bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune profile and radiological characteristics of progressive multifocal leukoencephalopathy
Authors: Zeiner Pia S. , Mann Leonhard , Filipski Katharina , Starzetz Tatjana , Forster Marie‐Therese , Ronellenfitsch Michael W. , Steinbach Joachim P. , Mittelbronn Michel , Wagner Marlies , Harter Patrick N. 
Published: October 2021

AbstractBackground and purposeProgressive multifocal leukoencephalopathy (PML) constitutes a severe disease with increasing incidence, mostly in the context of immunosuppressive therapies. A detailed understanding of immune response in PML appears critical for the treatment strategy. The aim was a comprehensive immunoprofiling and radiological characterization of magnetic resonance imaging (MRI) defined PML variants.MethodsAll biopsy‐confirmed PML patients (n = 15) treated in our department between January 2004 and July 2019 were retrospectively analysed. Data from MRI, histology as well as detailed clinical and outcome data were collected. The MRI‐defined variants of classical (cPML) and inflammatory (iPML) PML were discriminated based on the intensity of gadolinium enhancement. In these PML variants, intensity and localization (perivascular vs. parenchymal) of inflammation in MRI and histology as well as the cellular composition by immunohistochemistry were assessed. The size of the demyelinating lesions was correlated with immune cell infiltration.ResultsPatients with MRI‐defined iPML showed a stronger intensity of inflammation with an increased lymphocyte infiltration on histological level. Also, iPML was characterized by a predominantly perivascular inflammation. However, cPML patients also demonstrated certain inflammatory tissue alterations. Infiltration of CD163‐positive microglia and macrophage (M/M) subtypes correlated with PML lesion size.ConclusionsThe non‐invasive MRI‐based discrimination of PML variants allows for an estimation of inflammatory tissue alterations, although exhibiting limitations in MRI‐defined cPML. The association of a distinct phagocytic M/M subtype with the extent of demyelination might reflect disease progression.
A unifying hypothesis for the spawning migrations of temperate anguillid eels
Authors: Durif Caroline M. F. , Stockhausen Hans Hagen , Skiftesvik Anne Berit , Cresci Alessandro , Nyqvist Daniel , Browman Howard I. 
Published: October 2021

AbstractAnguillid eels grow in freshwater but spawn in the open ocean. The cues that guide eels over long distances to the spawning area are unknown. The Earth's magnetic field can provide directional and positional information and is likely used by catadromous eels during their spawning migration; as magnetosensitivity and compass orientation have been reported in eels. To test whether this is theoretically possible, we compared the migratory routes of five species of temperate eels that undertake long migrations with the geomagnetic field of their distribution/spawning areas. We found that, regardless of the species and although routes are different between life stages, larvae of those species always drift along paths of increasing magnetic inclination and intensity, while adults follow reverse gradients. This is consistent with an imprinting/retracing hypothesis. We propose a general navigation mechanism based on larvae imprinting on a target magnetic intensity (or inclination) at the hatching area and on the intensity (or inclination) gradient during larval drift. Years later, adults retrace the magnetic route by following the gradient of decreasing total intensity (or inclination) values that occurs towards lower latitudes. As they reach the target value, adults switch to compass orientation to stay on the target isoline and reach the spawning area. The proposed mechanism fits for all temperate eels examined. Knowledge about navigational strategies of eels is important to evaluate the effectiveness of management strategies that involve stocking of juveniles displaced from one area to another to rebuild local populations.
Response of Amazonian forests to mid‐Holocene drought: A model‐data comparison
Authors: Smith Richard J. , Singarayer Joy S. , Mayle Francis E. 
Published: October 2021

