bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic biomarkers for the response to the radiosensitizer nimorazole combined with RCTx: a pre-clinical trial in HNSCC xenografts
Authors: Koi Lydia , Bitto Verena , Weise Corina , Möbius Lisa , Linge Annett , Löck Steffen , Yaromina Ala , Besso María José , Valentini Chiara , Pfeifer Manuel , Overgaard Jens , Zips Daniel , Kurth Ina , Krause Mechthild , Baumann Michael
Published: August 2023

Background

Tumor hypoxia is associated with resistance to radiotherapy and chemotherapy. In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use.

Methods

Irradiations were performed with 30 fractions in 6 weeks combined with weekly cisplatin. Nimorazole was applied before each fraction, beginning with the first or after ten fractions. Effect of RCTx with or without addition of nimorazole was quantified as permanent local control after irradiation. For histological evaluation and targeted gene expression analysis, tumors were excised untreated or after ten fractions. Using quantitative image analysis, micromilieu parameters were determined.

Results

Nimorazole combined with RCTx significantly improved permanent local control in two tumor models, and showed a potential improvement in two additional models. In these four models, pimonidazole hypoxic volume (pHV) was significantly reduced after ten fractions of RCTx alone. Our results suggest that nimorazole combined with RCTx might improve TCR compared to RCTx alone if hypoxia is decreased during the course of RCTx but further experiments are warranted to verify this association. Differential gene expression analysis revealed 12 genes as potential for RCTx response. When evaluated in patients with HNSCC who were treated with primary RCTx, these genes were predictive for LRC.

Conclusions

Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC.
Cervical cancer screening and treatment for PLWHIV: experiences from an innovative program in Nigeria
Authors: Ogunsola Olabanjo Okunlola , Ajayi Oluseye Ayodele , Ojo Temitope Olumuyiwa , Osayi Emmanuel , Wudiri Kucheli , Amoo Babatunde , Ayoka-Ikechukwu Rita , Olumeyan Olufemi Ojuola , Ifechelobi Chukwuemeka , Okonkwo Prosper , Akinro Yewande
Published: August 2023

Background

We evaluated cervical cancer program for women living with HIV (WLHIV) to determine program screening rate, primary case finder screening accuracy and treatment and post-treatment screening rate among screen-positive patients.

Methods

A ten-month review of cervical cancer program data among WLHIV aged 15–49 years on HIV care across forty-one comprehensive ART sites, supported by APIN (a PEPFAR implementing partner) for cervical cancer screening and treatment in Nigeria, was conducted from October 2020 to July 2021. Initial screening was done using visual inspection with acetic acid (VIA) followed by a gynaecologist expert review through a program-designed software named AVIVA, as a confirmatory test. Associations were measured between the primary case finder screening accuracy and study covariates at p-value of 0.05.

Results

About 10,289 asymptomatic women aged 15–49 years living with HIV were screened for cervical cancer by primary case finders using VIA-based screening test. About 732 (7.1%) had a positive screening test suggestive of precancerous lesions or cervical cancer. Three hundred and fifteen (43.0%) of VIA positive women had treatment using thermal ablation and less than one-third (21.6%) of those treated came back for post-treatment screening test. Primary case finder screening sensitivity, specificity, positive predictive and negative predictive accuracy using gynaecologist review as confirmatory test were 60.8%, 71.5%, 41.7% and 84.5% respectively. Overall screening accuracy was 68.8%.

Conclusion and recommendations

This innovative approach to cervical cancer screening among WLHIV yielded modest results in preventing program error and wastages. Wider deployment of expert-based reviews of VIA though AVIVA software might be a veritable approach to improve screening accuracy in low resource settings.
Application of cement-augmented pedicle screws in elderly patients with spinal tuberculosis and severe osteoporosis: a preliminary study
Authors: Gao Shutao , Hu Yukun , Mamat Fulati , Liang Weidong , Mamat Mardan , Xun Chuanhui , Zhang Jian , Sheng Weibin
Published: August 2023

Objective

Surgical management of elderly patients with spinal tuberculosis and severe osteoporosis is challenging. Cement-augmented pedicle screws (CAPS) have been specifically designed for elderly patients with osteoporotic spines. Herein, we investigated the feasibility of CAPS applied in elderly patients with spinal tuberculosis and severe osteoporosis.

Methods

We retrospectively analyzed data of patients with spinal tuberculosis and severe osteoporosis between January 2017 and January 2021. Surgical data, including surgical duration and intraoperative blood loss, were recorded. Radiological parameters, such as correction of regional kyphotic angle and screw loosening, were also evaluated. Additionally, visual analog scores (VAS) and Oswestry disability index (ODI) were used to evaluate back pain and functional recovery, respectively. Erythrocyte sedimentation (ESR) and C-reactive protein (CRP) concentrations were detected to assess tuberculosis activity. The presence of complications and fusion rate was also assessed.

