bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlated physical and mental health composite scores for the RAND-36 and RAND-12 health surveys: can we keep them simple?
Authors: Andersen John Roger , Breivik Kyrre , Engelund Inger Elise , Iversen Marjolein M. , Kirkeleit Jorunn , Norekvål Tone Merete , Oterhals Kjersti , Storesund Anette 
Published: June 2022

Abstract
Background
The RAND-36 and RAND-12 (equivalent to versions 1 of the SF-36 Health Survey and SF-12 Health Survey, respectively) are widely used measures of health-related quality of life. However, there are diverging views regarding how to create the physical health and mental health composite scores of these questionnaires. We present a simple approach using an unweighted linear combination of subscale scores for constructing composite scores for physical and mental health that assumes these scores should be free to correlate. The aim of this study was to investigate the criterion validity and convergent validity of these scores.

Methods
We investigated oblique and unweighted RAND-36/12 composite scores from a random sample of the general Norwegian population (N = 2107). Criterion validity was tested by examining the correlation between unweighted composite scores and weighted scores derived from oblique principal component analysis. Convergent validity was examined by analysing the associations between the different composite scores, age, gender, body mass index, physical activity, rheumatic disease, and depression.

Results
The correlations between the composite scores derived by the two methods were substantial (r = 0.97 to 0.99) for both the RAND-36 and RAND-12. The effect sizes of the associations between the oblique versus the unweighted composite scores and other variables had comparable magnitudes.

Conclusion
The unweighted RAND-36 and RAND-12 composite scores demonstrated satisfactory criterion validity and convergent validity. This suggests that if the physical and mental composite scores are free to be correlated, the calculation of these composite scores can be kept simple.
Platelets involved tumor cell EMT during circulation: communications and interventions
Authors: Wang Xiaoying , Zhao Songyan , Wang Zhaoxia , Gao Tao 
Published: June 2022

AbstractDistant spreading of metastatic tumor cells is still the leading cause of tumor death. Metastatic spreading is a complex process, in which epithelial-mesenchymal transition (EMT) is the primary and key event to promote it. Presently, extensive reviews have given insights on the occurrence of EMT at the primary tumor site that depends on invasive properties of tumor cells and the tumor-associated microenvironment. However, essential roles of circulation environment involved in tumor cell EMT is not well summarized. As a main constituent of the blood, platelet is increasingly found to work as an important activator to induce EMT. Therefore, this review aims to emphasize the novel role of platelet in EMT through signal communications between platelets and circulation tumor cells, and illustrate potent interventions aiming at their communications. It may give a complementary view of EMT in addition to the tissue microenvironment, help for better understand the hematogenous metastasis, and also illustrate theoretical and practical basis for the targeted inhibition.
Enhanced immune activation within the tumor microenvironment and circulation of female high-risk melanoma patients and improved survival with adjuvant CTLA4 blockade compared to males
Authors: Saad Mariam , Lee Sandra J. , Tan Aik Choon , El Naqa Issam M. , Hodi F. Stephen , Butterfield Lisa H. , LaFramboise William A. , Storkus Walter , Karunamurthy Arivarasan D. , Conejo-Garcia Jose , Hwu Patrick , Streicher Howard , Sondak Vernon K. , Kirkwood John M. , Tarhini Ahmad A. 
Published: June 2022

Abstract
Background
We hypothesized that a gender difference in clinical response may exist to adjuvant CTLA4 blockade with ipilimumab versus high-dose IFNα (HDI). We investigated differences in candidate immune biomarkers in the circulation and tumor microenvironment (TME).

Patients and methods
This gender-based analysis was nested within the E1609 trial that tested adjuvant therapy with ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus HDI in high risk resected melanoma. We investigated gender differences in treatment efficacy with ipi3 and ipi10 versus HDI while adjusting for age, stage, ECOG performance (PS), ulceration, primary tumor status and lymph node number. Forest plots were created to compare overall survival (OS) and relapse free survival (RFS) between ipi and HDI. Gene expression profiling (GEP) was performed on tumors of 718 (454 male, 264 female) patients. Similarly, serum and peripheral blood mononuclear cells (PBMC) samples were tested for soluble and cellular biomarkers (N = 321 patients; 109 female and 212 male).

