bluuebunny/crossref_metadata_2025_split huggingface dataset:
An update on precision genome editing by homology-directed repair in plants
Authors: Chen Jilin , Li Shaoya , He Yubing , Li Jingying , Xia Lanqin 
Published: January 2022

Abstract
Beneficial alleles derived from local landraces or related species, or even orthologs from other plant species, are often caused by differences of one or several single-nucleotide polymorphisms or indels in either the promoter region or the encoding region of a gene and often account for major differences in agriculturally important traits. Clustered regularly interspaced short palindromic repeats-associated endonuclease Cas9 system (CRISPR/Cas9)-mediated precision genome editing enables targeted allele replacement or insertion of flag or foreign genes at specific loci via homology-directed repair (HDR); however, HDR efficiency is low due to the intrinsic rare occurrence of HDR and insufficient DNA repair template in the proximity of a double-stranded break (DSB). Precise replacement of the targeted gene with elite alleles from landraces or relatives into a commercial variety through genome editing has been a holy grail in the crop genome editing field. In this update, we briefly summarize CRISPR/Cas-mediated HDR in plants. We describe diverse strategies to improve HDR efficiency by manipulating the DNA repair pathway, timing DSB induction, and donor delivery, and so on. Lastly, we outline open questions and challenges in HDR-mediated precision genome editing in both plant biological research and crop improvement.
Antilocution and trust in the workplace: Perceptions of higher education trained police recruits in England and Wales
Authors: Rogers Colin , Turner James , Birch Philip 
Published: January 2022

Abstract
This study seeks to examine the relationship between antilocution and trust in the workplace by reflecting on the perceptions of police officers who are undertaking the new Higher Education (HE) pathway into the policing profession in England and Wales. This relationship is considered through Allport (1979). ‘The Nature of Prejudice. New York, NY: Perseus’ concept of antilocution and the lens of trust in the workplace, to understand how new police students think they are regarded by their policing colleagues and its impact on practice. Utilizing a survey of police students from five different forces in England and Wales, indicative results suggest that, whilst broadly supportive of new police officers, there may be some division regarding their education and training pathway through higher education, engendering levels of prejudice and bias towards the new recruits. Police student responses indicate that many of them feel that more is expected of them and that they are under closer supervision because they have undertaken the Higher Education route. Arguably, this prejudice and bias have an adverse effect on trust within the workplace, a concept which is front and centre of policing which ultimately can have a negative impact on public safety and security. The results of this study indicate that the interaction between new recruits (out-group) and established colleagues (in-group) is complex and not straightforward, and suggested implications for police practice are presented.
Short Selling ETFs
Authors: Li Frank Weikai , Zhu Qifei 
Published: January 2022

Abstract
We provide novel evidence that arbitrageurs use exchange-traded funds (ETFs) as an avenue to circumvent short-sale constraints at the stock level. Using a large sample of U.S. equity ETF holdings, we document that shorting activity on ETFs rises with the difficulty of shorting underlying stocks. Stocks heavily shorted via their holding ETFs underperform those that are lightly shorted. The return predictability of ETF shorting is distinct from stock-level shorting measures and is concentrated among stocks that face severe arbitrage constraints. These findings suggest that ETFs allow arbitrageurs to target overpriced stocks that are otherwise difficult to short. (JEL G12, G14)
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Carbamylation of β2-glycoprotein I generates new autoantigens for antiphospholipid syndrome: a new tool for diagnosis of ‘seronegative’ patients
Authors: Capozzi Antonella , Truglia Simona , Buttari Brigitta , Recalchi Serena , Riitano Gloria , Manganelli Valeria , Mancuso Silvia , Alessandri Cristiano , Longo Agostina , Mattei Vincenzo , Profumo Elisabetta , Garofalo Tina , Misasi Roberta , Conti Fabrizio , Sorice Maurizio 
Published: January 2022

Abstract

Objectives
Antiphospholipid syndrome (APS) is a prothrombotic condition defined by recurrent thrombosis, pregnancy complications and circulating antiphospholipid antibodies (aPL), including anti-β2-glycoprotein I (β2-GPI). In clinical practice it is possible to find patients with APS persistently negative for the aPL tests according to Sydney criteria (‘seronegative APS’, SN-APS). Recently, several autoimmune responses have been described as a consequence of post-translational modifications of their target autoantigens. This study was undertaken to test carbamylated-β2-GPI (Carb-β2-GPI) as a new autoantigen of APS.

