bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Novel Class of Photolyases as Possible Ancestors of Their Family
Authors: Xu Lei , Chen Simeng , Wen Bin , Shi Hao , Chi Changbiao , Liu Chenxi , Wang Kangyu , Tao Xianglin , Wang Ming , Lv Jun , Yan Liang , Ling Liefeng , Zhu Guoping 
Published: June 2021

Abstract
UV irradiation induces the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts in DNA. These two types of lesions can be directly photorepaired by CPD photolyases and 6-4 photolyases, respectively. Recently, a new class of 6-4 photolyases named iron–sulfur bacterial cryptochromes and photolyases (FeS-BCPs) were found, which were considered as the ancestors of all photolyases and their homologs—cryptochromes. However, a controversy exists regarding 6-4 photoproducts only constituting ∼10–30% of the total UV-induced lesions that primordial organisms would hardly survive without a CPD repair enzyme. By extensive phylogenetic analyses, we identified a novel class of proteins, all from eubacteria. They have relatively high similarity to class I/III CPD photolyases, especially in the putative substrate-binding and FAD-binding regions. However, these proteins are shorter, and they lack the “N-terminal α/β domain” of normal photolyases. Therefore, we named them short photolyase-like. Nevertheless, similar to FeS-BCPs, some of short photolyase-likes also contain four conserved cysteines, which may also coordinate an iron–sulfur cluster as FeS-BCPs. A member from Rhodococcus fascians was cloned and expressed. It was demonstrated that the protein contains a FAD cofactor and an iron–sulfur cluster, and has CPD repair activity. It was speculated that this novel class of photolyases may be the real ancestors of the cryptochrome/photolyase family.
Dissecting the Fitness Costs of Complex Mutations
Authors: Yubero Pablo , Poyatos Juan F 
Published: June 2021

Abstract
The fitness cost of complex pleiotropic mutations is generally difficult to assess. On the one hand, it is necessary to identify which molecular properties are directly altered by the mutation. On the other, this alteration modifies the activity of many genetic targets with uncertain consequences. Here, we examine the possibility of addressing these challenges by identifying unique predictors of these costs. To this aim, we consider mutations in the RNA polymerase (RNAP) in Escherichia coli as a model of complex mutations. Changes in RNAP modify the global program of transcriptional regulation, with many consequences. Among others is the difficulty to decouple the direct effect of the mutation from the response of the whole system to such mutation. A problem that we solve quantitatively with data of a set of constitutive genes, those on which the global program acts most directly. We provide a statistical framework that incorporates the direct effects and other molecular variables linked to this program as predictors, which leads to the identification that some genes are more suitable to determine costs than others. Therefore, we not only identified which molecular properties best anticipate fitness, but we also present the paradoxical result that, despite pleiotropy, specific genes serve as more solid predictors. These results have connotations for the understanding of the architecture of robustness in biological systems.
Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF–DDX19B interaction
Authors: Park Yeonkyoung , Park Joori , Hwang Hyun Jung , Kim Leehyeon , Jeong Kwon , Song Hyun Kyu , Rufener Simone C , Mühlemann Oliver , Kim Yoon Ki 
Published: June 2021

Abstract
Newly synthesized mRNA is translated during its export through the nuclear pore complex, when its 5′-cap structure is still bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein (CBP) 80 and CBP20. Despite its critical role in mRNA surveillance, the mechanism by which CBC-dependent translation (CT) is regulated remains unknown. Here, we demonstrate that the CT initiation factor (CTIF) is tethered in a translationally incompetent manner to the perinuclear region by the DEAD-box helicase 19B (DDX19B). DDX19B hands over CTIF to CBP80, which is associated with the 5′-cap of a newly exported mRNA. The resulting CBP80–CTIF complex then initiates CT in the perinuclear region. We also show that impeding the interaction between CTIF and DDX19B leads to uncontrolled CT throughout the cytosol, consequently dysregulating nonsense-mediated mRNA decay. Altogether, our data provide molecular evidence supporting the importance of tight control of local translation in the perinuclear region.
Deep learning-based automatic tumor burden assessment of pediatric high-grade gliomas, medulloblastomas, and other leptomeningeal seeding tumors
Authors: Peng Jian , Kim Daniel D , Patel Jay B , Zeng Xiaowei , Huang Jiaer , Chang Ken , Xun Xinping , Zhang Chen , Sollee John , Wu Jing , Dalal Deepa J , Feng Xue , Zhou Hao , Zhu Chengzhang , Zou Beiji , Jin Ke , Wen Patrick Y , Boxerman Jerrold L , Warren Katherine E , Poussaint Tina Y , States Lisa J , Kalpathy-Cramer Jayashree , Yang Li , Huang Raymond Y , Bai Harrison X 
Published: June 2021

