bluuebunny/crossref_metadata_2025 huggingface dataset:
NICU and postpartum nurse perspectives on involving fathers in newborn care: a qualitative study
Authors: Buek Katharine W. , Cortez Dagoberto , Mandell Dorothy J.
Published: February 2021

Background

Perinatal care nurses are well positioned to provide the education and support new fathers need to navigate the transition to fatherhood and to encourage positive father involvement from the earliest hours of a child’s life. To effectively serve fathers in perinatal settings, it is important to understand the attitudes, beliefs, and behaviors of healthcare providers that may encourage and engage them, or alternatively alienate and discourage them.

Methods

This qualitative study involved structured interviews with ten NICU and postpartum nurses from hospitals in two large Texas cities. The interview protocol was designed to elicit descriptive information about nurses’ attitudes and beliefs, sense of efficacy and intention for working with fathers, as well as their father-directed behaviors. Nurses were recruited for the study using a purposive sampling approach. Interviews were conducted by telephone and lasted approximately 25 to 35 min. Data were analyzed using a qualitative descriptive approach.

Results

Overall, study participants held very positive subjective attitudes toward fathers and father involvement. Nevertheless, many of the nurses signaled normative beliefs based on race/ethnicity, gender, and culture that may moderate their intention to engage with fathers. Participants also indicated that their education as well as the culture of perinatal healthcare are focused almost entirely on the mother-baby dyad. In line with this focus on mothers, participants comments reflected a normative belief that fathers are secondary caregivers to their newborns, there to help when the mother is unavailable.

Conclusions

Nurse attitudes and practices that place mothers in the role of primary caregiver may be interpreted by fathers as excluding or disregarding them. Further research is needed to validate the results of this small-scale study, and to assess whether and how provider attitudes impact their practices in educating and engaging fathers in newborn care.
Utilisation of sexual and reproductive health services among street children and young adults in Kampala, Uganda: does migration matter?
Authors: Bwambale Mulekya F. , Bukuluki Paul , Moyer Cheryl A. , Van den Borne Bart H. W.
Published: February 2021

Background

While the nexus of migration and health outcomes is well acknowledged, the effect of rural–urban migration on the use of sexual and reproductive health (SRH) services has received less attention. We assessed the effect of rural–urban migration on the use of SRH services, while controlling for confounding, and whether there is a difference in the use of SRH services among migrant and non-migrant street children and young adults.

Methods

Data were collected from 513 street children and young adults aged 12–24 years, using venue-based time-space sampling (VBTS). We performed multivariate logistic regression analysis using Stata 16.0 to identify factors associated with SRH services use, with rural–urban migration status as the main predictor. Participants were further classified as new migrants (≤ 2 years of stay in city), established migrants (> 2 years of stay in city) or non-migrants (lifelong native street children) with no rural–urban migration history.

Results

Overall, 18.13% of the street children and young adults had used contraception/family planning, 58.67% had tested for human immunodeficiency virus (HIV) and knew their status and 34.70% had been screened for sexually transmitted infections (STIs). Non-migrants were 2.70 times more likely to use SRH services (HIV testing, STI screening and family planning) compared to the migrants (aOR = 2.70, 95% CI 1.23–5.97). Other factors associated with SRH services use among street children and young adults include age (aOR = 4.70, 95% CI 2.87–7.68), schooling status (aOR = 0.33, 95% CI 0.15–0.76), knowledge of place of care (aOR = 2.71, 95% CI 1.64–4.46) and access to SRH information (aOR = 3.23, 95% CI 2.00–5.24).

Conclusions

SRH services utilisation among migrant street children and young adults is low compared to their non-migrant counterparts and is independently associated with migration status, age, schooling status, knowledge of place of care and access to SRH information. Our findings call for the need to design and implement multi-dimensional interventions to increase the use of SRH services among street children and young adults, while taking into consideration their migration patterns.
Screening for optimal protease producing Bacillus licheniformis strains with polymer-based controlled-release fed-batch microtiter plates
Authors: Habicher Tobias , Klein Tobias , Becker Jacqueline , Daub Andreas , Büchs Jochen
Published: February 2021

Background

Substrate-limited fed-batch conditions have the favorable effect of preventing overflow metabolism, catabolite repression, oxygen limitation or inhibition caused by elevated substrate or osmotic concentrations. Due to these favorable effects, fed-batch mode is predominantly used in industrial production processes. In contrast, screening processes are usually performed in microtiter plates operated in batch mode. This leads to a different physiological state of the production organism in early screening and can misguide the selection of potential production strains. To close the gap between screening and production conditions, new techniques to enable fed-batch mode in microtiter plates have been described. One of these systems is the ready-to-use and disposable polymer-based controlled-release fed-batch microtiter plate (fed-batch MTP). In this work, the fed-batch MTP was applied to establish a glucose-limited fed-batch screening procedure for industrially relevant protease producing Bacillus licheniformis strains.

