bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining temporal features of BOLD-based cerebrovascular reactivity in clinical populations
Authors: Marchena-Romero Kayley-Jasmin , Ji Xiang , Sommer Rosa , Centen Andrew , Ramirez Joel , Poulin Joshua M. , Mikulis David , Thrippleton Michael , Wardlaw Joanna , Lim Andrew , Black Sandra E. , MacIntosh Bradley J. 
Published: June 2023

BackgroundConventional cerebrovascular reactivity (CVR) estimation has demonstrated that many brain diseases and/or conditions are associated with altered CVR. Despite the clinical potential of CVR, characterization of temporal features of a CVR challenge remains uncommon. This work is motivated by the need to develop CVR parameters that characterize individual temporal features of a CVR challenge.MethodsData were collected from 54 adults and recruited based on these criteria: (1) Alzheimer’s disease diagnosis or subcortical Vascular Cognitive Impairment, (2) sleep apnea, and (3) subjective cognitive impairment concerns. We investigated signal changes in blood oxygenation level dependent (BOLD) contrast images with respect to hypercapnic and normocapnic CVR transition periods during a gas manipulation paradigm. We developed a model-free, non-parametric CVR metric after considering a range of responses through simulations to characterize BOLD signal changes that occur when transitioning from normocapnia to hypercapnia. The non-parametric CVR measure was used to examine regional differences across the insula, hippocampus, thalamus, and centrum semiovale. We also examined the BOLD signal transition from hypercapnia back to normocapnia.ResultsWe found a linear association between isolated temporal features of successive CO2 challenges. Our study concluded that the transition rate from hypercapnia to normocapnia was significantly associated with the second CVR response across all regions of interest (p &lt; 0.001), and this association was highest in the hippocampus (R2 = 0.57, p &lt; 0.0125).Conclusion This study demonstrates that it is feasible to examine individual responses associated with normocapnic and hypercapnic transition periods of a BOLD-based CVR experiment. Studying these features can provide insight on between-subject differences in CVR.
STNet: shape and texture joint learning through two-stream network for knowledge-guided image recognition
Authors: Wang Xijing , Han Hongcheng , Xu Mengrui , Li Shengpeng , Zhang Dong , Du Shaoyi , Xu Meifeng 
Published: June 2023

IntroductionThe human brain processes shape and texture information separately through different neurons in the visual system. In intelligent computer-aided imaging diagnosis, pre-trained feature extractors are commonly used in various medical image recognition methods, common pre-training datasets such as ImageNet tend to improve the texture representation of the model but make it ignore many shape features. Weak shape feature representation is disadvantageous for some tasks that focus on shape features in medical image analysis.MethodsInspired by the function of neurons in the human brain, in this paper, we proposed a shape-and-texture-biased two-stream network to enhance the shape feature representation in knowledge-guided medical image analysis. First, the two-stream network shape-biased stream and a texture-biased stream are constructed through classification and segmentation multi-task joint learning. Second, we propose pyramid-grouped convolution to enhance the texture feature representation and introduce deformable convolution to enhance the shape feature extraction. Third, we used a channel-attention-based feature selection module in shape and texture feature fusion to focus on the key features and eliminate information redundancy caused by feature fusion. Finally, aiming at the problem of model optimization difficulty caused by the imbalance in the number of benign and malignant samples in medical images, an asymmetric loss function was introduced to improve the robustness of the model.Results and conclusionWe applied our method to the melanoma recognition task on ISIC-2019 and XJTU-MM datasets, which focus on both the texture and shape of the lesions. The experimental results on dermoscopic image recognition and pathological image recognition datasets show the proposed method outperforms the compared algorithms and prove the effectiveness of our method.
Single-cell RNA sequencing of neural stem cells derived from human trisomic iPSCs reveals the abnormalities during neural differentiation of Down syndrome
Authors: Qiu Jia-jun , Liu Yan-na , Wei Hao , Zeng Fanyi , Yan Jing-bin 
Published: June 2023

