bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeny and evolution of chloroplast tRNAs in Adoxaceae
Authors: Zhong Qiu‐Yi , Fu Xiao‐Gang , Zhang Ting‐Ting , Zhou Tong , Yue Ming , Liu Jian‐Ni , Li Zhong‐Hu
Published: January 2021

Chloroplasts are semiautonomous organelles found in photosynthetic plants. The major functions of chloroplasts include photosynthesis and carbon fixation, which are mainly regulated by its circular genomes. In the highly conserved chloroplast genome, the chloroplast transfer RNA genes (cp tRNA) play important roles in protein translation within chloroplasts. However, the evolution of cp tRNAs remains unclear. Thus, in the present study, we investigated the evolutionary characteristics of chloroplast tRNAs in five Adoxaceae species using 185 tRNA gene sequences. In total, 37 tRNAs encoding 28 anticodons are found in the chloroplast genome in Adoxaceae species. Some consensus sequences are found within the Ψ‐stem and anticodon loop of the tRNAs. Some putative novel structures were also identified, including a new stem located in the variable region of tRNATyr in a similar manner to the anticodon stem. Furthermore, phylogenetic and evolutionary analyses indicated that synonymous tRNAs may have evolved from multiple ancestors and frequent tRNA duplications during the evolutionary process may have been primarily caused by positive selection and adaptive evolution. The transition and transversion rates are uneven among different tRNA isotypes. For all tRNAs, the transition rate is greater with a transition/transversion bias of 3.13. Phylogenetic analysis of cp tRNA suggested that the type I introns in different taxa (including eukaryote organisms and cyanobacteria) share the conserved sequences “U‐U‐x2‐C” and “U‐x‐G‐x2‐T,” thereby indicating the diverse cyanobacterial origins of organelles. This detailed study of cp tRNAs in Adoxaceae may facilitate further investigations of the evolution, phylogeny, structure, and related functions of chloroplast tRNAs.
Impact of primary care involvement and setting on multidisciplinary heart failure management: a systematic review and meta‐analysis
Authors: Raat Willem , Smeets Miek , Janssens Stefan , Vaes Bert
Published: January 2021

Multidisciplinary disease management programmes (DMPs) are a cornerstone of modern guideline‐recommended care for heart failure (HF). Few programmes are community initiated or involve primary care professionals, despite the importance of home‐based care for HF. We compared the outcomes of different multidisciplinary HF DMPs in relation to their recruitment setting and involvement of primary care health professionals. We conducted a systematic review and meta‐analysis of randomized controlled trials published in MEDLINE, Embase, and Cochrane between 2000 and 2020 using Cochrane Collaboration methodology. Our meta‐analysis included 19 randomized controlled trials (7577 patients), classified according to recruitment setting and involvement of primary care professionals. Thirteen studies recruited in the hospital (n = 5243 patients) and six in the community (n = 2334 patients). Only six studies involved primary care professionals (n = 3427 patients), with two of these recruited in the community (n = 225 patients). Multidisciplinary HF DMPs that recruited in the community had no significant effect on all‐cause and HF readmissions nor on mortality, irrespective of primary care involvement. Studies that recruited in the hospital demonstrated a significant reduction in mortality (relative risk 0.87, 95% confidence interval [CI] [0.76, 0.98]), HF readmissions (0.70, 95% CI [0.54, 0.89]), and all‐cause readmissions (0.72, 95% CI [0.60, 0.87]). However, the difference in effect size between recruitment setting and involvement of primary care was not significant in a meta‐regression analysis. Multidisciplinary HF DMPs that recruit in the community have no significant effect on mortality or hospital readmissions, unlike DMPs that recruit in the hospital, although the difference in effect size was not significant in a meta‐regression analysis. Only six multidisciplinary studies involved primary care professionals. Given demographic evolutions and the importance of integrated home‐based care for patients with HF, future multidisciplinary HF DMPs should consider integrating primary care professionals and evaluating the effectiveness of this model.
A widening gap between boys and girls in musculoskeletal complaints, while growing up from age 11 to age 20 ‐ the PIAMA birth Cohort study
Authors: Picavet H Susan J. , Gehring Ulrike , van Haselen Amanda , Koppelman Gerard H. , van de Putte Elise M. , Vader Sarah , van der Wouden J.(Hans) C. , Schmits Ruben J. H. , Smit Henriette A. , Wijga Alet
Published: January 2021

Introduction

The adolescent years represent a key period for the development of musculoskeletal complaints (MSC) and the differences between boys and girls. We evaluated the prevalence and course of MSC and factors associated with MSC while growing up from age 11 to age 20.

Methods

Questionnaire‐based data at age 11 (n = 2,638), age 14 (n = 2,517), age 17 (n = 2,094) and at age 20 (n = 2,206) from the ongoing Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort were analyzed. MSC refers to pain of lower back, upper‐ and/or lower extremities. A multivariable logistic regression analysis was used to evaluate a number of factors in relation to persistent pain (pain reported at three out of four measurements).

