bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel exploration via negatively correlated search
Authors: Yang Peng , Yang Qi , Tang Ke , Yao Xin
Published: July 2021

Effective exploration is key to a successful search process. The recently proposed negatively correlated search (NCS) tries to achieve this by coordinated parallel exploration, where a set of search processes are driven to be negatively correlated so that different promising areas of the search space can be visited simultaneously. Despite successful applications of NCS, the negatively correlated search behaviors were mostly devised by intuition, while deeper (e.g., mathematical) understanding is missing. In this paper, a more principled NCS, namely NCNES, is presented, showing that the parallel exploration is equivalent to a process of seeking probabilistic models that both lead to solutions of high quality and are distant from previous obtained probabilistic models. Reinforcement learning, for which exploration is of particular importance, are considered for empirical assessment. The proposed NCNES is applied to directly train a deep convolution network with 1.7 million connection weights for playing Atari games. Empirical results show that the significant advantages of NCNES, especially on games with uncertain and delayed rewards, can be highly owed to the effective parallel exploration ability.
Post-Induction Treatment for Acute Myeloid Leukemia: Something Change?
Authors: Jaramillo Sonia , Schlenk Richard F.
Published: July 2021

Purpose of Review

Until recently, improvement in terms of survival for patients with acute myeloid leukemia (AML) was achieved mostly in younger patients with dose intensification of conventional chemotherapy and a broadening use of allogeneic hematopoietic cell transplantation (allo-HCT) whereas the results remained dismal and very stable in patients older than 60 years. The current review highlights the recent developments in standard intensive post-remission chemotherapy, evidence for the use of recently approved agents, and discusses the relevance of measurable residual disease (MRD) measurement in treatment adaptation.

Recent Findings

Current approvals of midostaurin, venetoclax, gemtuzumab ozogamicin, VYXEOS, ivosidenib, enasidenib, glasdegib, and CC-486 have changed the structure, aim, and schedule of consolidation therapy, and new, well-tolerated agents are being evaluated as maintenance therapies. Furthermore, MRD assessment has been implemented to guide the duration and type of consolidation and maintenance therapy as well as indicate the optimal timing of allo-HCT.

Novel therapies have changed the structure and perspective of post-remission therapy in AML for both young and elderly patients. In addition, MRD assessment could guide the type, duration, and intensity of consolidation and maintenance therapy.
WEE1 Inhibitor: Clinical Development
Authors: Kong Anthony , Mehanna Hisham
Published: July 2021

Purpose of Review

WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents.

Recent Findings

Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies.

There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.
Defense Sector Politics
Authors: Grimes Collin
Published: July 2021

Ownership and control of defense industrial firms affords the military power, autonomy, and a claim to economic rents. Why do some countries succeed at shifting some or all such firms from military to civilian ownership and control, while others do not? I argue that differing configurations of relative civilian and military coalitional and institutional strength contribute to outcomes. Civilian and military must find party and executive-branch allies who can compete for them to craft or defeat legislation affecting their interests, but coalition building alone is insufficient. Actors must also cultivate executive bureaucratic institutions able to design and implement policies promoting their interests. How coalitions and institutions form, ossify, or fail to develop is assessed through a comparative study of Chile, Argentina (1983–1989), and Argentina (1989–1997).
Beyond Psychological Safety – the Role of Direct Supervisor Behavior in Fostering Learning from Errors at the Workplace
Authors: Smeets Laura , Gijselaers Wim H. , Meuwissen Roger H. G. , Grohnert Therese
Published: July 2021

This study explores how direct supervisors can hinder or enhance how professionals learn from their errors. Extant research has often focused on psychological safety as the main condition for this kind of learning to take place. We expand prior research by exploring which behaviors of direct supervisors effectively facilitate learning from errors in concert with psychological safety. We conducted semi-structured interviews among 23 professionals to gain detailed insights into their thoughts, needs, and the difficulties they encounter. Through content analysis, we identified four critical supervisor behaviors that participants viewed as facilitating learning from errors next to fostering a psychologically safe work environment: (1) providing timely feedback, (2) guidance and elaborate feedback, (3) being accessible and personally involved, (4) organizing joint evaluations. Based on our findings, recommendations are formulated for supervisors that aim to facilitate professionals’ learning from errors and their professional development.
Neue Therapiemöglichkeiten des bullösen Pemphigoids
Authors: Griss Johannes
Published: July 2021

Das bullöse Pemphigoid ist die häufigste autoimmun-blasenbildende Hauterkrankung. Es betrifft fast ausschließlich Patienten im fortgeschrittenen Alter und damit eine von vornherein vulnerable Patientenpopulation. Aufgrund seiner laufend steigenden Inzidenz wird das bullöse Pemphigoid zu einer immer größeren Belastung für Gesundheitssysteme. In dieser Arbeit sollen die primären klinischen Erscheinungsformen des bullösen Pemphigoids und deren Diagnostik besprochen werden. Der Schwerpunkt liegt jedoch in einer Übersicht bestehender Therapien und der Studienlage zu deren Wirksamkeit. Gerade für schwere Verläufe stellt neuerdings eine Therapie mit Rituximab einen großen Fortschritt in den therapeutischen Möglichkeiten dar. Abschließend werden die Daten einer IgE-Blockade mit Omalizumab bzw. mit einer Blockade von IL-4/IL-13 mittels Dupilumab vorgestellt. Diese neuen Therapien zeigen bereits eine vielversprechende Wirksamkeit und sind spannende Optionen zur Behandlung dieser immer häufiger werdenden Erkrankung.
Wie Hautalterung und Hautkrebs zusammenhängen
Authors: Posch Christian
Published: July 2021

