bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognising socio-cultural barriers while seeking early detection services for breast cancer: a study from a Universal Health Coverage setting in India
Authors: Sawhney Riya , Nathani Priyansh , Patil Priti , Bhandarkar Prashant , Veetil Deepa Kizhakke , Venghateri Jubina Balan , Roy Nobhojit , Gadgil Anita
Published: September 2023

Background

Breast cancer is the commonest cancer among women in India, yet the uptake of early detection programs is poor. This leads to late presentation, advanced stage at the time of diagnosis, and high mortality. Poor accessibility and affordability are the most commonly cited barriers to screening: we analyse socio-cultural factors influencing the uptake of early detection programmes in a Universal Health Coverage (UHC) setting in India, where geographical and financial barriers were mitigated.

Methods

Two hundred seventy-two women engaging in an awareness-based early detection program were recruited by randomization as the participant (P) group. A further 272 women who did not participate in the early detection programme were recruited as non-participants (NP). None of the groups were previously screened for breast cancer. Interviews were conducted using a 19-point questionnaire, consisting of closed-ended questions regarding demographics and social, cultural, spiritual and trust-related barriers.

Results

The overall awareness about breast cancer was high among both groups. None of the groups reported accessibility-related barriers. Participants were more educated (58.09% vs 47.43%,p = 0.02) and belonged to nuclear families (83.59% vs 76.75%,p = 0.05). Although they reported more fear of isolation due to stigma (25% vs 14%,p = 0.001), they had greater knowledge about breast cancer and trust in the health system compared to non-participants.

Conclusions

The major socio-cultural barriers identified were joint family setups, lower education and awareness, and lack of trust in healthcare professionals. As more countries progress towards UHC, recognising socio-cultural barriers to seeking breast health services is essential in order to formulate context-specific solutions to increase the uptake of early detection and screening services.
The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer
Authors: Divoux Jordane , Florent Romane , Jacobs Margaux , Lequesne Justine , Grellard Jean-Michel , San Chankannira , Grossi Sara , Kerdja Katia , Clarisse Bénédicte , Boudier Gwenaelle , Cherifi François , Briand Mélanie , Dolivet Enora , Johnson Alisson , Dubois Brice , Harter Valentin , Lacroix Joëlle , Raboutet Charlotte , Marie Brigitte , Rousseau Nathalie , Blanc-Fournier Cécile , Vaur Dominique , Figeac Martin , Poulain Laurent , Weiswald Louis-Bastien , Emile George
Published: September 2023

Background

Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient’s tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients.

Method

The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model.

Discussion

This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation.

Trial registration

The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.
Treatment strategy for BVO-ME based on long-term outcomes correlating retinal structure by OCT image and visual acuity
Authors: Hattori Yuki , Fujiwara Ryo , Mori Hidetsugu , Kimura Motoki , Yamada Haruhiko , Takahashi Kanji
Published: September 2023

Background

Intravitreal anti-vascular endothelial growth factor (VEGF) is a mainstream treatment for reducing ME secondary to BRVO (BVO-ME). Regrettably, most reports of intravitreal anti-VEGF for BVO-ME have disclosed only short-term outcomes. Here, we characterized long-term indicators for the visual prognosis of patients with BVO-ME, including the correlation between retinal structure by OCT and visual acuity.

Methods

Patients with BVO-ME were retrospectively recruited based on clinical records in Kansai Medical University Hospital from June 2012 to March 2022. This study enrolled patients with vision loss who received intravitreal injection of anti-VEGF for BVO-ME. Inclusion criteria were that patients received intravitreal injection of anti-VEGF as their first treatment and were followed for at least 36 months. Exclusion criteria were those patients with ocular disease other than BRVO or who had been previously treated for BVO-ME. Patients were divided into two groups according to BCVA at the final visit: Group A (≥ 0.7) and Group B (< 0.7).

Results

Forty-seven eyes from 45 patients were assessed. The mean follow-up period from initial to final visit was 64.38 ± 15.07 (range, 38–100) months. BCVA in Group A (n = 32) was significantly greater than in Group B (n = 15) at all timepoints. The ratio that the number of eyes which the EZ band and the foveal bulge were intact in Group A was higher than in Group B (p = 0.0004 and p = 0.0002, respectively). The ratio that the number of eyes which recurrence SRD was observed by the final visit in Group A was lower than in Group B (p = 0.0485).

