bluuebunny/crossref_metadata_2025 huggingface dataset:
Family carers’ narratives of the financial consequences of young onset dementia
Authors: Bayly Melanie , O’Connell Megan E. , Kortzman August , Peacock Shelley , Morgan Debra G. , Kirk Andrew
Published: April 2021

Individuals with young onset dementia and their families face unique challenges, such as disruptions to their life cycle and relationships and a dearth of appropriate supports. Financial consequences have also been noted in the literature yet have not been explored in-depth. The purpose of this research was to qualitatively explore carers’ experiences of financial consequences resulting from the young onset dementia of a family member and how these consequences may be managed. Eight carers (7 women and 1 man) provided a written online narrative about their journey with young onset dementia and any financial consequences experienced, with open-ended prompts to elicit details not yet shared. Narratives were inductively coded and analyzed using a thematic narrative approach. Carers described a voluntary or involuntary end to employment for the person with young onset dementia around the time of diagnosis. This engendered ongoing and anticipated financial consequences, combined with the need for carers to balance employment with the provision of care (which often meant early retirement for spousal carers). Common themes were tension between the needs to provide care and earn income, altered financial prospects, costs of care, and lack of available and accessible supports to ameliorate financial consequences. Findings illustrate the reality of financial consequences across the trajectory of young onset dementia. These consequences may manifest differently for spousal and child carers and are not being adequately addressed by existing supports.
MHD compressible fluid with variable thermal conductivity through a ciliated channel
Authors: Rafaqat Rida , Khan Ambreen Asfar
Published: April 2021

This paper employs to discuss the cilia induced flow of a compressible Jeffrey fluid with variable characteristic of thermal conductivity. Thermal conductivity is thermally variable. Effects of thermal radiation and MHD are also explored. The velocity slip at the wall is also considered. Flow equations have been modeled mathematically and tackled analytically using regular perturbation method. A proper attention is given to plot and discuss the behavior of quantities of interest against the relevant parameters. We explore growth of temperature with Mach number but this growth is strongly visible in supersonic regime as compared to the subsonic regime. The discoveries of the current model have noteworthy yields, which can be pertinent in various areas of aircraft industry, geophysics, biological transport processes, and in the operation of other mechanical devices.
Comparison of mothership versus drip-and-ship models in treating patients with acute ischemic stroke: A systematic review and meta-analysis
Authors: Mohamed Ahmed , Fatima Nida , Shuaib Ashfaq , Saqqur Maher
Published: April 2021

Introduction

There is controversy if direct to comprehensive center “mothership” or stopping at primary center for thrombolysis before transfer to comprehensive center “drip-and-ship” are best models of treatment of acute stroke. In this study, we compare mothership and drip-and-ship models to evaluate the best option of functional outcome.

Methods

Studies between 1990 and 2020 were extracted from online electronic databases. Clinical outcomes, critical time measurements, functional independence, and mortality were then compared.

Results

A total of 7824 patients’ data were retrieved from 13 publications (3 randomized control trials and 10 retrospective ones). In addition, 4639 (59.3%) patients were treated under mothership model, and 3185 (40.7%) followed the drip-and-ship model with mean age of 70.01 ± 3.58 versus 69.03 ± 3.36; p < 0.001, respectively. The National Institute Health Stroke Scale was 15.57 ± 3.83 for the mothership and 15.72 ± 2.99 for the drip-and-ship model (p ≤ 0.001). The mean symptoms onset-to-puncture time was significantly shorter in the mothership group compared to the drip-and-ship (159.69 min vs. 223.89 min; p ≤ 0.001, respectively). Moreover, the collected data indicated no significant difference between symptom’s onset to intravenous thrombolysis time and stroke onset-to-successful recanalization time (p = 0.205 and p ≤ 0.001, respectively). Patients had significantly worse functional outcome (modified Rankin score) (3–6) at 90 days in the drip-and-ship model (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.13–1.92, p < 0.004) and 1.49-folds higher likelihood of symptomatic intracerebral hemorrhage (OR: 1.49, 95% CI: 1.22–1.81, p < 0.0001) compared to mothership. However, there were no statistically significant difference in terms of mortality (OR: 1.16, 95% CI: 0.87–1.55, p = 0.32) and successful recanalization (OR: 1.12, 95% CI: 0.76–1.65, p = 0.56) between the two models of care.

