requiring provisional coverage for other prescribing providers. This paper also reviews supplemental services and barriers to implementation. The Veterans Integrated Services Network (VISN) 6 Clinical Resource Hub‐Telemental Health (CRH‐TMH) is a centralized interdisciplinary team that provides telemental health services to veterans through coordination with their local Veterans Health Administration Health Care Systems located in North Carolina and Virginia. The MH CPPs serve as advanced practice providers with a scope of practice that authorizes prescriptive authority including controlled substances. The VISN 6 CRH‐TMH program was initiated in 2020 and expanded from one MH CPP to include three MH CPPs and a MH CPP supervisor. Since initiation, the MH CPPs have supported 10 outpatient MH clinics. From October 2021 to March 2023, the MH CPPs have completed 5080 clinical encounters. The MH CPPs decreased phone appointments and increased the percentage of video‐to‐home encounters from 56% in fiscal year 2021 to 91% by March fiscal year 23. Virtual same‐day access was implemented at three locations and the substance use disorder program provided timely access to life‐saving treatments. The joint intake clinic optimized veterans' intake into the MH clinic by the therapist providing diagnostic services and the CPP performing CMM during the same appointment. The telehealth learning experience increased training opportunities for residents. The success of this initiative further supports the expansion of MH CPPs as advanced practice providers.
Exposure of quantum dots in the nervous system: Central nervous system risks and the blood–brain barrier interface
Authors: Guan Shujing , Tang Meng
Published: December 2023

Quantum dots currently possess significant importance in the field of biomedical science. Upon introduction into the body, quantum dots exhibit a tendency to accumulate in diverse tissues including the central nervous system (CNS). Consequently, it becomes imperative to devote specific attention to their potential toxic effects. Moreover, the preservation of optimal CNS function relies heavily on blood–brain barrier (BBB) integrity, thereby necessitating its prioritization in neurotoxicological investigations. A more comprehensive understanding of the BBB and CNS characteristics, along with the underlying mechanisms that may contribute to neurotoxicity, will greatly aid researchers in the development of effective design strategies. This article offers an in‐depth look at the methods used to reduce the harmful effects of quantum dots on the nervous system, alongside the progression of effective treatments for brain‐related conditions. The focal point of this discussion is the BBB and its intricate association with the CNS and neurotoxicology. The discourse commences by recent advancements in the medical application of quantum dots are examined. Subsequently, elucidating the mechanisms through which quantum dots infiltrate the human body and traverse into the brain. Additionally, the discourse delves into the factors that facilitate the passage of quantum dots across the BBB, primarily encompassing the physicochemical properties of quantum dots and the BBB's inherent capacity for self‐permeability alteration. Furthermore, a concluding summary is presented, emphasizing existing research deficiencies and identifying promising avenues for further investigation within this field.
Expanded molecular detection of MPL codon p.W515 and p.S505N mutations in myeloproliferative neoplasms
Authors: Miller Eric W. , Lamberson Celeste M. , Akabari Ratilal R. , Nasr Michel R. , Sperber Steven M.
Published: December 2023

Background

Patients negative for the JAK2 p.V617F somatic variant are frequently reflexed to testing for MPL exon 10 variants. Detection of these variants via multiplexed allele‐specific PCR followed by fragment analysis has been previously published. The present study builds on this concept by improving the detection of the p.W515A variant, adding a second allele‐specific primer to detect the p.W515R variant, and incorporating an improved primer for p.S505N detection.

Methods

The W515 amplification employs 5′‐labeled allele‐specific forward primers to detect p.W515K, p.W515L, p.W515R, and p.W515A. The p.S505N amplification includes an allele‐specific reverse primer with a tail extension. Fragments were subject to capillary electrophoresis on an ABI 3500 Genetic Analyzer and analyzed using GeneMapper 6.0 (Thermo Fisher Scientific).

Results

Thirty MPL‐negative and 13 MPL‐positive samples previously tested by a reference laboratory were tested with the MPL LDT. Results were 100% concordant. The MPL LDT has a limit of detection of at least 5% VAF for the p.W515 variants and 10% VAF for the p.S505N variant.

