bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Worst-Case Scenario”: Recovery Between Repeated High-Intensity Efforts in Rugby League Match-Play
Authors: Gabbett Tim J.
Published: December 2022

Background:

Repeated high-intensity effort (RHIE) activity is known to be a critical component of high-intensity, intermittent team sports. Despite the importance of this quality, there are few studies comparing the RHIE activity of higher- and lower-ranked teams competing in the same competition. This study characterized the distribution of recovery times between RHIE in Top 4 and Bottom 4 semi-elite rugby league players.

Hypothesis:

Players from Top 4 teams will engage in a greater frequency of RHIE bouts than Bottom 4 teams, with shorter recovery periods between consecutive efforts.

Study Design:

Cohort study.

Methods:

A total of 104 semi-elite rugby league players from 11 teams wore global positioning system units during 28 Queensland Cup rugby league matches. Recovery between efforts was classified as <10, 11 to 20, 21 to 30, 31 to 60, and 61 to 120 seconds.

Results:

The majority of RHIE bouts were performed with ≤10 seconds recovery between efforts for both Top 4 and Bottom 4 teams. Top 4 teams performed a greater proportion of RHIE bouts with ≤10 seconds recovery between efforts than Bottom 4 teams (effect size [ES], 0.27 ± 0.19), while only trivial differences (ES, 0.17 ± 0.20) were found between Top 4 and Bottom 4 teams for the proportion of RHIE with 61 to 120 seconds recovery between efforts. Wide-running forwards from Top 4 teams performed a greater proportion of RHIE bouts with ≤10 seconds recovery between efforts (ES, 0.59 ± 0.40) and a smaller proportion of RHIE bouts with 61 to 120 seconds recovery between efforts (ES, 0.62 ± 0.38) than wide-running forwards from Bottom 4 teams.

Conclusion:

Rugby league players perform proportionally more RHIE bouts with ≤10 seconds recovery between efforts than any other recovery duration. In addition, Top 4 teams are more likely to complete a greater proportion of short (≤10 seconds) recovery RHIE bouts than Bottom 4 teams.

Clinical Relevance:

These findings demonstrate the demanding nature of RHIE activity in rugby league. To be successful, teams should train for these demanding passages of play.
Defining working time versus rest time: An analysis of the recent CJEU case law on stand-by time
Authors: Mitrus Leszek
Published: December 2022

The article explores the evolution of the CJEU jurisprudence following on from the Matzak case. It provides an analysis of the most recent judgments on stand-by time, including those in case C-344/19 Radiotelevizija Slovenija, case C-580/19 Stadt Offenbach am Main, case C-107/19 Dopravní podnik hl. m. Prahy, and case C-214/20 Dublin City Council. The disputes concerned workers on stand-by duty who were not required to be physically present at the location expressly designated by the employer, but were expected to resume work within a short or very short period of time if necessary. In order to classify stand-by periods as working time or rest periods under the Directive 2003/88, the CJEU analyses whether the constraints imposed on the worker are such as to affect, objectively and very significantly, the possibility for the latter freely to manage the time during which his or her professional services are not required and to pursue his or her own interests. Moreover, the CJEU requires that employers cannot establish periods of stand-by time that are so long or so frequent that they constitute a risk to the safety or health of workers, irrespective of those periods being classified as rest periods. In the author's opinion, the required response time is a decisive and most important factor in the assessment. If the reaction period is very short, then in principle the stand-by time constitutes working time. Where the situation is not prima facie clear, additional secondary criteria should be taken into account. The factors that fall within the scope of an employer's managerial competences and pertain to an organisation's operational needs, and also the type of work performed by the worker, are relevant in assessing the legal characterisation of a particular stand-by period. The evaluation should not be affected by factors that remain beyond employer's control, e.g., the location of the workplace, the worker's residence, and distance between them.
A reappraisal of the phylogeny and historical biogeography of Sparganium (Typhaceae) using complete chloroplast genomes
Authors: Zhang Qiaoyu , Belyakov Eugeny A. , Lapirov Alexander G. , Zhao Yixuan , Freeland Joanna , Xu Xinwei
Published: December 2022

Background

Sparganium (Typhaceae) is a widespread temperate genus of ecologically important aquatic plants. Previous reconstructions of the phylogenetic relationships among Sparganium species are incompletely resolved partly because they were based on molecular markers comprising < 7,000 bp. Here, we sequenced and assembled the complete chloroplast genomes from 19 Sparganium samples representing 15 putative species and three putative subspecies in order to explore chloroplast genome evolution in this genus, clarify taxonomic lineages, estimate the divergence times of Sparganium species, and reconstruct aspects of the biogeographic history of the genus.

Results

The 19 chloroplast genomes shared a conserved genome structure, gene content, and gene order. Our phylogenomic analysis presented a well-resolved phylogeny with robust support for most clades. Non-monophyly was revealed in three species: S. erectum, S. eurycarpum, and S. stoloniferum. Divergence time estimates suggest that the two subgenera of Sparganium split from each other ca. 30.67 Ma in the middle Oligocene. The subgenus Xanthosparganium diversified in the late Oligocene and Miocene, while the subgenus Sparganium diversified in the late Pliocene and Pleistocene. Ancestral area reconstruction suggested that the two subgenera may have originated in East Eurasia and North America.

