bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant genomics in Africa: present and prospects
Authors: Ghazal Hassan , Adam Yagoub , Idrissi Azami Abdellah , Sehli Sofia , Nyarko Hannah N. , Chaouni Bouchra , Olasehinde Grace , Isewon Itunuoluwa , Adebiyi Marion , Ajani Olayinka , Matovu Enock , Obembe Olawole , Ajamma Yvonne , Kuzamunu Gaston , Pandam Salifu Samson , Kayondo Jonathan , Benkahla Alia , Adebiyi Ezekiel 
Published: April 2021

SUMMARYPlants are the world’s most consumed goods. They are of high economic value and bring many health benefits. In most countries in Africa, the supply and quality of food will rise to meet the growing population’s increasing demand. Genomics and other biotechnology tools offer the opportunity to improve subsistence crops and medicinal herbs in the continent. Significant advances have been made in plant genomics, which have enhanced our knowledge of the molecular processes underlying both plant quality and yield. The sequencing of complex genomes of African plant species, facilitated by the continuously evolving next‐generation sequencing technologies and advanced bioinformatics approaches, has provided new opportunities for crop improvement. This review summarizes the achievements of genome sequencing projects of endemic African plants in the last two decades. We also present perspectives and challenges for future plant genomic studies that will accelerate important plant breeding programs for African communities. These challenges include a lack of basic facilities, a lack of sequencing and bioinformatics facilities, and a lack of skills to design genomics studies. However, it is imperative to state that African countries have become key players in the plant genome revolution and genome derived‐biotechnology. Therefore, African governments should invest in public plant genomics research and applications, establish bioinformatics platforms and training programs, and stimulate university and industry partnerships to fully deploy plant genomics, particularly in the fields of agriculture and medicine.
Contributions to $$ZZV^*$$ ($$V=\gamma ,Z,Z'$$) couplings from CP violating flavor changing couplings
Authors: Hernández-Juárez A. I. , Moyotl A. , Tavares-Velasco G. 
Published: April 2021

AbstractThe one-loop contributions to the trilinear neutral gauge boson couplings $$ZZV^*$$

Z
Z

V
∗

($$V=\gamma ,Z,Z'$$

V
=
γ
,
Z
,

Z
′

), parametrized in terms of one CP-conserving $$f_5^{V}$$

f
5
V

and one CP-violating $$f_4^{V}$$

f
4
V

form factors, are calculated in models with CP-violating flavor changing neutral current couplings mediated by the Z gauge boson and an extra neutral gauge boson $$Z'$$

Z
′

. Analytical results are presented in terms of Passarino-Veltman scalar functions. Constraints on the vector and axial couplings of the Z gauge boson $$\left| g_{{VZ}}^{tu}\right| < 0.0096$$

g

VZ

tu

<
0.0096

and $$\left| g_{{VZ}}^{tc}\right| <0.011$$

g

VZ

tc

<
0.011

are obtained from the current experimental data on the $$t\rightarrow Z q$$

t
→
Z
q

decays. It is found that in the case of the $$ZZ\gamma ^*$$

Z
Z

γ
∗

vertex the only non-vanishing form factor is $$f_5^{\gamma }$$

f
5
γ

, which can be of the order of $$10^{-3}$$

10

-
3

, whereas for the $$ZZZ^*$$

Z
Z

Z
∗

vertex both form factors $$f_5^{Z}$$

f
5
Z

and $$f_4^{Z}$$

f
4
Z

are non-vanishing and can be of the order of $$10^{-6}$$

10

-
6

and $$10^{-5}$$

10

-
5

, respectively. Our estimates for $$f_5^{\gamma }$$

f
5
γ

and $$f_5^{Z}$$

f
5
Z

are smaller than those predicted by the standard model, where $$f_4^{Z}$$

f
4
Z

is absent up to the one loop level. We also estimate the $$ZZ{Z'}^{*}$$

Z
Z

Z
′

∗

form factors arising from both diagonal and non-diagonal $$Z'$$

Z
′

couplings within a few extension models. It is found that in the diagonal case $$f_{5}^{Z'}$$

f

5

Z
′

is the only non-vanishing form factor and its real and imaginary parts can be of the order of $$10^{-1}$$

