bluuebunny/crossref_metadata_2025 huggingface dataset:
BCG induced lower urinary tract symptoms during treatment for NMIBC—Mechanisms and management strategies
Authors: Bourlotos Georgia , Baigent William , Hong Matthew , Plagakis Sophie , Grundy Luke
Published: January 2024

Non-muscle invasive bladder cancer (NMIBC) accounts for ~70–75% of total bladder cancer tumors and requires effective early intervention to avert progression. The cornerstone of high-risk NMIBC treatment involves trans-urethral resection of the tumor followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, BCG therapy is commonly accompanied by significant lower urinary tract symptoms (LUTS) including urinary urgency, urinary frequency, dysuria, and pelvic pain which can undermine treatment adherence and clinical outcomes. Despite this burden, the mechanisms underlying the development of BCG-induced LUTS have yet to be characterized. This review provides a unique perspective on the mechanisms thought to be responsible for the development of BCG-induced LUTS by focussing on the sensory nerves responsible for bladder sensory transduction. This review focuses on how the physiological response to BCG, including inflammation, urothelial permeability, and direct interactions between BCG and sensory nerves could drive bladder afferent sensitization leading to the development of LUTS. Additionally, this review provides an up-to-date summary of the latest clinical data exploring interventions to relieve BCG-induced LUTS, including therapeutic targeting of bladder contractions, inflammation, increased bladder permeability, and direct inhibition of bladder sensory signaling. Addressing the clinical burden of BCG-induced LUTS holds significant potential to enhance patient quality of life, treatment compliance, and overall outcomes in NMIBC management. However, the lack of knowledge on the pathophysiological mechanisms that drive BCG-induced LUTS has limited the development of novel and efficacious therapeutic options. Further research is urgently required to unravel the mechanisms that drive BCG-induced LUTS.
Hearing loss, hearing aid use, and performance on the Montreal cognitive assessment (MoCA): findings from the HUNT study in Norway
Authors: Moradi Shahram , Engdahl Bo , Johannessen Aud , Selbæk Geir , Aarhus Lisa , Haanes Gro Gade
Published: January 2024

Purpose

To evaluate the associations between hearing status and hearing aid use and performance on the Montreal Cognitive Assessment (MoCA) in older adults in a cross-sectional study in Norway.

Methods

This study utilized data from the fourth wave of the Trøndelag Health Study (HUNT4, 2017–2019). Hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz (or PTA4) in the better hearing ear were used to determine participants’ hearing status [normal hearing (PTA4 hearing threshold, ≤ 15 dB), or slight (PTA4, 16–25 dB), mild (PTA4, 26–40 dB), moderate (PTA4, 41–55 dB), or severe (PTA4, ≥ 56 dB) hearing loss]. Both standard scoring and alternate MoCA scoring for people with hearing loss (deleting MoCA items that rely on auditory function) were used in data analysis. The analysis was adjusted for the confounders age, sex, education, and health covariates.

Results

The pattern of results for the alternate scoring was similar to that for standard scoring. Compared with the normal-hearing group, only individuals with moderate or severe hearing loss performed worse in the MoCA. In addition, people with slight hearing loss performed better in the MoCA than those with moderate or severe hearing loss. Within the hearing loss group, hearing aid use was associated with better performance in the MoCA. No interaction was observed between hearing aid use and participants’ hearing status with performance on the MoCA test.

Conclusion

While hearing loss was associated with poorer performance in the MoCA, hearing aid use was found to be associated with better performance in the MoCA. Future randomized control trials are needed to further examine the efficacy of hearing aid use on the MoCA performance. When compared with standard scoring, the alternate MoCA scoring had no effect on the pattern of results.
Effect of deep brain stimulation compared with drug therapy alone on the progression of Parkinson’s disease
Authors: Dong Wenwen , Qiu Chang , Lu Yue , Luo Bei , Jiang Xu , Chang Lei , Yan Jiuqi , Sun Jian , Liu Weiguo , Zhang Li , Zhang Wenbin
Published: January 2024

Background

Parkinson’s disease (PD) symptoms deteriorate with disease progression. Although deep brain stimulation (DBS) can effectively improve the motor signs of PD patients, it is not yet known whether DBS surgery, which is an invasive treatment modality, may change the progression of PD.

Objective

The aim of this work was to compare the effect of DBS with that of drug treatment on the progression of PD.

Methods

A total of 77 patients with PD with the Hoehn and Yahr scale (HY) stage of 2.5 or 3 were included, and were divided into 34 in the drug therapy alone group (Drug-G) and 43 in the DBS therapy group (DBS-G). All patients were subjected to a follow-up of 2 years, and disease severity was assessed by the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), the Montreal Cognitive Assessment (MOCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) scores. In addition, the quality of life of patients and the burden on their family were assessed by the 39-item PD questionnaire (PDQ-39) scores, daily levodopa equivalent dose (LED), patient’s annual treatment-related costs, and the Zarit Caregiver Burden Scale (ZCBS) score. The changes in relevant scale scores between the two groups were compared at each follow-up stage.

