bluuebunny/crossref_metadata_2025 huggingface dataset:
Regorafenib-related erythrocytosis in metastatic extra-gastrointestinal stromal tumor: a case report
Authors: Fassi Elena , Amoroso Vito , Cosentini Deborah , Ferrari Vittorio , Laganà Marta , Berruti Alfredo , di Mauro Pierluigi
Published: August 2024

Introduction

Regorafenib is an oral multi-targeted tyrosine kinase inhibitor (TKI) indicated for the treatment of various tumor types, including metastatic gastrointestinal stromal tumors (GIST), as a third-line systemic therapy. Erythrocytosis, which is characterized by an increase in erythrocyte count, hemoglobin, and hematocrit levels, has been described as a side effect of some antiangiogenic TKIs but has never been associated with regorafenib administration.

Case presentation

An extra-GIST was diagnosed in a 58-year-old woman after she underwent surgery to remove a pelvic mass. Three years later, systemic therapy with imatinib was started due to pelvic disease recurrence. However, after six months, due to disease progression, we prescribed sunitinib, which the patient received for four years. Regorafenib was initiated in June 2019, and after six months, we noted an increase in the erythrocytes’ count and hemoglobin (Hb) levels. Given that the patient had clinical benefit and hematocrit was within normal range, we only monitored the blood cell count and continued to give regorafenib at the same dose. The drug was then stopped for over six weeks due to hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and Hb levels returned to normal. Therefore, we decided to restart regorafenib at a lower dose. However, Hb levels rose again in conjunction with increased hematocrit, resulting in the need for multiple phlebotomies. We attempted to restart regorafenib every other day, but it was unsuccessful, so we stopped it permanently in May 2023, and all values returned to normal.

Conclusion

Regorafenib may cause secondary erythrocytosis that could not be dose-related, as this case report suggests. Secondary erythrocytosis might be a marker of TKI efficacy, given the patient’s prolonged clinical benefit during regorafenib treatment (48 months). In patients receiving regorafenib, monitoring blood count as well as any symptoms associated with erythrocytosis may be suggested.
Sexual dimorphism of colorectal cancer in humans and colorectal tumors in a murine model
Authors: Rodríguez-Santiago Yair , Terrazas-Valdés Luis Ignacio , Nava-Castro Karen Elizabeth , Del Río-Araiza Víctor Hugo , Garay-Canales Claudia Angélica , Morales-Montor Jorge
Published: August 2024

Introduction

In colorectal cancer, men exhibit a higher incidence than women, and there is a disturbance in the levels of sex steroids in serum in patients with this disease. Consistently, in animals, males have greater tumor growth than females in diverse models. Nevertheless, the role of sex steroids is not well established. For that, we analyzed the effect of the principal gonadal sex steroids in both sexes. We determined sex as a statistically risk factor for colorectal cancer with data obtained from GLOBOCAN database.

Methods

To induce colorectal tumors, we used the gold standard chemical method of azoxymethane and dextran sulphate of sodium. To evaluate the role of sex steroids, we gonadectomized independent males and female animals, reconstituting and substituting them with 17β estradiol and dihydrotestosterone. Finally, we determined, in vitro, the proliferation of a human cell line exposed to 17β estradiol, testosterone, or dihydrotestosterone. Sex, as a risk factor for colorectal cancer, showed a statistically significant susceptibility of men over 50 years old.

Results

In vivo, males develop a greater number of tumors and with a larger size than females. In males, orchiectomy prevents tumor growth, whereas in females, ovariectomy promotes the development of neoplasms. DHT acts as a protumoral agent in both sexes. 17β estradiol reduces tumor growth in females but enhances it in males, showing a dimorphic effect. In vitro studies reveal that estradiol decreases the proliferation of the HCT-116 colon cancer cell line, while testosterone boosts proliferation in these cells. Interestingly, dihydrotestosterone does not influence proliferation.
Tailoring treatment for elderly bladder cancer: a case report of personalized management of high-grade urothelial carcinoma with papillary features
Authors: Nikolaidis Christos G. , Gyriki Despoina , Anitsakis Charalambos , Stavropoulou Elisavet
Published: August 2024

This case study presents the diagnostic and therapeutic course of a 72-year-old male patient with a history of high-grade urothelial carcinoma with papillary features. The report outlines the patient’s initial presentation, the intervention strategies employed, including transurethral resection and intravesical Bacillus Calmette-Guérin (BCG) therapy, the subsequent complications and clinical decisions following the intense symptoms post-treatment. The study highlights the challenges in managing bladder cancer in elderly patients, considering the tumor’s characteristics, treatment responses, and the patient’s quality of life.
Bibliometric analysis of bone metastases from lung cancer research from 2004 to 2023
Authors: Tang Jing , Gu Zhangui , Yang Zongqiang , Ma Long , Liu Qiang , Shi Jiandang , Niu Ningkui , Wang Yanyang
Published: August 2024

Background

Bone metastases of lung cancer (BMLC) severely diminish patients’ quality of life due to bone-related events, and the lack of clear guidelines globally regarding medical and surgical treatment significantly reduces patient survival. While knowledge about BMLC has grown exponentially over the past two decades, a comprehensive and objective bibliometric analysis remains absent.

