bluuebunny/crossref_metadata_2025 huggingface dataset:
Trophoblast retrieval from the cervical canal to predict abnormal pregnancy early in gestation: a pilot study
Authors: Yang Xiaoke , Du Liuyezi , Li Yue , Liang Lin , Ma Linlin , Wang Shaowei
Published: March 2023

Background

The current detection of fetal chromosomal abnormalities by non-invasive prenatal testing (NIPT) mainly relies on the cell free DNA(cfDNA) in the maternal blood. However, a gestational age of less than 12 weeks or a high maternal BMI affects cfDNA fetal fraction and further the detection by NIPT negatively. In this study, we aim to retrieve the trophoblast cells from the maternal cervix to develop a new sampling method for NIPT enabling an earlier use of NIPT.

Methods

We enrolled three patients who wanted to undergo induced abortion at Beijing Hospital between January 2022 and March 2022. Peripheral blood, cervix specimen, and the abortion tissue were collected and processed for each patient. Allele frequencies of the mutated gene loci of the maternal blood and the cervix sample were compared and the Sex Determining Region Y (SRY) gene was tested.

Results

The allele frequencies of the mutated gene loci showed no significant difference between the maternal blood and the cervix sample. But we successfully detected signal of the SRY gene in the cervix sample of the only patient carrying a male fetus.

Conclusions

The detection of the SRY gene in a cervix sample indicated a successful retrieval of trophoblast cells from the cervix canal. Further study needs to be conducted to verify our finding before its application to the clinical settings.
Non-adherence to WHO’s recommended 8-contact model: geospatial analysis of the 2017 Maternal Health Survey
Authors: Dickson Kwamena Sekyi , Boateng Ebenezer N. K. , Adde Kenneth Setorwu , Ameyaw Edward Kwabena , Munro-Kramer Michelle L.
Published: March 2023

Introduction

Evidence shows that most women in Ghana do not meet the minimum 8-contact model for antenatal care as recommended by WHO with only 31.2%-41.9% of them meeting the recommendation. To the best of our knowledge, no study in Ghana has examined women’s noncompliance with the WHO’s recommended 8-contact model for antenatal care using geospatial analysis, as this study sets out to do.

Methods

We sourced data from the recent version of the Ghana Maternal Health Survey which was executed in 2017. A sample of 10,077 women with complete data participated in this study. The link between the explanatory variables and the outcome variable was investigated using binary and multivariate logistic regression models and Spatial analyses such as spatial autocorrelation (Moran's I), hotspot, cluster and outlier analysis, and geographically weighted regression were conducted using ArcMap version 10.7.

Results

Districts found in the north-eastern and south-western parts of the country were more likely to experience noncompliance with ANC. Women staying within the middle belt without health insurance were more likely (17–29%) to be noncompliant with ANC. Women with low community socioeconomic status were found to be more likely (17–34%) to be noncompliant with ANC in the eastern parts of Ghana.

Conclusion

The study has shown that in order to achieve targets one and three of Sustainable Development Goal 3, the government of Ghana, the Ministry of Health, together with the Ghana Health Service may have to intensify health education in the identified areas to highlight the importance of adherence to the WHO recommendations on ANC 8-contact model.
Association of neutrophil–lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy
Authors: Huang Karen , Prasad Sharan , Ma Sung Jun , Yu Han , Iovoli Austin J. , Farrugia Mark K. , Dexter Elizabeth U. , Demmy Todd L. , Malik Nadia K. , Singh Anurag K.
Published: March 2023

Background

The role of neutrophil–lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT.

Methods

A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil–lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan–Meier, and propensity score matching were performed to evaluate outcomes.

Results

A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02–1.10,p = 0.005) and PFS (aHR 1.05, 95% CI 1.01–1.09,p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05–1.18,p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching.

Conclusions

Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.
Characteristics and clinical course of thyroid abnormalities arisen in long term survivors of childhood cancer
Authors: Jin Hye Young , Lee Jun Ah. , Park Meerim , Lee Dong-Eun , Park Hyeon Jin
Published: March 2023

Background

Thyroid abnormality is a common late effect seen in childhood cancer survivors (CCSs). We analyzed the prevalence and risk factors of thyroid abnormalities based on diagnoses and treatment modalities in CCSs.

Methods

The medical records of 257 CCSs who were diagnosed with cancer less than 20 year of age were retrospectively reviewed. The median age was 11.8 years (0.1–19.8). The median follow-up period after completion of therapy was 9.6 years (5.0–19.5).

Results

Of 257 subjects, thyroid abnormalities were identified in 107 (41.6%). Sixty-five out of 257 (25.3%) had subclinical hypothyroidism, and 16 (6.2%) developed central hypothyroidism. Five CCSs (1.9%) had primary overt hypothyroidism. Five (1.9%) and 6 (2.3%) CCSs were diagnosed with autoimmune thyroiditis and thyroid cancer, respectively. Among the different diagnostic groups, thyroid abnormalities were frequent in the brain tumor or Hodgkin disease or nasopharyngeal cancer groups. CCSs who received irradiation directly or near hypothalamus-pituitary-thyroid (HPT) axis had more thyroid abnormalities compared to the rest CCSs (P < 0.0001). CCSs who were treated with SCT had an increased prevalence of thyroid abnormalities (60.5%) compared to the other CCSs (37.9%) (P = 0.0069). Forty-five (42%) of 107 subjects with thyroid abnormalities had normalized thyroid hormone levels at the last follow-up. Irradiation directly or near HPT axis were thought to be a predicting factor of persistent subclinical hypothyroidism.