Results

To achieve equal initial growth conditions for different clones with the fed-batch MTP, a two-step batch preculture procedure was developed. Based on this preculture procedure, the standard deviation of the protease activity of glucose-limited fed-batch main culture cultivations in the fed-batch MTP was ± 10%. The determination of the number of replicates revealed that a minimum of 6 parallel cultivations were necessary to identify clones with a statistically significant increased or decreased protease activity. The developed glucose-limited fed-batch screening procedure was applied to 13 industrially-relevant clones from two B. licheniformis strain lineages. It was found that 12 out of 13 clones (92%) were classified similarly as in a lab-scale fed-batch fermenter process operated under glucose-limited conditions. When the microtiter plate screening process was performed in batch mode, only 5 out of 13 clones (38%) were classified similarly as in the lab-scale fed-batch fermenter process.

Conclusion

The glucose-limited fed-batch screening process outperformed the usual batch screening process in terms of the predictability of the clone performance under glucose-limited fed-batch fermenter conditions. These results highlight that the implementation of glucose-limited fed-batch conditions already in microtiter plate scale is crucial to increase the precision of identifying improved protease producing B. licheniformis strains. Hence, the fed-batch MTP represents an efficient high-throughput screening tool that aims at closing the gap between screening and production conditions.
Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer
Authors: Liu Yaqian , Pan Bo , Qu Weikun , Cao Yilong , Li Jun , Zhao Haidong
Published: February 2021

Background

Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.

Methods

In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan–Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan–Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound‐healing and transwell migration assay.

Results

We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC.

Conclusion

This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.
Iodine status five years after the adjustment of universal salt iodization: a cross-sectional study in Fujian Province, China
Authors: Lin Yixuan , Chen Diqun , Wu Jiani , Chen Zhihui
Published: February 2021

Background

Universal salt iodization program was introduced to China to eliminate iodine deficiency disorders in 1995. In 2012, Fujian Province decreased the concentration of iodized table salt according to the national unified requirement. This study aimed to assess the effect on iodine status after the adjustment, providing evidence for further adjustment in Fujian Province.

Methods

Sampling units were selected by multistage cluster sampling method. In each sampling unit, table salt was collected from 30 households. A total of 2,471 people in 2009 and 4,806 people in 2017 provided urine samples and were included in this cross-sectional analysis. Median iodized salt concentration and median urine iodine concentration were present by median and interquartile range.

Results

Median iodized salt decreased from 29.8 mg/kg in 2009 to 23.9 mg/kg in 2017. The median urinary iodine concentrations for school-age children in 2017 in coastal urban area, non-coastal urban area, coastal rural area and non-coastal rural area were 163.6µg/L (interquartile range = 100.1–252.0µg/L), 198.9µg/L (interquartile range = 128.0-294.0µg/L), 181.8µg/L (interquartile range = 114.1–257.0µg/L) and 218.2µg/L (interquartile range = 148.1-306.5µg/L), respectively. The median urinary iodine concentrations for adults in 2017 in these areas were 151.1µg/L (interquartile range = 98.3-231.7µg/L), 168.7µg/L (interquartile range = 109.6–242.0µg/L), 167.7µg/L (interquartile range = 105.7-245.7µg/L) and 182.7µg/L (interquartile range = 117.1-258.9µg/L). The median urinary iodine concentrations for pregnant women in 2017 in these areas were 157.7µg/L (interquartile range = 106.9-223.8µg/L), 141.5µg/L (interquartile range = 97.7-207.6µg/L), 127.3µg/L (interquartile range = 90.0-184.5µg/L) and 144.8µg/L (interquartile range = 99.9-184.5µg/L). The median urinary iodine concentrations for lactating women in 2017 in these areas were 122.7µg/L (interquartile range = 84.1–172.0µg/L), 123.7µg/L (interquartile range = 70.7-184.7µg/L), 105.8µg/L (interquartile range = 67.1-152.3µg/L) and 110.2µg/L (interquartile range = 74.1-170.3µg/L).