Conclusion

Patients in the mothership model have significantly improved functional independence and recovery. Further studies are needed as the data from prospectively randomized studies are not of sufficient quality to make definite recommendations.
Validation of a smartphone application and wearable sensor for measurements of wrist motions
Authors: Engstrand Fredrik , Tesselaar Erik , Gestblom Rickard , Farnebo Simon
Published: April 2021

We developed a smartphone application to measure wrist motion using the mobile device’s built-in motion sensors or connecting it via Bluetooth to a wearable sensor. Measurement of wrist motion with this method was assessed in 33 participants on two occasions and compared with those obtained with a standard goniometer. The test–retest reproducibility in healthy individuals ranged from good to excellent (intraclass correlation (ICC) 0.76–0.95) for all motions, both with and without the wearable sensor. These results improved to excellent (ICC 0.90–0.96) on the second test day, suggesting a learning effect. The day-to-day reproducibility was overall better with the wearable sensor (mean ICC 0.87) compared with the application without using sensor or goniometer (mean ICC 0.82 and 0.60, respectively). This study suggests that smartphone-based measurements of wrist range of motion are feasible and highly accurate, making it a powerful tool for outcome studies after wrist surgery.
Implications of extreme serum neurofilament light chain levels for the management of patients with relapsing multiple sclerosis
Authors: Engel Sinah , Protopapa Maria , Steffen Falk , Papanastasiou Vakis , Nicolaou Christoforos , Protopapas Michalis , Zipp Frauke , Bittner Stefan , Luessi Felix
Published: April 2021

Background:

Serum neurofilament light chain (sNfL) is a promising biomarker to complement the decision-making process in multiple sclerosis (MS) patients. However, although sNfL levels are able to detect disease activity and to predict future disability, the growing evidence has not yet been translated into practicable recommendations for an implementation into clinical routine.

Methods:

The observation of a patient with extensive inflammatory activity in magnetic resonance imaging (MRI) along with an extremely high sNfL level in the absence of any clinical symptoms prompted us to investigate common characteristics of our MS patients with the highest sNfL levels in a retrospective cohort study. The 97.5th percentile was chosen as a cut-off value because the mean sNfL level of the resulting extreme neurofilament light chain (NfL) cohort corresponded well to the sNfL level of the presented case. Patient characterization included clinical and MRI assessment with a focus on disease activity markers. sNfL levels were determined by single molecule array.

Results:

The 97.5th percentile of our MS cohort (958 sNfL measurements in 455 patients) corresponded to a threshold value of 46.1 pg/ml. The mean sNfL level of the extreme sNfL cohort ( n = 24) was 95.6 pg/ml (standard deviation 68.4). Interestingly, only 15 patients suffered from a relapse at the time point of sample collection, whereas nine patients showed no signs of clinical disease activity. sNfL levels of patients with and without relapse did not differ [median 81.3 pg/ml (interquartile range [IQR] 48.0–128) versus 80.2 pg/ml (IQR 46.4–97.6), p = 0.815]. The proportion of patients with contrast-enhancing lesions was high and also did not differ between patients with and without relapse (92.9% versus 87.5%, p = 0.538); 78.9% of the patients not receiving a high-efficacious therapy had ongoing disease activity during a 2-year follow-up.

Conclusion:

Extremely high sNfL levels are indicative of subclinical disease activity and might complement treatment decisions in ambiguous cases.
An unusual case of aggressive malignant spread of epithelioid hemangioendothelioma
Authors: Hickman Ashley D , Bezerra Evandro D , Roden Anja C , Houdek Matthew T , Barlow Jonathan D , Robinson Steven I , Wahner Hendrickson Andrea E
Published: April 2021

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm which typically originates from liver, lung, or bone. Due to the low incidence of disease, the most effective treatment is not easily studied and much of the information known about EHE has been learned through case reports and case series. In this case, we will present an uncommon form of primary soft tissue EHE with local recurrence, bone metastasis, and lymphangitic spread to the lungs leading to respiratory failure. Imaging of the chest was atypical for EHE with intraseptal thickening and hilar lymphadenopathy. Respiratory failure was progressive despite aggressive multimodal treatment. This case highlights an unusually aggressive recurrence and metastasis of primary soft tissue EHE with atypical pulmonary imaging findings.
A note on the cavitation phenomenon in metallic plates perforated by sharp-nosed rigid projectiles
Authors: Rosenberg Zvi , Vayig Yaniv , Malka-Markovitz Alon
Published: April 2021

We explore the perforation process of metallic plates impacted by rigid sharp-nosed projectiles at high velocities. In particular, we are looking at the diameters of the penetration hole in the plates through a series of 2D numerical simulations, in order to check for the occurrence of cavitation in finite-thickness plates. This phenomenon has not been observed by previous workers and we were looking for its effect on the perforation process. Our simulations show that for every projectile/plate pair there is a certain impact velocity which marks the onset of cavitation. These threshold velocities depend on the normalized thickness of the plates, as well as on their effective strength. Our simulations are supported by the results from perforation tests on plates made of a low strength lead-antimony alloy. The main conclusion from our work is that analytical models for plate perforation should take into account the cavitation phenomenon, especially for high velocity impacts.
Showing They Care (Or Don’t): Affective Publics and Ambivalent Climate Activism on TikTok
Authors: Hautea Samantha , Parks Perry , Takahashi Bruno , Zeng Jing
Published: April 2021

