bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Different Livestock Manure Ratios on the Decomposition Process of Aerobic Composting of Wheat Straw
Authors: Fan Tingyu , Zhang Xuemiao , Wan Yi , Deng Ruilai , Zhu Houhong , Wang Xihao , Wang Shun , Wang Xingming
Published: November 2023

Aerobic composting is an effective method of resource treatment for agricultural and forestry solid waste; however, while wheat straw is usually used as a conditioner and is not the main body as in aerobic composting, wheat straw is abundant in annual production, and fertilization is one of the main ways of resource utilization of wheat straw, how to use wheat straw as the main body of aerobic composting for efficient treatment is, therefore, a meaningful research direction. In this paper, to achieve the efficient and economic resource utilization of wheat straw and livestock manure, aerobic composting was carried out with wheat straw as the main body, and pig manure and cow manure were mixed with wheat straw crops at ratios of 20%, 30%, and 40%, respectively, for barrel suspension composting. The changes in pH, EC, NH4+-N, NO3−-N, TN, TP, organic matter and seed germination index, and shoot length inhibition rate before and after composting were compared between treatment groups using different material ratios in the aerobic composting process. The changes in the physicochemical properties and nutrient elements of compost products were studied. The results show that the co-composting of livestock manure and wheat straw can promote the decomposition of the pile, and the addition of 40% cow manure and 30% pig manure has the best effect in promoting decay. In contrast, the addition of excessive pig manure inhibits the decomposition of the pile. Organic matter degradation in the treatment groups using cow manure was more effective than in those using pig manure, and the best results were obtained with 40% cow manure. The pile was alkaline at the end of each treatment, and the wheat straw compost treated with 40% cow manure had the best nitrogen and phosphorus retention. The wheat straw compost treated with 40% cow manure had the highest integrated degree of decomposition, which promoted the deterioration of the pile and provided a research basis for the use of wheat straw as an efficient resource.
The Perception of the Body Condition of Cats and Dogs by French Pet Owners and the Factors Influencing Underestimation
Authors: Blanchard Tiphaine , Hoummady Sara , Banuls Damien , Roche Mélanie , Bynens Aurélie , Meunier Michel , Dos Santos Natalia , Tissaoui Emna , Rouch-Buck Pétra , Fantinati Marco , Priymenko Nathalie
Published: November 2023

Managing pet obesity relies heavily on the active involvement of owners; however, a key challenge arises from misperceptions about their own pet’s body condition. Given evolving societal dynamics like the body positivity movement, understanding owners’ perceptions is increasingly pivotal. To evaluate the differences in owners’ perception, this study compared the use of verbal and visual body condition score scales versus the established nine-point body condition score system. The factors linked to underestimation were further specifically investigated. Owners of healthy adult dogs and cats attending vaccination consultations in Veterinary Hospitals in France between 2020 and 2022 were recruited. They were required to assess their pets’ body condition initially using an oral description and then with the nine-point BCS visual scale. Their assessments were then compared with the BCS determined by veterinary health care personnel, considered the primary investigator. A total of 304 dogs and 270 cats were included in the study. It was observed that 27% of dog owners and 24% of cat owners underestimated their pets’ body condition. Among dog and cat owners, factors associated with the underestimation of body condition were the pets’ overweight status and having children. This discovery emphasizes the need for a holistic One Health approach that prioritizes the health and well-being of both humans and their pets. When it comes to pet owners evaluating their pets’ body condition, underestimation proved to be the predominant misperception. Addressing this issue requires comprehensive education to empower owners to recognize and comprehend their pets’ overweight status, a critical step for the overall well-being of companion animals.
Parturition and Neonatal Parameters of Three Species of Rhinoceros under Managed Care in the United States
Authors: Brenner Emily E. , Howard Lauren L. , Capiro Jonnie , Hernandez Jorge A.
Published: November 2023

Rhinoceros species range from near threatened to critically endangered due to habitat loss and poaching. A sustainable ex situ breeding population is critically important to maintain genetic diversity and help ensure the survival of the species; however, not all populations under human care are self-sustaining. While rhinoceros reproductive physiology and pathology have been well studied, there is still a paucity of information describing the normal parameters of parturition and neonatal landmarks. Using video recordings, medical records, and keeper logs, we reviewed and compared data regarding the parturition of three rhinoceros species (black rhinoceros (BR) (Diceros bicornis), n = 4; greater one-horned rhinoceros (GOHR) (Rhinoceros unicornis), n = 21; and southern white rhinoceros (SWR) (Ceratotherium simum simum), n = 22) managed under human care in the United States. Using equine parameters as a model for comparison, we compiled the following data: the signs of impending parturition, durations of the parturition phases, calving presentation, frequency of dystocia or stillbirth, and time from birth to neonatal landmarks. Data from 47 births, including 26 videos, were examined. The durations of parturition phases I, II, and III had median lengths of 153 min (n = 18), 28 min (n = 21), and 205 min (n = 15), respectively. Anterior presentation of the calf was observed in 59% births, whereas posterior presentation occurred in 41% births. Posterior calving presentation was associated with a longer phase II of parturition (p = 0.04), although more data are needed to determine whether the posterior presentation of the calf carries a higher risk for stillbirth. Most (83%) stillbirths occurred in GOHR, indicating that this species might be at a higher risk for stillbirth compared to SWR (17%) (p = 0.07). The median time from birth to the calf standing was longer in the GOHR (64 min) compared to the SWR (30 min) (p = 0.02). Detailed descriptions of the parturition parameters and neonatal landmarks in rhinoceros will aid facilities with rhinoceros breeding programs to recognize abnormalities in the parturient or post-partum periods and guide indications for veterinary intervention.
Lateralised Behavioural Responses in Livestock to Environmental Stressors: Implications for Using Infrared Thermography to Assess Welfare Conditions
Authors: Goma Amira A. , Uddin Jashim , Kieson Emily
Published: November 2023

