bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasonically Assisted Cutting of Histological Sections for Reducing the Environmental and Financial Impact of Microtomy
Authors: Wang Dong , De Becker Daniel , Roy Anish
Published: April 2022

Modern-day microtomy requires high precision equipment to thinly section biological tissues. The sectioned tissue must be of good quality not showing cutting tracks or so-called artefacts. The quality of these sections is dependent on the blade wear, which is related to the hardness of the tissue sample, cutting angle and cutting speed. A test rig has been designed and manufactured to allow these parameters to be controlled. This has allowed for the blade wear to be analysed and quantified, and this has been completed for both ultrasonically assisted and conventional cutting. The obtained results showed a 25.2% decrease in average blade roughness after 38 cuts when using the ultrasonically assisted cutting regime. The data also showed no adverse effect on the quality of the slides produced when using this cutting methodology. Finally, the cutting force measured for both cutting regimes showed that ultrasonically assisted cutting required less force compared to conventional cutting. With the reduction of surface roughness and force, it is possible to state that ultrasonically assisted cutting reduces the wear of the blade, thereby increasing the life of the blades. An increase of just 10% in blade life would yield a cost saving of approximately 25% thereby reducing the environmental and financial impact of microtomy.
The olfactory bulb coordinates the ventral hippocampus–medial prefrontal cortex circuit during spatial working memory performance
Authors: Salimi Morteza , Tabasi Farhad , Nazari Milad , Ghazvineh Sepideh , Raoufy Mohammad Reza
Published: April 2022

Neural oscillations synchronize the activity of brain regions during cognitive functions, such as spatial working memory. Olfactory bulb (OB) oscillations are ubiquitous rhythms that can modulate neocortical and limbic regions. However, the functional connectivity between the OB and areas contributing to spatial working memory, such as the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), is less understood. Hence, we investigated functional interaction between OB and the vHPC–mPFC circuit during the spatial working memory performance in rats. To this end, we analyzed the simultaneously recorded local field potentials from OB, vHPC, and mPFC when rats explored the Y-maze and compared the brain activities of correct trials vs. wrong trials. We found that coupling between the vHPC and mPFC was augmented during correct trials. The enhanced coherence of OB activity with the vHPC–mPFC circuit at delta (< 4 Hz) and gamma (50–80 Hz) ranges were observed during correct trials. The cross-frequency analysis revealed that the OB delta phase increased the mPFC gamma power within corrected trials, indicating a modulatory role of OB oscillations on mPFC activity during correct trials. Moreover, the correlation between OB oscillations and the vHPC–mPFC circuit was increased at the delta range during correct trials, exhibiting enhanced synchronized activity of these regions during the cognitive task. We demonstrated a functional engagement of OB connectivity with the vHPC–mPFC circuit during spatial working memory task performance.
Comprehensive evaluation of structural variant genotyping methods based on long-read sequencing data
Authors: Duan Xiaoke , Pan Mingpei , Fan Shaohua
Published: April 2022

Background

Structural variants (SVs) play a crucial role in gene regulation, trait association, and disease in humans. SV genotyping has been extensively applied in genomics research and clinical diagnosis. Although a growing number of SV genotyping methods for long reads have been developed, a comprehensive performance assessment of these methods has yet to be done.

Results

Based on one simulated and three real SV datasets, we performed an in-depth evaluation of five SV genotyping methods, including cuteSV, LRcaller, Sniffles, SVJedi, and VaPoR. The results show that for insertions and deletions, cuteSV and LRcaller have similar F1 scores (cuteSV, insertions: 0.69–0.90, deletions: 0.77–0.90 and LRcaller, insertions: 0.67–0.87, deletions: 0.74–0.91) and are superior to other methods. For duplications, inversions, and translocations, LRcaller yields the most accurate genotyping results (0.84, 0.68, and 0.47, respectively). When genotyping SVs located in tandem repeat region or with imprecise breakpoints, cuteSV (insertions and deletions) and LRcaller (duplications, inversions, and translocations) are better than other methods. In addition, we observed a decrease in F1 scores when the SV size increased. Finally, our analyses suggest that the F1 scores of these methods reach the point of diminishing returns at 20× depth of coverage.

Conclusions

We present an in-depth benchmark study of long-read SV genotyping methods. Our results highlight the advantages and disadvantages of each genotyping method, which provide practical guidance for optimal application selection and prospective directions for tool improvement.
Effects of growth years on ginsenoside biosynthesis of wild ginseng and cultivated ginseng
Authors: Fang Xiaoxue , Wang Manqi , Zhou Xinteng , Wang Huan , Wang Huaying , Xiao Hongxing
Published: April 2022

Background

Ginsenoside, as the main active substance in ginseng, has the function of treating various diseases. However, the ginsenosides content of cultivated ginseng is obviously affected by the growth years, but the molecular mechanism is not clear. In addition, there are significant differences in morphology and physiology between wild ginseng and cultivated ginseng, and the effect of growth years on ginsenoside synthesis not yet understood in wild ginseng.