The microvideo platform TikTok has emerged as a popular hub for self-expression and social activism, particularly for youth, but use of the platform’s affective affordances to spread awareness of important issues has not been adequately studied. Through an exploratory multimodal discourse analysis of a sample of popular climate change-hashtagged TikTok videos, we examine how affordances of visibility, editability, and association facilitate the formation of affective publics on TikTok. We describe how TikTok’s features allow creators to construct and propagate multi-layered, affect-laden messages with varying degrees of earnestness, humor, and ambiguity. Finally, we identify recurring affective themes in popular climate change messages by studying not just in-frame content but also the discursive, intertextual, and memetic linkages that propagate affective publics. Collectively, these audiovisual expressions of personal engagement and awareness demonstrate how media affordances can abet, amplify, and confuse discussions of global issues online. These affordances facilitate a unique kind of activism by helping non-expert users intervene in a discussion that generally takes place among scientists and journalists: the question of how serious a problem climate change is and what to do about it.
Mobilization, Mass Perceptions, and (Dis)information: “New” and “Old” Media Consumption Patterns and Protest
Authors: Onuch Olga , Mateo Emma , Waller Julian G.
Published: April 2021

When people join in moments of mass protest, what role do different media sources play in their mobilization? Do the same media sources align with positive views of mass mobilizations among the public in their aftermath? And, what is the relationship between media consumption patterns and believing disinformation about protest events? Addressing these questions helps us to better understand not only what brings crowds onto the streets, but also what shapes perceptions of, and disinformation about mass mobilization among the wider population. Employing original data from a nationally representative panel survey in Ukraine ( Hale, Colton, Onuch, & Kravets, 2014 ) conducted shortly after the 2013–2014 EuroMaidan mobilization, we examine patterns of media consumption among both participants and non-participants, as well as protest supporters and non-supporters. We also explore variation in media consumption among those who believe and reject disinformation about the EuroMaidan. We test hypotheses, prominent in current protest literature, related to the influence of “new” (social media and online news) and “old” media (television) on protest behavior and attitudes. Making use of the significance of 2014 Ukraine as a testing ground for Russian disinformation tactics, we also specifically test for consumption of Russian-owned television. Our findings indicate that frequent consumption of “old” media, specifically Russian-owned television, is significantly associated with both mobilization in and positive perceptions of protest and is a better predictor of believing “fake news” than consuming “new” media sources.
Adding an international lens to the university striving model: How both global and national indicators influence the Chinese higher education hierarchy
Authors: M. Allen Ryan
Published: April 2021

Institutions that are most attuned to university rankings are known as “strivers.” These striving universities chase prestige by altering policies to match league table indicators, while also benchmarking against elite universities within the domestic hierarchy. However, this model has mostly been ascribed to studies in the United States and it has not been considered in non-Western contexts. Through interviews with 48 academics and administrators from Chinese universities, the research explores striving behaviors in China and expands the US-centric model to include global competition with international rankings. The findings show that striving universities in China have placed considerable emphasis on international rankings, but distinctions from the central government have still dominated competition within the domestic hierarchy. Pressures from the various rankings must be balanced between the local and global. These new considerations offer a global outlook on the domestic university striving model.
Distress Migration Among Ultra-poor Households in Western Odisha
Authors: Tripathy S. N.
Published: April 2021

Consequent upon loss of employment and income due to frequent incidence of droughts, the marginal farmers, land less agricultural labourers and the poverty-stricken weaker sections of population migrate to developed regions in search of employment as a survival strategy. Trickle Up, as a part of its commitment towards reduction of extreme poverty, has been implementing the ‘graduation model’ 1 in many countries in Asia. In Odisha, since the year 2015, TU, in collaboration with Odisha Livelihood Mission (OLM), has been operating the graduation model at Bangomunda block in Balangir district (Odisha) to mitigate distress migration among the ultra-poor households. 2 An attempt has been made in this study to analyse the socio-economic impact of TU–OLM intervention of programmes on distress migrants in western Odisha.
Platelet-Rich Plasma Releasate Promotes Early Healing in Tendon After Acute Injury
Authors: Yu Tung-Yang , Pang Jong-Hwei S. , Lin Li-Ping , Cheng Ju-Wen , Liu Shih-Jung , Tsai Wen-Chung
Published: April 2021

Background:

Acute tendon injury can limit motion and thereby inhibit tendon healing. Positive results have been found after the use of platelet-rich plasma (PRP) to treat tendon injury; however, the early effects of PRP on tendon regeneration are not known.

Purpose/Hypothesis:

The purpose of this study was to evaluate the effects of PRP releasate (PRPr) on the early stages of tendon healing in a rat partial tenotomy model. It was hypothesized that PRPr can promote early healing of an Achilles tendon in rats.

Study Design:

Controlled laboratory study.

Methods:

PRP was prepared by a 2-step method of manual platelet concentration from 10 rats. PRPr was isolated from the clotted preparation after activation by thrombin and was applied to an Achilles tendon on 1 side of 30 rats on the second day after partial tenotomy, with normal saline used as the control on the other side. Achilles tendon samples were harvested 5 and 10 days after tenotomy. At each time point, 15 Achilles tendon samples were obtained, of which 5 samples were evaluated by Masson trichrome staining, apoptosis, and cell proliferation, while the other 10 samples were tested for tensile strength using a material testing machine.

