bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint inference about the AUC and Youden index for paired biomarkers
Authors: Yin Jingjing , Samawi Hani , Tian Lili
Published: October 2021

It is common to compare biomarkers' diagnostic or prognostic performance using some summary ROC measures such as the area under the ROC curve (AUC) or the Youden index. We propose to compare two paired biomarkers using both the AUC and the Youden index since the two indices describe different aspects of the ROC curve. This comparison can be made by estimating the joint confidence region (an elliptical area) of the differences of the paired AUCs and the Youden indices. Furthermore, for deciding if one marker is better than the other in terms of both the and the Youden index (J), we can test or against and using the paired differences. The construction of such a joint hypothesis is an example of the multivariate order‐restricted hypotheses. For such a hypothesis, we propose and compare three testing procedures: (1) the intersection‐union test (); (2) the conditional test; and (3) the joint test. The performance of the proposed inference methods was evaluated and compared through simulations. The simulation results demonstrate that the proposed joint confidence region maintains the desired confidence level, and all three tests maintain the type I error under the null. Furthermore, among the three proposed testing methods, the conditional test is the preferred approach with markedly larger power consistently than the other two competing methods.
Investigations on train‐induced vibration and vibration control of an over‐track building using thick‐layer rubber bearings
Authors: Zhou Ying , Ma Kaiqiang , Chen Peng , Lu Decheng , Wu Hao
Published: October 2021

A large number of over‐track buildings have been designed in metropolis during the recent decades for adapting to rapid urbanization and saving land resources. However, the over‐track buildings are potentially affected by train‐induced vibration that may cause discomfort or health problem for residents, which in turn needs to be carefully evaluated. In this study, the responses of a high‐rise over‐track building with three different transfer types have been investigated using the recorded three‐dimensional accelerations from in‐situ tests. By performing time history analyses, the vibration responses of the fixed structure, traditional rubber bearing (TrRB) isolated, and thick‐layer rubber bearing (ThRB) isolated structures are analyzed and evaluated, respectively. The results show that the most evident vibration is in the vertical direction with vibration energy mainly concentrated among the high frequencies. Thereafter, the effects of vibration control by using different isolation technologies are compared. It is demonstrated that the abilities to isolate vertical train‐induced vibration could be enhanced by using ThRB while the horizontal isolation performance is still guaranteed. Then the reason for the variation of vibration amplitude along the building height is discussed. This research enriches the train‐induced vibration database and exemplifies the vibration mitigation control and design for over‐track buildings.
„Risk it“ – warum Frauen ohne Schwangerschaftsabsicht nicht verhüten
Authors: Helfferich Cornelia , Holz Janet-Lynn , Knittel Tilmann , Olejniczak Laura , Schmidt Franziska
Published: October 2021

Hintergrund

Trotz allgemein bekannten Verhütungsmethoden und flächendeckendem Zugang zu Verhütungsmitteln lässt sich beobachten, dass Frauen in westlichen Industriegesellschaften auch bei fehlender Schwangerschaftsabsicht oftmals nicht verhüten und schwanger werden.

Ziel der Arbeit

Die in diesem Beitrag durchgeführten Analysen zielen darauf ab, die Verbreitung des Phänomens der Nichtanwendung von Verhütung für Deutschland einzuschätzen und ein besseres Verständnis für die Gründe zu gewinnen, warum Frauen eine unbeabsichtigte Schwangerschaft riskieren.

Material und Methoden

Anhand von quantitativen Befragungsdaten zu 17.400 Schwangerschaften und von 116 offenen qualitativen Interviews aus der im Auftrag der Bundeszentrale für gesundheitliche Aufklärung (BZgA) durchgeführten Studie „frauen leben 3. Familienplanung im Lebenslauf von Frauen“ sind Aussagen zur Verbreitung der Nichtverwendung von Verhütungsmethoden trotz fehlender Schwangerschaftsabsicht und zu den dahinterliegenden Gründen möglich.

Ergebnisse

Die angegebenen Gründe für die Nichtverwendung von Verhütung lassen sich 3 sehr unterschiedlichen Motivlagen zuordnen: a) Spielen mit einem Kinderwunsch, was von knapp einem Drittel genannt wird, b) individuelle und strukturelle Hürden, wie z. B. gesundheitliche Vorbehalte oder zu hohe Kosten, und c) irrtümliche Annahme, nicht schwanger werden zu können. Es zeigt sich, dass diese Motive je nach biografischer Situation unterschiedlich verbreitet sind.

Diskussion

Die Ergebnisse weisen auf die Notwendigkeit eines differenzierteren Verständnisses unbeabsichtigter Schwangerschaften und zwar sowohl in der Forschung als auch der Prävention hin.

