bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mosaic variegated aneuploidy syndrome 2 with biallelic novel CEP57 splice site variation in Indian siblings: Expanding the clinical and molecular spectrum
Authors: Langeh Nitika , Saluja Sumedha , Ethayathulla Abdul Samath , Jana Manisha , Shukla Rashmi , Palanichamy Jayanth Kumar , Gupta Neerja 
Published: January 2023

AbstractMosaic variegated aneuploidy syndrome 2 (MVA2) (MIM# 614114) is a rare autosomal recessive condition caused by biallelic loss of function variants in the CEP57 gene. MVA2 is characterized by a variable phenotype ranging from poor growth to facial dysmorphism, short stature and congenital heart defects. Only 11 families and 5 pathogenic variants of MVA2 have been described so far. Intragenic duplication of 11 nucleotides (c.915_925dup11) in homozygous or compound heterozygous state is the commonest genetic aberration (10/13). We describe the first Indian family with two siblings with a novel homozygous splice site variant (c.382+2T>C) in CEP57. Molecular characterization demonstrated skipping of exon 3 due to the variant with protein modeling predicting subsequent complete loss of function. This is the first report of a splice site variation in CEP57 leading to MVA2.
Joint longitudinal and time‐to‐event modelling compared with standard Cox modelling in patients with type 2 diabetes with and without established cardiovascular disease: An analysis of the EXSCEL trial
Authors: Oulhaj Abderrahim , Aziz Faisal , Suliman Abubaker , Iqbal Nayyar , Coleman Ruth L. , Holman Rury R. , Sourij Harald 
Published: January 2023

AbstractAimTo demonstrate the gain in predictive performance when cardiovascular disease (CVD) risk prediction tools (RPTs) incorporate repeated rather than only single measurements of risk factors.Materials and methodsWe used data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to compare the quality of predictions of future major adverse cardiovascular events (MACE) with the Cox proportional hazards model (using single values of risk factors) compared to the Bayesian joint model (using repeated measures of risk factors). The risk of MACE was calculated in patients with type 2 diabetes with and without established CVD. We assessed the predictive ability of the following cardiovascular risk factors: glycated haemoglobin, high‐density lipoprotein cholesterol (HDL‐C), non‐HDL‐C, triglycerides, estimated glomerular filtration rate, low‐density lipoprotein cholesterol (LDL‐C), total cholesterol, and systolic blood pressure (SBP) using the time‐dependent area under the receiver‐operating characteristic curve (aROC) for discrimination and the time‐dependent Brier score for calibration.ResultsIn participants without history of CVD, the aROC of SBP increased from 0.62 to 0.69 when repeated rather than only single measurements of SBP were incorporated into the predictive model. Similarly, the aROC increased from 0.67 to 0.80 when repeated rather than only single measurements of both SBP and LDL‐C were incorporated into the predictive model. For all other investigated cardiovascular risk factors, the measures of discrimination and calibration both improved when using the joint model as compared to the Cox proportional hazards model. The improvement was evident in participants with and without history of CVD but was more pronounced in the latter group.ConclusionsThe analysis demonstrates that the joint modelling approach, considering trajectories of cardiovascular risk factors, provides superior predictive performance compared to standard RPTs that use only a single timepoint.
Modelling the population dynamics of an exploited, tropical fish species playing a fundamental role in aquatic ecosystems
Authors: Benito Erika J. , Ladino Lilia M. , Ramírez‐Gil Hernando 
Published: January 2023

AbstractThe coporo, Prochilodus mariae, plays a fundamental role in aquatic ecosystems as a detritivorous species facilitating the flow of carbon to the rest of the ecosystem's food web. It is also one of the most exploited freshwater fish species. Fishing, pollution and environmental changes in the Orinoquia region of Colombia have considerably reduced its population size. We analysed the population dynamics of P. mariae during an annual river cycle, including extreme drought and flood scenarios, by means of a mathematical model and simulations. The model we propose is novel because it relates biological, ecological and environmental factors to the population dynamics, including reproduction, growth in size and biomass of fish, recruitment, predation, fishing mortality and river flow. The proposed mathematical model apparently gives an approximate description of the population dynamics of P. mariae for 2010 because a good fit of the model to the catch data of the species of that year was obtained. The simulations showed that the first 3 months of the year are crucial for the species because this is when it is most affected by a combination of fishing, biological factors which increase natural mortality (e.g. upstream migration and predation) and environmental factors (e.g. low river flow). Hypothetical scenarios show that local extinction could occur if fishing were to increase and river flow were to decrease.
Characterization, pathogenicity and host range studies of Paecilomyces formosus associated with dieback of Christ's thorn trees (Paliurus spina‐christi Mill.) in Iran
Authors: Rostami Taha , Jamali Samad 
Published: January 2023

