bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis
Authors: Anderson Jeanne E. , Tefferi Ayalew , Craig Fiona , Holmberg Leona , Chauncey Thomas , Appelbaum Frederick R. , Guardiola Philippe , Callander Natalie , Freytes Cesar , Gazitt Yair , Razvillas Betty , Deeg H. Joachim 
Published: July 2002

AbstractCurrent therapeutic options for myeloid metaplasia with myelofibrosis (MMM) are limited. A pilot study was conducted of autologous peripheral blood stem cell (PBSC) collection in 27, followed by transplantation in 21 patients with MMM. The median age was 59 (range 45-75) years. PBSCs were mobilized at steady state (n = 2), after granulocyte colony-stimulating factor (G-CSF) alone (n = 17), or after anthracycline-cytarabine induction plus G-CSF (n = 8). A median of 11.6 × 106 (range 0 to 410 × 106) CD34+ cells per kilogram were collected. Twenty-one patients then underwent myeloablation with oral busulfan (16 mg/kg) and PBSC transplantation. The median times to neutrophil and platelet recovery after transplantation were 21 (range 10-96) and 21 (range, 13 to ≥ 246) days, respectively. Five patients received back-up PBSC infusion because of delayed neutrophil or platelet recovery. The median follow-up is 390 (range 70-1623) days after transplantation, and the 2-year actuarial survival is 61%. After transplantion, 6 patients died: 3 of nonrelapse causes (1 within 100 days of PBSC infusion) and 3 of disease progression. Erythroid response (hemoglobin ≥ 100 g/L [10 gm/dL] without transfusion for ≥ 8 weeks) occurred in 10 of 17 anemic patients. Four of 8 patients with a platelet count less than 100 × 109/L (100 000/μL) responded with a durable platelet count more than 100 × 109/L (100 000/μL). Symptomatic splenomegaly improved in 7 of 10 patients. It is concluded that (1) PBSC collection was feasible and stable engraftment occurred after transplantation in most patients with MMM, (2) myeloablation with busulfan was associated with acceptable toxicity, (3) a significant proportion of patients derived clinical benefit after treatment, and (4) further investigation of this novel approach is warranted.
Calcium signaling inhibits interleukin-12 production and activates CD83+ dendritic cells that induce Th2 cell development
Authors: Faries Mark B. , Bedrosian Isabelle , Xu Shuwen , Koski Gary , Roros James G. , Moise Mirielle A. , Nguyen Hung Q. , Engels Friederike H. C. , Cohen Peter A. , Czerniecki Brian J. 
Published: July 2002

AbstractMature dendritic cells (DCs), in addition to providing costimulation, can define the Th1, in contrast to the Th2, nature of a T-cell response through the production of cytokines and chemokines. Because calcium signaling alone causes rapid DC maturation of both normal and transformed myeloid cells, it was evaluated whether calcium-mobilized DCs polarize T cells toward a Th1 or a Th2 phenotype. After human monocytes were cultured for 24 hours in serum-free medium and granulocyte-macrophage colony-stimulating factor to produce immature DCs, additional overnight culture with either calcium ionophore (CI) or interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble CD40L resulted in phenotypically mature DCs that produced interleukin-8 (IL-8) and displayed marked expression of CD80, CD86, CD40, CD54, CD83, DC-LAMP, and RelB. DCs matured by IFN-γ, TNF-α, and soluble CD40L were additionally distinguished by undetectable CD4 expression, marked secretion of IL-12, IL-6, and MIP-1β, and preferential ability to promote Th1/Tc1 characteristics during T-cell sensitization. In contrast, DCs matured by CI treatment were distinguished by CD4 expression, modest or absent levels of IL-12, IL-6, and MIP-1β, and preferential ability to promote Th2/Tc2 characteristics. Calcium signaling selectively antagonized IL-12 production by mature DCs activated with IFN-γ, TNF-α, and soluble CD40L. Although the activation of DCs by calcium signals is largely mediated through calcineurin phosphatase, the inhibition of IL-12 production by calcium signaling was independent of this enzyme. Naturally occurring calcium fluxes in immature DCs, therefore, negatively regulate Dc1 differentiation while promoting Dc2 characteristics and Th2/Tc2 polarization. Calcium-mobilized DCs may have clinical usefulness in treating disease states with excessive Th1/Tc1 activity, such as graft-versus-host disease or autoimmunity.
Persistent preswitch clonotypic myeloma cells correlate with decreased survival: evidence for isotype switching within the myeloma clone
Authors: Reiman Tony , Seeberger Karen , Taylor Brian J. , Szczepek Agnieszka J. , Hanson John , Mant Michael J. , Coupland Robert W. , Belch Andrew R. , Pilarski Linda M. 
Published: July 2002

