bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of problem-based learning tutor seniority on medical students’ emotions: an equivalence study
Authors: Nomura Osamu , Abe Tatsuki , Soma Yuki , Tomita Hirofumi , Kijima Hiroshi
Published: June 2023

Background

The effectiveness of peer learning has been recognized and discussed by many scholars, and implemented in the formal curriculums of medical schools internationally. However, there is a general dearth of studies in measuring the objective outcomes in learning.

Methods

We investigated the objective effect of near-peer learning on tutee’s emotions and its equivalence within the formal curriculum of a clinical reasoning Problem Based Learning session in a Japanese medical school. Fourth-year medical students were assigned to the group tutored by 6th-year students or by faculties. The positive activating emotion, positive deactivating emotion, negative activating emotion, negative deactivating emotion, Neutral emotion were measured using the Japanese version of the Medical Emotion Scale (J-MES), and self-efficacy scores were also assessed. We calculated the mean differences of these variables between the faculty and the peer tutor groups and were statistically analyzed the equivalence of these scores. The equivalence margin was defined as a score of 0.4 for J-MES and 10.0 for the self-efficacy score, respectively.

Results

Of the 143 eligible participant students, 90 were allocated to the peer tutor group and 53 were allocated to the faculty group. There was no significant difference between the groups. The 95% confidence interval of the mean score difference for positive activating emotions (–0.22 to 0.15), positive deactivating emotions (–0.35 to 0.18), negative activating emotions (–0.20 to 0.22), negative deactivating emotions (–0.20 to 0.23), and self-efficacy (–6.83 to 5.04) were withing the predetermined equivalence margins for emotion scores, meaning that equivalence was confirmed for these variables.

Conclusions

Emotional outcomes were equivalent between near-peer PBL sessions and faculty-led sessions. This comparative measurement of the emotional outcomes in near-peer learning contributes to understanding PBL in the field of medical education.
Physicians’ professionalism from the patients’ perspective: a qualitative study at a single-family practice in Saudi Arabia
Authors: AlFaris Eiad , Irfan Farhana , Abouammoh Noura , Zakaria Nasriah , Ahmed Abdullah MA , Kasule Omar , Aldosari Dina M , AlSahli Nora A , Alshibani Mohammed Ghatar , Ponnamperuma Gominda
Published: June 2023

Introduction

Professionalism is a crucial component of medical practice. It is a culturally sensitive notion that generally consists of behaviors, values, communication, and relationships. This study is a qualitative study exploring physician professionalism from the patients’ perspective.

Methods

Focus group discussions with patients attending a family medicine center attached to a tertiary care hospital were carried out using the four gates model of Arabian medical professionalism that is appropriate to Arab culture. Discussions with patients were recorded and transcribed. Data were thematically analyzed using NVivo software.

Results

Three main themes emerged from the data. (1) In dealing with patients, participants expected respect but understood delays in seeing physicians due to their busy schedules. In communication, participants expected to be informed about their health conditions and to have their questions answered. (2) In dealing with tasks, participants expected proper examination and transparency of diagnosis, but some expected the physician to know everything and did not appreciate them seeking outside opinions. They expected to see the same physician at every visit. (3) In physician characteristics preferences, participants preferred friendly smiling physicians. Some cared about the outer appearance of the physician whereas others did not.

Discussion/conclusions

The findings of the study explained only two themes of the four gates model namely dealing with patients and dealing with tasks. Cultural competence and how to benefit from patients’ perceptions to be an ideal physician should be incorporated into the process of physicians’ training.
Sexual education for university students and the community in a european project: study protocol
Authors: Soto-Fernández I. , Fernández-Cézar R. , Aguiar Frias A. M. , Dias H. , Santiago C. , Gradellini C. , Aaberg V. , García-López V. , Gómez-Cantarino S.
Published: June 2023

Background

The World Health Organisation (WHO) calls on stakeholders to give Higher Education a key educational importance for the future of Europe. Within the content of the training programmes at university, sexuality emerges as a relevant topic in the nursing degree, to promote integral health from a holistic perspective. However, research on the presence of sexuality at the curricular level in Higher Education suggests that it is incomplete and underdeveloped.

