bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontal sinuses and human evolution
Authors: Balzeau Antoine , Albessard-Ball Lou , Kubicka Anna Maria , Filippo Andréa , Beaudet Amélie , Santos Elena , Bienvenu Thibault , Arsuaga Juan-Luis , Bartsiokas Antonis , Berger Lee , Bermúdez de Castro José María , Brunet Michel , Carlson Kristian J. , Daura Joan , Gorgoulis Vassilis G. , Grine Frederick E. , Harvati Katerina , Hawks John , Herries Andy , Hublin Jean-Jacques , Hui Jiaming , Ives Rachel , Joordens Josephine A. , Kaifu Yousuke , Kouloukoussa Mirsini , Léger Baptiste , Lordkipanidze David , Margvelashvili Ann , Martin Jesse , Martinón-Torres María , May Hila , Mounier Aurélien , du Plessis Anton , Rae Todd , Röding Carolin , Sanz Montserrat , Semal Patrick , Stratford Dominic , Stringer Chris , Tawane Mirriam , Temming Heiko , Tsoukala Evangelia , Zilhão João , Zipfel Bernhard , Buck Laura T.
Published: October 2022

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species’ holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of
Homo erectus
. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species.
Megafauna extinctions produce idiosyncratic Anthropocene assemblages
Authors: Amir Zachary , Moore Jonathan H. , Negret Pablo Jose , Luskin Matthew Scott
Published: October 2022

The “trophic downgrading of planet Earth” refers to the systematic decline of the world’s largest vertebrates. However, our understanding of why megafauna extinction risk varies through time and the importance of site- or species-specific factors remain unclear. Here, we unravel the unexpected variability in remaining terrestrial megafauna assemblages across 10 Southeast Asian tropical forests. Consistent with global trends, every landscape experienced Holocene and/or Anthropocene megafauna extirpations, and the four most disturbed landscapes experienced 2.5 times more extirpations than the six least disturbed landscapes. However, there were no consistent size- or guild-related trends, no two tropical forests had identical assemblages, and the abundance of four species showed positive relationships with forest degradation and humans. Our results suggest that the region’s megafauna assemblages are the product of a convoluted geoclimatic legacy interacting with modern disturbances and that some megafauna may persist in degraded tropical forests near settlements with sufficient poaching controls.
Nanoscale coherent phonon spectroscopy
Authors: Liu Shuyi , Hammud Adnan , Hamada Ikutaro , Wolf Martin , Müller Melanie , Kumagai Takashi
Published: October 2022

Coherent phonon spectroscopy can provide microscopic insight into ultrafast lattice dynamics and its coupling to other degrees of freedom under nonequilibrium conditions. Ultrafast optical spectroscopy is a well-established method to study coherent phonons, but the diffraction limit has hampered observing their local dynamics directly. Here, we demonstrate nanoscale coherent phonon spectroscopy using ultrafast laser–induced scanning tunneling microscopy in a plasmonic junction. Coherent phonons are locally excited in ultrathin zinc oxide films by the tightly confined plasmonic field and are probed via the photoinduced tunneling current through an electronic resonance of the zinc oxide film. Concurrently performed tip-enhanced Raman spectroscopy allows us to identify the involved phonon modes. In contrast to the Raman spectra, the phonon dynamics observed in coherent phonon spectroscopy exhibit strong nanoscale spatial variations that are correlated with the distribution of the electronic local density of states resolved by scanning tunneling spectroscopy.
Decoupling the role of RORγt in the differentiation and effector function of T
H
17 cells
Authors: Zhong Xiancai , Wu Hongmin , Zhang Wencan , Gwack Yousang , Shang Weirong , Lee Kyle O. , Isakov Noah , He Zhiheng , Sun Zuoming
Published: October 2022

RORγt is known to instruct the differentiation of T helper 17 (T
H
17) cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORγt plays a distinct role in the differentiation and effector function of T
H
17 cells. Here, we show that mutation of RORγt lysine-256, a ubiquitination site, to arginine (K256R) separates the RORγt role in these two functions. Preventing ubiquitination at K256 via arginine substitution does not affect RORγt-dependent thymocyte development, and T
H
17 differentiation in vitro and in vivo, however, greatly impaired the pathogenesis of T
H
17 cell–mediated experimental autoimmune encephalomyelitis (EAE). Mechanistically, K256R mutation impairs RORγt to bind to and activate
Runx1
expression critical for T
H
17-mediated EAE. Thus, RORγt regulates the effector function of T
H
17 cells in addition to T
H
17 differentiation. This work informs the development of RORγt-based therapies that specifically target the effector function of T
H
17 cells responsible for autoimmunity.
Self-assembly and structure of a clathrin-independent AP-1:Arf1 tubular membrane coat
Authors: Hooy Richard M. , Iwamoto Yuichiro , Tudorica Dan A. , Ren Xuefeng , Hurley James H.
Published: October 2022