Results:

Compared with saline-treated control tendons, the PRPr-treated tendons showed increased collagen synthesis near the cut edge and fewer apoptotic cells ( P = .01). An immunohistochemical analysis revealed more Ki-67–positive cells but fewer cluster of differentiation (CD) 68+ (ED1+) macrophages in PRPr tendons compared with saline-treated tendons ( P < .01). Tendons treated with PRPr also showed higher ultimate tensile strength than those treated with saline ( P = .03).

Conclusion:

PRPr treatment promotes tissue recovery in the early phase of tendon healing by stimulating tendon cell proliferation and collagen production while inhibiting cell apoptosis and CD68+ (ED1+) macrophage infiltration.

Clinical Relevance:

These findings suggest that with PRPr treatment, higher loads can be applied to the healing tendon at an earlier time, which can help the patient resume activity earlier.
An Anthropological Analysis of the Invisibility of Dalits of India in the Environmental Discourse: A Tale of Subjugation, Alienation and Resistance
Authors: Pandey Shubham , Nagarkoti Priyanshi
Published: April 2021

Ever since the onset of discourses around environment protection in India, different perspectives have come up to evaluate our natural environment. Nevertheless, even in their totality, they fail to provide a complete picture of the environmental struggles in India. This is partly because the ‘the Dalit perspective’ remains missing from the tales of ‘environmentalism’ that India has seen in the recent past. In India, there has been a complete subjugation of the Dalit perspective from the mainstream environmental discourses. So far as this subjugation goes, it is far from innocent and has a strong socio-political undercurrent, which creates a hegemonic structure within which the Indian Dalit loses his voice altogether. The authors, through the medium of this article, have made attempts to discover the forces which are at work in obliterating the Dalit perspectives from mainstream environmental discourse. The authors have tried to answer the questions that have characterized the subjugation in many different ways: Whether the missing of Dalits narratives is due to the monopolization of the discourses by the ‘upper caste’ and upper-class writings in India? The article will inquire how much truth is there in such allegations. More so, some light will be thrown on the structural framework of environment protection, and find answers as to how the structure of ‘environmental movements’ in India alienate the Dalits from actively participating in it. Further, the authors seek to unravel the politics of identity in India and how it affects the environment protection and subjugate the Dalit narrative. This will be done by taking into account some prominent Dalit symbols which have become tools for suppression by the state to cause the death of any resistance that comes from within the marginalized Dalit population of India. This article is solely an academic enquiry into the dialectical relationship that exists between the Dalits, the caste politics and the environments. The aim is to determine the reasons and consequences of subjugation and alienation of the Dalits from the environmental discourse.
Datta Bhagat’s Routes and Escape Routes and Vijay Tendulkar’s Kanyadaan: Critiquing the Dalit
Authors: Bhattacharyya Joydeep
Published: April 2021

This article seeks to understand Indian theatre’s take on Dalit politics of our time through a critical reading of two post-independence plays—Datta Bhagat’s Routes and Escape Routes and Vijay Tendulkar’s Kanyadaan. Politically, ‘Dalit’ becomes important only after 1947 in post-independence and post-colonial India or more specifically from the 1970s. In the post-Ambedkar phase of Dalit re/configuration, they begin to self-assert through politics, art, and literature, most effectively and convincingly, only with the rise of Dalit Panthers and in the aftermath of the implementation of Mandal Commission’s recommendation for Other Backward Classes (OBC) reservation. The article tries to examine the fresh critique of the Dalit vis-à-vis the upper caste-centric society, undertaken in this crucial context of reconfiguration and from beyond any traditional parameter of understanding, and map, through the plays, the plurality hidden within the perceived monolith of Dalit consciousness. Consequently, Dalit experiences against the backdrop of their struggle are laid bare, and unfamiliar realities come out to upset our comfortable knowledge about this large segment of Indian society.
Low-dose decitabine modulates T-cell homeostasis and restores immune tolerance in immune thrombocytopenia
Authors: Han Panpan , Hou Yu , Zhao Yajing , Liu Yang , Yu Tianshu , Sun Yunqi , Wang Haoyi , Xu Pengcheng , Li Guosheng , Sun Tao , Hu Xiang , Liu Xinguang , Li Lizhen , Peng Jun , Zhou Hai , Hou Ming
Published: April 2021