Methods

This is a protocol for a long-term, multi-centre, exploratory, descriptive, and cross-sectional study with a quantitative and qualitative approach lasting two years. The research will be carried out in the educational community, including, on the one hand, students, and professors and health professionals of nursing programmes from five universities in different parts of the world (Portugal, Spain, Italy, and the United States), and on the other hand, women, young people, and immigrants from these communities. The study will have several target populations. Firstly, the target is nursing students, with whom the aim is to define their perspective on the sexuality content taught at the university, and their level of knowledge. Secondly university professors and health professionals, with whom we will check their perspective on sexuality in the classroom, as well as their level of knowledge in this field. And finally, we will work with the community (women, young people, and immigrants) to whom we will try to bring sexuality from a useful and enjoyable perspective. In order to measure these variables in the protocol, instruments such as questionnaires and semi-structured interviews will be used. During data collection, ethical principles will be guaranteed and informed consent will be requested from the participants.

Discussion

The results of the research will have a high curricular impact on the educational community, and will last over time, since the tools generated in the project will be included as part of nursing training programmes. In addition, participation in the project will improve health education for health professionals and at the community level on sexuality in both urban and rural populations.
Matching medical staff to long term care facilities to respond to COVID-19 outbreak
Authors: Zarei Hamid Reza , Ghanbarpour Mamaghani Mahsa , Ergun Ozlem , Yu Patricia , Winchester Leanne , Chen Elizabeth
Published: June 2023

Background

Staff shortage is a long-standing issue in long term care facilities (LTCFs) that worsened with the COVID-19 outbreak. Different states in the US have employed various tools to alleviate this issue in LTCFs. We describe the actions taken by the Commonwealth of Massachusetts to assist LTCFs in addressing the staff shortage issue and their outcomes. Therefore, the main question of this study is how to create a central mechanism to allocate severely limited medical staff to healthcare centers during emergencies.

Methods

For the Commonwealth of Massachusetts, we developed a mathematical programming model to match severely limited available staff with LTCF demand requests submitted through a designed portal. To find feasible matches and prioritize facility needs, we incorporated restrictions and preferences for both sides. For staff, we considered maximum mileage they are willing to travel, available by date, and short- or long-term work preferences. For LTCFs, we considered their demand quantities for different positions and the level of urgency for their demand. As a secondary goal of this study, by using the feedback entries data received from the LTCFs on their matches, we developed statistical models to determine the most salient features that induced the LTCFs to submit feedback.

Results

We used the developed portal to complete about 150 matching sessions in 14 months to match staff to LTCFs in Massachusetts. LTCFs provided feedback for 2,542 matches including 2,064 intentions to hire the matched staff during this time. Further analysis indicated that nursing homes and facilities that entered higher levels of demand to the portal were more likely to provide feedback on the matches and facilities that were prioritized in the matching process due to whole facility testing or low staffing levels were less likely to do so. On the staffing side, matches that involved more experienced staff and staff who can work afternoons, evenings, and overnight were more likely to generate feedback from the facility that they were matched to.

Conclusion

Developing a central matching framework to match medical staff to LTCFs at the time of a public health emergency could be an efficient tool for responding to staffing shortages. Such central approaches that help allocate a severely limited resource efficiently during a public emergency can be developed and used for different resource types, as well as provide crucial demand and supply information in different regions and/or demographics.
Retrospective analysis of factors influencing the implementation of a program to address unprofessional behaviour and improve culture in Australian hospitals
Authors: Churruca Kate , Westbrook Johanna , Bagot Kathleen L , McMullan Ryan D , Urwin Rachel , Cunningham Neil , Mitchell Rebecca , Hibbert Peter , Sunderland Neroli , Loh Erwin , Taylor Natalie
Published: June 2023

Background

Unprofessional behaviour among hospital staff is common. Such behaviour negatively impacts on staff wellbeing and patient outcomes. Professional accountability programs collect information about unprofessional staff behaviour from colleagues or patients, providing this as informal feedback to raise awareness, promote reflection, and change behaviour. Despite increased adoption, studies have not assessed the implementation of these programs utilising implementation theory. This study aims to (1) identify factors influencing the implementation of a whole-of-hospital professional accountability and culture change program, Ethos, implemented in eight hospitals within a large healthcare provider group, and (2) examine whether expert recommended implementation strategies were intuitively used during implementation, and the degree to which they were operationalised to address identified barriers.

Method

Data relating to implementation of Ethos from organisational documents, interviews with senior and middle management, and surveys of hospital staff and peer messengers were obtained and coded in NVivo using the Consolidated Framework for Implementation Research (CFIR). Implementation strategies to address identified barriers were generated using Expert Recommendations for Implementing Change (ERIC) strategies and used in a second round of targeted coding, then assessed for degree of alignment to contextual barriers.

