bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Brain Activity Following Auricular Point Acupressure in Chemotherapy-Induced Neuropathy: A Pilot Longitudinal Functional Magnetic Resonance Imaging Study
Authors: Yeh Chao Hsing , Caswell Keenan , Pandiri Sonaali , Sair Haris , Lukkahatai Nada , Campbell Claudia M , Stearns Vered , Van de Castle Barbara , Perrin Nancy , Smith Thomas J , Saligan Leorey N 
Published: February 2020

Background The objective of this study was to investigate the dynamic brain activity following auricular point acupressure (APA) in chemotherapy-induced neuropathy (CIN). Methods Participants received 4 weeks of APA in an open-pilot trial with repeated observation. Along with the clinical self-reported CIN outcomes, objective outcomes were measured over the course of the treatment by physiological changes in pain sensory thresholds from quantitative sensory testing (QST) and repeated functional magnetic resonance imaging scans. Results After 4 weeks of APA, participants had reported clinically significant improvements (ie, ≥30%) in a reduction of CIN symptoms (including pain, numbness, tingling, and stiffness) in lower extremity stiffness (32%), reduced foot sensitivity (13%), and higher pain threshold (13%). Across the 11 intrinsic brain networks examined, there was a trend toward significance of the connectivity of the basal ganglia network (BGN) to the salience network (SAL), which was decreased pre-APA versus immediate-APA (effect size [ES] = 1.04, P = .07). The BGN also demonstrated decreased connectivity with the language network pre-APA versus delayed imaging post-APA (ES = −0.92, P = .07). Furthermore, there was increased executive control network (ECN) and SAL within-network connectivity comparing pre-APA to delayed imaging post-APA, trending toward significance (ES = 0.41, P = .09 and ES = 0.17, P = .09, respectively). Conclusion The changes in connectivity and activity within or between the ECN, SAL, and BGN from pre- to post-APA suggest ongoing alterations in brain functional connectivity following APA, particularly in the insula, anterior cingulate, and dorsolateral prefrontal cortices, which play significant roles in pain, memory, and cognitive function.
High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML
Authors: Simon Laura , Spinella Jean-François , Yao Chi-Yuan , Lavallée Vincent-Philippe , Boivin Isabel , Boucher Geneviève , Audemard Eric , Bordeleau Marie-Eve , Lemieux Sébastien , Hébert Josée , Sauvageau Guy 
Published: February 2020

Abstract
RUNX1 is mutated in ∼10% of adult acute myeloid leukemia (AML). Although most RUNX1 mutations in this disease are believed to be acquired, they can also be germline. Indeed, germline RUNX1 mutations result in the well-described autosomal-dominant familial platelet disorder with predisposition to hematologic malignancies (RUNX1-FPD, FPD/AML, FPDMM); ∼44% of affected individuals progress to AML or myelodysplastic syndromes. Using the Leucegene RUNX1 AML patient group, we sought to investigate the proportion of germline vs acquired RUNX1 mutations in this cohort. Our results showed that 30% of RUNX1 mutations in our AML cohort are germline. Molecular profiling revealed higher frequencies of NRAS mutations and other mutations known to activate various signaling pathways in these patients with RUNX1 germline–mutated AML. Moreover, 2 patients (mother and son) had co-occurrence of RUNX1 and CEBPA germline mutations, with variable AML disease onset at 59 and 27 years, respectively. Together, these data suggest a higher than anticipated frequency of germline RUNX1 mutations in the Leucegene cohort and further highlight the importance of testing for RUNX1 mutations in instances in which allogeneic stem cell transplantation using a related donor is envisioned.
FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia
Authors: Long Jun , Jia Ming-Yuan , Fang Wei-Yue , Chen Xin-Jie , Mu Li-Li , Wang Zhong-Yu , Shen Yan , Xiang Ru-Fang , Wang Li-Ning , Wang Ling , Jiang Chuan-He , Jiang Jie-Ling , Zhang Wen-Jun , Sun Yi-Dan , Chang Li , Gao Wen-Hui , Wang Ying , Li Jun-Min , Hong Deng-Li , Liang Ai-Bin , Hu Jiong 
Published: February 2020

