bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic blockade of proBDNF inhibited the expansion and altered the transcriptomic expression in CD3+B220+cells in MRL/lpr lupus mice
Authors: Zha An-Hui , Luo Cong , Shen Wei-Yun , Fu Di , Dai Ru-Ping 
Published: December 2022

ObjectivesThe overexpansion of CD3+B220+cells is the hallmark and main pathological mechanism of clinical manifestations of spontaneously developed MRL/lpr mice, which are primarily used as a mouse model of SLE. Our recent report demonstrated that blocking brain-derived neurotrophic factor precursor (proBDNF) suppressed the antibody-secreting cell differentiation and proliferation and inhibited the progression of SLE; however, the effect of proBDNF blockade on these CD3+B220+cells in MRL/lpr mice is unclear.MethodsTo explore the effect of proBDNF on CD3+B220+cells, MRL/lpr mice at 12 weeks old were intraperitoneally injected with monoclonal anti-proBDNF antibody (McAb-proB) or control IgG continuously for 8 weeks. The manifestations in mice were observed, and peripheral blood and splenocytes were collected and analysed via flow cytometry at 20 weeks old. In addition, splenic CD3+B220+cells were subjected to RNA sequencing (RNA-seq) analysis to identify transcriptomic alterations.ResultsCD3+B220+cells in peripheral blood (p=0.0101) and spleen (p<0.0001) were expanded in MRL/lpr mice. Meanwhile, inhibition of proBDNF signalling reduced the percentage of CD3+B220+cells in peripheral blood (p=0.0036) and spleen (p=0.0280), alleviated lymphadenopathy, reduced urine protein level (p<0.0001) and increased the body weight (p=0.0493). RNA-seq revealed 501 upregulated and 206 downregulated genes in splenic CD3+B220+cells in McAb-proB-treated MRL/lpr mice compared with IgG-treated mice. The differentially expressed genes were found to be involved in apoptosis, tumour necrosis factor signalling, and T cell differentiation and proliferation.ConclusionSystemic blockade of proBDNF inhibited the overexpansion of CD3+B220+cells and altered their signals related to cell cycle, cell apoptosis and the immune response, which may contribute to the attenuation of disease symptoms in murine lupus.
Misaligned Chromosomes are a Major Source of Chromosomal Instability in Breast Cancer
Authors: Tucker John B. , Bonema Sarah C. , García-Varela Rebeca , Denu Ryan A. , Hu Yang , McGregor Stephanie M. , Burkard Mark E. , Weaver Beth A. 
Published: December 2022

Chromosomal instability (CIN), the persistent reshuffling of chromosomes during mitosis, is a hallmark of human cancers that contributes to tumor heterogeneity and has been implicated in driving metastasis and altering responses to therapy. Though multiple mechanisms can produce CIN, lagging chromosomes generated from abnormal merotelic attachments are the major cause of CIN in a variety of cell lines, and are expected to predominate in cancer. Here, we quantify CIN in breast cancer using a tumor microarray, matched primary and metastatic samples, and patient-derived organoids from primary breast cancer. Surprisingly, misaligned chromosomes are more common than lagging chromosomes and represent a major source of CIN in primary and metastatic tumors. This feature of breast cancers is conserved in a majority of breast cancer cell lines. Importantly, though a portion of misaligned chromosomes align before anaphase onset, the fraction that remain represents the largest source of CIN in these cells. Metastatic breast cancers exhibit higher rates of CIN than matched primary cancers, primarily due to increases in misaligned chromosomes. Whether CIN causes immune activation or evasion is controversial. We find that misaligned chromosomes result in immune-activating micronuclei substantially less frequently than lagging and bridge chromosomes and that breast cancers with greater frequencies of lagging chromosomes and chromosome bridges recruit more stromal tumor-infiltrating lymphocytes. These data indicate misaligned chromosomes represent a major mechanism of CIN in breast cancer and provide support for differential immunostimulatory effects of specific types of CIN.Significance:We surveyed the single-cell landscape of mitotic defects that generate CIN in primary and metastatic breast cancer and relevant models. Misaligned chromosomes predominate, and are less immunostimulatory than other chromosome segregation errors.
Annular pancreas in neonate patients
Authors: Carvalho Sarah , Barreiros Lucas , Binatti Carlos Eduardo , Paganoti Guilherme de Freitas , Costa Graziela de Araújo , Meyer Viviane Mauro Corrêa 
Published: December 2022