Methods

A comprehensive bibliometric analysis was conducted on relevant literature on BMLC extracted from the Web of Science database from 2004 to 2023 by Biblioshiny, VOSviewer, Scimago Graphica, CiteSpace, and Microsoft Office Excel Professional Plus 2016 software. 936 papers related to BMLC were extracted from the Web of Science Core Collection (WoSCC). The number of publications, countries, institutions, global collaborations, authors, journals, keywords, thematic trends, and cited references were then visualized. Finally, the research status and development direction in the last 20 years were analyzed.

Results

This study included a total of 936 papers on BMLC from 2004 to 2023. There has been a steady increase in global publications each year, peaking in 2021. China had the highest number of publications, followed by Japan and the United States. Additionally, China had the most citations with an H-index of 35, while the US followed with an H-index of 34, highlighting their significant contributions to the field. “Frontiers in Oncology” had the highest number of publications. CiteSpace analysis identified “lung cancer,” “bone metastasis,” and “survival” as the top high-frequency keywords, encapsulating the core research focus. Keyword clustering analysis revealed six main clusters representing the primary research directions. Burst analysis of keywords showed that “skeletal complications” had the highest burst intensity from 2005 to 2013, while recent research trends include “immunotherapy” and “denosumab,” with bursts from 2021 to 2023. Trend topic analysis indicated that “non-small cell lung cancer,” “immunotherapy,” and “immune checkpoint inhibitors” represent the cutting-edge research directions in this field.

Conclusion

This article reveals the current status and trend of research on BMLC, which is increasing worldwide. China and the United States have contributed the most, but international cooperative research on BMLC should be strengthened. The pathogenesis, early prevention, and individualized treatment of BMLC need to be strengthened for further study, and immunotherapy is the next hotspot of lung cancer bone metastasis research.
Impact of postoperative necrotizing enterocolitis after neonatal cardiac surgery on neurodevelopmental outcome at 1 year of age
Authors: Knirsch Walter , De Silvestro Alexandra , Rathke Verena , L’Ebraly Christelle , Natterer Julia C. , Schneider Juliane , Sekarski Nicole , Latal Beatrice , Borradori-Tolsa Cristina , Bouhabib Maya S. , Fuhrer Kradolfer Katharina , Glöckler Martin , Hutter Damian , Pfluger Marc R. , Kaiser Lena , Polito Angelo , Kelly-Geyer Janet F. , von Rhein Michael ,   the Swiss ORCHID group
Published: August 2024

Objectives

We analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age.

Methods

Using data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III).

Results

The included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p < 0.05; 49 with vs. 32 days without NEC, p < 0.05). The Bayley III scores of the analyzed patients determined at an age of 11.5 ± 1.5 months showed cognitive (CCS) (102.2 ± 15.0) and language scores (LCS) (93.8 ± 13.1) in the normal range and motor composite scores (MCS) (88.7 ± 15.9) in the low-normal range. After adjusting for socioeconomic status and CHD type, patients with NEC had lower CCS scores [β = −11.2 (SE 5.6), p = 0.049]. Using a cumulative risk score including NEC, we found a higher risk score to be associated with both lower CCS [β = −2.8 (SE 1.3), p = 0.030] and lower MCS [β = −3.20 (SE 1.3), p = 0.016].

Conclusions

Postoperative NEC is associated with longer ICU and hospital LOS and contributes together with other complications to impaired ND outcome at 1 year of age. In the future, national and international patient registries may provide the opportunity to analyze large cohorts and better identify the impact of modifiable perioperative risk factors on ND outcome.

Clinical Trial Registration

ClinicalTrials.gov identifier: NCT05996211.
Anomalous pulmonary venous drainage due to malposition of septum primum: two case reports and literature review
Authors: Yang Yan , Zhao Jianshe , Dong Chunhua , Yi Minggang , Gao Xin
Published: August 2024

Background

Anomalous pulmonary venous connection with malposition of septum primum (MSP) is a rare pediatric cardiovascular malformation. Although reports in the literature are scarce, accurate pre-operative imaging diagnosis is crucial for selecting the appropriate clinical intervention and determining the prognosis for affected children.

Case description

In both case reports, the cardiovascular malformations were incidental findings. In the second case, an enlarged cardiac silhouette was observed on chest x-ray due to pneumonia, which was subsequently confirmed by ultrasound. Combined with computed tomography angiography examination, the diagnosis of MSP-type anomalous pulmonary venous connection was established.

