bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the diagnostic value of transcranial electrical stimulation (TES) to assess neuronal functional integrity in horses
Authors: Journée Sanne Lotte , Journée Henricus Louis , Bergmann Wilhelmina , Chantziaras Ilias , Vanderperren Katrien , Raes Els , Reed Stephen Michael , de Bruijn Cornelis Marinus , Berends Hanneke Irene , Delesalle Cathérine John Ghislaine
Published: April 2024

Medical imaging allows for the visualization of spinal cord compression sites; however, it is impossible to assess the impact of visible stenotic sites on neuronal functioning, which is crucial information to formulate a correct prognosis and install targeted therapy. It is hypothesized that with the transcranial electrical stimulation (TES) technique, neurological impairment can be reliably diagnosed.

Objective

To evaluate the ability of the TES technique to assess neuronal functional integrity in ataxic horses by recording TES-induced muscular evoked potentials (MEPs) in three different muscles and to structurally involve multiple ancillary diagnostic techniques, such as clinical neurological examination, plain radiography (RX) with ratio assessment, contrast myelography, and post-mortem gross and histopathological examination.

Methods

Nine ataxic horses, showing combined fore and hindlimb ataxia (grades 2–4), were involved, together with 12 healthy horses. TES-induced MEPs were recorded bilaterally at the level of the trapezius (TR), the extensor carpi radialis (ECR), and tibialis cranialis (TC) muscles. Two Board-certified radiologists evaluated intra- and inter-sagittal diameter ratios on RX, reductions of dorsal contrast columns, and dural diameters (range skull-T1). Post-mortem gross pathological and segmental histopathological examination was also performed by a Board-certified pathologist.

Results

TES-MEP latencies were significantly prolonged in both ECR and TC in all ataxic horses as opposed to the healthy horses. The TR showed a mixed pattern of normal and prolonged latency times. TES-MEP amplitudes were the least discriminative between healthy and ataxic horses. Youden’s cutoff latencies for ataxic horses were 24.6 ms for the ECR and 45.5 ms for the TC (sensitivity and specificity of 100%). For healthy horses, maximum latency values were 22 and 37 ms, respectively. RX revealed spinal cord compression in 8 out of 9 involved ataxic horses with positive predictive values of 0–100%. All ataxic horses showed multi-segmental Wallerian degeneration. All pathological changes recorded in the white matter of the spinal cord were widely dispersed across all cervical segments, whereas gray matter damage was more localized at the specific segmental level.

Conclusion

TES-MEP latencies are highly sensitive to detect impairment of spinal cord motor functions for mild-to-severe ataxia (grades 2–4).
Case report: Prostatic malakoplakia: a rare disease that has a profile mimicking prostate cancer
Authors: Ren Yelei , Chen Weihao , Zhang Mengni , Zhang Xuhui , Zhou Jiaojiao , Li Yongzhong , Cai Diming
Published: April 2024

Prostatic malakoplakia (PMP) is a rare inflammatory disease, and misdiagnosis on imaging is a major reason for unnecessary punctures; however, information on imaging is even rarer. Five patients with PMP between May 2022 and February 2023 were enrolled in this study to summarize the imaging manifestations. All patients underwent ultrasound (US)-guided prostate biopsy and were confirmed by pathology, and the presence of prostate cancer was also excluded by pathology. The five patients, with a median age of 71 years (range = 58–74 years), had a median total prostate-specific antigen (T-PSA) of 10.40 ng/mL (range = 1.74–63.42 ng/mL). In two patients, chest computed tomography showed pulmonary infections. All patients underwent magnetic resonance imaging (MRI). Of these patients, four had a Prostate Imaging–Reporting and Data System (PIRADS) score of 5, while one had a score of 4. The lesions were mostly distributed in the peripheral zone of the prostate and appeared as a high signal on T1-weighted imaging (T1WI) and a low signal on T2-weighted imaging (T2WI). In the US examination, four patients had abnormal prostate morphology, with an unsmooth envelope and non-uniform parenchymal echogenicity. Four patients had increased prostate volume. US showed a hypoechoic nodule with non-uniform internal echogenicity, and an abundant internal blood flow signal was detected by color Doppler US. PSA, MRI, and US were not specific for PMP in our study, but we found that a history of co-infection may be helpful in an accurate diagnosis and to avoid unnecessary biopsy.
Fat fraction quantification with MRI estimates tumor proliferation of hepatocellular carcinoma
Authors: Huang Mengqi , Zhang Fan , Li Zhen , Luo Yan , Li Jiali , Wang Zixiong , Ma Liya , Chen Gen , Hu Xuemei
Published: April 2024

Purpose

To assess the utility of fat fraction quantification using quantitative multi-echo Dixon for evaluating tumor proliferation and microvascular invasion (MVI) in hepatocellular carcinoma (HCC).

Methods

A total of 66 patients with resection and histopathologic confirmed HCC were enrolled. Preoperative MRI with proton density fat fraction and R2* mapping was analyzed. Intratumoral and peritumoral regions were delineated with manually placed regions of interest at the maximum level of intratumoral fat. Correlation analysis explored the relationship between fat fraction and Ki67. The fat fraction and R2* were compared between high Ki67(>30%) and low Ki67 nodules, and between MVI negative and positive groups. Receiver operating characteristic (ROC) analysis was used for further analysis if statistically different.