The adaptor protein (AP) complexes not only form the inner layer of clathrin coats but also have clathrin-independent roles in membrane traffic whose mechanisms are unknown. HIV-1 Nef hijacks AP-1 to sequester major histocompatibility complex class I (MHC-I), evading immune detection. We found that AP-1:Arf1:Nef:MHC-I forms a coat on tubulated membranes without clathrin and determined its structure. The coat assembles via Arf1 dimer interfaces. AP-1–positive tubules are enriched in cells upon clathrin knockdown. Nef localizes preferentially to AP-1 tubules in cells, explaining how Nef sequesters MHC-I. Coat contact residues are conserved across Arf isoforms and the Arf-dependent AP complexes AP-1, AP-3, and AP-4. Thus, AP complexes can self-assemble with Arf1 into tubular coats without clathrin or other scaffolding factors. The AP-1:Arf1 coat defines the structural basis of a broader class of tubulovesicular membrane coats as an intermediate in clathrin vesicle formation from internal membranes and as an MHC-I sequestration mechanism in HIV-1 infection.
Supplemental Material: Topographic development of a compressional mountain range, the western Transverse Ranges of California, USA, resulted from localized uplift along individual structures and regional uplift from deeper shortening
Authors: Onderdonk N. , al. et
Published: October 2022

Contains PDF and radial plots of luminescence data (Item A), log-log plots of cumulative incision vs age for fluvial terraces (Item B), and profiles of terrace surfaces displaced by faults (Item C)
Factors affecting delay in the presentation of breast cancer symptoms among women in Gaza, occupied Palestinian territory: a cross-sectional survey
Authors: Abo Al-Shiekh Samira S , Alajerami Yasser S , Abushab Khaled M , Najim Ahmed A , AlWaheidi Shaymaa , Davies Elizabeth A
Published: October 2022

Objective

To identify factors related to women’s delay in presenting with breast cancer symptoms to improve diagnosis in the occupied Palestinian territory (oPt).

Design

Cross-sectional.

Setting

Two government cancer hospitals.

Participants

A consecutive sample of 130 Palestinian women living in Gaza with newly diagnosed breast cancer were approached in the waiting rooms of cancer hospitals in Gaza between 1 January 2017 and 31 December 2017. 120 women took part and returned the completed questionnaire.

Primary and secondary outcome measures

Clinical information about breast cancer was collected from hospital cancer records. An interval of 3 months or more between women’s self-discovery of symptoms and their first presentation to a medical provider was considered as a delay.

Results

94% (122/130) of women attending cancer hospitals in Gaza agreed to take part in the study. Their mean age was 51 years (range: 23–72), 33.6% (31/122) had a family history of breast cancer and 74.5% (41/55) of those whose cancer stage was known had been diagnosed at stage III or IV. Around one-half (62/122) said they had not recognised the seriousness of their breast changes but only 20% (24/122) of women delayed seeking healthcare by 3 months and more. The two only factors associated to late presentation were that the woman considered their symptoms not serious (p<0.001) and lack of pain (p=0.012). Lower socioeconomic status, older age, lower education and negative family history of breast cancer were not statistically associated with women’s delay.

Conclusions

Women’s awareness about the seriousness of breast changes and the critical importance of seeking prompt diagnosis needs to be improved using context-relevant and evidence-based awareness campaigns. This should be accompanied with training of female nurses on promoting early detection and improvement in diagnostic facilities to ensure timely diagnosis of cancer in the oPt.
Tayside Screening For Cardiac Events (TASCFORCE) study: a prospective cardiovascular risk screening study
Authors: Lambert Matthew A , Houston J Graeme , Littleford Roberta , Fitton Catherine A , Struthers Allan , Sullivan Frank , Gandy Stephen , Belch Jill J F
Published: October 2022

Purpose

Risk factor-based models struggle to accurately predict the development of cardiovascular disease (CVD) at the level of the individual. Ways of identifying people with low predicted risk who will develop CVD would allow stratified advice and support informed treatment decisions about the initiation or adjustment of preventive medication, and this is the aim of this prospective cohort study.

Participants

The Tayside Screening for Cardiac Events (TASCFORCE) study recruited men and women aged≥40 years, free from known CVD, with a predicted 10-year risk of coronary heart disease<20%. If B-type natriuretic peptide (BNP) was greater than their gender median, participants were offered a whole-body contrast-enhanced MRI (WBCE-MRI) scan (cardiac imaging, whole-body angiography to determine left ventricular parameters, delayed gadolinium enhancement, atheroma burden). Blood, including DNA, was stored for future biomarker assays. Participants are being followed up using electronic record-linkage cardiovascular outcomes.

Findings to date

4423 (1740, 39.3% men) were recruited. Mean age was 52.3 years with a median BNP of 7.50 ng/L and 15.30 ng/L for men and women, respectively. 602 had a predicted 10-year risk of 10%–19.9%, with the remainder<10%. Age, female sex, ex-smoking status, lower heart rate, higher high-density lipoprotein and lower total cholesterol were independently associated with higher log10 BNP levels. Mean left ventricular mass was 129.2 g and 87.0 g in men and women, respectively.