IntroductionDown syndrome (DS) is the most common genetic condition that causes intellectual disability in humans. The molecular mechanisms behind the DS phenotype remain unclear. Therefore, in this study, we present new findings on its molecular mechanisms through single-cell RNA sequencing.MethodsInduced pluripotent stem cells (iPSCs) from the patients with DS and the normal control (NC) patients were differentiated into iPSCs-derived neural stem cells (NSCs). Single-cell RNA sequencing was performed to achieve a comprehensive single-cell level differentiation roadmap for DS-iPSCs. Biological experiments were also performed to validate the findings.Results and DiscussionThe results demonstrated that iPSCs can differentiate into NSCs in both DS and NC samples. Furthermore, 19,422 cells were obtained from iPSC samples (8,500 cells for DS and 10,922 cells for the NC) and 16,506 cells from NSC samples (7,182 cells for DS and 9,324 cells for the NC), which had differentiated from the iPSCs. A cluster of DS-iPSCs, named DS-iPSCs-not differentiated (DSi-PSCs-ND), which had abnormal expression patterns compared with NC-iPSCs, were demonstrated to be unable to differentiate into DS-NSCs. Further analysis of the differentially expressed genes revealed that inhibitor of differentiation family (ID family) members, which exhibited abnormal expression patterns throughout the differentiation process from DS-iPSCs to DS-NSCs, may potentially have contributed to the neural differentiation of DS-iPSCs. Moreover, abnormal differentiation fate was observed in DS-NSCs, which resulted in the increased differentiation of glial cells, such as astrocytes, but decreased differentiation into neuronal cells. Furthermore, functional analysis demonstrated that DS-NSCs and DS-NPCs had disorders in axon and visual system development. The present study provided a new insight into the pathogenesis of DS.
Transcriptomic and proteomic profiling of the anterior cingulate cortex in neuropathic pain model rats
Authors: Qiu Xin-Tong , Guo Chen , Ma Li-Tian , Li Xin-Ning , Zhang Qi-Yan , Huang Fen-Sheng , Zhang Ming-Ming , Bai Yang , Liang Guo-Biao , Li Yun-Qing 
Published: June 2023

BackgroundNeuropathic pain (NP) takes a heavy toll on individual life quality, yet gaps in its molecular characterization persist and effective therapy is lacking. This study aimed to provide comprehensive knowledge by combining transcriptomic and proteomic data of molecular correlates of NP in the anterior cingulate cortex (ACC), a cortical hub responsible for affective pain processing.MethodsThe NP model was established by spared nerve injury (SNI) in Sprague–Dawley rats. RNA sequencing and proteomic data from the ACC tissue isolated from sham and SNI rats 2 weeks after surgery were integrated to compare their gene and protein expression profiles. Bioinformatic analyses were performed to figure out the functions and signaling pathways of the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) enriched in.ResultsTranscriptomic analysis identified a total of 788 DEGs (with 49 genes upregulated) after SNI surgery, while proteomic analysis found 222 DEPs (with 89 proteins upregulated). While Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the DEGs suggested that most of the altered genes were involved in synaptic transmission and plasticity, bioinformatics analysis of the DEPs revealed novel critical pathways associated with autophagy, mitophagy, and peroxisome. Notably, we noticed functionally important NP-related changes in the protein that occurred in the absence of corresponding changes at the level of transcription. Venn diagram analysis of the transcriptomic and proteomic data identified 10 overlapping targets, among which only three genes (XK-related protein 4, NIPA-like domain-containing 3, and homeodomain-interacting protein kinase 3) showed concordance in the directions of change and strong correlations between mRNA and protein levels.ConclusionThe present study identified novel pathways in the ACC in addition to confirming previously reported mechanisms for NP etiology, and provided novel mechanistic insights for future research on NP treatment. These findings also imply that mRNA profiling alone fails to provide a complete landscape of molecular pain in the ACC. Therefore, explorations of changes at the level of protein are necessary to understand NP processes that are not transcriptionally modulated.
Novel blood product transfusion regimen to prevent clotting and citrate accumulation during continuous renal replacement therapy with regional citrate anticoagulation in children
Authors: Sun Yuelin , Li Dong , Bai Ke , Xu Feng , Liu Chengjun , Dang Hongxing 
Published: June 2023