Our previous clinical study showed that low-dose decitabine exhibited sustained responses in nearly half of patients with refractory immune thrombocytopenia (ITP). The long-term efficacy of decitabine in ITP is not likely due to its simple role in increasing platelet production. Whether decitabine has the potential to restore immune tolerance in ITP is unknown. In this study, we analyzed the effect of decitabine on T-cell subpopulations in ITP in vitro and in vivo. We found that low-dose decitabine promoted the generation and differentiation of regulatory T (Treg) cells and augmented their immunosuppressive function. Splenocytes from CD61 knockout mice immunized with CD61+ platelets were transferred into severe combined immunodeficient mouse recipients to induce a murine model of ITP. Low-dose decitabine alleviated thrombocytopenia and restored the balance between Treg and helper T (Th) cells in active ITP mice. Treg deletion and depletion offset the effect of decitabine in restoring CD4+ T-cell subpopulations in ITP mice. For patients who received low-dose decitabine, the quantity and function of Treg cells were substantially improved, whereas Th1 and Th17 cells were suppressed compared with the pretreatment levels. Next-generation RNA-sequencing and cytokine analysis showed that low-dose decitabine rebalanced T-cell homeostasis, decreased proinflammatory cytokines, and downregulated phosphorylated STAT3 in patients with ITP. STAT3 inhibition analysis suggested that low-dose decitabine might restore Treg cells by inhibiting STAT3 activation. In conclusion, our data indicate that the immunomodulatory effect of decitabine provides one possible mechanistic explanation for the sustained response achieved by low-dose decitabine in ITP.
A comprehensive transcriptome signature of murine hematopoietic stem cell aging
Authors: Flohr Svendsen Arthur , Yang Daozheng , Kim KyungMok , Lazare Seka , Skinder Natalia , Zwart Erik , Mura-Meszaros Anna , Ausema Albertina , von Eyss Björn , de Haan Gerald , Bystrykh Leonid
Published: April 2021

We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using 2 independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp (P-selectin), the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally “young-like” HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics or deletion of Dnmt3a/b molecularly resembles HSC rejuvenation or aging, respectively.
14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T and myeloid immature acute leukemia
Authors: Di Giacomo Danika , La Starza Roberta , Gorello Paolo , Pellanera Fabrizia , Kalender Atak Zeynep , De Keersmaecker Kim , Pierini Valentina , Harrison Christine J , Arniani Silvia , Moretti Martina , Testoni Nicoletta , De Santis Giovanna , Roti Giovanni , Matteucci Caterina , Bassan Renato , Vandenberghe Peter , Aerts Stein , Cools Jan , Bornhauser Beat , Bourquin Jean-Pierre , Piazza Rocco , Mecucci Cristina
Published: April 2021

Acute leukemias (AL) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by co-expression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML M0 or M1), T/myeloid mixed phenotype acute leukemia (T/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32/BCL11B are the cytogenetic hallmark of this entity. In our screening of 915 hematological malignancies, there were 202 AML and 333 T-cell Acute Lymphoblastic Leukemia (T-ALL) (58 ETP, 178 non-ETP, 8 T/M MPAL, 89 not otherwise specified). We identified 20 cases of immature leukemias (4% of AML and 3,6% of T-ALL) harbouring four types of 14q32/BCL11B translocations: t(2,14)(q22.3;q32) (n=7), t(6;14)(q25.3;q32) (n=9), t(7;14)(q21.2;q32) (n=2) and t(8;14)(q24.2;q32) (n=2). The t(2;14) produced a ZEB2-BCL11B fusion transcript, while the other three rearrangements displaced transcriptionally active enhancer sequences close to BCL11B without producing fusion genes. All translocations resulted in the activation of BCL11B, a regulator of T-cell differentiation associated with transcriptional corepressor complexes in mammalian cells. The expression of BCL11B behaved as a disease biomarker, which was present at diagnosis but not in remission. Deregulation of BCL11B co-occurred with variants at FLT3 and at epigenetic modulators, most frequently DNMT3A, TET2 and/or WT1 gene. Transcriptome analysis identified a specific expression signature, with significant downregulation of BCL11B targets, and clearly separating BCL11B positive AL from AML, T-ALL, and ETP-ALL. Remarkably, ex-vivo drug sensitivity profile identified a panel of compounds with effective antileukemic activity.
What’s new in the pathogenesis and treatment of therapy-related myeloid neoplasms
Authors: Voso Maria Teresa , Falconi Giulia , Fabiani Emiliano
Published: April 2021

Therapy-related myeloid neoplasms (t-MNs) include diseases onsetting in patients treated with chemo- and/or radiotherapy for a primary cancer, or an autoimmune disorder. Genomic variants, in particular, in familial cancer genes, may play a predisposing role. Recent advances in deep sequencing techniques have shed light on the pathogenesis of t-MNs, identifying clonal hematopoiesis of indeterminate potential (CHIP) as a frequent first step in the multihit model of t-MNs. CHIP is often detectable prior to any cytotoxic treatment, probably setting the fertile genomic background for secondary leukemogenesis. The evolution pattern toward t-MNs is then a complex process, shaped by the type of cancer therapy, the aging process, and the individual exposures, that favor additional hits, such as the acquisition of TP53 mutations and unfavorable karyotype abnormalities. The pathogenesis of t-MNs differs from MN associated with environmental exposure. Indeed, the genetic aberration patterns of MN developing in atomic bomb survivors show few mutations in classical DNA methylation genes, and a high prevalence of 11q and ATM alterations, together with TP53 mutations. Survival in t-MNs is poor. In addition to the biology of t-MNs, the patient’s previous disease history and the remission status at t-MN diagnosis are significant factors contributing to unfavorable outcome. New drugs active in secondary leukemias include CPX-351, or venetoclax in combination with hypomethylating agents, monoclonal antibodies as magrolimab, or targeted drugs against pathogenic mutations. Allogeneic stem cell transplantation remains the best currently available therapeutic option with curative intent for fit patients with unfavorable genetic profiles.
RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury
Authors: Huang Yumin , Wang Yingge , Duan Zuowei , Liang Jingyan , Xu Yijun , Zhang Shuai , Tang Tieyu
Published: April 2021