Future plans

The TASCFORCE study is investigating the ability of a screening programme, using BNP and WBCE-MRI, at the time of enrolment, to evaluate prediction of CVD in a population at low/intermediate risk. Blood stored for future biomarker analyses will allow testing/development of novel biomarkers. We believe this could be a new UK Framingham study allowing study for many years to come.

Clinical trial registration

ISRCTN38976321.
Association between different infection profiles and one-year outcomes in ANCA-associated vasculitis: a retrospective study with monthly infection screening
Authors: Xu Tingting , Chen Zijin , Jiang Mengdi , Ma Hunkun , Jin Kexin , Wang Zhiyu , Wang Chongjian , Xu Jing , Zhang Wen
Published: October 2022

Objectives

This study aimed to explore clinical features of early infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to identify the association between the infection profile of patients with AAV during the first 3 months and 1-year survival.

Methods

A total of 415 newly diagnosed patients with AAV in the Department of Nephrology at Shanghai Ruijin Hospital from 2000 to 2018 were included. Four Cox regression models were used to analyse the association based on demographics, comorbidities, laboratory baseline index and therapy parameter. Infection screening was carried out monthly during the first 3 months after diagnosis.

Results

In all, 377 episodes of infection were identified among 220 patients during the first 3 months. The overall survival after 1 year was 73.0%. Respiratory infection (210 episodes/164 persons) accounted for more than half of infections. Infection was independently associated with 1-year mortality (adjusted HR 2.32, 95% CI 1.27 to 4.23, p=0.006) after adjustment. Respiratory infection (adjusted HR 4.36, 95% CI 2.86 to 8.06, p<0.001), Gram-negative bacterial infection (adjusted HR 1.71, 95% CI 1.01 to 2.91, p=0.047) and fungal infection (adjusted HR 1.77, 95% CI 1.07 to 2.94, p=0.026) was identified as a risk factor for 1-year mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis (adjusted HR 0.55, 95% CI 0.31 to 0.97, p=0.040) was protective for 1-year mortality.

Conclusions

Infections, particularly respiratory infections, are a common and important class of complication in patients with AAV and are associated with early mortality. TMP-SMX prophylaxis might be necessary to improve short-term outcome. More consideration of infectious risk and regular infection screening should be given.
Short-time Fourier transform and embedding method for recurrence quantification analysis of EEG time series
Authors: Furman Łukasz , Duch Włodzisław , Minati Ludovico , Tołpa Krzysztof
Published: October 2022

Electroencephalography (EEG) allows recording of cortical activity at high temporal resolution. Creating features useful for the analysis of the EEG recording can be challenging. Here we introduce a new method of pre-processing the time-series for the analysis of the resting state and binary task classification using recurrence quantification analysis (RQA) and compare it with the existing state-of-the-art approach based on signal embedding. To reveal patterns that unfold brain dynamics, we present a new pipeline that does not rely on selection of embedding parameters for RQA. Instead of using EEG time-series signals directly, Short-term Fourier transform (STFT) is used to generate new time-series, based on the power spectra from sliding, overlapping windows. Recurrence plots are created in a standard way from embedded EEG signals, and the STFT vectors. The efficiency of RQA features extracted from such plots is compared in classification of EEG segments that correspond to open and closed eye conditions. In contrast to the common approaches to such analysis, no filtering into separate frequency bands was needed. Differences between the two representations of EEG signals are illustrated using histograms of RQA features and UMAP plots. Classification results at the 95.9% level were obtained using selected features for less than 10 electrodes.
A review and tectonic interpretation of the Taconian–Grampian tract between Newfoundland and Scotland: diachronous accretion of an extensive forearc–arc–backarc system to a hyperextended Laurentian margin and subsequent subduction polarity reversal
Authors: van Staal Cees R. , Dewey John F.
Published: October 2022

The Taconian–Grampian tract was characterized by a diachronous collision of a north-facing oceanic arc–forearc terrane and associated backarc basins with an irregular Laurentian margin with hyperextended segments. Hyperextension produced outboard continental terranes, separated by exhumed subcontinental mantle from the inboard margin. The exhumed mantle facilitated continued subduction of the extended margin after it had entered the trench. Enhanced slab-rollback resulted in spreading in lenticular backarc basins, which gradually transitioned along-strike into extensional arcs where rollback was less. Obduction of the oceanic elements onto the irregular Laurentian margin was followed by diachronous slab breakoff and a subduction polarity reversal, such that south- and north-dipping subduction zones locally were coeval along-strike. The polarity flip changed the convergence obliquity from dextral to sinistral and was accompanied by shallowing of the subducting slab near the end of the Middle Ordovician. Strike-slip movements locally juxtaposed segments where tectonic events occurred at different times, producing conflicting relationships. Slab breakoff produced punctuated magmatism, largely driven by mantle-derived melts, and drove and/or enhanced metamorphism in the overlying and enveloping crustal rocks. Boninite was generated episodically over a time span of 32 myr; the oldest Cambrian phase in the Lushs Bight Oceanic Tract (LBOT) and correlatives was associated with subduction initiation.
A Multi-type Classifier Ensemble for Detecting Fake Reviews Through Textual-based Feature Extraction
Authors: Budhi Gregorius Satia , Chiong Raymond
Published: October 2022