Results

Four enablers, seven barriers, and three mixed factors were found, including perceived limitations in the confidential nature of the online messaging tool (‘Design quality and packaging’), which had downstream challenges for the capacity to provide feedback about utilisation of Ethos (‘Goals and Feedback’, ‘Access to Knowledge and Information’). Fourteen recommended implementation strategies were used, however, only four of these were operationalised to completely address contextual barriers.

Conclusion

Aspects of the inner setting (e.g., ‘Leadership Engagement’, ‘Tension for Change’) had the greatest influence on implementation and should be considered prior to the implementation of future professional accountability programs. Theory can improve understanding of factors affecting implementation, and support strategies to address them.
Alcohol consumption and all-cause and cause-specific mortality among US adults: prospective cohort study
Authors: Tian Yalan , Liu Jiahui , Zhao Yue , Jiang Nana , Liu Xiao , Zhao Gang , Wang Xia
Published: June 2023

Background

Previous studies have shown inconsistent findings regarding the association of light to moderate alcohol consumption with cause-specific mortality. Therefore, this study sought to examine the prospective association of alcohol consumption with all-cause and cause-specific mortality in the US population.

Methods

This was a population-based cohort study of adults aged 18 years or older in the National Health Interview Survey (1997 to 2014) with linkage to the National Death Index records through December 31, 2019. Self-reported alcohol consumption was categorized into seven groups (lifetime abstainers; former infrequent or regular drinkers; and current infrequent, light, moderate, or heavy drinkers). The main outcome was all-cause and cause-specific mortality.

Results

During an average follow-up of 12.65 years, among the 918,529 participants (mean age 46.1 years; 48.0% male), 141,512 adults died from all causes, 43,979 from cardiovascular disease (CVD), 33,222 from cancer, 8246 from chronic lower respiratory tract diseases, 5572 from accidents (unintentional injuries), 4776 from Alzheimer’s disease, 4845 from diabetes mellitus, 2815 from influenza and pneumonia, and 2692 from nephritis, nephrotic syndrome, or nephrosis. Compared with lifetime abstainers, current infrequent, light, or moderate drinkers were at a lower risk of mortality from all causes [infrequent—hazard ratio: 0.87; 95% confidence interval: 0.84 to 0.90; light: 0.77; 0.75 to 0.79; moderate 0.82; 0.80 to 0.85], CVD, chronic lower respiratory tract diseases, Alzheimer’s disease, and influenza and pneumonia. Also, light or moderate drinkers were associated with lower risk of mortality from diabetes mellitus and nephritis, nephrotic syndrome, or nephrosis. In contrast, heavy drinkers had a significantly higher risk of mortality from all causes, cancer, and accidents (unintentional injuries). Furthermore, binge drinking ≥ 1 day/week was associated with a higher risk of mortality from all causes (1.15; 1.09 to 1.22), cancer (1.22; 1.10 to 1.35), and accidents (unintentional injuries) (1.39; 1.11 to 1.74).

Conclusions

Infrequent, light, and moderate alcohol consumption were inversely associated with mortality from all causes, CVD, chronic lower respiratory tract diseases, Alzheimer’s disease, and influenza and pneumonia. Light or moderate alcohol consumption might also have a beneficial effect on mortality from diabetes mellitus and nephritis, nephrotic syndrome, or nephrosis. However, heavy or binge had a higher risk of all-cause, cancer, and accidents (unintentional injuries) mortality.
Circular RNA hsa_circ_0064559 affects tumor cell growth and progression of colorectal cancer
Authors: Zhen Ya’nan , Sun Guodong , Chen Cunbao , Li Jianqi , Xiao Ruixue , Xu Zhongfa
Published: June 2023

Background

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC.

Methods

Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction.

Results

Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown.

Conclusions

The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy.
Histological transformation to signet-ring cell carcinoma in a patient with clinically aggressive poorly differentiated adenocarcinoma of the ascending colon after response to chemotherapy plus cetuximab: a case report
Authors: Nagano Hideki , Ohyama Shigekazu , Sato Atsushi , Igarashi Jun , Yamamoto Tomoko , Kadoya Masumi , Kobayashi Mikiko
Published: June 2023

Background

Alteration of chemosensitivity or tumor aggressiveness in response to chemotherapy has been reported, and liquid biopsy assessment during chemotherapy for colorectal cancers has confirmed the acquisition of mutations in various oncogenes. However, the occurrence of histological transformation seems to be extremely rare in colorectal cancers, and the few existing case reports of this transformation are from lung cancer and breast cancer. In this report, we describe the histological transformation of clinically aggressive scirrhous-type poorly differentiated adenocarcinoma of the ascending colon to signet-ring cell carcinoma in almost all recurrent tumors that were confirmed by autopsy after response to chemotherapy plus cetuximab.