Objective: Reinforce that, despite being a rare condition, annular pancreas must be considered as a differential diagnosis for intestinal obstructions in the newborn period. Case description: This case report refers to a 13-days newborn admitted to the emergency room presenting with postprandial vomiting and progressive weight loss since maternity discharge. The patient did not respond to initial interventions that included IV antibiotics and insertion of a nasogastric tube. A contrasted study of the upper digestive tract (esophagus, stomach and duodenum) found a luminal narrowing on the second duodenal portion. The patient was submitted to an exploratory laparotomy which found a pancreatic-tissue ring involving the second part of the duodenum. Despite rare, we reinforce that annular pancreas must be considered as a differential diagnosis for intestinal obstructions in the newborn period. Comments: Annular pancreas is a rare congenital defect in which a ring of pancreatic tissue encircles the duodenum, causing different degrees of intestinal obstruction.
Aortic Stress Activates an Adaptive Program in Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength and Protects Against Aneurysm and Dissection in Mice
Authors: Zhang Chen , Li Yanming , Chakraborty Abhijit , Li Yang , Rebello Kimberly R. , Ren Pingping , Luo Wei , Zhang Lin , Lu Hong S. , Cassis Lisa A. , Coselli Joseph S. , Daugherty Alan , LeMaire Scott A. , Shen Ying H. 
Published: December 2022

Background:
When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to AngII (angiotensin II) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD).

Methods:

We performed single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the direct effects of YAP (yes-associated protein) on the SMC adaptive response in vitro. The role of YAP in AAD development was further evaluated in AngII-infused mice with SMC-specific
Yap
deletion.

Results:

In wild-type mice, AngII infusion increased medial thickness in the thoracic aorta. Single-cell RNA sequencing analysis revealed an adaptive response in thoracic SMCs characterized by upregulated genes with roles in wound healing, elastin and collagen production, proliferation, migration, cytoskeleton organization, cell-matrix focal adhesion, and PI3K-PKB/Akt (phosphoinositide-3-kinase–protein kinase B/Akt) and TGF-β (transforming growth factor beta) signaling. ScATAC-seq analysis showed increased chromatin accessibility at regulatory regions of adaptive genes and revealed the mechanical sensor YAP/transcriptional enhanced associate domains as a top candidate transcription complex driving the expression of these genes (eg,
Lox, Col5a2, Tgfb2
). In cultured human aortic SMCs, cyclic stretch activated YAP, which directly bound to adaptive gene regulatory regions (eg,
Lox
) and increased their transcript abundance. SMC-specific
Yap
deletion in mice compromised this adaptive response in SMCs, leading to an increased AAD incidence.

Conclusions:
Aortic stress triggers the systemic epigenetic induction of an adaptive response (eg, wound healing, proliferation, matrix organization) in thoracic aortic SMCs that depends on functional biomechanical signal transduction (eg, YAP signaling). Our study highlights the importance of the adaptive response in maintaining aortic homeostasis and preventing AAD in mice.
Pollen morphology of selected taxa of Valeriana (Caprifoliaceae): taxonomic and evolutionary implications
Authors: TSYMBALYUK ZOYA M. , IVANOVA DANIELLA , BELL CHARLES D. , NITSENKO LYUDMILA M. 
Published: December 2022