Conclusions

Comprehensive imaging examinations are essential in reducing misdiagnosis and achieving an accurate diagnosis of MSP-type anomalous pulmonary venous connection. The typical imaging findings for MSP-type anomalous pulmonary venous connection include absence or hypoplasia of the superior limbic band of the septum secundum, leftward displacement of the septum primum, and partial or total pulmonary vein drainage into the anatomical right atrium.
Nano-drug delivery systems (NDDS) in metabolic dysfunction-associated steatotic liver disease (MASLD): current status, prospects and challenges
Authors: Yang Ying , Wang Xiaojing
Published: August 2024

About one-third of the global population suffers from metabolic dysfunction-associated steatotic liver disease (MASLD), but specific treatments for MASLD have long been lacking, primarily due to the unclear etiology of the disease. In addition to lifestyle modifications and weight loss surgery, pharmacotherapy is the most common treatment among MASLD patients, and these drugs typically target the pathogenic factors of MASLD. However, bioavailability, efficacy, and side effects all limit the maximum therapeutic potential of the drugs. With the development of nanomedicine, recent years have seen attempts to combine MASLD pharmacotherapy with nanomaterials, such as liposomes, polymer nanoparticles, micelles, and cocrystals, which effectively improves the water solubility and targeting of the drugs, thereby enhancing therapeutic efficacy and reducing toxic side effects, offering new perspectives and futures for the treatment of MASLD.
Differing temperature dependencies of functional homologs zebrafish Abcb4 and human ABCB1
Authors: Luckenbach Till , Burkhardt-Medicke Kathleen
Published: August 2024

The ATP binding cassette (ABC) transporters human ABCB1 and zebrafish (Danio rerio) Abcb4 are functionally homologous multixenobiotic/multidrug (MXR/MDR) efflux transporters that confer the efflux of a broad range of diverse chemical compounds from the cell. As ATPases, the transporters utilize the energy released by ATP cleavage for protein conformation changes and concomitant active transport of substrate compounds. The temperatures, at which human ABCB1 and zebrafish Abcb4 need to function, can substantially differ: Whereas the ambient temperature of human ABCB1, which is that of the human body, is constant, zebrafish Abcb4 has to be active in a wider temperature range as the body temperature of zebrafish can considerably vary, depending on the ambient water temperature (18°C–40°C). Here, we examined the effect of temperature on the ATPase activities of recombinant human ABCB1 and zebrafish Abcb4 generated with the baculovirus expression system. Incubation temperatures for enzyme reactions were set to 37°C and 27°C, corresponding to the human body temperature and the cultivation temperature of zebrafish in our lab, respectively. For stimulation and inhibition of zebrafish Abcb4 and human ABCB1 ATPase activities verapamil and cyclosporin A were added at different concentrations and 50% effect concentrations (EC50) were determined. The different temperatures had a stronger effect on the human ABCB1 than on the zebrafish Abcb4 ATPase: Differences between EC50 values for verapamil at 37°C and 27°C, respectively, were 1.8-fold for human ABCB1 but only 1.2-fold for zebrafish Abcb4. Activation energies (Ea) of basal and verapamil-stimulated ATPases, calculated based on the Arrhenius equation, were 2-fold (basal) and 1.5-fold (verapamil-stimulated) higher for human ABCB1 than for zebrafish Abcb4. The differences between zebrafish Abcb4 and human ABCB1 ATPases in temperature sensitivity and activation energy could be important for the comparison of the functional properties of the two transporter proteins in the context of pharmaco-/toxicokinetics. Related to this, our finding that at equal reaction conditions the zebrafish Abcb4 ATPase activity tended to be generally higher than that of human ABCB1 may also be important, as this may point to a higher substrate compound transport rate of Abcb4.
Data mining and safety analysis of dual orexin receptor antagonists (DORAs): a real-world pharmacovigilance study based on the FAERS database
Authors: Jiang Manxue , Li Hao , Kong Lingti
Published: August 2024

Objective

Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, four signal detection methods were applied to mine adverse drug events (ADEs) related to use of dual orexin receptor antagonists (DORAs) to provide reference for safe clinical use.

Research design and Methods

Data collected from Q3rd 2014 to Q4th 2023 were obtained from the FAERS database. According to the preferred terminology (PT) and systematic organ classification (SOC) of MedDRA v.26.0, the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used to detect ADE signals.

Results

A total of 11,857 DORAs-related adverse reactions were detected, reported with suvorexant, lemborexant, and daridorexant as the main suspected drugs was 8717584, and 2556, respectively. A higher proportion of females than males were reported (57.27% vs. 33.04%). The top 20 positive PT signals from three DORAs showed that “sleep paralysis” ranked first. “Brain fog” was stronger following daridorexant but was not detected for the other two drugs, and “sleep sex” and “dyssomnia” were stronger in suvorexant but not in the other two drugs. Additionally, some PTs occurred that were not included in drug instructions, such as “hangover” and “hypnagogic hallucination.”

