bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systeme zur automatisierten Insulinabgabe (AID-Systeme)
Authors: Thomas Andreas , Kolassa Ralf 
Published: April 2022

ZUSAMMENFASSUNGEs war ein langersehnter Traum von Patienten mit Typ-1-Diabetes, automatisierte Insulinabgabesysteme anwenden zu können, die ohne wesentliche Aktivitäten seitens der Anwender den Glukoseverlauf weitgehend im Glukosezielbereich regeln. Bedingt durch die Verfügbarkeit von CGM-Systemen, welche mit hinreichend hoher Genauigkeit und Sicherheit die Glukosekonzentration im Unterhautfettgewebe messen und diese dem Algorithmus einer Insulinpumpe übermitteln, konnten nach der ersten Zulassung der MiniMed 670G im Jahr 2016, besonders aber ab 2020, den Patienten zahlreiche AID-Systeme zur Verfügung gestellt werden. Nachfolgend werden diese Systeme kurz dargestellt und deren Merkmale erläutert. Es wird herausgestellt, dass es aktuell noch keine vollkommen automatisiert das Insulin abgebenden Systeme gibt, sondern Hybrid-Formen, bei denen die Patienten zumindest noch den Mahlzeitenbolus manuell abgeben müssen. Voll-AID-Systeme sind aber in der Entwicklung.
Cochlear Implantation of Auditory Neuropathy
Authors: Trautwein Patricia G. , Sininger Yvonne S. , Nelson Ralph 
Published: April 2022

AbstractAuditory neuropathy (AN) is a hearing disorder that presents with a grossly abnormal or absent neural response as measured by evoked potentials in the presence of normal outer hair cell function evidenced by present otoacoustic emissions or cochlear microphonics. Rehabilitation for patients with AN is challenging due to abnormal temporal encoding at the auditory nerve leading to severely impaired speech perception. Although patients with AN may demonstrate improvement in thresholds with amplification, temporal encoding dysfunction, and consequently speech perception degradation, is not alleviated by amplification. Another issue is the heterogeneity of the AN population in terms of audiologic and neurologic findings, in addition to uncertain etiology and pathophysiology. For children with prelingual onset of AN, development of auditory and oral communication skills is particularly compromised. All children with hearing loss in the severe-to-profound range who do not benefit from conventional amplification can be considered candidates for a cochlear implant (CI). This paper presents a case study of a child with AN who received a CI. Whereas no synchronous neural response auditory brainstem response could be elicited to acoustic stimuli, an electrically evoked auditory nerve action potential was evident following implantation, suggesting restoration to some degree of neural synchrony. Significant improvement in speech perception was found post-CI. Recommendation to implant all patients with AN would be premature, but these findings suggest that electrical stimulation in some cases of auditory neuropathy can be a viable option.
Abbreviations: AN = auditory neuropathy, CI = cochlear implant, CM = cochlear microphonic, DSL = desired sensation level, EAP = electrically evoked compound action potential, ESP = Early Speech Perception test, IHC = inner hair cells, LTASS = long-term average speech spectrum, NRT = neural response telemetry, OAE = otoacoustic emission, TAC = Test of Auditory Comprehension, TEOAE = transient evoked otoacoustic emission
Just Noticeable and Objectionable Group Delays in Digital Hearing Aids
Authors: Agnew Jeremy , Thornton Jeffrey M. 
Published: April 2022

AbstractGroup delay in a digital signal processing (DSP) hearing aid may be perceived as an echo in the sound heard by a wearer listening to his or her own voice, due to a combination of unprocessed sound received at the ear through head and air pathways and delayed sound reaching the eardrum through the hearing aid. Depending on the amount, this delay may be audible or objectionable and can even result in auditory confusion. This study presents results from 18 subjects listening to their own voices through a DSP hearing aid with a variable group delay. The subjects varied the length of the delay and determined the amounts that were noticeable and objectionable as compared to the undelayed condition, while listening to their own amplified voices. Results indicated that a delay of 3 to 5 msec was noticeable to the listeners in 76 percent of the trials, and a delay of longer than 10 msec was objectionable 90 percent of the time.
Abbreviations: DAF = delayed auditory feedback, DSP = digital signal processing, KEMAR = Knowles Electronics manikin for acoustic research
「粵語語法學習概覽」的建構
Authors: Tam Hugo Wing-Yu 
Published: April 2022