Conclusions

Subclinical hypothyroidism was common in CCSs. CCSs with irradiation directly or near HPT axis were at risk for persistent thyroid dysfunction.
Non-mosaic trisomy 22 and congenital heart surgery using the shared decision making model: a case report
Authors: Phung Vivien , Singh Kathryn E. , Danon Saar , Tan Christopher A. , Dabagh Sarah
Published: March 2023

Background

Liveborn infants with non-mosaic trisomy 22 are rarely described in the medical literature. Reported lifespan of these patients ranges from minutes to 3 years, with the absence of cardiac anomalies associated with longer-term survival. The landscape for offering cardiac surgery to patients with rare autosomal trisomies is currently evolving, as has been demonstrated recently in trisomies 13 and 18. However, limited available data on patients with rare autosomal trisomies provides a significant challenge in perinatal counseling, especially when there are options for surgical intervention.

Case presentation

In this case report, we describe an infant born at term with prenatally diagnosed apparently non-mosaic trisomy 22 and multiple cardiac anomalies, including a double outlet right ventricle, hypoplastic aortic valve and severe aortic arch hypoplasia, who underwent cardiac surgery. The decisions made by her family lending to her progress and survival to this day were made with a focus on the shared decision making model and support in the prenatal and perinatal period. We also review the published data on survival and quality of life after cardiac surgery in infants with rare trisomies.

Conclusions

This patient is the only known case of apparently non-mosaic trisomy 22 in the literature who has undergone cardiac surgery with significant survival benefit. This case highlights the impact of using a shared decision making model when there is prognostic uncertainty.
Video-based e-learning program for schoolteachers to support children of parents with mental illness: a cluster randomized trial
Authors: Kageyama Masako , Matsushita Atsunori , Kobayashi Ayuna , Sakamoto Taku , Endo Yasuhiro , Sakae Setsuko , Koide Keiko , Saita Ryotaro , Kosaka Hiyuka , Iga Satoko , Yokoyama Keiko
Published: March 2023

Background

Some children of parents with mental illness need support. This study aimed to develop and test the effectiveness of an e-learning program for training elementary schoolteachers to support children of parents with mental illness.

Methods

The program, which included a 30-min video-based e-learning program, aimed to help schoolteachers gain basic knowledge about mental illness and children of parents with mental illness, recognize children in need of support, and gain confidence in supporting them. A school-based cluster randomized controlled trial was conducted, and the schools were randomly divided into intervention and control groups. The teachers at these schools signed up for the program and participated individually. The outcome measures for the schoolteachers were evaluated at three time points: baseline (T1), post (T2), and one month later (T3). Along with the Sense of Coping Difficulty subscale (primary outcome measure), the following self-developed outcome measures were used: actual behaviors and attitude toward supporting children, knowledge, and self-assessment of program goals achievement. The Sense of Coping Difficulty subscale results at T3 were compared between the groups. Effectiveness over time was assessed for all the outcome measures. The interaction between baseline and intervention effects on the Sense of Coping Difficulty subscale was analyzed. As a part of the process evaluation, open-ended text responses were analyzed qualitatively.

Results

Baseline responses were collected from 87 participants in the intervention group and 84 in the control group. The total score of the Sense of Coping Difficulty subscale at T3 was significantly lower in the intervention group than in the control group (p = 0.007). Over time, a significant effect was observed on the Sense of Coping Difficulty subscale, actual behavior, knowledge of onset timing and probability of onset, and achievement of all program goals. Exploratory analysis was particularly effective for those who encountered a high level of difficulty in supporting children. The participants’ text responses indicated that they planned to look carefully at children's backgrounds and stay close to them in the future.

Conclusions

The program was effective for schoolteachers in supporting children of parents with mental illness.

Trial registration

UMIN000045483; 14/09/2021.
Minimally invasive plate osteosynthesis (MIPO) for distal humeral fractures: a cadaveric study and first clinical application
Authors: Hofmann Valeska , Diepold Julian , Moursy Mohamed , Birke Marco T. , Deininger Christian , Wichlas Florian
Published: March 2023

Background

The indication for minimally invasive plate osteosynthesis (MIPO) may include articular fractures depending on the fracture pattern. The goal of this study was to evaluate the feasibility of the MIPO technique for extra- and intra-articular distal humeral fractures.

Methods

The feasibility of the MIPO technique was assessed on 8 cadaveric elbows and 2 clinical cases. The four surgical approaches tested included a 20-mm ulnar incision, a 20-mm dorsoradial incision, and two incisions for olecranon osteotomy (A and B). Surgical incision A was 40 mm on the osteotomy level of the olecranon, and surgical incision B was an extension of the radial incision toward the osteotomy of the olecranon (80 mm).

The four approaches were tested on 4 extra-articular (AO 13 A3) fractures and 4 intra-articular (AO 13 C3) fractures.