The financial impact of online reviews has prompted some fraudulent sellers to generate fake consumer reviews for either promoting their products or discrediting competing products. In this study, we propose a novel ensemble model—the
Multi-type Classifier Ensemble (MtCE)
—combined with a textual-based featuring method, which is relatively independent of the system, to detect fake online consumer reviews. Unlike other ensemble models that utilise only the same type of single classifier, our proposed ensemble utilises several customised machine learning classifiers (including deep learning models) as its base classifiers. The results of our experiments show that the MtCE can adequately detect fake reviews, and that it outperforms other single and ensemble methods in terms of accuracy and other measurements for all the relevant public datasets used in this study. Moreover, if set correctly, the parameters of MtCE, such as base-classifier types, the total number of base classifiers, bootstrap, and the method to vote on output (e.g., majority or priority), can further improve the performance of the proposed ensemble.
RegCPython: A Register-based Python Interpreter for Better Performance
Authors: Zhang Qiang , Xu Lei , Xu Baowen
Published: October 2022

Interpreters are widely used in the implementation of many programming languages, such as Python, Perl, and Java. Even though various JIT compilers emerge in an endless stream, interpretation efficiency still plays a critical role in program performance. Does a stack-based interpreter or a register-based interpreter perform better? The pros and cons of the pair of architectures have long been discussed. The stack architecture is attractive for its concise model and compact bytecode, but our study finds that the register-based interpreter can also be implemented easily and that its bytecode size only grows by a small margin. Moreover, the latter turns out to be appreciably faster. Specifically, we implemented an open source Python interpreter named RegCPython based on CPython v3.10.1. The former is register based, while the latter is stack based. Without changes in syntax, Application Programming Interface, and Application Binary Interface, RegCPython is excellently compatible with CPython, as it does not break existing syntax or interfaces. It achieves a speedup of 1.287 on the most favorable benchmark and 0.977 even on the most unfavorable benchmark. For all Python-intensive benchmarks, the average speedup reaches 1.120 on x86 and 1.130 on ARM. Our evaluation work, which also serves as an empirical study, provides a detailed performance survey of both interpreters on modern hardware. It points out that the register-based interpreters are more efficient mainly due to the elimination of machine instructions needed, while changes in branch mispredictions and cache misses have a limited impact on performance. Additionally, it confirms that the register-based implementation is also satisfactory in terms of memory footprint, compilation cost, and implementation complexity.
Computational Graphs for Matrix Functions
Authors: Jarlebring Elias , Fasi Massimiliano , Ringh Emil
Published: October 2022

Many numerical methods for evaluating matrix functions can be naturally viewed as computational graphs. Rephrasing these methods as directed acyclic graphs (DAGs) is a particularly effective approach to study existing techniques, improve them, and eventually derive new ones. The accuracy of these matrix techniques can be characterized by the accuracy of their scalar counterparts, thus designing algorithms for matrix functions can be regarded as a scalar-valued optimization problem. The derivatives needed during the optimization can be calculated automatically by exploiting the structure of the DAG in a fashion analogous to backpropagation. This article describes
GraphMatFun.jl
, a Julia package that offers the means to generate and manipulate computational graphs, optimize their coefficients, and generate Julia, MATLAB, and C code to evaluate them efficiently at a matrix argument. The software also provides tools to estimate the accuracy of a graph-based algorithm and thus obtain numerically reliable methods. For the exponential, for example, using a particular form (degree-optimal) of polynomials produces implementations that in many cases are cheaper, in terms of computational cost, than the Padé-based techniques typically used in mathematical software. The optimized graphs and the corresponding generated code are available online.
Generalized Symmetries in Condensed Matter
Authors: McGreevy John
Published: October 2022

Recent advances in our understanding of symmetry in quantum many-body systems offer the possibility of a generalized Landau paradigm that encompasses all equilibrium phases of matter. This is a brief and elementary review of some of these developments.
The Value and Impacts of Academic Public Health Departments
Authors: Erwin Paul C. , Grubaugh Julie H. , Mazzucca-Ragan Stephanie , Brownson Ross C.
Published: October 2022

The academic health department (AHD) is a partnership between an academic institution and a governmental health agency. These partnerships are meant to provide mutual benefits that include opportunities for student field placements and internships, practice-informed curriculum, and practice-based research. The term academic health department dates back only to 2000, although there are several examples of academic–practice partnerships prior to that date. In addition to AHDs that have been established over the past two decades, other forms of academic–practice engagement provide similar mutual benefits, such as prevention research centers and public health training centers. Current research on AHDs explores how these partnerships matter regarding the outputs, outcomes, and impacts of the units that comprise them. This review also considers the most recent perspectives on how AHDs have responded to the COVID-19 pandemic and how they might advance public health's efforts to address structural racism and promote health equity.
Impact of Surface Roughness and Material Properties of Inert Electrodes on the Threshold Voltages and Their Distributions of ReRAM Memory Cells
Authors: Chakraborty Amrita , Al-Mamun Mohammad , Orlowski Marius
Published: October 2022

