bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Oral Symptoms and Physical Activity after COVID-19 among Adolescents
Authors:   The Korean Society of Oral Health Science, Kim Young-Suk , Min Hee-Hong
Published: September 2023

Objectives: The purpose of this study was to evaluate the relationship between oral symptoms and physical activity after COVID-19 among adolescents.
Methods: A total of 54,835 adolescents were included in our study.
Results: In this group of participants with decreased physical activity, the rates of experienced toothache, gingival bleeding, and tooth sensitivity were higher (57.0%, 56.0%, and 55.8%, respectively) than equaled or increased groups (p<0.001). The risk of toothache, gingival bleeding, experience of tooth sensitivity was 1.38 (95% CI: 1.31-1.47) times, 1.33 (95% CI: 1.25-1.42) times, 1.43 (95% CI: 1.35-1.50) times higher, respectively among participants with decreased physical activity after COVID-19.
Conclusions: We found that changes in physical activity among adolescents are related to oral symptoms.
Oral Nursing Education in Intensive Care Units (ICU) and the Need for Dedicated Personnel
Authors:   The Korean Society of Oral Health Science, Kim Na-Yoon , Kim Seul-Gi , Jang Bo-Myung , Ko Ye-Hee , Oh Se-Yun , Kim Bo-Ram
Published: September 2023

Objectives: To investigate the performance of oral nursing in intensive care units after COVID-19 and identify the factors affecting it and to gather data for preparing a system to improve the oral nursing environment.
Methods: From April 1 to May 31, 2023, online self-completed questionnaires were filled out by nurses working in intensive care units at higher hospital across South Korea.
Results: A significant correlation was found between the perception of poor oral care in seriously ill patients and the demand for oral management education in serious patients.
Conclusions: To provide effective oral care for critically ill patients, oral care implementation and education should be strengthened in cooperation with oral experts, and a system for heightening the importance and improving the environment of oral care in intensive care units is needed.
The Effects of Dental Hygiene Students' Interpersonal Ability and Resilience on Clinical Practice Stress
Authors:   The Korean Society of Oral Health Science, You Eun-Ji , Lee Hye-Jin
Published: September 2023

Objectives: This study aimed to investigate the effect of interpersonal ability and resilience on clinical practice stress in dental hygiene students which was experienced at clinical practice.
Methods: The participants were 173 dental hygiene students. Data was collected from May 1 to 30, 2022.
Results: Factors influencing clinical practice stress showed significant relationships in practice period, grades, resilience, and practice institutions, and the explanatory power was 35.6%.
Conclusions: As a result, in order to reduce the stress of dental hygiene students in clinical practice, it is necessary to identify factors in practice institutions that affect clinical practice stress, and counseling with psychologists and psychological reinforcement programs to improve students' resilience and interpersonal skills.
Awareness Survey Analysis for Interdisciplinary Unification of Dental Hygiene
Authors:   The Korean Society of Oral Health Science, Lee Sun-Mi , Seong Mi Gyung , Kim Chang-Hee , Son Jung-Hui , Moon Hee-Jung , Lim Mi-Hee , Choi Sung-Mi , Kang Hyun-Kyung , Goo Hyo-Jin , Kang Yong-Ju , Lee Min-kyung , Hwang Sun-Young , Kim Young-im
Published: September 2023

Objectives: The purpose of this study was to investigate the perceptions of dental hygiene professors, current students, and dental hygienists about interdisciplinary unification.
Methods: This study The questionnaire consisted of general characteristics, specific opinions on academic unification. The data were analyzed using descriptive statistics, t-test, and ANOVA.
Results: The proportion of professors, 64.5% of dental hygienists, and 61.4% of students in favor of dental hygiene (majors) and academic unification was 84.0% (p<0.001). Regarding student competencies during the four-year transition, the overall mean for competencies was 4.09 for professors, 3.69 for students, and 3.51 for dental hygienists (p<0.001).
Conclusions: Curriculum standardization is necessary for systematic and professional education in dental hygiene.
Equine maternal aging affects the metabolomic profile of oocytes and follicular cells during different maturation time points
Authors: Catandi G. D. , Bresnahan D. R. , Peters S. O. , Fresa K. J. , Maclellan L. J. , Broeckling C. D. , Carnevale E. M.
Published: September 2023

Introduction: Oocyte quality and fertility decline with advanced maternal age. During maturation within the ovarian follicle, the oocyte relies on the associated somatic cells, specifically cumulus and granulosa cells, to acquire essential components for developmental capacity.

Methods: A nontargeted metabolomics approach was used to investigate the effects of mare age on different cell types within the dominant, follicular-phase follicle at three time points during maturation. Metabolomic analyses from single oocytes and associated cumulus and granulosa cells allowed correlations of metabolite abundance among cell types.

