cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.6714092.v3
title: Role of the MAPK/cJun NH<sub>2</sub>-terminal kinase signaling pathway in starvation-induced autophagy

description: Autophagy is required for cellular homeostasis and can determine cell viability in response to stress. It is established that MTOR is a master regulator of starvation-induced macroautophagy/autophagy, but recent studies have also implicated an essential role for the MAPK8/cJun NH<sub>2</sub>-terminal kinase 1 signal transduction pathway. We found that MAPK8/JNK1 and MAPK9/JNK2 were not required for autophagy caused by starvation or MTOR inhibition in murine fibroblasts and epithelial cells. These data demonstrate that MAPK8/9 has no required role in starvation-induced autophagy. We conclude that the role of MAPK8/9 in autophagy may be context-dependent and more complex than previously considered. <b>Abbreviations</b>: AKT: thymoma viral proto-oncogene;ALB: albumin; ATG4: autophagy related 4; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine diphosphate; DMEM: Dulbecco’s modified Eagle’s medium; EDTA: ethylenediaminetetraacetic acid; EBSS: Earle’s balanced salt solution; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HRAS: Harvey rat sarcoma virus oncogene; IgG: Immunoglobulin G; MAPK3/ERK1: mitogen-activated protein kinase 3; MAPK8/JNK1: mitogen-activated protein kinase 8; MAPK9/JNK2: mitogen-activated protein kinase 9; MAPK10/JNK3: mitogen-activated protein kinase 10; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70: ribosomal protein S6 kinase, polypeptide 1; PPARA: peroxisome proliferator activated receptor alpha; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TORC1: target of rapamycin complex 1; TORC2: target of rapamycin complex 2; TRP53: transforming related protein 53; TUBA: tubulin alpha; UV: ultraviolet; WT: wild-type
DOI: 10.6084/m9.figshare.6714092
title: Role of the MAPK/cJun NH<sub>2</sub>-terminal kinase signaling pathway in starvation-induced autophagy

description: Autophagy is required for cellular homeostasis and can determine cell viability in response to stress. It is established that MTOR is a master regulator of starvation-induced macroautophagy/autophagy, but recent studies have also implicated an essential role for the MAPK8/cJun NH<sub>2</sub>-terminal kinase 1 signal transduction pathway. We found that MAPK8/JNK1 and MAPK9/JNK2 were not required for autophagy caused by starvation or MTOR inhibition in murine fibroblasts and epithelial cells. These data demonstrate that MAPK8/9 has no required role in starvation-induced autophagy. We conclude that the role of MAPK8/9 in autophagy may be context-dependent and more complex than previously considered. <b>Abbreviations</b>: AKT: thymoma viral proto-oncogene;ALB: albumin; ATG4: autophagy related 4; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine diphosphate; DMEM: Dulbecco’s modified Eagle’s medium; EDTA: ethylenediaminetetraacetic acid; EBSS: Earle’s balanced salt solution; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HRAS: Harvey rat sarcoma virus oncogene; IgG: Immunoglobulin G; MAPK3/ERK1: mitogen-activated protein kinase 3; MAPK8/JNK1: mitogen-activated protein kinase 8; MAPK9/JNK2: mitogen-activated protein kinase 9; MAPK10/JNK3: mitogen-activated protein kinase 10; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70: ribosomal protein S6 kinase, polypeptide 1; PPARA: peroxisome proliferator activated receptor alpha; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TORC1: target of rapamycin complex 1; TORC2: target of rapamycin complex 2; TRP53: transforming related protein 53; TUBA: tubulin alpha; UV: ultraviolet; WT: wild-type
DOI: 10.6084/m9.figshare.6714092.v2
title: Role of the MAPK/cJun NH<sub>2</sub>-terminal kinase signaling pathway in starvation-induced autophagy

