bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking AIM at serious illness: implementing an access to investigational medicines expanded access program
Authors: Joly Meghan Morrison , Edwards Terri L. , Jerome Rebecca N. , Mainor Alex , Bernard Gordon R. , Pulley Jill M.
Published: October 2023

When seriously ill patients have exhausted all treatment options available as part of usual care, the use of investigational agents may be warranted. Food and Drug Administration’s (FDA) Expanded Access (EA) pathway provides a mechanism for these patient’s physicians to pursue use of an investigational agent outside of a clinical trial when trial enrollment is not a feasible option. Though FDA has recently implemented processes to significantly streamline the regulatory portion of the process, the overall pathway has several time-consuming components including communication with the pharmaceutical company and the associated institutional requirements for EA use (contracting, Institutional Review Board [IRB], pharmacy, billing). Here, we present our experience building infrastructure at the Vanderbilt University Medical Center (VUMC) to support physicians and patients in pursuing EA, called the Access to Investigational Medicines (AIM) Platform, aligning the needs and responsibilities of institutional stakeholders and streamlining to ensure efficiency and regulatory compliance. Since its launch, the AIM team has experienced steady growth, supporting 40 EA cases for drugs/biologics, including both single patient cases and intermediate-size EA protocols in the emergent and non-emergent setting. As the EA pathway is a complex process that requires expert facilitation, we propose prioritizing EA support infrastructure at major academic medical centers as an essential regulatory knowledge function.
Study on secondary metabolites of endophytic fungus Diaporthe sp. AC1 induced by tryptophan analogs
Authors: Zhang Shikai , Xu Qing , Ji Changbo , Han Xiaoyu , Zhou Yang , Liang Chao , Ma Linran , Sun Weijian , Li Yanling , Yang Zhengyou , Zhao Fengchun , Tian Yuan
Published: October 2023

Small molecule-induced fermentation of the endophytic fungus Diaporthe sp. AC1 originated from Artemisia argyi was executed to investigate its secondary metabolites. It was fermented in a culture medium containing 5-hydroxytryptophan (5-HTP), 1-methyl-L-tryptophan (1-MT), and tryptamine (TA), respectively. The antibacterial activities of crude extracts against pathogenic bacteria and pathogenic fungi were determined by using the Oxford cup method, while the cytotoxicity of crude extracts against cancer cells was determined by using the MTT method. The results showed that the secondary metabolites of Diaporthe sp. AC1 induced by 1-MT exhibited optimal antibacterial activity and tumor cytotoxicity. The induction conditions of 1-MT were optimized, and the antibacterial activities and tumor cytotoxicity of crude extracts under different induction conditions were investigated. As indicated, the optimal moment for 1-MT addition was before inoculation and its optimal concentration was 0.25 mM. Under these conditions, Diaporthe sp. AC1 was fermented and approximately 12 g of crude extracts was obtained. The crude extracts were then separated and purified to acquire nine monomer compounds, including three new compounds (1–3) and six known compounds (4–9). The antibacterial activities of the compounds against pathogenic bacteria and pathogenic fungi were investigated by using the microdilution method, while their cytotoxicity against cancer cells was analyzed by using the MTT method. The results demonstrated that Compound 1 exhibited moderate antibacterial activities against Verticillium dahlia, Fusarium graminearum, and Botrytis cinerea, as well as a low inhibitory activity against Listeria monocytogenes. Nevertheless, Compound 1 showed significant cytotoxicity against five cancer cells, with IC50 ranging from 12.26 to 52.52 μM. Compounds 2 and 3 exhibited negligible biological activity, while other compounds showed detectable inhibitory activities against pathogenic bacteria and cancer cells.
Suaeda australis and its associated rhizosphere microbiota: a comparison of the nutrient removal potential between different shrimp farm sediments in New Caledonia
Authors: Colette Marie , Guentas Linda , Della Patrona Luc , Ansquer Dominique , Callac Nolwenn
Published: October 2023