AbstractChrist's thorn (Paliurus spina‐christi Mill.) tree is an important and valuable forestry species and has significant potential in afforestation and reforestation systems. In recent years, dieback symptoms were observed on Paliurus spina‐christi trees in Gilan‐e Gharb region of Kermanshah province, west Iran. During 2020 to 2021, Christ's thorn trees that exhibit branch dieback symptoms were sampled for fungal isolations. The pathogenicity tests, biochemical assay of growth, acid production on creatine sucrose agar (CREA) medium and morphological and molecular investigations (ITS and β‐tubulin regions) identified Paecilomyces formosus as a dieback causal agent. This is the first report of P. formosus pathogenicity on Paliurus spina‐christi trees. Furthermore, disease severity was assayed on 11 tree species under three different temperatures 15, 25 and 35°C. Disease severity caused by all isolates on detached branches was greater at 35°C than at 15 and 25°C. This study presents the host range of this pathogen and showed that these potential hosts are prone to this pathogen under high temperatures, which forest trees experienced in recent decades.
The Drosophila dopamine 2‐like receptor D2R (Dop2R) is required in the blood brain barrier for male courtship
Authors: Love Cameron R. , Gautam Sumit , Lama Chamala , Le Nhu Hoa , Dauwalder Brigitte 
Published: January 2023

AbstractThe blood brain barrier (BBB) has the essential function to protect the brain from potentially hazardous molecules while also enabling controlled selective uptake. How these processes and signaling inside BBB cells control neuronal function is an intense area of interest. Signaling in the adult Drosophila BBB is required for normal male courtship behavior and relies on male‐specific molecules in the BBB. Here we show that the dopamine receptor D2R is expressed in the BBB and is required in mature males for normal mating behavior. Conditional adult male knockdown of D2R in BBB cells causes courtship defects. The courtship defects observed in genetic D2R mutants can be rescued by expression of normal D2R specifically in the BBB of adult males. Drosophila BBB cells are glial cells. Our findings thus identify a specific glial function for the DR2 receptor and dopamine signaling in the regulation of a complex behavior.
Iron‐mediated anaerobic ammonium oxidation recorded in the early Archean ferruginous ocean
Authors: Pellerin Alice , Thomazo Christophe , Ader Magali , Marin‐Carbonne Johanna , Alleon Julien , Vennin Emmanuelle , Hofmann Axel 
Published: January 2023

AbstractThe nitrogen isotopic composition of organic matter is controlled by metabolic activity and redox speciation and has therefore largely been used to uncover the early evolution of life and ocean oxygenation. Specifically, positive δ15N values found in well‐preserved sedimentary rocks are often interpreted as reflecting the stability of a nitrate pool sustained by water column partial oxygenation. This study adds much‐needed data to the sparse Paleoarchean record, providing carbon and nitrogen concentrations and isotopic compositions for more than fifty samples from the 3.4 Ga Buck Reef Chert sedimentary deposit (BRC, Barberton Greenstone Belt). In the overall anoxic and ferruginous conditions of the BRC depositional environment, these samples yield positive δ15N values up to +6.1‰. We argue that without a stable pool of nitrates, these values are best explained by non‐quantitative oxidation of ammonium via the Feammox pathway, a metabolic co‐cycling between iron and nitrogen through the oxidation of ammonium in the presence of iron oxides. Our data contribute to the understanding of how the nitrogen cycle operated under reducing, anoxic, and ferruginous conditions, which are relevant to most of the Archean. Most importantly, they invite to carefully consider the meaning of positive δ15N signatures in Archean sediments.
Tertiary lymphoid structures in breast ductal carcinoma in situ correlate with adverse pathological parameters
Authors: Zeng Lixia , Koh Valerie Cui Yun , Chen Xiao‐Yang , Tan Puay Hoon 
Published: January 2023