description: Autophagy is required for cellular homeostasis and can determine cell viability in response to stress. It is established that MTOR is a master regulator of starvation-induced macroautophagy/autophagy, but recent studies have also implicated an essential role for the MAPK8/cJun NH<sub>2</sub>-terminal kinase 1 signal transduction pathway. We found that MAPK8/JNK1 and MAPK9/JNK2 were not required for autophagy caused by starvation or MTOR inhibition in murine fibroblasts and epithelial cells. These data demonstrate that MAPK8/9 has no required role in starvation-induced autophagy. We conclude that the role of MAPK8/9 in autophagy may be context-dependent and more complex than previously considered. <b>Abbreviations</b>: AKT: thymoma viral proto-oncogene;ALB: albumin; ATG4: autophagy related 4; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine diphosphate; DMEM: Dulbecco’s modified Eagle’s medium; EDTA: ethylenediaminetetraacetic acid; EBSS: Earle’s balanced salt solution; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HRAS: Harvey rat sarcoma virus oncogene; IgG: Immunoglobulin G; MAPK3/ERK1: mitogen-activated protein kinase 3; MAPK8/JNK1: mitogen-activated protein kinase 8; MAPK9/JNK2: mitogen-activated protein kinase 9; MAPK10/JNK3: mitogen-activated protein kinase 10; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70: ribosomal protein S6 kinase, polypeptide 1; PPARA: peroxisome proliferator activated receptor alpha; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TORC1: target of rapamycin complex 1; TORC2: target of rapamycin complex 2; TRP53: transforming related protein 53; TUBA: tubulin alpha; UV: ultraviolet; WT: wild-type
DOI: 10.6084/m9.figshare.6724466
title: Autophagic reliance promotes metabolic reprogramming in oncogenic KRAS-driven tumorigenesis

description: Defects in basal autophagy limit the nutrient supply from recycling of intracellular constituents. Despite our understanding of the prosurvival role of macroautophagy/autophagy, how nutrient deprivation, caused by compromised autophagy, affects oncogenic KRAS-driven tumor progression is poorly understood. Here, we demonstrate that conditional impairment of the autophagy gene <i>Atg5</i> (<i>atg5-</i>KO) extends the survival of KRAS<sup>G12V</sup>-driven tumor-bearing mice by 38%. <i>atg5-</i>KO tumors spread more slowly during late tumorigenesis, despite a faster onset. <i>atg5-</i>KO tumor cells displayed reduced mitochondrial function and increased mitochondrial fragmentation. Metabolite profiles indicated a deficiency in the nonessential amino acid asparagine despite a compensatory overexpression of ASNS (asparagine synthetase), key enzyme for <i>de novo</i> asparagine synthesis. Inhibition of either autophagy or ASNS reduced KRAS<sup>G12V</sup>-driven tumor cell proliferation, migration, and invasion, which was rescued by asparagine supplementation or knockdown of MFF (mitochondrial fission factor). Finally, these observations were reflected in human cancer-derived data, linking ASNS overexpression with poor clinical outcome in multiple cancers. Together, our data document a widespread yet specific asparagine homeostasis control by autophagy and ASNS, highlighting the previously unrecognized role of autophagy in suppressing the metabolic barriers of low asparagine and excessive mitochondrial fragmentation to permit malignant KRAS-driven tumor progression.
DOI: 10.6084/m9.figshare.6724466.v4
title: Autophagic reliance promotes metabolic reprogramming in oncogenic KRAS-driven tumorigenesis