ObjectiveIntroduce a novel protocol to prevent clotting and citrate accumulation (CA) from blood product transfusion (BPT) during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in children.MethodsWe prospectively compared fresh frozen plasma (FFP) and platelet transfusions between the two BPT protocols, direct transfusion protocol (DTP) and partial replacement of citrate transfusion protocol (PRCTP), in terms of the risks of clotting, citric accumulation (CA), and hypocalcemia. For DTP, blood products were directly transfused without any adjustment to the original RCA-CRRT regimen. For PRCTP, the blood products were infused into the CRRT circulation near the sodium citrate infusion point, and the dosage of 4% sodium citrate was reduced depending on the dosage of sodium citrate in the blood products. Basic information and clinical data were recorded for all children. Heart rate, blood pressure, ionized calcium (iCa) and various pressure parameters were recorded before, during and after BPT, as well as coagulation indicators, electrolytes, and blood cell counts before and after BPT.ResultsTwenty-six children received 44 PRCTPs and 15 children received 20 DTPs. The two groups had similar in vitro ionized calcium (iCa) concentrations (PRCTP: 0.33 ± 0.06 mmol/L, DTP: 0.31 ± 0.04 mmol/L), total filter lifespan (PRCTP: 49.33 ± 18.58, DTP: 50.65 ± 13.57 h), and filter lifespan after BPT (PRCTP: 25.31 ± 13.87, DTP: 23.39 ± 11.34 h). There was no visible filter clotting during BPT in any of the two groups. The two groups had no significant differences in arterial pressure, venous pressure, and transmembrane pressure before, during, or after BPT. Neither treatment led to significant decreases in WBC, RBC, or hemoglobin. The platelet transfusion group and the FFP group each had no significant decrease in platelets, and no significant increases in PT, APTT, and D-dimer. The most clinically significant changes were in the DTP group, in which the ratio of total calcium to ionized calcium (T/iCa) increased from 2.06 ± 0.19 to 2.52 ± 0.35, the percentage of patients with T/iCa above 2.5 increased from 5.0% to 45%, and the level of in vivo iCa increased from 1.02 ± 0.11 to 1.06 ± 0.09 mmol/L (all p &lt; 0.05). Changes in these three indicators were not significant in the PRCTP group.ConclusionNeither protocol was associated with filter clotting during RCA-CRRT. However, PRCTP was superior to DTP because it did not increase the risk of CA and hypocalcemia.
Forensic age estimation in living children: how accurate is the Greulich-Pyle method in Sabah, East Malaysia?
Authors: Nang Khin Mya , Ismail Abdul Jabbar , Tangaperumal Anithaa , Wynn Aye Aye , Thein Tin Tin , Hayati Firdaus , Teh Yong Guang 
Published: June 2023