Results

Prevalence of MSC increased from 14.2% at age 11 to 22.1% at age 20 for boys, and from 17.4% at age 11 to 37.9% at age 20 for girls. Persistent pain was found among 5.1% of the boys and 16.5% of the girls. Being bullied, sleeping problems and tiredness during the day were significantly associated with persistent pain, in both boys and girls, while the latter two were more prevalent among girls. Self‐reported (sports‐) accidents, and among girls also early onset of puberty, were also significantly associated with persistent pain, but lifestyle factors, such as physical activity and smoking, were not.

Conclusion

The prevalence of MSC increases during adolescence, with a widening gap between boys and girls. The factors associated with MSC are similar in boys and girls, though the prevalence of some of these differ by sex.

Significance

Measuring a group of youngsters 4 times between age 11 and 20 shows an increase in the percentage reporting musculoskeletal complaints (MSC) with a widening gap between girls and boys, with more pain among girls. Boys and girls do hardly differ with respect to factors associated with MSC, being mainly psychosocial factors and (sports) accidents.
Age differences in cognitive–affective processes in adults with chronic pain
Authors: Murray Caitlin B. , Patel Kushang V. , Twiddy Hanah , Sturgeon John A. , Palermo Tonya M.
Published: January 2021

Background

Chronic pain is associated with significant physical and psychological impairments across the adult lifespan. However, there is a relative gap in knowledge on individual differences that predict pain‐related functioning. The current study highlights one important source of individual variation: age.

Methods

We used cross‐sectional data from a large treatment‐seeking cohort of 2,905 adults (M age = 46.6 [13.1]; 71.8% women) presenting to a tertiary pain centre in the United Kingdom to determine age differences in cognitive‐affective processes (catastrophizing, acceptance, self‐efficacy), including their differential patterns and effects on disability and depression.

Results

Older adults (ages 65–75) were found to experience higher pain acceptance and pain self‐efficacy compared to both middle‐aged (ages 40–64) and young adult (ages 18–39) age groups. Older adults also experienced lower levels of catasophizing compared to middle‐age adults. Testing age as a moderator, we found that the relationships of pain self‐efficacy and acceptance with depression as well as the relationship between pain self‐efficacy and disability were comparatively weakest among older adults and strongest among young adults. Similarly, the relationship between pain catastrophizing and depression was relatively stronger for young and middle‐aged adults compared to older adults.

Conclusions

Age‐related differences in psychological mechanisms that influence pain‐related functioning present unique challenges and opportunities for scientists and clinicians to improve our understanding and treatment of pain across the lifespan. Additional work is needed to refine our knowledge of age‐related differences in cognitive‐affective, biopsychosocial dimensions of chronic pain and to develop and test the efficacy of age‐tailored interventions.

Significance

Our cross‐sectional analysis of 2,905 treatment‐seeking adults with chronic pain presenting to a tertiary care center in the United Kingdom revealed distinct age differences in cognitive‐affective linked to disability and depression. This study contributes to the limited knowledge on age‐related variance in psychological mechanisms underlying adjustment to chronic pain. Promising avenues for future research include refining our understanding of age‐related differences in cognitive–affective, biopsychosocial dimensions of chronic pain and elucidating the most salient treatment targets among different age groups.
Contraceptive discontinuation and switching in urban Istanbul region in Turkey
Authors: Kurutas Sebahat , Sato Ryoko , Huber‐Krum Sarah , Baykal Simay Sevval , Rohr Julia , Karadon Duygu , Kaur Navdep , Okcuoğlu Bahar Ayca , Esmer Yılmaz , Canning David , Shah Iqbal
Published: January 2021

Objective

To evaluate rates of contraceptive discontinuation and method switching and examine their determinants in Istanbul, Turkey, because discontinuation of modern contraception leading to unintended pregnancy is a public health concern.

Methods

We conducted a cross‐sectional household survey between March and June 2018 among 4224 married women of reproductive age (16–44 years). Information on contraceptive use and discontinuation for the 31 months preceding the survey was recorded in a monthly calendar. Using single and multiple decrement life‐table methods, we calculated the overall discontinuation and the cause‐specific discontinuation rates.

Results

The 12‐month overall discontinuation rate was 12.32%. Intrauterine devices had the lowest discontinuation rate (7.12%). The most common reasons for discontinuation were the desire to become pregnant (6.56%) and method failure (2.76%). One in three episodes of discontinuation was not followed by method switching (32.16%). Age, education, and the method type were predictive of contraceptive discontinuation.

Conclusion

To reduce method failure, women should be provided with information about method effectiveness, correct use of methods, and what to do if they anticipate their method failed (e.g., emergency contraception). Programs should focus on improving knowledge about discontinuation and method failure. Contraceptive counseling should also emphasize timely switching to an effective method after discontinuation.
iTRAQ‐based proteomic analysis of the molecular mechanisms and downstream effects of fatty acid synthase in osteosarcoma cells
Authors: Fu Dahua , Liu Shuochuan , Liu Jiaming , Chen Wenzhao , Long Xinhua , Chen Xuanyin , Zhou Yang , Zheng Yibin , Huang Shanhu
Published: January 2021

Background

Fatty acid synthase (FASN) is a lipogenic enzyme that participates in tumor progression. We previously showed that FASN is dysregulated in OS malignancy, but the molecular mechanism(s) of these effects remained unclear.