Shrimp rearing generate organic waste that is trapped in the pond sediment. In excess, these wastes may impair aquaculture ecosystem and shrimps’ health. To promote the biological oxidation of accumulated organic waste, the pond is drained and dried at the end of each production cycle. However, this practice is not always conducive to maintaining microbial decomposition activities in sediments. Shrimp production in New Caledonia is no exception to this problem of pollution of pond bottoms. One promising way of treating this waste would be bioremediation, using a native halophyte plant and its microbiota. Thus, this study explored the nutrient removal potential of Suaeda australis and its microbiota on sediments from four shrimp farms. Suaeda australis was grown in an experimental greenhouse for 6 months. In order to mimic the drying out of the sediments, pots containing only sediments were left to dry in the open air without halophytes. An analysis of the chemical composition and active microbiota was carried out initially and after 6 months in the sediments of the halophyte cultures and in the dry sediments for each farm, respectively. In the initial state, the chemical parameters and the microbial diversity of the sediment varied considerably from one farm to another. Growing Suaeda australis reduced the nitrogen, phosphorus and sulfur content in all type of sediment. However, this reduction varied significantly from one sediment to another. The rhizosphere of Suaeda australis is mainly composed of micro-organisms belonging to the Alphaproteobacteria class. However, the families recruited from this class vary depending on the farm in question. Depending on the sediment, the variation in microbiota leads to different putative biochemical functions. For two of the farms, a similar reduction in nitrogen concentration was observed in both dry and cultivated sediments. This suggests that certain initial chemical characteristics of the sediments influence the nutrient removal efficiency of Suaeda australis. Our study therefore highlights the need to control the pH of sediments before cultivation or in dry sediments in order to ensure optimal microbial decomposition of organic waste and nutrient cycling.
A comprehensive investigation of protein expression profiles in L. monocytogenes exposed to thermal abuse, mild acid, and salt stress conditions
Authors: D'Onofrio Federica , Schirone Maria , Krasteva Ivanka , Tittarelli Manuela , Iannetti Luigi , Pomilio Francesco , Torresi Marina , Paparella Antonello , D'Alterio Nicola , Luciani Mirella
Published: October 2023

Preventing L. monocytogenes infection is crucial for food safety, considering its widespread presence in the environment and its association with contaminated RTE foods. The pathogen's ability to persist under adverse conditions, for example, in food processing facilities, is linked to virulence and resistance mechanisms, including biofilm formation. In this study, the protein expression patterns of two L. monocytogenes 1/2a strains, grown under environmental stressors (mild acidic pH, thermal abuse, and high concentration of NaCl), were investigated. Protein identification and prediction were performed by nLC-ESI-MS/MS and nine different bioinformatic software programs, respectively. Gene enrichment analysis was carried out by STRING v11.05. A total of 1,215 proteins were identified, of which 335 were non-cytosolic proteins and 265 were immunogenic proteins. Proteomic analysis revealed differences in protein expression between L. monocytogenes strains in stressful conditions. The two strains exhibited unique protein expression profiles linked to stress response, virulence, and pathogenesis. Studying the proteomic profiles of such microorganisms provides information about adaptation and potential treatments, highlighting their genetic diversity and demonstrating the utility of bioinformatics and proteomics for a broader analysis of pathogens.
Awareness and knowledge of female genital schistosomiasis in a population with high endemicity: a cross-sectional study in Madagascar
Authors: Rausche Pia , Rakotoarivelo Rivo Andry , Rakotozandrindrainy Raphael , Rakotomalala Rivo Solotiana , Ratefiarisoa Sonya , Rasamoelina Tahinamandranto , Kutz Jean-Marc , Jaeger Anna , Hoeppner Yannick , Lorenz Eva , May Jürgen , Puradiredja Dewi Ismajani , Fusco Daniela
Published: October 2023

Introduction

Female genital schistosomiasis (FGS) is a neglected disease with long-term physical and psychosocial consequences, affecting approximately 50 million women worldwide and generally representing an unmet medical need on a global scale. FGS is the chronic manifestation of a persistent infection with Schistosoma haematobium. FGS services are not routinely offered in endemic settings with a small percentage of women at risk receiving adequate care. Madagascar has over 60% prevalence of FGS and no guidelines for the management of the disease. This study aimed to determine FGS knowledge among women and health care workers (HCWs) in a highly endemic area of Madagascar.

Methods

A convenience sampling strategy was used for this cross-sectional study. Descriptive statistics including proportions and 95% confidence intervals (CI) were calculated, reporting socio-demographic characteristics of the population. Knowledge sources were evaluated descriptively. Binary Poisson regression with robust standard errors was performed; crude (CPR) and adjusted prevalence ratio (APR) with 95% CIs were calculated.

Results

A total of 783 participants were included in the study. Among women, 11.3% (n = 78) were aware of FGS while among the HCWs 53.8% (n = 50) were aware of FGS. The highest level of knowledge was observed among women in an urban setting [24%, (n = 31)] and among those with a university education/vocational training [23% (n = 13)]. A lower APR of FGS knowledge was observed in peri-urban [APR 0.25 (95% CI: 0.15; 0.45)] and rural [APR 0.37 (95% CI 0.22; 0.63)] settings in comparison to the urban setting. Most HCWs reported other HCWs [40% (n = 20)] while women mainly reported their family [32% (n = 25)] as being their main source of information in the 6 months prior to the survey.

