bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporomandibular joint articular disc position and shape in skeletal Class III
Authors: Tagawa Daniella Torres , Franco Alexandre de Albuquerque , Puchnick Andrea , Wolosker Angela Maria Borri , Florez Bruna Maluza , Dominguez Gladys Cristina , Yamashita Helio Kiitiro , Cevidanes Lucia Helena Soares , Aidar Luis Antonio de Arruda , Junior Henrique Carrete
Published: August 2022

Objective

To compare the position and shape of the temporomandibular joint (TMJ) articular disc among the sagittal and vertical skeletal patterns in Angle Class III, Class III subdivision malocclusion and normal occlusion. The null hypothesis was that there was no difference in disc position and shape in different (1) malocclusions and (2) skeletal patterns.

Methods

This cross‐sectional observational study evaluated 105 patients divided into 3 groups: Class III (33, 9.39 ± 1.96 years), Class III subdivision (45, 9.51 ± 1.59 years) and a normal occlusion (27, 10.24 ± 0.87 years) was included as healthy control. Severity of the maxilla‐mandibular anteroposterior discrepancy and vertical facial pattern were determined using 2D cephalometry, and the position and shape of the articular discs were evaluated in magnetic resonance images. Statistical parametric and non‐parametric tests and Kappa analysis for intra‐observer and inter‐observer assessment were used (p ≤ .05).

Results

Significant between‐group differences were found in articular disc position. In the normal occlusion group, all the articular discs were well positioned. In Class III and Class III subdivision, the discs were displaced in 30.3% and 12.2% of the TMJs, respectively. Sagittal and vertical skeletal patterns did not affect the findings significantly. The Class III subdivision malocclusion group is probably different from the other groups, showing 97.7% of biconcave discs in both TMJs.

Conclusion

The longitudinal follow‐up of this sample becomes relevant as the two groups with malocclusion in the pre‐peak phase of pubertal growth showed differences in the prevalence of displacement and form of the articular disc, with no association with their vertical facial characteristics.
3D Killer Turn Angle in Transtibial Posterior Cruciate Ligament Reconstruction Is Determined by the Graft Turning Angle both in the Sagittal and Coronal Planes
Authors: Jia Gengxin , Tang Yuchen , Liu Zhongcheng , Peng Bo , Da Lijun , Yang Jun , Liu Xiaolong , Ma Ming , Han Hua , Wu Meng , Geng Bin , Xia Yayi , Teng Yuanjun
Published: August 2022

Objective

During the transtibial posterior cruciate ligament (PCL) reconstruction, surgeons commonly pay more attention to the graft turning angle in the sagittal plane (GASP), but the graft turning angle in the coronal plane (GACP) is always neglected. This study hypothesized that the three‐dimensional (3D) killer turn angle was determined by both the GASP and GACP, and aimed to quantitively analyze the effects of the GASP and GACP on the 3D killer turn angle.

Methods

This was an in‐vitro computer simulation study of transtibial PCL reconstruction using 3D knee models. Patients with knee injuries who were CT scanned were selected from the CT database (April 2019 to January 2021) at a local hospital for reviewing. A total of 60 3D knees were simulated based on the knees' CT data. The femoral and tibial PCL attachment were located on the 3D knee model using the Rhinoceros software. The tibial tunnels were simulated based on different GASP and GACP. The effects of the GASP and GACP on the 3D killer turn angle were quantitatively analyzed. One‐way analysis of variance was used to compare the outcomes in different groups. The regression analysis was performed to identify variables of the GASP and GACP which significantly affected 3D killer turn angle.

Results

The 3D killer turn angle showed a significant proportional relationship not only with the GASP (r2 > 0.868, P < 0.001), but also with the GACP (r2 > 0.467, P < 0.001). Every 10° change of the GACP caused 2.8° to 4.4° change of the 3D killer turn angle, whereas every 10° change of the GASP caused 6.4° to 9.2° change of the 3D killer turn angle.

Conclusions

The 3D killer turn angle was significantly affected by both the GASP and GACP. During the transtibial PCL reconstruction, the proximal anterolateral tibial tunnel approach could increase the 3D killer turn angle more obviously compared with the most distal anteromedial tibial tunnel approach. To minimize the killer turn effect, both the GASP and GACP were required to be considered to increase.
Two novel CreERT2 transgenic mouse lines to study melanocytic cells in vivo
Authors: Stüfchen Isabel , Beckervordersandforth Ruth , Fischer Stefan , Kappelmann‐Fenzl Melanie , Bosserhoff Anja Katrin , Beyer Felix
Published: August 2022

The skin of adult mammals protects from radiation, physical and chemical insults. While melanocytes and melanocyte‐producing stem cells contribute to proper skin function in healthy organisms, dysfunction of these cells can lead to the generation of malignant melanoma—the deadliest type of skin cancer. Addressing cells of the melanocyte lineage in vivo represents a prerequisite for the understanding of melanoma on cellular level and the development of preventive and treatment strategies. Here, the inducible Cre‐loxP‐system has emerged as a promising tool to specifically target, monitor, and modulate cells in adult mice. Re‐analysis of existing sequencing data sets of melanocytic cells revealed that genes with a known function in neural cells, including neural stem cells (Aldh1L1 and Nestin), are also expressed in melanocytic cells. Therefore, in this study, we explored whether the promoter activity of Nestin and Aldh1L1 can serve to target cells of the melanocyte lineage using the inducible CreERT2‐loxP‐system. Using an immunohistochemical approach and different time points of analysis, we were able to map the melanocytic fate of recombined stem cells in the adult hair follicle of Nestin‐CreERT2 and Aldh1L1‐CreERT2 transgenic mice. Thus, we here present two new mouse models and propose their use to study and putatively modulate adult melanocytic cells in vivo.
Isolation and characterization of Streptomyces spp. from potato and peanut in Israel
Authors: Chalupowicz Laura , Tsror (Lahkim) Leah , Hazanovsky Marina , Erlich Orly , Reuven Michal , Dror Orit , Lebiush Sara , Manulis‐Sasson Shulamit
Published: August 2022