Abstract
Internal tandem duplication (ITD) mutations within the FMS-like receptor tyrosine kinase-3 (FLT3) can be found in up to 25% to 30% of acute myeloid leukemia (AML) patients and confer a poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs) have shown clinical responses, they cannot eliminate primitive FLT3-ITD+ AML cells, which are potential sources of relapse. Therefore, elucidating the mechanisms underlying FLT3-ITD+ AML maintenance and drug resistance is essential to develop novel effective treatment strategies. Here, we demonstrate that FLT3 inhibition induces histone deacetylase 8 (HDAC8) upregulation through FOXO1- and FOXO3-mediated transactivation in FLT3-ITD+ AML cells. Upregulated HDAC8 deacetylates and inactivates p53, leading to leukemia maintenance and drug resistance upon TKI treatment. Genetic or pharmacological inhibition of HDAC8 reactivates p53, abrogates leukemia maintenance, and significantly enhances TKI-mediated elimination of FLT3-ITD+ AML cells. Importantly, in FLT3-ITD+ AML patient–derived xenograft models, the combination of FLT3 TKI (AC220) and an HDAC8 inhibitor (22d) significantly inhibits leukemia progression and effectively reduces primitive FLT3-ITD+ AML cells. Moreover, we extend these findings to an AML subtype harboring another tyrosine kinase–activating mutation. In conclusion, our study demonstrates that HDAC8 upregulation is an important mechanism to resist TKIs and promote leukemia maintenance and suggests that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation–harboring leukemias.
A high-fat diet delays plasmin generation in a thrombomodulin-dependent manner in mice
Authors: Miszta Adam , Kopec Anna K. , Pant Asmita , Holle Lori A. , Byrnes James R. , Lawrence Daniel A. , Hansen Kirk C. , Flick Matthew J. , Luyendyk James P. , de Laat Bas , Wolberg Alisa S. 
Published: February 2020

AbstractObesity is a prevalent prothrombotic risk factor marked by enhanced fibrin formation and suppressed fibrinolysis. Fibrin both promotes thrombotic events and drives obesity pathophysiology, but a lack of essential analytical tools has left fibrinolytic mechanisms affected by obesity poorly defined. Using a plasmin-specific fluorogenic substrate, we developed a plasmin generation (PG) assay for mouse plasma that is sensitive to tissue plasminogen activator, α2-antiplasmin, active plasminogen activator inhibitor (PAI-1), and fibrin formation, but not fibrin crosslinking. Compared with plasmas from mice fed a control diet, plasmas from mice fed a high-fat diet (HFD) showed delayed PG and reduced PG velocity. Concurrent to impaired PG, HFD also enhanced thrombin generation (TG). The collective impact of abnormal TG and PG in HFD-fed mice produced normal fibrin formation kinetics but delayed fibrinolysis. Functional and proteomic analyses determined that delayed PG in HFD-fed mice was not due to altered levels of plasminogen, α2-antiplasmin, or fibrinogen. Changes in PG were also not explained by elevated PAI-1 because active PAI-1 concentrations required to inhibit the PG assay were 100-fold higher than circulating concentrations in mice. HFD-fed mice had increased circulating thrombomodulin, and inhibiting thrombomodulin or thrombin-activatable fibrinolysis inhibitor (TAFI) normalized PG, revealing a thrombomodulin- and TAFI-dependent antifibrinolytic mechanism. Integrating kinetic parameters to calculate the metric of TG/PG ratio revealed a quantifiable net shift toward a prothrombotic phenotype in HFD-fed mice. Integrating TG and PG measurements may define a prothrombotic risk factor in diet-induced obesity.
RISUG® as a male contraceptive: journey from bench to bedside
Authors: Khilwani Barkha , Badar Ayesha , Ansari Abdul S. , Lohiya Nirmal K. 
Published: February 2020