Discussion and conclusions

Our study shows limited awareness and knowledge of FGS among population groups in the highly endemic Boeny region of Madagascar. With this study we contribute to identifying an important health gap in Madagascar, which relates to a disease that can silently affect millions of women worldwide. In alignment with the targets of the NTD roadmap, addressing schistosomiasis requires a paradigm shift for its control and management including a greater focus on chronic forms of the disease.
An adaptive control framework based multi-modal information-driven dance composition model for musical robots
Authors: Xu Fumei , Xia Yu , Wu Xiaorun
Published: October 2023

Currently, most robot dances are pre-compiled, the requirement of manual adjustment of relevant parameters and meta-action to change the dancing to another type of music would greatly reduce its function. To overcome the gap, this study proposed a dance composition model for mobile robots based on multimodal information. The model consists of three parts. (1) Extraction of multimodal information. The temporal structure feature method of structure analysis framework is used to divide audio music files into music structures; then, a hierarchical emotion detection framework is used to extract information (rhythm, emotion, tension, etc.) for each segmented music structure; calculating the safety of the current car and surrounding objects in motion; finally, extracting the stage color of the robot's location, corresponding to the relevant atmosphere emotions. (2) Initialize the dance library. Dance composition is divided into four categories based on the classification of music emotions; in addition, each type of dance composition is divided into skilled composition and general dance composition. (3) The total path length can be obtained by combining multimodal information based on different emotions, initial speeds, and music structure periods; then, target point planning can be carried out based on the specific dance composition selected. An adaptive control framework based on the Cerebellar Model Articulation Controller (CMAC) and compensation controllers is used to track the target point trajectory, and finally, the selected dance composition is formed. Mobile robot dance composition provides a new method and concept for humanoid robot dance composition.
Changes in heme oxygenase level during development affect the adult life of Drosophila melanogaster
Authors: Bilska Bernadetta , Damulewicz Milena , Abaquita Terence Al L. , Pyza Elzbieta
Published: October 2023

Heme oxygenase (HO) has been shown to control various cellular processes in both mammals and Drosophila melanogaster. Here, we investigated how changes in HO levels in neurons and glial cells during development affect adult flies, by using the TARGET Drosophila system to manipulate the expression of the ho gene. The obtained data showed differences in adult survival, maximum lifespan, climbing, locomotor activity, and sleep, which depended on the level of HO (after ho up-regulation or downregulation), the timing of expression (chronic or at specific developmental stages), cell types (neurons or glia), sex (males or females), and age of flies. In addition to ho, the effects of changing the mRNA level of the Drosophila CNC factor gene (NRF2 homolog in mammals and master regulator of HO), were also examined to compare with those observed after changing ho expression. We showed that HO levels in neurons and glia must be maintained at an appropriate physiological level during development to ensure the well-being of adults. We also found that the downregulation of ho in either neurons or glia in the brain is compensated by ho expressed in the retina.
Differential effects on TDP-43, piezo-2, tight-junction proteins in various brain regions following repetitive low-intensity blast overpressure
Authors: Heyburn Lanier , Dahal Shataakshi , Abutarboush Rania , Reed Eileen , Urioste Rodrigo , Batuure Andrew , Wilder Donna , Ahlers Stephen T. , Long Joseph B. , Sajja Venkatasivasai Sujith
Published: October 2023

Introduction

Mild traumatic brain injury (mTBI) caused by repetitive low-intensity blast overpressure (relBOP) in military personnel exposed to breaching and heavy weapons is often unrecognized and is understudied. Exposure to relBOP poses the risk of developing abnormal behavioral and psychological changes such as altered cognitive function, anxiety, and depression, all of which can severely compromise the quality of the life of the affected individual. Due to the structural and anatomical heterogeneity of the brain, understanding the potentially varied effects of relBOP in different regions of the brain could lend insights into the risks from exposures.

Methods

In this study, using a rodent model of relBOP and western blotting for protein expression we showed the differential expression of various neuropathological proteins like TDP-43, tight junction proteins (claudin-5, occludin, and glial fibrillary acidic protein (GFAP)) and a mechanosensitive protein (piezo-2) in different regions of the brain at different intensities and frequency of blast.

Results

Our key results include (i) significant increase in claudin-5 after 1x blast of 6.5 psi in all three regions and no definitive pattern with higher number of blasts, (ii) significant increase in piezo-2 at 1x followed by significant decrease after multiple blasts in the cortex, (iii) significant increase in piezo-2 with increasing number of blasts in frontal cortex and mixed pattern of expression in hippocampus and (iv) mixed pattern of TDP-3 and GFAP expression in all the regions of brain.

Discussion

These results suggest that there are not definitive patterns of changes in these marker proteins with increase in intensity and/or frequency of blast exposure in any particular region; the changes in expression of these proteins are different among the regions. We also found that the orientation of blast exposure (e.g. front vs. side exposure) affects the altered expression of these proteins.
Not all bad decisions are alike: approach and avoidant bad decisions are associated with distinct network organization
Authors: Lyons Siraj , Depue Brendan Eliot
Published: October 2023

Introduction

Decisions under ambiguity occurs daily for everyone. Subsequently, we all deliberate upon options to initiate an action most appropriate for current goal demands. Researchers has attempted to identify factors which contribute to risk taking, alongside the neurocircuitry underpinning it. Empirically, uncertain decision making is frequently assessed using the Iowa Gambling Task (IGT). Research have reliably identified varying regions implicating two broader circuits known as the reward and salience networks. However, considerable work has focused on contrasting “good” versus “bad” decisions.

