bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid microRNAs as potential biomarkers in Alzheimer’s disease
Authors: Noor Eddin Ahmed , Hamsho Khaled , Adi Ghaith , Al-Rimawi Mohammed , Alfuwais Mohammed , Abdul Rab Saleha , Alkattan Khaled , Yaqinuddin Ahmed
Published: July 2023

Alzheimer’s disease (AD) is the leading form of dementia worldwide, but its early detection and diagnosis remain a challenge. MicroRNAs (miRNAs) are a group of small endogenous RNA molecules that regulate mRNA expression. Recent evidence suggests miRNAs play an important role in the five major hallmarks of AD pathophysiology: amyloidogenesis, tauopathy, neuroinflammation, synaptic dysfunction, and neuronal death. Compared to traditional biomarkers of AD, miRNAs display a greater degree of stability in cerebrospinal fluid. Moreover, aberrant changes in miRNA expression can be measured over time to monitor and guide patient treatment. Specific miRNA profiles and combinations may also be used to distinguish AD subjects from normal controls and other causes of dementia. Because of these properties, miRNAs are now being considered as promising and potential biomarkers of AD. This review comprehensively summarizes the diagnostic potential and regulatory roles miRNAs play in AD.
Locus coeruleus inhibition of vibrissal responses in the trigeminal subnucleus caudalis are reduced in a diabetic mouse model
Authors: Mesa-Lombardo Alberto , García-Magro Nuria , Nuñez Angel , Martin Yasmina B.
Published: July 2023

Diabetic neuropathy is the loss of sensory function beginning distally in the lower extremities, which is also characterized by pain and substantial morbidity. Furthermore, the locus coeruleus (LC) nucleus has been proposed to play an important role in descending pain control through the activation of α2-noradrenergic (NA) receptors in the spinal dorsal horn. We studied, on control and diabetic mice, the effect of electrical stimulation of the LC nucleus on the tactile responses in the caudalis division of the spinal trigeminal nucleus (Sp5C), which is involved in the relay of orofacial nociceptive information. Diabetes was induced in young adult C57BL/6J mice with one intraperitoneal injection of streptozotocin (50 mg/kg) daily for 5 days. The diabetic animals showed pain in the orofacial area because they had a decrease in the withdrawal threshold to the mechanical stimulation in the vibrissal pad. LC electrical stimulation induced the inhibition of vibrissal responses in the Sp5C neurons when applied at 50 and 100 ms before vibrissal stimulation in the control mice; however, the inhibition was reduced in the diabetic mice. These effects may be due to a reduction in the tyrosine hydroxylase positive (TH+) fibers in the Sp5C, as was observed in diabetic mice. LC-evoked inhibition was decreased by an intraperitoneal injection of the antagonist of the α2-NA receptors, yohimbine, indicating that it was due to the activation of α2-NA receptors. The decrease in the LC-evoked inhibition in the diabetic mice was partially recovered when clonidine, a non-selective α2-agonist, was injected intraperitoneally. These findings suggest that in diabetes, there is a reduction in the NA inputs from the LC in the Sp5C that may favor the development of chronic pain.
Changes in synaptic inputs to dI3 INs and MNs after complete transection in adult mice
Authors: Goltash Sara , Stevens Shannon J. , Topcu Emine , Bui Tuan V.
Published: July 2023

Introduction

Spinal cord injury (SCI) is a debilitating condition that disrupts the communication between the brain and the spinal cord. Several studies have sought to determine how to revive dormant spinal circuits caudal to the lesion to restore movements in paralyzed patients. So far, recovery levels in human patients have been modest at best. In contrast, animal models of SCI exhibit more recovery of lost function. Previous work from our lab has identified dI3 interneurons as a spinal neuron population central to the recovery of locomotor function in spinalized mice. We seek to determine the changes in the circuitry of dI3 interneurons and motoneurons following SCI in adult mice.

Methods

After a complete transection of the spinal cord at T9-T11 level in transgenic Isl1:YFP mice and subsequent treadmill training at various time points of recovery following surgery, we examined changes in three key circuits involving dI3 interneurons and motoneurons: (1) Sensory inputs from proprioceptive and cutaneous afferents, (2) Presynaptic inhibition of sensory inputs, and (3) Central excitatory glutamatergic synapses from spinal neurons onto dI3 INs and motoneurons. Furthermore, we examined the possible role of treadmill training on changes in synaptic connectivity to dI3 interneurons and motoneurons.

Results

Our data suggests that VGLUT1+ inputs to dI3 interneurons decrease transiently or only at later stages after injury, whereas levels of VGLUT1+ remain the same for motoneurons after injury. Levels of VGLUT2+ inputs to dI3 INs and MNs may show transient increases but fall below levels seen in sham-operated mice after a period of time. Levels of presynaptic inhibition to VGLUT1+ inputs to dI3 INs and MNs can rise shortly after SCI, but those increases do not persist. However, levels of presynaptic inhibition to VGLUT1+ inputs never fell below levels observed in sham-operated mice. For some synaptic inputs studied, levels were higher in spinal cord-injured animals that received treadmill training, but these increases were observed only at some time points.

