bluuebunny/crossref_metadata_2025 huggingface dataset:
Langzeitverlauf nach chirurgischer Therapie der gastroösophagealen Refluxkrankheit
Authors: Gehwolf Philipp , Wykypiel Heinz
Published: January 2022

Die gastroösophageale Refluxkrankheit (GERD) ist die häufigste Erkrankung des oberen Gastrointestinaltrakts. Das Spektrum der Refluxkrankheit ist breit und reicht von milden Symptomen bis hin zu Komplikationen wie Blutung, Strikturen und Krebs. Die jährliche Inzidenz, also das Neuauftreten der GERD, wird auf 4,5–5,4 % geschätzt. Die wichtigsten Prädiktoren sind: männliches Geschlecht, Übergewicht (BMI > 25), regelmäßiger Alkoholkonsum und Rauchen. Die Pathophysiologie einer GERD basiert auf einer defekten Antirefluxbarriere. Treibende Kraft ist dabei der abdominothorakale Druckgradient, der zeitlebens auf den gastroösophagealen Übergang einwirkt und diesen Richtung thorakal verlagern kann. Die Diagnosestellung umfasst Symptomerhebung, Gastroskopie inklusiver Probenentnahme und der funktionellen Abklärung. Die Indikation zur Operation sowie die Wahl des Verfahrens wird individuell abgestimmt. Langzeitbeobachtungen (über 20 Jahre) einzelner Zentren und die Qualitätssicherung großer internationaler Gesellschaften attestieren der chirurgischen Antirefluxtherapie exzellente Lebensqualität und sehr gute Refluxkontrolle. Eigene Daten untermauern dieses Ergebnis ebenfalls.
Numerical investigation of particle motion at the steel—slag interface in continuous casting using VOF method and dynamic overset grids
Authors: Zhang Xiaomeng , Pirker Stefan , Saeedipour Mahdi
Published: January 2022

The capillary interactions are prominent for a micro-sized particle at the steel—slag interface. In this study, the dynamics of a spherical particle interacting with the steel—slag interface is numerically investigated using the volume of fluid method in combination with the overset grid technique to account for particle motion. The simulations have shown the particle’s separation process at the interface and successfully captured the formation and continuous evolution of a meniscus in the course of particle motion. A sensitivity analysis on the effect of different physical parameters in the steel—slag—particle system is also conducted. The result indicates that the wettability of particle with the slag phase is the main factor affecting particle separation behavior (trapped at the interface or fully separated into slag). Higher interfacial tension of fluid interface and smaller particle size can speed up the particle motion but have less effect on the equilibrium position for particle staying at the interface. In comparison, particle density shows a minor influence when the motion is dominated by the capillary effect. By taking account of the effect of meniscus and capillary forces on a particle, this study provides a more accurate simulation of particle motion in the vicinity of the steel—slag interface and enables further investigation of more complex situations.
Predictors of COVID-19 Fatality: A Worldwide Analysis of the Pandemic over Time and in Latin America
Authors: Rojas Dayana , Saavedra Jorge , Petrova Mariya , Pan Yue , Szapocznik José
Published: January 2022

SARS-CoV-2 has infected over one hundred million people worldwide and has affected Latin America particularly severely in terms of both cases and deaths. This study aims to determine the association between SARS-CoV-2 testing and COVID-19 fatality rate worldwide over 8 months and to examine how this relationship differs between Latin America and all other countries. This cross-sectional study used March 2021 data from 169 countries. Multivariate regressions predicted COVID-19 fatality (outcome) from the number of SARS-CoV-2 tests (exposure), while controlling for other predictors. Results for March 2021 were compared to results from June 2020. Additionally, results for Latin America were also compared to all other countries except Latin American for March 2021. SARS-CoV-2 testing was associated with a significant decrease in COVID-19 fatality rate in both June 2020 and March 2021 (RR = 0.92; 95% CI 0.87–0.96 and RR = 0.86; 95% CI 0.74–1.00, respectively). SARS-CoV-2 testing was associated with a significant decrease in COVID-19 fatality rate in Latin American countries but not in all other countries (RR = 0.45; 95% CI 0.23–0.89 and RR = 0.95; 95% CI 0.82–1.11, respectively). However, the difference between the risk ratios for June 2020 and March 2021 and between the risk ratios for Latin America and all other countries were not statistically significant. Increased SARS-CoV-2 testing may be a significant predictor of lower COVID-19 case fatality rate, specifically in Latin American countries, due to the existence of a strong association, which may have driven the worldwide results.
Pontormo and the Art of Devotion in Renaissance Italy
Authors: Maratsos Jessica A.
Published: January 2022