Case presentation

A 59-year-old woman visited our hospital with whole abdominal pain and body weight loss and was diagnosed with scirrhous-type poorly differentiated adenocarcinoma of the ascending colon with aggressive lymph node metastases. The intrinsic chemosensitivity of the tumors was evident upon initiation of mFOLFOX6 plus cetuximab therapy, and right hemicolectomy was performed, and the tumor obviously remained in the peripancreatic area, paraaortic region, or other retroperitoneal areas. The ascending colon tumors mainly consisted of poorly differentiated adenocarcinoma and were not associated with signet-ring cell components except for minute clusters in a few lymphatic emboli in the main tumor. Chemotherapy was continued, and metastases were eliminated at 8 months after the operation; this response was maintained for an additional 4 months. Discontinuation of chemotherapy plus cetuximab resulted in immediate tumor recurrence and rapid expansion, and the patient died of the recurrent tumor 1 year and 2 months after the operation. Autopsy specimens revealed that almost all of the recurrent tumors exhibited transformation and consisted of signet-ring cell histology.

Conclusion

This case might suggest that various oncogene mutations or epigenetic changes resulting from chemotherapy, especially regimens that include cetuximab, contribute to the transformation of non-signet-ring cell colorectal carcinoma to signet-ring cell carcinoma histology and can promote the aggressive clinical progression characteristic of signet-ring cell carcinoma.
Significance of ypTNM stage in determining the prognosis and therapy after surgery for locally advanced rectal cancer
Authors: Chen Yue , Sun Jiayu , Dong Xinxin , Sun Deyu , Qu Yanli
Published: June 2023

Background

In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described.

Methods

This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis.

Results

Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133–42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811–4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015–3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728–2.806, P = 0.294).

Conclusions

We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.
Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases
Authors: Rzepka Dinah , Schenker Hannah , Geinitz Hans , Silberberger Elisabeth , Kaudewitz Dorothee , Schuster Barbara , Kuhlmann Lukas , Schonath Miriam , Ayala Gaona Horacio , Aschacher Bernhard , Fietkau Rainer , Schett Georg , Distel Luitpold
Published: June 2023

Background

The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy.

Methods

Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed.

Results

Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established.

Conclusions

It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.
Establishment and validation of a prognostic pomogram in unresectable hepatocellular carcinoma treated with intensity modulated radiotherapy: a real world study
Authors: Long Meiying , Li Jianxu , He Meiling , Qiu Jialin , Zhang Ruijun , Liu Yingchun , Liang Chunfeng , Lu Haiyan , Pang Yadan , Zhou Hongmei , Yu Hongping , Qiu Moqin
Published: June 2023

Background

To establish a prognostic model to predict the overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with intensity modulated radiotherapy (IMRT).

Methods

The unresectable HCC patients treated with IMRT were retrospectively analyzed and randomized into development cohort (n = 237) and validation cohort (n = 103) in a 7:3 ratio. We developed a prognosis model with the multivariate Cox regression analysis in the development cohort to derive the predictive nomogram, which was then validated in the validation cohort. Model performance was evaluated by the c-index, the area under curve(AUC) and the calibration plot.

Results

A total of 340 patients were enrolled. Tumor numbers > 3 (HR = 1.69, 95% CI = 1.21–2.37), AFP ≥ 400 ng/ml (HR = 1.52, 95% CI = 1.10–2.10), PLT < 100 × 10^9(HR = 1.7495% CI = 1.11–2.73), ALP > 150U/L (HR = 1.65, 95% CI = 1.15–2.37) and prior surgery (HR = 0.63, 95% CI = 0.43–0.93) were independent prognostic factors. The nomogram based on independent factors was constructed. The c-index for OS prediction was 0.658 (95% CI, 0.647–0.804) and 0.683 (95% CI, 0.580–0.785) in the development and validation cohort, respectively. The nomogram demonstrated good discriminative ability with AUC rates of 0.726, 0.739 and 0.753 at 1-year, 2-year and 3-year models in the development cohort, and 0.715, 0.756 and 0.780 in the validation cohort, respectively. Additionally, good prognostic discrimination of the nomogram is also reflected in stratifying patients into two subgroups with distinct prognosis.