Lateralised behavioural responses to environmental stressors have become more frequently used as indicators of social welfare in animals. These lateralised behavioural responses are under the control of asymmetrical brain functions as part of the primary functions of most vertebrates and assist in primary social and survival functions. Lateralised behavioural responses originating from the left hemisphere are responsible for processing familiar conditions, while the right hemisphere is responsible for responding to novel stimuli in the environment. The forced lateralisation and side preference tests have been used to determine the visual lateralised behavioural responses in livestock to environmental stressors. Limb preference during movement has also been used to determine motor lateralisation. Although behavioural investigations in livestock have recorded lateralised behavioural responses to environmental stressors, there are still limitations in the implication of lateralisation to other conditions, such as restraint and invasive procedures. Thus, it is important to have a non-invasive measure for these lateralised behavioural responses. Recently, lateralised behavioural responses have been correlated with the use of infrared temperature of external body surfaces, such as the eyes and coronary bands of limbs. This review summarised the different forms of the lateralised behavioural responses in livestock, especially cattle and horses, to environmental stressors, and the association between these responses and the relevant external body surfaces’ infrared temperature, with the purpose of improving the use of non-invasive measures in assessing welfare conditions in animals. The combination of the lateralised behavioural responses and infrared temperature of external body surfaces to environmental stressors could improve the assessment strategies of welfare conditions and the related additional husbandry interventions that could be applied to improve the welfare of farm animals.
Peripheral Giant Cell Granuloma in Pregnancy: A Case Report
Authors: Alcaraz Baturoni Francisco Javier , Zepeda Nuño José Sergio , Nolasco González Brenda Fernanda , Ramos Solano Moisés , Martínez Nieto Melissa , Lomelí Martínez Sarah Monserrat
Published: November 2023

Peripheral giant cell granuloma (PGCG) is an asymptomatic, non-neoplastic, and proliferative lesion of unknown etiology. Possible pre-disposing factors, such as hormonal changes during pregnancy, have been suggested. However, the association between PGCG and pregnancy is controversial. There are few reported clinical cases of pregnancy-associated PGCG in the literature, and they occurred only in the lower jaw. The present report is on a 35-year-old female patient at 36 weeks of gestation who presented with a PGCG in the central and lateral incisors of the upper jaw. Management consisted of complete surgical excision of the lesion along with a margin of healthy tissue under local anesthesia, followed by curettage of the adjacent fibers of the affected bony wall. The patient experienced adequate healing without complications. The diagnosis of PGCG was based on clinical characteristics, imaging examinations, and histopathological confirmation. The patient underwent postoperative follow-up evaluations at 3, 6, and 12 months, and there were no signs of recurrence.
Wavelet Analysis of Ozone Driving Factors Based on ~20 Years of Ozonesonde Measurements in Beijing
Authors: Zeng Yunshu , Zhang Jinqiang , Li Yajuan , Liu Sichang , Chen Hongbin
Published: November 2023

A long-term vertical ozone observational dataset has been provided during 2001–2019 by ozonesonde measurements in Beijing on the North China Plain. Previous studies using this dataset primarily focused on the vertical characteristics of climatological ozone and its variation; however, the driving factors of ozone variation have not been well discussed. In this study, by applying the wavelet analysis method (including continuous wavelet transform and cross wavelet) and sliding correlation coefficients to ~20 years of ozonesonde measurements collected in Beijing, we analyzed the dominant modes of ozone column variability within three height ranges over Beijing (total column ozone: TOT; stratospheric column ozone: SCO; and tropospheric column ozone: TCO). Moreover, we also preliminarily discussed the relationship between these three ozone columns and the El Niño Southern Oscillation (ENSO), Quasi-biennial Oscillation (QBO), and 11-year solar activity cycle. The results revealed that the ozone columns within the three height ranges predominantly adhered to interannual variability patterns, and the short-term variabilities in TOT and SCO may have been related to eruptive volcanic activity. In comparison to the TOT and SCO, the TCO was more susceptible to the forcing influences of high-frequency factors such as pollutant transport. Similar to the results in other mid-latitude regions, strong ENSO and QBO signals were revealed in the interannual ozone column variability over Beijing. The TOT and SCO showed positive anomalous responses to ENSO warm-phase events, and the peak of the ENSO warm phase led the winter peaks of the TOT and SCO by approximately 3–6 months. During the strong cold–warm transition phase in 2009–2012, the TOT and SCO showed a significant positive correlation with the ENSO index. The strong seasonality of the meridional circulation process driven by the QBO led to a significant positive correlation between the QBO index and the TOT and SCO in the interannual cycle, except for two periods of abnormal QBO fluctuations in 2010–2012 and 2015–2017, whereas the TCO showed a time-lagged correlation of approximately 3 months in the annual cycle relative to the QBO due to the influence of the thermodynamic tropopause. In addition, analysis of the F10.7 index and the ozone columns revealed that the ozone columns over Beijing exhibited lagged responses to the peaks of sunspot activity, and there was no obvious correlation between ozone columns and 11-year solar activity cycle. Given the complex driving mechanism of the climatic factors on local ozone variability, the preliminary results obtained in this study still require further validation using longer time series of observational data and the combination of chemical models and more auxiliary data.
Re-Engineering Dew-Harvesting Cactus Macrostructures to Enhance Water Collection as an Adaptive Climate Change Strategy: An Experimental Comparison
Authors: Malik Tegwen , Gethin David , Boy Frederic , Davies Gareth , Parker Andrew
Published: November 2023