Results

The median fat fraction of tumor (tFF) was higher than peritumor liver (5.24% vs 3.51%, P=0.012). The tFF was negatively correlated with Ki67 (r=-0.306, P=0.012), and tFF of high Ki67 nodules was lower than that of low Ki67 nodules (2.10% vs 4.90%, P=0.001). The tFF was a good estimator for low proliferation nodules (AUC 0.747, cut-off 3.39%, sensitivity 0.778, specificity 0.692). There was no significant difference in tFF and R2* between MVI positive and negative nodules (3.00% vs 2.90%, P=0.784; 55.80s-1 vs 49.15s-1, P=0.227).

Conclusion

We infer that intratumor fat can be identified in HCC and fat fraction quantification using quantitative multi-echo Dixon can distinguish low proliferative HCCs.
Impact of neoadjuvant relugolix on patient-reported sexual function and bother
Authors: Hsueh Jessica Y. , Gallagher Lindsey , Koh Min Ji , Eden Shaine , Shah Sarthak , Wells Markus , Danner Malika , Zwart Alan , Ayoob Marilyn , Kumar Deepak , Leger Paul , Dawson Nancy A. , Suy Simeng , Rubin Rachel , Collins Sean P.
Published: April 2024

Introduction

Sexual function following local treatment for prostate cancer is an important quality of life concern. Relugolix is a novel oral GnRH receptor antagonist used in combination with radiation therapy in the treatment of unfavorable prostate cancer. It has been shown to achieve rapid and profound testosterone suppression. As a result, these very low testosterone levels may impact both sexual functioning and perceptions. This prospective study sought to assess neoadjuvant relugolix-induced sexual dysfunction prior to stereotactic body radiation therapy (SBRT).

Methods

Between March 2021 and September 2023, 87 patients with localized prostate cancer were treated with neoadjuvant relugolix followed by SBRT per an institutional protocol. Sexual function and bother were assessed via the sexual domain of the validated Expanded Prostate Index Composite (EPIC-26) survey. Responses were collected for each patient at pre-treatment baseline and after several months of relugolix. A Utilization of Sexual Medications/Devices questionnaire was administered at the same time points to assess erectile aid usage.

Results

The median age was 72 years and 43% of patients were non-white. The median baseline Sexual Health Inventory for Men (SHIM) score was 13 and 41.7% of patients utilized sexual aids prior to relugolix. Patients initiated relugolix at a median of 4.5 months (2-14 months) prior to SBRT. 95% and 87% of patients achieved effective castration (≤ 50 ng/dL) and profound castration (< 20 ng/dl) at SBRT initiation, respectively. Ability to have an erection, ability to reach orgasm, quality of erections, frequency of erections, and overall sexual function significantly declined following relugolix. There was a non- significant increase in sexual bother.

Discussion

In concordance with known side effects of androgen deprivation therapy (ADT), neoadjuvant relugolix was associated with a significant decline in self-reported sexual function. However, patients indicated only a minimal and non-significant increase in bother. Future investigations should compare outcomes while on relugolix directly to GnRH agonist-induced sexual dysfunction.
Closed reduction and intramedullary nails for acute completely displaced femoral diaphysis fracture in children aged 2–6
Authors: Qiao Fei , Shang Xinpeng , Jiang Fei
Published: April 2024

Background

The management of femoral fractures in children aged two to six years is still controversial. The purpose of this study was to assess the results of closed reduction and elastic stable intramedullary nail (ESIN) fixation in completely displaced fractures of the femoral diaphysis in children in this age group.

Methods

A retrospective review of all children with acute completely displaced fractures of the femoral diaphysis in children aged 2–6 years treated from 2013 to 2020 was performed. A total of 34 patients were treated who met the inclusion criteria: Group 1: 21 fractures (transverse and short oblique); Group 2: 13 fractures (long oblique and spiral) that underwent closed reduction and elastic stable intramedullary nail (ESIN) fixation. No differences existed between the 2 groups with respect to age, extremity, sex, time to treatment, mechanism of injury, or fracture displacement. Demographic characteristics and radiographs were reviewed, and the following parameters were documented: surgery time, time to union, return to activities, range of motion of knee joints, and complications. Major complications were defined as those with presumptive long-term side effects or those requiring a reoperation. No major complications were observed in the two groups. All included fractures were treated by a single senior paediatric surgeon. The mean follow-up period was 28.4 months (range 24–45 months). The level of significance was set at p < 0.05.