摘要
隨著亞洲經濟崛起和全球人口流動的持續增長，近年來粵語作為第二語言的教學開始受到重視。粵語學習者大多認為缺乏有系統的教材，使得要長期地學習粵語變得非常困難。本文的研究目的是建構出「粵語語法學習概覽」（Cantonese
Grammar
Profile），步驟如下：一、抽取現有教材中的語法點；二、參照語法工具書和參考書，對語法點進行分類；三、判斷現有教材中的語法點是否符合教學語法理論中對語法點的定義；四、討論是否有必要進一步把語法學習目標整併或刪除。本文除了提出了新的語法點判斷原則，也制訂出涵蓋歐洲共同語言參考架構中A1和A2級的語法點，共246項語法能力描述（grammatical
competence descriptor）。本文亦呼籲專家學者和香港政府盡快成立研發小組，針對香港和其他粵語區的多語多文環境，制訂粵語粵文能力標準體系，以期使課程規劃者、教材編者和考評人員有更全面的共同參照依據。
Fatigue related changes in rearfoot eversion: a means of functionally grouping runners?
Authors: Langley Ben 
Published: April 2022

ABSTRACTFatigue alters rearfoot kinematics on an individual basis and may offer a means of functionally grouping runners. This proof of concept study aimed to determine whether fatigue related changes in rearfoot eversion could be used to functionally group runners. Sixteen male recreational runners had their frontal plane rearfoot kinematics recorded by a three‐dimensional motion capture system before and after a 5km run. The magnitude of change in frontal plane rearfoot kinematics pre‐ to post‐fatigue was calculated and K‐means clustering used to identify functional groups based upon these changes. T‐tests with statistical parametric mapping were used to compare fatigue related changes both within and between clusters. Two clusters or functional groups were evident within the data set. Nine participants were allocated to cluster 1 and displayed small and insignificant changes in frontal plane rearfoot motion post‐fatigue. In contrast, the remaining seven participants were assigned to cluster 2 and displayed significant increases in rearfoot eversion between 3 and 84% of the stance phase post‐fatigue. These findings prove the concept that fatigue related changes in rearfoot eversion can be used to functionally group participants. Additionally, the differing fatigue related changes reported by each group may alter the injury risk, training and footwear needs of each group.

Highlights
Fatigue related changes in frontal plane rearfoot motion can be used to functionally group individuals.
Cluster 1 display small and insignificant fatigue related changes, which suggests they can maintain their habitual movement pathway.
Cluster 2 displayed significant increases in rearfoot eversion for the majority of the stance phase, suggesting an inability to maintain their habitual movement pathway, which may increase injury risk.
Image convolution-based experimental technique for flame front detection and dimension estimation: a case study on laminar-to-transition jet diffusion flame height measurement
Authors: De León-Ruiz J E , Carvajal-Mariscal I , De La Cruz-Ávila M , Klapp J , Guzmán J E V 
Published: April 2022

Abstract
A computationally-supported experimental technique is presented, to measure height of luminous flames, using convolution and density-based spatial clustering for image processing. The experimental setup employs a high-definition camera array to capture flame imagery from 0°, 45° and 90° visualization planes. The volumetric fuel flow was ranged from 350 to 1800 cc min−1 and images of the resulting flame structure were captured and measured. Results show that output measurements are affected by both the volumetric fuel flow and the visualization plane. Whilst the former is evidently the most significant factor, the latter was found to be relevant, since several flame features, particularly, flame tilt and flickering, are only perceivable through specific visualization planes; attributed to uneven flame structure due non-homogeneous thermal stress. The experimental technique proposed yields an overall statistical tolerance of 1.29 cm and an expanded uncertainty of 0.609 cm (∼11.5%). From these results, the test is considered successful and the proposed experimental technique is deemed to be on par with the already existing ones. The utilization of spatial density clustering of image gridded data has only been tested for this implementation; being severely constrained by the sample size and density variability of the data. Consequently, care should be exercised. Nonetheless, this approach was found to inherently recognize flame front edge, and mitigate variations of pixel value due change in flame intensity, normalizing image processing, hence, it is proposed as a viable alternative for flame feature/structure visualization and estimation, and further research is encouraged.
Genomic profile of radiation-induced early-onset mouse B-cell lymphoma recapitulates features of Philadelphia chromosome-like acute lymphoblastic leukemia in humans
Authors: Tachibana Hirotaka , Daino Kazuhiro , Ishikawa Atsuko , Morioka Takamitsu , Shang Yi , Ogawa Mari , Matsuura Akira , Shimada Yoshiya , Kakinuma Shizuko 
Published: April 2022

