bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings
Authors: Taniguchi Shuichi , Yamauchi Takahiro , Choi Ilseung , Fukuhara Noriko , Potluri Jalaja , Salem Ahmed Hamed , Hong Wan-Jen , Honda Hideyuki , Nishimura Yasuko , Okubo Sumiko , Usuki Kensuke 
Published: March 2021

Abstract

Background
Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75 years) or those ineligible for induction chemotherapy due to co-morbidities.

Methods
In this phase 1/2 study (NCT02265731), Japanese patients (≥60 years) with untreated (ineligible for induction chemotherapy) or relapsed/refractory acute myeloid leukaemia received oral venetoclax 400 mg/day (3-day ramp up in cycle 1) plus subcutaneous or intravenous azacitidine 75 mg/m2 on days 1–7 per 28-day cycle until disease progression or unacceptable toxicity.

Results
As of 10 December 2019, six patients were enrolled (median age: 75 years; untreated: n = 5; relapsed/refractory: n = 1); median treatment duration: 10.3 months (range, 0.7–29.4). Most common grade ≥ 3 adverse events were lymphopaenia and febrile neutropaenia (n = 4 each). Four patients reported serious adverse events; only an event of grade 3 fungal pneumonia was considered possibly related to both study drugs, requiring dose interruption of venetoclax and delay of azacitidine. Five (83%) patients had responses (complete remission: n = 3). Median time to first response of complete remission/complete remission with incomplete count recovery was 1.0 month (range, 0.8–5.5); median overall survival: 15.7 months (95% confidence interval: 6.2, not reached).

Conclusions
Venetoclax plus azacitidine was well tolerated and showed high response rates in Japanese patients with acute myeloid leukaemia.
Statistics of collision parameters computed from 2D simulations
Authors: Süli Á 
Published: March 2021

ABSTRACTThere are two popular ways to speed up simulations of planet formation via increasing the collision probability: (i) confine motion to 2D, (ii) artificially enhance the physical radii of the bodies by an expansion factor. In this paper, I have performed 100 simulations each containing 104 interacting bodies and computed the collision parameters from the results of the runs. Each run was executed for a lower and a higher accuracy parameter. The main goal is to determine the probability distribution functions of the collision parameters and their dependence on the expansion factor. A simple method is devised to improve the determination of the collision parameters from the simulation data. It was shown that the distribution of the impact parameter is uniform and independent of the expansion factor. For real collisions, the impact velocity is greater than 1 mutual escape velocity, a finding that can be explained using the two-body problem. The results cast some doubts on simulations of the terrestrial planets’ final accretion that have assumed merge. Collision outcome maps were created adopting the fragmentation model of recent studies to estimate the number of different types of collisions. A detailed comparison with earlier works indicates that there are similarities as well as significant differences between the different works. The results indicate that as the planetary disc matures and the masses of the bodies differ progressively than the majority of collisions lead to mass growth either via partial accretion or via graze-and-merge collision.
Mitigation of X-ray induced DNA damages and expression of DNA-repair genes by antioxidative Potentilla fulgens root extract and its ethyl-acetate fraction in mammalian cells
Authors: Tripathy Debabrata , Upadhyay Ravi , Singh Chongtham Sovachandra , Boruah Nabamita , Mandal Nripendranath , Chatterjee Anupam 
Published: March 2021

Abstract
Potentilla fulgens is a medicinal plant in North-East India whose root is reported to have anti-diabetic, anticarcinogenic and antioxidant properties. The potential of hydro-alcoholic extract of P. fulgens root (PRE) for providing protection to mammalian cells exposed to ionising radiation was investigated in this study. The methanolic extract of PRE shows an enhanced radical scavenging ability in a concentration dependent manner. PRE-pre-treatment to stimulated human blood lymphocytes (HBLs) reduced the frequency of deletion and exchange aberrations induced by X-irradiation. Similar protection of chromosome aberrations was also observed in mouse bone marrow cells (BMCs) where mice were given PRE extract (1 mg extract/day/mice) ad libitum in the drinking water for 45 days before whole-body X-irradiation. Of the various extracts prepared by partitioning of the methanol extract, the ethyl-acetate (EA) fraction was found to possess better antioxidant, radical scavenging and DNA-damage reduction activities. PRE-pre-treatment also reduced the radiation-induced cell-cycle delay effectively in HBL. In HEK-293 cells, PRE reduced radiation-induced G2-block in cell kinetics. Interestingly, PRE-treatment alone increased the concentration of endogenous glutathione (GSH) in mouse BMC and in stimulated HBL along with the elevated expression of γ-glutamyl-cysteine synthetase heavy/catalytic subunit, a key determinant of GSH synthesis. Studies on expression of two DNA-repair genes revealed that there was a marked increase in the expression of GADD45 and H2AX genes after X-irradiation in stimulated HBL, and such expression was reduced significantly if PRE-treatment was given prior to radiation. The present findings show the ability of PRE to reduce radiation-induced DNA damages probably by free radical scavenging whereas modulation of expression of DNA-repair genes’ and endogenous GSH-increment emerge as effective strategies. The present study is the first report on the selected medicinal plant species that suggests it to be a potential natural radioprotector when used as root extract or its EA fraction for mitigating radiation toxicity.
Persistent post-covid symptoms in healthcare workers
Authors: Gaber T A-Z K , Ashish A , Unsworth A 
Published: March 2021

