bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensively dissecting the hub regulation of PkaC on high‐productivity and pellet macromorphology in citric acid producing Aspergillus niger
Authors: Zheng Xiaomei , Cairns Timothy C. , Ni Xiaomei , Zhang Lihui , Zhai Huanhuan , Meyer Vera , Zheng Ping , Sun Jibin 
Published: February 2022

SummaryAspergillus niger, an important industrial workhorse for citric acid production, is characterized by polar hyphal growth with complex pelleted, clumped or dispersed macromorphologies in submerged culture. Although organic acid titres are dramatically impacted by these growth types, studies that assess productivity and macromorphological changes are limited. Herein, we functionally analysed the role of the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) signalling cascade during fermentation by disrupting and conditionally expressing the pkaC gene. pkaC played multiple roles during hyphal, colony and conidiophore growth. By overexpressing pkaC, we could concomitantly modify hyphal growth at the pellet surface and improve citric acid titres up to 1.87‐fold. By quantitatively analysing hundreds of pellets during pilot fermentation experiments, we provide the first comprehensive correlation between A. niger pellet surface morphology and citric acid production. Finally, by intracellular metabolomics analysis and weighted gene coexpression network analysis (WGCNA) following titration of pkaC expression, we unveil the metabolomic and transcriptomic basis underpin hyperproductivity and pellet growth. Taken together, this study confirms pkaC as hub regulator linking submerged macromorphology and citric acid production and provides high‐priority genetic leads for future strain engineering programmes.
Strengthening Cybersecurity of Water Infrastructure through Legislative Actions
Authors: You Jongeun 
Published: February 2022

AbstractMany water and wastewater utilities are vulnerable to cyberattacks and cyber intrusions. The COVID‐19 pandemic has exacerbated this weakness by moving water‐related employees to remote work, which has increased vulnerability to cyber threats. However, policymakers recognize the need to strengthen the cybersecurity resilience of water infrastructure, as evidenced by legislative activity. This article reviews four cases of recently adopted cybersecurity legislation at the federal and state levels. The empirical focus is on (1) the America’s Water Infrastructure Act of 2018, (2) the Internet of Things Cybersecurity Improvement Act of 2020, (3) the New Jersey Water Quality Accountability Act, and (4) the New York Water Supply Emergency Plans. The legislative review recapitulates the core components of these legislative efforts to amplify strategies for securing and improving water infrastructure.
Streaming code across audiences and performers: An analysis of computer science communities of inquiry on Twitch.tv
Authors: Gandolfi Enrico , Ferdig Richard E. , Clements Robert 
Published: February 2022

AbstractLive streaming platforms like Twitch.tv count millions of viewers and performers, pointing to novel practices and interactions. Instructional applications of this phenomenon are rising with thematic channels and shows aimed at teaching and debating a variety of subjects ranging from art to programming. However, few research publications have specifically explored trends in pedagogical strategies and learning behaviours of viewing audiences. This study responded to this need by analysing computer science shows on Twitch.tv. A total of 40 hours of live streaming were analysed within a Community of Inquiry framework using the concepts of social affordances, computational thinking, and teaching style. Data collected from both expert and novice streamers included streamers' actions, on‐screen activity, and online discussions. Results pointed to specific tactics employed by both performers and viewers for exploring computer science issues and dynamics together, with instances of peer‐tutoring, construed learning, and significant transparency, even when top‐down instruction was staged.
Practitioners notesWhat is already known about this topic

Live streaming is a popular media practice all around the world, with Twitch.tv as the leading hosting platform.
A rising number of live streaming shows are focusing on education and learning topics, from STEM to art.
What this paper adds

A first exploration of instructional streaming focused on computer science education.
An analysis of best practices in instructional streaming in terms of community building, teaching style, and computational thinking processes.
A better understanding of how communities of inquiry can be hosted on Twitch.tv.
Implications for practice and/or policy