Conclusion

The non-monophyletic nature of three putative species underscores the necessity of taxonomic revision for Sparganium: S. stoloniferum subsp. choui may be more appropriately identified as S. choui, and subspecies of S. erectum may be in fact distinct species. The estimated diversification times of the two subgenera correspond to their species and nucleotide diversities. The likely ancestral area for most of subgenus Xanthosparganium was East Eurasia and North America from where it dispersed into West Eurasia and Australia. Most of subgenus Sparganium likely originated in North America and then dispersed into Eurasia. Our study demonstrates some of the ways in which complete chloroplast genome sequences can provide new insights into the evolution, phylogeny, and biogeography of the genus Sparganium.
Two-dimensional speckle tracking echocardiography help identify breast cancer therapeutics–related cardiac dysfunction
Authors: Liu Wei , Li Wei , Li Hairu , Li Ziyao , Zhao Peng , Guo Zihong , Liu Cong , Sun Litao , Wang Zhenzhen
Published: December 2022

Background

Cancer therapeutics–related cardiac dysfunction (CTRCD) from different chemotherapy strategies are underdetermined by echocardiography. As an imaging marker of subclinical cardiac dysfunction, two-dimensional speckle tracking echocardiography (2D-STE) may assist in identifying the impact patterns of different CTRCD.

Methods

A total of 67 consecutive patients with invasive ductal breast carcinoma who will undertake neoadjuvant chemotherapy were enrolled and grouped according to their different chemotherapy regimens based on their biopsy results. Group A included 34 patients who received anthracycline without trastuzumab, whereas Group B had 33 patients who received trastuzumab without anthracycline. Echocardiography was performed at three time-points, i.e., baseline (T0), cycle-2 (T2), and cycle-4 (T4) of chemotherapy. Conventional echocardiographic measurements and 2D-STE strain values, and myocardial work (MW) parameters, were compared between different groups at different time-points.

Results

The mean age had no statistical difference between the two groups. E/e′ was the only conventional echocardiographic parameter that had variation in group A (P < 0.05). Compared with baseline, GLS in group A decreased at T2, and GCS decreased at T4 (P < 0.05). GLS and GCS in group B both decreased at T4 (P < 0.05). More patients in group A had a more than 15% fall of baseline GLS rather than GCS at T2 (P < 0.05), however, there was no difference of either GLS or GCS decline rate at T4 between the two groups. All the MW parameters in group A had variations overtime, whereas only GCW in group B (P < 0.05).

Conclusion

Early subclinical myocardial dysfunction can be identified by 2D-STE in breast cancer patients with chemotherapy, and GLS provides profound value in demonstrating the temporal changes in early myocardial damage induced by anthracycline. LV contractility injury in patients with trastuzumab may be mild at first but increases in severity with exposure time as early as cycle-4. Awareness of these differences may help to stratify the prevention of late cardiovascular events caused by different CTRCDs. In addition, GCW may be the most sensitive myocardial work parameter of CTRCD.
Seizure from water intoxication following bowel preparation: a case report
Authors: Chiang Ting-Hsuan , Tan Jui-Hsiang , Chang Chun-Chao , Fang Kuan-Chieh
Published: December 2022

Background

Bowel preparation prior to colonoscopic examination is generally considered a safe process. Hyponatremia is a complication that has been reported in literature during bowel preparation. Individuals who develop severe symptomatic hyponatremia are often older and have comorbidities such as hypothyroidism, chronic kidney disease, or adrenal insufficiency. However, other mechanisms and circumstances can also lead to this potentially fatal complication.

Case presentation

We present a unique case of a patient who developed seizure prior to colonoscopy due to acute hyponatremia without any well-known risk factors. With the subsequent diagnosis of water intoxication, the use of desmopressin was believed to have contributed to this serious complication.

Conclusion

In addition to the use of certain well-documented medications and the presence of comorbidities that can lead to hyponatremia, clinicians should also be aware of the use of desmopressin as an important risk factor. Thorough history taking can guide individualized bowel preparation regimens to minimize the risk of undesired complications.
Comparison of clinical effects between early follicular prolonged GnRH agonist protocol and GnRH antagonist protocol in 3310 cycles: a retrospective study
Authors: Gui Juan , Ni Yuan , Liu Qian , Wang Xiaochen , Xie Qingzhen
Published: December 2022

Background

It is the duty of doctors to choose a safe, simple, economic and effective controlled ovulation stimulation (COS) protocol for the patients. This study aims to compare the clinical effects of the early follicular prolonged GnRH agonist (EFPL) and GnRH antagonist (GnRH-Ant) protocols, hoping to provide some reference for clinicians when choosing COS program.