The spinal structures found on Copiapoa cinerea var. haseltoniana, an efficient dew-harvesting cactus, were fabricated and evaluated both in a climate chamber and outdoors in dewy conditions. A mix of aluminium and steel was used to fabricate these surfaces, with aluminium being used for everything but the replicated spine features, which were constructed from steel. Each surface was entirely coated with a highly emissive paint containing an alumina–silicate OPUR additive. Three replica versions (stem only, spine only, and stem & spine) were compared to a flat planar reference surface. Experimental results demonstrated that all three biomimetic macro-structured surfaces significantly enhanced dew harvesting compared to the reference surface. It was established that the stem & spine replica, spine replica, and stem replica all demonstrated significantly more dew harvesting, with mean efficiency ratios in respect of the reference surface of 1.08 ± 0.03, 1.08 ± 0.02, and 1.02 ± 0.01, respectively. Furthermore, the method of surface water collection was found to influence the water collection rate. The diagonal run-off flow across a flat planar surface was 34% more efficient than the parallel run-off flow on the same surface. These findings provide valuable insights for the construction and installation of biomimetic-inspired dew-harvesting devices, particularly in regions that are most challenged by decreasing dew yields as a result of climate change.
Research on the Construction Method of Heat Island Network Resistance Surface Based on County Perspective
Authors: Cheng Shiyun , Li Shuai , Qi Feng
Published: November 2023

The urban heat island effect is a typical feature of urban climates. Problems associated with urban heat islands include an increase in energy consumption and health issues resulting from a reduction in thermal comfort. The method of constructing a heat island network, which helps identify and analyze urban heat island phenomena, has become a focus of research in areas such as the effect of urban greening on the heat island effect. Considering this, Landsat remote sensing images from Tiantai County, Taizhou City, were used to identify and analyze the distribution characteristics of heat island patches in Tiantai County as a whole, using morphological spatial pattern analysis (MSPA) combined with the model of minimum cumulative resistance (MCR). Simultaneously, based on the local climate zones theory, the resistance value was calculated to construct the Tiantai County heat island network, and the following conclusions were formed after analyzing the results: (1) The final constructed heat island network consists of 20 important heat island sources, 60 important heat island corridors, and 130 general heat island corridors. (2) The important heat-island-source land matrix consists primarily of an impermeable surface, bare soil, and sand. Important heat island corridors are mostly found in the impermeable surface area. (3) According to calculations, dense trees have a resistance value of 100. Water bodies and scattered trees have resistance values of 10 and 5, respectively. They all have a blocking effect on the heat island.
Catalog of Geomagnetic Storms with Dst Index ≤ −50 nT and Their Solar and Interplanetary Origin (1996–2019)
Authors: Miteva Rositsa , Samwel Susan W.
Published: November 2023

We present a comprehensive catalog of geomagnetic storms (GSs) with a Dst index ≤−50 nT detected during solar cycles (SCs) 23 and 24 (1996–2019). About 550 events were identified in the Kyoto database and used as a starting point for this study. The solar origin of the GSs, in terms of coronal mass ejections (CMEs), solar flares (SFs), and in situ-observed energetic particles, was identified where possible using temporal constraints and wide Earth-directed ejecta. In addition, any accompanied interplanetary (IP) sources, such as ICMEs and IP shock waves detected at 1 AU, are also considered. The resulting occurrence rates and correlation plots are presented and discussed in the space weather framework.
I-CPA: An Improved Carnivorous Plant Algorithm for Solar Photovoltaic Parameter Identification Problem
Authors: Beşkirli Ayşe , Dağ İdiris
Published: November 2023

The carnivorous plant algorithm (CPA), which was recently proposed for solving optimization problems, is a population-based optimization algorithm inspired by plants. In this study, the exploitation phase of the CPA was improved with the teaching factor strategy in order to achieve a balance between the exploration and exploitation capabilities of CPA, minimize getting stuck in local minima, and produce more stable results. The improved CPA is called the I-CPA. To test the performance of the proposed I-CPA, it was applied to CEC2017 functions. In addition, the proposed I-CPA was applied to the problem of identifying the optimum parameter values of various solar photovoltaic modules, which is one of the real-world optimization problems. According to the experimental results, the best value of the root mean square error (RMSE) ratio between the standard data and simulation data was obtained with the I-CPA method. The Friedman mean rank statistical analyses were also performed for both problems. As a result of the analyses, it was observed that the I-CPA produced statistically significant results compared to some classical and modern metaheuristics. Thus, it can be said that the proposed I-CPA achieves successful and competitive results in identifying the parameters of solar photovoltaic modules.
Biosensors for Odor Detection: A Review
Authors: Deng Hongchao , Nakamoto Takamichi
Published: November 2023