Results

The UPDRS-III score of the patients in the “off” state increased from year to year in both groups, and the degree of increase of this score was greater in the DBS-G than in the Drug-G group. The MOCA score in both groups began to decline in the 2nd year of follow-up, and the decline was greater in the Drug-G than in the DBS-G group. DBS treatment did not affect patients’ psychiatric disorders. The PDQ39, LED, costs, and ZCBS were negatively correlated with the follow-up time in patients in the DBS-G group, and positively correlated with the follow-up time in patients in the Drug-G.

Conclusion

PD is progressive regardless of treatment. The findings from this follow-up study suggest that the disease progression of patients in DBS-G may be slightly faster compared to the drug-G, but the advantages of DBS are also evident. Indeed, DBS better improves patient’s motor signs and quality of life and reduces the family burden. In addition, DBS has less impact on patients in terms of cognitive and mental effects.
Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF
Authors: Wu Ling , Arvai Stephanie , Wang Shih-Hsiu J. , Liu Andy J. , Xu Bin
Published: January 2024

Alzheimer’s disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as “tauopathies”, with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF Aβ42 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of Aβ or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.
Non-invasive low-cost deep tissue blood flow measurement with integrated Diffuse Speckle Contrast Spectroscopy
Authors: Biswas Arindam , Mohammad Penaz Parveen Sultana , Moka Sadhu , Takshi Arash , Parthasarathy Ashwin B.
Published: January 2024

Diffuse Correlation Spectroscopy (DCS) is a widely used non-invasive measurement technique to quantitatively measure deep tissue blood flow. Conventional implementations of DCS use expensive single photon counters as detecting elements and optical probes with bulky fiber optic cables. In recent years, newer approaches to blood flow measurement such as Diffuse Speckle Contrast Analysis (DSCA) and Speckle Contrast Optical Spectroscopy (SCOS), have adapted speckle contrast analysis methods to simplify deep tissue blood flow measurements using cameras and single photon counting avalanche detector arrays as detectors. Here, we introduce and demonstrate integrated Diffuse Speckle Contrast Spectroscopy (iDSCS), a novel optical sensor setup which leverages diffuse speckle contrast analysis for probe-level quantitative measurement of tissue blood flow. iDSCS uses a standard photodiode configured in photovoltaic mode to integrate photon intensity fluctuations over multiple integration durations using a custom electronic circuit, as opposed to the high frequency sampling of photon counts with DCS. We show that the iDSCS device is sensitive to deep-tissue blood flow measurements with experiments on a human forearm and compare the sensitivity and dynamic range of the device to a conventional DCS instrument. The iDSCS device features a low-cost, low-power, small form factor instrument design that will enable wireless probe-level measurements of deep tissue blood flow.
Effects of the royal jelly consumption on post-stroke complications in patients with ischemic stroke: results of a randomized controlled trial
Authors: Karimi Elham , Arab Arman , Sepidarkish Mahdi , Khorvash Fariborz , Saadatnia Mohammad , Amani Reza
Published: January 2024

Aims

There is a paucity of evidence regarding the benefit of royal jelly (RJ) on post-stroke complications in patients with ischemic stroke. To address this knowledge gap, this randomized, triple-blind, placebo-controlled clinical trial was carried out to determine the effects of RJ consumption on post-stroke clinical outcomes.

Methods

Of 64 eligible ischemic stroke patients (45–80 years), 32 were randomized to the RJ and 32 to the placebo groups and completed a 12-week intervention. The intervention group was advised to receive 1,000 mg of RJ dragee daily after breakfast. Post-stroke complications including cognition, fatigue, mental health, and appetite, along with serum levels of brain-derived neurotrophic factor (BDNF), and mid-upper arm circumference (MUAC) were assessed in groups pre-and post-intervention.

Results

After 12 weeks of RJ consumption, cognitive function [adjusted mean difference, 4.71; 95% confidence interval (CI), 1.75 to 7.67], serum levels of BDNF (adjusted mean difference, 0.36; 95% CI, 0.05 to 0.67), stress (adjusted mean difference, −3.33; 95% CI, −6.50 to −0.17), and appetite (adjusted mean difference, 1.38; 95% CI, 0.19 to 2.56) were significantly improved. However, the findings for fatigue (adjusted mean difference, −4.32; 95% CI, −10.28 to 1.63), depression (adjusted mean difference, −1.71; 95% CI, −5.58 to 2.16), anxiety (adjusted mean difference, −2.50; 95% CI, −5.50 to 0.49), and MUAC (adjusted mean difference, 0.36; 95% CI, −0.11 to 0.84) were less favorable.

Conclusion

Findings support the benefits of RJ consumption in improving post-stroke complications and clinical outcomes.

Clinical trial registration: https://www.irct.ir/trial/59275, Identifier IRCT20180818040827N4.
Causal effects of human serum metabolites on occurrence and progress indicators of chronic kidney disease: a two-sample Mendelian randomization study
Authors: Yin Yu , Shan Conghui , Han Qianguang , Chen Congcong , Wang Zijie , Huang Zhengkai , Chen Hao , Sun Li , Fei Shuang , Tao Jun , Han Zhijian , Tan Ruoyun , Gu Min , Ju Xiaobing
Published: January 2024

Background

Chronic kidney disease (CKD) is often accompanied by alterations in the metabolic profile of the body, yet the causative role of these metabolic changes in the onset of CKD remains a subject of ongoing debate. This study investigates the causative links between metabolites and CKD by leveraging the results of genomewide association study (GWAS) from 486 blood metabolites, employing bulk two-sample Mendelian randomization (MR) analyses. Building on the metabolites that exhibit a causal relationship with CKD, we delve deeper using enrichment analysis to identify the metabolic pathways that may contribute to the development and progression of CKD.