Methods

We examined differentially expressed proteins (DEPs) in FASN‐silenced osteosarcoma 143B cells and their parental cells by isobaric tags for relative and absolute quantitation (iTRAQ). Differentially expressed proteins were classified using GO and KEGG analysis. The association between FASN and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) was confirmed using qPCR, Western blot, and immunohistochemistry. The function of HNRNPA1 in osteosarcoma was determined using CCK‐8, colony formation, wound healing, transwell migration, and invasion assays.

Results

Among the 4971 identified proteins, 567 DEPs (325 upregulated and 242 downregulated) were identified. The top 10 upregulated proteins comprised HIST1H2AB, INA, INTS5, MTCH2, EIF1, MAPK1IP1L, PXK, RPS27, PM20D2, and ZNF800, while the top 10 downregulated proteins comprised NDRG1, CNTLN, STON2, GDF7, HECTD3, HBB, TPM1, PPP4R4, PTTG1IP, and PLCB3. Bioinformatic analysis indicated that the DEPs were related to cellular processes, metabolic processes, biological regulation, binding, and catalytic activity. HNRNPA1 was dysregulated in FASN‐silenced 143B and HOS cells. qPCR, Western blot, and immunohistochemistry showed that FASN expression positively correlates with HNRNPA1 expression. Further studies indicated that HNRNPA1 correlates with OS diagnosis and prognosis. And HNRNPA1 silence inhibits the proliferation, migration, and invasion in OS cells.

Conclusion

HNRNPA1 acts as targets downstream of FASN and potential biomarker and oncogene in OS.
Atomic force microscopy studies of enamel, inner enamel, dentin, and cementum in canine teeth
Authors: Solaymani Shahram , Nezafat Negin Beryani , Ţălu Ştefan , Shafiekhani Azizollah , Dalouji Vali , Amiri Ali , Rezaee Sahar , Morozov Ilya A.
Published: January 2021

The main goal of the present work is to explore the three dimensional (3‐D) atomic force microscopy (AFM) images of human teeth and investigating their micromorphology. For this purpose, 10 fresh and permanent canine teeth were selected from a group of 40‐year‐old men who were candidate for the experimental processes. Afterward, they were all applied for studying the morphology of their hard tissues. The tapping mode of AFM was used to characterize the surface micromorphology on the square areas of 1 μm × 1 μm (512 × 512 pts). AFM results and surface stereometric analysis indicate the relationships between the micromorphology of the surface and the structural properties of these tissues across the length scales. As can be seen, the surface of cementum has the most irregular topography (D = 2.87 ± 0.01) while the most regular topography (D = 2.43 ± 0.01) is found in dentin. Furthermore, the more and less regularity of the surface have been found in inner enamel (Sq = 26.26 nm) and dentin (Sq = 41.28 nm), respectively. Stereometric and fractal analyses give valuable information about human canine teeth via 3‐D micromorphology.
Increased Risk of Parkinson's Disease in Patients With Schizophrenia Spectrum Disorders
Authors: Kuusimäki Tomi , Al‐Abdulrasul Haidar , Kurki Samu , Hietala Jarmo , Hartikainen Sirpa , Koponen Marjaana , Tolppanen Anna‐Maija , Kaasinen Valtteri
Published: January 2021

Background

PD comorbid with schizophrenia has been considered rare because these diseases associate with opposite alterations in the brain dopamine system. The objective of this study was to investigate the risk of PD after a diagnosis of a schizophrenia spectrum disorder.

Methods

Regionally, this was a retrospective record‐based case–control study. The cohort included 3045 PD patients treated 2004–2019 in southwestern Finland. Nationally this was a nested case–control study using registers to examine Finnish patients who received a clinically confirmed PD diagnosis 1996–2015 (n = 22,189). PD patients with previously diagnosed schizophrenia spectrum disorder (separate analysis for schizophrenia) were included. Comparable non‐PD control groups were derived from both data sets. All PD diagnoses were based on individual clinical examinations by certified neurologists.

Results

In PD patients, the prevalence of earlier schizophrenia spectrum disorder was 0.76% in regional data and 1.50% in nationwide data. In age‐matched controls, the prevalence in the regional and national data was 0.16% and 1.31%, respectively. The odds ratio for PD after schizophrenia spectrum disorder diagnosis was 4.63 (95% CI, 1.76–12.19; P < 0.01) in the regional data and 1.17 (95% CI, 1.04–1.31; P < 0.01) in the national data.

