bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childbirth and motherhood in women with motor disability due to a rare condition: an exploratory study
Authors: Dommergues Marc , Candilis Drina , Becerra Ludivine , Thoueille Edith , Cohen David , Viaux-Savelon Sylvie 
Published: April 2021

Abstract
Background
Rare diseases may result in motor impairment, which in turn may affect parenthood. Our purpose was to evaluate perinatal outcomes, parenting needs, mother-infant interactions and infant development in a set of volunteer women with motor impairment due to a rare disease. In a parenting support institution, we recruited a consecutive series of 22 volunteer pregnant women or young mothers, recorded perinatal outcomes, and followed mother-infant interaction and relationship and infant development up to 14 months postpartum. Cases with intellectual or psychic disability were not included.

Results
There were 11 genetic diseases (2 Spinal Muscular Atrophy, 1 Charcot-Marie-Tooth, 1 autosomal dominants myopathy, 1 mitochondrial disease, 2 Elhers-Danlos, 1 Friedreich ataxia, 1 spinocerebellar ataxia, 1 tetrahydrobiopterine deficiency,1 Ectrodactyly), and 11 rare non-genetic conditions (2 spine tumors, 2 strokes, 1 juvenile chronic arthritis, 3 birth injuries, 1 inflammatory myopathy, 1 congenital amputation, and 1 traumatic amputation). These resulted in 10 impairments of four limbs, 4 impairments of both lower limbs, 7 unilateral impairments, and one distal tremor. Social deprivation Epices score, Cutrona social support scale, Edinburg Postnatal Depression scale, and Spielberger State/Trait Anxiety Inventory were unremarkable. Perinatal outcome: 4 gestational diabetes, 1 pre-eclampsia, 9 caesareans, 6 assisted and 7 spontaneous vaginal deliveries, 20 term live-births and 2 premature deliveries (35–36 weeks). Twelve women declared they were self-sufficient for daily activities; six declared they were self-sufficient to provide basic care to their baby. Distribution of the Brunet-Lezine child development score was normal. The parent-infant relationship global assessment scale (PIR-GAS) was well adapted in 2 cases, adapted in 8, perturbed in 7, significantly perturbed in 2, and distressed in 3 (mean 71.8; 95% CI 49.6–93.9). This was unrelated to any somatic or emotional characteristics of the participants. Coding interactive behavior revealed that infant engagement was lower and infant avoidance greater than in controls (p < 0.05).

Conclusion
Infant development was normal, but mother-infant interactions were altered in half of the participants independently from the degree of motor impairment, underscoring the need for parenting support, even for parents who are self-sufficient in daily activities.
A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa
Authors: Tang Jean Yuh , Marinkovich M. Peter , Lucas Eleanor , Gorell Emily , Chiou Albert , Lu Ying , Gillon Jodie , Patel Dipen , Rudin Dan 
Published: April 2021

Abstract
Background/objective
Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic collagen disorder characterized by skin fragility leading to blistering, wounds, and scarring. There are currently no approved curative therapies. The objective of this manuscript is to provide a comprehensive literature review of the disease burden caused by RDEB.

Methods
A systematic literature review was conducted in MEDLINE and Embase in accordance with PRISMA guidelines. Observational and interventional studies on the economic, clinical, or humanistic burden of RDEB were included.

Results
Sixty-five studies were included in the review. Patients had considerable wound burden, with 60% reporting wounds covering more than 30% of their body. Increases in pain and itch were seen with larger wound size. Chronic wounds were larger and more painful than recurrent wounds. Commonly reported symptoms and complications included lesions and blistering, anemia, nail dystrophy and loss, milia, infections, musculoskeletal contractures, strictures or stenoses, constipation, malnutrition/nutritional problems, pseudosyndactyly, ocular manifestations, and dental caries. Many patients underwent esophageal dilation (29–74%; median dilations, 2–6) and gastrostomy tube placement (8–58%). In the severely affected population, risk of squamous cell carcinoma (SCC) was 76% and mortality from SCC reached 84% by age 40. Patients with RDEB experienced worsened quality of life (QOL), decreased functioning and social activities, and increased pain and itch when compared to other EB subtypes, other skin diseases, and the general population. Families of patients reported experiencing high rates of burden including financial burden (50–54%) and negative impact on private life (79%). Direct medical costs were high, though reported in few studies; annual payer-borne total medical costs in Ireland were $84,534 and annual patient-borne medical costs in Korea were $7392. Estimated annual US costs for wound dressings ranged from $4000 to $245,000. Patients spent considerable time changing dressings: often daily (13–54% of patients) with up to three hours per change (15–40%).