Results

Reduction and plate fixation of all distal humeral fractures (8 cadaveric) with and without osteotomy was feasible. However, when using approach B, the soft tissue tension is reduced due to the wider incision. Nevertheless, both approaches A and B showed the same adequate intra-articular fracture control and reduction.

Conclusion

The MIPO technique for reduction and plate fixation in distal humeral fractures is feasible.

Level of evidence

As a feasibility study, this study cannot be clearly classified into a level of evidence. It corresponds most closely to level IV.
A revamped MIC-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk
Authors: Zhang Hai , Chen Ying , Wu Bomeng , Chen Ying , He Haiquan , Gong Lanjuan , Zhou Linrong , Li Cui , Xie Jing , Lin Wanli
Published: March 2023

Background

The purpose of this study was to investigate the effect of our revamped MIE-McKeown operation on postoperative gastrointestinal function recovery.

Methods

This revamped MIE-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk and with the tubular stomach buried throughout esophageal bed and azygos arch, has been implemented from July 2020 to July 2021 by the same medical team of Gaozhou People's Hospital thoracic surgery for 13 times. Preoperative clinical data, main intraoperative indicators and postoperative complications were observed.

Results

All patients had esophageal malignant tumors at the level of middle and lower thoracic non-azygous venous arch, with preoperative clinical stage CT1-2N0M0 stage i-ii. V-vst test was performed on the 7th postoperative day, and 10 patients were found to have no loss of safety/efficacy. There were 2 cases with impaired efficacy and no impaired safety, 1 case with impaired safety. There were 1 cases of pulmonary infection, 1 cases of anastomotic fistula combined with pleural and gastric fistula, 2 cases of hoarseness, 2 cases of arrhythmia, 10 cases of swallowing function were grade i, 2 cases of swallowing function were grade iii, 1 case of swallowing function was grade iv in watian drinking water test one month after operation.

Conclusions

Merit of this revamped MIE-McKeown operation is well preserving the integrity of azygos arch of vagus nerve and bronchial artery, and it is technically safe and feasible. No postoperative mechanical obstruction of thoracostomach, huge thoracostomach and gastrointestinal dysfunction occurs.
Association between periodontitis and disc structural failure in older adults with lumbar degenerative disorders: A prospective cohort study
Authors: Chen Xiaolong , Xue Dong , Zhao Ying , Cui Peng , Wang Peng , Wang Yu , Lu Shi-bao
Published: March 2023

Background

Bacterial microbiome as a putative trigger of inflammation might indicate the cascade of mouth-gut-disc axis for causing intervertebral disc (IVD) structural failures (such as IVD degeneration and endplate change) processed. However, direct evidence for the mouth-gut-disc axis still unclear. Therefore, it is interesting to explore periodontal inflammation related to IVD structural failures and clinical outcomes.

Methods

This prospective cohort study enrolled older adults (aged ≥ 75 years) who scheduled to undergo elective open lumbar spine surgery. Demographic, radiological, clinical, and periodontal parameters were recorded. Independent samples t-test and Pearson’s correlation analysis were calculated.

Results

A total of 141 patients with lumbar degenerative disorders (56 males and 85 females; age 79.73 ± 3.34 years) were divided into edentulous group (19 patients), No/Mild group (84 patients), and Moderate/Severe group (38 patients). The incidence rates of IVD degeneration in each lumbar segmental level based on Pfirrmann grade and endplate change in the fourth and fifth lumbar vertebrae, and Visual Analogue Scale (VAS) low back pain (LBP) and leg pain of patients at preoperative in dentate group was significantly higher compared with edentulous group, especially the comparisons between Moderate/Severe and edentulous groups. There were no significant differences in the range of motion, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope, and disc height between dentate and edentulous groups. There was a positive association between plaque index (PLI) and pain scores (VAS LBP: r = 0.215, P = 0.030 and VAS leg pain: r = 0.309, P = 0.005), but no significant difference in Oswestry disability index (ODI) score.

Conclusion

Results show that the severity of periodontitis is associated with higher incidence rates of IVD degeneration and endplate change and clinical outcomes in older adults with lumbar degenerative disorders. Furthermore, the discovery of these relationships unveils a novel mechanism through which the alterations in oral microbiome composition potentially promote IVD degeneration and pain.
Sarcomatoid urothelial carcinoma of the renal pelvis treated with immunotherapy
Authors: Anraku Tsutomu , Hashidate Hideki , Nakahara Asa , Imai Tomoyuki , Kawakami Yoshiaki
Published: March 2023

Background

Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy.

Case presentation

A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer—sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission.

Conclusions

The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.
Bacterial biofilm prevalence in dental unit waterlines: a systematic review and meta-analysis
Authors: Bayani Mojtaba , Raisolvaezin Kiyavash , Almasi-Hashiani Amir , Mirhoseini Seyed Hamed
Published: March 2023

Backgrounds

Numerous studies have shown that dental unit water lines (DUWLs) are often contaminated by a wide range of micro-organisms (bacteria, fungi, protozoa) and various prevalence have been reported for it in previous studies. Therefore, this review study aims to describe the prevalence of bacterial biofilm contamination of DUWLs.