Als Limitation und damit als Bedarf für künftige Forschungen erweist sich, dass im Rahmen der Studie der Einfluss des (Sexual‑)Partners auf das Verhütungsverhalten der Frauen und auf die Gewolltheit der Schwangerschaft anhand der erhobenen Daten nicht untersucht werden kann.
Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case–control study
Authors: Ichimura Takenori , Hinata Miwa , Ichikura Daisuke , Suzuki Shinya
Published: October 2021

Purpose

The immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia—idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis.

Methods

Eleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects.

Results

The odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03–0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease.

Conclusion

The administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.
Interactive Virtual Reality versus Vignette-Based Assessment of Children’s Aggressive Social Information Processing
Authors: Verhoef Rogier E. J. , Verhulp Esmée E. , van Dijk Anouk , de Castro Bram O.
Published: October 2021

This study examined whether interactive Virtual Reality (VR) provides a more ecologically valid assessment of children’s aggressive social information processing (SIP) and aggressive responses than a standard vignette-based assessment. We developed a virtual classroom where children could meet and play games with virtual peers. Participants were boys (N = 184; ages 7–13) from regular education and special education for children with disruptive behavior problems. They reported on their SIP in four scenarios (i.e., two instrumental gain and two provocation scenarios) presented through both interactive VR and vignettes. Teachers reported on children’s real-life aggressive behavior and reactive and proactive motives for aggression. Results demonstrated that children found the interactive VR assessment more emotionally engaging and immersive than the vignette-based assessment. Moreover, compared to vignettes, the interactive VR assessment evoked higher levels of aggressive SIP and responses in provocation scenarios only. Results supported the enhanced predictive validity of the interactive VR assessment of children’s aggressive SIP and responses, which predicted children’s real-life aggression above and beyond the vignette-based assessment with 2 to 12% additional explained variance. Similar results were found for children’s real-life reactive and proactive motives for aggression, with 3 to 12% additional variance explained by interactive VR above and beyond vignettes. Interactive VR did not, however, evoke larger individual differences (i.e., variances) in children’s aggressive SIP and responses than vignettes. Together, these findings suggest that interactive VR provides a more ecologically valid method to assess children’s aggressive SIP and responses than hypothetical vignettes.
Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study
Authors: Huang Yen-Chu , Lee Jiann-Der , Pan Yi-Ting , Weng Hsu-Huei , Yang Jen-Tsung , Lin Leng-Chieh , Tsai Yuan-Hsiung
Published: October 2021

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.
Is Income Inequality Influenced by Financial Knowledge? A Macroeconomic and Longitudinal Analysis
Authors: Oliver-Márquez Francisco J. , Guarnido-Rueda Almudena , Amate-Fortes Ignacio , Martínez-Navarro Diego
Published: October 2021

Our objective is to analyze whether financial knowledge influences income inequality. For this purpose, we resort to a new index of financial knowledge that differs from the existing ones in that it is both longitudinal and macroeconomic. We use this index as one of the explanatory variables of the Net Gini Index in our panel data estimations. Based on a sample of 63 countries over the period 2008–2014, our results allow us to conclude that financial knowledge is related to income inequality and that, moreover, this relationship is non-linear. Thus, increases in financial knowledge could reduce income inequality when starting from relatively low levels of such knowledge. However, at a certain threshold, the income redistributive effect of financial knowledge could disappear or even reverse. Even so, national strategies for financial education could be useful to achieve economic equity in those countries where financial knowledge levels are low. In addition, we shed light on the effect that other variables (such as institutional quality or under-education) have on income inequality.
The Confidence Density for Correlation
Authors: Taraldsen Gunnar
Published: October 2021

Inference for correlation is central in statistics. From a Bayesian viewpoint, the final most complete outcome of inference for the correlation is the posterior distribution. An explicit formula for the posterior density for the correlation for the binormal is derived. This posterior is an optimal confidence distribution and corresponds to a standard objective prior. It coincides with the fiducial introduced by R.A. Fisher in 1930 in his first paper on fiducial inference. C.R. Rao derived an explicit elegant formula for this fiducial density, but the new formula using hypergeometric functions is better suited for numerical calculations. Several examples on real data are presented for illustration. A brief review of the connections between confidence distributions and Bayesian and fiducial inference is given in an Appendix.
On the existence of four or more curved foldings with common creases and crease patterns
Authors: Honda A. , Naokawa K. , Saji K. , Umehara M. , Yamada K.
Published: October 2021

Consider an oriented curve $$\Gamma $$
Γ
in a domain D in the plane $${\varvec{R}}^2$$

R

2

. Thinking of D as a piece of paper, one can make a curved folding in the Euclidean space $${\varvec{R}}^3$$

R

3

. This can be expressed as the image of an “origami map” $$\Phi :D\rightarrow {\varvec{R}}^3$$

Φ
:
D
→

R

3

such that $$\Gamma $$
Γ
is the singular set of $$\Phi $$
Φ
, the word “origami” coming from the Japanese term for paper folding. We call the singular set image $$C:=\Phi (\Gamma )$$