Conclusions

Schizophrenia spectrum disorder increases the risk of PD later in life. This association was observed in both individual patient data and nationwide register data. Therefore, despite the opposite dopaminergic disease mechanisms, schizophrenia spectrum disorder increases rather than decreases the risk of PD. The increased PD risk could be related to risk‐altering effects of dopamine receptor antagonists or to the increased vulnerability of the dopamine system induced by illness phase‐dependent dopamine dysregulation in schizophrenia/schizophrenia spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
A phase I trial of the CDK 4/6 inhibitor palbociclib in pediatric patients with progressive brain tumors: A Pediatric Brain Tumor Consortium study (PBTC‐042)
Authors: Van Mater David , Gururangan Sridharan , Becher Oren , Campagne Olivia , Leary Sarah , Phillips Joanna J. , Huang Jie , Lin Tong , Poussaint Tina Young , Goldman Stewart , Baxter Patricia , Dhall Girish , Robinson Giles , DeWire‐Schottmiller Mariko , Hwang Eugene I. , Stewart Clinton F. , Onar‐Thomas Arzu , Dunkel Ira J. , Fouladi Maryam
Published: January 2021

Background

Disruption of cell‐cycle regulators is a potential therapeutic target for brain tumors in children and adolescents. The aim of this study was to determine the maximum tolerated dose (MTD) and describe toxicities related to palbociclib, a selective cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor in pediatric patients with progressive/refractory brain tumors with intact retinoblastoma protein.

Methods

Palbociclib was administered orally starting at 50 mg/m2 daily for the first 21 days of a 28‐day course. Dose escalation was according to the Rolling‐6 statistical design in less heavily (stratum I) and heavily pretreated (stratum II) patients, and MTD was determined separately for each group. Pharmacokinetic studies were performed during the first course, and pharmacodynamic studies were conducted to evaluate relationships between drug levels and toxicities.

Results

A total of 21 patients were enrolled on stratum I and 14 patients on stratum II. The MTD for both strata was 75 mg/m2. Palbociclib absorption (mean Tmax between 4.9 and 6.6 h) and elimination (mean half‐life between 11.3 and 19.5 h) were assessed. The most common toxicity was myelosuppression. Higher palbociclib exposure was associated with grade 3/4 neutropenia and leukopenia. Dose limiting toxicities included grade 4 neutropenia and grade 3 thrombocytopenia and dehydration. No patients had an objective response to palbociclib therapy.

Conclusions

Palbociclib was safely administered to children and adolescents at a dosage of 75 mg/m2 for 21 consecutive days followed by seven days of rest in both strata. Future studies will establish its optimal utilization in pediatric patients with brain tumors.
Pharmacotherapy considerations in transgender individuals living with human immunodeficiency virus
Authors: Badowski Melissa E. , Britt Nicholas , Huesgen Emily C. , Lewis Michelle M. , Miller Misty M. , Nowak Kathleen , Sherman Elizabeth , Smith Renata O.
Published: January 2021

Pharmacotherapy considerations are often a concern for transgender individuals who are living with human immunodeficiency virus (HIV) due to concerns for drug–drug interactions between their hormone and antiretroviral therapies. Many of the first‐line therapies offered to patients for the management of HIV have reduced concerns for safety, resistance, and drug–drug interactions. In this review, we highlight common medications and important considerations for caring for transgender people living with HIV.
Geometry and complexity of path integrals in inhomogeneous CFTs
Authors: Caputa Paweł , MacCormack Ian
Published: January 2021

Abstract

In this work we develop the path integral optimization in a class of inhomogeneous 2d CFTs constructed by putting an ordinary CFT on a space with a position dependent metric. After setting up and solving the general optimization problem, we study specific examples, including the Möbius, SSD and Rainbow deformed CFTs, and analyze path integral geometries and complexity for universal classes of states in these models. We find that metrics for optimal path integrals coincide with particular slices of AdS3 geometries, on which Einstein’s equations are equivalent to the condition for minimal path integral complexity. We also find that while leading divergences of path integral complexity remain unchanged, constant contributions are modified in a universal, position dependent manner. Moreover, we analyze entanglement entropies in inhomogeneous CFTs and show that they satisfy Hill’s equations, which can be used to extract the energy density consistent with the first law of entanglement. Our findings not only support comparisons between slices of bulk spacetimes and circuits of path integrations, but also demonstrate that path integral geometries and complexity serve as a powerful tool for understanding the interesting physics of inhomogeneous systems.
Gravitational cubic-in-spin interaction at the next-to-leading post-Newtonian order
Authors: Levi Michèle , Mougiakakos Stavros , Vieira Mariana
Published: January 2021