Conclusions

We constructed a prognostic nomogram for predicting the survival of patients with unresectable HCC treated with IMRT.
Identification of Fangjihuangqi Decoction as a late-stage autophagy inhibitor with an adjuvant anti-tumor effect against non-small cell lung cancer
Authors: Chen Qiugu , Liao Yuan , Liu Yujiao , Song Yue , Jiang Junbo , zhang Zhen , Li Anqi , zheng Mengyi , Chen Xiaoyi , Zhao Tingxiu , Gu Jiangyong , Tan Yuhui , Liu Xiaoyi , Jiang Yanjun , Wang Kun , Yi Hua , Xiao Jianyong , Hu Shan
Published: June 2023

Background

Clinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells.

Methods

We observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ.

Results

We observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC.

Conclusion

Collectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells.
Infiltrating myeloid cell diversity determines oncological characteristics and clinical outcomes in breast cancer
Authors: Yang Chenxuan , Liu Jiaxiang , Zhao Shuangtao , Shang Qingyao , Ren Fei , Feng Kexin , Zhang Ruixuan , Kang Xiyu , Wang Xin , Wang Xiang
Published: June 2023

Background

Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast cancer tumor microenvironment (TME), target therapies that harness the anti-tumor potential of myeloid cells are currently being evaluated in clinical trials. However, the landscape and dynamic transition of myeloid cells in breast cancer TME are still largely unknown.

Methods

Myeloid cells were characterized in the single-cell data and extracted with a deconvolution algorithm to be assessed in bulk-sequencing data. We used the Shannon index to describe the diversity of infiltrating myeloid cells. A 5-gene surrogate scoring system was then constructed and evaluated to infer the myeloid cell diversity in a clinically feasible manner.

Results

We dissected the breast cancer infiltrating myeloid cells into 15 subgroups including macrophages, dendritic cells (DCs), and monocytes. Mac_CCL4 had the highest angiogenic activity, Mac_APOE and Mac_CXCL10 were highly active in cytokine secretion, and the DCs had upregulated antigen presentation pathways. The infiltrating myeloid diversity was calculated in the deconvoluted bulk-sequencing data, and we found that higher myeloid diversity was robustly associated with more favorable clinical outcomes, higher neoadjuvant therapy responses, and a higher rate of somatic mutations. We then used machine learning methods to perform feature selection and reduction, which generated a clinical-friendly scoring system consisting of 5 genes (C3, CD27, GFPT2, GMFG, and HLA-DPB1) that could be used to predict clinical outcomes in breast cancer patients.

Conclusions

Our study explored the heterogeneity and plasticity of breast cancer infiltrating myeloid cells. By using a novel combination of bioinformatic approaches, we proposed the myeloid diversity index as a new prognostic metric and constructed a clinically practical scoring system to guide future patient evaluation and risk stratification.

Graphical Abstract
Global posture reeducation compared with segmental muscle stretching exercises in the treatment of fibromyalgia: a randomized controlled trial
Authors: Matsutani Luciana Akemi , Sousa do Espírito Santo Adriana de , Ciscato Marina , Yuan Susan Lee King , Marques Amelia Pasqual
Published: June 2023

Background

Muscle stretching exercises preserve corporal flexibility and decrease the retraction and shortening of myofascial and articular structures. These exercises are recommended for the treatment of fibromyalgia (FM). The purpose of the study was to verify and compare the effect of muscle stretching exercises on FM patients based on the global posture reeducation method against segmental muscle stretching exercises, both used in concert with an educational approach rooted in cognitive behavioral therapy.

Methods

Forty adults with FM were randomly allocated into two groups: global and segmental. The two kinds of therapies were performed in 10 individual sessions once a week. Two assessments were made: one at baseline and one at the end of therapy. The primary outcome variable was pain intensity (Visual Analog Scale). The secondary outcome variables were multidimensional pain (McGill Pain Questionnaire), the pain threshold at tender points (dolorimetry), attitudes toward chronic pain (Survey of Pain Attitudes-Brief Version), body posture (Postural Assessment Software Protocol), postural control (Modified Clinical Test of Sensory Interaction on Balance), flexibility (sit-and-reach test), the impact of FM on quality of life (Fibromyalgia Impact Questionnaire, FIQ), and self-reported perceptions and body self-care.

Results

At the end of treatment, there were no statistically significant differences between the groups in the outcome variables. Furthermore, the groups presented lower pain intensity (baseline vs. final; global group: 6 ± 1.8 vs. 2.2 ± 1.6 cm, p<0.01; segmental group: 6.3 ± 2.1 vs. 2.5 ± 1.7 cm, p<0.01), higher pain threshold (p ≤ 0.01), lower total FIQ score (p < 0.01), and greater postural control (p < 0.01) after treatment.

