bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glimpsing the raging seas that stop swans: A qualitative look at living with multimorbidity and pain in patients from a tertiary care service
Authors: Favarato Maria Helena , Germani Ana Claudia Camargo Gonçalves , Martins Milton de Arruda 
Published: March 2021

Multimorbidity requires complex and ongoing care. Understanding the subjective illness experience is critical to effective care. Literature isn’t clear about illness perception in patients with multimorbidity followed in services of high complexity. This study aims to investigate the illness experience based on narratives about daily living and symptoms of patients with multimorbidity and pain in a tertiary health care service. Methods: Qualitative narrative inquiry design with framework analysis from semi-structured interviews at a tertiary internal medicine outpatient clinic. Patients with Elixhauser comorbidity index ≧3 or and pain during the last week were included. Framework analysis was performed using 3 main patterns of illness experience from a previous study: “Gliding swan” (Resilience); “Stormy Seas” (Vulnerability); and “Stuck adrift” (Disruption); and identifying subthemes. One case study was selected from each main category. 43 patients, 14 classified as “gliding swan,” 12 as “stormy seas” and 17 as “stuck adrift.” Within the “gliding swan” group, positive examples of how to navigate through physical and emotional factors to sustain their wellbeing based on comprehension; In the “stormy seas” group, themes revolved around vulnerability, burden and ambiguity in relation to the health team. In the “stuck adrift” group the main content was about overwhelmed feelings and limitations. Conclusion(s): Narratives brought the content about lacking personalized understanding of diseases, with great emotional repercussion. Some meaningful anchors were highlighted. This study reinforces multimorbidity and pain interact and that healthcare professional should be aware of the turbulences that can disturb navigation in the raging seas of long-term multimorbid conditions.
Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR–T-cell responses against ALL
Authors: Zheng Wenting , Wei Jun , Zebley Caitlin C. , Jones Lindsay L. , Dhungana Yogesh , Wang Yong-Dong , Mavuluri Jayadev , Long Lingyun , Fan Yiping , Youngblood Ben , Chi Hongbo , Geiger Terrence L. 
Published: March 2021

Abstract
Chimeric antigen receptor (CAR)–T-cell therapeutic efficacy is associated with long-term T-cell persistence and acquisition of memory. Memory-subset formation requires T-cell factor 1 (TCF-1), a master transcription factor for which few regulators have been identified. Here, we demonstrate using an immune-competent mouse model of B-cell acute lymphoblastic leukemia (ALL; B-ALL) that Regnase-1 deficiency promotes TCF-1 expression to enhance CAR–T-cell expansion and memory-like cell formation. This leads to improved CAR-T–mediated tumor clearance, sustained remissions, and protection against secondary tumor challenge. Phenotypic, transcriptional, and epigenetic profiling identified increased tumor-dependent programming of Regnase-1–deficient CAR-T cells into TCF-1+ precursor exhausted T cells (TPEX) characterized by upregulation of both memory and exhaustion markers. Regnase-1 directly targets Tcf7 messenger RNA (mRNA); its deficiency augments TCF-1 expression leading to the formation of TPEX that support long-term CAR–T-cell persistence and function. Regnase-1 deficiency also reduces exhaustion and enhances the activity of TCF-1− CAR-T cells. We further validate these findings in human CAR-T cells, where Regnase-1 deficiency mediates enhanced tumor clearance in a xenograft B-ALL model. This is associated with increased persistence and expansion of a TCF-1+ CAR–T-cell population. Our findings demonstrate the pivotal roles of TPEX, Regnase-1, and TCF-1 in mediating CAR–T-cell persistence and recall responses, and identify Regnase-1 as a modulator of human CAR–T-cell longevity and potency that may be manipulated for improved therapeutic efficacy.
Adnexal masses during pregnancy: management for a better approach
Authors: Martone Simona , Troìa Libera , Luisi Stefano 
Published: March 2021