Results

Transcriptome sequencing on the roots, stems and leaves of cultivated ginseng and wild ginseng with different growth years was performed in this study, exploring the effect of growth years on gene expression in ginseng. The number of differentially expressed genes (DEGs) from comparison groups in cultivated ginseng was higher than that in wild ginseng. The result of weighted gene co-expression network analysis (WGCNA) showed that growth years significantly affected the gene expression of Mitogen-activated protein kinases (MAPK) signaling pathway and terpenoid backbone biosynthesis pathway in cultivated ginseng, but had no effects in wild ginseng. Furthermore, the growth years had significant effects on the genes related to ginsenoside synthesis in cultivated ginseng, and the effects were different in the roots, stems and leaves. However, it had little influence on the expression of genes related to ginsenoside synthesis in wild ginseng. Growth years might affect the expression of genes for ginsenoside synthesis by influencing the expression of these transcription factors (TFs), like my elob lastosis (MYB), NAM, ATAF1 and 2, and CUC2 (NAC), APETALA2/ethylene-responsive factor (AP2/ERF), basic helix-loop-helix (bHLH) and WRKY, etc., thereby affecting the content of ginsenosides.

Conclusions

This study complemented the gaps in the genetic information of wild ginseng in different growth periods and helped to clarify the potential mechanisms of the effect of growth years on the physiological state in wild ginseng and cultivated ginseng, which also provided a new insight into the mechanism of ginsenoside regulation.
Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy
Authors: Bess Shelby N. , Greening Gage J. , Rajaram Narasimhan , Muldoon Timothy J.
Published: April 2022

Background

Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macrophages (TAMs) and promote tumor angiogenesis. Changes in vascularization can be non-invasively assessed via diffuse reflectance spectroscopy using hemoglobin concentrations and oxygenation in a localized tumor volume. In this study, we examine whether blockade of monocyte recruitment via CCL2 (macrophage chemoattractant protein-1) leads to enhanced sensitivity of 5-fluorouracil (5-FU) in a CT26-Balb/c mouse model of CRC. It was hypothesized that the blockade of TAMs will alter tumor perfusion, increasing chemotherapy response. A subcutaneous tumor model using Balb/c mice injected with CT26 colon carcinoma cells received either a saline or isotype control, anti-CCL2, 5-FU, or a combination of anti-CCL2 and 5-FU.

Results

Findings show that 12 days post-treatment, monocyte recruitment was significantly reduced by approximately 61% in the combination group. This shows that the addition of anti-CCL2 to 5-FU slowed the fold-change (change from the original measurement to the final measurement) in tumor volume from Day 0 to Day 12 (~ 5 fold). Modest improvements in oxygen saturation (~ 30%) were observed in the combination group.

Conclusion

The findings in this work suggest that the blockade of CCL2 is sufficient in the reduction of TAMs that are recruited into the tumor microenvironment and has the ability to modestly alter tumor perfusion during early-tumor response to treatment even though the overall benefit is relatively modest.
Learning to predict in-hospital mortality risk in the intensive care unit with attention-based temporal convolution network
Authors: Chen Yu-wen , Li Yu-jie , Deng Peng , Yang Zhi-yong , Zhong Kun-hua , Zhang Li-ge , Chen Yang , Zhi Hong-yu , Hu Xiao-yan , Gu Jian-teng , Ning Jiao-lin , Lu Kai-zhi , Zhang Ju , Xia Zheng-yuan , Qin Xiao-lin , Yi Bin
Published: April 2022

Background

Dynamic prediction of patient mortality risk in the ICU with time series data is limited due to high dimensionality, uncertainty in sampling intervals, and other issues. A new deep learning method, temporal convolution network (TCN), makes it possible to deal with complex clinical time series data in ICU. We aimed to develop and validate it to predict mortality risk using time series data from MIMIC III dataset.

Methods

A total of 21,139 records of ICU stays were analysed and 17 physiological variables from the MIMIC III dataset were used to predict mortality risk. Then we compared the model performance of the attention-based TCN with that of traditional artificial intelligence (AI) methods.

Results

The area under receiver operating characteristic (AUCROC) and area under precision-recall curve (AUC-PR) of attention-based TCN for predicting the mortality risk 48 h after ICU admission were 0.837 (0.824 -0.850) and 0.454, respectively. The sensitivity and specificity of attention-based TCN were 67.1% and 82.6%, respectively, compared to the traditional AI method, which had a low sensitivity (< 50%).

Conclusions

The attention-based TCN model achieved better performance in the prediction of mortality risk with time series data than traditional AI methods and conventional score-based models. The attention-based TCN mortality risk model has the potential for helping decision-making for critical patients.