Conclusions

Muscle stretching exercises based on global posture reeducation and segmental muscle stretching exercises, both used in concert with an educational approach rooted in cognitive behavioral therapy, reduced the pain intensity and impact of FM on quality of life. These exercises also improved FM patients’ pain threshold at tender points, attitudes toward chronic pain, and postural control. There were no differences between global posture reeducation and segmental muscle stretching exercises.

Trial registration

ClinicalTrials.gov NCT02384603. Registered on 10 March 2015.
The genetic structure of populations of Isthmiophora melis (Schrank, 1788) (Digenea: Echinostomatidae). Does the host’s diet matter?
Authors: Zaleśny Grzegorz , Kanarek Gerard , Pyrka Ewa , Kołodziej-Sobocińska Marta , Zalewski Andrzej , Hildebrand Joanna
Published: June 2023

Background

Here we provide a comparative analysis of the genetic structure of populations (based on nad1 mtDNA) of Isthmiophora melis isolated from the American mink (Neogale vison), an introduced invasive species, commonly occurring in the territory of Poland, and from the striped field mouse (Apodemus agrarius).

Methods

A total of 133 specimens of I. melis were obtained from naturally infected N. vison collected from six localities in Poland (108 samples) and 25 individuals of I. melis from A. agrarius. All sequences of the nad1 gene obtained during the present study were assembled and aligned. The standard statistics for haplotype composition, i.e., the number of haplotypes, haplotype diversity, nucleotide diversity, and average number of nucleotide differences, were calculated. Haplotype analysis and visualization of haplotype frequency among populations were performed using a median-joining network.

Results

Based on the samples collected from different localities in Poland, our study revealed that the overall genetic diversity of I. melis isolated from the American mink and of the striped field mouse do not differ significantly. The median-joining network showed that the three main haplotypes are in the centre of a star-like structure, with the remaining haplotypes as the satellites, reflecting the recent expansion of the populations.

Conclusions

The overall genetic diversity of I. melis isolated from the American mink and striped field mouse reveals a high level of homogeneity. Moreover, regional differences in the food composition of the definitive hosts play an important role in shaping the genetic structure of the trematode populations.

Graphical Abstract
Silencing LncRNA SNHG16 suppresses the diabetic inflammatory response by targeting the miR-212-3p/NF-κB signaling pathway
Authors: Huang Linjuan , Xiong Shengxi , Liu Hanshuang , Zhang Ranran , Wu Ying , Hu Xiaolei
Published: June 2023

Background

Long noncoding RNAs (LncRNAs) have been identified to play an important role in diabetes. The aim of the present study was to determine the expression and function of small nucleolar RNA host gene 16 (SNHG16) in diabetic inflammation.

Methods

For the in vitro experiments, quantitative real-time PCR (qRT-PCR), Western blotting and immunofluorescence were used to detect LncRNA SNHG16 expression in the high-glucose state. The potential microRNA sponge target of LncRNA SNHG16, miR-212-3p, was detected by dual-luciferase reporter analysis and qRT-PCR. For the in vivo experiments, glucose changes in mice were detected after si-SNHG16 treatment, and SNHG16 and inflammatory factor expression in kidney tissues were detected by qRT-PCR and immunohistochemistry.

Results

LncRNA SNHG16 was upregulated in diabetic patients, HG-induced THP-1 cells, and diabetic mice. Silencing SNHG16 inhibited the diabetic inflammatory response and the development of diabetic nephropathy. miR-212-3p was found to be directly dependent on LncRNA SNHG16. miR-212-3p could inhibitor P65 phosphorylation in THP-1 cells. The miR-212-3p inhibitor reversed the action of si-SNHG16 in THP-1 cells and induced an inflammatory response in THP-1 cells. LncRNA SNHG16 was also found to be higher in the peripheral blood of diabetic patients than in the normal person. The area under the ROC curve is 0.813.

Conclusion

These data suggested that silencing LncRNA SNHG16 suppresses diabetic inflammatory responses by competitively binding miR-212-3p to regulate NF-κB. LncRNA SNHG16 can be used as a novel biomarker for patients with type 2 diabetes.
Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study
Authors: Liu Hailang , Wu Wei , Xiang Wei , Yuan Jingdong
Published: June 2023

Background

Previous observational studies have reported that lifestyle factors, metabolic factors and socioeconomic status are associated with the development of female pelvic organ prolapse (POP); however, whether these associations are causal remains unclear. The current study aimed to assess the causal effect of lifestyle factors, metabolic factors and socioeconomic status on POP risk.