Methods

This is a systematic review and meta-analysis in which the related keywords in different international databases, including Medline (via PubMed) and Scopus were searched. The retrieved studies were screened and the required data were extracted from the included studies. Three standard methods including American Dental Association (ADA), The Center for Disease Control and Prevention (CDC) and contaminated > 100 CFU/ml(C-100) standards were used to assess the bacterial biofilm contamination of DUWLs. All studies that calculated the prevalence of bacterial biofilm contamination of DUWLs, and English full-text studies were included in the meta-analysis. Studies that did not have relevant data or used unusual laboratory methods were excluded. Methodological risk of bias was assessed by a related checklist and finally, the data were pooled by fixed or random-effect models.

Results

Seven hundred and thirty-six studies were identified and screened and 26 related studies were included in the meta-analysis. The oldest included study was published in 1976 and the most recent study was published in 2020. According to the ADA, CDC and C-100 standards, the prevalence of bacterial contamination was estimated to be 85.0% (95% confidence interval (CI): 66.0–94.0%), 77.0% (95%CI: 66.0–85.0%) and 69.0% (95%CI: 67.0–71.0%), respectively. The prevalence of Legionella Pneumophila and Pseudomonas Aeruginosa in DUWLs was estimated to be 12.0% (95%CI: 10.0–14.0%) and 8.0% (95%CI: 2.0–24.0%), respectively.

Conclusion

The results of this review study suggested a high prevalence of bacterial biofilm in DUWLs; therefore, the use of appropriate disinfecting protocol is recommended to reduce the prevalence of contamination and reduce the probable cross-infection.
Cardiac arrest caused by the application of pituitrin during laparoscopic myomectomy
Authors: Li Jia-Rui , Liao Xin , Lv Feng-Qiong , Li Hui
Published: March 2023

Background

Pituitrin injection solution is an indispensable hemostatic utilized in clinical practice and is widely used in myomectomy. However, there have been reports of adverse reactions leading to gastrointestinal injury, hyponatremia and hypokalemia, anaphylaxis, cardiac arrest, etc. Thus, the safety of pituitrin should be taken seriously.

Case presentation

In the present study, three cases of cardiac arrest caused by pituitrin injection during laparoscopic myomectomy, who were successfully resuscitated in our hospital, are reported.

Conclusion

The clinical data and surgical procedures in the patient should be analyzed to find the causes of cardiac arrest. Medication and resuscitation should be summarized to ensure the safety of the patient.
Effect of PCL nanofiber mats coated with chitosan microcapsules containing cinnamon essential oil for wound healing
Authors: Osanloo Mahmoud , Noori Fariba , Tavassoli Alireza , Ataollahi Mohammad Reza , Davoodi Ali , Seifalah-Zade Morteza , Taghinezhad Ali , Fereydouni Narges , Goodarzi Arash
Published: March 2023

Introduction

Cinnamon is one of the most common spices that has been studied for its anti-inflammatory, antioxidant, and antibacterial properties in wound healing. The purpose of this study was to evaluate the effectiveness of polycaprolactone nanofiber mats coated with chitosan microcapsules loaded with cinnamon essential oil in wound healing.

Material and methods

For this purpose, chitosan microcapsules containing cinnamon essential oil (µCS-CiZ) were prepared by ion gelation and PCL nanofibers by electrospinning. The size of the µCS-CiZ and the morphology of nanofibers were evaluated by DLS and FESEM methods. In order to evaluate wound healing, 48 rats in 4 groups of Control, µCS-CiZ, PCL, and PCL + µCS-CiZ and were examined on days 7, 14, and 21 in terms of macroscopy (wound closure rate) and histology (edema, inflammation, vascularity, fibrotic tissue, and re-epithelialization).

Results

The particle size of the µCS-CiZ and the diameter of the nanofibers were estimated at about 6.33 ± 1.27 μm and 228 ± 33 nm, respectively. On day 21, both µCS-CiZ and PCL groups showed a significant decrease in wound size compared to the control group (P < 0.001). The PCL + µCS-CiZ group also showed a significant decrease compared to the µCS-CiZ (P < 0.05) and PCL groups (P < 0.05). Histological results showed further reduction of edema, inflammation, and vascularity in granulation tissue and appearance of moderate to marked fibrotic tissue in PCL + µCS-CiZ group compared with the other groups.

Conclusion

The results of the study showed that the combined use of PCL + µCS-CiZ indicates a synergistic effect on improving wound healing.
Antiviral and ROS scavenging potential of Carica papaya Linn and Psidium guajava leaves extract against HIV-1 infection
Authors: Jadaun Pratiksha , Shah Prachibahen , Harshithkumar R. , Said Madhukar S. , Bhoite Shubhangi P. , Bokuri Sowmya , Ravindran Selvan , Mishra Neetu , Mukherjee Anupam
Published: March 2023

