bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the relationship between specific executive functions and functional decline among community-dwelling older adults: results from a prospective pilot study
Authors: Verreckt Emilie , Grimm Elise , Agrigoroaei Stefan , de Saint Hubert Marie , Philippot Pierre , Cremer Gérald , Schoevaerdts Didier
Published: December 2022

Background

As cognitive functions and, more specifically, executive functions (EF) seem to influence autonomy among the elderly, we investigated the role of each of the five EF sub-components (inhibition, spontaneous flexibility, reactive flexibility, planning, and updating in working memory) for the risk of functional decline.

Method

A total of 137 community-dwelling participants over 75 years of age were included in a prospective cohort study and assigned to three groups: individuals with neuro-degenerative cognitive disorders, those having cognitive disorders with non-degenerative aetiology, and a control group without any cognitive problems. We measured each EF sub-component and assessed functional decline by evaluating basic (b-ADL) and instrumental activities of daily living (i-ADL) at baseline and 6 months later. We conducted three separate multiple logistic regression models to examine the extent to which the five EF facets predicted overall functional decline at the end of the follow-up period.

Results

We found that people who exhibited a decline in b-ADLs or/and i-ADLs over 6 months had worse performance on inhibition and two flexibility tasks than those who did not experience a decline. The results suggest that decliners have more difficulties in managing unforeseen events. Inhibition and updating in working memory predicted a decline in b-ADL while spontaneous and reactive flexibilities predicted a decline in i-ADL.

Conclusion

In our sample, specific executive dysfunctions were associated with a decline in functional status. With respect to the risk of decline in b-ADL, deficits in inhibition may represent a risk factor, as it regulates over-learned activities. Bothtypes of flexibility, which allow the shifting and generating of adaptive responses, predicted decline in i-ADL. In sum, paying more attention to particular EF profiles would help clinicians to anticipate some aspects of functional decline.
Artificial intelligence for the prediction of acute kidney injury during the perioperative period: systematic review and Meta-analysis of diagnostic test accuracy
Authors: Zhang Hanfei , Wang Amanda Y. , Wu Shukun , Ngo Johnathan , Feng Yunlin , He Xin , Zhang Yingfeng , Wu Xingwei , Hong Daqing
Published: December 2022

Background

Acute kidney injury (AKI) is independently associated with morbidity and mortality in a wide range of surgical settings. Nowadays, with the increasing use of electronic health records (EHR), advances in patient information retrieval, and cost reduction in clinical informatics, artificial intelligence is increasingly being used to improve early recognition and management for perioperative AKI. However, there is no quantitative synthesis of the performance of these methods. We conducted this systematic review and meta-analysis to estimate the sensitivity and specificity of artificial intelligence for the prediction of acute kidney injury during the perioperative period.

Methods

Pubmed, Embase, and Cochrane Library were searched to 2nd October 2021. Studies presenting diagnostic performance of artificial intelligence in the early detection of perioperative acute kidney injury were included. True positives, false positives, true negatives and false negatives were pooled to collate specificity and sensitivity with 95% CIs and results were portrayed in forest plots. The risk of bias of eligible studies was assessed using the PROBAST tool.

Results

Nineteen studies involving 304,076 patients were included. Quantitative random-effects meta-analysis using the Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model revealed pooled sensitivity, specificity, and diagnostic odds ratio of 0.77 (95% CI: 0.73 to 0.81),0.75 (95% CI: 0.71 to 0.80), and 10.7 (95% CI 8.5 to 13.5), respectively. Threshold effect was found to be the only source of heterogeneity, and there was no evidence of publication bias.

Conclusions

Our review demonstrates the promising performance of artificial intelligence for early prediction of perioperative AKI. The limitations of lacking external validation performance and being conducted only at a single center should be overcome.

Trial registration

This study was not registered with PROSPERO.
Influence of ADHD, especially attention-deficit characteristics, on the course of alcohol-dependent individuals
Authors: Yoshimura Atsushi , Matsushita Sachio , Kimura Mitsuru , Yoneda Jun-ichi , Maesato Hitoshi , Yokoyama Akira , Higuchi Susumu
Published: December 2022

Background

While several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined.

Methods

This study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated.

Results

The presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of “Recurrence” and lower rates of “Abstinence” and “Controlled drinking” (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003).