Results

A total of 15 patients were included in this study. The surgical duration was 263.0 ± 56.2 min, with an average blood loss of 378.7 ± 237.0 ml. The correction of regional kyphotic angle was 12.4° ± 15.0°, and it was well maintained until the final follow-up. The mean VAS decreased from 6.0 ± 1.2 points to 0.5 ± 0.6 points, and ODI reduced from 37.8% ± 7.6% to 8.3% ± 2.8% (P < 0.01). At the final follow-up, ESR and CRP levels were within normal range. Bony fusion occurred in all patients, with an average fusion duration of 8.8 ± 1.5 months. No cases of pedicle screw pullout, screw loosening, or pseudoarthrosis occurred. Tuberculosis recurrence and dissemination were not observed during the follow-ups.

Conclusions

CAPS fixation is an effective and safe technique to achieve solid fixation and favorable clinical outcomes in elderly patients with spinal tuberculosis and severe osteoporosis.
Pairwise association of upper extremity musculoskeletal conditions: large population investigation from PERSIAN cohort study
Authors: Daliri Mahla , Khosravi Farideh , Shakeri Mohammad-T. , Ebrahimzadeh Mohammad H , Moradi Ali
Published: August 2023

Background

People with one area of upper extremity musculoskeletal conditions (UEMSCs) may have other. We aim to determine how frequent is the ipsilateral coexistence of common UEMSCs apparent on interview and examination.

Methods

This is a large population cross-sectional study conducted as part of the PERSIAN cohort study int Mashhad University of Medical Sciences (MUMS). The study aimed to evaluate individuals for symptoms and signs of the following conditions: carpal tunnel syndrome (CTS), lateral epicondylitis (LE), trapeziometacarpal osteoarthritis (TMC OA), DeQuervain’s tendinopathy, trigger digit (TD), ganglion cyst, and rotator cuff tendinopathy (RCT). The primary outcomes of the study are (1) to determine the side-specific relative risk of each UEMSC coexisting with the second condition, and (2) to identify predictive factors of each UEMSC using side-specific multivariate logistic regression analysis.

Results

We conducted a study involving 4737 individuals from the staff of MUMS and found significant pairwise associations among UEMSCs on a side-specific basis. Women had more chance of having DeQuervain’s disease (β = 6.3), CTS (β = 3.5), ganglion cyst (β = 2.5), TMC OA (β = 2.3), and RCT (β = 2.0). Each condition (dependent variable) was associated with others (predictors) as follows: CTS: RCT (β = 5.9), TMC OA (β = 4.7), TD (β = 2.9), and LE (β = 2.5). TMC OA: LE (β = 6.4), TD (β = 5.4), RCT (β = 4.3), and CTS (β = 4.1). LE: RCT (β = 8.1), TMC OA (β = 6.4), and CTS (β = 2.5). DeQuervain’s disease: TD (β = 13.6), RCT (β = 4.5), and LE (β = 3.8). TD: CTS (β = 8.8), ganglion cyst (β = 7.6), DeQuervain’s disease (β = 5.7), and TMC OA (β = 4.3). RCT: LE (β = 5.8), TMC OA (β = 5.5), CTS (β = 5.2), and DeQuervain’s disease (β = 4.3). Ganglion cyst: TD (β = 4.8).

Conclusion

Our study reports significant increased frequency of the UEMSCs among patients who already have one of the diseases, in a large sample size study.

Level of Evidence Level II (Differential Diagnosis/Symptom Prevalence Study).
MicroRNA-338-3p helps regulate ovarian function by affecting granulosa cell function and early follicular development
Authors: Xu Ziwen , Zhang Tongwei , Hu Jingyi , Zhang Junya , Yang Guang , He Jiahuan , Wang Huihui , Jiang Ran , Yao Guidong
Published: August 2023

Background

Follicular development in mammalian ovaries is a complex and dynamic process, and the interactions and regulatory-feedback loop between the follicular microenvironment, granulosa cells (GCs), and oocytes can affect follicular development and normal ovary functions. Abnormalities in any part of the process may cause abnormal follicular development, resulting in infertility. Hence, exploring the pathogenesis of abnormal follicular development is extremely important for diagnosing and treating infertile women.

Methods

RNA sequencing was performed with ovarian cortical tissues established in vitro. In situ-hybridization assays were performed to study microRNA-338-3p (miR-338-3p) expressed in GCs and oocytes. In vitro culture models were established with GCs and neonatal mouse ovaries to study the biological effects of miR-338-3p. We also performed in vivo experiments by injecting adeno-associated virus vectors that drive miR-338-3p overexpression into the mouse ovarian bursae.