C
:
=
Φ
(
Γ
)

the crease of $$\Phi $$
Φ
and the singular set $$\Gamma $$
Γ
the crease pattern of $$\Phi $$
Φ
. We are interested in the number of origami maps whose creases and crease patterns are C and $$\Gamma $$
Γ
, respectively. Two such possibilities have been known. In the authors’ previous work, two other new possibilities and an explicit example with four such non-congruent distinct curved foldings were established. In this paper, we determine the possible values for the number N of congruence classes of curved foldings with the same crease and crease pattern. As a consequence, if C is a non-closed simple arc, then $$N=4$$

N
=
4

if and only if both $$\Gamma $$
Γ
and C do not admit any symmetries. On the other hand, when C is a closed curve, there are infinitely many distinct possibilities for curved foldings with the same crease and crease pattern, in general.
Barriers to cross-disciplinary knowledge flow: The case of medical education research
Authors: Albert Mathieu , Rowland Paula , Friesen Farah , Laberge Suzanne
Published: October 2021

Introduction The medical education research field operates at the crossroads of two distinct academic worlds: higher education and medicine. As such, this field provides a unique opportunity to explore new forms of cross-disciplinary knowledge exchange. Methods Cross-disciplinary knowledge flow in medical education research was examined by looking at citation patterns in the five journals with the highest impact factor in 2017. To grasp the specificities of the knowledge flow in medical education, the field of higher education was used as a comparator. In total, 2031 citations from 64 medical education and 41 higher education articles published in 2017 were examined. Results Medical education researchers draw on a narrower range of knowledge communities than their peers in higher education. Medical education researchers predominantly cite articles published in health and medical education journals (80% of all citations), and to a lesser extent, articles published in education and social science journals. In higher education, while the largest share of the cited literature is internal to the domain (36%), researchers cite literature from across the social science spectrum. Findings suggest that higher education scholars engage in conversations with academics from a broader range of communities and perspectives than their medical education colleagues. Discussion Using Pierre Bourdieu’s concepts of doxa and field, it is argued that the variety of epistemic cultures entering the higher education research space contributes to its interdisciplinary nature. Conversely, the existence of a relatively homogeneous epistemic culture in medicine potentially impedes cross-disciplinary knowledge exchange.
Introduction of the Modified Neuroanatomy Motivation Questionnaire and Its Role in Comparing Medical Student Attitudes Towards Learning Neuroanatomy Between Neuro-enthusiasts and Standard Students
Authors: Hall Samuel , Kurn Octavia , Anbu Deepika , Nagy Eva , Dean Oliver , Robson Alistair , Taylor Charles , Elmansouri Ahmad , Geoghegan Kate , Payne December , Myers Matthew , Stephens Jonny , Merzougui Wassim , Border Scott
Published: October 2021

Background

Neurophobia has been identified as a potential barrier to adequate knowledge of neurology in the medical community, and therefore to patient safety. There is a drive to identify the source of neurophobia, in the hope of tackling it. Comparing the learning motivations of standard medical students with those who enjoy neuroanatomy may be a way of doing this.

Methods

The science motivation questionnaire (SMQ) was modified for neuroanatomy. It was distributed to three cohorts of second year medical students and students attending the extracurricular National Undergraduate Neuroanatomy Competition (NUNC). Cohen’s D test for effect size was used to compare standard medical students and those attending the NUNC.

Results

Five hundred ninety-seven questionnaires were completed by second year students, and 320 by NUNC attendees. The differences in motivation to learn neuroanatomy between the 2 groups mainly fell into themes of career motivation, personal relevance, intrinsic motivation and assessment anxiety.

Conclusion

This study has demonstrated the use of the SMQ in neuroanatomy, and found differences in motivators to learn neuroanatomy between self-selecting “neurophiles” and standard medical students, mainly relating to intrinsic motivation and its role in their lives. More research is needed to further explore these differences and how they might apply to interventions in medical school curricula.
Augmented-Reality-basierte Assistenz für das Anlernen manueller und roboterunterstützter Montageprozesse
Authors: Hegenberg Jens , Schmidt Ludger
Published: October 2021

Durch eine zunehmend flexibilisierte Produktion und relativ hohe Personalfluktuation bei einfachen Tätigkeiten wird das Anlernen neuer Mitarbeitender bzw. für neue oder geänderte Produktionsprozesse zunehmend relevanter. Konventionelle Anlernmethoden, bspw. durch Demonstration oder Arbeitspläne, haben Schwächen (bspw. binden sie zusätzliche Arbeitskraft oder sind kognitiv anspruchsvoll), die durch ein Augmented-Reality-(AR-)basiertes Assistenzsystem kompensiert werden können. Ein AR-Assistenzsystem zum Anlernen eines tatsächlichen industriellen Montageprozesses wurde in einer vergleichenden Studie mit 16 Versuchspersonen gegenüber einer konventionellen Papieranleitung evaluiert. Bzgl. Gebrauchstauglichkeit und Beanspruchung deuten sich die Stärken des AR-Ansatzes an. In den Subskalen Anstrengung und Frustration zeigt sich eine statistisch signifikante Reduktion der Beanspruchung. Bezüglich der Montagezeiten konnten statistisch signifikante Vorteile erzielt werden. Ergänzend wurde in einer zweiten Studie eine Videoanleitung mit der AR-Anleitung verglichen.