Pollen morphology of 34 herbarium specimens belonging to 17 taxa of the genus Valeriana was studied using light and scanning electron microscopy. The aim of this research was to evaluate the taxonomical value of palynomorphological data for species-specific identification. Pollen grains are monads, radially symmetrical, isopolar, tricolpate, oblate to prolate (P/E = 0.69–1.59); medium- or large-sized (P = 26.60–66.50 µm; E = 23.94–57.19 µm). Colpi are long, medium-length or short, with acute, obtuse or rounded ends. Four types and eight subtypes of exine sculpture were recognised: type I—echinate-verrucate (5 spp.), type II—echinate-nanoechinate-verrucate (10), type III—echinate-microechinate-nanoechinate-verrucate (1), type IV—echinate-microechinate-nanoechinate (1). Additional characters of taxa of Valeriana diagnostic at species level for the purposes of taxonomy are: size of pollen and colpi, exine sculpture: presence/absence of verrucae, their form, size and form of echini/microechini/nanoechini, their number, pattern of tectum in areas between echini, exine thickness in mesocolpia and apocolpia. Our palynomorphological data support the results of molecular phylogenetic studies. The close phylogenetic relationships of the species V. montana, V. tripteris, V. supina and V. pyrenaica are also supported by their palynomorphological characters, such as exine sculpture (type I). Cluster analysis mainly supports the definition of pollen types and subtypes (based on qualitative data), since species are grouped as five separate branches. The pollen grains of five taxa were analysed for the first time in the current study.
Efficacy of same-day versus next-day administration of pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide: A retrospective multi-site analysis
Authors: Hobbs Jacob , Lowe Jan , Ferdinand Abigale , Shook Anna , Beck Bradley , Blais Danielle , Borchardt Cole , Xu Bing 
Published: December 2022

Introduction Administering pegfilgrastim on the same day as chemotherapy can improve patient satisfaction through convenience and may increase the utilization of cost-effective biosimilars compared to next-day administration, but the effect on clinical outcomes with commonly used breast cancer regimens is unclear. Methods This multi-site, retrospective cohort study included breast cancer patients age 18 years or older who received dose-dense doxorubicin and cyclophosphamide (ddAC) and pegfilgrastim between 1 June 2016 and 31 May 2020. Pegfilgrastim was given on the same day as chemotherapy at one site and the day after chemotherapy at the other two sites. The primary endpoint compared the incidence of febrile neutropenia associated with pegfilgrastim administration timing. Results A total of 360 patients were reviewed (146 same-day administration and 214 next-day administration). In the same-day group 36 patients (24.6%) developed FN compared to 25 patients (11.7%) in the next-day group ( p = 0.002). Same-day administration also significantly increased the incidences of additional acute care visits (11.6% vs 2.8%, p = 0.0016), grade ≥ 3 neutropenia (38.4% vs 13.6%, p < 0.0001), chemotherapy dose reductions (21.2% vs 6.1%, p < 0.0001), and antibiotic use (26.7% vs 12.6%, p = 0.001). Same-day administration did not significantly increase the rate of hospitalization (15% vs 11.2%, p = 0.36) and delay of next chemotherapy cycle by ≥1 day (8.2% vs 6.1%, p = 0.57) due to neutropenic complications. Conclusions Administering pegfilgrastim on the same day as ddAC led to a significant increase in neutropenic complications. This study confirms the need to administer pegfilgrastim the day after chemotherapy in breast cancer patients receiving ddAC.
Management of simultaneous bilateral immune-mediated peripheral ulcerative keratitis
Authors: Kamra Dhruv , Chappadi Kiranmayi , Dudam Rajkiran , Murthy Somasheila I 
Published: December 2022