Results

Thirty-four children with acute completely displaced fractures of the femoral diaphysis were included: Group 1: 21 fractures; Group 2: 13 fractures. The patients included 15 girls (44.1%) and 19 boys (55.9%), with an average age of 4.4 years (range 2.8 to 6.5 years). The mean follow-up period was 28.4 months (range 24.2–45.0 months). The demographic characteristics did not differ between the two groups of patients. Overall, successful closed reduction and elastic stable intramedullary nail (ESIN) fixation could be achieved in all 34 patients. The mean surgical time was 40.4 and 43.0 min in Group 1 and Group 2, respectively (p = 0.857). Fluoroscopy time was not significantly different between the two groups (37.0 vs. 36.1 s, respectively; p = 0.247). Cosmetic results were described as good and satisfactory by all patients. There were no refractures and no incidences of nonunion or growth arrest in the proximal epiphysis. Only two patients suffered from a superficial infection, which was resolved after the pins were shortened and oral antibiotics were administered.

Conclusion

Closed reduction and elastic stable intramedullary nail (ESIN) fixation can be successfully used to treat completely displaced fractures of the femoral diaphysis in children aged two to six years. This technique is efficient and minimally invasive, and the results are satisfactory.
Cymensifin A: a promising pharmaceutical candidate to defeat lung cancer via cellular reactive oxygen species-mediated apoptosis
Authors: Soares Bruno Cesar Costa , Khine Hnin Ei Ei , Sritularak Boonchoo , Chanvorachote Pithi , Alduina Rosa , Sungthong Rungroch , Chaotham Chatchai
Published: April 2024

Background: The upgrade of natural products for cancer treatment is essential since current anticancer drugs still pose severe side effects. Cymensifin A (Cym A) isolated from an orchid Cymbidium ensifolium has shown its potential to induce the death of several cancer cells; however, its underlying molecular mechanisms are hitherto unknown.

Methods: Here, we conducted a set of in vitro preliminary tests to assess the cytotoxic effects of Cym A on non-small-cell lung cancer (NSCLC) cells (A549, H23, H292, and H460). A flow cytometry system and Western blot analyses were employed to unveil molecular mechanisms underlying cancer cell apoptosis caused by Cym A.

Results: Cym A at 25–50 μM caused the death of all NSCLC cells tested, and its cytotoxicity was comparable to cisplatin, a currently used anticancer drug. The compound induced apoptosis of all NSCLC cells in a dose-dependent manner (5–50 μM), proven by flow cytometry, but H460 cells showed more resistance compared to other cells tested. Cym A-treated H460 cells demonstrated increased reactive oxygen species (ROS) and downregulated antioxidants (catalase, superoxide dismutase, and thioredoxin). The compound also upregulated the tumor suppressor P53 and the pro-apoptotic protein BAX but downregulated pro-survival proteins (BCL-2 and MCL-1) and deactivated survival signals (AKT and ERK) in H460 cells. Cym A was proven to trigger cellular ROS formation, but P53 and BAX were 2-fold more activated by Cym A compared to those treated with hydrogen peroxide. Our findings also supported that Cym A exerted its roles in the downregulation of nuclear factor erythroid 2–related factor 2 (a regulator of cellular antioxidant activity) and the increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase 3/7 during apoptosis.

Conclusion: We propose that Cym A induces lung cancer cell death via ROS-mediated apoptosis, while the modulation of cellular ROS/antioxidant activity, the upregulation of P53 and BAX, the downregulation or deactivation of BCL-2, MCL-1, AKT, and ERK, and the increased cleavage of PARP and caspase 3/7, were the elucidated underlying molecular mechanisms of this phytochemical. The compound can be a promising candidate for future anticancer drug development.
Do future healthcare professionals advocate for pharmacogenomics? A study on medical and health sciences undergraduate students
Authors: Al-Suhail Hanan , Omar Mohammad , Rubaeih Majd , Mubarak Tamer , Koufaki Margarita-Ioanna , Kanaris Ioannis , Mounaged Favio , Patrinos George P. , Saber-Ayad Maha
Published: April 2024

Pharmacogenomics (PGx) is a rapidly changing field of genomics in which healthcare professionals play an important role in its implementation in the clinical setting, however PGx level of adoption remains low. This study aims to investigate the attitude, self-confidence, level of knowledge, and their impact on health sciences undergraduate students’ intentions to adopt PGx in clinical practice using a questionnaire developed based on the Theory of Planned Behavior (TPB). A model was proposed and a questionnaire was developed that was distributed to 467 undergraduate students of all academic years from four different departments of the University of Sharjah (UoS) including medical, dental, nursing, and pharmacy students from September 2022 to November 2022. Descriptive statistics along with factor analysis and regression analysis were conducted. The proposed model had a good internal consistency and fit. Attitude was the factor with the greatest impact on student’s intentions followed by self-confidence and barriers. The level of knowledge had a meaningless impact. The majority of students shared a positive attitude and were aware of PGx benefits. Almost 60% of the respondents showed a high level of knowledge, while 50% of them were confident of implementing PGx in their clinical practice. Many students were prone to adopt PGx in their future careers. PGx testing cost and the lack of reimbursement were the most important barriers. Overall, students shared a positive intention and were prone to adopt PGx. In the future, it would be important to investigate the differences between gender, year of studies, and area of studies studies and their impact on students’ intentions.
Ferroptosis and the ubiquitin-proteasome system: exploring treatment targets in cancer
Authors: Din Muhammad Azhar Ud , Lin Yan , Wang Naijian , Wang Bo , Mao Fei
Published: April 2024