The paper explores the impact of the surface roughness (SR) and other material properties of metal electrodes on the statistical distributions of the switching threshold voltages, Vform, Vset, and Vreset, of a resistive memory (ReRAM) cell. The surface roughness of Pt, Ru, Co, and Cu in Cu/TaOx/Pt, Cu/TaOx/Ru, and Cu/TaOx/Co devices is extensively characterized and related to the switching characteristics of the devices. We find that SF has both impacts on the mean and on the standard deviation of the Vform, Vset, and partly also on the Vresetdistributions. The surface roughness of free metal surfaces of Pt, Ru, and Co when annealed at 600 °C and 900 °C is found to increase significantly, but this increase is substantially suppressed when passivated by the thin switching layer of the solid electrolyte, such as TaOxor SiO2. The increase of SR of those metals with increasing temperature correlates well with their melting temperature. Overall, we find that the differences in surface roughness along with material properties such as the thermal conductivity and work function explain well the differences between the distributions of the threshold voltages of the ReRAM devices with Pt, Ru, and Co serving as the inert electrode.
Synergetic Effect of CeO2 Doping on Structural and Tribological Behavior of Fe-Al2O3 Metal Matrix Nanocomposites
Authors: Gupta Pallav , Ahamad Naseem , Kumar Devendra , Gupta Niraj , Chaudhary Vijay , Gupta Sumit , Khanna Virat , Chaudhary Vishal
Published: October 2022

Cerium oxide (CeO2) doped iron (Fe) - alumina (Al2O3) Metal Matrix Nanocomposites have been studied in this article. Doped with 0.5 and 1.0 percent CeO2, the nanocomposites in this system were made in the lab. Weighing, Powder milling, die pressing, and sintering at 1100 °C for one hour in an atmosphere-controlled furnace were used to develop the specimens. Microstructural inspection of a worn-out surface on the prepared specimens was carried out in addition to the phase determination and microstructural assessment that were performed on the fabricated specimens. Fe, Al2O3, CeO2, and FeAl2O4 phases were all seen in the XRD data. There were nano dispersion of FeAl2O4 and CeO2 particles in the dense phase microstructure of the produced samples. Increasing the amount of cerium oxide in the material resulted in an increase in both density and hardness. The specimen’s wear rate was shown to decrease with an increase in cerium oxide content %. The present developed material will be useful for heavy duty applications like railway wagon wheels.
Deep learning-based prediction of coronary artery stenosis resistance
Authors: Sun Hao , Liu Jincheng , Feng Yili , Xi Xiaolu , Xu Ke , Zhang Liyuan , Liu Jian , Li Bao , Liu Youjun
Published: October 2022

This study developed a multi-input back-propagation neural network (BPNN) that can be used to predict coronary artery stenosis resistance by inputting vascular geometric parameters and blood flow. Compared with previous studies, the network developed in this study can accurately and rapidly predict coronary artery stenosis resistance, which can not only meet clinical requirements but also reduce the cost of calculation duration. This study contributes to the noninvasive methods for the numerical calculation of fractional flow reserve derived from coronary CT angiography (FFRCT) and indicates that this technique can potentially be used for evaluating myocardial ischemia.
Plasticity of cerebral microvascular structure and mechanics during hypertension and following recovery of arterial pressure
Authors: Sabharwal Rasna , Chapleau Mark W. , Gerhold Thomas D. , Baumbach Gary L. , Faraci Frank M.
Published: October 2022

Changes in vascular structure contribute to vascular events and loss of brain health. We examined the inherent structural plasticity of cerebral arterioles during and after a period of hypertension. Arteriolar wall thickness, diameter, wall-to-lumen ratio, and biological stiffness changed rapidly during hypertension and recovered with blood pressure. In contrast, inward remodeling developed slowly and did not recover. This lack of recovery of arteriolar diameter has implications for the long-term impact of hypertension on vascular determinants of brain health.
Smad3 promotes adverse cardiovascular remodeling and dysfunction in doxorubicin-treated hearts
Authors: Cobb Melissa S. , Tao Shixin , Shortt Katherine , Girgis Magdy , Hauptman Jeryl , Schriewer Jill , Chin Zaphrirah , Dorfman Edward , Campbell Kyle , Heruth Daniel P. , Shohet Ralph V. , Dawn Buddhadeb , Konorev Eugene A.
Published: October 2022

Microvascular endothelial cells in the heart accumulate more intravenously administered doxorubicin than nonendothelial cardiac cell types. The treatment enhanced the TGF-β/Smad3 pathway and elicited endothelial cell senescence and inflammatory responses followed by adverse cardiac remodeling and dysfunction in wild-type but not Smad3-deficient animals. Our study suggests that the TGF-β/Smad3 pathway contributes to the development of doxorubicin cardiomyopathy and the potential value of novel approaches to ameliorate cardiotoxicity by targeting the Smad3 transcription factor.
Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes
Authors: Sun Haoyu , Du Yong , Kumar Rinki , Buchkovich Nicholas , He Pingnian
Published: October 2022

