bluuebunny/crossref_metadata_2025 huggingface dataset:
Oligomers of hepatitis A virus (HAV) capsid protein VP1 generated in a heterologous expression system
Authors: Nain Anshu , Kumar Mohit , Banerjee Manidipa
Published: April 2022

Background

The quasi-enveloped picornavirus, Hepatitis A Virus (HAV), causes acute hepatitis in humans and infects approximately 1.5 million individuals a year, which does not include the asymptomatically infected population. Several severe outbreaks in developing nations in recent years have highlighted the reduction in HAV endemicity, which increases the risk of infections in the vulnerable population. The current HAV vaccines are based on growing wildtype or attenuated virus in cell culture, which raises the cost of production. For generation of cheaper, subunit vaccines or strategies for antibody-based diagnostics, production of viral structural proteins in recombinant form in easily accessible expression systems is a priority.

Results

We attempted several strategies for recombinant production of one of the major capsid proteins VP1, from HAV, in the E. coli expression system. Several efforts resulted in the formation of soluble aggregates or tight association of VP1 with the bacterial chaperone GroEL. Correctly folded VP1 was eventually generated in a discrete oligomeric form upon purification of the protein from inclusion bodies and refolding. The oligomers resemble oligomers of capsid proteins from other picornaviruses and appear to have the correct secondary and antigenic surface structure.

Conclusions

VP1 oligomers generated in the bacterial expression system can be utilized for understanding the molecular pathway of HAV capsid assembly and may also have potential biomedical usages in prevention and diagnostics of HAV infections.
Infection age as a predictor of epidemiological metrics for malaria
Authors: Henry John M. , Carter Austin , Smith David L.
Published: April 2022

Background

Accurate estimation of the burden of Plasmodium falciparum is essential for strategic planning for control and elimination. Due in part to the extreme heterogeneity in malaria exposure, immunity, other causes of disease, direct measurements of fever and disease attributable to malaria can be difficult. This can make a comparison of epidemiological metrics both within and between populations hard to interpret. An essential part of untangling this is an understanding of the complex time-course of malaria infections.

Methods

Historic data from malariatherapy infections, in which individuals were intentionally infected with malaria parasites, were reexamined in aggregate. In this analysis, the age of each infection was examined as a potential predictor describing aggregate patterns across all infections. A series of piecewise linear and generalized linear regressions were performed to highlight the infection age-dependent patterns in both parasitaemia and gametocytaemia, and from parasitaemia and gametocytaemia to fever and transmission probabilities, respectively.

Results

The observed duration of untreated patent infection was 130 days. As infections progressed, the fraction of infections subpatent by microscopy was seen to increase steadily. The time-averaged malaria infections had three distinct phases in parasitaemia: a growth phase for the first 6 days of patency, a rapid decline from day 6 to day 18, and a slowly declining chronic phase for the remaining duration of the infection. During the growth phase, parasite densities increased sharply to a peak. Densities sharply decline for a short period of time after the peak. During the chronic phase, infections declined steadily as infections age. gametocytaemia was strongly correlated with lagged asexual parasitaemia. Fever rates and transmission efficiency were strongly correlated with parasitaemia and gametocytaemia. The comparison between raw data and prediction from the age of infection has good qualitative agreement across all quantities of interest for predicting averaged effects.

Conclusion

The age of infection was established as a potentially useful covariate for malaria epidemiology. Infection age can be estimated given a history of exposure, and accounting for exposure history may potentially provide a new way to estimate malaria-attributable fever rates, transmission efficiency, and patent fraction in immunologically naïve individuals such as children and people in low-transmission regions. These data were collected from American adults with neurosyphilis, so there are reasons to be cautious about extending the quantitative results reported here to general populations in malaria-endemic regions. Understanding how immune responses modify these statistical relationships given past exposure is key for being able to apply these results more broadly.
Light-triggered multifunctional nanoplatform for efficient cancer photo-immunotherapy
Authors: Yue Juan , Mei Qian , Wang Panyong , Miao Peng , Dong Wen-Fei , Li Li
Published: April 2022

Cancer immunotherapy is limited by the immune escape of tumor cells and adverse effects. Photo-immunotherapy, the combination of immunotherapy and phototherapy (such as photodynamic therapy (PDT) and photothermal therapy (PTT)), can improve the effectiveness of immunotherapy in cancer treatment. Here, we first explored mesoporous hexagonal core–shell zinc porphyrin-silica nanoparticles (MPSNs), which are composed of a zinc porphyrin core and a mesoporous silica shell, and exhibit high laser-triggered photodynamic and photothermal activity, as well as outstanding drug loading capacity. In other words, MPSNs can be used not only as excellent photosensitizers for photo-immunotherapy, but also as an ideal drug carrier to achieve more efficient synergy. After loading with R837 (imiquimod, a toll-like receptor-7 agonist), MPSNs@R837 will elicit high-efficiency immunogenic cell death via PDT and PTT, and promote dendritic cell maturation after the PH-responsive release of R837, thereby, inducing tumor-specific immune responses. When combined with a programmed death ligand-1 checkpoint blockade, the photo-immunotherapy system markedly restrains primary tumors and metastatic tumors with negligible systemic toxicity. Therefore, the therapeutic strategy of integrating PTT, PDT and checkpoint blockade, shows great potential for suppressing cancer metastasis.