Conclusions

The integrity of the EZ band and an intact foveal bulge were significant predictors for visual acuity. In contrast, recurrent SRD led to poor visual acuity in the long term, even if BCVA was good in the short term.
A multicentre neonatal interventional randomised controlled trial of nebulized surfactant for preterm infants with respiratory distress: Neo-INSPIRe trial protocol
Authors: Lategan Ilse , Durand David , Harrison Michael , Nakwa Firdose , Van Wyk Lizelle , Velaphi Sithembiso , Horn Alan , Kali Gugu , Soll Roger , Ehret Danielle , Zar Heather , Tooke Lloyd
Published: September 2023

Introduction

Respiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce. Recent trials from high-resourced countries utilising aerosolized surfactant have had a low quality of evidence and varying outcomes.

Methods and analysis

The Neo-INSPIRe trial is an unblinded, multicentre, randomised trial of a novel aerosolized surfactant drug/device combination. Inclusion criteria include preterm infants of 27–34+6 weeks’ gestational age who weigh 900-1999g and who require CPAP with a fraction of inspired oxygen (FiO2) of 0.25–0.35 in the first 2–24 h of age. Infants are randomised 1:1 to control (CPAP alone) or intervention (CPAP with aerosolized surfactant). The primary outcome is the need for intratracheal bolus surfactant instillation within 72 h of age. Secondary outcomes include the incidence of reaching failure criteria (persistent FiO2 of > 0.40, severe apnoea or severe work of breathing), the need for and duration of ventilation and respiratory support, bronchopulmonary dysplasia and selected co-morbidities of prematurity. Assuming a 40% relative risk reduction to reduce the proportion of infants requiring intratracheal bolus surfactant from 45 to 27%, the study will aim to enrol 232 infants for the study to have a power of 80% to detect a significant difference with a type 1 error of 0.05.

Ethics and dissemination

Ethical approval has been granted by the relevant human research ethics committees at University of Cape Town (HREC 681/2022), University of the Witwatersrand HREC (221112) and Stellenbosch University (M23/02/004).

Trial registration

PACTR202307490670785
The effect of social media campaign on parental knowledge, attitudes and practices regarding the use of children car seats in the Gulf region
Authors: Bakhurji Eman A. , M. Alqahtani Albandari , M. Alwashmi Ezdehar , S. Husain Manayer , Gaffar Balgis O.
Published: September 2023

Background

Motor vehicle crashes (MVCs) are the leading cause of child deaths in the Gulf Cooperation Council. This study aimed to investigate the effect of a social media educational campaign on parents' knowledge of child safety seats.

Methods

We conducted a pre-post interventional study as an online educational module in Arabic and English. The module link was shared on social media and was accompanied by a pre-post survey that included questions about demographics, knowledge, and practices of car seat use.

Results

A total of 303 participants completed the campaign, with 23.8% fathers and 76.2% mothers answered the survey. The majority of participants were from Saudi Arabia (95.7%), while 4.3% were from other Gulf Cooperation Council (GCC) countries. Most parents agreed on the importance of organizing awareness campaigns and having a law to enforce the use of car seats. The pre-survey mean knowledge score was 11.64, which significantly increased to 13.1 in the post-survey (p < 0.001).

Conclusions

The intervention of the educational campaign through social media resulted in a significant increase in parents' knowledge and awareness of the importance of using car seats correctly. This study highlights the potential effectiveness of social media campaigns in improving parents' knowledge and awareness of child safety seats.
Arthroscopic treatment of deep gluteal syndrome and the application value of high-frequency ultrasound
Authors: Sun Guanjun , Fu Weili , Li Qingshan , Yin Yi
Published: September 2023

Purpose

This study aimed to evaluate the efficacy of arthroscopic sciatic neurolysis for treating deep gluteal syndrome (DGS) and to analyse the application value of high-frequency ultrasound during perioperative period.

Methods

Between June 2020 and February 2022, 30 patients with DGS who underwent failed conservative treatment were retrospectively analysed. Lateral arthroscopic exploration of the deep gluteal space and sciatic neurolysis were performed. In addition to pelvic X-ray, lumbar disc and hip magnetic resonance imaging (MRI), ultrasonography of the sciatic nerve was also performed in all patients. The visual analogue scale pain score (VAS), modified Harris hip score (mHHS) and Benson symptom-rating scale were used to evaluate the clinical efficacy. The correlation between preoperative sciatic nerve ultrasound and arthroscopic findings was analysed.

Results

The median follow-up for these patients was 13 months (range,12–21 months). Preoperative ultrasonography showed precise morphological changes in 26 sciatic nerves of patients. The VAS score decreased from 5.0 (4.0, 6.0) preoperatively to 0.5 (0, 1.0) postoperatively (p < 0.001), and the mHHS increased from 64.0 (57.0, 67.0) preoperatively to 95.0 (93.0, 97.0) postoperatively (p < 0.001). The Benson symptom score was excellent in 15 cases, good in 12 cases, fair in 2 cases, poor in 1 case; thus, the score was excellent or good in 90% of the cases. Preoperative ultrasound diagnosis and intra-operative findings matched up in all cases. There were four cases of transient numbness in the posterior thigh.