Abstract

In this work we derive for the first time the complete gravitational cubic-in-spin effective action at the next-to-leading order in the post-Newtonian (PN) expansion for the interaction of generic compact binaries via the effective field theory for gravitating spinning objects, which we extend in this work. This sector, which enters at the fourth and a half PN (4.5PN) order for rapidly-rotating compact objects, completes finite-size effects up to this PN order, and is the first sector completed beyond the current state of the art for generic compact binary dynamics at the 4PN order. At this order in spins with gravitational nonlinearities we have to take into account additional terms, which arise from a new type of worldline couplings, due to the fact that at this order the Tulczyjew gauge for the rotational degrees of freedom, which involves the linear momentum, can no longer be approximated only in terms of the four-velocity. One of the main motivations for us to tackle this sector is also to see what happens when we go to a sector, which corresponds to the gravitational Compton scattering with quantum spins larger than one, and maybe possibly also get an insight on the inability to uniquely fix its amplitude from factorization when spins larger than two are involved. A general observation that we can clearly make already is that even-parity sectors in the order of the spin are easier to handle than odd ones. In the quantum context this corresponds to the greater ease of dealing with bosons compared to fermions.
Automorphic forms and fermion masses
Authors: Ding Gui-Jun , Feruglio Ferruccio , Liu Xiang-Gan
Published: January 2021

Abstract

We extend the framework of modular invariant supersymmetric theories to encompass invariance under more general discrete groups Γ, that allow the presence of several moduli and make connection with the theory of automorphic forms. Moduli span a coset space G/K, where G is a Lie group and K is a compact subgroup of G, modded out by Γ. For a general choice of G, K, Γ and a generic matter content, we explicitly construct a minimal Kähler potential and a general superpotential, for both rigid and local $$ \mathcal{N} $$
N
= 1 supersymmetric theories. We also specialize our construction to the case G = Sp(2g, ℝ), K = U(g) and Γ = Sp(2g, ℤ), whose automorphic forms are Siegel modular forms. We show how our general theory can be consistently restricted to multi-dimensional regions of the moduli space enjoying residual symmetries. After choosing g = 2, we present several examples of models for lepton and quark masses where Yukawa couplings are Siegel modular forms of level 2.
Analysis of Hydroacoustic Signals Associated to the Loss of the Argentinian ARA San Juan Submarine
Authors: Vergoz Julien , Cansi Yves , Cano Yoann , Gaillard Pierre
Published: January 2021

On November 15, 2017, an event related to the disappearance of the Argentine military submarine ARA San Juan was detected by two hydrophone triplet stations of the IMS network, established to enforce the nuclear test ban treaty (CTBT). From the two direct hydroacoustic arrivals recorded at 6000 and 8000 km from the localized wreckage, calculated location based on hydroacoustic data only is poorly constrained, and the associated uncertainties are large. In an attempt to interpret the recorded signals, an air dropped calibration grenade was conducted by the Argentine Navy two weeks later, on December 1, 2017, near the last known position of the submarine. From the comparison of temporal and spectral features of both events, we confirm the impulsive nature of the San Juan event. Array processing was performed with a progressive multi-channel correlation method (PMCC). Fine propagation details of direct arrivals are very well resolved in time-frequency space and thirteen secondary arrivals are revealed for the San Juan event, within the fifteen minutes following direct arrivals. The detections presented in this paper were calculated with DTK-PMCC software embedded in the NDC-In-A-Box virtual machine, and can be reproduced by any CTBTO principal user (Member State user which can access raw waveform data and data bulletins). All the identified late arrivals are associated to reflections or refractions from seamounts, islands and the South American continental Slope. The accurate identification of all the reflectors allows to significantly improve the source location accuracy: 95% confidence ellipse area has been reduced by a factor of 100 compared to location obtained from direct arrivals only, and the estimated location is 3.5 km from the known location of the wreckage. The originality of the relocation method is that it is based on the joint inversion of both San Juan and calibration events unknown parameters, and from the selection of only a well-chosen subset of secondary arrivals. Its calculation did not require either the need of advanced oceanographic specifications, or sophisticated methods requiring heavy computational means. Finally, a detailed cepstral analysis of the direct and secondary arrivals has allowed to detect the existence of a second impulse (doublet) in the signals associated to both San Juan and calibration events. Unlike the calibration event, the anisotropic character of the delays measured from the San Juan cepstra suggests that the 15 November signal was generated by two impulsive acoustic sources closely separated in space and time over scales comparable to the size of the submarine. This study demonstrates the capability of the hydroacoustic component of the IMS network to accomplish its mission of Comprehensive Nuclear-Test-Ban Treaty monitoring.
Variations in Apparent Stress and b Value Preceding the 2010 Mw8.8 Bio-Bío, Chile Earthquake
Authors: Li Yane , Chen Xuezhong
Published: January 2021