description: Defects in basal autophagy limit the nutrient supply from recycling of intracellular constituents. Despite our understanding of the prosurvival role of macroautophagy/autophagy, how nutrient deprivation, caused by compromised autophagy, affects oncogenic KRAS-driven tumor progression is poorly understood. Here, we demonstrate that conditional impairment of the autophagy gene <i>Atg5</i> (<i>atg5-</i>KO) extends the survival of KRAS<sup>G12V</sup>-driven tumor-bearing mice by 38%. <i>atg5-</i>KO tumors spread more slowly during late tumorigenesis, despite a faster onset. <i>atg5-</i>KO tumor cells displayed reduced mitochondrial function and increased mitochondrial fragmentation. Metabolite profiles indicated a deficiency in the nonessential amino acid asparagine despite a compensatory overexpression of ASNS (asparagine synthetase), key enzyme for <i>de novo</i> asparagine synthesis. Inhibition of either autophagy or ASNS reduced KRAS<sup>G12V</sup>-driven tumor cell proliferation, migration, and invasion, which was rescued by asparagine supplementation or knockdown of MFF (mitochondrial fission factor). Finally, these observations were reflected in human cancer-derived data, linking ASNS overexpression with poor clinical outcome in multiple cancers. Together, our data document a widespread yet specific asparagine homeostasis control by autophagy and ASNS, highlighting the previously unrecognized role of autophagy in suppressing the metabolic barriers of low asparagine and excessive mitochondrial fragmentation to permit malignant KRAS-driven tumor progression.
DOI: 10.6084/m9.figshare.6724466.v3
title: Autophagic reliance promotes metabolic reprogramming in oncogenic KRAS-driven tumorigenesis

description: Defects in basal autophagy limit the nutrient supply from recycling of intracellular constituents. Despite our understanding of the prosurvival role of macroautophagy/autophagy, how nutrient deprivation, caused by compromised autophagy, affects oncogenic KRAS-driven tumor progression is poorly understood. Here, we demonstrate that conditional impairment of the autophagy gene <i>Atg5</i> (<i>atg5-</i>KO) extends the survival of KRAS<sup>G12V</sup>-driven tumor-bearing mice by 38%. <i>atg5-</i>KO tumors spread more slowly during late tumorigenesis, despite a faster onset. <i>atg5-</i>KO tumor cells displayed reduced mitochondrial function and increased mitochondrial fragmentation. Metabolite profiles indicated a deficiency in the nonessential amino acid asparagine despite a compensatory overexpression of ASNS (asparagine synthetase), key enzyme for <i>de novo</i> asparagine synthesis. Inhibition of either autophagy or ASNS reduced KRAS<sup>G12V</sup>-driven tumor cell proliferation, migration, and invasion, which was rescued by asparagine supplementation or knockdown of MFF (mitochondrial fission factor). Finally, these observations were reflected in human cancer-derived data, linking ASNS overexpression with poor clinical outcome in multiple cancers. Together, our data document a widespread yet specific asparagine homeostasis control by autophagy and ASNS, highlighting the previously unrecognized role of autophagy in suppressing the metabolic barriers of low asparagine and excessive mitochondrial fragmentation to permit malignant KRAS-driven tumor progression.
DOI: 10.6084/m9.figshare.6964409
title: <i>Drosophila</i> Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

description: Rab2 is a conserved Rab GTPase with a well-established role in secretory pathway function and phagocytosis. Here we demonstrate that <i>Drosophila</i> Rab2 is recruited to late endosomal membranes, where it controls the fusion of LAMP-containing biosynthetic carriers and lysosomes to late endosomes. In contrast, the lysosomal GTPase Gie/Arl8 is only required for late endosome-lysosome fusion, but not for the delivery of LAMP to the endocytic pathway. We also find that Rab2 is required for the fusion of autophagosomes to the endolysosomal pathway, but not for the biogenesis of lysosome-related organelles. Surprisingly, Rab2 does not rely on HOPS-mediated vesicular fusion for recruitment to late endosomal membranes. Our work suggests that <i>Drosophila</i> Rab2 is a central regulator of the endolysosomal and macroautophagic/autophagic pathways by controlling the major heterotypic fusion processes at the late endosome.
DOI: 10.6084/m9.figshare.6555140.v1
title: A Pseudo-Receiver Domain in Atg32 is Required for Mitophagy