Discussion

These results suggest remodeling of spinal circuits involving spinal interneurons that have previously been implicated in the recovery of locomotor function after spinal cord injury in mice.
Empirical mode decomposition of local field potential data from optogenetic experiments
Authors: Oprisan Sorinel A. , Clementsmith Xandre , Tompa Tamas , Lavin Antonieta
Published: July 2023

Introduction

This study investigated the effects of cocaine administration and parvalbumin-type interneuron stimulation on local field potentials (LFPs) recorded in vivo from the medial prefrontal cortex (mPFC) of six mice using optogenetic tools.

Methods

The local network was subject to a brief 10 ms laser pulse, and the response was recorded for 2 s over 100 trials for each of the six subjects who showed stable coupling between the mPFC and the optrode. Due to the strong non-stationary and nonlinearity of the LFP, we used the adaptive, data-driven, Empirical Mode Decomposition (EMD) method to decompose the signal into orthogonal Intrinsic Mode Functions (IMFs).

Results

Through trial and error, we found that seven is the optimum number of orthogonal IMFs that overlaps with known frequency bands of brain activity. We found that the Index of Orthogonality (IO) of IMF amplitudes was close to zero. The Index of Energy Conservation (IEC) for each decomposition was close to unity, as expected for orthogonal decompositions. We found that the power density distribution vs. frequency follows a power law with an average scaling exponent of ~1.4 over the entire range of IMF frequencies 2–2,000 Hz.

Discussion

The scaling exponent is slightly smaller for cocaine than the control, suggesting that neural activity avalanches under cocaine have longer life spans and sizes.
Time of day dependent longitudinal changes in resting-state fMRI
Authors: Vaisvilaite Liucija , Andersson Micael , Salami Alireza , Specht Karsten
Published: July 2023

Longitudinal studies have become more common in the past years due to their superiority over cross-sectional samples. In light of the ongoing replication crisis, the factors that may introduce variability in resting-state networks have been widely debated. This publication aimed to address the potential sources of variability, namely, time of day, sex, and age, in longitudinal studies within individual resting-state fMRI data. DCM was used to analyze the fMRI time series, extracting EC connectivity measures and parameters that define the BOLD signal. In addition, a two-way ANOVA was used to assess the change in EC and parameters that define the BOLD signal between data collection waves. The results indicate that time of day and gender have significant model evidence for the parameters that define the BOLD signal but not EC. From the ANOVA analysis, findings indicate that there was a significant change in the two nodes of the DMN and their connections with the fronto-parietal network. Overall, these findings suggest that in addition to age and gender, which are commonly accounted for in the fMRI data collection, studies should note the time of day, possibly treating it as a covariate in longitudinal samples.
Abnormal regional spontaneous neural activity and functional connectivity in thyroid-associated ophthalmopathy patients with different activity: a resting-state fMRI study
Authors: Jiang Mengda , Zhang Haiyang , Liu Yuting , Wu Shuo , Qu Jialu , Tang Yan , Song Yang , Li Yinwei , Sun Jing , Zhu Ling , Zhou Huifang , Tao Xiaofeng
Published: July 2023

Purpose

We aimed to evaluate the spontaneous neuronal activity and functional connectivity pattern variations using resting-state functional magnetic resonance imaging (rs-fMRI) measures, such as amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and functional connectivity (FC), in patients with thyroid-associated ophthalmopathy (TAO).

Method

A total of 24 active TAO patients, 26 inactive TAO patients, and 27 matched healthy controls (HCs) were included. First, ALFF and fALFF were used to detect local neural activity changes, the MRI data were analyzed, and regions with group differences were taken as seeds. Second, FC analysis was performed to explore the altered connection between seeds and other brain regions. A correlation analysis was performed to assess the relationship between functional brain activity and clinical indices and neuropsychiatric behaviors.

Results

Compared to HCs, both active and inactive TAO patients exhibited significantly lower ALFF values in the right calcarine (Calcarine_R) and left postcentral gyrus (Postcentral_L). Active TAO patients also showed significantly higher ALFF values in the left caudate nucleus (Caudate_L) and increased fALFF values in the superior lobe of the right cerebellum (Cerebelum_Crus1_R). Moreover, both active and inactive TAO patients demonstrated decreased FC within the left postcentral gyrus (Postcentral_L) compared to HCs. Additionally, active TAO patients exhibited lower FC compared to inactive TAO patients. The ALFF values in the Calcarine_R of active TAO patients positively correlated with disease duration (r = 0.5892, p = 0.0049) and the Hamilton Anxiety Rating Scale (HARS; r = 0.5377, p = 0.0119). Furthermore, the ALFF value in the Calcarine_R of inactive TAO patients negatively correlated with visual functioning (r = −0.5449, p = 0.0072), while the ALFF values in the Caudate_L of active TAO patients positively correlated with visual functioning (r = 0.6496, p = 0.0014).