Trial registration

Data used for the prediction of mortality risk were extracted from the freely accessible MIMIC III dataset. The project was approved by the Institutional Review Boards of Beth Israel Deaconess Medical Center (Boston, MA) and the Massachusetts Institute of Technology (Cambridge, MA). Requirement for individual patient consent was waived because the project did not impact clinical care and all protected health information was deidentified. The data were accessed via a data use agreement between PhysioNet, a National Institutes of Health–supported data repository (https://www.physionet.org/), and one of us (Yu-wen Chen, Certification Number: 28341490). All methods were carried out in accordance with the institutional guidelines and regulations.
Implementation of a machine learning application in preoperative risk assessment for hip repair surgery
Authors: Li Yu-Yu , Wang Jhi-Joung , Huang Sheng-Han , Kuo Chi-Lin , Chen Jen-Yin , Liu Chung-Feng , Chu Chin-Chen
Published: April 2022

Background

This study aims to develop a machine learning-based application in a real-world medical domain to assist anesthesiologists in assessing the risk of complications in patients after a hip surgery.

Methods

Data from adult patients who underwent hip repair surgery at Chi-Mei Medical Center and its 2 branch hospitals from January 1, 2013, to March 31, 2020, were analyzed. Patients with incomplete data were excluded. A total of 22 features were included in the algorithms, including demographics, comorbidities, and major preoperative laboratory data from the database. The primary outcome was a composite of adverse events (in-hospital mortality, acute myocardial infarction, stroke, respiratory, hepatic and renal failure, and sepsis). Secondary outcomes were intensive care unit (ICU) admission and prolonged length of stay (PLOS). The data obtained were imported into 7 machine learning algorithms to predict the risk of adverse outcomes. Seventy percent of the data were randomly selected for training, leaving 30% for testing. The performances of the models were evaluated by the area under the receiver operating characteristic curve (AUROC). The optimal algorithm with the highest AUROC was used to build a web-based application, then integrated into the hospital information system (HIS) for clinical use.

Results

Data from 4,448 patients were analyzed; 102 (2.3%), 160 (3.6%), and 401 (9.0%) patients had primary composite adverse outcomes, ICU admission, and PLOS, respectively. Our optimal model had a superior performance (AUROC by DeLong test) than that of ASA-PS in predicting the primary composite outcomes (0.810 vs. 0.629, p < 0.01), ICU admission (0.835 vs. 0.692, p < 0.01), and PLOS (0.832 vs. 0.618, p < 0.01).

Conclusions

The hospital-specific machine learning model outperformed the ASA-PS in risk assessment. This web-based application gained high satisfaction from anesthesiologists after online use.
A comparison between the adductor pollicis muscle and the abductor digiti minimi muscle using electromyography AF-201P in rocuronium-induced neuromuscular block: a prospective comparative study
Authors: Iwasaki Hajime , Sato Hanae , Takagi Shunichi , Kitajima Osamu , Luthe Sarah Kyuragi , Suzuki Takahiro
Published: April 2022

Background

The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P.

Methods

Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 (TOFC2) was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to TOF count of 1 (TOFC1), time from first PTC to TOFC1 (PTC-TOF time), time to TOFC2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland–Altman analysis. Data are expressed as mean ± standard deviation.

Results

Nineteen patients were included in the analysis. Time to first PTC was significantly faster at the ADM muscle than the AP muscle (24.4 ± 11.4 min vs 32.4 ± 13.1 min, p = 0.006). PTC-TOF time was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3 min vs 12.4 ± 10.6 min, p = 0.019). There were no significant differences in time to TOFC2 and sugammadex-facilitated recovery between the two muscles. Bland–Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles.

Conclusions

The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG.

Trial registration

UMIN-CTR (Registration No. UMIN000044904). Registered 19 July 2021 -Retrospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000051290.
Dexmedetomidine improved one-lung ventilation-induced cognitive dysfunction in rats
Authors: Li Mengyun , Jin Zhe , Zhan Jia , Wang Yanlin , Chen Kai
Published: April 2022

Background

One-lung ventilation (OLV) is widely used in thoracic surgery. However, OLV may also increase CERO2 and aggravate delayed cognitive recovery. Here, we aimed to investigate the effect of dexmedetomidine (DEX) on cognitive function in rats undergoing OLV.

Methods

Sprague-Dawley rats were randomly divided into two-lung ventilation (TLV) group, OLV group and OLV treated with DEX group. Group DEX received 25 μg/kg DEX i.p. 30 min before induction. After mechanical ventilation (MV), Morris water maze (MWM) test was carried out to examine spatial memory function. Western blotting was used to detect pERK1/2, pCREB, Bcl-2 and BAX in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the hippocampal CA1 region.

Results

Post-MV, compared with group OLV, group DEX showed increases in percentage of target quadrant time (P < 0.05), platform crossings (P < 0.05), a reduction in CERO2 (P < 0.05), and pERK1/2, pCREB, and Bcl-2 significantly increased (P < 0.01 or P < 0.05), while BAX significantly decreased (P < 0.01), besides, a less damaged synaptic structure was observed in group DEX.

Conclusions

DEX improved post-MV cognitive function in rats undergoing OLV, reduced cerebral oxygen consumption, protected synaptic structure and upregulated ERK1/2-CREB anti-apoptotic signaling pathway in hippocampal CA1 region.
“I have always lived with the disease in the family”: family adaptation to hereditary cancer-risk
Authors: Silva Eliana , Gomes Pedro , Matos Paula M. , Silva Eunice R. , Silva João , Brandão Catarina , Castro Fernando , Neves Maria Carolina , Sales Célia M. D.
Published: April 2022

Background

Hereditary cancer syndromes have been conceptualized as a family level process. The present study explores the complexity and challenges of family adaptation to the hereditary cancer syndrome, in the context of genetic counseling and long-term cancer risk management and follow-up surveillance.