Ferroptosis is an emerging mode of programmed cell death fueled by iron buildup and lipid peroxidation. Recent evidence points to the function of ferroptosis in the aetiology and development of cancer and other disorders. Consequently, harnessing iron death for disease treatment has diverted the interest of the researchers in the field of basic and clinical research. The ubiquitin-proteasome system (UPS) represents a primary protein degradation pathway in eukaryotes. It involves labelling proteins to be degraded by ubiquitin (Ub), followed by recognition and degradation by the proteasome. Dysfunction of the UPS can contribute to diverse pathological processes, emphasizing the importance of maintaining organismal homeostasis. The regulation of protein stability is a critical component of the intricate molecular mechanism underlying iron death. Moreover, the intricate involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for targeted treatment strategies. Besides, it highlights the potential of ferroptosis as a promising target for cancer therapy, emphasizing the combination between ferroptosis and the UPS. The molecular mechanisms underlying ferroptosis, including key regulators such as glutathione peroxidase 4 (GPX4), cysteine/glutamate transporter (system XC-), and iron metabolism, are thoroughly examined, alongside the role of the UPS in modulating the abundance and activity of crucial proteins for ferroptotic cell death, such as GPX4, and nuclear factor erythroid 2–related factor 2 (NRF2). As a pivotal regulatory system for macromolecular homeostasis, the UPS substantially impacts ferroptosis by directly or indirectly modulating iron death-related molecules or associated signaling pathways. This review explores the involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for the targeted treatment of diseases associated with ferroptosis.
Hyperspectral imaging for the detection of plant pathogens in seeds: recent developments and challenges
Authors: Ferreira Luciellen da Costa , Carvalho Ian Carlos Bispo , Jorge Lúcio André de Castro , Quezado-Duval Alice Maria , Rossato Maurício
Published: April 2024

Food security, a critical concern amid global population growth, faces challenges in sustainable agricultural production due to significant yield losses caused by plant diseases, with a multitude of them caused by seedborne plant pathogen. With the expansion of the international seed market with global movement of this propagative plant material, and considering that about 90% of economically important crops grown from seeds, seed pathology emerged as an important discipline. Seed health testing is presently part of quality analysis and carried out by seed enterprises and governmental institutions looking forward to exclude a new pathogen in a country or site. The development of seedborne pathogens detection methods has been following the plant pathogen detection and diagnosis advances, from the use of cultivation on semi-selective media, to antibodies and DNA-based techniques. Hyperspectral imaging (HSI) associated with artificial intelligence can be considered the new frontier for seedborne pathogen detection with high accuracy in discriminating infected from healthy seeds. The development of the process consists of standardization of methods and protocols with the validation of spectral signatures for presence and incidence of contamined seeds. Concurrently, epidemiological studies correlating this information with disease outbreaks would help in determining the acceptable thresholds of seed contamination. Despite the high costs of equipment and the necessity for interdisciplinary collaboration, it is anticipated that health seed certifying programs and seed suppliers will benefit from the adoption of HSI techniques in the near future.
Acceptability and content validity of suicidality screening items: a qualitative study with perinatal women
Authors: Dudeney Elizabeth , Coates Rose , Ayers Susan , McCabe Rose
Published: April 2024

Background

Suicide is a leading cause of death for perinatal women. It is estimated that up to 50% of women with mental health issues during pregnancy and/or after birth are not identified, despite regular contact with healthcare services. Screening items are one way in which perinatal women needing support could be identified. However, research examining the content validity and acceptability of suicide-related screening items with perinatal women is limited.

Aims

This study sought to: (i) assess the acceptability and content validity of 16 suicide-related items that have been administered and/or validated in perinatal populations; and (ii) explore the potential barriers and facilitators that may affect how women respond to these items when administered during pregnancy and after birth.

Methods

Twenty-one cognitive and semi-structured interviews were conducted with pregnant and postnatal women in the UK. The sample included women who had experienced self-reported mental health problems and/or suicidality during the perinatal period, and those who had not. Interviews were transcribed verbatim, and a coding framework based on the Theoretical Framework of Acceptability was applied to explore the data using deductive and inductive approaches.

Results

Findings indicated that the acceptability and content validity of suicide-related items were largely unacceptable to perinatal women in their current form. Women found terms such as ‘better off dead’ or ‘killing myself’ uncomfortable. Most women preferred the phrase ‘ending your life’ as this felt less confronting. Comprehensibility was also problematic. Many women did not interpret ‘harming myself’ to include suicidality, nor did they feel that abstract language such as ‘leave this world’ was direct enough in relation to suicide. Stigma, fear, and shame was central to non-disclosure. Response options and recall periods further affected the content validity of items, which created additional barriers for identifying those needing support.