Conclusion

We found that the Caudate_L and Cerebelum_Crus1_R related to motor control and coordination in active TAO patients exhibit significant compensatory mechanisms; whereas, the Calcarine_R and Postcentral_L related to visual and somatosensory cortices show varying degrees of impairment. Our findings complement the functional neural mechanism of TAO.
Gene expression analysis in recurrent benign paroxysmal positional vertigo: a preliminary study
Authors: Oh Eun Hye , Lee Jin-Ok , Kim Hyun Sung , Park Ji-Yun , Choi Seo Young , Choi Kwang-Dong , Kim Ji-Soo , Choi Jae-Hwan
Published: July 2023

Objectives

This study aimed to determine the pathophysiology of recurrent benign paroxysmal positional vertigo (BPPV) in young patients using gene expression profiling combined with bioinformatics analysis.

Methods

Total RNA was extracted from the whole blood of four young patients with recurrent BPPV and four controls. The differentially expressed genes (DEGs) between the groups were screened using a microarray analysis based on the cutoff criteria of |log2 fold change| > 1 and an adjusted p-value of < 0.05. Functional enrichment analysis of DEGs was performed using Gene Ontology analysis, and the protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of the Interacting Genes database.

Results

A total of 39 DEGs were detected between the BPPV and control samples, comprising 33 upregulated DEGs and six downregulated DEGs in the BPPV group. Functional enrichment analysis indicated that the upregulated DEGs were significantly enriched in terms related to metabolic processes and the immune system. Two main pathways were extracted from the PPI network: one was associated with oxidative phosphorylation and stress and the other with the adaptive immune system and extracellular matrix degradation.

Conclusion

The findings of our bioinformatics analysis indicated that oxidative stress or extracellular matrix degradation due to immune-mediated inflammatory responses may contribute to the development of recurrent BPPV in young patients.
Hyperbaric oxygen therapy as an adjunct to corticosteroid treatment in sudden sensorineural hearing loss: a retrospective study
Authors: Skarzynski Piotr H. , Kolodziejak Aleksandra , Gos Elżbieta , Skarzynska Magdalena B. , Czajka Natalia , Skarzynski Henryk
Published: July 2023

Background

A retrospective clinical study was conducted to test the impact of including hyperbaric oxygen therapy in the treatment of patients with sudden sensorineural hearing loss (SSNHL).

Materials and methods

A total of 63 adult patients with sudden sensorineural hearing loss diagnosed between 2015 and 2023 were divided into two groups: 36 patients treated with intratympanic glucocorticoid and orally administered glucocorticoid who also underwent hyperbaric oxygen therapy and 27 patients treated with intratympanic glucocorticoid and prolonged orally administered glucocorticoid (without hyperbaric oxygen therapy). An audiological evaluation was performed using pure-tone audiometry.

Results

Average hearing gain as measured by pure tone average was 12.5 dB HL (+/- 19.9 dB HL) in the patients treated with steroids combined with HBOT, and was 14.1 dB HL (+/- 17.9 dB) in the patients treated with steroids alone. Successful treatment (complete recovery or marked improvement) was observed in 27.8% of the patients in the first group and in 25.5% in the second group. There was no statistically significant difference between the groups.

Conclusion

Both groups of patients—those treated with glucocorticoids and those treated with glucocorticoids and HBOT—had similar hearing outcomes. A prospective, controlled, and randomized study would provide more reliable knowledge about the efficacy of HBOT in treating SSNHL.
“InMotion”—Mixed physical exercise program with creative movement as an intervention for adults with schizophrenia: study protocol for a randomized controlled trial
Authors: Poikonen Hanna , Duberg Anna , Eriksson Mats , Eriksson-Crommert Martin , Lund Majja , Möller Margareta , Msghina Mussie
Published: July 2023

Background

Schizophrenia is among the world’s top 10 causes of long-term disability with symptoms that lead to major problems in social and occupational functioning, and in self-care. Therefore, it is important to investigate the efficacy of complementary treatment options for conventionally used antipsychotic medication, such as physical training, and psychosocial interventions.

Objective

To combine aerobic and strength training with cognitive, emotional and social stimulation in one intervention for people with schizophrenia and test the feasibility and effects of this intervention.

Methods

The study is a mixed-method randomized controlled trial to evaluate the effects of a 12-week intervention for adults with schizophrenia. The treatment group (30 participants) will receive the intervention in addition to standard care and the control group (30 participants) only standard care. The intervention consists of 24 biweekly sessions with a duration of 60 min. The pre-test (weeks from 4 to 2 prior to the intervention) and post-test (week 12) include clinical measure (PANSS), quality of life, social performance, movement quantity, brain function and eye tracking measures. In addition, a treatment subgroup of 12–15 participants and their family member or other next of kin will complete a qualitative interview as a part of their post-test. Two follow-up tests, including clinical, quality of life, brain function and eye tracking will be made at 6 and 12 months from the completion of the intervention to both study groups. The primary outcome is change in negative symptoms. Secondary outcome measures include general and positive symptoms, quality of life, social performance, movement quantity, brain function and eye tracking. Explorative outcome includes patient and family member or other next of kin interview.

Results

Pilot data was collected by June 2023 and the main data collection will begin in September 2023. The final follow-up is anticipated to be completed by 2026.