Both lauded and criticized for his pictorial eclecticism, the Florentine artist Jacopo Carrucci, known as Pontormo, created some of the most visually striking religious images of the Renaissance.  These paintings, which challenged prevailing illusionistic conventions, mark a unique contribution into the complex relationship between artistic innovation and Christian traditions in the first half of the sixteenth century. Pontormo's sacred works are generally interpreted as objects that reflect either pure aesthetic experimentation, or personal and cultural anxiety. Jessica Maratsos, however, argues that Pontormo employed stylistic change deliberately for novel devotional purposes. As a painter, he was interested in the various modes of expression and communication - direct address, tactile evocation, affective incitement - as deployed in a wide spectrum of devotional culture, from sacri monti, to Michelangelo's marble sculptures, to evangelical lectures delivered at the Accademia Fiorentina. Maratsos shows how Pontormo translated these modes in ways that prompt a critical rethinking of Renaissance devotional art.
Aerothermodynamics and Jet Propulsion
Authors: Cizmas Paul G. A.
Published: January 2022

Get up to speed with this robust introduction to the aerothermodynamics principles underpinning jet propulsion, and learn how to apply these principles to jet engine components. Suitable for undergraduate students in aerospace and mechanical engineering, and for professional engineers working in jet propulsion, this textbook includes consistent emphasis on fundamental phenomena and key governing equations, providing students with a solid theoretical grounding on which to build practical understanding; clear derivations from first principles, enabling students to follow the reasoning behind key assumptions and decisions, and successfully apply these approaches to new problems; practical examples grounded in real-world jet propulsion scenarios illustrate new concepts throughout the book, giving students an early introduction to jet and rocket engine considerations; and online materials for course instructors, including solutions, figures, and software resources, to enhance student teaching.
Beyond Reassurance: The Reputational Effect of Cultural Reforms in Peace Agreements
Authors: Fontana Giuditta , Masiero Ilaria
Published: January 2022

We explore whether including cultural reforms in an intra-state peace accord facilitates its success. We distinguish between accommodationist and integrationist cultural provisions and employ a mixed research method combining negative binomial regression on a data set of all intra-state political agreements concluded between 1989 and 2017, and an in-depth analysis of the 1998 Good Friday Agreement for Northern Ireland. We recognize the important reassuring effect of accommodationist cultural reforms in separatist conflicts. However, we also find that they have an important and hitherto overlooked reputational effect across all conflict types. By enhancing the reputation of negotiating leaders, accommodationist cultural provisions contribute to ending violence by preventing leadership challenges, rebel fragmentation and remobilization across all civil conflicts. By the same logic, and despite the overwhelming emphasis of peace agreements on integrationist cultural initiatives, integrationist cultural reforms problematize leaders' ability to commit to pacts and to ensure compliance among their rank and file.
Epidemics from the Population Perspective
Authors: Fuller Jonathan
Published: January 2022

Many epidemics consist in individuals spreading infection to others. From the population perspective, they also have population characteristics important in modeling, explaining, and intervening in epidemics. I analyze epidemiology’s contemporary population perspective through the example of epidemics by examining two central principles attributed to Geoffrey Rose: a distinction between the causes of cases and the causes of incidence, and between “high-risk” and “population” strategies of prevention. Both principles require revision or clarification to capture the sense in which they describe distinct perspectives on the same phenomenon (such as an epidemic), each perspective capturing a different level of contrastive analysis.
The Bound State Answer to the Special Composition Question
Authors: Calosi Claudio
Published: January 2022

This paper provides the first thorough assessment of a physics-based answer, the Bound State Answer (BSA), to the Special Composition Question (SCQ). According to the BSA some objects compose something if they are in a common bound state. The reasons to endorse such an answer, in particular, motivations coming from empirical adequacy and conservativeness, precision, simplicity, and parsimony, are critically addressed. I then go on to compare the BSA to other moderate answers to the SCQ and consider whether objections raised against such answers can be raised against the BSA as well. I finally relate the discussion with mereological pluralism.
Symmetries as Humean Metalaws
Authors: Duguid Callum
Published: January 2022

Symmetry principles are a central part of contemporary physics, yet there has been surprisingly little metaphysical work done on them. This article develops the Wignerian treatment of symmetries as higher-order laws—metalaws—within a Humean framework of lawhood. Lange has raised two obstacles to Humean metalaws, and the article shows that the account has the resources available to respond to both. It is argued that this framework for Humean metalaws stands as an example of naturalistic metaphysics, able to bring Humeanism into contact with the practice of actual science without giving up on the central denial of necessary connections.
THE TENSION BETWEEN THE REAL AND THE PAPER DEAL CONCERNING “NO ORAL MODIFICATION” CLAUSES
Authors: Finkelstein Elad , Lifshitz Shahar
Published: January 2022

This article proposes a new model for the regulation of no oral modification (NOM) clauses. First, the article seeks to offer a deeper understanding of the wishes of the parties in contracts from the perspective of parties' autonomy, distinguishing between intentions focused on the legal relationships and those focused on extra-contractual relations. Second, we explain how enforcement of NOM clauses may influence the parties' relations. Third, the article includes an economic analysis clarifying the roles of efficiency and institutional considerations in the NOM phenomenon. Applying the results of our analysis, we propose a comprehensive model for regulating NOM clauses. The key innovation of the model is context-dependent regulation differentiating among sophisticated and equally powerful parties, unsophisticated parties of equal power, and relationships with power disparities. Our model also offers an auxiliary test to help distinguish between parties' legal relationships and their extra-contractual relations.
Local environmental context determines the colonisation of leaf shelters by arthropods: an experimental study
Authors: Novais Samuel , Hernández-Ortiz Vicente , Rodríguez-Hernández Karla , Quesada Mauricio , Fernandes G. Wilson , Bañol-Pérez Carolina , Sánchez-García Edgar A. , Aldaba-Núñez Fabian A. , Méndez-Vázquez Luis J. , Ochoa Manuel , Zurita-Solís Marisol A. , Aguirre-Jaimes Armando
Published: January 2022

