bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal evolution in inherited marrow failure syndromes predicts disease progression
Authors: Schratz Kristen E. 
Published: December 2023

Abstract
Progression to myelodysplastic syndromes (MDS) and acute myeloid leukemia is one of the most serious complications of the inherited bone marrow failure and MDS-predisposition syndromes. Given the lack of predictive markers, this risk can also be a source of great uncertainty and anxiety to patients and their providers alike. Recent data show that some acquired mutations may provide a window into this risk. While maladaptive mechanisms, such as monosomy 7, are associated with a high risk of leukemogenesis, mutations that offset the inherited defect (known as somatic genetic rescue) may attenuate this risk. Somatic mutations that are shared with age-acquired clonal hematopoiesis mutations also show syndrome-specific patterns that may provide additional data as to disease risk. This review focuses on recent progress in this area with an emphasis on the biological underpinnings and interpretation of these patterns for patient care decisions.
Management of pregnant women who have bleeding disorders
Authors: James Andra H. , Pacheco Luis D. , Konkle Barbara A. 
Published: December 2023

Abstract
Bleeding disorders, including von Willebrand disease (VWD), hemophilia, other coagulation factor deficiencies, platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Successful management of bleeding disorders in pregnant women requires not only an understanding of bleeding disorders but also an understanding of when and how bleeding occurs in pregnancy. Bleeding does not occur during a normal pregnancy with a healthy placenta. Bleeding occurs during pregnancy when there is an interruption of the normal utero-placental interface, during miscarriage, during an ectopic pregnancy, or at the time of placental separation at the conclusion of pregnancy. Although mild platelet defects may be more prevalent, the most commonly diagnosed bleeding disorder among women is VWD. Other bleeding disorders are less common, but hemophilia carriers are unique in that they are at risk of bleeding themselves and of giving birth to an affected male infant. General guidance for maternal management of a woman who is moderately or severely affected includes obtaining coagulation factor levels at a minimum in the third trimester; planning for delivery at a center with hemostasis expertise; and anticipating the need for hemostatic agents. General guidance for fetal management includes pre-pregnancy counseling; the option of preimplantation genetic testing for hemophilia; delivery at a tertiary care center with pediatric hematology and newborn intensive care; consideration of cesarean delivery of a potentially severely affected infant; and avoidance of invasive procedures such as scalp electrodes and operative vaginal delivery in any potentially affected infant.
Prevention, diagnosis, and management of PE and DVT in pregnant women
Authors: Kevane Barry , Áinle Fionnuala Ní 
Published: December 2023

Abstract
Venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality worldwide. Despite the impact of VTE on pregnant and postpartum people and on society, guidelines addressing prevention, diagnosis, and management of VTE in pregnant and postpartum people frequently are based on recommendations from expert opinion and are extrapolated from data in nonpregnant populations. Pregnant individuals are frequently excluded from clinical trials, which is a barrier to providing safe, effective care. Anchoring to a case discussion, this review provides an update on recently published and ongoing randomized clinical trials (RCTs), prospective clinical management studies, and other research in this area. It highlights, in particular, the results of the Highlow RCT, which addresses optimal prevention of recurrence during pregnancy in people with prior VTE. Finally, we raise awareness of the impact of national and international clinical trial networks on the conduct of RCTs in pregnancy. We conclude, based on these data, that academic VTE clinical trials in pregnant women can and must be done.
MSM and blood donation: shifting to individualized risk assessment
Authors: Goldman Mindy 
Published: December 2023

Abstract
Deferring donors at higher risk for transfusion transmissible infections is an important part of ensuring blood safety. The deferral for gay, bisexual, and other men who have sex with men (gbMSM) was implemented in the 1980s in many countries, since they were identified as a high-risk group for AIDS/HIV. With the introduction of increasingly sensitive HIV antibody testing, augmented by nucleic acid testing, the window period for HIV infection—when a donor may be infectious but have negative test results—has shrunk dramatically. In Canada, this has led to progressively shorter deferral periods for gbMSM, decreasing from a permanent deferral for sex with another male since 1977 to a 5-year, 12-month, and eventually 3-month deferral period. These time-based deferrals maintained safety; however, they are seen as stigmatizing by many and still result in the deferral of sexually active gbMSM. More recently, several countries have moved to a donor screening approach based on assessing sexual risk behaviors in all donors. This article outlines research supporting changes in policy, current eligibility screening policies in several countries, and preliminary results postimplementation of new eligibility policies in Canada in September 2022.
IV iron formulations and use in adults
Authors: Van Doren Layla , Auerbach Michael 
Published: December 2023