This study provides the first evidence that over 90% of human plasma microparticles express ACE2 that binds SARS-CoV-2 S protein with high affinity. Thus, the highly elevated adhesive circulating microparticles identified in patients with diabetes not only have greater SARS-CoV-2 binding capacity but also enable additional viral entry through virus-bound microparticle-endothelium interactions and enhanced infection. These findings reveal a novel mechanistic insight into the adverse outcomes of COVID-19 in patients with diabetes.
The healthy heart does not control a specific cardiac output: a plea for a new interpretation of normal cardiac function
Authors: Stöhr Eric J.
Published: October 2022

The current evidence suggests that the healthy heart does not sense the optimal cardiac output (Q̇) because the different organ systems that influence cardiac function do not interact to adjust their individual responses toward a specific Q̇. Consequently, it is conceivable that the complex cycle of cardiac contraction and relaxation must occur for reasons other than to produce a specific target Q̇ and that there is likely a yet undiscovered overarching principle in the cardiovascular system that explains the combined effects of the prevailing preload, afterload, and contractility. Future research should embrace the possibility of a different purpose to cardiac function than previously assumed and examine the biological capacity of this fascinating organ accordingly.
Short-Term Efficacy of High-Intensity Laser Therapy in Alleviating Pain in Patients with Knee Osteoarthritis: A Single-Blind Randomised Controlled Trial
Authors: Siriratna Punpetch , Ratanasutiranont Chompoonuch , Manissorn Thongsuk , Santiniyom Nonthalee , Chira-Adisai Waree
Published: October 2022

Objectives. The aim of the study is to evaluate the efficacy of high-intensity laser therapy (HILT) on pain reduction in patients with knee osteoarthritis (OA). Methods. Forty-two patients diagnosed with primary knee OA, with a Kellgren–Lawrence classification of 2–4, were recruited into the study. The patients were randomly allocated to two groups: HILT and control. The intervention group received HILT (energy density of 22.39 J/cm2, 562.5 joule/session), while the control group received a sham laser, which was done 2–3 sessions per week for a total of 10 sessions. Both the groups also received the same conservative treatment. The main outcome measures were the visual analogue scale (VAS) and the modified Thai version of the Western Ontario and McMaster Universities Osteoarthritis Index (T-WOMAC) which were evaluated at baseline and immediately after treatment completion. Results. At the end of the study, the overall analysis showed a significant decrease in VAS and T-WOMAC scores in both the groups; a greater decrease in scores was found in the HILT group than in the control group (

p
<
0.001

). The between-group comparison also showed a significant difference in VAS, but not in the T-WOMAC score, favouring HILT (

p
<
0.05

). Conclusion. The HILT plus conservative treatment can help alleviate pain in patients with knee OA. The findings of the present study could be used in clinical practice to add HILT as another noninvasive treatment option for knee OA. This could be advantageous, particularly for individuals who are at high risk of surgery due to multiple comorbidities or older people. Trial Registration. This clinical trial registration was performed at Clinical.gov (NCT04889885).
Finite Element Analysis of the Effect of Tightening Torque on the Connection Stability of a Two-Piece Zirconia Implant System
Authors: Choi Hyunsuk , Hong Min-Ho
Published: October 2022

Purpose. Loosening and fracture of abutment screws are one of the most common complications in implant-retained fixed prostheses. Thus, applying the proper tightening torque to the abutment screw is important for preventing the loosening effect of the abutment screw and ensuring the stability of the implant fixture-abutment connection. Therefore, in this study, we aimed to investigate the effect of the tightening torque of the abutment screw on the stability of the fixture-abutment connection in a two-piece zirconia implant system using finite element analysis (FEA). Materials and Methods. The two-piece zirconia implant structures used in this study were designed using the CATIA program. The abutment screws with tightening torques of 25 (TT-25), 35 (TT-35), and 45 (TT-45) N·cm were assumed to fix the abutment and fixture. Vertical (200 N) and oblique (100 N) loads were applied to the finite element model generated for FEA simulation, and the stress levels and distributions were investigated. Results. The TT-45 group exhibited the highest von Mises stress in the abutment and fixture, followed by the TT-35 and TT-25 groups. The von Mises and minimal principal stresses of the abutment screw were also highest in the TT-45 group, followed by the TT-35 and TT-25 groups. In all three groups, the area with the highest stress concentration was located at the point of contact with the bottom of the screw head. Furthermore, the TT-25 group showed the highest safety factor value. The TT-35 group showed a safety factor value similar to the safe minimum standard, while the TT-45 group showed a lower safety factor value. Conclusion. When a torque of 35 N cm was applied to the two-piece zirconia implant system, it showed a maximum stress value close to 660 MPa (75% of the yield strength of the Ti-6Al-4V alloy), which is the optimal preload recommended for abutment screws.
Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma
Authors: Zhang Yunxin , Zhang Wentao , Xia Wenlong , Xia Junwei , Zhang Haishan
Published: October 2022