Animals can easily detect hundreds of thousands of odors in the environment with high sensitivity and selectivity. With the progress of biological olfactory research, scientists have extracted multiple biomaterials and integrated them with different transducers thus generating numerous biosensors. Those biosensors inherit the sensing ability of living organisms and present excellent detection performance. In this paper, we mainly introduce odor biosensors based on substances from animal olfactory systems. Several instances of organ/tissue-based, cell-based, and protein-based biosensors are described and compared. Furthermore, we list some other biological materials such as peptide, nanovesicle, enzyme, and aptamer that are also utilized in odor biosensors. In addition, we illustrate the further developments of odor biosensors.
The Pathophysiology of Gilles de la Tourette Syndrome: Changes in Saccade Performance by Low-Dose L-Dopa and Dopamine Receptor Blockers
Authors: Terao Yasuo , Nomura Yoshiko , Fukuda Hideki , Hikosaka Okihide , Kimura Kazue , Matsuda Shun-ichi , Yugeta Akihiro , Fisicaro Francesco , Hoshino Kyoko , Ugawa Yoshikazu
Published: November 2023

Aim: To elucidate the pathophysiology of Gilles de la Tourette syndrome (GTS), which is associated with prior use of dopamine receptor antagonists (blockers) and treatment by L-Dopa, through saccade performance. Method: In 226 male GTS patients (5–14 years), we followed vocal and motor tics and obsessive–compulsive disorder (OCD) after discontinuing blockers at the first visit starting with low-dose L-Dopa. We recorded visual- (VGS) and memory-guided saccades (MGS) in 110 patients and 26 normal participants. Results: At the first visit, prior blocker users exhibited more severe vocal tics and OCD, but not motor tics, which persisted during follow-up. Patients treated with L-Dopa showed greater improvement of motor tics, but not vocal tics and OCD. Patients with and without blocker use showed similarly impaired MGS performance, while patients with blocker use showed more prominently impaired inhibitory control of saccades, associated with vocal tics and OCD. Discussion: Impaired MGS performance suggested a mild hypodopaminergic state causing reduced direct pathway activity in the (oculo-)motor loops of the basal ganglia–thalamocortical circuit. Blocker use may aggravate vocal tics and OCD due to disinhibition within the associative and limbic loops. The findings provide a rationale for discouraging blocker use and using low-dose L-Dopa in GTS.
The Influence of Resistance Training Experience on the Efficacy of Motor Imagery for Acutely Increasing Corticospinal Excitability
Authors: Parsowith Emily J. , Stock Matt S. , Girts Ryan M. , Beausejour Jonathan P. , Alberto Ariel , Carr Joshua C. , Harmon Kylie K.
Published: November 2023

Both motor imagery and resistance–training enhance motor function and corticospinal excitability. We tested the hypothesis that young participants with significant resistance–training experience would show heightened corticospinal excitability during a single session of motor imagery training. Fifty-six participants (mean ± SD age = 22 ± 2 years) were divided into resistance–trained and untrained groups. Forty-one upper-body resistance trained (21 males, 20 females; mean ± SD relative one repetition maximum bench press = 0.922 ± 0.317 kg/kg) and 15 untrained (4 males, 11 females; mean ± SD relative one repetition maximum bench press = 0.566 ± 0.175 kg/kg) participants visited the laboratory on three separate occasions. The first visit served as the familiarization session. During visits 2 and 3, participants engaged in a hand/wrist motor imagery protocol or rested quietly (control condition) in a randomized order. Before and after the interventions, single-pulse transcranial magnetic stimulation (TMS) over the motor cortex was used to measure resting motor–evoked potential amplitude of the first dorsal interosseous muscle. Our main finding was that motor imagery acutely increased corticospinal excitability by ~64% (marginal means pre = 784.1 µV, post = 1246.6 µV; p < 0.001, d = 0.487). However, there was no evidence that the increase in corticospinal excitability was influenced by resistance–training experience. We suspect that our results may have been influenced by the specific nature of the motor imagery task. Our findings have important implications for motor imagery prescription and suggest that motor imagery training may be equally beneficial for both resistance–trained and untrained populations. This study was prospectively registered at ClinicalTrials.gov (Identifier: NCT03889548).
The Novel Antipsychotic Lumateperone (Iti-007) in the Treatment of Schizophrenia: A Systematic Review
Authors: Longo Giulio , Cicolini Angelica , Orsolini Laura , Volpe Umberto
Published: November 2023

