bluuebunny/crossref_metadata_2025_split huggingface dataset:
PhieABEs: a PAM‐less/free high‐efficiency adenine base editor toolbox with wide target scope in plants
Authors: Tan Jiantao , Zeng Dongchang , Zhao Yanchang , Wang Yaxi , Liu Taoli , Li Shuangchun , Xue Yang , Luo Yuyu , Xie Xianrong , Chen Letian , Liu Yao‐Guang , Zhu Qinlong 
Published: January 2022

SummaryAdenine base editors (ABEs), which are generally engineered adenosine deaminases and Cas variants, introduce site‐specific A‐to‐G mutations for agronomic trait improvement. However, notably varying editing efficiencies, restrictive requirements for protospacer‐adjacent motifs (PAMs) and a narrow editing window greatly limit their application. Here, we developed a robust high‐efficiency ABE (PhieABE) toolbox for plants by fusing an evolved, highly active form of the adenosine deaminase TadA8e and a single‐stranded DNA‐binding domain (DBD), based on PAM‐less/free Streptococcus pyogenes Cas9 (SpCas9) nickase variants that recognize the PAM NGN (for SpCas9n‐NG and SpGn) or NNN (for SpRYn). By targeting 29 representative targets in rice and assessing the results, we demonstrate that PhieABEs have significantly improved base‐editing activity, expanded target range and broader editing windows compared to the ABE7.10 and general ABE8e systems. Among these PhieABEs, hyper ABE8e‐DBD‐SpRYn (hyABE8e‐SpRY) showed nearly 100% editing efficiency at some tested sites, with a high proportion of homozygous base substitutions in the editing windows and no single guide RNA (sgRNA)‐dependent off‐target changes. The original sgRNA was more compatible with PhieABEs than the evolved sgRNA. In conclusion, the DBD fusion effectively promotes base‐editing efficiency, and this novel PhieABE toolbox should have wide applications in plant functional genomics and crop improvement.
Knowledge about oral manifestations of systemic diseases among medical and dental students from Jordan: An interdisciplinary educational gap
Authors: Hassona Yazan , Salim Nesreen A. , Tarboush Nafez , Sartawi Samiha , Alrashdan Mohammad S. , Rajab Lamis , Sawair Faleh 
Published: January 2022

AbstractObjectiveTo assess the ability of medical students to recognize oral manifestation of selected systemic diseases and compare their performance with dental students.Materials and MethodsA total of 400 senior medical and dental students were approached to participate. The study protocol involved two parts; a self‐administered survey and a direct interview involving clinical photographs for oral signs of systemic diseases.ResultsA total of 283 (70.8%) agreed to participate and completed the two‐ part study. The study population was made of 110 (38.9%) [82 females and 28 males] dental students, and 173(61.1%) [98 females and 75 males] medical students. The knowledge score regarding questions about the normal mouth and oral structures was 15.7 ± 6 out of 22. Dental students had a significantly higher knowledge score about normal mouth and oral structures (20.9 ± 4; range from 17 to 22) compared to medical students (10.6 ± 7; range from 4 to 21) (p = .029). The knowledge score regarding questions about oral manifestations of systemic diseases was 26.8 ± 6 out of 40. Dental students had a significantly higher knowledge score about oral manifestations of systemic diseases (30.8 ± 7; range from 15 to 37) compared to medical students (22.9 ± 4; range from 10 to 36) (p = .031). Only 24.3% (n = 42) medical students reported having adequate training to be able to distinguish between normal mouth and diseases. Nearly all medical students (91.3%; n = 158) felt that it is important to have more formal training in oral examination and disease diagnosis.ConclusionMedical students lack adequate knowledge, diagnostic ability, and confidence with regard to diagnosis of oral signs of systemic diseases. To ensure that medical students have necessary skills in assessing oral diseases, curricula revisions and modifications are required, and specific oral health‐related learning outcomes should be introduced and reinforced through clinical training.
The Miocene deep‐seated spontaneous coal‐seam fire in the Upper Silesian Coal Basin (S Poland) and its geotectonic trigger mechanism
Authors: Nawrocki Jerzy , Ciesielczuk Justyna , Jura Dominik , Fabiańska Monika J. , Misz‐Kennan Magdalena 
Published: January 2022