Conclusions

The overall urinary iodine concentrations among school-age children, adults and lactating women dramatically decreased after implementing the new standard. Almost all of them were iodine adequate, suggesting we reached the expected aim of iodized salt adjustment. However, pregnant women were iodine insufficient after adjustment. Therefore, we should continue the surveillance of iodine status of populations and focus on the additional iodine supplement strategies for pregnant women.
Two-step cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei with high peritoneal carcinomatosis index
Authors: Trilling Bertrand , Brind’Amour Alexandre , Hamad Raphael , Tremblay Jean-Francois , Dubé Pierre , Mitchell Andrew , Sidéris Lucas
Published: February 2021

Background

Complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only curative treatment for pseudomyxoma peritonei (PMP) arising from the appendix. High peritoneal carcinomatosis index (PCI) is associated with an increased risk of surgical complications. The objective of this study was to present the results of a planned two-step surgical strategy to decrease postoperative morbidity and improve resectability of patients with very high PCI.

Methods

All consecutive patients who underwent a planned two-step surgical approach for PMP between January 2012 and March 2020 were retrospectively included. This approach was offered for patients with low-grade PMP with PCI > 28 for which feasibility of a complete CRS in one operation was uncertain. The first surgery included a complete CRS of the inframesocolic compartment and omentectomy. HIPEC was delivered at the second surgery, after complete CRS of the supramesocolic compartment. Postoperative morbidity was assessed using the Clavien-Dindo classification and survival results were also collected.

Results

Eight patients underwent the two-step approach. The median PCI was 33 (29–39) and the median time between the two procedures was 111 days (90–212 days). One patient was deemed unresectable at the second surgery. The rate of major morbidity was 0% for the first step and 25% for the second step, with no mortality. Median follow-up was 53.8 months (3–73 months).

Conclusion

A two-step surgical management for low-grade PMP patients with very high PCI is safe and feasible, with acceptable postoperative morbidity and no compromise on oncological outcomes.
Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules
Authors: Devarbhavi Praveenkumar , Telang Lata , Vastrad Basavaraj , Tengli Anandkumar , Vastrad Chanabasayya , Kotturshetti Iranna
Published: February 2021

To enhance understanding of polycystic ovary syndrome (PCOS) at the molecular level; this investigation intends to examine the genes and pathways associated with PCOS by using an integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing data GSE84958 derived from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) between PCOS samples and normal controls were identified. We performed a functional enrichment analysis. A protein-protein interaction (PPI) network, miRNA- target genes and TF - target gene networks, were constructed and visualized, with which the hub gene nodes were identified. Validation of hub genes was performed by using receiver operating characteristic (ROC) and RT-PCR. Small drug molecules were predicted by using molecular docking. A total of 739 DEGs were identified, of which 360 genes were up regulated and 379 genes were down regulated. GO enrichment analysis revealed that up regulated genes were mainly involved in peptide metabolic process, organelle envelope and RNA binding and the down regulated genes were significantly enriched in plasma membrane bounded cell projection organization, neuron projection and DNA-binding transcription factor activity, RNA polymerase II-specific. REACTOME pathway enrichment analysis revealed that the up regulated genes were mainly enriched in translation and respiratory electron transport and the down regulated genes were mainly enriched in generic transcription pathway and transmembrane transport of small molecules. The top 10 hub genes (SAA1, ADCY6, POLR2K, RPS15, RPS15A, CTNND1, ESR1, NEDD4L, KNTC1 and NGFR) were identified from PPI network, miRNA - target gene network and TF - target gene network. The modules analysis showed that genes in modules were mainly associated with the transport of respiratory electrons and signaling NGF, respectively. We find a series of crucial genes along with the pathways that were most closely related with PCOS initiation and advancement. Our investigations provide a more detailed molecular mechanism for the progression of PCOS, detail information on the potential biomarkers and therapeutic targets.
Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread
Authors: Pinto Daniel O. , Al Sharif Sarah , Mensah Gifty , Cowen Maria , Khatkar Pooja , Erickson James , Branscome Heather , Lattanze Thomas , DeMarino Catherine , Alem Farhang , Magni Ruben , Zhou Weidong , Alais Sandrine , Dutartre Hélène , El-Hage Nazira , Mahieux Renaud , Liotta Lance A. , Kashanchi Fatah
Published: February 2021

Background

The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell–cell contact.