Abstract
Intravenous iron has become a major component of the therapeutic armamentarium for iron deficiency and iron deficiency anemia. The earliest formulations were associated with unacceptable toxicity. Newer formulations, with complex carbohydrate cores that bind elemental iron more tightly, allow the administration of full therapeutic doses in 15 to 60 minutes. Nonetheless, a folklore of danger, fueled by earlier formulations no longer available, continues to foment caution. Complement-mediated minor infusion reactions, referred to as complement activation-related pseudo-allergy, resolve without therapy. Inappropriate intervention with vasopressors and H1 blockers converts these minor reactions into hemodynamically significant adverse events. Four new formulations, low-molecular-weight iron dextran, ferumoxytol, ferric carboxymaltose, and ferric derisomaltose, all approved for the treatment of iron deficiency in a host of conditions, are now widely used with an excellent safety profile. Herein, the administration, safety, indications, and management of infusion reactions are discussed. Treatment-emergent hypophosphatemia, a newly recognized side effect for some formulations, is also reviewed. Based on the preponderance of published evidence, intravenous iron should be moved up-front for the treatment of iron deficiency and iron deficiency anemia in those conditions in which oral iron is suboptimal.
Medical consult: aHUS, TTP? How to distinguish and what to do
Authors: Story Charlotte M. , Gerber Gloria F , Chaturvedi Shruti 
Published: December 2023

Abstract
Immune thrombotic thrombocytopenic purpura (iTTP) caused by an autoantibody-mediated deficiency of ADAMTS13 and atypical hemolytic syndrome (aHUS) caused by alternative complement dysregulation are the most common primary thrombotic microangiopathies (TMAs). The evaluation of a patient with TMA is a medical emergency since it is critical to quickly distinguish iTTP and aHUS from other causes of TMA. Untreated iTTP is rapidly fatal, and delays in initiating complement inhibition in aHUS increase the risk of irreversible renal failure. An ADAMTS13 activity level of less than 10% is diagnostic of iTTP in the appropriate clinical setting. In settings where rapid-turnaround ADAMTS13 testing is not available, clinical features and clinical prediction tools are useful to identify patients who should receive emergent plasma exchange. We present an evidence-based approach to the initial (first 24 hours) diagnosis and management of iTTP and review the clinical and laboratory features that can be used to identify patients with aHUS who will benefit from early C5 blockade. We also discuss the potential use of complement blockade to improve outcomes in selected patients with secondary TMA.
Improving long-term outcomes with intensive induction chemotherapy for patients with AML
Authors: Röllig Christoph 
Published: December 2023

Abstract
Intensive chemotherapy in combination with allogeneic hematopoietic cell transplantation and supportive care can induce long-term remissions in around 50% of acute myeloid leukemia patients eligible for intensive treatment. Several treatment optimization trials helped to refine schedule and dosing of the historic “7 + 3” combination. Together with the addition of novel agents, increased efficacy and tolerability led to improved long-term outcomes. Unsatisfactory outcomes in fit elderly patients and unfavorable genetic subgroups have raised the question of whether less-intensive venetoclax-based approaches may be beneficial as an alternative. Although tempting and worth exploring, this issue will remain controversial until the results of randomized comparisons appear. To date, intensive chemotherapy remains the only evident curative treatment option for long-term disease eradication in a fixed treatment time. With the advent of more novel agents and advances in minimal residual disease (MRD) detection and maintenance approaches, the face of intensive treatment could change in many ways. Several are being explored in clinical trials, such as (1) combinations of more than 1 novel agent with the intensive backbone, (2) head-to-head comparisons of novel agents, (3) replacement or dose reduction of cytotoxic components such as anthracyclines, and (4) MRD-guided escalation and de-escalation strategies. The combination of intensive treatment with individualized tailored innovative strategies will most certainly reduce treatment-related toxicities and increase the chances for long-term remission in the future.
Acute lymphoblastic leukemia in young adults: which up-front treatment?
Authors: Molina John C. , Rotz Seth 
Published: December 2023