Methods

We performed semi-structured interviews with 13 participants with one of the following hereditary cancer syndromes: Lynch Syndrome, Hereditary Diffuse Gastric Cancer Syndrome, Hereditary Breast and Ovarian Cancer Syndrome, or Familial Adenomatous Polyposis. The interview was developed through a participatory approach with the involvement of healthcare professionals and individuals with first-hand experience of living with the hereditary cancer syndromes.

Results

The family is the main source of information and emotional support to deal with hereditary cancer syndromes. Multiple individual adaptation processes and communal coping networks interact, influencing the emotional and health-related behavior of family members. This is affected and affects the family’s communication and its’ members reactions to disclosure, with consequent changes in relationships.

Conclusions

The systemic interdependent dynamics of family adaptation calls for family-centered care of genetic cancer syndromes.
Promoting cultural change towards dementia friendly communities: a multi-level intervention in Japan
Authors: Tsuda Shuji , Inagaki Hiroki , Okamura Tsuyoshi , Sugiyama Mika , Ogawa Madoka , Miyamae Fumiko , Edahiro Ayako , Ura Chiaki , Sakuma Naoko , Awata Shuichi
Published: April 2022

Background

Effective strategies to develop dementia-friendly communities (DFCs) are needed in aging societies. We aimed to propose a strategy to develop DFCs from a Japanese perspective and to evaluate an intervention program that adopted the strategy.

Methods

This study implemented a multi-level intervention that emphasized nurturing community social capital in a large apartment complex in the Tokyo metropolitan area in 2017. We offered an inclusive café that was open for extended hours as a place to socialize and a center for activities that included monthly public lectures. Individual consultation on daily life issues was also available for free at the café. Postal surveys were sent out to all older residents aged 70 years and older in 2016 and 2019. With a one-group pre-test and post-test design, we assessed changes in the proportion of older residents who had social interaction with friends and those who were confident about living in the community, even if they were living with dementia.

Results

Totals of 2633 and 2696 residents completed the pre and post-intervention surveys, respectively. The mean age of the pre-intervention respondents was 77.4 years; 45.7% lived alone and 7.7% reported living with impaired cognitive function. The proportion of men who had regular social interaction and were confident about living in their community with dementia increased significantly from 38.8 to 44.5% (p = 0.0080) and from 34.1 to 38.3% (p = 0.045), respectively. Similar significant increases were observed in the subgroup of men living with impaired cognitive function, but not in the same subgroup for women.

Conclusions

The intervention benefitted male residents who were less likely to be involved in the community’s web of social networks at baseline. A strategy to create DFCs that emphasizes nurturing community social capital can form a foundation for DFCs.

Trial registration

This study was retrospectively registered in the University hospital Medical Information Network (UMIN) Clinical Trial Registry (registry number:UMIN000038193, date of registration: Oct 3, 2019).
Talking about chronic pain in family settings: a glimpse of older persons’ everyday realities
Authors: Merminod Gilles , Weber Orest , Semlali Imane , Terrier Anamaria , Decosterd Isabelle , Rubli Truchard Eve , Singy Pascal
Published: April 2022

Background

The expression of chronic pain remains a delicate matter for those older persons who suffer from this condition. If many studies highlight the difficulties of putting pain into words, scarce are those that take into account how given social networks can facilitate or prevent its expression. Based on a qualitative study that explores the communication about chronic pain in older persons’ social network, this article reports on this key issue of talking about health in later life within family settings and provides clinicians with information about the way older persons with chronic conditions perceive their everyday realities and social relations.

Methods

A multidisciplinary research team (medicine, linguistics and psychology) interviewed 49 persons with chronic pain, all from the French-speaking part of Switzerland, aged 75 and older, without any major cognitive or auditory impairments. After transcription, the interviews were analyzed by combining content and discourse analysis with social network theories.

Results

Communication about chronic pain depends significantly on the position of the interlocutors within the family structure, with a preference for direct relatives or individuals with similar difficulties. In social networks, the ability to communicate about chronic pain is both a resource (by allowing older persons to get help or by strengthening interpersonal relations) and a challenge (by threatening their autonomy, social relations or self-esteem).

Conclusions

The study shows the predominance of the nuclear family (partner, children) in communication relating specifically to the everyday management of chronic pain. This state of affairs is, nevertheless, balanced by issues of (loss of) autonomy. These findings, in line with current trends in geriatrics, could benefit future reflections on the scope and limits of including relatives in the care of older patients with chronic conditions.
Improving access to pre-exposure prophylaxis for adolescent girls and young women: recommendations from healthcare providers in eastern Zimbabwe
Authors: Skovdal Morten , Magoge-Mandizvidza Phyllis , Dzamatira Freedom , Maswera Rufurwokuda , Nyamukapa Constance , Thomas Ranjeeta , Mugurungi Owen , Gregson Simon
Published: April 2022

Background

In sub-Saharan Africa, adolescent girls and young women (AGYW) are at high risk of acquiring HIV. A growing number of sub-Saharan African countries are beginning to avail pre-exposure prophylaxis, or PrEP, but with limited success. Unpacking strategies to overcome barriers to the uptake of PrEP is critical to prevent HIV amongst AGYW. This article explores health professionals’ views and recommendations on what is required to increase uptake of PrEP.