Praktische Relevanz: Die Digitalisierung der Produktion erlaubt nach Kundenwunsch individualisierte Produkte, die mit einer flexibilisierten Produktion einhergehen. Einfache Montageprozesse ändern sich daher häufiger vollständig oder in Teilen. Außerdem wechseln Mitarbeitende aufgrund der monotonen und repetitiven Tätigkeiten häufiger. All das führt zu einem Bedarf an regelmäßigen Anlernprozessen. Ein AR-Assistenzsystem erscheint als aussichtsreicher Ansatz, wobei die Gebrauchstauglichkeit besonders im Fokus stehen sollte, da wenig technische Kenntnisse vorausgesetzt werden können.
Zinc oxide-induced changes to sunscreen ingredient efficacy and toxicity under UV irradiation
Authors: Ginzburg Aurora L. , Blackburn Richard S. , Santillan Claudia , Truong Lisa , Tanguay Robyn L. , Hutchison James E.
Published: October 2021

Sunscreen safety and efficacy is generally evaluated based upon the properties of the individual chemicals in a formulation. However, the photostability of sunscreens has been shown to be highly dependent on the mixture of chemicals present. To better understand how sunscreen formulation influences stability, and to establish a foundation for probing the influence of zinc oxide additives, we formulated five different small-molecule based ultraviolet-filter (UV-filter) mixtures with a Sun Protection Factor (SPF) of 15. These mixtures contained active ingredients approved in either the United States or European Union and were designed to represent formulations of actual products on the market. We evaluated the photostability and toxicity of these mixtures in the absence and presence of zinc oxide after UV exposure for two hours. Changes in UV absorbance were minimal for all five small-molecule-based mixtures without zinc oxide. The presence of either micro- or nano-sized zinc oxide caused significant small-molecule photodegradation and the degraded mixtures exhibited higher levels of toxicity in embryonic zebrafish assays. This study suggests that caution must be taken when formulating sunscreens containing both zinc oxide and small-molecule UV-filters to avoid unintended consequences during use.

Graphic abstract
Semi-global leader-following output consensus of heterogeneous systems subject to actuator position and rate saturation
Authors: Zhou Panpan , Chen Ben M.
Published: October 2021

We study in this paper a semi-global leader-following output consensus problem for multiple heterogeneous linear systems in the presence of actuator position and rate saturation over a directed topology. For each follower, via the low gain feedback design technique and output regulation theory, both a state feedback consensus protocol and an output feedback consensus protocol are constructed. In the output feedback case, different distributed observers are designed for the informed followers and uninformed followers to estimate the state of the leader and the follower itself. We show that the semi-global leader-following output consensus of heterogeneous linear systems can be achieved by the two consensus protocols if each follower is reachable from the leader in the directed communication topology.
Factors Impacting Postoperative Opioid Use Among Patients Undergoing Implantation of Inflatable Penile Prosthesis
Authors: Ehlers Mark E. , Mohan Charan S. , Akerman Jason P. , McGowan Micah , McCormick Benjamin J. , Hacker Kathryn E. , Coward R. Matthew , Figler Bradley D.
Published: October 2021

Background

While there is an increasing burden of chronic postoperative opioid use and opioid abuse in the United States, opioid use following inflatable penile prosthesis (IPP) surgery has not been well described.

Aim

Describe postoperative opioid use following IPP surgery.

Methods

Seventy-four consecutive patients undergoing IPP implantation by a single surgeon were enrolled. Self-reported diaries tracked the type and amount of medication taken for 2 weeks following IPP surgery. High opioid consumers were defined as those consuming more than the median amount (10 mg) of opioids during the first 2 weeks postoperatively. Multivariate analyses were performed using stepwise backward elimination.

Outcomes

Quantification of opioid use postoperatively and factors related to high opioid use.

RESULTS

Fifty-six patients were included after 7 were excluded for preoperative opioid use and 11 were excluded for inability to contact. Median age was 67.5. Devices used were Boston Scientific (41, 73%) and Coloplast (15, 27%). All patients received local anesthetic. Most surgeries (44, 79%) were performed as outpatient. Preoperative analgesia with acetaminophen, celecoxib, and pregabalin was administered in 44 (78%), 44 (78%), and 28 (50%) of cases respectively; 32 (57%) of patients received 2 medications, 21 (36%) received three medications. In hospital median morphine equivalents was 7.5 (interquartile range [IQR] 0–7.5). Oxycodone prescribed at discharge was 50 mg (29, 52%), 75 mg (4; 7%), and 100 mg (23; 41%). Median milligrams of oxycodone used was 10 mg (IQR 0–23.5) at 7 days and 10 (IQR 0–37.5) at 14 days postdischarge. On univariate analysis, factors associated with an increased likelihood of high opioid use were morphine equivalents utilized in hospital (odds ratio [OR] 1.13, P < .05) and milligrams oxycodone prescribed at discharge (OR 1.05, P < .001) while patient demographics, procedure characteristics, and analgesic types were not found to be predictive of high opioid use. On multivariate analysis, milligrams oxycodone prescribed at discharge (OR 1.04, P < .005) were associated with an increased likelihood of high opioid use after discharge.