Results

Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood–brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell–cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen.

Conclusions

Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread.
A usability study in patients with stroke using MERLIN, a robotic system based on serious games for upper limb rehabilitation in the home setting
Authors: Guillén-Climent Silvia , Garzo Ainara , Muñoz-Alcaraz María Nieves , Casado-Adam Pablo , Arcas-Ruiz-Ruano Javier , Mejías-Ruiz Manuela , Mayordomo-Riera Fernando Jesús
Published: February 2021

Background

Neuroscience and neurotechnology are transforming stroke rehabilitation. Robotic devices, in addition to telerehabilitation, are increasingly being used to train the upper limbs after stroke, and their use at home allows us to extend institutional rehabilitation by increasing and prolonging therapy. The aim of this study is to assess the usability of the MERLIN robotic system based on serious games for upper limb rehabilitation in people with stroke in the home environment.

Methods

9 participants with a stroke in three different stages of recovery (subacute, short-term chronic and long-term chronic) with impaired arm/hand function, were recruited to use the MERLIN system for 3 weeks: 1 week training at the Maimonides Biomedical Research Institute of Cordoba (IMIBIC), and 2 weeks at the patients’ homes. To evaluate usability, the System Usability Scale (SUS), Adapted Intrinsic Motivation Inventory (IMI), Quebec User Evaluation of Satisfaction with assistive Technology (QUEST), and the ArmAssist Usability Assessment Questionnaire were used in the post-intervention. Clinical outcomes for upper limb motor function were assessed pre- and post-intervention.

Results

9 patients participated in and completed the study. The usability assessment reported a high level of satisfaction: mean SUS score 71.94 % (SD = 16.38), mean QUEST scale 3.81 (SD = 0.38), and mean Adapted IMI score 6.12 (SD = 1.36). The results of the ArmAssist Questionnaire showed an average of 6 out of 7, which indicates that MERLIN is extremely intuitive, easy to learn and easy to use. Regarding clinical assessment, the Fugl-Meyer scores showed moderate improvements from pre- to post-intervention in the total score of motor function (p = 0.002). There were no significant changes in the Modified Ashworth scale outcomes (p = 0.169).

Conclusions

This usability study indicates that home-based rehabilitation for upper limbs with the MERLIN system is safe, useful, feasible and motivating. Telerehabilitation constitutes a major step forward in the use of intensive rehabilitation at home.

Trial registration ClinicalTrials.gov, NCT04405609. Registered 06 January 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04405609
Pod pepper vein yellows virus, a new recombinant polerovirus infecting Capsicum frutescens in Yunnan province, China
Authors: Zhao Kuangjie , Yin Yueyan , Hua Mengying , Wang Shaoxiang , Mo Xiaohan , Yuan Enping , Zheng Hongying , Lin Lin , Chen Hairu , Lu Yuwen , Chen Jianping , Peng Jiejun , Yan Fei
Published: February 2021

Pepper vein yellows viruses (PeVYV) are phloem-restricted viruses in the genus Polerovirus, family Luteoviridae. Typical viral symptoms of PeVYV including interveinal yellowing of leaves and upward leaf curling were observed in pod pepper plants (Capsicum frutescens) growing in Wenshan city, Yunnan province, China. The complete genome sequence of a virus from a sample of these plants was determined by next-generation sequencing and RT-PCR. Pod pepper vein yellows virus (PoPeVYV) (MT188667) has a genome of 6015 nucleotides, and the characteristic genome organization of a member of the genus Polerovirus. In the 5′ half of its genome (encoding P0 to P4), PoPeVYV is most similar (93.1% nt identity) to PeVYV-3 (Pepper vein yellows virus 3) (KP326573) but diverges greatly in the 3′-part encoding P5, where it is most similar (91.7% nt identity) to tobacco vein distorting virus (TVDV, EF529624) suggesting a recombinant origin. Recombination analysis predicted a single recombination event affecting nucleotide positions 4126 to 5192 nt, with PeVYV-3 as the major parent but with the region 4126–5192 nt derived from TVDV as the minor parent. A full-length clone of PoPeVYV was constructed and shown to be infectious in C. frutescens by RT-PCR and the presence of icosahedral viral particles.
Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas
Authors: Hadi Indrawati , Reitz Daniel , Bodensohn Raphael , Roengvoraphoj Olarn , Lietke Stefanie , Niyazi Maximilian , Tonn Jörg-Christian , Belka Claus , Thon Niklas , Nachbichler Silke Birgit
Published: February 2021

Purpose

Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown.