Conclusion

The InMotion study will provide new knowledge on the feasibility, efficacy, and experiences of a novel intervention for adults with schizophrenia. The hypothesis is that regular participation in the intervention will reduce clinical symptoms, normalize physiological measures such as brain activation, and contribute to new active habits for the participants.

Trial registration

ClinicalTrials.gov, identifier NCT05673941.
Donepezil combined with traditional Chinese medicine has promising efficacy on mild cognitive impairment: a systematic review and meta-analysis
Authors: Yu Si-jia , Tang Hui-ling , Li Wei-hong , Bin Chen-li , Liu Zhang , Tang Zhao-hui , Liang Jing-hong
Published: July 2023

Objective

Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI.

Methods

We conducted a comprehensive search of various databases, including Medline (via PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA.

Results

Our meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: −0.02 to 2.96).

Conclusion

The combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution.
Contrastive self-supervised representation learning without negative samples for multimodal human action recognition
Authors: Yang Huaigang , Ren Ziliang , Yuan Huaqiang , Xu Zhenyu , Zhou Jun
Published: July 2023

Action recognition is an important component of human-computer interaction, and multimodal feature representation and learning methods can be used to improve recognition performance due to the interrelation and complementarity between different modalities. However, due to the lack of large-scale labeled samples, the performance of existing ConvNets-based methods are severely constrained. In this paper, a novel and effective multi-modal feature representation and contrastive self-supervised learning framework is proposed to improve the action recognition performance of models and the generalization ability of application scenarios. The proposed recognition framework employs weight sharing between two branches and does not require negative samples, which could effectively learn useful feature representations by using multimodal unlabeled data, e.g., skeleton sequence and inertial measurement unit signal (IMU). The extensive experiments are conducted on two benchmarks: UTD-MHAD and MMAct, and the results show that our proposed recognition framework outperforms both unimodal and multimodal baselines in action retrieval, semi-supervised learning, and zero-shot learning scenarios.
Association between digestive diseases and sarcopenia among Chinese middle-aged and older adults: a prospective cohort study based on nationally representative survey
Authors: Cui Guanghui , Li Shaojie , Ye Hui , Yang Yao , Chu Yingming , Jia Xiaofen , Feng Yue , Lin Miaomiao , Zhang Xuezhi
Published: July 2023

Objectives

Patients with digestive diseases frequently suffer from dyspepsia and malabsorption, which may lead to muscle loss due to malnutrition. However, it is not clear whether digestive diseases are associated with sarcopenia. This study aims to explore the longitudinal association between digestive diseases and sarcopenia in middle-aged and older adults based on a nationally representative survey from China.

Methods

We used a prospective cohort study including 7,025 middle-aged and older adults aged ≥45 years from the 2011 to 2015 waves China Health and Retirement Longitudinal Study (CHARLS). Digestive diseases were identified using self-report. The assessment of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 Consensus and included three components of muscle strength, physical performance, and muscle mass. Cox hazards regression was used to examine the association between digestive diseases and sarcopenia.

Results

The prevalence of digestive diseases and the incidence of sarcopenia in middle-aged and older adults were 22.6% (95% CI = 21.6–23.6%) and 8.5% (95% CI = 7.8–9.1%). After adjusting for 15 covariates composed of three sets (demographic characteristics, lifestyles, and health status), digestive diseases were associated with a higher risk of sarcopenia (HR = 1.241, 95% CI = 1.034–1.490, P < 0.05). The associations were more pronounced among men, older adults aged 60–79, rural residents, and married people. In addition, the association between digestive diseases and sarcopenia was robust in the sensitivity analysis.

Conclusion

Digestive diseases were associated with an increased risk of sarcopenia in middle-aged and older adults aged ≥45 years. Early intervention of digestive diseases may help to reduce the incidence of sarcopenia in middle-aged and older adults.
Cinnamon essential oil vapor alleviates the reduction of aroma-related volatiles in cold-stored “Feicheng” peach using HS-GC-IMS
Authors: Wang Dan , Zhang Jing , Chen Wen-yu , Zhai Hao , Jiang Yang
Published: July 2023

“Feicheng” peach is popular for its unique aroma, but its defect of being highly sensitive to chilling injury (CI) often leads to aroma loss and internal browning. Essential oils (EOs) are often used to enhance the antioxidant capacity of plants and fruits, as well as to trigger their defense against biotic/abiotic stresses. This study aimed to examine the effect of cinnamon essential oil (CEO) vapor treatment on the aroma quality of peach fruit during cold storage using HS-GC-IMS. The results showed that 50 μL/L CEO vapor reduced the severity of internal browning (IB) in peaches at the stage of 7 ~ 21 d during refrigeration (Significantly, the L* value was higher and the IB index was lower than that of control, p < 0.05). Meanwhile, the evident reduction or loss of aroma content caused by CI was restored to a higher level than the control (p < 0.05). Furthermore, CEO treatment promoted the release of aroma-related volatiles as evidenced by more propyl acetate, and the dimer of amyl acetate, isoamyl acetate, butyl acetate detected than that on harvest day and no-treated group after 21 d of cold storage plus 2 d of shelf life. Genes of PpLOX1, PpLOX2, PpHPL1 and PpADH1 associated with aroma-related volatile biosynthesis revealed higher transcript abundance in peach fruits treated with CEO than the control (p < 0.05). Overall, our study demonstrated that CEO in vapor phase may be beneficial to alleviate the quality deterioration in aroma and flesh color of “Feicheng” peaches caused by CI, which lays a theoretical reference for maintaining postharvest quality of peach fruits.
A review: The nutrition components, active substances and flavonoid accumulation of Tartary buckwheat sprouts and innovative physical technology for seeds germinating
Authors: Dong Yulu , Wang Nan , Wang Shunmin , Wang Junzhen , Peng Wenping
Published: July 2023