Conclusion

ADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment.
Efficacy of adjunctive intensive transcranial direct current stimulation of different cortices in treatment-resistant depression: a study protocol for a randomized double-blinded sham-controlled trial
Authors: Chen Yiming , Lyu Dongbin , Wang Fan , Huang Qinte , Yang Weichieh , Zhang Mengke , Wei Zheyi , Shi Shuxiang , Kong Shuqi , Chen Shentse , He Shuang , Yang Vivien , Fang Yiru , Hong Wu
Published: December 2022

Background

Treatment-resistant depression (TRD) carries a high economic burden worldwide. Transcranial direct current stimulation (tDCS) is advantageous for improving cognition and can be safely used in the treatment of depression. The effectiveness of tDCS of the left and right orbitofrontal cortex (OFC) as adjuvant treatment in patients with TRD has rarely been explored. Therefore, the objective of this trial is to evaluate the effectiveness there of when administering left dorsolateral prefrontal cortex (DLPFC) positive stimulation or OFC negative stimulation in patients with TRD.

Methods

Ninety eligible participants will be recruited to receive intervention at Shanghai Mental Health Center. Treatment will be randomly assigned in a double-blind fashion. Participants will receive either DLPFC (n = 30), OFC (n = 30), or sham (n = 30) tDCS, while continuing their usual pharmacotherapy at a stable dosage for at least 2 weeks before enrollment and throughout the stimulation period. All participants will receive 20 weekday stimulation sessions of 60 minutes duration each. Participants in the active group will be stimulated at 2 mA throughout the session, whereas the sham group will receive only a brief period of stimulation to mimic the sensation. After 20 stimulation sessions, no further treatment will be administered. Measurements will be conducted at regular points throughout and at 8 weeks after trial completion. The primary outcome is the change in the 17-item Hamilton Depression Rating Scale (HAMD-17) score after 20 sessions. Secondary outcomes were defined as changes in other measurement scales, cognitive function, resting-state functional magnetic resonance imaging (rs-fMRI), and serum biomarkers.

Discussion

We hypothesize that, in contrast to the sham group, both the active DLPFC and OFC tDCS groups will show superiority in HAMD-17 score reduction after 5, 10, and 20 sessions. Moreover, associations of the improvement of depressive symptoms with variations in rs-fMRI and TRD-related biomarkers will be evaluated. Our study may suggest that adjunctive intensive tDCS with left DLPFC positive stimulation or right OFC negative stimulation may be effective as a novel method to relieve depressive symptoms in patients with TRD. The variation of rs-fMRI, biomarkers could be used as a potential prediction model of treatment efficacy in TRD.

Trial registration

The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2200058030. Date of registration: March 27, 2022. Recruitment started in September 2022 and is ongoing.
Relationship between attitudes toward COVID-19 infection, depression and anxiety: a cross-sectional survey in Japan
Authors: Hazumi Megumi , Okazaki Emi , Usuda Kentaro , Kataoka Mayumi , Nishi Daisuke
Published: December 2022

Background

Although negative attitudes are known to develop with experiences of COVID-19 infection, it remains unclear whether such attitudes contribute to depression and anxiety as sequelae of COVID-19. We aimed to investigate the relationships between attitude towards COVID-19 infection and post-COVID-19 depression and anxiety.

Methods

A cross-sectional survey of COVID-19 recovered patients was conducted from July to September 2021 in Japan. Outcome variables, depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7); scores of 10 and above were identified as having symptoms of depression and anxiety, respectively. Exposure variables were whether participants were experiencing the following attitude strongly: threat to life due to COVID-19 infection, helplessness regarding COVID-19 infection, blaming a third party who did not restrain from going outside, blaming themselves for their COVID-19 infection, worry about spreading the infection to others, and self-stigma (Self-Stigma Scale-Short). Modified Poisson regression analyses were performed to analyze the findings.

Results

A total of 6016 responses were included in the analyses. The proportion of depression was 19.88%, and anxiety was 11.47%. The threat of life due to COVID-19 infection, helplessness regarding COVID-19 infection, blaming oneself for their COVID-19 infection, and self-stigma were significantly associated with depression and anxiety after adjusting covariates. Blaming the third party who did not restrain from going outside was associated with anxiety. There was no association between the worry about spreading infection to others and depression or anxiety.

Conclusion

Negative attitudes, including self-stigma with the experience of COVID-19 infection, were related to depression and anxiety. Further studies confirming whether countermeasures for preventing or decreasing the negative attitude towards COVID-19 infection mitigate these symptoms are needed.
Worsening effect of testosterone deficiency on males with heart failure with preserved ejection fraction
Authors: Hamam Ahmed , Abou-Omar Mahmoud , Rabah Hanem , Khattab Haidy , Alaarag Ahmed
Published: December 2022

Background

Heart failure with preserved ejection fraction (HFpEF)is challenging. Patients usually have normal LV size and ejection fraction. This clinical syndrome develops from a complex interaction of several risk factors that cause organ dysfunction and clinical symptoms. There’s evidence that testosterone deficiency is associated with a worse cardiometabolic profile and increased inflammatory markers. We thought that these changes might have an impact on heart failure pathogenesis. We aimed to study the relationship between testosterone level and symptoms in HFpEF.