Lumateperone (also known as ITI-007 or ITI-722) represents a novel second-generation medication characterized by a favorable safety and tolerability profile. This is attributed to its notable selectivity for D2 receptors within specific regions of the brain. The U.S. Food and Drug Administration (FDA) granted approval for the treatment of schizophrenia in adults in December 2019. Additionally, it gained approval for addressing depressive episodes associated with bipolar I and II disorders in adults, either as a standalone therapy or in conjunction with lithium or valproate, in December 2021. The objective of this investigation is to systematically review the existing literature to assess the safety, tolerability, and efficacy of lumateperone in the treatment of schizophrenia. Lumateperone has demonstrated effectiveness in addressing positive, negative, and cognitive symptoms associated with schizophrenia. The evaluation of safety indicators in the reviewed studies indicates that lumateperone is deemed to be a well-tolerated and safe antipsychotic. Additional research is warranted to explore lumateperone’s efficacy in managing major depressive disorders, behavioral issues in Alzheimer’s disease and dementia, sleep maintenance insomnia, bipolar disorders, and personality disorders.
Stress and Right Prefrontal Transcranial Direct Current Stimulation (tDCS) Interactive Effects on Visual Working Memory and Learning
Authors: Ankri Yael L. E. , Braw Yoram C. , Meiron Oded
Published: November 2023

Stress impacts prefrontal cortex (PFC) activity and modulates working memory performance. In a recent study, stimulating the dorsolateral PFC (dlPFC) using transcranial direct current stimulation (tDCS) interacted with social stress in modulating participants’ working memory. More specifically, stress disrupted the enhancing effects of dlPFC tDCS on working memory performance. The current study aimed to further explore these initial findings by randomizing healthy females to four experimental conditions (N = 130); stimulation (right dlPFC tDCS vs. sham) and stress manipulation (social stress vs. control). Participants performed cognitive tasks (i.e., visual working memory task and a visual declarative memory task) at baseline and post-stimulation. They also completed self-report measures of stress and anxiety. A significant stimulation × stress interaction was evident in the declarative memory (One-Card Learning, OCL) task, while working memory performance was unaffected. Though tDCS stimulation and stress did not interact to affect working memory, further research is warranted as these initial findings suggest that immediate visual-memory learning may be affected by these factors. The limited number of earlier studies, as well as the variability in their designs, provides additional impetus for studying the interactive effects of stress and tDCS on human visual learning.
Visualization and Characterization of the Brain Regional Heterogeneity of Astrocyte–Astrocyte Structural Interactions by Using Improved Iontophoresis with Dual-Fluorescent Dyes
Authors: Li Qingran , Zhou Bin , Su Mengchan , Liao Ping , Lei Fan , Li Xin , Liao Daqing , Zhang Xia , Jiang Ruotian
Published: November 2023

Astrocytes are morphologically intricate cells and actively modulate the function of the brain. Through numerous fine processes, astrocytes come into contact with neurons, blood vessels, and other glia cells. Emerging evidence has shown that astrocytes exhibit brain regional diversity in their morphology, transcriptome, calcium signaling, and functions. However, little is known about the brain regional heterogeneity of astrocyte–astrocyte structural interaction. So far, the visualization and characterization of the morphological features of adjacent astrocytes have been difficult, and as a result, it is still well-accepted that astrocytes in the adult brain share non-overlapped territory. In contrast, employing an approach that combines viral labeling with dual-fluorescent dyes iontophoresis under brightfield and imaging using confocal microscopy allows for the efficient and specific labeling of adjacent astrocytes, enabling a comprehensive visualization of their fine processes and the degree of their territorial overlap. Our study in the hypothalamic regions of the brain revealed a marked spatial overlap among adjacent astrocytes, which differs from the conventional understanding based on more extensively studied regions, like the hippocampus. Additionally, we revealed the heterogeneity of the astrocyte–neuron ratio across brain regions and conducted an assessment of the photostability and labeling efficiency of fluorescent dyes used for labeling adjacent astrocytes. Our study provides new insights for studying the morphological heterogeneity of astrocytes across the central nervous system.
Nurturing the Positive Mental Health of Autistic Children, Adolescents and Adults alongside That of Their Family Care-Givers: A Review of Reviews
Authors: McConkey Roy
Published: November 2023

The rising prevalence of autism internationally has been accompanied by an increased appreciation of the poorer mental health experienced by people with this condition and also of their family care-givers. In particular, higher incidences of anxiety and depression are reported in high-income nations and these conditions are likely to be under-recognised and under-reported in lower-resourced regions or countries. Mainstream mental health services seem to be ill-equipped to respond adequately to the needs of autistic persons and their care-givers. This literature review of 29 recently published reviews covering nearly 1000 journal articles summarises the insights and strategies that have been shown to promote the mental health and emotional wellbeing of autistic persons. In particular, a focus on family-centred, community-based supports is recommended that aim to enhance social communication, extend social connections and promote an individual’s self-esteem, self-determination and social motivation. These low-cost interventions are especially pertinent in low-resourced settings, but they can be used internationally to prevent mental illness and assist in the treatment of anxiety and depression in autistic persons and their family carers. The priority is to focus on primary-care responses with cross-sectoral working rather than investing in high-cost psychiatric provision.
An Optimized Method to Culture Human Primary Lung Tumor Cell Spheroids
Authors: Mueggler Amanda , Pilotto Eléa , Perriraz-Mayer Nadja , Jiang Sicong , Addeo Alfredo , Bédat Benoît , Karenovics Wolfram , Triponez Frédéric , Serre-Beinier Véronique
Published: November 2023