Results and Discussion: Overall, many of the age-related changes in metabolite abundance point to Impaired mitochondrial metabolic function and oxidative stress in oocytes and follicular cells. Supporting findings include a higher abundance of glutamic acid and triglycerides and lower abundance of ceramides in oocytes and somatic follicular cells from old than young mares. Lower abundance of alanine in all follicular cell types from old mares, suggests limited anaerobic energy metabolism. The results also indicate impaired transfer of carbohydrate and free fatty acid substrates from cumulus cells to the oocytes of old mares, potentially related to disruption of transzonal projections between the cell types. The identification of age-associated alterations in the abundance of specific metabolites and their correlations among cells contribute to our understanding of follicular dysfunction with maternal aging.
Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy
Authors: Shafiq Nusrat , Mehroze Aiman , Sarwar Warda , Arshad Uzma , Parveen Shagufta , Rashid Maryam , Farooq Ariba , Rafiq Naila , Wondmie Gezahign Fentahun , Bin Jardan Yousef A. , Brogi Simone , Bourhia Mohammed
Published: September 2023

Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study.
Transcriptional analysis of human peripheral blood mononuclear cells stimulated by Mycobacterium tuberculosis antigen
Authors: Wei Jing , Guo Fangzheng , Song Yamin , Xu Kun , Lin Feiyang , Li Kangsheng , Li Baiqing , Qian Zhongqing , Wang Xiaojing , Wang Hongtao , Xu Tao
Published: September 2023

Background

Mycobacterium tuberculosis antigen (Mtb-Ag) is a polypeptide component with a molecular weight of 10-14 kDa that is obtained from the supernatant of the H37Ra strain after heat treatment. It stimulates the activation and proliferation of γδT cells in the blood to produce an immune response against tuberculosis. Mtb-Ag is therefore crucial for classifying and detecting the central genes and key pathways involved in TB initiation and progression.

Methods

In this study, we performed high-throughput RNA sequencing of peripheral blood mononuclear cells (PBMC) from Mtb-Ag-stimulated and control samples to identify differentially expressed genes and used them for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Meanwhile, we used PPI protein interaction network and Cytoscape analysis to identify key genes and qRT-PCR to verify differential gene expression. Single-gene enrichment analysis (GSEA) was used further to elucidate the potential biological functions of key genes. Analysis of immune cell infiltration and correlation of key genes with immune cells after Mtb-Ag-stimulated using R language.

Results

We identified 597 differentially expressed genes in Mtb-Ag stimulated PBMCs. KEGG and GSEA enrichment analyzed the cellular pathways related to immune function, and DEGs were found to be primarily involved in the TNF signaling pathway, the IL-17 signaling pathway, the JAK-STAT signaling pathway, cytokine-cytokine receptor interactions, and the NF-κB signaling pathway. Wayne analysis using GSEA, KEGG, and the protein-protein interaction (PPI) network showed that 34 genes, including PTGS2, IL-1β, IL-6, TNF and IFN-γ et al., were co-expressed in the five pathways and all were up-regulated by Mtb-Ag stimulation. Twenty-four DEGs were identified using qRT-PCR, including fourteen up-regulated genes (SERPINB7, IL20, IFNG, CSF2, PTGS2, TNF-α, IL36G, IL6, IL10, IL1A, CXCL1, CXCL8, IL4, and CXCL3) and ten down-regulated genes (RTN1, CSF1R CD14, C5AR1, CXCL16, PLXNB2, OLIG1, EEPD1, ENG, and CCR1). These findings were consistent with the RNA-Seq results.

Conclusion

The transcriptomic features associated with Mtb-Ag provide the scientific basis for exploring the intracellular immune mechanisms against Mtb. However, more studies on these DEGs in pathways associated with Mtb-Ag stimulation are needed to elucidate the underlying pathologic mechanisms of Mtb-Ag during Mtb infection.
Early developmental stages of a Lower Ordovician marrellid from Morocco suggest simple ontogenetic niche differentiation in early euarthropods
Authors: Laibl Lukáš , Gueriau Pierre , Saleh Farid , Pérez-Peris Francesc , Lustri Lorenzo , Drage Harriet B. , Bath Enright Orla G. , Potin Gaëtan J.-M. , Daley Allison C.
Published: September 2023

Early developmental stages of euarthropods are exceptionally rare in the fossil record. This hampers our understanding of the biology, phylogeny, and development of this extremely diverse metazoan group. Herein, we use classical paleontological methods in combination with synchrotron X-ray microtomography to explore the morphology in ca. 480 million-year-old early developmental stages of the Lower Ordovician Fezouata Shale marrellid euarthropod. These stages range between 3.8 and 5.3 mm in length and are characterized by three distinct pairs of gently curved spines that projects from the head shield. The first pair of cephalic appendages are represented by uniramous antenullae of a sensory function. The second pair of cephalic appendages is robust, and had an anchoring or stabilizing function. The third cephalic appendage pair is composed of long cylindrical podomeres and was used for walking. The trunk appendages are biramous and consist of an endopod and a lamellate exopod. Two anterior trunk endopods are composed of long slender podomeres and were used for walking, while the more posterior trunk endopods bear robust endites and associated setae and were used for food gathering. The trunk of the earliest developmental stages is composed of thirteen segments, in contrast to more than 22 segments in the adult trunk. The similar appendage morphology and differentiation along the body is evident in adult individuals of the Fezouata marrellid, suggesting these different developmental stages shared similar methods of locomotion and food processing. Given that adults and juveniles are often preserved in the same or nearby sites, the niche differentiation between these life stages would be the result of the absolute smaller appendage size in immature stages compared to larger adults, effectively differentiating the size of food resources consumed by each. In addition, the delicate setae present in the posterior trunk appendages of early developmental stages might have been used to capture smaller food particles. This simple mode of ontogenetic niche differentiation might have been common in the early diverging euarthropod groups.
Characteristics of vegetation carbon sink carrying capacity and restoration potential of China in recent 40 years
Authors: Wu Luhua , Zhang Yun , Luo Guangjie , Chen Dan , Yang Dongni , Yang Yifan , Tian Fengxia
Published: September 2023