Antiretroviral therapy is the only treatment option for HIV-infected patients; however, it has certain drawbacks in terms of developing multiple toxic side effects. Thus, there is a continuous need to explore safe and efficacious anti-retroviral agents. Carica papaya Linn and Psidium guajava are known for their various biological activities. In this study, we characterized the bioactive fractions of methanolic leaves extract from both plants using the High-resolution electrospray ionization mass spectrometry (HR-ESI–MS) technique, followed by the investigation of their potential as anti-HIV-1 and antioxidant agents through in vitro mechanistic assays. The anti-HIV-1 activity was examined in TZM-bl cells through luciferase gene assay against two different clades of HIV-1 strains, whereas the intracellular ROS generation was analyzed by Fluorescence-Activated Cell Sorting. Additionally, the mechanisms of action of these phyto-extracts were determined through the Time-of-addition assay. The characterization of Carica papaya Linn and Psidium guajava leaves extract through HR-ESI–MS fragmentation showed high enrichment of various alkaloids, glycosides, lipids, phenolic compounds, terpenes, and fatty acids like bioactive constituents. Both the phyto-extracts were found to be less toxic and exhibited potent antiviral activity against HIV-1 strains. Furthermore, the phyto-extracts also showed a decreased intracellular ROS in HIV-1 infected cells due to their high antioxidant potential. Overall, our study suggests the anti-HIV-1 potential of Carica papaya Linn and Psidium guajava leaves extract due to the synergistic action of multiple bioactive constituents.
Interdisciplinary education affects student learning: a focus group study
Authors: Oudenampsen Jessica , van de Pol Marjolein , Blijlevens Nicole , Das Enny
Published: March 2023

Background

In order to best prepare medical students for their increasingly complex future career, interdisciplinary higher education is swiftly gaining popularity. However, the implementation of interdisciplinary learning in medical education is challenging. The present study deepens the understanding of the challenges and opportunities inherent to the implementation of an interdisciplinary course. We elucidated the attitudes and beliefs of students participating in a newly developed interdisciplinary minor, in which students of medicine (MS) and communication and information sciences (CISS) were involved.

Methods

We conducted four semi-structured focus group interviews, of which two were held before, and two were held after the course. Seven MS and six CISS participated voluntarily. A pre-arranged interview guide was used. The interviews were recorded and afterwards systematically analyzed with the ‘constant comparative analysis’ technique.

Results

The focus group interviews revealed three differences in epistemics between students in terms of 1) curriculum content, 2) educational formats and 3) student’s competence perceptions. These factors influenced the way students evaluated themselves, each other and the interdisciplinary course.

Conclusions

We conclude that factors that influence interdisciplinary learning are personal epistemics, individual learning preferences, and the synergy that is achieved throughout interdisciplinary learning. Organizing the dialogue among students of different disciplines could make students aware of inequalities, implicated biases and assigned status of different student groups. These empirical results are crucial to tailor interdisciplinary education to each specific discipline and to take interdisciplinary learning to a higher level of maturity.
Silencing of heat shock protein 90 (hsp90): Effect on development and infectivity of Ichthyophthirius multifiliis
Authors: Saleh Mona , Abdel-Baki Abdel-Azeem S. , Dkhil Mohamed A. , El-Matbouli Mansour , Al-Quraishy Saleh
Published: March 2023

Background

Recently, an increasing number of ichthyophthiriasis outbreaks has been reported, leading to high economic losses in fisheries and aquaculture. Although several strategies, including chemotherapeutics and immunoprophylaxis, have been implemented to control the parasite, no effective method is available. Hence, it is crucial to discover novel drug targets and vaccine candidates against Ichthyophthirius multifiliis. For this reason, understanding the parasite stage biology, host–pathogen interactions, molecular factors, regulation of major aspects during the invasion, and signaling pathways of the parasite can promote further prospects for disease management. Unfortunately, functional studies have been hampered in this ciliate due to the lack of robust methods for efficient nucleic acid delivery and genetic manipulation. In the current study, we used antisense technology to investigate the effects of targeted gene knockdown on the development and infectivity of I. multifiliis. Antisense oligonucleotides (ASOs) and their gold nanoconjugates were used to silence the heat shock protein 90 (hsp90) of I. multifiliis. Parasite stages were monitored for motility and development. In addition, the ability of the treated parasites to infect fish and cause disease was evaluated.

Results

We demonstrated that ASOs were rapidly internalized by I. multifiliis and distributed diffusely throughout the cytosol. Knocking down of I. multifiliis hsp90 dramatically limited the growth and development of the parasite. In vivo exposure of common carp (Cyprinus carpio) showed reduced infectivity of ASO-treated theronts compared with the control group. No mortalities were recorded in the fish groups exposed to theronts pre-treated with ASOs compared with the 100% mortality observed in the non-treated control fish.

Conclusion

This study presents a gene regulation approach for investigating gene function in I. multifiliis in vitro. In addition, we provide genetic evidence for the crucial role of hsp90 in the growth and development of the parasite, suggesting hsp90 as a novel therapeutic target for successful disease management. Further, this study introduces a useful tool and provides a significant contribution to the assessing and understanding of gene function in I. multifiliis.
Estimated glucose disposal rate is associated with retinopathy and kidney disease in young people with type 1 diabetes: a nationwide observational study
Authors: Linn Wedén , Persson Martina , Rathsman Björn , Ludvigsson Johnny , Lind Marcus , Andersson Franko Mikael , Nyström Thomas
Published: March 2023

Aims

The aim of this study was to investigate the association between estimated glucose disposal rate (eGDR), a proxy for insulin resistance, and retinopathy or kidney disease, i.e. micro-, or macroalbuminuria, in young individuals with type 1 diabetes (T1D).