Abstract
Epidemiological studies have revealed a radiation-related increase in the risk of developing acute lymphoblastic leukemia (ALL). Our recent study revealed early induction and increased risk of precursor B-cell (pB) lymphomas in mice after radiation exposure. However, the genomic landscape of radiation-induced B-cell lymphomas remains unclear. To identify the relevant genetic alterations in mice, whole-exome sequencing was performed on both early-onset and late-onset B-cell lymphomas that developed spontaneously or after gamma-irradiation. In addition to multiple driver mutations, the data revealed that interstitial deletion of chromosome 4, including Pax5, and missense mutations in Jak3 are unique genomic alterations in radiation-induced, early-onset B-cell lymphomas. RNA sequencing revealed a pB-cell-type gene-expression profile with no involvement of known fusion genes for human ALLs in the early-onset B-cell lymphomas. Activation of Jak3/Stat5 signaling in early-onset B-cell lymphomas was validated using western capillary electrophoresis. Those features were similar to those of Philadelphia chromosome-like ALL. Our data suggest a critical role for Pax5 loss-of-function mutations in initiating B-cell leukemogenesis coupled with activation of Jak3/Stat5 signaling as a basis for the rapid development of radiation-induced pB-ALL. These molecular signatures for radiation-induced cancers will inform both risk assessment and potential targeted therapies for pB-ALL.
The impact of pausing the Oxford-AstraZeneca COVID-19 vaccine on uptake in Europe: a difference-in-differences analysis
Authors: Jain Vageesh , Lorgelly Paula 
Published: April 2022

Abstract

Background
Several countries paused their rollouts of the Oxford-AstraZeneca coronavirus disease-19 (COVID-19) vaccine in mid-March 2021 due to concerns about vaccine-induced thrombosis and thrombocytopenia. Many warned that this risked damaging public confidence during a critical period of pandemic response. This study investigated whether the pause in the use of the Oxford-AstraZeneca vaccine had an impact on subsequent vaccine uptake in European countries.

Methods
We used a difference-in-differences approach capitalizing on the fact that some countries halted their rollouts whilst others did not. A longitudinal panel was constructed for European Economic Area countries spanning 15 weeks in early 2021. Media reports were used to identify countries that paused the Oxford-AstraZeneca vaccine and the timing of this. Data on vaccine uptake were available through the European Centre for Disease Control and Prevention COVID-19 Vaccine Tracker. Difference-in-differences linear regression models controlled for key confounders that could influence vaccine uptake, and country and week fixed effects. Further models and robustness checks were performed.

Results
The panel included 28 countries, with 19 in the intervention group and 9 in the control group. Pausing the Oxford-AstraZeneca vaccine was associated with a 0.52% decrease in uptake for the first dose of a COVID-19 vaccine and a 1.49% decrease in the uptake for both doses, comparing countries that paused to those that did not. These estimates are not statistically significant (P = 0.86 and 0.39, respectively). For the Oxford-AstraZeneca vaccine only, the pause was associated with a 0.56% increase in uptake for the first dose and a 0.07% decrease in uptake for both doses. These estimates are also not statistically significant (P = 0.56 and 0.51, respectively). All our findings are robust to sensitivity analyses.