Methods

A retrospective study included 3310 ovum pick up cycles undergoing assisted reproductive technology during January 2019 to May 2022 in Renmin Hospital of Wuhan University. Propensity Score Matching (PSM) and multivariable logistic regression analysis were used to improve the comparability between the two protocols. Subgroups were divided according to age, body mass index (BMI) and anti-Mullerian hormone (AMH). The live birth rate (LBR) and clinical pregnancy rate (CPR) were the primary outcomes.

Results

After PSM, the endometrial thickness, fresh embryo transplantation rate, chemical pregnancy rate, CPR were significantly higher in EFPL group than that in GnRH-Ant group (P < 0.001). The E2, LH, P values on trigger day were significantly lower in EFPL group (P < 0.001). The cycle cancellation rate was significantly reduced in EFPL group (P < 0.001). However, the total amount of Gn and duration of Gn were significantly increased in the EFPL group (P < 0.001). Multivariable logistic regression analysis showed that the LBR was significantly higher in EFPL group after matching [OR (95%CI), 1.86 (1.13, 3.05), P = 0.02], especially for those with age < 35 years [OR (95%CI), 1.95 (1.14, 3.34), P = 0.02], BMI < 24 kg/m2 [OR (95%CI), 2.08 (1.14, 3.80), P = 0.02], AMH levels ≥ 4.5 ng/ml [OR (95%CI), 4.19 (1.53, 11.43), P < 0.01].

Conclusion

EFPL regimen is more suitable to elicit live birth for those young patients with BMI < 24 kg/m2 and AMH ≥ 4.5 ng/ml. However, for patients with decreased ovarian reserve or advanced age, EFPL regimen has no advantage over the GnRH-Ant regimen.
Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface
Authors: Yang Menglu , Lennikov Anton , Chang Karen , Ashok Ajay , Lee Cherin , Cho Kin-Sang , Utheim Tor Paaske , Dartt Darlene A. , Chen Dong Feng
Published: December 2022

Purpose

Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown.

Method

TcES or transpalpebral ES (TpES) was conducted in C57BL6j mice for 14 days. The contralateral eyes were used as non-stimulated controls. Levels of intracellular [Ca2+] ([Ca2+]i) were assessed by Fura-2AM. The conductance resistances of the eye under various ES conditions were measured in vivo by an oscilloscope.

Results

Although TcES did not affect tear production, it significantly induced damage to the ocular surface, as revealed by corneal fluorescein staining that was accompanied by significantly decreased mucin (MUC) 4 expression compared to the control. Similar effects of ES were detected in cultured primary corneal epithelium cells, showing decreased MUC4 and ZO-1 levels after the ES in vitro. In addition, TcES decreased secretion of MUC5AC from the conjunctiva in vivo, which was also corroborated in goblet cell cultures, where ES significantly attenuated carbachol-induced [Ca2+]i increase. In contrast to TcES, transpalpebral ES (TpES) did not induce corneal fluorescein staining while significantly increasing tear production. Importantly, the conductive resistance from orbital skin to the TpES was significantly smaller than that from the cornea to the retina in TcES.

Conclusion

TcES, but not TpES, induces corneal epithelial damage in mice by disrupting mucin homeostasis. TpES thus may represent a safer and more effective ES approach for treating retinal neurodegeneration clinically.
Neutrophil CD64 index for diagnosis of infectious disease in the pediatric ICU: a single-center prospective study
Authors: Cao Lu-Lu , Wang Wei-Wei , Zhao Li , Li Ji-Ru , Kong Xiang-Mei , Zhu Yue-Niu , Zhu Xiao-Dong
Published: December 2022

Background

Infection is a major cause of death in children, and it is particularly important to identify biological indicators of early infection. Previous studies showed that the neutrophil CD64 (nCD64) index may be a useful biomarker for infection. The purpose of this study was to investigate use of the nCD64 index to identify infection in children from a pediatric ICU (PICU) in China.

Methods

This prospective observational study enrolled 201 children who were admitted to our PICU and were divided into an infection group and a non-infection group. In each patient, C-reactive protein (CRP), nCD64 index, procalcitonin (PCT), and white blood cell count were measured during the first 24 h after admission. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity, specificity, and diagnostic value of the nCD64 index for infection.

Results

Among all 201 children, the infection group had greater levels of CRP, nCD64 index, and PCT (all p < 0.05). ROC analysis indicated the nCD64 index had a sensitivity of 68.8%, specificity of 90.7%, accuracy of 80.5%, and an optimal cut-off value of 0.14, which had better diagnostic value than CRP or PCT. For children with postoperative fever, the nCD64 index also distinguished systemic inflammatory response syndrome (SIRS) from infection with accuracy of 79%.

Conclusions

The nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU.
The effect of the demonstration-based progressive muscle relaxation technique on stress and anxiety in nurses caring for COVID-19 patients: a randomized clinical trial
Authors: Ganjeali Samaneh , Farsi Zahra , Sajadi Seyedeh Azam , Zarea Kourosh
Published: December 2022

Background

Caring for patients with coronavirus disease 2019 (COVID-19) challenges nurses and causes them to experience stress and anxiety. From this perspective, it is of utmost importance to develop quick and effective intervention strategies to prevent numerous complications. This study aimed to investigate the effect of the progressive muscle relaxation technique, using the demonstration method on the stress and anxiety of nurses who care for COVID-19 patients.