Conclusion

In this study, four algorithms (ROR, PRR, BCPNN, and MGPS) were used to mine the safety signals of DORAs. We identified some potential ADE signals that can promote the rational use of DORAs and improve their safety.
Inertial measurement unit-based real-time feedback gait immediately changes gait parameters in older inpatients: a pilot study
Authors: Miyazaki Takasuke , Kiyama Ryoji , Takeshita Yasufumi , Shimose Daichi , Araki Sota , Matsuura Hisanori , Uto Yuki , Nakashima Shobu , Nakai Yuki , Kawada Masayuki
Published: August 2024

The effect of gait feedback training for older people remains unclear, and such training methods have not been adapted in clinical settings. This study aimed to examine whether inertial measurement unit (IMU)-based real-time feedback gait for older inpatients immediately changes gait parameters. Seven older inpatients (mean age: 76.0 years) performed three types of 60-s gait trials with real-time feedback in each of the following categories: walking spontaneously (no feedback trial); focused on increasing the ankle plantarflexion angle during late stance (ankle trial); and focused on increasing the leg extension angle, which is defined by the location of the ankle joint relative to the hip joint in the sagittal plane, during late stance (leg trial). Tilt angles and accelerations of the pelvis and lower limb segments were measured using seven IMUs in pre- and post-feedback trials. To examine the immediate effects of IMU-based real-time feedback gait, multiple comparisons of the change in gait parameters were conducted. Real-time feedback increased gait speed, but it did not significantly differ in the control (p = 0.176), ankle (p = 0.237), and leg trials (p = 0.398). Step length was significantly increased after the ankle trial (p = 0.043, r = 0.77: large effect size). Regarding changes in gait kinematics, the leg trial increased leg extension angle compared to the no feedback trial (p = 0.048, r = 0.77: large effect size). IMU-based real-time feedback gait changed gait kinematics immediately, and this suggests the feasibility of a clinical application for overground gait training in older people.
Evaluation of hydroponic systems for organic lettuce production in controlled environment
Authors: Chowdhury Milon , Samarakoon Uttara C. , Altland James E.
Published: August 2024

Organic farming methods, including the use of organic substrates, fertilizers, pesticides, and biological control, are gaining popularity in controlled environment agriculture (CEA) due to economic benefits and environmental sustainability. However, despite several studies focusing on the preparation and evaluation of liquid organic fertilizers, none have explored the compatibility of these fertilizers with different hydroponic systems. Therefore, the objective of this study was to evaluate lettuce production using a liquid organic fertilizer under different hydroponic systems. Four distinct hydroponic methods were selected: nutrient film technique (NFT), deep water culture (DWC) (liquid culture systems), and Dutch bucket (DB), regular plastic container (RPC) (substrate-based systems). ‘Green Butter’ lettuce was grown using a liquid organic fertilizer (Espartan) for four weeks. Shoot growth parameters (e.g., shoot width, number of leaves, leaf area, foliar chlorophyll content, fresh weight, and dry weight) and root growth parameters (e.g., root length, fresh weight, and dry weight) were measured. The growth difference of lettuce under the DB and RPC systems was negligible, but the growth in RPC was 29% to 60% and 15% to 44% higher than the NFT and DWC systems, respectively, for shoot width, number of leaves, leaf area, shoot fresh weight and dry weight. Root parameters were nearly identical for the NFT and DWC systems but significantly lower (21% to 94%) than the substrate-based DB and RPC systems. Although lettuce grown in the NFT system showed the least growth, its mineral content in the leaf tissue was comparable or sometimes higher than that of substrate-based hydroponic systems. In conclusion, the tested liquid organic fertilizer is suitable for substrate-based hydroponic systems; however, further evaluation of different liquid organic fertilizers, and crop species is required.
Analysis of plant pararetrovirus promoter sequence(s) for developing a useful synthetic promoter with enhanced activity in rice, pearl millet, and tobacco plants
Authors: Kumari Khushbu , Sherpa Tsheten , Dey Nrisingha
Published: August 2024

Promoters are one of the most important components for many gene-based research as they can fine-tune precise gene expression. Many unique plant promoters have been characterized, but strong promoters with dual expression in both monocot and dicot systems are still lacking. In this study, we attempted to make such a promoter by combining specific domains from monocot-infecting pararetroviral-based promoters sugarcane bacilliform virus (SCBV) and banana streak virus (BSV) to a strong dicot-infecting pararetroviral-based promoter mirabilis mosaic virus (MMV). The generated chimeric promoters, MS, SM, MB, and BM, were tested in monocot and dicot systems and further validated in transgenic tobacco plants. We found that the developed chimeric promoters were species-specific (monocot or dicot), which depended on their respective core promoter (CP) region. Furthermore, with this knowledge, deletion-hybrid promoters were developed and evaluated, which led to the development of a unique dual-expressing promoter, MSD3, with high gene expression efficiency (GUS and GFP reporter genes) in rice, pearl millet, and tobacco plants. We conclude that the MSD3 promoter can be an important genetic tool and will be valuable in plant biology research and application.
Evaluation of genetic diversity among olive trees (Olea europaea L.) from Jordan
Authors: Al-Kilani Mazen A. , Taranto Francesca , D’Agostino Nunzio , Montemurro Cinzia , Belaj Angjelina , Ayoub Salam , Albdaiwi Randa , Hasan Shireen , Al-Abdallat Ayed M.
Published: August 2024