Conclusions

Existing suicide-related screening items may not be acceptable to perinatal women. Maternity practitioners and researchers should consider the phrasing, clarity, context, and framing of screening items when discussing suicidality with perinatal women to ensure potential barriers are not being reinforced. The development of specific suicidality screening measures that are acceptable, appropriate, and relevant to perinatal women are warranted.
An online survey on public awareness of drug clinical trials in inland cities of northern China
Authors: Wang Li , Zhang Ruiguang , Liu Jingxuan , Xu Rui , Zhao Lili , Li Enze , Zhang Yurong
Published: April 2024

Objective

The aims of this survey were to investigate the public awareness of drug clinical trials (DCTs) and willingness to participate the DCTs, and provide references for propaganda and science popularization of DCTs.

Methods

A self-designed questionnaire named “an online survey questionnaire on public awareness of DCTs” was used to conduct an online survey from January to March 2022. The demographic characteristics and the response of participants to the awareness and willingness to participate the DCTs were collected. The factors affecting the public awareness of DCTs were analyzed by single factor and binary logistic regression analysis.

Results

One thousand three hundred eighty valid questionnaires were collected, and the respondents’ awareness rate of DCTs was 61.1%. Thirteen demographic characteristics including age, gender, education, occupation, work fields, household type, marital status, city type, income, medical insurance, medical expenditure, pressure to seek medical care, financial pressure, both significantly affected the qualified rate of participants’ awareness of DCTs (p < 0.001) by single factor analysis. Binary logistic regression analysis indicated that education level, work fields, city type, medical insurance, and medical expenditure affected independently the participants’ awareness rate of DCTs (p < 0.001). 52.9% of the participants were willing to take part in DCTs. “to promote medical progress” (54.4%) or “believe doctors” (31.1%) were the most frequent reasons for subjects participating in DCTs.

Conclusion

The public awareness rate of DCTs and the willingness to participate in drug clinical were significantly affected by the demographic characteristics of subjects. Thus, targeting the needs of the public, propaganda, and science popularization of DCTs should be carried out and served public health.
The application of metaverse in occupational health
Authors: Tang Yufu , Liang Hongying , Zhan Jingming
Published: April 2024

Background

The metaverse, as a new digital interactive platform, is garnering significant attention and exploration across industries due to technological advancements and societal digital transformation. In occupational health, there is immense potential for leveraging the metaverse to enhance work environments and occupational health management. It offers companies more efficient and intelligent solutions for occupational health management while providing employees with safer and more comfortable work environments.

Methods

A comprehensive literature search was conducted using PubMed, Web of Science, IEEE Xplore, and Google Scholar databases to identify relevant studies published between January 2015 and March 2024. The search terms included “metaverse,” “virtual reality,” “occupational health,” “workplace safety,” “job training,” and “telemedicine.” The selected articles were analyzed, and key findings were summarized narratively.

Results

The review summarizes the broad application prospects of metaverse technology in immersive training, occupational risk identification and assessment, and occupational disease monitoring and diagnosis. However, applying the metaverse in occupational health also faces challenges such as inadequate technical standards, data privacy issues, human health hazards, high costs, personnel training, and lagging regulations.

Conclusion

Metaverse offers new possibilities for addressing the numerous challenges faced in occupational health and has broad application prospects. In the future, collaborative efforts from multiple stakeholders will be necessary to promote the sustainable development of metaverse technology in occupational health and better protect workers’ occupational health.
Accounting for water quality—A framework for agricultural water use
Authors: Karimi Poolad , Chapman Deborah V. , Valieva Svetlana , Li Ruyi , Talbi Amal
Published: April 2024

Driven by increasing water demand, scarcity concerns, and climate change impacts, numerous countries prioritize solutions for enhanced water use efficiency. However, these solutions often focus primarily on managing water quantities to improve water productivity in agriculture, urban, and industrial sectors. Effective and sustainable water use, however, requires monitoring and management of both water quantity and quality. Traditionally, water quantity and water quality have been managed separately, often by different government agencies with different missions and limited interaction. Ensuring sufficient water quantity for agriculture and food production often takes precedence over managing water quality. Water accounting, as a tool for allocating and managing water quantity is now widely accepted and numerous examples of successful implementation exist worldwide. However, the concept of incorporating water quality into water accounting has not yet been widely promoted. Measuring both quantity and quality in the same water bodies is a fundamental principle of assessment of impacts on water quality through the determination of loads. The load is the amount of a given substance or pollutant for a given period of time. Using the key steps necessary for the development of a water quality monitoring and assessment programme, a framework has been developed that can be applied to water accounting projects using typical water accounting applications. Two examples of potential applications are used to consider the technical, institutional, and financial requirements. Implementing a framework for incorporating water quality monitoring and assessment into water accounting should contribute substantially to the need for more water quality data at global scale. Such data are required to facilitate achievement of Sustainable Development Goal 6 “Ensure availability and sustainable management of water and sanitation for all” through more efficient water resources management and greater awareness of water quality impacts in the agricultural water use sector.
ICH S1 prospective evaluation study: weight of evidence approach to predict outcome and value of 2-year rat carcinogenicity studies. A report from the regulatory authorities subgroup
Authors: Bourcier Todd , McGovern Timothy , Cavaliero Tania , Ebere Geoffrey , Nishikawa Akiyoshi , Nishimura Jihei , Ogawa Kumiko , Pasanen Markku , Vespa Alisa , Van der Laan Jan Willem
Published: April 2024

Introduction: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) initiated a process in 2012 to revise the S1B Guideline “Testing for Carcinogenicity of Pharmaceuticals”. Previous retrospective analysis indicated the importance of histopathological risk factors in chronic toxicity studies, evidence of endocrine perturbation, and positive genetic toxicology results as potentially predictive indicators of carcinogenic risk. In addition, a relationship between pharmacodynamic activity and carcinogenicity outcome in long-term rodent studies has been reported. It was postulated that these factors could be evaluated in a Weight-of-Evidence (WoE) approach to predict the outcome of a 2-year rat study.