AbstractEven after decades of research men still lack reliable and reversible contraceptive methods comparable to female methods of contraception. Traditional methods of male contraception present a high failure rate and also involve high risk both when used for contraception and for protection against sexually transmitted diseases. Various chemical, hormonal, immunological, vas based and herbal methods of contraception have been examined by scientists world over during the past four decades. Among the possible lead approaches, exogenous hormonal contraception, either alone or in combination with progesterone or antiandrogen, is being viewed at low profile because of their insufficiency in inducing uniform suppression of spermatogenesis and steroid related long term complications. As an alternative to vasectomy, among various intravasal devices being examined, RISUG® (Reversible Inhibition of Sperm Under Guidance), a co-polymer of styrene and maleic anhydride offers long term contraception with safety, efficacy and it can be delivered by no-scalpel injection. Thus it is the only male contraceptive procedure currently under Phase- III Clinical Trial. The non-invasive reversal technique, successfully demonstrated in langur monkeys and functional reversal achieved with dimethyl sulphoxide (DMSO) and sodium bicarbonate (NaHCO3) in rats and rabbits with safety at F1 generation (first filial generation) have projected RISUG® as a better alternative to vasectomy. In this narrative review we revisit the long journey of RISUG® beginning with formulation on a bench towards reaching the market as a safe and effective contraceptive method, discussing various milestones and roadblocks of this expedition awaiting the mandatory regulatory clearance from the Government of India. Successful completion of ongoing phase III clinical trials with demonstration of reversal in human volunteers will give an indigenously developed male contraceptive to the world.
Evolutionary history of two cryptic species of northern African jerboas
Authors: Moutinho Ana Filipa , Serén Nina , Paupério Joana , Silva Teresa Luísa , Martínez-Freiría Fernando , Sotelo Graciela , Faria Rui , Mappes Tapio , Alves Paulo Célio , Brito José Carlos , Boratyński Zbyszek 
Published: February 2020

AbstractBackgroundClimatic variation and geologic change both play significant roles in shaping species distributions, thus affecting their evolutionary history. In Sahara-Sahel, climatic oscillations shifted the desert extent during the Pliocene-Pleistocene interval, triggering the diversification of several species. Here, we investigated how these biogeographical and ecological events have shaped patterns of genetic diversity and divergence in African Jerboas, desert specialist rodents. We focused on two sister and cryptic species,Jaculus jaculusandJ. hirtipes, where we (1) evaluated their genetic differentiation, (2) reconstructed their evolutionary and demographic history; (3) tested the level of gene flow between them, and (4) assessed their ecological niche divergence.ResultsThe analyses based on 231 individuals sampled throughout North Africa, 8 sequence fragments (one mitochondrial and seven single copy nuclear DNA, including two candidate genes for fur coloration:MC1RandAgouti), 6 microsatellite markers and ecological modelling revealed: (1) two distinct genetic lineages with overlapping distributions, in agreement with their classification as different species,J. jaculusandJ. hirtipes, with (2) low levels of gene flow and strong species divergence, (3) high haplotypic diversity without evident geographic structure within species, and (4) a low level of large-scale ecological divergence between the two taxa, suggesting species micro-habitat specialization.ConclusionsOverall, our results suggest a speciation event that occurred during the Pliocene-Pleistocene transition. The contemporary distribution of genetic variation suggests ongoing population expansions. Despite the largely overlapping distributions at a macrogeographic scale, our genetic results suggest that the two species remain reproductively isolated, as only negligible levels of gene flow were observed. The overlapping ecological preferences at a macro-geographic scale and the ecological divergence at the micro-habitat scale suggest that local adaptation may have played a crucial role in the speciation process of these species.
High-throughput quantification of protein structural change reveals potential mechanisms of temperature adaptation in Mytilus mussels
Authors: Chao Ying-Chen , Merritt Melanie , Schaefferkoetter Devin , Evans Tyler G. 
Published: February 2020

AbstractBackgroundTemperature exerts a strong influence on protein evolution: species living in thermally distinct environments often exhibit adaptive differences in protein structure and function. However, previous research on protein temperature adaptation has focused on small numbers of proteins and on proteins adapted to extreme temperatures. Consequently, less is known about the types and quantity of evolutionary change that occurs to proteins when organisms adapt to small shifts in environmental temperature. In this study, these uncertainties were addressed by developing software that enabled comparison of structural changes associated with temperature adaptation (hydrogen bonding, salt bridge formation, and amino acid use) among large numbers of proteins from warm- and cold-adapted species of marine mussels,Mytilus galloprovincialisandMytilus trossulus, respectively.ResultsSmall differences in habitat temperature that characterize the evolutionary history ofMytilusmussels were sufficient to cause protein structural changes consistent with temperature adaptation. Hydrogen bonds and salt bridges that increase stability and protect against heat-induced denaturation were more abundant in proteins from warm-adaptedM. galloprovincialiscompared with proteins from cold-adaptedM. trossulus. These structural changes were related to deviations in the use of polar and charged amino acids that facilitate formation of hydrogen bonds and salt bridges within proteins, respectively. Enzymes, in particular those within antioxidant and cell death pathways, were over-represented among proteins with the most hydrogen bonds and salt bridges in warm-adaptedM. galloprovincialis. Unlike extremophile proteins, temperature adaptation inMytilusproteins did not involve substantial changes in the number of hydrophobic or large volume amino acids, nor in the content of glycine or proline.ConclusionsSmall shifts in organism temperature tolerance, such as that needed to cope with climate warming, may result from structural and functional changes to a small percentage of the proteome. Proteins in which function is dependent on large conformational change, notably enzymes, may be particularly sensitive to temperature perturbation and represent foci for natural selection. Protein temperature adaptation can occur through different types and frequencies of structural change, and adaptive mechanisms used to cope with small shifts in habitat temperature appear different from mechanisms used to retain protein function at temperature extremes.
Transcriptome profiling of differentially expressed genes in cytoplasmic male-sterile line and its fertility restorer line in pigeon pea (Cajanus cajan L.)
Authors: Saxena Swati , Sahu Sarika , Kaila Tanvi , Nigam Deepti , Chaduvla Pavan K. , Rao A. R. , Sanand Sandhya , Singh N. K. , Gaikwad Kishor 
Published: February 2020