AbstractThe incidence of adnexal masses, due to large use of ultrasound during pregnancy, has considerably increased during last years. Large percentage of ovarian masses found during pregnancy consists in simple cysts and they tend to disappear spontaneously during pregnancy. There are still a percentage of masses that persist in second and third trimester that need to be monitored and, sometimes, surgically removed. If the mass increases in size, sometimes, it is itself an indication for delivery via cesarean section. Keeping in mind that adnexal masses diagnosed in pregnancy are generally benign, it is essential to consider that ovarian cancer still represents the second gynecological tumor for incidence after cervical cancer during pregnancy. Most patients are clinically asymptomatic and diagnosis is often a random finding during scheduled ultrasound for pregnancy follow-up. Sometimes, the finding of an ovarian mass requires other imaging technique such as magnetic resonance imaging. Computed tomography is avoided during pregnancy due to negative effects on fetus. Treatment option should be discussed and a multidisciplinary approach is required to set ad individualized plan, considering both mother and fetus. Sometimes the differential diagnosis between benign masses and malignancy is not feasible only through imaging, so that surgical intervention with histological examination is mandatory, even during pregnancy. Plus, although ovarian cyst torsion, hemorrhage, or rupture is uncommon in pregnancy, some women may require emergency surgery for these complications. Until 90s pregnancy was considered an absolute contraindication for laparoscopy, but nowadays both open surgery and laparoscopy can be performed considering mass diameter, gestational age, and surgical expertise. Emerging data are indeed confirming the advantages of laparoscopic surgery compared with laparotomy in term of recovery and need for medical care. The purpose of this review is to assess the incidence of adnexal masses during pregnancy and examine their impact on obstetric outcomes.
Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers
Authors: Viailly Pierre-Julien , Sater Vincent , Viennot Mathieu , Bohers Elodie , Vergne Nicolas , Berard Caroline , Dauchel Hélène , Lecroq Thierry , Celebi Alison , Ruminy Philippe , Marchand Vinciane , Lanic Marie-Delphine , Dubois Sydney , Penther Dominique , Tilly Hervé , Mareschal Sylvain , Jardin Fabrice 
Published: March 2021

Abstract
Background
Recently, copy number variations (CNV) impacting genes involved in oncogenic pathways have attracted an increasing attention to manage disease susceptibility. CNV is one of the most important somatic aberrations in the genome of tumor cells. Oncogene activation and tumor suppressor gene inactivation are often attributed to copy number gain/amplification or deletion, respectively, in many cancer types and stages. Recent advances in next generation sequencing protocols allow for the addition of unique molecular identifiers (UMI) to each read. Each targeted DNA fragment is labeled with a unique random nucleotide sequence added to sequencing primers. UMI are especially useful for CNV detection by making each DNA molecule in a population of reads distinct.

Results
Here, we present molecular Copy Number Alteration (mCNA), a new methodology allowing the detection of copy number changes using UMI. The algorithm is composed of four main steps: the construction of UMI count matrices, the use of control samples to construct a pseudo-reference, the computation of log-ratios, the segmentation and finally the statistical inference of abnormal segmented breaks. We demonstrate the success of mCNA on a dataset of patients suffering from Diffuse Large B-cell Lymphoma and we highlight that mCNA results have a strong correlation with comparative genomic hybridization.

Conclusion
We provide mCNA, a new approach for CNV detection, freely available at https://gitlab.com/pierrejulien.viailly/mcna/ under MIT license. mCNA can significantly improve detection accuracy of CNV changes by using UMI.
Genome-wide identification, characterization, and expression analysis of the NAC transcription factor family in orchardgrass (Dactylis glomerata L.)
Authors: Yang Zhongfu , Nie Gang , Feng Guangyan , Han Jiating , Huang Linkai , Zhang Xinquan 
Published: March 2021

Abstract
Background
Orchardgrass (Dactylis glomerata L.) is one of the most important cool-season perennial forage grasses that is widely cultivated in the world and is highly tolerant to stressful conditions. However, little is known about the mechanisms underlying this tolerance. The NAC (NAM, ATAF1/2, and CUC2) transcription factor family is a large plant-specific gene family that actively participates in plant growth, development, and response to abiotic stress. At present, owing to the absence of genomic information, NAC genes have not been systematically studied in orchardgrass. The recent release of the complete genome sequence of orchardgrass provided a basic platform for the investigation of DgNAC proteins.