Results

Sequencing analysis showed that miR-338-3p was expressed at significantly higher levels in ovarian cortical tissues derived from patients with ovarian insufficiency than in cortical tissues derived from patients with normal ovarian function; miR-338-3p was also significantly highly expressed in the GCs of patients with diminished ovarian reserve (P < 0.05). In situ-hybridization assays revealed that miR-338-3p was expressed in the cytoplasm of GCs and oocytes. Using in vitro culture models of granulosa cells, we found that miR-338-3p overexpression significantly suppressed the proliferation and oestradiol-production capacity of GCs (P < 0.05). In vitro culture models of neonatal mouse ovaries indicated that miR-338-3p overexpression suppressed the early follicular development in mouse ovaries. Further analysis revealed that miR-338-3p might be involved in transforming growth factor β-dependent regulation of granulosa cell proliferation and, thus, early follicular development. Injecting miR-338-3p-overexpression vectors into the mouse ovarian bursae showed that miR-338-3p down-regulated the oocyte mitochondrial membrane potential in mice and disrupted mouse oestrous cycles.

Conclusion

miR-338-3p can affect early follicular development and normal ovary functions by interfering with the proliferation and oestradiol production of GCs. We systematically elucidated the regulatory effect of miR-338-3p on follicular development and the underlying mechanism, which can inspire new studies on the diagnosis and treatment of diseases associated with follicular development abnormalities.
Distribution areas and monthly dynamic distribution changes of three Aedes species in China: Aedes aegypti, Aedes albopictus and Aedes vexans
Authors: Li Yuepeng , An Qi , Sun Zhuo , Gao Xiang , Wang Hongbin
Published: August 2023

Background

Mosquitoes play an absolute role in the spread of epidemic arbovirus diseases. Worldwide, Aedes aegypti and Aedes albopictus are the main vectors responsible for the spread of these mosquito-borne diseases. Aedes vexans, a mosquito species native to China, also carries mosquito-borne viruses, such as dengue fever virus and Japanese encephalitis virus, but research on this mosquito has been inadequate. Mapping the potential distribution range of and monthly change in the distribution of these three Aedes species is of particular importance for mosquito surveillance, eradication and disease control.

Methods

Monitoring data were collected for the three Aedes species in China. Long-term temperature and precipitation data (2001–2021) and land cover data were used to represent various climate and environmental conditions. An ecological niche model was developed using a maximum entropy modeling method to predict the current optimum habitat areas for the three Aedes species and to obtain important variables influencing their monthly distribution.

Results

The distribution model for the three Aedes species performed well, with an area under the receiver operating characteristic curve value of 0.991 for Ae. aegypti, 0.928 for Ae. albopictus and 0.940 for Ae. vexans. Analysis of the distribution change and mapping of the optimum habitat range for each Aedes species for each month demonstrated that temperature, precipitation and construction land were important factors influencing the distribution of these three Aedes species.

Conclusions

In China, Aedes aegypti is mainly concentrated in a few tropical regions and along the Yunnan border; Aedes albopictus is widely distributed throughout most of the country, except for the arid and semi-arid regions of northwest China; and Aedes vexans is mainly found in the northern regions. Our results provide a basis for the timing and location of surveillance efforts for high-priority mosquitoes.

Graphical abstract
Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents
Authors: Larsen Michael , He Fan , Kawasawa Yuka Imamura , Berg Arthur , Vgontzas Alexandros N. , Liao Duanping , Bixler Edward O. , Fernandez-Mendoza Julio
Published: August 2023

Introduction

The onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation.

Results

The gene-wide analysis indicated differential methylation within or around 1818 unique genes across the sleep initiation measurements using self-report, actigraphy (ACT), and polysomnography (PSG), while GWAS-informed analysis yielded 67 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG). DNA methylation within 12 genes was associated with both subjective and PSG-measured SOL, 31 with both ACT- and PSG-measured SOL, 19 with both subjective and ACT-measured SOL, and one gene (SMG1P2) had methylation sites associated with subjective, ACT- and PSG-measured SOL.

Conclusions

Objective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Additionally, our data provide evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNA methylation in and around genes involved in circadian regulation (i.e.,RASD1,RAI1), cardiometabolic disorders (i.e.,FADS1,WNK1,SLC5A6), and neuropsychiatric disorders (i.e.,PRR7,SDK1,FAM172A). If validated, these sites may provide valuable targets for early detection and prevention of disorders involving prolonged or delayed SOT, such as insomnia, delayed sleep phase, and their comorbidity.
Associations between nutrients in one-carbon metabolism and fetal DNA methylation in pregnancies with or without gestational diabetes mellitus
Authors: Kadam Isma’il , Dalloul Mudar , Hausser Jeanette , Huntley Monique , Hoepner Lori , Fordjour Lawrence , Hittelman Joan , Saxena Anjana , Liu Jia , Futterman Itamar D. , Minkoff Howard , Jiang Xinyin
Published: August 2023

Background

Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B12, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM.

Results

In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25–33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = − 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = − 0.13, p = 0.049 and r = − 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = − 0.28, p = 0.015).