Abstract
Background
Pigeon pea (Cajanus cajan L.) is the sixth major legume crop widely cultivated in the Indian sub-continent, Africa, and South-east Asia. Cytoplasmic male-sterility (CMS) is the incompetence of flowering plants to produce viable pollens during anther development. CMS has been extensively utilized for commercial hybrid seeds production in pigeon pea. However, the molecular basis governing CMS in pigeon pea remains unclear and undetermined. In this study transcriptome analysis for exploring differentially expressed genes (DEGs) between cytoplasmic male-sterile line (AKCMS11) and its fertility restorer line (AKPR303) was performed using Illumina paired-end sequencing.

Results
A total of 3167 DEGs were identified, of which 1432 were up-regulated and 1390 were down-regulated in AKCMS11 in comparison to AKPR303. By querying, all the 3167 DEGs against TAIR database, 34 pigeon pea homologous genes were identified, few involved in pollen development (EMS1, MS1, ARF17) and encoding MYB and bHLH transcription factors with lower expression in the sterile buds, implying their possible role in pollen sterility. Many of these DEGs implicated in carbon metabolism, tricarboxylic acid cycle (TCA), oxidative phosphorylation and elimination of reactive oxygen species (ROS) showed reduced expression in the AKCMS11 (sterile) buds.

Conclusion
The comparative transcriptome findings suggest the potential role of these DEGs in pollen development or abortion, pointing towards their involvement in cytoplasmic male-sterility in pigeon pea. The candidate DEGs identified in this investigation will be highly significant for further research, as they could lend a comprehensive basis in unravelling the molecular mechanism governing CMS in pigeon pea.
The TIR-NB-LRR pair DSC1 and WRKY19 contributes to basal immunity of Arabidopsis to the root-knot nematode Meloidogyne incognita
Authors: Warmerdam Sonja , Sterken Mark G. , Sukarta Octavina C. A. , van Schaik Casper C. , Oortwijn Marian E. P. , Lozano-Torres Jose L. , Bakker Jaap , Smant Geert , Goverse Aska 
Published: February 2020

AbstractBackgroundRoot-knot nematodes transform vascular host cells into permanent feeding structures to withdraw nutrients from the host plant. Ecotypes ofArabidopsis thalianacan display large quantitative variation in susceptibility to the root-knot nematodeMeloidogyne incognita, which is thought to be independent of dominant major resistance genes. However, in an earlier genome-wide association study of the interaction between Arabidopsis andM. incognitawe identified a quantitative trait locus harboring homologs of dominant resistance genes but with minor effect on susceptibility to theM. incognitapopulation tested.ResultsHere, we report on the characterization of two of these genes encoding the TIR-NB-LRR immune receptor DSC1 (DOMINANT SUPPRESSOR OF Camta 3 NUMBER 1) and the TIR-NB-LRR-WRKY-MAPx protein WRKY19 in nematode-infected Arabidopsis roots. Nematode infection studies and whole transcriptome analyses using the Arabidopsis mutants showed thatDSC1andWRKY19co-regulate susceptibility of Arabidopsis toM. incognita.ConclusionGiven the head-to-head orientation ofDSC1andWRKY19in the Arabidopsis genome our data suggests that both genes may function as a TIR-NB-LRR immune receptor pair. Unlike other TIR-NB-LRR pairs involved in dominant disease resistance in plants, DSC1 and WRKY19 most likely regulate basal levels of immunity to root-knot nematodes.
Perceptions and practices of general practitioners on providing oral health care to people with diabetes - a qualitative study
Authors: Poudel Prakash , Griffiths Rhonda , Wong Vincent W. , Arora Amit , Flack Jeff R. , Khoo Chee L. , George Ajesh 
Published: February 2020