Conclusion

Current MPL assays are predominantly focused on p.W515L/K and p.S505N mutations. We have engineered an MPL test for detecting p.W515A/L/K/R and p.S505N variants, thereby increasing the diagnostic yield with little additional expense or technician time.
Temporospatial dynamics of the morphogenesis of the rabbit retina from prenatal to postnatal life: Light and electron microscopic study
Authors: El‐Desoky Sara M. M. , Elhanbaly Ruwaida , Hifny Abdalla , Ibrahim Nagwa , Gaber Wafaa
Published: December 2023

The retina consists of various cell types arranged in eight cell layers and two membranes that originate from the neuroectodermal cells. In this study, the timing of differentiation and distribution of the cellular components and the layers of the rabbit retina are investigated using light and electron microscopy and immunohistochemical techniques. There were 32 rabbit embryos and 12 rabbits used. The rabbit retina begins its prenatal development on the 10th day of gestation in the form of optic cup. The process of neuro‐ and gliogenesis occurs in several stages: In the first stage, the ganglionic cells are differentiated at the 15th day. The second stage includes the differentiation of Muller, amacrine, and cone cells on the 23rd day. The differentiation of bipolar, horizontal, and rod cells and formation of the inner segments of the photoreceptors consider the late stage that occurs by the 27th and 30th day of gestation. On the first week of age postnatally, the outer segments of the photoreceptors are developed. S100 protein is expressed by the Muller cells and its processes that traverse the retina from the outer to the inner limiting membranes. Calretinin is intensely labeled within the amacrine and displaced amacrine cells. Ganglionic cells exhibited moderate immunoreactivity for calretinin confined to their cytoplasm and dendrites. In conclusion, all stages of neuro‐ and gliogenesis of the rabbit retina occur during the embryonic period. Then, the retina continues its development postnatally by formation of the photoreceptor outer segments and all layers of the retina become established.

Research Highlights

The aim of this study is to investigate the morphogenesis of the rabbit retina during pre‐ and postnatal life.

The primordia of the retina could be observed in the form of the optic cup. The ganglionic cells are the first cells to differentiate, while the photoreceptor cells are the last.

S100 protein is expressed by the Muller cells and its processes. Calretinin is intensely labeled in the amacrine and displaced amacrine cells and moderately expressed in the cytoplasm and dendrites of ganglionic cells.
Comprehensive systematic review and pooled analysis of real‐world studies evaluating immunomodulator and biologic therapies for chronic pouchitis treatment
Authors: Khoo Emi , Lee Andrew , Neeman Teresa , An Yoon‐Kyo , Begun Jakob
Published: December 2023

Background and Aim

Pouchitis is a common complication after restorative ileal pouch–anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic‐dependent or antibiotic‐refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15–20% of patients, is challenging to treat. The efficacy of second‐line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real‐world efficacy data from peer‐reviewed full‐text manuscripts, focusing on immunomodulator and biologic therapies in CP.

Methods

Embase and PubMed databases were searched for full‐text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti‐integrin, and interleukin‐12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed.

Results

Pooled analysis comprised 20 full‐text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35–59%) and clinical remission rate was 35% (95% CI: 21–52%). Overall endoscopic response and remission rates were 41% (95% CI: 18–68%) and 15% (95% CI: 5–39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable.

Conclusion

The real‐world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti‐TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real‐world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.
The rationale for a carbon ion radiation therapy facility in Australia
Authors: Thwaites David I. , Prokopovich Dale A. , Garrett Richard F. , Haworth Annette , Rosenfeld Anatoly , Ahern Verity
Published: December 2023

Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under‐construction proton therapy facility in Adelaide, other potential proton centres and an under‐evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide‐ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.
Evolution of therapy for locally advanced rectal cancer
Authors: Altomare Nicole J. , Mulcahy Mary F.
Published: December 2023

Rectal cancer is a prevalent disease worldwide. The standard treatment of locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy followed by surgery and adjuvant systemic chemotherapy. Studies have been done to determine the best sequence of treatments to improve survival, cure rate and long term toxicity profile. In this paper, we will review the literature regarding the evolution of LARC treatment.
Sentinel lymph node mapping in endometrial cancer: Current evidence and practice
Authors: Salman Lina , Cusimano Maria C. , Marchocki Zibi , Ferguson Sarah E.
Published: December 2023