AbstractMultiple myeloma (MM) is identified by unique immunoglobulin heavy chain (IgH) variable diversity joining region gene rearrangements, termed clonotypic, and an M protein termed the “clinical” isotype. Transcripts encoding clonotypic pre and postswitch IgH isotypes were identified in MM peripheral blood mononuclear cells (PBMCs), bone marrow (BM), and mobilized blood. For 29 patients, 38 BM, 17 mobilized blood, and 334 sequential PBMC samples were analyzed at diagnosis, before and after transplantation for 2 to 107 months. The clinical clonotypic isotype was readily detectable and persisted throughout treatment. Eighty-two percent of BM and 38% of PBMC samples also expressed nonclinical clonotypic isotypes. Clonotypic immunoglobulin M (IgM) was detectable in 68% of BM and 25% of PBMC samples. Nonclinical clonotypic isotypes were detected in 41% of mobilized blood samples, but clonotypic IgM was detected in only 12%. Patients with persistent clonotypic IgM expression had adverse prognostic features at diagnosis (lower hemoglobin, higher β2-microglobulin) and higher numbers of BM plasma cells compared with patients with infrequent/absent clonotypic IgM. Patients with persistent clonotypic IgM expression had significantly poorer survival than patients with infrequent IgM expression (P < .0001). In a multivariate analysis, persistent clonotypic IgM expression in the blood correlated independently with poor survival (P = .01). In nonobese diabetic severe combined immunodeficiency mice, xenografted MM cells expressed clinical and nonclinical postswitch clonotypic isotypes. MM expressing clonotypic IgM engrafted both primary and secondary mice, indicating their persistence within the murine BM. This study demonstrates that MM clonotypic cells expressing preswitch transcripts are tied to disease burden and outcomes. Because MM pathology involves postswitch plasma cells, this raises the possibility that IgH isotype switching in MM may accompany worsening disease.
Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study
Authors: Mannucci Pier M. , Chediak Juan , Hanna Wahid , Byrnes John , Ledford Marlies , Ewenstein Bruce M. , Retzios Anastassios D. , Kapelan Barbara A. , Schwartz Richard S. , Kessler Craig ,   the Alphanate Study Group
Published: July 2002

Abstract
Among patients with von Willebrand disease (VWD) who are unresponsive to desmopressin therapy, replacement with plasma-derived concentrates is the treatment of choice. Because prospective studies are lacking, such treatment has been largely empirical. A multicenter, prospective study has been conducted in 81 patients with VWD (15 patients with type 1, 34 with type 2, and 32 with type 3 disease) to investigate the efficacy of a high-purity factor VIII/von Willebrand factor (FVIII/VWF) concentrate for treatment of bleeding and surgical prophylaxis. Two preparations of the concentrate—one virally inactivated with solvent detergent, the other with an additional heat-treatment step—were evaluated. Pharmacokinetic parameters were similar for both preparations. Using pre-established dosages based on the results of pharmacokinetic studies, 53 patients were administered either preparation for the treatment of 87 bleeding episodes, and 39 patients were treated prophylactically for 71 surgical or invasive procedures. Sixty-five (74.7%) and 10 (11.5%) of the bleeding episodes were controlled with 1 or 2 infusions, respectively. Patients with severe type 3 VWD typically required more infusions and higher doses, at shorter time intervals, than did patients with generally milder types 1 and 2. Among patients undergoing surgical procedures, blood loss was lower than that predicted prospectively, and losses exceeding the predicted value did not correlate with the postinfusion skin bleeding time. In conclusion, the concentrate effectively stopped active bleeding and provided adequate hemostasis for surgical or invasive procedures, even in the absence of bleeding time correction.
Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release
Authors: Chandra Joya , Mansson Emma , Gogvadze Vladimir , Kaufmann Scott H. , Albertioni Freidoun , Orrenius Sten 
Published: July 2002