Potato common scab (CS) and peanut pod wart diseases cause substantial economic losses every year in Israel. In this comprehensive study on the Streptomyces spp. population, isolates were collected during 2004–2016 from potato tubers with symptoms grown in Israel, seed tubers imported from Europe and from peanut pods with symptoms grown in Israel. A total of 142 isolates were characterized by PCR using three primer sets (txtA, tomA and nec1 genes) and by three pathogenicity tests. Seven species were identified among the isolates, S. bottropensis, S. europaeiscabiei, S. griseus, S. scabiei, S. sampsonii, S. turgidiscabies, and S. venezuelae. S. europaeiscabiei was the most dominant among isolates from imported seed tubers, while S. scabiei and S. turgidiscabies were isolated from tubers grown in Israel. Isolates originating from peanuts were significantly more virulent than those from imported seed tubers, as determined by a pathogenicity assay on radish plants. The presence of pathogenic Streptomyces was detected by quantitative PCR (qPCR) in 289 soil samples collected from 31 commercial potato fields with CS history. Eighty percent to 100% of samples collected from fields with a high disease incidence on tubers (50%) gave positive results in qPCR, whereas in samples collected from fields with low CS incidence (2%–30%) the qPCR results were very variable. Potato seed lots imported from Europe during 2008–2021 were found contaminated with CS symptoms at different levels on visual examination. The results of this study indicate that Streptomyces species, in particular S. europaeiscabiei, were introduced to Israel through seed lots imported from Europe.
Phytolith‐occluded carbon in leaves of Dendrocalamus Ronganensis influenced by drought during growing season
Authors: Li Rencheng , Chen Xiaofang , Wen Mengdan , Vachula Richard S. , Tan Shuhui , Dong Haiyan , Zhou Lintong , Gu Zhitao , Xu Mengtong
Published: August 2022

Being an important carbon (C) sink, phytolith‐occluded carbon (PhytOC) has been investigated in various soil–plant systems. However, the effects of environmental factors (i.e., drought) on phytoliths, including altered deposition in plant tissues, morphological variation, and amounts of carbon occluded within phytoliths, are less studied. In this study, we analyzed the monthly variations of phytolith production and PhytOC in the leaves of Dendrocalamus ronganensis grown on a karst mountain in southwestern China during a drought year. This study thus sought to understand the effects of drought on phytolith formation, morphological variations and carbon sequestration within phytoliths in plants. Our results showed that the phytolith assemblages and PhytOC between new and old leaves differed significantly and varied with plant growth stages. The average PhytOC values of old leaves and tip leaves were 3.2% and 2.2%, respectively. In particular, both PhytOC and proportions of ELONGATE, BULLIFORM FLABELLATE, and STOMA phytoliths in tip leaves significantly decreased from September to January the following year because of drought effects. This study suggests that PhytOC in plants varies between phytolith morphotypes and is significantly affected by plant growth stage and hydrologic conditions. This indicates that we can improve the efficiency of phytolith carbon sequestration in plants by improving the soil water conditions required for plant growth.
The Procreation Asymmetry Destabilized: Analogs and Acting for People's Sake
Authors: Aaron Jonas H.
Published: August 2022

Is there a pro tanto moral reason to create a life merely because it would be good for the person living it? Proponents of the procreation asymmetry claim there is not. Defending this controversial no reason claim, some have suggested that it is well in line with other phenomena in the moral realm: there is no reason to give a promise merely because one would keep it, and there is no reason to procreate merely to increase the extent of justice in the world. Allegedly, some analogs extend so far as to support a unified theory of the no reason claim and the nonidentity thesis, that is, the view that of two persons leading lives of positive wellbeing, there is a reason to create the person with higher wellbeing. I dismantle the proposed analogs and show that they fail to meet various desiderata. Moreover, I refute Johann Frick's argument that the no reason claim follows from the assumption that reasons of beneficence are reasons to act for the sake of people. By criticizing attractive defenses for the no reason claim, I weaken its plausibility.
Women adjusting their sails: The role of motility in women's livelihood strategies in a fishing village in Tamil Nadu, India
Authors: Azmi Fazeeha , Lund Ragnhild
Published: August 2022