In den letzten Jahren hat die Wissenschaft um biologische Prozesse der (Haut‑)Alterung enorm an Fahrt aufgenommen. Alterung und die damit assoziierten Erkrankungen werden nicht mehr als unausweichliches Schicksal angesehen, sondern als ein hochkomplexes System, in das dank moderner Technologien Einblick genommen werden kann und das zum Vorteil der Gesundheit manipuliert werden kann. Botox und Filler haben im Feld der Biogerontologie keinen Stellenwert, denn es geht um grundlegende biochemische Mechanismen der zellulären und organismalen Alterung – und deren Eindämmung. Der nachfolgende Artikel bewegt sich im Spannungsfeld einiger typischer Charakteristika des Alterns und der Karzinogenese mit dem Ziel, Gemeinsamkeiten und Überlappungen aufzuzeigen, die in Zukunft medizinisch genutzt werden könnten. Hierbei müssen gesamtgesundheitliche Ansätze, die vor allem das Ziel der Tumorvorbeugung haben, von individuellen Therapiekonzepten unterschieden werden, die das Ziel verfolgen, eine manifeste Hauttumorerkrankung zu behandeln. Beide Konzepte haben ihren Stellenwert. Vier Kernelemente der (Haut‑)Alterung sollen genauer beleuchtet werden: genomische Instabilität, epigenetische Modifikationen, Seneszenz und gestörte interzelluläre Kommunikation.
Innovation intensity and skills in firms across five European countries
Authors: Falk Martin , Hagsten Eva
Published: July 2021

This study attempts to establish the importance of specific formally achieved higher skills for the innovation intensity in firms across a group of European countries. Innovation expenditures are calculated as the ratio to turnover and the main explanatory variable is the proportion of highly skilled employees (tertiary education in ICT-oriented or other fields). The analysis employs official data on innovation activities (Community Innovation Survey) in firms for the period 2004–2010, linked to registers on education and businesses as well as to the Structural Business Statistics including 34,000 observations. Estimation results show a strong significantly positive relationship between the innovation intensity and the proportion of highly ICT skilled employees. Higher skills outside the field of ICT are also important for the innovation activities. Control variables reveal that the innovation intensity significantly increases with joint national and EU funding while the role of firm age varies. The significant and negative link to firm size reveals a lack of advantages of scale, a finding possibly related to the use of a comprehensive measure of innovation activities. There are also indications that industry affiliation is essential for the innovation intensity.
Exploring persuasion knowledge in food advertising: an empirical analysis
Authors: Mohr Svenja , Kühl Rainer
Published: July 2021

Food purchase decisions are characterized by habitual purchase behavior and low consumer involvement. The main aim of food marketing is to influence food consumers, for example, through advertising. In order to illustrate the interaction between consumers and marketers, Friestad and Wright (1994) developed the Persuasion Knowledge Model. The Persuasion Knowledge Model postulates that consumers’ dealing with persuasion attempts depends on three knowledge factors: persuasion, agent, and topic knowledge. In this paper, we apply the Persuasion Knowledge Model to food advertising. Based on an online survey with German students (n = 420), a structural equation analysis is used to investigate how persuasion knowledge determinants influence food consumers’ avoidance of the persuasion attempt which is presented as a hypothetical but typical food advertisement. Results show that the dependent variable beliefs about consumers’ avoidance of the persuasion attempt is negatively influenced by consumers’ beliefs about psychological mediators in the advertisement and by consumers’ beliefs about the appropriateness and effectiveness of the persuasion tactic. The determinant consumers’ beliefs about persuasion coping goals and tactics positively influences consumers’ avoidance of the persuasion attempt. From these findings, we derive recommendations for food industry advertisers and consumer education.
Culture vs. distance: comparing the effects of geographic segmentation variables on tourists’ destination images based on social media data
Authors: Wu Mengtong , Jiang Chao , Zhang Yi , Cao Jingjing , Cheng Ying , Liu Yu
Published: July 2021