Methods

The present investigation attempted a unique approach to analyzing the modified IGT acquired during fMRI (n = 24) and focused on active and passive bad decisions to identify potential internetwork connectivity, dissociable connectivity patterns between approach and avoidant bad decisions, and their relationship with personality traits, which can be linked with behavioral approach styles.

Results

Network cluster analyses revealed general internetwork connectivity when passing (avoiding) good decks; however, the OFC was functionally disconnected from the rest of the selected brain regions when playing (approaching) bad decks. Decreased reward responsiveness was linked to increased functional connectivity between the lateral OFC and aSMG, while drive was associated with increased functional connectivity between dACC and aINS.

Discussion

We report evidence that approach and avoidant bad decisions are associated with distinct neural communication patterns. Avoidant decisions were marked by substantial network integration and coherence, contrasted with the general scarcity of internetwork communication observed for approach decisions. Furthermore, the present investigation observed preliminary evidence of personality traits linked with neural communication between salience and reward evaluative networks.
Alteration of static and dynamic intrinsic brain activity induced by short-term spinal cord stimulation in postherpetic neuralgia patients
Authors: Bu Chunxiao , Ren Huan , Lv Qingqing , Bu Huilian , Gao Xinyu , Zheng Ruiping , Huang Huiyu , Wang Weijian , Wei Yarui , Cheng Jingliang , Zhang Yong
Published: October 2023

Introduction

Short-term spinal cord stimulation (stSCS) is an effective treatment for postherpetic neuralgia (PHN). However, how exactly stSCS affects time-dynamic intrinsic brain activity in PHN patients is not clear. The purpose of this study was to examine the static and dynamic variability of neural activity in PHN patients after stSCS.

Methods

In this study, 10 patients with PHN underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline and after SCS. The amplitude of low-frequency fluctuations (ALFF) and dynamic ALFF (dALFF) were used to investigate the static and dynamic variability of neural activity in PHN patients after stSCS. We additionally examined the associations between clinical parameters and functional changes in the brain.

Results

There was a significant increase in dALFF in the left precuneus and right superior parietal gyrus, and a decrease in dALFF in the left inferior temporal gyrus, right gyrus rectus, left superior temporal gyrus, right orbitofrontal cortex, and left orbitofrontal cortex. There was significantly increased ALFF in the right inferior temporal gyrus, and decreased ALFF in the right lingual gyrus, left superior parietal gyrus, right superior parietal gyrus, and left precuneus. Furthermore, Pittsburgh sleep quality index scores were positively associated with dALFF changes in the left superior temporal gyrus and left orbitofrontal cortex. Hospital anxiety and depression scale scores and continuous pain scores exhibited significant negative correlation with dALFF changes in the right superior parietal gyrus.

Conclusion

This study indicated that stSCS is able to cause dALFF changes in PHN patients, thus stSCS might alter brain functions to relieve pain, sleep, and mood symptoms. The findings provide new insights into the mechanisms of stSCS efficacy in the treatment of patients with PHN.
Weight stigma and fat phobia in Poland – attitudes towards people living with obesity and the level of knowledge about obesity among the social media internet respondents and medical professionals
Authors: Świder Karolina , Baska Alicja , Babicki Mateusz , Mastalerz-Migas Agnieszka , Kłoda Karolina
Published: October 2023

Introduction

Obesity often subjects individuals to stigmatization, impacting self-esteem, contributing to depression, social isolation, and even exacerbating weight gain. Our research aimed to evaluate weight stigma, fat phobia, their expressions, and obesity-related knowledge among social media internet respondents and medical practitioners in Poland.

Methods

Conducted through Computer-Assisted Web Interview (CAWI), our study employed the Fat Phobia Scale (FPS) and tailored questions, analyzing 1705 questionnaires.

Results

The respondents averaged a score of 3.60  ±  0.62 on the FPS. Interestingly, men exhibited higher stigma levels than women. Variables like BMI, residency, and interactions with people having obesity did not significantly impact stigma levels. Approximately 74.0% of respondents found individuals with obesity less attractive than those with normal weight, while 32.2% identified obesity as a cause of shame. Only 69.1% were aware of the BMI-based obesity diagnosis criterion.

Conclusion

Given limited knowledge of Poland’s weight stigma landscape, our research yields crucial insights for shaping social campaigns and enhancing educational initiatives in obesity management for healthcare professionals. Further studies will be instrumental in addressing patient and practitioner needs effectively.
Mathematical modeling of radiotherapy: impact of model selection on estimating minimum radiation dose for tumor control
Authors: Kutuva Achyudhan R. , Caudell Jimmy J. , Yamoah Kosj , Enderling Heiko , Zahid Mohammad U.
Published: October 2023

Introduction

Radiation therapy (RT) is one of the most common anticancer therapies. Yet, current radiation oncology practice does not adapt RT dose for individual patients, despite wide interpatient variability in radiosensitivity and accompanying treatment response. We have previously shown that mechanistic mathematical modeling of tumor volume dynamics can simulate volumetric response to RT for individual patients and estimation personalized RT dose for optimal tumor volume reduction. However, understanding the implications of the choice of the underlying RT response model is critical when calculating personalized RT dose.