description: Mitochondria are targeted for degradation by mitophagy, a selective form of autophagy. In <i>Saccharomyces cerevisiae</i>, mitophagy is dependent on the autophagy receptor, Atg32, an outer mitochondrial membrane protein. Once activated, Atg32 recruits the autophagy machinery to mitochondria, facilitating mitochondrial capture in phagophores, the precursors to autophagosomes. However, the mechanism of Atg32 activation remains poorly understood. To investigate this crucial step in mitophagy regulation, we examined the structure of Atg32. We have identified a structured domain in Atg32 that is essential for the initiation of mitophagy, as it is required for the proteolysis of the C-terminal domain of Atg32 and the subsequent recruitment of Atg11. The solution structure of this domain was determined by NMR spectroscopy, revealing that Atg32 contains a previously undescribed pseudo-receiver (PsR) domain. Our data suggests that the PsR domain of Atg32 regulates Atg32 activation and the initiation of mitophagy.
DOI: 10.6084/m9.figshare.6964409.v1
title: <i>Drosophila</i> Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

description: Rab2 is a conserved Rab GTPase with a well-established role in secretory pathway function and phagocytosis. Here we demonstrate that <i>Drosophila</i> Rab2 is recruited to late endosomal membranes, where it controls the fusion of LAMP-containing biosynthetic carriers and lysosomes to late endosomes. In contrast, the lysosomal GTPase Gie/Arl8 is only required for late endosome-lysosome fusion, but not for the delivery of LAMP to the endocytic pathway. We also find that Rab2 is required for the fusion of autophagosomes to the endolysosomal pathway, but not for the biogenesis of lysosome-related organelles. Surprisingly, Rab2 does not rely on HOPS-mediated vesicular fusion for recruitment to late endosomal membranes. Our work suggests that <i>Drosophila</i> Rab2 is a central regulator of the endolysosomal and macroautophagic/autophagic pathways by controlling the major heterotypic fusion processes at the late endosome.
DOI: 10.6084/m9.figshare.24579757.v1
title: Supplementary Material for: Treatment strategies and prognosis for moderate stroke patients in China

description: Introduction: Moderate stroke patients with National Institutes of Health Stroke Scale (NIHSS) score of 4–10 and without intravenous thrombolysis or endovascular treatment are basically excluded from current secondary prevention trials. We aimed to explore the effectiveness of mono- vs. dual-antiplatelet (DAPT) treatment strategies against subsequent stroke for these patients in a nationwide cohort.
Methods: Data were derived from the Third China National Stroke Registry (CNSR-Ш). In this prospective nationwide cohort, moderate ischemic stroke patients with NIHSS 4–10 and without intravenous thrombolysis or endovascular treatment were included and categorized into mono- or dual-antiplatelet groups. Demographics, medical history, NIHSS score, imaging and laboratory data were collected. The outcomes were stroke recurrence and all-cause mortality at 3 months and at 1 year, respectively. Cox proportional-hazards models were utilized to investigate the association of treatment strategies and prognosis.
Results: Of a total of 2 414 patients enrolled in the study, 1 633 (67.6%) received clopidogrel or aspirin and 781 (32.4%) received DAPT. Recurrent stroke occurred in 108 (6.6%) patients of the mono-antiplatelt group and 40 (5.1%) patients of the DAPT group ( adjusted hazard ratio [aHR] 0.73, 95% confidential interval [CI] 0.47-1.13, P=0.16) at 3 months, and the rate of stroke recurrence was 10.7% in the mono-antiplatelet group and 8.6% in the DAPT group ( aHR 0.81, 95% CI 0.58-1.13, P=0.22) at 12 months. The DAPT paradigm was not significantly associated with death at 3 months (0.6% vs 0.3%, a HR 0.28, 95%CI 0.04-2.25) but significantly reduced the mortality at 12 months (2.3% vs 1.0%, aHR 0.41, 95% CI 0.17-0.98, P=0.046).
Conclusions: In moderate stroke patients presenting within 24 hours of symptom onset, the addition of clopidogrel 75 mg to aspirin might not be associated with lower risk of recurrent stroke than aspirin or clopidogrel alone.
DOI: 10.6084/m9.figshare.24754113
title: Supplementary Material for: Are traumatic disintegration, detachment, and dissociation separate pathogenic processes related to attachment trauma? A working hypothesis for clinicians and researchers

