bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of a ferroptosis-related signature for prediction of the prognosis and tumor microenvironment in patients with chromophobe renal cell carcinoma
Authors: Liu Shuai , Yao Yu , Hou Mingyu , Mei Jingchang , Sun Lijiang , Zhang Guiming
Published: November 2023

Background

Ferroptosis is a novel form of regulated cell death that is different from other forms, which has an important role in tumor growth inhibition. The purpose of this study was to construct and validate a prognostic signature related to ferroptosis in chromophobe renal cell carcinoma (ChRCC) and to explore its role in immune cell infiltration and systemic therapy.

Methods

The gene expression profiles of ChRCC patients obtained from The Cancer Genome Atlas (TCGA) database were used to identify differentially expressed prognostic ferroptosis-related genes (FRGs) by univariate Cox proportional hazards analyses. Ferroptosis molecular subtypes were obtained by consensus clustering analysis. The FRG-based signature in the training set was established by least absolute shrinkage and selection operator analysis and verified in the testing set. The association between molecular subtypes and the prognostic signature and immune microenvironment was explored to predict responses to immunotherapy. Immunohistochemistry was used to verify expression of the FRG-based signature externally.

Results

ChRCC patients were divided into two FRG subtypes. Two FRGs (TFRC and SLC7A11) were identified to construct the prognostic signature. The high-risk group and cluster 2 had worse overall survival than the low-risk group and cluster 1, respectively. The low-risk group and cluster 1 had higher levels of immune cell infiltration and expression of MHC and immune checkpoint molecules than the high-risk group and cluster 2. The risk score was a predictor of overall survival and had a good predictive ability, which was verified in the testing set and evaluated by ROC and calibration curves. The high-risk group had a higher tumor mutation burden. The different sensitivities of targeted drugs in patients with different risks were evaluated. External immunohistochemical analysis showed that TFRC and SLC7A11 were highly expressed in tumor tissues compared with para-cancer normal tissues, and the expression level was significantly associated with a more advanced stage and worse cancer-specific survival.

Conclusions

An FRG signature was identified and validated to predict the clinicopathological features and prognosis of ChRCC. A significant association between the signature and immune cell infiltration, immune checkpoint expression, and drug response is helpful to guide comprehensive treatment of ChRCC.
Self-esteem in new light: a qualitative study of experiences of internet-based cognitive behaviour therapy for low self-esteem in adolescents
Authors: Berg Matilda , Klemetz Helena , Lindegaard Tomas , Andersson Gerhard
Published: November 2023

Background

Low self-esteem is common and can be impairing for adolescents. Treatments that primarily target low-esteem are lacking. Internet-delivered cognitive behaviour therapy (ICBT) is a treatment that can be used for adolescents but ICBT is yet to be evaluated for low self-esteem using qualitative methods. The aim of this study was to investigate experiences of participating in a novel ICBT treatment for adolescents suffering from low self-esteem.

Method

Fifteen adolescent girls who had received ICBT consented to participate in a semi-structured qualitative telephone interview at post-treatment. Data were analysed and categorised using inductive Thematic Analysis.

Results

Four overarching themes were identified; (1) Increased awareness and agency in difficult situations, (2) Enhanced self-image, (3) Unique but not alone, and (4) Widened understanding and new perspectives. Participants reported positive changes in their thinking and behaviour, as well as helpful learning experiences in relation to themselves and their self-esteem. For instance, participants described a more self-accepting attitude, learned how to manage negative thoughts, and experienced an increased sense of connection to others.

Conclusion

The results suggest that ICBT is experienced as helpful and will inform further use and development of ICBT for low self-esteem. Future studies should validate and further evaluate experiences of ICBT for low self-esteem in other settings and in particular for boys as the study only include female participants.
Using sequential bone cutting to titrate soft tissue balance in total knee arthroplasty effectively minimizes soft tissue release
Authors: Chen Mingxue , Yang Dejin , Shao Hongyi , Rui Shouwei , Cao Yuefeng , Zhou Yixin
Published: November 2023

Background

Achieving soft tissue balance while maintaining limb alignment within acceptable boundaries is crucial for successful total knee arthroplasty (TKA). We proposed a sequential bone cutting (SBC) technique to titrate the soft tissue balance in robot-assisted TKA to achieve the desired balance with minimum soft tissue release.

Methods

In total, 106 robot-assisted TKAs using the SBC technique were included. The preoperative hip-knee-ankle angle (HKA) was < 10° in 76 and ≥ 10° in 30 knees. The gaps were initially balanced with the help of the pre-resection balancing provided by the robotic system. Soft tissue balance and alignment were quantitatively measured after the initial bone cutting and final bone cutting. Additional adjustments (bone recuts and soft tissue releases) required to address soft tissue imbalance after initial bone cutting were recorded. The frequencies of soft tissue releases, soft tissue balance, and resultant alignment ≤ 3° were compared between non-severe (HKA < 10°) and severe deformity (HKA ≥ 10°) groups.