Methods

We studied 120 male patients with HFpEF. According to New York Heart Association (NYHA), patients were classified into I, II and III classes; class IV patients were excluded. All patients were subjected to clinical and echocardiographic examinations. In addition, we measured serum testosterone, cardio-metabolic profile, intracellular adhesive molecule-1(ICAM-1), P-selectin and nitric oxide (NO) levels.

Results

Patients with testosterone deficiency had worse NYHA class and higher BNP P = (0.001). Additionally, they had a significantly worse metabolic profile; higher total cholesterol, triglycerides, LDL cholesterol, fasting insulin and HOMA-IR P = (0.005, 0.001, 0.001, 0.001), respectively.

Also, they had higher inflammatory markers and worse endothelial functional parameters; (ICAM-1, NO and P- selectin) P = (0.001).

Age, BNP and testosterone deficiency can be used as independent predictors of NYHA class III symptoms with a Testosterone cutoff value of 2.7 ng/ml.

Conclusion

Testosterone deficiency could be used as an independent predictor of symptom severity in HFpEF, and it aggravates systemic inflammation and endothelial dysfunction in these patients.
Utilization of long-acting contraceptive methods and associated factors among married women in Farta Woreda, Northwest Ethiopia: a community-based mixed method study
Authors: Aychew Eden Workneh , Bekele Yibeltal Alemu , Ayele Alemu Degu , Dessie Anteneh Mengist , Dagnew Gizachew Worku
Published: December 2022

Background

Although long-acting contraceptive methods are highly effective, safe, and provide uninterrupted protection from unintended pregnancy compared to short-acting methods, evidences suggest that majority of women were relayed on short-acting contraceptive methods. Thus, this study aimed to determine the level of long-acting contraceptive methods utilization and associated factors among married women in Farta Woreda, Northwest Ethiopia, 2021.

Methods

A community-based cross-sectional study supplemented with qualitative data was performed among 556 married women from March 1 to 31, 2021. A semi-structured interviewer-administered questionnaire and interview guides were used to collect the data. The data were entered into Epi data version 4.6 and analyzed by SPSS version 23 software. The association between variables was analyzed using bivariate and multivariable binary logistic regression. The level of statistically significant association was determined at a P-value < 0.05. After translation and transcription, manual thematic analysis was applied to the qualitative data.

Results

The magnitude of long-acting contraceptive methods among married women in Farta Woreda was found to be 14.3% [95% CI 11.5–17.6]. Previous use of long-acting contraceptive methods (AOR = 5.83, 95% CI 3.03, 11.21), positive attitude towards long-acting contraceptives (AOR = 2.74, 95% CI 1.48, 5.07), having formal education for husbands’ (AOR = 3.05, 95% CI 1.5, 6.21), and poor wealth index (AOR = 3.39, 95% CI 1.33, 8.67) were positively associated with utilization of long-acting contraceptive methods. Moreover, fear of side effects, misconceptions, and partner opposition were the most commonly identified barriers by the qualitative data.

Conclusion

Utilization of long-acting contraceptives among married women in Farta Woreda was low as compared to the 2020/21 national reproductive health strategy plan to increase the long-acting reversible and permanent contraceptive methods use to 50%. Previous use of long-acting contraceptives, positive attitude towards long-acting contraceptives, husband education, and household wealth index was found to be significantly associated with long-acting contraceptive utilization. Hence, it is better to work more on changing women's attitudes and increasing husband education.
Transcriptomics and metabolomics reveal changes in the regulatory mechanisms of osteosarcoma under different culture methods in vitro
Authors: Yang Sen , Tian Zhi , Feng Yi , Zhang Kun , Pan Yongchun , Li Yuan , Wang Zhichao , Wei Wenhao , Qiao Xiaochen , Zhou Ruhao , Yan Lei , Li Qian , Guo Hua , Yuan Jie , Li Pengcui , Lv Zhi
Published: December 2022

Background

Recently, increasing attention has been drawn to the impact of the tumor microenvironment (TME) on the occurrence and progression of malignant tumors. A variety of 3D culture techniques have been used to simulate TME in vitro. The purpose of this study was to reveal the differences in transcriptional and metabolic levels between osteosarcoma (OS) 2D cells, 3D cells, 3D cell-printed tissue, isolated tissue, and transplanted tumor tissue in vivo.

Methods

We cultured the OS Saos-2 cell line under different culture methods as 2D cells, 3D cells, 3D cell-printed tissue and isolated tissue for 14 days and transplanted tumors in vivo as a control group. Through transcriptomic and metabonomic analyses, we determined the changes in gene expression and metabolites in OS tissues under different culture methods.