Methods

Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models.

Results

Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence.

Conclusion

The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.
Can internal mammary lymph nodes irradiation bring survival benefits for breast cancer patients? A systematic review and meta-analysis of 12,705 patients in 12 studies
Authors: Jia Sicong , Liu Zhikun , Zhang Jun , Zhao Chenguang , Zhu Longyu , Kong Jie , Han Huina , Shang Yuguang , Shen Dongxing , Duan Xuejuan
Published: February 2021

Objective

To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in breast cancer patients.

Methods

The computer searched PubMed, EMBASE, Web of science, CNKI, Wanfang Medical Network, the Chinese Biomedical Literature Database to find clinical studies on internal mammary lymph node irradiation (IMNI) in breast cancer. The quality of the included literature was evaluated according to the Newcastle–Ottawa scale. Stata14 software was used for meta-analysis.

Results

A total of 12,705 patients in 12 articles were included for meta-analyzed. Compared with patients who unirradiated internal mammary lymph nodes (non-IMNI), the risk of death for patients after IMNI was reduced by 11% (HR 0.89, 95% CI 0.79–1.00, P = 0.0470); DFS of group mixed N+ patients (high risk group) was significantly improved after IMNI (HR 0.58, 95% CI 0.49–0.69, P < 0.001). Further subgroup analysis shows that compared with non-IMNI, DFS was significantly increased in N1or ypN1 subgroup (HR 0.65, 95% CI 0.49–0.87, P = 0.003) and N2or ypN2 subgroup (HR 0.51, 95% CI 0.37–0.70, P < 0.001) after IMNI, but there was no statistical difference in DFS between the IMNI and non-IMNI groups in N0 subgroup (HR 1.02 95% CI 0.87–1.20, P = 0.794) and N3 or ypN3 subgroup (HR 0.85, 95% CI 0.49–1.45, P = 0.547). No serious incidents were reported in all the included studies, and most of the acute and late side effects were mild and tolerable.

Conclusion

Under modern radiotherapy techniques, IMNI can safely and effectively bring clinical benefits to N1–2 breast cancer patients, but its role in N0, N3 breast cancer patients remains to be further studied.
No evidence for preferential X-chromosome inactivation as the main cause of divergent phenotypes in sisters with X-linked hypohidrotic ectodermal dysplasia
Authors: Körber Laura , Schneider Holm , Fleischer Nicole , Maier-Wohlfart Sigrun
Published: February 2021

Background

X-linked hypohidrotic ectodermal dysplasia (XLHED), a rare genetic disorder, affects the normal development of ectodermal derivatives, such as hair, skin, teeth, and sweat glands. It is caused by pathogenic variants of the gene EDA and defined by a triad of hypotrichosis, hypo- or anodontia, and hypo- or anhidrosis which may lead to life-threatening hyperthermia. Although female carriers are less severely affected than male patients, they display symptoms, too, with high phenotypic variability. This study aimed to elucidate whether phenotypic differences in female XLHED patients with identical EDA genotypes might be explained by deviating X-chromosome inactivation (XI) patterns.

Methods

Six families, each consisting of two sisters with the same EDA variant and their parents (with either mother or father being carrier of the variant), participated in this study. XLHED-related data like sweating ability, dental status, facial dysmorphism, and skin issues were assessed. We determined the women`s individual XI patterns in peripheral blood leukocytes by the human androgen receptor assay and collated the results with phenotypic features.

Results

The surprisingly large inter- and intrafamilial variability of symptoms in affected females was not explicable by the pathogenic variants. Our cohort showed no higher rate of nonrandom XI in peripheral blood leukocytes than the general female population. Furthermore, skewed XI patterns in favour of the mutated alleles were not associated with more severe phenotypes.