Conclusions

In conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.
The functional effects of Piezo channels in mesenchymal stem cells
Authors: Huang Zhilong , Huang Yingying , Ning Xiner , Li Haodi , Li Qiqi , Wu Junjie
Published: August 2023

Mesenchymal stem cells (MSCs) are widely used in cell therapy, tissue engineering, and regenerative medicine because of their self-renewal, pluripotency, and immunomodulatory properties. The microenvironment in which MSCs are located significantly affects their physiological functions. The microenvironment directly or indirectly affects cell behavior through biophysical, biochemical, or other means. Among them, the mechanical signals provided to MSCs by the microenvironment have a particularly pronounced effect on their physiological functions and can affect osteogenic differentiation, chondrogenic differentiation, and senescence in MSCs. Mechanosensitive ion channels such as Piezo1 and Piezo2 are important in transducing mechanical signals, and these channels are widely distributed in sites such as skin, bladder, kidney, lung, sensory neurons, and dorsal root ganglia. Although there have been numerous studies on Piezo channels in MSCs in recent years, the function of Piezo channels in MSCs is still not well understood, and there has been no summary of their relationship to illustrate which physiological functions of MSCs are affected by Piezo channels and the possible underlying mechanisms. Therefore, based on the members, structures, and functions of Piezo ion channels and the fundamental information of MSCs, this paper focused on summarizing the advances in Piezo channels in MSCs from various tissue sources to provide new ideas for future research and practical applications of Piezo channels and MSCs.
Construction of a bacteriophage-derived recombinase system in Bacillus licheniformis for gene deletion
Authors: Xue Fang , Ma Xufan , Luo Cheng , Li Dongliang , Shi Guiyang , Li Youran
Published: August 2023

Bacillus licheniformis and its related strains have found extensive applications in diverse industries, agriculture, and medicine. However, the current breeding methods for this strain primarily rely on natural screening and traditional mutagenesis. The limited availability of efficient genetic engineering tools, particularly recombination techniques, has hindered further advancements in its applications. In this study, we conducted a comprehensive investigation to identify and characterize a recombinase, RecT, derived from a Bacillus phage. Remarkably, the recombinase exhibited a 105-fold enhancement in the recombination efficiency of the strain. To facilitate genome editing, we developed a system based on the conditional expression of RecT using a rhamnose-inducible promoter (Prha). The efficacy of this system was evaluated by deleting the amyL gene, which encodes an α-amylase. Our findings revealed that the induction time and concentration of rhamnose, along with the generation time of the strain, significantly influenced the editing efficiency. Optimal conditions for genome editing were determined as follows: the wild-type strain was initially transformed with the genome editing plasmid, followed by cultivation and induction with 1.5% rhamnose for 8 h. Subsequently, the strain was further cultured for an additional 24 h, equivalent to approximately three generations. Consequently, the recombination efficiency reached an impressive 16.67%. This study represents a significant advancement in enhancing the recombination efficiency of B. licheniformis through the utilization of a RecT-based recombination system. Moreover, it provides a highly effective genome editing tool for genetic engineering applications in this strain.
Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue
Authors: Vollrath Shirin , Matits Lynn , Schellenberg Jana , Kirsten Johannes , Steinacker Jürgen M. , Bizjak Daniel A.
Published: August 2023

Introduction

Fatigue is a common symptom in post-COVID-19 patients. Individuals with fatigue often perform less well compared to healthy peers or without fatigue. It is not yet clear to what extent fatigue is related to the inability to reach maximum exhaustion during physical exercise.

Methods

A symptom-based questionnaire based on the Carruthers guidelines (2003) was used for reporting the presence of fatigue and further symptoms related to COVID-19 from 85 participants (60.0% male, 33.5 ± 11.9 years). Cardiopulmonary exercise testing (CPET) and lactate measurement at the end of the test were conducted. Objective and subjective exhaustion criteria according to Wasserman of physically active individuals with fatigue (FS) were compared to those without fatigue (NFS).

Results

Differences between FS and NFS were found in Peak V̇O2/BM (p < 0.001) and Max Power/BM (p < 0.001). FS were more likely to suffer from further persistent symptoms (p < 0.05). The exhaustion criterion Max. lactate was reached significantly more often by NFS individuals.

Conclusion

Although the aerobic performance (Max Power/BM) and the metabolic rate (Peak V̇O2/BM and Max. lactate) of FS were lower compared to NFS, they were equally able to reach objective exhaustion criteria. The decreased number of FS who reached the lactate criteria and the decreased V̇O2 peak indicates a change in metabolism. Other persistent post-COVID-19 symptoms besides fatigue may also impair performance, trainability and the ability to reach objective exhaustion.

Trial registration Trial registration: DRKS00023717; date of registration: 15.06.2021 (retrospectively registered).
The early negative bias of social semantics: evidence from behavioral and ERP studies
Authors: Fan Xinfang , Xu Qiang , Liu Juan , Xing Hongwei , Ning Liangyu , Chen Qingwei , Yang Yaping
Published: August 2023

Background

Compared to nonsocial information, the human brain is more highly sensitive to social information. As a kind of typical social semantic information, the words describing person traits differ from the nonsocial semantic information describing inanimate objects in many ways. It remains to be seen whether the processing of trait words has a valence asymmetric and whether it differs from the processing of nonsocial semantic information in terms of behavioral responses and neural temporal processes.