Abstract

Background
Longitudinal measurement of tumor burden with magnetic resonance imaging (MRI) is an essential component of response assessment in pediatric brain tumors. We developed a fully automated pipeline for the segmentation of tumors in pediatric high-grade gliomas, medulloblastomas, and leptomeningeal seeding tumors. We further developed an algorithm for automatic 2D and volumetric size measurement of tumors.

Methods
The preoperative and postoperative cohorts were randomly split into training and testing sets in a 4:1 ratio. A 3D U-Net neural network was trained to automatically segment the tumor on T1 contrast-enhanced and T2/FLAIR images. The product of the maximum bidimensional diameters according to the RAPNO (Response Assessment in Pediatric Neuro-Oncology) criteria (AutoRAPNO) was determined. Performance was compared to that of 2 expert human raters who performed assessments independently. Volumetric measurements of predicted and expert segmentations were computationally derived and compared.

Results
A total of 794 preoperative MRIs from 794 patients and 1003 postoperative MRIs from 122 patients were included. There was excellent agreement of volumes between preoperative and postoperative predicted and manual segmentations, with intraclass correlation coefficients (ICCs) of 0.912 and 0.960 for the 2 preoperative and 0.947 and 0.896 for the 2 postoperative models. There was high agreement between AutoRAPNO scores on predicted segmentations and manually calculated scores based on manual segmentations (Rater 2 ICC = 0.909; Rater 3 ICC = 0.851). Lastly, the performance of AutoRAPNO was superior in repeatability to that of human raters for MRIs with multiple lesions.

Conclusions
Our automated deep learning pipeline demonstrates potential utility for response assessment in pediatric brain tumors. The tool should be further validated in prospective studies.
Regulation of carotenoid and chlorophyll pools in hesperidia, anatomically unique fruits found only in Citrus
Authors: Zhu Kaijie , Zheng Xiongjie , Ye Junli , Huang Yue , Chen Hongyan , Mei Xuehan , Xie Zongzhou , Cao Lixin , Zeng Yunliu , Larkin Robert M. , Xu Qiang , Perez-Roman Estela , Talón Manuel , Zumajo-Cardona Cecilia , Wurtzel Eleanore T. , Deng Xiuxin 
Published: June 2021

Abstract
Domesticated citrus varieties are woody perennials and interspecific hybrid crops of global economic and nutritional importance. The citrus fruit “hesperidium” is a unique morphological innovation not found in any other plant lineage. Efforts to improve the nutritional quality of the fruit are predicated on understanding the underlying regulatory mechanisms responsible for fruit development, including temporal control of chlorophyll degradation and carotenoid biosynthesis. Here, we investigated the molecular basis of the navel orange (Citrus sinensis) brown flavedo mutation, which conditions flavedo that is brown instead of orange. To overcome the limitations of using traditional genetic approaches in citrus and other woody perennials, we developed a strategy to elucidate the underlying genetic lesion. We used a multi-omics approach to collect data from several genetic sources and plant chimeras to successfully decipher this mutation. The multi-omics strategy applied here will be valuable in driving future gene discovery efforts in citrus as well as in other woody perennial plants. The comparison of transcriptomic and genomic data from multiple genotypes and plant sectors revealed an underlying lesion in the gene encoding STAY-GREEN (SGR) protein, which simultaneously regulates carotenoid biosynthesis and chlorophyll degradation. However, unlike SGR of other plant species, we found that the carotenoid and chlorophyll regulatory activities could be uncoupled in the case of certain SGR alleles in citrus and thus we propose a model for the molecular mechanism underlying the brown flavedo phenotype. The economic and nutritional value of citrus makes these findings of wide interest. The strategy implemented, and the results obtained, constitute an advance for agro-industry by driving opportunities for citrus crop improvement.
Migraine Monitoring in the Time of COVID-19: Triggers and Protectors During a Pandemic
Authors: Schiano di Cola Francesca , Caratozzolo Salvatore , Di Cesare Marco , Liberini Paolo , Rao Renata , Padovani Alessandro 
Published: June 2021

Abstract

Objective
Aim of the present observational study was to assess the impact of coronavirus disease 2019 (COVID-19) quarantine on migraine and evaluate potential influencing factors. Previous studies reported mixed results regarding clinical outcome during quarantine in patients with migraine. In particular, data from areas strongly affected by COVID-19 pandemic are missing.