Surgical staging with total hysterectomy, bilateral salpingo‐oophorectomy, and lymph node assessment is the standard of care for patients with clinical early‐stage endometrial cancer. Traditionally, complete pelvic and para‐aortic lymphadenectomy (LND) was performed to assess for nodal metastases; however, numerous prospective studies have demonstrated that sentinel lymph node biopsy has similar diagnostic accuracy, and is an acceptable alternative to complete LND. This has led to a paradigm shift in endometrial cancer staging.
Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites
Authors: Karalis John D. , Ju Michelle R. , Feig Rachel , Estrella Raechelle , Pettigrew Morgan F. , Alterio Rodrigo E. , Abreu Andres A. , Farah Emile , Sawas Tarek , Sanford Nina N. , Sanjeevaiah Aravind , Hammer Suntrea T. G. , Porembka Matthew R. , Wang Sam C.
Published: December 2023

Background

Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease‐oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan.

Methods

We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era.

Results

Fifty‐four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04).

Conclusions

Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.
Good morning, sunshine: How time‐of‐day of complaint submittal can affect customer satisfaction with company response time
Authors: Garner Della , Tatara Jennifer H. , Jha Subhash
Published: December 2023

Traditional models of consumer behavior assume that customers perceive factors, e.g., time, in a rational manner throughout the day. For example, the same time period of an hour should, fundamentally, be evaluated as the same as an hour in the afternoon. Yet, across three experimental studies, we find evidence counter to this belief. Under the theoretical framework of the categorization of time, we posit that the unconscious categorization of time influences our satisfaction with company response time due to perceptions of time and resource depletion. We empirically demonstrate that the time‐of‐day of complaint submission impacts satisfaction with company response time such that the same company response time will be perceived as more satisfying in the morning than when received in the afternoon. This previously overlooked relationship builds on a robust and growing literature examining timing strategies in service recovery. We provide both low/no‐cost initiatives as well as strategic timing prioritization for marketing practitioners to maximize customer satisfaction with firm response time.
Identifying the Influence of Stacking Sequence on Mechanical and Vibration Properties of Bamboo/Glass‐Epoxy Composites
Authors: Munde Yashwant , Panigrahi Abhilasha , Chandekar Gautam , Shinde Avinash , Siva Irulappasamy
Published: December 2023

The consumption of renewable materials such as natural fiber reinforced composites is highlighted in many engineering applications because of their degradable and environmentally friendly properties. Composite with dedicated natural fibers is limited their use to semi‐structural applications because of their hydrophobic nature and instability under dynamic load. Present research work is attempted to develop woven bamboo (B)/Glass (G) hybrid epoxy composites. The dedicated (BBBB and GGGG) and hybridized composites with different stacking sequences fabricated through the compression molding process and their mechanical and dynamic mechanical properties are investigated. In mechanical properties, the flexural strength and flexural modulus for the GBBG layered composites are best at 210 and 6256 MPa respectively, close to the dedicated glass composite. Impact strength at around 342–368 J m−1 is observed for all hybrids which are extremely good when compared to pure bamboo composite. Experimental modal analysis is also executed to evaluate the dynamic properties as fundamental natural frequencies and the damping ratio. The GBGB composite possesses a fundamental frequency of 25.1 Hz and a damping ratio of 0.0301. The damping of hybrid composites is improved by 96% compared to GGGG stacked composites. The experimental results are well in agreement with the analytical results. These developed bamboo/glass hybrid composites can be a better alternative composite material in semi‐structural applications.
A Critical Review on Tribological and Mechanical Characteristics of Hybrid Polymer Composite Materials
Authors: Abhang Laxman B. , Dalwe Yash D. , Pawar Deepak S. , Karandikar Pratibha M.
Published: December 2023