AbstractThere is a major concern for the fate of Amazonia over the coming century in the face of anthropogenic climate change. A key area of uncertainty is the scale of rainforest dieback to be expected under a future, drier climate. In this study, we use the middle Holocene (ca. 6000 years before present) as an approximate analogue for a drier future, given that palaeoclimate data show much of Amazonia was significantly drier than present at this time. Here, we use an ensemble of climate and vegetation models to explore the sensitivity of Amazonian biomes to mid‐Holocene climate change. For this, we employ three dynamic vegetation models (JULES, IBIS, and SDGVM) forced by the bias‐corrected mid‐Holocene climate simulations from seven models that participated in the Palaeoclimate Modelling Intercomparison Project 3 (PMIP3). These model outputs are compared with a multi‐proxy palaeoecological dataset to gain a better understanding of where in Amazonia we have most confidence in the mid‐Holocene vegetation simulations. A robust feature of all simulations and palaeodata is that the central Amazonian rainforest biome is unaffected by mid‐Holocene drought. Greater divergence in mid‐Holocene simulations exists in ecotonal eastern and southern Amazonia. Vegetation models driven with climate models that simulate a drier mid‐Holocene (100–150 mm per year decrease) better capture the observed (palaeodata) tropical forest dieback in these areas. Based on the relationship between simulated rainfall decrease and vegetation change, we find indications that in southern Amazonia the rate of tropical forest dieback was ~125,000 km2 per 100 mm rainfall decrease in the mid‐Holocene. This provides a baseline sensitivity of tropical forests to drought for this region (without human‐driven changes to greenhouse gases, fire, and deforestation). We highlight the need for more palaeoecological and palaeoclimate data across lowland Amazonia to constrain model responses.
Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study
Authors: Janbain Maissa , Enjolras Nathalie , Bolbos Radu , Brevet Marie , Bordet Jean‐Claude , Dargaud Yesim 
Published: October 2021

AbstractBackgroundPatients with severe haemophilia have impaired haemostatic response, delayed clot formation and fibrin clots that are vulnerable to fibrinolysis. Emicizumab is a bispecific antibody that mimics activity of activated factor VIII (FVIII) and increases haemostatic capacity to the level of moderate‐to‐mild haemophilia, thereby used for prophylaxis. Regardless of the impressive clinical performance of emicizumab, breakthrough bleeds may still occur. We aimed to study, in FVIII knockout mice (FVIII‐KO), whether haemostasis is improved with the addition of tranexamic acid (TxAc) to emicizumab.MethodsFVIII‐KO mice received prophylaxis with emicizumab or emicizumab+TxAc before trauma. FVIII‐KO mice were given emicizumab 1.5 mg/kg via IV injection. A second retro‐orbital IV injection containing human FIX and FX (both 100U/kg) was given 24 h later and 5 min before the tail amputation or knee trauma. After trauma‐induced knee joint bleeding, magnetic resonance imaging (MRI), and histological analysis were used to compare haemostatic efficacy of the two prophylactic strategies. Thrombin generation (TG) was measured and clots obtained with TG experiment were analysed by scanning electron microscopy.ResultsIn FVIII‐KO mice, blood loss after tail clip was lower after prophylaxis with emicizumab+TxAc compared to emicizumab. MRI results and histological analysis of knee joints showed that the addition of TxAc significantly decreased joint bleeding. Fibrin fibre diameters of mice treated with emicizumab only was thicker than those who received combined prophylaxis with emicizumab+TxAc.ConclusionOur results suggest a potential benefit of TxAc when used in combination with emicizumab in prophylactic settings, especially in patients presenting breakthrough bleeds.
No overall impact on rate of weight gain with integrase inhibitor‐containing regimens in antiretroviral‐naïve adults
Authors: Burns James E. , Stirrup Oliver , Waters Laura , Dunn David , Gilson Richard , Pett Sarah L. 
Published: October 2021

AbstractObjectivesIntegrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment‐naïve adults with HIV‐1 attending a UK centre who started regimens including raltegravir or dolutegravir.MethodsA retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre‐ and post‐ART initiation, who started a three‐drug regimen with ≥ 6 months duration and achieved virological suppression (< 50 copies/mL) within 6 months were included. A random effects model with linear slope pre‐ and post‐ART was used, adjusting for age, gender, ethnicity, ART regimen, backbone and year of initiation.ResultsThe cohort included 390 adults; 88.7% were male, 66.4% were of white ethnicity, their median age was 40 years, there was a median of six weight measurements, 2.2 years from diagnosis to ART initiation, 2.9 years from ART to the last weight measurement, and weight and body mass index at initiation were 75 kg and 24.1 kg/m2 respectively. Of these, 254 (65%) started an INSTI. The average pre‐ART rate of weight gain was 0.44 kg/year [95% confidence interval (CI): 0.19–0.70], increasing to 0.88 kg/year (0.63–1.10, p = 0.04) after ART initiation. Our adjusted model found no evidence of an association between ART regimen and rate of weight gain.ConclusionsWeight increased in the cohort both pre‐ and post‐ART. We found no evidence of a higher rate of weight gain following ART initiation with an INSTI compared with other regimens.
Long‐term outcomes for children and adolescents with Kaposi sarcoma
Authors: Silverstein Allison , Kamiyango William , Villiera Jimmy , Peckham‐Gregory Erin C. , McAtee Casey L. , Scheurer Michael E. , Cox Carrie M. , Kovarik Carrie L. , Campbell Liane R. , Allen Carl E. , Mehta Parth S. , Kazembe Peter N. , Ozuah Nmazuo W. , El‐Mallawany Nader Kim 
Published: October 2021