This study aimed to identify and evaluate the genetic diversity of olive trees in Jordan, a country located in the eastern Mediterranean, where olive domestication originated. For this purpose, a total of 386 olive trees were analyzed, including 338 collected from two surveys (JOCC-1 and JOCC-2) across seven regions, and 48 selected accessions from the Olive Germplasm Bank of Jordan (JGBOC). These trees underwent comprehensive phenotypic and molecular characterization using different tools. Significant differences in morphological traits were detected among tested regions using the Chi-square test. Principal components analysis revealed that fruit color change and growth habit as the most discriminating traits, segregating the trees into two groups, with the first group including the Kanabisi cultivar and the second group including the Kfari Baladi cultivar. Utilizing Kompetitive Allele Specific PCR assay, two sets of informative SNPs were used for the genetic diversity analysis. Cladograms were constructed using the maximum likelihood method, revealing a consistent pattern where two clades containing identical genotypes were observed to cluster with the Kfari Baladi or Kanabisi. In addition, the SNP data was used to perform a comparative analysis with the Worldwide Olive Germplasm Bank of Córdoba, which revealed 73 unreported olive genotypes from Jordan. Genetic structure analyses using Discriminant Analysis of Principal Components (DAPC) identified four clusters with distinctive patterns of relatedness among 149 unique accessions, including 52 olive accessions from various Mediterranean countries (IOCC-3). ADMIXTURE analysis revealed four genetic clusters, consistent with the clustering observed in DAPC and cladogram analysis, indicating a high level of genetic admixture among Jordanian olive germplasm. In conclusion, the results show that olive trees in Jordan are highly diverse, providing valuable information for future conservation and management plans.
Culturally contextualized suicide prevention for international students: new opportunities for research and practice
Authors: McKay Samuel , Meza Jocelyn I.
Published: August 2024

The rising incidence of suicide-related thoughts and behaviors among international students presents a significant public health challenge and growing concern among college campuses. Current intervention strategies often rely on Western-centric and colonized approaches developed and tested with primarily Western, Educated, Industrialized, Rich and Democratic (WEIRD) samples. Exclusion and historical underrepresentation of ethnoracially minoritized groups in suicide prevention treatment trials create gaps in advancing our science because they often miss the cultural contextualization crucial for effective prevention and intervention in diverse groups from different countries of origin. To address the limitations of these Western-centric strategies, we explored existing prevention recommendations and approaches through the lens of an expanded version of the newly developed Protective Factors Framework, tailored for non-Western cultural perspectives. We propose significant opportunities for enhancing current practices and point to promising future directions. The primary areas for development include: (1) bolstering community empowerment and ownership, (2) refining mechanisms of change to encompass multicultural viewpoints, and (3) focusing on effective implementation and thorough evaluation for ongoing refinement. This methodology not only shows promise for enhancing international student suicide prevention but also offers insights for broader application in suicide prevention among other culturally diverse populations.
Promoting theory of mind and emotion understanding in preschool settings: an exploratory training study
Authors: Grazzani Ilaria
Published: August 2024

Introduction

This new exploratory study is part of a larger ongoing follow-up project. Its specific aim was to verify whether an innovative European Program, primarily designed to enhance children’s social and emotional learning, led to gains in theory of mind and emotion understanding when implemented in preschool settings.

Methods

Thirty-four children (mean age: 56.4 months; SD: 10.1; range: 40–70 months) participated in the study. They were randomly and equally divided into a training group and a control group. The training sample completed eight linguistic-conversational activities drawn from the Program, in groups of 5 to 6 children, over 8 weeks. The activities were based on listening to stories and/or watching videos and then thinking and talking about the inner world (thoughts and emotions) of the story characters as well as the participants’ own inner states. During the training phase, the children in the control group engaged in drawing or free play activities. At both the pre-test and post-test phases of the study, all the children completed a language test, a battery of theory of mind (ToM) tasks (including ‘change of location’ and ‘unexpected content’ tasks), and the Test of Emotion Comprehension which evaluates nine components of emotion understanding (EU). The validated national versions of the tests were administered in all cases.

Results

Significant differences were identified between the training and control groups. Indeed, the participants in the Program training activities, which were based on conversational exchanges between an adult and a group of children, as well as among the children themselves, outperformed the control participants on both overall theory of mind and overall emotion understanding. A more detailed analysis showed that the training group outperformed the control group in relation to both specific components of EU and the ‘change of location’ ToM task.