Methods

In conducting the Mendelian randomization analysis, we treated the GWAS data for 486 metabolic traits as exposure variables while using GWAS data for estimated glomerular filtration rate based on serum creatinine (eGFRcrea), microalbuminuria, and the urinary albumin-to-creatinine ratio (UACR) sourced from the CKDGen consortium as the outcome variables. Inverse-variance weighting (IVW) analysis was used to identify metabolites with a causal relationship to outcome. Using Bonferroni correction, metabolites with more robust causal relationships are screened. Additionally, the IVW-positive results were supplemented with the weighted median, MR-Egger, weighted mode, and simple mode. Furthermore, we performed sensitivity analyses using the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out (LOO) test. Pathway enrichment analysis was conducted using two databases, KEGG and SMPDB, for eligible metabolites.

Results

During the batch Mendelian randomization (MR) analyses, upon completion of the inverse-variance weighted (IVW) approach, sensitivity analysis, and directional consistency checks, 78 metabolites were found to meet the criteria. The following four metabolites satisfy Bonferroni correction: mannose, N-acetylornithine, glycine, and bilirubin (Z, Z), and mannose is causally related to all outcomes of CKD. By pathway enrichment analysis, we identified eight metabolic pathways that contribute to CKD occurrence and progression.

Conclusion

Based on the present analysis, mannose met Bonferroni correction and had causal associations with CKD, eGFRcrea, microalbuminuria, and UACR. As a potential target for CKD diagnosis and treatment, mannose is believed to play an important role in the occurrence and development of CKD.
Random cellulose acetate nanofibers: a breakthrough for cultivated meat production
Authors: Santos Ana Elisa Antunes dos , Guadalupe Jorge Luís , Albergaria Juliano Douglas Silva , Almeida Itallo Augusto , Moreira Amanda Maria Siqueira , Copola Aline Gonçalves Lio , Araújo Isabella Paula de , de Paula Ana Maria , Neves Bernardo Ruegger Almeida , Santos João Paulo Ferreira , da Silva Aline Bruna , Jorge Erika Cristina , Andrade Luciana de Oliveira
Published: January 2024

Overcoming the challenge of creating thick, tissue-resembling muscle constructs is paramount in the field of cultivated meat production. This study investigates the remarkable potential of random cellulose acetate nanofibers (CAN) as a transformative scaffold for muscle tissue engineering (MTE), specifically in the context of cultivated meat applications. Through a comparative analysis between random and aligned CAN, utilizing C2C12 and H9c2 myoblasts, we unveil the unparalleled capabilities of random CAN in facilitating muscle differentiation, independent of differentiation media, by exploiting the YAP/TAZ-related mechanotransduction pathway. In addition, we have successfully developed a novel process for stacking cell-loaded CAN sheets, enabling the production of a three-dimensional meat product. C2C12 and H9c2 loaded CAN sheets were stacked (up to four layers) to form a ~300–400 μm thick tissue 2 cm in length, organized in a mesh of uniaxial aligned cells. To further demonstrate the effectiveness of this methodology for cultivated meat purposes, we have generated thick and viable constructs using chicken muscle satellite cells (cSCs) and random CAN. This groundbreaking discovery offers a cost-effective and biomimetic solution for cultivating and differentiating muscle cells, forging a crucial link between tissue engineering and the pursuit of sustainable and affordable cultivated meat production.
Effect of sarcopenia on survival in patients after pancreatic surgery: a systematic review and meta-analysis
Authors: Zhong Lei , Liu Jifeng , Xia Mingquan , Zhang Yunshu , Liu Shuo , Tan Guang
Published: January 2024

Background

Numerous studies have reported sarcopenia to be associated with unfavorable outcomes in patients who have undergone pancreatectomy. Therefore, in this meta-analysis, we examined the relationship between sarcopenia and survival after pancreatic surgery.

Methods

PubMed, Embase, and Cochrane Library were searched for studies that examined the association between sarcopenia and survival after pancreatic surgery from the inception of the database until June 1, 2023. Hazard ratio (HR) for overall survival (OS) and/or progression-free survival (PFS) of sarcopenia and pancreatic surgery were extracted from the selected studies and random or fixed-effect models were used to summarize the data according to the heterogeneity. Publication bias was assessed using Egger’s linear regression test and a funnel plot.

Results

Sixteen studies met the inclusion criteria. For 13 aggregated univariate and 16 multivariate estimates, sarcopenia was associated with decreased OS (univariate analysis: HR 1.69, 95% CI 1.48–1.93; multivariate analysis: HR 1.69; 95% CI 1.39–2.05, I2 = 77.4%). Furthermore, sarcopenia was significantly associated with poor PFS of pancreatic resection (Change to univariate analysis: HR 1.74, 95% CI 1.47–2.05; multivariate analysis: HR 1.54; 95% CI 1.23–1.93, I2 = 63%).