Compared with the common grain, Tartary buckwheat enjoys higher nutritional value. Some distinctive nutrition associated with physiological activity of Tartary buckwheat is valuable in medicine. In addition, it’s a good feed crop. In the paper, the main components (starch, protein, amino acid, fatty acid and mineral) and polyphenol bioactive components in Tartary buckwheat and its sprouts were reviewed, and the accumulation of flavonoids in sprouts during germination, especially the methods, synthetic pathways and mechanisms of flavonoid accumulation was summarized. The research on bioactive components and health benefits of Tartary buckwheat also were reviewed. Besides, the applications of innovative physical technology including microwave, magnetic, electromagnetic, ultrasonic, and light were also mentioned and highlighted, which could promote the enrichment of some active substances during seeds germination and growth of Tartary buckwheat sprouts. It would give a good support and benefit for the research and processing of Tartary buckwheat and its sprouts in next day.
Development of a dynamic risk system for predicting the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer after thulium laser resection of bladder tumor or transurethral resection of bladder tumor followed by intravesical BCG instillation
Authors: Sun Jian-Xuan , An Ye , Xu Meng-Yao , Liu Chen-Qian , Xu Jin-Zhou , Xia Qi-Dong , Wang Shao-Gang
Published: July 2023

Background

The high recurrence rate of non-muscle-invasive bladder cancer (NMIBC) after tumor resection brings huge physical and financial burdens for patients. Several predictive models that predict the recurrence of patients with NMIBC have drawbacks in clinical practice. With the rapid development of therapeutic methods, more factors should be taken into consideration when constructing predictive model.

Methods

We retrospectively enrolled 90 patients who were diagnosed as intermediate- or high-risk NMIBC and received a Thulium laser resection of bladder tumor (TmLRBT) or transurethral resection of bladder tumor (TURBT) followed by BCG instillation. Univariate Cox regression analysis and multivariate Cox regression analysis were performed to screen out the independent prognostic factors of recurrence free survival (RFS). A nomogram and risk index were constructed using these prognostic factors.

Results

In this study, 22 patients suffered recurrence; 37 patients (41%) received TmLRBT, and over 90% patients completed intravesical BCG instillation for one year. The univariate Cox regression showed that surgery (TURBT vs TmLRBT), previous bladder tumor, tumor number, pathological stage, post-operative catheterization and number of BCG therapy were associated with RFS. The multivariate Cox regression revealed that surgery (TURBT vs TmLRBT) (HR = 3.16, 95%CI [1.02 – 9.83]); previous bladder tumor (HR = 4.03, 95%CI [1.41 – 11.54]); number of BCG therapy (HR = 0.89, 95%CI [0.84 – 0.95]) were independent prognostic factors. A nomogram was constructed and exhibited excellent capability in predicting the RFS with an AUC of 0.789, 0.848, 0.806 at 6-, 12- and 24-months respectively and a c-index of 0.822. Also, the calibration curve and decision curve analysis were performed to verify the predictive efficacy. The risk index was derived from the nomogram and also exhibited favorable capability in predicting the progression free survival (PFS) of patients.

Conclusions

Patients who received TmLRBT, without previous bladder tumor history and had more intravesical BCG instillations are likely to have better RFS. The nomogram and the risk index which were constructed to predict the RFS and PFS of patients may help urologists to make clinical decisions and aid in precision medicine.
A radiomics model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma
Authors: Li Changfeng , Wang Qiang , Zou Mengda , Cai Ping , Li Xuesong , Feng Kai , Zhang Leida , Sparrelid Ernesto , Brismar Torkel B. , Ma Kuansheng
Published: July 2023

Background

Post-hepatectomy liver failure (PHLF) is a fatal complication after liver resection in patients with hepatocellular carcinoma (HCC). It is of clinical importance to estimate the risk of PHLF preoperatively.

Aims

This study aimed to develop and validate a prediction model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging to estimate the risk of PHLF in patients with HCC.

Methods

A total of 276 patients were retrospectively included and randomly divided into training and test cohorts (194:82). Clinicopathological variables were assessed to identify significant indicators for PHLF prediction. Radiomics features were extracted from the normal liver parenchyma at the hepatobiliary phase and the reproducible, robust and non-redundant ones were filtered for modeling. Prediction models were developed using clinicopathological variables (Clin-model), radiomics features (Rad-model), and their combination.