Conclusions
As new COVID-19 vaccines emerge, regulators should be cautious to deviate from usual protocols if further investigation on clinical or epidemiological grounds is warranted.
FRAND for Dominant Digital Platforms: Enhancing the Way Essential Inputs are Accessed, Transferred and Shared
Authors: Matos Tarcila , Torres-Sarmiento Carolina 
Published: April 2022

Abstract
Dominant digital platforms (DDPs) are dynamic and can control the market with the aid of features such as network externalities, economies of scale and scope and the accumulation of inputs including data and algorithms. In this competitive imbalance, new companies face a greater challenge to enter the market, which in turn reinforces concentration. Different policy proposals have been discussed to address these issues and to enhance access to as well as transfer and sharing of essential inputs between DDPs and other market players. One proposal has been to apply the fair, reasonable and non-discriminatory (FRAND) model, traditionally used in the information and communication technology (ICT) sector in the context of DDPs. Considering the evolving nature of digital markets and the peculiarities of DDPs, the paper analyses the role of FRAND in providing access to crucial data and other essential inputs among digital market players.
Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role forMCM10in replication timing regulation
Authors: Caballero Madison , Ge Tiffany , Rebelo Ana Rita , Seo Seungmae , Kim Sean , Brooks Kayla , Zuccaro Michael , Kanagaraj Radhakrishnan , Vershkov Dan , Kim Dongsung , Smogorzewska Agata , Smolka Marcus , Benvenisty Nissim , West Stephen C , Egli Dieter , Mace Emily M , Koren Amnon 
Published: April 2022

AbstractCellular proliferation depends on the accurate and timely replication of the genome. Several genetic diseases are caused by mutations in key DNA replication genes; however, it remains unclear whether these genes influence the normal program of DNA replication timing. Similarly, the factors that regulate DNA replication dynamics are poorly understood. To systematically identify trans-acting modulators of replication timing, we profiled replication in 184 cell lines from three cell types, encompassing 60 different gene knockouts or genetic diseases. Through a rigorous approach that considers the background variability of replication timing, we concluded that most samples displayed normal replication timing. However, mutations in two genes showed consistently abnormal replication timing. The first gene was RIF1, a known modulator of replication timing. The second was MCM10, a highly conserved member of the pre-replication complex. Cells from a single patient carrying MCM10 mutations demonstrated replication timing variability comprising 46% of the genome and at different locations than RIF1 knockouts. Replication timing alterations in the mutated MCM10 cells were predominantly comprised of replication delays and initiation site gains and losses. Taken together, this study demonstrates the remarkable robustness of the human replication timing program and reveals MCM10 as a novel candidate modulator of DNA replication timing.
Prevalence of and Factors Associated with Respiratory Symptoms Among Patients with Inflammatory Bowel Disease: A Prospective Study
Authors: Valentin Simon , Renel Brian , Manneville Florian , Caron Bénédicte , Choukour Myriam , Guillaumot Anne , Chaouat Ari , Poussel Mathias , Chateau Thomas , Peyrin-Biroulet Carina , Achit Hamza , Peyrin-Biroulet Laurent , Chabot François 
Published: April 2022

Abstract

Background
No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease.

Methods
In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease.

Results
There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn’s disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms.

Conclusions
Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations.
Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors
Authors: de Britto Evangelista Guilherme Ferreira , Figueiredo Amanda Braga , de Barros e Silva Milton José , Gollob Kenneth J 
Published: April 2022