Colon cancer is the most common malignant tumor of the gastrointestinal tract, and approximately 80%–90% of colon cancers are colon adenocarcinomas (COADs). This study aimed to screen key microRNAs (miRNAs) associated with COAD. Differentially expressed (DE) miRNAs were screened between COAD and adjacent cancer samples based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas obtained from datasets. The miRNAs of interest were validated using quantitative real-time polymerase chain reaction. Moreover, the effects of hsa-miR-135b-5p on the biological behavior of COAD cells were observed. To obtain the target genes of hsa-miR-135b-5p, transcriptome sequencing of the SW480 cells was performed, followed by protein-protein interaction (PPI) network and hsa-miR-135b-5p-target gene regulatory network construction and prognostic analysis. Downregulation of hsa-miR-135b-5p significantly inhibited SW480 cell proliferation, migration, and invasion and significantly facilitated apoptosis (

P

 < 0.05). A total of 3384 DEmRNAs were screened, and enrichment analysis showed that the upregulated mRNAs were enriched in 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 326 Gene Ontology Biological Processes (GO-BPs) while the downregulated mRNAs were enriched in 20 KEGG pathways and 276 GO-BPs. A PPI network was then constructed, and H2BC14, H2BC3, and H4C11 had a higher degree. In addition, a total of 352 hsa-miR-135b-5p-gene regulatory relationships were identified. Prognostic analysis showed that FOXN2, NSA2, MYCBP, DIRAS2, DESI1, and RAB33B had prognostic significance (

P

 < 0.05). In addition, the validation analysis results showed that FOXN2, NSA2, and DESI1 were significantly expressed between the miR-135b-5p-inhibitor and negative control groups (

P

 < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting FOXN2, NSA2, MYCBP, DIRAS2, DESI1, and RAB33B.
Bio-Tribocorrosion of Titanium Dental Implants and Its Toxicological Implications: A Scoping Review
Authors: Gaur Sumit , Agnihotri Rupali , Albin Sacharia
Published: October 2022

Bio-tribocorrosion is a phenomenon that combines the essentials of tribology (friction, wear, and lubrication) and corrosion with microbiological processes. Lately, it has gained attention in implant dentistry because dental implants are exposed to wear, friction, and biofilm formation in the corrosive oral environment. They may degrade upon exposure to various microbial, biochemical, and electrochemical factors in the oral cavity. The mechanical movement of the implant components produces friction and wear that facilitates the release of metal ions, promoting adverse oro-systemic reactions. This review describes the bio-tribocorrosion of the titanium (Ti) dental implants in the oral cavity and its toxicological implications. The original research related to the bio-tribo or tribocorrosion of the dental implants was searched in electronic databases like Medline (Pubmed), Embase, Scopus, and Web of Science. About 34 studies included in the review showed that factors like the type of Ti, oral biofilm, acidic pH, fluorides, and micromovements during mastication promote bio-tribocorrosion of the Ti dental implants. Among the various grades of Ti, grade V, i.e., Ti6Al4V alloy, is most susceptible to tribocorrosion. Oral pathogens like Streptococcus mutans and Porphyromonas gingivalis produce acids and lipopolysaccharides (LPS) that cause pitting corrosion and degrade the TiO2. The low pH and high fluoride concentration in saliva hinder passive film formation and promote metal corrosion. The released metal ions promote inflammatory reactions and bone destruction in the surrounding tissues resulting in peri-implantitis, allergies, and hyper-sensitivity reactions. However, further validation of the role of bio-tribocorrosion on the durability of the Ti dental implants and Ti toxicity is warranted through clinical trials.
Adherence to Dietary Recommendation and Its Associated Factors among People with Type 2 Diabetes: A Cross-Sectional Study in Nepal
Authors: Baral Jijeebisha , Karki Khem Bahadur , Thapa Pratibha , Timalsina Ashish , Bhandari Rama , Bhandari Rabindra , Kharel Bijaya , Adhikari Nabin
Published: October 2022

Introduction. Intensive lifestyle modification including a healthy diet changes the diagnostic status of patient from prediabetes to nondiabetes. In type 2 diabetes, improper eating habits increase insulin resistance. This study is aimed at assessing adherence to the dietary recommendation and its associated factors among people with type 2 diabetes. Methods. A cross-sectional descriptive study was conducted among systematically sampled type 2 diabetic patients using interview on Gandaki Medical College Teaching Hospital and Diabetes, Thyroid, and Endocrinology Care Center, Pokhara. The Perceived Dietary Adherence Questionnaire was used to assess dietary adherence. Data was entered in EpiData version 3.1 and analyzed on SPSS version 20. Logistic regression with adjusted odds ratio and the corresponding 95% confidence intervals were used to find out significance of association. Results. Among 204 participants, only 15.7% of the participants had good dietary adherence. The mean age and standard deviation were