Studies have greatly explored the role of microRNAs (miRNAs) in cerebral ischemia/reperfusion injury (CI/RI). But the specific mechanism of miR-326-5p in CI/RI is still elusive. Hence, this study was to unmask the mechanism of miR-326-5p/signal transducer and activator of transcription-3 (STAT3) axis in CI/RI. Two models (oxygen and glucose deprivation [OGD] in primary rat cortical neurons and middle cerebral artery occlusion [MCAO] in Sprague–Dawley rats) were established to mimic CI/RI in vitro and in vivo, respectively. Loss- and gain-of function assays were performed with OGD-treated neurons and with MCAO rats. Afterward, viability, apoptosis, oxidative stress and mitochondrial membrane potential in OGD-treated neurons were tested, as well as pathological changes, apoptosis and mitochondrial membrane potential in brain tissues of MCAO rats. Mitofusin-2 (Mfn2), miR-326-5p and STAT3 expression in OGD-treated neurons and in brain tissues of MCAO rats were detected. Mfn2 and miR-326-5p were reduced, and STAT3 was elevated in OGD-treated neurons and brain tissues of MCAO rats. miR-326-5p targeted and negatively regulated STAT3 expression. Restoring miR-326-5p or reducing STAT3 reinforced viability, inhibited apoptosis and oxidative stress, increased mitochondrial membrane potential and increased Mfn2 expression in OGD-treated neurons. Up-regulating miR-326-5p or down-regulating STAT3 relieved pathological changes, inhibited apoptosis and elevated mitochondrial membrane potential and Mfn2 expression in brain tissues of rats with MCAO. This study elucidates that up-regulated miR-326-5p or down-regulated STAT3 protects against CI/RI by elevating Mfn2 expression.
Open-loop analysis on sympathetically mediated arterial pressure and urine output responses in spontaneously hypertensive rats: effect of renal denervation
Authors: Kawada Toru , Nishikawa Takuya , Suehara Satoru , Sawada Satoshi , Tanaka Tetsuo , Uenohara Minako , Yamamoto Hiromi , Sugimachi Masaru
Published: April 2021

Primary acute sympathetic activation (PASA) causes a subsequent arterial pressure (AP) elevation. In this case, an antidiuretic effect via the renal innervation and pressure diuresis can act antagonistically on the kidneys. We examined the effect of PASA on urine output in spontaneously hypertensive rats (SHR) 4–7 days after unilateral renal denervation (RDN) (n = 9). The slope of the plot of urine flow versus AP was positive (0.120 ± 0.031 μL min−1 kg−1 mmHg−1) on the intact side, but it was less than 1/3 of the slope observed previously in normotensive Wistar–Kyoto rats (WKY). RDN did not normalize the slope of urine flow versus AP (0.179 ± 0.025 μL min−1 kg−1 mmHg−1, P = 0.098 versus the intact side). The urine flow at the operating point of the AP tended to be greater on the denervated than the intact side (29.0 ± 1.8 vs. 25.3 ± 1.9 μL min−1 kg−1, P = 0.055). The percent increase (17.2 ± 7.2%) was not different from that observed previously in WKY. Although high-resting sympathetic nerve activity is prerequisite for maintaining hypertension in SHR, the effect of sympathetic innervation on the urine output function was not greater than that in WKY.
FINDER: an automated software package to annotate eukaryotic genes from RNA-Seq data and associated protein sequences
Authors: Banerjee Sagnik , Bhandary Priyanka , Woodhouse Margaret , Sen Taner Z. , Wise Roger P. , Andorf Carson M.
Published: April 2021

Background

Gene annotation in eukaryotes is a non-trivial task that requires meticulous analysis of accumulated transcript data. Challenges include transcriptionally active regions of the genome that contain overlapping genes, genes that produce numerous transcripts, transposable elements and numerous diverse sequence repeats. Currently available gene annotation software applications depend on pre-constructed full-length gene sequence assemblies which are not guaranteed to be error-free. The origins of these sequences are often uncertain, making it difficult to identify and rectify errors in them. This hinders the creation of an accurate and holistic representation of the transcriptomic landscape across multiple tissue types and experimental conditions. Therefore, to gauge the extent of diversity in gene structures, a comprehensive analysis of genome-wide expression data is imperative.

Results

We present FINDER, a fully automated computational tool that optimizes the entire process of annotating genes and transcript structures. Unlike current state-of-the-art pipelines, FINDER automates the RNA-Seq pre-processing step by working directly with raw sequence reads and optimizes gene prediction from BRAKER2 by supplementing these reads with associated proteins. The FINDER pipeline (1) reports transcripts and recognizes genes that are expressed under specific conditions, (2) generates all possible alternatively spliced transcripts from expressed RNA-Seq data, (3) analyzes read coverage patterns to modify existing transcript models and create new ones, and (4) scores genes as high- or low-confidence based on the available evidence across multiple datasets. We demonstrate the ability of FINDER to automatically annotate a diverse pool of genomes from eight species.

