bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges and opportunities in research funding for neurovascular diseases from a clinical researcher's perspective
Authors: Ospel Johanna Maria , McDonough Rosalie , Ganesh Aravind , Sehgal Arshia , Kappelhof Manon , Kashani Nima , Klijn Catharina JM , Hill Michael , Saver Jeffrey , Goyal Mayank 
Published: March 2022

Background & Purpose Neurovascular research is underfunded, imposing substantial challenges on clinical researchers in the field of neurovascular diseases. We explored what physicians perceive to be the greatest challenges with regard to neurovascular research funding, and how they think the funding crisis in neurovascular research could be overcome. Methods We performed an international, multi-disciplinary survey among physicians involved in the medical care of patients with neurovascular diseases. After providing their demographic data, physicians were asked closed-ended questions on their personal opinion regarding challenges in neurovascular research funding, and how these challenges could be overcome. Physicians also described in their own words what they perceived to be the biggest challenges in obtaining funding. Data were analyzed using descriptive statistics and response clustering. Results Of 233 participating physicians (70.4% male,82.8% senior staff) from 48 countries, 217(97.4%) perceived the discrepancy between required and available funding to be a problem;172(73.8%) considered it a major problem. High competitiveness (61/118 available free text responses[51.7%]), time-consuming application processes (28/118[23.7%]) and administrative requirements (25/118[21.1%]) were identified as key obstacles. Traditional big funding agencies were perceived to be most capable of closing the neurovascular research funding gap, followed by specialty-specific organizations and industry, while philanthropy and crowdfunding were perceived to be less important. Conclusion The gap between required and available funding was perceived to be a major problem in neurovascular research, with high competitiveness, time-consuming funding processes and excessive administrative requirements being the key obstacles to obtaining funding. Traditional funding agencies were perceived to be most capable of closing this funding gap.
Pressor therapy in acute ischaemic stroke: an updated systematic review
Authors: Strømsnes Torbjørn Austveg , Kaugerud Hagen Truls Jørgen , Ouyang Menglu , Wang Xia , Chen Chen , Rygg Silje-Emilie , Hewson David , Lenthall Rob , McConachie Norman , Izzath Wazim , Bath Philip M , Dhillon Permesh Singh , Podlasek Anna , England Timothy , Sprigg Nikola , Robinson Thompson G , Advani Rajiv , Ihle-Hansen Hege , Sandset Else Charlotte , Krishnan Kailash 
Published: March 2022

Background Low blood pressure (BP) in acute ischaemic stroke (AIS) is associated with poor functional outcome, death, or severe disability. Increasing BP might benefit patients with post-stroke hypotension including those with potentially salvageable ischaemic penumbra. This updated systematic review considers the present evidence regarding the use of vasopressors in AIS. Methods We searched the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and trial databases using a structured search strategy. We examined reference lists of relevant publications for additional studies examining BP elevation in AIS. Results We included 27 studies involving 1886 patients. Nine studies assessed increasing BP during acute reperfusion therapy (intravenous thrombolysis, mechanical thrombectomy, intra-arterial thrombolysis or combined). Eighteen studies tested BP elevation alone. Phenylephrine was the most commonly used agent to increase BP (n = 16 studies), followed by norepinephrine (n = 6), epinephrine (n = 3) and dopamine (n = 2). Because of small patient numbers and study heterogeneity, a meta-analysis was not possible. Overall, BP elevation was feasible in patients with fluctuating or worsening neurological symptoms, large vessel occlusion with labile BP, sustained post-stroke hypotension and ineligible for intravenous thrombolysis or after acute reperfusion therapy. The effects on functional outcomes were largely unknown and close monitoring is advised if such intervention is undertaken. Conclusion Although theoretical arguments support increasing BP to improve cerebral blood flow and sustain the ischaemic penumbra in selected AIS patients, the data are limited and results largely inconclusive. Large, randomised controlled trials are needed to identify the optimal BP target, agent, duration of treatment and effects on clinical outcomes.
Prediction of outcomes after second-line treatment for acute graft-versus-host disease
Authors: Vo Phuong , Gooley Ted A. , Carpenter Paul A. , Sorror Mohamed L. , MacMillan Margaret L. , DeFor Todd E. , Martin Paul J. 
Published: March 2022