Methods

We conducted a two-sample Mendelian randomization (MR) study based on summary-level data from the largest available genome-wide association studies (GWAS) to evaluate whether lifestyle factors, metabolic factors and socioeconomic status are causally related to POP. We used single nucleotide polymorphisms that are strongly associated with exposure at the genome-wide significance level (P < 5 × 10–8) as instrumental variables from genome-wide association studies. The method of random-effect inverse-variance weighting (IVW) was used as the primary analysis method, supplemented with the weighted median, MR-Egger and the MR pleiotropy residual sum and outlier applied to verify the MR assumptions. Two-step MR was conducted to investigate potential intermediate factors that are on the causal pathway from exposure to POP.

Results

There were associations with POP for genetically predicted waist-to-hip ratio (WHR) (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01–1.03 per SD-increase, P < 0.001), WHR adjusted for body mass index (WHRadjBMI) (OR 1.017, 95% CI 1.01–1.025 per SD-increase, P < 0.001) and education attainment (OR 0.986, 95% CI 0.98–0.991 per SD-increase) in the meta-analysis. Additionally, genetically predicted coffee consumption (OR per 50% increase 0.67, 95% CI 0.47–0.96, P = 0.03), vigorous physical activity (OR 0.83, 95% CI 0.69–0.98, P = 0.043) and high-density lipoprotein cholesterol (HDL-C) (OR 0.91, 95% CI 0.84–0.98 per SD-increase, P = 0.049) were inversely associated with POP in the FinnGen Consortium. The mediation analysis showed that the indirect effects of education attainment on POP were partly mediated by WHR and WHRadjBMI, with a mediated proportion of 27% and 13% in the UK Biobank study, respectively.

Conclusions

Our study provides MR evidence of a robust causal association of WHR, WHRadjBMI and education attainment with POP.
CLOCK inhibits the proliferation of porcine ovarian granulosa cells by targeting ASB9
Authors: Huang Liang , Yuan Huan , Shi Shengjie , Song Xiangrong , Zhang Lutong , Zhou Xiaoge , Gao Lei , Pang Weijun , Yang Gongshe , Chu Guiyan
Published: June 2023

Background

Clock circadian regulator (CLOCK) is a core factor of the mammalian biological clock system in regulating female fertility and ovarian physiology. However, CLOCK's specific function and molecular mechanism in porcine granulosa cells (GCs) remain unclear. In this study, we focused on CLOCK’s effects on GC proliferation.

Results

CLOCK significantly inhibited cell proliferation in porcine GCs. CLOCK decreased the expression of cell cycle-related genes, including CCNB1, CCNE1, and CDK4 at the mRNA and protein levels. CDKN1A levels were upregulated by CLOCK. ASB9 is a newly-identified target of CLOCK that inhibits GC proliferation; CLOCK binds to the E-box element in the ASB9 promoter.

Conclusions

These findings suggest that CLOCK inhibits the proliferation of porcine ovarian GCs by increasing ASB9 level.
Circumstances, policing, and attrition of multiple compared to single perpetrator rape cases within the South African criminal justice system
Authors: Machisa Mercilene Tanyaradzwa , Jina Ruxana , Labuschagne Gerard , Vetten Lisa , Loots Lizle , Jewkes Rachel
Published: June 2023

Background

Research into the circumstances of rape, and criminal justice system responses, is pivotal to informing prevention and improving the likelihood of justice for victims. In this paper, we explore the differences in the circumstances of multiple-perpetrator rapes (MPRs) and single-perpetrator rapes (SPRs), their case management, and attrition, and describe areas for improvemensuplt around rape response within the South African criminal justice system.

Methods

The sample comprised 3952 rape cases reported to the South African Police Services (SAPS) in 2012, selected through a multi-stage random sampling of 172 police stations from a total of 1164 police stations in the nine provinces, followed by the random selection of cases from each station’s case list. Data were abstracted from police dockets, medico-legal examination forms, charge sheets, and trial transcripts. MPRs were defined as cases in which more than one perpetrator had sexual contact with the victim during a single incident, i.e., sexually assaulted or raped. Descriptive statistics and Chi-square tests for associations were used to compare MPRs and SPRs in circumstances of the rape, case management, and attrition.