Material and Methods

Using data from the Swedish pediatric registry for diabetes (SweDiabKids) and the registry for adults (NDR), all individuals with T1D with a duration of diabetes of less than 10 years between 1998 and 2017 were included. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) for two cohorts: retinopathy cohort or kidney disease cohort, stratified by eGDR categories: < 4, 4 to 5.99, 6 to 7.99, and ≥ 8 mg/kg/min (reference).

Results

A total of 22 146 (10 289 retinopathy cohort, and 11 857 kidney disease cohort with an overlapping of 9575) children and adults with T1D (median age 21 years, female 42% and diabetes duration of 6 and 7 years, respectively for the cohorts) were studied. During a median follow-up of 4.8 years (IQR 2.6–7.7) there were 5040 (24.7%), 1909 (48.1%), 504 (52.3%) and 179 (57.6%) events for retinopathy in individuals with an eGDR ≥ 8, 7.99 to 6, 5.99 to 4, and < 4 mg/kg/min, respectively. Corresponding numbers for kidney disease was 1321 (6.5%), 526 (13.3%), 255 (26.8%) and 145 (46.6%). After multiple adjustments for different covariates, individuals with an eGDR 7.99 to 6, 5.99 to 4 and < 4 mg/kg/min, had an increased risk of retinopathy compared to those with an eGDR ≥ 8 mg/kg/min (adjusted HRs, 95% CIs) 1.29 (1.20 to 1.40); 1.50 (1.31 to 1.71) and 1.74 (1.41 to 2.14). Corresponding numbers for kidney disease was (adjusted HRs, 95% CIs) 1.30 (1.11 to 1.52); 1.58 (1.25 to 1.99) and 1.33 (0.95 to 1.86), respectively.

Conclusions

eGDR, a proxy for insulin resistance, is associated with retinopathy and kidney disease in young adults with T1D. The risk of retinopathy increased with lower eGDR. The risk of kidney disease also increased with lower eGDR; however results show no association between the lowest eGDR and kidney disease. eGDR can be helpful to identify young T1D individuals at risk.
Exosomal MFI2-AS1 sponge miR-107 promotes non-small cell lung cancer progression through NFAT5
Authors: Xu Jingwei , Wang Hui , Shi Baoyu , Li Ning , Xu Guopeng , Yan Xiaopei , Xu Li
Published: March 2023

Background

Non-small cell lung cancer is a heterogeneous disease driven by extensive molecular alterations. Exosomes are small vesicles with diameters ranging from 30 to 150 nm released by various cell types and are important mediators of information transmission in tumor cells. Exosomes contain proteins, lipids, and various types of nucleic acids, including miRNAs and even DNA and RNA. MFI2 Antisense RNA 1 (MFI2-AS1) is a long noncoding RNA known to promote cell proliferation, metastasis and invasion in a variety of malignancies.

Methods

The relative expression of MFI2-AS1 in NSCLC tissues was examined using RNA fluorescence in situ hybridization (FISH) staining. Transwell migration and wound healing assays were used to analyze cell migration and invasion abilities. Tube formation is used to assess angiogenic capacity. CCK8 was used to assess cell proliferation ability. RNA immunoprecipitation (RIP) experiments confirmed that MFI2-AS1 acts as a competing endogenous RNA (ceRNA) for miR-107. Dual-luciferase reporter assays were used to identify potential binding between MFI2-miRNA and target mRNA. In vivo experiments were performed by injecting exosomes into subcutaneous tumors to establish animal models.

Result

Exosomal MFI2-AS1 increases NFAT5 expression by sponging miR-107, which in turn activates the PI3K/AKT pathway. We found that the MFI2-AS1/miR-107/NFAT5 axis plays an important role in exosome-mediated NSCLC progression, is involved in pre-metastatic niche formation, and can be used as a blood-based biomarker for NSCLC metastasis.

Conclusion

We demonstrate that MFI2-AS1 is upregulated in exosomes secreted by metastatic NSCLC cells and can be transferred to HUVECs, promoting angiogenesis and migration.
Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma
Authors: Hu Zongqiang , Chen Gang , Zhao Yingpeng , Gao Hongqiang , Li Laibang , Yin Yanfeng , Jiang Jie , Wang Li , Mang Yuanyi , Gao Yang , Zhang Shengning , Ran Jianghua , Li Li
Published: March 2023

Background

Circular RNAs (circRNAs) can be encapsulated into exosomes to participate in intercellular communication, affecting the malignant progression of a variety of tumors. Dysfunction of CD8 + T cells is the main factor in immune escape from hepatocellular carcinoma (HCC). Nevertheless, the effect of exosome-derived circRNAs on CD8 + T-cell dysfunction needs further exploration.