Results

At the transcriptional level, 166 differentially expressed genes were found, including the SMAD family, ID family, BMP family and other related genes, and they were enriched in the TGF-β signaling pathway, complement and coagulation cascades, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, ferroptosis, cGMP-PKG signaling pathway and other pathways. At the metabolic level, 362 metabolites were significantly changed and enriched in metabolic pathways such as the Fc Epsilon RI signaling pathway, histidine metabolism, primary bile acid biosynthesis, steroid biosynthesis, protein digestion and absorption, ferroptosis, and arachidonic acid metabolism. After integrating the transcriptome and metabolomics data, it was found that 44 metabolic pathways were changed, and the significantly enriched pathways were ferroptosis and pyrimidine metabolism.

Conclusion

Different culture methods affect the gene expression and metabolite generation of OS Saos-2 cells. Moreover, the cell and tissue culture method in vitro cannot completely simulate TME in vivo, and the ferroptosis and pyrimidine metabolism pathways mediate the functional changes of OS Saos-2 cells in different microenvironments.
Challenges of design, implementation, acceptability, and potential for, biomedical technologies in the Peruvian Amazon
Authors: Bressan Tiana , Valdivia-Gago Andrea , Silvera-Ccallo Rosa M. , Llanos-Cuentas Alejandro , Condor Daniel F. , Padilla-Huamantinco Pierre G. , Vilcarromero Stalin , Miranda J. Jaime , Zavaleta-Cortijo Carol
Published: December 2022

Background

Biomedical technologies have the potential to be advantageous in remote communities. However, information about barriers faced by users of technology in general and in remote Indigenous communities is scarce. The purpose of this study was to characterize the leading challenges faced by researchers who have used biomedical technologies in the Peruvian Amazon.

Methods

This exploratory, qualitative study with a phenomenological approach depicts the lived experience of participants who were researchers with experience working with biomedical technologies in the Peruvian Amazon in the past five years. Analysis was based on three core themes: design, implementation, and acceptability. Sub-themes included environment, community, and culture. Of the 24 potential participants identified and contacted, 14 agreed to participate, and 13 met inclusion criteria and completed semi-structured interviews. Results were sent to each participant with the opportunity to provide feedback and partake in a 30-minute validation meeting. Five participants consented to a follow-up meeting to validate the results and provide further understanding.

Results

Participants recognized significant challenges, including technologies designed out-of-context, difficulty transporting the technologies through the Amazon, the impact of the physical environment (e.g., humidity, flooding), and limited existing infrastructure, such as electricity and appropriately trained health personnel. Participants also identified cultural factors, including the need to address past experiences with technology and health interventions, understand and appropriately communicate community benefits, and understand the effect of demographics (e.g., age, education) on the acceptance and uptake of technology. Complementary challenges, such as corruption in authority and waste disposal, and recommendations for technological and health interventions such as co-design were also identified.

Conclusions

This study proposes that technological and health interventions without efforts to respect local cultures and health priorities, or understand and anticipate contextual challenges, will not meet its goal of improving access to healthcare in remote Amazon communities. Furthermore, the implications of corruption on health services, and improper waste disposal on the environment may lead to more detrimental health inequities.
Efficacy of probiotic Streptococcus thermophilus in counteracting TGF-β1-induced fibrotic response in normal human dermal fibroblasts
Authors: Lombardi Francesca , Augello Francesca Rosaria , Artone Serena , Bahiti Blerina , Sheldon Jenna Marie , Giuliani Maurizio , Cifone Maria Grazia , Palumbo Paola , Cinque Benedetta
Published: December 2022

Background

Abnormal and deregulated skin wound healing associated with prolonged inflammation may result in dermal fibrosis. Since the current therapeutic strategies revealed unsatisfactory, the investigation of alternative approaches such as those based on the use of specific probiotic strains could provide promising therapeutic options. In this study, we aimed to evaluate whether the lysate from S. thermophilus could antagonize the fibrogenic effects of TGF-β1 in normal human dermal fibroblasts (NHDF).

Methods

NHDF were exposed to TGF-β1 to establish a fibrotic phenotype. Proliferation rate and cell number were measured using the IncuCyte® Live Cell Imager system and the trypan blue dye exclusion test. Phenoconversion markers (α-SMA and fibronectin) and collagen I levels were assessed by western blot and immunofluorescence. The mRNA levels of TGF-β1 were evaluated by RT-PCR. The Smad2/3 phosphorylation level as well as β-catenin and PPARγ expression, were assessed by western blot. The cell contractility function and migration of NHDF were studied using collagen gel retraction assay, and scratch wound healing assay, respectively. The effects of S. thermophilus lysate, alone or combined with TGF-β1, were evaluated on all of the above-listed parameters and markers associated with TGF-β1-induced fibrotic phenotype.