Method

Taking person and object names as priming stimuli and adjective words only used for describing humans or objects as target stimuli, the present study aimed to investigate the processing characteristics of social and nonsocial semantic information by recording both behavioral and ERP data.

Results

Behavioral results showed that the response times for negative words were significantly slower than those for positive words whether for social or nonsocial semantic information. The accuracy rates of negative words were significantly lower than those of positive words when the targets were social words which is contrary to the nonsocial words. The ERP results indicated that there was a negative bias effect on the processing of both types of information during the whole time course of brain neural activity; that is, the P2, N400, and LPP amplitudes elicited by negative words were larger than those elicited by positive words; However, the negative bias effect of social semantic information started at the early perceptual stage which was significantly earlier than the onset of negative bias of nonsocial semantic information, and was significantly affected by the prime type. In addition, there was a significant semantic conflict N400 effect only for nonsocial semantic information.

Conclusions

Overall, the present study revealed the existence of an early negative bias of social information and provided evidence for the specificity of social information.
Artificial intelligence learning landscape of triple-negative breast cancer uncovers new opportunities for enhancing outcomes and immunotherapy responses
Authors: Li Shuyu , Zhang Nan , Zhang Hao , Zhou Ran , Li Zirui , Yang Xue , Wu Wantao , Li Hanning , Luo Peng , Wang Zeyu , Dai Ziyu , Liang Xisong , Wen Jie , Zhang Xun , Zhang Bo , Cheng Quan , Zhang Qi , Yang Zhifang
Published: August 2023

Triple-negative breast cancer (TNBC) is a relatively aggressive breast cancer subtype due to tumor relapse, drug resistance, and multi-organ metastatic properties. Identifying reliable biomarkers to predict prognosis and precisely guide TNBC immunotherapy is still an unmet clinical need. To address this issue, we successfully constructed a novel 25 machine learning (ML) algorithms-based immune infiltrating cell (IIC) associated signature of TNBC (MLIIC), achieved by multiple transcriptome data of purified immune cells, TNBC cell lines, and TNBC entities. The TSI index was employed to determine IIC-RNAs that were accompanied by an expression pattern of upregulation in immune cells and downregulation in TNBC cells. LassoLR, Boruta, Xgboost, SVM, RF, and Pamr were utilized for further obtaining the optimal IIC-RNAs. Following univariate Cox regression analysis, LassoCox, CoxBoost, and RSF were utilized for the dimensionality reduction of IIC-RNAs from a prognostic perspective. RSF, Ranger, ObliqueRSF, Rpart, CoxPH, SurvivalSVM, CoxBoost, GlmBoost, SuperPC, StepwiseCox, Enet, LassoCox, CForest, Akritas, BlackBoost, PlsRcox, SurvReg, GBM, and CTree were used for determining the most potent MLIIC signature. Consequently, this MLIIC signature was correlated significantly with survival status validated by four independent TNBC cohorts. Also, the MLIIC signature had a superior predictive capability for TNBC prognosis, compared with 148 previously reported signatures. In addition, MLIIC signature scores developed by immunofluorescent staining of tissue arrays from TNBC patients showed a substantial prognostic value. In TNBC immunotherapy, the low MLIIC profile demonstrated significant immune-responsive efficacy in a dataset of multiple cancer types. MLIIC signature could also predict m6A epigenetic regulation which controls T cell homeostasis. Therefore, this well-established MLIIC signature is a robust predictive indicator for TNBC prognosis and the benefit of immunotherapy, thus providing an efficient tool for combating TNBC.
“I think there has to be a mutual respect for there to be value”: Evaluating patient engagement in a national clinical trial on de-implementation of low value care
Authors: Etchegary Holly , Linklater Stefanie , Duquette D.’Arcy , Wilkinson Gloria , Francis Vanessa , Gionet Erin , Patey Andrea M. , Grimshaw Jeremy M.
Published: August 2023

Background

The evaluation of patient engagement in research is understudied and under-reported, making it difficult to know what engagement strategies work best and when. We provide the results of an evaluation of patient engagement in a large Canadian research program focused on the de-implementation of low-value care. We aimed to evaluate the experience and impact of patient engagement in the study.

Methods

An online cross-sectional survey was administered using Microsoft Forms to (1) researchers and study staff and (2) patient partners. The survey was developed following iterative reviews by the project’s patient partnership council and evaluation committee. Survey content areas included opinions on patient engagement to date, including challenges to engagement and suggestions for improvement. Patient partners also evaluated the partnership council. Descriptive statistics including counts and percentages described Likert scale survey items, while open comments were analyzed using descriptive content analysis.

Results

The survey response rate was 46% (17/37). There were positive attitudes about the value of patient engagement in this project. There was also a high degree of willingness to be involved with patient engagement in future projects, whether as a patient partner or as a researcher including patients on the research team. Most patient partners felt their contributions to the project were valued by researchers and study research staff. Open comments revealed that a co-design approach and full inclusion on the research team were integral to demonstrating the value of patient partner input. Areas for improvement included more frequent and ongoing communication among all team members, as well as earlier training about patient engagement, particularly addressing role expectations and role clarity.