Results

Soft tissue balance was achieved in 45 knees (42.5%) after initial bone cutting and in 93 knees (87.7%) after final balancing. The postoperative alignment was within 3° from neutral in 87 knees (82.1%) and 3–5° in 17 knees (16.0%). For unbalanced knees (n = 61) after initial bone cutting, soft tissue release was avoided by SBC in 37 knees (60.7%) and was deemed necessary in 24 knees (39.3%). Soft tissue release was more likely to be avoided in the non-severe deformity cohort (86.8% [33 of 38]) than in the severe deformity cohort (17.4% [4 of 23]; p < 0.001). The non-severe deformity cohort showed a significantly higher rate of resultant alignment ≤ 3° from neutral than the severe deformity cohort (90.8% vs. 60.0%; p < 0.001).

Conclusion

Pre-resection balancing is inappropriate to ensure soft tissue balance. The SBC technique is effective in minimizing soft tissue release while maintaining overall alignment within acceptable boundaries.
Comparison of endoscopic bilateral areolar and robotic-assisted bilateral axillo-breast approach thyroidectomy in differentiated thyroid carcinoma: a propensity-matched retrospective cohort study
Authors: Fu Xiaokang , Ma Yunhan , Hou Yiqi , Liu Yuan , Zheng Luming
Published: November 2023

Background

Robot-assisted and endoscopic thyroidectomy are superior to conventional open thyroidectomy in improving cosmetic outcomes and postoperative quality of life. The procedure of these thyroidectomies was similar in terms of surgical view, feasibility, and invasiveness. However, it remains uncertain whether the robotic-assisted bilateral axilla-breast approach (BABA) was superior to the endoscopic bilateral areolar approach (BAA) thyroidectomy. This study aimed to investigate the clinical benefit of these two surgical procedures to evaluate the difference between these two surgical procedures by comparing the pathological and surgical outcomes of endoscopic BAA and robotic-assisted BABA thyroidectomy in differentiated thyroid carcinoma.

Methods

From November 2018 to September 2021, 278 patients with differentiated thyroid carcinoma underwent BABA robot-assisted, and 49 underwent BAA approach endoscopic thyroidectomy. Of these patients, we analyzed 42 and 135 patients of endoscopic and robotic matched pairs using 1:4 propensity score matching and retrospective cohort study methods. These two groups were retrospectively compared by surgical outcomes, clinicopathological characteristics, and postoperative complications.

Results

The mean operation time was significantly longer in the EG than in the RG (p < 0.001), The number of retrieved lymph nodes was significantly lower in the ET group than in the RT group (p < 0.001). The mean maximum diameter of the thyroid was more expansive in the EG than in the RG (p = 0.04). There were no significant differences in the total drainage amount and drain insertion days between the two groups (p = 0.241, p = 0.316, respectively). Both groups showed that cosmetic satisfaction (p = 0.837) and pain score (p = 0.077) were similar. There were no significant differences in complication frequencies.

Conclusion

Robotic and endoscopic thyroidectomy are similar minimally invasive thyroid surgeries, each with its advantages, both of which can achieve the expected surgical outcomes.

Trial registration

Retrospectively registered.
Double J stent combined with pyelostomy tube in pediatric laparoscopic pyeloplasty: a 5-year clinical experience in a single center
Authors: Chen Zhiqiang , Wang Yunjin , Wu Changwei , Chen Hong , Cui Xu , Zhou Chaoming
Published: November 2023

Objective

To compare the outcome of using a double J (DJ) stent combined with pyelostomy tube with a DJ stent alone in laparoscopic pyeloplasty (LP) for pediatric ureteropelvic junction obstruction (UPJO).

Methods

A retrospective review of all patients with UPJO treated with LP between January 2017 and November 2021 was conducted in our center. According to different postoperative drainage methods patients were divided into a DJ stent group (52 cases) and a DJ stent combined with pyelostomy tube group (combination group, 41 cases). Operative time, bleeding volume, perirenal drainage stent removal time, postoperative hospital stay, postoperative complications, and renal function recovery were compared between the two groups. Renal ultrasound and diuretic renogram (DR) were used for preoperative and postoperative follow-up.