10

-
1

–$$10^{-2}$$

10

-
2

and $$ 10^{-2}$$

10

-
2

–$$10^{-3}$$

10

-
3

, respectively, with the dominant contributions arising from the light quarks and leptons. In the non-diagonal case $$f_{5}^{Z^\prime }$$

f

5

Z
′

can be of the order of $$10^{-4}$$

10

-
4

, whereas $$f_4^{Z'}$$

f
4

Z
′

can reach values as large as $$10^{-7}$$

10

-
7

–$$10^{-8}$$

10

-
8

, with the largest contributions arising from the $$Z'tq$$

Z
′

t
q

couplings.
Treatment of Miller I Mandibular Gingival Recessions Using PRF vs. Connective Graft
Authors: Garzon Hernan S. , Alfonso Camilo , Vega Francisco J. , García Andrea , Muñoz Ana , Jaimes Gustavo , Isaza Katherine , Rivera Katherine 
Published: April 2021

Gingival recession (GR) can cause aesthetic and functional problems. Using connective tissue graft (CTG) and coronally advanced flap (CAF) is considered the technique of choice for treating GR. Considering the morbidity resulting from taking CTG, different alternative biomaterials have been described, including plasma-rich fibrin (PRF) membrane. Studies in lower teeth are few because of the complexity of the factors that can influence obtaining less predictable outcomes. Objective. To compare between CAF + PRF and CAF + CTG in the treatment of lower teeth Miller I gingival recession. Methodology. Split-mouth included 26 isolated GR (13 in each side of the mouth). The left side was treated with CAF + PRF and the right side with CAF + CTG. Clinical variables, probing depth (PD), GR, keratinized tissue (KT), vestibular soft tissue thickness (VSTT), and teeth sensitivity (TS), were assessed at the baseline. GR, KT, VSTT, extraoral inflammation (EI), and patient discomfort (PaD) were assessed at 45 days. Results. Statistically greater VSTT at 45 days was obtained using CAF + CTG (

p

< 0.05). Less EI and PaD were obtained using CAF + PRF (

p

< 0.05). No change was observed in GR, KT, and TS values in the intergroup or intragroup comparisons. Conclusion. Even with the limitations of this study, using PRF and CTG in lower teeth demonstrated an improvement in terms of root coverage, although it was without a total percentage of coverage. Regarding the VSTT, better results were obtained using the CTG + CAF, suggesting eventually long-term stable clinical results. We suggest a combined technique for future investigations.
Oncogenic KRAS Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis
Authors: Kim Michael P. , Li Xinqun , Deng Jenying , Zhang Yun , Dai Bingbing , Allton Kendra L. , Hughes Tara G. , Siangco Christian , Augustine Jithesh J. , Kang Ya'an , McDaniel Joy M. , Xiong Shunbin , Koay Eugene J. , McAllister Florencia , Bristow Christopher A. , Heffernan Timothy P. , Maitra Anirban , Liu Bin , Barton Michelle C. , Wasylishen Amanda R. , Fleming Jason B. , Lozano Guillermina 
Published: April 2021

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic KRAS mutations prevail in 95% of PDAC tumors and co-occur with genetic alterations in the TP53 tumor suppressor in nearly 70% of patients. Most TP53 alterations are missense mutations that exhibit gain-of-function phenotypes that include increased invasiveness and metastasis, yet the extent of direct cooperation between KRAS effectors and mutant p53 remains largely undefined. We show that oncogenic KRAS effectors activate CREB1 to allow physical interactions with mutant p53 that hyperactivate multiple prometastatic transcriptional networks. Specifically, mutant p53 and CREB1 upregulate the prometastatic, pioneer transcription factor FOXA1, activating its transcriptional network while promoting WNT/β-catenin signaling, together driving PDAC metastasis. Pharmacologic CREB1 inhibition dramatically reduced FOXA1 and β-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic KRAS and mutant p53 to mitigate metastasis.