AbstractObjectivesKaposi sarcoma (KS) is one of the most common childhood cancers in eastern and central Africa. It has become a treatable disease with increasing availability of antiretroviral therapy (ART) and chemotherapy. We aimed to fill the data gap in establishing whether long‐term survival is achievable for children in low‐income countries.MethodsWe retrospectively analysed data for children and adolescents aged ≤ 18.9 years diagnosed with HIV‐related or endemic KS from 2006 to 2015 who received standardized institutional treatment regimens utilizing chemotherapy plus ART (if HIV‐positive) at a tertiary care public hospital in Lilongwe, Malawi. Long‐term survival was analysed and mortality was associated with KS for those with refractory/progressive disease at the time of death.ResultsThere were 207 children/adolescents with KS (90.8% HIV‐related); 36.7% were alive, 54.6% had died, and 8.7% had been lost to follow‐up. The median follow‐up time for survivors was 6.9 years (range 4.2–13.9 years). Death occurred at a median of 5.3 months after KS diagnosis (range 0.1–123 months). KS progression was associated with mortality for most (61%) early deaths (survival time of < 6 months); conversely, KS was associated with a minority (31%) of late‐onset deaths (after 24 months). The 7‐year overall survival was 37% [95% confidence interval (CI) 30–44%] and was higher for those diagnosed between 2011 and 2015 compared to 2006–2010: 42% (95% CI 33–51%) versus 29% (95% CI 20–39%), respectively (P = 0.01). Among the 66 HIV‐positive survivors, 58% were still on first‐line ART.ConclusionsLong‐term survival is possible for pediatric KS in low‐resource settings. Despite better survival in more recent years, there remains room for improvement.
The success rate of interphase fluorescence in situ hybridization in plasma cell disorders can be improved using unconventional sources of plasma cells
Authors: Panakkal Vandana , Rana Sonia , Rathore Shailja , Anshu Anshu , Balakrishnan Anand , Singh Charanpreet , Jandial Aditya , Sachdeva Man Updesh Singh , Varma Neelam , Lad Deepesh , Malhotra Pankaj , Sreedharanunni Sreejesh 
Published: October 2021

AbstractBackgroundImmunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real‐world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders.Materials and MethodsA retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure.ResultsImmunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with <10% PCs and 318/352 (90.3%) with ≥10% PCs in BM aspirate; P = .003). Among cases with unsuccessful IMCS (<10% PCs; n = 21 and ≥10% PCs; n = 34), an alternate source could be used successfully in 34 (62%) patients and includes air‐dried trephine biopsy imprint smears (n = 28) with aggregates or sheets of PCs, fine‐needle aspiration smears/biopsy from plasmacytoma (n = 5), and ascitic fluid (n = 1). 284/395 (71.9%) patients with successful IMCS and all 34 cases with an alternate source of PCs showed at least one cytogenetic abnormality on four‐probe FISH.ConclusionVariations in the sample quality together with significant variation in the number of PCs between BM aspirate and the trephine biopsy imprint smears/biopsy reduce the success rate of IMCS in a real‐world scenario and necessitate utilization of patient‐specific alternate sources of PCs like a trephine biopsy imprint or cytology smears from extramedullary sources for successful FISH testing in PC neoplasms.
Tensions experienced by teachers of Dutch culturally diverse senior secondary vocational education and training: An exploratory study
Authors: Tielman Kennedy , Wesselink Renate , den Brok Perry 
Published: October 2021