Culture and distance are two major factors for geographically segmenting tourists in tourism marketing and advertising. Previous empirical studies on the destination image, however, have examined extensively the effect of the culture while inadequately the effect of the distance, let alone comparing the effects of the two variables. Using social media data, this study compares the effect of distance-based segments of tourists with that of culture-based segments in producing diverse perceived images of a destination. From Sina Weibo data, 282,532 Chinese mainland tourists who visited Suzhou, China during 2012–2016 and their perceived destination images are extracted and analyzed. The main results include: 1) for distance-based segments, the image differences increased with distance and the short-haul tourists perceived a more comprehensive image than the long-haul tourists; 2) for culture-based segments, the image differences were clear and relatively complex, while tourists from Wuyue cultural region had similar image perceptions with the local visitors; 3) the q-statistic of the Geodetector method shows that the culture-based segmentation can explain 65.8% of image variations while the distance-based segmentation can explain 46.6% of image variations, suggesting that culture is a more appropriate variable to segment the tourism market.
Weight Loss Through Bariatric Surgery in Men Presents Beneficial Effects on Sexual Function, Symptoms of Testosterone Deficiency, and Hormonal Profile
Authors: Machado Felipe Pioner , Rhoden Ernani Luis , Pioner Sérgio Ricardo , Halmenschlager Graziele , de Souza Luis Vinicius Bastos , Lisot Bruno Chao , Drachler Igor Pires
Published: July 2021

Introduction

Male obesity has a negative correlation with plasma testosterone (T) levels and sexual function (SF).

Aim

To evaluate the effect of weight loss through bariatric surgery (BS) on SF, low T symptoms, and hormonal profiles in obese men.

Methods

Thirty-three men who underwent BS participated in this cohort study. Before surgery, all participants underwent clinical examinations, including anthropometric, lipid, glycemic, and hormonal evaluations. SF was evaluated using the International Index of Erectile Function (IIEF) questionnaire; low T symptoms were evaluated using the Aging Males’ Symptoms (AMS) and Androgen Deficiency in the Aging Male (ADAM) questionnaires. The participants were reevaluated 6 months post-surgery.

Main outcome measures

Sex hormone profile, SF, and low T symptoms

Results

After BS, a significant increase in mean total T (201 ± 111–548 ± 190 ng/dL, P < .001), free T (5.8 ± 2.8–9.3 ± 3.4 ng/dL, P < .001), bioavailable T (110.3 ± 57.8–198.6 ± 74.3 ng/dL, P < .001), and sexual hormone-binding globulin (19.8 ± 13.7–54.6 ± 23.2 nmol/L, P < .001) levels. There was a significant decrease in estradiol (64.6 ± 27.4–29.2 ± 20.0 [pg/mL], P < .001). SF significantly improved. The total IIEF score increased 5.2 points (62.3 ± 7.4–67.5 ± 7.4, P = .004), erectile function subdomain increased 2.4 points (25.7 ± 4.1–28.1 ± 3.9, P = .011), desire subdomain increased 1.0 points (8.3 ± 1.5–9.3 ± 1.6, P = .006), and intercourse satisfaction subdomain increased 1.2 points (11.4 ± 1.9–12.6 ± 1.8, P = .012). Post-surgery, a 44% reduction (P = .001) was observed in the positive ADAM questionnaire, and improvements in all domains of the AMS questionnaire were found (P < .001).

Conclusion

Significant weight loss through BS improves erectile function, hormonal profile, and symptoms of T deficiency.

Machado FP, Rhoden EL, Pioner SR, et al. Weight Loss Through Bariatric Surgery in Men Presents Beneficial Effects on Sexual Function, Symptoms of Testosterone Deficiency, and Hormonal Profile. Sex Med 2021;9:100400.
The Relationship Between Hematologic Parameters and Erectile Dysfunction
Authors: Liao Zhangcheng , Tang Yuxin , Li Xiucheng , Li Dongjie
Published: July 2021

Introduction

Certain hematologic parameters related to blood cells, known as the biomarkers that predict cardiovascular disease, might be potential predictors of erectile dysfunction (ED) due to the shared pathophysiology between ED and cardiovascular disease .

Aim

To investigate the relationship between ED and these hematologic parameters and the clinical significance of hematologic parameters for the diagnosis of ED.

Methods

A total of 113 male patients diagnosed with ED were included in this study. Blood samples were collected before 10:00 AM for blood cells examination, biochemical tests, and sex hormone analysis. Another 212 healthy controls without ED from the health management center was included as the control group. The relationship between hematologic parameters and ED was assessed by comparing differences in body mass index (BMI), biochemical indexes and hematologic parameters between the 2 groups, and the diagnostic value of hematologic parameters for ED was also examined and compared.

Main outcome measures

International Index of Erectile Function, hematologic parameters

Results

The neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in ED patients were significantly higher than those in healthy controls, whereas the lymphocyte count (LC) was significantly lower than that in healthy controls. After adjusting for age, BMI, uric acid (UA), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), increases in the NC, NLR, and PLR and a decrease in the LC were shown to be independent risk factors for ED. Receiver operating characteristic (ROC) curve analysis showed that the NLR exhibited better diagnostic performance for ED than the other parameters.