Methods

The study draws on interview data from 12 providers of HIV prevention services in eastern Zimbabwe. The healthcare providers were purposefully recruited from a mix of rural and urban health facilities offering PrEP. The interviews were transcribed and imported into NVivo 12 for thematic coding and network analysis.

Results

Our analysis revealed six broad strategies and 15 concrete recommendations which detail the range of elements healthcare providers consider central for facilitating engagement with PrEP. The healthcare providers called for: (1) PrEP marketing campaigns; (2) youth-friendly services or corners; (3) improved PrEP delivery mechanisms; (4) improvements in PrEP treatment; (5) greater engagement with key stakeholders, including with young people themselves; and (6) elimination of costs associated with PrEP use. These recommendations exemplify an awareness amongst healthcare providers that PrEP access is contingent on a range of factors both inside and outside of the clinical setting.

Conclusions

Healthcare providers are at the frontline of the HIV epidemic response. Their community-embeddedness, coupled with their interactions and encounters with AGYW, make them well positioned to articulate context-specific measures for improving access to PrEP. Importantly, the breadth of their recommendations suggests recognition of PrEP use as a complex social practice that requires integration of a combination of interventions, spanning biomedical, structural, and behavioural domains.
Development, feasibility and acceptability of a self-efficacy-enhancing smartphone application among pregnant women with gestational diabetes mellitus: single- arm pilot clinical trial
Authors: Al Hashmi Iman , Alsabti Hilal , Al Omari Omar , Al Nasseri Yusra , Khalaf Atika
Published: April 2022

Background

There is growing attention to the use of mHealth technologies to promote glycemic control for women with GDM around the world, but research on promoting a change in health behaviors is lacking. This study aimed to document the process of designing, developing, and testing the feasibility and acceptability of the SEESPA.

Methods

This single-arm pilot clinical trial study included 15 pregnant women with GDM. Following SEESPA development (e.g., goal setting and action plan, role modeling, motivational messages, mastery of experiences, and tracking healthy behaviors), all participants were provided access to use the SEESPA for 4 weeks. Feasibility outcomes assessed were rates of recruitment, retention rate, success rate of transmitting motivational text messages, rate of participants acknowledging receipt of text messages, and success rate of recording healthy behaviors. Acceptability outcomes were determined by asking open-ended questions through telephone interview at 4-week post-intervention.

Results

Fifteen randomly selected women consented to participate in the study, with a 60.0% (n = 9) retention rate at post-trial intervention and 40.0% (n = 6) trial dropout. Two motivational text messages per week were sent to all participants. Of these, 68.1% were acknowledged by the participants. Study participants reported that SEESPA is useful, effective, and they felt satisfied about it. In addition, they brought few suggestions that will be integrated on the final version of the app.

Conclusions

and Clinical Relevance.

The developed innovative SEESPA is a feasible and acceptable intervention for behavioral modifications among women with GDM, and is ready to be tested in a larger RCT study which is expected to inform the health policymakers to integrate SEESPA with the antenatal health care practice of women with GDM, specifically in developing countries where there is a greater risk of developing GDM complications among mothers and their infants.

Trial registration.

The study is registered on September 16, 2019 (ACTRN12619001278123p) by the Australian New Zealand Clinical Trials Registry.
Characterization of SN38-resistant T47D breast cancer cell sublines overexpressing BCRP, MRP1, MRP2, MRP3, and MRP4
Authors: Lee Hee-Jeong , Choi Cheol-Hee
Published: April 2022

Background

Although several novel resistant breast cancer cell lines have been established, only a few resistant breast cancer cell lines overexpress breast cancer resistance proteins (BCRP). The aim of this study was to establish new resistant breast cancer cell lines overexpressing BCRP using SN38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of irinotecan and was to discover genes and mechanisms associated with multidrug resistance.

Methods

SN38-resistant T47D breast cancer cell sublines were selected from the wild-type T47D cells by gradually increasing SN38 concentration. The sensitivity of the cells to anti-cancer drugs was assessed by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Expression profiles of the resistance-related transporters were examined using RT-qPCR, and western blot analysis. Intracellular fluorescent dye accumulation in the resistant cells was determined using flow cytometry.