Improving vegetation carbon sink is a key measure for China to achieve the goal of carbon neutrality. However, the gradual saturation of vegetation carbon fixation under the constraints of climate change and human activities has limited the long-term and sustainable growth of vegetation carbon sinks, resulting in significant uncertainty in understanding future carbon sink capacity and recovery potential. In this study, NPP has been selected as a carbon sink indicator to quantitatively evaluated the carbon sink carrying capacity (CSCC) and the carbon sink resilience (CSR) of China. Results demonstrated that (1) the NPP of vegetation cover areas in China exhibited an increasing trend from 1981 to 2018, with an average growth rate of 1.66 g C m−2 yr.−1 and a total net NPP increase of 0.32 P g C. (2) The average CSCC in China was 658.59 g C m−2 yr.−1, with a total amount of 4.13 Pg C yr.−1. The NPP exceeded 60% of CSCC in various years, and the total NPP in 2018 was 3.26 Pg C yr.−1, which reached 78.74% of CSCC. In the future, carbon sink that can be increased is 0.88 Pg C yr.−1, with an increase proportion of 21.26%. (3) From 2000 to 2018, the NPP of vegetation-covered area (VCA) in China had generally maintained a positive succession trend with the stronger CSR. Only four provinces (HUN, CQ, AH, and JS) in China showed the extremely strong levels of CSR. The study has revealed the huge and sustainable CSCC and restoration potential in China over the past 40 years, and has provided spatial positioning and theoretical guidance for future ecological carbon sink restoration and benefit assessment.
Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma
Authors: Matchett Emily C. , Kornbluth Jacki
Published: September 2023

Introduction

Over the last decade, there have been many advancements in the therapeutic treatment of multiple myeloma (MM), including the use of natural killer (NK) cells. However, despite promising results from clinical trials, there are concerns over the use of NK cell-based therapy. Cells often undergo growth arrest, limiting their experimental utility; donor cells are extremely heterogeneous, resulting in content variability; and patients receiving allogeneic cells are at risk for graft-versus-host disease and/or cytokine release syndrome. Extracellular vesicles (EVs) have emerged as a new natural therapeutic tool. EVs are known to carry cargo derived from the parent cell from which they originate. NK cells play an important role in the innate immune system, targeting and killing tumor cells. This has led many researchers to isolate EVs from NK cells for their cytotoxic potential.

Methods

In this study, we isolated EVs from the NK cell line, NK3.3, which was derived from the peripheral blood of a healthy donor. Currently, it is the only normal human NK cell line reported with all the functional characteristics of healthy NK cells. To address the issue of growth arrest, we immortalized NK3.3 cells with lentivirus encoding the catalytic subunit of human telomerase htert (NK3.3-LTV). EVs from these cells were isolated using a modified polyethylene glycol (PEG)-acetate precipitation protocol to simplify processing and increase EV yield.

Results and conclusions

We demonstrated that NK3.3-LTV EVs target both sensitive and drug-resistant MM cell lines as well as primary patient MM cells in vitro, decreasing proliferation and inducing apoptotic cell death as well as or better than EVs from non-immortalized cells with no toxicity towards normal cells. This study is the first step towards developing an immunotherapeutic product designed to treat patients with relapsed/refractory MM.
Real-world outcomes of immunotherapy-based neoadjuvant therapy in resectable non-small cell lung cancer
Authors: Shen Jie , Gu Linping , Qi Yuwen , Yao Yaxian , Lu Shun , Chen Zhiwei
Published: September 2023

Objectives

Recent clinical studies have demonstrated that immunotherapy-based neoadjuvant therapy have promising effectiveness for patients with resectable non-small cell lung cancer (NSCLC) in terms of pathologic response. Therefore, we performed this study to investigate whether immunotherapy-based neoadjuvant therapy is effective and safe for patients with resectable NSCLC.

Materials and methods

This open-label observational two-arm clinical study was performed at Shanghai Chest Hospital in China with patients who had resectable NSCLC and received two to three cycles of immunotherapy-based neoadjuvant therapy or neoadjuvant chemotherapy alone, followed by surgical resection. The primary endpoint was a major pathologic response (MPR). The secondary endpoints include a complete pathological response (pCR), a radiologic response to neoadjuvant therapy (TRR), event-free survival (EFS), and overall survival (OS).