The magnitude of facilitation by shelter-building engineers on community structure is expected to be greater when they increase limited resources in the environment. We evaluated the influence of local environmental context on the colonisation of leaf shelters by arthropods in a Mexican evergreen tropical rainforest. We compared the species richness and abundance of arthropods (total and for different guilds) colonising artificially rolled leaves in habitats differing in understory heterogeneity (forest edge > old-growth forests > living fences). Arthropod abundance of the most representative arthropod taxa (i.e., Araneae, Blattodea, Collembola and Psocoptera) colonising the rolled leaves was greater at forest edge, a trend also observed for average arthropod abundance, and for detritivore and predator guilds. In addition, fewer arthropod species and individuals colonised the rolled leaves in the living fence habitat, a trend also observed for most arthropod guilds. As forest edge is expected to have a greater arthropod diversity and stronger density-dependent interactions, a greater limitation of refuges from competitors or predators may have determined the higher colonisation of the rolled leaves in this habitat. Our results demonstrate that local environment context is an important factor that affects the colonisation of arthropods in leaf shelters.
Association of Dietary Approaches to Stop Hypertension diet and Mediterranean diet with blood pressure in less-developed ethnic minority regions
Authors: Dai Suyao , Xiao Xiong , Xu Chuanzhi , Jiao Yan , Qin Zixiu , Meng Jiantong , Zuo Haojiang , Zeng Peibin , Tang Dan , Wu Xinyu , Nima Qucuo , Quzong Deji , Zhao Xing
Published: January 2022

Objective:

We aimed to investigate the associations of Dietary Approaches to Stop Hypertension (DASH)-style diet and Mediterranean-style diet with blood pressure (BP) in less-developed ethnic minority regions (LEMR).

Design:

Cross-sectional study.

Setting:

Dietary intakes were assessed by a validated FFQ. Dietary quality was assessed by the DASH-style diet score and the alternative Mediterranean-style diet (aMED) score. The association between dietary quality and BP was evaluated using multivariate linear regression model. We further examined those associations in subgroups of BP level.

Participants:

A total of 81 433 adults from the China Multi-Ethnic Cohort (CMEC) study were included in this study.

Results:

In the overall population, compared with the lowest quintile, the highest quintile of DASH-style diet score was negatively associated with systolic BP (SBP) (coefficient –2·78, 95 % CI –3·15, –2·41; Pfor trend < 0·001), while the highest quintile of aMED score had a weaker negative association with SBP (coefficient –1·43, 95 % CI –1·81, –1·05; Pfor trend < 0·001). Both dietary indices also showed a weaker effect on diastolic BP (coefficient for DASH-style diet –1·06, 95 % CI –1·30, –0·82; coefficient for aMED –0·43, 95 % CI –0·68, –0·19). In the subgroup analysis, both dietary indices showed a stronger beneficial effect on SBP in the hypertension group than in either of the other subgroups.

Conclusion:

Our results indicated that the healthy diet originating from Western developed countries can also have beneficial effects on BP in LEMR. DASH-style diet may be a more appropriate recommendation than aMED as part of a dietary strategy to control BP, especially in hypertensive patients.
Did Volcanoes Accelerate the Fall of Chinese Dynasties?
Authors: Hornyak Tim
Published: January 2022

After analyzing ice cores and historical documents, researchers found a link between eruptions and political change in China over the past 2 millennia.
A qualitative analysis of dental professionals’ beliefs and concerns about providing aerosol generating procedures early in the COVID-19 pandemic
Authors: Cousins Matthew , Patel Kajal , Araujo Mariana , Beaton Laura , Scott Claire , Stirling Douglas , Young Linda , Knights Jennifer
Published: January 2022

Introduction

In response to the COVID-19 pandemic, the Scottish Dental Clinical Effectiveness Programme (SDCEP) initiated a rapid review of the evidence related to the generation and mitigation of aerosols in dental practice. To support this review, a survey was distributed to better understand the provision of aerosol generating procedures (AGPs) in dentistry.

Methods

An online questionnaire was distributed to dental professionals asking about their current practice and beliefs about AGPs. Data were analysed using qualitative content analysis.

Results

Analysis revealed confusion and uncertainty regarding mitigation of AGPs. There was also frustration and scepticism over the risk of SARS-COV-2 transmission within dental settings, the evidence underpinning the restrictions and the leadership and guidance being provided, as well as concern over financial implications and patient and staff safety.