Results

The SN38-resistant T47D breast cancer cell sublines T47D/SN120 and T47D/SN150 were established after long-term exposure (more than 16 months) of wild-type T47D cells to 120 nM and 150 nM SN38, respectively. T47D/SN120 and T47D/SN150 cells were more resistant to SN38 (14.5 and 59.1 times, respectively), irinotecan (1.5 and 3.7 times, respectively), and topotecan (4.9 and 12 times, respectively), than the wild-type parental cells. Both T47D/SN120 and T47D/SN150 sublines were cross-resistant to various anti-cancer drugs. These resistant sublines overexpressed mRNAs of MRP1, MRP2, MRP3, MRP4, and BCRP. The DNA methylase inhibitor 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor trichostatin A increased the expression levels of BCRP, MRP1, MRP2, MRP3, and MRP4 transcripts in T47D/WT cells. Fluorescent dye accumulation was found to be lower in T47D/SN120 and T47D/SN150 cells, compared to that in T47D/WT cells. However, treatment with known chemosensitizers increased the intracellular fluorescent dye accumulation and sensitivity of anti-tumor agents.

Conclusion

T47D/SN120 and T47D/SN150 cells overexpressed MRP1, MRP2, MRP3, MRP4, and BCRP, which might be due to the suppression of epigenetic gene silencing via DNA hypermethylation and histone deacetylation. Although these resistant cells present a higher resistance to various anti-cancer drugs than their parental wild-type cells, multidrug resistance was overcome by treatment with chemosensitizers. These SN38 resistant T47D breast cancer cell sublines expressing resistance proteins can be useful for the development of new chemosensitizers.
BIRC5 regulates inflammatory tumor microenvironment-induced aggravation of penile cancer development in vitro and in vivo
Authors: Zhao Yang , Liu Songlin , Li Shuhang , Zhang Gang , Tian Aimin , Wan Yinxu
Published: April 2022

Background

Baculoviral IAP repeat containing 5 (BIRC5) is overexpressed and plays as a key regulator in the progression of various human carcinomas. The inflammatory tumor microenvironment (ITM) is closely associated with the development of cancers. However, the role of BIRC5 in penile cancer (PC) and the ITM-induced abnormal progression of PC is still obscure.

Methods

In this study, serum and tissues of patients with PC were recruited to evaluate the expression profile of BIRC5. We used PC cell lines (Penl1 and Penl2) and constructed a PC xenograft mice model to explore the effects of the silencing of BIRC5 on proliferation, migration, invasion and tumor growth, as well as survival of mice. Besides, interferon (IFN)-γ was utilized to mimic the ITM of PC cells.

Results

Our results showed that BIRC5 was dramatically upregulated in the serum and tissues of PC patients, as well as PC cell lines. Knockdown of BIRC5 inhibited the proliferation, migration and invasion of PC cells. Meanwhile, it suppressed PC xenograft tumor growth and improved mice survival. Moreover, IFN-γ significantly aggravated PC progression both in vivo and in vitro while the silencing of BIRC5 reversed these unfavorable effects.

Conclusions

Taken together, our data revealed that BIRC5 silencing inhibited aggravation of PC cell processes and tumor development induced by ITM. This suggested that BIRC5 may function as a diagnosis and therapy target of PC in the future.
Identification of the potential biological target molecules related to primary open-angle glaucoma
Authors: Li Hongyu , Ye Zi , Li Zhaohui
Published: April 2022

Background

To identify the potential biological target molecules and the corresponding interaction networks in primary open-angle glaucoma (POAG) development.

Methods

The microarray datasets of GSE138125 and GSE27276 concerning lncRNA and mRNA expression profiles in trabecular meshwork of POAG were downloaded from the Gene Expression Omnibus database. The R software was applied to identify differentially expressed (DE) lncRNAs and mRNAs in POAG, and to perform GO and KEGG functional enrichment analysis. Protein–protein interaction (PPI) network and module analysis, and lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network were performed by Cytoscape software.

Results

A total of 567 DE-mRNAs were identified from GSE138125 and GSE27276, including 298 up-regulated and 269 down-regulated mRNAs, which were found enriching in biological processes of extracellular matrix organization and epidermis development, respectively. KEGG pathway enrichment analysis further revealed that module genes in PPI network were primarily involved in the AGE-PAGE, PI3K-Akt and TGF-β signaling pathways. Moreover, 897 up-regulated and 1036 down-regulated DE-lncRNAs were identified from GSE138125. Through literature review and databases searching, we obtained 712 lncRNA-miRNA and 337 miRNA-mRNA pairs based on the selected eight POAG-related miRNAs. After excluding 702 lncRNAs and 284 mRNAs that were not comprised in the DE-lncRNA and DE-mRNAs, a total of 53 lncRNA nodes, eight miRNA nodes, 10 mRNA nodes, and 78 edges were included in the final ceRNA network.

Conclusions

This study demonstrated the lncRNA and mRNA expression profiles of trabecular meshwork in POAG patients and the normal controls, and identified potentially ceRNAs and pathways which might improve the pathogenic understanding of this ocular disease.
Hepatitis B and pregnancy: understanding the experiences of care among pregnant women and recent mothers in metropolitan Melbourne
Authors: Ahad Marvad , Wallace Jack , Xiao Yinzong , van Gemert Caroline , Bennett Gabrielle , Darby Jonathan , Desmond Paul , Hall Samuel , Holmes Jacinta , Papaluca Tim , Glasgow Susanne , Thompson Alexander , Hellard Margaret , Doyle Joseph , Howell Jessica
Published: April 2022

Background

Pregnant women are a priority group for hepatitis B testing. Guideline-based care during antenatal and post-partum periods aims to prevent mother-to-child transmission of hepatitis B virus and lower the risk of liver complications in mothers. This qualitative study explored knowledge of hepatitis B and experiences of hepatitis B related care among pregnant women and mothers.