Methods

This randomized clinical trial was conducted in 2021. Forty-six nurses working in two referral hospitals with wards for COVID-19 patients in Tehran, Iran recruited by convenience sampling method and then randomly assigned to experimental or control groups. The nurses in the experimental group educated the progressive muscle relaxation by the demonstration method, and they were encouraged to practice it. The Depression Anxiety Stress Scale-21 was utilized to measure the stress and anxiety levels in the nurses.

Results

Before the intervention, the levels of stress in the experimental and control groups were 13.91 ± 2.41 vs. 14.34 ± 2.74 (p = 0.571), and their anxiety was 13.34 ± 3.41 vs. 12.78 ± 2.21 (p = 0.510), respectively. After the intervention, the levels of stress in the experimental and control groups were 10.95 ± 2.01 vs. 14.17 ± 2.34 (p < 0.001), and their anxiety was 9.47 ± 2.37 vs. 12.91 ± 1.85 (p < 0.001), respectively. Moreover, the levels of stress and anxiety in the experimental group significantly diminished after intervention (p < 0.001), but no significant changes were observed in the control group (p > 0.05).

Conclusion

Concerning the effectiveness of the progressive muscle relaxation technique in relieving the stress and anxiety of the nurses caring for COVID-19 patients, it is suggested to include this relaxation technique in nursing courses.
Impact of social and cultural factors on incidence, transmission and control of Coronavirus disease in Iran: a qualitative study
Authors: Falla-Aliabadi Saeed , Heydari Ahad , Fatemi Farin , Yoshany Nooshin , Lotfi Mohammad Hasan , Sarsangi Alireza , Hanna Fahad
Published: December 2022

Introduction

COVID-19 pandemic has had mixed reactions from nations, people and governments about ways to cope with, prevent and control the disease. The current study identifies social, cultural and policy factors affecting the incidence and control of Coronavirus disease in Iran.

Methods

A qualitative study consists of content analysis as well as the views of 20 experienced and knowledgeable subjects specialized in social and cultural health management. The data were gathered using three semi-structured interviews and then continued by 17 semi-structured interviews. Data analysis was done using Graneheim approach. After each interview, the recorded audio files transcript and reviewed. Then codes extracted and divided to categories and sub-categories.

Results

There are distinct social and cultural factors in coping with Coronavirus disease. These consisted of three categories of governance, individual and community related factors. A total of 17 subcategories and 215 primary codes that were extracted from the text of interviews as variables of the study and in relation to the research question. Ten subdomains of governance including vaccination, political issues, knowledge, support services, administrative services, transportation, health and treatment, culturalization, legislation and, managerial and financial policies impacted the spread and mitigation of the pandemic at various levels.

Conclusion

The management of pandemics requires a comprehensive capacity for identifying and determining social and cultural criteria. A healthy partnership between governments and the community may be required to remove unnecessary obstacles that hinder public health attempt to alleviate the risk. The obtained criteria and indicators from this study may be utilized by policy makers in an attempt to strengthen protocols for mitigating pandemics. Further studies may be warranted to confirm these findings.
Arthroscopic repair of rotator cuff injury with bioabsorbable suture anchor vs. all-suture anchor: a non-inferiority study
Authors: Di Gennaro Stefano , Lecce Domenico , Tarantino Alessio , De Cupis Mauro , Bassetti Erica , Scarnera Pierpaolo , Ciminello Enrico , Calvisi Vittorio
Published: December 2022

Background

Compare all-suture anchors to traditional anchors through clinical and radiological evaluation at pre-established end-points.

Materials and methods

We performed a two-arms non-inferiority study on all-suture anchor (2.3 iconix™, Stryker) device with respect to traditional anchor (5.5 healix Advance™ BR, Depuy/Mitek) device under unpaired samples with size equal to 30 patients per group, all suffering from supraspinatus tendon rupture. We administrated DASH (Disabilities of the Arm, Shoulder and Hand); constant; and SST (Simple Shoulder Test) questionnaires in pre-operative, 3 ± 1 months post-intervention and 8 ± 1 months post-intervention. Questionnaires scores were the primary outcome. We also evaluated RMI at 3 and at 8 months after surgery to assess the presence of oedema or any loosening of the implant.

Results

All-suture anchor approach has been proven to have non-inferior performances with respect to traditional anchor approach, according to questionnaires scores at the 3-month endpoint. We observed 26 patients with oedema by MRI (18 in control group, 6 in experimental group). In the 8-month endpoint we found persistent edema in 12 patients (all treated with healix), 2 had mobilitazions (healix), 10 had partial retears (8 healix, 2 iconix) and 1 implant failure (healix).

Conclusions

All suture devices have clinical and functional results comparable to traditional devices, while they tend to give fewer complications in terms of bone edema, loosening and retear rate. The effectiveness of all-suture devices should be further investigated in rotator cuff suture arthroscopic revision surgery, given the advantages they offer.
Triglyceride glucose index was linearly associated with abdominal aortic calcification based on NHANES 2013–2014
Authors: Zhou Ying , Zhi Fu , Gao Beibei , Liao Shengen
Published: December 2022

Purpose

To study the relationship between the TyG index and the risk of AAC.