Graphical Abstract
Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer
Authors: Xiao Shihan , Yang Chen , Zhang Yang , Lai Chen
Published: April 2022

Background

The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored.

Methods

We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database.

Results

B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity.

Conclusions

The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer.
Comparing methods for handling missing cost and quality of life data in the Early Endovenous Ablation in Venous Ulceration trial
Authors: Diop Modou , Epstein David
Published: April 2022

Objectives

This study compares methods for handling missing data to conduct cost-effectiveness analysis in the context of a clinical study.

Methods

Patients in the Early Endovenous Ablation in Venous Ulceration (EVRA) trial had between 1 year and 5.5 years (median 3 years) of follow-up under early or deferred endovenous ablation. This study compares complete-case-analysis (CCA), multiple imputation using linear regression (MILR) and using predictive mean matching (MIPMM), Bayesian parametric approach using the R package missingHE (BPA), repeated measures fixed effect (RMFE) and repeated measures mixed model (RMM). The outcomes were total mean costs and total mean quality-adjusted life years (QALYs) at different time horizons (1 year, 3 years and 5 years).

Results

All methods found no statistically significant difference in cost at the 5% level in all time horizons, and all methods found statistically significantly greater mean QALY at year 1. By year 3, only BPA showed a statistically significant difference in QALY between treatments. Standard errors differed substantially between the methods employed.

Conclusion

CCA can be biased if data are MAR and is wasteful of the data. Hence the results for CCA are likely to be inaccurate. Other methods coincide in suggesting that early intervention is cost-effective at a threshold of £30,000 per QALY 1, 3 and 5 years. However, the variation in the results across the methods does generate some additional methodological uncertainty, underlining the importance of conducting sensitivity analyses using alternative approaches.
Cancer combination therapies by angiogenesis inhibitors; a comprehensive review
Authors: Ansari Mohammad Javed , Bokov Dmitry , Markov Alexander , Jalil Abduladheem Turki , Shalaby Mohammed Nader , Suksatan Wanich , Chupradit Supat , AL-Ghamdi Hasan S. , Shomali Navid , Zamani Amir , Mohammadi Ali , Dadashpour Mehdi
Published: April 2022

Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines.
Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons
Authors: Naimi Adel , Mohammed Rebar N. , Raji Ahmed , Chupradit Supat , Yumashev Alexei Valerievich , Suksatan Wanich , Shalaby Mohammed Nader , Thangavelu Lakshmi , Kamrava Siavash , Shomali Navid , Sohrabi Armin D. , Adili Ali , Noroozi-Aghideh Ali , Razeghian Ehsan
Published: April 2022

The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor of the immune system by a myriad of mechanisms. After that, scientists focused on the immune checkpoint molecules mainly. Thereby, much effort was spent to progress novel strategies for suppressing these inhibitory axes, resulting in the evolution of immune checkpoint inhibitors (ICIs). Then, ICIs have become a promising approach and shaped a paradigm shift in tumor immunotherapies. CTLA-4 plays an influential role in attenuation of the induction of naïve and memory T cells by engagement with its responding ligands like B7-1 (CD80) and B7-2 (CD86). Besides, PD-1 is predominantly implicated in adjusting T cell function in peripheral tissues through its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. Given their suppressive effects on anti-tumor immunity, it has firmly been documented that ICIs based therapies can be practical and rational therapeutic approaches to treat cancer patients. Nonetheless, tumor inherent or acquired resistance to ICI and some treatment-related toxicities restrict their application in the clinic. The current review will deliver a comprehensive overview of the ICI application to treat human tumors alone or in combination with other modalities to support more desired outcomes and lower toxicities in cancer patients.
A specific, non-immune system-related isoform of the human inducible nitric oxide synthase is expressed during differentiation of human stem cells into various cell types
Authors: Gather Fabian , Ihrig-Biedert Irmgard , Kohlhas Paul , Krutenko Tamara , Peitz Michael , Brüstle Oliver , Pautz Andrea , Kleinert Hartmut
Published: April 2022

Background

NOS2 expression is mostly found in bacteria-exposed or cytokine-treated tissues and is mostly connected to innate immune reactions. There are three isoforms of NOS2 (NOS2-1 to -3). In RNA-seq data sets, analyzing inflammatory gene expression, only expression of the NOS2-1 mRNA isoform is detected. However, the expression of NOS2 in differentiating human pluripotent stems (hPSCs) has not been analyzed yet.