Abstract

Background
Recent reports suggest a higher incidence of COVID-19 infections among healthcare workers (HCW). However, information about the long-term complications affecting this population is lacking.

Aims
Investigation of long-term impact of COVID-19 in HCW.

Methods
Seropositivity for SARS-CoV-2 antibodies was evaluated for the majority of HCW in an English teaching hospital 2 months following the peak of COVID-19 first wave. A questionnaire investigating the long-term complications was sent through global e-mail to HCW 4 months following the peak of the wave enquiring about the persistent health issues still affecting them at that point.

Results
Out of 3759 subjects tested for SARS-CoV-2 antibodies, 932 were positive (24%). Forty-five per cent of 138 HCW responding to the questionnaire reported persistent symptoms with 32% struggling to cope 3–4 months following the peak of the wave. Moderate-to-severe fatigue stood out as the most disabling symptom (39%) but mild-to-moderate shortness of breath, anxiety and sleep disturbance were almost universal in the subjects still struggling with symptoms. Only 16% consulted their general practitioner (GP) about their symptoms with only 2% taking sick leave after recovering from the acute illness.

Conclusions
Our data suggest that about a third of HCW who responded to the survey were still struggling to cope with the symptoms of what is now known as long covid several months after the acute COVID-19 infections. The overwhelming majority of this group seem to be reluctant to neither seek medical advice nor take sick leave.
Swing Pricing and Fragility in Open-End Mutual Funds
Authors: Jin Dunhong , Kacperczyk Marcin , Kahraman Bige , Suntheim Felix 
Published: March 2021

AbstractHow can fragility be averted in open-end mutual funds? In recent years, markets have observed an innovation that changed the way open-end funds are priced. Alternative pricing rules (known as swing pricing) adjust funds’ net asset values to pass on funds’ trading costs to transacting shareholders. Using unique data on investor-level transactions in U.K. corporate bond funds, we show that swing pricing eliminates the first-mover advantage arising from the traditional pricing rule and significantly reduces outflows during market stress. Swing pricing also reduces concavity in the flow-performance relationship and dilution in fund performance.
The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study
Authors: Smigielski Lukasz , Wotruba Diana , Treyer Valerie , Rössler Julian , Papiol Sergi , Falkai Peter , Grünblatt Edna , Walitza Susanne , Rössler Wulf 
Published: March 2021

AbstractBackgroundBetween unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics.MethodThis work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined.ResultsAn inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis–stress models.ConclusionsAdversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.
Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance
Authors: Rodríguez-Baño Jesús , Rossolini Gian Maria , Schultsz Constance , Tacconelli Evelina , Murthy Srinivas , Ohmagari Norio , Holmes Alison , Bachmann Till , Goossens Herman , Canton Rafael , Roberts Adam P , Henriques-Normark Birgitta , Clancy Cornelius J , Huttner Benedikt , Fagerstedt Patriq , Lahiri Shawon , Kaushic Charu , Hoffman Steven J , Warren Margo , Zoubiane Ghada , Essack Sabiha , Laxminarayan Ramanan , Plant Laura 
Published: March 2021