Practitioners can harness this study's results for informing better educational streaming.
Educators may refer to this article's highlights for selecting and evaluating educational streaming shows.
Policy makers will be able to use this article's insights for monitoring and re‐applying effective computer science activities in other educational environments.
Piloting the Circle of Security Parenting group with parents of children with a learning disability: An exploratory case study
Authors: Birdsey Nicola , McElwee Jennifer , Best Lara , Muddle Sarah , Vincent Regine 
Published: February 2022

AbstractBackgroundThe Circle of Security Parenting programme is a manualised parenting intervention that aims to enhance secure attachment and improve relationships between children and their caregivers. It is gaining global popularity and acquiring emerging support. Researchers are increasingly interested in its effectiveness in enhancing parent–child attachment, improving parent psychological flexibility and reducing parental stress. However, research to date has predominantly focused on parents of typically developing children, despite the Circle of Security Parenting intervention being used as a parenting programme in specialist services for children with learning disabilities. There is, however, no clear evidence that this programme meets the diverse needs of parents who encounter additional challenges that may impact on the development of secure parent–child attachment relationships. This case study aims to pilot a seven‐session Circle of Security Parenting programme for parents of children with learning disabilities.MethodsFour participants completed pre‐ and post‐intervention outcome measures specified by Circle of Security Parenting, including: the Parental Stress Scale, Parental Acceptance Questionnaire, Acceptance and Action Questionnaire II and the Caregiver Helplessness Questionnaire.FindingsQuantitative results are mixed, and did not demonstrate the improvements in parental stress or psychological flexibility that might be expected. Qualitative accounts of participants' experiences offer potential explanations for the findings that may be unique to parents of children with learning disabilities.ConclusionThis paper recognises that further research is needed to identify evidence‐based programmes that meet the needs of this population.
A new amplicon‐based gene panel for next generation sequencing characterization of meningiomas
Authors: Mawrin Christian , Koch Ralf , Waldt Natalie , Sandalcioglu I. Erol , Braunsdorf Werner E. K. , Warnke Jan‐Peter , Goehre Felix , Meisel Hans‐Jürgen , Ewald Christian , Neyazi Sina , Schüller Ulrich , Kirches Elmar 
Published: February 2022

AbstractMeningiomas are the most frequent primary intracranial tumors. The considerable variety of histological subtypes has been expanded by the definition of molecular alterations, which can improve both diagnostic accuracy and determination of individual patient's outcome. According to the upcoming WHO classification of brain tumors, the in‐time analysis of frequent molecular events in meningiomas may become mandatory to define meningioma subtypes. We have compiled a custom‐made amplicon‐based next generation sequencing (NGS) meningioma panel covering the most frequent known recurrent mutations in 15 different genes. In an unselected consecutive meningioma cohort (109 patients) analyzed over a period of 12 months, we detected mutations in 11 different genes, with most frequent alterations in NF2 (43%), AKT1E17K (15%), and TRAF7 (13%). In 39 tumors (36%), two different mutations were detected, with NF2 and SUFU (n = 5) and KLF4 and TRAF7 (n = 5) being the most frequent combinations. No alterations were found in POLR2A, CDKN2A, CDKN2B, and BAP1, and no homozygous CDKN2A/B deletion was detected. NF2 mutations were found in tumors of all WHO grades, whereas mutations in KLF4, TRAF7, and SMO were restricted to WHO grade I meningiomas. In contrast, SMARCE1 and TERT mutations were associated with WHO grade II meningiomas (according to the WHO classification 2016). The distribution of mutations across histological subtypes or tumor localization was in line with the existing literature, with typical combinations like KLF4K409Q/TRAF7 for secretory meningiomas and preferential skull base localization of meningiomas harboring SMO and AKT1E17K mutations. Thus, we present a custom‐made NGS meningioma panel providing a time and cost‐efficient reliable detection of relevant somatic molecular alterations in meningiomas suitable for daily routine.
Molecular neuropathology of brain‐invasive meningiomas
Authors: von Spreckelsen Niklas , Kesseler Christoph , Brokinkel Benjamin , Goldbrunner Roland , Perry Arie , Mawrin Christian 
Published: February 2022