Methods

Public available RNA-seq databases were screened for data of hPSCs during differentiation to different target cells. An isoform specific algorithm was used to analyze NOS2 mRNA isoform expression. In addition, we differentiated four different human iPSC cell lines toward cortical neurons and analyzed NOS2 mRNA expression by qRT-PCR and 5′-RACE. The functionality of the NOS2-2 protein was analyzed by transient transfection of expression clones in human DLD1 cells and nitrate measurement in the supernatant of these cells.

Results

In RNA-seq databases we detected a transient expression of the NOS2 mRNA during the differentiation of hPSCs to cardiomyocytes, chondrocytes, mesenchymal stromal cells, neurons, syncytiotrophoblast cells, and trophoblasts. NOS2 mRNA isoform specific analyses showed, that the transiently expressed NOS2 mRNA in differentiating hPSC (NOS2-2; “diff-iNOS”) differ remarkably from the already described NOS2 transcript found in colon or induced islets (NOS2-1; “immuno-iNOS”). Also, analysis of the NOS2 mRNA- and protein expression during the differentiation of four different hiPSC lines towards cortical neurons showed a transient expression of the NOS2 mRNA and NOS2 protein on day 18 of the differentiation course. 5′-RACE experiments and isoform specific qRT-PCR analyses revealed that only the NOS2-2 mRNA isoform was expressed in these experiments. To analyze the functionality of the NOS2-2 protein, we transfected human DLD-1 cells with tetracycline inducible expression clones encoding the NOS2-1- or -2 coding sequence. After induction of the NOS2-1 or -2 mRNA expression by tetracycline a similar nitrate production was measured proofing the functionality of the NOS2-2 protein isoform.

Conclusions

Our data show that a differentiation specific NOS2 isoform (NOS2-2) is transiently expressed during differentiation of hPSC.
Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke
Authors: Li Xuan , Lyu Jingjun , Li Ran , Jain Vaibhav , Shen Yuntian , del Águila Ángela , Hoffmann Ulrike , Sheng Huaxin , Yang Wei
Published: April 2022

Background

Ischemic stroke is a medical emergency that primarily affects the elderly. A complex immune response in the post-stroke brain constitutes a key component of stroke pathophysiology. This study aimed to determine how stroke affects immune cell populations in the aged brain based on molecular profiles of individual cells.

Methods

Single-cell RNA sequencing and a new transient ischemic stroke mouse model with late reperfusion were used.

Results

We generated, for the first time, a composite picture of immune cell populations in the stroke aged brain at single-cell resolution. We discovered at least 6 microglial subsets in the stroke aged brain, including a potentially stroke-specific subtype. Moreover, we identified major cell subpopulations formed by infiltrated myeloid cells after stroke, and revealed their unique molecular profiles.

Conclusions

This study provided the first scRNA-seq data set for immune cells in the stroke aged brain, and offered novel insights into post-stroke immune cell heterogeneity.
“Being able to do whatever you wanna do as a woman is important:” a qualitative exploration of contraception as a frame of reference for HIV prevention with PrEP
Authors: Murphy Emma Chew , Danvers Antoinette , Zamudio Andrés Ramírez , Avila Karina , Proehl Meghan , Gonzalez-Argoti Tatiana , Mantell Joanne E. , Bauman Laurie J. , Dolan Siobhan M.
Published: April 2022

Background

Use of HIV PrEP (pre-exposure prophylaxis) is a strategic tool in the effort to end the HIV epidemic. 20% of new HIV infections in the US are among cis-gender women, yet they comprise only 5% of all PrEP users. Black women disproportionately bear the burden of new HIV acquisition and accounted for almost 60% of new HIV diagnoses among women in 2018. Increasing understanding and uptake of PrEP among women at risk of HIV acquisition in alignment with their reproductive values and preferences is key to increasing PrEP uptake and decreasing HIV burden in this population.

Objective

This study examines how experiences with contraception among women of color shape their perceptions and preferences regarding HIV PrEP to inform counseling that aligns with their reproductive values.

Methods

Women aged 18–45 who self-identified as Black or Latina were recruited at an academic medical center in the Bronx from June 2018 to July 2019. We enrolled 30 participants seeking family planning care (10), prenatal care (10), or care for sexually transmitted infections (10). Participants completed a brief written survey assessing their risk of HIV acquisition. Semi-structured, face-to-face interviews were then audio-recorded, transcribed, and entered into Dedoose. Grounded theory and constant comparison approaches were used to analyze the data.

Results

Twenty-one participants (70%) screened positive for HIV acquisition risk. Four had received information on PrEP from a medical provider prior to the interview. Three themes emerged from the qualitative analysis: (1) Similar to oral contraception, women conceptualized PrEP as a “daily pill” to support their reproductive health; (2) Women perceived PrEP as a tool to support autonomy and pleasure in their sexual health; (3) Like birth control, women desired multiple delivery options for HIV prophylaxis.