Methods
One hundred and seventy patients, previously assessed at the Headache Centre—ASST Spedali Civili Brescia, underwent a telephonic interview regarding migraine features and clinical, occupational, and lifestyle variables.

Results
Compared to baseline, during quarantine, we found a significant overall reduction in migraine days (14.7 ± 0.6 vs 12.3 ± 0.7, P &lt; .001), with 47.1% patients reporting a clinical improvement. Outdoor living spaces (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.7–3.07, P = .009), a positive attitude throughout quarantine (OR 4.12, 95% CI 2.3–7.1, P = 0.03), working full-time (OR 1.03, 95% CI 0.5–1.9, P &lt; .001) and a baseline diagnosis of chronic migraine (OR 1.4, 95% CI 1.1–2.02, P = 0.002) were associated with an increased chance of migraine improvement. Being single (OR 1.5, 95% CI 1.1–2.01, P = .05) and physical inactivity (OR 1.3, 95% CI 1.1–1.6, P = .02) were associated with an increased risk of worsening.

Conclusions
Quarantine had an overall positive impact on migraine. Based on our results, we hypothesize the reduction of daily hassles and challenges might be the main reason for such improvement.
Psoriasis and coronary heart disease—not as severe as predicted
Authors: Hadi Y , Or T , Moady G , Atar S 
Published: June 2021

Abstract

Background
Psoriasis is a systemic disorder involved in several disease processes, including cancer, metabolic syndrome and cardiovascular disease (CVD). Previous studies showed that psoriasis is most likely an independent risk factor for CVD, yet the extent of its impact on CVD and the extent of coronary artery disease (CAD) remains unclear. We investigated the correlation of psoriasis to the severity of CAD in age and gender-matched patients with CAD with and without psoriasis.

Methods
This is a retrospective, case–control study of 59 patients with psoriasis who underwent coronary angiography were matched using a computer software to 59 patients without psoriasis according to age, gender, smoking status, hyperlipidemia, hypertension and diabetes. CAD severity was defined according to number of affected vessels (single vs. multiple) and location of lesions (proximal vs. distal).

Results
CAD severity was significantly higher in the control group compared to the psoriasis group (P = 0.038). Among patients with psoriasis, 20.3% were disease free or with low severity (42.4%), while only 37.3% had severe CAD. Among patients without psoriasis, the majority had severe CAD (57.6%), followed by low severity (30.5%) or disease free (11.9%). We did not find an association of prior treatment with anti-inflammatory medications and the severity of CAD.

Conclusions
Our results show that although psoriasis may be a risk factor for CAD, psoriatic patients have a less severe CAD compared to the general population. The use of anti-inflammatory medications does not explain this finding.
Integrating imaging and biomarker assessment to better define psoriatic arthritis and predict response to biologic therapy
Authors: Elliott Ashley , McGonagle Dennis , Rooney Madeleine 
Published: June 2021

AbstractThe treatment options for PsA have substantially expanded over the last decade. Approximately 40% of patients will not respond to first-line anti-TNF-α therapies. There is limited data to help clinicians select the most appropriate biologic therapy for PsA patients, including guidance for decisions on biologic therapy switching. In this review we will examine the current understanding of predictors of response to treatment. Imaging technology has evolved to allow us to better study psoriatic disease and define disease activity, including synovitis and enthesitis. Enthesitis is implicated in the pathogenesis, diagnosis and prognosis of PsA. It appears to be a common thread among all of the various PsA clinical presentations. Enthesitis mainly manifests as tenderness, which is difficult to distinguish from FM, chronic pain and mechanically associated enthesopathy, and it might be relevant for understanding the apparent 40% failure of existing therapy. Excess adipose tissue makes if more difficult to detect joint swelling clinically, as many PsA patients have very high BMIs. Integrating imaging and clinical assessment with biomarker analysis could help to deliver stratified medicine in PsA and allow better treatment decision making. This could include which patients require ongoing biologic therapy, which class of biologic therapy that should be, and who alternatively requires management of non-inflammatory disease.
Governing varieties of mission-oriented innovation policies: A new typology
Authors: Wittmann Florian , Hufnagl Miriam , Lindner Ralf , Roth Florian , Edler Jakob 
Published: June 2021