Conclusion

Sarcopenia may be a significant prognostic factor for a shortened survival following pancreatectomy since it is linked to an elevated risk of mortality. Further studies are required to understand how sarcopenia affects long-term results after pancreatic resection.

Systematic review registrationRegistration ID: CRD42023438208 https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
Case report: Wernicke–Korsakoff syndrome after bariatric surgery
Authors: Bento Margarida Alves , Vieira João Barriga , Silva Maria Leonor , Camolas José
Published: January 2024

Vitamin and mineral deficiencies are prevalent nutritional disorders following bariatric surgery. Although they are more prevalent after malabsorptive procedures such as bypass, they also occur in restrictive procedures such as gastric sleeve. The mechanisms that lead to the occurrence of these deficits are related to the presence of poor nutritional intake or poor adherence to multivitamins and multimineral supplementation. Wernicke–Korsakoff syndrome (WKS) is an acute neurological disorder resulting from thiamine deficiency. This syndrome is composed of two distinct phases: first, Wernicke Encephalopathy (WE), the acute phase of this syndrome, which is characterized by a triad of mental confusion, ocular signs, and ataxia, followed by the chronic phase of WKS, called Korsakoff’s syndrome (KS), which is known for the presence of anterograde amnesia and confabulation. We aimed to report a case of a patient with WKS after bariatric surgery. The patient’s retrospective chart review was performed in order to retrieve the relevant clinical data. The patient was a 24-year-old female student with a BMI of 48 kg/m2 who underwent sleeve gastrectomy surgery for morbid obesity. Over the following 2 months, recovery from surgery was complicated by non-specific symptoms such as nausea, recurrent vomiting, and a significant reduction in food intake, which led the patient to visit the emergency department six times with hospitalization on the last occasion for a definitive diagnosis. During the 15 days of hospitalization, the patient developed ocular diplopia, nystagmus, complaints of rotatory vertigo, and gait abnormalities. A magnetic resonance imaging of the head was performed but revealed no significant changes. After a formal neurological assessment, treatment with parenteral thiamine (100 mg, three times a day) was started without prior dosing. The observed clinical improvement confirmed the diagnosis of WKS. Bariatric surgery may contribute to thiamine deficiency and, consequently, to WKS. Education about the adverse consequences of malnourishment is mandatory before and after the surgery. Investigation of nutritional deficiencies both pre- and post-operatively is crucial in order to prevent complications such as WKS.
Deep learning based on 68Ga-PSMA-11 PET/CT for predicting pathological upgrading in patients with prostate cancer
Authors: Zang Shiming , Jiang Cuiping , Zhang Lele , Fu Jingjing , Meng Qingle , Wu Wenyu , Shao Guoqiang , Sun Hongbin , Jia Ruipeng , Wang Feng
Published: January 2024

Objectives

To explore the feasibility and importance of deep learning (DL) based on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT in predicting pathological upgrading from biopsy to radical prostatectomy (RP) in patients with prostate cancer (PCa).

Methods

In this retrospective study, all patients underwent 68Ga-PSMA-11 PET/CT, transrectal ultrasound (TRUS)-guided systematic biopsy, and RP for PCa sequentially between January 2017 and December 2022. Two DL models (three-dimensional [3D] ResNet-18 and 3D DenseNet-121) based on 68Ga-PSMA-11 PET and support vector machine (SVM) models integrating clinical data with DL signature were constructed. The model performance was evaluated using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity.

Results

Of 109 patients, 87 (44 upgrading, 43 non-upgrading) were included in the training set and 22 (11 upgrading, 11 non-upgrading) in the test set. The combined SVM model, incorporating clinical features and signature of 3D ResNet-18 model, demonstrated satisfactory prediction in the test set with an AUC value of 0.628 (95% confidence interval [CI]: 0.365, 0.891) and accuracy of 0.727 (95% CI: 0.498, 0.893).

Conclusion

A DL method based on 68Ga-PSMA-11 PET may have a role in predicting pathological upgrading from biopsy to RP in patients with PCa.
Preclinical and clinical studies of a tumor targeting IL-12 immunocytokine
Authors: Minnar Christine M. , Lui Grace , Gulley James L. , Schlom Jeffrey , Gameiro Sofia R.
Published: January 2024

The clinical success of immune checkpoint inhibitors (ICIs) has demonstrated the promise and challenges of cancer immunotherapy. There is an unmet need to develop novel cancer therapies that can provide clinical benefit for most patients with solid malignancies, which harbor innate or acquired resistance to ICIs. Interleukin-12 (IL-12) is a promising cytokine for cancer therapy given its direct stimulatory effects on innate and adaptive immunity. However, unfavorable pharmacokinetics and a narrow therapeutic index render recombinant IL-12 (rIL-12) less attractive as a cancer therapy. NHS-IL12 is a fusion protein of IL-12 and NHS76 (human IgG1) antibody engineered to target single and double stranded DNA present in necrotic areas solid tumors. In preclinical tumor models, NHS-IL12 elicited significant Th1 immune activation and tumor suppressive effects, primarily mediated by NK and CD8+ T lymphocytes, with engagement of myeloid immunity. NHS-IL12 is currently being evaluated clinically in combination with various therapeutic modalities, including chemotherapy, radiation therapy, immune checkpoint inhibition, vaccines, and epigenetic modulation. Here we review the preclinical and clinical studies involving NHS-IL12 for the treatment of solid malignancies.
Self-regulation training for people with knee osteoarthritis: a protocol for a feasibility randomised control trial (MiNT trial)
Authors: Mani Ramakrishnan , Adhia Divya Bharatkumar , Awatere Sharon , Gray Andrew Robert , Mathew Jerin , Wilson Luke Charles , Still Amanda , Jackson David , Hudson Ben , Zeidan Fadel , Fillingim Roger , De Ridder Dirk
Published: January 2024