AimsTo investigate tertiary lymphoid structures (TLSs) in ductal carcinoma in situ (DCIS) of the breast and their correlation with pathological features, immune cell markers and clinical outcomes.Methods and resultsMorphological identification of TLSs in 198 DCIS cases incorporated B and T cell zones with high endothelial venules. TLS positivity was defined as ≥ 1 TLSs in lesional areas, while TLS area percentage was divided into two categories: low (TLSs < 5%) and high (TLSs ≥ 5%). Previously reported biomarkers included ER, PR, HER2, CD68, CD163, CD4, CD8 and PD‐L1. TLSs were observed in 24.7% (49 of 198) of cases, with a mean diameter of 0.44 mm (median = 0.4 mm, range = 0.12–1.43 mm). TLSs were significantly associated with higher nuclear grade, presence of necrosis, hormone receptor negativity/HER2 positivity, triple negativity, tumour infiltrating lymphocytes (TILs) and immune related biomarkers such as FOXP3, CD163, CD4 and CD4/CD8 ratio (all P < 0.05). There were no significant associations between TLSs and recurrence, but a combination of TLSshigh with FOXP3+, CD4high, CD4/CD8 ratiohigh and CD68high individually, compared with all other combinations, disclosed significantly poorer disease‐free survival (DFS) for ipsilateral invasive recurrence (IIR) on both Kaplan–Meier and multivariable Cox regression analyses (all P < 0.05).ConclusionsTLSs in DCIS were associated with unfavourable prognostic features, TILs and immune cell markers in our study. TLSshigh/FoxP3+, TLSshigh/CD4high, TLSshigh/(CD4/CD8) ratiohigh and TLSshigh/CD68high were independent factors for poorer DFS for IIR. Further exploration of the pathological significance of TLSs may provide a clinical basis for their recognition as an important structure and functional unit in the tumour immune microenvironment.
Revealing the tension: The relationship between high fall risk categorization and low patient mobility
Authors: Capo‐Lugo Carmen E. , Young Daniel L. , Farley Holley , Aquino Carla , McLaughlin Kevin , Colantuoni Elizabeth , Friedman Lisa Aronson , Kumble Sowmya , Hoyer Erik H. 
Published: January 2023

AbstractBackgroundUsing an inpatient fall risk assessment tool helps categorize patients into risk groups which can then be targeted with fall prevention strategies. While potentially important in preventing patient injury, fall risk assessment may unintentionally lead to reduced mobility among hospitalized patients. Here we examined the relationship between fall risk assessment and ambulatory status among hospitalized patients.MethodsWe conducted a retrospective cohort study of consecutively admitted adult patients (n = 48,271) to a quaternary urban hospital that provides care for patients of broad socioeconomic and demographic backgrounds. Non‐ambulatory status, the primary outcome, was defined as a median Johns Hopkins Highest Level of Mobility <6 (i.e., patient walks less than 10 steps) throughout hospitalization. The primary exposure variable was the Johns Hopkins Fall Risk Assessment Tool (JHFRAT) category (Low, Moderate, High). The capacity to ambulate was assessed using the Activity Measure for Post‐Acute Care (AM‐PAC). Multivariable regression analysis controlled for clinical demographics, JHFRAT items, AM‐PAC, comorbidity count, and length of stay.Results8% of patients at low risk for falls were non‐ambulatory, compared to 25% and 54% of patients at moderate and high risk for falls, respectively. Patients categorized as high risk and moderate risk for falls were 4.6 (95% CI: 3.9–5.5) and 2.6 (95% CI: 2.4–2.9) times more likely to be non‐ambulatory compared to patients categorized as low risk, respectively. For patients with high ambulatory potential (AM‐PAC 18–24), those categorized as high risk for falls were 4.3 (95% CI: 3.5–5.3) times more likely to be non‐ambulatory compared to patients categorized as low risk.ConclusionsPatients categorized into higher fall risk groups had decreased mobility throughout their hospitalization, even when they had the functional capacity to ambulate.
Neuron‐restrictive silencer factor/repressor element 1‐silencing transcription factor (NRSF/REST) controls spatial K+ buffering in primary cortical astrocytes
Authors: Centonze Eleonora , Marte Antonella , Albini Martina , Rocchi Anna , Cesca Fabrizia , Chiacchiaretta Martina , Floss Thomas , Baldelli Pietro , Ferroni Stefano , Benfenati Fabio , Valente Pierluigi 
Published: January 2023