Lung cancer is the leading cause of cancer mortality worldwide, with a median survival rate at 5 years of less than 20%. While molecular mapping aids in selecting appropriate therapies, it cannot predict personalized treatment response and long-term efficacy. For addressing these challenges, there is a great need for functional tests. Within this context, we developed patient-derived spheroids (PDS) from tumor and adjacent normal tissue to biomimic the respective tissue for assessing the personalized drug treatment response in vitro. Surgically resected lung specimens were used to generate spheroids using a two-step culture procedure. Flow cytometry and immune staining enabled the characterization of different cell populations resulting from the lung samples. PDS phenotype, cell proliferation and apoptosis were evaluated. Differential gene expression between tumor and adjacent normal tissue was analyzed via RT-qPCR. PDS drug sensitivity was assessed using a cell metabolic assay in response to two chemotherapeutic drug combinations. Cellular and molecular analysis revealed the proportion of epithelial cells, fibroblasts, and immune cells in the patients’ tissue samples. Subsequently, PDS models from tumor and normal lung were successfully established using the expanded epithelial cells. As a proof of concept, an analysis of the drug treatment using PDS of lung adenoid cystic carcinoma exhibited a dose-dependent effect in response to cisplatin/etoposide and cisplatin/paclitaxel. Our spheroid model of both tumor and non-tumor lung cells holds great promise for enhancing the treatment efficacy in the cancer patients.
Tertiary Inpatient Palliative Care within Region-Wide Services: A Retrospective Examination of Psychosocial and Medical Demographics at Admissions
Authors: Feldstain Andrea , Buote Lauren , de Groot Janet M. , Hughes Jennifer , Sinnarajah Aynharan
Published: November 2023

Palliative care offers symptom relief and improved quality of life. Tertiary palliative care units (TPCUs) focus on complex suffering under the care of specialist palliative physicians and interdisciplinary teams. The Intensive Palliative Care Unit (IPCU) is a TPCU integrated in well-developed region-wide palliative services in Calgary, Canada. We compared the population accessing the IPCU to published data from other Canadian sites. Methods: A retrospective chart review was conducted using 8 sample months over a 2-year period. We gleaned psychosocial and medical demographics alongside the self-reported symptom burden on the Edmonton Symptom Assessment System. Descriptive statistics were calculated. Results: Adults (n = 117) with cancer admitted to the IPCU were 5–10 years younger, had later-stage cancer, and had higher discharges to preferred locations than other published Canadian TPCUs. Up to two months before admission, most commonly reported symptoms were consistent with the outpatient literature although with higher reported intensity. Discussion: With more advanced disease, younger age, and elevated symptom burden before admission, the IPCU still discharged patients to preferred locations at higher rates than other sites. This may be due to integration in the region’s organized palliative care services. Conclusion: With proper integration, a TPCU may be able to improve quality of life and reduce deaths in hospitals.
Five-Fraction Proton Therapy for the Treatment of Skull Base Chordomas and Chondrosarcomas: Early Results of a Prospective Series and Description of a Clinical Trial
Authors: Sallabanda Morena , Vera Juan , Pérez Juan , Matute Raúl , Montero Marta , de Pablo Ana , Cerrón Fernando , Valero Mireia , Castro Juan , Mazal Alejandro , Miralbell Raymond
Published: November 2023

(1) Background: Our purpose is to describe the design of a phase II clinical trial on 5-fraction proton therapy for chordomas and chondrosarcomas of the skull base and to present early results in terms of local control and clinical tolerance of the first prospective series. (2) Methods: A dose of 37.5 GyRBE in five fractions was proposed for chordomas and 35 GyRBE in five fractions for chondrosarcomas. The established inclusion criteria are age ≥ 18 years, Karnofsky Performance Status ≥ 70%, clinical target volume up to 50 cc, and compliance with dose restrictions to the critical organs. Pencil beam scanning was used for treatment planning, employing four to six beams. (3) Results: A total of 11 patients (6 chordomas and 5 chondrosarcomas) were included. The median follow-up was 12 months (9–15 months) with 100% local control. Acute grade I–II headache (64%), grade I asthenia and alopecia (45%), grade I nausea (27%), and grade I dysphagia (18%) were described. Late toxicity was present in two patients with grade 3 temporal lobe necrosis. (4) Conclusions: Hypofractionated proton therapy is showing encouraging preliminary results. However, to fully assess the efficacy of this therapeutic approach, future trials with adequate sample sizes and extended follow-ups are necessary.
Is There a Place for Brachytherapy in Vulvar Cancer? A Narrative Review
Authors: Cordoba Sofia , Cordoba Abel , Gil Beatriz , Benlloch Raquel , Rodriguez Silvia , Najjari-Jamal Dina , Santana Sofía , Bresson Lucie , de la Fuente Cristina , Romero Jesús
Published: November 2023