Methods

The effect of circCCAR1 on the tumorigenesis and metastasis of HCC was assessed by in vitro and in vivo functional experiments. The function of circCCAR1 in CD8 + T-cell dysfunction was measured by enzyme-linked immunosorbent assay (ELISA), western blotting and flow cytometry. Chromatin immunoprecipitation, biotinylated RNA pull-down, RNA immunoprecipitation, and MS2 pull-down assays were used to the exploration of mechanism. A mouse model with reconstituted human immune system components (huNSG mice) was constructed to explore the role of exosomal circCCAR1 in the resistance to anti-PD1 therapy in HCC.

Results

Increased circCCAR1 levels existed in tumor tissues and exosomes in the plasma of HCC patients, in the culture supernatant and HCC cells. CircCCAR1 accelerated the growth and metastasis of HCC in vitro and in vivo. E1A binding protein p300 (EP300) and eukaryotic translation initiation factor 4A3 (EIF4A3) promoted the biogenesis of circCCAR1, and Wilms tumor 1-associated protein (WTAP)-mediated m6A modification enhanced circCCAR1 stability by binding insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). CircCCAR1 acted as a sponge for miR-127-5p to upregulate its target WTAP and a feedback loop comprising circCCAR1/miR-127-5p/WTAP axis was formed. CircCCAR1 is secreted by HCC cells in a heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1)-dependent manner. Exosomal circCCAR1 was taken in by CD8 + T cells and caused dysfunction of CD8 + T cells by stabilizing the PD-1 protein. CircCCAR1 promoted resistance to anti-PD1 immunotherapy. Furthermore, increased cell division cycle and apoptosis regulator 1 (CCAR1) induced by EP300 promoted the binding of CCAR1 and β-catenin protein, which further enhanced the transcription of PD-L1.

Conclusions

The circCCAR1/miR-127-5p/WTAP feedback loop enhances the growth and metastasis of HCC. Exosomal circCCAR1 released by HCC cells contributes to immunosuppression by facilitating CD8 + T-cell dysfunction in HCC. CircCCAR1 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for HCC patients.
Moderate-intensity stepping in older adults: insights from treadmill walking and daily living
Authors: Yates T. , Henson J , McBride P. , Maylor B , Herring L. Y. , Sargeant J. A. , Davies M. J. , Dempsey P. C. , Rowlands A. V. , Edwardson C. L.
Published: March 2023

Background

A step cadence of 100 steps/minute is widely used to define moderate-intensity walking. However, the generalizability of this threshold to different populations needs further research. We investigate moderate-intensity step cadence values during treadmill walking and daily living in older adults.

Methods

Older adults (≥ 60 years) were recruited from urban community venues. Data collection included 7 days of physical activity measured by an activPAL3™ thigh worn device, followed by a laboratory visit involving a 60-min assessment of resting metabolic rate, then a treadmill assessment with expired gas measured using a breath-by-breath analyser and steps measured by an activPAL3™. Treadmill stages were undertaken in a random order and lasted 5 min each at speeds of 1, 2, 3, 4 and 5 km/h. Metabolic equivalent values were determined for each stage as standardised values (METSstandard) and as multiples of resting metabolic rate (METSrelative). A value of 3 METSstandard defined moderate-intensity stepping. Segmented generalised estimating equations modelled the association between step cadence and MET values.

Results

The study included 53 participants (median age = 75, years, BMI = 28.0 kg/m2, 45.3% women). At 2 km/h, the median METSstandard and METSrelative values were above 3 with a median cadence of 81.00 (IQR 72.00, 88.67) steps/minute. The predicted cadence at 3 METSstandard was 70.3 (95% CI 61.4, 75.8) steps/minute. During free-living, participants undertook median (IQR) of 6988 (5933, 9211) steps/day, of which 2554 (1297, 4456) steps/day were undertaken in continuous stepping bouts lasting ≥ 1 min. For bouted daily steps, 96.4% (90.7%, 98.9%) were undertaken at ≥ 70 steps/minute.

Conclusion

A threshold as low as 70 steps/minute may be reflective of moderate-intensity stepping in older adults, with the vast majority of all bouted free-living stepping occurring above this threshold.
UGRP1-modulated MARCO+ alveolar macrophages contribute to age-related lung fibrosis
Authors: Chen Yongyan , Hao Xiaolei , Li Ming , Tian Zhigang , Cheng Min
Published: March 2023

The aging lungs are vulnerable to chronic pulmonary diseases; however, the underlying mechanisms are not well understood. In this study, we compared the aging lungs of 20–24-month-old mice with the young of 10–16-week-old mice, and found that aging airway epithelial cells significantly upregulated the expression of uteroglobin-related protein 1 (UGRP1), which was responsible for the higher levels of CCL6 in the aging lungs. Alveolar macrophages (AMs) changed intrinsically with aging, exhibiting a decrease in cell number and altered gene expression. Using terminal differentiation trajectories, a population of MARCO+ AMs with the ability to produce CCL6 was identified in the aging lungs. Upregulated UGRP1was demonstrated to modulate CCL6 production of AMs in the UGRP1-MARCO pair in vivo and in vitro. Furthermore, MARCO+ AMs aggravated bleomycin-induced pulmonary fibrosis in a CCL6-dependent manner in the aged mice, and blocking MARCO or neutralizing CCL6 significantly inhibited pulmonary fibrosis, similar to the depletion of AMs. The age-related upregulation of UGRP1 and MARCO+ AMs, involved in the progression of lung fibrosis, was also observed in human lung tissues. Thus, UGRP1 modulated MARCO+ AMs regarding the age-related lung fibrosis in a CCL6-dependent manner, which is key to establishing optimal targeting for the aging population.
An immersive virtual reality system for ecological assessment of peripersonal and extrapersonal unilateral spatial neglect
Authors: Perez-Marcos Daniel , Ronchi Roberta , Giroux Arthur , Brenet Fanny , Serino Andrea , Tadi Tej , Blanke Olaf
Published: March 2023