Conclusions

Arthroscopic sciatic neurolysis is a safe and effective treatment option for DGS patients who fail conservative treatment. Ultrasound diagnosis matched the arthroscopic findings perfectly. Preoperative Doppler ultrasound can assist surgical decision-making, guide intraoperative release.
Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial
Authors: Thomsen Ruth Stoklund , Nilsen Tom Ivar Lund , Haugeberg Glenn , Sitter Beathe , Kavanaugh Arthur , Pedersen Susanne Juhl , Hoff Mari
Published: September 2023

Background

In psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine.

Methods

We randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups.

Results

Proportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%.

The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine.

Conclusion

In PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI.

Trial registration

ClinicalTrials.gov NCT02995460 (16/12/2016).
Bipedicular percutaneous kyphoplasty versus unipedicular percutaneous kyphoplasty in the treatment of asymmetric osteoporotic vertebral compression fractures: a case control study
Authors: Liu Lei , Song Feifei , Shang Jie , Zhang Jianwei , Ma Chao , Liu Guangpu , Han Meng
Published: September 2023

Background

Bipedicular/unipedicular percutaneous kyphoplasty are common treatments for OVCF, and there are no studies to show which is more beneficial for AVCF. The purpose of this study was to investigate the clinical efficacy of BPKP or UPKP in the treatment of AVCF.

Methods

The clinical data of AVCF patients treated by PKP were retrospectively analyzed. They were divided into two groups according to the surgical approach. General demographic data, perioperative complications, and general information related to surgery were recorded for both groups. The preoperative and postoperative vertebral height difference, vertebral local Cobb angle, lumbar pain VAS score and lumbar JOA score were counted for both groups. The above data were compared preoperatively, postoperatively and between the two groups.

Results

25 patients with AVCF were successfully included and all were followed up for at least 12 months, with no complications during the follow-up period. 10 patients in the BPKP group and 15 patients in the UPKP group, with no statistically significant differences in general information between the two groups. The VAS scores of patients in the BPKP group were lower than those in the UPKP group at 12 months after surgery, and the differences were statistically significant, and there were no statistically significant differences between the two groups at other follow-up time points. In the BPKP group, 80% of patients had symmetrical and more homogeneous bone cement dispersion. 50% of patients in the UPKP group had a lateral distribution of bone cement and uneven bone cement distribution, and the difference in bone cement distribution between the two groups was statistically significant.

Conclusion

For the treatment of AVCF, the clinical efficacy of both surgical approaches is basically the same. The distribution of cement is more symmetrical and uniformly diffused in the BPKP group, and the clinical efficacy VAS score is lower in the long-term follow-up. Bipedicular percutaneous kyphoplasty is recommended for the treatment of AVCF.

The ethical review batch number

XZXY-LJ-20161208-047.
Comparison of topical purslane & topical 0.1% triamcinolone acetonide in the management of oral lichen planus - a double blinded clinical trial
Authors: Murugan Arul Jothi , Ganesan Anuradha , Aniyan Yesoda K. , Lakshmi Krithika Chandrasekar , Asokan Kannan
Published: September 2023

Aim and background

Oral lichen planus (OLP) is a chronic autoimmune mucocutaneous disorder of unknown etiology and treatment is targeted at alleviating symptoms. At present, corticosteroids are the mainstay treatment, and their side effects hamper their long-term use, demanding alternative therapy. This study intended to assess the efficacy of topical purslane (Portulaca oleracea) at two concentrations, 5% and 10%, in OLP and to compare the level of clinical improvement in comparison to topical 0.1% triamcinolone acetonide gel.

Materials and methods

After sample size determination, thirty-four subjects confirmed histopathologically with OLP were included in the study. They were divided into 3 groups, Group 1(Control) was treated with 0.1% triamcinolone acetonide, and Group 2(Case) and 3 (Case) were treated with topical purslane 5% and 10%, respectively. They were examined at baseline, 14 days, 30 days, 60 days, and 90 days. Clinical improvement was then analyzed at the end of 90 days using a visual analog scale (VAS) and Thongprasom’s criteria.

Results

The study was analyzed statistically and a P value of < 0.05 was considered statistically significant. Intragroup comparison revealed a statistically significant difference between the five time periods (baseline, 14 days, 30 days, 60 days, and 90 days) for the study variables (burning sensation, pain, lesion score, clinical response, symptomatic response) for all three groups (p = 0.001). Alleviation of all symptoms and remission of the lesion were noted for all three groups at the end of three months.