Methods

We enrolled 1,486 participants from the National Health and Nutrition Examination Survey (NHANES). The TyG index was calculated in the log-transformed of triglycerides multipled by glucose, and the presence of AAC was diagnosed as AAC score above than 0.

Results

Our suggested found that TyG level was positively correlated with the presence of AAC and log-transformed AAC score. After adjusted for other variables, comparing with the lowest quartile of TyG index, the highest quartile of TyG level was significantly associated with the presence of AAC (OR 2.12, 95%CI 1.05–4.35, p = 0.038) and severe AAC (OR 2.12, 95%CI 1.05–4.35, p = 0.038).

Conclusions

TyG index was significantly associated with the risk of AAC and severe AAC, which could be a marker in clinical practice.
Hospice preference of the family decision-makers for cancer patients in China: an exploratory study
Authors: Yao Nian , Chen Hao , Lai Xiaobin
Published: December 2022

Background

The reasons for hospice underuse in China need exploration from the perspective of patients with cancer and their families. Furthermore, existing literature about hospice decision-making among Chinese families with cancer patients is limited. This study aimed to investigate the awareness of hospice care among families with cancer patients, their preference for healthcare at the end-of-life stage of care, and the predictors of hospice preference.

Methods

This was an exploratory study conducted between July 2021 and January 2022. Overall, 300 decision-makers of cancer patients were recruited from the oncology ward of seven hospitals in Shanghai, China. Of these, 285 valid responses were included in the data analysis. A self-developed questionnaire about their preference for healthcare when the patient was at the end-of-life stage was completed. Descriptive analysis, t-test, chi-square test, and multivariable logistic regression were conducted to analyze the data.

Results

Only 46.0% of the participants have heard of hospice care. Most participants (78.2%) reported no introduction to hospice care from their doctors. More than half of the participants (58.2%) did not have a preference for healthcare at the end-of-life stage. Seventy-eight (65.5%) of the 119 participants who had a preference chose hospice care, and the other 41 participants (34.5%) refused hospice care. Having heard of hospice care had a significant impact on preferring healthcare at the end-of-life stage (adjusted OR = 14.346, 95%CI 7.219–28.509, p < 0.001). Not being sure whether the doctor introduced hospice care before had a significant impact on having no preference for healthcare at the end-of-life stage (adjusted OR = 0.180, 95%CI 0.052–0.617, p = 0.006). Another family member being cared for at home had a significant impact on the participants’ hospice preference (adjusted OR = 2.739, 95%CI 1.159–6.470, p = 0.022).

Conclusion

The end-of-life communication between healthcare providers and the families of cancer patients is insufficient. More efforts should be made in increasing the awareness of hospice care among patients with cancer and their families. Further study is needed to explore the reasons for a lack of discussion on hospice options between healthcare providers and the patients’ families. Additionally, the impact of the at-home care burden on the hospice choice of families with cancer patients requires further study.
Is there an increase over time in the complexity of teacher questions and student responses in case-based clinical seminars? A cross-sectional video study
Authors: Gartmeier Martin , Hapfelmeier Alexander , Grünewald Marc , Häusler Janina , Pfurtscheller Theresa , Seidel Tina , Berberat Pascal
Published: December 2022

Background

Case-based group discussions (CBGD) are a specific, interaction-focused format dedicated to fostering medical students’ skills in applying basic biomedical knowledge to patient cases. Existing conceptions of CBGD suggest that a gradient towards increased opportunities for students to make elaborative verbal contributions is an important element of such seminars. To verify this assumption, we investigate empirically if clinical teachers progress from more basic, knowledge-oriented questions towards more advanced, elaboration-oriented questions in such seminars.

Methods

We videotaped 21 different clinical teachers and 398 medical students in 32 CBGD-seminars on surgery and internal medicine. We coded closed-reproductive and open-elaborative teacher questions as well as reproductive and elaborative student responses to these questions. Inter-rater reliability was satisfactory. To determine trends regarding the teacher questions / student responses, we compared eight time-segments of equal duration per seminar.

Results

Overall, clinical teachers asked more closed-reproductive than open-elaborative questions. Students gave more reproductive than elaborative responses. Regarding the frequencies of these forms of teacher questions / student responses, we found no significant differences over time.

Conclusions

Clinical teachers did not deliberately modify the types of questions over time to push students towards more elaborative responses. We conclude that the critical question to which degree promising teaching approaches are actually put into clinical teaching practice should be raised more purposefully in medical education research.
Developing and validating a survival prediction model based on blood exosomal ceRNA network in patients with PAAD
Authors: Wang Shanshan , Xu Lijun , Zhu Kangle , Zhu Huixia , Zhang Dan , Wang Chongyu , Wang Qingqing
Published: December 2022

Background

Among the most lethal cancers, pancreatic adenocarcinoma (PAAD) is an essential component of digestive system malignancies that still lacks effective diagnosis and treatment methods. As exosomes and competing endogenous RNA (ceRNA) regulatory networks in tumors go deeper, we expect to construct a ceRNA regulatory network derived from blood exosomes of PAAD patients by bioinformatics methods and develop a survival prediction model based on it.