BackgroundThe Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist (GP Atlas) is the most widely used method of determining the bone age (BA) of a child. It is also a widely accepted method for forensic age determination. As there is limited local bone age data for forensic age estimation, the purpose of this study was to assess the accuracy of the GP Atlas for forensic age determination in living Sabahan children.MethodThis study recruited 182 children between the ages of 9 years to 18 years. BA estimation of the left-hand anteroposterior radiographs were performed by two experienced radiologists using the Greulich-Pyle method.ResultsThe BA estimates from two radiologists had very high interobserver reliability (ICC 0.937) and a strong positive interobserver correlation (r &gt; 0.90). The GP method, significantly and consistently underestimated chronological age (CA) by 0.7, 0.6 and 0.7 years in overall children, boys and girls respectively with minimal errors. Mean absolute error and root of mean squared error for overall children was 1.5 and 2.2 years respectively, while mean absolute percentage error was 11.6%. This underestimation was consistent across all age groups but was statistically significant only at 13–13.9 and 17–18.9 years old age groups.ConclusionDespite high interobserver reliability of BA estimation using the GP Atlas, this method consistently underestimates the age of the child in all children to a significant degree, for both boys and girls across all age groups, with an acceptably low level of error metrics. Our findings suggest that locally validated GP Atlas or other type of assessments (artificial intelligence or machine learning) are needed for assessment of BA to accurately predict CA, since current GP Atlas standards significantly underestimated chronological age with minimal error for children in Sabah. A larger population-based study would be necessary for establishing a validated atlas of a bone age in Malaysia.
In silico analysis of the solute carrier (SLC) family in cancer indicates a link among DNA methylation, metabolic adaptation, drug response, and immune reactivity
Authors: Lavoro Alessandro , Falzone Luca , Tomasello Barbara , Conti Giuseppe Nicolò , Libra Massimo , Candido Saverio 
Published: June 2023

Introduction: The oncogenic transformation is driven by genetic and epigenetic alterations influencing cancer cell fate. These alterations also result in metabolic reprogramming by modulating the expression of membrane Solute Carrier (SLC) transporters involved in biomolecules trafficking. SLCs act as tumor suppressors or promoters influencing cancer methylome, tumor growth, immune-escape, and chemoresistance.Methods: This in silico study aimed to identify the deregulated SLCs in various tumor types compared to normal tissues by analyzing the TCGA Target GTEx dataset. Furthermore, the relationship between SLCs expression and the most relevant tumor features was tackled along with their genetic regulation mediated by DNA methylation.Results: We identified 62 differentially expressed SLCs, including the downregulated SLC25A27 and SLC17A7, as well as the upregulated SLC27A2 and SLC12A8. Notably, SLC4A4 and SLC7A11 expression was associated with favorable and unfavorable outcome, respectively. Moreover, SLC6A14, SLC34A2, and SLC1A2 were linked to tumor immune responsiveness. Interestingly, SLC24A5 and SLC45A2 positively correlated with anti-MEK and anti-RAF sensitivity. The expression of relevant SLCs was correlated with hypo- and hyper-methylation of promoter and body region, showing an established DNA methylation pattern. Noteworthy, the positive association of cg06690548 (SLC7A11) methylation with cancer outcome suggests the independent predictive role of DNA methylation at a single nucleotide resolution.Discussion: Although our in silico overview revealed a wide heterogeneity depending on different SLCs functions and tumor types, we identified key SLCs and pointed out the role of DNA methylation as regulatory mechanism of their expression. Overall, these findings deserve further studies to identify novel cancer biomarkers and promising therapeutic targets.
Long-term follow-up of a multimodal day clinic, group-based treatment program for patients with very high risk for complex posttraumatic stress disorder, and for patients with non-complex trauma-related disorders
Authors: Bever-Philipps Anke , Silbermann Andrea , Morawa Eva , Schäflein Eva , Stemmler Mark , Erim Yesim 
Published: June 2023