We calculated apparent stresses for 70 earthquakes (MW ≥ 5.0) occurring in the aftershock region of the 2010MW8.8 Bio-Bío earthquake from January 1990 to September 2019. We identified that the average apparent stress was approximately 0.487 MPa between January 1990 and December 2005 and approximately 1.063 MPa within the period from January 2006 to January 2010. The latter one is 2.2-fold greater than the former, representing a significant difference as determined by a z test, with a 99% confidence level. Moreover, we analyzed the temporal evolution of the apparent stress and found that apparent stress rapidly increased from 0.43 to 1.2 MPa during the pre-event period from March 2006 to the occurrence of the Bio-BíoMW8.8 mainshock, and this increased apparent stress was found to be significant at the 98% confidence level. Furthermore, we calculated the spatial distribution of the apparent stress in the study region and observed two higher-apparent-stress regions, within one of which the epicenter of theMW8.8 event was located. On the basis of the inverse correlation betweenbvalue and stress, the temporal evolution and spatial distribution ofbvalues were calculated and compared with those of the apparent stress. The comparison showed that thebvalues decreased approximately 4 years before the occurrence of the mainshock, while the apparent stress increased substantially; for the region of lowerb, the apparent stress is higher, and vice versa. Therefore, the inverse correlation betweenbvalue and stress is supported by the results obtained in the present study and can be probably considered as one of the precursors to great earthquakes.
CLASSIFICATION OF 3-GRADED CAUSAL SUBALGEBRAS OF REAL SIMPLE LIE ALGEBRAS
Authors: OEH D.
Published: January 2021

Let ($$ \mathfrak{g} $$g, τ) be a real simple symmetric Lie algebra and letW⊂$$ \mathfrak{g} $$gbe an invariant closed convex cone which is pointed and generating withτ(W) = −W. For elementsh∈$$ \mathfrak{g} $$gwithτ(h) =h, we classify the Lie algebras$$ \mathfrak{g} $$g(W,τ,h) which are generated by the closed convex cones$$ {C}_{\pm}\left(W,\tau, h\right):= \left(\pm W\right)\cap {\mathfrak{g}}_{\pm 1}^{-\tau }(h) $$C±Wτh≔±W∩g±1−τh, where$$ {\mathfrak{g}}_{\pm 1}^{-\tau }(h):= \left\{x\in \mathfrak{g}:\tau (x)=-x\left[h,x\right]=\pm x\right\} $$g±1−τh≔x∈g:τx=−xhx=±x. These cones occur naturally as the skew-symmetric parts of the Lie wedges of endomorphism semigroups of certain standard subspaces. We prove in particular that, if$$ \mathfrak{g} $$g(W,τ,h) is non-trivial, then it is either a hermitian simple Lie algebra of tube type or a direct sum of two Lie algebras of this type. Moreover, we give for each hermitian simple Lie algebra and each equivalence class of involutive automorphismsτof$$ \mathfrak{g} $$gwithτ(W) = −Wa list of possible subalgebras$$ \mathfrak{g} $$g(W,τ,h) up to isomorphy.
The pathophysiology of stress urinary incontinence: a systematic review and meta-analysis
Authors: Falah-Hassani Kobra , Reeves Joanna , Shiri Rahman , Hickling Duane , McLean Linda
Published: January 2021

Introduction and hypothesis

To evaluate the evidence for pathologies underlying stress urinary incontinence (SUI) in women.

Methods

For the data sources, a structured search of the peer-reviewed literature (English language; 1960–April 2020) was conducted using predefined key terms in PubMed and Embase. Google Scholar was also searched. Peer-reviewed manuscripts that reported on anatomical, physiological or functional differences between females with signs and/or symptoms consistent with SUI and a concurrently recruited control group of continent females without any substantive urogynecological symptoms. Of 4629 publications screened, 84 met the inclusion criteria and were retained, among which 24 were included in meta-analyses.

Results

Selection bias was moderate to high; < 25% of studies controlled for major confounding variables for SUI (e.g., age, BMI and parity). There was a lack of standardization of methods among studies, and several measurement issues were identified. Results were synthesized qualitatively, and, where possible, random-effects meta-analyses were conducted. Deficits in urethral and bladder neck structure and support, neuromuscular and mechanical function of the striated urethral sphincter (SUS) and levator ani muscles all appear to be associated with SUI. Meta-analyses showed that observed bladder neck dilation and lower functional urethral length, bladder neck support and maximum urethral closure pressures are strong characteristic signs of SUI.

Conclusion

The pathology of SUI is multifactorial, with strong evidence pointing to bladder neck and urethral incompetence. While there is also evidence of impaired urethral support and levator ani function, standardized approaches to measurement are needed to generate higher levels of evidence.
Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival
Authors: Kamai Takao , Kijima Toshiki , Tsuzuki Toyonori , Nukui Akinori , Abe Hideyuki , Arai Kyoko , Yoshida Ken-Ichiro
Published: January 2021

Background

Adenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both.

Methods

In 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody.

Results

Increased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti–PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival.

Conclusions

Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.
Prognostic Factors in Curative Resected Locoregional Small Intestine Neuroendocrine Neoplasms
Authors: Evers Maximilian , Rinke Anja , Rütz Johannes , Ramaswamy Annette , Maurer Elisabeth , Bartsch Detlef K.
Published: January 2021

Background

Small intestinal neuroendocrine neoplasms (SI‐NEN) are rare, and only about 40% of patients are diagnosed without distant metastases. Aim of the study was to identify prognostic factors in patients with potentially curative resected locoregional SI‐NEN.