Methods

Blood exosome sequencing data of PAAD patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, lncRNA, and circRNA were differentially analyzed by R. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Then, we conducted GO and KEGG enrichment analysis of mRNA in the ceRNA network. Genes that express differently in pancreatic cancer tissues compared with normal tissues and associate with survival (P < 0.05) were determined as Hub genes by GEPIA. We identified optimal prognosis-related differentially expressed mRNAs (DEmRNAs) and generated a risk score model by performing univariate and multivariate Cox regression analyses.

Results

205 DEmRNAs, 118 differentially expressed lncRNAs (DElncRNAs), and 98 differentially expressed circRNAs (DEcircRNAs) were screened out. We constructed the ceRNA network, and a total of 26 mRNA nodes, 7 lncRNA nodes, 6 circRNA nodes, and 16 miRNA nodes were identified. KEGG enrichment analysis showed that the DEmRNAs in the regulatory network were mainly enriched in Human papillomavirus infection, PI3K-Akt signaling pathway, Osteoclast differentiation, and ECM-receptor interaction. Next, six hub genes (S100A14, KRT8, KRT19, MAL2, MYO5B, PSCA) were determined through GEPIA. They all showed significantly increased expression in cancer tissues compared with control groups, and their high expression pointed to adverse survival. Two optimal prognostic-related DEmRNAs, MYO5B (HR = 1.41, P < 0.05) and PSCA (HR = 1.10, P < 0.05) were included to construct the survival prediction model.

Conclusion

In this study, we successfully constructed a ceRNA regulatory network in blood exosomes from PAAD patients and developed a two-gene survival prediction model that provided new targets which shall aid in diagnosing and treating PAAD.
Exercise capacity and physical activity in COPD patients treated with a LAMA/LABA combination: a systematic review and meta-analysis
Authors: Miravitlles Marc , García-Rivero Juan Luís , Ribera Xavier , Galera Jordi , García Alejandra , Palomino Rosa , Pomares Xavier
Published: December 2022

Background

Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes.

Methods

A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted.

Results

Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0–1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities.

Conclusions

LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.
Retraction Note: α-santalol inhibits the angiogenesis and growth of human prostate tumor growth by targeting vascular endothelial growth factor receptor 2-mediated AKT/mTOR/P70S6K signaling pathway
Authors: Saraswati Sarita , Kumar Shakti , Alhaider Abdulqader A.
Published: December 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1476-4598-12-147.
Obtaining EQ-5D-3L utility index from the health status scale of traditional Chinese medicine (TCM-HSS) based on a mapping study
Authors: Wang Li , Lu Yuqiong , Dai Zhanjing , Shi Penghua , Xu Jiayi , Chang Feng , Lu Yun
Published: December 2022

Background

Almost all traditional Chinese medicine (TCM) quality of life measures are non-preference-based measures (non-PBMs), which do not provide utilities for cost-utility analysis in pharmacoeconomic evaluation. Whereas the mapping has become a new instrument to obtain utilities, which builds a bridge between non-PBMs and PBMs.

Purpose

To develop mapping algorithms from the health status scale of traditional Chinese medicine (TCM-HSS) onto the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L).

Methods

The cross-sectional data were collected by questionnaire survey from a tertiary hospital visit population and community residents in China, and randomly divided into training and validation set by 2:1. Based on the training set, direct and indirect mapping methods (7 regression methods and 4 model specifications) were conducted to establish alternative models, which were comprehensively evaluated based on the validation set by mean absolute error, root mean square error, and Spearman correlation coefficient between predicted and observed values. Based on the whole sample, the preferred mapping algorithm was developed.

Results

A total of 639 samples were included, with an average age of 45.24 years and 61.66% of respondents were female. The mean EQ-5D-3L index was 0.9225 [SD = 0.1458], and the mean TCM-HSS index was 3.4144 [SD = 3.1154]. The final mapping algorithm was a two-part regression model including the TCM-HSS subscales, interaction terms, and demographic covariates (age and gender). The prediction performance was good. The mean error was 0.0003, the mean absolute error was 0.0566, the root mean square error was 0.1039, and 83.10% of the prediction errors were within 0.1; the Spearman correlation coefficient between predicted and observed EQ-5D-3L values was 0.6479.

Conclusion

It is the first study to develop a mapping algorithm between the TCM-HSS and EQ-5D-3L, which demonstrates excellent prediction accuracy and estimates utility value for economic evaluation from TCM quality of life measures.
Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma
Authors: Zhang Zhenshan , Wu Leilei , Li Juan , Chen Jiayan , Yu Qi , Yao Hui , Xu Yaping , Liu Liang
Published: December 2022

Background

Zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing proteins have been reported to be associated with many tumors’ development. However, in tumor initiation and progression, the role of ZBTB9, one of the protein family, and its prognostic value were yet to be elucidated in Liver Hepatocellular Carcinoma (LIHC).