Abstract
Antibiotic use in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients during the COVID-19 pandemic has exceeded the incidence of bacterial coinfections and secondary infections, suggesting inappropriate and excessive prescribing. Even in settings with established antimicrobial stewardship (AMS) programmes, there were weaknesses exposed regarding appropriate antibiotic use in the context of the pandemic. Moreover, antimicrobial resistance (AMR) surveillance and AMS have been deprioritised with diversion of health system resources to the pandemic response. This experience highlights deficiencies in AMR containment and mitigation strategies that require urgent attention from clinical and scientific communities. These include the need to implement diagnostic stewardship to assess the global incidence of coinfections and secondary infections in COVID-19 patients, including those by multidrug-resistant pathogens, to identify patients most likely to benefit from antibiotic treatment and identify when antibiotics can be safely withheld, de-escalated or discontinued. Long-term global surveillance of clinical and societal antibiotic use and resistance trends is required to prepare for subsequent changes in AMR epidemiology, while ensuring uninterrupted supply chains and preventing drug shortages and stock outs. These interventions present implementation challenges in resource-constrained settings, making a case for implementation research on AMR. Knowledge and support for these practices will come from internationally coordinated, targeted research on AMR, supporting the preparation for future challenges from emerging AMR in the context of the current COVID-19 pandemic or future pandemics.
Laboratory-based diagnosis of scabies: a review of the current status
Authors: Siddig Emmanuel Edwar , Hay Roderick 
Published: March 2021

Abstract
Scabies is a neglected tropical disease (NTD) of the skin that is caused by the mite Sarcoptes scabiei. It is considered to be an important public health problem in many regions. The disease is at its most prevalent in low-resource countries where there are overcrowded living conditions coupled with poor hygiene. In some regions, mass drug administration using ivermectin is a key population-based approach to the control of scabies. Before starting a patient on specific treatment, confirming the diagnosis by accurate and rapid identification of the organism is critical. Different laboratory-based techniques for scabies have been developed in the last few decades. These include direct microscopy and histopathology. More recently, serological testing, dermoscopy and different molecular techniques have been developed as diagnostic methods for scabies. To date, none of these, apart from microscopy and dermoscopy, has been translated into routine clinical laboratory practice. A simple point-of-care or laboratory test would provide a rapid and confirmed diagnosis and early institution of effective treatment. In this review we present an update on the laboratory techniques currently in use for the identification of scabies.
Ancient gene duplications in RNA viruses revealed by protein tertiary structure comparisons
Authors: Cisneros-Martínez Alejandro Miguel , Becerra Arturo , Lazcano Antonio 
Published: March 2021

AbstractTo date only a handful of duplicated genes have been described in RNA viruses. This shortage can be attributed to different factors, including the RNA viruses with high mutation rate that would make a large genome more prone to acquire deleterious mutations. This may explain why sequence-based approaches have only found duplications in their most recent evolutionary history. To detect earlier duplications, we performed protein tertiary structure comparisons for every RNA virus family represented in the Protein Data Bank. We present a list of thirty pairs of possible paralogs with &lt;30 per cent sequence identity. It is argued that these pairs are the outcome of six duplication events. These include the α and β subunits of the fungal toxin KP6 present in the dsRNA Ustilago maydis virus (family Totiviridae), the SARS-CoV (Coronaviridae) nsp3 domains SUD-N, SUD-M and X-domain, the Picornavirales (families Picornaviridae, Dicistroviridae, Iflaviridae and Secoviridae) capsid proteins VP1, VP2 and VP3, and the Enterovirus (family Picornaviridae) 3C and 2A cysteine-proteases. Protein tertiary structure comparisons may reveal more duplication events as more three-dimensional protein structures are determined and suggests that, although still rare, gene duplications may be more frequent in RNA viruses than previously thought.Keywords: gene duplications; RNA viruses.
Utilization of an Online Education Module and Standardized Patient Simulation Experience to Improve Nursing Student Learning Outcomes With Heart Failure Patients
Authors: De Silva Sriyani Ramyalatha , Gates Michael G. , Waczek Allison D. 
Published: March 2021

Abstract
The aim of this experimental study was to examine whether nursing students’ participation in an online comprehensive heart failure educational module enhances their knowledge and ability to apply heart failure education skills in a simulated standardized nurse-patient interaction. Findings suggest that students who received a heart failure educational module scored significantly higher on both an exam of heart failure knowledge and a simulated nurse-patient interaction. The results suggest that large gains can be made in nursing education by using innovative teaching strategies that move beyond normal classroom/lecture teaching techniques.
Effectiveness of a Home-Based Exercise Intervention in the Fitness Profile of Hispanic Survivors of Breast Cancer
Authors: Ortiz Alexis , Hughes Daniel C. , Mama Scherezade K. , Tirado-Gomez Maribel , Liao Yue , Song JaeJoon , Gonzalez Velda , Basen-Engquist Karen 
Published: March 2021

Background:
Home-based exercise interventions might be a desirable long-term option for breast cancer survivors to enhance compliance and long-term health benefits.

Purpose:
To assess the effectiveness of a home-based intervention aimed at helping survivors of breast cancer meet the physical activity guidelines of the American College of Sports Medicine.