Results
Using the recently released orchardgrass genome database, a total of 108 NAC (DgNAC) genes were identified in the orchardgrass genome database and named based on their chromosomal location. Phylogenetic analysis showed that the DgNAC proteins were distributed in 14 subgroups based on homology with NAC proteins in Arabidopsis, including the orchardgrass-specific subgroup Dg_NAC. Gene structure analysis suggested that the number of exons varied from 1 to 15, and multitudinous DgNAC genes contained three exons. Chromosomal mapping analysis found that the DgNAC genes were unevenly distributed on seven orchardgrass chromosomes. For the gene expression analysis, the expression levels of DgNAC genes in different tissues and floral bud developmental stages were quite different. Quantitative real-time PCR analysis showed distinct expression patterns of 12 DgNAC genes in response to different abiotic stresses. The results from the RNA-seq data revealed that orchardgrass-specific NAC exhibited expression preference or specificity in diverse abiotic stress responses, and the results indicated that these genes may play an important role in the adaptation of orchardgrass under different environments.

Conclusions
In the current study, a comprehensive and systematic genome-wide analysis of the NAC gene family in orchardgrass was first performed. A total of 108 NAC genes were identified in orchardgrass, and the expression of NAC genes during plant growth and floral bud development and response to various abiotic stresses were investigated. These results will be helpful for further functional characteristic descriptions of DgNAC genes and the improvement of orchardgrass in breeding programs.
Comparative transcriptomic analysis of thermally stressed Arabidopsis thaliana meiotic recombination mutants
Authors: Huang Jiyue , Wang Hongkuan , Wang Yingxiang , Copenhaver Gregory P. 
Published: March 2021

Abstract
Background
Meiosis is a specialized cell division that underpins sexual reproduction in most eukaryotes. During meiosis, interhomolog meiotic recombination facilitates accurate chromosome segregation and generates genetic diversity by shuffling parental alleles in the gametes. The frequency of meiotic recombination in Arabidopsis has a U-shaped curve in response to environmental temperature, and is dependent on the Type I, crossover (CO) interference-sensitive pathway. The mechanisms that modulate recombination frequency in response to temperature are not yet known.

Results
In this study, we compare the transcriptomes of thermally-stressed meiotic-stage anthers from msh4 and mus81 mutants that mediate the Type I and Type II meiotic recombination pathways, respectively. We show that heat stress reduces the number of expressed genes regardless of genotype. In addition, msh4 mutants have a distinct gene expression pattern compared to mus81 and wild type controls. Interestingly, ASY1, which encodes a HORMA domain protein that is a component of meiotic chromosome axes, is up-regulated in wild type and mus81 but not in msh4. In addition, SDS the meiosis-specific cyclin-like gene, DMC1 the meiosis-specific recombinase, SYN1/REC8 the meiosis-specific cohesion complex component, and SWI1 which functions in meiotic sister chromatid cohesion are up-regulated in all three genotypes. We also characterize 51 novel, previously unannotated transcripts, and show that their promoter regions are associated with A-rich meiotic recombination hotspot motifs.

Conclusions
Our transcriptomic analysis of msh4 and mus81 mutants enhances our understanding of how the Type I and Type II meiotic CO pathway respond to environmental temperature stress and might provide a strategy to manipulate recombination levels in plants.
Preliminary review on the prevalence, proportion, geographical distribution, and characteristics of naturally acquired Plasmodium cynomolgi infection in mosquitoes, macaques, and humans: a systematic review and meta-analysis
Authors: Kotepui Manas , Masangkay Frederick Ramirez , Kotepui Kwuntida Uthaisar , Milanez Giovanni De Jesus 
Published: March 2021

Abstract
Background
Plasmodium cynomolgi is a simian malaria parasite that has been reported as a naturally acquired human infection. The present study aims to systematically review reports on naturally acquired P. cynomolgi in humans, mosquitoes, and macaques to provide relevant data for pre-emptive surveillance and preparation in the event of an outbreak of zoonotic malaria in Southeast Asia.