Methods
β2-GPI was carbamylated by potassium cyanate and used to investigate its effect on monocyte-derived dendritic cell (moDC) phenotype and function. Sera from 114 SN-APS patients, 60 APS, 20 patients with RA, 20 non-APS thrombosis and 50 healthy donors were analysed for anti-Carb-β2-GPI by ELISA.

Results
Carb-β2-GPI is able to activate moDCs, inducing upregulation of CD80, CD86 and CD40, activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-κB, and IL-12p70 release. Serological results showed that both 37/114 SN-APS (32.46%) and 23/60 APS (38.33%) patients resulted positive for anti-Carb-β2-GPI. Interestingly, SN-APS patients who tested positive for anti-Carb-β2-GPI showed a higher prevalence of thrombocytopenia (P = 0.04, likelihood positive ratio of 3.9).

Conclusion
Data obtained from both functional tests on moDCs and immunological approaches prompted identification of Carb-β2-GPI as a ‘new’ antigenic target in APS. In particular, anti-Carb-β2-GPI revealed a potential usefulness in identification of a significant proportion of SN-APS patients. Moreover, since patients who tested positive for anti-Carb-β2-GPI reported a high risk of thrombocytopenia, this test may be considered a suitable approach in the clinical evaluation of SN-APS.
Effective connectivity of the human mirror neuron system during social cognition
Authors: Sadeghi Sadjad , Schmidt Stephanie N L , Mier Daniela , Hass Joachim 
Published: January 2022

Abstract
The human mirror neuron system (MNS) can be considered the neural basis of social cognition. Identifying the global network structure of this system can provide significant progress in the field. In this study, we use dynamic causal modeling (DCM) to determine the effective connectivity between central regions of the MNS for the first time during different social cognition tasks. Sixty-seven healthy participants completed fMRI scanning while performing social cognition tasks, including imitation, empathy and theory of mind. Superior temporal sulcus (STS), inferior parietal lobule (IPL) and Brodmann area 44 (BA44) formed the regions of interest for DCM. Varying connectivity patterns, 540 models were built and fitted for each participant. By applying group-level analysis, Bayesian model selection and Bayesian model averaging, the optimal family and model for all experimental tasks were found. For all social-cognitive processes, effective connectivity from STS to IPL and from STS to BA44 was found. For imitation, additional mutual connections occurred between STS and BA44, as well as BA44 and IPL. The results suggest inverse models in which the motor regions BA44 and IPL receive sensory information from the STS. In contrast, for imitation, a sensory loop with an exchange of motor-to-sensory and sensory-to-motor information seems to exist.
Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia
Authors: Davidson Michael , Saoud Jay , Staner Corinne , Noel Nadine , Werner Sandra , Luthringer Elisabeth , Walling David , Weiser Mark , Harvey Philip D , Strauss Gregory P , Luthringer Remy 
Published: January 2022

Abstract

Background
This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma2, and α1A-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population.

Methods
Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms. The primary endpoint was the PANSS-derived Negative Symptom Factor Score (NSFS) and the key secondary endpoint was Personal and Social Performance scale (PSP) total score.

Results
NSFS scores were lower (improved) for roluperidone 64 mg compared to placebo and marginally missing statistical significance for the intent-to-treat (ITT) analysis data set (P ≤ .064), but reached nominal significance (P ≤ .044) for the modified-ITT (m-ITT) data set. Changes in PSP total score were statistically significantly better on roluperidone 64 mg compared to placebo for both ITT and m-ITT (P ≤ .021 and P ≤ .017, respectively).