Discussion

The results of this exploratory study suggest that the Program is effective at enhancing preschoolers’ social understanding and thus merits implementation in preschool settings.
Duration mismatch negativity under varying deviant conditions in individuals with high schizotypal traits
Authors: Deng Jue , Zhang Yuanjun , Lu Liqin , Ou Yuanhua , Lai Xianghui , Chen Siwei , Ye Yiduo
Published: August 2024

Background

Although impaired auditory mismatch negativity (MMN) has consistently been found in individuals with schizophrenia, there are few and inconsistent reports on nonclinical individuals with schizotypy. To date, no studies have thoroughly assessed MMN with different degrees of deviant oddballs in nonclinical schizotypal samples. The aim of this study was to examine the extent of duration MMN (dMMN) amplitudes under two deviant duration conditions (large and small) in nonclinical participants with high schizotypal traits.

Methods

An extreme-group design was utilized, in which 63 participants from the schizotypy and control groups were selected from a pool of 1519 young adults using the Schizotypal Personality Questionnaire (SPQ). MMN was measured using passive duration oddball paradigms. Basic demographic information and musical backgrounds were assessed and matched, while depression and anxiety were evaluated and controlled for. The repeated measures analysis of covariance was utilized to evaluate differences in dMMN between groups. The Bonferroni correction was applied for multiple comparisons. Partial correlation and multiple linear regression analyses were conducted to investigate the association between dMMN amplitudes and SPQ scores.

Results

The amplitudes of dMMN at Cz were significantly increased under the large deviance condition in nonclinical schizotypal individuals (F = 4.36, p = .04). Large-deviance dMMN amplitudes at Fz were positively correlated with mild cognitive-perceptual symptoms in the control group (rp = .42, p = .03). However, as schizophrenia-like symptoms worsened and approached the clinical threshold for schizophrenia, small-deviance dMMN amplitudes at Cz showed negative associations with the cognitive-perceptual factor in the schizotypy group (rp = -.40, p = .04).

Conclusion

These results suggest the importance of considering the degree of deviation in duration when implementing the auditory oddball paradigm among nonclinical participants with schizotypal traits. In addition, our findings reveal a potential non-linear relationship between bottom-up auditory processing and the positive dimension of the schizophrenia spectrum.
Illness-related variables and abnormalities of resting-state brain activity in schizophrenia
Authors: Giuliani Luigi , Pezzella Pasquale , Giordano Giulia Maria , Fazio Leonardo , Mucci Armida , Perrottelli Andrea , Blasi Giuseppe , Amore Mario , Rocca Paola , Rossi Alessandro , Bertolino Alessandro , Galderisi Silvana , Maj Mario
Published: August 2024

Background

The development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features.

Methods

Sixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables.

Results

Attention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity.

Conclusion

Neurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes.
Bridging disciplines-key to success when implementing planetary health in medical training curricula
Authors: Malmqvist Ebba , Oudin Anna
Published: August 2024

Planetary health is being or should be added to medical training curricula in accordance with association consensus. Several articles published in recent years have addressed concern on the implementation, and the challenges that can occur if not addressed properly. This scoping narrative literature review focuses on planetary health as a concept, as well as challenges and suggested solutions to address these challenges. Planetary health is an important concept and needs to be addressed in all medical training. We found that one main challenge is implementation without ensuring the right competences and resources. Medically trained teachers set out to understand and teach complex natural and social systems. At some institutions the time allocated to teach planetary health is limited or non-existent. Case studies and student led teaching are solutions suggested, while other argue that true interdisciplinarity by inviting experts are more in line with what we expect from other subjects. In conclusion, the roots of planetary health, the enormous health risks at stake and nature of the subject requires medical training to adopt a true inter/trans-disciplinary approach to succeed. It might not be expected for all students to become planetary health experts, but all need a general understanding of the most important aspects and values.
Are we ready to integrate 3D culture systems in acute myeloid leukemia and bone marrow microenvironment research?
Authors: Sharipol Azmeer , Frisch Benjamin J.
Published: August 2024

Acute myeloid leukemia (AML) is the most aggressive adult leukemia and results in a dismal 5-year survival rate of less than 30%. While research has primarily focused on identifying intrinsic mutations driving leukemogenesis, the role of the bone marrow microenvironment (BMME) in disease progression remains poorly understood. For this purpose, conventional 2D cultures inadequately replicate the complex BMME interactions crucial for the maintenance of normal hematopoiesis and leukemia pathogenesis. In recent years, 3D cultures or microphysiological systems (MPS), have emerged as promising tools for in vitro modeling of the human BMME. These approaches provide a promise for a more physiologically relevant platform for investigating the mechanistic underpinnings of AML interactions with BMME components, as well as exploring chemoresistance mechanisms and facilitating drug discovery efforts. This review discusses the considerations in biomaterials, biophysical, and biochemical factors to develop the BMME in vitro for AML studies, the state-of-the-art 3D models of the BMME, and the challenges and prospects of adopting MPS for AML research.
Uncovering an emerging policy direction for Australian energy and future fuels using a “participatory decision-making” framework
Authors: Kambo Amrita , Kannampuzha Leo , Arratia-Solar Andrea , Witt Katherine
Published: August 2024