Discussion

The frustration and concerns expressed by respondents mirrored findings from other recent studies and suggest there is a need for reflection within the profession so that lessons can be learned to better support staff and patients.

Conclusion

Understanding the profession’s views about AGP provision contributed to the SDCEP rapid review and provides insights to help inform policymakers and leaders in anticipation not only of future pandemics but in considering the success of any large scale and/or rapid organisational change.
Focal adhesion kinase plays a dual role in TRAIL resistance and metastatic outgrowth of malignant melanoma
Authors: Del Mistro Greta , Riemann Shamala , Schindler Sebastian , Beissert Stefan , Kontermann Roland E. , Ginolhac Aurelien , Halder Rashi , Presta Luana , Sinkkonen Lasse , Sauter Thomas , Kulms Dagmar
Published: January 2022

Despite remarkable advances in therapeutic interventions, malignant melanoma (MM) remains a life-threating disease. Following high initial response rates to targeted kinase-inhibition metastases quickly acquire resistance and present with enhanced tumor progression and invasion, demanding alternative treatment options. We show 2nd generation hexameric TRAIL-receptor-agonist IZI1551 (IZI) to effectively induce apoptosis in MM cells irrespective of the intrinsic BRAF/NRAS mutation status. Conditioning to the EC50 dose of IZI converted the phenotype of IZI-sensitive parental MM cells into a fast proliferating and invasive, IZI-resistant metastasis. Mechanistically, we identified focal adhesion kinase (FAK) to play a dual role in phenotype-switching. In the cytosol, activated FAK triggers survival pathways in a PI3K- and MAPK-dependent manner. In the nucleus, the FERM domain of FAK prevents activation of wtp53, as being expressed in the majority of MM, and consequently intrinsic apoptosis. Caspase-8-mediated cleavage of FAK as well as FAK knockdown, and pharmacological inhibition, respectively, reverted the metastatic phenotype-switch and restored IZI responsiveness. FAK inhibition also re-sensitized MM cells isolated from patient metastasis that had relapsed from targeted kinase inhibition to cell death, irrespective of the intrinsic BRAF/NRAS mutation status. Hence, FAK-inhibition alone or in combination with 2nd generation TRAIL-receptor agonists may be recommended for treatment of initially resistant and relapsed MM, respectively.
Danger signal extracellular calcium initiates differentiation of monocytes into SPP1/osteopontin-producing macrophages
Authors: Murthy Supriya , Karkossa Isabel , Schmidt Caroline , Hoffmann Anne , Hagemann Tobias , Rothe Kathrin , Seifert Olga , Anderegg Ulf , von Bergen Martin , Schubert Kristin , Rossol Manuela
Published: January 2022

The danger signal extracellular calcium is pathophysiologically increased in the synovial fluid of patients with rheumatoid arthritis (RA). Calcium activates the NLRP3-inflammasome via the calcium-sensing receptor in monocytes/macrophages primed by lipopolysaccharide, and this effect is mediated by the uptake of calciprotein particles (CPPs) formed out of calcium, phosphate, and fetuin-A. Aim of the study was to unravel the influence of calcium on monocytes when the priming signal is not present. Monocytes were isolated from the blood of healthy controls and RA patients. Macrophages were characterized using scRNA-seq, DNA microarray, and proteomics. Imaging flow cytometry was utilized to study intracellular events. Here we show that extracellular calcium and CPPs lead to the differentiation of monocytes into calcium-macrophages when the priming signal is absent. Additional growth factors are not needed, and differentiation is triggered by calcium-dependent CPP-uptake, lysosomal alkalization due to CPP overload, and TFEB- and STAT3-dependent increased transcription of the lysosomal gene network. Calcium-macrophages have a needle-like shape, are characterized by excessive, constitutive SPP1/osteopontin production and a strong pro-inflammatory cytokine response. Calcium-macrophages differentiated out of RA monocytes show a stronger manifestation of this phenotype, suggesting the differentiation process might lead to the pro-inflammatory macrophage response seen in the RA synovial membrane.
Multimodal CTC detection using stem cell antigen-specific immunosilica particles and immunofluorescent quantum dots
Authors: Sobhanan Jeladhara , Takano Yuta , Sugino Sakiko , Hirata Eri , Yamamura Shohei , Biju Vasudevanpillai
Published: January 2022

Amid the COVID-19 pandemic, cancer continues to be the most devastating disease worldwide. Liquid biopsy of circulating tumor cells (CTCs) has recently become a painless and noninvasive tool for obtaining carcinoma cell samples for molecular profiling. Here, we report efficient detection and collection of cancer cells in blood samples by combining stem cell antigen (CD44)-specific immunosilica particles and immunofluorescent quantum dots with spectrally and temporally resolved single-photon counting. We accurately detect 1–10 cells among 100 cancer cells of the breast, lungs, or cervix in 1 mL blood samples. In addition, the bright and narrowband emission of CdSe/ZnS quantum dots enables temporally and spectrally resolved photon counting for multiplexed cancer cell detection. The cancer cell-specific and large immunosilica particles helped us collect the specific cells. We validate the detection efficiency and multimodality of this strategy by time-stamped and energy-dispersed single-photon counting of orange- and red-emitting quantum dots and green-fluorescing nuclei stained with Syto-13/25 dye. Thus, the present work highlights the prospects of multimodal CTC detection for noninvasive cancer screening and postsurgical or therapeutic follow-up.
A measurement strategy to address disparities across household energy burdens
Authors: Scheier Eric , Kittner Noah
Published: January 2022