Conclusion

Increases in the NC, NLR, and PLR and a decrease in the LC significantly increased the risk of ED. The NC, LC, NLR and PLR could contribute to the diagnosis and assessment of ED. Zhangcheng L, Yuxin T, Xiucheng L and Dongjie L, et al. The Relationship Between Hematologic Parameters and Erectile Dysfunction. Sex Med 2021;9:100401.
Sildenafil Citrate and Risk of Biochemical Recurrence in Prostate Cancer Patients Treated with Radiation Therapy: Post-Hoc Analysis of a Randomized Controlled Trial
Authors: Haseltine Justin M. , Hopkins Margaret , Schofield Elizabeth , Kollmeier Marisa A. , Shasha Daniel , Gorovets Daniel , McBride Sean M. , Mulhall John P. , Zelefsky Michael J.
Published: July 2021

Background

Sildenafil citrate has been shown to be protective of sexual function when given concurrently and following prostate radiation therapy (RT), but some evidence suggests an increased biochemical recurrence (BCR) risk in patients taking sildenafil after radical prostatectomy.

Aim

To evaluate whether sildenafil use is associated with increased risk of BCR in patients receiving prostate RT, we performed a secondary analysis of a randomized placebo-controlled trial (RPCT) that compared sildenafil citrate to placebo during and after prostate RT.

Methods

The study population consisted of prostate cancer patients who initiated radiation treatment at our institution and participated in our multi-institutional RPCT that compared 6 months of sildenafil 50 mg once a day to placebo with a 24-month follow-up. Androgen deprivation therapy (ADT) was allowed. Prostate cancer prognostic risk grouping was not an exclusion criterion, but most study participants had low- or intermediate-risk prostate cancer. Statistical analysis was performed using Kaplan-Meier plots and log-rank testing.

Outcomes

The primary outcomes of this report were biochemical recurrence and overall survival rates, where BCR was defined according to the Phoenix definition.

RESULTS

Data of 162 men were analyzed. Nine men had inadequate PSA follow-up and the remaining 153 men were included in the final report. Median age was 61 years. At a median follow-up of 8.3 years (range: 3.0–12.2), 5/94 (5.3%) and 2/59 (3.4%) patients developed BCR in the sildenafil and placebo groups, respectively. The 6-year BCR-free survival was 98.8% for all patients, 98.1% for the sildenafil cohort, and 100% for the placebo cohort. The 10-year BCR-free survival was 94.4% for all patients, 95.6% for the sildenafil cohort, and 92.9% for the placebo cohort. There was no difference in BCR-free survival between the sildenafil and placebo groups by log-rank comparison (p = 0.36).

Clinical implications

This analysis informs clinical decision making about the safety of using sildenafil during and after prostate RT.

Strengths and limitations

This study included patients who were treated in the setting of a prospective, randomized placebo-controlled trial, and who attained high medication compliance. However, the study was limited by the post-hoc nature of the analysis, use of ADT in some patients, inadequate study power to detect a difference in BCR between sildenafil and placebo groups.

CONCLUSION

Prophylactic sildenafil citrate was not associated with biochemical recurrence risk in prostate cancer patients treated with radiation. However, the study was inadequately powered to definitively conclude a negative finding.
Compressive Imaging: Structure, Sampling, Learning
Authors: Adcock Ben , Hansen Anders C.
Published: July 2021

Accurate, robust and fast image reconstruction is a critical task in many scientific, industrial and medical applications. Over the last decade, image reconstruction has been revolutionized by the rise of compressive imaging. It has fundamentally changed the way modern image reconstruction is performed. This in-depth treatment of the subject commences with a practical introduction to compressive imaging, supplemented with examples and downloadable code, intended for readers without extensive background in the subject. Next, it introduces core topics in compressive imaging – including compressed sensing, wavelets and optimization – in a concise yet rigorous way, before providing a detailed treatment of the mathematics of compressive imaging. The final part is devoted to recent trends in compressive imaging: deep learning and neural networks. With an eye to the next decade of imaging research, and using both empirical and mathematical insights, it examines the potential benefits and the pitfalls of these latest approaches.
Multiple correlation sequences not approximable by nilsequences
Authors: BRIËT JOP , GREEN BEN
Published: July 2021

We show that there is a measure-preserving system
$(X,\mathscr {B}, \mu , T)$
together with functions
$F_0, F_1, F_2 \in L^{\infty }(\mu )$
such that the correlation sequence
$C_{F_0, F_1, F_2}(n) = \int _X F_0 \cdot T^n F_1 \cdot T^{2n} F_2 \, d\mu $
is not an approximate integral combination of
$2$
-step nilsequences.
EVALUATION OF CONVOLUTION SUMS AND FORk = a · b= 21, 33, AND 35
Authors: PUSHPA K. , VASUKI K. R.
Published: July 2021

The article focuses on the evaluation of convolution sums$${W_k}(n): = \mathop \sum \nolimits_{_{m < {n \over k}}} \sigma (m)\sigma (n - km)$$involving the sum of divisor function$$\sigma (n)$$fork=21, 33, and 35. In this article, our aim is to obtain certain Eisenstein series of level 21 and use them to evaluate the convolution sums for level 21. We also make use of the existing Eisenstein series identities for level 33 and 35 in evaluating the convolution sums for level 33 and 35. Most of the convolution sums were evaluated using the theory of modular forms, whereas we have devised a technique which is free from the theory of modular forms. As an application, we determine a formula for the number of representations of a positive integernby the octonary quadratic form$$(x_1^2 + {x_1}{x_2} + ax_2^2 + x_3^2 + {x_3}{x_4} + ax_4^2) + b(x_5^2 + {x_5}{x_6} + ax_6^2 + x_7^2 + {x_7}{x_8} + ax_8^2)$$, for (a, b)=(1, 7), (1, 11), (2, 3), and (2, 5).
The restricted Burnside problem for Moufang loops
Authors: GRISHKOV ALEXANDER , SABININA LIUDMILA , ZELMANOV EFIM
Published: July 2021