Introduction

Knee osteoarthritis (OA) is a chronic secondary musculoskeletal pain condition resulting in disability, reduced quality of life, and high societal costs. Pain associated with knee OA is linked to increased sensitivity in sensory, cognitive, and emotional areas of the brain. Self-regulation training targeting brain functioning related to pain experience could reduce pain and its associated disability. Self-regulatory treatments such as mindfulness meditation (MM) and electroencephalography neurofeedback (EEG-NF) training improve clinical outcomes in people with knee OA. A feasibility clinical trial can address factors that could inform the design of the full trial investigating the effectiveness of self-regulation training programmes in people with knee OA. This clinical trial will evaluate the feasibility, safety, acceptability, experience and perceptions of the self-regulatory training programmes.

Methods

The proposed feasibility trial is based on a double-blind (outcome assessor and investigators), three-arm (MM usual care, EEG-NF + usual care and usual care control group) randomised controlled parallel clinical trial. Participants with knee OA will be recruited from the community and healthcare practices. A research assistant (RA) will administer both interventions (20-min sessions, four sessions each week, and 12 sessions over three successive weeks). Feasibility measures (participant recruitment rate, adherence to interventions, retention rate), safety, and acceptability of interventions will be recorded. An RA blinded to the group allocation will record secondary outcomes at baseline, immediately post-intervention (4th week), and 3 months post-intervention. The quantitative outcome measures will be descriptively summarised. The qualitative interviews will evaluate the participants' experiences and perceptions regarding various aspects of the trial, which includes identifying the barriers and facilitators in participating in the trial, evaluating their opinions on the research procedures, such as their preferences for the study site, and determining the level of acceptability of the interventions as potential clinical treatments for managing knee OA. Māori participant perceptions of how assessment and training practices could be acceptable to a Māori worldview will be explored. The interviews will be audio-recorded and analysed thematically.

Discussion

This trial will provide evidence on the feasibility, safety, and acceptability of the MM and EEG-NF training in people with knee OA, thus informing the design of a full randomised clinical control trial.
FIB-4 and APRI scores for progressive liver fibrosis diagnosis in children with biliary atresia
Authors: Lyu Hongyu , Ye Yongqin , Wang Bin
Published: January 2024

Introduction

Finding non-invasive methods to predict the degree of liver fibrosis is very important in managing children with biliary atresia. Therefore, we explored the predictive value of APRI, FIB-4, and serological markers for liver fibrosis in children with biliary atresia.

Methods

This study retrospectively reviewed data from children diagnosed with BA between March and December 2022. Liver tissue pathology specimens were obtained during surgery. The serum markers were measured within 2 days before the Kasai procedure or liver transplantation. The aspartate aminotransferase-to-platelet ratio index (APRI) and the four-factor-based fibrosis index (FIB-4) were calculated. The outcome was the diagnosis of progressive liver fibrosis.

Results

This study reviewed the data from 41 children with biliary atresia. APRI had 52% sensitivity and 83% specificity for progressive liver fibrosis, while FIB-4 had 83% sensitivity and 67% specificity. Their areas under the curve were not significantly different from those of conventional markers.

Conclusion

Although they were not better than conventional markers, APRI and FIB-4 can be used as follow-up markers for progressive liver fibrosis in patients with biliary atresia, but their predictive value was moderate. Additional studies are necessary to determine whether they could be combined with other markers to improve their predictive value.
Evaluation of potentially inappropriate medications for the elderly according to beers, STOPP, START, and Chinese criteria
Authors: Zhu Xiaojuan , Zhang Feng , Zhao Yong , Zhang Wen , Zhang Yahui , Wang Jianchun
Published: January 2024

Objective: Polypharmacy prevalence is increasing worldwide, and it is becoming more popular among the elderly. This study aimed to compare the prevalence of potentially inappropriate medications (PIMs) using the Beers criteria (2019 edition), criteria for potentially inappropriate medications for older adults in China (Chinese criteria), Screening Tool of Older Persons’ Prescriptions (STOPP), and Screening Tool to Alert to Right Treatment (START) criteria and to identify risk factors associated with PIM use.

Methods: This was a cross-sectional study with a sample of 276 inpatients aged ≥65 years old from January 2020 to June 2020. A cross-sectional study was conducted to analyze PIMs based on the Beers (2019 edition), Chinese, STOPP, and START criteria. PIMs use was analysed based on four different criteria and logistic regression analysis was used to investigate independent factors associated with PIM use.