Conclusion

Purslane is a magical herb with a plethora of rich nutrients, ease in accessibility and devoid of side effects. It was concluded that its preparation is beneficial and can be a safer alternative long-term drug for the management of OLP.

Clinical significance

With available literature evidence, our present study is the first of its kind to formulate a topical gel with purslane to treat symptomatic OLP. Our study had a longer follow-up of 3 months compared to other studies in the literature.
The effect of recurrent application of concentrated platelet-rich fibrin inside the extraction socket on the hard and soft tissues. a randomized controlled trial
Authors: Lahham Cezar , Ta’a Mahmoud Abu , Lahham Elias , Michael Saleem , Zarif Wael
Published: September 2023

Background

Platelet-rich fibrin (PRF) is commonly used for ridge preservation following tooth extraction. However, its effectiveness diminishes over a period of two weeks as it is resorbed and loses its biological activities. Therefore, this clinical study aims to evaluate the effect of recurrent application of concentrated PRF (C-PRF) inside the extraction socket on the hard and soft tissue alterations.

Methods

Twenty patients requiring single tooth extraction and replacement with a dental implant were randomized into one of two ridge preservation approaches: Advanced PRF plus alone (Control group) or advanced PRF plus with the recurrent application of a C-PRF inside the socket every two weeks for 2 months (four times). The ridge width, the ridge height, and the soft tissue thickness were assessed clinically at the baseline and reassessed after 3 months from tooth extraction during implant surgery. Then the amount of hard tissue loss and soft tissue alterations were calculated.

Results

There was a statistically significant difference in the amount of hard tissue loss between groups in the third month. The amount of horizontal ridge loss for the control and test groups were 2.9 ± 0.7 mm and 1.9 ± 0.5 mm, respectively (p-value < 0.05). The vertical bone loss for control and test groups were 1.8 ± 0.5 mm and 1.0 ± 0.3 mm, respectively (p-value < 0.05). Additionally, for the soft tissue thickness, there was no statistical difference between the groups (p-value > 0.05).

Conclusion

Within the limitations of this study, the recurrent application of C-PRF in the extraction socket could decrease the amount of ridge alteration following tooth extraction and may play a role in the bone regeneration procedures.

Trial registration

Registered on ClinicalTrials.gov (ID: NCT05492357, on 08/08/2022).
A fruit extract of Styphnolobium japonicum (L.) counteracts oxidative stress and mediates neuroprotection in Caenorhabditis elegans
Authors: Thabit Sara , Handoussa Heba , ElSayed Nesrine S. , Breitinger Hans-Georg , Breitinger Ulrike , Wink Michael
Published: September 2023

Background

Despite its widespread uses in Chinese and European medicine, Styphnolobium japonicum (Chinese scholar tree, formerly Sophora japonicum) has not been extensively investigated for its potential to protect against neurodegenerative processes and to promote resistance to oxidative stress. In this study, we evaluated the neuroprotective activities of a hydroalcoholic extract from Chinese scholar tree fruits that could be possibly linked to its antioxidant properties using Caenorhabditis elegans as a well-established in vivo model.

Methods

Survival rate in mutant daf-16 and skn-1 worms, stressed by the pro-oxidant juglone and treated with the extract, was tested. Localization of the transcription factors SKN-1 and DAF-16, and expression of gst-4 were measured. For evaluation of neuroprotective effects, formation of polyglutamine (polyQ40) clusters, α-synuclein aggregates, loss of amphid sensilla (ASH) neuronal function, and amyloid β (Aβ) accumulation (as markers for Huntington’s, Parkinson’s, and Alzheimer’s) was examined.

Results

The extract, which contains substantial amounts of phenolic phytochemicals, showed an increase in the survival rate of worms challenged with juglone in daf-16 mutants but not in skn-1 mutants. The transcription factor SKN-1 was activated by the extract, while DAF-16 was not affected. Upon application of the extract, a significant decline in GST-4 levels, polyQ40 cluster formation, number of lost ASH sensory neurons, α-synuclein aggregation, and paralysis resulting from Aβ accumulation was observed.

Conclusions

Styphnolobium japonicum fruit extract activated the SKN-1/Nrf2 pathway, resulting in oxidative stress resistance. It revealed promising pharmacological activities towards treatment of Huntington’s, Parkinson’s, and Alzheimer’s diseases. Polyphenolics from Styphnolobium japonicum may be a promising route towards treatment of CNS disorders, but need to be tested in other in vivo systems.
A urinary assay for mutation and methylation biomarkers in the diagnosis and recurrence prediction of non-muscle invasive bladder cancer patients
Authors: Huang Hai , Liu Ao , Liang Yiming , Xin Yaqun , Liu Jiacheng , Hao Yining , Huang Da , Chen Lu , Li Wei , Jiang Guangliang , Huang Yuhua , Xu Yaoting , Zhang Jie , Ma Tonghui , Xu Danfeng , Gao Yi
Published: September 2023

Background

Currently, the clinical strategy for diagnosis of non-muscle invasive bladder cancer (NMIBC) such as cystoscopy and cytology are invasive and/or with limited accuracy. OncoUrine, a urinary assay for mutation and methylation biomarkers, have showed a high accuracy in the detection of upper tract urinary carcinoma (UTUC) patients with hematuria. The aim of this study is to evaluate the performance of OncoUrine in diagnosis of NMIBC patients.