Abstract
Significant improvements have occurred for adolescent and young adult (AYA) B-cell acute lymphoblastic leukemia (B-ALL) patients following the widespread adoption of “pediatric-inspired” treatment regimens for AYA patients cared for in adult oncology settings. However, for AYA patients, aged 15 to 39, an outcomes gap remains in B-ALL, necessitating the incorporation of novel therapies into up-front treatment regimens. As a result, clinical trial enrollment remains the current standard of care for AYA B-ALL across disease subtypes when available and accessible. Currently, several up-front trials are looking to incorporate the use of inotuzumab, blinatumomab, and chimeric antigen receptor T-cell therapy into existing chemotherapy backbones for AYA patients, as well as tyrosine kinase inhibitors for both Philadelphia-positive (Ph+) and Ph-like B-ALL. In addition to ongoing attempts to improve up-front treatments by incorporating immunotherapy and targeted approaches, the increased use of next generation sequencing for measurable residual disease evaluation has led to superior risk-stratification and a decreased need to pursue consolidative hematopoietic stem cell transplantation during the first complete remission for many patients.
Checkpoint inhibitors
Authors: Kroll Michael H. 
Published: December 2023

Abstract
Immune checkpoint inhibitors are a class of antineoplastic therapies that unleash immune cells to kill malignant cells. These medications commonly cause immune-related adverse effects due to activated adaptive and innate immune cells, autoantibody production, and/or cytokine dysregulation. Hematologic toxicities are rare and of uncertain mechanism, and therefore management is often based on experiences with familiar conditions involving these perturbed immune responses. Management is challenging because one must attend to the hematologic toxicity while simultaneously attending to the malignancy, with the imperative that therapeutic effects be maintained or minimally interrupted when possible.
Compromised trigemino-coerulean coupling in migraine sensitization can be prevented by blocking beta-receptors in the locus coeruleus
Authors: Signoret-Genest Jérémy , Barnet Maxime , Gabrielli François , Aissouni Youssef , Artola Alain , Dallel Radhouane , Antri Myriam , Tovote Philip , Monconduit Lénaïc 
Published: December 2023

Abstract
Background
Migraine is a disabling neurological disorder, characterized by recurrent headaches. During migraine attacks, individuals often experience sensory symptoms such as cutaneous allodynia which indicates the presence of central sensitization. This sensitization is prevented by oral administration of propranolol, a common first-line medication for migraine prophylaxis, that also normalized the activation of the locus coeruleus (LC), considered as the main origin of descending noradrenergic pain controls. We hypothesized that the basal modulation of trigeminal sensory processing by the locus coeruleus is shifted towards more facilitation in migraineurs and that prophylactic action of propranolol may be attributed to a direct action in LC through beta-adrenergic receptors.

Methods
We used simultaneous in vivo extracellular recordings from the trigeminocervical complex (TCC) and LC of male Sprague–Dawley rats to characterize the relationship between these two areas following repeated meningeal inflammatory soup infusions. Von Frey Hairs and air-puff were used to test periorbital mechanical allodynia. RNAscope and patch-clamp recordings allowed us to examine the action mechanism of propranolol.

Results
We found a strong synchronization between TCC and LC spontaneous activities, with a precession of the LC, suggesting the LC drives TCC excitability. Following repeated dural-evoked trigeminal activations, we observed a disruption in coupling of activity within LC and TCC. This suggested an involvement of the two regions’ interactions in the development of sensitization. Furthermore, we showed the co-expression of alpha-2A and beta-2 adrenergic receptors within LC neurons. Finally propranolol microinjections into the LC prevented trigeminal sensitization by desynchronizing and decreasing LC neuronal activity.

Conclusions
Altogether these results suggest that trigemino-coerulean coupling plays a pivotal role in migraine progression, and that propranolol’s prophylactic effects involve, to some extent, the modulation of LC activity through beta-2 adrenergic receptors. This insight reveals new mechanistic aspects of LC control over sensory processing.
Phenotypic and genotypic characterization of colistin-resistant Escherichia Coli with mcr-4, mcr-5, mcr-6, and mcr-9 genes from broiler chicken and farm environment
Authors: Lemlem Mulu , Aklilu Erkihun , Mohamed Maizan , Kamaruzzaman Nor Fadhilah , Zakaria Zunita , Harun Azian , Devan Susmita Seenu , Kamaruzaman Intan Noor Aina , Reduan Mohd Farhan Hanif , Saravanan Muthupandian 
Published: December 2023