Methods

We used R software and online bioinformatics analysis tools such as GEPIA2, cBioPortal, TIMER2, Metascape, UALCAN, STRING, TISIDB, and COSMIC to investigate ZBTB9’s characteristics and function in LIHC, including abnormal expression, carcinogenic role, related signaling pathways and prognostic value. Furthermore, cell experiments (such as formation, wound healing, and transwell assays) and analyses based on clinical samples (such as immunohistochemistry (IHC) and promoter methylation analysis) were conducted to verify pivotal conclusions.

Results

ZBTB9 was overexpressed in LIHC samples compared to adjacent normal tissues. Through the analysis of genomic alteration and promoter hypomethylation, the clinical value and etiology of abnormal expression of ZBTB9 were preliminarily exlpored. Subsequent evidence showed that it could result in tumor progression and poor prognosis via activating cell cycle, DNA repair, MYC, and KRAS-associated signaling pathways as well as rendering immune dysregulation. After the knockdown of ZBTB9, evidently inhibited capacities of tumor cells proliferation and migration were observed. These results together indicated that ZBTB9 could be a promising prognostic biomarker and had the potential value to offer novel therapeutic targets for LIHC treatment.

Conclusions

ZBTB9 was identified as a novel biomarker to predict the prognosis and tumor progression in LIHC, and a promising therapeutic target to invert tumor development.
A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer
Authors: Han Shengbo , Wang Decai , Huang Yan , Zeng Zhu , Xu Peng , Xiong Hewei , Ke Zunxiang , Zhang Ya , Hu Yuhang , Wang Fan , Wang Jie , Zhao Yong , Zhuo Wenfeng , Zhao Gang
Published: December 2022

Background

Research has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells.

Methods

Immunofluorescence analyses were conducted to examine the differential distribution of Schwann cells within colon cancer tissues and normal colon tissues. CCK8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the interaction between colon cancer cells and Schwann cells. Exosomes derived from colon cancer cells were isolated to further explore the effect of colon cancer cells on Schwann cells. Gain- and loss-of function experiments, luciferase reporter assays, chromatin immunoprecipitation assays, and immunohistochemistry assays were performed to reveal the cross-talk between colon cancer cells and Schwann cells. Furthermore, colon cancer cells co-cultured with Schwann cells were transplanted into nude mice for evaluating their effect on tumor proliferation and metastasis in vivo.

Results

The clinicopathological characteristics indicated that Schwann cells were enriched in colon cancer tissues and were associated with tumor metastasis and poor prognosis. The co-culture of Schwann cells with colon cancer cells promoted the proliferation and migration of colon cancer cells and Schwann cells, which was mediated by nerve growth factor (NGF) secreted from Schwann cells. Exosomal miR-21-5p released by colon cancer cells inhibited VHL expression in Schwann cells, which in turn stabilized the HIF-1α protein and increased the transcription of NGF. Meanwhile, the Schwann cells-derived NGF activated TrkA/ERK/ELK1/ZEB1 signaling pathway in colon cancer cells, which further enhanced the expression of exosomal miR-21-5p. Inhibition of either NGF or miR-21-5p significantly inhibited the proliferation and metastasis of transplanted colon cancer cells in nude mice. Coincidently, miR-21-5p was positively associated with the expression of NGF, p-ERK, p-ELK1, and ZEB1 in human colon cancer tissues.

Conclusions

Our results implicated a reciprocal communication between colon cancer cells and Schwan cells that promoted the proliferation and metastasis of colon cancer, and identified NGF and exosomal miR-21-5p as potential therapeutic targets for the treatment of colon cancer.
Strobealign: flexible seed size enables ultra-fast and accurate read alignment
Authors: Sahlin Kristoffer
Published: December 2022

Read alignment is often the computational bottleneck in analyses. Recently, several advances have been made on seeding methods for fast sequence comparison. We combine two such methods, syncmers and strobemers, in a novel seeding approach for constructing dynamic-sized fuzzy seeds and implement the method in a short-read aligner, strobealign. The seeding is fast to construct and effectively reduces repetitiveness in the seeding step, as shown using a novel metric E-hits. strobealign is several times faster than traditional aligners at similar and sometimes higher accuracy while being both faster and more accurate than more recently proposed aligners for short reads of lengths 150nt and longer. Availability: https://github.com/ksahlin/strobealign
Calculating variant penetrance from family history of disease and average family size in population-scale data
Authors: Spargo Thomas P. , Opie-Martin Sarah , Bowles Harry , Lewis Cathryn M. , Iacoangeli Alfredo , Al-Chalabi Ammar
Published: December 2022

Background

Genetic penetrance is the probability of a phenotype when harbouring a particular pathogenic variant. Accurate penetrance estimates are important across biomedical fields including genetic counselling, disease research, and gene therapy. However, existing approaches for penetrance estimation require, for instance, large family pedigrees or availability of large databases of people affected and not affected by a disease.