Conclusion
Patients with RDEB and their families/caregivers experience significant economic, humanistic, and clinical burden. Further research is needed to better understand the costs of disease, how the burden of disease changes over the patient lifetime and to better characterize QOL impact, and how RDEB compares with other chronic, debilitating disorders.
Assessing the integrity of auditory processing and sensory memory in adults with cystinosis (CTNS gene mutations)
Authors: Francisco Ana A. , Berruti Alaina S. , Kaskel Frederick J. , Foxe John J. , Molholm Sophie 
Published: April 2021

AbstractBackgroundCystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function in adulthood. We previously demonstrated intact auditory sensory processing, accompanied by mild sensory memory difficulties, in children and adolescents with cystinosis.MethodsWe investigated whether further progressive decrements in these processes would be observed in adults with cystinosis, comparing high-density auditory-evoked potential (AEP) recordings from adults with cystinosis (N = 15; ages: 19–38 years) to those of age-matched controls (N = 17). We employed a duration oddball paradigm with different stimulation rates, in which participants passively listened to regularly occurring standard tones interspersed with infrequently occurring deviant tones. Analyses focused on AEP components reflecting auditory sensory-perceptual processing (N1 and P2), sensory memory (mismatch negativity, MMN), and attentional orienting (P3a).ResultsOverall, adults with cystinosis produced highly similar sensory-perceptual AEP responses to those observed in controls suggesting intact early auditory cortical processing. However, significantly increased P2 and P3a amplitudes and reduced MMN at slower stimulation rates were observed, suggesting mild-to-moderate changes in auditory sensory memory and attentional processing. While cognitive testing revealed lower scores on verbal IQ and perceptual reasoning in cystinosis, these did not correlate with the AEP measures.ConclusionsThese neurophysiological data point to the emergence of subtle auditory processing deficits in early adulthood in cystinosis, warranting further investigation of memory and attentional processes in this population, and of their consequences for perceptual and cognitive function.
Effectiveness of a Community-based Group Mindfulness Program tailored for Arabic and Bangla-speaking Migrants
Authors: Blignault Ilse , Saab Hend , Woodland Lisa , Mannan Haider , Kaur Arshdeep 
Published: April 2021

Abstract
Background
Migrant communities are often underserved by mainstream mental health services resulting in high rates of untreated psychological distress. This collaborative study built on evidence that mindfulness-based interventions delivered in-language and culturally tailored were acceptable and clinically effective for Arabic speakers in Australia. It aimed to establish whether a group mindfulness program produced expected outcomes under normal operational conditions, and to test its scalability and its transferability to Bangla speakers.

Methods
A 5-week mindfulness program was delivered to 15 Arabic-speaking and 8 Bangla-speaking groups in community settings. The mixed-methods evaluation incorporated a pre-post study. Descriptive statistics were used to summarise the socio-demographic data, group attendance and home practice. Differences in DASS 21 and K10 scores from pre to post-intervention were tested using the nonparametric sign test for paired samples (two-sided). Multiple linear regression analysis was performed to determine the effects of selected sociodemographic variables, group attendance and home practice on clinical outcomes, based on intention to treat. Content analysis was used to examine the qualitative data.

Results
The program attracted 168 Arabic speakers and 103 Bangla speakers aged 16 years and over, mostly women. Cultural acceptability was evident in the overall 80% completion rate, with 78% of Arabic speakers and 84% of Bangla speakers retained. Both language groups showed clinically and statistically significant improvements in mental health outcomes on the DASS21 and K10. Thirty new referrals were made to mental health services. Participant feedback emphasised the benefits for their everyday lives. All but one participant reported sharing the mindfulness skills with others.

Conclusions
Across multiple and diverse groups of Arabic and Bangla speakers in Sydney, the community-based group mindfulness program was shown to have high levels of cultural acceptability and relevance. It resulted in clinically and statistically significant improvements in mental health outcomes, facilitated access to mental health care and boosted mental health literacy. This innovative, low-intensity, in-language mental health intervention that was originally developed for Arabic speakers is scalable. It is also transferable—with cultural tailoring—to Bangla speakers.
Attentional variability and avoidance of hostile stimuli decrease aggression in Chinese male juvenile delinquents
Authors: Zhao Ziyi , Yu Xianglian , Ren Zhihong , Zhang Lin , Li Xu 
Published: April 2021

Abstract
Background
As a prominent issue worldwide, juveniles’ aggressive and violent crimes have attracted much interest in recent years. Based on the social information processing model, the present study aimed to evaluate the Chinese male juvenile delinquents’ attention bias towards hostile stimuli from both static and dynamic perspectives. Additionally, the predictive effect of attention bias on aggressive behavior and the moderating effect of group (juvenile delinquents and the controls with no criminal history) were also investigated.

Methods
The hostile attention bias and aggressive behavior of 76 juvenile delinquents (Mage = 17.5 years, SD = 0.59 years) and 67 controls (Mage = 18.3 years, SD = 0.73 years) were measured with the emotional dot-probe task, emotional Stroop task, and the Chinese version of the Buss & Perry aggression questionnaire, respectively.

Results
The results showed that compared with controls, juvenile delinquents showed more attention biases towards hostile faces and words, and demonstrated higher levels of physical aggression and anger. Furthermore, the type of participants moderated the relationship between hostile attention bias and aggressive behavior. For juvenile delinquents, attention bias away from hostile stimuli and attention variability negatively predicted anger, while for controls, attention variability positively predicted self-directed aggression.