Methods

Patients with curative resected locoregional SI‐NEN (ENETS stages I‐III) were retrieved from a prospective data base. Demographic, surgical and pathological data of patients with and without disease recurrence were retrospectively analyzed using univariate and multivariate analysis.

Results

In a 20‐year period, 65 of 203 (32%) patients with SI‐NEN were operated for stages I–III disease. Thirty‐eight (58.5%) patients were men, and the median age at surgery was 59 (range 37–87) years. After median follow‐up of 65 months, 14 patients experienced disease relapse median 28.5 (range 6–122) months after initial surgery, of which 2 died due to their disease. Multivariate analysis revealed age ≥ 60 years (HR = 6.41, 95% CI 1.38–29.67, p = 0.017), tumor size ≥ 2 cm (HR = 26.54, 95% CI 4.46–157.62, p < 0.001), lymph node ratio > 0.5 (HR 7.18, 95% CI 1.74–29.74, p = 0.007) and multifocal tumor growth (HR = 6.98, 95% CI 1.66–29.39, p = 0.008) as independent negative prognostic factors and right hemicolectomy compared to segmental small bowel resection (HR = 0.04, 95% CI 0.01–0.24, p < 0.001) as independent protector against recurrence.

Conclusion

Patients with locoregional SI‐NEN with an age ≥ 60 years, tumor size ≥ 2 cm, lymph node ratio > 0.5 and multiple small bowel tumor foci have an increased risk for recurrence and might benefit from adjuvant treatment. In contrast, right hemicolectomy of ileal SI‐NEN seems to reduce the risk of recurrence.
Low value of whole-body dual-modality [18f]fluorodeoxyglucose positron emission tomography/computed tomography in primary staging of stage I–II nasopharyngeal carcinoma: a nest case-control study
Authors: Xiao Bei-Bei , Chen Qiu-Yan , Sun Xue-Song , Li Ji-Bin , Luo Dong-hua , Sun Rui , Lin Da-Feng , Zhang Xu , Fan Wei , Lv Xiao-Fei , Han Lu-Jun , Wen Yue-Feng , Yuan Li , Guo Shan-Shan , Liu Li-Ting , Liu Sai-Lan , Tang Qing-Nan , Liang Yu-Jing , Li Xiao-Yun , Lin Chao , Guo Ling , Mai Hai-Qiang , Tang Lin-Quan
Published: January 2021

Objectives

The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy.

Methods

A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat.

Results

Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival.

Conclusions

This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging.

Key Points

• PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions.

• No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.
Intraseasonal SST–precipitation relationship in a coupled reanalysis experiment using the MRI coupled atmosphere–ocean data assimilation system
Authors: Kobayashi Chiaki , Fujii Yosuke , Ishikawa Ichiro
Published: January 2021

To evaluate the atmosphere–ocean coupled data assimilation system developed at the Meteorological Research Institute, the lead-lag relation between the intraseasonal variations (with a time scale of 20–100 days) in precipitation and sea surface temperature (SST) is examined in the tropics. It is shown that the relationship over the tropical western Pacific in the coupled reanalysis experiment (CDA) follows the observed relationship more closely than that in the uncoupled reanalysis experiment (UCPL). However, the lead-lag correlations with the observed SST are almost identical between precipitations in CDA and UCPL, indicating that the atmospheric component is strongly constrained by atmospheric observations and hardly affected by the SSTs as boundary conditions. Better representation of the SST–precipitation relationship in CDA is, thus, mostly due to the SST variation modified by the model physics. Comparison with additional reanalysis experiments using coupled and uncoupled systems that assimilate only in-situ observations without satellite observations suggests that the coupled model's physics complements the relatively weak observation constraints and reduces the degradation of the SST–precipitation relationship. Additional analysis for CDA suggests that the warming-to-cooling (cooling-to-warming) transition of the surface net flux, which is in phase with precipitation, is delayed from the positive (negative) peak of SST due to downward heat propagation in the ocean. Comparison of the oceanic near-surface temperature field with observation data indicates that the downward propagation of heat signals is too fast in CDA, resulting in smaller lags of transitions of the net heat flux and precipitation behind SST peaks.
A detailed analysis of pediatric surgical malpractice claims in Germany: what is the probability of a pediatric surgeon to be accused or convicted?
Authors: Mahler Sara , Gianicolo Emilio , Muensterer Oliver J.
Published: January 2021

Aim of the study

Pediatric surgeons treat a vulnerable population in which unfavorable outcome can lead to substantial long-term costs, placing them at risk for malpractice claims. This study aims to characterize the frequency and circumstances in which malpractice claims were successfully brought against pediatric surgeons in Germany over the last 5 years.

Materials and methods

Anonymous data on medical treatment errors and payments were acquired from the Federal Chamber of Physicians from 2014 through 2018 and analyzed for most frequent diagnoses and circumstances that resulted in accusation or conviction. Those claims that were successfully rebutted were compared to as controls. Lifetime risk for being involved in litigation and its outcome was calculated.