Purpose Peripheral ulcerative keratitis (PUK) is a sight threatening disease, often immune mediated and can rapidly progress to corneal perforation. Here we report the successful management of simultaneous bilateral peripheral ulcerative keratitis presenting with corneal perforation with surgical intervention and systemic immunosuppression. Case description A 41-year-old female presented with similarly located super-nasal peripheral ulcerative keratitis (PUK) in both eyes and focal area of adjoining scleritis in the left eye. Serological investigations for systemic immune-mediated conditions showed positive rheumatoid factor test. She underwent cyanoacrylate glue application in both eyes, and was started on topical and oral corticosteroids and oral immunomodulators, and the right eye stabilized. The left eye required a second surgical intervention with a corneal patch graft following which the condition stabilized. Conclusion and importance This case highlights the importance of investigating for an underlying systemic etiology in PUK and the role of systemic immunosuppression prior to and after surgical intervention in order to arrest the disease and prevent recurrences.
Mechanical thrombectomy in stroke patients of advanced age with score-based prediction of outcome
Authors: Laugesen Nicolaj Grønbæk , Brandt Andreas Hjelm , Stavngaard Trine , Højgaard Joan , Hansen Klaus , Truelsen Thomas 
Published: December 2022

Background Stroke patients ≥80 years constituted only 15% in randomised trials on mechanical thrombectomy (MT), but is a considerable higher proportion in clinical practice. Association of clinical variables collected before MT with functional outcome has not been independently described in these patients, while being important in the decision of patient eligibility for MT. Methods We included patients consecutively at a single centre (2017–2021) categorised as octogenarians (age: 80–89 years) or nonagenarians (age: 90–99 years). Functional outcome at 90 days was defined as fair (modified Rankin Scale (mRS) 0–3) or poor (mRS 4–6). Clinical variables collected before MT were analysed for association with shift of mRS in a poor direction. Significant predictors were used to produce a risk score of fair outcome. Significance was set at the p < 0.05 level. Results Nonagenarians (n = 43, 15.5%) compared to octogenarians (n = 235, 84.5%) less likely achieved fair outcome (20.9% vs. 46.0%, p < 0.01) with higher mortality (65.1% vs. 31.9%, p < 0.01). Significant predictors of outcome were: age, adjusted odds ratio (aOR) = 0.91 (95% confidence interval (CI): 0.86–0.97); pre-stroke mRS, aOR = 0.57 (95% CI: 0.44–0.73); National Institute of Health Stroke Scale at admission, aOR = 0.91 (95% CI: 0.87–0.95); Alberta Stroke Program Early Computed Tomography, aOR = 1.23 (95% CI: 1.05–1.45). After bootstrap validation, the area under the curve of the risk score was 0.74 and the optimal cut-off for fair outcome was a score of >7 points. Conclusions One in two octogenarians achieved fair outcome, however, only one in five nonagenarians had fair outcome. The clinical risk score could be considered as guidance when deciding patient eligibility for MT.
Endovascular thrombectomy for acute ischaemic stroke improves and maintains function in the very elderly: A multicentre propensity score matched analysis
Authors: Dunphy Harriette , Garcia-Esperon Carlos , Beom Hong Jae , Manoczki Csilla , Wilson Duncan , Lim Alvin Chew Beng , Beharry James , Bivard Andrew , Hasnain Md Golam , Krauss Martin , Collecutt Wayne , Miteff Ferdi , Spratt Neil , Parsons Mark W , Alan Barber Peter , Ranta Annemarei , Fink John N , Wu Teddy Y 
Published: December 2022

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors. Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (<80 years) using retrospective data from consecutive patients receiving EVT from four comprehensive stroke centres in New Zealand and Australia. We used propensity score matching or multivariable logistic regression to account for confounders. Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11–21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0–2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p < 0.01). There was no difference between the very elderly and the less-old in the proportion of patients who returned to baseline function at 90 days (56 (18.7%) vs 62 (20.7%), p = 0.54). All-cause 90-day mortality was higher in the very elderly (75 (25%) vs 49 (16.3%), p < 0.01), without a difference in symptomatic haemorrhage (very elderly 11 (3.7%) vs 6 (2.0%), p = 0.33). In the multivariable logistic regression models, the very elderly were significantly associated with reduced odds of good 90-day outcome (OR 0.49, 95% CI 0.34–0.69, p < 0.01) but not with return to baseline function (OR 0.85, 90% CI 0.54–1.29, p = 0.45) after adjusting for confounders. Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.
Prognostic role of different findings at echocardiography in acute pulmonary embolism: a critical review and meta-analysis
Authors: Cimini Ludovica Anna , Candeloro Matteo , Pływaczewska Magdalena , Maraziti Giorgio , Di Nisio Marcello , Pruszczyk Piotr , Agnelli Giancarlo , Becattini Cecilia 
Published: December 2022

