bluuebunny/crossref_metadata_2025_split huggingface dataset:
The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy
Authors: Qian Kewen , Fu Wenyan , Li Tian , Zhao Jian , Lei Changhai , Hu Shi 
Published: September 2022

AbstractExtracellular vesicles (EVs) facilitate the extracellular transfer of proteins, lipids, and nucleic acids and mediate intercellular communication among multiple cells in the tumour environment. Small extracellular vesicles (sEVs) are defined as EVs range in diameter from approximately 50 to 150 nm. Tumour-derived sEVs (TDsEVs) and immune cell-derived sEVs have significant immunological activities and participate in cancer progression and immune responses. Cancer-specific molecules have been identified on TDsEVs and can function as biomarkers for cancer diagnosis and prognosis, as well as allergens for TDsEVs-based vaccination. Various monocytes, including but not limited to dendritic cells (DCs), B cells, T cells, natural killer (NK) cells, macrophages, and myeloid-derived suppressor cells (MDSCs), secrete sEVs that regulate immune responses in the complex immune network with either protumour or antitumour effects. After engineered modification, sEVs from immune cells and other donor cells can provide improved targeting and biological effects. Combined with their naïve characteristics, these engineered sEVs hold great potential as drug carriers. When used in a variety of cancer therapies, they can adjunctly enhance the safety and antitumor efficacy of multiple therapeutics. In summary, both naïve sEVs in the tumour environment and engineered sEVs with effector cargoes are regarded as showing promising potential for use in cancer diagnostics and therapeutics.
The clinical evaluation of electroacupuncture combined with mindfulness meditation for overweight and obesity: study protocol for a randomized sham-controlled clinical trial
Authors: Chung Ching Yee , Yang Angela Wei Hong , Foe Alexander , Li Mingdi , Lenon George Binh 
Published: September 2022

Abstract
Background
Overweight and obesity have reached an epidemic level which impacts individual health and creates a financial burden worldwide. Evidence has shown that electroacupuncture is effective for weight loss when combined with lifestyle intervention, while mindfulness meditation can enhance the outcome of weight loss programs. This study aims to evaluate the safety and the add-on effect of electroacupuncture and mindfulness meditation for weight management in overweight and obesity.

Methods/design
This is a sham-controlled, three-armed randomized clinical trial. A total of 165 participants with BMI between 25 and 39.99 and aged between 18 and 60 who meet the inclusion and exclusion criteria will be randomized into [1] electroacupuncture plus mindfulness meditation group, [2] sham electroacupuncture plus mindfulness meditation group, and [3] electroacupuncture only group. The total duration of this study will be 22 weeks, which consists of a 2-week run-in period, a 12-week intervention period, and an 8-week follow-up period. Participants will receive 12 weekly treatments during the intervention period. Primary outcomes will include body mass index, waist and hip ratio, and body composition. Secondary outcomes will be measured by the Weight-Related Symptom Measure, Obesity and Weight Loss Quality of Life, the Power of Food Scale, and the Chinese medicine differential diagnosis questionnaire. Outcomes will be assessed at the baseline, and endpoints of the 3rd, 6th, 9th, 12th, 14th, 16th, and 20th week.

Discussion
This clinical trial will investigate the add-on effect of two combined interventions for weight loss treatment. The findings of this study may contribute to the development of a cost-effective and multidisciplinary weight management approach.

Trial registration
Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000964213. Registered on 07 June 2018.
A single-center, randomized, parallel design study to evaluate the efficacy of donepezil in improving visuospatial abilities in patients with mild cognitive impairment using eye-tracker: the COG-EYE study protocol for a phase II trial
Authors: Kim Ko Woon , Wang Qi , Koo Se Hee , Shin Byoung-Soo 
Published: September 2022

Abstract
Background
Cholinesterase inhibitors (ChEIs) decrease long-term cognitive decline in patients with Alzheimer’s disease (AD); however, there is little evidence that ChEIs affect cognitive test scores in patients with mild cognitive impairment (MCI). Conventional endpoints, such as cognitive tests or clinical rating scores, may lack the sensitivity to subtle treatment effects in participants with MCI. Therefore, there is an immediate need to refocus on direct physiological assessments to detect the effects of ChEIs in patients with MCI due to AD.

Methods
We propose a randomized controlled trial to evaluate the effect of donepezil, a ChEI, on patients with MCI due to AD. We plan to recruit 78 participants (39 in each arm) with MCI who had amyloid positron emission tomography (PET)-positive results for this open-label study. To evaluate subtle differences, we will measure eye-tracking metrics and digital pen data while participants perform the simplified Rey Complex Figure (RCFT) and clock drawing tests. The primary outcome is a change in the ratio of the number of fixations (working space/perceptual space) performed using the simplified RCFT, from baseline to 12 weeks, as assessed using eye-tracking metrics. The secondary outcomes are changes in general cognition, clinical severity, activities of daily living, and visuospatial function assessed using standard rating scores and digital pen data. The analyses of the primary and secondary outcomes will be based on the difference in changes during follow-up between the donepezil and control groups using the t-test or Mann–Whitney U test, as well as adjusting for baseline values.