Methods

In this study, we evaluate the mathematical implications and biological effects of 2 models of RT response on dose personalization: (1) cytotoxicity to cancer cells that lead to direct tumor volume reduction (DVR) and (2) radiation responses to the tumor microenvironment that lead to tumor carrying capacity reduction (CCR) and subsequent tumor shrinkage. Tumor growth was simulated as logistic growth with pre-treatment dynamics being described in the proliferation saturation index (PSI). The effect of RT was simulated according to each respective model for a standard schedule of fractionated RT with 2 Gy weekday fractions. Parameter sweeps were evaluated for the intrinsic tumor growth rate and the radiosensitivity parameter for both models to observe the qualitative impact of each model parameter. We then calculated the minimum RT dose required for locoregional tumor control (LRC) across all combinations of the full range of radiosensitvity and proliferation saturation values.

Results

Both models estimate that patients with higher radiosensitivity will require a lower RT dose to achieve LRC. However, the two models make opposite estimates on the impact of PSI on the minimum RT dose for LRC: the DVR model estimates that tumors with higher PSI values will require a higher RT dose to achieve LRC, while the CCR model estimates that higher PSI values will require a lower RT dose to achieve LRC.

Discussion

Ultimately, these results show the importance of understanding which model best describes tumor growth and treatment response in a particular setting, before using any such model to make estimates for personalized treatment recommendations.
Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials
Authors: Liang Zhanpeng , Liu Liwen , Li Wenxia , Lai Huiqin , Li Luzhen , Wu Jiaming , Zhang Huatang , Fang Cantu
Published: October 2023

Objective

Zolbetuximab is a “first-in-class” chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma.

Methods

The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).

Results

This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68–0.84) and PFS (HR = 0.64; 95% CI: 0.50–0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82–1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55–0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44–0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common.

Conclusion

This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).
Evaluating the use of a customized digital navigation program to optimize bowel preparation in pediatric colonsocopy
Authors: Dankner Lauren , Quiros Jose Antonio , Volpert Diana , Atreja Ashish
Published: October 2023

Introduction

Adequate bowel preparation is essential for optimal colonoscopy diagnosis and/or intervention. However, suboptimal bowel preparation occurs in as many as 1 in 3 pediatric colonoscopies, leading to missed diagnoses, procedural complications, wasted resources, and increased costs. We aimed to evaluate the effect of an automated Pediatric Colonoscopy Digital Navigation Program (PC-DNP) on the quality of colonoscopy preparation among pediatric patients.

Methods

The PC-DNP sent patients timely weight-based bowel preparation instructions, video and text-based educational modules, logistical information, and appointment reminders prior to their scheduled diagnostic and/or therapeutic colonoscopies. Physician reported bowel preparation quality among patients/caregivers who were prescribed the PC-DNP were compared to bowel preparation quality of a historical sample of patients/caregivers who received standard care instructions.

Results

We found that the PC-DNP group had significantly higher bowel preparation quality than the standard care group.

Conclusions

These results demonstrated that automated DNPs may be easily implemented into the pediatric gastroenterologists' practice and may help streamline and improve bowel preparation in pediatric patients.
Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study
Authors: Pan Mingming , Wang Guihua , Zhou Li , Xu Yan , Yao Li , Wu Chaoqing , Mei Changlin , Zhao Zhanzheng , Sun Dong , Guan Tianjun , Chen Qinkai , Shi Ming , Xu Hui , Zeng Weifang , Li Fangqiong , Yan Rui , Liu Bi-Cheng
Published: October 2023

Background: HSK21542, a novel selective peripherally-restricted κ-opioid receptor agonist has been proven to be a safe and effective analgesic and antipruritic drug in both in vitro and in vivo studies. We aimed to evaluate its safety, pharmacokinetics and efficacy in hemodialysis patients over a 1-week treatment period, and to establish the optimal dosage for a further 12-week stage 2 trial.

Methods: In this multiple ascending dose study, hemodialysis patients were randomly assigned to receive HSK21542 (0.05–0.80 μg/kg), or a placebo three times within 2.5 h at the end of each dialysis session for 1 week. Safety evaluations included reports of treatment-emergent adverse events (TEAEs); pharmacokinetics and efficacy outcomes were also assessed.

Results: Among the 44 screened patients, 41 were enrolled and completed the trial. The overall incidence of TEAEs was higher in the HSK21542 group compared to the placebo group, with an incidence of 75.0%, 50.0%, 75.0%, and 88.9% in the range of 0.05–0.80 μg/kg. All TEAEs were grade 1 or 2 in severity. HSK21542 exhibited linear pharmacokinetics characteristics within the dose range 0.05–0.80 μg/kg, without drug accumulation after multiple-doses. Compared to the placebo, a significant decrease of the weekly mean Worst Itching Intensity Numerical Rating Scale was found in the HSK21542-0.30 μg/kg group (p = 0.046), but without significant improvement in the Skindex-16 score.