This review paper presents tribological and mechanical characteristics of hybrid polymer composite materials that exhibit low friction and low wear. Polymer fiber reinforced materials possess low weight and high specific quality along with high specific stiffness. This study targets a critical review of wear and frictional characteristics of hybrid polymer composite materials. Tribological properties have been evaluated by various researchers using a rotating pin‐on‐disc tribometer and reciprocating wear testing machine. Most likely filler materials are carbon, graphite, nano silica, bronze, glass fibers, MoS2, and polytetrafluoroethylene (PTFE) added in the polyether ether ketone (PEEK), polyamide 66, thermoses polymer, etc. It improves mechanical and tribological properties of hybrid composite materials. This review paper aims to highlights the comparative study of various fillers added in PEEK, Polyamide 66, and thermoses polymer hybrid materials. Recently hybrid composites are used in wide range of applications since it has light weight and high strength.
A multicenter single‐arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2‐positive breast cancer
Authors: Shi Qiyun , Qi Xiaowei , Tang Peng , Fan Linjun , Chen Li , Wang Shushu , Liang Yan , Hu Ying , Wang Minghao , Ren Lin , Zhang Guozhi , Tan Xuanni , Yuan Long , Du Junze , Wu Xiujuan , Wang Mengyuan , Che Hongying , Lv Pengwei , Chen Dejie , Hu Jinhui , Li Qiuyun , Zhang Yanwu , Yang Kunxian , Zhong Yuan , Chen Chuang , Zhou Zemin , Qian Liyuan , Zhang Jingwei , Ma Mingde , Sun Yi , Zhang Yi , Jiang Jun
Published: December 2023

The objective of this multicenter, single‐arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy‐THPy) in the treatment of patients with stage II–III HER2‐positive breast cancer. The present study enrolled patients with stage II–III HER2‐positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21‐day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention‐to‐treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7–75.8%), while the objective response rate was 89.1%. In the post‐hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy‐THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II–III HER2‐positive breast cancer.
Receptor tyrosine kinases: biological functions and anticancer targeted therapy
Authors: Zhang Nan , Li Yongsheng
Published: December 2023

Receptor tyrosine kinases (RTKs) are a class of protein kinases that play crucial roles in various cellular processes, including cell migration, morphological differentiation, cell growth, and angiogenesis. In humans, 58 RTKs have been identified and categorized into 20 distinct families based on the composition of their extracellular regions. RTKs are primarily activated by specific ligands that bind to their extracellular region. They not only regulate tumor transformation, proliferation, metastasis, drug resistance, and angiogenesis, but also initiate and maintain the self‐renewal and cloning ability of cancer stem cells. Accurate diagnosis and grading of tumors with dysregulated RTKs are essential in clinical practice. There is a growing body of evidence supporting the benefits of RTKs‐targeted therapies for cancer patients, and researchers are actively exploring new targets and developing targeted agents. However, further optimization of RTK inhibitors is necessary to effectively target the diverse RTK alterations observed in human cancers. This review provides insights into the classification, structure, activation mechanisms, and expression of RTKs in tumors. It also highlights the research advances in RTKs targeted anticancer therapy and emphasizes their significance in optimizing cancer diagnosis and treatment strategies.
Nrf2/PHB2 alleviates mitochondrial damage and protects against Staphylococcus aureus‐induced acute lung injury
Authors: Jin Si‐Hao , Sun Jiao‐Jiao , Liu Gang , Shen Li‐Juan , Weng Yuan , Li Jin‐You , Chen Min , Wang Ying‐Ying , Gao Zhi‐Qi , Jiang Feng‐Juan , Li Sheng‐Peng , Chen Dan , Pang Qing‐Feng , Wu Ya‐Xian , Wang Zhi‐Qiang
Published: December 2023

Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA‐induced ALI (SA‐ALI) remains unclear. In this study, serum samples were collected from SA‐sepsis patients, and a SA‐ALI mouse model was established by grouping WT and Nrf2−/− mice after 6 h of intraperitoneal injection. A cell model simulating SA‐ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA‐sepsis patients, negatively correlated with the severity of ALI. In SA‐ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation‐induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA‐ALI. The p‐Nrf2/total‐Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA‐treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual‐luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA‐ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.
Premonitory Urge in Patients with Tics and Functional Tic‐like Behaviors
Authors: Szejko Natalia , Fletcher Julian , Martino Davide , Pringsheim Tamara
Published: December 2023

Background

Premonitory urges (PU) are well described in primary tics, but their frequency and intensity in functional tic‐like behaviors (FTLB) are unclear.

Objective

To study the experience of PU in patients with FTLB.

Methods

We compared the results of the premonitory urge for tics scale (PUTS) in adults with tics and FTLB in the University of Calgary Adult Tic Registry.

Results

We included 83 patients with tics and 40 with FTLB. When comparing patients with tics, FTLB with tics and FTLB only, we did not detect significant differences either in the total PUTS score (P = 0.39), or in any of the individual PUTS item sub‐scores (P values ranging between 0.11 and 0.99).