Methods: The ICH S1B(R1) Expert Working Group (EWG) conducted a Prospective Evaluation Study (PES) to determine the regulatory feasibility of this WoE approach. Drug Regulatory Authorities (DRAs) evaluated 49 Carcinogenicity Assessment Documents (CADs), which describe the WoE for submitted pharmaceutical compounds. Each compound was categorized into a carcinogenic risk category including a statement of the value of the 2-year rat study. The outcome of the completed 2-year rat studies was evaluated in relation to the prospective CAD to determine the accuracy of predictions.

Results: Based on the results of the PES, the EWG concluded that the evaluation process for assessing human carcinogenic risk of pharmaceuticals described in ICH S1B could be expanded to include a WoE approach. Approximately 27% of 2-year rat studies could be avoided in cases where DRAs and sponsors unanimously agreed that such a study would not add value.

Discussion: Key factors supporting a WoE assessment were identified: data that inform carcinogenic potential based on drug target biology and the primary pharmacologic mechanism of the parent compound and major human metabolites; results from secondary pharmacology screens for this compound and major human metabolites that inform carcinogenic risk; histopathology data from repeated-dose toxicity studies; evidence for hormonal perturbation; genotoxicity data; and evidence of immune modulation. The outcome of the PES indicates that a WoE approach can be used in place of conducting a 2-year rat study for some pharmaceuticals. These data were used by the ICH S1B(R1) EWG to write the R1 Addendum to the S1B Guideline published in August 2022.
Paired metagenomic and chemical evaluation of aflatoxin-contaminated dog kibble
Authors: Ottesen Andrea , Kocurek Brandon , Reed Elizabeth , Commichaux Seth , Mammel Mark , Ramachandran Padmini , McDermott Patrick , Flannery Brenna M. , Strain Errol
Published: April 2024

Introduction

Identification of chemical toxins from complex or highly processed foods can present ‘needle in the haystack’ challenges for chemists. Metagenomic data can be used to guide chemical toxicity evaluations by providing DNA-based description of the wholistic composition (eukaryotic, bacterial, protozoal, viral, and antimicrobial resistance) of foods suspected to harbor toxins, allergens, or pathogens. This type of information can focus chemistry-based diagnostics, improve hazard characterization and risk assessment, and address data gaps. Additionally, there is increasing recognition that simultaneously co-occurring mycotoxins, either from single or multiple species, can impact dietary toxicity exposure. Metagenomic data provides a way to address data gaps related to co-occurrence of multiple fungal species.

Methods

Paired metagenomic and chemical data were used to evaluate aflatoxin-contaminated kibble with known levels of specific mycotoxins. Kibble was ground to a fine powder for both chemical and molecular analyses. Chemical analyses were performed with Liquid Chromatography Mass Spectrometry (LCMS) and according to the AOAC Official method 2005.08: Aflatoxins in Corn, Raw Peanuts, and Peanut Butter using Liquid Chromatography with Post-Column Photochemical Derivatization. Metagenomes were created from DNA extracted from ground kibble and sequenced on an Illumina NextSeq 2000 with an average sequence depth of 180 million reads per replicate.

Results and discussion

Metagenomic data demonstrated that the abundance of DNA from putative aflatoxigenic Aspergillus spp. correlated with the levels of aflatoxin quantified by LCMS. Metagenomic data also identified an expansive range of co-occurring fungal taxa which may produce additional mycotoxins. DNA data paired with chemical data provides a novel modality to address current data gaps surrounding dietary mycotoxin exposure, toxigenic fungal taxonomy, and mycotoxins of emerging concern.
Impacting Robustness in Deep Learning-Based NIDS through Poisoning Attacks
Authors: Alahmed Shahad , Alasad Qutaiba , Yuan Jiann-Shiun , Alawad Mohammed
Published: April 2024