Conclusions
Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning in patients with schizophrenia. Study registration: Eudra-CT: 2017-003333-29; NCT03397134.
Local political turnover, R&D investment leap and corporate innovation performance: Evidence from China
Authors: Jiang Zhenyu , Wang Zongjun , Feng Chengxiao , Yi Lin 
Published: January 2022

AbstractThis study explores how local political turnover affects corporate R&D investment and innovation performance in an emerging economy like China. Based on the panel data of 956 listed firms in China, we found that local officials’ turnover has a direct negative effect on both R&D investment leap and corporate innovation performance. Furthermore, local officials’ turnover inhibits innovation performance provided the new officials are transferred from other places but improves innovation performance provided the old officials are dismissed for corruption or other violations. Finally, R&D investment leap positively moderate the relationship between local officials’ turnover and corporate innovation performance. These findings contribute to the literature on how political uncertainty at the regional level affects R&D and innovation activities at the firm level and provide significant guidance for both the government and manufacturers in China.
What counts: Making sense of metrics of research value
Authors: Williams Kate 
Published: January 2022

Abstract
There is no singular way of measuring the value of research. There are multiple criteria of evaluation given by different fields, including academia but also others, such as policy, media, and application. One measure of value within the academy is citations, while indications of wider value are now offered by altmetrics. This study investigates research value using a novel design focusing on the World Bank, which illuminates the complex relationship between valuations given by metrics and by peer review. Three theoretical categories, representing the most extreme examples of value, were identified: ‘exceptionals’, highest in both citations and altmetrics; ‘scholars’, highest in citations and lowest in altmetrics; and ‘influencers’, highest in altmetrics and lowest in citations. Qualitative analysis of 18 interviews using abstracts from each category revealed key differences in ascribed characteristics and judgements. This article provides a novel conception of research value across fields.
Magnitude of SARS-CoV-2 Infection and Outcome in Paediatric Surgical Inpatients during the First Wave of Pandemic at a Tertiary Care Children’s Hospital in India
Authors: Prajapati Sahaj , Choudhury Subhasis Roy , Aditya M , Maheshwari Anu , Anirudha Abhay J , Sarin Yogesh Kumar 
Published: January 2022

Abstract
This study was conducted at a tertiary care centre of Delhi, to assess the magnitude of SARS-CoV-2 disease and outcome in paediatric surgical inpatients. All the admitted patients were evaluated excluding outpatients and minor procedures. Out of 312 operated patients 2.88% patients were SARS-CoV-2 positive and out of 167 non-operative patients 6.58% were SARS-CoV-2 positive. These patients received standard care as per guidelines using standard protective measures and were discharged home. Only 1 death occurred due to perforation peritonitis with sepsis. The overall prevalence of SARS-CoV-2 in paediatric surgical patients was 4.17% and SARS-CoV-2 positive patients had similar outcomes as compared to non-SARS-CoV-2 patients.
Angiotensin-Converting Enzyme 2 Expression Is Detectable in Keratinocytes, Cutaneous Appendages, and Blood Vessels by Multiplex RNA In Situ Hybridization
Authors: Ganier Clarisse , Harun Nasrat , Peplow Imogen , Du-Harpur Xinyi , Arthurs Callum , Watt Fiona M. , Lynch Magnus D. 
Published: January 2022

ABSTRACT

OBJECTIVE
The angiotensin-converting enzyme 2 (ACE2) receptor mediates uptake of SARS-CoV-2, the virus responsible for COVID-19. Previous work analyzing publicly available bulk RNA-sequencing data sets has shown the expression of ACE2 in human keratinocytes. This finding is potentially relevant for the etiology of COVID-19-associated rashes and might also suggest a possible entry mechanism for the SARS-CoV-2 virus. In this study, the authors examined the spatial localization of ACE2 mRNA in vivo.