Results

Exposure to the S. thermophilus lysate significantly reduced the key mediators and events involved in the abnormal activation of myofibroblasts by TGF-β1 within the fibrotic profile. The S. thermophilus treatment significantly reduced cell proliferation, migration, and myo-differentiation. In addition, the treatment with probiotic lysate reduced the α-SMA, fibronectin, collagen-I expression levels, and affected the collagen contraction ability of activated dermal fibroblasts. Moreover, the probiotic targeted the TGF-β1 signaling, reducing Smad2/3 activation, TGF-β1 mRNA level, and β-catenin expression through the upregulation of PPARγ.

Conclusion

This is the first report showing that S. thermophilus lysate had a remarkable anti-fibrotic effect in TGF-β1-activated NHDF by inhibiting Smad signaling. Notably, the probiotic was able to reduce β-catenin and increase PPARγ levels. The findings support our point that S. thermophilus may help prevent or treat hypertrophic scarring and keloids.
A simple and effective method to purify and activate T cells for successful generation of chimeric antigen receptor T (CAR-T) cells from patients with high monocyte count
Authors: Wang Haiying , Tsao Shih-Ting , Gu Mingyuan , Fu Chengbing , He Feng , Li Xiu , Zhang Mian , Li Na , Hu Hong-Ming
Published: December 2022

Background

Chimeric antigen receptor T (CAR-T) cells are genetically modified T cells with redirected specificity and potent T-cell-mediated cytotoxicity toward malignant cells. Despite several CAR-T products being approved and commercialized in the USA, Europe, and China, CAR-T products still require additional optimization to ensure reproducible and cost-effective manufacture. Here, we investigated the critical parameters in the CD3+T-cell isolation process that significantly impacted CAR-T manufacturing's success.

Methods

CAR-T cells were prepared from cryopreserved peripheral blood mononuclear cells (PBMC). The thawed PBMC was rested overnight before the CD3+T cell isolation process using CTS™Dynabeads™CD3/CD28. Different isolation media, cell-bead co-incubation time, and cell density were examined in this study. Activated CD3+T cells were transduced with a gamma retroviral vector carrying the CD19 or BCMA CAR sequence. The CAR-T cells proliferated in a culture medium supplemented with interleukin 2 (IL-2).

Results

CD14+monocytes hindered T-cell isolation when X-VIVO 15 basic medium was used as the selection buffer. The activation of T cells was blocked because monocytes actively engulfed CD3/28 beads. In contrast, when DPBS was the selection medium, the T-cell isolation and activation were no longer blocked, even in patients whose PBMC contained abnormally high CD14+monocytes and a low level of CD3+T cells.

Conclusions

In this study, we discovered that selecting CD3+T-cell isolation media is critical for improving T-cell activation, transduction, and CAR-T proliferation. Using DPBS as a CD3+T cell isolation buffer significantly improved the success rate and shortened the duration of CAR-T production. The optimized process has been successfully applied in our ongoing clinical trials.

Trial registrationNCT03798509: Human CD19 Targeted T Cells Injection Therapy for Relapsed and Refractory CD19-positive Leukemia. Date of registration: January 10, 2019. NCT03720457: Human CD19 Targeted T Cells Injection (CD19 CAR-T) Therapy for Relapsed and Refractory CD19-positive Lymphoma. Date of registration: October 25, 2018. NCT04003168: Human BCMA Targeted T Cells Injection Therapy for BCMA-positive Relapsed/Refractory Multiple Myeloma. Date of registration: July 1, 2019
Reliability and validity of physical examination tests for the assessment of ankle instability
Authors: Beynon Amber , Le May Sylvie , Theroux Jean
Published: December 2022

Introduction

Clinicians rely on certain physical examination tests to diagnose and potentially grade ankle sprains and ankle instability. Diagnostic error and inaccurate prognosis may have important repercussions for clinical decision-making and patient outcomes. Therefore, it is important to recognize the diagnostic value of orthopaedic tests through understanding the reliability and validity of these tests.

Objective

To systematically review and report evidence on the reliability and validity of orthopaedic tests for the diagnosis of ankle sprains and instability.

Methods

PubMed, CINAHL, Scopus, and Cochrane databases were searched from inception to December 2021. In addition, the reference list of included studies, located systematic reviews, and orthopaedic textbooks were searched. All articles reporting reliability or validity of physical examination or orthopaedic tests to diagnose ankle instability or sprains were included. Methodological quality of the reliability and the validity studies was assessed with The Quality Appraisal for Reliability studies checklist and the Quality Assessment of Diagnostic Accuracy Studies-2 respectively. We identified the number of times the orthopaedic test was investigated and the validity and/or reliability of each test.

