bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating miR-16-5p, miR-92a-3p and miR-451a are biomarkers of lung cancer in Tunisian patients
Authors: Boutabba Alya , Missaoui Fadoua , Dlala Akram , Kamoun Hela , Ben Salem Khalil , Gabsi Amira , Rejeb Hadhemi , Letessier Anne , Miotto Benoit , Marrakchi Raja
Published: April 2024

Lung cancer is one of the most common type of cancer and, despite significant advances in screening and diagnosis approaches, a large proportion of patients at diagnosis still present advanced stages of the disease with distant metastasis and bad prognosis. Finding and validating biomarkers of lung cancer is therefore essential. Such studies are often conducted on European, American and Asian populations and the relevance of these biomarkers in other populations remains less clear. In that prospect, we investigated the expression level of seven microRNAs, chosen from the medical literature (miR-16-5p, miR-92a-3p, miR-103a-3p, miR-375-3p, miR-451a, miR-520-3p and miR-let-7e-5p), in the blood of Tunisian lung cancer patients, treated or not by chemotherapy, and healthy control individuals. We found that high expression levels of circulating miR-16-5p, miR-92a-3p and miR-451a in the plasma of untreated patients discriminate them from healthy control individuals. In addition, miR-16-5p and miR-451a expression levels are significantly reduced in the plasma of chemotherapy-treated patients compared to untreated patients. Our results confirmed previous work in other populations worldwide and provide further evidence that circulating miR-16-5p, miR-92a-3p and miR-451a potentially regulate key pathways involved in the initiation and progression of cancer.
Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study
Authors: Li Jia , Gao Xuedi , Sun Xiaoming , Li Hao , Wei Jiaheng , Lv Lin , Zhu Liangming
Published: April 2024

Background

Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes.

Methods

We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR–Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR–Egger intercept test, MR-PRESSO global test, and leave-one-out method.

Result

Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level,VeillonellaandCoprobacterwere positively correlated with ESCA, whereasPrevotella9,Eubacterium oxidoreducens group, andTuricibacterwere negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC),Flavonifractorexhibited a positive correlation, whileActinomycesexhibited a negative correlation.

Conclusion

Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.
Two patients with Knobloch syndrome due to mutation in COL8A1 gene: case report and review of the literature
Authors: Ogreden Tulin Aras , Erdoğan Gürkan
Published: April 2024

Background

Knobloch syndrome (KNO, OMIM # 267,750) is a rare ciliopathy group sydrome characterized by a collagen synthesis disorder. It represents an uncommon cause of pediatric retinal detachment. This report presents two cases with different COL18A1 gene mutations, complicated by retinal detachment.

Case presentation

Both cases exhibited high myopia and various degrees of occipital skull defect. The first case, a female, had bilateral congenital retinal detachment, posterior embryotoxon, and strabismus. The second case, a male, had unilateral congenital retinal detachment and neuromotor developmental delay. The first case, diagnosed in the early months of life, underwent successful retinal reattachment surgery. However, surgery was not performed on the second case, who presented with late-stage unilateral retinal detachment and pre-phthisis.

Conclusions

The report describes two patients with Knobloch syndrome, one of whom responded favorably to surgery for retinal detachment in both eyes. Successful anatomical results were achieved with early surgical interventions. It is essential to recognize the phenotypic and genetic heterogeneity within KNO.
Alternatives to dental opioid prescribing after tooth extraction (ADOPT): protocol for a stepped wedge cluster randomized trial
Authors: Oyler Douglas R. , Westgate Philip M. , Walsh Sharon L. , Dolly Prothro Jennifer , Miller Craig S. , Roberts Monica F. , Freeman Patricia R. , Knudsen Hannah K. , Lang Maggie , Dominguez-Fernandez Enif , Rojas-Ramirez Marcia V.
Published: April 2024

Background

Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations.

Methods

This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12–25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant’s electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants’ perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.).

Discussion

This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA.