This article draws on research conducted in a fishing village in southern India to examine the ways in which middle‐aged women in a precarious socio‐economic position used mobility and immobility strategies to improve their livelihoods, both inside and outside of fisheries. Kaufmann et al.'s (2004) work on motility is applied to show how the mobility decisions and livelihood needs and plans of five women (occupying different socio‐economic positions) were influenced by socio‐economic structures. The study shows that the women's mobility decisions allowed them to improve their socio‐economic positions and reconfigure their gendered identities in the local village, outside the fishing sector. Motility (which encapsulates socio‐spatial mobility) empowered these women by allowing them to move out of the increasingly precarious small‐scale fisheries industry. We argue that the concept of motility provides a useful analytical framework for understanding mobility, and we use the women's narratives to exemplify this claim.
Set to fail: Affective dynamics in a resistance training program designed to reach muscle concentric failure
Authors: Bastos Vasco , Andrade Ana Jesus , Rodrigues Filipe , Monteiro Diogo , Cid Luis , Teixeira Diogo Santos
Published: August 2022

Grounded in hedonic assumptions, evidence suggests that people tend to engage in activities they consider pleasurable and enjoyable, while trying to avoid pain and displeasure. This suggests that the dynamic between positive and negative affect can influence current behavior and the intentions to continue performing. Regarding resistance training (RT), research focusing on how to promote a better affective response is still scarce and much needed. Given existing limitations and theoretical suggestions, a RT program was developed and applied to recreational exercisers in a quasi‐experimental design aiming to (1) explore the affective response dynamic through an assessment after the last set of each exercise; and (2) analyze possible differences of preference and tolerance profiles in affective variables (core affect and enjoyment). For that purpose, 43 participants (21 male and 22 female; Mage = 34.69 ± 6.71 years; Mexperience = 8.32 ± 4.54 years; MBMI = 24.26 ± 2.64 kg/m2) accepted to participate in this study. Descriptive statistics, correlational, and group comparisons analyses were performed to provide evidence for proposed objectives. The present study showed that measures of affective valence/arousal applied immediately after a set represents a feasible and ecologically valid approach to tap core affect. Results presented evidence that recreationally trained exercisers in a common RT program would need a minimum of one measurement to assess the affective response. However, additional assessments could refine the understanding of exercise pleasurable experience. Results also suggest that exercisers with distinct profiles of preference/tolerance depicted differentiated patterns for the affective response, possibly justifying a distinct approach when promoting affective regulation.
Characterization of the novel HLA‐C*17:01:18 allele by sequencing‐based typing
Authors: Cargou Marine , Elsermans Vincent , Top Isabelle , Wojciechowski Elodie , Visentin Jonathan
Published: August 2022

HLA‐C*17:01:18 differs from HLA‐C*17:01:01:05 by one nucleotide substitution in codon 18 in exon 2.
Hospital‐level variation in rates of postpartum hemorrhage in California
Authors: Davis Rudolph , Guo Nan , Bentley Jason , Sie Lillian , Ansari Jessica , Bateman Brian , Main Elliot , Butwick Alexander J.
Published: August 2022

Background

To examine the extent of hospital‐level variation in risk‐adjusted rates of postpartum hemorrhage (PPH).

Study design and Methods

We performed a cross‐sectional study examining live births in 257 California hospitals between 2011 and 2015 using linked birth certificate and maternal discharge data. PPH was measured using International Classification of Diseases Codes version 9. Mixed‐effects logistic regression models were used to examine the presence and extent of hospital‐level variation in PPH before and after adjustment for patient‐level risk factors and select hospital characteristics (teaching status and annual delivery volume). Risk‐adjusted rates of PPH were estimated for each hospital. The extent of hospital variation was evaluated using the median odds ratio (MOR) and intraclass correlation coefficient (ICC).

Results

Our study cohort comprised 1,904,479 women who had a live birth delivery hospitalization at 247 hospitals. The median, lowest, and highest hospital‐specific rates of PPH were 3.48%, 0.54%, and 12.0%, respectively. Similar rates were observed after adjustment for patient and hospital factors (3.44%, 0.60%, and 11.48%). After adjustment, the proportion of the total variation in PPH rates attributable to the hospital was low, with a MOR of 2.02 (95% confidence interval [CI]: 1.89–2.15) and ICC of 14.3% (95% CI: 11.9%–16.3%).

Discussion

Wide variability exists in the rate of PPH across hospitals in California, not attributable to patient factors, hospital teaching status, and hospital annual delivery volume. Determining whether differences in hospital quality of care explain the unaccounted‐for variation in hospital‐level PPH rates should be a public health priority.
INTRODUCTION: FIVE STEPS TOWARD A RELIGION–AI DIALOGUE
Authors: Vestrucci Andrea
Published: August 2022

This introduction to the thematic section of Zygon: Journal of Religion and Science on “Artificial Intelligence and Religion: Recent Advances and Future Directions” outlines the five articles by dividing them into two groups: the three that analyze the impact of recent advances in subsymbolic artificial intelligence (AI) on religion and theology, and the two that explore theological concepts in symbolic AI environments. These five articles are five steps toward a strong, deep, and interdisciplinary dialogue between the research in religion and the research in AI.
On the Corruption of Communication: A Theory of Deception
Authors: Wijaya Bambang Sukma
Published: August 2022