AbstractInvasion of brain tissue by meningiomas has been identified as one key factor for meningioma recurrence. The identification of meningioma tumor tissue surrounded by brain tissue in neurosurgical samples has been touted as a criterion for atypical meningioma (CNS WHO grade 2), but is only rarely seen in the absence of other high‐grade features, with brain‐invasive otherwise benign (BIOB) meningiomas remaining controversial. While post‐surgery irradiation therapy might be initiated in brain‐invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarize preclinical models studying targeted therapies with potential inhibitory effects.
Tattoo-like dermatitis left after fire-needle therapy
Authors: Han Ning , Wang Yu , Xu Jia , Lu Hongguang 
Published: February 2022

AbstractTraditional Chinese medical theory holds that fire acupuncture can relieve neuropathic pain, and in many Asian countries, acupuncture has been used as one of the methods to relieve herpes zoster nerve pain. Sometimes, the patterns left on the skin by the needles may be very confusing to the practitioner who sees the patient. Recently, we saw a patient with puzzling tattoo-like dermatitis on his skin, and upon further questioning, he had recently undergone a fire-needle treatment and was left with this pattern.
Forecasting the influence of conservation strategies on landscape connectivity
Authors: Mozelewski Tina G. , Robbins Zachary J. , Scheller Robert M. 
Published: February 2022

AbstractMaintaining and enhancing landscape connectivity reduces biodiversity declines due to habitat fragmentation. Uncertainty remains, however, about the effectiveness of conservation for enhancing connectivity for multiple species on dynamic landscapes, especially over long time horizons. We forecasted landscape connectivity from 2020 to 2100 under four common conservation land‐acquisition strategies: acquiring the lowest cost land, acquiring land clustered around already established conservation areas, acquiring land with high geodiversity characteristics, and acquiring land opportunistically. We used graph theoretic metrics to quantify landscape connectivity across these four strategies, evaluating connectivity for four ecologically relevant species guilds that represent endpoints along a spectrum of vagility and habitat specificity: long‐ versus short‐distance dispersal ability and habitat specialists versus generalists. We applied our method to central North Carolina and incorporated landscape dynamics, including forest growth, succession, disturbance, and management. Landscape connectivity improved for specialist species under all conservation strategies employed, although increases were highly variable across strategies. For generalist species, connectivity improvements were negligible. Overall, clustering the development of new protected areas around land already designated for conservation yielded the largest improvements in connectivity; increases were several orders of magnitude beyond current landscape connectivity for long‐ and short‐distance dispersing specialist species. Conserving the lowest cost land contributed the least to connectivity. Our approach provides insight into the connectivity contributions of a suite of conservation alternatives prior to on‐the‐ground implementation and, therefore, can inform connectivity planning to maximize conservation benefit.
Impact of disease‐modifying therapies on humoral and cellular immune‐responses following SARS‐CoV‐2 vaccination in MS patients
Authors: Trümpelmann Susan , Schulte‐Mecklenbeck Andreas , Steinberg Olga V. , Wirth Timo , Fobker Manfred , Lohmann Lisa , Lünemann Jan D. , Wiendl Heinz , Gross Catharina C. , Klotz Luisa 
Published: February 2022

AbstractThe impact of distinct disease‐modifying therapies (DMTs) on severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccination efficacy in patients with multiple sclerosis (MS) is still enigmatic. In this prospective comparative study, we investigated humoral and cellular immune‐responses in patients with MS receiving interferon beta, natalizumab, and ocrelizumab pre‐vaccination and 6 weeks post second SARS‐CoV‐2 vaccination. Healthy individuals and interferon beta‐treated patients generated robust humoral and cellular immune‐responses. Although humoral immune responses were diminished in ocrelizumab‐treated patients, cellular immune‐responses were reduced in natalizumab‐treated patients. Thus, both humoral and cellular immune responses should be closely monitored in patients on DMTs. Whereas patients with a poor cellular immune‐response may benefit from additional vaccination cycles, patients with a diminished humoral immune‐response may benefit from a treatment with SARS‐CoV‐2 antibodies in case of an infection.
Preventing all‐cause hospitalizations in type 2 diabetes with sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: A narrative review and proposed clinical approach
Authors: Schechter Meir , Fischer Matan , Mosenzon Ofri 
Published: February 2022