Results

Overall, sixteen studies were included. Three studies assessed reliability, eight assessed validity, and five evaluated both. Overall, fifteen tests were evaluated, none demonstrated robust reliability and validity scores. The anterolateral talar palpation test reported the highest diagnostic accuracy. Further, the anterior drawer test, the anterolateral talar palpation, the reverse anterior lateral drawer test, and palpation of the anterior talofibular ligament reported the highest sensitivity. The highest specificity was attributed to the anterior drawer test, the anterolateral drawer test, the reverse anterior lateral drawer test, tenderness on palpation of the proximal fibular, and the squeeze test.

Conclusion

Overall, the diagnostic accuracy, reliability, and validity of physical examination tests for the assessment of ankle instability were limited. Physical examination tests should not be used in isolation, but rather in combination with the clinical history to diagnose an ankle sprain. Preliminary evidence suggests that the overall validity of physical examination for the ankle may be better if conducted five days after the injury rather than within 48 h of injury.
Effect of ACDF combined with different degrees of partial resection of uncovertebral joints on cervical stability and degeneration: a three-dimensional finite element analysis
Authors: Guo Wei , Jiang Yuan , Zhu Yang , Huang Jingwen
Published: December 2022

Background

To evaluate the influence of the resection of different amounts of the uncovertebral joints on the stability of the cervical spine by comparing and analyzing the stress distribution and peak displacement characteristics of the internal fixation structures and endplates.

Methods

After obtaining the CT data of a 34-year-old male healthy cervical spine, a three-dimensional finite element model was established and verified. The three-dimensional finite element method was used to establish the models of anterior cervical compression fusion and internal fixation surgical implants and anterior cervical compression fusion and internal fixation combined with the partial resection of different amounts of the unilateral or bilateral uncovertebral joints. The models were tested under six working conditions: flexion, extension, left bending, right bending, left rotation, and right rotation. The surgical models were compared regarding the stress distribution of the titanium mesh, titanium plate and screw, and endplate, and the peak displacement of the vertebral body.

Results

There were no significant differences in the stress distribution and peak displacement of the vertebral body of ACDF combined with different amounts of uncovertebral joint resection in the states of flexion and extension. However, there were significant increases in the stress distribution and peak displacement of the vertebral body in the states of left and right bending and rotation. In the states of left and right bending and rotation, the stress distribution and peak displacement of the vertebral body were significantly greater in the models with bilateral partial resection of the uncovertebral joints than in the models with unilateral partial resection of the uncovertebral joints. Bilateral resection of the uncovertebral joints by 30–40% and unilateral resection of the uncovertebral joints by 40–50% resulted in the greatest increases in the maximum stress distribution of the titanium plate and screw and the peak displacement of the vertebral body.

Conclusion

Finite element analysis of the biomechanical changes in the cervical spine showed that anterior cervical compression fusion and internal fixation combined with bilateral resection of less than 30% of the uncovertebral joints or unilateral resection of less than 40% of the uncovertebral joints had little effect on the stability of the cervical spine.
Surface electroencephalographic neurofeedback improves sustained attention in ADHD: a meta-analysis of randomized controlled trials
Authors: Chiu Hsien‐Jane , Sun Cheuk-Kwan , Fan Hsin-Yi , Tzang Ruu‐Fen , Wang Ming-Yu , Cheng Ying-Chih , Cheng Yu-Shian , Yeh Pin-Yang , Chung Weilun
Published: December 2022

Background

The efficacy of surface electroencephalographic neurofeedback (EEG-NF) for improving attentional performance assessed by laboratory measures in patients with attention-deficit/hyperactivity disorder (ADHD) remains unclear.

Methods

Following the PRISMA guidelines, the PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials on the efficacy of surface EEG-NF against ADHD focusing on attentional performance evaluated by laboratory measures from inception to January 2022.

Results

Fourteen eligible studies were analyzed. Of the 718 participants involved, 429 diagnosed with ADHD received EEG-NF treatment. Significant improvement in attentional performance in ADHD subjects receiving EEG-NF was noted compared to their comparators (p < 0.01). Besides, there was a significant EEG-NF-associated beneficial effect on sustained attention (Hedges’ g = 0.32, p < 0.01), whereas the impact on selective attention (p = 0.57) and working memory (p = 0.59) was limited. Moreover, protocol including beta wave enhancement was superior to that only focusing on reducing theta/beta ratio or modulation of slow cortical potential. Subgroup analyses showed that three sessions per week of EEG-NF produced the best effect, while the efficacy of surface EEG-NF was much poorer (Hedges’ g = 0.05) when only studies that blinded their participants from knowledge of treatment allocation were included. No significant difference was noted in the improvement of attentional performance 6–12 months after EEG-NF intervention (n = 3, p = 0.42).