Conclusions

Patients with FTLB report PU at similar frequency and intensity to patients with tics. This finding confirms that PU are not a useful feature to discriminate FTLB from tics.
Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa
Authors: Brissenden James A. , Scerbak Teresa , Albin Roger L. , Lee Taraz G.
Published: December 2023

Background

Impaired movement vigor (bradykinesia) is a cardinal feature of Parkinson's disease (PD) and hypothesized to result from abnormal motivational processes—impaired motivation‐vigor coupling. Dopamine replacement therapy (DRT) improves bradykinesia, but the response to DRT is multifaceted, comprising a short‐duration response (SDR) and a long‐duration response (LDR) only manifesting with chronic treatment. Prior experiments assessing motivation‐vigor coupling in PD used chronically treated subjects, obscuring the roles of the SDR and LDR.

Methods

To disambiguate the SDR and LDR, 11 de novo PD subjects (6 male [M]:5 female [F]; mean age, 67) were studied before treatment, after an acute levodopa (l‐dopa) dose, and in both the practical “off” (LDR) and “on” (LDR + SDR) states after chronic stable treatment. At each visit, subjects were characterized with a standard battery including the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) and an incentivized joystick task to assess motor performance in response to varying rewards.

Results

l‐Dopa induced a robust SDR and LDR, with further improvement in the combined SDR + LDR state. At baseline, after acute treatment (SDR), and after LDR induction, subjects did not exhibit the normal increase in movement speed with increasing reward. Only in the combined SDR + LDR state was there restoration of motivation‐vigor coupling.

Conclusions

Although consistent with prior results in chronically treated PD subjects, the significant improvement in motor performance observed with the SDR and LDR suggests that bradykinesia is not solely secondary to deficient modulation of motivational processes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
The Gut Microbiome and Acute Leukemia: Implications for Early Diagnostic and New Therapies
Authors: Huang Xinwei , Cai Haibo , Zhao Yanqin , Kang Yongbo
Published: December 2023

Acute leukemia (AL), one of the hematological malignancies, shows high heterogeneity. Tremendous progresses are achieved in treating AL with novel targeted drugs and allogeneic hematopoietic stem cell transplantation, there are numerous issues including pathogenesis, early diagnosis, and therapeutic efficacy of AL to be solved. In recent years, an increasing number of studies regarding microbiome have shed more lights on the role of gut microbiota in promoting AL progression. Mechanisms related to the role of gut microbiota in enhancing AL genesis are summarized in the present work, especially on critical pathways like leaky gut, bacterial dysbiosis, microorganism‐related molecular patterns, and bacterial metabolites, resulting in AL development. Additionally, the potential of gut microbiota as the biomarker for early AL diagnosis is discussed. It also outlooks therapies targeting gut microbiota for preventing AL development.
Simulation of ionization charge carrier cascade time and density for a new radiation detection method based on modulation of optical properties
Authors: Jeong Diana , Tao Li , Song Xin Ran , Adams Zander , Zhang Xin , Wang Jinghui , Levin Craig S.
Published: December 2023

Background

In time‐of‐flight PET, image quality and accuracy can be enhanced by improving the annihilation photon pair coincidence time resolution, which is the variation in the arrival time difference between the two annihilation photons emitted from each positron decay in the patient. Recent studies suggest direct detection of ionization tracks and their resulting modulation of optical properties, instead of scintillation, can improve the CTR significantly, potentially down to less than 10 ps CTR. However, the arrival times of the 511 keV photons are not predictable, leading to challenges in the spatiotemporal localization characterization of the induced charge carriers in the detector crystal.

Purpose

To establish an optimized experimental setup for measuring ionization induced modulation of optical properties, it is critical to develop a versatile simulation algorithm that can handle multiple detector material properties and time‐resolved charge carrier dynamics.

Methods

We expanded our previous algorithm and simulated ionization tracks, cascade time and induced charge carrier density over time in different materials. For designing a proof‐of‐concept experiment, we simulated ultrafast electrons and free‐electron x‐ray photons for timing characterization along with alpha and beta particles for higher spatial localization.

Results

With 3 MeV ultrafast electrons, by reducing detector crystal thickness, we can effectively reduce the ionization cascade time to 0.79 ps and deposited energy to 198.5 keV, which is on the order of the desired 511 keV energy. Alpha source simulations produced a cascade time of 2.45 ps and charge carrier density of 6.39 × 1020 cm−3. Compared to the previous results obtained from 511 keV photon‐induced ionization track simulations, the cascade time displayed similar characteristics, while the charge density was found to be higher. These findings suggest that alpha sources have the potential to generate a stronger ionization‐induced signal using the modulation of optical properties as the detection mechanism.