Conclusion: HSK21542 was well tolerated in the dose range 0.05–0.80 μg/kg in hemodialysis patients. HSK21542-0.3 μg/kg exhibited promising efficacy in patients with moderate to severe pruritus and warrants a further Stage 2 trial.

Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT04470154.
Partial substitution of chemical fertilizer by Trichoderma biofertilizer improved nitrogen use efficiency in wolfberry (Lycium chinense) in coastal saline land
Authors: Yan Kun , Mei Huimin , Ruan Yanan , Yu Shunyang , Su Hongyan , Zhi Yibo , Li Suxin , Sun Yanan
Published: October 2023

A two-year field trial was conducted to investigate the effects of partial substitution of chemical fertilizer (CF) by Trichoderma biofertilizer (TF) on nitrogen (N) use efficiency and associated mechanisms in wolfberry (Lycium chinense) in coastal saline land. As with plant biomass and fruit yield, apparent N use efficiency and plant N accumulation were also higher with TF plus 75% CF than 100% CF, indicating that TF substitution promoted plant growth and N uptake. As a reason, TF substitution stabilized soil N supply by mitigating steep deceases in soil NH4+-N and NO3–N concentrations in the second half of growing seasons. TF substitution also increased carbon (C) fixation according to higher photosynthetic rate (Pn) and stable 13C abundance with TF plus 75% CF than 100% CF. Importantly, leaf N accumulation significantly and positively related with Pn, biomass, and fruit yield, and structural equation modeling also confirmed the importance of the causal relation of N accumulation coupled with C fixation for biomass and yield formation. Consequently, physiological and agronomical N use efficiencies were significantly higher with TF plus 75% CF than 100% CF. Overall, partial substitution of CF by TF improved N use efficiency in wolfberry in coastal saline land by stabilizing soil N supply and coupling N accumulation with C fixation.
Tomato disease object detection method combining prior knowledge attention mechanism and multiscale features
Authors: Liu Jun , Wang Xuewei
Published: October 2023

To address the challenges of insufficient accuracy in detecting tomato disease object detection caused by dense target distributions, large-scale variations, and poor feature information of small objects in complex backgrounds, this study proposes the tomato disease object detection method that integrates prior knowledge attention mechanism and multi-scale features (PKAMMF). Firstly, the visual features of tomato disease images are fused with prior knowledge through the prior knowledge attention mechanism to obtain enhanced visual features corresponding to tomato diseases. Secondly, a new feature fusion layer is constructed in the Neck section to reduce feature loss. Furthermore, a specialized prediction layer specifically designed to improve the model’s ability to detect small targets is incorporated. Finally, a new loss function known as A-SIOU (Adaptive Structured IoU) is employed to optimize the performance of the model in terms of bounding box regression. The experimental results on the self-built tomato disease dataset demonstrate the effectiveness of the proposed approach, and it achieves a mean average precision (mAP) of 91.96%, which is a 3.86% improvement compared to baseline methods. The results show significant improvements in the detection performance of multi-scale tomato disease objects.
Genome-wide association mapping for yield-related traits in soybean (Glycine max) under well-watered and drought-stressed conditions
Authors: Li Shengyou , Cao Yongqiang , Wang Changling , Yan Chunjuan , Sun Xugang , Zhang Lijun , Wang Wenbin , Song Shuhong
Published: October 2023

Soybean (Glycine max) productivity is significantly reduced by drought stress. Breeders are aiming to improve soybean grain yields both under well-watered (WW) and drought-stressed (DS) conditions, however, little is known about the genetic architecture of yield-related traits. Here, a panel of 188 soybean germplasm was used in a genome wide association study (GWAS) to identify single nucleotide polymorphism (SNP) markers linked to yield-related traits including pod number per plant (PN), biomass per plant (BM) and seed weight per plant (SW). The SLAF-seq genotyping was conducted on the population and three phenotype traits were examined in WW and DS conditions in four environments. Based on best linear unbiased prediction (BLUP) data and individual environmental analyses, 39 SNPs were significantly associated with three soybean traits under two conditions, which were tagged to 26 genomic regions by linkage disequilibrium (LD) analysis. Of these, six QTLs qPN-WW19.1, qPN-DS8.8, qBM-WW1, qBM-DS17.4, qSW-WW4 and qSW-DS8 were identified controlling PN, BM and SW of soybean. There were larger proportions of favorable haplotypes for locus qPN-WW19.1 and qSW-WW4 rather than qBM-WW1, qBM-DS17.4, qPN-DS8.8 and qSW-DS8 in both landraces and improved cultivars. In addition, several putative candidate genes such as Glyma.19G211300, Glyma.17G057100 and Glyma.04G124800, encoding E3 ubiquitin-protein ligase BAH1, WRKY transcription factor 11 and protein zinc induced facilitator-like 1, respectively, were predicted. We propose that the further exploration of these locus will facilitate accelerating breeding for high-yield soybean cultivars.
Actual and symbolic prisons, Black men, and the freedom-unfreedom paradox: interrogating the bad faith of racialized oppression in a post-accountable United States
Authors: Smith Darron T. , Harris Brenda G.
Published: October 2023