Energy inequity is an issue of increasing urgency. Few policy-relevant datasets evaluate the energy burden of typical American households. Here, we develop a framework using Net Energy Analysis and household socioeconomic data to measure systematic energy inequity among critical groups that need policy attention. We find substantial instances of energy poverty in the United States – 16% of households experience energy poverty as presently defined as spending more than 6% of household income on energy expenditures. More than 5.2 million households above the Federal Poverty Line face energy poverty, disproportionately burdening Black, Hispanic, and Native American communities. For solar, wind, and energy efficiency to address socioeconomic mobility, programs must reduce energy expenditures by expanding eligibility requirements for support and access to improved conservation measures, efficiency upgrades, and distributed renewables. We recommend the United States develop a more inclusive federal energy poverty categorization that increases assistance for household energy costs.
Observation of second sound in graphite over 200 K
Authors: Ding Zhiwei , Chen Ke , Song Bai , Shin Jungwoo , Maznev Alexei A. , Nelson Keith A. , Chen Gang
Published: January 2022

Second sound refers to the phenomenon of heat propagation as temperature waves in the phonon hydrodynamic transport regime. We directly observe second sound in graphite at temperatures of over 200 K using a sub-picosecond transient grating technique. The experimentally determined dispersion relation of the thermal-wave velocity increases with decreasing grating period, consistent with first-principles-based solution of the Peierls-Boltzmann transport equation. Through simulation, we reveal this increase as a result of thermal zero sound—the thermal waves due to ballistic phonons. Our experimental findings are well explained with the interplay among three groups of phonons: ballistic, diffusive, and hydrodynamic phonons. Our ab initio calculations further predict a large isotope effect on the properties of thermal waves and the existence of second sound at room temperature in isotopically pure graphite.
Can electric fields drive chemistry for an aqueous microdroplet?
Authors: Hao Hongxia , Leven Itai , Head-Gordon Teresa
Published: January 2022

Reaction rates of common organic reactions have been reported to increase by one to six orders of magnitude in aqueous microdroplets compared to bulk solution, but the reasons for the rate acceleration are poorly understood. Using a coarse-grained electron model that describes structural organization and electron densities for water droplets without the expense of ab initio methods, we investigate the electric field distributions at the air-water interface to understand the origin of surface reactivity. We find that electric field alignments along free O–H bonds at the surface are ~16 MV/cm larger on average than that found for O–H bonds in the interior of the water droplet. Furthermore, electric field distributions can be an order of magnitude larger than the average due to non-linear coupling of intramolecular solvent polarization with intermolecular solvent modes which may contribute to even greater surface reactivity for weakening or breaking chemical bonds at the droplet surface.
Identification of a Kitaev quantum spin liquid by magnetic field angle dependence
Authors: Hwang Kyusung , Go Ara , Seong Ji Heon , Shibauchi Takasada , Moon Eun-Gook
Published: January 2022

Quantum spin liquids realize massive entanglement and fractional quasiparticles from localized spins, proposed as an avenue for quantum science and technology. In particular, topological quantum computations are suggested in the non-abelian phase of Kitaev quantum spin liquid with Majorana fermions, and detection of Majorana fermions is one of the most outstanding problems in modern condensed matter physics. Here, we propose a concrete way to identify the non-abelian Kitaev quantum spin liquid by magnetic field angle dependence. Topologically protected critical lines exist on a plane of magnetic field angles, and their shapes are determined by microscopic spin interactions. A chirality operator plays a key role in demonstrating microscopic dependences of the critical lines. We also show that the chirality operator can be used to evaluate topological properties of the non-abelian Kitaev quantum spin liquid without relying on Majorana fermion descriptions. Experimental criteria for the non-abelian spin liquid state are provided for future experiments.
HIF-1 Interacts with TRIM28 and DNA-PK to release paused RNA polymerase II and activate target gene transcription in response to hypoxia
Authors: Yang Yongkang , Lu Haiquan , Chen Chelsey , Lyu Yajing , Cole Robert N. , Semenza Gregg L.
Published: January 2022