Results

A total of 51 patients was included in this clinical study, of which 31 patients received immunotherapy-based neoadjuvant therapy and 20 patients received neoadjuvant chemotherapy alone. The percentage of patients achieving a major pathologic response was 41.9% with immunotherapy-based neoadjuvant therapy and 15.0% (95% CI, 0.008 to 0.468; P = 0.043) with neoadjuvant chemotherapy alone. The percentage of patients with pathologic complete response was 19.4% in the immunotherapy-based group and 5% (95% CI, -0.069 to 0.318; P = 0.223) in the chemotherapy group. The radiographic response rate was 71% after immunotherapy-based neoadjuvant therapy and 60% (95% CI, -0.143 to 0.359; P = 0.417) after neoadjuvant chemotherapy. At a median follow-up of 28 months, the median EFS and OS endpoints were not reached.

Conclusions

Neoadjuvant immunotherapy offers a considerable advantage over chemotherapy alone for resectable NSCLC in terms of the major pathologic response. Moreover, it did not enhance the risk of adverse events or hinder surgical resection.
Effects of duration of long-acting GnRH agonist downregulation on assisted reproductive technology outcomes in patients with adenomyosis: a retrospective cohort study
Authors: Li Yexing , Ge Li , Yang Xiaohe , Cui Linlin , Chen Zi-Jiang
Published: September 2023

Objectives

To elucidate the relationship between long-acting GnRH agonist (GnRHa) downregulation and assisted reproductive technology (ART) outcomes and identify the optimal duration of downregulation in patients with adenomyosis.

Design

Retrospective cohort study.

Participants

The study was designed to evaluate ART outcomes in adenomyosis patients with and without GnRHa downregulation between January 2016 and December 2020. A total of 374 patients with adenomyosis (621 cycles) were included with 281 cycles in downregulation group versus 340 cycles in non-downregulation group. After 1:1 propensity score matching (PSM), a sample size of 272 cycles in each group was matched. The matched downregulation group was further divided into 1-month (147 cycles), 2-months (72 cycles), and ≥3 months downregulation (53 cycles) subgroups. Stratification analysis was conducted on pregnancy outcomes in 239 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles.

Results

The downregulation group had larger mean diameter of initial uterus and higher proportion of severer dysmenorrhea compared to non-downregulation group. The pregnancy-related parameters in GnRHa downregulation group were similar to those in non-downregulation group, except for higher late miscarriage rate (MR) (13.4% vs. 3.1%, P = 0.003). The subgroup comparisons in fresh ET cycles indicated that implantation rate (75.0% vs. 39.2%, P = 0.002), biochemical pregnancy rate (91.7% vs. 56.0%, P = 0.036) and clinical pregnancy rate (83.3% vs. 47.0%, P = 0.016) could be improved by prolonged GnRHa downregulation (≥3 months), whereas late MR was difficult to be reversed (30.0% vs. 3.2%, P = 0.017). In FET cycles, higher MR (53.6% vs. 29.9%, P = 0.029; 58.8% vs. 29.9%, P = 0.026) and lower live birth rate (18.8% vs. 34.1%, P = 0.023; 17.1% vs. 34.1%, P = 0.037) were observed in the 1-month and ≥3 months downregulation group, while no differences were found in the 2-months downregulation group compared to the non-downregulation group.

Conclusion

In patients with severer adenomyosis, long-acting GnRHa downregulation might be correlated with improved ART outcomes. In fresh ET cycles, prolonged downregulation (≥3 months) might be beneficial to improve live birth rate, which needed to be verified by further study with larger sample. In FET cycles, the optimal duration of downregulation was not certain and still needed further exploration.
Dynamic changes of rumen bacteria and their fermentative ability in high-producing dairy cows during the late perinatal period
Authors: Mao Yongxia , Wang Feifei , Kong Weiyi , Wang Ruiling , Liu Xin , Ding Hui , Ma Yun , Guo Yansheng
Published: September 2023

Background

High-producing dairy cows face varying degrees of metabolic stress and challenges during the late perinatal period, resulting in ruminal bacteria abundance and their fermentative ability occurring as a series of changes. However, the dynamic changes are still not clear.

Aims/methods

Ten healthy, high-producing Holstein dairy cows with similar body conditions and the same parity were selected, and ruminal fluid from the dairy cows at postpartum 0, 7, 14, and 21 d was collected before morning feeding. 16S rRNA high-throughput sequencing, GC-MS/MS targeted metabolomics, and UPLC-MS/MS untargeted metabolomics were applied in the study to investigate the dynamic changes within 21 d postpartum.