Conclusion
Attentional variability and avoidance of hostile stimuli are expected to reduce the aggressive level of Chinese male juvenile delinquents. The relationship between attention bias and aggression should be further considered and applied in the clinical practice.
CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer
Authors: Chen Shi , Yang Can , Wang Zu-Wei , Hu Jian-Fei , Pan Jing-Jing , Liao Cheng-Yu , Zhang Jia-Qiang , Chen Jiang-Zhi , Huang Yi , Huang Long , Zhan Qian , Tian Yi-Feng , Shen Bai-Yong , Wang Yao-Dong 
Published: April 2021

AbstractBackgroundBoth aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear.MethodsRNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser(SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10(METTL14exon10) and Cyclin L2exon6.3skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10and Cyclin L2exon6.3skipping were surveyed.ResultsCLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10skipping while promoted Cyclin L2exon6.3skipping. In addition, aberrant METTL14exon 10skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3promoted proliferation of PDAC cells.ConclusionsThe CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.
Validation of the Critical-Care Pain Observation Tool-Neuro in brain-injured adults in the intensive care unit: a prospective cohort study
Authors: Gélinas Céline , Bérubé Mélanie , Puntillo Kathleen A. , Boitor Madalina , Richard-Lalonde Melissa , Bernard Francis , Williams Virginie , Joffe Aaron M. , Steiner Craig , Marsh Rebekah , Rose Louise , Dale Craig M. , Tsoller Darina M. , Choinière Manon , Streiner David L. 
Published: April 2021

Abstract
Background
Pain assessment in brain-injured patients in the intensive care unit (ICU) is challenging and existing scales may not be representative of behavioral reactions expressed by this specific group. This study aimed to validate the French-Canadian and English revised versions of the Critical-Care Pain Observation Tool (CPOT-Neuro) for brain-injured ICU patients.

Methods
A prospective cohort study was conducted in three Canadian and one American sites. Patients with a traumatic or a non-traumatic brain injury were assessed with the CPOT-Neuro by trained raters (i.e., research staff and ICU nurses) before, during, and after nociceptive procedures (i.e., turning and other) and non-nociceptive procedures (i.e., non-invasive blood pressure, soft touch). Patients who were conscious and delirium-free were asked to provide their self-report of pain intensity (0–10). A first data set was completed for all participants (n = 226), and a second data set (n = 87) was obtained when a change in the level of consciousness (LOC) was observed after study enrollment. Three LOC groups were included: (a) unconscious (Glasgow Coma Scale or GCS 4–8); (b) altered LOC (GCS 9–12); and (c) conscious (GCS 13–15).

Results
Higher CPOT-Neuro scores were found during nociceptive procedures compared to rest and non-nociceptive procedures in both data sets (p < 0.001). CPOT-Neuro scores were not different across LOC groups. Moderate correlations between CPOT-Neuro and self-reported pain intensity scores were found at rest and during nociceptive procedures (Spearman rho > 0.40 and > 0.60, respectively). CPOT-Neuro cut-off scores ≥ 2 and ≥ 3 were found to adequately classify mild to severe self-reported pain ≥ 1 and moderate to severe self-reported pain ≥ 5, respectively. Interrater reliability of raters’ CPOT-Neuro scores was supported with intraclass correlation coefficients > 0.69.

Conclusions
The CPOT-Neuro was found to be valid in this multi-site sample of brain-injured ICU patients at various LOC. Implementation studies are necessary to evaluate the tool’s performance in clinical practice.
Breast adipose tissue macrophages (BATMs) have a stronger correlation with breast cancer survival than breast tumor stroma macrophages (BTSMs)
Authors: Lin Lili , Kuhn Christina , Ditsch Nina , Kolben Thomas , Czogalla Bastian , Beyer Susanne , Trillsch Fabian , Schmoeckel Elisa , Mayr Doris , Mahner Sven , Jeschke Udo , Hester Anna 
Published: April 2021

Abstract
Background
An abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately.

Methods
Two hundred ninety-eight BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease-free survival (DFS) and overall survival (OS).

Results
The amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p = 2.98E−15). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p = 0.000011), and all triple-negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p = 0.000401) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p = 0.000002).

Conclusion
Our findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs—eventually in combination with targeting the EP3-pathway—might be promising for future therapies.
Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication
Authors: Gillard Gareth B. , Grønvold Lars , Røsæg Line L. , Holen Matilde Mengkrog , Monsen Øystein , Koop Ben F. , Rondeau Eric B. , Gundappa Manu Kumar , Mendoza John , Macqueen Daniel J. , Rohlfs Rori V. , Sandve Simen R. , Hvidsten Torgeir R. 
Published: April 2021

AbstractBackgroundWhole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80–100 million years ago.ResultsWe find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards lower expression and possible pseudogenization. Loss of expression in one ohnolog is significantly associated with transposable element insertions in promoters and likely driven by selection on gene dosage including selection on stoichiometric balance. We also find symmetric expression shifts, and these are associated with genes under strong evolutionary constraints such as ribosome subunit genes. This possibly reflects selection operating to achieve a gene dose reduction while avoiding accumulation of “toxic mutations”. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one likely source of novel binding sites driving tissue-specific gains in expression.ConclusionsOur results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.