AbstractThe purine nucleoside 2-chlorodeoxyadenosine (CdA) is often used in leukemia therapy. Its efficacy, however, is compromised by the emergence of resistant cells. In the present study, 3 CdA-resistant cell lines were generated and characterized. Their ability to accumulate 2-chloroadenosine triphosphate (CdATP) varied, reflecting differences in activities of deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Nonetheless, the selected lines were uniformly resistant to CdA-induced apoptosis, as assessed by caspase activation and DNA fragmentation. In contrast, cytosols from resistant cells were capable of robust caspase activation when incubated in the presence of cytochrome c and dATP. Moreover, replacement of dATP with CdATP also resulted in caspase activation in the parental and some of the resistant cell lines. Strikingly, CdA-induced decreases in mitochondrial transmembrane potential and release of cytochrome c from mitochondria were observed in the parental cells but not in any resistant lines. The lack of cytochrome c release correlated with an increased ability of mitochondria from resistant cells to sequester free Ca2+. Consistent with this enhanced Ca2+buffering capacity, an early increase in cytosolic Ca2+after CdA treatment of parental cells but not resistant cells was detected. Furthermore, CdA-resistant cells were selectively cross-resistant to thapsigargin but not to staurosporine- or Fas-induced apoptosis. In addition, CdA-induced caspase-3 activation and DNA fragmentation were inhibited by the Ca2+ chelator BAPTA-AM in sensitive cells. Taken together, the data indicate that the mechanism of resistance to CdA may be dictated by changes in Ca2+-sensitive mitochondrial events.
Voice Rehabilitation After Total Laryngectomy and Postoperative Radiation Therapy
Authors: Mendenhall William M. , Morris Christopher G. , Stringer Scott P. , Amdur Robert J. , Hinerman Russell W. , Villaret Douglas B. , Robbins K. Thomas 
Published: July 2002

PURPOSE: The purpose of this study was to evaluate voice rehabilitation after laryngectomy and postoperative irradiation for patients with squamous cell carcinoma of the larynx and hypopharynx. PATIENTS AND METHODS: Between December 1983 and December 1998, 173 patients underwent a total laryngectomy and postoperative irradiation and had follow-up from 3 to 188 months (median, 38 months). Three patients were lost to follow-up at 63, 39, and 4 months after treatment. All other living patients had follow-up for 2 years or longer. Twelve (7%) patients had incomplete data pertaining to voice rehabilitation. RESULTS: Data pertaining to voice rehabilitation were available at 2 to 3 years and longer and 5 years and longer after treatment for 118 and 69 patients, respectively. The methods of voice rehabilitation at 2 to 3 years and longer and 5 years and longer were as follows: tracheoesophageal, 27% and 19%; artificial larynx, 50% and 57%; esophageal, 1% and 3%; nonvocal, 17% and 14%; and no data, 5% and 7%, respectively. CONCLUSION: The most common form of voice rehabilitation after total laryngectomy and postoperative radiation therapy is the artificial larynx. Although the tracheoesophageal puncture is a technique frequently promoted by clinicians as a superior method, a relatively small subset of patients are successfully rehabilitated long-term. However, of those who undergo a tracheoesophageal puncture, approximately half will use this method of voice rehabilitation long term.
Phase II Trial of Weekly Single-Agent Paclitaxel in Platinum/Paclitaxel-Refractory Ovarian Cancer
Authors: Markman Maurie , Hall James , Spitz Daniel , Weiner Sheldon , Carson Linda , Van Le Linda , Baker Mark 
Published: July 2002