Conclusions

We found no evidence for preferential XI in female XLHED patients and no distinct correlation between XLHED-related phenotypic features and XI patterns. Phenotypic variability seems to be evoked by other genetic or epigenetic factors.
Natural progression of cardiac features and long-term effects of enzyme replacement therapy in Taiwanese patients with mucopolysaccharidosis II
Authors: Lin Hsiang-Yu , Chen Ming-Ren , Lee Chung-Lin , Lin Shan-Miao , Hung Chung-Lieh , Niu Dau-Ming , Chang Tung-Ming , Chuang Chih-Kuang , Lin Shuan-Pei
Published: February 2021

Background

Cardiac abnormalities have been observed in patients with mucopolysaccharidosis type II (MPS II). The aim of this study was to investigate the cardiac features and natural progression of Taiwanese patients with MPS II, and evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function.

Methods

The medical records and echocardiograms of 48 Taiwanese patients with MPS II (median age, 6.9 years; age range, 0.1–27.9 years) were reviewed. The relationships between age and each echocardiographic parameter were analyzed.

Results

The mean z-scores of left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter were 1.10, 2.70, 0.95 and 1.91, respectively. Z scores > 2 were identified in 33%, 54%, 13%, and 46% for LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (MR) (56%), followed by aortic regurgitation (AR) (33%). The severity of mitral stenosis (MS), MR, aortic stenosis (AS), AR, and the existence of valvular heart disease were all positively correlated with increasing age (p < 0.01). We also compared the echocardiographic parameters between two groups: (1) 12 patients who had up to 17 years of follow-up echocardiographic data without ERT, and (2) nine patients who had up to 12 years of follow-up data with ERT. The results showed that z-score changes of LVMI significantly improved in the patients who received ERT compared to those who did not receive ERT (0.05 versus 1.52, p < 0.05). However, the severity score changes of MS, MR, AS, and AR all showed gradual progression in both groups (p > 0.05).

Conclusions

High prevalence rates of valvular heart disease and cardiac hypertrophy were observed in the MPS II patients in this study. The existence and severity of cardiac hypertrophy and valvular heart disease in these patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS II appeared to be effective in stabilizing or reducing the progression of cardiac hypertrophy, but it only had a limited effect on valvulopathy.
Correction to: Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML
Authors: Yilmaz Musa , Alfayez Mansour , DiNardo Courtney D. , Borthakur Gautam , Kadia Tapan M. , Konopleva Marina Y. , Loghavi Sanam , Kanagal-Shamanna Rashmi , Patel Keyur P. , Jabbour Elias J. , Garcia‑Manero Guillermo , Pemmaraju Naveen , Pierce Sherry A. , Ghayas Issa , Short Nicholas J. , Montalban-Bravo Guillermo , Takahashi Koichi , Assi Rita , Alotaibi Ahmad S. , Ohanian Maro , Andreeff Michael , Cortes Jorge E. , Kantarjian Hagop M. , Ravandi Farhad , Daver Naval G.
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Use and impact of high intensity treatments in patients with traumatic brain injury across Europe: a CENTER-TBI analysis
Authors:   the CENTER-TBI investigators and participants, Huijben Jilske A. , Dixit Abhishek , Stocchetti Nino , Maas Andrew I. R. , Lingsma Hester F. , van der Jagt Mathieu , Nelson David , Citerio Giuseppe , Wilson Lindsay , Menon David K. , Ercole Ari
Published: February 2021

Purpose

To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs).

Methods

We studied high TIL treatments (metabolic suppression, hypothermia (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP.

Results

313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0–2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome.

Conclusion

Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies.

Take home message

Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments.

Trial registration

The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, https://clinicaltrials.gov/ct2/show/NCT02210221?id=NCT02210221&draw=1&rank=1 and with Resource Identification Portal (RRID: SCR_015582).
MEDALT: single-cell copy number lineage tracing enabling gene discovery
Authors: Wang Fang , Wang Qihan , Mohanty Vakul , Liang Shaoheng , Dou Jinzhuang , Han Jincheng , Minussi Darlan Conterno , Gao Ruli , Ding Li , Navin Nicholas , Chen Ken
Published: February 2021

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.