Results

A total of 52 patients were in the DJ stent group and 41 patients in the combination group. The mean hospital stay was 6.46 ± 2.66 days in the DJ stent group and 5.22 ± 1.63 days in the combination group (p < 0.05). Postoperative complications developed in 14 out of 52 patients in the DJ stent group (26.9%), while complications developed in 8 out of 41 patients in the combination group (19.5%) (p > 0.05). Non-catheter-related complications developed in 10/52 patients in the DJ stent group (19.2%) and only 1/41 patients in the combination group (2.4%) (p < 0.05). The renal function and renal cortex thickness in both groups were improved.

Conclusion

Both the DJ stent drainage and the DJ stent combined with pyelostomy drainage are safe and effective. We should fully consider the patient’s preoperative and intraoperative conditions and choose appropriate drainage methods. A DJ stent combined with pyelostomy tube can reduce non-catheter related complications, facilitate postoperative recovery, and the hospital stay was significantly shorter than the DJ stent group. However, it is necessary to pay attention to the nursing treatment of the pyelostomy tube and guard against the occurrence of pyelostomy tube shedding.
Neutrophil-to-lymphocyte ratio as a promising non-invasive biomarker for symptom assessment and diagnosis of interstitial cystitis/bladder pain syndrome
Authors: Ke Hanwei , Zhu Lin , Wang Qi , Xu Kexin
Published: November 2023

Background

Our study aims to investigate the association between the serum neutrophil-to-lymphocyte ratio (NLR) and interstitial cystitis (IC), as well as to explore whether NLR can serve as a diagnostic marker to distinguish IC from overactive bladder (OAB). We postulate that elevated NLR levels are intricately linked to the onset and clinical presentation of IC, and that the NLR profiles in OAB patients exhibit discernible disparities from those of IC patients.

Methods

In a retrospective analysis, we scrutinized the medical records of 70 women diagnosed with IC/BPS, 20 women diagnosed with OAB, and a randomly selected cohort of 150 healthy women who underwent physical examinations during the same temporal frame. A comprehensive panel of blood tests was administered to all participants, and NLR was determined through the calculation of the neutrophil-to-lymphocyte proportion. Additionally, symptom assessment questionnaires and urination diaries were collected from IC/BPS patients.

Results

NLR levels exhibited significant distinctions among the IC/BPS, Normal, and OAB groups (P < 0.001). Within the IC/BPS group, Hunner type interstitial cystitis (HIC) demonstrated notably divergent NLR levels in comparison to non-Hunner type interstitial cystitis (NHIC) (p = 0.001). Additionally, we observed positive correlations between NLR and Nighttime voids (r = 0.268, p = 0.029), ICPI (r = 0.327, p = 0.007), ICSI (r = 0.369, p = 0.002), PUF Symptom Scale (r = 0.263, p = 0.032), and PUF (r = 0.297, p = 0.015). The receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.765 for NLR in distinguishing IC/BPS from the Normal group, and an AUC of 0.707 in discerning IC from OAB. Furthermore, the AUC of NLR was 0.723 for identifying HIC and NHIC patients.

Conclusions

Our study unveils the prospective utility of serum NLR as a promising biomarker for both diagnostic and symptom evaluation purposes in IC/BPS patients. It effectively demarcates this condition from OAB, which presents with similar clinical features. Consequently, NLR demonstrates potential as a non-invasive diagnostic instrument to distinguish between the subtypes of IC, particularly HIC and NHIC, which manifest similar symptoms within the IC/BPS spectrum.
Comparative diagnostic accuracy of the IOTA SRR and LR2 scoring systems for discriminating between malignant and Benign Adnexal masses by junior physicians in Chinese patients: a retrospective observational study
Authors: Tian Cai , Wen Shu-Bin , Zhao Cong-Ying , Yan Xiao-Nan , Du Jie-Xian
Published: November 2023

Background

The accuracy of ultrasound in distinguishing benign from malignant adnexal masses is highly correlated with the experience of ultrasound physicians. In China, most of ultrasound differentiation is done by junior physicians.

Purpose

To compare the diagnostic performance of the International Ovarian Tumour Analysis (IOTA) Simple Rules Risk (SRR) and IOTA Logistic Regression Model 2 (LR2) scoring systems in Chinese patients with adnexal masses.

Methods

Retrospective analysis of ovarian cancer tumor patients who underwent surgery at a hospital in China from January 2016 to December 2021. Screening patients with at least one adnexal mass on inclusion and exclusion criteria. Two trained junior physicians evaluated each mass using the two scoring systems. A receiver operating characteristic curve was used to test the diagnostic performance of each system.