Results

The results displayed that the structures of ruminal bacteria were significantly altered from 0 to 7 d postpartum (R = 0.486, P = 0.002), reflecting the significantly declining abundances of Euryarchaeota and Chloroflexi phyla and Christensenellaceae, Methanobrevibacter, and Flexilinea genera (P < 0.05) and the obviously ascending abundances of Ruminococcaceae, Moryella, Pseudobutyrivibrio, and Prevotellaceae genera at 7 d postpartum (P < 0.05). The structures of ruminal bacteria also varied significantly from 7 to 14 d postpartum (R = 0.125, P = 0.022), reflecting the reducing abundances of Christensenellaceae, Ruminococcaceae, and Moryella genera (P < 0.05), and the elevating abundances of Sharpea and Olsenella genera at 14 d postpartum (P < 0.05). The metabolic profiles of ruminal SCFAs were obviously varied from 0 to 7 d postpartum, resulting in higher levels of propionic acid, butyric acid, and valeric acid at 7 d postpartum (P < 0.05); the metabolic profiles of other ruminal metabolites were significantly shifted from 0 to 7 d postpartum, with 27 significantly elevated metabolites and 35 apparently reduced metabolites (P < 0.05). The correlation analysis indicated that propionic acid was positively correlated with Prevotellaceae and Ruminococcaceae (P < 0.05), negatively correlated with Methanobrevibacter (P < 0.01); butyric acid was positively associated with Prevotellaceae, Ruminococcaceae, and Pseudobutyrivibrio (P < 0.05), negatively associated with Christensenellaceae (P < 0.01); valeric acid was positively linked with Prevotellaceae and Ruminococcaceae (P < 0.05); pyridoxal was positively correlated with Flexilinea and Methanobrevibacter (P < 0.05) and negatively correlated with Ruminococcaceae (P < 0.01); tyramine was negatively linked with Ruminococcaceae (P < 0.01).

Conclusion

The findings contribute to the decision of nutritional management and prevention of metabolic diseases in high-producing dairy cows during the late perinatal period.
Endoscopic transorbital resection of the temporal lobe: anatomic qualitative and quantitative study
Authors: De Rosa Andrea , Mosteiro Alejandra , Guizzardi Giulia , Roldán Pedro , Torales Jorge , Matas Fassi Jessica , Cavallo Luigi Maria , Solari Domenico , Prats-Galino Alberto , Di Somma Alberto , Enseñat Joaquim
Published: September 2023

Objective

Starting from an anatomic study describing the possibility of reaching the temporal region through an endoscopic transorbital approach, many clinical reports have now demonstrated the applicability of this strategy when dealing with intra-axial lesions. The study aimed to provide both a qualitative anatomic description of the temporal region, as seen through a transorbital perspective, and a quantitative analysis of the amount of temporal lobe resection achievable via this route.

Material and methods

A total of four cadaveric heads (eight sides) were dissected at the Laboratory of Surgical Neuroanatomy (LSNA) of the University of Barcelona, Spain. A stepwise description of the resection of the temporal lobe through a transorbital perspective is provided. Qualitative anatomical descriptions and quantitative analysis of the amount of the resection were evaluated by means of pre- and post-dissection CT and MRI scans, and three-dimensional reconstructions were made by means of BrainLab®Software.

Results

The transorbital route gives easy access to the temporal region, without the need for extensive bone removal. The resection of the temporal lobe proceeded in a subpial fashion, mimicking what happens in a surgical scenario. According to our quantitative analysis, the mean volume removed was 51.26%, with the most superior and lateral portion of the temporal lobe being the most difficult to reach.

Conclusion

This anatomic study provides qualitative and quantitative details about the resection of the temporal lobe via an endoscopic transorbital approach. Our results showed that the resection of more than half of the temporal lobe is possible through this surgical corridor. While the anterior, inferior, and mesial portions of the temporal lobe were easily accessible, the most superior and lateral segment was more difficult to reach and resect. Our study serves as an integration to the current anatomic knowledge and clinical practice knowledge highlighting and also as a starting point for further anatomic studies addressing more selected segments of the temporal lobe, i.e., the mesial temporal region.
Local minimization of prediction errors drives learning of invariant object representations in a generative network model of visual perception
Authors: Brucklacher Matthias , Bohté Sander M. , Mejias Jorge F. , Pennartz Cyriel M. A.
Published: September 2023

The ventral visual processing hierarchy of the cortex needs to fulfill at least two key functions: perceived objects must be mapped to high-level representations invariantly of the precise viewing conditions, and a generative model must be learned that allows, for instance, to fill in occluded information guided by visual experience. Here, we show how a multilayered predictive coding network can learn to recognize objects from the bottom up and to generate specific representations via a top-down pathway through a single learning rule: the local minimization of prediction errors. Trained on sequences of continuously transformed objects, neurons in the highest network area become tuned to object identity invariant of precise position, comparable to inferotemporal neurons in macaques. Drawing on this, the dynamic properties of invariant object representations reproduce experimentally observed hierarchies of timescales from low to high levels of the ventral processing stream. The predicted faster decorrelation of error-neuron activity compared to representation neurons is of relevance for the experimental search for neural correlates of prediction errors. Lastly, the generative capacity of the network is confirmed by reconstructing specific object images, robust to partial occlusion of the inputs. By learning invariance from temporal continuity within a generative model, the approach generalizes the predictive coding framework to dynamic inputs in a more biologically plausible way than self-supervised networks with non-local error-backpropagation. This was achieved simply by shifting the training paradigm to dynamic inputs, with little change in architecture and learning rule from static input-reconstructing Hebbian predictive coding networks.
Hypometabolic patterns of focal cortical dysplasia in PET-MRI co-registration imaging: a retrospective evaluation in a series of 83 patients
Authors: Wang Xiu , Hu Wenhan , Shao Xiaoqiu , Zheng Zhong , Ai Lin , Sang Lin , Zhang Chao , Zhang Jian-guo , Zhang Kai
Published: September 2023

Objective

To characterize the PET-MRI co-registration of hypometabolic patterns in focal cortical dysplasia (FCD) types I and II and provide some suggestions in presurgical evaluation of epilepsy surgery.