The source code of our study is available at https://github.com/KChen-lab/MEDALT.
Study protocol: a core outcome set for perinatal interventions for congenital diaphragmatic hernia
Authors: Vergote Simen , De Bie Felix , Bosteels Jan , Hedrick Holly , Duffy James , Power Beverley , Benachi Alexandra , De Coppi Paolo , Fernandes Caraciolo , Lally Kevin , Reiss Irwin , Deprest Jan
Published: February 2021

Background

Congenital diaphragmatic hernia (CDH) is, depending of the severity, a birth defect associated with significant mortality and morbidity. Prenatal screening by ultrasound may detect this condition and comprehensive assessment of severity is possible, allowing for in utero referral to an experienced centre for planned delivery. In an effort to improve outcomes, prenatal interventions to stimulate lung development were proposed. Along the same lines, new postnatal management strategies are being developed. In order to enable proper comparison of novel perinatal interventions as well as outcomes, a set of uniform and relevant outcome measures is required. Core outcome sets (COS) are agreed, clearly defined sets of outcomes to be measured in a standardised manner and reported consistently. Herein we aim to describe the methodology we will use to define a COS for perinatal and neonatal outcomes of foetuses and newborns with congenital diaphragmatic hernia and to draft a dissemination and implementation plan.

Methods

We will use the methodology described in the Core Outcome Measures in Effectiveness Trials (COMET) Initiative Handbook. An international steering group will be created to guide the development of the COS. We are systematically reviewing the literature to identify all potential relevant pre- and neonatal outcomes previously used in studies on perinatal interventions for CDH. We will build a consensus on these core outcomes in a stakeholder group using the Delphi method. After completion, a stakeholder meeting will decide on a final COS, using a modified Nominal Group Technique. Thereafter, we will review potential definitions and measurements of these outcomes, and again a consensus meeting will be organised, to finalise the COS before dissemination.

Discussion

We have started a procedure to develop a COS for studies on perinatal interventions for congenital diaphragmatic hernia, with the purpose of improving the quality of research, guide clinical practice and improve patient care and eventual use in future clinical trials, systematic reviews and clinical practice guidelines.

Trial registration

We prospectively registered this study in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42019124399) and The Core Outcome Measures in Effectiveness Trials (COMET) Initiative (registration number:1296).
Synthesis, antibiotic structure–activity relationships, and cellulose dissolution studies of new room-temperature ionic liquids derived from lignin
Authors: Liu Shihong , Gonzalez Michael , Kong Celine , Weir Scott , Socha Aaron M.
Published: February 2021

Background

Ionic liquids (ILs) are promising pretreatment solvents for lignocellulosic biomass, but are largely prepared from petroleum precursors. Benzaldehydes from depolymerized lignin, such as vanillin, syringaldehyde, and 4-methoxy benzaldehyde, represent renewable feedstocks for the synthesis of ionic liquids. We herein report syntheses of novel lignin-derived ionic liquids, with extended N-alkyl chains, and examine their melting points, cellulose dissolution capacities, and toxicity profiles against Daphnia magna and E. coli strain 1A1. The latter organism has been engineered to produce isoprenol, a drop-in biofuel and precursor for commodity chemicals.

Results

The new N,N-diethyl and N,N-dipropyl methyl benzylammonium ILs were liquids at room temperature, showing 75–100 °C decreased melting points as compared to their N,N,N-trimethyl benzylammonium analog. Extension of N-alkyl chains also increased antibacterial activity threefold, while ionic liquids prepared from vanillin showed 2- to 4-fold lower toxicity as compared to those prepared from syringaldehyde and 4-methoxybenzaldehyde. The trend of antibacterial activity for anions of lignin-derived ILs was found to be methanesulfonate < acetate < hydroxide. Microcrystalline cellulose dissolution, from 2 to 4 wt% after 20 min at 100 °C, was observed in all new ILs using light microscopy and IR spectroscopy.

Conclusions

Ionic liquids prepared from H-, S- and G-lignin oxidation products provided differential cytotoxic activity against E. coli and D. magna, suggesting these compounds could be tailored for application specificity within a biorefinery.
HDL cholesterol efflux capacity and lipid profile in patients with systemic sclerosis
Authors: Ferraz-Amaro Iván , Delgado-Frías Esmeralda , Hernández-Hernández Vanesa , Sánchez-Pérez Hiurma , de Armas-Rillo Laura , Armas-González Estefanía , Machado José David , Diaz-González Federico
Published: February 2021

Objective

It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients with respect to controls and whether these changes were associated with disease-related data.

Methods

Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences.

Results

The multivariable analysis adjusted for demographic characteristics, cardiovascular risk factors, and lipid-related molecules showed that total cholesterol (beta coefficient: − 22 [95%CI – 37 to – 7], p = 0.004), triglycerides (beta coefficient: 24 [95%CI 2–47], p = 0.033), lipoprotein A (beta coefficient: 22 [95%CI 2–43], p = 0.033), and CEC (beta coefficient: – 6 [95%CI − 10 to – 2]%,p = 0.002) were significantly different between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: – 0.21 [95%CI – 0.37 to – 0.05]%, p = 0.011) after multivariable adjustment.