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that acts as a regulator of oxygen (O2) homeostasis in metazoan species by binding to hypoxia response elements (HREs) and activating the transcription of hundreds of genes in response to reduced O2 availability. RNA polymerase II (Pol II) initiates transcription of many HIF target genes under non-hypoxic conditions but pauses after approximately 30–60 nucleotides and requires HIF-1 binding for release. Here we report that in hypoxic breast cancer cells, HIF-1 recruits TRIM28 and DNA-dependent protein kinase (DNA-PK) to HREs to release paused Pol II. We show that HIF-1α and TRIM28 assemble the catalytically-active DNA-PK heterotrimer, which phosphorylates TRIM28 at serine-824, enabling recruitment of CDK9, which phosphorylates serine-2 of the Pol II large subunit C-terminal domain as well as the negative elongation factor to release paused Pol II, thereby stimulating productive transcriptional elongation. Our studies reveal a molecular mechanism by which HIF-1 stimulates gene transcription and reveal that the anticancer effects of drugs targeting DNA-PK in breast cancer may be due in part to their inhibition of HIF-dependent transcription.
Electronic nature of charge density wave and electron-phonon coupling in kagome superconductor KV3Sb5
Authors: Luo Hailan , Gao Qiang , Liu Hongxiong , Gu Yuhao , Wu Dingsong , Yi Changjiang , Jia Junjie , Wu Shilong , Luo Xiangyu , Xu Yu , Zhao Lin , Wang Qingyan , Mao Hanqing , Liu Guodong , Zhu Zhihai , Shi Youguo , Jiang Kun , Hu Jiangping , Xu Zuyan , Zhou X. J.
Published: January 2022

The Kagome superconductors AV3Sb5 (A = K, Rb, Cs) have received enormous attention due to their nontrivial topological electronic structure, anomalous physical properties and superconductivity. Unconventional charge density wave (CDW) has been detected in AV3Sb5. High-precision electronic structure determination is essential to understand its origin. Here we unveil electronic nature of the CDW phase in our high-resolution angle-resolved photoemission measurements on KV3Sb5. We have observed CDW-induced Fermi surface reconstruction and the associated band folding. The CDW-induced band splitting and the associated gap opening have been revealed at the boundary of the pristine and reconstructed Brillouin zones. The Fermi surface- and momentum-dependent CDW gap is measured and the strongly anisotropic CDW gap is observed for all the V-derived Fermi surface. In particular, we have observed signatures of the electron-phonon coupling in KV3Sb5. These results provide key insights in understanding the nature of the CDW state and its interplay with superconductivity in AV3Sb5 superconductors.
Ductal carcinoma in situ: a risk prediction model for the underestimation of invasive breast cancer
Authors: Park Ko Woon , Kim Seon Woo , Han Heewon , Park Minsu , Han Boo-Kyung , Ko Eun Young , Choi Ji Soo , Cho Eun Yoon , Cho Soo Youn , Ko Eun Sook
Published: January 2022

Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) may be diagnosed with invasive breast cancer after excision. We evaluated the preoperative clinical and imaging predictors of DCIS that were associated with an upgrade to invasive carcinoma on final pathology and also compared the diagnostic performance of various statistical models. We reviewed the medical records; including mammography, ultrasound (US), and magnetic resonance imaging (MRI) findings; of 644 patients who were preoperatively diagnosed with DCIS and who underwent surgery between January 2012 and September 2018. Logistic regression and three machine learning methods were applied to predict DCIS underestimation. Among 644 DCIS biopsies, 161 (25%) underestimated invasive breast cancers. In multivariable analysis, suspicious axillary lymph nodes (LNs) on US (odds ratio [OR], 12.16; 95% confidence interval [CI], 4.94–29.95; P < 0.001) and high nuclear grade (OR, 1.90; 95% CI, 1.24–2.91; P = 0.003) were associated with underestimation. Cases with biopsy performed using vacuum-assisted biopsy (VAB) (OR, 0.42; 95% CI, 0.27–0.65; P < 0.001) and lesion size <2 cm on mammography (OR, 0.45; 95% CI, 0.22–0.90; P = 0.021) and MRI (OR, 0.29; 95% CI, 0.09–0.94; P = 0.037) were less likely to be upgraded. No significant differences in performance were observed between logistic regression and machine learning models. Our results suggest that biopsy device, high nuclear grade, presence of suspicious axillary LN on US, and lesion size on mammography or MRI were independent predictors of DCIS underestimation.
All-fiber source and sorter for multimode correlated photons
Authors: Sulimany Kfir , Bromberg Yaron
Published: January 2022

Photons occupying multiple spatial modes hold a great promise for implementing high-dimensional quantum communication. We use spontaneous four-wave mixing to generate multimode photon pairs in a few-mode fiber. We show the photons are correlated in the fiber mode basis using an all-fiber mode sorter. Our demonstration offers an essential building block for realizing high-dimensional quantum protocols based on standard, commercially available fibers, in an all-fiber configuration.
Native point defects and their implications for the Dirac point gap at MnBi2Te4(0001)
Authors: Garnica M. , Otrokov M. M. , Aguilar P. Casado , Klimovskikh I. I. , Estyunin D. , Aliev Z. S. , Amiraslanov I. R. , Abdullayev N. A. , Zverev V. N. , Babanly M. B. , Mamedov N. T. , Shikin A. M. , Arnau A. , de Parga A. L. Vázquez , Chulkov E. V. , Miranda R.
Published: January 2022