Methods

We retrospectively analyzed PET-MRI co-registration imaging data from a cohort of 83 epilepsy patients with histologically confirmed FCD types I and II. Hypometabolic patterns were classified into 4 types: bottom of sulcus hypometabolism (BOSH), single island of sulcus hypometabolism (SIOS), single gyrus or sulcus hypometabolism (SGOS), and multiple gyri and sulci hypometabolism (MGOS).

Results

Most of cases that were overlooked by conventional MRI and PET evaluation but positive in PET-MRI co-registration were focalized lesions in dorsolateral frontal lobe (9/15) and FCD type IIa was the most prevalent pathological type (11/15). The FCD histological types (p = 0.027) and locations (p < 0.001) were independent predictors of PET-MRI co-registration hypometabolic patterns. Focalized hypometabolic patterns (BOSH, SIOS, SGOS) were primarily observed in the frontal lobe (33/39) and FCD type II (43/62) and extensive pattern (MGOS) in temporal lobe (18/20) and FCD type I (16/21; p < 0.005).

Conclusion

PET-MRI co-registration enhanced the detection of FCD type IIa compared with conventional MRI and PET reading. The hypometabolic patterns of FCD type I and temporal lobe FCD were more extensive than those of FCD type II and frontal lobe FCD, respectively. The predilection of focalized hypometabolic patterns in frontal lobe FCD suggested that subtle lesions should be checked carefully in patients with suspected frontal lobe epilepsy.
PGC-1α regulates critical period onset/closure, mediating cortical plasticity
Authors: Zhang Wei-Jun , Shi Hou-Zhen , Guo Mei-Na , Xu Long-Fei , Zhai Hong-Ru , Liu Zi-Zhong , Zhu Yong-Qiang , Zhang Wei-Ning , Wang Jia
Published: September 2023

Peroxisome proliferator-activated receptor PPARγ coactivator-α (PGC-1α) is concentrated in inhibitory interneurons and plays a vital role in neuropsychiatric diseases. We previously reported some characteristic features of schizophrenia (SZ) in GABAergic neuron-specific Pgc-1alpha knockout (KO) mice (Dlx5/6-Cre: Pgc−1alphaf/f). However, there is a fundamental gap in the molecular mechanism by which the Pgc-1alpha gene is involved in the neurobehavioral abnormalities of SZ. The loss of critical period (CP) triggers–maturations of parvalbumin interneurons (PVIs) and brakes—and the formation of perineuronal nets (PNNs) implicates mistimed trajectories during adult brain development. In this study, using the Pgc-1alpha KO mouse line, we investigated the association of Pgc-1alpha gene deletion with SZ-like behavioral deficits, PVI maturation, PNN integrity and synaptic ultrastructure. These findings suggest that Pgc-1alpha gene deletion resulted in a failure of CP onset and closure, thereby prolonging cortical plasticity timing. To determine whether the manipulation of the PNN structure is a potential method of altering neuronal plasticity, GM6001, a broad-spectrum matrix metalloproteinase (MMP)-inhibitor was applied. Here we confirmed that the treatment could effectively correct the CP plasticity window and ameliorate the synaptic ultrastructure in the Pgc-1alpha KO brain. Moreover, the intervention effect on neuronal plasticity was followed by the rescue of short-term habituation deficits and the mitigation of aberrant salience, which are some characteristic features of SZ. Taken collectively, these findings suggest that the role of PGC-1α in regulating cortical plasticity is mediated, at least partially, through the regulation of CP onset/closure. Strategically introduced reinforcement of molecular brakes may be a novel preventive therapy for psychiatric disorders associated with PGC-1α dysregulation.
Human BBB-on-a-chip reveals barrier disruption, endothelial inflammation, and T cell migration under neuroinflammatory conditions
Authors: Nair Arya Lekshmi , Groenendijk Linda , Overdevest Roos , Fowke Tania M. , Annida Rumaisha , Mocellin Orsola , de Vries Helga E. , Wevers Nienke R.
Published: September 2023