Drawing on systemic racism theory, white racial framing and the notion of bad faith as the connecting, justifying thread between ideals of freedom and equality and actions realizing unfreedom and inequities, this essay explores the alchemy of race, masculinity, and racialized oppression and its consequences for Black men past and present in United States society. This essay’s aim is to trace the historical ideologies and cultural practices, relations, and normative standards that have contributed to, and hence must be challenged to confront, the inequitable, race-based relations of power, and privilege at the root of institutionalized injustices. To do so, this essay interrogates the dissonance of bad faith as a corrective mode of truth telling to highlight and tap the equity potential of Black men’s collective, historical rejections of the White mainstream’s conflicting definitions and deceptive reasonings requisite for pushing toward racial justice, healing, and peace.
Effects of physical exercise on non-suicidal self-injury in adolescents: the chain mediating role of perceived social support and self-concept
Authors: Yu Haoran , Mu Qinglei , Li Ke
Published: October 2023

Objective

To study the effect of physical exercise on non-suicidal self-injury in adolescents and to verify the chain mediating role of perceived social support and self-concept. Methods: A survey study was conducted on 1,426 adolescents in Chengdu, Sichuan Province. A chain mediation model was used to verify whether perceived social support and self-concept played a mediating role.

Results

Physical exercise was significantly negatively associated with non-suicidal self-injury in adolescents (β = −0.53, p < 0.01) and significantly positively associated with perceived social support and self-concept (β = 0.52, 0.54, p < 0.01), and perceived social support and self-concept were significantly negatively associated with non-suicidal self-injury (β = −0.59, p < 0.01; β = −0.64, p < 0.01), and perceived social support was able to significantly and positively associate self-concept (β = 0.76, p < 0.01).

Conclusion

Perceived social support and self-concept play a chain mediating role in the effect of physical exercise on non-suicidal self-injury in adolescents, and it is recommended that the development of perceived social support and self-concept be emphasized during adolescents’ development, which has the potential to reduce the incidence of non-suicidal self-injurious behaviors in adolescents.
Hispanic/Latinx ethnic differences in the relationships between behavioral inhibition, anxiety, and substance use in youth from the ABCD cohort
Authors: Correa Kelly A. , Delfel Everett L. , Wallace Alexander L. , III William E. Pelham , Jacobus Joanna
Published: October 2023

Introduction

Elevated levels of behavioral inhibition (BI) may connote risk for both anxiety and substance use disorders. BI has consistently been shown to be associated with increased levels of anxiety, while the association between BI and substance use has been mixed. It is possible that the relationship between BI and substance use varies by individual difference factors. Hispanic/Latinx (H/L) youth in particular may have stronger relationships between BI, anxiety, and substance use.

Methods

The present study therefore evaluated (1) the prospective relationships between BI [assessed via self-reported behavioral inhibition system (BIS) scale scores], anxiety, and substance use in youth (n = 11,876) across baseline, 1-, and 2-year follow-ups of the Adolescent Brain Cognitive Development (ABCD) Study (ages 9–12) and (2) whether these relationships differed by H/L ethnicity while covarying for average behavioral approach system scores, race, sex, age, highest parental income, highest parental education, and past-year substance use (for analyses involving substance use outcomes).

Results

Baseline levels of BIS scores predicted increased anxiety symptoms at both 1- and 2-year follow-ups and did not differ by H/L ethnicity. Baseline levels of BIS scores also prospectively predicted increased likelihood of substance use at 2-year follow-up, but only for H/L youth and not at 1-year follow-up.

Discussion

High scores on the BIS scale contribute risk to anxiety across ethnicities and may uniquely contribute to risk for substance use in H/L youth.
Joint family consultations for psychiatric inpatients with severe eating disorders transitioning to adulthood: psychoanalytic design of a therapeutic setting
Authors: Putois Olivier , Riegert Myriam , Bahi Nadine , Pires Joël , De Luca Manuella
Published: October 2023