We study the surface crystalline and electronic structures of the antiferromagnetic topological insulator MnBi2Te4 using scanning tunneling microscopy/spectroscopy (STM/S), micro(μ)-laser angle-resolved photoemission spectroscopy (ARPES), and density functional theory calculations. Our STM images reveal native point defects at the surface that we identify as BiTe antisites and MnBi substitutions. Bulk X-ray diffraction further evidences the presence of the Mn-Bi intermixing. Overall, our characterizations suggest that the defects concentration is nonuniform within crystals and differs from sample to sample. Consistently, the ARPES and STS experiments reveal that the Dirac point gap of the topological surface state is different for different samples and sample cleavages, respectively. Our calculations show that the antiparallel alignment of the MnBi moments with respect to those of the Mn layer can indeed cause a strong reduction of the Dirac point gap size. The present study provides important insights into a highly debated issue of the MnBi2Te4 Dirac point gap.
Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy
Authors: Villanueva Paola , Wadia Ushma , Crawford Nigel , Messina Nicole L. , Kollmann Tobias R. , Lucas Michaela , Manning Laurens , Richmond Peter , Pittet Laure F. , Curtis Nigel
Published: January 2022

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.
Genetic continuity of Indo-Iranian speakers since the Iron Age in southern Central Asia
Authors: Guarino-Vignon Perle , Marchi Nina , Bendezu-Sarmiento Julio , Heyer Evelyne , Bon Céline
Published: January 2022

Since prehistoric times, southern Central Asia has been at the crossroads of the movement of people, culture, and goods. Today, the Central Asian populations are divided into two cultural and linguistic groups: the Indo-Iranian and the Turko-Mongolian groups. Previous genetic studies unveiled that migrations from East Asia contributed to the spread of Turko-Mongolian populations in Central Asia and the partial replacement of the Indo-Iranian populations. However, little is known about the origin of the latters. To shed light on this, we compare the genetic data on two current-day Indo-Iranian populations — Yaghnobis and Tajiks — with genome-wide data from published ancient individuals. The present Indo-Iranian populations from Central Asia display a strong genetic continuity with Iron Age samples from Turkmenistan and Tajikistan. We model Yaghnobis as a mixture of 93% Iron Age individual from Turkmenistan and 7% from Baikal. For the Tajiks, we observe a higher Baikal ancestry and an additional admixture event with a South Asian population. Our results, therefore, suggest that in addition to a complex history, Central Asia shows a remarkable genetic continuity since the Iron Age, with only limited gene flow.
Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer
Authors: Hsu Ju-Yi , Chang Chee-Jen , Cheng Jur-Shan
Published: January 2022

Individuals diagnosed with metastatic triple-negative breast cancer (mTNBC) suffer worse survival rates than their metastatic non-TNBC counterparts. There is little information on survival, treatment patterns, and medical costs of mTNBC patients in Asia. Therefore, this study aimed to examine 5-year survival, regimens of first-line systemic therapy, and healthcare costs of mTNBC patients in Taiwan. Adult females newly diagnosed with TNBC and non-TNBC as well as their survival data, treatment regimens and costs of health services were identified and retrieved from the Cancer Registry database, Death Registry database, and National Health Insurance (NHI) claims database. A total of 9691 (19.27%) women were identified as TNBC among overall BC. The 5-year overall survival rate of TNBC and non-TNBC was 81.28% and 86.50%, respectively, and that of mTNBC and metastatic non-TNBC was 10.81% and 33.46%, respectively. The majority of mTNBC patients received combination therapy as their first-line treatment (78.14%). The 5-year total cost in patients with metastatic non-TNBC and with mTNBC was NTD1,808,693 and NTD803,445, respectively. Higher CCI scores were associated with an increased risk of death and lower probability of receiving combination chemotherapy. Older age was associated with lower 5-year medical costs. In sum, mTNBC patients suffered from poorer survival and incurred lower medical costs than their metastatic non-TNBC counterparts. Future research will be needed when there are more treatment options available for mTNBC patients.
Opto-electrical bimodal recording of neural activity in awake head-restrained mice
Authors: Cobar Luis Fernando , Kashef Alireza , Bose Krishnashish , Tashiro Ayumu
Published: January 2022

Electrical and optical monitoring of neural activity is major approaches for studying brain functions. Each has its own set of advantages and disadvantages, such as the ability to determine cell types and temporal resolution. Although opto-electrical bimodal recording is beneficial by enabling us to exploit the strength of both approaches, it has not been widely used. In this study, we devised three methods of bimodal recording from a deep brain structure in awake head-fixed mice by chronically implanting a gradient-index (GRIN) lens and electrodes. First, we attached four stainless steel electrodes to the side of a GRIN lens and implanted them in a mouse expressing GCaMP6f in astrocytes. We simultaneously recorded local field potential (LFP) and GCaMP6f signal in astrocytes in the hippocampal CA1 area. Second, implanting a silicon probe electrode mounted on a custom-made microdrive within the focal volume of a GRIN lens, we performed bimodal recording in the CA1 area. We monitored LFP and fluorescent changes of GCaMP6s-expressing neurons in the CA1. Third, we designed a 3D-printed scaffold to serve as a microdrive for a silicon probe and a holder for a GRIN lens. This scaffold simplifies the implantation process and makes it easier to place the lens and probe accurately. Using this method, we recorded single unit activity and LFP electrically and GCaMP6f signals of single neurons optically. Thus, we show that these opto-electrical bimodal recording methods using a GRIN lens and electrodes are viable approaches in awake head-fixed mice.
Cortical morphology predicts placebo response in multiple sclerosis
Authors: Cherkasova Mariya V. , Fu Jessie F. , Jarrett Michael , Johnson Poljanka , Abel Shawna , Tam Roger , Rauscher Alexander , Sossi Vesna , Kolind Shannon , Li David K. B. , Sadovnick A. Dessa , Machan Lindsay , Girard J. Marc , Emond Francois , Vosoughi Reza , Traboulsee Anthony , Stoessl A. Jon
Published: January 2022