Conclusions

Our data revealed that despite some challenges, team members recognized the value of patient engagement in research and agreed project decisions had been impacted by patient partner input. Ongoing communication was highlighted as an area for improvement, as well as earlier training and ongoing support for all team members, but particularly researchers and study staff. In response to evaluation data, the team has reinstated a quarterly newsletter and plans to use specific patient engagement planning templates across study sites for all project activities. These tools should help make expectations clear for all team members and contribute to a positive patient engagement experience. Findings can inform patient engagement planning and evaluation for other health research projects.
Vitamin D Binding Protein and Postsurgical Outcomes and Tissue Injury Markers After Hip Fracture: A Prospective Study
Authors: Meng Lingqiong , Wang Xiangbing , Carson Jeffrey L , Schlussel Yvette , Shapses Sue A
Published: August 2023

Context

Hip fracture is a serious injury that can lead to increased morbidity and mortality. Vitamin D binding protein (DBP) is a potential prognostic indicator of outcomes since it is important for actin scavenging and inflammation after tissue injury.

Objective

To determine whether circulating DBP is associated with mobility or mortality after hip fracture and its association with acute tissue injury markers.

Methods

Post hoc analysis of a multisite North American prospective study of 260 patients with hip fracture; mobility assessed at 30 and 60 days and mortality at 60 days after repair surgery. Biochemical markers were measured before, and 2 to 4 days after surgery. Tissue injury markers were measured in 100 randomly selected patients and controls. The primary outcome was mobility and mortality by DBP tertiles. Secondary outcomes were assessment of pre- and postoperative biomarkers.

Results

Among all patients (81 ± 9 years, BMI 25 ± 4 kg/m2; 72% female), the highest DBP tertile had greater mobility at 30 (OR: 2.66; 95% CI: 1.43, 4.92; P = .002) and 60 days (OR: 2.31; 95% CI: 1.17, 4.54; P = .014) and reduced mortality (OR: 0.18; 95% CI: 0.04, 0.86; P = .032) compared with the lowest DBP tertile (<28.0 mg/dL). Total 25-hydroxyvitamin-D did not differ between tertiles (22.0 ± 9.5 ng/mL). Circulating DBP and gelsolin were lower and interleukin-6, C-reactive protein, and F-actin were higher (P < .01) in patients vs controls, and worsened (P < .01) after surgery.

Conclusion

High circulating DBP concentrations are associated with better mobility and reduced mortality after hip fracture surgery. The role of DBP as an acute phase reactant to tissue injury and clinical outcomes should be addressed in future study.
Hirschsprung's Disease - Review of Clinical Features, Diagnosis and Treatment
Authors: Tkaczyk Rafał , Świątek Gabriela , Tomczyk Jakub , Sosnowska Weronika , Tomkiewicz Maria , Taracha Kalina , Tomkiewicz Maciej , Brzozowska Aleksandra , Trusz Kornelia , Wanat Iwona
Published: August 2023

Introduction and purpose: Hirschsprung's disease, also known as congenital aganglionic megacolon, is a rare congenital disorder that affects the large intestine. Due to the absence of ganglion cells, the affected segment of the colon becomes narrow and unable to relax. The disease is present from birth but may not always be immediately apparent. In this paper, we will attempt to present the current state of knowledge regarding the diagnosis and treatment of Hirschsprung's disease, based on the analysis of literature available on the PubMed platform.

Description of the state of knowledge: Hirschsprung's disease (HSCR), also known as congenital aganglionosis of the colon, involves abnormal migration, proliferation, and differentiation of neural crest cells, leading to the absence of autonomic nerve ganglia within the colon. HSCR is associated with mutations in several genes, with RET, GDNF, EDNRB and SOX10 being identified as the main causes of the disease. Mutations in the RET gene are associated with the hereditary form of Hirschsprung's disease. Symptoms of HSCR appear in newborns and may include bilious vomiting, diarrhea associated with enterocolitis, failure to pass meconium within the first 24 hours of life, impaired peristalsis, jaundice, feeding difficulties, and progressive abdominal distension.

Summary: Diagnosis is typically made based on clinical presentation, imaging studies, and biopsy. Treatment usually involves surgery to remove the affected segment of the colon and reconnect the healthy portions. Although postoperative complications are relatively common, long-term studies suggest that the majority of children with Hirschsprung's disease function well in society.
Is Splenectomy still the best treatment for Autoimmune hemolytic anemia
Authors: Chomicz Malwina , Puszkarz Aleksandra , Łukaszewska Anna , Łukaszewska Ewa , Bąk Mateusz , Guzik Natalia , Bik Tomasz , Gaj Łukasz , Drozdowska Katarzyna , Łukaszewska-Stanik Katarzyna
Published: August 2023

Introduction:

Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases that includes AIHA with warm type antibodies, cold agglutinin disease (CAD), mixed type AIHA, paroxysmal cold hemoglobinuria, and atypical AIHA.