ClinicalTrials.gov

NCT06275191.
Ginger inhibits the invasion of ovarian cancer cells SKOV3 through CLDN7, CLDN11 and CD274 m6A methylation modifications
Authors: Zhang Xiaoyu , Zhang Hairong , Zhu Lin , Xia Lei
Published: April 2024

Background

Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC.

Methods

The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays.

Results

Ginger significantly reduced the m6A level of OC cells SKOV3. The 3’UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3.

Conclusions

Ginger inhibits ovarian cancer cells’ SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.
Therapeutic effect of curcumin nanoemulsion on cystic echinococcosis in BALB/c mice: a computerized tomography (CT) scan and histopathologic study evaluation
Authors: Ghanimatdan Mohamad , Sadjjadi Seyed Mahmoud , Mikaeili Fattaneh , Teimouri Aref , Jafari Seyed Hamed , Derakhshanfar Amin , Hashemi-Hafshejani Saeideh
Published: April 2024

Background

This study aimed to determine the therapeutic efficacy of curcumin nanoemulsion (CUR-NE) in mice infected with Echinococcus granulosus sensu stricto protoscoleces.

Methods

Forty-two inbred BALB/c mice were divided into seven groups of six animals each. Six groups were inoculated intra-peritoneally with 1500 viable E. granulosus protoscoleces, followed for six months and used as infected groups. The infected groups were named as: CEI1 to CEI6 accordingly. The 7th group was not inoculated and was named cystic echinococcosis noninfected group (CENI7). CEI1 and CEI2 groups received 40 mg/kg/day and 20 mg/kg/day curcumin nanoemulsion (CUR-NE), respectively. CEI3 received nanoemulsion without curcumin (NE-no CUR), CEI4 received curcumin suspension (CUR-S) 40 mg/kg/day, CEI5 received albendazole 150 mg/kg/day and CEI6 received sterile phosphate-buffered saline (PBS). CENI7 group received CUR-NE 40 mg/kg/day. Drugs administration was started after six months post-inoculations of protoscoleces and continued for 60 days in all groups. The secondary CE cyst area was evaluated by computed tomography (CT) scan for each mouse before treatment and on the days 30 and 60 post-treatment. The CT scan measurement results were compared before and after treatment. After the euthanasia of the mice on the 60th day, the cyst area was also measured after autopsy and, the histopathological changes of the secondary cysts for each group were observed. The therapeutic efficacy of CUR-NE in infected groups was evaluated by two methods: CT scan and autopsied cyst measurements.

Results

Septal calcification in three groups of infected mice (CEI1, CEI2, and CEI4) was revealed by CT scan. The therapeutic efficacy of CUR-NE 40 mg/kg/day (CEI1 group) was 24.6 ± 26.89% by CT scan measurement and 55.16 ± 32.37% by autopsied cysts measurements. The extensive destructive effects of CUR-NE 40 mg/kg/day (CEI1 group) on the wall layers of secondary CE cysts were confirmed by histopathology.

Conclusion

The current study demonstrated a significant therapeutic effect of CUR-NE (40 mg/kg/day) on secondary CE cysts in BALB/c mice. An apparent septal calcification of several cysts revealed by CT scan and the destructive effect on CE cysts observed in histopathology are two critical key factors that suggest curcumin nanoemulsion could be a potential treatment for cystic echinococcosis.
Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response
Authors: Lim Chiyeon , Lim Sehyun , Moon So-Jung , Cho Suin
Published: April 2024

Background

In traditional Asian medicine, dried rhizomes of Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma [CR]) have long been used to treat pain disorders that affect the head and face such as headaches. Furthermore, they have been used primarily for blood circulation improvement or as an analgesic and anti-inflammatory medicine. This study aimed to investigate the neuroprotective effects of a methanol extract of CR (CRex) on ischemic stroke in mice caused by middle cerebral artery occlusion (MCAO).