description: Background. Despite its high prevalence in all psychiatric disorders and its widely demonstrated clinical relevance as a marker of both clinical severity and poorer treatment response, a scientifically validated definition of dissociation remains controversial, and the understanding of its pathogenesis is still somewhat lacking. Furthermore, although most clinicians commonly refer to dissociation as a single unitary concept, the empirical evidence strongly supports the paucity of a one-dimensional approach to dissociation. Summary. Resonating with the clinical and neuroscientific data on this topic, this article aims to provide a working hypothesis suggesting that the wide variety of psychopathological phenomena that are currently improperly lumped into the category of dissociation are in fact produced by at least three different pathogenic processes involved in developmental trauma, namely, traumatic disintegration, detachment responses, and dissociation. Key Messages. This hypothesis should, therefore, be considered a starting point for a better understanding of the complex manifestations and processes currently overly attributed to dissociation per se.
DOI: 10.6084/m9.figshare.24745629
title: Supplementary Material for: Long Term Treatment of Unresectable Pseudomyxoma Peritonei with multiple treatments of Intratumoral Bromelain and Acetylcysteine (BromAc): a case report

description: Pseudomyxoma peritonei (PMP) is a rare peritoneal malignancy characterised by the progressive accumulation of mucinous material and tumour within the abdomen and pelvis. Percutaneous drainage of mucin may be a non-surgical option for relief of symptoms, however it remains difficult due to the high viscosity of mucin, with numerous case reports reporting difficulty removing material through medium-bore catheters alone. BromAc is a therapy currently undergoing development which dissolves mucinous tumour masses and allows for extraction. This report describes the case of a patient who has had multiple treatments with BromAc over four years.
DOI: 10.25919/xkvm-rs37
title: Parkes observations for project P885 semester 2023OCTS_06

description: We request a continued modest monitoring cadence of once every 10 days for two radio magnetars, to track their rotation, flux density, and polarisation. 1E 1547.0-5408 has recently suffered a 'hiccup' in radiative properties as well as in its rotation, and the mid-term response to this event remains unclear. Swift J1818.0-1607 remains quite dynamic, and the unique UWL capabilities provide new opportunities to probe still mysterious radio emission mechanisms in magnetars. We will observe XTE J1810-197 and PSR J1622-4950, which ceased emission a year ago, less frequently. The overall request is 18 hours.
DOI: 10.6084/m9.figshare.24722193
title: Supplementary Material for: Treatment and prognosis of newly diagnosed advanced-stage extranodal natural killer / T cell lymphoma: a single-center real-world study across two decades

description: Introduction: Although there is now a consensus on asparaginase-based chemotherapy regimens in treatment of advanced-stage extranodal natural killer / T cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified.

Methods: Newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations.

Results: The study included 83 newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase- compared to non-asparaginase-based regimens significantly prolonged PFS (P=0.007; HR=0.48, P=0.020) and showed a tendency to improve OS (P=0.064; HR=0.74, P=0.359). Gemcitabine-based regimens also exhibited a trend towards improved PFS (P=0.048; HR=0.59, P=0.164) and OS (P=0.008; HR=0.67, P=0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (P=0.020; HR=0.40, P=0.022) and slightly better OS (P=0.054; HR=0.79, P=0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (P=0.051) and OS (P=0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months.

Conclusion: Asparaginase and gemcitabine alone brought favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.
DOI: 10.6084/m9.figshare.24495898
title: Supplementary Material for: Monogenic Causes Identified in 23.68% of Children with Steroid Resistant Nephrotic Syndrome: A Single-Centre Study

description: Introduction: Steroid resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20 – 30% of SRNS patients. 
Methods: We used whole exome sequencing (WES) to explore the genetic causes of SRNS in children. Totally 101 patients with SRNS, and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature.
Results: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4(3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel, and have not been previously reported in literature. 
Conclusion: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early onset and extrarenal phenotypes.