Conclusions

Our results demonstrated the satisfactory effectiveness of surface EEG-NF for improving sustained attention, especially when beta wave enhancement was included, despite its failure to sustain a long-term effect. Further large-scale trials are warranted to support our findings.
Single-cell transcriptome reveals dominant subgenome expression and transcriptional response to heat stress in Chinese cabbage
Authors: Sun Xiaoxue , Feng Daling , Liu Mengyang , Qin Ruixin , Li Yan , Lu Yin , Zhang Xiaomeng , Wang Yanhua , Shen Shuxing , Ma Wei , Zhao Jianjun
Published: December 2022

Background

Chinese cabbage (Brassica rapa ssp. pekinensis) experienced a whole-genome triplication event and thus has three subgenomes: least fractioned, medium fractioned, and most fractioned subgenome. Environmental changes affect leaf development, which in turn influence the yield. To improve the yield and resistance to different climate scenarios, a comprehensive understanding of leaf development is required including insights into the full diversity of cell types and transcriptional networks underlying their specificity.

Results

Here, we generate the transcriptional landscape of Chinese cabbage leaf at single-cell resolution by performing single-cell RNA sequencing of 30,000 individual cells. We characterize seven major cell types with 19 transcriptionally distinct cell clusters based on the expression of the reported marker genes. We find that genes in the least fractioned subgenome are predominantly expressed compared with those in the medium and most fractioned subgenomes in different cell types. Moreover, we generate a single-cell transcriptional map of leaves in response to high temperature. We find that heat stress not only affects gene expression in a cell type-specific manner but also impacts subgenome dominance.

Conclusions

Our study highlights the transcriptional networks in different cell types and provides a better understanding of transcriptional regulation during leaf development and transcriptional response to heat stress in Chinese cabbage.
Persisting neuropsychiatric symptoms, Alzheimer’s disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate
Authors: Ouanes Sami , Rabl Miriam , Clark Christopher , Kirschbaum Clemens , Popp Julius
Published: December 2022

Introduction

Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer’s disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol.

Objectives

We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology.

Methods

One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms’ changes over time, baseline CSF cortisol and DHEAS, and AD pathology.

Results

Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months.

Conclusion

Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.
PD-1 and LAG-3-positive T cells are associated with clinical outcomes of relapsed/refractory multiple myeloma patients
Authors: Chen Ming , Zhu Jinlian , Yang Xuedong , Yao Jianxin , Liu Yuqing , Liu Qiang
Published: December 2022

Objective

To investigate the frequency of PD-1 and LAG-3-positive T cells in relapsed/refractory multiple myeloma (RRMM) patients and its clinical significance.

Methods

This prospective observational study enrolled a total of 71 RRMM patients, as well as 70 MM patients (non-refractory) and 70 healthy individuals during January 2018 to March 2021. The frequency of circulating CD4+ and CD8+ T cells expressing PD-1 and LAG-3 was analyzed using flow cytometry. Serum cytokines of IL-6, IL-17, CRP, TNF-α and TGF-β were evaluated by enzyme linked immunosorbent assay (ELISA).

Results

Significant higher 1-year mortality rate was found in RRMM patients compared with the MM patients. In both CD4+ and CD8+ T cells, the frequencies of PD-1+, LAG-3+ and PD-1+/LAG-3+ T cells were markedly higher in the RRMM patients and the deceased patients, compared with the MM patients and the survival patients, respectively. All cytokines were remarkably higher in RRMM and MM patients than in the healthy control, while only serum levels of IL-6 and IL-17 were markedly higher in RRMM patients compared with the MM patients. Positive correlation was observed among the IL-6, IL-17 and the frequencies of circulating T cells in both CD4+ and CD8+ T cells in RRMM and MM patients. The frequency of CD8+PD-1+LAG-3+ T cells showed the best sensitivity 82.61% and specificity 76.06% for diagnosis of RRMM using ROC curve. Meanwhile, the frequency of CD4+PD-1+ cells showed the best sensitivity 84.00% and specificity 97.35% for prediction of patients’ mortality by ROC curve. The frequencies of CD4+PD-1+, CD8+PD-1+/LAG-3+, as well as IL-6, IL-17 and TNF-α were found as risk factors for incidence of RRMM in all MM patients.