The rapid expansion and pervasive reach of the internet in recent years have raised concerns about evolving and adaptable online threats, particularly with the extensive integration of Machine Learning (ML) systems into our daily routines. These systems are increasingly becoming targets of malicious attacks that seek to distort their functionality through the concept of poisoning. Such attacks aim to warp the intended operations of these services, deviating them from their true purpose. Poisoning renders systems susceptible to unauthorized access, enabling illicit users to masquerade as legitimate ones, compromising the integrity of smart technology-based systems like Network Intrusion Detection Systems (NIDSs). Therefore, it is necessary to continue working on studying the resilience of deep learning network systems while there are poisoning attacks, specifically interfering with the integrity of data conveyed over networks. This paper explores the resilience of deep learning (DL)—based NIDSs against untethered white-box attacks. More specifically, it introduces a designed poisoning attack technique geared especially for deep learning by adding various amounts of altered instances into training datasets at diverse rates and then investigating the attack’s influence on model performance. We observe that increasing injection rates (from 1% to 50%) and random amplified distribution have slightly affected the overall performance of the system, which is represented by accuracy (0.93) at the end of the experiments. However, the rest of the results related to the other measures, such as PPV (0.082), FPR (0.29), and MSE (0.67), indicate that the data manipulation poisoning attacks impact the deep learning model. These findings shed light on the vulnerability of DL-based NIDS under poisoning attacks, emphasizing the significance of securing such systems against these sophisticated threats, for which defense techniques should be considered. Our analysis, supported by experimental results, shows that the generated poisoned data have significantly impacted the model performance and are hard to be detected.
State Observer-Based Conditioned Reverse-Path Method for Nonlinear System Identification
Authors: Oveisi Atta , Gogilan Umaaran , Keighobadi Jafar , Nestorović Tamara
Published: April 2024

In light of the complex behavior of vibrating structures, their reliable modeling plays a crucial role in the analysis and system design for vibration control. In this paper, the reverse-path (RP) method is revisited, further developed, and applied to modeling a nonlinear system, particularly with respect to the identification of the frequency response function for a nominal underlying linear system and the determination of the structural nonlinearities. The present approach aims to overcome the requirement for measuring all nonlinear system states all the time during operation. Especially in large-scale systems, this might be a tedious task and often practically infeasible since it would require having individual sensors assigned for each state involved in the design process. In addition, the proper placement and simultaneous operation of a large number of transducers would represent further difficulty. To overcome those issues, we have proposed state estimation in light of the observability criteria, which significantly reduces the number of required sensor elements. To this end, relying on the optimal sensor placement problem, the state estimation process reduces to the solution of Kalman filtering. On this ground, the problem of nonlinear system identification for large-scale systems can be addressed using the observer-based conditioned RP method (OBCRP) proposed in this paper. In contrast to the classical RP method, the current one can potentially handle local and distributed nonlinearities. Moreover, in addition to the state estimation and in comparison to the orthogonal RP method, a new frequency-dependent weighting is introduced in this paper, which results in superior nonlinear system identification performances. Implementation of the method is demonstrated on a multi-degree-of-freedom discretized lumped mass system, representing a substitute model of a physical counterpart used for the identification of the model parameters.
Artificial Intelligence Approach in Aerospace for Error Mitigation
Authors: Bautista-Hernández Jorge , Martín-Prats María Ángeles
Published: April 2024

Many of the reports created at assembly lines, where all components of an aircraft are installed, frequently indicate that errors threaten safety. The proposed methodology in this study evaluates error prediction and risk mitigation to prevent failures and their consequences. The results linked to a typical electrical harness manufacture of a military aircraft estimated reductions of 93% in time and 90% in error during the creation of engineering manufacturing processes using AI techniques. However, traditional risk assessments methods struggle to identify and mitigate errors effectively. Thus, developing an advanced methodology to ensure systems safety is needed. This paper addresses how innovative AI technology solutions can overcome these challenges, mitigate error risks, and enhance safety in aerospace. Technologies, such as artificial intelligence, predictive algorithms, machine learning, and automation, can play a key role in enhancing safety. The aim of this study is to develop a model that considers the factors that can potentially contribute to error creation, through an artificial intelligence (AI) approach. The specific AI techniques used such as support vector machine, random forest, logistic regression, K-nearest neighbor, and XGBoost (Python 3.8.5) show good performance for use in error mitigation. We have compared the modeled values obtained in this study with the experimental ones. The results confirm that the best metrics are obtained by using support vector machine and logistic regression. The smallest deviation between the measured and modeled values for these AI methods do not exceed 5%. Furthermore, using advancements in machine learning methods can enhance error mitigation in aerospace. The use of AutoML can play a key role in automatically finding an appropriate model which provides the best performance metrics and therefore the most reliable forecast for data prediction and error mitigation.
A Comparative Study on the Operational Efficiency of Joystick and Touch Screen Control Methods for Sugarcane Harvesters
Authors: Wu Xiaoyu , Liu Sha
Published: April 2024