Conclusions

This work provides a guideline to understand, design and optimize an experimental platform that is highly sensitive and temporally precise enough to detect single 511 keV photon interactions with a goal to advance CTR for ToF‐PET.
COACT: Coronary artery centerline tracker
Authors: Li Xiaogang , Ji Lianchang , Zhang Rongrong , You Hongrui , Xu Lisheng , Greenwald Stephen E. , Sun Yu , Zhang Libo , Yang Benqiang
Published: December 2023

Background

The curved planar reformation (CPR) technique is one of the most commonly used methods in clinical practice to locate coronary arteries in medical images.

Purpose

The artery centerline is the cornerstone for the generation of the CPR image. Here, we describe the development of a new fully automatic artery centerline tracker with the aim of increasing the efficiency and accuracy of the process.

Methods

We propose a COronary artery Centerline Tracker (COACT) framework which consists of an ostium point finder (OPFinder) model, an intersection point detector (IPDetector) model and a set of centerline tracking strategies. The output of OPFinder is the ostium points. The function of the IPDetector is to predict the intersections of a sample sphere and the centerlines. The centerline tracking process starts from two ostium points detected by the OPFinder, and combines the results of the IPDetector with a series of strategies to gradually reconstruct the coronary artery centerline tree.

Results

Two coronary CT angiography (CCTA) datasets were used to validate the models. Dataset1 contains 160 cases (32 for test and 128 for training) and dataset2 contains 70 cases (20 for test and 50 for training). The results show that the average distance between the ostium points predicted by the OPFinder and the manually annotated ostium points was 0.88 mm, which is similar to the differences between the results obtained by two observers (0.85 mm). For the IPDetector, the average overlap of the predicted and ground truth intersection points was 97.82% and this is also close to the inter‐observer agreement of 98.50%. For the entire coronary centerline tree, the overlap between the results obtained by COACT and the gold standard was 94.33%, which is slightly lower than the inter‐observer agreement, 98.39%.

Conclusions

We have developed a fully automatic centerline tracking method for CCTA scans and achieved a satisfactory result. The proposed algorithms are also incorporated in the medical image analysis platform TIMESlice (https://slice‐doc.netlify.app) for further studies.
Blockchain and crypto forensics: Investigating crypto frauds
Authors: Agarwal Udit , Rishiwal Vinay , Tanwar Sudeep , Yadav Mano
Published: December 2023

In the past few years, cryptocurrency has gained widespread acceptance because of its decentralized nature, quick and secure transactions, and potential for investment and speculation. But the increased popularity has also led to increased cryptocurrency fraud, including scams, phishing attacks, Ponzi schemes, and other criminal activities. Although there is little documentation of cryptocurrency fraud, an in‐depth study is essential to recognize various scams in different cryptocurrencies. To fill this gap, a study investigated cryptocurrency‐related fraud in various cryptocurrencies and provided a taxonomy of crypto‐forensics and forensic blockchain. In addition, we have introduced an architecture that integrates artificial intelligence (AI) and blockchain technologies to investigate and protect against instances of cryptocurrency fraud. The suggested design's effectiveness was evaluated using several machine learning (ML) classification algorithms. The conclusion of the evaluation confirmed that the random forest (RF) classifier performed the best, delivering the highest level of accuracy, that is, 97.5%. Once the ML classifiers detect cryptocurrency fraud, the information is securely stored in the InterPlanetary File System (IPFS); the document's hash is also stored in the blockchain using smart contracts. Law enforcement can leverage blockchain technology to secure access to fraudulent cryptographic transactions. The proposed architecture was tested for bandwidth utilization. Despite the potential benefits of blockchain and crypto‐forensics, several issues and challenges remain, including privacy concerns, standardization, and difficulty identifying fraud between crypto‐currencies. Finally, the paper discusses various problems and challenges in blockchain and crypto forensics to investigate cryptocurrency fraud.
The effect of corporate–nonprofit partnerships on intention to donate and volunteer: It's the why not the what
Authors: Wang Rong , Shumate Michelle
Published: December 2023