AbstractSenior secondary vocational education and training (SSVET) is highly culturally diverse, with a majority of students having an immigrant background. Teachers in culturally diverse classes are more often confronted with tensions in their daily practice and they are uncertain of how to manage these tensions. This exploratory study investigated what value‐based tensions teachers encountered when teaching in culturally diverse SSVET classes. Furthermore, the reported tensions by teachers were examined in terms of (inadequate) knowledge, skills and (hindering) attitudes as a possible cause to deal effectively with the experienced tensions. We collected interview data from 16 SSVET teachers from five schools, each with more than 60% of students with immigrant backgrounds. The results showed that most of the value‐based tensions that the SSVET teachers encountered were related to the intercultural loaded values diversity and respect. Next to tensions related to values also found in prior research, teachers additionally reported tensions with regard to professional ethics & stance of students, which seems unique to SSVET. Most experienced tensions were perceived as being caused by self‐reported lack of skills. Less often, teachers experienced a shortage of knowledge or hindering attitudes when faced with these tensions in culturally diverse SSVET classes.
Clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap
Authors: Zhang Xinling , Ding Pengbing , Wang Guanhuier , Chen Yujie , Yang Xin , Zhao Zhenmin , Bi Hongsen 
Published: October 2021

AbstractWe aimed to explore the clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap. Five patients who underwent pedicled axial flap transfer to repair a large area of skin and soft tissue defects in our hospital were included in this retrospective study. Detailed information including general data and clinical data, such as preoperative complication, type of primary wound, the distance between the primary wound and the donor site (cm), postoperative complications, and types of axial flap were collected. The patients had good joint movement at 6 months after pedicle amputation. At 48 hours after transplantation, except for the last patient (NO.5), there were no obvious complications such as blood supply disorder, infection, and incision dehiscence of the patients, and the flaps survived well. Just after pedicle amputation, 3 and 6 months after pedicle amputation, the flaps survived well with good local morphology. Forty‐eight hours after operation, part of the distal flap in the last patient (NO.5) was necrotic. After 6 months of pedicle amputation, part of the flap was transferred to the distal wound again. At 6 months after pedicle amputation, these patients could accept local scars even though the scar of the last patient was obvious. The secondary pedicle amputation of the repair of distal defects with axial flap could avoid the compression of the vascular pedicle in the subcutaneous tunnel between the donor site and the primary wound, which may ensure the bold supply and increase the survival rate of the flap.
The relationship between crystal structure and modified microwave dielectric properties of Ca3SnSi2‐xGexO9 ceramics
Authors: Du Kang , Yin Chang‐Zhi , Guo Yan‐Bo , Wang Xiao‐Chuan , Lu Wen‐Zhong , Ta Shi‐Wo , Hu Chun‐Yuan , Lei Wen 
Published: October 2021

AbstractCa3SnSi2‐xGexO9 (0 ≤ x ≤ 0.8) and (1–y) Ca3SnSi1.6Ge0.4O9 – y CaSnSiO5 – 2 wt% LiF (y = 0.4 and 0.5) microwave dielectric ceramics were prepared by traditional solid‐state reaction through sintering at 1250°C–1425°C for 5 h and at 875°C for 2 h, respectively. Ge4+ replaced Si4+, and Ca3SnSi2‐xGexO9 (0 ≤ x ≤ 0.4) solid solutions were obtained. At 0.1 ≤ x ≤ 0.4, the Ge4+ substitution for Si4+ decreased the sintering temperature of Ca3SnSi2‐xGexO9 from 1425 to 1300°C, the SnO6 octahedral distortions, and the average CaO7 decahedral distortions, which affected the τf value. The large average decahedral distortions corresponded with nearer‐zero τf values at Ca3SnSi2‐xGexO9 (0.1 ≤ x ≤ 0.4) ceramics. The τf value and sintering temperature of Ca3SnSi2‐xGexO9 (x = 0.4) ceramic were adjusted to near‐zero by CaSnSiO5 and decreased to 875°C upon the addition of 2 wt% LiF. The (1 – y) Ca3SnSi1.6Ge0.4O9 – y CaSnSiO5 – 2 wt% LiF (y = 0.5) ceramic sintered at 875°C for 2 h exhibited good microwave dielectric properties: εr = 10.3, Q × f = 14 300 GHz (at 12.2 GHz), and τf = ‒5.8 ppm/°C.
NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells
Authors: Somazu Shinpei , Tanaka Yoichi , Tamai Minori , Watanabe Atsushi , Kagami Keiko , Abe Masako , Harama Daisuke , Shinohara Tamao , Akahane Koshi , Goi Kumiko , Sugita Kanji , Moriyama Takaya , Yang Jun , Goto Hiroaki , Minegishi Masayoshi , Iwamoto Shotaro , Takita Junko , Inukai Takeshi 
Published: October 2021