Results
The subgroups of female, stage IIIC, PS = 1, ulcerated primary, in-transit metastasis demonstrated significant improvement in RFS and/or OS with ipi3 versus HDI. Female gender was significant for both OS and RFS and was further explored. In the RFS comparison, a multivariate Cox regression model including significant variables indicated a significant interaction between gender and treatment (P = 0.024). In peripheral blood, percentages of CD3+ T cells (P = 0.024) and CD3+ CD4+ helper T cells (P = 0.0001) were higher in females compared to males. Trends toward higher circulating levels of IL1β (P = 0.07) and IL6 (P = 0.06) were also found in females. Males had higher percentages of monocytes (P = 0.03) with trends toward higher percentages of regulatory T cells (T-reg). Tumor GEP analysis supported enhanced infiltration with immune cells including gammadelta T cells (P = 0.005), NK cells (P = 0.01), dendritic cells (P = 0.01), CD4+ T cells (P = 0.03), CD8+ T cells (P = 0.03) and T-reg (P = 0.008) in the tumors of females compared to males and a higher T-effector and IFNγ gene signature score (P = 0.0244).

Conclusion
Female gender was associated with adjuvant CTLA4 blockade clinical benefits and female patients were more likely to have evidence of type1 immune activation within the TME and the circulation.
Trial registration ClinicalTrials.gov NCT01274338. Registered 11 January 2011, https://www.clinicaltrials.gov/ct2/show/NCT01274338
A gene prognostic index from cellular senescence predicting metastasis and radioresistance for prostate cancer
Authors: Feng Dechao , Li Dengxiong , Shi Xu , Xiong Qiao , Zhang Facai , Wei Qiang , Yang Lu 
Published: June 2022

Abstract
Background
Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa.

Methods
We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages.

Results
We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50–23.93, p < 0.001), consistent with the results in the TCGA database (HR: 1.60, 95% CI 1.03–2.47, p = 0.038). Furthermore, CSGPI had high diagnostic accuracy distinguishing radioresistance from no radioresistance (AUC: 0.938, 95% CI 0.834–1.000). GSEA showed that high-risk patients were highly associated with apoptosis, cell cycle, ribosome, base excision repair, aminoacyl-tRNA biosynthesis, and mismatch repair. For immune checkpoint analysis, we found that PDCD1LG2 and CD226 were expressed at significantly higher levels in patients with metastasis than in those without metastasis. In addition, higher expression of CD226 significantly increased the risk of metastasis (HR: 3.65, 95% CI 1.58–8.42, p = 0.006). We observed that AZD7762, PHA-793887, PI-103, and SNX-2112 might be sensitive to ALDH2 and ALCAM, and PC3 could be the potential cell line used to investigate the interaction among ALDH2, ALCAM, and the above drugs.

Conclusions
We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.
Muscle contributions to pre-swing biomechanical tasks influence swing leg mechanics in individuals post-stroke during walking
Authors: Brough Lydia G. , Kautz Steven A. , Neptune Richard R. 
Published: June 2022

Abstract
Background
Successful walking requires the execution of the pre-swing biomechanical tasks of body propulsion and leg swing initiation, which are often impaired post-stroke. While excess rectus femoris activity during swing is often associated with low knee flexion, previous work has suggested that deficits in propulsion and leg swing initiation may also contribute. The purpose of this study was to determine underlying causes of propulsion, leg swing initiation and knee flexion deficits in pre-swing and their link to stiff knee gait in individuals post-stroke.

Methods
Musculoskeletal models and forward dynamic simulations were developed for individuals post-stroke (n = 15) and healthy participants (n = 5). Linear regressions were used to evaluate the relationships between peak knee flexion, braking and propulsion symmetry, and individual muscle contributions to braking, propulsion, knee flexion in pre-swing, and leg swing initiation.

Results
Four out of fifteen of individuals post-stroke had higher plantarflexor contributions to propulsion and seven out of fifteen had higher vasti contributions to braking on their paretic leg relative to their nonparetic leg. Higher gastrocnemius contributions to propulsion predicted paretic propulsion symmetry (p = 0.005) while soleus contributions did not. Higher vasti contributions to braking in pre-swing predicted lower knee flexion (p = 0.022). The rectus femoris had minimal contributions to lower knee flexion acceleration in pre-swing compared to contributions from the vasti. However, for some individuals with low knee flexion, during pre-swing the rectus femoris absorbed more power and the iliopsoas contributed less power to the paretic leg. Total musculotendon work done on the paretic leg in pre-swing did not predict knee flexion during swing.

Conclusions
These results emphasize the multiple causes of propulsion asymmetry in individuals post-stroke, including low plantarflexor contributions to propulsion, increased vasti contributions to braking and reliance on compensatory mechanisms. The results also show that the rectus femoris is not a major contributor to knee flexion in pre-swing, but absorbs more power from the paretic leg in pre-swing in some individuals with stiff knee gait. These results highlight the need to identify individual causes of propulsion and knee flexion deficits to design more effective rehabilitation strategies.
Soft robotic exosuit augmented high intensity gait training on stroke survivors: a pilot study
Authors: Shin Sung Yul , Hohl Kristen , Giffhorn Matt , Awad Louis N. , Walsh Conor J. , Jayaraman Arun 
Published: June 2022

Abstract
Background
Stroke is a leading cause of serious gait impairments and restoring walking ability is a major goal of physical therapy interventions. Soft robotic exosuits are portable, lightweight, and unobtrusive assistive devices designed to improve the mobility of post-stroke individuals through facilitation of more natural paretic limb function during walking training. However, it is unknown whether long-term gait training using soft robotic exosuits will clinically impact gait function and quality of movement post-stroke.