Methods

C57BL/6 mice were given a 1.5-h transient MCAO (MCAO control and CRex groups); CRex was administered in the mice of the CRex group at 1,000–3,000 mg/kg either once (single dose) or twice (twice dose) before MCAO. The mechanism behind the neuroprotective effects of CRex was examined using the following techniques: brain infarction volume, edema, neurological deficit, novel object recognition test (NORT), forepaw grip strength, and immuno-fluorescence staining.

Results

Pretreating the mice with CRex once at 1,000 or 3,000 mg/kg and twice at 1,000 mg/kg 1 h before MCAO, brought about a significantly decrease in the infarction volumes. Furthermore, pretreating mice with CRex once at 3,000 mg/kg 1 h before MCAO significantly suppressed the reduction of forepaw grip strength of MCAO-induced mice. In the MCAO-induced group, preadministration of CRex inhibited the reduction in the discrimination ratio brought on by MCAO in a similar manner. CRex exhibited these effects by suppressing the activation of astrocytes and microglia, which regulated the inflammatory response.

Conclusions

This study proposes a novel development for the treatment of ischemic stroke and provides evidence favoring the use of L. chuanxiong rhizomes against ischemic stroke.
Equitable access to quality injury care; Equi-Injury project protocol for prioritizing interventions in four low- or middle-income countries: a mixed method study
Authors:   Equi-Injury Group, Davies Justine , Chu Kathryn , Tabiri Stephen , Byiringiro Jean Claude , Bekele Abebe , Razzak Junaid , D’Ambruoso Lucia , Ignatowicz Agnieszka , Bojke Laura , Nkonki Lungiswa , Laurenzi Christina , Sitch Alice , Bagahirwa Irene , Belli Antonio , Sam Napoleon Bellua , Amberbir Alemayehu , Whitaker John , Ndangurura Denys , Ghalichi Leila , MacQuene Tamlyn , Tshabalala Ntombekhaya , Fikadu Berhe Derbew , Nepomuscene Ntezimana Jean , Agbeko Anita Eseenam , Sarfo-Antwi Frederick , Babar Chand Zaheer , Wajidali Zabin , Sahibjan Fazila , Atiq Huba , Mali Yonela , Tshabalala Zola , Khalfe Faieeza , Nodo Olwethu , Umwali Ghislaine , Twizeyimana Eric , Mugisha Nadine , Munyura Ngirabeza Oda , Nakure Solange , Ishimwe Sage Marie Consolatrice , Nzasabimana Pascal , Dramani Adams , Acquaye Jane , Tanweer Ahmed
Published: April 2024

Background

Equitable access to quality care after injury is an essential step for improved health outcomes in low- and middle-income countries (LMICs). We introduce the Equi-Injury project, in which we will use integrated frameworks to understand how to improve equitable access to quality care after injury in four LMICs: Ghana, Pakistan, Rwanda and South Africa.

Methods

This project has 5 work packages (WPs) as well as essential cross-cutting pillars of community engagement, capacity building and cross-country learning. In WP1, we will identify needs, barriers, and facilitators to impactful stakeholder engagement in developing and prioritising policy solutions. In WP2, we will collect data on patient care and outcomes after injuries. In WP3, we will develop an injury pathway model to understand which elements in the pathway of injury response, care and treatment have the biggest impact on health and economic outcomes. In WP4, we will work with stakeholders to gain consensus on solutions to address identified issues; these solutions will be implemented and tested in future research. In WP5, in order to ascertain where learning is transferable across contexts, we will identify which outcomes are shared across countries. The study has received approval from ethical review boards (ERBs) of all partner countries in South Africa, Rwanda, Ghana, Pakistan and the University of Birmingham.