Background

Unilateral spatial neglect (USN) is a debilitating neuropsychological syndrome that often follows brain injury, in particular a stroke affecting the right hemisphere. In current clinical practice, the assessment of neglect is based on old-fashioned paper-and-pencil and behavioral tasks, and sometimes relies on the examiner’s subjective judgment. Therefore, there is a need for more exhaustive, objective and ecological assessments of USN.

Methods

In this paper, we present two tasks in immersive virtual reality to assess peripersonal and extrapersonal USN. The tasks are designed with several levels of difficulty to increase sensitivity of the assessment. We then validate the feasibility of both assessments in a group of healthy adult participants.

Results

We report data from a study with a group of neurologically unimpaired participants (N = 39). The results yield positive feedback on comfort, usability and design of the tasks. We propose new objective scores based on participant’s performance captured by head gaze and hand position information, including, for instance, time of exploration, moving time towards left/right and time-to-reach, which could be used for the evaluation of the attentional spatial bias with neurological patients. Together with the number of omissions, the new proposed parameters can result in lateralized index ratios as a measure of asymmetry in space exploration.

Conclusions

We presented two innovative assessments for USN based on immersive virtual reality, evaluating the far and the near space, using ecological tasks in multimodal, realistic environments. The proposed protocols and objective scores can help distinguish neurological patients with and without USN.
Spatiotemporal expression patterns of genes coding for plasmalemmal chloride transporters and channels in neurological diseases
Authors: Huang Yanruo , Wang Qihang , Peng Yunsong , Du Wenjie , Wang Qi , Qi Jiangtao , Hao Zijian , Wang Yingwei
Published: March 2023

Neuronal voltage changes which are dependent on chloride transporters and channels are involved in forming neural functions during early development and maintaining their stability until adulthood. The intracellular chloride concentration maintains a steady state, which is delicately regulated by various genes coding for chloride transporters and channels (GClTC) on the plasmalemma; however, the synergistic effect of these genes in central nervous system disorders remains unclear. In this study, we first defined 10 gene clusters with similar temporal expression patterns, and identified 41 GClTC related to brain developmental process. Then, we found 4 clusters containing 22 GClTC were enriched for the neuronal functions. The GClTC from different clusters presented distinct cell type preferences and anatomical heterogeneity. We also observed strong correlations between clustered genes and diseases, most of which were nervous system disorders. Finally, we found that one of the most well-known GClTC, SLC12A2, had a more profound effect on glial cell-related diseases than on neuron-related diseases, which was in accordance with our observation that SLC12A2 was mainly expressed in oligodendrocytes during brain development. Our findings provide a more comprehensive understanding of the temporal and spatial expression characteristics of GClTC, which can help us understand the complex roles of GClTC in the development of the healthy human brain and the etiology of brain disorders.
Similar outcomes following non-first-degree and first-degree related donor haploidentical hematopoietic cell transplantation for acute leukemia patients in complete remission: a study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Ye Yishan , Labopin Myriam , Chen Jia , Gulbas Zafer , Zhang Xi , Koc Yener , Blaise Didier , Ciceri Fabio , Polge Emmanuelle , Houhou Mohamed , Li Lin , Luo Yi , Wu Depei , Huang He , Mohty Mohamad , Gorin Norbert-Claude
Published: March 2023

There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed. Exact matching and propensity score matching was used. The NFD-to-FD ratio was 1:3. 2703 patients (AML: n = 2047; ALL: n = 656) in CR received a first HAPLO from either NFD (n = 154) or FD (n = 2549) related donors in 177 EBMT centers. 123 NFD and 324 FD HAPLO were included for analysis after matching. Median patient age was 35.6 and 37.2 for the NFD and FD cohorts, respectively. Both cohorts reached good engraftment rates (NFD: 95.7% vs. FD, 95.6%; p = 0.78). The 2-year relapse incidence (NFD, 21.1% vs. FD, 22.6%; p = 0.84) and non-relapse mortality (NRM) (NFD, 13.2% vs. FD, 17.7%; p = 0.33) were not significantly different. The 2-year overall survival (OS) (NFD, 71.8% vs. FD, 68.3%; p = 0.56), leukemia-free survival (LFS) (NFD, 65.7% vs. FD, 59.7%; p = 0.6) and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) (NFD, 50.9% vs. FD, 47.8%; p = 0.69) also showed no significant differences. The two cohorts showed no difference in terms of cumulative day 180 grade II-IV, grade III-IV acute GVHD, 2-year cumulative incidences of chronic and extensive chronic GVHD. For HAPLO in patients with acute leukemia, NFD related donors could be equivalent substitutions when FD related donors are not available.