We prove that for positive integers
$m \geq 1, n \geq 1$
and a prime number
$p \neq 2,3$
there are finitely many finite m-generated Moufang loops of exponent
$p^n$
.
A note on the four-dimensional clasp number of knots
Authors: FELLER PETER , PARK JUNGHWAN
Published: July 2021

Among the knots that are the connected sum of two torus knots with cobordism distance 1, we characterise those that have 4-dimensional clasp number at least 2, and we show that their n-fold connected self-sum has 4-dimensional clasp number at least 2n. Our proof works in the topological category. To contrast this, we build a family of topologically slice knots for which the n-fold connected self-sum has 4-ball genus n and 4-dimensional clasp number at least 2n.
Age and Sex-Specific Associations in Health Risk Factors for Chronic Disease: Evidence from the Atlantic Partnership for Tomorrow’s Health (PATH) Cohort
Authors: DeClercq Vanessa , Sweeney Ellen
Published: July 2021

The objective of this study was to discern health risk factors for chronic disease by age and sex in a Canadian cohort. Participants of the Atlantic Partnership for Tomorrow’s Health (PATH) cohort with health risk factor data (physical activity, smoking, alcohol consumption, diet, body mass index [BMI]) were included (n = 16,165). Multivariable logistic regression models were used to evaluate the relationship among health risk factors, age, and sex. Regression analysis revealed that the odds of engaging in high levels of physical activity and having a BMI ≥ 25 was lower for females than males across all age groups, whereas the odds of abdominal obesity was substantially higher for females of all ages than for males. The odds of habitually consuming alcohol was lower for females of all ages than for males, and the odds of being a former/current smoker was lower for older (57–74 years of age) females than for males. The odds of consuming five or more servings of fruit and vegetables per day was higher for females of all ages than for males. There are evident differences in health risk factors for males and for females, as well as across age groups, and public health efforts need to account for the role played by sex and age in addressing chronic disease burden in Canadian adults.
Fleeting gestures and changing styles of greeting: researching daily life in British towns in the long eighteenth century
Authors: Corfield Penelope J.
Published: July 2021

Researching the history of daily greetings is challenging, because references are casual and scattered through many sources. Nonetheless, some broad trends are apparent. In eighteenth-century Britain, the old tradition of deep bowing and curtseying was slowly attenuating into a brisker touching of the cap or head (for men) and a quick bob (for women). Yet that transition was not the whole story. Simultaneously, a new form of urban greeting, in the form of the handshake, was emerging. The strengths and weaknesses of many different sources are here assessed, including novels, plays, letters, diaries, etiquette books, travelogues and legal depositions, as well as artwork. Strategies for analysis are identified, with a warning against generalizing from single references in single sources. Finally, the emergence of the handshake among the middle class in Britain's eighteenth-century towns gives a clear signal that socio-cultural change does not invariably start at the ‘top’ and ‘trickle down’.
First experiences of local pulse wave velocity measurements in 4D-MRI	in focally stented femoropopliteal arteries
Authors: Hermann Ingo , Shchetynska-Marinova Tetyana , Amendt Klaus , Hohneck Anna-Lena , Schönberg Stefan O. , Zöllner Frank G. , Sigl Martin
Published: July 2021

Summary: Background: In peripheral arterial disease (PAD) the femoropopliteal (FP) artery is the most frequently recanalized lower limb artery. Stent-based interventions change the biomechanical properties of FP arteries. However, no clinical tool for functional imaging is established for quantitative measurements in vivo. Four-dimensional-flow magnetic resonance imaging enables a detailed evaluation of the hemodynamics of the central and – more challenging – the peripheral arteries. The present study aimed to determine the feasibility of assessing pulse wave velocities (PWV) as a marker of vessel stiffness in PAD patients with multiple spot stents and to compare the values with age-matched subjects and young-adult healthy subjects. Patients and methods: Contrast-free 4D-flow MRI was performed in seven PAD patients with focally stented FP arteries, five age-matched subjects after exclusion of PAD, and five young, healthy adults. PWV values were calculated from flow curves by using the foot-to-foot method. Results: Four-D-flow MRI sequences offering high spatial and temporal resolution enables quantification of flow velocity measurements and estimation of PWVs. Assessment of segmental PWV as a surrogate of vascular stiffness in focally stented femoral arteries is feasible. PWV values across all groups were 15.6±5.2 m/s, 13.3±4.1 m/s, and 9.9±2.2 m/s in PAD patients, senior-aged volunteers, and young-adult volunteers respectively. PWV values in PAD patients were similar with those in the senior-aged volunteers group (15.6±5.2 vs. 13.3 ±4.1 years, p=0.43). However, when compared to the young-adult volunteers, PAD patients had a statistically significantly higher mean local PWV (15.6±5.2 m/s vs. 9.9±2.2 m/s, p<0.05). Conclusions: Calculating segmental PWV in the femoral arteries is feasible in PAD patients with focally stented FP arteries. PWV values in PAD patients were similar to those in senior-aged volunteers, both of which were higher than in young-adult volunteers.
Reactivation Potential of Intraplate Faults in the Western Quebec Seismic Zone, Eastern Canada
Authors: Rimando Jeremy M. , Peace Alexander L.
Published: July 2021