Discussion

This health system evaluation project aims to provide a deeper understanding of injury care and develop evidence-based interventions within and across partner countries in four diverse LMICs. Strong partnership with multiple stakeholders will facilitate utilisation of the results for the co-development of sustainable interventions.
Low long-lasting insecticidal net use in malaria elimination areas in Southern Ethiopia: results from community based cross-sectional study
Authors: Endriyas Misganu , Kassa Mekidim , Chisha Yilma , Mekonnen Emebet , Misganaw Tebeje , Loha Eskindir , Astatkie Ayalew
Published: April 2024

Background

Despite remarkable progress in malaria burden reduction, malaria continues to be a major public health problem globally. Ethiopia has been distributing long-lasting insecticidal nets (LLINs) for free and nationwide distribution was completed in 2016. However, evidence suggests that the utilization of LLINs varies from setting to setting and from time to time due to different factors, and up-to-date evidence is required for LLIN related decision-making. Hence, this study was designed to assess LLIN utilization and its determinants in the Southern Nations, Nationalities, and People’s Region (SNNPR) of Ethiopia.

Methods

A community-based cross-sectional study was conducted in Southern Ethiopia in 2019. Using multi-stage sampling, a total of 2466 households were included. The region was stratified based on the annual malaria index as high, moderate, low, and free strata. Cluster sampling was then applied to select households from high, moderate, and low strata. Data on LLIN ownership, utilization and different determinant factors were collected using household questionnaire. SurveyCTO was used to collect data and data was managed using Stata 15. Descriptive statistics and multilevel mixed-effects logistic regression were performed to identify the determinants of utilization of LLINs. Effect measures were reported using adjusted odds ratio (AOR) with 95% CI.

Results

From a total of 2466 households, 48.7% of households had at least one LLIN. LLIN adequacy based on family size was 23% while it was15.7% based on universal access and 29.2% based on sleeping space. From 1202 households that possessed LLIN(s), 66.0% of households reported that they slept under LLIN the night preceding the survey. However, when the total population in all surveyed households were considered, only 22.9% of household members slept under LLIN the night preceding the survey. Malaria endemicity, educational status, wealth status, and knowledge about malaria were associated with LLINs utilization. In addition, reasons for non-use included perceived absence of malaria, side effects of LLIN, conditions of LLINs, inconvenient space and low awareness.

Conclusion

Low LLIN coverage and low utilization were noted. A low level of utilization was associated with malaria endemicity, wealth status and level of awareness. Distribution of LLIN and continuous follow-up with community awareness creation activities are vital to improve coverage and utilization of LLINs, and to ensure the country’s malaria elimination goal.
Crosstalk between metabolism and cell death in tumorigenesis
Authors: Yang Shichao , Hu Caden , Chen Xiaomei , Tang Yi , Li Juanjuan , Yang Hanqing , Yang Yi , Ying Binwu , Xiao Xue , Li Shang‑Ze , Gu Li , Zhu Yahui
Published: April 2024

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.
Association of the habitual dietary intake with the fatty liver index and effect modification by metabotypes in the population-based KORA-Fit study
Authors: Schepp M. , Freuer D. , Wawro N. , Peters A. , Heier M. , Teupser D. , Meisinger C. , Linseisen J.
Published: April 2024

Background

Non-alcoholic fatty liver disease (NAFLD) is an emerging threat for public health with diet being a major risk factor in disease development and progression. However, the effects of habitual food consumption on fatty liver are still inconclusive as well as the proposed role of the individuals’ metabolic profiles. Therefore, the aim of our study is to examine the associations between diet and NAFLD with an emphasis on the influence of specific metabotypes in the general population.

Methods

A total of 689 participants (304 men and 385 women) of the KORA-Fit (S4) survey, a follow-up study of the population-based KORA cohort study running in the Region of Augsburg, Germany, were included in this analysis. Dietary information was derived from repeated 24-h food lists and a food frequency questionnaire. The intake of energy and energy-providing nutrients were calculated using the national food composition database. The presence of fatty liver was quantified by the fatty liver index (FLI), and metabotypes were calculated using K-means clustering. Multivariable linear regression models were used for the analysis of habitual food groups and FLI; for the evaluation of macronutrients, energy substitution models were applied.