Vulvar cancer is a relatively rare neoplasm. The essential treatment is surgery for the primary tumour. However, postoperative recurrence rates are high, even in early-stage disease when tumour-free surgical margins are achieved or in the absence of associated risk factors (lymph node metastases, deep stromal invasion or invasion of the lymphatic vascular space). Radiotherapy plays an important role in the treatment of vulvar cancer. Adjuvant treatment after surgery as well as primary treatment of locally advanced vulvar cancer (LAVC) is composed of two key radiotherapy treatment scenarios, external beam radiation therapy (EBRT) either combined or not combined with brachytherapy (BT). In a recurrence setting, where surgery is not an option, BT alone or in combination with EBRT can be used. Compared to EBRT, BT has the radiobiological potential to improve dose to the target volume, minimise the dose to organs at risk, and facilitate hypofractionated-accelerated treatment. This narrative review presents recent data on the role of BT in the treatment of primary and/or recurrent vulvar cancer, including radiobiological, clinical, and therapeutic aspects.
Targeted Therapies for Kirsten Rat Sarcoma (KRAS) G12C Mutant Metastatic Non-Small-Cell Lung Cancers
Authors: O’Leary Cian , Murphy Grace , Yeung Yong , Tang Ming , Jain Vikram , O’Leary Connor G
Published: November 2023

Non-small-cell lung cancer (NSCLC) is a prevalent and often fatal malignancy. Advancements in targeted therapies have improved outcomes for NSCLC patients in the last decade. Kirsten rat sarcoma virus (KRAS) is a commonly mutated oncogene in NSCLC, contributing to tumorigenesis and proliferation. Though classically difficult to target, recently developed KRAS G12C inhibitors (sotorasib and adagrasib) have now overcome this therapeutic hurdle. We discuss the evidence for these medications, their pitfalls and adverse effects, as well as future directions in this space. Though these medications demonstrate substantial response rates in a heavily pre-treated advanced NSCLC cohort, as phase-3 evidence does not yet demonstrate an overall survival benefit versus standard-of-care chemotherapy, docetaxel. Additionally, these medications appear to have a negative interaction in combination with immunotherapies, with substantially greater hepatotoxicity rates observed. Despite this, it is undeniable that these medications represent an important advancement in targeted and personalised oncological treatment. Current and future trials assessing these medications in combination and through sequencing strategies will likely yield further clinically meaningful outcomes to guide treatment in this patient cohort.
Epigenetic and Genetic Keys to Fight HPV-Related Cancers
Authors: Folliero Veronica , Dell’Annunziata Federica , Chianese Annalisa , Morone Maria , Mensitieri Francesca , Di Spirito Federica , Mollo Antonio , Amato Massimo , Galdiero Massimiliano , Dal Piaz Fabrizio , Pagliano Pasquale , Rinaldi Luca , Franci Gianluigi
Published: November 2023

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our understanding of the disease. Recent investigations have unveiled the capacity of viral oncoproteins to influence epigenetic changes within HPV-related tumors, and conversely, these tumors exert an influence on the surrounding epigenetic landscape. Given the escalating occurrence of HPV-triggered tumors and the deficiency of efficacious treatments, substantial challenges emerge. A promising avenue to address this challenge lies in epigenetic modulators. This review aggregates and dissects potential epigenetic modulators capable of combatting HPV-associated infections and diseases. By delving into these modulators, novel avenues for therapeutic interventions against HPV-linked cancers have come to the fore.
Novel Developments in the Treatment of Multiple Myeloma-Associated Bone Disease
Authors: Johansen Martin , Levring Mette Bøegh , Stokbro Kasper , Diaz-delCastillo Marta , Khan Abdul Ahad , Wickstroem Line Adsbøll , Gundesen Michael Tveden , Kristensen Ida Bruun , Nyvold Charlotte Guldborg , Andersen Mikkel Østerheden , Andersen Thomas Levin , Abildgaard Niels , Lund Thomas
Published: November 2023

Osteolytic bone disease is present in about 80% of patients with multiple myeloma at the time of diagnosis. Managing bone disease in patients with multiple myeloma is a challenge and requires a multi-faceted treatment approach with medication, surgery, and radiation. The established treatments with intravenous or subcutaneous antiresorptives can cause debilitating adverse events for patients, mainly osteonecrosis of the jaw, which, traditionally, has been difficult to manage. Now, oral surgery is recommended and proven successful in 60–85% of patients. Patients with spinal involvement may benefit from surgery in the form of vertebroplasty and kyphoplasty for pain relief, improved mobility, and reestablished sagittal balance, as well as the restoration of vertebral height. These procedures are considered safe, but the full therapeutic impact needs to be investigated further. Ixazomib, the first oral proteasome inhibitor, increases osteoblast differentiation, and recently published preliminary results in patients treated with Ixazomib maintenance have promisingly shown increased trabecular volume caused by prolonged bone formation activity. Other novel potential treatment strategies are discussed as well.
Disparities in Receipt of National Comprehensive Cancer Network Guideline-Adherent Care and Outcomes among Women with Triple-Negative Breast Cancer by Race/Ethnicity, Socioeconomic Status, and Insurance Type
Authors: Ubbaonu Chimezie D. , Chang Jenny , Ziogas Argyrios , Mehta Rita S. , Kansal Kari J. , Zell Jason A.
Published: November 2023