AbstractMany governments in Europe and beyond have subscribed to mission-oriented innovation policies (MOIPs), aiming to steer innovation systems to directly address grand societal challenges. The emerging diversity of MOIPs, however, creates difficulties to define this approach and assess its effectiveness and efficiency. In this paper, we propose a new typology for MOIPs. It consists of four ideal types of missions and extends the established dichotomy of transformer and accelerator missions. The framework emphasizes the role of the state in MOIPs, drawing attention to the implementation process and governance requirements as key features of mission implementation. A first application across the diverse missions of the German Hightech Strategy 2025 demonstrates the analytical value of the framework and allows identifying type-specific challenges. In sum, the new typology and its operationalization improve the understanding of MOIPs and enhance the possibilities for systematic comparisons and impact assessments.
Case report of acute liver injury caused by the eszopiclone in a patient with chronic liver disease
Authors: Wu Tong , Yu Ge , Li Zhaoxia , Xin Guijie 
Published: June 2021

Abstract

Rationale:
Eszopiclone, sold under the brand name Lunesta, is a new type of non-benzodiazepine hypnotic. Eszopiclone is a zopiclone dextrorotation, which is classified as a cyclopyrrolone. It functions by binding gamma-aminobutyric acid (GABA) receptors. Compared with benzodiazepines hypnotics, eszopiclone has higher selectivity for certain subunits of the GABA(A) receptor. So far, there are no reports about the elevation of serum enzymes or severe liver injury caused by eszopiclone. Here, we present a case report of acute liver injury following eszopiclone treatment in a patient with chronic hepatitis B virus (HBV).

Patient concerns:
The patient was a 53-year-old female with a 36-year history of positive HBV markers. Due to poor sleep, the patient took trazodone hydrochloride orally for 1 year. After hospital admission for positive hepatitis B pathogenic markers, abdominal distension, fatigue, and aggravation, she was treated with eszopiclone under the guidance of the mental health department.

Diagnoses:
Her transaminase levels increased abnormally after eszopiclone treatment and rapidly decreased after drug withdrawal. This was determined to be an acute liver injury event. liver-protecting treatment was maintained. Considering the patient's anxiety and depression, the patient's family members refused a liver biopsy.

Outcomes:
Transaminase levels decreased rapidly within one week, and the patient continued to take trazodone hydrochloride after discharge. No adverse events occurred in the follow-up period.

Lessons:
Sleep disorders are more common in patients with chronic diseases, especially patients with chronic liver disease. Recently, it has become common for patients with hepatitis B and C to use antidepressants along with antiviral treatment. Patients with chronic hepatitis B or C may have a threefold risk of liver dysfunction after receiving antituberculosis treatment.
[1,2]
A proinflammatory environment induced by actively replicating the hepatitis virus may alter the detoxication process and increase drug toxicity.
[3]
At this time, the safety of other drugs should be reevaluated. Although hepatitis and liver injury are listed as rare adverse reactions of eszopiclone, this case is the first to report the eszopiclone-involved acute liver injury.
HIV viral exposure and mortality in a multicenter ambulatory HIV adult cohort, United States, 1995–2016
Authors: Palella Frank J. , Armon Carl , Cole Stephen R. , Hart Rachel , Tedaldi Ellen , Novak Richard , Battalora Linda , Purinton Stacey , Li Jun , Buchacz Kate 
Published: June 2021