Results: The mean number of medications used by the elderly population was nine (range, 0–28). A total of 252 patients (accounting for 91.30%) took five or more medications and 120 patients (accounting for 43.48%) took 10 or more medications. The prevalence rates of PIMs were 66.30% (183/276), 55.07% (152/276), 26.45% (73/276), and 64.13% (177/276) determined by the Beers, Chinese, STOPP, and START criteria, respectively. The top PIMs screened using the Beers, Chinese, and STOPP criteria were proton pump inhibitors, clopidogrel, and benzodiazepines, respectively. Missed use of ACEI in patients with systolic heart failure and/or coronary artery disease was found to be the most common potential prescription omission (PPOs) analyzed using the START criteria. Logistic regression analysis showed that the strongest predictor of PIMs, as determined by all four criteria, was an increased number of medications (p < 0.001). Age was another risk factor for PIMs based on the STOPP criteria in our study (p < 0.05).

Conclusion: Polypharmacy and PIMs were common in our study, and the risk of PIMs correlated with polypharmacy. Application of the Beers, Chinese, STOPP, and START criteria is a useful tool for detecting PIM use.
Intestinal microbiome-targeted therapies improve liver function in alcohol-related liver disease by restoring bifidobacteria: a systematic review and meta-analysis
Authors: Chi Xin , Sun Xiu , Cheng Danying , Liu Shunai , Q. Pan Calvin , Xing Huichun
Published: January 2024

Objective: To systematically evaluate the efficacy of intestinal microbiome-targeted therapies (MTTs) in alcohol-related liver disease (ALD).

Methods: With pre-specified keywords and strategies, we searched databases including Cochrane Library, PubMed, EMBASE, CNKI, Wanfang Data, and Weipu for RCTs on intestinal MTTs in ALD patients from January 2000 to May 2021. Two researchers independently conducted literature screening, data extraction, and quality evaluation according to the eligible criteria. Outcomes of interest included the effects of intestinal MTTs on ALT, AST, GGT, TBIL, TNF-α, IL-6, intestinal Escherichia coli, and Bifidobacteria when compared to the control group. Pooled data were compiled and analyzed with Revman 5.4 software.

Results: Among 5 RCTs included with 456 ALD patients who received probiotics, the therapeutic pooled effects in the experimental group were the followings: ALT (MD = −7.16.95% CI: 10.71∼-3.60; p < 0.0001)、AST (MD = −25.11.95% CI: 30.57∼-19.47; p < 0.00001)、GGT (MD = −6.72.95% CI: 11.91∼-1.53; p = 0.01)、IL-6(SMD = −0.82.95% CI: 1.10∼-0.54; p < 0.00001), which were significantly better than those in the placebo or standard treatment group respectively, while the difference of TBIL (SMD = −0.06, 95%CI: 0.29–0.16; p = 0.59), TNF-α(SMD = −0.53.95% CI: 1.57–0.50; p = 0.31)in the two groups was not significant. After intestinal MTT treatment, the number of intestinal Bifidobacteria increased significantly (MD = 0.79.95% CI: 0.00–1.58; p = 0.05)in the experimental group. However, there were no significant changes in the number of E. coli in both groups (SMD = −0.29.95% CI: 0.92–0.34; p = 0.36).

Conclusion: Intestinal MTTs can significantly improve liver function, associated with the increase of intestinal Bifidobacteria, which may be beneficial to ALD.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246067, Identifier CRD42021246067.
Xanthine oxidase inhibitors treatment or discontinuation effects on mortality: evidence of xanthine oxidase inhibitors withdrawal syndrome
Authors: Kuwabara Masanari , Nakai Michikazu , Sumita Yoko , Iwanaga Yoshitaka , Ae Ryusuke , Kodama Takahide , Hisatome Ichiro , Kamatani Naoyuki
Published: January 2024

Objectives: This study investigates the impact of xanthine oxidase inhibitors (XOI) on mortality in patients with cardiovascular diseases. XOI withdrawal has been reported to increased mortality risk due to rapid adenosine triphosphate (ATP) deficiency. This study aims to determine whether XOI treatment reduces mortality and whether XOI withdrawal increases mortality.

Methods: This is a real-world database study using the Japanese Registry of All Cardiac and Vascular Diseases (J-ROAD). We analyzed 1,648,891 hospitalized patients aged 20–90 with acute coronary syndrome or heart failure. In the first study, mortality rates were compared between patients without urate-lowering agents (n = 1,292,486) and those with XOI agents (n = 315,388, excluding 41,017 on other urate-lowering agents). In the second study, mortality rates were compared between the XOI continuous medication group (n = 226,261) and the XOI withdrawal group (n = 89,127).

Results: After multiple adjustments, XOI treatment group showed significantly lower mortality compared with that without any urate-lowering agent (odds ratio (OR), 0.576, 95% confidence interval (CI), 0.567–0.587, p < .001). In the sub-analysis, the group with allopurinol (OR, 0.578; 95% CI, 0.557–0.600), febuxostat (OR, 0.610; 95% CI, 0.599–0.622), and topiroxostat (HR, 0.545; 95% CI, 0.473–0.628) showed lower OR of mortality compared with that without any urate-lowering agent. XOI withdrawal group led to significantly higher death rates compared to XOI continuous group (19.8% vs. 0.03%; p < .001).