The blood-brain barrier (BBB) is a highly selective barrier that ensures a homeostatic environment for the central nervous system (CNS). BBB dysfunction, inflammation, and immune cell infiltration are hallmarks of many CNS disorders, including multiple sclerosis and stroke. Physiologically relevant human in vitro models of the BBB are essential to improve our understanding of its function in health and disease, identify novel drug targets, and assess potential new therapies. We present a BBB-on-a-chip model comprising human brain microvascular endothelial cells (HBMECs) cultured in a microfluidic platform that allows parallel culture of 40 chips. In each chip, a perfused HBMEC vessel was grown against an extracellular matrix gel in a membrane-free manner. BBBs-on-chips were exposed to varying concentrations of pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) to mimic inflammation. The effect of the inflammatory conditions was studied by assessing the BBBs-on-chips’ barrier function, cell morphology, and expression of cell adhesion molecules. Primary human T cells were perfused through the lumen of the BBBs-on-chips to study T cell adhesion, extravasation, and migration. Under inflammatory conditions, the BBBs-on-chips showed decreased trans-endothelial electrical resistance (TEER), increased permeability to sodium fluorescein, and aberrant cell morphology in a concentration-dependent manner. Moreover, we observed increased expression of cell adhesion molecules and concomitant monocyte adhesion. T cells extravasated from the inflamed blood vessels and migrated towards a C-X-C Motif Chemokine Ligand 12 (CXCL12) gradient. T cell adhesion was significantly reduced and a trend towards decreased migration was observed in presence of Natalizumab, an antibody drug that blocks very late antigen-4 (VLA-4) and is used in the treatment of multiple sclerosis. In conclusion, we demonstrate a high-throughput microfluidic model of the human BBB that can be used to model neuroinflammation and assess anti-inflammatory and barrier-restoring interventions to fight neurological disorders.
The efficacy and safety of different systemic combination therapies on advanced hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Li Ping , Hu Ming , Liu Mei , Ren Xiangyu , Liu Donghong , Liu Jiluo , Yin Jianhua , Tan Xiaojie , Cao Guangwen
Published: September 2023

Background and aims

Systemic combinations have recently brought significant therapeutic benefits for advanced hepatocellular carcinoma (aHCC). To design the most effective combination regimens, a systematic review (PROSPERO ID: CRD42022321949) was conducted to evaluate the efficacy and safety of systemic combinations on aHCC.

Methods

We retrieved all the studies from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI) using the Medical Subject Headings (MeSH) terms until December 21, 2022. The effect indicators (hazard ratio [HR], relative risk [RR], and median) were pooled by a fixed- or random-effects model. A subgroup analysis was conducted according to types and specific therapies.

Results

In total, 88 eligible studies were selected from 7249 potential records. Each kind of combination treatment (chemotherapy plus chemotherapy, targeted plus immune checkpoint inhibitor (ICI) therapy, targeted plus chemotherapy, and targeted plus targeted therapy) had a better objective response rate (ORR) in patients with aHCC, compared to the monotherapy mostly with sorafenib (RR: 1.57 [1.44–1.71]; I2 = 30%). Of those, targeted plus ICI therapy showed better therapeutic efficiency in overall survival (median: 15.02 [12.67–17.38]), progression-free survival (median: 7.08 [6.42–7.74]), and ORR (RR: 1.81 [1.55–2.13]), compared to the monotherapy. Specifically, Atezo plus Beva showed all those benefits. Our pooled result showed all the combinations had increased ≥3 Grade treatment-related adverse events (TrAEs), with an RR of 1.25 [95% CI: 1.15–1.36], compared to the monotherapy.

Conclusion

The systemic combinations, especially targeted plus ICI therapy, including Atezo plus Beva, significantly improve clinical outcomes but increase side effects in patients with aHCC. Future trials should concentrate on improvement in therapeutic efficiency and reduction of toxicity of targeted plus ICI therapy.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42022321949.
Double outlet right ventricle
Authors: Bell-Cheddar Yolandee , Devine William A. , Diaz-Castrillon Carlos-Eduardo , Seese Laura , Castro-Medina Mario , Morales Raymond , Follansbee Christopher W. , Alsaied Tarek , Lin Jiuann-Huey I.
Published: September 2023

This review article addresses the history, morphology, anatomy, medical management, and different surgical options for patients with double outlet right ventricle.
Ustekinumab trough levels in children with Crohn’s disease refractory to anti-tumor necrosis factor agents: a prospective case series of off-label use
Authors: Bouhuys Marleen , Mian Paola , van Rheenen Patrick F.
Published: September 2023

Background: Ustekinumab is used off-label in pediatric Crohn’s disease refractory to anti-tumor necrosis factor. Data on optimal dosing, target trough levels, and potential benefit of therapeutic drug monitoring in children treated with ustekinumab are limited.

Materials and Methods: We describe a series of six adolescents who consented to be treated with ustekinumab. We measured their trough levels, C-reactive protein, and fecal calprotectin before every administration.

Results: Standard adult dosing was effective to achieve biochemical remission (fecal calprotectin < 250 mg/kg) in one patient and clinical remission (resolution of symptoms) in another. The other four patients failed to respond on standard dosing and underwent intravenous re-induction and interval shortening to increase ustekinumab trough levels. This resulted in biochemical remission in one patient and clinical remission in another, suggesting an exposure–response relationship. The remaining two patients had no therapeutic benefit, and ustekinumab was discontinued.

Conclusion: In this report, we show that ustekinumab can induce remission in pediatric patients with anti-tumor necrosis factor refractory Crohn’s disease. It is worth escalating the dose before abandoning the drug as ineffective. Prospective studies in children are needed to determine long-term efficacy of ustekinumab, usefulness of therapeutic drug monitoring strategies, and, if applicable, optimal target trough levels.
Analysis of drug resistance in pulmonary tuberculosis patients with positive sputum tuberculosis culture in Northeast China
Authors: Sichen Li , Rui Wang , Yue Yang , Xin Liu , Youbin Cui , Ze Tang , Hongfei Cai
Published: September 2023

Objective: The objective of this study is to determine the drug resistance status of pulmonary tuberculosis patients in Jilin Province.