Significance:
Oncogenic KRAS and mutant p53 are the most commonly mutated oncogene and tumor suppressor gene in human cancers, yet direct interactions between these genetic drivers remain undefined. We identified a cooperative node between oncogenic KRAS effectors and mutant p53 that can be therapeutically targeted to undermine cooperation and mitigate metastasis.
This article is highlighted in the In This Issue feature, p. 1861
Lysine Demethylase 5A Is Required for MYC-Driven Transcription in Multiple Myeloma
Authors: Ohguchi Hiroto , Park Paul M.C. , Wang Tingjian , Gryder Berkley E. , Ogiya Daisuke , Kurata Keiji , Zhang Xiaofeng , Li Deyao , Pei Chengkui , Masuda Takeshi , Johansson Catrine , Wimalasena Virangika K. , Kim Yong , Hino Shinjiro , Usuki Shingo , Kawano Yawara , Samur Mehmet K. , Tai Yu-Tzu , Munshi Nikhil C. , Matsuoka Masao , Ohtsuki Sumio , Nakao Mitsuyoshi , Minami Takashi , Lauberth Shannon , Khan Javed , Oppermann Udo , Durbin Adam D. , Anderson Kenneth C. , Hideshima Teru , Qi Jun 
Published: April 2021

Abstract

Lysine demethylase 5A (KDM5A) is a negative regulator of histone H3 lysine 4 trimethy­lation (H3K4me3), a histone mark associated with activate gene transcription. We identify that KDM5A interacts with the P-TEFb complex and cooperates with MYC to control MYC-targeted genes in multiple myeloma cells. We develop a cell-permeable and selective KDM5 inhibitor, JQKD82, that increases H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output in vitro and in vivo. Using genetic ablation together with our inhibitor, we establish that KDM5A supports MYC target gene transcription independent of MYC itself by supporting TFIIH (CDK7)- and P-TEFb (CDK9)–mediated phosphorylation of RNAPII. These data identify KDM5A as a unique vulnerability in multiple myeloma functioning through regulation of MYC target gene transcription and establish JQKD82 as a tool compound to block KDM5A function as a potential therapeutic strategy for multiple myeloma.

Significance:
We delineate the function of KDM5A in activating the MYC-driven transcriptional landscape. We develop a cell-permeable KDM5 inhibitor to define the activating role of KDM5A on MYC target gene expression and implicate the therapeutic potential of this compound in mouse models and multiple myeloma patient samples.
See related video from the AACR Annual Meeting 2021: https://vimeo.com/554896826
ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment
Authors: Bianchi Giada , Czarnecki Peter G. , Ho Matthew , Roccaro Aldo M. , Sacco Antonio , Kawano Yawara , Gullà Annamaria , Samur Anil Aktas , Chen Tianzeng , Wen Kenneth , Tai Yu-Tzu , Moscvin Maria , Wu Xinchen , Camci-Unal Gulden , Da Vià Matteo C. , Bolli Niccolo' , Sewastianik Tomasz , Carrasco Ruben D. , Ghobrial Irene M. , Anderson Kenneth C. 
Published: April 2021