AbstractPatients with type 2 diabetes (T2D) are at increased risk for hospital admissions, and acute hospitalizations are associated with a worse prognosis. However, outcomes related to all‐cause hospital admissions (ACHAs) were often overlooked in trials that demonstrated the cardiovascular and kidney benefits of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs). This review includes a contemporary literature summary of emerging data regarding the effects of SGLT2 inhibitors and GLP‐1RAs on ACHAs. The role of SGLT2 inhibitors in preventing ACHAs was shown in exploratory investigations of several randomized controlled trials (RCTs) and was further supported by real‐world evidence (RWE). However, the association between GLP‐1RA use and lower ACHA risk was mainly shown through RWE, with minimal available RCT data. We also discuss the advantages and challenges of studying ACHAs. Finally, we propose an easily memorized (“ABCDE” acronym) clinical approach to evaluating T2D status and treatment in admitted patients, as they transition from hospital to community care. This systematic approach may assist clinicians in recognizing possible pitfalls in T2D management, thereby preventing subsequent hospitalizations and improving patient prognoses. While acute admission can sometimes be perceived as a management failure, it should also be viewed as an opportunity to take action to prevent the next hospitalization.
Researcher effects in survey‐based research: Insights from research in South Sudan
Authors: Tomiak Kerstin 
Published: February 2022

SummaryMotivationIn policy‐relevant and applied research in international development, the evidence‐based turn has led to increasing donor demand for evidence that is neutral, objective, and value‐free. Rather than this positivist understanding, the article argues for reflexivity and acknowledgement of positionality to help overcome potential researcher effects.PurposeDrawing on the example of survey research in South Sudan, the article argues that social relations between the researcher, surveyors, and participants shape the research process and hence knowledge creation. It examines why survey research conducted under similar circumstances led to distinctive data sets.Methods and approachThe argument is based on comparing survey data gathered by two groups of locally hired surveyors in South Sudan and subsequent semi‐structured interviews with them.FindingsThe data show that the researcher's positionality, broadly conceived, influenced data collection. The way the locally hired surveyors perceived the lead researcher and the economically challenging environment of South Sudan—a country severely embroiled in violent conflict—affected the data that were gathered with a social survey, and consequently affected knowledge production.Policy implicationsThe article contributes to the literature that argues that researcher effects also occur in quantitative research. It shows that in policy‐relevant research reflexivity is necessary to strengthen research results. Researchers working in conflict‐affected, impoverished environments, and donors requesting evaluation and measurement, should be encouraged to take positionality into account and to ask questions about research practices.
Plasma neurofilament light chain as a biomarker for fatal familial insomnia
Authors: Hermann Peter , Canaslan Sezgi , Villar‐Piqué Anna , Bunck Timothy , Goebel Stefan , Llorens Franc , Schmitz Matthias , Zerr Inga 
Published: February 2022

AbstractBackground and purposeFatal familial insomnia is a rare hereditary prion disease associated with the D178N‐129M PRNP mutation. Early diagnosis is difficult, because the clinical syndrome may overlap with affective disorders. In addition, most known cerebrospinal fluid biomarkers for prion diseases and magnetic resonance imaging do not show a good diagnostic accuracy for fatal familial insomnia. In this context, data on plasma biomarkers are scarce.MethodsWe analyzed levels of neurofilament light chain, glial fibrillary acidic protein, chitinase‐3‐like protein 1, calcium‐binding protein B, and total tau protein in six serial plasma samples from a patient with fatal familial insomnia. Subsequently, plasma neurofilament light chain was analyzed in n = 25 patients and n = 19 controls. The diagnostic accuracy and associations with disease stage and duration were explored.ResultsAmong all biomarker candidates in the case study, only neurofilament light chain levels showed a constant evolution and increased over time. They discriminated fatal familial insomnia from controls with an area under the curve of 0.992 (95% confidence interval [CI] = 0.974–1) in the case–control study. Higher concentrations were associated with methionine homozygosity at codon 129 PRNP (p = 0.006), shorter total disease duration (rho = −0.467, p = 0.019, 95% CI = −0.790 to −0.015), and shorter time from sampling to death (rho = −0.467, p = 0.019, 95% CI = −0.773 to −0.019).ConclusionsPlasma neurofilament light chain may be a valuable minimally invasive diagnostic biomarker for fatal familial insomnia after clinical onset. Most important, stage‐related increase and association with disease duration indicate potential as a prognostic marker and as a surrogate marker in clinical trials.
Infantile spasms: Assessing the diagnostic yield of an institutional guideline and the impact of etiology on long‐term treatment response
Authors: Chourasia Nitish , Yuskaitis Christopher J. , Libenson Mark H. , Bergin Ann M. , Liu Shanshan , Zhang Bo , Poduri Annapurna , Harini Chellamani 
Published: February 2022