Despite significant insights into the neural mechanisms of acute placebo responses, less is known about longer-term placebo responses, such as those seen in clinical trials, or their interactions with brain disease. We examined brain correlates of placebo responses in a randomized trial of a then controversial and now disproved endovascular treatment for multiple sclerosis. Patients received either balloon or sham extracranial venoplasty and were followed for 48 weeks. Venoplasty had no therapeutic effect, but a subset of both venoplasty- and sham-treated patients reported a transient improvement in health-related quality of life, suggesting a placebo response. Placebo responders did not differ from non-responders in total MRI T2 lesion load, count or location, nor were there differences in normalized brain volume, regional grey or white matter volume or cortical thickness (CT). However, responders had higher lesion activity. Graph theoretical analysis of CT covariance showed that non-responders had a more small-world-like CT architecture. In non-responders, lesion load was inversely associated with CT in somatosensory, motor and association areas, precuneus, and insula, primarily in the right hemisphere. In responders, lesion load was unrelated to CT. The neuropathological process in MS may produce in some a cortical configuration less capable of generating sustained placebo responses.
Piezoelectric energy harvester with double cantilever beam undergoing coupled bending-torsion vibrations by width-splitting method
Authors: Song Jiawen , Sun Guihong , Zeng Xin , Li Xiangwen , Bai Quan , Zheng Xuejun
Published: January 2022

We propose piezoelectric energy harvester (PEH) with double-cantilever-beam (DCB) undergoing coupled bending-torsion vibrations by combining width-splitting method and asymmetric mass, in order that more ambient energy could be harvested from environmental vibration with multiple-frequency excitation. The geometrical dimensions are optimized for PEHDCB, when the maximum of output peak voltages Up-max and resonance frequency difference (Δf0) between the first and second modes are chosen as optimization objectives based on orthogonal test method. The energy harvesting efficiency is evaluated by the proportion of half-power bandwidth and quality factor, and the experimental and simulation results are compared to verify reliability. The Up-max1 and Pp-max1 are increased 25.2% and 57.3% for PEHDCB under the multi-frequency excitation, when the split-width method is applied into PEH with single-cantilever-beam (SCB) undergoing coupled bending-torsion vibrations. The deviations of Up-max1 and f0 are at the ranges of 4.9–14.2% and 2.2–2.5% for PEHDCB under the different mass ratios, and the measurement reliability is acceptable considering incomplete clamping, damping and inevitable assembly effects. The energy harvesting efficiency of PEHDCB presented is much higher than that of the conventional PEHSCB from environmental vibration with multiple-frequency excitation.
Spatiotemporal dynamics of syphilis in pregnant women and congenital syphilis in the state of São Paulo, Brazil
Authors: Medeiros Joelma Alexandra Ruberti , Yamamura Mellina , da Silva Zilda Pereira , Domingues Carmen Silvia Bruniera , Waldman Eliseu Alves , Chiaravalloti-Neto Francisco
Published: January 2022

We aimed to estimate the occurrence of syphilis in pregnant women (SPW) and congenital syphilis (CS) in the municipalities of the state of São Paulo (SP) and evaluate their relationship with socioeconomic, demographic, and health care variables. We developed an ecological study based on secondary data of SPW and CS with spatiotemporal components from 645 municipalities in SP including data from 2007 to 2018. We modeled the data in a Bayesian context, considered spatial and temporal random effects, and used binomial negative probability distributions. We found a continuous increase in the relative temporal risk of SPW, from 2007 to 2018, and CS, from 2007 to 2017, when their incidences increased by 8.6 and 6.6 times, respectively. This increase occurred en bloc in practically all municipalities of SP. The increase in SPW was associated with teenage pregnancy, municipalities with a large number of inhabitants, and acquired immunodeficiency syndrome (AIDS) incidence. The increase in CS was associated with municipalities with a large number of inhabitants, incomplete antenatal care, and AIDS incidence. Although actions to control these diseases are required in all municipalities of SP, the identification of high-risk areas points to priority regions for development.
Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids
Authors: Singh Lovepreet , Fontinha Diana , Francisco Denise , Prudêncio Miguel , Singh Kamaljit
Published: January 2022

With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.