Results

A higher consumption of nuts and whole grains, and a better diet quality (according to Alternate Healthy Eating Index and Mediterranean Diet Score) were associated with lower FLI values, while the intake of soft drinks, meat, fish and eggs were associated with a higher FLI. The isocaloric substitution of carbohydrates with polyunsaturated fatty acids was associated with a decreased FLI, while substitution with monounsaturated fatty acids and protein showed increased FLI. Statistically significant interactions with the metabotype were observed for most food groups.

Conclusion

The consumption of plant-based food groups, including nuts and whole grains, and diet quality, were associated with lower FLI values, whereas the intake of soft drinks and products of animal origin (meat, fish, eggs) were associated with a higher FLI. The observed statistically significant interactions with the metabotype for most food groups could help to develop targeted prevention strategies on a population-based level if confirmed in independent prospective studies.
Acceptance and commitment therapy adapted for women with infertility: a pilot study of the Infertility ACTion program
Authors: Balsom Ashley A. , Klest Bridget , Sander Bethany , Gordon Jennifer L.
Published: April 2024

Background

Approximately one in six couples are currently infertile, defined as unable to achieve pregnancy despite 12 or more months of active attempts to conceive. Experiencing infertility has been disproportionately associated with an array of psychological difficulties, particularly in women. However, currently available psychological interventions have had minimal benefits for distress, anxiety, or depression related to infertility.

Methods

A one-arm pilot study was conducted to test the acceptability of a newly created acceptance and commitment therapy-based self-guided program—Infertility ACTion. Twenty women, located in Canada, completed the program and completed measures assessing expectancy of improvement, treatment credibility, participant satisfaction, treatment completion and retention, psychological flexibility, fertility quality of life, depression, and anxiety. Participants were also asked to provide feedback on how the researchers could improve the intervention. Paired sample t-tests were conducted to compare pre- and post-intervention outcomes.

Results

Sixteen out of 20 participants completed the entire intervention. Reported treatment expectancy, credibility and satisfaction were favorable. Eighty-one percent of participants reported that they would recommend the program to a friend and 88% thought the program was worth their time. Medium increases in psychological flexibility and fertility quality of life were observed. Improvements in anxious and depressive symptoms were in the small to medium range but were not significant. Participants had several recommendations for program improvement.

Conclusions

This acceptance and commitment therapy-based self-guided program proved to be an acceptable treatment for infertility-related distress. Participant feedback will be used to adjust the current intervention in preparation for a more rigorous randomized-controlled trial testing this program.
Online prediction of sustained muscle force from individual motor unit activities using adaptive surface EMG decomposition
Authors: Zhao Haowen , Sun Yong , Wei Chengzhuang , Xia Yuanfei , Zhou Ping , Zhang Xu
Published: April 2024

Decoding movement intentions from motor unit (MU) activities to represent neural drive information plays a central role in establishing neural interfaces, but there remains a great challenge for obtaining precise MU activities during sustained muscle contractions. In this paper, we presented an online muscle force prediction method driven by individual MU activities that were decomposed from prolonged surface electromyogram (SEMG) signals in real time. In the training stage of the proposed method, a set of separation vectors was initialized for decomposing MU activities. After transferring each decomposed MU activity into a twitch force train according to its action potential waveform, a neural network was designed and trained for predicting muscle force. In the subsequent online stage, a practical double-thread-parallel algorithm was developed. One frontend thread predicted the muscle force in real time utilizing the trained network and the other backend thread simultaneously updated the separation vectors. To assess the performance of the proposed method, SEMG signals were recorded from the abductor pollicis brevis muscles of eight subjects and the contraction force was simultaneously collected. With the update procedure in the backend thread, the force prediction performance of the proposed method was significantly improved in terms of lower root mean square deviation (RMSD) of around 10% and higher fitness (R2) of around 0.90, outperforming two conventional methods. This study provides a promising technique for real-time myoelectric applications in movement control and health.
Investigation of the pressure value while performing biceps tenodesis for superior capsuler reconstruction
Authors: Bilgin Emre , Kilinc Bekir Eray , Arican Cigdem Dicle , Yilmaz Baris
Published: April 2024

Background

To compare the histopathological results of biceps tenodesis (BT) performed with normal, low, and high pressures for superior capsule reconstruction (SCR) in rabbits with massive rotator cuff tears.