Results

A total of 144 adnexal masses were retrospectively collected. Forty masses were histologically diagnosed as malignant. Compared with premenopausal women, postmenopausal women had a much higher rate of malignant masses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of the SRR was 97.5% (95% CI: 86.8 -99.9%), 82.7% (95% CI: 74.0 -89.4%), 68.4% (95% CI: 58.7 -76.8%) and 98.9% (95% CI: 92.5 -99.8%). The sensitivity, specificity, PPV, NPV of the LR2 were 90.0% (95% CI: 76.5 -97.2%), 89.4% (95% CI: 81.9 -94.6%), 76.6% (95% CI: 65.0 -85.2%), and 95.9% (95% CI: 90.2 -98.3%). There was good agreement between two scoring systems, with 84.03% total agreement and a kappa value of 0.783 (95% CI: 0.70-0.864). The areas under the curve for predicting malignant tumours using SRR and LR2 were similar for all patients (P > 0.05 ).

Conclusion

The two scoring systems can effectively distinguish benign from malignant adnexal masses. Both scoring systems have high diagnostic efficacy, and diagnostic efficacy is stable, which can provide an important reference for clinical decision making.
Factors affecting quality of life in women with breast cancer: a path analysis
Authors: Faroughi Farnaz , Fathnezhad-Kazemi Azita , Sarbakhsh Parvin
Published: November 2023

Background

Breast cancer may negatively affect people’s quality of life. We investigated the predictors of quality of life in women with breast cancer with the mediating role of resilience.

Method

In a cross-sectional design, 218 patients completed a survey referring to the Valiasr International Hospital Oncology Center in Tabriz, Iran. Four validated self-report measures assessed HRQoL as measured by the SF-12, Resilience, Hope, and Perceived Social Support (MSPs). The mediating roles of resilience between HRQoL and the fitness of the proposed model were investigated using path analysis. SPSS version 24 software and Lisrel 8.8 software were used for data analysis.

Results

The results of path analysis showed that the final model had a good fit to the data (Chi-Square/ degrees of freedom (Normed Chi2) = 2.08, RMSEA = 0.014, goodness fit index = 0.99, both comparative fit index = 0.99 both CFI = 0.99 and IFI = 1). In this model, age and psychosocial factors predicted health-related quality of life.

Conclusions

Age and psychosocial factors especially social support are important components in predicting health-related quality of life among those suffering from breast cancer.
Practice of defensive medicine among surgeons in Ethiopia: cross-sectional study
Authors: Assefa Eskinder Amare , Teferi Yonas Ademe , Alemu Birhanu Nega , Genetu Abraham
Published: November 2023

Background

Defensive medicine is physicians’ deviation from standard medical care which is primarily intended either to reduce or avoid medico legal litigation. Although the Federal Ethics Committee review in Ethiopia has shown that applications for medical/surgical error investigation claims are increasing at an alarming rate, there is no study to date done to estimate the degree of defensive practice done by the physicians with an intention of avoiding this increasing legal claim. This study assessed the practice of defensive medicine among highly litigious disciplines (surgery) and described factors associated with its practice.

Methods

Cross sectional quantitative study using online survey questionnaires was conducted to assess the degree of defensive practice and six factors (age, years of experience, specialty, monthly income, place of practice and previous medico legal history) associated with its practice were assessed among surgeons working in Ethiopia.

Results

A total of 430 surgeons directly received an online survey questionnaire and 236 of them successfully completed the questionnaire making the response rate 51.2%. Nearly half of the study participants (51.7%) were aware of the concept of defensive medicine and 174 (74%) reported performing one form of defensive practice. Twenty-nine (12.3%) of the participants have legal dispute history, though only 1.3% of them ended up in penalty. Avoiding high risk procedures was the commonest defensive act performed by 60% of the participants, followed by ordering tests unnecessarily (52.1%). Multinomial logistic regression model showed that there was no association between age of the participant, place of practice, year of experience and defensive practice. This model also showed that cardiothoracic and vascular surgeons perform less defensively than surgeons with other specialty with P value of 0.02.

Conclusion

The practice of defensive medicine is widespread among surveyed Ethiopian surgeons and further studies are required to objectively estimate the effect of defensive practice on the health care system of the country. Policy makers need to develop strategy towards decreasing this high rate of defensive practice.
Polygenic risk for triglyceride levels in the presence of a high impact rare variant
Authors: Ying Shengjie , Heung Tracy , Thiruvahindrapuram Bhooma , Engchuan Worrawat , Yin Yue , Blagojevic Christina , Zhang Zhaolei , Hegele Robert A. , Yuen Ryan K. C. , Bassett Anne S.
Published: November 2023

Background

Elevated triglyceride (TG) levels are a heritable and modifiable risk factor for cardiovascular disease and have well-established associations with common genetic variation captured in a polygenic risk score (PRS). In young adulthood, the 22q11.2 microdeletion conveys a 2-fold increased risk for mild-moderate hypertriglyceridemia. This study aimed to assess the role of the TG-PRS in individuals with this elevated baseline risk for mild-moderate hypertriglyceridemia.