Abstract
Immune checkpoint inhibitors (ICI) have provided new hope for cancer patients, and in particular for patients with tumors that are immunologically active and classified as hot tumors. These tumors express antigenic and tumor microenvironment (TME) characteristics that make them potential candidates for therapy with checkpoint inhibitors that aim to reactivate the immune response such as anti-PD-1 and anti-CTLA-4. Examples of potentially responsive cancers are, melanoma, non-small cell lung cancer and several other metastatic or unresectable tumors with genetic instability: DNA mismatch repair deficiency (dMMR), microsatellite instability-high (MSI-H), or with a high tumor mutational burden (TMB). Immunotherapy using checkpoint inhibitors is typically associated with adverse events (AEs) that are milder than those with chemotherapy. However, a significant percentage of patients develop short-term immune-related AEs (irAEs) which range from mild (~70%) to severe cases (~13%) that can lead to modifications of the checkpoint inhibitor therapy and in some cases, death. While some studies have investigated immune mechanisms behind the development of irAEs, much more research is needed to understand the mechanisms and to develop interventions that could attenuate severe irAEs, while maintaining the anti-tumor response intact. Moreover, studies to identify biomarkers that can predict the likelihood of a patient developing severe irAEs would be of great clinical importance. Here we discuss some of the clinical ramifications of irAEs, potential immune mechanisms behind their development and studies that have investigated potentially useful biomarkers of irAEs development.
Ultrastructural characteristics of finger-like membrane protrusions in cell competition
Authors: Kamasaki Tomoko , Uehara Ryota , Fujita Yasuyuki 
Published: April 2022

Abstract
A small number of oncogenic mutated cells sporadically arise within the epithelial monolayer. Newly emerging Ras- or Src-transformed epithelial cells are often apically eliminated during competitive interactions between normal and transformed cells. Our recent electron microscopy (EM) analyses revealed that characteristic finger-like membrane protrusions are formed at the interface between normal and RasV12-transformed cells via the cdc42–formin-binding protein 17 (FBP17) pathway, potentially playing a positive role in intercellular recognition during apical extrusion. However, the spatial distribution and ultrastructural characteristics of finger-like protrusions remain unknown. In this study, we performed both X–Y and X–Z EM analyses of finger-like protrusions during the apical extrusion of RasV12-transformed cells. Quantification of the distribution and widths of the protrusions showed comparable results between the X–Y and X–Z sections. Finger-like protrusions were observed throughout the cell boundary between normal and RasV12 cells, except for apicalmost tight junctions. In addition, a non-cell-autonomous reduction in protrusion widths was observed between RasV12 cells and surrounding normal cells under the mix culture condition. In the finger-like protrusions, intercellular adhesions via thin electron-dense plaques were observed, implying that immature and transient forms of desmosomes, adherens junctions or unknown weak adhesions were distributed. Interestingly, unlike RasV12-transformed cells, Src-transformed cells form fewer evident protrusions, and FBP17 in Src cells is dispensable for apical extrusion. Collectively, these results suggest that the dynamic reorganization of intercellular adhesions via finger-like protrusions may positively control cell competition between normal and RasV12-transformed cells. Furthermore, our data indicate a cell context–dependent diversity in the modes of apical extrusion.
The role of paleontological data in bryophyte systematics
Authors: Bippus Alexander C , Flores Jorge R , Hyvönen Jaakko , Tomescu Alexandru M F 
Published: April 2022

Abstract
Systematics reconstructs tempo and mode in biological evolution by resolving the phylogenetic fabric of biodiversity. The staggering duration and complexity of evolution, coupled with loss of information (extinction), render exhaustive reconstruction of the evolutionary history of life unattainable. Instead, we sample its products—phenotypes and genotypes—to generate phylogenetic hypotheses, which we sequentially reassess and update against new data. Current consensus in evolutionary biology emphasizes fossil integration in total-evidence analyses, requiring in-depth understanding of fossils—age, phenotypes, and systematic affinities—and a detailed morphological framework uniting fossil and extant taxa. Bryophytes present a special case: deep evolutionary history but sparse fossil record and phenotypic diversity encompassing small dimensional scales. We review how these peculiarities shape fossil inclusion in bryophyte systematics. Paucity of the bryophyte fossil record, driven primarily by phenotypic (small plant size) and ecological constraints (patchy substrate-hugging populations), and incomplete exploration, results in many morphologically isolated, taxonomically ambiguous fossil taxa. Nevertheless, instances of exquisite preservation and pioneering studies demonstrate the feasibility of including bryophyte fossils in evolutionary inference. Further progress will arise from developing extensive morphological matrices for bryophytes, continued exploration of the fossil record, re-evaluation of previously described fossils, and training specialists in identification and characterization of bryophyte fossils, and in bryophyte morphology.