Clinical Implications

Increased understanding of opioid use after IPP surgery may improve prescribing patterns after discharge.

Strengths & Limitations

This study quantified post discharge opioid use over the first 14 postoperative days. It is limited by single surgeon, small sample size, and retrospective design.

CONCLUSION

Provider opioid prescribing patterns were associated with high opioid consumption postoperatively and a substantial amount of opioids prescribed at discharge remain unused by patients, suggesting that we can reduce or replace the amount of opioids that are prescribed.
Information Certainty Influences the Attitudes of Students and Teachers Towards COVID-19
Authors: de la Vega Ricardo , Ruíz Barquín Roberto , Boros Szilvia , Szabo Attila
Published: October 2021

The COVID-19 pandemic struck Spain severely from the beginning. Prevention via information that fosters knowledge, reasonable concern, control, and personal care is the most effective means to slow down the pandemic. In this intervention field study, first, we assessed actual knowledge, concern, control, and care about the COVID-19 in 111 Spanish university teachers and students. Subsequently, we randomly assigned them to two groups. One group (n = 53) received uncertain information about prevention measures, whereas the other group (n = 58) received certain information. Analysis of covariance, using baseline measures as covariates, revealed that the group receiving the certain information reported an immediately increased perceived control and personal care about the pandemic. These findings suggest that measures that are known to be effective in COVID-19 prevention, if communicated with certainty (i.e., solid evidence), could influence people's attitudes, possibly through the schematic organisation of new information.
Between Hoffmann and Goethe: The Young Brahms as Reader
Authors: PHILLIPS REUBEN
Published: October 2021

This article provides a critical account of Brahms’s early collection of quotations, aphorisms and poems commonly known asDes jungen Kreislers Schatzkästleinin the context of the composer’s youthful engagement with German literature. Drawing on archival materials housed in Vienna, it evaluates the 1909 publication of theSchatzkästleinby the Deutsche Brahms-Gesellschaft and traces Brahms’s path in assembling his quotations to reveal borrowings from sources he encountered in the Schumann house in Düsseldorf in 1854. The second section of the article considers the different modes of reading implied by Brahms’s collection, while the third reflects on the artistic worldview articulated by the assembled entries. While scholars have viewed theSchatzkästleinlargely as evidence of Brahms’s adolescent infatuation with the writings of the German Romantics, this investigation emphasizes the competing conceptions of artistry present in these fascinatingly messy notebooks and argues that this youthful collection points to the important role played by literature in the development of Brahms’s distinctive musical sensibility.
Does the introduction of a formal neutropenic sepsis protocol improve therapeutic radiographer confidence and competence at recognising sepsis within the radiotherapy department?
Authors: Clayton Adam , Griffiths Siân , Gilbert Philippa
Published: October 2021

Aim:

The aim of this service review was to review whether implementing a formal training package increased therapeutic radiographer confidence and competence in recognising neutropenic sepsis in radiotherapy patients. In addition, authors also investigated whether the introduction of a weekly National Early Warning Score (NEWS) protocol had been successful in identifying cases of neutropenic sepsis.

Material and Methods:

Therapeutic radiographer (n = 13) views on the new protocol were collected through an online questionnaire. A review of the clinical observation sheets of patients who received chemo-radiotherapy (n = 49) between 18 April 2019 and 31 October 2019 was undertaken. Information on disease site, NEWS scores, number of patients who had become neutropenic and action taken by therapeutic radiographers was collected.

Results:

The majority of respondents to the questionnaire found that training benefitted both professionals and patients. Some challenges were highlighted relating to increased workload. For patients receiving regular observations, NEWS scores ranged from 0 to 4. When a patient scored on NEWS, the most common score was 1 across all treatment sites except cervix.