Methods

We studied a deeply phenotyped cohort of adults (n = 157, median age 34 years) with a 22q11.2 microdeletion and available genome sequencing, lipid level, and other clinical data. The association between a previously developed TG-PRS and TG levels was assessed using a multivariable regression model adjusting for effects of sex, BMI, and other covariates. We also constructed receiver operating characteristic (ROC) curves using logistic regression models to assess the ability of TG-PRS and significant clinical variables to predict mild-moderate hypertriglyceridemia status.

Results

The TG-PRS was a significant predictor of TG-levels (p = 1.52E-04), along with male sex and BMI, in a multivariable model (pmodel = 7.26E-05). The effect of TG-PRS appeared to be slightly stronger in individuals with obesity (BMI ≥ 30) (beta = 0.4617) than without (beta = 0.1778), in a model unadjusted for other covariates (p-interaction = 0.045). Among ROC curves constructed, the inclusion of TG-PRS, sex, and BMI as predictor variables produced the greatest area under the curve (0.749) for classifying those with mild-moderate hypertriglyceridemia, achieving an optimal sensitivity and specificity of 0.746 and 0.707, respectively.

Conclusions

These results demonstrate that in addition to significant effects of sex and BMI, genome-wide common variation captured in a PRS also contributes to the variable expression of the 22q11.2 microdeletion with respect to elevated TG levels.
Association between the triglyceride-glucose index and 1-year major adverse cardiovascular events in patients with coronary heart disease and hypertension
Authors: Tao Shiyi , Yu Lintong , Li Jun , Huang Li , Huang Xuanchun , Zhang Wenjie , Xie Zicong , Tan Yuqing , Yang Deshuang
Published: November 2023

Background

The triglyceride-glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of coronary heart disease (CHD). However, its prognostic value in patients with CHD and hypertension remains unclear. This study aimed to evaluate the association between the TyG index and the 1-year risk of major adverse cardiovascular events (MACEs) in patients with CHD and hypertension.

Methods

The data for the study were taken from the Hospital Information System database in China-Japan Friendship Hospital which contained over 10,000 cardiovascular admissions from 2019 to 2022. The Boruta algorithm was performed for feature selection. The study used univariable analysis, multivariable logistic regression analysis, and restricted cubic spline (RCS) regression to evaluate the association between the TyG index and the 1-year risk of MACEs in patients with CHD and hypertension.

Results

After applying inclusion and exclusion criteria, a total of 810 patients with CHD and hypertension were included in the study with a median TyG index of 8.85 (8.48, 9.18). Using the lowest TyG index quartile as the reference, the fully adjusted ORs (95% CIs) for 1-year MACEs for TyG index Q2, Q3, and Q4 were 1.001 (0.986 ~ 1.016), 1.047 (1.032 ~ 1.062), and 1.760 (1.268 ~ 2.444), respectively. After adjusting for all confounders, we found that those with the highest TyG index had a 47.0% increased risk of MACEs over the 1-year follow-up (OR 1.470, 95% CI 1.071 ~ 2.018). The results in the subgroup analysis were similar to the main analyses. RCS model suggested that the TyG index was nonlinearly associated with the 1-year risk of MACEs (P for nonlinear < 0.001).

Conclusion

This study shows that the elevated TyG index is a potential marker of adverse prognosis among patients with CHD and hypertension and informs the development of clinical decisions to improve outcomes.
Ensuring Indigenous co-leadership in health research: a Can-SOLVE CKD case example
Authors: Woods Cathy , Settee Craig , Beaucage Mary , Robinson-Settee Helen , Desjarlais Arlene , Adams Evan , Turner Catherine , King Malcolm , Pokiak Letitia , Wilson Mary , Voyageur Evelyn , Large Chantel , McGavock Jonathan , Kappel Joanne , Chiu Helen , Beardy Tamara , Flett Isabelle , Scholey James , Harris Heather , Jones Jocelyn , Nahanee Latash Maurice , Nahanee Delhia ,   on behalf of the Can-SOLVE CKD Indigenous Peoples’ Engagement, Research Council (IPERC), Beaucage Mary , Desjarlais Arlene , Woods Cathy , Fontaine George , King Malcolm , Voyageur Evelyn , McGavock Jonathan , Beardy Tamara , Saucier Donna , Flett Isabelle , Ross Darrell , Cook Tannyce , Pokiak Letitia , Nahanee Latash Maurice , Nahanee Delhia , Kappel Joanne , Dart Allison
Published: November 2023

Background

Indigenous people are insightful and informed about their own health and wellness, yet their visions, strengths and knowledge are rarely incorporated into health research. This can lead to subpar engagement or irrelevant research practices, which exacerbates the existing health inequities Indigenous people experience compared to the non-Indigenous population. Data consistently underscores the importance of Indigenous self-determination in research as a means to address health inequities. However, there are few formal methods to support this goal within the existing research context, which is dominated by Western perspectives.