Objective
The objective of this pilot study was to examine the therapeutic effects of soft robotic exosuit-augmented gait training on clinical and biomechanical gait outcomes in chronic post-stroke individuals.

Methods
Five post-stroke individuals received high intensity gait training augmented with a soft robotic exosuit, delivered in 18 sessions over 6–8 weeks. Performance based clinical outcomes and biomechanical gait quality parameters were measured at baseline, midpoint, and completion.

Results
Clinically meaningful improvements were observed in walking speed ($$p$$
p
< 0.05) and endurance ($$p$$
p
< 0.01) together with other traditional gait related outcomes. The gait quality measures including hip ($$p$$
p
< 0.01) and knee ($$p$$
p
< 0.05) flexion/extension exhibited an increase in range of motion in a symmetric manner ($$p$$
p
< 0.05). We also observed an increase in bilateral ankle angular velocities ($$p$$
p
< 0.05), suggesting biomechanical improvements in walking function.

Conclusions
The results in this study offer preliminary evidence that a soft robotic exosuit can be a useful tool to augment high intensity gait training in a clinical setting. This study justifies more expanded research on soft exosuit technology with a larger post-stroke population for more reliable generalization.
Trial registration This study is registered with ClinicalTrials.gov (ID: NCT04251091)
Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses
Authors: Choublier Nina , Taghi Meryam , Menet Marie-Claude , Le Gall Morgane , Bruce Johanna , Chafey Philippe , Guillonneau François , Moreau Amélie , Denizot Claire , Parmentier Yannick , Nakib Samir , Borderie Didier , Bouzinba-Segard Haniaa , Couraud Pierre-Olivier , Bourdoulous Sandrine , Declèves Xavier 
Published: June 2022

AbstractEndothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral ECs, less is known about the molecular responses of microvascular brain ECs which constitute the blood–brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm−2 SS for 3 days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong protective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins and did not afect either the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain ECs to SS and on the importance of SS for optimizing in vitro BBB models.
WeCoNET: a host–pathogen interactome database for deciphering crucial molecular networks of wheat-common bunt cross-talk mechanisms
Authors: Kataria Raghav , Kaundal Rakesh 
Published: June 2022

Abstract
Background
Triticum aestivum is the most important staple food grain of the world. In recent years, the outbreak of a major seed-borne disease, common bunt, in wheat resulted in reduced quality and quantity of the crop. The disease is caused by two fungal pathogens, Tilletia caries and Tilletia laevis, which show high similarity to each other in terms of life cycle, germination, and disease symptoms. The host–pathogen protein–protein interactions play a crucial role in initiating the disease infection mechanism as well as in plant defense responses. Due to the availability of limited information on Tilletia species, the elucidation of infection mechanisms is hampered.

Results
We constructed a database WeCoNET (http://bioinfo.usu.edu/weconet/), providing functional annotations of the pathogen proteins and various tools to exploit host–pathogen interactions and other relevant information. The database implements a host–pathogen interactomics tool to predict protein–protein interactions, followed by network visualization, BLAST search tool, advanced ‘keywords-based’ search module, etc. Other features in the database include various functional annotations of host and pathogen proteins such as gene ontology terms, functional domains, and subcellular localization. The pathogen proteins that serve as effector and secretory proteins have also been incorporated in the database, along with their respective descriptions. Additionally, the host proteins that serve as transcription factors were predicted, and are available along with the respective transcription factor family and KEGG pathway to which they belong.

Conclusion
WeCoNET is a comprehensive, efficient resource to the molecular biologists engaged in understanding the molecular mechanisms behind the common bunt infection in wheat. The data integrated into the database can also be beneficial to the breeders for the development of common bunt-resistant cultivars.
High-dose stereotactic radiotherapy boost in the treatment of squamous cell carcinoma of the head and neck region
Authors: Polanowski Paweł , Pietruszka Agnieszka , Księżniak-Baran Dorota , Grządziel Aleksandra , Chmielik Ewa , Kentnowski Marek , Amrogowicz Natalia , Składowski Krzysztof , Polanowska Katarzyna 
Published: June 2022

Abstract
Background
Surgical resection with adjuvant concurrent radiochemotherapy is the standard of care for stage III–IV oral cavity cancer. In some cases, the dynamic course of the disease is out of the prepared schedule of treatment. In that event, a stereotactic radiosurgery boost might be the only chance for disease control.