Discussion
This study is designed to determine whether eye-tracking metrics can detect the effect of donepezil on visuospatial dysfunction more sensitively in patients with MCI. It is expected that multimodal data, such as eye-tracking and digital pen data, may provide helpful biomarkers for identifying subtle changes that are difficult to measure using conventional methods.

Trial registration
Clinical Research Information Service, Republic of Korea (CRIS, cris.nih.go.kr) KCT0006236. Registered on June 10, 2021.
Technological advances in the serological diagnosis of Chagas disease in dogs and cats: a systematic review
Authors: Freitas Natália Erdens Maron , Habib Fernanda Lopes , Santos Emily Ferreira , Silva Ângelo Antônio Oliveira , Fontes Natália Dantas , Leony Leonardo Maia , Sampaio Daniel Dias , de Almeida Marcio Cerqueira , Dantas-Torres Filipe , Santos Fred Luciano Neves 
Published: September 2022

AbstractBackgroundChagas disease (CD) is caused byTrypanosoma cruzi, which is transmitted mainly through the feces/urine of infected triatomine bugs. The acute phase lasts 2–3 months and is characterized by high parasitemia and nonspecific symptoms, whereas the lifelong chronic phase features symptoms affecting the heart and/or digestive tract occurring in 30–40% of infected individuals. As in humans, cardiac abnormalities are observed inT. cruzi-infected dogs and cats. We reviewed the technological advances in the serological diagnosis of CD in dogs and cats.MethodsA review of the published literature during the last 54 years (1968–2022) on the epidemiology, clinical features, diagnosis, treatment and prevention of CD in dogs and cats was conducted.ResultsUsing predefined eligibility criteria for a search of the published literature, we retrieved and screened 436 publications. Of these, 84 original studies were considered for inclusion in this review. Dogs and cats are considered as sentinels, potentially indicating an activeT. cruzitransmission and thus the risk for human infection. Although dogs and cats are reputed to be important for maintaining theT. cruzidomestic transmission cycle, there are no commercial tests to detect past or active infections in these animals. Most published research on CD in dogs and cats have used in-house serological tests prepared with native and/or full-length recombinant antigens, resulting in variable diagnostic performance. In recent years, chimeric antigens have been used to improve the diagnosis of chronic CD in humans with encouraging results. Some of them have high performance values (> 95%) and extremely low cross-reactivity rates forLeishmaniaspp., especially the antigens IBMP-8.1 to IBMP-8.4. The diagnostic performance of IBMP antigens was also investigated in dogs, showing high diagnostic performance with negligible cross-reactivity with anti-Leishmania infantumantibodies.ConclusionsThe development of a commercial immunodiagnostic tool to identify past or activeT. cruziinfections in dogs and cats is urgently needed. The use of chimeric recombinantT. cruziantigens may help to fill this gap and is discussed in this review.Graphical Abstract
Identification of Jingmen tick virus (JMTV) in Amblyomma testudinarium from Fujian Province, southeastern China
Authors: Zhang Yuli , Li Zhenfeng , Pang Zheng , Wu Zhen , Lin Zhijuan , Niu Guoyu 
Published: September 2022

Abstract
Background
Jingmen tick virus (JMTV) is a newly discovered tick-borne virus that can cause disease in humans. This virus has been authenticated as being extremely widespread worldwide and as posing a significant threat to public health and safety.

Methods
We collected 35 ticks belonging to two tick species from wild boars in Nanping, Fujian Province, China. JMTV-specific genes were amplified by qRT-PCR and nested PCR to confirm the presence of this pathogen.

Results
More than one third of of all ticks collected (11/35) were positive for JMTV. Viral sequences were obtained from three of the JMTV-positive ticks, including the complete genomic sequence from one tick. This was the first time that JMTV was identified in the hard-bodied tick Amblyomma testudinarium. Phylogenetic analysis revealed that JMTV from Fujian Province shared > 90% identity with other isolates derived from China, but was distinct from those reported in France and Cambodia.

Conclusions
JMTV is characterized by relatively low mutations and has its own local adaptive characteristics in different regions. Our findings provide molecular evidence of the presence of JMTV in an overlooked tick species from an area not unrecognized as being endemic. They also suggest that JMTV occupies a wider geographical distribution than currently believed and is a potential disease vector.