Abstract
Acute graft-versus-host disease (GVHD) requiring second-line treatment represents a highly morbid complication of allogenic hematopoietic cell transplantation (HCT). Recent studies have defined short-term outcomes after second-line treatment for acute GVHD, but longer-term outcomes have not been well defined. We examined overall survival (OS) and failure-free-survival (FFS) of 216 patient who had HCT who received second-line treatment for acute GVHD. Failure time for FFS was defined as the earliest of death, relapse, or implementation of third-line treatment. Multivariable Cox regression was used to identify risk factors for mortality and failure, and predictive models were derived for 6- and 12-month mortality. Point estimates of OS at 6 and 12 months were 59% (95% confidence interval [CI], 52-65) and 52% (95% CI, 45-68), respectively. Point estimates of FFS at 6 and 12 months were 42% (95% CI, 35-48) and 37% (95% CI, 31-43), respectively. Predictive models for both end points included serum albumin and total bilirubin concentrations at the onset of second-line treatment, patient age at onset of second-line therapy, and a combination of abdominal pain/stage 4 gut involvement. Optimism-corrected areas under the receiver-operator characteristic curve and Brier scores were 77.4 and 0.169 for 6-month mortality, respectively, and 80.0 and 0.169 for 12-month mortality. We identify risk factors associated with mortality and failure after second-line treatment of acute GVHD, provide historical benchmarks for assessment of FFS and OS in other studies, and propose predictive models for 6- and 12-month mortality that could be used to generate population-specific benchmarks.
Molecular hydrogen is a potential protective agent in the management of acute lung injury
Authors: Zhang Yan , Zhang Jin , Fu Zhiling 
Published: March 2022

AbstractAcute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.
Characterization of mercerized cellulose nanofibrils prepared by aqueous counter collision process
Authors: Tatsumi Daisuke , Kanda Atsushi , Kondo Tetsuo 
Published: March 2022

AbstractCellulose nanofibrils (CNFs) obtained by aqueous counter collision (ACC) methods have amphiphilic Janus-type properties, which appear markedly for ACC–CNFs prepared from bacterial nanocellulose (BNC) pellicles. The amphiphilic Janus-type surface is exposed because of the mechanism involved in ACC pulverizing of cellulose materials, in which the predominant interactions of the (2 0 0) lattice plane of the cellulose I crystal structure are weak interplanar van der Waals interactions. Such selective cleavage is more likely to occur for highly crystalline BNC. This study focused on alkali-mercerized cellulose samples, which are of lower crystallinity than BNC. The mercerized raw materials were subjected to ACC treatments and their fiber morphologies, crystallinities, and surface properties were compared to those of ACC–CNFs from native samples. In particular, the Wide-angle X-ray diffraction (WAXD) results suggested that the cleavage was most likely to occur at the (1 1 0) plane in nanofibrils derived from cellulose II, unlike (2 0 0) lattice plane for the case of cellulose I. Accordingly, the entire results indicate that the properties of the ACC-treated mercerized CNFs differ greatly from those of conventional ACC–CNFs composed of cellulose I crystalline structure. This is presumably because ACC nanopulverization proceeds depending on the surface structure and crystalline morphology of the raw material.
Senescence-associated reprogramming induced by interleukin-1 impairs response to EGFR neutralization
Authors: Romaniello Donatella , Gelfo Valerio , Pagano Federica , Ferlizza Enea , Sgarzi Michela , Mazzeschi Martina , Morselli Alessandra , Miano Carmen , D’Uva Gabriele , Lauriola Mattia 
Published: March 2022

Abstract
Background
EGFR targeting is currently the main treatment strategy for metastatic colorectal cancer (mCRC). Results of different clinical trials show that patients with wild-type KRAS and BRAF benefit from anti-EGFR monoclonal antibodies (moAbs) cetuximab (CTX) or panitumumab. Unfortunately, despite initial response, patients soon became refractory. Tumor heterogeneity and multiple escaping routes have been addressed as the main culprit, and, behind genomic alterations already described, changes in signaling pathways induced by drug pressure are emerging as mechanisms of acquired resistance. We previously reported an association between reduced sensitivity to CTX and increased expression of IL-1. However, how IL-1 mediates CTX resistance in mCRC is still unclear.