Abstract

The bone marrow (BM) microenvironment actively promotes multiple myeloma pathogenesis, and therapies targeting both cancer cells and the niche are highly effective. We were interested in identifying novel signaling pathways supporting multiple myeloma–BM cross-talk. Mutations in the transmembrane receptor Roundabout 1 (ROBO1) were recently identified in patients with multiple myeloma; however, their functional consequences are uncertain. Through protein structure–function studies, we discovered that ROBO1 is necessary for multiple myeloma adhesion to BM stromal and endothelial cells and that ROBO1 knockout (KO) compromises BM homing and engraftment in a disseminated mouse model. ROBO1 KO significantly decreases multiple myeloma proliferation in vitro and intra- and extramedullary tumor growth in vivo. Mechanistically, the ROBO1 C-terminus is cleaved in a ligand-independent fashion and is sufficient to promote multiple myeloma proliferation. Vice versa, mutants lacking the cytoplasmic domain, including the human-derived G674* truncation, act dominantly negative. Interactomic and RNA-sequencing studies suggest that ROBO1 may be involved in RNA processing, supporting further studies.

Significance:
ROBO1 is highly expressed in t(4;14) multiple myeloma and supports homing and dissemination to the BM niche. ROBO1 knockout causes reduced tumor growth in intramedullary and extramedullary myeloma animal models, while the ROBO1 C-terminus is cleaved in multiple fragments and it is necessary and sufficient to sustain myeloma proliferation.
Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy
Authors: Jeha Sima , Choi John , Roberts Kathryn G. , Pei Deqing , Coustan-Smith Elaine , Inaba Hiroto , Rubnitz Jeffrey E. , Ribeiro Raul C. , Gruber Tanja A. , Raimondi Susana C. , Karol Seth E. , Qu Chunxu , Brady Samuel W. , Gu Zhaohui , Yang Jun J. , Cheng Cheng , Downing James R. , Evans Williams E. , Relling Mary V. , Campana Dario , Mullighan Charles G. , Pui Ching-Hon 
Published: April 2021

Abstract

We evaluated clinical significance of recently identified subtypes of acute lymphoblastic leukemia (ALL) in 598 children treated with minimal residual disease (MRD)–directed therapy. Among the 16 B-cell ALL (B-ALL) and 8 T-cell ALL subtypes identified by next-generation sequencing, ETV6–RUNX1, high-hyperdiploid, and DUX4-rearranged B-ALL had the best 5-year event-free survival rates (95.0%–98.4%); TCF3–PBX1, PAX5-altered (PAX5alt), T-cell, early T-cell precursor (ETP), intrachromosomal amplification of chromosome 21 (iAMP21), and hypodiploid ALL intermediate rates (80.0%–88.2%); and BCR–ABL1, BCR–ABL1-like, ETV6–RUNX1-like, and KMT2A-rearranged ALL the worst rates (64.1%–76.2%). All but 3 of the 142 patients with day 8 blood MRD &lt;0.01% remained in remission. Among new subtypes, intensified therapy based on day 15 MRD ≥1% improved outcome of DUX4-rearranged, BCR–ABL1-like, and ZNF384-rearranged ALL, and achievement of day 42 MRD &lt;0.01% did not preclude relapse of PAX5alt, MEF2D-rearranged, and ETV6–RUNX1-like ALL. Thus, new subtypes including DUX4-rearranged, PAX5alt, BCR–ABL1-like, ETV6–RUNX1-like, MEF2D-rearranged, and ZNF384-rearranged ALL have important prognostic and therapeutic implications.

Significance:
Genomic analyses and MRD should be used together for risk-directed treatment of childhood ALL. Six recently described subtypes—DUX4-rearranged, PAX5alt, BCR–ABL1-like, ETV6–RUNX1-like, MEF2D-rearranged, and ZNF384-rearranged ALL—had prognostic and therapeutic significance with contemporary risk-directed treatment.
See related commentary by Segers and Cools, p. 294.
See related video from the AACR Annual Meeting 2021: https://vimeo.com/558556916
asean and the Rakhine Crisis: Balancing Non-interference, Accountability, and Strategic Interests in Responding to Atrocities in Myanmar
Authors: Morada Noel M. 
Published: April 2021