Methods

In this multicenter prospective study, a total of 203 patients were enrolled, including 60 patients present with hematuria and 143 NMIBC patients under recurrence surveillance. Urine samples were collected before cystoscopy to undergo OncoUrine test. OncoUrine performance was calculated compared to clinical standard methods in hematuria cohort and recurrence surveillance cohort, respectively. Furthermore, NMIBC patients were followed up with a median time of 20.5 months (range 0.03 to 24.03 months) to assess the predictive value of OncoUrine during recurrence monitoring.

Results

For bladder cancer diagnosis, OncoUrine tested 47 samples and achieved a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 80% (95% CI 44.2–96.5)/91.9% (95% CI 77.0–97.9)/72.7% (95% CI 39.3–92.7)/94.4% (95% CI 80.0–99.0) (kappa value 69.4%, 95% CI 44.4–94.3), indicating 72.3% of unnecessary cystoscopy. For recurrence diagnosis, OncoUrine tested 93 samples, and the sensitivity/specificity/PPV/NPV was 100% (95% CI 59.8–100.0)/68.2% (95% CI 57.1–77.7)/22.9% (95% CI 11.0–40.6)/100% (95% CI 92.3–100.0) (kappa value 27.0%, 95% CI 11.1–42.8), indicating 62.4% of spared cystoscopy. What is more, OncoUrine correctly predicted 80% (20/25) of final recurrence with 12/25 (48%) patients who were OncoUrine positive, but cystoscopy negative was followed with recurrence during follow-up. The test result of OncoUrine was also found significantly correlated with recurrence free survival (RFS) of NMIBC patients (median 34.4-month vs unreached; HR 6.0, 95% CI 2.7–13.5, P < 0.0001).

Conclusions

OncoUrine showed potential value to reduce the frequency of unnecessary cystoscopy and the healthcare cost of bladder cancer patients. Patients with positive test results represented a population who were at high risk of recurrence and thus should be subject to frequent surveillance to ensure timely detection of any potential recurrence. This study has been registered in ClinicalTrials.gov with the number NCT04994197 posted on August 2021.
Ubiquitin-specific peptidase 5 facilitates cancer stem cell-like properties in lung cancer by deubiquitinating β-catenin
Authors: Tung Chia-Hao , Wu Jia-En , Huang Meng-Fan , Wang Wen-Lung , Wu Yi-Ying , Tsai Yao-Tsung , Hsu Xiu-Rui , Lin Sheng-Hsiang , Chen Yuh-Ling , Hong Tse-Ming
Published: September 2023

Background

Lung cancer has the highest mortality rate in the world, and mounting evidence suggests that cancer stem cells (CSCs) are associated with poor prognosis, recurrence, and metastasis of lung cancer. It is urgent to identify new biomarkers and therapeutic targets for targeting lung CSCs.

Methods

We computed the single-sample gene set enrichment analysis (ssGSEA) of 1554 Reactome gene sets to identify the mRNA expression-based stemness index (mRNAsi)-associated pathways using the genome-wide RNA sequencing data of 509 patients from The Cancer Genome Atlas (TCGA) cohort of lung adenocarcinoma (LUAD). Phenotypic effects of ubiquitin-specific peptidase 5 (USP5) on the CSC-like properties and metastasis were examined by in vitro sphere formation assay, migration assay, invasion assay, and in vivo xenografted animal models. Cycloheximide chase assay, co-immunoprecipitation assay, and deubiquitination assay were performed to confirm the effect of USP5 on the deubiquitination of β-catenin.

Results

We demonstrated that USP5 expression were positively correlated with the stemness-associated signatures and poor outcomes in lung cancer specimens. Silencing of endogenous USP5 reduced CSC-like characteristics, epithelial-mesenchymal transition (EMT), and metastasis in vitro and in vivo. Furthermore, USP5 interacted with β-catenin, which resulted in deubiquitination, stabilization of β-catenin, and activation of Wnt/β-catenin pathway. Accordingly, expression of USP5 was positively correlated with the enrichment score of the Wnt/TCF pathway signature in human lung cancer. Silencing of β-catenin expression suppressed USP5-enhancing sphere formation. Targeting USP5 with the small molecule WP1130 promoted the degradation of β-catenin, and showed great inhibitory effects on sphere formation, migration, and invasion. Finally, we identified a poor-prognosis subset of tumors characterized by high levels of USP5, Wnt signaling score, and Stemness score in both TCGA-LUAD and Rousseaux_2013 datasets.