Results

The PHLF incidence rate was 24% in the whole cohort. The combined model, consisting of albumin–bilirubin (ALBI) score, indocyanine green retention test at 15 min (ICG-R15), and Rad-score (derived from 16 radiomics features) outperformed the Clin-model and the Rad-model. It yielded an area under the receiver operating characteristic curve (AUC) of 0.84 (95% confidence interval (CI): 0.77–0.90) in the training cohort and 0.82 (95% CI: 0.72–0.91) in the test cohort. The model demonstrated a good consistency by the Hosmer–Lemeshow test and the calibration curve. The combined model was visualized as a nomogram for estimating individual risk of PHLF.

Conclusion

A model combining clinicopathological risk factors and radiomics signature can be applied to identify patients with high risk of PHLF and serve as a decision aid when planning surgery treatment in patients with HCC.
Detection of genomic mutations in blood and urine free circulating tumour DNA in patients with inoperable and metastatic lung adenocarcinoma harbouring an EGFR mutation in tissue: a UK pilot study
Authors: Brooks Helen , Li Ling , Addeo Alfredo , Stevens Megan , Comins Charles , Oltean Sebastian
Published: July 2023

The development of methodologies to analyse circulating tumour DNA (ctDNA) in the blood or urine of cancer patients provides an invaluable resource that can be used for diagnosis and prognosis and to evaluate response to treatments. Lung cancer has seen in the last years a revolution in treatment strategy with the use of several classes of EGFR inhibitors. However, almost invariably, resistance to such therapies appears. In this paper, we describe a pilot, longitudinal study with 20 patients with confirmed EGFR mutations in tissue biopsy for lung cancer. The objective of the study was to determine whether ctDNA from plasma and/or urine could be used to monitor the EGFR mutational status of patients with confirmed EGFR mutation-positive non-small cell lung cancer (NSCLC) during treatment with EGFR inhibitors. Blood and urine were collected monthly over periods ranging from 6 to 16 months. CtDNA was analysed in each patient for the presence of several known mutations that predispose to resistance to EGFR inhibitors. We have proven that serial monitoring of ctDNA from both plasma and urine is feasible and that patients are willing to participate in this process. We have also shown that longitudinal ctDNA monitoring may detect resistance mutations before the development of radiological and clinical disease progression.
Factors associated with failure to start consolidation durvalumab after definitive chemoradiation for locally advanced NSCLC
Authors: Langberg Christian Wilhelm , Horndalsveen Henrik , Helland Åslaug , Haakensen Vilde Drageset
Published: July 2023

Introduction

The introduction of consolidation immunotherapy after chemoradiotherapy has improved outcome for patients with locally advanced non-small cell lung cancer. However, not all patients receive this treatment. This study identifies factors associated with failure to start durvalumab as consolidation therapy with the aim of optimizing treatment, supportive care and prehabilitation to ensure that more patients complete the planned treatment.

Materials and methods

Patients from two clinical trials and a named patient use program, were included in this study. All patients received platinum-doublet chemotherapy concomitant with radiotherapy to a total dose of 60-66 gray. Patient characteristics, cancer treatment, toxicity, performance status and laboratory data before and after chemoradiotherapy were recorded and patients who never started durvalumab were compared with those who did.

Results

A total of 101 patients were included, of which 83 started treatments with durvalumab after chemoradiotherapy. The 18 patients who did not start durvalumab had significantly higher lactate dehydrogenase at baseline and a worse performance status, cumulative toxicity and higher c-reactive protein after completed chemoradiotherapy. Data also suggest that pre-treatment diabetes and reduced hemoglobin and/or diffusion capacity of the lungs for carbon monoxide contribute to the risk of treatment abruption.

Conclusion

Treatment plan disruption rate was 18%. Systemic inflammation and performance status were associated with failure to receive durvalumab after chemoradiation. Further studies are needed to confirm findings and prospective trials should investigate whether prehabilitation and supportive treatment could help more patients finishing the planned treatment.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT03798535; NCT04392505.
Research progress on pleiotropic neuroprotective drugs for traumatic brain injury
Authors: Zhao Qinghui , Li Huige , Li Hongru , Zhang Jianhua
Published: July 2023

Traumatic brain injury (TBI) has become one of the most important causes of death and disability worldwide. A series of neuroinflammatory responses induced after TBI are key factors for persistent neuronal damage, but at the same time, such inflammatory responses can also promote debris removal and tissue repair after TBI. The concept of pleiotropic neuroprotection delves beyond the single-target treatment approach, considering the multifaceted impacts following TBI. This notion embarks deeper into the research-oriented treatment paradigm, focusing on multi-target interventions that inhibit post-TBI neuroinflammation with enhanced therapeutic efficacy. With an enriched comprehension of TBI’s physiological mechanisms, this review dissects the advancements in developing pleiotropic neuroprotective pharmaceuticals to mitigate TBI. The aim is to provide insights that may contribute to the early clinical management of the condition.
Pregnancy related hormones increase CYP3A mediated buprenorphine metabolism in human hepatocytes: a comparison to CYP3A substrates nifedipine and midazolam
Authors: Fashe Muluneh M. , Miner Taryn A. , Fallon John K. , Schauer Amanda P. , Sykes Craig , Smith Philip C. , Lee Craig R.
Published: July 2023

Introduction:Pregnancy increases the clearance of CYP3A4 substrate drugs and pregnancy-related hormones (PRHs) induce hepatic CYP3A4 expression and metabolism. However, it remains unclear to what extent the magnitude of PRH-evoked changes in hepatic CYP3A metabolism varies across multiple substrates. This study quantified the impact of PRHs on CYP3A protein concentrations and buprenorphine metabolism in human hepatocytes, and compared the magnitude of these effects to nifedipine and midazolam metabolism.