Abstract
asean has not collectively responded to the Rakhine crisis since 2017 from the perspective of the Responsibility to Protect (R2P) principle and has failed to put a stop to the atrocities against the Rohingyas in Myanmar. This article argues that there is less support in the region for invoking the non-interference principle in dealing with Myanmar on the Rohingya issue even as some members have called for its relaxation and use of constructive engagement instead. As international pressure in pursuit of justice and accountability increased, so did calls from within the region for asean to do more beyond just providing humanitarian assistance to affected communities in Rakhine. Even so, asean consciously avoids pressing too hard on the issue of accountability as this could force the government and the military in Myanmar to totally disengage with asean and the international community on the Rakhine crisis, as well as push Nay Pyi Daw further into China’s embrace and thus undermine asean’s strategic interests in the region.
“World without End”
Authors: Meganck Erik 
Published: April 2021

Abstract
In this article, I want to make the following points, none of which are totally new, but their constellation here is meant to be challenging. First, world is not a (Cartesian) thing but an event, the event of sense. This event is opening and meaning – verbal tense. God may be a philosophical name of this event. This is recognized by late-modern religious atheist thought. This thought differs from modern scientific rationalism in that the latter’s so-called areligious atheism is actually a hyperreligious theism. On the way, the alleged opposition between philosophy and theology, between thought and faith is seen to erode. The core matter of this philosophy of religion will be the absolute reference, the system of objectivity and the holiness of the name. All this because of a prefix a- that has its sense turned inside out by the death of God.
Umbrella Review on Non-Statin Lipid-Lowering Therapy
Authors: Beshir Semira Abdi , Hussain Nadia , Elnor Asim Ahmed , Said Amira S. A. 
Published: April 2021

Dyslipidemia, particularly increased low-density lipoprotein cholesterol (LDL-C) levels, are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. There is an unmet need for ASCVD risk reduction even with the optimal use of statin therapy, which has led to an ongoing search for novel targets for cholesterol reduction to decrease ASCVD events. Objectives: The main aim of this review was to summarize current evidence on approved and emerging non-statin lipid-lowering therapies. Methods and Materials: Recent literature on U.S. FDA approved non-statin lipid-lowering therapies and evolving lipid-lowering drugs currently under development was reviewed. Results and Discussion: In the past 20 years, the emergence of non-statin cholesterol-lowering drugs has changed the landscape of dyslipidemia management. Food and Drug Administration approval of non-statin lipid-lowering therapies such as ezetimibe, proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab), bempedoic acid and combination of bempedoic acid and ezetimibe, evinacumab and other triglyceride-lowering agents (eg, icosapent ethyl) has emerged. The European Commission has also recently approved inclisiran for treatment of hypercholesterolemia and mixed hypercholesterolemia even though FDA has put the approval of this drug on hold. Recent guidelines have incorporated PCSK9 inhibitors to treat patients with primary hyperlipidemia and patients with very high-risk ASCVD, who could not achieve adequate lipid-lowering with combination therapy of maximally tolerated statin and ezetimibe. Icosapent ethyl use as an adjunct therapy to statins is also recommended to reduce the risk of ASCVD in patients with hypertriglyceridemia. Conclusion: Despite cost limitations, the uptake of PCSK9 inhibitors is increasing. Approval of bempedoic acid alone or in combination with ezetimibe has provided additional oral lipid-lowering drug alternatives to ezetimibe. Various lipid-lowering drug targets are under investigation.
Difficulty in articulation following left progressive blurred vision
Authors: Lee An-Ting , Chen Wei-Dar , Lai Chien-Hsiung 
Published: April 2021