Methods
Under CTX treatment, the upregulation of IL-1R1 expression and a senescence program in sensitive colorectal cancer (CRC) cell lines is examined over time using qPCR, immunoblotting, and immunofluorescence.

Results
In sensitive CRC cells, IL-1 appeared responsible for a CTX-mediated G0 phase arrest. On the contrary, CTX-resistant CRC cells (CXR) maintained high mRNA levels of IL-1R1 and a post-senescence reprogramming, as indicated by increased SNAIL expression. Interestingly, treatment of CXR cells with a recombinant decoy, able to sequester the soluble form of IL-1, pushed CTX-resistant CRC cells back into a stage of senescence, thus blocking their proliferation. Our model suggests a trans-regulatory mechanism mediated by IL-1 on EGFR signaling. By establishing senescence and regulating EGFR activity and expression, IL-1 exposure ultimately bestows resistance.

Conclusions
To sum up, our findings point to the combined blockage of IL-1R and EGFR as a promising therapeutical approach to restore sensitivity to EGFR-targeting monoclonal antibodies.
Extending the theory of planned behavior to predict and nudge toward the subscription to a public transport ticket
Authors: Hauslbauer Andrea Lucia , Schade Jens , Drexler Corinna Emmely , Petzoldt Tibor 
Published: March 2022

AbstractIntroductionTo reduce pollution from motorized private cars, a modal shift toward more sustainable modes, such as public transport, is desired. A first step to achieving this is the subscription to a public transport ticket. It was investigated if an extended version of thetheory of planned behavioris suited to predict subscription to a public transport ticket, and ifenvironmental concern—the channel through which many sustainable transport modes are advertised—plays a significant role. It was further examined if nudging serves as an effective measure in convincing employees to subscribe to the offered ticket.Nudgesencourage desired behaviors by changing the information set that individuals face when taking decisions; in this paper, this includes favorabledefaultsand the manipulation of thesocial norm. Since nudges lack a coherent theory, it was tested if these nudges can be integrated into the aforementioned theory.MethodBy means of an online experiment, participants (N = 373) were randomly assigned to different nudging conditions or a control condition. The questionnaire mimicked a working contract, including the decision for or against a subscription to the ticket.ResultsResults of structural equation modeling revealed that the theory predicted the purchase decision well, yet the impact ofenvironmental concernwas surprisingly low. Most tickets were purchased in the default condition, but no nudge reached statistical significance.Discussion and ConclusionThe limitations of nudging in the transport sector are discussed, along with the effectiveness of advertising public transport through an environmental lens.
TADreg: a versatile regression framework for TAD identification, differential analysis and rearranged 3D genome prediction
Authors: Mourad Raphaël 
Published: March 2022

Abstract
Background/Aim
In higher eukaryotes, the three-dimensional (3D) organization of the genome is intimately related to numerous key biological functions including gene expression, DNA repair and DNA replication regulations. Alteration of 3D organization, in particular topologically associating domains (TADs), is detrimental to the organism and can give rise to a broad range of diseases such as cancers.

Methods
Here, we propose a versatile regression framework which not only identifies TADs in a fast and accurate manner, but also detects differential TAD borders across conditions for which few methods exist, and predicts 3D genome reorganization after chromosomal rearrangement. Moreover, the framework is biologically meaningful, has an intuitive interpretation and is easy to visualize.