AbstractObjectiveNeuroimaging and genetic testing have been proposed for diagnostic evaluation of infantile spasms (IS), establishing etiology in ~60% of multicenter IS cohorts. A retrospective analysis of the yield of diagnostic etiology following an institutionally established guideline for investigation/treatment of IS was conducted, and the association between etiological subgroups and sustained response to standard treatment was evaluated.MethodsEtiology of IS, neuroimaging, and genetic results were extracted from clinical records. Etiology was categorized as acquired or nonacquired, the latter including syndromic patients, nonsyndromic patients with confirmed etiology, and unknown cases. Regression analyses, using clinical variables including subtypes of etiology, were conducted to determine which factors correlated with favorable (spasm freedom at last follow‐up after two or fewer standard treatments) versus unfavorable treatment outcome (refractory spasms despite two standard treatments or relapse).ResultsWe included 127 IS patients (60% males) with a follow‐up of 2.4 years (range = .6–5 years). All patients had neuroimaging, and 95% of patients in the nonacquired category (103 of 108 patients) had genetic testing. Etiology was identified in 103 of 127 (81%, 95% confidence interval = .73–.86). At last follow‐up, 42 (33%) patients had favorable treatment outcome. No difference in treatment response was observed between acquired and nonacquired etiologies. Among patients with nonacquired etiologies, developmental delay prior to spasms onset increased the odds of unfavorable treatment outcome (p = .014), whereas a clearly recognizable dysmorphic/syndromic etiology was associated with a lower risk for treatment failure (p = .034). In nonacquired etiology without a recognizable dysmorphic/syndrome but with a genetic etiology, unfavorable treatment outcome was more likely (p = .043).SignificanceRigorous evaluation with neuroimaging and genetic testing yields an etiological diagnosis in most patients with IS. Among patients with a nonacquired etiology, those with recognizable dysmorphic/syndromic diagnosis had a higher likelihood of a favorable treatment outcome, whereas the absence of such a finding, when associated with an identifiable genetic diagnosis, was associated with unfavorable treatment outcomes.
Neurovascular unit dysfunction as a mechanism of seizures and epilepsy during aging
Authors: van Vliet Erwin A. , Marchi Nicola 
Published: February 2022

AbstractThe term neurovascular unit (NVU) describes the structural and functional liaison between specialized brain endothelium, glial and mural cells, and neurons. Within the NVU, the blood‐brain barrier (BBB) is the microvascular structure regulating neuronal physiology and immune cross‐talk, and its properties adapt to brain aging. Here, we analyze a research framework where NVU dysfunction, caused by acute insults or disease progression in the aging brain, represents a converging mechanism underlying late‐onset seizures or epilepsy and neurological or neurodegenerative sequelae. Furthermore, seizure activity may accelerate brain aging by sustaining regional NVU dysfunction, and a cerebrovascular pathology may link seizures to comorbidities. Next, we focus on NVU diagnostic approaches that could be tailored to seizure conditions in the elderly. We also examine the impending disease‐modifying strategies based on the restoration of the NVU and, more in general, the homeostatic control of anti‐ and pro‐inflammatory players. We conclude with an outlook on current pre‐clinical knowledge gaps and clinical challenges pertinent to seizure onset and conditions in an aging population.