Purpose: To report a case of Paracentral acute middle maculopathy (PAMM) caused by severe internal carotid artery (ICA) stenosis and discuss the correlation between PAMM and ICA stenosis. Case description: A 67-year-old male patient presented with left acute blurred vision for 1 week. The best-corrected visual acuity of the left eye was 0.01. Funduscopic examination showed multiple grayish patches around the left macula. Optical coherence tomography (OCT) demonstrated train-track hyperreflective lesions over the inner nuclear layer of the left eye. Afterwards, he experienced sudden slurred speech with fair comprehension. Magnetic resonance imaging and angiography of the brain demonstrated left lacunar infarction with severe left ICA stenosis. After anticoagulant therapy, his dysarthria and left visual acuity were improved significantly. Conclusions: To our knowledge, PAMM in coincidence with lacunar infarction induced by ICA stenosis is firstly described in the literature. PAMM could be a critical warning of ICA stenosis, and this case can alert ophthalmologists to survey ICA stenosis in patients with PAMM.
Clinical predictors of recurrent cephalic arch stenosis and impact of the access flow reduction on the patency rate
Authors: Kim Yaeni , Kim Hyung Duk , Chung Byung Ha , Park Cheol Whee , Yang Chul Woo , Kim Yong-Soo 
Published: April 2021

Objective: Despite the widespread use of conventional percutaneous transluminal angioplasty (PTA), recurrence of cephalic arch stenosis (CAS), and low patency rate after PTA remain challenging problem. We aimed to identify the clinical predictors of recurrence of CAS and evaluate the effect of the access flow reduction on the fistula patency rate in patients with recurrent CAS. Methods: In 1118 angiographies of 220 patients with CAS, access circuit patency rates after PTA and potential clinical predictors of recurrence of CAS were assessed. The effect of the banding procedure was evaluated in terms of post-interventional primary patency rate, and the number of interventions per access-year. Results: At 3, 6, and 12 months after the first PTA on CAS, the post-interventional access circuit primary patency rates were 68.8%, 40.5%, and 25.1%, respectively. High CV to CA ratio (the ratio of the maximal diameter of the distal cephalic vein to the diameter of the cephalic arch) (Hazard ratio (HR), 1.437; 95% confidence interval (CI), 1.036–1.992) and involvement of the proximal segment of cephalic arch (HR, 1.828; 95% CI, 1.194–2.801) were significant predictors of recurrent CAS. For those with recurrent CAS (>3 times/year) and an access flow rate >1.5 L/minute, endovascular banding procedure was performed. The banding procedure significantly reduced the number of interventions per access-year ( t = 3.299, p = 0.005 and t = 2.989, p = 0.007, respectively). Post-interventional access circuit primary patency rate after banding was significantly higher than that before banding ( p = 0.01). Conclusions: High CV to CA ratio and involvement of the proximal segment of the cephalic arch are independent clinical predictors of recurrent CAS. Endovascular banding might delay recurrence of CAS in patients with high CV to CA ratio and high access flow.
The code-mixing of the Senegalese migrants in Italy
Authors: Tramutoli Laura 
Published: April 2021

Aims and objectives/purpose/research questions: This paper describes and analyses the speech from the Senegalese migrant community in the city of Pescara (Italy) from a contact-linguistics perspective. The focus is on the phenomena of code-mixing found when the Italian language, that of the host community, is added to the complex repertoire of Wolof/French multilingual speakers. Design/methodology/approach: The patterns of code-mixing and the composition of trilingual speech are presented and discussed following the Muysken grammatical model for classifying features of language-contact discourse. Data and analysis: Primary data have been collected recording spontaneous interactions among a group of first-generation migrants that have lived in Italy for about 10 years and are all speakers of a fluent learner-variety of Italian. Findings/conclusions: It will be shown that insertional and alternational code-mixing patterns are present in both the bilingual (French/Wolof) and the trilingual (Italian/French/Wolof) speech, but with different degrees of variation and distribution. Originality: Besides documenting the trilingual speech framed in a specific yet new migration contact setting, the author considers the role that the two languages of prestige, French and Italian, play within the structural composition of both types of code-mixing, especially with regards to their relationship with Wolof. Significance/implications: The results achieved contribute to the general theory of the grammatical model by reaffirming the properties of the patterns of insertion and alternation, but also by revealing other ambiguous forms of code-mixing that might suggest a future revision of the model.