Conclusions

Contraception may serve as a frame of reference when counseling about PrEP among cis-women at risk of acquiring HIV. Our study suggests that this approach re-contextualizes counseling on PrEP within a sex-positive framework that prioritizes pleasure, safety, and autonomy as integral to sexual and reproductive wellness. Consideration of historically marginalized women’s experiences with contraception and reproductive values may facilitate their use of PrEP.
Molecular detection and phylogenetic analysis of porcine circovirus type 3 in Tibetan pigs on the Qinghai-Tibet Plateau of China
Authors: Pan Yangyang , Qiu Shantong , Chen Rui , Zhang Tiantian , Liang Linfeng , Wang Meng , Baloch Abdul Rasheed , Wang Libin , Zhang Qian , Yu Sijiu
Published: April 2022

Background

Porcine circovirus type 3 (PCV3) has been confirmed to infect pigs, posing a health risk and making pigs more susceptible to other pathogens. After the first report of PCV3 infection in the United States, its prevalence was determined in pigs suffering from clinical digestive or respiratory diseases in several other regions, including the Sichuan and Gansu provinces of China. In this study, we describe the frequency of PCV3 detection in Tibetan pigs inhabiting three different provinces surrounding the Qinghai-Tibet Plateau of China.

Methods

A total of 316 samples from diarrheic animals and 182 samples from healthy animals were collected in a randomized manner. Conventional PCR was applied for PCV3 DNA detection. The conserved regions of the PCV3 gene were analyzed with MEGA 7.1 software to design specific primers to sequence entire Cap genes in PCV3 strains, and the sequences were then used to confirm the subtypes of PCV3 in the positive samples. Prediction of the amino acid sequences by nucleotide sequence translation was also performed to compare the point mutations in the entire Cap protein. Twenty PCV3 whole-genomic sequences were used for genome phylogenetic analyses of PCV3 and sequence alignments with 22 other reference strains.

Results

We found that the prevalence of the virus was significantly higher in samples from pigs with diarrhoea than that in samples from healthy pigs. Phylogenetic analysis of Cap proteins demonstrated that the 20 PCV3 strains formed three clades, including PCV3a (8/20, 40.00%), PCV3b (5/20, 25%) and PCV3c (7/20, 35.00%). The complete genome sequence revealed that these strains formed one branch in the phylogenetic tree. Sequence analysis showed that the Cap proteins of the 20 different viral strains shared between 95.84 and 99.18% nucleotide identity. Cap protein sequence analyses showed that the positivity rate of PCV3a was highest in the samples from pigs with diarrhoea. In comparison, PCV3c was the most elevated subtype in the healthy samples. There was no mutation at a specific site in the amino acid sequences of the entire Cap protein from different PCV3 subtype strains from heathy samples. There was a mutation at site 113 in PCV3a, site 129 in PCV3b, and site 116 in PCV3c.

Conclusion

Our present data provide evidence that PCV3 is prevalent in Tibetan pigs at high altitudes in China, and the higher prevalence rates of the PCV3a and PCV3b subtypes in samples from pigs with diarrhoea further indicate that the genotypes should not be neglected during surveys of the pathogenicity of PCV3. Phylogenetic and genetic diversity analyses suggested that the continuous evolution, adaptation and mechanisms of pathogenicity of PCV3 in Tibetan pigs living in this special environment should be further studied.
Is the urinary iodine/creatinine ratio applicable to assess short term individual iodine status in Chinese adults? Comparison of iodine estimates from 24-h urine and timed-spot urine samples in different periods of the day
Authors: Liu Zhuan , Lin Yixuan , Wu Jiani , Chen Diqun , Wu Xiaoyan , Lan Ying , Chen Zhihui
Published: April 2022

Background

Urinary iodine concentration (UIC) is routinely used to evaluate the population iodine status while the uniform method for the individual level assessment is uncertain.

Objectives

To explore the 24-h urinary iodine excretion (UIE) in five different periods of the day and the corresponding prediction equations respect by the use of creatinine-corrected UIC.

Methods

We collected 24-h, spot and fasting urine in five periods of the day to estimate 24-h UIE by the six different prediction equations. We compared the estimated creatinine-corrected UIC to the collected 24-h UIE and identified the most suitable equations in each period of the day.

Results

Among the six different prediction equations, the equation of Kawasaki T was the best to estimate the 24-h UIE by fasting urine among Chinese adults. Among the five periods of time, the equation of Knudsen N was the best to estimate the 24-h UIE in the non-morning period.

Conclusion

Urinary iodine status at the individual level could be estimated by different creatinine-based equations at different periods of the day.
‘A disease like any other’ traditional, complementary and alternative medicine use and perspectives in the context of COVID-19 among the Congolese community in Belgium
Authors: De Meyer Emiel , Van Damme Patrick , de la Peña Eduardo , Ceuterick Melissa
Published: April 2022

Background

As a hard-hit area during the COVID-19 pandemic, Belgium knew the highest mortality among people from sub-Saharan African descent, compared to any other group living in the country. After migration, people often maintain traditional perceptions and habits regarding health and healthcare, resulting in a high prevalence of traditional, complementary and alternative medicine use among different migrant communities in northern urban settings. Despite being the largest community of sub-Saharan African descent in Belgium, little is known on ethnobotanical practices of the Belgian Congolese community. We therefore conducted an exploratory study on the use of medicinal plants in the context of COVID-19 and perceptions on this new disease among members of the Congolese community in Belgium.