Background: The National Comprehensive Cancer Network guidelines were designed to improve patient outcomes. Here, we examine factors that may contribute to outcomes and guideline adherence in patients with triple-negative breast cancer. Methods: This was a retrospective cohort study of women with triple-negative breast cancer using the California Cancer Registry. Adherent treatment was defined as the receipt of a combination of surgery, lymph node assessment, adjuvant radiation, and/or chemotherapy. A multivariable logistic regression was used to determine the effects of independent variables on adherence to the NCCN guidelines. Disease-specific survival was calculated using Cox regression analysis. Results: A total of 16,858 women were analyzed. Black and Hispanic patients were less likely to receive guideline-adherent care (OR 0.82, 95%CI 0.73–0.92 and OR 0.87, 95%CI 0.79–0.95, respectively) compared to White patients. Hazard ratios adjusted for adherent care showed that Black patients had increased disease-specific mortality (HR 1.28, 95%CI 1.16–1.42, p < 0.0001) compared to White patients. Conclusions: A significant majority of breast cancer patients in California continue to receive non-guideline-adherent care. Non-Hispanic Black patients and patients from lower SES quintile groups were less likely to receive guideline-adherent care. Patients with non-adherent care had worse disease-specific survival compared to recipients of NCCN guideline-adherent care.
Longitudinal Study of Advanced Non-Small Cell Lung Cancer with Initial Durable Clinical Benefit to Immunotherapy: Strategies for Anti-PD-1/PD-L1 Continuation beyond Progression
Authors: Pourmir Ivan , Elaidi Reza , Maaradji Zineb , De Saint Basile Hortense , Ung Monivann , Ismaili Mohammed , Fournier Laure , Rance Bastien , Gibault Laure , Ben Dhiab Rym , Gazeau Benoit , Fabre Elizabeth
Published: November 2023

Background and aim: A better understanding of resistance to checkpoint inhibitors is essential to define subsequent treatments in advanced non-small cell lung cancer. By characterizing clinical and radiological features of progression after anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1), we aimed to define therapeutic strategies in patients with initial durable clinical benefit. Patients and methods: This monocentric, retrospective study included patients who presented progressive disease (PD) according to RECIST 1.1 criteria after anti-PD-1/PD-L1 monotherapy. Patients were classified into two groups, “primary resistance” and “Progressive Disease (PD) after Durable Clinical Benefit (DCB)”, according to the Society of Immunotherapy of Cancer classification. We compared the post-progression survival (PPS) of both groups and analyzed the patterns of progression. An exploratory analysis was performed using the tumor growth rate (TGR) to assess the global growth kinetics of cancer and the persistent benefit of immunotherapy beyond PD after DCB. Results: A total of 148 patients were included; 105 of them presented “primary resistance” and 43 “PD after DCB”. The median PPS was 5.2 months (95% CI: 2.6–6.5) for primary resistance (p < 0.0001) vs. 21.3 months (95% CI: 18.5–36.3) for “PD after DCB”, and the multivariable hazard ratio was 0.14 (95% CI: 0.07–0.30). The oligoprogression pattern was frequent in the “PD after DCB” group (76.7%) and occurred mostly in pre-existing lesions (72.1%). TGR deceleration suggested a persistent benefit of PD-1/PD-L1 blockade in 44.2% of cases. Conclusions: PD after DCB is an independent factor of longer post-progression survival with specific patterns that prompt to contemplate loco-regional treatments. TGR is a promising tool to assess the residual benefit of immunotherapy and justify the continuation of immunotherapy in addition to radiotherapy or surgery.
Alternating Gemcitabine/Nab-Paclitaxel (GA) and 5-FU/Leucovorin/Irinotecan (FOLFIRI) as First-Line Treatment for De Novo Metastatic Pancreatic Cancer (MPC): Safety and Effect
Authors: Schroeder Brett A. , Mandelson Margaret T. , Picozzi Vincent J.
Published: November 2023

Background: Both gemcitabine- and 5-fluorouracil (5-FU)-based chemotherapy regimens have demonstrated efficacy in metastatic pancreatic cancer (MPC). Alternating these regimens may reduce toxicity, slow resistant cancer biology emergence, and provide a platform for the addition of other therapeutic agents. Alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) in MPC has previously been reported at our own institution and elsewhere. An extension of our institutional observations is reported here. Methods: Patient eligibility required the following: biopsy-proven de novo MPC, no prior evidence of disease on CT, ECOG performance status (PS) ≤ 2, and bi-dimensionally measurable disease. Treatment (Tx) entailed gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 1, (8), 15 alternating every 8 weeks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 weeks. Tx spanned up to 12 cycles. Tx thereafter was decided following patient/physician discussion. Results: Median overall survival (mOS) was 13.2 months (95% CI 10.9–16.5 months). Median progression-free survival (mPFS) was 8.5 months (95% CI, 7.1–9.9). The 6-, 12-, 18-, and 24-month OS rates were 88%, 54%, 36%, and 20%, respectively. The disease control rate at 16 weeks was 83% (37% PR, 46% SD). Hematologic toxicity grade ≥ 3 included 9.3% anemia, 10.2% neutropenia, and 4.6% thrombocytopenia. Neutrophil growth factors were not used in this cohort. Non-hematologic toxicities grade ≥ 3 included neuropathy 0.9%, nausea/vomiting 0.9%, and diarrhea 0.9%. No patients experienced mucositis on this regimen. Conclusions: Alternating GA/FOLFIRI in MPC has a favorable toxicity profile in comparison to current standard regimens. Median OS was at least competitive with standard regimens, and longer-term (18 and 24 months) OS seemed particularly encouraging. Treatment for ≥48 weeks and ECOG PS of zero at the time of treatment initiation were prognostically significant. Further investigation using this regimen including randomized comparisons, the incorporation of molecular data, and use of additional agents is merited.