Main text

Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is a patient-oriented research network in Canada that recognizes the need to create the space to facilitate Indigenous self-determination in research. Indigenous members of the network therefore created and evolved a unique group, called the Indigenous Peoples' Engagement and Research Council (IPERC). IPERC plays a critical role in informing Can-SOLVE CKD research priorities, as well as creating tools to support Indigenous-specific research and engagement. This approach ensures that Indigenous voices and knowledge are critical threads within the fabric of the network’s operations and research projects. Here, we describe the methods taken to create a council such as IPERC, and provide examples of initiatives by the council that aim to increase Indigenous representation, participation and partnership in research. We share lessons learned on what factors contribute to the success of IPERC, which could be valuable for other organizations interested in creating Indigenous-led research councils.

Conclusion

Indigenous self-determination in research is critical for addressing health inequities. Here, we present a unique model, led by a council of diverse Indigenous people, which could help reduce health equities and lead to a better era of research for everyone.
Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells
Authors: Wang Muhong , Deng Chunyu , Yang Cheng , Yan Mingze , Lu Haibo , Zhang Yan , Liu Honghao , Tong Zhekuan , Ma Jiaao , Wang Jiaming , Zhang Yan , Wang Jiahao , Xuan Yuhong , Cheng Haiyue , Zhao Kai , Zhang Jiaqi , Chai Cuicui , Li Mingzhe , Yu Zhiwei
Published: November 2023

The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.

Graphical Abstract
Re-defining wearable robots: a multidisciplinary approach towards a unified terminology
Authors: Massardi Stefano , Briem Kristín , Veneman Jan F. , Torricelli Diego , Moreno Juan C.
Published: November 2023

Effective communication is especially important in the wearable robots (WRs) community, which encloses a great variety of devices across different application domains, e.g., healthcare, occupational, and consumer. In this paper we present a vocabulary of terms with the aim to create a common understanding of terms and concepts among the different fields of expertise relevant in the WRs community. Our goal is to develop shared documentation that could serve as a reference to facilitate the use of accepted definitions in the field. The presented vocabulary is the result of different focus group discussions among experts in the field. The resulting document was then validated by presenting it to the WR community through an online survey. The results of the survey highlight a strong agreement in terms of acceptance of the vocabulary, its usefulness, and applicability of the proposed definitions as well as an overall appreciation for its purpose and target. This work represents a pilot study providing unique material for the WR community, encouraging the use of shared agreed definitions. The reported version of the vocabulary has been made available as a live document in a github repository, for public commenting and further improvements.
Testing spasticity mechanisms in chronic stroke before and after intervention with contralesional motor cortex 1 Hz rTMS and physiotherapy
Authors: Mahmoud Wala , Hultborn Hans , Zuluaga Jagoba , Zrenner Christoph , Zrenner Brigitte , Ziemann Ulf , Ramos-Murguialday Ander
Published: November 2023

Background

Previous studies showed that repetitive transcranial magnetic stimulation (rTMS) reduces spasticity after stroke. However, clinical assessments like the modified Ashworth scale, cannot discriminate stretch reflex-mediated stiffness (spasticity) from passive stiffness components of resistance to muscle stretch. The mechanisms through which rTMS might influence spasticity are also not understood.

Methods

We measured the effects of contralesional motor cortex 1 Hz rTMS (1200 pulses + 50 min physiotherapy: 3×/week, for 4–6 weeks) on spasticity of the wrist flexor muscles in 54 chronic stroke patients using a hand-held dynamometer for objective quantification of the stretch reflex response. In addition, we measured the excitability of three spinal mechanisms thought to be related to post-stroke spasticity: post-activation depression, presynaptic inhibition and reciprocal inhibition before and after the intervention. Effects on motor impairment and function were also assessed using standardized stroke-specific clinical scales.

Results

The stretch reflex-mediated torque in the wrist flexors was significantly reduced after the intervention, while no change was detected in the passive stiffness. Additionally, there was a significant improvement in the clinical tests of motor impairment and function. There were no significant changes in the excitability of any of the measured spinal mechanisms.