AbstractThe deep‐seated spontaneous coal‐seam fire occurred in the southwestern part of the Upper Silesian Coal Basin (S Poland), confirmed by oxygenated compounds emission to over‐ and underlying rocks. The fire was dated at 19.2–19.8 Ma using the 39Ar‐40Ar method and palaeomagnetism. It was initiated in the Carpathian foreland thanks to a normal faulting in response to thrust‐loaded deflections of the Carpathian foreland lithosphere during collision of tectonic plates (Alcapa and stable Europe). The orogenic loading caused this normal faulting in the foreland and triggering the flexural mechanism of foredeep subsidence and forebulge uplift. Thanks to the dating of rocks affected by the spontaneous coal fire initiated during the rapid uplift of coal‐bearing rocks, when they became exposed to the aeration zone, the age of these mountain‐building processes in the Carpathians has been precisely defined.
Dacryocystitis in dogs caused by foreign bodies—Diagnosis and therapy in 14 Cases
Authors: Steinmetz Andrea , Dohmann Gustavo Werner Jara , Blobner Claudia Christine 
Published: January 2022

AbstractObjectiveTo describe foreign bodies (FBs) in the nasolacrimal sac of dogs, the history, and simple diagnostic and therapeutic approaches.Animals studiedFourteen dogs of different breeds, ages, and sexes were presented with unilateral dacryocystitis and had been treated without success for over 1–8 months.ProceduresPatient history, including prior treatment, was obtained from medical records. Slit‐lamp examination was performed in all cases (SL 17, Kowa Company Ltd.). Jones tests 1 and/or 2 were performed in 13/14 cases. Dacryocystotomy was initiated with an incision into one canaliculus until the lacrimal sac was exposed and could be explored. After extracting the FB from the nasolacrimal sac, the surgical wound and canaliculus were left open. Aftercare included the administration of antibiotic eye drops with or without dexamethasone and systemic analgesia.ResultsAll 14 dogs were mesocephalic. Four of them were Dachshunds. Dacryocystotomy revealed plant‐related FBs in all cases. The purulent discharge disappeared immediately after removal and did not recur during follow‐up.ConclusionsA simple dacryocystotomy is recommended for dogs with a strong suspicion of a foreign body in the lacrimal drainage system. Dacryocystorhinography appears to be an optional tool in these cases.
Publication rate and evidence‐based evaluation of abstracts presented at the veterinary endoscopy society annual meeting (2004‐2019)
Authors: Moy‐Trigilio Karen E. , Buote Nicole J. , Parry Stephen 
Published: January 2022

AbstractObjectiveTo determine the rate of full‐length publication for the 2004‐2019 Veterinary Endoscopy Society (VES) annual meeting abstracts and to identify abstract and author characteristics as predictors of publication.Study designObservational bibliographical study.Sample populationThree hundred and eighty‐nine abstracts.MethodsAbstracts from 2004‐2019 Veterinary Endoscopy Society (VES) proceedings and matching full‐length publications retrieved from bibliographic databases were systematically reviewed. Variables assessed included species, specimen type (cadaver, live animal, etc.), subdiscipline (orthopedics, internal medicine, etc.), institution, country of origin, study design, level of evidence (LoE), time to publication, number of authors, their credentials, and gender. Logistic regression, Fisher's exact tests and t‐tests were used to assess the bivariate relationship between publication and characteristics of the authors and publications.ResultsThe overall publication rate for presented abstracts published as full‐length articles in peer‐reviewed journals was 26%. Median time from abstract presentation to full‐length article publication was 430 days. Factors associated with full‐length article publication were identified: affiliated institution (P = .01), species studied (P = .04), subdiscipline focus (P = .01), level of evidence (P = .01), number of authors (P = .01), and first author's gender (P = .03).ConclusionVeterinary Endoscopy Society abstracts were commonly categorized into a lower LoE. Abstracts from academic institutions regarding canine patients and soft tissue surgery topics were more likely to be published. Abstracts citing female first authors or with more than 1 author had higher odds of publication.Clinical significanceData reported provide authors with predictors for publication and identify topics for research opportunities. Veterinary specialty societies may utilize this information when evaluating abstracts.
Photoacoustic monitoring of angiogenesis predicts response to therapy in healing wounds
Authors: Mantri Yash , Tsujimoto Jason , Donovan Brian , Fernandes Christopher C. , Garimella Pranav S. , Penny William F. , Anderson Caesar A. , Jokerst Jesse V. 
Published: January 2022