Conclusions

These findings reveal a clinical evidence for USP5-enhanced Wnt/β-catenin signaling in promoting lung cancer stemness and metastasis, implying that targeting USP5 could provide beneficial effects to improve lung cancer therapeutics.
Could vaccinating adults against malaria materially reduce adult mortality in high-transmission areas?
Authors: Gelband Hellen , Carshon-Marsh Ronald , Ansumana Rashid , Swaray Ibrahim Bob , Pandey Arjun , Aimone Ashley , Bogoch Isaac , Eikelboom John , Jha Prabhat
Published: September 2023

After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.
Extracellular matrix-induced signaling pathways in mesenchymal stem/stromal cells
Authors: Novoseletskaya Ekaterina Sergeevna , Evdokimov Pavel Vladimirovich , Efimenko Anastasia Yurievna
Published: September 2023

The extracellular matrix (ECM) is a crucial component of the stem cell microenvironment, or stem-cell niches, and contributes to the regulation of cell behavior and fate. Accumulating evidence indicates that different types of stem cells possess a large variety of molecules responsible for interactions with the ECM, mediating specific epigenetic rearrangements and corresponding changes in transcriptome profile. Signals from the ECM are crucial at all stages of ontogenesis, including embryonic and postnatal development, as well as tissue renewal and repair. The ECM could regulate stem cell transition from a quiescent state to readiness to perceive the signals of differentiation induction (competence) and the transition between different stages of differentiation (commitment). Currently, to unveil the complex networks of cellular signaling from the ECM, multiple approaches including screening methods, the analysis of the cell matrixome, and the creation of predictive networks of protein–protein interactions based on experimental data are used. In this review, we consider the existing evidence regarded the contribution of ECM-induced intracellular signaling pathways into the regulation of stem cell differentiation focusing on mesenchymal stem/stromal cells (MSCs) as well-studied type of postnatal stem cells totally depended on signals from ECM. Furthermore, we propose a system biology-based approach for the prediction of ECM-mediated signal transduction pathways in target cells.
Increased expression of OPN contributes to idiopathic pulmonary fibrosis and indicates a poor prognosis
Authors: Ji Jie , Zheng Shudan , Liu Yuxin , Xie Tian , Zhu Xiaoyu , Nie Yang , Shen Yi , Han Xiaodong
Published: September 2023

Background

Idiopathic pulmonary fibrosis (IPF) is fibrotic lung disease with no effective treatment. It is characterized by destruction of alveolar structure and pulmonary interstitial fibrosis, leading to dyspnea and even asphyxia death of patients. Epithelial-mesenchymal transition (EMT) is considered to be a driving factor in the pathogenesis of IPF. Osteopontin (OPN) is a secreted protein widely present in the extracellular matrix and involved in the occurrence and development of a variety of diseases.

Methods

The original datasets were obtained from NCBI GEO databases analyzed with the online tool GEO2R and EasyGEO. Bleomycin induced mouse pulmonary fibrosis model and OPN/OPN-biotin treated mouse model were established to investigate the role of OPN in mouse pulmonary fibrosis and the target cells of OPN. A549 cells and HBE cells were used to explore the mechanism of OPN-induced epithelial-mesenchymal transition (EMT) in epithelial cells and mass spectrometry was used to detect OPN downstream receptors. Precision-cut lung slices and lentivirus-treated mice with pulmonary fibrosis were used to examine the therapeutic effect of OPN and its downstream pathways on pulmonary fibrosis.

Results

We demonstrate that the content of OPN in IPF bronchoalveolar lavage fluid (BALF) is high compared to the normal groups, and its expression level is correlated with prognosis. At the animal level, OPN was highly expressed at all stages of pulmonary fibrosis in mice, and the bronchoalveolar lavage fluid (BALF) could accurately reflect its expression in the lung. Next, we reveal that OPN was mainly expressed by macrophages and the main target cells of OPN were epithelial cells. Mice developed pulmonary fibrosis accompanied after treating the mice with OPN. Both in vitro and in vivo experiments confirmed that OPN could induce EMT of alveolar epithelial cells. Mechanistically, OPN binding triggered phosphorylation of FAK by CD44, thus activating snail1-mediated profibrotic protein synthesis. Inhibition of FAK phosphorylation and its downstream pathways can effectively alleviate pulmonary fibrosis in precision sections of lung tissue (PCLS) assay. OPN knockdown in bleomycin-induced lung fibrosis mice led to significantly less fibrosis.