Conclusion: XOI treatment for patients with cardiovascular diseases is associated with reduced mortality. Conversely, XOI withdrawal is linked to elevated mortality risk. This emphasizes the importance of both prescribing and discontinuing XOI carefully to optimize patient outcomes.
Pterostilbene in the treatment of inflammatory and oncological diseases
Authors: Liu Peijun , Tang Weihua , Xiang Kali , Li Guangcai
Published: January 2024

Pterostilbene (PTS), a naturally occurring analog of resveratrol (RSV), has garnered significant attention due to its potential therapeutic effects in treating inflammatory and oncological diseases. This comprehensive review elucidates the pharmacological properties, mechanisms of action, and therapeutic potential of PTS. Various studies indicate that PTS exhibits anti-inflammatory, antioxidant, and antitumour properties, potentially making it a promising candidate for clinical applications. Its influence on regulatory pathways like NF-κB and PI3K/Akt underscores its diverse strategies in addressing diseases. Additionally, PTS showcases a favorable pharmacokinetic profile with better oral bioavailability compared to other stilbenoids, thus enhancing its therapeutic potential. Given these findings, there is an increased interest in incorporating PTS into treatment regimens for inflammatory and cancer-related conditions. However, more extensive clinical trials are imperative to establish its safety and efficacy in diverse patient populations.
Effects of scutellarin on the mechanism of cardiovascular diseases: a review
Authors: Zhang Xinyu , Yin Tong , Wang Yincang , Du Jiazhe , Dou Jinjin , Zhang Xiwu
Published: January 2024

Cardiovascular diseases represent a significant worldwide problem, jeopardizing individuals’ physical and mental wellbeing as well as their quality of life as a result of their widespread incidence and fatality. With the aging society, the occurrence of Cardiovascular diseases is progressively rising each year. However, although drugs developed for treating Cardiovascular diseases have clear targets and proven efficacy, they still carry certain toxic and side effect risks. Therefore, finding safe, effective, and practical treatment options is crucial. Scutellarin is the primary constituent of Erigeron breviscapus (Vant.) Hand-Mazz. This article aims to establish a theoretical foundation for the creation and use of secure, productive, and logical medications for Scutellarin in curing heart-related illnesses. Additionally, the examination and analysis of the signal pathway and its associated mechanisms with regard to the employment of SCU in treating heart diseases will impart innovative resolving concepts for the treatment and prevention of Cardiovascular diseases.
Unveiling the landscape of cytokine research in glioma immunotherapy: a scientometrics analysis
Authors: Zhang Hongyu , Chen Ying , Jiang Xinzhan , Gu Qiang , Yao Jiahao , Wang Xuefeng , Wu Jianghua
Published: January 2024

Background: Cytokines modulate the glioma tumor microenvironment, influencing occurrence, progression, and treatment response. Strategic cytokine application may improve glioma immunotherapy outcomes. Gliomas remain refractory to standard therapeutic modalities, but immunotherapy shows promise given the integral immunomodulatory roles of cytokines. However, systematic evaluation of cytokine glioma immunotherapy research is absent. Bibliometric mapping of the research landscape, recognition of impactful contributions, and elucidation of evolutive trajectories and hot topics has yet to occur, potentially guiding future efforts. Here, we analyzed the structure, evolution, trends, and hotspots of the cytokine glioma immunotherapy research field, subsequently focusing on avenues for future investigation.

Methods: This investigation conducted comprehensive bibliometric analyses on a corpus of 1529 English-language publications, from 1 January 2000, to 4 October 2023, extracted from the Web of Science database. The study employed tools including Microsoft Excel, Origin, VOSviewer, CiteSpace, and the Bibliometrix R package, to systematically assess trends in publication, contributions from various countries, institutions, authors, and journals, as well as to examine literature co-citation and keyword distributions within the domain of cytokines for glioma immunotherapy. The application of these methodologies facilitated a detailed exploration of the hotspots, the underlying knowledge structure, and the developments in the field of cytokines for glioma immunotherapy.

Results: This bibliometric analysis revealed an exponential growth in annual publications, with the United States, China, and Germany as top contributors. Reviews constituted 17% and research articles 83% of total publications. Analysis of keywords like “interleukin-13,” “TGF-beta,” and “dendritic cells” indicated progression from foundational cytokine therapies to sophisticated understanding of the tumor microenvironment and immune dynamics. Key research avenues encompassed the tumor microenvironment, epidermal growth factor receptor, clinical trials, and interleukin pathways. This comprehensive quantitative mapping of the glioma immunotherapy cytokine literature provides valuable insights to advance future research and therapeutic development.