Results

There were 129 medical malpractice claims over the 5-year observation period. Medical error was confirmed in 56 cases (43%); the rest were successfully appealed. The risk of the prototypical German pediatric surgeon to be accused was 5.24% and to be convicted 2.27% per year in practice. The most common reasons for conviction (alone or in combination) were surgical-technical errors (23%), treatment delay (21%), insufficient workup (17%), incorrect diagnosis (17%), and incomplete consent (16%).The most frequent circumstances leading to a conviction were trauma (27%), inguinal hernia (7%), circumcision (7%), testicular torsion (7%), acute abdomen (7%), and appendicitis (5%).

Conclusion

Over a 40-year career, pediatric surgeons in Germany face an average calculated risk of 2.1 to be accused and 0.9 to be convicted of malpractice claims. Certain circumstances pose higher risks for litigation than others. Knowledge of these patterns may help practitioners avoid medicolegal confrontation.
Clonal sector analysis and cell ablation confirm a function for DORNROESCHEN-LIKE in founder cells and the vasculature in Arabidopsis
Authors: Glowa Dorothea , Comelli Petra , Chandler John W. , Werr Wolfgang
Published: January 2021

Main conclusion

Inducible lineage analysis and cell ablation via conditional toxin expression in cells expressing the DORNRÖSCHEN-LIKE transcription factor represent an effective and complementary adjunct to conventional methods of functional gene analysis.

Classical methods of functional gene analysis via mutational and expression studies possess inherent limitations, and therefore, the function of a large proportion of transcription factors remains unknown. We have employed two complementary, indirect methods to obtain functional information for the AP2/ERF transcription factor DORNRÖSCHEN-LIKE (DRNL), which is dynamically expressed in flowers and marks lateral organ founder cells. An inducible, two-component Cre–Lox system was used to express beta-glucuronidase GUS in cells expressingDRNL, to perform a sector analysis that reveals lineages of cells that transiently expressedDRNLthroughout plant development. In a complementary approach, an inducible system was used to ablate cells expressingDRNLusing diphtheria toxin A chain, to visualise the phenotypic consequences. These complementary analyses demonstrate thatDRNLfunctionally marks founder cells of leaves and floral organs. Clonal sectors also included the vasculature of the leaves and petals, implicating a previously unidentified role for DRNL in provasculature development, which was confirmed in cotyledons by closer analysis ofdrnlmutants. Our findings demonstrate that inducible gene-specific lineage analysis and cell ablation via conditional toxin expression represent an effective and informative adjunct to conventional methods of functional gene analysis.
Computational study on lateral and medial wear characterization in knee implants by a multibody dynamic system
Authors: Fekete G.
Published: January 2021

Wear is one of the main mechanical factors that limits the survival of total knee replacements (TKRs) and it is known to be highly dependent on the local kinematics of the knee joint. In this study, an analytical wear model was coupled to a multibody dynamic model to obtain wear distribution at the lateral and medial contact plateaus of different TKRs. The major aim was to analyze if wear distribution on the contact plateaus can be an indicator of elevated tibiofemoral misalignment which can lead to rapid TKR failure. For the multibody dynamic simulations, commercial and prototype TKR geometries were used, coupled with an augmented Archard’s law. Squat movement was chosen due to its importance both in sports and in everyday life. As a conclusion, a new parameter, denoted as wear imbalance, is introduced, which can indicate whether a TKR, due to its geometrical features, is prone to be subjected to elevated wear and failure.
No experimental evidence for vector-free, long-range, upstream dispersal of adult Asian clams [Corbicula fluminea (Müller, 1774)]
Authors: Pernecker Bálint , Czirok Attila , Mauchart Péter , Boda Pál , Móra Arnold , Csabai Zoltán
Published: January 2021

The Asian clam (Corbicula fluminea) is one of the rapidly spreading, very successful aquatic invasive species, which has become established widely in many parts of the world. Its spread is assumed to be by both passive and active dispersal. However, the importance of active pedal movement in dispersal is hardly known. Since there was no direct evidence of this phenomenon, field observations were combined with laboratory experiments to find out if the clams move upstream actively, and how this is affected by the quality of the substrate, the density of the clams, and the water velocity. Field observations were conducted at a small watercourse with no waterborne transport. Experiments were done in an indoor artificial stream system, where the distances moved by adult clams were measured via digital image analysis. Substrate grain size, starting density of clams, and water velocity significantly affected clam movement. Fine grain sediment and slow flow velocity both facilitated spread, while there was no clear pattern of density-dependent dispersal. Also, we found no clear preference for either upstream or downstream movement. The maximum distance moved in the lab experiments predicts no more than 0.15 km/y active pedal movement in an upstream direction, while our field observations detected a much faster (0.5–11 km/y) upstream movement, which might be explained by passive dispersal, such as via human transport and ecto- or endozoochory. Overall, it seems that active movement of the species cannot read to long-distance migration.