Increasingly, nonprofits and corporations publicly communicate about their partnerships. Guided by Information Integration Theory, this paper examines how information about a nonprofit's relationship with a corporation relates to individuals' intention to donate and volunteer. This research used a two‐study experimental design. Study 1 (N = 966) examined how partnership explanations and evaluation were related to the two outcomes. Study 2 (N = 970) further examined whether specific information about partnerships, including type, duration, and communication source, was integrated with existing knowledge to relate to the outcomes. Partnership evaluation consistently related to stakeholders' intention to support nonprofits, and it mediated the effect of partnership explanations on the intention to volunteer. Furthermore, partnership type was significantly related to the two outcomes, while duration and source of communication were not.
Identifying Phosphodiesterase‐5 Inhibitors with Drug Repurposing Approach: Implications in Vasodysfunctional Disorders
Authors: Khan Mohd Shahnawaz , Mohammad Hamza Ahmad , Shahwan Moyad , Yadav Dharmendra Kumar , Anwar Saleha , Shamsi Anas
Published: December 2023

Phosphodiesterase type 5 (PDE5) is a multidomain protein that plays a crucial role in regulating cellular cyclic guanosine monophosphate (cGMP), a key signaling molecule involved in various physiological processes. Dysregulation of PDE5 and cGMP signaling is associated with a range of vasodysfunctional disorders, necessitating the development of effective therapeutic interventions. This study adopts comprehensive approach, combining virtual screening and molecular dynamics (MD) simulations, to repurpose FDA‐approved drugs as potential PDE5 inhibitors. The initial focus involves selecting compounds based on their binding affinity. Shortlisted compounds undergo a meticulous analysis for their drug profiling and biological significance, followed by the activity evaluation and interaction analysis. Notably, based on binding potential and drug profiling, two molecules, Dutasteride and Spironolactone, demonstrate strong potential as PDE5 inhibitors. Furthermore, all atom MD simulations were employed (500 ns) to explore dynamic behavior of Dutasteride and Spironolactone in complexes with PDE5. Principal components analysis (PCA) and free energy landscape (FEL) analyses are further leveraged to decipher that the binding of Dutasteride and Spironolactone stabilizes the structure of PDE5 with minimal conformational changes. In summary, Dutasteride and Spironolactone exhibit remarkable affinity for PDE5 and possess characteristics that suggest their potential as therapeutic agents for conditions associated with PDE5 dysfunction.
Mixing Minimizes the Risks of Water Tank Stratification
Authors: Thompson Bethany
Published: December 2023

Thermal stratification in a water tank threatens its structural integrity and the quality of the water it stores. A mixer can create a stable water environment and prolong a tank's life.
Ductile‐Iron Pipe Endures Wildfire Temperature Test
Authors: Horn L. Gregg
Published: December 2023

Wildfires on average burn at 1472°F. To determine how a ductile‐iron pipeline would perform in ultra‐high temperatures, a sample pipe assembly was tested.
Construction, molecular docking simulation and evaluation of electrochemical properties of polymeric nanospheres comprising novel synthesized monomer via green microemulsion polymerization
Authors: Sobh Rokaya A. , Magar Hend S. , Fahim Asmaa M. , Hashem M.S.
Published: December 2023

In recent years, the invention of polymers have attracted attention due to their unique properties. (E)‐2‐cyano‐N‐cyclohexyl‐3‐(dimethyl amino) acrylamide (CHAA) is a new type of functional monomer created by the usage of 2‐cyano‐N‐cyclohexylacetamide (3) and dimethylformamide‐dimethylacetal (DMF‐DMA) utilized microwave energy as a green technology. In addition, polymers with significant nanosphere groups were obtained by polymerizing a new synthetic monomer (CHAA) with methyl methacrylate (MMA), dimethylaminoethyl methacrylate (DMAEMA) and acrylic acid (AA) using microemulsion polymerization technology. These polymer nanospheres were approved by different spectroscopic analyzes, such as FT‐IR, TEM, TGA, and H1NMR. New structurally defined poly (MMA/DMAEMA/AA/CHAA) nanospheres with an equivalent spherical diameter close to 50 nm and high thermal stability were obtained. In addition, these new polymer nanospheres exhibit good electrochemical performance and greater specific values compared to compound (CHAA) or poly (MMA/DMAEMA/AA). This is very important for the supercapacitor due to the fact that the voltammetry plots of these nanospheres display a well‐known hysteresis cycle. The newly synthesized polymer nanospheres exhibited antibacterial activity, which was confirmed by molecular docking simulations with different affinities. Also, the DFT investigation of the polymeric nanosphere was optimized utilizing B3LYP/6‐31(G) basis set and determination physical decribitors.
Preparation and characterization of colorless and transparent semi‐alicyclic fluoro‐containing polyimide nanocomposite films with enhanced high‐temperature dimensional stability via incorporation of colloidal silica nanofillers
Authors: Wang Zhenzhong , Yuan Shunqi , Ren Xi , He Zhibin , Pan Zhen , Yang Changxu , Han Shujun , Qi Yuexin , Yu Haifeng , Liu Jingang
Published: December 2023