AbstractChronic wounds are a major health problem that cause the medical infrastructure billions of dollars every year. Chronic wounds are often difficult to heal and cause significant discomfort. Although wound specialists have numerous therapeutic modalities at their disposal, tools that could three dimensional‐map wound bed physiology and guide therapy do not exist. Visual cues are the current standard but are limited to surface assessment; clinicians rely on experience to predict response to therapy. Photoacoustic (PA) ultrasound (US) is a non‐invasive, hybrid imaging modality that can solve these major limitations. PA relies on the contrast generated by haemoglobin in blood which allows it to map local angiogenesis, tissue perfusion and oxygen saturation—all critical parameters for wound healing. This work evaluates the use of PA‐US to monitor angiogenesis and stratify patients responding versus not‐responding to therapy. We imaged 19 patients with 22 wounds once a week for at least 3 weeks. Our findings suggest that PA imaging directly visualises angiogenesis. Patients responding to therapy showed clear signs of angiogenesis and an increased rate of PA increase (p = 0.002). These responders had a significant and negative correlation between PA intensity and wound size. Hypertension was correlated to impaired angiogenesis in non‐responsive patients. The rate of PA increase and hence the rate of angiogenesis was able to predict healing times within 30 days from the start of monitoring (power = 88%, alpha = 0.05). This early response detection system could help inform management and treatment strategies while improving outcomes and reducing costs.
Four-mode squeezed states: two-field quantum systems and the symplectic group $$\mathrm {Sp}(4,{\mathbb {R}})$$
Authors: Colas Thomas , Grain Julien , Vennin Vincent 
Published: January 2022

AbstractWe construct the four-mode squeezed states and study their physical properties. These states describe two linearly-coupled quantum scalar fields, which makes them physically relevant in various contexts such as cosmology. They are shown to generalise the usual two-mode squeezed states of single-field systems, with additional transfers of quanta between the fields. To build them in the Fock space, we use the symplectic structure of the phase space. For this reason, we first present a pedagogical analysis of the symplectic group $$\mathrm {Sp}(4,{\mathbb {R}})$$

Sp
(
4
,
R
)

and its Lie algebra, from which we construct the four-mode squeezed states and discuss their structure. We also study the reduced single-field system obtained by tracing out one of the two fields. This procedure being easier in the phase space, it motivates the use of the Wigner function which we introduce as an alternative description of the state. It allows us to discuss environmental effects in the case of linear interactions. In particular, we find that there is always a range of interaction coupling for which decoherence occurs without substantially affecting the power spectra (hence the observables) of the system.
Sex Differences in Factors Associated With Progression of Aortic Valve Calcification in the General Population
Authors: Diederichsen Axel , Lindholt Jes Sanddal , Møller Jacob Eifer , Gerke Oke , Rasmussen Lars Melholt , Dahl Jordi S. 
Published: January 2022

Background:
Guidelines recommend measurement of the aortic valve calcification (AVC) score to help differentiate between severe and nonsevere aortic stenosis, but a paucity exists in data about AVC in the general population. The aim of this study was to describe the natural history of AVC progression in the general population and to identify potential sex differences in factors associated with this progression rate.