Results

Seventeen percent of cases were MPRs. MPRs were comparably more violent crimes with a higher frequency of aggressive tactics employed by perpetrators, for example, abductions, firearms use, and threats to kill. Overall, cases were often poorly handled by police, and there were deviations from standard policing and investigation procedures; we found more evidence of this with MPRs compared to SPRs. MPR cases were most likely to have been closed by police due to undetected perpetrators in combination with other victim reasons. The weaker investigations of MPRs were associated with higher attrition rates compared to SPRs, firstly at the police investigation and subsequent stages.

Conclusions

The findings confirm differences in case management, patterns of attrition and trajectories of MPRs compared to SPRs. In an overall context of high rape case attrition and impunity for perpetrators, MPR victims are even less likely to see justice served than SPR victims. There needs to be much more effective supervision of rape case investigations by SAPS, particularly in MPR cases. Continual investigator training strengthened supervision and better resourcing are necessary to improve MPRs detection and convictions in adherence to the Directives for rape policing.
3D Printed Orthopaedic External Fixation Devices: A Systematic Review
Authors: O’Connor Hunter A. , Adams Luke W. , MacFadden Lisa N. , Skelley Nathan Wm.
Published: June 2023

Background

External fixators are complex, expensive orthopaedic devices used to stabilize high-energy and complex fractures of the extremities. Although the technology has advanced dramatically over the last several decades, the mechanical goals for fracture stabilization of these devices have remained unchanged. Three-dimensional (3D) printing technology has the potential to advance the practice and access to external fixation devices in orthopaedics. This publication aims to systematically review and synthesize the current literature on 3D printed external fixation devices for managing orthopaedic trauma fractures.

Methods

The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols were followed for this manuscript with minor exceptions. PubMed, Embase, Cochrane Review, Google Scholar, and Scopus online databases were systematically searched. Two independent reviewers screened the search results based on predetermined inclusion and exclusion criteria related to 3D printing and external fixation of fractures.

Results

Nine studies met the inclusion criteria. These included one mechanical testing study, two computational simulation studies, three feasibility studies, and three clinical case studies. Fixator designs and materials varied significantly between authors. Mechanical testing revealed similar strength to traditional metal external fixators. Across all clinical studies, five patients underwent definitive treatment with 3D printed external fixators. They all had satisfactory reduction and healing with no reported complications.

Conclusions

The current literature on this topic is heterogeneous, with highly variable external fixator designs and testing techniques. A small and limited number of studies in the scientific literature have analyzed the use of 3D printing in this area of orthopaedic surgery. 3D printed external fixation design advancements have yielded promising results in several small clinical case studies. However, additional studies on a larger scale with standardized testing and reporting techniques are needed.
A systematic review of the print media representation of ketamine treatments for psychiatric disorders
Authors: Thornton Nicollette L. R. , Kawalsky Jason , Milton Alyssa , Klinner Christiane , Schokman Aaron , Stratton Elizabeth , Loo Colleen K. , Glozier Nick
Published: June 2023

Background

Public and patient expectations of treatment influence health behaviours and decision-making.

Aims

We aimed to understand how the media has portrayed the therapeutic use of ketamine in psychiatry.

Method

We systematically searched electronic databases for print and online news articles about ketamine for psychiatric disorders. The top ten UK, USA, Canadian and Australian newspapers by circulation and any trade and consumer magazines indexed in the databases were searched from 2015 to 2020. Article content was quantitatively coded with a framework encompassing treatment indication, descriptions of prior use, references to research, benefits and harms, treatment access and process, patient and professional testimony, tone and factual basis.

Results

We found 119 articles, peaking in March 2019 when the United States Food and Drug Administration approved esketamine. Ketamine treatment was portrayed in an extremely positive light (n= 82, 68.9%), with significant contributions of positive testimony from key opinion leaders (e.g. clinicians). Positive research results and ketamine's rapid antidepressant effect (n= 87, 73.1%) were frequently emphasised, with little reference to longer-term safety and efficacy. Side-effects were frequently reported (n= 96, 80.7%), predominantly ketamine's acute psychotomimetic effects and the potential for addiction and misuse, and rarely cardiovascular and bladder effects. Not infrequently, key opinion leaders were quoted as being overly optimistic compared with the existing evidence base.

Conclusions

Information pertinent to patient help-seeking and treatment expectations is being communicated through the media and supported by key opinion leaders, although some quotes go well beyond the evidence base. Clinicians should be aware of this and may need to address their patients’ beliefs directly.