Introduction

An online deliberative engagement process was undertaken with members of the general public to understand what they value or would like to change about the energy system, within the broader context of decarbonizing Australia's energy networks, identifying a role for future fuels (hydrogen and biogas). Citizens developed a set of principles that could guide Australia's path toward a low-carbon energy future, reflecting on expectations they place upon energy transition. Next, citizens' principles were shared with policy-makers in government and policy-influencers from the energy industry using an online interactive workshop.

Methods

This study analyses policy-makers and -influencers response to citizens' guiding principles using the 'diamond of participatory decision-making' framework for analysis. Convergence and divergence in diverse, complex and rich views across cohorts and implications thereupon energy policy were identified.

Results

Although considerable alignment between multi-stakeholders' views was noted, key areas of divergence, or what is called the “groan zone” were easily identified in relation to social and environmental justice issues. This groan zone highlights the struggles that energy policy-makers face -the need to listen and respond to citizens' voices, vs. the need for practical and workable policies that also support overarching government or industry objectives.

Discussion

Policy making when the views of different stakeholders align is relatively straightforward. However, this is not the case where the expectations diverge. More creative measures will be needed to address divergent views and expectations whilst maintaining procedural fairness, in this case, using democratic deliberative engagement processes. While the use of deliberative processes is gaining momentum worldwide, particularly concerning climate change and energy transition policies, this paper also highlights the benefits of conducting a robust post facto analysis of the content of the processes. Areas of alignment, where policy can be made and implemented relatively easily without contention are identified. Other areas (such as making electrification mandatory) might be more complex or have unwanted negative social and environmental justice effects. Overall, this paper bridges an analytical gap between “expectation studies” and participatory research. By borrowing terminology from a participatory research framework we sharpen the concepts in “expectation studies” from a consensus, inclusion and diversity standpoint.
Neuronavigation in glioma resection: current applications, challenges, and clinical outcomes
Authors: Sulangi Albert Joseph , Husain Adam , Lei Haoyi , Okun Jessica
Published: August 2024

Background

Glioma resection aims for maximal tumor removal while preserving neurological function. Neuronavigation systems (NS), with intraoperative imaging, have revolutionized this process through precise tumor localization and detailed anatomical navigation.

Objective

To assess the efficacy and breadth of neuronavigation and intraoperative imaging in glioma resections, identify operational challenges, and provide educational insights to medical students and non-neurosurgeons regarding their practical applications.

Methods

This systematic review analyzed studies from 2012 to 2023 on glioma patients undergoing surgical resection with neuronavigation, sourced from MEDLINE (PubMed), Embase, and Web of Science. A database-specific search strategy was employed, with independent reviewers screening for eligibility using Rayyan and extracting data using the Joanna Briggs Institute (JBI) tool.

Results

The integration of neuronavigation systems with intraoperative imaging modalities such as iMRI, iUS, and 5-ALA significantly enhances gross total resection (GTR) rates and extent of resection (EOR). While advanced technology improves surgical outcomes, it does not universally reduce operative times, and its impact on long-term survival varies. Combinations like NS + iMRI and NS + 5-ALA + iMRI achieve higher GTR rates compared to NS alone, indicating that advanced imaging adjuncts enhance tumor resection accuracy and success. The results underscore the multifaceted nature of successful surgical outcomes.

Conclusions

Integrating intraoperative imaging with neuronavigation improves glioma resection. Ongoing research is vital to refine technology, enhance accuracy, reduce costs, and improve training, considering various factors impacting patient survival.
Severe acute respiratory syndrome coronavirus-2 seroprevalence in non-vaccinated people living with HIV in Uganda during 2022
Authors: Ainembabazi Provia , Najjemba Letisha , Musaazi Joseph , Hönemann Mario , Castelnuovo Barbara , von Braun Amrei
Published: August 2024