Findings:

Implementing a neutropenic sepsis protocol appears to be beneficial to therapeutic radiographers as professionals, increasing their confidence in patient assessment and monitoring. Regular observations may help to identify deteriorating patients alongside clinical judgement and symptom reviews.
Anisotropic Pn Tomography of Alaska and Adjacent Regions
Authors: He Yuhui , Lü Yan
Published: October 2021

We use Pn tomography with coordinate rotation to image in Alaska and adjacent areas and obtain a new Pn velocity and anisotropy model. The observed Pn velocities correlate well with the local geological structures. Low Pn velocities are observed beneath the Aleutian volcanic arc, which may reveal partial melting related to plate dehydration. However, it is separated by a distinct high‐velocity anomaly, suggesting a slab tear. The slightly low Pn velocities beneath the Denali volcanic gap suggest that a small amount of magma is produced but is insufficient to form surface volcanoes. We observe sharp bending of the fast directions on the two sides of the northeast edge of the Yakutat Plate, which reveals the plate’s bending. Large‐scale low velocities are observed beneath the northwestern Cordillera, which may be due to the upwelling of hot material from the deep mantle. The Pn fast directions are parallel to the Queen Charlotte‐Fairweather fault system, consistent with the shear strain direction of the faults, reflecting that the influence of the plate boundary is far‐reaching and that the deformation of the crust and the upper mantle is coupled. Our study provides new constraints on the complex deformation beneath Alaska and adjacent areas.
The Impact of Family Bereavement Interventions: Qualitative Feedback Identifies Needs
Authors: Henning Ellen , Germann Julie N. , Holder Nicholas , Nakonezny Paul , Loftin Sara , Redondo-Doan Bridget , Jones Lisa , Petty Laurie Ames , Pratt Chelsea , Garza-Saenz Monica , Isaacs Thomas , Liu Kevin , Winick Naomi
Published: October 2021

Objective: To present a synthesis of program improvement evaluations of two approaches to bereavement support for families: (a) weekend family camps providing developmentally targeted grief education and social support for children and parents, and (b) a wait-list control randomized trial of a parent bereavement group intervention. Method: Families eligible for camp experienced a child’s death (from any cause) and have surviving children at home. No-cost twice-yearly weekend camps include support sessions and family activities like fishing. After each retreat, parents and children complete an anonymous evaluation. We analyzed forms from 2009–2014 using the constant comparative method to devise a code structure and identify themes to understand camp impact. The second intervention, the bereavement group, included English and Spanish speaking parents of children who died from cancer. They were initially randomized to intervention and wait-list control groups. Intervention included six-weekly sessions of a bereavement program. Participants were invited to a postintervention focus group to better understand reasons for participation, the value of the group, and their support needs. Results: Qualitative findings from both groups strongly indicate that bereaved parents have specific ongoing needs that can be addressed through family- or parent-focused interventions. Families identified benefits including being able to openly express feelings with peers who truly understand, gaining an understanding of individual and developmental differences in the grief process, improved mood and coping, and enhanced relationships/communication within their families. Conclusions: Bereaved parents, in a subclinical range for mental health concerns, identified the need for ongoing support and benefited from organized peer-support.

Implications for Impact Statement

After the death of a child, even parents who are functioning well have a profound need for ongoing peer support. Regardless of the length of time since the death, discussions with other parents whose child has died gives them a sense of normality, eases suffering, and enhances their interactions with surviving children/family members regardless. Pediatric health institutions have a responsibility to provide a continuum of care to families, including bereavement care.
GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells
Authors: Liu Yujuan , Wang Jiyin , Yang Ruixiang , Cheng Yuning , Zhou Yue , Li Hui , Jiang Wei , Zhang Xiaowei
Published: October 2021

Golgi protein 73 (GP73) and alpha fetoprotein (AFP) serve as biomarkers for the diagnosis of hepatocellular carcinoma (HCC), and their serum levels correlate with patients’ outcomes. However, the mechanisms underlying these correlations are unknown. Here we show that GP73 increased the secretion of AFP through direct binding to AFP, thereby promoting the proliferation and metastasis of HCC cells that expressed AFP and its receptor (AFPR). Extracellular GP73 contributed to the proliferation and metastasis of HCC cells independent of AFP and AFPR. Moreover, extracellular AFP and GP73 synergized to enhance the malignant phenotype of HCC cells. Furthermore, extracellular GP73 and AFP inhibited the antitumor effects of sorafenib and synergistically increased the drug resistance of HCC cells. These findings, which reveal the mechanism of GP73-mediated secretion of AFP and its effects on the malignant phenotype of HCC cells, provide a comprehensive theoretical basis for the diagnosis and treatment of HCC and identify potential drug targets.
Neuroinflammation in schizophrenia: the role of nuclear factor kappa B
Authors: Murphy Caitlin E. , Walker Adam K. , Weickert Cynthia Shannon
Published: October 2021