53.03
±
11.90

years. Factors such as participants living in single family (AOR 2.7, 95% CI 1.0-7.4), participants who could afford recommended diet (AOR 2.9, 95% CI 1.0-8.3), participants having self-control on food (AOR 4.1, 95% CI 1.2-14.1), participants who were engaged in moderate to heavy physical activities (AOR 3.3, 95% CI 1.2-9.2), and participants who had adherence to medication (AOR 3.5, 95% CI 1.2-10.1) were significantly associated with adherence to dietary recommendation. Conclusions. Adherence to dietary recommendation among people with type 2 diabetes was low. Factors such as family type, affordability of recommended diet, self-control on food, physical activity, and medication adherence were significantly associated with adherence to dietary recommendations among people with type 2 diabetes. These factors should be considered by nutrition counselors and clinical decision-makers in patient counseling regarding dietary adherence.
DLX2 Is a Potential Immune-Related Prognostic Indicator Associated with Remodeling of Tumor Microenvironment in Lung Squamous Cell Carcinoma: An Integrated Bioinformatical Analysis
Authors: Huang Liling , Xie Tongji , Zhao Fuqiang , Feng Yu , Zhu Haohua , Tang Le , Han Xiaohong , Shi Yuankai
Published: October 2022

Background. It is still an unmet clinical need to identify potent biomarkers for immunotherapy on patients with lung squamous cell carcinoma (LUSC). Methods. In this study, we explored the differentially expressed genes (DEGs) that were simultaneously correlated with four pathways (i.e. CD8+αβT cell proliferation/differentiation/activation pathways and ferroptosis pathway) and possibly related to the remodeling of tumor microenvironment via the TCGA-LUSC dataset. Besides, four GEO datasets (GSE157009, GSE157010, GSE19188, and GSE126045) and IMvigor210 dataset were utilized for confirmation and validation. Results. The co-downregulated DEG DLX2 was selected for further analysis. Function enrichment analysis revealed that low-expression of DLX2 was closely related to various immune-related pathways like T/B/NK cell mediated immunity, interferon gamma/alpha response, and various autoimmune disease. DLX2-downregulated group was enriched in more immune-activating cells and lower tumor immune dysfunction and exclusion (TIDE) score. Via the Cancer Immunome Atlas (TCIA) database, lower expression of DLX2 was also found to be associated with better IPS score of PD-1/PD-L1 blockade (

p
<
0.001

) as well as CTLA-4 combined with PD-1/PD-L1 blockade (

p
<
0.001

). Furthermore, patients in DLX2-low group were found to have significant longer median OS than those in DLX2-high group in IMvigor210 dataset (10.8 vs 7.4 months; hazard ratio [HR]=0.74, 95% confidence interval [95%CI] 0.57-0.96;

p
=
0.024

). Conclusions. Our study on an integrated bioinformatical analysis implied that DLX2 could be served as a promising indicator for remodeling tumor microenvironment status and predicting ICI response of patients with LUSC.
Application of Food Mechanics and Oral Processing in Modelling First Bite of Grilled Meat
Authors: Djekic Ilija V. , Ilic Jovan G. , Sołowiej Bartosz G. , Djekić Rastko I. , Tomasevic Igor B.
Published: October 2022

This study analyzed the potential of modelling meat mastication by using pork and poultry meat as food with different physical properties under different grilling temperatures. For the purpose of modelling oral processing, temporal dominance of sensations and finite element methods were employed. A panel with ten subjects was trained and used for oral processing analysis and temporal dominance of sensations revealing in-mouth sensations and mastication characteristics. In parallel, the second aim was to evaluate the mechanical properties of the samples and explore the potential of simulating the first bite using the finite element method. Based on the textural parameters, a 3D model of grilled meat was created and a first-bite simulation was performed. A higher level of differences was observed comparing the number of chews for pork meat compared to poultry meat. The chewing rate showed a statistical difference with values in the range of 1.31 chews/s to 1.46 chews/s for pork meat and between 1.36 chews/s and 1.42 chews/s for poultry meat. Firmness was the predominant sensory attribute recognized by panelists at the beginning of mastication, which confirmed our approach used for first-bite modelling. Simulation results show the growth of internal stress following the jaw’s path. Presented models demonstrate that the highest values are around teeth pressure and lead to a conclusion that upon biting, the meat structure will suffer irreversible damage dividing the grilled meat into two pieces, as it happens during the first bite. The main conclusion of this study is that by combining results from oral processing and testing of mechanical properties of the grilled products, it is possible to simulate the first bite.
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial
Authors: Elía Andrés , Saldain Leo , Vanzulli Silvia I. , Helguero Luisa A. , Lamb Caroline A. , Fabris Victoria , Pataccini Gabriela , Martínez-Vazquez Paula , Burruchaga Javier , Caillet-Bois Ines , Spengler Eunice , Acosta Haab Gabriela , Liguori Marcos , Castets Alejandra , Lovisi Silvia , Abascal María F. , Novaro Virginia , Sánchez Jana , Muñoz Javier , Belizán José M. , Abba Martín C. , Gass Hugo , Rojas Paola , Lanari Claudia
Published: October 2022

Purpose:

Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA/PRB isoform ratio (MIPRA; NCT02651844).

Patients and Methods:

Twenty patients with luminal breast carcinomas with PRA/PRB > 1.5 (determined by Western blots), and PR ≥ 50%, naïve from previous treatment, were included for mifepristone treatment (200 mg/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment.

Results:

A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (P = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.

Conclusions:

Our results support the use of mifepristone in patients with luminal breast cancer with high PRA/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients.

See related commentary by Ronchi and Brisken, p. 833