Methods

We conducted 16 in-depth semi-structured interviews with people of Congolese descent currently living in Belgium. Participants were selected using purposive sampling. Medicinal plant use in the context of COVID-19 was recorded through free-listing. Data on narratives, ideas and perceptions on the origin, cause/aetiology and overall measures against COVID-19 (including vaccination) were collected. Interview transcripts were analysed using thematic analysis.

Results

Four overarching themes emerged from our data. Firstly, participants perceived the representation of the severity of COVID-19 by the Belgian media and government—and by extend by all governmental agencies in the global north—as exaggerated. As a result, traditional and complementary treatments were seen as feasible options to treat symptoms of the disease. Fifteen forms of traditional, complementary and alternative medicine were documented, of which thirteen were plants. Participants seem to fold back on their Congolese identity and traditional knowledge in seeking coping strategies to deal with the COVID-19 pandemic. Finally, institutional postcolonial distrust did not only seem to lead to distrust in official messages on the COVID-19 pandemic but also to feelings of vaccination hesitancy.

Conclusion

In the context of the COVID-19 pandemic, participants in our study retreated to, reshaped and adapted traditional and culture-bound knowledge. This study suggests that the fragile and sensitive relationship between sub-Saharan African migrant groups and other social/ethnic groups in Belgium might play a role in their sensitivity to health-threatening situations, such as the COVID-19 pandemic.
Shift-work and breastfeeding for women returning to work in a manufacturing workplace in Taiwan
Authors: Tsai Su-Ying
Published: April 2022

Background

Although breastfeeding-friendly workplaces are provided to promote an employed mother’s breastfeeding intention, few studies have explored breastfeeding intentions and behavior after a mother returns to work on a shift work or non-shift work schedule. To explore the impact of breastfeeding-friendly support on the intention of working mothers with different work schedules to continue breastfeeding, we conducted a survey at a female labor-intensive electronics manufacturer in Taiwan from August 2011 to April 2012.

Methods

Female workers who met the inclusion criteria (maternity leave between January 2009 and January 2011) were invited to participate in the survey. A structured questionnaire survey was administered to 715 working mothers employed at an electronics manufacturing plant in Tainan Science Park in Southern Taiwan. The questionnaire content included female employee demographic characteristics, employment characteristics, continued breastfeeding behavior after returning to work, access to lactation rooms, and employee perception of the breastfeeding policy and support when raising their most recently born child.

Results

A total of 715 employed mothers’ data were collected. Of the shift workers, 90.1% breastfed during maternity leave, but the breastfeeding rates after returning to work decreased to 21.5% for one to six months and 17.9% for more than six months. Of the non-shift workers, 87.6% breastfed during maternity leave and the breastfeeding rates after returning to work were 24.1% for one to six months and 34.6% for more than six months. Using a lactation room and taking advantage of breast-pumping breaks were significant factors for continuing to breastfeed one to six months after returning to work and more than six months after returning to work among shift workers and non-shift workers. In addition, among non-shift workers, a higher education level of the mother (odds ratio (OR) = 9.57) and partner support (OR = 4.89) had positive effects toward a mother continuing breastfeeding for more than six months after returning to work.

Conclusions

Workplaces or employers should provide more support to encourage employed mothers to take advantage of the breastfeeding room and breast-pumping breaks, enhance the frequency of the usage of lactation rooms, and increase the rate of continued breastfeeding.
Correlation between changes of pelvic bone marrow fat content and hematological toxicity in concurrent chemoradiotherapy for cervical cancer
Authors: Wang Cong , Qin Xiaohang , Gong Guanzhong , Wang Lizhen , Su Ya , Yin Yong
Published: April 2022

Objectives

To quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts.

Methods

The data of 54 patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and > 50 Gy doses were analyzed. Spearman’s rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment.

Results

The lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5–30 Gy compared to RT-end, while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5–10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5–10 Gy (r = 0.554, P = 0.017).

Conclusion

MRI IDEAL IQ imaging is a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention to.
A cycle generative adversarial network for improving the quality of four-dimensional cone-beam computed tomography images
Authors: Usui Keisuke , Ogawa Koichi , Goto Masami , Sakano Yasuaki , Kyougoku Shinsuke , Daida Hiroyuki
Published: April 2022

Background

Four-dimensional cone-beam computed tomography (4D-CBCT) can visualize moving tumors, thus adaptive radiation therapy (ART) could be improved if 4D-CBCT were used. However, 4D-CBCT images suffer from severe imaging artifacts. The aim of this study is to investigate the use of synthetic 4D-CBCT (sCT) images created by a cycle generative adversarial network (CycleGAN) for ART for lung cancer.