Conclusion: This study has identified remaining knowledge gaps regarding the role of cytokines in glioma immunotherapy. Future research will likely focus on the tumor microenvironment, cancer vaccines, epidermal growth factor receptor, and interleukin-13 receptor alpha 2. Glioma immunotherapy development will continue through investigations into resistance mechanisms, microglia and macrophage biology, and interactions within the complex tumor microenvironment.
Predictors of sustained physical activity: behaviour, bodily health, and the living environment
Authors: Diaconașu Delia Elena , Stoleriu Iulian , Câmpanu Ioana Andreea , Andrei Ana-Maria , Boncu Ștefan , Honceriu Cezar , Mocanu Veronica , Juravle Georgiana
Published: January 2024

This study examined the determinants of sustained physical activity. Eighty-four participants undertook a 7-weeks walking regime (i.e., a 1-h biometrically-monitored walk, at least 5 days/week), with bioelectrical impedance (BIA) and total cholesterol capillary blood measurements performed before and after programme. To investigate behavioural habit formation, 7 weeks after walking termination, all participants were interviewed and (health) re-tested. Data were modelled with an artificial neural network (ANN) cascading algorithm. Our results highlight the successful prediction of continued physical activity by considering one’s physical fitness state, the environmental living context, and risk for cardiovascular disease. Importantly, those artificial neural network models also taking body mass index (BMI) and blood cholesterol as predictors excel at predicting walking continuation (i.e., predictions with 93% predictability). These results are first to highlight the type and importance of available physiological drivers in maintaining a sustained physical activity regime such as walking. They are discussed within the framework of habit formation and the nowadays health and/or wellbeing focus.
Mitochondrial-related microRNAs and their roles in cellular senescence
Authors: Luo Ling , An Xingna , Xiao Yinghui , Sun Xiguang , Li Sijie , Wang Yingzhao , Sun Weixia , Yu Dehai
Published: January 2024

Aging is a natural aspect of mammalian life. Although cellular mortality is inevitable, various diseases can hasten the aging process, resulting in abnormal or premature senescence. As cells age, they experience distinctive morphological and biochemical shifts, compromising their functions. Research has illuminated that cellular senescence coincides with significant alterations in the microRNA (miRNA) expression profile. Notably, a subset of aging-associated miRNAs, originally encoded by nuclear DNA, relocate to mitochondria, manifesting a mitochondria-specific presence. Additionally, mitochondria themselves house miRNAs encoded by mitochondrial DNA (mtDNA). These mitochondria-residing miRNAs, collectively referred to as mitochondrial miRNAs (mitomiRs), have been shown to influence mtDNA transcription and protein synthesis, thereby impacting mitochondrial functionality and cellular behavior. Recent studies suggest that mitomiRs serve as critical sensors for cellular senescence, exerting control over mitochondrial homeostasis and influencing metabolic reprogramming, redox equilibrium, apoptosis, mitophagy, and calcium homeostasis-all processes intimately connected to senescence. This review synthesizes current findings on mitomiRs, their mitochondrial targets, and functions, while also exploring their involvement in cellular aging. Our goal is to shed light on the potential molecular mechanisms by which mitomiRs contribute to the aging process.
The filling factor of the sEMG signal at low contraction forces in the quadriceps muscles is influenced by the thickness of the subcutaneous layer
Authors: Rodriguez-Falces Javier , Malanda Armando , Mariscal Cristina , Navallas Javier
Published: January 2024

Introduction: It has been shown that, for male subjects, the sEMG activity at low contraction forces is normally “pulsatile”, i.e., formed by a few large-amplitude MUPs, coming from the most superficial motor units. The subcutaneous layer thickness, known to be greater in females than males, influences the electrode detection volume. Here, we investigated the influence of the subcutaneous layer thickness on the type of sEMG activity (pulsatile vs. continuous) at low contraction forces.

Methods: Voluntary surface EMG signals were recorded from the quadriceps muscles of healthy males and females as force was gradually increased from 0% to 40% MVC. The sEMG filling process was examined by measuring the EMG filling factor, computed from the non-central moments of the rectified sEMG signal.

Results: 1) The sEMG activity at low contraction forces was “continuous” in the VL, VM and RF of females, whereas this sEMG activity was “pulsatile” in the VL and VM of males. 2) The filling factor at low contraction forces was lower in males than females for the VL (p = 0.003) and VM (p = 0.002), but not for the RF (p = 0.54). 3) The subcutaneous layer was significantly thicker in females than males for the VL (p = 0.001), VM (p = 0.001), and RF (p = 0.003). 4) A significant correlation was found in the vastus muscles between the subcutaneous layer thickness and the filling factor (p < 0.05).

Discussion: The present results indicate that the sEMG activity at low contraction forces in the female quadriceps muscles is “continuous” due to the thick subcutaneous layer of these muscles, which impedes an accurate assessment of the sEMG filling process.
Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism
Authors: Li Xia , Hu Shuying , Cai Yaoting , Liu Xuelian , Luo Jing , Wu Tao
Published: January 2024

Glucose metabolism is of critical importance for cell growth and proliferation, the disorders of which have been widely implicated in cancer progression. Glucose uptake is achieved differently by normal cells and cancer cells. Even in an aerobic environment, cancer cells tend to undergo metabolism through glycolysis rather than the oxidative phosphorylation pathway. Disordered metabolic syndrome is characterized by elevated levels of metabolites that can cause changes in the tumor microenvironment, thereby promoting tumor recurrence and metastasis. The activation of glycolysis-related proteins and transcription factors is involved in the regulation of cellular glucose metabolism. Changes in glucose metabolism activity are closely related to activation of protein kinase B (PKB/AKT). This review discusses recent findings on the regulation of glucose metabolism by AKT in tumors. Furthermore, the review summarizes the potential importance of AKT in the regulation of each process throughout glucose metabolism to provide a theoretical basis for AKT as a target for cancers.