Case presentation
Here, we present a case study of a patient with oral cancer who underwent surgery. During adjuvant radiotherapy, a metastatic cervical lymph node was diagnosed based on fine-needle aspiration biopsy. To increase the total dose to the metastatic tumor, a stereotactic radiosurgery boost of 1 × 18 Gy was performed two days after the last fraction of conventional radiotherapy. The early and late tolerance of this treatment were positive. During the 18-month follow-up, locoregional recurrence was not detected. The patient died due to secondary malignancy.

Conclusions
This paper shows that a stereotactic radiosurgery boost added to adjuvant conventional radiotherapy is an effective approach permitting the maintenance of good local control in well-selected patients.
Femoral periprosthetic fracture treatment using the Ortho-Bridge System: a biomechanical study
Authors: Long Yuntao , Qi Yubin , Zuo Guilai , Zhang Qingjie , Liu Zhenlin , Wang Wen 
Published: June 2022

Abstract
Background
We undertook a comparative biomechanical study of type B1 fractures around femoral prostheses following cemented hip arthroplasty using the Ortho-Bridge System (OBS) and a locking compression plate/locking attachment plate structure (LCP + LAP). We aimed to investigate the biomechanical characteristics and advantages of the OBS compared with LCP + LAP when treating this fracture type.

Methods
An OBS fixation model was designed based on OBS and LCP + LAP fixation characteristics. The LCP + LAP combination (Group A) and three different OBS combinations (Groups B, C, and D) were used to fix a B1 fracture model with a femoral periprosthetic fracture. Axial compression and torsion experiments were then performed using simple and comminuted fracture models. The axial compression failure experiment was carried out, and the model stiffness during axial compression, torsion angle in torsion test, and vertical load in the final failure test were collected.

Results
When simulating simple oblique fractures, no significant difference was found among the four groups in terms of stiffness in the axial compression experiment (P = 0.257). The torsion angle of the LCP + LAP system was significantly higher compared with the OBS system (P < 0.05). When simulating a comminuted fracture, the experimental data for axial compression showed that the rigidity measurements of the three combinations of the OBS system were higher compared with the LCP + LAP system (P = 0.000) and that the torsion angles of three combinations of the OBS system were smaller compared with the LCP + LAP system (P < 0.05). In the axial compression failure test, the fixed failure mode of the LCP + LAP system was the destruction of the contact cortex at the fracture site, whereas the failure modes in the three OBS combinations involved fracture around the screws above the osteotomy and destruction of the contact cortex at the fracture site.

Conclusions
The findings revealed that the OBS produced superior biomechanical outcomes compared with LCP + LAP, especially for the bridging two-rod dual cortex. According to the performance observed after model axial compression destruction, the OBS was fixed and provided greater stress dispersion, which might make it more suitable for facilitating early functional movement and avoiding the failure of internal fixation.
Varus morphology and its surgical implication in osteoarthritic knee and total knee arthroplasty
Authors: Suardi Chiara , Stimolo Davide , Zanna Luigi , Carulli Christian , Fabrizio Matassi , Civinini Roberto , Innocenti Matteo 
Published: June 2022

Abstract
Background
Knee varus alignment represents a notorious cause of knee osteoarthritis. It can be caused by tibial deformity, combined tibial–femoral deformity and/or ligament imbalance. Understanding malalignment is crucial in total knee arthroplasty to restore frontal plane neutral mechanical axis. The aim of this study was to determine which factor contributes the most to varus osteoarthritic knee and its related surgical implications in performing a total knee arthroplasty.

Methods
We retrospectively evaluated 140 patients operated for total knee arthroplasty due to a varus knee. Full-leg hip to ankle preoperative X-rays were taken. Radiological parameters recorded were: mechanical axis deviation, hip–knee–ankle, anatomical–mechanical angle, medial neck shaft angle, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), lateral proximal femoral angle, lateral distal tibial angle (LDTA), femoral bowing, and length of tibia and femur. We also determined ideals tibial and femoral cuts in mm according to mechanical alignment technique. A R2 was calculated based on the linear regression between the predicted values and the observed data.

Results
The greatest contributor to arthritic varus (R = 0.444) was MPTA. Minor contributors were mLDFA (R = 0.076), JLCA (R = 0.1554), LDTA (R = 0.065), and femoral bowing (R = 0.049). We recorded an average of 7.6 mm in lateral tibial cut thickness to restore neutral alignment.

Conclusions
The radiological major contributor to osteoarthritic varus knee alignment is related to proximal tibia deformity. As a surgical consequence, during performing total knee arthroplasty, the majority of the correction should therefore be made on tibial cut.