The intraplate western Quebec seismic zone (WQSZ) in eastern Canada experiences moderate seismicity that mainly results from reactivation of inherited structures under the present‐day, NE‐SW‐striking regional maximum horizontal stress (SH) and, possibly to a minor extent, through stress perturbations in response to glacio‐isostatic adjustment. This work comprises the first numerical stress simulation‐based study that predicts the preferred spatial distribution, trends, and sense of slip of contemporary fault reactivation, which may have implications for possible fault segmentation patterns in the WQSZ. We show that mostly NNW‐SSE to NW‐SE‐striking faults exhibit the highest slip tendency values. Spatial patterns of slip tendency and kinematics of reactivation are consistent with the observed seismicity. In an area where Quaternary‐active faults have yet to be systematically identified, we have narrowed down areas to focus on for more detailed, future neotectonic investigations that could provide sound foundation for seismic hazard assessments. This study demonstrates the applicability of slip tendency analysis to identifying potentially active faults in stable continental regions worldwide.
Two‐Stage Transition From Gilbert to Hyperpycnal Delta in Reservoir
Authors: Lai Steven Yueh Jen , Wu Fu‐Chun
Published: July 2021

Deltas are a most common form of reservoir sedimentation. When the river inflows switch between homopycnal and hyperpycnal, morphological transitions between Gilbert and hyperpycnal deltas take place. So far, however, detailed studies on how such transitions occur and quantitative descriptions of the processes have been rare. Here, we study experimentally the deltaic transitions in response to the switch of flow type. Our results show that transition from hyperpycnal to Gilbert delta is purely depositional. This contrasts the transition from Gilbert to hyperpycnal delta, which is a two‐stage process involving both erosion and deposition. During the first stage, hyperpycnal flows modify the existing Gilbert delta into a subaqueous foundation, over which hyperpycnal delta develops and progrades into the basin during the second stage. After transition, hyperpycnal deltas migrate at higher speeds to recover the non‐transitioned trajectories. Diffusion‐based models are found well suited to describing the self‐similar morphodynamics of the two‐stage process.
Mitochondrial quality control in intervertebral disc degeneration
Authors: Song Yu , Lu Saideng , Geng Wen , Feng Xiaobo , Luo Rongjin , Li Gaocai , Yang Cao
Published: July 2021

Intervertebral disc degeneration (IDD) is a common and early-onset pathogenesis in the human lifespan that can increase the risk of low back pain. More clarification of the molecular mechanisms associated with the onset and progression of IDD is likely to help establish novel preventive and therapeutic strategies. Recently, mitochondria have been increasingly recognized as participants in regulating glycolytic metabolism, which has historically been regarded as the main metabolic pathway in intervertebral discs due to their avascular properties. Indeed, mitochondrial structural and functional disruption has been observed in degenerated nucleus pulposus (NP) cells and intervertebral discs. Multilevel and well-orchestrated strategies, namely, mitochondrial quality control (MQC), are involved in the maintenance of mitochondrial integrity, mitochondrial proteostasis, the mitochondrial antioxidant system, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Here, we address the key evidence and current knowledge of the role of mitochondrial function in the IDD process and consider how MQC strategies contribute to the protective and detrimental properties of mitochondria in NP cell function. The relevant potential therapeutic treatments targeting MQC for IDD intervention are also summarized. Further clarification of the functional and synergistic mechanisms among MQC mechanisms may provide useful clues for use in developing novel IDD treatments.
USP29-mediated HIF1α stabilization is associated with Sorafenib resistance of hepatocellular carcinoma cells by upregulating glycolysis
Authors: Gao Ruize , Buechel David , Kalathur Ravi K. R. , Morini Marco F. , Coto-Llerena Mairene , Ercan Caner , Piscuoglio Salvatore , Chen Qian , Blumer Tanja , Wang Xueya , Dazert Eva , Heim Markus H. , Hall Michael N. , Tang Fengyuan , Christofori Gerhard
Published: July 2021

Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In hepatocellular carcinoma (HCC), aberrant expression of hypoxia-inducible factor 1 α (HIF1α) and increased aerobic glycolysis metabolism are drivers of resistance to therapy with the multi-kinase inhibitor Sorafenib. However, it has remained unknown how HIF1α is activated and how its activity and the subsequent induction of aerobic glycolysis promote Sorafenib resistance in HCC. Here, we report the ubiquitin-specific peptidase USP29 as a new regulator of HIF1α and of aerobic glycolysis during the development of Sorafenib resistance in HCC. In particular, we identified USP29 as a critical deubiquitylase (DUB) of HIF1α, which directly deubiquitylates and stabilizes HIF1α and, thus, promotes its transcriptional activity. Among the transcriptional targets of HIF1α is the gene encoding hexokinase 2 (HK2), a key enzyme of the glycolytic pathway. The absence of USP29, and thus of HIF1α transcriptional activity, reduces the levels of aerobic glycolysis and restores sensitivity to Sorafenib in Sorafenib-resistant HCC cells in vitro and in xenograft transplantation mouse models in vivo. Notably, the absence of USP29 and high HK2 expression levels correlate with the response of HCC patients to Sorafenib therapy. Together, the data demonstrate that, as a DUB of HIF1α, USP29 promotes Sorafenib resistance in HCC cells, in parts by upregulating glycolysis, thereby opening new avenues for therapeutically targeting Sorafenib-resistant HCC in patients.
Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites
Authors: Cha Soojin , Lee Esak , Won Hong-Hee
Published: July 2021

Metastasis is the major cause of death in breast cancer patients. Although previous large-scale analyses have identified frequently altered genes specific to metastatic breast cancer (MBC) compared with those in primary breast cancer (PBC), metastatic site-specific altered genes in MBC remain largely uncharacterized. Moreover, large-scale analyses are required owing to the low expected frequency of such alterations, likely caused by tumor heterogeneity and late dissemination of breast cancer. To clarify MBC-specific genetic alterations, we integrated publicly available clinical and mutation data of 261 genes, including MBC drivers, from 4268 MBC and 5217 PBC patients from eight different cohorts. We performed meta-analyses and logistic regression analyses to identify MBC-enriched genetic alterations relative to those in PBC across 15 different metastatic site sets. We identified 11 genes that were more frequently altered in MBC samples from pan-metastatic sites, including four genes (SMARCA4, TSC2, ATRX, and AURKA) which were not identified previously. ARID2 mutations were enriched in treatment-naïve de novo and post-treatment MBC samples, compared with that in treatment-naïve PBC samples. In metastatic site-specific analyses, associations of ESR1 with liver metastasis and RICTOR with bone metastasis were significant, regardless of intrinsic subtypes. Among the 15 metastatic site sets, ESR1 mutations were enriched in the liver and depleted in the lymph nodes, whereas TP53 mutations showed an opposite trend. Seven potential MBC driver mutations showed similar preferential enrichment in specific metastatic sites. This large-scale study identified new MBC genetic alterations according to various metastatic sites and highlights their potential role in breast cancer organotropism.
Shear induced deformation twinning evolution in thermoelectric InSb
Authors: Lu Zhongtao , Huang Ben , Li Guodong , Zhang Xiaolian , An Qi , Duan Bo , Zhai Pengcheng , Zhang Qingjie , Goddard William A.
Published: July 2021

Twin boundary (TB) engineering has been widely applied to enhance the strength and plasticity of metals and alloys, but is rarely adopted in thermoelectric (TE) semiconductors. Our previous first-principles results showed that nanotwins can strengthen TE Indium Antimony (InSb) through In–Sb covalent bond rearrangement at the TBs. Herein, we further show that shear-induced deformation twinning enhances plasticity of InSb. We demonstrate this by employing large-scale molecular dynamics (MD) to follow the shear stress response of flawless single-crystal InSb along various slip systems. We observed that the maximum shear strain for the $$(111)[11\bar 2]$$

(

111

)

[

11

2

¯

]

slip system can be up to 0.85 due to shear-induced deformation twinning. We attribute this deformation twinning to the “catching bond” involving breaking and re-formation of In–Sb bond in InSb. This finding opens up a strategy to increase the plasticity of TE InSb by deformation twinning, which is expected to be implemented in other isotypic III–V semiconductors with zinc blende structure.
The landscape of driver mutations in cutaneous squamous cell carcinoma
Authors: Chang Darwin , Shain A. Hunter
Published: July 2021

Cutaneous squamous cell carcinoma is a form of skin cancer originating from keratinocytes in the skin. It is the second most common type of cancer and is responsible for an estimated 8000 deaths per year in the United States. Compared to other cancer subtypes with similar incidences and death tolls, our understanding of the somatic mutations driving cutaneous squamous cell carcinoma is limited. The main challenge is that these tumors have high mutation burdens, primarily a consequence of UV-radiation-induced DNA damage from sunlight, making it difficult to distinguish driver mutations from passenger mutations. We overcame this challenge by performing a meta-analysis of publicly available sequencing data covering 105 tumors from 10 different studies. Moreover, we eliminated tumors with issues, such as low neoplastic cell content, and from the tumors that passed quality control, we utilized multiple strategies to reveal genes under selection. In total, we nominated 30 cancer genes. Among the more novel genes, mutations frequently affected EP300, PBRM1, USP28, and CHUK. Collectively, mutations in the NOTCH and p53 pathways were ubiquitous, and to a lesser extent, mutations affected genes in the Hippo pathway, genes in the Ras/MAPK/PI3K pathway, genes critical for cell-cycle checkpoint control, and genes encoding chromatin remodeling factors. Taken together, our study provides a catalog of driver genes in cutaneous squamous cell carcinoma, offering points of therapeutic intervention and insights into the biology of cutaneous squamous cell carcinoma.
Serum lipid profile among sporadic and familial forms of Parkinson’s disease
Authors: Macías-García Daniel , Periñán María Teresa , Muñoz-Delgado Laura , Jimenez-Jaraba María Valle , Labrador-Espinosa Miguel Ángel , Jesús Silvia , Buiza-Rueda Dolores , Méndez-Del Barrio Carlota , Adarmes-Gómez Astrid , Gómez-Garre Pilar , Mir Pablo
Published: July 2021