METHODS AND RESULTS
The authors analyzed several publicly available single-cell RNA-sequencing data sets. They determined spatial localization of ACE2 mRNA using multiplex RNA in situ hybridization in human skin.

CONCLUSIONS
Both analyses supported ACE2 expression in keratinocytes and skin vasculature, which could reflect a potential cutaneous entry point for SARS-CoV-2, particularly in damaged or broken skin. Moreover, ACE2 expression in vascular endothelial cells may support direct, virally mediated mechanisms in the etiology of the chilblain-like acral eruption that is seen in patients with COVID-19.
Learning Curves in Open, Laparoscopic, and Robotic Pancreatic Surgery
Authors: Müller P. C. , Kuemmerli C. , Cizmic A. , Sinz S. , Probst P. , de Santibanes M. , Shrikhande S. V. , Tschuor C. , Loos M. , Mehrabi A. , Z’graggen K. , Müller-Stich B. P. , Hackert T. , Büchler M. W. , Nickel F. 
Published: January 2022

Objective:
To depict and analyze learning curves for open, laparoscopic, and robotic pancreatoduodenectomy (PD) and distal pancreatectomy (DP).

Background:
Formal training is recommended for safe introduction of pancreatic surgery but definitions of learning curves vary and have not been standardized.

Methods:
A systematic search on PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in pancreatic surgery. Primary outcome was the number needed to reach the learning curve as defined by the included studies. Secondary outcomes included endpoints defining learning curves, methods of analysis (statistical/arbitrary), and classification of learning phases.

Results:
Out of 1115 articles, 66 studies with 14,206 patients were included. Thirty-five studies (53%) based the learning curve analysis on statistical calculations. Most often used parameters to define learning curves were operative time (n = 51), blood loss (n = 17), and complications (n = 10). The number of procedures to surpass a first phase of learning curve was 30 (20–50) for open PD, 39 (11–60) for laparoscopic PD, 25 (8–100) for robotic PD (P = 0.521), 16 (3–17) for laparoscopic DP, and 15 (5–37) for robotic DP (P = 0.914). In a three-phase model, intraoperative parameters improved earlier (first to second phase: operating time –15%, blood loss –29%) whereas postoperative parameters improved later (second to third phase: complications –46%, postoperative pancreatic fistula –48%). Studies with higher sample sizes showed higher numbers of procedures needed to overcome the learning curve (rho = 0.64, P < 0.001).

Conclusions:
This study summarizes learning curves for open-, laparoscopic-, and robotic pancreatic surgery with different definitions, analysis methods, and confounding factors. A standardized reporting of learning curves and definition of phases (competency, proficiency, mastery) is desirable and proposed.
Challenging the Subcostal Incision Scar with the Two-staged Abdominoplasty: An Innovative Approach
Authors: Mahabbat Nehal A. , Shah Mardan Qutaiba N.M. , Mohamed Abbas O. , Almarshad Felwa A. , Mrad Mohamed Amir , Al-Qattan Mohammad M. , Hashem Fuad K. 
Published: January 2022

Summary:
Abdominoplasty is a commonly sought-after procedure due to its life-transforming results, but is limited, as in any other operation, by a number of contraindications. One of these contraindications is a subcostal scar, which may jeopardize blood supply to the upper flap of the abdominoplasty, resulting in skin necrosis. Herein, we challenge this dogma by introducing the two-staged abdominoplasty with the utilization of a delayed flap in a 48-year-old multiparous woman presenting with a Kocher incision of open cholecystectomy, with good results and a complication-free course of 3 postoperative months. We recommend this approach in patients with subcostal scars. However, more research into the utilization of delayed flaps in abdominoplasty should be done to have a more well-founded conclusion.
A Modified Rhomboid Flap for Medial Canthal Reconstruction
Authors: Tasch Christoph , Pattiss Alexander , Lanthaler Monika , Pierer Gerhard 
Published: January 2022

Background:
The reconstruction of medial canthal defects is often challenging in achieving continuity of color and texture, obtaining adequate tissue for large defects, and the reproduction of natural external appearance with inconspicuous scars. We describe a technique for reconstruction of the medial canthal area, using a modified rhomboid flap.