Reducing cumbersome mechanical control components is one of the trends of modern agricultural machinery towards a high degree of automation. Whether the control components of sugarcane harvesters can gradually be replaced by central control screens, similar to car cabins, is an unresolved question. At the level of human machine interaction, this involves comparing the efficiency between joystick and touch screen control. This paper conducts a simulated experiment to compare and study the efficiency and user experience of joystick and touch screen control in adjusting the topper and base cutter heights of sugarcane harvesters, aiming to provide a reasonable basis for the design of control interfaces in sugarcane harvester cabins. The electromyographic signals, experiment duration, and subjective cognitive evaluations of participants in both the topper and base cutter groups were analyzed. The results showed that the efficiency, learnability, and ease of use of different control methods varied under different operational tasks. For the topper that corresponds to the operating behavior and height transformation in real time, joystick control demonstrated superior ease of use and operational efficiency compared to touch screen control, with weaker learnability. There was no discernible difference in muscle activation levels between the two control methods. Consequently, joystick control is deemed more suitable for the height adjustment of the topper. Regarding the base cutter with non-real-time mapping of operating behavior and height changes, no significant disparity in ease of use and learnability was observed between the two control methods. Touch screen control yielded lower muscle activation levels and garners higher overall subjective cognitive scale ratings. Thus, touch screen control is considered more suitable for base cutter height adjustment. Lastly, the paper proposes the optimal combination of software and hardware for control components in sugarcane harvester cabins, and provides an objective and multidimensional experimental analysis method for future research on similar human machine interaction interfaces.
Feasibility Assessment of Stakeholder Benefits in Community-Based Agritourism through University Social Responsibility Practices
Authors: Chassang Levinus , Hsieh Chi-Jen , Li Tzu-Ning , Hsieh Chi-Ming
Published: April 2024

This study selected the TaiAn rural community in Taiwan as the study site. TaiAn collaborated with local universities to implement the University Social Responsibility (USR) practice through community-based agritourism (CBA). The social exchange theory (SET) was adopted as a theoretical framework to weigh the costs and benefits perceived among different stakeholders (residents, tourists, students, and lecturers) regarding CBA development. The research purpose was to explore the determinants of support for sustainable CBA using a mixed quantitative and qualitative approach based on the SET. The empirical results from 117 completed surveys indicated that Agricultural Experiential Benefits, Perceived Environmental Impacts, and Mental Health Benefits positively influenced tourists’ support for CBA. The qualitative interview results also supported the notion that agriculture students, faculty, and community members could derive various benefits from participating in USR practices within local communities. Theoretical and managerial implications were proposed for marketers and policymakers to gain a deep understanding of CBA practices.
Differences in Soil Microflora between the Two Chinese Geographical Indication Products of “Tricholoma matsutake Shangri-la” and “T. matsutake Nanhua”
Authors: Yao Chunxin , Yu Ping , Yang Jisheng , Liu Jiaxun , Zi Zhengquan , Li Defen , Liang Mingtai , Tian Guoting
Published: April 2024

Tricholoma matsutake is a kind of ectomycorrhizal fungus. In addition to its vital influence on symbiotic plants, the impact of the soil microbial community on the growth and development of T. matsutake has been garnering attention. To clarify the differences in soil microflora between “T. matsutake Shangri-la” and “T. matsutake Nanhua”, and the effects of soil bacteria and fungi on the growth and development of T. matsutake, this study took the soil of “T. matsutake Shangri-la” and “T. matsutake Nanhua” at different developmental stages. A total of 7694 bacterial OTUs and 2170 fungal OTUs were obtained through microbial omics based on amplicon sequencing. The results indicate that the α diversity and composition of the soil microorganisms in the T. matsutake Shangri-la shiro were higher than those of the T. matsutake Nanhua. It is affected by species, geographical locations, and the growth period of matsutake. Matsutake mycelia also recruit certain types of bacteria and fungi in the stage of fruiting body development. Both bacteria and fungi positively and negatively regulate the fruiting body development of matsutake mushrooms. This study will provide a basis for the semi-artificial cultivation of matsutake.
Productive, Environmental and Economic Effects of Organic and Conventional Farms—Case Study from Poland
Authors: Feledyn-Szewczyk Beata , Kopiński Jerzy
Published: April 2024

Due to the changes in the agricultural sector, there is a demand among policymakers, administration, advisors and farmers for comparisons of the economic efficiency of organic versus conventional farms and their environmental impact. The authors of the paper hypothesised that in some conditions, organic farms can reach similar productive and economic results as conventional farms and, at the same time, achieve better environmental effects. The aim of the research was to compare the production, environmental and economic effects of selected organic and conventional farms from eastern Poland (mixed, crop production, animal production). The basis for the comparative analysis was the data from 12 farms obtained using the questionnaire method (direct interview) from the years 2020 to 2021. The yields of cereals in the tested organic farms were about one-third lower than the average obtained on conventional farms. Total organic crop production in cereal units per ha was 43% of conventional production. Balances of NPK indicated surpluses or deficiency, which suggested that in both systems nutrient management should be improved and optimised. The compared groups of organic farms generally had higher economic efficiency—both with and without subsidies—than conventional farms, despite the fact that the latter obtained significantly higher incomes. Gross farm income on conventional farms was higher than on organic farms by 28%, but conventional farms had higher direct costs by 332% than organic ones. As a result, the economic efficiency of agricultural production of organic farms was higher by 59% than conventional farms. The lower level of inputs incurred on organic farms was the main factor determining their high economic efficiency. Organic farms pursuing an intensive model of agricultural production (milk production), but also with specialisation in crop production, proved to be the most economically efficient. Despite diversified production, reducing the income risk, the mixed production, both organic and conventional, in the studied set of farms turned out to be the least profitable, indicating the need to support it. It is suggested that moderate specialisation increases the efficiency of management in organic farming.