Brain cholesterol metabolism has been described as altered in Parkinson’s disease (PD) patients. Serum lipid levels have been widely studied in PD with controversial results among different populations and age groups. The present study is aimed at determining if the serum lipid profile could be influenced by the genetic background of PD patients. We included 403 PD patients (342 sporadic PD patients, 30 GBA-associated PD patients, and 31 LRRK2-associated PD patients) and 654 healthy controls (HCs). Total cholesterol, HDL, LDL, and triglycerides were measured in peripheral blood. Analysis of covariance adjusting for sex and age (ANCOVA) and post hoc tests were applied to determine the differences within lipid profiles among the groups. Multivariate ANCOVA revealed significant differences among the groups within cholesterol and LDL levels. GBA-associated PD patients had significantly lower levels of total cholesterol and LDL compared to LRRK2-associated PD patients and HCs. The different serum cholesterol levels in GBA-associated PD might be related to diverse pathogenic mechanisms. Our results support the hypothesis of lipid metabolism disruption as one of the main PD pathogenic mechanisms in patients with GBA-associated PD. Further studies would be necessary to explore their clinical implications.
COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries
Authors: Solís Arce Julio S. , Warren Shana S. , Meriggi Niccolò F. , Scacco Alexandra , McMurry Nina , Voors Maarten , Syunyaev Georgiy , Malik Amyn Abdul , Aboutajdine Samya , Adeojo Opeyemi , Anigo Deborah , Armand Alex , Asad Saher , Atyera Martin , Augsburg Britta , Awasthi Manisha , Ayesiga Gloria Eden , Bancalari Antonella , Björkman Nyqvist Martina , Borisova Ekaterina , Bosancianu Constantin Manuel , Cabra García Magarita Rosa , Cheema Ali , Collins Elliott , Cuccaro Filippo , Farooqi Ahsan Zia , Fatima Tatheer , Fracchia Mattia , Galindo Soria Mery Len , Guariso Andrea , Hasanain Ali , Jaramillo Sofía , Kallon Sellu , Kamwesigye Anthony , Kharel Arjun , Kreps Sarah , Levine Madison , Littman Rebecca , Malik Mohammad , Manirabaruta Gisele , Mfura Jean Léodomir Habarimana , Momoh Fatoma , Mucauque Alberto , Mussa Imamo , Nsabimana Jean Aime , Obara Isaac , Otálora María Juliana , Ouédraogo Béchir Wendemi , Pare Touba Bakary , Platas Melina R. , Polanco Laura , Qureshi Javaeria Ashraf , Raheem Mariam , Ramakrishna Vasudha , Rendrá Ismail , Shah Taimur , Shaked Sarene Eyla , Shapiro Jacob N. , Svensson Jakob , Tariq Ahsan , Tchibozo Achille Mignondo , Tiwana Hamid Ali , Trivedi Bhartendu , Vernot Corey , Vicente Pedro C. , Weissinger Laurin B. , Zafar Basit , Zhang Baobao , Karlan Dean , Callen Michael , Teachout Matthieu , Humphreys Macartan , Mobarak Ahmed Mushfiq , Omer Saad B.
Published: July 2021

Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
Microplastic contamination of the drilling bivalve Hiatella arctica in Arctic rhodolith beds
Authors: Teichert Sebastian , Löder Martin G. J. , Pyko Ines , Mordek Marlene , Schulbert Christian , Wisshak Max , Laforsch Christian
Published: July 2021

There is an increasing number of studies reporting microplastic (MP) contamination in the Arctic environment. We analysed MP abundance in samples from a marine Arctic ecosystem that has not been investigated in this context and that features a high biodiversity: hollow rhodoliths gouged by the bivalve Hiatella arctica. This bivalve is a filter feeder that potentially accumulates MPs and may therefore reflect MP contamination of the rhodolith ecosystem at northern Svalbard. Our analyses revealed that 100% of the examined specimens were contaminated with MP, ranging between one and 184 MP particles per bivalve in samples from two water depths. Polymer composition and abundance differed strongly between both water depths: samples from 40 m water depth showed a generally higher concentration of MPs and were clearly dominated by polystyrene, samples from 27 m water depth were more balanced in composition, mainly consisting of polyethylene, polyethylene terephthalate, and polypropylene. Long-term consequences of MP contamination in the investigated bivalve species and for the rhodolith bed ecosystem are yet unclear. However, the uptake of MPs may potentially impact H. arctica and consequently its functioning as ecosystem engineers in Arctic rhodolith beds.