Conclusion

Our data suggest that OPN mediates lung fibrosis through EMT, implicating its potential therapeutic target and prognostic indicator role for IPF. OPN may be a target for the diagnosis and treatment of IPF.
The heterogeneity and clonal evolution analysis of the advanced prostate cancer with castration resistance
Authors: Liu Ao , Gao Yi , Wang Qi , Lin Wenhao , Ma Zhiyang , Yang Xiaoqun , Chen Lu , Xu Danfeng
Published: September 2023

Background

Nowadays, the incidence rate of advanced and metastatic prostate cancer at the first time of diagnosis grows higher in China yearly. At present, androgen deprivation therapy (ADT) is the primary treatment of advanced prostate cancer. However, after several years of ADT, most patients will ultimately progress to castration-resistant prostate cancer (CRPC). Previous studies mainly focus on Caucasian and very few on East Asian patients.

Methods

In this study, the pre- and post-ADT tumor samples were collected from five Chinese patients with advanced prostate cancer. The whole-exome sequencing, tumor heterogeneity, and clonal evolution pattern were analyzed.

Results

The results showed that the gene mutation pattern and heterogeneity changed significantly after androgen deprivation therapy. Tumor Mutational Burden (TMB) and Copy Number Alteration (CNA) were substantially reduced in the post-treatment group, but the Mutant-allele tumor heterogeneity (MATH), Socio-Demographic Index (SDI), Intratumor heterogeneity (ITH), and weighted Genome Instability Index (wGII) had no significant difference. According to the clone types and characteristics, the presence of main clones in five pre-and post-treatment samples, the clonal evolution pattern can be further classified into two sub-groups (the Homogeneous origin clonal model or the Heterogeneous origin clonal model). The Progression-free survival (PFS) of the patients with the “Homogeneous origin clonal model” was shorter than the “Heterogeneous origin clonal model”. The longer PFS might relate to MUC7 and MUC5B mutations repaired. ZNF91 mutation might be responsible for resistance to ADT resistance.

Conclusion

Our findings revealed potential genetic regulators to predict the castration resistance and provide insights into the castration resistance processes in advanced prostate cancer. The crosstalk between clonal evolution patterns and tumor microenvironment may also play a role in castration resistance. A multicenter-research including larger populations with different background are needed to confirm our conclusion in the future.
Immunologic constant of rejection as a predictive biomarker of immune checkpoint inhibitors efficacy in non-small cell lung cancer
Authors: Mogenet Alice , Finetti Pascal , Denicolai Emilie , Greillier Laurent , Boudou-Rouquette Pascaline , Goldwasser François , Lumet Gwenael , Ceccarelli Michele , Birnbaum Daniel , Bedognetti Davide , Mamessier Emilie , Barlesi Fabrice , Bertucci François , Tomasini Pascale
Published: September 2023

Background

Anti-PD1/PDL1 immune checkpoint inhibitors (ICI) transformed the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, the response rate remains disappointing and toxicity may be life-threatening, making urgent identification of biomarkers predictive for efficacy. Immunologic Constant of Rejection signature (ICR) is a 20-gene expression signature of cytotoxic immune response with prognostic value in some solid cancers. Our objective was to assess its predictive value for benefit from anti-PD1/PDL1 in patients with advanced NSCLC.

Methods

We retrospectively profiled 44 primary tumors derived from NSCLC patients treated with ICI as single-agent in at least the second-line metastatic setting. Transcriptomic analysis was performed using the nCounter® analysis system and the PanCancer Immune Profiling Panel. We then pooled our data with clinico-biological data from four public gene expression data sets, leading to a total of 162 NSCLC patients treated with single-agent anti-PD1/PDL1. ICR was applied to all samples and correlation was searched between ICR classes and the Durable Clinical Benefit (DCB), defined as stable disease or objective response according to RECIST 1.1 for a minimum of 6 months after the start of ICI.

Results

The DCB rate was 29%; 22% of samples were classified as ICR1, 30% ICR2, 22% ICR3, and 26% ICR4. These classes were not associated with the clinico-pathological variables, but showed enrichment from ICR1 to ICR4 in quantitative/qualitative markers of immune response. ICR2-4 class was associated with a 5.65-fold DCB rate when compared with ICR1 class. In multivariate analysis, ICR classification remained associated with DCB, independently from PDL1 expression and other predictive immune signatures. By contrast, it was not associated with disease-free survival in 556 NSCLC TCGA patients untreated with ICI.