Methods: A retrospective survey was conducted on 395 sputum culture TB-positive patients admitted to the tuberculosis hospital in Jilin Province in 2019. Sputum samples were cultured in acidic Roche medium. Drug sensitivity testing was conducted using the proportional method. Sensitivity was reported if the percentage of drug resistance was less than 1%, and resistance was reported if the percentage was ≥1%. Statistical analysis was performed using SPSS 22.0.

Results: 395 tuberculosis patients with positive sputum tuberculosis culture were included in the study, with 102 being initially treated and 293 being retreated. The study population consisted of 283 males and 112 females. Sex, age, nationality, occupation, marital status, diabetes comorbidity, initial treatment, normal health status, BCG vaccine vaccination, smoking, and alcohol consumption were considered as factors that may affect the rate of multidrug resistance. And only the history of treatment (initial treatment) was associated with multidrug resistance (p = 0.032). This indicates that retreatment is the most significant risk factor for the occurrence of multidrug resistance in tuberculosis. The multidrug resistance rate in retreated patients is 3.764 times higher than that in initially treated patients.

Conclusion: The prevalence of multidrug-resistant is higher in retreated patients compared to initially treated patients in the study population. Multidrug resistance is only associated with the treatment history (initial retreatment) and not with other factors.
Interchangeability between factor analysis, logistic IRT, and normal ogive IRT
Authors: Cho Eunseong
Published: September 2023

In existing studies, it has been argued that factor analysis (FA) is equivalent to item response theory (IRT) and that IRT models that use different functions (i.e., logistic and normal ogive) are also interchangeable. However, these arguments have weak links. The proof of equivalence between FA and normal ogive IRT assumes a normal distribution. The interchangeability between the logistic and normal ogive IRT models depends on a scaling constant, but few scholars have examined whether the usual values of 1.7 or 1.702 maximize interchangeability. This study addresses these issues through Monte Carlo simulations. First, the FA model produces almost identical results to those of the normal ogive model even under severe nonnormality. Second, no single scaling constant maximizes the interchangeability between logistic and normal ogive models. Instead, users should choose different scaling constants depending on their purpose in using a model and the number of response categories (i.e., dichotomous or polytomous). Third, the interchangeability between logistic and normal ogive models is determined by several conditions. The interchangeability is high if the data are dichotomous or if the latent variables follow a symmetric distribution, and vice versa. In summary, the interchangeability between FA and normal ogive models is greater than expected, but that between logistic and normal ogive models is not.
Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia
Authors: Perellón-Alfonso Ruben , Oblak Aleš , Kuclar Matija , Škrlj Blaž , Pileckyte Indre , Škodlar Borut , Pregelj Peter , Abellaneda-Pérez Kilian , Bartrés-Faz David , Repovš Grega , Bon Jurij
Published: September 2023

Introduction

Patients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm.

Methods

We tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM.

Results

The DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs.

Discussion

These results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities.
Polish adaptation of the Dimensional Anhedonia Rating Scale (DARS) - validation in the clinical sample
Authors: Gorostowicz Aleksandra , Rizvi Sakina J. , Kennedy Sidney H. , Chrobak Adrian Andrzej , Dudek Dominika , Cyranka Katarzyna , Piekarska Joanna , Krawczyk Eve , Siwek Marcin
Published: September 2023

Background

Anhedonia is the core symptom of depression. Its presence has been linked to worsened prognosis. The Dimensional Anhedonia Rating Scale (DARS) is a scale measuring desire, motivation, effort and consummatory pleasure across different domains. The aim of this paper was to confirm factor structure, assess reliability and validity of the Polish adaptation of the DARS in a clinical sample of patients with mood disorders and healthy controls (HC).

Methods

The study sample included 161 participants aged 18–65 years - 34 HC, 72 patients with bipolar disorder and 55 with major depressive disorder (in depressive episode or remission). Reliability of the Polish adaptation of the DARS was assessed using Cronbach’s α and the average inter-item correlation (AIC). Convergent and divergent validity was established by Pearson’s correlations between the DARS and the Snaith-Hamilton Pleasure Scale (SHAPS), the Quick Inventory of Depressive Symptomatology- self-report (QIDS-SR), the Hospital Anxiety and Depression Scale (HADS). The structure of the scale was examined by factor analysis.

Results

The factor structure was consistent with the original scale. Strong internal consistency for the DARS total score (Cronbach’s α = 0.95) and all subscales (0.86–0.93) was observed. The DARS demonstrated good convergent (moderate to strong correlations with measures of anhedonia and depression) and divergent validity (weak correlations with anxiety level).

Conclusion

The Polish DARS demonstrated excellent internal consistency and very good validity. The scale is a valuable contribution to the psychometrics of anhedonia measures in patients with mood disorders.