Methods

Unpaired thoracic 4D-CBCT images and four-dimensional multislice computed tomography (4D-MSCT) images of 20 lung-cancer patients were used for training. High-quality sCT lung images generated by the CycleGAN model were tested on another 10 cases. The mean and mean absolute errors were calculated to assess changes in the computed tomography number. The structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) were used to compare the sCT and original 4D-CBCT images. Moreover, a volumetric modulation arc therapy plan with a dose of 48 Gy in four fractions was recalculated using the sCT images and compared with ideal dose distributions observed in 4D-MSCT images.

Results

The generated sCT images had fewer artifacts, and lung tumor regions were clearly observed in the sCT images. The mean and mean absolute errors were near 0 Hounsfield units in all organ regions. The SSIM and PSNR results were significantly improved in the sCT images by approximately 51% and 18%, respectively. Moreover, the results of gamma analysis were significantly improved; the pass rate reached over 90% in the doses recalculated using the sCT images. Moreover, each organ dose index of the sCT images agreed well with those of the 4D-MSCT images and were within approximately 5%.

Conclusions

The proposed CycleGAN enhances the quality of 4D-CBCT images, making them comparable to 4D-MSCT images. Thus, clinical implementation of sCT-based ART for lung cancer is feasible.
Novel computer aided diagnostic models on multimodality medical images to differentiate well differentiated liposarcomas from lipomas approached by deep learning methods
Authors: Yang Yuhan , Zhou Yin , Zhou Chen , Ma Xuelei
Published: April 2022

Background

Deep learning methods have great potential to predict tumor characterization, such as histological diagnosis and genetic aberration. The objective of this study was to evaluate and validate the predictive performance of multimodality imaging-derived models using computer-aided diagnostic (CAD) methods for prediction of MDM2 gene amplification to identify well-differentiated liposarcoma (WDLPS) and lipoma.

Materials and methods

All 127 patients from two institutions were included with 89 patients in one institution for model training and 38 patients in the other institution for external validation between January 2012 and December 2018. For each modality, handcrafted radiomics analysis with manual segmentation was applied to extract 851 features for each modality, and six pretrained convolutional neural networks (CNNs) extracted 512–2048 deep learning features automatically. Extracted imaging-based features were selected via univariate filter selection methods and the recursive feature elimination algorithm, which were then classified by support vector machine for model construction. Integrated with two significant clinical variables, age and LDH level, a clinical-radiological model was constructed for identification WDLPS and lipoma. All differentiation models were evaluated using the area under the receiver operating characteristics curve (AUC) and their 95% confidence interval (CI).

Results

The multimodality model on deep learning features extracted from ResNet50 algorithm (RN-DL model) performed great differentiation performance with an AUC of 0.995 (95% CI 0.987–1.000) for the training cohort, and an AUC of 0.950 (95% CI 0.886–1.000), accuracy of 92.11%, sensitivity of 95.00% (95% CI 73.06–99.74%), specificity of 88.89% (95% CI 63.93–98.05%) in external validation. The integrated clinical-radiological model represented an AUC of 0.996 (95% CI 0.989–1.000) for the training cohort, and an AUC of 0.942 (95% CI 0.867–1.000), accuracy of 86.84%, sensitivity of 95.00% (95% CI 73.06–99.74%), and specificity of 77.78% (95% CI 51.92–92.63%) in external validation.

Conclusions

Imaging-based multimodality models represent effective discrimination abilities between WDLPS and lipoma via CAD methods, and might be a practicable approach in assistance of treatment decision.
Health utilities and costs for neuromyelitis optica spectrum disorder
Authors: Hughes Dyfrig A. , Bourke Siobhan , Jones Angela , Bhatt Rikesh , Huda Saif , Mutch Kerry , Jacob Anu
Published: April 2022

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, neurological disease that places a significant burden on patients, their carers, and healthcare systems.

Objectives

To estimate patient and carer health utilities and costs of NMOSD within the UK setting.

Methods

Patients with NMOSD and their carers, recruited via a regional specialist treatment centre, completed a postal questionnaire that included a resource use measure, the EuroQoL (EQ)-5D-5L, EQ-5D-VAS, Vision and Quality of Life Index (VisQoL), Carer Experience Survey (CES) and the Expanded Disability Status Scale (EDSS). The questionnaire asked about respondents’ use of health and community care services, non-medical costs, informal care and work capacity. Data were analysed descriptively. Uncertainties in costs and utilities were assessed using bootstrap analysis.