Currently CAD is defined as chronic, clonal lymphoproliferative disease, while presence of cold agglutinin in gastrointestinal tract is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies against red blood cells (RBCs), these antibodies cause premature destruction of erythrocytes. The pathogenesis of AIHA is complex and still not yet fully understood.

 Aim of study:

The purpose of the study was to review the literature on the treatment options for Autoimmune Hemolytic Anemia

 Materials and methods: A systemic review was conducted using PubMed, ScienceDirect, Google Scholar databases. The search strategy was based on following terms: Aiha, splenectomy autoimmune anemia, aiha treatment,

Results and Conclusions:

Based on the review of the medical literature, we believe that Splenectomy is no longer the most effective method of treating any type of AIHA and the Rituximab treatment presented by us seems to be safer and definitely less burdensome for the patient.

Of course, splenectomy is still used in AIHA - but nowadays it is more limited due to the very high effectiveness of the described non-surgical treatment
The effect of antioxidants on the course and prevention of Alzheimer's disease on the example of vitamin E
Authors: Gawryś Agnieszka , Cholewa Małgorzata Maria , Kromer Agata , Wilk Joanna , Cichoń Katarzyna , Zapała Magdalena Alicja , Łapaj Monika , Chyćko Małgorzata , Środoń Agnieszka , Czarnota Julia
Published: August 2023

Introduction and purpose of the workAlzheimer's disease is the most common cause of dementia. A small proportion of cases have a genetic etiology. Other factors that influence the development of Alzheimer's disease include old age, family history of the disease, head trauma, hypertension in middle age, excessive body weight, diabetes, as well as elevated plasma cholesterol levels. In the course of this disease, there is accumulation of β-amyloid and intracellular neurofibrillary tangles (NETs) phosphorylated tau. Oxidative stress is a significant factor influencing induction in the course of Alzheimer's disease. The aim of this study is to investigate the role of vitamin E on the course and prevention of Alzheimer's disease. State of the knowledgeCurrently, there is no known effective treatment or prevention of Alzheimer's disease. Given the properties of vitamin E, it seems reasonable to conduct research on its possible positive effects in the prevention and treatment of Alzheimer's disease. Numerous studies have been conducted to determine the role of vitamin E supplementation in the course of this disease. Many of them have shown a positive effect of eating a diet rich in vitamin E or taking this vitamin in the form of supplements on slowing the rate of progression of the disease and reducing the risk of its onset. However, there are also studies in which the role of vitamin E has not been confirmed.SummaryDue to its properties, vitamin E can be considered as a means to reduce the risk of developing and progressing Alzheimer’s disease, but studies conducted so far are ambiguous on this issue. Further analysis should be carried out to confirm the efficacy of vitamin E in Alzheimer’s disease.
Anxiety disorders - a common problem about which we still don’t know enough
Authors: Giżewska Kamila , Lorenc Karol , Bielawska Olga , Łoś Tomasz , Kuc Michał , Rogala Maciej , Jabłońska Klaudia , Gulbicka Marta
Published: August 2023

Anxiety disorders are the most common mental disorders. Up to one-third of the population suffers from them during their lifetime. An important problem is also the lack of awareness of patients about their disease. Only half of the anxiety disorders are diagnosed. Only a fifth of people suffering from anxiety disorders sought help from a specialist doctor. Only a third of patients are offered pharmacological treatment. The main symptom of this disease is an increased and intense feeling of anxiety. It is also associated with many other physical symptoms. It is correlative with a reduced quality of life and functioning in society. Diagnosis of anxiety disorders is very difficult due to the lack of specific imaging and laboratory tests that may be helpful in making or suggest a diagnosis. There is also a correlation between these disorders and the occurrence of depressive disorders, which is why the problem is complex and requires increased diagnostic sensitivity. Worldwide, anxiety disorders are underdiagnosed and undertreated, that's why it's so important to be aware of this disease entity. Prompt intervention by a physician is very important due to the increased frequency of suicides. The basic treatment is medication therapy with drugs from the SSRI and SNRI group combined with cognitive-behavioral therapy. Quick diagnosis and implementation of treatment contributes to a significant improvement in the quality of life of patients.
Rosacea – a modern view of diagnostics and treatment
Authors: Gawęda Agnieszka , Babiak Rafał , Bajak Karolina , Czuchryta Paulina , Domańska Anastazja , Grabek Agata , Rutkowska Julia , Rzęsa-Tokarczyk Żaneta , Skorek Klaudia , Urbańczyk Agnieszka
Published: August 2023

Introduction: Rosacea is a chronic inflammatory skin disease affecting central region of the face. Main symptoms consist of erythema, flushing, telangiectasia, phymatous changes and inflammatory papules and pustules. It can also affect eyes, causing blepharitis, conjunctivitis, keratitis or lid margin telangiectasia. Rosacea can negatively affect the quality of life, causing low self-esteem, avoidance of social interactions and mental health issues such as anxiety and depression. There are two classifications of rosacea, one from 2002 focusing on subtypes, and new phenotype-based classification. Phenotype-based approach allows individual management of each patient instead of categorizing by predefined subtype. Due to increased frequency of Demodex infestation in patients with rosacea, diagnosis and treatment of demodicosis can be helpful in management of rosacea. General treatment of rosacea consists of combination of oral and topical therapies, choosing adequate skincare cosmetics, laser therapies and avoidance of identified trigger factors specific for the patient.