AbstractNeuron‐restrictive silencer factor/repressor element 1 (RE1)‐silencing transcription factor (NRSF/REST) is a transcriptional repressor of a large cluster of neural genes containing RE1 motifs in their promoter region. NRSF/REST is ubiquitously expressed in non‐neuronal cells, including astrocytes, while it is down‐regulated during neuronal differentiation. While neuronal NRSF/REST homeostatically regulates intrinsic excitability and synaptic transmission, the role of the high NRSF/REST expression levels in the homeostatic functions of astrocytes is poorly understood. Here, we investigated the functional consequences of NRSF/REST deletion in primary cortical astrocytes derived from NRSF/REST conditional knockout mice (KO). We found that NRSF/REST KO astrocyte displayed a markedly reduced activity of inward rectifying K+ channels subtype 4.1 (Kir4.1) underlying spatial K+ buffering that was associated with a decreased expression and activity of the glutamate transporter‐1 (GLT‐1) responsible for glutamate uptake by astrocytes. The effects of the impaired astrocyte homeostatic functions on neuronal activity were investigated by co‐culturing wild‐type hippocampal neurons with NRSF/REST KO astrocytes. Interestingly, neurons experienced increased neuronal excitability at high firing rates associated with decrease after hyperpolarization and increased amplitude of excitatory postsynaptic currents. The data indicate that astrocytic NRSF/REST directly participates in neural circuit homeostasis by regulating intrinsic excitability and excitatory transmission and that dysfunctions of NRSF/REST expression in astrocytes may contribute to the pathogenesis of neurological disorders.image
Nurses knowledge, attitudes and education needs towards acute pain management in hospital settings: A meta‐analysis
Authors: McCabe Catherine , Feeney Aoife , Basa Muluken , Eustace‐Cook Jessica , McCann Margaret 
Published: January 2023

AbstractBackgroundEffective pain assessment and management is widely reported as sub optimal due to inadequate knowledge and negative attitudes among nurses.AimTo determine nurses’ attitudes, knowledge and education needs towards acute pain management in acute hospital settingsMethodsPRISMA (2021) and guidelines from the University of York, CRD (2009) informed the design and conduct of this review. We included studies with registered nurses involved in direct adult patient care and acute pain management in hospital settings.Seven databases were searched (10 June 2020 and 21 January 2022): Medline (EBSCO), EMBASE (Ovid), CINAHL Complete (EBSCO), PsycINFO (EBSCO), Applied Social Science Index and Abstracts (ASSIA), Web of Science and the WHO Library Global Index Medicus.The review outcomes were nurses’ knowledge, attitudes and education needs towards acute pain assessment and management. The CASP Cohort Assessment tool was used to independently conduct a quality assessment of included studies. Data extraction was conducted by paired reviewers working independently of each other. A meta‐analysis of findings relating to nurses’ knowledge and attitudes towards acute pain management was undertaken using MedCalc software.ResultsTen articles with 1,478 participants met the inclusion criteria. Five studies addressed the review items of knowledge and attitudes while the remaining studies focused on knowledge alone. No study measured educational needs. This meta‐analysis found that only 45.59% (95% CI: 20.46–71.97) of the 1090 respondents had adequate or above adequate levels of knowledge about acute pain management. The proportion of participants with positive attitudes was 25.76% (95% CI: 11.01–44.12).DiscussionHigh levels of variability exists across the included studies which reduces their comparability. To improve homogeneity and comparability, adaptation of instruments should be kept to a minimum. Reporting knowledge and attitudes separately may highlight education, both theoretical and clinical as the focus for improving assessment and management of acute pain.
Some observations on remote delivery of eye‐movement desensitisation and reprocessing to people with intellectual disabilities
Authors: Unwin Gemma , Stenfert‐Kroese Biza , Rogers Gemma , Swain Sophie , Hiles Steve , Clifford Clair , Farrell Derek , Willner Paul 
Published: January 2023