AbstractBackgroundColistin is an antibiotic used as a last-resort to treat multidrug-resistant Gram-negative bacterial infections. Colistin had been used for a long time in veterinary medicine for disease control and as a growth promoter in food-producing animals. This excessive use of colistin in food animals causes an increase in colistin resistance. This study aimed to determine molecular characteristics of colistin-resistantEscherichia coliin broiler chicken and chicken farm environments.ResultsFour hundred fifty-three cloacal and farm environment samples were collected from six different commercial chicken farms in Kelantan, Malaysia.E. coliwas isolated using standard bacteriological methods, and the isolates were tested for antimicrobial susceptibility using disc diffusion and colistin minimum inhibitory concentration (MIC) by broth microdilution. Multiplex PCR was used to detectmcrgenes, and DNA sequencing was used to confirm the resistance genes. Virulence gene detection, phylogroup, and multilocus sequence typing (MLST) were done to further characterize theE. coliisolates. Out of the 425 (94%; 425/453)E. coliisolated from the chicken and farm environment samples, 10.8% (48/425) isolates were carrying one or more colistin-resistance encoding genes. Of the 48 colistin-resistant isolates, 54.2% (26/48) of themcrpositive isolates were genotypically and phenotypically resistant to colistin with MIC of colistin ≥ 4 μg/ml. The most prominentmcrgene detected wasmcr-1(47.9%; 23/48), followed bymcr-8(18.8%; 9/48), mcr-7 (14.5%; 7/48),mcr-6(12.5%; 6/48),mcr-4(2.1%; 1/48),mcr-5(2.1%; 1/48), andmcr-9(2.1%; 1/48) genes. OneE. coliisolate originating from the fecal sample was found to harbor bothmcr-4andmcr-6genes and another isolate from the drinking water sample was carryingmcr-1andmcr-8genes. The majority of themcrpositive isolates were categorized under phylogroup A followed by phylogroup B1. The most prevalent sequence typing (ST) was ST1771 (n = 4) followed by ST206 (n = 3). 100% of themcrpositiveE. coliisolates were multidrug resistant. The most frequently detected virulence genes amongmcrpositiveE. coliisolates were ast (38%; 18/48) followed byiss(23%; 11/48). This is the first research to report the prevalence ofmcr-4, mcr-5, mcr-6, mcr-7,andmcr-8genes inE. colifrom broiler chickens and farm environments in Malaysia.ConclusionOur findings suggest that broiler chickens and broiler farm environments could be reservoirs of colistin-resistantE. coli, posing a risk to public health and food safety.
Symptomatic intracranial hemorrhage mediates the association between eosinophils and 90-day outcomes after mechanical thrombectomy for acute ischemic stroke
Authors: Yu Shuhong , Wang Xiaocui , Huang Hao , Luo Yi , Guo Zhiliang 
Published: December 2023

Abstract
Background
Decreased eosinophil level is associated with poor outcomes after mechanical thrombectomy in patients with acute ischemic stroke (AIS), but the underlying mechanism of this association is elusive. We aimed to assess the mediation effect of symptomatic intracranial hemorrhage (sICH) on the aforementioned association.

Methods
A total of 328 consecutive AIS patients undergoing mechanical thrombectomy between May 2017 and March 2021 were analyzed. SICH was defined as any evidence of brain hemorrhage on CT scan with neurological deterioration. Regression analysis was used to assess the effect of eosinophils on sICH, and its effect on poor outcome. Mediation analysis was performed to assess the proportion of total effect by sICH on the association between eosinophils and poor outcome.

Results
Multivariate analysis revealed an independent association between eosinophil count and sICH after adjusting for potential confounders (odds ratio, 0.00; 95% CI, 0.00–0.01; P = 0.0141), which is consistent with the result of eosinophil count (dichotomous) as a categorical variable (odds ratio, 0.22; 95% CI, 0.11–0.46; P < 0.0001). Eosinophil count was negatively associated with poor outcome (odds ratio, 0.00; 95% CI, 0.00–0.02; P = 0.0021). Mediation analysis revealed that sICH partially mediated the negative relationship between eosinophil count and poor outcome (indirect effect=-0.1896; 95%CI: -0.3654 – -0.03, P < 0.001).