Methods:Sandwich-cultured human hepatocytes (SCHH) from female donors were exposed to PRHs, administered in combination across a range of physiologically relevant concentrations, for 72 h. Absolute protein concentrations of CYP3A4, CYP3A5, and CYP3A7 in SCHH membrane fractions were quantified by nanoLC-MS/MS, and norbuprenorphine (nor-BUP), dehydro-nifedipine (dehydro-NIF), and 1-hydroxy-midazolam (1-OH-MDZ) formation was evaluated.

Results:Compared to control, PRH exposure increased CYP3A4, CYP3A7, and total CYP3A protein concentrations, but not CYP3A5 concentrations, and increased nor-BUP, dehydro-NIF, and 1-OH-MDZ formation in a concentration-dependent manner. The formation of nor-BUP, dehydro-NIF, and 1-OH-MDZ each positively correlated with PRH-mediated changes in total CYP3A protein concentrations. The PRH-evoked increase in nor-BUP formation was evident in all donors; however, the PRH induction of dehydro-NIF and 1-OH-MDZ formation was diminished in a hepatocyte donor with high basal CYP3A5 expression.

Discussion:These findings demonstrate that PRHs increase buprenorphine, nifedipine, and midazolam metabolism in SCHH via induction of CYP3A4 and total CYP3A protein concentrations, and the magnitude of these effects vary across hepatocyte donors in a substrate-specific manner. These data provide insight into the contribution of PRH induction of CYP3A4 metabolism to increased buprenorphine clearance during pregnancy.
Deep learning-based quantitative phase microscopy
Authors: Wang Wenjian , Ali Nauman , Ma Ying , Dong Zhao , Zuo Chao , Gao Peng
Published: July 2023

Quantitative phase microscopy (QPM) is a powerful tool for label-free and noninvasive imaging of transparent specimens. In this paper, we propose a novel QPM approach that utilizes deep learning to reconstruct accurately the phase image of transparent specimens from a defocus bright-field image. A U-net based model is used to learn the mapping relation from the defocus intensity image to the phase distribution of a sample. Both the off-axis hologram and defocused bright-field image are recorded in pair for thousands of virtual samples generated by using a spatial light modulator. After the network is trained with the above data set, the network can fast and accurately reconstruct the phase information through a defocus bright-field intensity image. We envisage that this method will be widely applied in life science and industrial detection.
Glucolipid metabolism improvement in impaired glucose tolerance subjects consuming a Quinoa-based diet: a randomized parallel clinical trial
Authors: Zeng Hongli , Cai Xiangsheng , Qiu Zhenyang , Liang Yuchan , Huang Lu
Published: July 2023

Purpose: To investigate the effects of quinoa on glucose and lipid metabolism, and the prognosis in people with impaired glucose tolerance.

Methods: One hundred and thirty-eight patients diagnosed with impaired glucose tolerance following a glucose tolerance test in Guangzhou Cadre Health Management Center were selected and randomly divided into quinoa intervention and control groups, according to the digital table method. After 1 year of follow-up, the differences in blood glucose, blood lipid, glycosylated hemoglobin and other indicators were compared. The disease prognosis between the two groups was also compared.

Results: The 2 h postprandial blood glucose, glycosylated hemoglobin, insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, body mass index, waist circumference, systolic and diastolic blood pressure after intervention in the quinoa group were significantly lower than before intervention. In contrast, high-density lipoprotein cholesterol was higher than before intervention and is statistically significant (p < 0.05). After 1 year of follow-up, the control group’s glycosylated hemoglobin and body mass index are higher than before intervention, and are statistically significant (p < 0.05). The 2 h postprandial blood glucose, glycosylated hemoglobin, insulin resistance index, body mass index, and mean diastolic blood pressure in the quinoa group are statistically significantly lower than in the control group, while high-density lipoprotein cholesterol is higher (p < 0.05). The rate of conversion to diabetes for participants in the quinoa group (7.8%) is statistically significantly lower than in the control group (20.3%) (χ2 = 12.760, p = 0.002). Logistic regression analysis showed that quinoa consumption is a protective factor against delaying the progression of diabetes (p < 0.05).