Methods:
Eighty-nine women (age: 55.4 ± 10 years; body mass index: 31 ± 6.5 kg/m2) from 2 cancer centers serving Hispanic women participated in this study. Women underwent a baseline assessment of cardiorespiratory fitness, muscle endurance and strength, flexibility, range of motion, and extremity disability. After baseline measures, women were randomized into a control or exercise group. The exercise intervention consisted of a walking program, elastic band strengthening, and flexibility exercises performed at home. The outcome measures were reassessed 16 weeks after baseline measures.

Results:
The intervention showed a strong effect of time on muscle strength and shoulder range of motion, and time and group for self-reported disability. There were no differences in sedentary behavior, physical fitness, and disability measures across intervention groups, including both exercise groups combined and changes over time between intervention groups.

Conclusion:
It appears that a home-based intervention affects only upper-body strength and related disability, indicating that other components might need closer monitoring for significant changes to occur across time.
Supportive care practice: do we need guidelines?
Authors: Olver Ian 
Published: March 2021

Purpose of review
To review the role of evidence-based clinical practice guidelines in promoting the quality and consistency of supportive care in oncology to meet the needs of practitioners and patients.

Recent findings
To maintain quality, guidelines must be regularly updated in terms of content as new treatment modalities like immunotherapy are introduced, adapted to new methodologies such as the application of artificial intelligence, adoption of multiple symptoms or orphan symptoms and capture new endpoints such a patient-reported outcomes. This helps prevent a major barrier to implementation; negative attitudes of practitioners towards guidelines. Digital guidelines provide greater opportunities for dissemination, ease of updating and can be linked to education modules. The quality must be assured by critically appraising the literature and then grading the level of evidence of the guidelines. The benefits of supportive care guidelines include guidance for clinical decision-making in a changing field, continuing professional development of practitioners, a source of information for patients and in highlighting the gaps where further research is necessary.

Summary
The implications are that guidelines are required for supportive care in cancer but they must be constantly updated and evolve in their structure, the rigour of appraisal and content to promote quality care.
Cannabis Use in Older Adults: A Perspective
Authors: Solomon Haley V. , Greenstein Aaron P. , DeLisi Lynn E. 
Published: March 2021

Abstract
The prevalence of cannabis use among older adults (aged 65 and above) for both recreational and medicinal purposes has significantly increased in recent years. Information regarding the safety of cannabis in this population is important since aging is associated with metabolic changes, multiple morbidities, increases in prescription medication use, and an overall decline in functioning. In this Perspectives article, we review special considerations pertinent to older adults—specifically, the impact of cannabis on cognition and on falls and injuries, its drug interactions, and its potential medicinal applications for treating the behavioral and psychological symptoms of dementia. Knowledge about the role of cannabis in brain health, injury risk, and drug interactions remains limited since the available evidence stems primarily from adolescent and young adult cohorts, plus a limited number of small observational studies with older adults. In terms of utilizing certain cannabinoids to treat the behavioral and psychological symptoms of dementia, some studies have found promising results, but because of the lack of consistency in the literature, it is premature to draw conclusions. Controlled research trials specifically with geriatric participants are needed to understand the effects of cannabis use in this vulnerable population.
Metabolic Regulation of the NLRP3 Inflammasome
Authors: Ye Qizhen , Chen Sheng , Wang Di 
Published: March 2021

Abstract
The progression of many diseases is accompanied by inflammation, in which inflammasomes play an important role. Inflammasomes are large multimolecular complexes present in the cytosol of stimulated immune cells, which mediate the activation of caspase-1 and the secretion of cytokines, leading to cellular pyroptosis. During this process, metabolic regulation of the inflammasome is gaining increasing attention in this field. This review focuses on a major inflammasome, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and discusses the role and significance of its metabolic regulation.
Macrophage-Mediated Defensive Mechanisms Involving Zinc Homeostasis in Bacterial Infection
Authors: Na-Phatthalung Pinanong , Min Junxia , Wang Fudi 
Published: March 2021

Abstract
Zinc homeostasis in macrophages is essential for maintaining their antimicrobial functions, and a growing body of evidence indicates that both zinc depletion and excess zinc in myeloid cells decrease bacterial survival. In macrophages, maintaining intracellular and extracellular zinc levels via zinc transporter proteins, including Slc30a and Slc39a family members, plays an important role in the response to immunological signals and infection. Recently, studies have found that macrophages utilize a variety of zinc-modulating mechanisms, thus expanding our knowledge regarding the role that zinc plays in response to bacterial infection. Here, we review recent progress with respect to altered zinc metabolism in macrophages and the consequences with respect to fighting invading pathogens.