Results

117 patients and 74 informal carers responded to the survey. Patients’ mean EQ-5D-5L and VisQoL health utilities (95% central range) were 0.54 (− 0.29, 1.00) and 0.79 (0.11, 0.99), respectively. EQ-5D-5L utility decreased with increasing EDSS score bandings, from 0.80 (0.75, 0.85) for EDSS ≤ 4.0, to 0.20 (− 0.29, 0.56) for EDSS 8.0 to 9.5. Mean, 3-month total costs were £5623 (£2096, £12,156), but ranged from £562 (£381, £812) to £32,717 (£2888, £98,568) for these EDSS bandings. Carer-reported EQ-5D-5L utility and CES index scores were 0.85 (0.82, 0.89) and 57.67 (52.69, 62.66). Mean, 3-month costs of informal care were £13,150 to £24,560.

Conclusions

NMOSD has significant impacts on health utilities and NHS and carer costs. These data can be used as inputs to cost-effectiveness analyses of new medicines for NMOSD.
Stanniocalcin 1 promotes metastasis, lipid metabolism and cisplatin chemoresistance via the FOXC2/ITGB6 signaling axis in ovarian cancer
Authors: Lin Feikai , Li Xiaoduan , Wang Xinjing , Sun Huizhen , Wang Ziliang , Wang Xipeng
Published: April 2022

Background

Stanniocalcin 1 (STC1) plays an integral role in ovarian cancer (OC). However, the functional role of STC1 in metastasis, lipid metabolism and cisplatin (DDP) chemoresistance in OC is not fully understood.

Methods

Single-cell sequencing and IHC analysis were performed to reveal STC1 expression profiles in patient tissues. Metastasis, lipid metabolism and DDP chemoresistance were subsequently assessed. Cell-based in vitro and in vivo assays were subsequently conducted to gain insight into the underlying mechanism of STC1 in OC.

Results

Single-cell sequencing assays and IHC analysis verified that STC1 expression was significantly enhanced in OC tissues compared with para-carcinoma tissues, and it was further up-regulated in peritoneal metastasis tissues compared with OC tissues. In vitro and in vivo experiments demonstrated that STC1 promoted metastasis, lipid metabolism and DDP chemoresistance in OC. Simultaneously, STC1 promoted lipid metabolism by up-regulating lipid-related genes such as UCP1, TOM20 and perilipin1. Mechanistically, STC1 directly bound to integrin β6 (ITGB6) to activate the PI3K signaling pathway. Moreover, STC1 was directly regulated by Forkhead box C2 (FOXC2) in OC. Notably, targeting STC1 and the FOXC2/ITGB6 signaling axis was related to DDP chemoresistance in vitro.

Conclusions

Overall, these findings revealed that STC1 promoted metastasis, lipid metabolism and DDP chemoresistance via the FOXC2/ITGB6 signaling axis in OC. Thus, STC1 may be used as a prognostic indicator in patients with metastatic OC. Meanwhile, STC1 could be a therapeutic target in OC patients, especially those who have developed chemoresistance to DDP.
Case report: Birth achieved after effective ovarian stimulation combined with dexamethasone in a patient with resistant ovary syndrome
Authors: Li Huiying , Chang Tianli , Mu Hongbei , Xiang Wenpei
Published: April 2022

Background

Resistant ovary syndrome (ROS) is a rare endocrine disorder and there have been few reports of live births by affected patients. As gonadotropin resistance leads immature oocytes, some researchers reported few live births with in vitro maturation (IVM) of oocytes, but IVM is not always successful in ROS patients. Here, we report an original case of ROS, associated with Ig-FSHR in the serum, who achieved a live birth following ovarian stimulation combined with dexamethasone treatment.

Case presentation

The 30-year-old woman presented with secondary amenorrhea and infertility. Her serum FSH levels were found to be higher than normal, but in discordance with a normal anti-Müllerian hormone (AMH) level and antral follicle count. Genetic investigation found no mutations potentially affecting FSHR. With reference of previous ROS studies, the patient’s serum was analyzed for antibodies directed against FSHR and dot blot analysis showed strong reactivity with FSHR. Then, dexamethasone was proposed to the patient, and she successfully became pregnant, finally delivering a healthy girl by caesarean section.

Conclusion

To our best knowledge, this is the first report of the successful treatment of ROS using ovarian stimulation combined with dexamethasone. In some cases of ROS, high doses of exogenous gonadotropins in combination with immunosuppressive therapy could be an effective approach.
A laparoscopic one anastomosis gastric bypass with wrapping versus nonwrapping fundus of the excluded part of the stomach to treat obese patients (FundoRingOAGB trial): study protocol for a randomized controlled trial
Authors: Ospanov Oral , Yeleuov Galymzhan , Fursov Alexandr , Yelembayev Bakhtiyar , Fursov Roman , Sergazin Zhenis , Mustafin Adil
Published: April 2022

Background

Laparoscopic one anastomosis gastric bypass (LOAGB) is a simple variation of gastric bypass and has gained worldwide popularity with clinical outcomes similar to laparoscopic Roux-en-Y gastric bypass (LRYGB) for weight loss and management of comorbidities. However, biliary reflux to the esophagus negates the benefits of LOAGB. In addition, weight gain after LOAGB and after LRYGB is a major problem in bariatric surgery.