PURPOSE: We wished to critically examine the level of activity of weekly paclitaxel in a patient population with well-characterized platinum/paclitaxel-resistant (3-week schedule) ovarian cancer. PATIENTS AND METHODS: Eligibility criteria for this phase II trial included the following: ovarian and fallopian tube cancers or primary carcinoma of the peritoneum; prior initial therapy with platinum/paclitaxel; and failure to respond to treatment (progression or stable disease as best response), or a response duration of less than 3 months, or if the response was more than 3 months, retreatment with both agents required and failure to respond a second time or the response duration was less than 3 months. Measurable or assessable disease (CA-125 response criteria) was required. Patients received weekly paclitaxel (80 mg/m2) until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. RESULTS: Fifty-three patients (52 assessable for toxicity and 51 for response) were entered onto this multi-institution trial. Of 248 total cycles (887 doses), only 13 (1%) were modified (dose reduction or treatment delay) because of side effects. Therapy was discontinued in five patients because of toxicity (four because of peripheral neuropathy, and one because of painful fingernail beds). Thirteen patients (25%; 95% confidence interval, 13.5% to 37.5%) achieved an objective response (four by CA-125 criteria, and nine by ≥ 50% reduction of measurable disease). CONCLUSION: Weekly paclitaxel (80 mg/m2) is generally well tolerated and is an active second-line regimen against ovarian cancer that has demonstrated resistance to platinum/paclitaxel delivered on an every-3-week schedule.
Debarking harvesters simultaneously combat the European spruce bark beetle (Ips typographus) and conserve non‐target beetle diversity
Authors: Zarges Sebastian , Wohlert Jan , Kamp Johannes , Thorn Simon , Müller Jörg , Hagge Jonas 
Published: July 2024

Abstract

In the face of climate change, the European Spruce Bark Beetle (Ips typographus) breeding predominantly in Norway spruce (Picea abies) led to exceptional amounts of damaged timber in European forests. Up to now, if pest control is applied, damaged or weakened P. abies trees are either extracted by salvage logging or, when quantities are low, made unsuitable for breeding by manual debarking techniques. Both pest control interventions are costly, are often limited by the short timeframe of effectiveness and come with negative impacts on the non‐target biodiversity.

As alternatives for timely removal, a debarking head for harvesters for large scale disturbances and a bark gouging device for motor‐manual treatment have been developed in recent years to make breeding material unsuitable for bark beetles and reduce existing larvae.

Based on data from an experimental design with infested Norway spruce logs, we show that the harvester debarking head and the motor‐manual bark gouging regulate I. typographus populations efficiently, whereas a conventional harvester did not reduce the emerging bark beetles. Species assemblages of non‐target beetles living in the infested Norway spruce logs were altered from the natural species assemblages in control logs by processing logs with the debarking head or the bark gouging device but not by the conventional harvester. None of the bark treatments reduced non‐target beetle species richness in this experiment.

Practical implication. We endorse the debarking head and bark gouging as alternatives to salvage logging and manual debarking. This uncouples pest control from in‐time dependencies on the availability of transport capacities. The debarking head and bark gouging open up the opportunity to retain dead wood biomass in the forest, supporting ecological benefits and conservation goals. Particularly for protected areas these two new management options better balance requirements of pest control and biodiversity conservation.
The Changes of Mitochondria during Aging and Regeneration
Authors: Li Anqi , Qin Yuan , Gong Guohua 
Published: July 2024

AbstractAging and regeneration are opposite cellular processes. Aging refers to progressive dysfunction in most cells and tissues, and regeneration refers to the replacement of damaged or dysfunctional cells or tissues with existing adult or somatic stem cells. Various studies have shown that aging is accompanied by decreased regenerative abilities, indicating a link between them. The performance of any cellular process needs to be supported by the energy that is majorly produced by mitochondria. Thus, mitochondria may be a link between aging and regeneration. It should be interesting to discuss how mitochondria behave during aging and regeneration. The changes of mitochondria in aging and regeneration discussed in this review can provide a timely and necessary study of the causal roles of mitochondrial homeostasis in longevity and health.
DNA Tetrahedron Delivering miR‐21‐5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis
Authors: Qi Lei , Hong Shebin , Zhao Tong , Yan Jinge , Ge Weiwen , Wang Jing , Fang Xin , Jiang Weidong , Shen Steve GF , Zhang Lei 
Published: July 2024

AbstractCompromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone‐related miRNA, miRNA‐21‐5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR‐21‐5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN‐miR‐21‐5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O‐BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O‐EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN‐miR‐21‐5p mediated osteogenesis and senescence of O‐BMSCs. Also, TDN‐miR‐21‐5p can indirectly mediate osteogenesis and senescence of O‐BMSCs through pro‐angiogenic growth factors secreted from O‐EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN‐miR‐21‐5p to fabricate delivery scaffolds. TDN‐miR‐21‐5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic‐ and angiogenic‐related markers in senescent critical‐size cranial defects in vivo. Collectively, TDN‐miR‐21‐5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs‐based gene therapy.
M6A‐mediated upregulation of lncRNA TUG1 in liver cancer cells regulates the antitumor response of CD8+ T cells and phagocytosis of macrophages
Authors: Xi Qing , Yang Guangze , He Xue , Zhuang Hao , Li Li , Lin Bing , Wang Lingling , Wang Xianyang , Fang Chunqiang , Chen Qiurui , Yang Yongjie , Yu Zhaoan , Zhang Hao , Cai Wenqian , Li Yan , Shen Han , Liu Li , Zhang Rongxin 
Published: July 2024

AbstractTumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non‐coding RNA taurine‐upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3‐mediated m6A modification led to TUG1 upregulation is demonstrated. Knockdown of TUG1 inhibited tumor growth and metastasis, increased the infiltration of CD8+ T cells and M1‐like macrophages in tumors, promoted the activation of CD8+ T cells through PD‐L1, and improved the phagocytosis of macrophages through CD47. Mechanistically, TUG1 regulated PD‐L1 and CD47 expressions by acting as a sponge of miR‐141 and miR‐340, respectively. Meanwhile, TUG1 interacted with YBX1 to facilitate the upregulation of PD‐L1 and CD47 transcriptionally, which ultimately regulated tumor immune evasion. Clinically, TUG1 positively correlated with PD‐L1 and CD47 in HCC tissues. Moreover, the combination of Tug1‐siRNA therapy with a Pdl1 antibody effectively suppressed tumor growth. Therefore, the mechanism of TUG1 in regulating tumor immune evasion is revealed and can inform existing strategies targeting TUG1 for enhancing HCC immune therapy and drug development.
Spike‐Based Neuromorphic Hardware for Dynamic Tactile Perception with a Self‐Powered Mechanoreceptor Array
Authors: Lee Sang‐Won , Yun Seong‐Yun , Han Joon‐Kyu , Nho Young‐Hoon , Jeon Seung‐Bae , Choi Yang‐Kyu 
Published: July 2024

AbstractA self‐powered mechanoreceptor array is demonstrated using four mechanoreceptor cells for recognition of dynamic touch gestures. Each cell consists of a triboelectric nanogenerator (TENG) for touch sensing and a bi‐stable resistor (biristor) for spike encoding. It produces informative spike signals by sensing a force of an external touch and encoding the force into the number of spikes. An array of the mechanoreceptor cells is utilized to monitor various touch gestures and it successfully generated spike signals corresponding to all the gestures. To validate the practicality of the mechanoreceptor array, a spiking neural network (SNN), highly attractive for power consumption compared to the conventional von Neumann architecture, is used for the identification of touch gestures. The measured spiking signals are reflected as inputs for the SNN simulations. Consequently, touch gestures are classified with a high accuracy rate of 92.5%. The proposed mechanoreceptor array emerges as a promising candidate for a building block of tactile in‐sensor computing in the era of the Internet of Things (IoT), due to the low cost and high manufacturability of the TENG. This eliminates the need for a power supply, coupled with the intrinsic high throughput of the Si‐based biristor employing complementary metal–oxide–semiconductor (CMOS) technology.