Materials and methods

Thirty rabbits were divided into three groups. Rabbits 1–10 underwent SCR with BT at the same pressure (Group 1), value measured in the groove; 50% lower (Group 2); 50% higher (Group 3). After the 4-week follow-up, shoulder were en-bloc excised and histopathological evaluation was performed with modified Bonar’s scale. Results were compared between the groups, statistically.

Results

Extracellular matrix were significantly lower in group 2 compared to the other groups (p < 0.05). Cellularity levels were significantly lower in group 2 compared to the other groups (p < 0.05). Group 2 had no difference between the sides (p > 0.05). Group 2 had lower vascularity levels compared to the other groups (p = 0.01).

Dicsussion

When the biceps tendon was in the bicipital groove and in a more mobile state with lower pressure exposure. BT performed with a tension that creates less pressure than the biceps in the groove is more successful in SCR.
ROBot-assisted physical training of older patients during acUte hospitaliSaTion—study protocol for a randomised controlled trial (ROBUST)
Authors: Bertelsen Ann Sophia , Masud Tahir , Suetta Charlotte , Rosenbek Minet Lisbeth , Andersen Stig , Lauridsen Jørgen T. , Ryg Jesper
Published: April 2024

Background

During hospitalisation, older patients spend most of their time passive in bed, which increases the risk of functional decline and negative adverse outcomes. Our aim is to examine the impact of robot-assisted physical training on functional status in older geriatric patients during acute hospitalisation.

Methods

This is a single-centre investigator-blinded placebo-controlled randomised controlled trial including geriatric patients aged ≥ 65 years, able to ambulate before hospitalisation, and with expected length of stay ≥ 2 days. In addition to standard physiotherapy treatment, the intervention group receive active robot-assisted resistance training and the control group passive robot-assisted sham training. Exclusion criteria are as follows: ambulation without assistance at the time of inclusion, known severe dementia, delirium, patients who have received less than three training sessions at discharge, terminal illness, recent major surgery/lower extremity fracture, conditions contradicting the use of training robot, lower extremity metastases, deemed unsuitable for robot-assisted training by a healthcare professional, or weight > 165 kg. The primary outcome is functional status assessed by change in Barthel Index-100 and 30-s chair stand test between inclusion and day of discharge. Secondary outcomes include functional status at 1- and 3-month follow-up, quality of life, depression, concern about falling, falls, cognition, qualitative interviews, need of homecare, discharge destination, readmissions, healthcare costs, sarcopenia, muscle quantity (bioimpedance), and mortality.

Clinical meaningful change of the Barthel Index is 5 points. A recent study in geriatric patients reported a 6.9-point change following exercise. With a significance level of 5%, 80% power, and a drop-out rate of 20%, 244 participants per group (n = 488) are needed to detect the same mean difference. With a significance level of 5%, 80% power, and a drop-out rate of 20%, 74 participants per group (n = 148) are needed to detect a minimum clinical change of 2.6 repetitions for 30-s chair stand test. Recruitment started in January 2023 and is expected to continue for 19 months including follow-up.

Discussion

If our study shows that in-hospital robot-assisted training prevents functional decline in older patients, this may have a major impact on the individual patient due to increased wellbeing and a higher level of independency. In addition, society will benefit due to potential decrease in the need of municipality-delivered homecare following discharge.