BackgroundRight ventricle dysfunction (RVD) at echocardiography predicts mortality in patients with acute pulmonary embolism (PE), but heterogeneous definitions of RVD have been used. We performed a meta-analysis to assess the role of different definitions of RVD and of individual parameters of RVD as predictors of death.MethodsA systematic search for studies including patients with confirmed PE reporting on right ventricle (RV) assessment at echocardiography and death in the acute phase was performed. The primary study outcome was death in-hospital or at 30 days.ResultsRVD at echocardiography, regardless of its definition, was associated with increased risk of death (risk ratio 1.49, 95% CI 1.24–1.79, I2=64%) and PE-related death (risk ratio 3.77, 95% CI 1.61–8.80, I2=0%) in all-comers with PE, and with death in haemodynamically stable patients (risk ratio 1.52, 95% CI 1.15–2.00, I2=73%). The association with death was confirmed for RVD defined as the presence of at least one criterion or at least two criteria for RV overload. In all-comers with PE, increased RV/left ventricle (LV) ratio (risk ratio 1.61, 95% CI 1.90–2.39) and abnormal tricuspid annular plane systolic excursion (TAPSE) (risk ratio 2.29 CI 1.45–3.59) but not increased RV diameter were associated with death; in haemodynamically stable patients, neither RV/LV ratio (risk ratio 1.11, 95% CI 0.91–1.35) nor TAPSE (risk ratio 2.29, 95% CI 0.97–5.44) were significantly associated with death.ConclusionEchocardiography showing RVD is a useful tool for risk stratification in all-comers with acute PE and in haemodynamically stable patients. The prognostic value of individual parameters of RVD in haemodynamically stable patients remains controversial.
The value of walking: a systematic review on mobility and healthcare costs
Authors: Wohlrab Martin , Klenk Jochen , Delgado-Ortiz Laura , Chambers Michael , Rochester Lynn , Zuchowski Matthias , Schwab Matthias , Becker Clemens , Jaeger Simon U. 
Published: December 2022

Abstract
Background
The ability to walk is an important indicator of general health and mobility deficits have wide-ranging economic implications. We undertook a systematic review to elucidate the impact of walking parameters on health care costs.

Methods
Publications reporting on associations between health care costs and walking parameters were identified by a systematic literature search in MEDLINE, Embase, and manual reference screening, following the PRISMA reporting guidelines. First, titles and abstracts were screened by two independent reviewers followed by a review of the full articles if they met the inclusion criteria. Costs were converted to US-Dollars with inflation adjustment for 2021. A narrative synthesis was performed.

Results
Ten studies conducted between 2001 and 2021 fulfilled the inclusion criteria. Assessment of walking ability was carried out via patient reported outcomes, performance tests, or using wearable digital devices. Walking more than one hour per day, a faster walking speed and the ability to walk without impairments are associated with significant lower health care costs. A higher number of steps per day is associated with significant lower costs in two simulation studies, while in the study using a digital device, taking more than 10,000 steps per day is not significantly associated with lower direct costs. The heterogeneity of mobility assessments and of economic analyses both precluded a quantitative synthesis.

Conclusion
Cross-sectional and observational studies from this systematic review suggest a significant association of better walking performance with lower health care costs. Future health economic research and health technology assessments should use quantifiable mobility outcomes when evaluating new drugs or non-pharmacological interventions.