Result and conclusion
The novel regression ranks among top TAD callers. Moreover, it identifies new features of the genome we called TAD facilitators, and that are enriched with specific transcription factors. It also unveils the importance of cell-type specific transcription factors in establishing novel TAD borders during neuronal differentiation. Lastly, it compares favorably with the state-of-the-art method for predicting rearranged 3D genome.
Patterns of sex-biased dispersal are consistent with social and ecological constraints in a group-living cichlid fish
Authors: Bose Aneesh P. H. , Koch Lukas , Dabernig-Heinz Johanna , Grimm Jacqueline , Sefc Kristina M. , Jordan Alex 
Published: March 2022

AbstractBackgroundSex-biased dispersal is a common and widespread phenomenon that can fundamentally shape the genetic structure of the social environments in which animals live. For animals that live in and move between social groups, sex-biased dispersal can result in an asymmetry in the degree of relatedness among cohabiting males and females, which can have strong implications for their social evolution. In this study, we measured the relatedness structure within and across groups of a wild population ofNeolamprologus multifasciatus, a highly-social, shell-dwelling cichlid fish endemic to Lake Tanganyika, East Africa. In total, we genotyped 812 fish from 128 social groups at 20 microsatellite loci.Neolamprologus multifasciatuslive at high densities, and also experience strong ecological constraints on free movement throughout their habitat. At the same time, they exhibit sex differences in the degree of reproductive competition within their groups and this makes them an excellent model system for studying the factors associated with sex-biased dispersal.ResultsSocial groups ofN. multifasciatusconsist of multiple males and females living together. We found that cohabiting females were unrelated to one another (Lynch-Ritland estimates of relatedness = 0.045 ± 0.15, average ± SD), while males shared much higher, albeit variable, levels of relatedness to other males in their groups (0.23 ± 0.27). We uncovered a pronounced decline in relatedness between males living in separate groups as the spatial separation between them increased, a pattern that was not evident in females. Female dispersal was also markedly constrained by the distribution and availability of nearby territories to which they could emigrate.ConclusionsOur results indicate female-biased dispersal inN. multifasciatus.Our study also highlights how the spatial distribution of suitable dispersal destinations can influence the movement decisions of animals. We also emphasize how sex-biased dispersal can influence the relatedness structure of the social environment in which individuals interact and compete with one another.
Proteome and Transcriptome Analysis of Gonads Reveals Intersex in Gigantidas haimaensis
Authors: Shi Yu , Yao Gaoyou , Zhang Hua , Jia Huixia , Xiong Panpan , He Maoxian 
Published: March 2022

AbstractSex has proven to be one of the most intriguing areas of research across evolution, development, and ecology. Intersex or sex change occurs frequently in molluscs. The deep-sea mussel Gigantidas haimaensis often dominates within Haima cold seep ecosystems, but details of their reproduction remain unknown. Herein, we conducted a combined proteomic and transcriptomic analysis of G. haimaensis gonads to provide a systematic understanding of sexual development in deep-sea bivalves. A total of 2,452 out of 42,238 genes (5.81%) and 288 out of 7,089 proteins (4.06%) were significantly differentially expressed between ovaries and testes with a false discovery rate (FDR) <0.05. Candidate genes involved in sexual development were identified; among 12 differentially expressed genes between sexes, four ovary-biased genes (β-catenin, fem-1, forkhead box L2 and membrane progestin receptor α) were expressed significantly higher in males than females. Combining histological characteristics, we speculate that the males maybe intersex undergoing sex change, and implied that these genes may be involved in the process of male testis converting into female gonads in G. haimaensis. The results suggest that this adaptation may be based on local environmental factors, sedentary lifestyles, and patchy distribution, and sex change may facilitate adaptation to a changing environment and expansion of the population. The findings provide a valuable genetic resource to better understand the mechanisms of sex change and survival strategies in deep-sea bivalves.
Impact of the COVID-19 pandemic on infectious disease hospitalizations of neonates at a tertiary academic hospital: a cross-sectional study
Authors: Pan Jiarong , Zhan Canyang , Yuan Tianming , Sun Yi , Wang Weiyan , Chen Lihua 
Published: March 2022

Abstract
Background
To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on hospitalizations for neonatal infectious diseases.

Methods
We analyzed data for neonatal inpatients admitted at a tertiary academic hospital with a principal diagnosis of an infectious disease during January 2015 to December 2020. We compared hospitalizations in 2020 (COVID-19 cohort), corresponding with the impact of COVID-19 pandemic and associated containment measures, and the comparable 2015 to 2019 (pre-COVID-19 cohort).