Abstract
The aim of this study was to identify viral exposure (VE) measures and their relationship to mortality risk among persons with HIV.
Prospective multicenter observational study to compare VE formulae.
Eligible participants initiated first combination antiretroviral therapy (cART) between March 1, 1995 and June 30, 2015. We included 1645 participants followed for ≥6 months after starting first cART, with cART prescribed ≥75% of time, who underwent ≥2 plasma viral load (VL) and ≥1 CD4+ T-lymphocyte cell (CD4) measurement during observation. We evaluated all-cause mortality from 6 months after cART initiation until June 30, 2016. VE was quantified using 2 time-updated variables: viremia copy-years and percent of person-years (%PY) spent >200 or 50 copies/mL. Cox models were fit to estimate associations between VE and mortality.
Participants contributed 10,453 person years [py], with median 14 VLs per patient. Median %PY >200 or >50 were 10% (interquartile range: 1%–47%) and 26% (interquartile range: 6%–72%), respectively. There were 115 deaths, for an overall mortality rate of 1.19 per 100 person years. In univariate models, each measure of VE was significantly associated with mortality risk, as were older age, public insurance, injection drug use HIV risk history, and lower pre-cART CD4. Based on model fit, most recent viral load and %PY >200 copies/mL provided the best combination of VE factors to predict mortality, although all VE combinations evaluated performed well.
The combination of most recent VL and %PY >200 copies/mL best predicted mortality, although all evaluated VE measures performed well.
Catheter ablation for atrial fibrillation in left ventricular assist device
Authors: Chung Yu Jin , Choi Jin-Oh , Park Kyoung-Min 
Published: June 2021

Abstract

Introduction:
Mechanical circulatory support such as the left ventricular assist device (LVAD) has become widely implemented in the treatment of end-stage heart failure, whether as bridge-to-transplant or as destination therapy. The hemodynamic effects of arrhythmia on LVADs and its management are significant in determining the long-term outcome of these patients. Both atrial arrhythmia and ventricular arrhythmia are commonly seen after implantation of the device. There are no strict guidelines, however, on the need for intensive management of arrhythmias in LVAD. In this case report, we present a patient with new onset atrial fibrillation after LVAD implantation which leads to acute decompensating heart failure. The patient was treated with catheter ablation. The intervention demonstrated positive outcomes for this patient.

Patient concerns:
The patient was a Korean male, who presented with dyspnea, fatigue and generalized edema after persistent atrial fibrillation precipitated by implantation of the left ventricular assist device.

Diagnosis:
The patient was diagnosed with acute decompensating heart failure that was aggravated by recurrent atrial arrhythmia.

Intervention:
We attempted to relieve symptoms of right ventricular dysfunction by method of strict rhythm control in this patient. The patient underwent radiofrequency catheter ablation for recurrent atrial fibrillation.

Outcome:
The patient showed improved clinical symptoms, BNP levels, and echocardiogram parameters immediately after the procedure as well as during long term outpatient follow up.

Conclusion:
In this case report, we present the first successful case in Korea of atrial fibrillation in LVAD treated with catheter ablation. This case suggests setting catheter ablation as a routine first-line treatment for atrial arrhythmia in LVAD patients, especially when the arrhythmia predisposes the patient at risk for decompensating heart failure.
Molecular diagnosis of sex chromosome mosaics in fetal amniotic cells
Authors: Fan Zuqian , Weng Xunjin , Pan Zhijian , Fan Qiongying , Long Ju , Lin Guixian , Yang Qian , Sun Lei 
Published: June 2021

Abstract
Mosaicism can be observed in karyotype analyses of amniotic fluid cells. Differentiating between true mosaicism and pseudomosaicism and determining mosaic proportions can help avoid misjudgments by doctors and effectively reduce mental and physical harm to pregnant women. However, the detection of mosaicism and mosaic proportions via karyotype analysis and fluorescence in situ hybridization (FISH) is extremely complex. We have developed a novel approach, “segmental duplication quantitative fluorescent PCR” (SD-QF-PCR), to detect mosaicism and mosaic proportions.
In this study, twenty control samples and fourteen mosaic samples were tested by first-line karyotype analysis; by second-line karyotype analysis, SD-QF-PCR and FISH were used to reassess fetal sex chromosome mosaicism and mosaic proportions.
Detection of the 20 control samples by second-line karyotype analysis via FISH and SD-QF-PCR showed normal and consistent results. Among the 14 mosaic samples, the numbers of samples showing true mosaicism and pseudomosaicism detected by the three methods were 6 and 8, respectively.
Our study demonstrates that SD-QF-PCR can be used as a complementary method to traditional cytogenetic analysis of amniotic fluid mosaics and has clinical application value.