Methods
The protocol of the systematic review was registered at PROSPERO with approval ID CRD42020203046. Three databases (Web of Science, Scopus, and MEDLINE) were searched for studies reporting the prevalence of P. cynomolgi infections in Southeast Asian countries between 1946 and 2020. The pooled prevalence or pooled proportion of P. cynomolgi parasitemia in humans, mosquitoes, and macaques was estimated using a random-effects model. Differences in the clinical characteristics of P. cynomolgi infections were also estimated using a random-effects model and presented as pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs).

Results
Thirteen studies reporting on the prevalence of naturally acquired P. cynomolgi in humans (3 studies, 21 cases), mosquitoes (3 studies, 28 cases), and macaques (7 studies, 334 cases) were included. The results demonstrated that the pooled proportion of naturally acquired P. cynomolgi in humans was 1% (95% CI, 0.1%, I2, 0%), while the pooled proportion of P. cynomolgi infecting mosquitoes was 18% (95% CI, 10–26%, I2, 32.7%). The pooled prevalence of naturally acquired P. cynomolgi in macaques was 47% (95% CI, 27–67%, I2, 98.3%). Most of the cases of naturally acquired P. cynomolgi in humans were reported in Cambodia (62%) and Malaysia (38%), while cases of P. cynomolgi in macaques were reported in Malaysia (35.4%), Singapore (23.2%), Indonesia (17.3%), Philippines (8.5%), Laos (7.93%), and Cambodia (7.65%). Cases of P. cynomolgi in mosquitoes were reported in Vietnam (76.9%) and Malaysia (23.1%).

Conclusions
This study demonstrated the occurrence of naturally acquired P. cynomolgi infection in humans, mosquitoes, and macaques. Further studies of P. cynomolgi in asymptomatic human cases in areas where vectors and natural hosts are endemic are extensively needed if human infections with P. cynomolgi do become public health problems.
Assessing fetal movements in pregnancy: A qualitative evidence synthesis of women’s views, perspectives and experiences
Authors: Smith Valerie , Muldoon Kathryn , Brady Vivienne , Delaney Hannah 
Published: March 2021

AbstractBackgroundRaising awareness of the importance of fetal movements (FMs) and advising women on the appropriate action to take if they experience reduced FMs, is important for minimising or avoiding adverse perinatal outcomes. To gain insight and understanding of women’s perspectives of assessing FMs in pregnancy, we conducted a qualitative evidence synthesis.MethodsA qualitative evidence synthesis using thematic synthesis was conducted. Studies were eligible if they included pregnant women who were at least 20 weeks gestation and reported qualitative data from women on assessing FMs in pregnancy. MEDLINE, CINAHL, EMBASE, PsycINFO and Social Science Citation Index, from inception to July 2020, were searched. The methodological quality of included studies was assessed by at least two reviewers using an Evidence for Policy and Practice Information (EPPI)-Centre quality assessment tool. Data synthesis, using the Thomas and Harden framework, involved line by line coding of extracted data, establishing descriptive themes, and determining analytical themes. Confidence in the findings was assessed using GRADE CER-Qual.ResultsNine studies, involving 2193 women, were included in the review. The methodological quality of the studies was overall generally high. The synthesis revealed three dominant themes, and seven sub-themes that reflected women’s perspectives of assessing FMs in pregnancy. These were; 1) How women engage with FMs, with subthemes of informal engagement, formal engagement, and strategies to stimulate FMs; 2)‘ … like a feather inside my belly’- articulating and describing FMs, with sub-themes of sensations associated with FMs and timing and frequency of FMs; and 3) FMs and help/health seeking, with sub-themes of information sources and interacting with healthcare professionals. Confidence in the findings was either high or moderate, although two findings were rated low confidence and one very low.ConclusionThis qualitative evidence synthesis reveals that women informally engage with FMs during pregnancy. Women commonly adopt strategies to stimulate FMs when concerned. The use of the internet was a common source of obtaining information regarding FMs. Women require better support when contacting healthcare professionals about FMs. As only three of the nine included studies were exclusively qualitative in design, further qualitative studies exploring women’s perspective of assessing FMs in pregnancy are required.
The Food, Feelings, and Family Study: comparison of the efficacy of traditional methods, social media, and broadcast email to recruit pregnant women to an observational, longitudinal nutrition study
Authors: Smith Rebecca , Alvarez Crystal , Crixell Sylvia , Lane Michelle A. 
Published: March 2021