A cross-sectional study on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence among unvaccinated people living with HIV (PLWH) was conducted in Kampala, Uganda, in 2022. Data collection was done using a structured questionnaire. SARS-CoV-2 serologies were done using the Roche Elecsys Anti-SARS-CoV-2 S immunoassay, which assesses the adaptive humoral immune response to the SARS-CoV-2 Spike protein. A total of 575 PLWH (female n=355, 61.7%) with a median age of 49 years (IQR 39-55) were included. SARS-CoV-2 seroprevalence was 93%. The majority had antibody concentration levels ≥ 250 U/ml (n=383, 66.6%). Participants aged >55 years were significantly more likely to have lower antibody concentrations compared to younger participants (p-value < 0.001). A high BMI (≥ 30 kg/m2) was significantly associated with higher antibody concentrations (p-value 0.001). Concerning COVID-19 history, a small proportion of participants (n=79, 13.6%) reported contact with a known COVID-19 patient. Only 8.1% (n=47) had ever had a nasopharyngeal swab for SARS-CoV-2 RT-PCR done, and 3.1% (n=18) actually had a laboratory-confirmed SARS-CoV-2 infection in the past. SARS-CoV-2 seroprevalence was high among our study population, which may be attributed to the fact that the study took place right after all restrictions were lifted and the population was exposed to the dominant Omicron variant. Interestingly, only a small proportion of infections had been laboratory-confirmed.
Development of modular polymeric nanoparticles for drug delivery using amine reactive chemistry
Authors: Wong Calvin , Ho Emmanuel A.
Published: August 2024

Curcumin has been explored for its anti-cancer potential, but is severely limited by its hydrophobicity and sensitivity to light and water. In this study, poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized to encapsulate curcumin via single emulsion method to improve curcumin stability and bioavailability. The PLGA NPs were coated with oligomeric chitosan (COS) and RGD peptide (a peptide consisting of Arg-Gly-Asp) using amine-reactive chemistry (NHS and EDC). Both COS and RGD had been previously shown to accumulate and target many different types of cancer cells. NPs were characterised based on size distribution, zeta potential, and binding efficiency of RGD peptide. They were also evaluated on encapsulation efficiency, and stability, of curcumin within the NPs. OVCAR-3 cancer cells were treated with COS and RGD-coated PLGA NPs loaded with Coumarin-6 dye for fluorescent imaging of cell uptake. They were also treated with curcumin-loaded NPs to determine cytotoxicity and effectiveness of delivery. The NPs exhibited size distribution and zeta potential within expected values, though binding efficiency of RGD was low. Curcumin-loaded NPs showed significant increase in cytotoxicity over free (unencapsulated) curcumin, and void (empty) NPs, suggesting successful delivery of curcumin as an anti-cancer agent; the performance of COS and RGD coated NPs over bare PLGA NPs was inconclusive, however, optimization will be required to improve formulation during the coating steps. This method of NP synthesis serves as proof of concept for a modular solution to the development of various coated polymeric NPs for other drugs or applications.
The Level of Happiness and Its Relationship with Personal and Occupational Well-Being in Women Leaders at a Mexican University: An Exploratory Study
Authors: Ortiz-Meillón Viviana , Guerra-Leal Eva María , Vázquez-Parra José Carlos
Published: August 2024

This exploratory study aims to identify the state of well-being of a select group of women leaders in a Mexican university by analyzing the relationship between their perception of happiness and their satisfaction with their life and work. Through the application of a psychometric battery, this work examined how these leaders manage their well-being within an environment that is simultaneously empowering and demanding. Methodologically, a descriptive statistical analysis was performed, including a correlation analysis of all items. As a result, the research identified positive correlations between the variables age and positive perceptions of work and life, which are strongly associated with high personal and professional satisfaction. In addition, people who find their work rewarding and feel that their life is close to their ideal tend to be more satisfied in general. Although this study intended to be exploratory, it also sought to contribute a deeper understanding of the well-being status of women in university leadership positions in Mexico. In doing so, it filled an important gap in the literature on gender, leadership, and well-being in Latin American academia by highlighting the complexity of managing and supporting women in leadership positions.
Effects of Nail Biting (Onychophagy) on Upper Central Incisors in Children and Young Adolescents
Authors: Ciavarella Domenico , Montaruli Graziano , Giuliani Lidia , Bisceglia Maria , Laurenziello Michele , Fanelli Carlotta , Lorusso Mauro , Esposito Rosa , Tepedino Michele
Published: August 2024

Nail biting (NB) is a repetitive and uncontrolled parafunctional activity that can affect oral health by altering tooth shape and intraoral position. Nowadays, there is not enough scientific evidence about the impact of NB on teeth; therefore, this study aimed to evaluate the effects of NB on the length, width and inclination of upper central incisors. This retrospective study involved 76 patients, 40 males and 36 females, with a mean age of 10.6 ± 0.3 years. Digital scans of the maxillary arch of each patient were recorded. Next, the length, width and inclination of upper central incisors used and not used for NB were measured. Finally, data were analysed with a paired t-test. Statistical analysis showed statistically significant differences in the length and inclination of upper central incisors used for NB compared with those of upper central incisors not used for NB, while the width did not show a significant difference. There were relevant changes in upper central incisors subjected to NB, demonstrating that NB impairs the shape, morphology and inclination of teeth. Therefore, because of the potentially negative consequences of NB, it is recommended that NB not be underestimated.