This article elaborates on the issue of communication corruption, namely communicative actions or events that reduce the audience's right to receive messages entirely and correctly, according to normative (objective) and contemplative (subjective) facts. The literature study and reflectivity methods point out at least four main aspects of communication corruption theory: message, media, context, and behavior. This study also proposes a formula to measure and assess the extent to which communication is corrupt, considering communication needs and desires, authority and opportunity, communicative power, audience rights, conscience, and moral responsibility. Three forms of communication are very vulnerable to communication corruption: persuasion, imaging (both in the effort of impression building and impression laundering), and deception. Future studies can use this study as a theoretical and methodological reference. Practically, the findings and propositions of this research are helpful as reflections and guidelines for anticipating and minimizing communication corruption practices in daily and professional activities.
Nonlinear Energy Sink Inspired Design for Friction-Induced Vibration Suppression of Braking Systems
Authors: Zhu Lisha , Yuan Cong , Yao Guo , Li Huanjun , Gao Wei
Published: August 2022

In this paper, a nonlinear energy sink (NES) is designed and applied for the suppression of the friction-induced vibration (FIV) of a braking system. The equation of motion of the braking system, as well as the NES, is established by using the Lagrange equation. The nonlinear restoring force of the NES is realized by vertically paralleling two linear springs. The friction force between the wheel and the braking block is calculated by the Coulomb–Stribeck friction model. The variation of the wheel speed with the friction force is derived by the kinetic energy theorem. From the simulation, two-stage FIV systems are observed. The wheel speed decreases monotonically in the first stage and oscillates around 0 m/s in the second stage. The effects of the contact pressure and stiffness coefficient of the block on the FIV system are analyzed. By series connecting the NES to the braking block, the amplitude of FIV braking system can be reduced significantly in the first stage. Furthermore, the effects of the mass ratio between the block and the NES, and the damping coefficient of the NES on the FIV braking system are also discussed. This research can be helpful for the vibration suppression design of the braking system in vehicles.
Impact of Thermal Source-Sink Arrangements on Buoyant Convection in a Nanofluid-Filled Annular Enclosure
Authors: Reddy N. Keerthi , Sankar M. , Jang Bongsoo
Published: August 2022

This investigation is devoted to analyze the buoyancy-driven flow behavior and associated thermal dissipation rate in a nanofluid-filled annular region with five different single source-sink and three different dual source-sink arrangements along the vertical surfaces. The remaining region on the vertical boundaries and horizontal surfaces are kept adiabatic. Numerical simulations have been performed by employing the finite difference method. To analyze the impacts of different nanofluids, nanoparticle volume fraction, Rayleigh number, size, and arrangement of sources and sinks, the results are graphically represented through streamline and isotherm contours, thermal profiles, average Nusselt number, and cup-mixing temperature. The results showed that identifying an optimum location and length of source-sink with a proper selection of other control parameters can lead to enhanced thermal transport and thermal mixing in the enclosure. In particular, middle-middle thermally active location and placing source-sink separately on the vertical walls lead to the production of maximum heat transport compared to other single and dual source-sink arrangements, respectively. Also, among the two nanofluids considered in the current investigation, larger enhancement in thermal transport has been achieved for Cu-water nanofluid. The calculated enhancement ratio of the heat dissipation rate enhances with an increment in nanoparticle concentration.
Removal of Cavitation Using HDPE/LDPE Inline Section-Pipe
Authors: Fersi Mohamed , Triki Ali
Published: August 2022

This study dealt with the capacity of the inline technique to upgrade steel-pipe-based hydraulic systems with respect to magnitude attenuation and pressure-wave oscillation period expansion. This technique consisted in replacing a short-section of the induced transient pressure region with another of plastic material type, including high- or low-density polyethylene (HDPE or LDPE). The method of characteristics was implemented to discretize the extended one-dimensional water-Hammer Equations, embedding the Ramos et al. formulation. The comparison of the numerical solution with the observed data, quoted in the literature, and alternative numerical solution demonstrated the accuracy of the developed solver. The test case addressed a transient flow involving the cavitation onset. Results showed that the HDPE plastic-short-section-based layout of the inline technique provided the best tradeoff between magnitude attenuation and pressure-wave oscillation period expansion, in comparison with the LDPE plastic-short-section-based layout and the HDPE or LDPE material-based main-pipe systems.
Reliability and resistance projections for rhodium and iridium interconnects from first-principles
Authors: Lanzillo Nicholas A. , Edelstein Daniel C.
Published: August 2022

We apply first-principles simulations to evaluate several properties related to the resistance and reliability of rhodium and iridium interconnects. We find that both Rh and Ir have significantly higher activation energies of diffusion than state-of-the-art Cu interconnects, suggesting greatly improved resistance to electromigration failure. Since the practical integration of metal interconnects requires an adhesion liner, we calculate the metal-to-metal adhesion, surface scattering characteristics, and via resistance of four potential liner materials: TiN, TiO, TaN, and TaO. We find that TiO gives the strong metal-to-metal adhesion for both Rh and Ir, minimizing the risk of delamination. None of the four liner materials considered are found to have a significant impact on surface scattering of Rh or Ir, while the N-containing liners give lower via resistance than the O-containing liners. This work helps build a better understanding of fundamental material properties related to the practical integration of potential next-generation interconnect metals used for advanced semiconductor technology.
Phenotypic heterogeneity driven by plasticity of the intermediate EMT state governs disease progression and metastasis in breast cancer
Authors: Brown Meredith S. , Abdollahi Behnaz , Wilkins Owen M. , Lu Hanxu , Chakraborty Priyanka , Ognjenovic Nevena B. , Muller Kristen E. , Jolly Mohit Kumar , Christensen Brock C. , Hassanpour Saeed , Pattabiraman Diwakar R.
Published: August 2022