While family work is acknowledged as relevant in the care of eating disorders (EDs), not much literature has explored it in the period of transition from adolescence to young adulthood (16–18 to 30 y.o.). Yet this period is of significant importance in the prognosis and evolution of EDs; but its particular stakes require specific therapeutic settings–especially for inpatient EDs. In this paper, we start from the paradoxical observation that some families refuse this type of work in its usual form, with a family-dedicated therapist, and require to only exchange with the psychiatrist in charge of the treatment plan. We use a psychosomatic-informed psychoanalytic approach to shed light on this refusal as a latent denial of the contribution of family dynamics to the current symptom, and an unconscious tendency to stick to a dependency-laden family scheme. We then explain the conception of a specifically dedicated therapeutic setting, designed to address this specific type of resistance, offered to families as a therapeutic compromise designed to give them a specific position in the care of their child. In our joint therapeutic consultations, family dynamics are addressed on the basis of exchanges regarding treatment and in particular feeding. While such exchanges start from medical considerations, the therapeutic couple (psychiatrist-psychologist) uses them to address the parent and patient expectations underlying the symptom. We propose to call this act “inscription”; it enables a separation from the underlying dependency-oriented family scheme, while stressing the importance to care for associated parental anxieties.
Stacked ensemble deep learning for pancreas cancer classification using extreme gradient boosting
Authors: Bakasa Wilson , Viriri Serestina
Published: October 2023

Ensemble learning aims to improve prediction performance by combining several models or forecasts. However, how much and which ensemble learning techniques are useful in deep learning-based pipelines for pancreas computed tomography (CT) image classification is a challenge. Ensemble approaches are the most advanced solution to many machine learning problems. These techniques entail training multiple models and combining their predictions to improve the predictive performance of a single model. This article introduces the idea of Stacked Ensemble Deep Learning (SEDL), a pipeline for classifying pancreas CT medical images. The weak learners are Inception V3, VGG16, and ResNet34, and we employed a stacking ensemble. By combining the first-level predictions, an input train set for XGBoost, the ensemble model at the second level of prediction, is created. Extreme Gradient Boosting (XGBoost), employed as a strong learner, will make the final classification. Our findings showed that SEDL performed better, with a 98.8% ensemble accuracy, after some adjustments to the hyperparameters. The Cancer Imaging Archive (TCIA) public access dataset consists of 80 pancreas CT scans with a resolution of 512 * 512 pixels, from 53 male and 27 female subjects. A sample of two hundred and twenty-two images was used for training and testing data. We concluded that implementing the SEDL technique is an effective way to strengthen the robustness and increase the performance of the pipeline for classifying pancreas CT medical images. Interestingly, grouping like-minded or talented learners does not make a difference.
Linking current dental education to gerontological education to meet the oral health needs of growing aging populations
Authors: Tabrizi Maryam , Lee Wei-Chen
Published: October 2023

Objective

This study aimed to recognize the gaps in dental education by studying the current level of geriatric oral health training of recent graduated dentists who have been admitted into an Advanced Education in General Dentistry (AEGD) program.

Methods

The AEGD program was developed along with the Age-Friendly 4Ms model to enhance current dental education. We adopted the Rapid Cycle Quality Improvement model to test the effectiveness of the training for AEGD residents from 2019 to 2022. A total of 18 residents participated (6 residents each year). A 5-question survey was administered before and after the rotation and Wilcoxon signed-rank with Fisher Exact tests were conducted to compare pre- and post- rotation results.

Results

All 18 residents have completed pre- and post-program surveys. They self-reported minimal to no training in preparation to provide care to older adults with multiple chronic conditions. After the rotation, residents’ confidence in treating older adults was significantly increased (p = 0.011). Meanwhile, residents gained knowledge to apply the 4Ms framework (what matters, medication, mentation, and mobility) to their practices (p = 0.015) and provide age-friendly care for older adults.

Conclusion

The study identified and addressed the missing link in dental education to gerontological and geriatrics education. More clinical rotations and didactic training to equip residents with competences of providing geriatric oral health are strongly recommended.
Expression of p53 in toluidine blue positive oral squamous cell carcinoma lesions and expression of Ki67 in vinegar positive oral squamous cell carcinoma lesions
Authors: Bhalang Kanokporn , Danuthai Kittipong
Published: October 2023

The aims of this study were to investigate the sensitivity and specificity of toluidine blue and/or vinegar in oral cancer screening and to examine the correlation between clinical screening using toluidine blue and vinegar and the expression of the tumor marker p53 and proliferation marker Ki67, respectively. The study consisted of 87 patients with suspected oral squamous cell carcinoma lesions. Toluidine blue and/or vinegar were applied to the lesions, followed by biopsies. The tissues were diagnosed histopathologically and underwent immunohistochemical process for p53 or Ki67. The results revealed that the sensitivity and specificity of oral cancer screening using toluidine blue were 93% and 46%, respectively; whereas the sensitivity and specificity using vinegar were 85% and 81%, respectively. A statistically significant correlation between the use of vinegar and the expression of Ki67 (p = 0.019) was observed. Although there was a difference in the expression of p53 between specimens that were positive and negative to toluidine blue, the correlation did not reach a significant level. Based on the results from this study, vinegar has a lower sensitivity than toluidine blue but a higher specificity for oral cancer screening. The results of the clinical screening using vinegar correlated with the expression of Ki67 at the cellular level.