Trial registration

ClinicalTrials.gov NCT05782855. Registration date: March 24, 2023.
Cell fusing agent virus rarely transmits vertically in artificially infected laboratory-colonized Aedes aegypti mosquitoes
Authors: Nag Dilip K. , Efner Kathryn
Published: April 2024

Background

Vertical transmission (VT) of arboviruses (arthropod-borne viruses) can serve as an essential link in the transmission cycle during adverse environmental conditions. The extent of VT among mosquito-borne arboviruses can vary significantly among different virus families and even among different viruses within the same genus. For example, orthobunyaviruses exhibit a higher VT rate than orthoflaviviruses and alphaviruses. Mosquitoes are also the natural hosts of a large number of insect-specific viruses (ISV) that belong to several virus families, including Bunyaviridae, Flaviviridae, and Togaviridae. Cell fusing agent virus (CFAV), an insect-specific orthoflavivirus, displays higher VT rates than other dual-host orthoflaviviruses, such as Zika and dengue viruses. High VT rates require establishment of stabilized infections in the germinal tissues of female vectors. To delve deeper into understanding the mechanisms governing these differences in VT rates and the establishment of stabilized infections, the ovary infection patterns and VT of Zika virus (ZIKV) and CFAV were compared.

Methods

Laboratory colonized Aedes aegypti females were infected with either ZIKV or CFAV by intrathoracic injection. Ovary infection patterns were monitored by in situ hybridization using virus-specific probes, and VT was determined by detecting the presence of the virus among the progeny, using a reverse-transcription quantitative polymerase chain reaction (PCR) assay.

Results

Both ZIKV and CFAV infect mosquito ovaries after intrathoracic injection. Infections then become widespread following a non-infectious blood meal. VT rates of ZIKV are similar to previously reported results (3.33%). CFAV, on the contrary transmits vertically very rarely. VT was not observed in the first gonotrophic cycle following intrathoracic injection, and only rarely in the second gonotrophic cycle. VT of CFAV is mosquito population independent, since similar results were obtained with Aedes aegypti collected from two different geographic locations.

Conclusions

Although CFAV infects mosquito ovaries, the occurrence of VT remains infrequent in artificially infected Ae. aegypti, despite the observation of high VT rates in field-collected mosquitoes. These results suggest that infections of insect-specific viruses are stabilized in mosquitoes by some as yet unidentified mechanisms.

Graphical Abstract
Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer
Authors: Chen Dezhi , Cai Bo , Zhu Yingying , Ma Yimin , Yu Xiaoting , Xiong Jieqi , Shen Jiaying , Tie Weiwei , Zhang Yisheng , Guo Fei
Published: April 2024

Background

The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease.

Result

Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets.

Conclusions

Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.
Neuroimaging-guided diagnosis of possible FTLD-FUS pathology: a case report
Authors: Mathoux Gregory , Boccalini Cecilia , Lathuliere Aurelien , Scheffler Max , Frisoni Giovanni B. , Garibotto Valentina
Published: April 2024

Background

This case report presents a patient with progressive memory loss and choreiform movements.

Case presentation

Neuropsychological tests indicated multi-domain amnestic mild cognitive impairment (aMCI), and neurological examination revealed asymmetrical involuntary hyperkinetic movements. Imaging studies showed severe left-sided atrophy and hypometabolism in the left frontal and temporoparietal cortex. [18F]Flortaucipir PET exhibited moderately increased tracer uptake in hypometabolic areas. The diagnosis initially considered Alzheimer’s disease (AD), frontotemporal degeneration (FTD), and corticobasal degeneration (CBD), cerebral hemiatrophy syndrome, but imaging and cerebrospinal fluid analysis excluded AD and suggested fused-in-sarcoma-associated FTD (FTLD-FUS), a subtype of the behavioural variant of FTD.

Conclusions

Our case highlights that despite the lack of specific FUS biomarkers the combination of clinical features and neuroimaging biomarkers can guide choosing the most likely differential diagnosis in a complex neurological case. Imaging in particular allowed an accurate measure of the topography and severity of neurodegeneration and the exclusion of AD-related pathology.
Crosstalk between m6A modification and autophagy in cancer
Authors: Chen Tao , Zheng Liying , Luo Peiyue , Zou Jun , Li Wei , Chen Qi , Zou Junrong , Qian Biao
Published: April 2024