Conclusions

FINDER takes a completely automated approach to annotate genes directly from raw expression data. It is capable of processing eukaryotic genomes of all sizes and requires no manual supervision—ideal for bench researchers with limited experience in handling computational tools.
AutoDTI++: deep unsupervised learning for DTI prediction by autoencoders
Authors: Sajadi Seyedeh Zahra , Zare Chahooki Mohammad Ali , Gharaghani Sajjad , Abbasi Karim
Published: April 2021

Background

Drug–target interaction (DTI) plays a vital role in drug discovery. Identifying drug–target interactions related to wet-lab experiments are costly, laborious, and time-consuming. Therefore, computational methods to predict drug–target interactions are an essential task in the drug discovery process. Meanwhile, computational methods can reduce search space by proposing potential drugs already validated on wet-lab experiments. Recently, deep learning-based methods in drug-target interaction prediction have gotten more attention. Traditionally, DTI prediction methods' performance heavily depends on additional information, such as protein sequence and molecular structure of the drug, as well as deep supervised learning.

Results

This paper proposes a method based on deep unsupervised learning for drug-target interaction prediction called AutoDTI++. The proposed method includes three steps. The first step is to pre-process the interaction matrix. Since the interaction matrix is sparse, we solved the sparsity of the interaction matrix with drug fingerprints. Then, in the second step, the AutoDTI approach is introduced. In the third step, we post-preprocess the output of the AutoDTI model.

Conclusions

Experimental results have shown that we were able to improve the prediction performance. To this end, the proposed method has been compared to other algorithms using the same reference datasets. The proposed method indicates that the experimental results of running five repetitions of tenfold cross-validation on golden standard datasets (Nuclear Receptors, GPCRs, Ion channels, and Enzymes) achieve good performance with high accuracy.
Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method
Authors: Yoshino Yuta , Kumon Hiroshi , Mori Takaaki , Yoshida Taku , Tachibana Ayumi , Shimizu Hideaki , Iga Jun-ichi , Ueno Shu-ichi
Published: April 2021

Background

Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects.

Results

The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033).

Conclusions

Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.
Helicobacter pylori infection is correlated with the incidence of erosive oral lichen planus and the alteration of the oral microbiome composition
Authors: Li Shutong , Zhang Yangheng , Yang Zongcheng , Li Jingyuan , Li Ya , Li Huanjie , Li Wenjuan , Jia Jihui , Ge Shaohua , Sun Yundong
Published: April 2021

Background

Oral lichen planus (OLP), a common clinical oral disease, is associated with an increased risk of malignant transformation. The mechanism underlying the pathogenesis of OLP is unknown. Oral dysbacteriosis is reported to be one of the aetiological factors of OLP. AlthoughHelicobacter pyloriinfection is associated with various oral diseases, the correlation betweenH. pyloriinfection and OLP is unclear. This study aimed to investigate the effect ofH. pyloriinfection on OLP pathogenesis and oral microbiome composition in the Chinese population, which has a high incidence ofH. pyloriinfection.

Result

In this study, saliva samples of 30 patients with OLP (OLP group) and 21 negative controls (NC group) were collected.H. pyloriinfection was detected using the carbon-13-labeled urea breath test (UBT). The saliva samples were divided into the following four groups based on theH. pyloristatus:H. pylori-positive OLP (OLP+),H. pylori-positive NC (NC+),H. pylori-negative OLP (OLP−), andH. pylori-negative NC (NC−). Oral microbiome compositions were significantly different between the OLP and NC groups and between the OLP− and OLP+ groups. Compared with those in the OLP− group, those in the OLP+ group had a higher incidence of erosive OLP and higher levels of salivary cytokines. In contrast, the oral microbiome composition and cytokine levels were not significantly different between the NC− and NC+ groups.

Conclusions

This is the first report to demonstrate thatH. pyloriinfection is significantly correlated with the pathogenesis of erosive OLP.
Correction to: Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model
Authors: Guzmán-Ruiz Mara A. , Herrera-González Amor , Jiménez Adriana , Candelas-Juárez Alan , Quiroga-Lozano Crystal , Castillo-Díaz Claudia , Orta-Salazar Erika , Organista-Juárez Diana , Díaz-Cintra Sofía , Guevara-Guzmán Rosalinda
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Analysis of miRNA-mediated regulation of flowering induction in Lilium × formolongi
Authors: Zhang Qian , Zhao Yu-Qian , Gao Xue , Jia Gui-Xia
Published: April 2021

Background

MicroRNAs play pivotal roles in plant vegetative phase change and flowering induction via integrating into multiple flowering pathways. Lilium × formolongi is an important ornamental lily cultivar that can flower within one year after sowing. However, it remains unresolved how miRNA-mediated regulation networks contribute to the L. × formolongi characteristics of a short vegetative growth period and rapid flowering.