Conclusion: Adding quinoa to staple food intake can reduce postprandial blood glucose, and improve lipid metabolism and insulin resistance, delaying the progression of diabetes in people with impaired glucose tolerance.
Advances in exercise to alleviate sarcopenia in older adults by improving mitochondrial dysfunction
Authors: Zhu Yang , Zhou Xuchang , Zhu Aiyuan , Xiong Shijing , Xie Jun , Bai Zhenmin
Published: July 2023

Sarcopenia is a chronic degenerative disease affecting primarily older adults. A growing aging population is gradually increasing the number of patients suffering from sarcopenia, placing increasing financial pressure on patients’ families and society in general. There is a strong link between mitochondrial dysfunction and sarcopenia pathogenesis. As a result, treating sarcopenia by improving mitochondrial dysfunction is an effective strategy. Numerous studies have demonstrated that exercise has a positive effect on mitochondrial dysfunction when treating sarcopenia. Exercise promotes mitochondrial biogenesis and mitochondrial fusion/division to add new mitochondria or improve dysfunctional mitochondria while maintaining mitochondrial calcium homeostasis, mitochondrial antioxidant defense system, and mitochondrial autophagy to promote normal mitochondrial function. Furthermore, exercise can reduce mitochondrial damage caused by aging by inhibiting mitochondrial oxidative stress, mitochondrial DNA damage, and mitochondrial apoptosis. Exercise effectiveness depends on several factors, including exercise duration, exercise intensity, and exercise form. Therefore, Moderate-intensity exercise over 4 weeks potentially mitigates sarcopenia in older adults by ameliorating mitochondrial dysfunction. HIIT has demonstrated potential as a viable approach to addressing sarcopenia in aged rats. However, further investigation is required to validate its efficacy in treating sarcopenia in older adults.
bHLH transcription factor family identification, phylogeny, and its response to abiotic stress in Chenopodium quinoa
Authors: Xue Guoxing , Fan Yue , Zheng Chunyu , Yang Hao , Feng Liang , Chen Xingyu , Yang Yanqi , Yao Xin , Weng Wenfeng , Kong Lingyan , Liu Chuang , Cheng Jianping , Ruan Jingjun
Published: July 2023

The second-largest transcription factor superfamily in plants is that of the basic helix-loop-helix (bHLH) family, which plays an important complex physiological role in plant growth, tissue development, and environmental adaptation. Systematic research on the Chenopodium quinoa bHLH family will enable a better understanding of this species. Herein, authors used a variety of bioinformatics methods and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to explore the evolution and function of the 218 CqbHLH genes identified. A total of 218 CqbHLH transcription factor genes were identified in the whole genome, located on 18 chromosomes. A phylogenetic tree was constructed using the CqbHLH and AtbHLH proteins to determine their homology, and the members were divided into 20 subgroups and one unclustered gene. Authors also analyzed 218 CqbHLH genes, conservative motifs, chromosome diffusion, and gene replication. The author constructed one Neighbor-Joining (NJ) tree and a collinearity analysis map of the bHLH family in C. quinoa and six other plant species to study the evolutionary relationship and homology among multiple species. In addition, the expression levels of 20 CqbHLH members from different subgroups in various tissues, different fruit developmental stages, and six abiotic stresses were analyzed. Authors identified 218 CqbHLH genes and studied their biological functions, providing a basis for better understanding and further studying the bHLH family in quinoa.
Genome-wide genotyping data renew knowledge on genetic diversity of a worldwide alfalfa collection and give insights on genetic control of phenology traits
Authors: Pégard Marie , Barre Philippe , Delaunay Sabrina , Surault Fabien , Karagić Djura , Milić Dragan , Zorić Miroslav , Ruttink Tom , Julier Bernadette
Published: July 2023

China’s and Europe’s dependence on imported protein is a threat to the food self-sufficiency of these regions. It could be solved by growing more legumes, including alfalfa that is the highest protein producer under temperate climate. To create productive and high-value varieties, the use of large genetic diversity combined with genomic evaluation could improve current breeding programs. To study alfalfa diversity, we have used a set of 395 alfalfa accessions (i.e. populations), mainly from Europe, North and South America and China, with fall dormancy ranging from 3 to 7 on a scale of 11. Five breeders provided materials (617 accessions) that were compared to the 400 accessions. All accessions were genotyped using Genotyping-by-Sequencing (GBS) to obtain SNP allele frequency. These genomic data were used to describe genetic diversity and identify genetic groups. The accessions were phenotyped for phenology traits (fall dormancy and flowering date) at two locations (Lusignan in France, Novi Sad in Serbia) from 2018 to 2021. The QTL were detected by a Multi-Locus Mixed Model (mlmm). Subsequently, the quality of the genomic prediction for each trait was assessed. Cross-validation was used to assess the quality of prediction by testing GBLUP, Bayesian Ridge Regression (BRR), and Bayesian Lasso methods. A genetic structure with seven groups was found. Most of these groups were related to the geographical origin of the accessions and showed that European and American material is genetically distinct from Chinese material. Several QTL associated with fall dormancy were found and most of these were linked to genes. In our study, the infinitesimal methods showed a higher prediction quality than the Bayesian Lasso, and the genomic prediction achieved high (>0.75) predicting abilities in some cases. Our results are encouraging for alfalfa breeding by showing that it is possible to achieve high genomic prediction quality.