Methods:
Noncontrast cardiac computed tomography was performed in 1298 randomly selected women and men aged 65 to 74 years who participated in the DANCAVAS trial (Danish Cardiovascular Screening). Participants were invited to attend a reexamination after 4 years. The AVC score was measured at the computed tomography, and AVC progression (ΔAVC) was defined as the difference between AVC scores at baseline and follow-up. Multivariable regression analyses were performed to identify factors associated with ΔAVC.

Results:

Among the 1298 invited citizens, 823 accepted to participate in the follow-up examination. The mean age at follow-up was 73 years. Men had significantly higher AVC scores at baseline (median AVC score 13 Agatston Units [AU; interquartile range, 0–94 AU] versus 1 AU [interquartile range, 0–22 AU],
P
<0.001) and a higher ΔAVC (median 26 AU [interquartile range, 0–101 AU] versus 4 AU [interquartile range, 0–37 AU],
P
<0.001) than women. In the fully adjusted model, the most important factor associated with ΔAVC was the baseline AVC score. However, hypertension was associated with ΔAVC in women (incidence rate ratios, 1.58 [95% CI, 1.06–2.34],
P
=0.024) but not in men, whereas dyslipidemia was associated with ΔAVC in men (incidence rate ratio: 1.66 [95% CI, 1.18–2.34],
P
=0.004) but not in women.

Conclusions:
The magnitude of the AVC score was the most important marker of AVC progression. However, sex differences were significant; hence, dyslipidemia was associated with AVC progression only among men; hypertension with AVC progression only among women.

Registration:

URL:
https://www.isrctn.com
; Unique identifier: ISRCTN12157806.
Caspase-4/11–Mediated Pulmonary Artery Endothelial Cell Pyroptosis Contributes to Pulmonary Arterial Hypertension
Authors: Wu Yusi , Pan Bingjie , Zhang Zhen , Li Xiaohui , Leng Yiping , Ji Yong , Sun Kun , Chen Alex F. 
Published: January 2022

Background:
Endothelial dysfunction enhances vascular inflammation, which initiates pulmonary arterial hypertension (PAH) pathogenesis, further induces vascular remodeling and right ventricular failure. Activation of inflammatory caspases is an important initial event at the onset of pyroptosis. Studies have shown that caspase-1–mediated pyroptosis has played a crucial role in the pathogenesis of PAH. However, the role of caspase-11, another inflammatory caspase, remains to be elucidated. Therefore, the purpose of this study was to clarify the role of caspase-11 in the development of PAH and its mechanism on endothelial cell function.

Methods:
The role of caspase-11 in the progression of PAH and vascular remodeling was assessed in vivo. In vitro, the effect of caspase-4 silencing on the human pulmonary arterial endothelial cells pyroptosis was determined.

Results:

We confirmed that caspase-11 and its human homolog caspase-4 were activated in PAH animal models and TNF (tumor necrosis factor)-α–induced human pulmonary arterial endothelial cells. Caspase-11
−/−
relieved right ventricular systolic pressure, right ventricle hypertrophy, and vascular remodeling in Sugen-5416 combined with chronic hypoxia mice model. Meanwhile, pharmacological inhibition of caspase-11 with wedelolactone exhibited alleviated development of PAH on the monocrotaline-induced rat model. Moreover, knockdown of caspase-4 repressed the onset of TNF-α–induced pyroptosis in human pulmonary arterial endothelial cells and inhibited the activation of pyroptosis effector GSDMD (gasdermin D) and GSDME (gasdermin E).

Conclusions:
These observations identified the critical role of caspase-4/11 in the pyroptosis pathway to modulate pulmonary vascular dysfunction and accelerate the progression of PAH. Our findings provide a potential diagnostic and therapeutic target in PAH.
Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm
Authors: Zhang Chongyang , Mohan Amy , Shi Hangchuan , Yan Chen 
Published: January 2022

Background
cGMP‐hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP‐dependent protein kinase I (PKGI)–dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men.