Methods:
The technique is based on the use of a modified rhomboid flap for medial canthal defects—superiorly based on the root of the nose for defects mostly above the medial canthal tendon, inferiorly based on the cheek for defects mostly below the medial canthal tendon, and in cases of large defects, using a combination of the two flaps. We present a case series of five patients successfully reconstructed with the mentioned technique after resection of medial canthal basal cell carcinoma.

Results:
Of the five patients with a mean age of 76.2 years (range 62–84 years), reconstruction was performed in three patients with a superiorly based rhomboid flap, in one patient with an inferiorly based rhomboid flap, and in another patient with a large defect using a combination of the two flaps. Mean follow-up was 374.4 days (range 30–1247 days). All patients achieved a complete primary closure with no further surgery and satisfactory cosmetic and functional results.

Conclusion:
The modified rhomboid flap is a simple and reliable technique for all defects of the medial canthal area.
Severe Cherubism Treated with Curettage, Osteotomy, and Bony Repositioning: A Case Series of Three Patients
Authors: Moss Whitney , Pires Giovanna , Zahid Rehan , Tyrell Richard , Rhemtulla Irfan , Gociman Barbu 
Published: January 2022

Summary:
Cherubism is a rare, autosomal dominant condition characterized by the replacement of medullary bone by fibro-osseous lesions, predominantly in the bilateral maxillae and/or mandibles. The clinical presentation of cherubism can vary widely, from clinically undetectable to severe facial disfigurement. Although there are no established management guidelines for this condition, conservative management with observation is typically favored in most cases due to the possibility of spontaneous regression following puberty. In this article, we present three cases of moderate to severe cherubism managed with early surgical intervention utilizing curettage and osteotomy followed by bony repositioning. We aimed to show the feasibility and safety of this minimally invasive surgical technique in the management of moderate to severe cases of cherubism to provide improvement in patient quality of life, aesthetics, and function while also possibly mitigating the need for later reconstructive surgery.
Role of Skin Stretch on Local Vascular Permeability in Murine and Cell Culture Models
Authors: Demir Tuna , Takada Hiroya , Furuya Kishio , Sokabe Masahiro , Ogawa Rei 
Published: January 2022

Background:
Excessive mechanical forces, particularly skin stretch, have been implicated in pathological cutaneous scarring. We hypothesize that this reflects, in part, stretch-induced vessel leakage that provokes prolonged wound/scar inflammation. However, this has never been observed directly. Here, a mouse model was used to examine the effect of skin flap stretching on vascular permeability. An in vitro model with pseudocapillaries grown in a stretchable chamber was also used to determine the effect of stretching on endothelial cell morphology and ion channel activity.

Methods:
Murine skin flaps were stretched with a biaxial stretching device, after which FITC-conjugated-dextran was injected and imaged with fluorescence stereomicroscopy. Endothelial cells were induced to form pseudocapillary networks in an elastic chamber. The chamber was stretched and differential interference contrast microscopy was used to assess cell morphology. In other experiments, markers for Ca2+ influx and K+ efflux were added before a single stretch was conducted. Histamine served as a positive-control in all experiments.

Results:
Cyclic stretching (20%) increased the vascular permeability of skin flaps almost as strongly as histamine. Both stimuli also partially disrupted the pseudocapillary networks, induced cell contraction, and created gaps between the cells. Both stimuli caused sustained K+ efflux; stretching had a milder effect on Ca2+ influx.

Conclusions:
Excessive cyclical stretching strongly increased the vascular permeability of skin vessels and in vitro pseudocapillaries. This effect associated with increased K+ efflux and some Ca2+ influx. Inhibiting such early stretch-induced signaling events may be an effective strategy for treating and preventing hypertrophic scars and keloids.