The epithelial-to-mesenchymal transition (EMT) is frequently co-opted by cancer cells to enhance migratory and invasive cell traits. It is a key contributor to heterogeneity, chemoresistance, and metastasis in many carcinoma types, where the intermediate EMT state plays a critical tumor-initiating role. We isolate multiple distinct single-cell clones from the SUM149PT human breast cell line spanning the EMT spectrum having diverse migratory, tumor-initiating, and metastatic qualities, including three unique intermediates. Using a multiomics approach, we identify CBFβ as a key regulator of metastatic ability in the intermediate state. To quantify epithelial-mesenchymal heterogeneity within tumors, we develop an advanced multiplexed immunostaining approach using SUM149-derived orthotopic tumors and find that the EMT state and epithelial-mesenchymal heterogeneity are predictive of overall survival in a cohort of stage III breast cancer. Our model reveals previously unidentified insights into the complex EMT spectrum and its regulatory networks, as well as the contributions of epithelial-mesenchymal plasticity (EMP) in tumor heterogeneity in breast cancer.
Conserved conformational dynamics determine enzyme activity
Authors: Torgeson Kristiane R. , Clarkson Michael W. , Granata Daniele , Lindorff-Larsen Kresten , Page Rebecca , Peti Wolfgang
Published: August 2022

Homologous enzymes often exhibit different catalytic rates despite a fully conserved active site. The canonical view is that an enzyme sequence defines its structure and function and, more recently, that intrinsic protein dynamics at different time scales enable and/or promote catalytic activity. Here, we show that, using the protein tyrosine phosphatase PTP1B, residues surrounding the PTP1B active site promote dynamically coordinated chemistry necessary for PTP1B function. However, residues distant to the active site also undergo distinct intermediate time scale dynamics and these dynamics are correlated with its catalytic activity and thus allow for different catalytic rates in this enzyme family. We identify these previously undetected motions using coevolutionary coupling analysis and nuclear magnetic resonance spectroscopy. Our findings strongly indicate that conserved dynamics drives the enzymatic activity of the PTP family. Characterization of these conserved dynamics allows for the identification of novel regulatory elements (therapeutic binding pockets) that can be leveraged for the control of enzymes.
A scalable solid-state nanoporous network with atomic-level interaction design for carbon dioxide capture
Authors: Mao Haiyan , Tang Jing , Day Gregory S. , Peng Yucan , Wang Haoze , Xiao Xin , Yang Yufei , Jiang Yuanwen , Chen Shuo , Halat David M. , Lund Alicia , Lv Xudong , Zhang Wenbo , Yang Chongqing , Lin Zhou , Zhou Hong-Cai , Pines Alexander , Cui Yi , Reimer Jeffrey A.
Published: August 2022

Carbon capture and sequestration reduces carbon dioxide emissions and is critical in accomplishing carbon neutrality targets. Here, we demonstrate new sustainable, solid-state, polyamine-appended, cyanuric acid–stabilized melamine nanoporous networks (MNNs) via dynamic combinatorial chemistry (DCC) at the kilogram scale toward effective and high-capacity carbon dioxide capture. Polyamine-appended MNNs reaction mechanisms with carbon dioxide were elucidated with double-level DCC where two-dimensional heteronuclear chemical shift correlation nuclear magnetic resonance spectroscopy was performed to demonstrate the interatomic interactions. We distinguished ammonium carbamate pairs and a mix of ammonium carbamate and carbamic acid during carbon dioxide chemisorption. The coordination of polyamine and cyanuric acid modification endows MNNs with high adsorption capacity (1.82 millimoles per gram at 1 bar), fast adsorption time (less than 1 minute), low price, and extraordinary stability to cycling by flue gas. This work creates a general industrialization method toward carbon dioxide capture via DCC atomic-level design strategies.
Modulation of pre-mRNA structure by hnRNP proteins regulates alternative splicing of
MALT1
Authors: Jones Alisha N. , Graß Carina , Meininger Isabel , Geerlof Arie , Klostermann Melina , Zarnack Kathi , Krappmann Daniel , Sattler Michael
Published: August 2022

Alternative splicing plays key roles for cell type–specific regulation of protein function. It is controlled by cis-regulatory RNA elements that are recognized by RNA binding proteins (RBPs). The MALT1 paracaspase is a key factor of signaling pathways that mediate innate and adaptive immune responses. Alternative splicing of
MALT1
is critical for controlling optimal T cell activation. We demonstrate that
MALT1
splicing depends on RNA structural elements that sequester the splice sites of the alternatively spliced exon7. The RBPs hnRNP U and hnRNP L bind competitively to stem-loop RNA structures that involve the 5′ and 3′ splice sites flanking exon7. While hnRNP U stabilizes RNA stem-loop conformations that maintain exon7 skipping, hnRNP L disrupts these RNA elements to facilitate recruitment of the essential splicing factor U2AF2, thereby promoting exon7 inclusion. Our data represent a paradigm for the control of splice site selection by differential RBP binding and modulation of pre-mRNA structure.
Intracavity generation of glioma stem cell–specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy
Authors: Chen Chen , Jing Weiqiang , Chen Yu , Wang Ganyu , Abdalla Mohnad , Gao Lin , Han Maosen , Shi Chongdeng , Li Anning , Sun Peng , Jiang Xin , Yang Zhenmei , Zhang Shengchang , Zhang Jing , Tang Chunwei , Liu Ying , Zhang Rui , Xu Fengbo , Dong Baixiang , Li Xueen , Liu Minglu , Qiang Bangming , Sun Yanhua , Wei Xia , Li Jun , Hu Quanyin , Jiang Xinyi
Published: August 2022

Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating disease, yet effective strategies remain elusive. Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. Specifically, we demonstrate that the CAR gene–laden nanoporter in the hydrogel can introduce GSC-targeted CAR genes into MΦ nuclei after intracavity delivery to generate CAR-MΦs in mouse models of GBM. These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. In an orthotopic patient–derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell–specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies.
Altiratinib blocks
Toxoplasma gondii
and
Plasmodium falciparum
development by selectively targeting a spliceosome kinase
Authors: Swale Christopher , Bellini Valeria , Bowler Matthew W. , Flore Nardella , Brenier-Pinchart Marie-Pierre , Cannella Dominique , Belmudes Lucid , Mas Caroline , Couté Yohann , Laurent Fabrice , Scherf Artur , Bougdour Alexandre , Hakimi Mohamed-Ali
Published: August 2022

The Apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that include
Toxoplasma gondii
,
Plasmodium
, and
Cryptosporidium
spp., which infect humans and animals and cause severe parasitic diseases. Available therapeutics against these diseases are limited by suboptimal efficacy and frequent side effects, as well as the emergence and spread of resistance. We use a drug repurposing strategy and identify altiratinib, a compound originally developed to treat glioblastoma, as a promising drug candidate with broad spectrum activity against apicomplexans. Altiratinib is parasiticidal and blocks the development of intracellular zoites in the nanomolar range and with a high selectivity index when used against
T. gondii
. We have identified
Tg
PRP4K of
T. gondii
as the primary target of altiratinib using genetic target deconvolution, which highlighted key residues within the kinase catalytic site that conferred drug resistance when mutated. We have further elucidated the molecular basis of the inhibitory mechanism and species selectivity of altiratinib for
Tg
PRP4K and for its
Plasmodium falciparum
counterpart,
Pf
CLK3. Our data identified structural features critical for binding of the other
Pf
CLK3 inhibitor, TCMDC-135051. Consistent with the splicing control activity of this kinase family, we have shown that altiratinib can cause global disruption of splicing, primarily through intron retention in both
T. gondii
and
P. falciparum
. Thus, our data establish parasitic PRP4K/CLK3 as a potential pan-apicomplexan target whose repertoire of inhibitors can be expanded by the addition of altiratinib.
Passive Immunization with a Single Monoclonal Neutralizing Antibody Protects against Cutaneous and Mucosal Mouse Papillomavirus Infections
Authors: Brendle Sarah A. , Li Jingwei , Cladel Nancy M. , Balogh Karla K. , Booth Jennifer , Shearer Debra A. , Walter Vonn , Lu Song , Christensen Neil D. , Covington Danielle , DeBroff Jake , Milici Janice , Zhu Yusheng , Viscidi Raphael , Hu Jiafen
Published: August 2022

This is the first study testing a single monoclonal neutralizing antibody (MPV.A4) by passive immunization against papillomavirus infections at both cutaneous and mucosal sites in the same host in the mouse papillomavirus model. We demonstrated that MPV.A4 administered before viral inoculation can protect both male and female athymic mice against MmuPV1 infections at cutaneous and mucosal sites.
Blockade of the Adenylate Cyclase Toxin Synergizes with Opsonizing Antibodies to Protect Mice against Bordetella pertussis
Authors: DiVenere Andrea M. , Amengor Dzifa , Silva Rui P. , Goldsmith Jory A. , McLellan Jason S. , Maynard Jennifer A.
Published: August 2022

Despite high vaccine coverage in developed countries, the incidence of pertussis has increased in recent decades, often leading to severe consequences for sensitive groups, including infants. For this reason, improving the efficacy of pertussis vaccines is critical, and the addition of new antigens is a leading strategy to achieve this goal.
Genome Sequence of SN1, a Bacteriophage That Infects Sphaerotilus natans and Pseudomonas aeruginosa
Authors: Gunathilake K. M. Damitha , Tremblay Denise M. , Plante Pier-Luc , Jensen Ellen C. , Nickerson Kenneth W. , Moineau Sylvain
Published: August 2022

Phage SN1 infects
Sphaerotilus natans
and
Pseudomonas aeruginosa
strains. Its genome consists of 61,858 bp (64.3% GC) and 89 genes, including 32 with predicted functions. SN1 genome is very similar to
Pseudomonas
phage M6, which contains hypermodified thymidines. Genome analyses revealed similar base-modifying genes as those found in M6.
Supplemental Material: Growth of the southern Tian Shan-Pamir and its impact on central Asian climate
Authors: Richter Fabiana , al. et
Published: August 2022

Supplementary Methods 1: Structure and Shortening. Supplementary Methods 2: Trishear modeling. Supplementary Data 1: References for compiled thermochronology (AFT) data. Table S1: Carbonate δ13C (‰VPDB) and δ18O (‰VPDB) isotopic results and mean values; descriptions of samples and outcrops; interpretations of depositional environments. Table S2: Descriptions, interpreted paleoenvironments and references for locations in Figure 11. Table S3: U-Pb data unknowns. Table S4: U-Pb Temora-2 standard data. Table S5: Statistical analysis of detrital zircon data. Table S6: Location of detrital zircon samples.
Adrenal insufficiency due to high doses of maternal corticosteroid treatment in a premature baby
Authors: Blondel Florence , Pierron Charlotte , Scalais Emmanuel , Becker Marianne
Published: August 2022