AbstractIt is increasingly recognised that many people with intellectual disabilities suffer from post‐traumatic stress disorder (PTSD). Eye‐movement desensitisation and reprocessing (EMDR) has been proposed as a potentially helpful intervention that is less reliant on verbal skills than other effective treatments for PTSD and therefore could be more effective than verbal interventions for people with intellectual disabilities. The Trauma‐AID project is a randomised clinical trial (RCT) evaluating the effectiveness of a bespoke EMDR protocol for adults with intellectual disability and PTSD, which incorporates a prolonged phase of Psycho‐Education and Stabilisation (PES) prior to the trauma confrontation phase of EMDR. The COVID‐19 pandemic struck during the feasibility phase of the Trauma‐AID project, necessitating a second feasibility study to evaluate the acceptability and feasibility of remote or hybrid delivery of the PES + EMDR protocol. To this end, we conducted two online surveys of therapists followed by interviews with clients, carers and senior therapists. The surveys were analysed descriptively. Content analysis was used for client and carer interviews, and framework analysis for therapist interviews. All stakeholders reported positive experiences of EMDR; however, some challenges were identified. The majority of clients, carers and therapists interviewed reported that the intervention, whether PES alone or the full PES‐EMDR package, had improved symptoms of PTSD and psychological well‐being, and carers also reported decreases in challenging behaviour. A full account of the data is provided in four Supplementary Digital files. PES‐EMDR therapy appears both feasible and acceptable for clients with intellectual disabilities and therapists, whether delivered face‐to‐face or in a remote or hybrid mode, though remote working appears easier for the PES phase than the EMDR phase of the intervention.
Survival, remission, and quality of life in diabetic cats
Authors: Rothlin‐Zachrisson Ninni , Öhlund Malin , Röcklinsberg Helena , Ström Holst Bodil 
Published: January 2023

AbstractBackgroundRemission is documented in a substantial proportion of cats with diabetes. The effects of diabetes mellitus (DM) on the lives of cats and their owners should be considered when evaluating treatment success.ObjectivesTo study outcome in cats with DM and the impact DM has on the life situation of cat and owner.AnimalsDomestic and pedigree cats with a diagnosis of DM (n = 477) insured by a Swedish insurance company during 2009 to 2013.MethodsRetrospective cross‐sectional study. A questionnaire was sent to 1369 owners of cats diagnosed with DM. The questions concerned the cat, treatment, owner perceptions of the disease and treatment and disease outcome. Data were analyzed using multiple linear and logistic regression, with outcomes set as survival for more than 4 weeks after diagnosis, survival time, achieving remission, remission without relapse and quality of life (QoL) for the cat.ResultsThe response rate was 35%, leaving 477 questionnaires for analysis. The remission rate among treated cats was 29% (118/405). Feeding a commercially available wet diet was associated with both remission (OR 3.16, 95% confidence interval 1.27‐8.12) and remission without relapse (OR 14.8, 95% confidence interval 2.25‐153.8). Remission was associated with a better QoL for the cat.Conclusions and Clinical ImportanceThe association between feeding a commercially available wet diet and remission is important and strengthens the role of diet in treatment of DM in cats. Linking remission and a better QoL for the cat emphasizes remission as a goal in disease management.
Association of proteinuria and risk of incident atrial fibrillation in the general population: A prospective study of Kailuan study participants
Authors: Li Jie , Wang Yueying , Qi Wenwei , Zhang Nan , Tse Gary , Li Guangping , Wu Shouling , Liu Tong 
Published: January 2023

AbstractBackgroundProteinuria is a well‐known cardiovascular risk factor, but whether it independently increases the risk for atrial fibrillation (AF) in Chinese population is unknown. To address this deficiency, herein, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF.MethodsThis was a prospective cohort study of Kailuan study participants who underwent the 2006–2007 and 2010–2011 health checkups and was free from AF. Participants were classified into four groups based on the level of proteinuria: [−, trace (±), 1+, ≥2+]. The outcome was incident AF as confirmed by 12‐lead electrocardiography.ResultsDuring a median of 11.90 years of follow‐up, we documented 514 incident AF cases among 60,599 participants. Proteinuria was found in 6302 (10.40%) participants. Relative to participants without proteinuria at the baseline, those with proteinuria (≥2+) had an 83.9% higher risk (95% confidence interval [CI], 1.073–3.154, p = .0267) of developing AF, after adjusted for confounding variables. The result was consistent in the sensitivity analysis. Compared to consistently negative proteinuria, the risk of AF significantly increased in the aggravated proteinuria group (hazard ratio [HR] 1.552, 95% CI 1.140–2.114) and the persistent proteinuria group (HR 2.485, 95% CI 1.414–4.366). Among participants with resolved proteinuria (from positive to negative), the risk of incident AF was not significantly increased compared to those with persistently negative proteinuria (HR 1.300, 95% CI 0.743–2.276).ConclusionsProteinuria could be a modifiable risk factor for predicting AF development. Knowing the presence of proteinuria may improve risk stratification for decision‐making about AF prevention.