Conclusion

The frequency of PD-1 and LAG-3-positive T cells is associated with the clinical severity and inflammation in RRMM patients, which may also serve as potential biomarkers for its diagnosis.
Zearalenone disturbs the reproductive-immune axis in pigs: the role of gut microbial metabolites
Authors: Wang Shujin , Fu Wei , Zhao Xueya , Chang Xiaojiao , Liu Hujun , Zhou Lin , Li Jian , Cheng Rui , Wu Xin , Li Xi , Sun Changpo
Published: December 2022

Background

Exposure to zearalenone (ZEN, a widespread Fusarium mycotoxin) causes reproductive toxicity and immunotoxicity in farm animals, and it then poses potential threats to human health through the food chain. A systematic understanding of underlying mechanisms on mycotoxin-induced toxicity is necessary for overcoming potential threats to farm animals and humans. The gastrointestinal tract is a first-line defense against harmful mycotoxins; however, it remains unknown whether mycotoxin (e.g., ZEN)-induced toxicity on the reproductive-immune axis is linked to altered gut microbial metabolites. In this study, using pigs (during the three phases) as an important large animal model, we investigated whether ZEN-induced toxicity on immune defense in the reproductive-immune axis was involved in altered gut microbial-derived metabolites. Moreover, we observed whether the regulation of gut microbial-derived metabolites through engineering ZEN-degrading enzymes counteracted ZEN-induced toxicity on the gut-reproductive-immune axis.

Results

Here, we showed ZEN exposure impaired immune defense in the reproductive-immune axis of pigs during phase 1/2. This impairment was accompanied by altered gut microbial-derived metabolites [e.g., decreased butyrate production, and increased lipopolysaccharides (LPS) production]. Reduction of butyrate production impaired the intestinal barrier via a GPR109A-dependent manner, and together with increased LPS in plasma then aggravated the systemic inflammation, thus directly and/or indirectly disturbing immune defense in the reproductive-immune axis. To validate these findings, we further generated recombinant Bacillus subtilis 168-expressing ZEN-degrading enzyme ZLHY-6 (the Bs-Z6 strain) as a tool to test the feasibility of enzymatic removal of ZEN from mycotoxin-contaminated food. Notably, modified gut microbial metabolites (e.g., butyrate, LPS) through the recombinant Bs-Z6 strain counteracted ZEN-induced toxicity on the intestinal barrier, thus enhancing immune defense in the reproductive-immune axis of pigs during phase-3. Also, butyrate supplementation restored ZEN-induced abnormalities in the porcine small intestinal epithelial cell.

Conclusions

Altogether, these results highlight the role of gut microbial-derived metabolites in ZEN-induced toxicity on the gut-reproductive-immune axis. Importantly, targeting these gut microbial-derived metabolites opens a new window for novel preventative strategies or therapeutic interventions for mycotoxicosis associated to ZEN.
Temporal and spatial patterns and influencing factors of intangible cultural heritage: Ancient Qin-Shu roads, Western China
Authors: Liu Yuan , Chen Mo , Tian Yonggang
Published: December 2022

The ancient Qin-Shu roads corridor is one of the important cultural main corridors in China. Throughout China’s long historical and cultural evolution, today’s ancestors created a rich intangible cultural heritage along this route. Studying its intangible cultural heritage has important theoretical and practical significance for the protection and innovation of cultural heritage in this region. The purpose of this study is to analyze the spatial and temporal distribution characteristics of intangible cultural heritage along the ancient Qin-Shu roads and explore the main factors affecting its distribution. The nearest neighbor index, kernel density estimation, standard deviation ellipse, location entropy, buffer analysis and other methods were used. The results show that (1) The types of intangible cultural heritage of the ancient Qin-Shu roads are expressed in three echelons. Traditional handicrafts are the most numerous, folk custom and traditional music are the second most numerous, the other categories of ICH are third in quantity overall, among which traditional medicine and sports recreation competition are the scarcest. (2) The overall spatial distribution of intangible cultural heritage along the ancient Qin-Shu roads shows an agglomeration distribution. Its distribution pattern places the central cities (Xi'an, Chengdu and Chongqing) at the core, gradually spreading out and decreasing in density as it reaches peripheral districts and counties. There are significantly differ in the core areas of different types of intangible cultural heritage. (3) In the process of historical development, the intangible cultural heritage of the ancient Qin-Shu roads demonstrated an overall change pattern of “three rising and three falling”. That is, during Qin and Han Dynasties, Sui, Tang and Five Dynasties, and Ming and Qing Dynasties, culture flourished, while in Wei, Jin, Southern and Northern Dynasties, Song and Yuan Dynasties, modern times culture developed slowly. The overall trajectory of the center of gravity of intangible cultural heritage shifted from the northeast to the southwest. (4) Natural and human factors, such as topography, climate, transportation, traditional villages and population evolution, have an important impact on the spatial pattern of the intangible cultural heritage of the ancient Qin-Shu roads. The results of this study provide a useful reference for the theoretical research and practical management of intangible cultural heritage.