ObjectiveThe present study examined the follow-up of a multimodal day clinic group-based therapy program for patients with trauma-related disorders and investigated potential differences for patients with classic PTSD versus cPTSD.MethodSixty-six patients were contacted 6 and 12 months after discharge of our 8-week program and completed various questionnaires (Essen Trauma Inventory (ETI), Beck Depression Inventory-Revised (BDI-II), Screening scale of complex PTSD (SkPTBS), Patient Health Questionnaire (PHQ)-Somatization, as well as single items to therapy utilization and life events in the interim period). Due to organizational reasons a control group could not be included. Statistical analyses included repeated-measures ANOVA with cPTSD as between-subject factor.ResultsThe reduction of depressive symptoms at discharge was persistent at 6 and 12 months follow-up. Somatization symptoms were increased at discharge, but were leveled out at 6 months follow-up. The same effect was found for cPTSD symptoms in those patients with non-complex trauma-related disorders: Their increase of cPTSD symptoms was flattened at 6 months follow-up. Patients with a very high risk for cPTSD showed a strong linear reduction of cPTSD symptoms from admission to discharge and 6 months follow-up. cPTSD patients had a higher symptom load compared to patients without cPTSD on all time points and scales.ConclusionMultimodal, day clinic trauma-focused treatment is associated with positive changes even after 6 and 12 months. Positive therapy outcomes (reduced depression, reduced cPTSD symptoms for patients with a very high risk for cPTSD) could be maintained. However, PTSD symptomatology was not significantly reduced. Increases in somatoform symptoms were leveled out and can therefore be regarded as side effects of treatment, which may be connected with actualization of trauma in the intensive psychotherapeutic treatment. Further analyses should be applied in larger samples and a control group.
A sentiment analysis on online psychiatrist reviews to identify clinical attributes of psychiatrists that shape the therapeutic alliance
Authors: Park Soo Hwan , Cheng Christopher P. , Buehler Nicholas J. , Sanford Timothy , Torrey William 
Published: June 2023

BackgroundWhile online reviews from physician rating websites are increasingly utilized by healthcare providers to better understand patient needs, it remains difficult to objectively identify areas for improvement in providing psychiatric care.ObjectivesTo quantitatively characterize the sentiment of online written reviews of psychiatrists to determine clinical attributes that can be strengthened to improve psychiatrists’ therapeutic alliance with their patients.Materials and methodsSentiment scores of 6,400 written reviews of 400 US-based psychiatrists on a US-based online physician rating website were obtained through a natural-language-processing-based sentiment analysis. Relationships among sentiment scores, average star ratings, and demographics were examined. Linguistic analyses determined words and bigrams that were highly associated with reviews with the most positive and negative sentiment.FindingsSentiment scores were significantly correlated with average star ratings of the psychiatrists (R = 0.737, p &lt; 0.001). Psychiatrists who were younger (&lt; 56 years old) and/or practiced in the Northeast had significantly higher average star ratings than those older and/or practicing in the Southwest. Frequency analysis showed that positive reviews most frequently contained “time” (N = 1,138) and “caring” (N = 784) while negative reviews most frequently contained “medication” (N = 495) and “time” (N = 379). Logistic regression analysis revealed that reviews were more likely to be considered positive when they included “great listener” (OR = 16.89) and “comfortable” (OR = 10.72) and more likely to be negative when they included “meds” (OR = 0.55) and “side effect” (OR = 0.59).ConclusionPsychiatrists who are younger and located in the Northeast receive more positive reviews; there may be potential for demographic bias among patient reviewers. Patients positively rate psychiatrists who make them feel heard and comfortable but negatively rate encounters centered around medications and their side effects. Our study lends quantitative evidence to support the importance of thorough and empathetic communication of psychiatrists in building a strong therapeutic alliance.
Unmet healthcare needs, health outcomes, and health inequalities among older people in China
Authors: Wu Lili , Liu Qin , Fu Rao , Ma Jia 
Published: June 2023

ObjectiveThis study examines whether the experience of unmet healthcare needs in a large sample of Chinese adults aged 60 and over is associated with adverse health outcomes, and how this association varied across needs related to health conditions.Study designThe 2013 wave of the China Health and Retirement Longitudinal Study is examined. We adopted latent class analysis to identify groups based on health conditions. Then in each identified group, we examined the extent to which unmet needs were associated with self-rated health and depression. To understand the channels through which unmet needs adversely affected health outcomes, we examined the impact of unmet needs attributed to various factors.ResultsCompared to the mean, experiencing unmet outpatient needs is associated with a 3.4% decrease in self-rated health, and people are twice as likely to have depression symptoms (OR = 2.06). Health problems are even more severe when inpatient needs are not met. The frailest people are most affected by affordability-related unmet needs, while healthy people are most affected by unmet needs attributable to availability.ConclusionTo tackle unmet needs, direct measures for particular populations will be required in the future.