Methods

We present a method for penetrance estimation in autosomal dominant phenotypes. It examines the distribution of a variant among people affected (cases) and unaffected (controls) by a phenotype within population-scale data and can be operated using cases only by considering family disease history. It is validated through simulation studies and candidate variant-disease case studies.

Results

Our method yields penetrance estimates which align with those obtained via existing approaches in the Parkinson’s disease LRRK2 gene and pulmonary arterial hypertension BMPR2 gene case studies. In the amyotrophic lateral sclerosis case studies, examining penetrance for variants in the SOD1 and C9orf72 genes, we make novel penetrance estimates which correspond closely to understanding of the disease.

Conclusions

The present approach broadens the spectrum of traits for which reliable penetrance estimates can be obtained. It has substantial utility for facilitating the characterisation of disease risks associated with rare variants with an autosomal dominant inheritance pattern. The yielded estimates avoid any kinship-specific effects and can circumvent ascertainment biases common when sampling rare variants among control populations.
Implementation and evaluation of crowdsourcing in global health education
Authors: Cai Huanle , Zheng Huiqiong , Li Jinghua , Hao Chun , Gu Jing , Liao Jing , Hao Yuantao
Published: December 2022

Background

Current global health course is most set as elective course taught in traditional teacher-taught model with low credit and short term. Innovate teaching models are required. Crowdsourcing characterized by high flexibility and strong application-orientation holds its potential to enhance global health education. We applied crowdsourcing to global health teaching for undergraduates, aiming to develop and evaluate a new teaching model for global health education.

Methods

Crowdsourcing was implemented into traditional course-based teaching via introducing five COVID-19 related global health debates. Undergraduate students majoring in preventative medicine and nursing grouped in teams of 5–8, were asked to resolve these debates in reference to main content of the course and with manner they thought most effective to deliver the messages. Students' experience and teaching effect, were evaluated by questionnaires and teachers’ ratings, respectively. McNemar's test was used to compare the difference in students' experience before and after the course, and regression models were used to explore the influencing factors of the teaching effect.

Results

A total of 172 undergraduates were included, of which 122 (71%) were females. Students' evaluation of the new teaching model improved after the course, but were polarized. Students’ self-reported teaching effect averaged 67.53 ± 16.8 and the teachers’ rating score averaged 90.84 ± 4.9. Students majoring in preventive medicine, participated in student union, spent more time on revision, and had positive feedback on the new teaching model tended to perform better.

Conclusion

We innovatively implemented crowdsourcing into global health teaching, and found this new teaching model was positively received by undergraduate students with improved teaching effects. More studies are needed to optimize the implementation of crowdsourcing alike new methods into global health education, to enrich global health teaching models.
Analysis of composition and microstructure of diatom frustules in mud on the coast of Boryeong- city, South Korea
Authors: Bok Mi Kyung , Chin Chung Hwa , Choi Hee Jung , Ham Ju Hyun , Chang Byung Soo
Published: December 2022

The microstructure of diatom frustules found in mud sediments along the coast of Boryeong- city, South Korea, was observed using a scanning electron microscopy (SEM), and the constituent elements of diatoms were analyzed using energy-dispersive X-ray spectroscopy (EDS). Diatom frustules and clay minerals were present in the SEM images of the mud powder. High-magnification SEM images revealed that the surface of the frustules contained identically shaped circular pores, measuring 1 μm in diameter, arranged at regular intervals. This study revealed that the diatom shell fragments in the mud powder ranged in size from 3 to 30 μm, with an average thickness of approximately 2.5 μm. The elements Si, Al, Fe, K, Na, Mg, and Ti were detected while analyzing the frustule constituents, with Si being the primary component with the highest content.
Resource and Reimbursement Barriers to Comprehensive Cancer Care Delivery: An Analysis of Association of Community Cancer Centers Survey Data
Authors: Benson Al Bowen , Boehmer Leigh , Mi Xinlei , Kocherginsky Masha , Shivakumar Latha , Trosman Julia R. , Weldon Christine B. , Tina Shih Ya-Chen , Hahn Elizabeth A. , Kircher Sheetal M.
Published: December 2022

PURPOSE:

Comprehensive cancer care (CCC) delivery is recommended in guidelines and considered essential for high-quality cancer management. Barriers, such as insufficient reimbursement, prevent consistent access to and delivery of CCC. Association of Community Cancer Centers conducted a national survey to elucidate capacity and barriers to CCC delivery to inform policy and value-based payment reform.

METHODS:

Survey methodology included item generation with expert review, iterative piloting, and cognitive validity testing. In the final instrument, 27 supportive oncology services were assessed for availability, reasons not offered, and coverage/reimbursement.

RESULTS:

204 of 704 member programs completed survey questions. Despite most services being reported as offered, a minority were funded through insurance reimbursement. The services least likely to obtain reimbursement were those that address practical and family/childcare needs (0.7%), caregiver support (1.5%), advanced care directives (1.7%), spiritual services (1.8%), and navigation (2.7%). These findings did not vary by region or practice type.

CONCLUSION:

There is a lack of sufficient reimbursement, staffing, and budget to provide CCC across the United States. Care models and reimbursement policies must include CCC services to optimize delivery of cancer care.