Graphical abstract
Understanding reasons and factors for participation and non-participation to a medication adherence program for patients with diabetic kidney disease in Switzerland: a mixed methods study
Authors: Bandiera Carole , Lam Liliane , Locatelli Isabella , Dotta-Celio Jennifer , Duarte Dina , Wuerzner Gregoire , Pruijm Menno , Zanchi Anne , Schneider Marie P. 
Published: September 2022

AbstractBackgroundAn interprofessional medication adherence intervention led by pharmacists, combining motivational interviews and feedback with electronic monitor (EM) drug assessment, was offered to all consecutive patients with diabetic kidney disease (DKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) visiting their nephrologist or endocrinologist. Approximately 73% (202/275) of eligible patients declined to participate, and the factors and reasons for refusal were investigated.MethodsSociodemographic and clinical data of included patients and those who refused were collected retrospectively for those who had previously signed the general consent form. Multivariate logistic regression analysis was performed to identify independent variables associated with non-participation. Patients who refused or accepted the adherence study were invited to participate in semi-structured interviews. Verbatim transcription, thematic analysis, and inductive coding were performed.ResultsPatients who refused to participate were older (n = 123, mean age 67.7 years, SD:10.4) than those who accepted (n = 57, mean age 64.0 years, SD:10.0, p = 0.027) and the proportion of women was higher among them than among patients who accepted it (30.9% vs 12.3%, p = 0.007). The time from diabetes diagnosis was longer in patients who refused than in those who accepted (median 14.2 years IQR 6.9–22.7 vs. 8.6 years, IQR 4.5–15.9, p = 0.003). Factors associated with an increased risk of non-participation were female sex (OR 3.8, 95% CI 1.4–10.0, p = 0.007) and the time from diabetes diagnosis (OR 1.05, 95% CI 1.01–1.09, p = 0.019).The included patients who were interviewed (n = 14) found the interprofessional intervention useful to improve their medication management, support medication literacy, and motivation.Patients who refused to participate and who were interviewed (n = 16) explained no perceived need, did not agree to use EM, and perceived the study as a burden and shared that the study would have been beneficial if introduced earlier in their therapeutic journey. Other barriers emerged as difficult relationships with healthcare providers, lack of awareness of the pharmacist’s role, and negative perception of clinical research.ConclusionsInvestigating the factors and reasons for participation and non-participation in a study helps tailor intervention designs to the needs of polypharmacy patients. Patients who refused the adherence intervention may not be aware of the benefits of medication management and medication literacy. There is an urgent need to advocate for interprofessional outpatient collaborations to support medication adherence in patients with DKD.Trial registrationClinicaltrials.gov NCT04190251_PANDIA IRIS.
High-normal serum carcinoembryonic antigen levels and increased risk of diabetic peripheral neuropathy in type 2 diabetes
Authors: Wang Chun-hua , Yu Chao , Zhuang Lei , Xu Feng , Zhao Li-hua , Wang Xiao-hua , Ning Li-yan , Zhang Xiu-lin , Zhang Dong-mei , Wang Xue-qin , Su Jian-bin 
Published: September 2022

AbstractBackgroundIncreased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsAll subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate compositeZscores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN.ResultsWe ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the compositeZscore for latency (β = 0.132,t = 2.330,p = 0.021), amplitude (β = − 0.164,t = − 2.838,p = 0.005) and NCV (β = − 0.210,t = − 3.662,p < 0.001). Moreover, the prevalence of DPN in the first, second, third and fourth quartiles of CEA level was 12.9%, 19.0%, 29.4% and 40.4%, respectively (p for trend < 0.001); the corresponding adjusted odds ratios and 95% CIs for DPN in CEA quartiles were 1, 1.47 (0.45–4.82), 1.72 (0.54–5.53) and 4.58 (1.39–15.06), respectively. Furthermore, the optimal cut-off value of high-normal serum CEA to discriminate DPN was ≥ 2.66 ng/mL, with a Youden index of 0.28, sensitivity of 66.67% and specificity of 61.00%.ConclusionsIncreased serum CEA levels within the normal range are closely linked to dysfunction of peripheral nerve conduction and the risk of DPN, and high-normal serum CEA levels are a potential risk factor for DPN in T2D.
Healthy beverages may reduce the genetic risk of abdominal obesity and related metabolic comorbidities: a gene-diet interaction study in Iranian women
Authors: Gholami Fatemeh , Samadi Mahsa , Soveid Neda , Mirzaei Khadijeh 
Published: September 2022

Abstract
Background & aims
The nutrition transition in developing countries like Iran causes the increasing rise of obesity and abdominal obesity rates. However, it is not yet well proven that environmental modifications like improving the quality of beverage intake can be effective in people who have a genetic predisposition to obesity. So, in the present study, we examine the interaction between genetic predisposition and healthy beverage index (HBI) with abdominal obesity and obesity-related metabolic risk factors in overweight and obese women.