Results

In this study, the small RNA libraries and one degradome library were constructed for L. × formolongi during vegetative growth and flowering initiation, and 366 conserved miRNAs and 32 novel miRNAs were identified. Additionally, 84 miRNAs were significantly differentially expressed during development. A total of 396 targets of 185 miRNAs were identified and validated through degradome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that functions of the targets were top enriched in the cold and cadmium ion responses, pentose phosphate pathway and carbon fixation in photosynthetic organisms. Furthermore, among 23 differentially expressed miRNA-target pairs, the miR156s-LfSPL2, miR172a-LfAP2 and miR164a-LfNAC pairs as well as miR159a-LfSPL2 were found to be relevant to flowering based on the correlation analysis of expression profiles in the miRNA libraries, degradome and transcriptome. A coexpression regulatory network focused on differentially expressed pairs was also constructed by WGCNA, and 14 miRNAs were considered putative key miRNAs during vegetative development and flowering induction. miR156a/ d/ e showed particularly strong relationships with other miRNAs in the coexpression network.

Conclusions

This study provides cues for the further exploration of the regulatory mechanisms of short vegetative development and flowering in L. × formolongi.
Midterm follow up of transcatheter closure of coronary artery fistula with Nit-Occlud® patent ductus arteriosus coil
Authors: Amoozgar Hamid , Edraki Mohammad Reza , Naghshzan Amir , Mehdizadegan Nima , Mohammadi Hamid , Ajami Gholamhossein , Amirghofran Ahmad Ali
Published: April 2021

Background

Coronary artery fistula (CAF) is a rare congenital anomaly with a challenging scenario in children. This study reports our experience in transcatheter closure of CAF with Nit-Occlude PDA coil and midterm clinical and imaging follow-up.

Methods

Twelve children with congenital CAF between 2009 and 2019, mean age 2.05 ± 2.05 years (4 days to 7.2 years), mean weight 8.8 ± 4.83 (2.8–17 kg), who underwent transcatheter closure with PFM coil at the Namazi hospital, Shiraz, Iran, were reported. Echocardiography and electrocardiogram were done before and after the procedure (early, 3, and 6 months after), and Multi-slice computerized tomography or conventional coronary angiography was performed at least one year after closure.

Results

In a median follow-up of 5.5 years (range 13 months to 8 years), retrogradely closed fistula had no residual, and the fistula tract was wholly occluded, but in most anterogradely closed fistula, had a small residual, which made the fistula tract open and need additional coil closure.

Conclusions

Transcatheter closure of CAF with PFM coil is feasible and effective with low mortality and morbidity, although antegrade closure with this device may be accompanied by residual shunt and need for multiple coil insertion.
Hemodynamic change in patients with hypertrophic obstructive cardiomyopathy before and after alcohol septal ablation using 4D flow magnetic resonance imaging: a retrospective observational study
Authors: Suwa Kenichiro , Akita Keitaro , Iguchi Keisuke , Ushio Takasuke , Maekawa Yuichiro
Published: April 2021

Background

The hemodynamics in the left ventricle (LV) and the ascending aorta (AAO) before and after alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) is elucidated. Our objective was to evaluate the pattern changes in AAO and intra-LV flow assessed by four-dimensional (4D) flow magnetic resonance imaging (MRI) before and after ASA and to clarify the association between 4D flow MRI-derived hemodynamic characteristics and the peak pressure gradient (PPG) in patients with drug-refractory HOCM.

Methods

In this retrospective observational study, 11 patients with HOCM underwent 4D flow MRI before and a week after ASA. The 4D flow MRI included blood flow visualization and quantification using streamline images. The combined score of vortex and helix in AAO was analyzed. The duration and phase count of the AAO vortex or helix flow and the size of the intra-LV anterior vortex were quantified. The correlation between the changes in hemodynamics and the resting PPG at LV outflow tract was also analyzed. We used the paired t-test for the comparison between before and after ASA and the Pearson’s correlation coefficient for the analysis.

Results

The combined score for the incidence of vortex and/or helix flow in AAO after ASA was significantly lower than that before ASA (1.45 ± 0.52 vs. 1.09 ± 0.30, p = 0.046). The duration (744 ± 291 ms vs. 467 ± 258 ms, p < 0.001) and phase count (14.8 ± 4.4 phases vs. 10.5 ± 5.8 phases, p < 0.001) of the vortex or helix flow in AAO were significantly decreased after ASA. The LV anterior vortex area after ASA was significantly larger than that before ASA (1628 ± 420 mm2 vs. 2974 ± 539 mm2, p = 0.009). The delta phase count of the AAO vortex or helix before and a week after ASA was significantly correlated with delta PPG before and a week after ASA (R = 0.79, p = 0.004) and with delta PPG before and 6 months after ASA (R = 0.83, p = 0.002).

Conclusions

Lower vortex or helix flow in AAO and larger diastolic vortex flow in LV were observed after ASA, which suggests the possibility to detect the changes of aberrant hemodynamics in HOCM.