Results
14,468 cases admitted for neonatal infectious diseases were included in our study, with 1201 cases in the COVID-19 cohort and 13,267 cases in the pre-COVID-19 cohort. The leading causes of hospitalizations for neonatal infectious diseases remain being respiratory tract infections (median ratio = 0.461, 95% CI 0.335–0.551), sepsis (median ratio = 0.292, 95% CI 0.263–0.361), gastric intestinal infections (median ratio = 0.095, 95% CI 0.078–0.118) and dermatologic infections (median ratio = 0.058, 95% CI 0.047–0.083). The seasonality of neonatal infectious disease hospitalizations could be obviously observed, with the total number and the overall rate of hospitalizations for neonatal infectious diseases in the first and fourth quarters greater than that of hospitalizations for neonatal infectious diseases in the second and third quarters in each year (1362.67 ± 360.54 vs 1048.67 ± 279.23, P = 0.001; 8176/20020 vs 6292/19369, P < 0.001, respectively). Both the numbers and the proportions of hospitalizations for neonatal infectious diseases in different quarters of the COVID-19 cohort significantly decreased as compared with those forecasted with the data from the pre-COVID-19 cohort: the numbers per quarter (300.25 ± 57.33 vs 546.64 ± 100.43, P-value = 0.006), the first quarter (0.34 vs 0.40, P = 0.002), the second quarter (0.24 vs 0.30, P = 0.001), the third quarter (0.24 vs 0.28, P = 0.024), and the fourth quarter (0.29 vs 0.35, P = 0.003).

Conclusions
Despite the outbreak of the COVID-19 pandemic, the leading causes of hospitalizations for neonatal infectious diseases remain unchanged. The seasonality of neonatal infectious disease hospitalizations could be obviously observed. The numbers as well as the overall rates of hospitalizations for neonatal infectious diseases in the COVID-19 cohort dramatically declined with the impact of the COVID-19 pandemic and its mitigation measures.
Identifying postnatal anxiety: comparison of self-identified and self-reported anxiety using the Edinburgh Postnatal Depression Scale
Authors: Fellmeth Gracia , Harrison Siân , McNeill Jenny , Lynn Fiona , Redshaw Maggie , Alderdice Fiona 
Published: March 2022

Abstract
Background
Identifying women with perinatal anxiety is important in order to provide timely support and prevent adverse outcomes. Self-report instruments are commonly used in maternity settings. An alternative is to ask women directly whether they self-identify as having anxiety. We examine the agreement between self-reported and self-identified anxiety at 3 months postpartum and compare the characteristics of women with self-reported and self-identified anxiety.

Methods
A secondary analysis of national maternity surveys conducted in 2014 in England and Northern Ireland was conducted. Self-reported anxiety was assessed using the Edinburgh Postnatal Depression Scale anxiety subscale (EPDS-3A). Agreement between self-reported and self-identified anxiety was measured using Cohen’s kappa. Logistic regression was used to identify characteristics of women in each group.

Results
In our sample of 6752 women, 14.2% had self-reported anxiety, 5.9% had self-identified anxiety and 3.5% were positive on both measures. Among those with self-identified anxiety, 58.1% also had self-reported anxiety. Of those with self-reported anxiety, 24.4% also had self-identified anxiety. Statistical agreement between the two measures was minimal with Cohen’s kappa 0.283 at an EPDS-3A threshold of ≥6. Among both self-identified and self-reported anxiety groups, psychological factors were the strongest associated factors. Women with self-reported anxiety had higher odds of being from Northern Ireland (OR 1.81); having a mixed or unhappy reaction to the pregnancy (OR 1.65); living without a partner (aOR 1.37); and antenatal depression (aOR 1.32). Women with self-identified anxiety had higher odds of physical problems (OR 1.84); and being of Black or minority ethnicity (OR 0.39).

Conclusions
Asking postnatal women directly whether they self-identify as having anxiety identifies a different group of women from those who score highly on self-report measures. Women with self-identified anxiety may benefit from further follow-up and support.