Neuroinflammation, particularly in the dorsolateral prefrontal cortex, is well-established in a subset of people with schizophrenia, with significant increases in inflammatory markers including several cytokines. Yet the cause(s) of cortical inflammation in schizophrenia remains unknown. Clues as to potential microenvironmental triggers and/or intracellular deficits in immunoregulation may be gleaned from looking further upstream of effector immune molecules to transcription factors that control inflammatory gene expression. Here, we focus on the ‘master immune regulator’ nuclear factor kappa B (NF-κB) and review evidence in support of NF-κB dysregulation causing or contributing to neuroinflammation in patients. We discuss the utility of ‘immune biotyping’ as a tool to analyse immune-related transcripts and proteins in patient tissue, and the insights into cortical NF-κB in schizophrenia revealed by immune biotyping compared to studies treating patients as a single, homogenous group. Though the ubiquitous nature of NF-κB presents several hurdles for drug development, targeting this key immunoregulator with novel or repurposed therapeutics in schizophrenia is a relatively underexplored area that could aid in reducing symptoms of patients with active neuroinflammation.
Diet-induced obesity accelerates oral carcinogenesis by recruitment and functional enhancement of myeloid-derived suppressor cells
Authors: Peng Jianmin , Hu Qinchao , Chen Xijuan , Wang Chunyang , Zhang Jiayu , Ren Xianyue , Wang Yun , Tao Xiaoan , Li Huan , Song Ming , Cheng Bin , Wu Tong , Xia Juan
Published: October 2021

Although obesity has been associated with an increased risk and aggressiveness of many types of carcinoma, whether it promotes squamous cell carcinoma remains unclear. To reveal the role of obesity in oral squamous cell carcinoma (OSCC) initiation and development, we used 4NQO-induced OSCC model mice to examine the impact of dietary obesity on carcinogenesis. The results showed that high-fat diet (HFD)-induced obesity significantly promoted the incidence of OSCC and altered the local immune microenvironment with the expansion of CD11b+Gr1+myeloid-derived suppressor cells (MDSCs). The underlying mechanism that induced an immunosuppressive local microenvironment in obesity was the recruitment of MDSCs through the CCL9/CCR1 axis and enhancement of MDSC immunosuppressive function via intracellular fatty acid uptake. Furthermore, clinical samples verified the increase in infiltrated CD33+(a marker of human MDSCs) cells in obese OSCC patients, and data from the TCGA dataset confirmed that CD33 expression was positively correlated with local adipocytes in OSCC. Survival analysis showed that enrichment of adipocytes and high expression of CD33 were associated with poor prognosis in OSCC patients. Strikingly, depletion of MDSCs significantly ameliorated HFD-promoted carcinogenesis in 4NQO-induced model mice. These findings indicate that obesity is also an important risk factor for OSCC, and cancer immunotherapy, especially targeting MDSCs, may exhibit greater antitumor efficacy in obese patients.
Genomic analysis finds no evidence of canonical eukaryotic DNA processing complexes in a free-living protist
Authors: Salas-Leiva Dayana E. , Tromer Eelco C. , Curtis Bruce A. , Jerlström-Hultqvist Jon , Kolisko Martin , Yi Zhenzhen , Salas-Leiva Joan S. , Gallot-Lavallée Lucie , Williams Shelby K. , Kops Geert J. P. L. , Archibald John M. , Simpson Alastair G. B. , Roger Andrew J.
Published: October 2021

Cells replicate and segregate their DNA with precision. Previous studies showed that these regulated cell-cycle processes were present in the last eukaryotic common ancestor and that their core molecular parts are conserved across eukaryotes. However, some metamonad parasites have secondarily lost components of the DNA processing and segregation apparatuses. To clarify the evolutionary history of these systems in these unusual eukaryotes, we generated a genome assembly for the free-living metamonad Carpediemonas membranifera and carried out a comparative genomics analysis. Here, we show that parasitic and free-living metamonads harbor an incomplete set of proteins for processing and segregating DNA. Unexpectedly, Carpediemonas species are further streamlined, lacking the origin recognition complex, Cdc6 and most structural kinetochore subunits. Carpediemonas species are thus the first known eukaryotes that appear to lack this suite of conserved complexes, suggesting that they likely rely on yet-to-be-discovered or alternative mechanisms to carry out these fundamental processes.
Kondo effect and spin–orbit coupling in graphene quantum dots
Authors: Kurzmann Annika , Kleeorin Yaakov , Tong Chuyao , Garreis Rebekka , Knothe Angelika , Eich Marius , Mittag Christopher , Gold Carolin , de Vries Folkert Kornelis , Watanabe Kenji , Taniguchi Takashi , Fal’ko Vladimir , Meir Yigal , Ihn Thomas , Ensslin Klaus
Published: October 2021

The Kondo effect is a cornerstone in the study of strongly correlated fermions. The coherent exchange coupling of conduction electrons to local magnetic moments gives rise to a Kondo cloud that screens the impurity spin. Here we report on the interplay between spin–orbit interaction and the Kondo effect, that can lead to a underscreened Kondo effects in quantum dots in bilayer graphene. More generally, we introduce a different experimental platform for studying Kondo physics. In contrast to carbon nanotubes, where nanotube chirality determines spin–orbit coupling breaking the SU(4) symmetry of the electronic states relevant for the Kondo effect, we study a planar carbon material where a small spin–orbit coupling of nominally flat graphene is enhanced by zero-point out-of-plane phonons. The resulting two-electron triplet ground state in bilayer graphene dots provides a route to exploring the Kondo effect with a small spin–orbit interaction.
Angle-based wavefront sensing enabled by the near fields of flat optics
Authors: Yi Soongyu , Xiang Jin , Zhou Ming , Wu Zhicheng , Yang Lan , Yu Zongfu
Published: October 2021