Conclusions

We demonstrated that contralesional motor cortex 1 Hz rTMS and physiotherapy can reduce the stretch reflex-mediated component of resistance to muscle stretch without affecting passive stiffness in chronic stroke. The specific physiological mechanisms driving this spasticity reduction remain unresolved, as no changes were observed in the excitability of the investigated spinal mechanisms.
Implementation and dissemination of home- and community-based interventions for informal caregivers of people living with dementia: a systematic scoping review
Authors: Zhu Eden Meng , Buljac-Samardžić Martina , Ahaus Kees , Sevdalis Nick , Huijsman Robbert
Published: November 2023

Background

Informal caregivers of people with dementia (PwD) living at home are often the primary source of care, and, in their role, they often experience loss of quality of life. Implementation science knowledge is needed to optimize the real-world outcomes of evidence-based interventions (EBIs) for informal caregivers. This scoping review aims to systematically synthesize the literature that reports implementation strategies employed to deliver home- and community-based EBIs for informal caregivers of PwD, implementation outcomes, and the barriers and facilitators to implementation of these EBIs.

Methods

Embase, MEDLINE, Web of Science, and Cochrane Library were searched from inception to March 2021; included studies focused on “implementation science,” “home- and community-based interventions,” and “informal caregivers of people with dementia.” Titles and abstracts were screened using ASReview (an innovative AI-based tool for evidence reviews), and data extraction was guided by the ERIC taxonomy, the Implementation Outcome Framework, and the Consolidated Framework for Implementation Science Research; each framework was used to examine a unique element of implementation.

Results

Sixty-seven studies were included in the review. Multicomponent (26.9%) and eHealth (22.3%) interventions were most commonly reported, and 31.3% of included studies were guided by an implementation science framework. Training and education-related strategies and provision of interactive assistance were the implementation strategy clusters of the ERIC taxonomy where most implementation strategies were reported across the reviewed studies. Acceptability (82.1%), penetration (77.6%), and appropriateness (73.1%) were the most frequently reported implementation outcomes. Design quality and packaging (intervention component suitability) and cosmopolitanism (partnerships) constructs, and patient’s needs and resources and available resources (infrastructure) constructs as per the CFIR framework, reflected the most frequently reported barriers and facilitators to implementation.

Conclusion

Included studies focused largely on intervention outcomes rather than implementation outcomes and lacked detailed insights on inner and outer setting determinants of implementation success or failure. Recent publications suggest implementation science in dementia research is developing but remains in nascent stages, requiring future studies to apply implementation science knowledge to obtain more contextually relevant findings and to structurally examine the mechanisms through which implementation partners can strategically leverage existing resources and regional networks to streamline local implementation. Mapping local evidence ecosystems will facilitate structured implementation planning and support implementation-focused theory building.

Trial Registration

Not applicable.
Iatrogenic aortic dissection during aortic root replacement in an older Loeys–Dietz syndrome type III patient with no family history of aortic disease: a case report
Authors: Kato Kenichi , Nakamura Ken , Kato Kaho , Arai Shusuke , Hirooka Shuto , Kim Cholsu , Uchino Hideaki , Shimanuki Takao
Published: November 2023

Background

Iatrogenic aortic dissection during cardiac surgery is a rare but critical complication. At present, no strategies have been developed to prevent it. We herein report a case of intraoperative aortic dissection during aortic root replacement in an older patient with Loeys–Dietz syndrome type III who had no family history of aortic disease.

Case presentation

A 60-year-old man was admitted to the hospital for Stanford type B acute aortic dissection and given conservative treatment. He was found to have aortic root dilatation and severe aortic regurgitation. Thus, elective Bentall procedure was performed. Postoperative computed tomography showed new Stanford type A aortic dissection that may have developed due to aortic cannulation during surgery. The patient was given conservative treatment and successfully discharged to home at postoperative day 34. Although he had no family history of aortic disease, a genetic test revealed an unreported SMAD3 frameshift mutation (c.742_749dup, p. Gln252ThrfsTer7), and the patient was diagnosed with Loeys–Dietz syndrome type III.

Conclusion

In patients with connective tissue disorder, aortic manipulations may become the cause of critical complications. Avoiding the use of invasive techniques, such as cannulation and cross-clamping, and implementing treatment strategies, such as perfusion from other sites than the aorta and open distal anastomosis, can prevent these complications, and may be useful treatment modalities. The possibility of connective tissue disease should be considered even if the patient is older and has no family history of aortic disease.
Network pharmacology: a bright guiding light on the way to explore the personalized precise medication of traditional Chinese medicine
Authors: Li Ling , Yang Lele , Yang Liuqing , He Chunrong , He Yuxin , Chen Liping , Dong Qin , Zhang Huaiying , Chen Shiyun , Li Peng
Published: November 2023