Colorless and transparent semi‐alicyclic fluoro‐containing polyimide (PI) nanocomposite films with enhanced high‐temperature dimensional stability and sustained optical transparency were designed and prepared via incorporation of nano‐sized colloidal silica (SiO2) fillers into the PI matrix derived from hydrogenated pyromellitic dianhydride (HPMDA) and 2,2′‐bis[(4‐aminophenoxy)phenyl]hexafluoropropane (BDAF). The derived PI composite films, abbreviated as 6FCPI‐X in which X stands for the weight percent of the SiO2 in the composite films, exhibited superior thermal and comparable optical properties to the pristine 6FCPI‐0 (6FDA‐BDAF) matrix film. For example, as for the thermal properties, 6FCPI‐35 composite film showed a glass transition temperature (Tg) of 279.1°C and a residual weight ratio at 750°C (Rw750) of 66.1%, which were apparently higher than those of 6FCPI‐0 matrix (Tg = 272.2°C; Rw750 = 47.1%). More importantly, the 6FCPI/SiO2 nanocomposite films showed obviously lower linear coefficients of thermal expansion (CTE) values as compared with that of the 6FCPI‐0 matrix. 6FCPI‐35 composite film showed a CTE value of 36.1 × 10−6/K in the temperature range of 50–250°C, which was lower than half of that of the 6FCPI‐0 matrix (CTE = 77.9 × 10−6/K) in the same range of temperature. In addition, incorporation of nano‐sized colloidal SiO2 particles basically maintained the intrinsically good optical properties of the pristine 6FCPI‐0 matrix film. 6FCPI‐35 composite film showed the optical transmittances of 81.7%, 85.3%, and 87.2% at the wavelength of 400 nm (T400), 450 nm (T450), and 500 nm (T500), respectively, which were in the same level with those of the 6FCPI‐0 film (T400 = 84.0%; T450 = 86.3%; T500 = 87.6%). The 6FCPI series of nanocomposite films also exhibited similar CIE Lab color parameters, including the yellow indices (b*) lower than 2.0 and haze values lower than 1.0%.
Ultra‐fast curing of benzoxazine with surface modified fly ash‐assisted microwave: Achieving excellent comprehensive performances
Authors: Cao Yu , Liu Zhanxin , Jiang Jin , Song Ping , Shao Shuyang , Zhao Hui , Wang Zhi
Published: December 2023

Benzoxazine has aroused a lot of research interest because of its high mechanical performance and excellent thermal stability in polybenzoxazines. However, it suffers from its high curing temperature and long curing time, which necessitate resolution. This study addresses this issue by employing a surface‐modified fly ash‐assisted microwave curing method to achieve ultra‐fast benzoxazine curing within 15 min. The impact strength of the resulting cured product displayed an increasing‐then‐decreasing trend with the addition of fly ash, reaching a maximum impact strength of 18.71 ± 1.20 kJ/m2 at a 3% fly ash content. This value is 113.3% higher than the impact strength of pure PBA‐a. Additionally, when using the same amount of fly ash, the microwave‐cured product exhibited a flexural strength of up to 135.9 MPa and a flexural modulus of up to 6.71 GPa, surpassing those of pure PBA‐a by 28.7% and 33.1%, respectively. Moreover, the glass transition temperature (Tg) increased by 19.56°C. Furthermore, there was a slight improvement in flexural strength compared to the heat‐cured product, and no significant loss in thermal properties was observed. The method demonstrated in this study presents a novel approach for the rapid molding and preparation of benzoxazine in composites.