Conclusion
This study showed an important effect of sICH on the association between eosinophils and poor outcome.
Genome-wide expansion and reorganization during grass evolution: from 30 Mb chromosomes in rice and Brachypodium to 550 Mb in Avena
Authors: Liu Qing , Ye Lyuhan , Li Mingzhi , Wang Ziwei , Xiong Gui , Ye Yushi , Tu Tieyao , Schwarzacher Trude , Heslop-Harrison John Seymour 
Published: December 2023

Abstract
Background
The BOP (Bambusoideae, Oryzoideae, and Pooideae) clade of the Poaceae has a common ancestor, with similarities to the genomes of rice, Oryza sativa (2n = 24; genome size 389 Mb) and Brachypodium, Brachypodium distachyon (2n = 10; 271 Mb). We exploit chromosome-scale genome assemblies to show the nature of genomic expansion, structural variation, and chromosomal rearrangements from rice and Brachypodium, to diploids in the tribe Aveneae (e.g., Avena longiglumis, 2n = 2x = 14; 3,961 Mb assembled to 3,850 Mb in chromosomes).

Results
Most of the Avena chromosome arms show relatively uniform expansion over the 10-fold to 15-fold genome-size increase. Apart from non-coding sequence diversification and accumulation around the centromeres, blocks of genes are not interspersed with blocks of repeats, even in subterminal regions. As in the tribe Triticeae, blocks of conserved synteny are seen between the analyzed species with chromosome fusion, fission, and nesting (insertion) events showing deep evolutionary conservation of chromosome structure during genomic expansion. Unexpectedly, the terminal gene-rich chromosomal segments (representing about 50 Mb) show translocations between chromosomes during speciation, with homogenization of genome-specific repetitive elements within the tribe Aveneae. Newly-formed intergenomic translocations of similar extent are found in the hexaploid A. sativa.

Conclusions
The study provides insight into evolutionary mechanisms and speciation in the BOP clade, which is valuable for measurement of biodiversity, development of a clade-wide pangenome, and exploitation of genomic diversity through breeding programs in Poaceae.
Genome-wide analysis of the SCAMPs gene family of soybean and functional identification of GmSCAMP5 in salt tolerance
Authors: Wang Min , He Chuanrong , Shi Guangcheng , Yin Qiukai , Zhang Hanyue , Yang Wanmin , Yue Aiqin , Wang Lixiang , Du Weijun 
Published: December 2023

AbstractThe effect of salt damage on plants is mainly caused by the toxic effect of Na+. Studies showed that the secretory carrier membrane proteins were associated with the Na+ transport. However, the salt tolerance mechanism of secretory carrier protein (SCAMP) in soybean was yet to be defined. In this study, ten potential SCAMP genes distributed in seven soybean chromosomes were identified in the soybean genome. The phylogenetic tree of SCAMP domain sequences of several plants can divide SCAMPs into two groups. Most GmSCAMPs genes contained multiple Box4, MYB and MYC cis-elements indicated they may respond to abiotic stresses. We found that GmSCAMP1, GmSCAMP2 and GmSCAMP4 expressed in several tissues and GmSCAMP5 was significantly induced by salt stress. GmSCAMP5 showed the same expression patterns under NaCl treatment in salt-tolerant and salt-sensitive soybean varieties, but the induced time of GmSCAMP5 in salt-tolerant variety was earlier than that of salt-sensitive variety. To further study the effect of GmSCAMP5 on the salt tolerance of soybean plants, compared to GmSCAMP5-RNAi and EV-Control plants, GmSCAMP5-OE had less wilted leave and higher SPAD value. Compared to empty vector control, less trypan blue staining was observed in GmSCAMP5-OE leaves while more staining in GmSCAMP5-RNAi leaves. The Na+ of GmSCAMP5-RNAi plants leaves under NaCl stress were significantly higher than that in EV-Control plants, while significantly lower Na+ in GmSCAMP5-OE plants than in that EV-Control plants. The contents of leaves K+ of GmSCAMP5-RNAi, EV-Control, and GmSCAMP5-OE plants under NaCl stress were opposite to that of leaves Na+ content. Finally, salt stress-related genes NHX1, CLC1, TIP1, SOD1, and SOS1 in transformed hairy root changed significantly compared with the empty control. The research will provide novel information for study the molecular regulation mechanism of soybean salt tolerance.