Abstract
Background
It is well known that recruitment is a challenging aspect of any study involving human subjects. This challenge is exacerbated when the population sought is reticent to participate in research as is the case with pregnant women and individuals with depression. This paper compares recruitment methods used for the Food, Feelings, and Family Study, an observational, longitudinal pilot study concerning how diet and bisphenol A exposure affect maternal mood and cognitive function during and after pregnancy.

Methods
Pregnant women were recruited to this study over a period of 15 months using traditional methods, social media including paid and unpaid posts, and emails broadcast to the university community. Contingency analysis using the Pearson’s Chi-square test was used to determine if recruitment method was associated with likelihood of participation. T-tests were used to analyze Facebook advertisement success. ANOVAs and Fisher exact tests were used to determine if recruitment method was related to continuous and categorical demographics, respectively.

Results
Social media resulted in the largest number of recruits, followed by traditional methods and broadcast email. Women recruited through social media were less likely to participate. In contrast, use of broadcast email resulted in a smaller pool of recruits but these recruits were more likely to be eligible for and complete the study. Most women recruited via social media were the result of unpaid posts to the study’s Facebook page. Paid posts lasting at least 4 days were the most successful. Recruitment method was not associated with participant demographics.

Conclusions
Social media has the potential to recruit a large pool of potential subjects; however, when studies require a large time investment such as the case here, women recruited through social media are less likely to participate and complete the study than women recruited through other means.

Trial registration
N/A. This study does not describe a health care intervention.
KK-LC-1 may be an effective prognostic biomarker for gastric cancer
Authors: Ji Jun , Chen Jiahui , Wang Anqiang , Zhang Wei , Ju Hongge , Liu Yang , Li Leping 
Published: March 2021

Abstract
Background
The objective of the study was to detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyse the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis.

Methods
All of the 94 patients in this study were GC patients who underwent surgical resection. KK-LC-1 protein expression in GC tissue was detected by immunohistochemistry. This report applies the histological score (H-score) to evaluate KK-LC-1 expression. To calculate this indicator, the number of positive cells in each section and their staining intensity were converted to corresponding values. The expression of KK-LC-1 in the cytoplasm of cancer and normal tissues was scored to obtain their respective H values. The chi-square test, Kaplan-Meier method and Cox regression were used to analyse the linear association between KK-LC-1 expression and clinicopathological data and prognosis.

Results
In the cytoplasm, KK-LC-1 expression in tumour tissues was significantly higher than that in normal tissues (P < 0.001). Using the median H-score as the cut-off value, we discovered that GC patients with high levels of KK-LC-1 expression in the cytoplasm had favourable overall survival (OS) (P = 0.016), and this result was statistically significant in the Cox regression analysis. Additionally, a negative correlation was found between KK-LC-1 protein expression and the pathological grade of the tumour (P = 0.036), with significantly more KK-LC-1 protein expression observed in the intestinal type of GC than in the diffuse type (P = 0.008).

Conclusions
Our research data showed that KK-LC-1 expression was greater in GC tissues than in normal tissues, and higher KK-LC-1 expression was associated with longer OS of GC patients. KK-LC-1 can be used as a biomarker for a good prognosis in GC patients.