Method
Based on inclusion and exclusion criteria, 202 overweight or obese females were chosen for this cross-sectional study. Body composition, anthropometric measures, physical activity, and beverage intake data were collected and analyzed using recognized and trustworthy methodologies. Biochemical tests were performed on serum samples. A genetic risk score (GRS) was calculated based on the results of genetic tests. The predetermined HBI was calculated based on previous studies. A generalized linear model was used to estimate the interactions between GRS and HBI (GLM).

Results
We found significant interactions between GRS and HBI on WHR (β = − 0.39, CI: -0.07 to 0.001, P = 0.05) and WC (β = − 6.18, CI: − 13.41 to 1.05, P = 0.09). Also, there were significant gene-diet interactions for HBI and GRS on HDL (β = 7.09, CI: − 0.73 to 14.92, P = 0.07) and FBS (β = − 9.07, CI: − 18.63 to 0.47, P = 0.06).

Conclusions
These findings emphasize the HBI considering genetics appears to protect against the risks of abdominal obesity and metabolic associated obesity markers.
Applicability of devices available for the measurement of intracompartmental pressures: a cadaver study
Authors: Vogels Sanne , Ritchie Ewan D. , de Vries Djuna , Kleinrensink Gert-Jan , Verhofstad Michiel H. J. , Hoencamp Rigo 
Published: September 2022

Abstract
Purpose
The indication for surgical treatment of the chronic exertional compartment syndrome is evaluated by measuring intracompartmental pressures. The validity of these invasive intracompartmental pressure measurements are increasingly questioned in the absence of a standardized test protocol and uniform cut-off values. The aim of the current study was to test compartment pressure monitors and needles for uniformity, thereby supporting the physician’s choice in the selection of appropriate test materials.

Methods
A compartment syndrome was simulated in embalmed above-knee cadaveric leg specimen. Four different terminal devices (Compass manometer, Stryker device, Meritrans transduce, and arterial line) were tested with 22 different needle types. Legs were pressurized after introduction of the four terminal devices in the anterior compartment, using the same needle type. Pressure was recorded at a 30-second interval for 11 minutes in total. Before and after pressurization, the intravenous bag of saline was weighed.

Results
The simulation of a compartment syndrome resulted in intracompartmental pressure values exceeding 100 mmHg in 17 of the 22 legs (77%). In the other five legs, a smaller built-up of pressure was seen, although maximum intracompartmental pressure was in between 70 and 100 mmHg. The intraclass correlation coefficient was above 0.700 for all possible needle types. Excellent to good resemblance was seen in 16 out of 22 instrumental setups (73%). The mean volume of saline infusion required in runs that exceeded 100 mmHg (309 ± 116 ml) was significantly lower compared to the legs in which 100 mmHg was not achieved (451 ± 148 ml; p = 0.04).

Conclusion
The intracompartmental pressure recordings of the four terminal devices were comparable, when tested with a standardized pressurization model in a human cadaver model. None of the included terminal devices or needle types were found to be superior. The results provide evidence for more diverse material selection when logistic choices for intracompartmental pressure measurement devices are warranted.

Level of evidence
Level IV.
Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability
Authors: Ma Zhi-Qiang , Feng Ying-Tong , Guo Kai , Liu Dong , Shao Chang-Jian , Pan Ming-Hong , Zhang Yi-Meng , Zhang Yu-Xi , Lu Di , Huang Di , Zhang Fan , Wang Jin-Liang , Yang Bo , Han Jing , Yan Xiao-Long , Hu Yi 
Published: September 2022

Abstract
Background
Melatonin, a natural hormone secreted by the pineal gland, has been reported to exhibit antitumor properties through diverse mechanisms of action. However, the oncostatic function of melatonin on esophageal squamous cell carcinoma (ESCC) remains elusive. This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.

Methods
ESCC cell lines treated with or without melatonin were used in this study. In vitro colony formation and EdU incorporation assays, and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells. RNA-seq, qPCR, Western blotting, recombinant lentivirus-mediated target gene overexpression or knockdown, plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth. IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.

Results
Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7 (HDAC7), c-Myc and ubiquitin-specific peptidase 10 (USP10) in ESCC cells (P < 0.05). The expressions of HDAC7, c-Myc and USP10 in tumors were detected significantly higher than the paired normal tissues from 148 ESCC patients (P < 0.001). Then, the Kaplan–Meier survival analyses suggested that ESCC patients with high HDAC7, c-Myc or USP10 levels predicted worse overall survival (Log-rank P < 0.001). Co-IP and Western blotting analyses further revealed that HDAC7 physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription. Notably, our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth, and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells. Additionally, we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.

Conclusions
Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth, and provides the reference for identifying biomarkers and therapeutic targets for ESCC.