Conclusion

The 20-gene ICR signature was independently associated with benefit from anti-PD1/PDL1 ICI in patients with advanced NSCLC. Validation in larger retrospective and prospective series is warranted.
Brahma-related gene 1 acts as a profibrotic mediator and targeting it by micheliolide ameliorates peritoneal fibrosis
Authors: Li Shuting , Luo Congwei , Chen Sijia , Zhuang Yiyi , Ji Yue , Zeng Yiqun , Zeng Yao , He Xiaoyang , Xiao Jing , Wang Huizhen , Chen Xiaowen , Long Haibo , Peng Fenfen
Published: September 2023

Background

Progressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown.

Methods

The effects of MCL on BRG1-induced fibrotic responses and TGF-β1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed.

Results

BRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-β1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-β1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-β1-induced fibrotic responses and blocked TGF-β1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-β1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-β1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-β1-Smad2/3 signaling pathway.

Conclusion

Our research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.
Transcriptome profiling of patient-derived tumor xenografts suggests novel extracellular matrix-related signatures for gastric cancer prognosis prediction
Authors: Deng Ziqian , Guo Ting , Bi Jiwang , Wang Gangjian , Hu Ying , Du Hong , Zhou Yuan , Jia Shuqin , Xing Xiaofang , Ji Jiafu
Published: September 2023

Background

A major obstacle to the development of personalized therapies for gastric cancer (GC) is the prevalent heterogeneity at the intra-tumor, intra-patient, and inter-patient levels. Although the pathological stage and histological subtype diagnosis can approximately predict prognosis, GC heterogeneity is rarely considered. The extracellular matrix (ECM), a major component of the tumor microenvironment (TME), extensively interacts with tumor and immune cells, providing a possible proxy to investigate GC heterogeneity. However, ECM consists of numerous protein components, and there are no suitable models to screen ECM-related genes contributing to tumor growth and prognosis. We constructed patient-derived tumor xenograft (PDTX) models to obtain robust ECM-related transcriptomic signatures to improve GC prognosis prediction and therapy design.

Methods

One hundred twenty two primary GC tumor tissues were collected to construct PDTX models. The tumorigenesis rate and its relationship with GC prognosis were investigated. Transcriptome profiling was performed for PDTX-originating tumors, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to extract prognostic ECM signatures and establish PDTX tumorigenicity-related gene (PTG) scores. The predictive ability of the PTG score was validated using two independent cohorts. Finally, we combined PTG score, age, and pathological stage information to establish a robust nomogram for GC prognosis prediction.

Results

We found that PDTX tumorigenicity indicated a poor prognosis in patients with GC, even at the same pathological stage. Transcriptome profiling of PDTX-originating GC tissues and corresponding normal controls identified 383 differentially expressed genes, with enrichment of ECM-related genes. A robust prognosis prediction model using the PTG score showed robust performance in two validation cohorts. A high PTG score was associated with elevated M2 polarized macrophage and cancer-associated fibroblast infiltration. Finally, combining the PTG score with age and TNM stage resulted in a more effective prognostic model than age or TNM stage alone.

Conclusions

We found that ECM-related signatures may contribute to PDTX tumorigenesis and indicate a poor prognosis in GC. A feasible survival prediction model was built based on the PTG score, which was associated with immune cell infiltration. Together with patient ages and pathological TNM stages, PTG score could be a new approach for GC prognosis prediction.
Effectiveness and safety of outpatient rehabilitation versus home-based rehabilitation after knee arthroplasty: a systematic review and meta-analysis
Authors: Zhao BiXia , Liu Hui , Du Ke , Zhou Wei , Li Ying
Published: September 2023

Background

Rehabilitation post-knee arthroplasty is integral to regaining knee function and ensuring patients’ overall well-being. The debate over the relative effectiveness and safety of outpatient versus home-based rehabilitation persists.

Methods

A thorough literature review was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across four databases. Two researchers independently identified eligible studies centering on knee arthroplasty patients undergoing either outpatient or home-based rehabilitation. Study quality was assessed using the Cochrane Collaboration’s risk of bias tool, while continuous outcomes were subject to meta-analyses using Stata 17 software.

Results

Our analysis identified no significant differences in primary outcomes, including Range of Motion, Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Oxford Knee Score, and the Knee Society Score, between home-based and outpatient rehabilitation across different follow-up points. Adverse reactions, readmission rates, the need for manipulation under anesthesia, reoperation rate, and post-surgery complications were also similar between both groups. Home-based rehabilitation demonstrated cost-effectiveness, resulting in substantial annual savings. Furthermore, quality of life and patient satisfaction were found to be comparable in both rehabilitation methods.

Conclusions

Home-based rehabilitation post-knee arthroplasty appears as an effective, safe, and cost-efficient alternative to outpatient rehabilitation. Despite these findings, further multicenter, long-term randomized controlled trials are required to validate these findings and provide robust evidence to inform early rehabilitation choices post-knee arthroplasty.