The aim of this article is to describe the design and protocol of a randomized controlled trial comparing the outcomes of two methods of LOAGB: experimental method with wrapping versus standard method nonwrapping fundus of the excluded part of the stomach to prevent weight regain and biliary reflux after LOAGB.

Methods

The study was designed as a single-center prospective, interventional, randomized controlled trial. Masking: None (open label). Allocation: randomized. Enrollment: 100 obese patients. The relevant ethics committee approved the trial protocol.

The endpoints (body mass index, bile reflux in the esophagus, other reflux symptoms) will be assessed presurgery and postsurgery (12, 24, and 36 months postoperatively).

Discussion

With its 3-year follow-up time, this RCT will provide important data on the impact of wrapping the fundus of the excluded part of the stomach to prevent weight regain and biliary reflux after LOAGB.

Trial registration

ClinicalTrials.govNCT04834635. Registered on 8 April 2021.
Effect of m-health-based core stability exercise combined with self-compassion training for patients with non-specific chronic low back pain: study protocol for a randomized controlled trial
Authors: Fuming Zheng , Weihui Xiao , Jiajia Yang , Shufeng Liu , Yiyi Zheng , Wenjian Liang , Yan Li , Zhicheng Li , Siyun Zhang , Yingmin Zou , Yuyin Wang , Chuhuai Wang
Published: April 2022

Background

Non-specific chronic low back pain (NCLBP) has a high incidence, which has a significant impact on a patient’s body and mind and is a common condition affecting people’s quality of life. Core stability exercise (CSE) is a modestly effective treatment for NCLBP; however, CSE has only been shown to be a useful treatment option in the short term. Many clinical practice guidelines recommend the use of a biopsychosocial framework to guide the management of NCLBP. Self-compassion training (SCT) is a promising psychotherapy treatment option for NCLBP; however, there is still a lack of research on CSE combined with SCT. In this study, we will seek to determine whether CSE combined with SCT is an effective treatment option for patients with NCLBP compared to CSE alone.

Methods

In this study, we will randomize 166 adults with NCLBP to a combined SCT and CSE arm or a CSE alone arm (83 participants per group). Both interventions will consist of four weekly 1.5-h group sessions of CSE supplemented by home practice. The combined group protocol also includes 2 h of SCT before CSE. Interviewers masked to the treatment assignments will assess the outcomes at 4 and 16 weeks post-randomization. The primary outcomes are back pain disability (based on the Roland-Morris Disability Questionnaire) and pain intensity (NRS; average pain, worst pain, average pain) at 16 weeks.

Discussion

If SCT is found to enhance the effectiveness of CSE for patients with chronic back pain, the results of the study may promote the development of mind-body therapies for chronic low back pain.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100042810. Registered on 21 January 2021
The role of wood harvest from sustainably managed forests in the carbon cycle
Authors: Schulze Ernst Detlef , Bouriaud Olivier , Irslinger Roland , Valentini Riccardo
Published: April 2022

Key message

We investigate the flux balance of managed and protected forests and the effects of using wood.

Flux parameters of CO2 uptake and respiration do not differ between managed and protected forests.

Accounting of harvest as immediate emission by IPCC guidelines results in a bias of forest climate mitigation towards storage and neglects the avoidance of fossil-fuel use by wood use.
Pleural empyema caused by dropped gallstones after laparoscopic cholecystectomy for acute cholecystitis: a case report
Authors: Tokuda Aya , Maehira Hiromitsu , Iida Hiroya , Mori Haruki , Nitta Nobuhito , Maekawa Takeru , Takebayashi Katsushi , Kaida Sachiko , Miyake Toru , Kuroda Ryo , Yamamoto Haruka , Tani Masaji
Published: April 2022

Background

Dropped gallstones during laparoscopic cholecystectomy (LC) sometimes induce postoperative infectious complications. However, pleural empyema rarely occurs as a complication of LC.

Case presentation

We present the case of a 66-year-old woman with right pleural empyema. She previously underwent LC for acute gangrenous cholecystitis 11 months ago. The operative report revealed iatrogenic gallbladder perforation and stone spillage. The bacterial culture of the gallbladder bile was positive for Escherichia coli. Chest and abdominal computed tomography revealed right pleural effusion, perihepatic fluid collection, and multiple small radiopaque density masses. Although ultrasound-guided transthoracic drainage was performed, the drainage was incomplete, and systemic inflammatory reaction persisted. Consequently, thoracotomy and laparotomy with gallstone retrieval were performed, and the patient recovered completely. The patient has remained well without complications after 14 months of follow-up.

Conclusions

We report a rare case of pleural empyema caused by dropped gallstones after LC. This case emphasized the importance of completely retrieving the dropped gallstones to prevent late infectious complications after LC.