Autophagy is a cellular self-degradation process that plays a crucial role in maintaining metabolic functions in cells and organisms. Dysfunctional autophagy has been linked to various diseases, including cancer. In cancer, dysregulated autophagy is closely associated with the development of cancer and drug resistance, and it can have both oncogenic and oncostatic effects. Research evidence supports the connection between m6A modification and human diseases, particularly cancer. Abnormalities in m6A modification are involved in the initiation and progression of cancer by regulating the expression of oncogenes and oncostatic genes. There is an interaction between m6A modification and autophagy, both of which play significant roles in cancer. However, the molecular mechanisms underlying this relationship are still unclear. m6A modification can either directly inhibit autophagy or promote its initiation, but the complex relationship between m6A modification, autophagy, and cancer remains poorly understood. Therefore, this paper aims to review the dual role of m6A and autophagy in cancer, explore the impact of m6A modification on autophagy regulation, and discuss the crucial role of the m6A modification-autophagy axis in cancer progression and treatment resistance.
Molecular subtyping and the construction of a predictive model of colorectal cancer based on ion channel genes
Authors: Ai Lian-jie , Li Guo-dong , Chen Gang , Sun Zi-quan , Zhang Jin-ning , Liu Ming
Published: April 2024

Purpose

Colorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment.

Methods

A consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments.

Results

Four distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells.

Conclusions

Ion channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.
Extracellular vesicles-coupled miRNAs from oviduct and uterus modulate signaling pathways related to lipid metabolism and bovine early embryo development
Authors: Mazzarella Rosane , Cañón-Beltrán Karina , Cajas Yulia N. , Hamdi Meriem , González Encina M. , da Silveira Juliano C. , Leal Claudia L. V. , Rizos D.
Published: April 2024

Background

Extracellular vesicles (EVs) present in oviductal (OF) and uterine fluid (UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes (LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabolism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within EVs in maternal reproductive fluids, such as microRNAs (miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional mechanisms.

Results

This study evaluated miRNA cargo in OF-EVs from the early luteal phase and UF-EVs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LMGs and signaling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups. From the 20 differentially expressed miRNAs, 19 up-regulated in UF-EVs (bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one (bta-miR-148b) in OF-EVs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, MAPK, and lipid metabolism and degradation. Differences in miRNAs found in OF-EVs from the early luteal phase and UF-EVs from mid-luteal phase may reflect different environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and implantation.

Conclusions

Our study suggests that miRNAs within OF- and UF-EVs could modulate bovine embryo development and quality, providing insights into the intricate maternal-embryonic communication that might be involved in modulating lipid metabolism, immune response, and implantation during early pregnancy.
A compendium of ruminant gastrointestinal phage genomes revealed a higher proportion of lytic phages than in any other environments
Authors: Wu Yingjian , Gao Na , Sun Chuqing , Feng Tong , Liu Qingyou , Chen Wei-Hua
Published: April 2024

Background

Ruminants are important livestock animals that have a unique digestive system comprising multiple stomach compartments. Despite significant progress in the study of microbiome in the gastrointestinal tract (GIT) sites of ruminants, we still lack an understanding of the viral community of ruminants. Here, we surveyed its viral ecology using 2333 samples from 10 sites along the GIT of 8 ruminant species.

Results

We present the Unified Ruminant Phage Catalogue (URPC), a comprehensive survey of phages in the GITs of ruminants including 64,922 non-redundant phage genomes. We characterized the distributions of the phage genomes in different ruminants and GIT sites and found that most phages were organism-specific. We revealed that ~ 60% of the ruminant phages were lytic, which was the highest as compared with those in all other environments and certainly will facilitate their applications in microbial interventions. To further facilitate the future applications of the phages, we also constructed a comprehensive virus-bacteria/archaea interaction network and identified dozens of phages that may have lytic effects on methanogenic archaea.

Conclusions

The URPC dataset represents a useful resource for future microbial interventions to improve ruminant production and ecological environmental qualities. Phages have great potential for controlling pathogenic bacterial/archaeal species and reducing methane emissions. Our findings provide insights into the virome ecology research of the ruminant GIT and offer a starting point for future research on phage therapy in ruminants.