Methods

Semi-structured interviews were conducted with thirteen women with hepatitis B who were attending antenatal or post-partum hepatitis B care. The interviews were thematically analysed to assess knowledge and understanding of hepatitis B. Participants were recruited from specialist clinics in metropolitan Melbourne between August 2019 and May 2020.

Results

Four major themes were identified from interviews: (1) knowledge and understanding of hepatitis B, (2) treatment pathways, (3) accessing hepatitis B related care, and (4) disclosing status to friends. Most participants displayed an understanding of hepatitis B transmission, including mother to child transmission. The main motivator of post-partum attendance was reassurance gained concerning their child’s health. Sources of hepatitis B information included doctors, online information and family. Participants identified parents and siblings as sources of support and reported an unwillingness to disclose hepatitis B status to friends.

Conclusions

Women attending antenatal or post-partum care reported having overall positive experiences, particularly regarding reassurance of their child’s health, but displayed misconceptions around horizontal transmission. Knowledge gained from these results can contribute to the development of targeted models of care for pregnant women and mothers with young children to ensure their successful linkage to care.
A profile of injuries suffered by female soldiers serving in the Australian Army
Authors: Schram Ben , Orr Robin , Pope Rodney
Published: April 2022

Introduction

Female soldiers comprise an important component of any modern army, yet little research has been performed to investigate differences in the profiles of injuries reported by qualified female and male army personnel.

Aim

The aim of this study was to compare injury rates and patterns between female and male soldiers of the Australian Regular Army (ARA).

Methods

Data pertaining to all injuries reported by ARA members over a two-year period were accessed from the SENTINEL database and analysed descriptively. Findings regarding injury patterns were reported by most common location, nature, mechanism, and activity being performed at the time of injury. Injury incidence rates (IR) were calculated based on population size, and injury incidence rate ratios (IRR) comparing female and male injury rates were determined.

Results

A total of 8750 injuries were recorded across the two-year time period (2018–2020) of the study (minor injuries: n = 1766 female, n = 6870 male; serious injuries: n = 19 female, n = 95 male). Higher incidence rates of minor injuries were reported for female soldiers (IR = 20.75 injuries/100 soldiers/year) when compared to male soldiers (IR = 13.60 injuries/100 soldiers/year), with an IRR of 1.53 [95% CI = 1.46–1.60]. More serious injuries were reported at a similar rate between female (IR = 0.22/100 soldiers/year) and male soldiers (IR = 0.21/100 soldiers/year), with an IRR of 1.05 [95% CI = 0.65–1.72]. Female soldiers tended to report more ankle injuries than male soldiers who reported more knee injuries. Physical training and combat training were the most common causes of injury for both sexes.

Discussion

There were subtle differences in body locations of minor injuries within female and male soldiers. Both minor and more serious injury profiles were otherwise similar between sexes. Therefore, strategies required to minimise injuries in female soldiers may be similar in many respects to strategies required for male soldiers but require some differences to account for the subtle differences in body locations of injury, and so to ensure effectiveness across all personnel.
Impact of heterotopic ossification following lumbar total disk replacement: a systematic review
Authors: Hood Colleen , Zamani Reza , Akrami Mohammad
Published: April 2022

Background context

Lumbar total disc replacement (TDR) is an alternative to lumbar fusion in the treatment of lower back pain and reduces the risk of adjacent segment degeneration. Heterotopic ossification (HO) has been identified as a common complication following lumbar TDR.

Purpose

This systematic review aims to determine the prevalence, risk factors and clinical and radiological impact of HO following lumbar TDR.

Study Design

Systematic Review.

Methods

MEDLINE, Scopus, PubMed and Cochrane Central were searched for articles that referred to lumbar TDR and HO. The hits were assessed against inclusion and exclusion criteria. Data from each included study was extracted and analysed with respect to the study aims.

Results

Twenty-six studies were included in this review and the pooled prevalence of HO was estimated to be between 13.2% (participants) and 15.3% (vertebral levels). TDR clinical outcomes were not found to be reduced by HO and there was insufficient data to identify a given impact upon radiological outcomes. Age and follow up time were identified as potential risk factors for HO.

Conclusions

This review was hampered by inconsistencies in the reporting of HO across the studies. We therefore recommend that a set of guidelines should be produced to aid future researchers and reduce the risk of bias.
Factors influencing inconsistent leg length discrepancy in dysplastic hip osteoarthritis: a retrospective study
Authors: Takemoto Genta , Osawa Yusuke , Seki Taisuke , Takegami Yasuhiko , Ochiai Satoshi , Kato Daisaku , Imagama Shiro
Published: April 2022

Background

We aimed to examine the inconsistency between radiographic leg length discrepancy (R-LLD) and perceived LLD (P-LLD) in patients with dysplastic hip osteoarthritis and to evaluate the factors that can cause such inconsistency.