AbstractIn chemotherapy for childhood acute lymphoblastic leukaemia (ALL), maintenance therapy consisting of oral daily mercaptopurine and weekly methotrexate is important. NUDT15 variant genotype is reportedly highly associated with severe myelosuppression during maintenance therapy, particularly in Asian and Hispanic populations. It has also been demonstrated that acquired somatic mutations of the NT5C2 and PRPS1 genes, which are involved in thiopurine metabolism, are detectable in a portion of relapsed childhood ALL. To directly confirm the significance of the NUDT15 variant genotype and NT5C2 and PRPS1 mutations in thiopurine sensitivity of leukaemia cells in the intrinsic genes, we investigated 84 B‐cell precursor‐ALL (BCP‐ALL) cell lines. Three and 14 cell lines had homozygous and heterozygous variant diplotypes of the NUDT15 gene, respectively, while 4 and 2 cell lines that were exclusively established from the samples at relapse had the NT5C2 and PRPS1 mutations, respectively. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with DNA‐incorporated thioguanine levels after exposure to thioguanine at therapeutic concentration. Considering the continuous exposure during the maintenance therapy, we evaluated in vitro mercaptopurine sensitivity after 7‐day exposure. Mercaptopurine concentrations lethal to 50% of the leukaemia cells were comparable to therapeutic serum concentration of mercaptopurine. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with mercaptopurine sensitivity in 83 BCP‐ALL and 23 T‐ALL cell lines. The present study provides direct evidence to support the general principle showing that both inherited genotype and somatically acquired mutation are crucially implicated in the drug sensitivity of leukaemia cells.
miRNA‐34b/c regulates mucus secretion in RSV‐infected airway epithelial cells by targeting FGFR1
Authors: Li Wenkai , Du Xizi , Yang Yu , Yuan Lin , Yang Ming , Qin Ling , Wang Leyuan , Zhou Kai , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Xiao Gelei , Liu Chi 
Published: October 2021

AbstractRespiratory syncytial virus (RSV) infection in airway epithelial cells is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV‐related LRTI). However, the pathological processes of mucus hypersecretion in RSV‐infected airway epithelial cells remains unclear. The current study explores the involvement of miR‐34b/miR‐34c in mucus hypersecretion in RSV‐infected airway epithelial cells by targeting FGFR1. First, miR‐34b/miR‐34c and FGFR1 mRNA were quantified by qPCR in throat swab samples and cell lines, respectively. Then, the luciferase reporters’ assay was designed to verify the direct binding between FGFR1 and miR‐34b/miR‐34c. Finally, the involvement of AP‐1 signalling was assessed by western blot. This study identified that miR‐34b/miR‐34c was involved in c‐Jun‐regulated MUC5AC production by targeting FGFR1 in RSV‐infected airway epithelial cells. These results provide some useful insights into the molecular mechanisms of mucus hypersecretion which may also bring new potential strategies to improve mucus hypersecretion in RSV disease.
Testing potential mechanisms of conspecific sperm precedence in Drosophila pseudoobscura
Authors: Peckenpaugh Brooke , Castillo Dean M. , Moyle Leonie C. 
Published: October 2021

AbstractDrosophila pseudoobscura females that co‐occur with sister species D. persimilis show elevated fertilization by conspecific sperm when they mate with both a heterospecific and a conspecific male. This phenomenon, known as conspecific sperm precedence (CSP), has evolved as a mechanism to avoid maladaptive hybridization with D. persimilis. In this study, we assessed pericopulatory (during mating) and postcopulatory (after mating) traits in crosses with sympatric or allopatric D. pseudoobscura females and conspecific or heterospecific males to evaluate potential mechanisms of CSP in this system. We observed shorter copulation duration in crosses with sympatric females, but found no difference in quantity of sperm transferred or female reproductive tract toxicity between sympatry and allopatry. Our data show some support for the hypothesis that parasperm, a short, sterile sperm morph, can protect fertile eusperm from the D. pseudoobscura female reproductive tract, though it is unclear how this might affect patterns of sperm use in sympatry vs. allopatry. Overall, these results suggest that copulation duration could potentially contribute to the elevated CSP observed in sympatry.