Adrenal insufficiency (AI) in a newborn due to hypothalamic–pituitary–adrenal (HPA) axis suppression after maternal glucocorticoid therapy during pregnancy is a rare condition. We report an AI triggered by a nosocomial infection in a premature newborn. The suspected mechanism was the suppression of the HPA axis due to high doses of maternal glucocorticoid treatment during pregnancy. AI was revealed by recurrent hypoglycaemia and mild hyponatraemia during the neonatal period. His twin brother did not develop AI, showing the variable sensitivity of adrenal suppression after exposure to the same glucocorticoid dose. The affected boy was substituted with hydrocortisone until the age of 2 years. At this age, basal morning values for cortisol and Adrenocorticotropic hormone (ACTH) had normalised. The patient also suffers from galactosaemia. We suggest screening for AI, by testing for hypoglycaemia and hyponatraemia, in newborns who were exposed to high doses of maternal methylprednisolone treatment during the pregnancy and to include galactosaemia in national neonatal screening programmes.
Symptomatic and severe pulmonary hypertension due to hyperthyroidism
Authors: Itagaki Tadashi , Miura Takashi , Kasai Toshio , Ikeda Uichi
Published: August 2022

Hyperthyroidism has been recognised as the cause of secondary pulmonary hypertension (PH). However, several studies have reported that most PH cases due to hyperthyroidism are asymptomatic and not severe. Here, we report the case of a woman in her 30s with symptomatic and severe PH due to hyperthyroidism. She presented with a 2-month history of dyspnoea on exertion, palpitation and lower-extremity oedema. Echocardiography showed severe PH with estimated pulmonary arterial systolic pressure (ePASP) of 62 mm Hg. The diagnostic work-up showed severe PH due to hyperthyroidism. After treatment for hyperthyroidism, improvement of thyroid function contributed to a decrease in ePASP to 30 mm Hg. Similar to the present case, PH due to hyperthyroidism generally improves with the treatment of hyperthyroidism. Therefore, we must not overlook hyperthyroidism as a cause of PH and diagnose and start treatment for PH-causing hyperthyroidism at an early stage.
Autologous Stem Cells in Achilles Tendinopathy (ASCAT): protocol for a phase IIA, single-centre, proof-of-concept study
Authors: Goldberg Andrew J , Zaidi Razi , Brooking Deirdre , Kim Louise , Korda Michelle , Masci Lorenzo , Green Ruth , O’Donnell Paul , Smith Roger
Published: August 2022

Introduction

Achilles tendinopathy (AT) is a cause of pain and disability affecting both athletes and sedentary individuals. More than 150 000 people in the UK every year suffer from AT.

While there is much preclinical work on the use of stem cells in tendon pathology, there is a scarcity of clinical data looking at the use of mesenchymal stem cells to treat tendon disease and there does not appear to be any studies of the use of autologous cultured mesenchymal stem cells (MSCs) for AT. Our hypothesis is that autologous culture expanded MSCs implanted into an area of mid-portion AT will lead to improved pain-free mechanical function. The current paper presents the protocol for a phase IIa clinical study.

Methods and analysis

The presented protocol is for a non-commercial, single-arm, open-label, phase IIa proof-of-concept study. The study will recruit 10 participants and will follow them up for 6 months. Included will be patients aged 18–70 years with chronic mid-portion AT who have failed at least 6 months of non-operative management. Participants will have a bone marrow aspirate collected from the posterior iliac crest under either local or general anaesthetic. MSCs will be isolated and expanded from the bone marrow. Four to 6 weeks after the harvest, participants will undergo implantation of the culture expanded MSCs under local anaesthetic and ultrasound guidance. The primary outcome will be safety as defined by the incidence rate of serious adverse reaction. The secondary outcomes will be efficacy as measured by patient-reported outcome measures and radiological outcome using ultrasound techniques.

Ethics and dissemination

The protocol has been approved by the National Research Ethics Service Committee (London, Harrow; reference 13/LO/1670). Trial findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NCT02064062.
Online information in Spanish on probiotics, yoghurt, kefir, kombucha, fibre and prebiotics: an analysis of the quality of information and the certainty of the evidence supporting health claims
Authors: Prados-Bo Andreu , Rabassa Montserrat , Bosch Mireia , Casino Gonzalo
Published: August 2022

Objective

To examine the certainty of the evidence supporting health claims about probiotics, yoghurt, kefir, kombucha, fibre and prebiotics, and to assess the quality of online information in Spanish.

Design

Content analysis.

Methods

We compiled a data set of 114 web pages by searching six popular search phrases in Spanish relating to probiotics, yoghurt, kefir, kombucha, fibre and prebiotics on Google.es and coded them for typology and health claims. We examined the certainty of the evidence for health claims from systematic reviews. Information quality was assessed according to 10 criteria, where a web page: mentions scientific publications and reports their conclusions; quantifies relative and absolute effects; acknowledges some limitations; discusses certainty of evidence; reports the potential harms, alternatives and costs; and does not argue based on personal experiences.