Methods

We conducted a retrospective study on 120 patients. An inconsistent LLD was defined as a condition in which the P-LLD was shorter than the R-LLD by > 5 mm. We compared relevant data on the general characteristics of the patients and the radiological findings between consistent (group E, 92 cases [76.7%]) and inconsistent LLDs (group S, 28 cases [23.3%]).

Results

The number of patients with a history of hip surgery on the affected side and the Japanese Orthopedic Association classification pain scores were significantly higher in group S than in group E (32.1% vs. 10.8%, respectively; P = 0.015, and 21.7 ± 7.0 vs. 17.5 ± 8.2, respectively; P = 0.036). The pelvic oblique angle and length of the R-LLD were significantly higher in group S than in group E (2.9 ± 2.5° vs. 0.3 ± 2.3°, respectively; P < 0.01, and 17.2 ± 8.9 mm vs. 6.3 ± 8.4 mm, respectively; P < 0.01). Multivariate logistic analysis revealed that the pelvic oblique angle (odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.28–2.52; P < 0.01) and length of the R-LLD (OR: 2.75, 95% CI: 1.24–6.12; P = 0.013) were independent risk factors of inconsistent LLD.

Conclusion

The pelvic oblique angle and a long R-LLD were independent risk factors of inconsistent LLD in patients with dysplastic hip osteoarthritis. Therefore, hip surgeons should consider P-LLD rather than R-LLD to understand the need for conservative intervention.
Medical educators' experiences on medically unexplained symptoms and intercultural communication—an expert focus group study
Authors: Sallay Viola , Martos Tamás , Lucza Lilla , Weiland Anne , Stegers‐Jager Karen M. , Vermeir Peter , Mariman An Noelle Margareta , Csabai Márta
Published: April 2022

Background

Medically unexplained symptoms (MUS) are highly prevalent and remain challenging in healthcare and medical education, along with the increase in the importance of intercultural issues regarding MUS. However, less is known about the challenges of professionally addressing patients with MUS in the interprofessional and intercultural contexts. Thus, the present study aims to provide the first exploration of the experiences of medical specialists regarding treating MUS in intercultural contexts and inputs for training development on the intercultural aspects of MUS.

Methods

Three focus groups (totaln = 13) consisting of medical specialists from a Hungarian university who were teaching at the medical faculty in intercultural settings and also worked for the university health services were interviewed. The topics covered the participants' personal experiences on addressing MUS and the challenges of intercultural communication and the intercultural educational context. Thematic analysis was used to yield a qualitative account of the interviews as guided by the research questions.

Results

Representing the different aspects of medical specialists, the study identified three main themes in the experiences of medical specialists, namely, 1) the need to adapt to the personal world of patients and search for common frames to understand MUS, 2) the need to discover methods for adapting to cultural differences and 3) the need to enhance the interprofessional coordination of knowledge and practices.

Conclusions

The results are in line with the distinct conclusions of previous studies. Moreover, an integrated educational program on the intercultural aspects of MUS may address the main themes separately and, subsequently, support their integration. Therefore, the study discusses the manner in which an integrated educational program on the intercultural aspects of MUS may address the needs recognized in these aspects.
Competent and deficient provision of childbirth services: a descriptive observational study assessing the quality of intrapartum care in two provinces of the Democratic Republic of the Congo
Authors: Brenner Stephan , Madhavan Supriya , Nseya Céline Kanionga , Sese Claude , Fink Günther , Shapira Gil
Published: April 2022

Background

A majority of women in the Democratic Republic of the Congo (DRC) give birth in a health facility, but maternal and newborn mortality remains high. In rural areas, the quality of facility-based delivery care is often low. This study examines clinical quality of intrapartum care in two provinces of the DRC.

Methods

We observed process and input elements of delivery care provision at 29 facilities in Kwilu and Kwango provinces. Distinguishing non-performance attributable to provider behavior vs. input constraints, we compared both providers’ adherence to clinical standards (“competent care”) and non-adherence to processes for which required inputs were available (“deficient care”).

Results

Observing a total of 69 deliveries, care was most competent for partograph use (75% cases) and hemorrhage prevention (73%), but least for postpartum monitoring (4%). Competent care was significantly associated with higher case volumes (p = ·03), skilled birth attendance (p = ·05), and nulliparous women (p = ·02). Care was most deficient for infection prevention (62%) and timely care (49%) and associated with cases observed at hospitals and lower delivery volume.

Conclusions

Low quality was commonly not a result of missing equipment or supplies but related to providers’ non-adherence to standard protocols. Low case volumes and the absence of skilled attendants seemed to be main factors for sub-standard quality care. Birth assistance during labor stage 2 was the only intrapartum stage heavily affected by the unavailability of essential equipment. Future interventions should strengthen links between birth attendants’ practice to clinical protocols.