Network pharmacology can ascertain the therapeutic mechanism of drugs for treating diseases at the level of biological targets and pathways. The effective mechanism study of traditional Chinese medicine (TCM) characterized by multi-component, multi-targeted, and integrative efficacy, perfectly corresponds to the application of network pharmacology. Currently, network pharmacology has been widely utilized to clarify the mechanism of the physiological activity of TCM. In this review, we comprehensively summarize the application of network pharmacology in TCM to reveal its potential of verifying the phenotype and underlying causes of diseases, realizing the personalized and accurate application of TCM. We searched the literature using “TCM network pharmacology” and “network pharmacology” as keywords from Web of Science, PubMed, Google Scholar, as well as Chinese National Knowledge Infrastructure in the last decade. The origins, development, and application of network pharmacology are closely correlated with the study of TCM which has been applied in China for thousands of years. Network pharmacology and TCM have the same core idea and promote each other. A well-defined research strategy for network pharmacology has been utilized in several aspects of TCM research, including the elucidation of the biological basis of diseases and syndromes, the prediction of TCM targets, the screening of TCM active compounds, and the decipherment of mechanisms of TCM in treating diseases. However, several factors limit its application, such as the selection of databases and algorithms, the unstable quality of the research results, and the lack of standardization. This review aims to provide references and ideas for the research of TCM and to encourage the personalized and precise use of Chinese medicine.
Association of naturally acquired type-specific HPV antibodies and subsequent HPV re-detection: systematic review and meta-analysis
Authors: Yokoji Kana , Giguère Katia , Malagón Talía , Rönn Minttu M. , Mayaud Philippe , Kelly Helen , Delany-Moretlwe Sinead , Drolet Mélanie , Brisson Marc , Boily Marie-Claude , Maheu-Giroux Mathieu
Published: November 2023

Background

Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status.

Methods

We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status.

Results

We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61–0.80, NE = 11) and persistent HPV positivity (0.65, 95% CI 0.42–1.01, NE = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose–response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available.

Conclusion

We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.
‘I am tired, sad and kind’: self-evaluation and symptoms of depression in adolescents
Authors: Hards Emily , Orchard Faith , Reynolds Shirley
Published: November 2023

Introduction

Although self-evaluation i.e., negative perceptions of the self is a common depression symptom in adolescents, little is known about how this population spontaneously describe their self and available data on adolescent self-evaluation is limited. This study aimed to generate and report on a list of words used by healthy adolescents and those with elevated depression symptoms to describe their self-evaluation. Linguistic analysis (LIWC) was then used to compare self-evaluation between the two groups.

Methods

Adolescents aged 13–18 years (n = 549) completed a measure of depression symptoms (the Mood and Feelings Questionnaire) and a measure of self-evaluation (the Twenty Statements Test). Responses were then collated and presented in a freely accessible resource and coded using Linguistic Inquiry Word Count (LIWC) analysis.

Results

Self-evaluation words generated by adolescents were uploaded to a publicly accessible site for future research: https://doi.org/10.15125/BATH-01234. Adolescents with elevated depression symptoms described themselves as ‘Tired’ and ‘Sad’ more than healthy adolescents. However, there was no difference between groups in respect to their use of specific positive, prosocial self-evaluation ‘words’ (i.e., ‘Caring’ and ‘Kind). Following Linguistic Inquiry Word Count (LIWC) analysis, adolescents with elevated depression symptoms generated significantly more words than healthy adolescents, generated more words classified as negative emotion, anxiety and sadness and generated fewer words classified positive emotion than healthy adolescents.

Conclusions

As predicted by the cognitive model of depression, our findings suggest that adolescents with elevated symptoms of depression generated more negative self-evaluation words than healthy adolescents; however they also generated prosocial positive self-evaluation words at the same rate as non-depressed adolescents. These novel data therefore identify an ‘island’ of resilience that could be targeted and amplified by psychological treatments for adolescent depression, and thus provide an additional technique of change.
Cytogenomic features of Richter transformation
Authors: Woroniecka Renata , Rymkiewicz Grzegorz , Bystydzienski Zbigniew , Pienkowska-Grela Barbara , Rygier Jolanta , Malawska Natalia , Wojtkowska Katarzyna , Goral Nikolina , Blachnio Katarzyna , Chmielewski Marcin , Bartnik-Glaska Magdalena , Grygalewicz Beata
Published: November 2023

Background

Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (TP53) and proliferation (CDKN2A, MYC, NOTCH1) has been described as typical aberrations in RT.

Results

A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40–60% of cases) were represented by MYC rearrangement/gain, deletions of TP53 and CDKN2A, IGH rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant.

Conclusions

Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.