Methods and Results
AAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3‐aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre‐existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA.

Conclusions
Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.
Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis
Authors: Zuurbier Charlotte C.M. , Molenberg Rob , Mensing Liselore A. , Wermer Marieke J.H. , Juvela Seppo , Lindgren Antti E. , Jääskeläinen Juha E. , Koivisto Timo , Yamazaki Tomosato , Uyttenboogaart Maarten , van Dijk J. Marc C. , Aalbers Marlien W. , Morita Akio , Tominari Shinjiro , Arai Hajime , Nozaki Kazuhiko , Murayama Yuichi , Ishibashi Toshihiro , Takao Hiroyuki , Gondar Renato , Bijlenga Philippe , Rinkel Gabriel J.E. , Greving Jacoba P. , Ruigrok Ynte M. 
Published: January 2022

Background and Purpose:
In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture.

Methods:
We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage.

Results:
We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89–1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58–0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07–1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02–1.90).

Conclusions:
Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.
Infertility, Miscarriage, Stillbirth, and the Risk of Stroke Among Women: A Systematic Review and Meta-Analysis
Authors: Liang Chen , Chung Hsin-Fang , Dobson Annette J. , Mishra Gita D. 
Published: January 2022

Background and Purpose:
Stroke is one of the leading causes of mortality, and women are impacted more from stroke than men in terms of their absolute number and in having worse outcomes. A growing number of studies have explored the association between pregnancy complications, pregnancy outcomes, and stroke. Limited studies, however, have investigated links involving infertility, miscarriage, and stillbirth, which could plausibly be associated via a background of endocrine conditions, endothelial dysfunction, and chronic systematic inflammation. This review aims to summarize current evidence and provide up-to-date information on the associations of infertility, miscarriage, and stillbirth, with stroke incidence.

Methods:
A comprehensive literature search was conducted for cohort and case-control studies on associations between infertility, miscarriage, stillbirth, and stroke up to September 26, 2020. Seven databases were searched: PubMed, Embase, Cochrane, CINIHL, PsyclNFO, Wanfang, and CNKI. Random-effects models were used to estimate the pooled hazard ratios (HRs) and 95% CIs.

Results:
Sixteen cohort studies and 2 case-control studies enrolling 7 808 521 women were included in this meta-analysis. Women who had experienced miscarriage or stillbirth were at higher risk of stroke (miscarriage: HR, 1.07 [95% CI, 1.00–1.14]; stillbirth: HR, 1.38 [95% CI, 1.11–1.71]) than other women. The HRs of stroke for each additional miscarriage and stillbirth were 1.13 (95% CI, 0.96–1.33) and 1.25 (95% CI, 1.06–1.49), respectively. In subgroup analysis, increased risk of stroke was associated with repeated miscarriages and stillbirths (miscarriage ≥3: HR, 1.42 [95% CI, 1.05–1.90]; stillbirth ≥2: HR, 1.14 [95% CI, 1.04–1.26]). Associations between infertility and stroke were inconsistent and inconclusive (HR, 1.07 [95% CI, 0.87–1.32]).

Conclusions:
Miscarriage and stillbirth are associated with increased risk of stroke among women, which could be used as a contributing risk factor to help identify women at higher risk of stroke.
Erratum: Measuring and Improving Consistency in Pretrained Language
Models
Authors: Elazar Yanai , Kassner Nora , Ravfogel Shauli , Ravichander Abhilasha , Hovy Eduard , Schütze Hinrich , Goldberg Yoav 
Published: January 2022

Abstract
During production of this paper, an error was introduced to the formula on the bottom of the right column of page 1020. In the last two terms of the formula, the n and m subscripts were swapped. The correct formula is:Lc=∑n=1k∑m=n+1kDKL(Qnri∥Qmri)+DKL(Qmri∥Qnri)The paper has been updated.