Results

Gastrointestinal health (86.0%), general health (57.9%), cardiovascular health (53.5%) and immune system health (50.9%) were the most widely mentioned topics. Half of claims (52.6%, 70/133) were supported by evidence from systematic reviews. Probiotics had the highest number of claims supported by evidence and kombucha the lowest. The highest certainty was found for antibiotic-associated diarrhoea, necrotising enterocolitis and otitis (moderate) in probiotics and yoghurt, infectious diarrhoea and hepatic encephalopathy (moderate) in prebiotics, and cardiovascular health (high to moderate) and colorectal cancer (moderate) in fibre. On a scale of 0–10, the median information quality score for all web pages was 3. Only 18.4% reported study conclusions, 7.9% quantified the effects, 28.9% acknowledged some limitations in the research and 42.1% reported potential harms.

Conclusions

Most online health claims for dietary interventions intended for improving health through the gut microbiome are supported by low or very low certainty of evidence. Online information does not align with the evidence and is incomplete or unbalanced.
New Zealand cricket injury analysis based on 12 years of Accident Compensation Corporation data
Authors: Walter Sibi , King Doug , Hume Patria
Published: August 2022

Objectives

To provide epidemiological data for cricket injuries in New Zealand.

Methods

A retrospective analytical review using epidemiological cricket data obtained from the national Accident Compensation Corporation (ACC) for 2005–2016. Injury incidence was calculated per 1000 participants.

Results

There were 86 562 injuries (77 212 males and 9350 females) during the 12 years with higher injury incidence for males (64.1) than females (36.1). While cricket-related injury claims increased by 42.6%, the injury incidence decreased from 59.0 in 2006 to 42.8 in 2016. The pooled injury rate per 1000 participants was highest for hand/fingers (9.2) and lumbar (8.1) body regions, and for contact (44.7) activities. Players aged 10–20 years were more likely to experience injury.

Conclusions

Analysis of 12 years of ACC cricket-related injury claims showed only minimal reductions in injury incidence over the years. Therefore, cricket-related contact injuries to the hand/fingers and head need to be the focus of injury prevention programmes (eg, via promoting use of protective gear and correct technique), particularly in players aged 10–20 years.
Firework injuries remain high in years after legalisation: its impact on children
Authors: Galet Colette , Slagel Isaac , Froehlich Adam , Bobb Morgan , Lilienthal Michele , Fuchsen Elizabeth , Harland Karisa K , Pelaez Carlos A , Skeete Dionne A , Takacs Michael E
Published: August 2022

Purpose

We evaluated the impact of Senate Bill 489 passed in May 2017, allowing the sale and use of fireworks in Iowa 1 June to 8 July and 10 December to 3 January, on hospital presentations for firework injuries in the state. To identify the public health implications of this law, we conducted a detailed subanalysis of hospital presentations to the two level I trauma centres.

Methods

Hospital presentations for firework injuries from 1 June 2014 to 31 July 2019 were identified using the Iowa Hospital Admission database and registries and medical records of Iowa’s two level 1 trauma centres. Trauma centres’ data were reviewed to obtain demographics, injury information and hospital course. Prefirework and postfirework legalisation state data were compared using negative binomial regression analysis. Trauma centre data detailing injuries were compared using χ2and Mann-Whitney U tests as appropriate.

Results

Emergency department (ED) visits and hospital admissions for firework injuries increased in Iowa post-legalisation (B-estimate=0.598±0.073, p<0.001 and B-estimate=0.612±0.322, p=0.058, respectively). ED visits increased postlegalisation in July (73.6% vs 64.5%; p=0.008), reflecting an increase in paediatric admissions (81.8% vs 62.5%; p=0.006). Trauma centres’ data showed similar trends. The most common injury site across both study periods was the hands (48.5%), followed by the eyes (34.3%) and face (28.3%). Amputations increased from 0 prelegalisation to 16.2% postlegalisation.

Conclusion

Firework legalisation led to an increase in the number of admissions and more severe injuries.
Molecular imaging to support cancer immunotherapy
Authors: van de Donk Pim P , Oosting Sjoukje F , Knapen Daan G , van der Wekken Anthonie J , Brouwers Adrienne H , Lub-de Hooge Marjolijn N , de Groot Derk-Jan A , de Vries Elisabeth GE
Published: August 2022

The advent of immune checkpoint inhibitors has reinvigorated the field of immuno-oncology. These monoclonal antibody-based therapies allow the immune system to recognize and eliminate malignant cells. This has resulted in improved survival of patients across several tumor types. However, not all patients respond to immunotherapy therefore predictive biomarkers are important. There are only a few Food and Drug Administration-approved biomarkers to select patients for immunotherapy. These biomarkers do not consider the heterogeneity of tumor characteristics across lesions within a patient. New molecular imaging tracers allow for whole-body visualization with positron emission tomography (PET) of tumor and immune cell characteristics, and drug distribution, which might guide treatment decision making. Here, we summarize recent developments in molecular imaging of immune checkpoint molecules, such as PD-L1, PD-1, CTLA-4, and LAG-3. We discuss several molecular imaging approaches of immune cell subsets and briefly summarize the role of FDG-PET for evaluating cancer immunotherapy. The main focus is on developments in clinical molecular imaging studies, next to preclinical studies of interest given their potential translation to the clinic.