Abstract
Background
Poorly controlled diabetes leads to multiple complications including oral health problems. General practitioners (GPs) are at the forefront of management of chronic diseases in primary health care. Diabetes guidelines encourage a proactive role for GPs in oral health complications management in people with diabetes, yet little is known about this area of care. This study aimed to explore current practices, perceptions and barriers of GPs towards oral health care for people with diabetes.

Methods
We employed a qualitative research method utilising telephone interviews. Purposive and snowball sampling were used to recruit 12 GPs from Greater Sydney region. A thematic analysis involving an inductive approach was used to identify and analyse contextual patterns and themes.

Results
A majority of participants were males (n = 10), working in group practices (n = 11) with a mean ± SD age of 55 ± 11.4 years and 25 ± 13.6 years work experience. Three major themes emerged: oral health care practices in general practice settings; barriers and enablers to oral health care; and role of diabetes care providers in promoting oral health.
Most GPs acknowledged the importance of oral health care for people with diabetes, identifying their compromised immune capacity and greater risks of infections as risk factors. GPs reported 20–30% of their patients having oral health problems, however their current oral health care practices relating to education, risk assessment and referrals were reported as very limited.
GPs identified several barriers including time constraints, absence of referral pathways, and limited knowledge and training in promoting oral health care. They also reported patient barriers including oral health care costs and lower oral health awareness. GPs perceived that resources such as education/training, a standardised assessment tool and patient education materials could support them in promoting oral health care. GPs also perceived that other diabetes care providers such as diabetes educators could play an important role in promoting oral health.

Conclusions
Despite current recommendations, GPs’ current oral health care practices among people with diabetes are limited. Further strategies including capacity building GPs by developing appropriate oral health training programs and simple risk assessment tools along with accessible referral pathways are needed to address the current barriers.
Does the shoe really fit? Characterising ill-fitting footwear among community-dwelling older adults attending geriatric services: an observational cross-sectional study
Authors: O’Rourke B. , Walsh M. E. , Brophy R. , Vallely S. , Murphy N. , Conroy B. , Cunningham C. , Horgan N. F. 
Published: February 2020

AbstractBackgroundFalls in older people are common and can result in loss of confidence, fear of falling, restriction in activity and loss of independence. Causes of falls are multi-factorial. There is a paucity of research assessing the footwear characteristics among older people who are at high risk of falls, internationally and in the Irish setting. The aim of this study was to examine the proportion of older adults attending a geriatric day hospital in Ireland who were wearing incorrectly sized shoes.MethodsA consecutive sample of 111 older adults aged 60 years and over attending a geriatric day hospital in a large Irish teaching hospital was recruited. Demographic data including age, mobility, medications, co-habitation status, footwear worn at home and falls history were recorded. Shoe size and foot length were measured in millimetres using an internal shoe gauge and SATRA shoe size stick, respectively. Participants’ self-reported shoe size was recorded. Footwear was assessed using the Footwear Assessment Form (FAF). A Timed Up and Go (TUG) score was recorded. Functional independence was assessed using the Nottingham Extended Activities of Daily Living (NEADL) Scale. The primary outcome of interest in this study was selected as having footwear within the suggested range (10 to 15 mm) on at least one foot. Participants who met this definition were compared to those with ill-fitting footwear on both feet using Chi-square tests, T-tests or Mann–Whitney U tests.ResultsThe mean difference between shoe length and foot length was 18.6 mm (SD: 9.6 mm). Overall, 72% of participants were wearing footwear that did not fit correctly on both feet, 90% had shoes with smooth, partly worn or fully worn sole treading and 67% reported wearing slippers at home. Participant age, TUG score and NEADL score were not associated with ill-fitting footwear.ConclusionsWearing incorrectly fitting shoes and shoes with unsafe features was common among older adults attending geriatric day services in this study. A large number of participants reported wearing slippers at home.