The aim of the study: This study aims to gather current knowledge about classification, diagnostics, skincare and treatment of rosacea.

Materials and methods: This review was based on available data collected in the PubMed database, using the keywords: ‘rosacea’, ‘ocular rosacea’, ‘rosacea treatment’.

Conclusions: The treatment of rosacea requires selection of appropriate treatment depending on symptoms specific for the patient. Because of increased Demodex infestation present in some of the patients with rosacea, eradication can mitigate rosacea symptoms. Identification and avoidance of trigger factors and assortment of adequate skincare products are also substantial parts of management of rosacea and can alleviate rosacea symptoms.
Riga-Fede disease: report of a case in an infant
Authors: Hubka Joanna , Grużewska-Piotrowska Kinga , Grużewska Agnieszka , Pająk Monika , Wcisło Wojciech
Published: August 2023

Riga-Fede disease (RFD) is a rare, benign condition found in infants, characterized by ulcers in the oral mucosa, around the tongue and gums. It is caused by repeated injuries, caused by movements of the tongue over the lower incisors. It usually coexists with neonatal teeth. Although it starts as a small ulcer, it can progress to a large fibrous lesion. Symptoms include pain, swelling and difficulty swallowing and sucking. Early diagnosis and treatment are important to prevent late complications, including insufficient food intake, growth retardation and deformity of the tongue, gums, lips and floor of the mouth. The diagnosis is usually made on the basis of medical history and clinical features. The following paper presents the case of a 9-month-old boy with a lump occurring in the fundus of the mouth, at the base of the tongue.
Diagnosis and treatment in a case of uterine leiomyosarcoma - case report and review of the literature
Authors: Pająk Monika , Grużewska-Piotrowska Kinga , Hubka Joanna , Grużewska Agnieszka , Wcisło Wojciech
Published: August 2023

Introduction: Uterine leiomyosarcoma accounts for approximately 3%–7% of all uterine cancers and it is the most common subtype of uterine sarcoma. They are associated with high potential to both local recurrence and distant metastases, and they contribute to a significant proportion of uterine cancer deaths. Tumor stage is the single most important prognostic factor for uterine sarcomas. Presenting symptoms may be vague and mimic other benign uterine conditions.The aim of the study: This study aims to describe a case of uterine leiomyosarcoma and summarize current knowledge about classification, diagnostics and treatment.Materials and methods: The research method was a case study. This review was based on available data collected in the PubMed database and Google Scholar web search engine, using the key words: uterine leiomyosarcoma, uterine sarcoma, hysterectomy, gynecologic oncology.Conclusion: Surgery is considered the mainstay of treatment for sarcomas limited to the uterus. In patients with carcinosarcomas postoperative radiotherapy increases the local control. High rate of distant metastases suggests potential role of systemic therapy. However, the benefits of postoperative chemotherapy and endocrine therapy in high-risk patients are of no proven value in the adjuvant setting. These methods, in addition to palliative radiotherapy and surgery are used in recurrent and advanced disease.Keywords: uterine leiomyosarcoma, uterine sarcoma, hysterectomy, gynecologic oncology
Extrinsic allergic pneumonitis - classification, pathogenesis, diagnosis
Authors: Brzyska Anna , Kopiec Dominika , Kuzioła Karolina
Published: August 2023

Introduction and objective: Extrinsic allergic pneumonitis (AZPP) is an inflammatory disease of the lung parenchyma and bronchioles, caused by inhalation of organic and inorganic antigens. The pathhomechanism of the disease is based on the binding of the antigen with precipitins to form immune complexes that are responsible for the formation of acute inflammation in the lung tissue. The resulting inflammation is a type III and type IV hypersensitivity reaction. In the clinical course, azpp is divided into acute, subacute and chronic phases. The course of the disease varies depending on the type and duration of exposure to the antigen. It is most often manifested by shortness of breath, coughing and the progression of the disease leads to respiratory failure.

Review methods: While writing the thesis, a database was used, ie Pubmed and Google Scholar.

Brief description of the stage of knowledge: Extrinsic allergic pneumonitis requires a thorough differential diagnosis, which includes laboratory tests, functional tests, imaging tests, inhalation provocation tests and lung biopsy. The mainstay of treatment is to avoid exposure to the antigen. In severe disease, systemic corticosteroid therapy is indicated.

Summary: Correct diagnosis is a big problem because of the differences in symptoms and the severity of the disease among patients. Expanding the knowledge about the clinical course of the disease or its pathogenesis will affect the effectiveness of diagnostics and help to develop new methods of treatment.