Conclusion

SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.
CRBP-TS - evaluation of a home-based training and health care program for colorectal, breast, and prostate cancer using telemonitoring and self-management: study protocol for a randomized controlled trial
Authors: Falz Roberto , Thieme René , Tegtbur Uwe , Bischoff Christian , Leps Christian , Hillemanns Peter , Kohlhaw Kay , Klempnauer Jürgen , Lordick Florian , Stolzenburg Jens-Uwe , Aktas Bahriye , Weitz Jürgen , Bork Ulrich , Wimberger Pauline , Thomas Christian , Biemann Ronald , Jansen-Winkeln Boris , Schulze Antina , Gockel Ines , Busse Martin
Published: February 2021

Background

Physical training is recommended in various national and international guidelines for patients with cancer. Observational studies have shown that physical activity leads to reduced recurrence and mortality rates by 20–40% in colorectal, breast, and prostate cancer. Despite existing evidence, a systematic care structure is still lacking. The primary aim of this study is to implement and evaluate an online training platform to strengthen physical performance and patient empowerment after cancer surgery.

Methods

The evaluation will be conducted as a prospective multicenter randomized controlled trial with three subgroups (colorectal-, breast-, and prostate cancer). Each group will include 100 patients (total 300 patients including dropouts; clinical stages T1–3 and/or N+; M0 after surgery intervention) and the primary endpoint (13% increase in the maximal oxygen consumption during exercise) will be examined. The intervention group will receive a 6-month home-based online training (2–3 times per week strength-endurance training using video presentations), bidirectional activity feedback information, online communication, and online counseling. The control group (usual care) will be advised lifestyle improvement. In-hospital testing will be performed before, during, and after the intervention. In addition to cardiopulmonary capacity, tumor specific diagnostics (liquid biopsy, depression and fatigue assessment, metabolic and endothelial screening) will be applied.

Discussion

Due to the increasing incidence of cancer, associated with considerable mortality, morbidity and impaired quality of life, there is an imperative requirement for improved cancer care, of which structured physical training may become an integral component.

Trial registration

DRKS-ID: DRKS00020499; Registered 17 March 2020.
Mechanism of mesenchymal stem cells in spinal cord injury repair through macrophage polarization
Authors: An Nan , Yang Jiaxu , Wang Hequn , Sun Shengfeng , Wu Hao , Li Lisha , Li Meiying
Published: February 2021

Treatment and rehabilitation of spinal cord injury (SCI) is a major problem in clinical medicine. Modern medicine has achieved minimal progress in improving the functions of injured nerves in patients with SCI, mainly due to the complex pathophysiological changes that present after injury. Inflammatory reactions occurring after SCI are related to various functions of immune cells over time at different injury sites. Macrophages are important mediators of inflammatory reactions and are divided into two different subtypes (M1 and M2), which play important roles at different times after SCI. Mesenchymal stem cells (MSCs) are characterized by multi-differentiation and immunoregulatory potentials, and different treatments can have different effects on macrophage polarization. MSC transplantation has become a promising method for eliminating nerve injury caused by SCI and can help repair injured nerve tissues. Therapeutic effects are related to the induced formation of specific immune microenvironments, caused by influencing macrophage polarization, controlling the consequences of secondary injury after SCI, and assisting with function recovery. Herein, we review the mechanisms whereby MSCs affect macrophage-induced specific immune microenvironments, and discuss potential avenues of investigation for improving SCI treatment.
Local well-posedness of the inertial Qian–Sheng’s Q-tensor dynamical model near uniaxial equilibrium
Authors: Wang Xiaoyuan , Li Sirui , Wang Tingting
Published: February 2021

We consider the inertial Qian–Sheng’s Q-tensor dynamical model for the nematic liquid crystal flow, which can be viewed as a system coupling the hyperbolic-type equations for the Q-tensor parameter with the incompressible Navier–Stokes equations for the fluid velocity. We prove the existence and uniqueness of local in time strong solutions to the system with the initial data near uniaxial equilibrium. The proof is mainly based on the classical Friedrich method to construct approximate solutions and the closed energy estimate.