There is a long history of using angle sensors to measure wavefront. The best example is the Shack-Hartmann sensor. Compared to other methods of wavefront sensing, angle-based approach is more broadly used in industrial applications and scientific research. Its wide adoption is attributed to its fully integrated setup, robustness, and fast speed. However, there is a long-standing issue in its low spatial resolution, which is limited by the size of the angle sensor. Here we report a angle-based wavefront sensor to overcome this challenge. It uses ultra-compact angle sensor built from flat optics. It is directly integrated on focal plane array. This wavefront sensor inherits all the benefits of the angle-based method. Moreover, it improves the spatial sampling density by over two orders of magnitude. The drastically improved resolution allows angle-based sensors to be used for quantitative phase imaging, enabling capabilities such as video-frame recording of high-resolution surface topography.
Hexokinase 2-driven glycolysis in pericytes activates their contractility leading to tumor blood vessel abnormalities
Authors: Meng Ya-Ming , Jiang Xue , Zhao Xinbao , Meng Qiong , Wu Sangqing , Chen Yitian , Kong Xiangzhan , Qiu Xiaoyi , Su Liangping , Huang Cheng , Wang Minghui , Liu Chao , Wong Ping-Pui
Published: October 2021

Defective pericyte-endothelial cell interaction in tumors leads to a chaotic, poorly organized and dysfunctional vasculature. However, the underlying mechanism behind this is poorly studied. Herein, we develop a method that combines magnetic beads and flow cytometry cell sorting to isolate pericytes from tumors and normal adjacent tissues from patients with non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC). Pericytes from tumors show defective blood vessel supporting functions when comparing to those obtained from normal tissues. Mechanistically, combined proteomics and metabolic flux analysis reveals elevated hexokinase 2(HK2)-driven glycolysis in tumor pericytes, which up-regulates their ROCK2-MLC2 mediated contractility leading to impaired blood vessel supporting function. Clinically, high percentage of HK2 positive pericytes in blood vessels correlates with poor patient overall survival in NSCLC and HCC. Administration of a HK2 inhibitor induces pericyte-MLC2 driven tumor vasculature remodeling leading to enhanced drug delivery and efficacy against tumor growth. Overall, these data suggest that glycolysis in tumor pericytes regulates their blood vessel supporting role.
mTORC2 confers neuroprotection and potentiates immunity during virus infection
Authors: Suryawanshi Rahul K. , Patil Chandrashekhar D. , Agelidis Alex , Koganti Raghuram , Ames Joshua M. , Koujah Lulia , Yadavalli Tejabhiram , Madavaraju Krishnaraju , Shantz Lisa M. , Shukla Deepak
Published: October 2021

Herpes simplex virus type-1 (HSV-1) causes ocular and orofacial infections. In rare cases, HSV-1 can cause encephalitis, which leads to permanent brain injuries, memory loss or even death. Host factors protect humans from viral infections by activating the immune response. However, factors that confer neuroprotection during viral encephalitis are poorly understood. Here we show that mammalian target of rapamycin complex 2 (mTORC2) is essential for the survival of experimental animals after ocular HSV-1 infection in vivo. We find the loss of mTORC2 causes systemic HSV-1 infection due to defective innate and adaptive immune responses, and increased ocular and neuronal cell death that turns lethal for the infected mice. Furthermore, we find that mTORC2 mediated cell survival channels through the inactivation of the proapoptotic factor FoxO3a. Our results demonstrate how mTORC2 potentiates host defenses against viral infections and implicate mTORC2 as a necessary factor for survival of the infected host.
Multiple evolutionary origins and losses of tooth complexity in squamates
Authors: Lafuma Fabien , Corfe Ian J. , Clavel Julien , Di-Poï Nicolas
Published: October 2021

Teeth act as tools for acquiring and processing food, thus holding a prominent role in vertebrate evolution. In mammals, dental-dietary adaptations rely on tooth complexity variations controlled by cusp number and pattern. Complexity increase through cusp addition has dominated the diversification of mammals. However, studies of Mammalia alone cannot reveal patterns of tooth complexity conserved throughout vertebrate evolution. Here, we use morphometric and phylogenetic comparative methods across fossil and extant squamates to show they also repeatedly evolved increasingly complex teeth, but with more flexibility than mammals. Since the Late Jurassic, multiple-cusped teeth evolved over 20 times independently from a single-cusped common ancestor. Squamates frequently lost cusps and evolved varied multiple-cusped morphologies at heterogeneous rates. Tooth complexity evolved in correlation with changes in plant consumption, resulting in several major increases in speciation. Complex teeth played a critical role in vertebrate evolution outside Mammalia, with squamates exemplifying a more labile system of dental-dietary evolution.