bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance
Authors: Keyvani-Ghamsari Saeedeh , Khorsandi Khatereh , Rasul Azhar , Zaman Muhammad Khatir 
Published: July 2021

AbstractAt present, after extensive studies in the field of cancer, cancer stem cells (CSCs) have been proposed as a major factor in tumor initiation, progression, metastasis, and recurrence. CSCs are a subpopulation of bulk tumors, with stem cell-like properties and tumorigenic capabilities, having the abilities of self-renewal and differentiation, thereby being able to generate heterogeneous lineages of cancer cells and lead to resistance toward anti-tumor treatments. Highly resistant to conventional chemo- and radiotherapy, CSCs have heterogeneity and can migrate to different organs and metastasize. Recent studies have demonstrated that the population of CSCs and the progression of cancer are increased by the deregulation of different epigenetic pathways having effects on gene expression patterns and key pathways connected with cell proliferation and survival. Further, epigenetic modifications (DNA methylation, histone modifications, and RNA methylations) have been revealed to be key drivers in the formation and maintenance of CSCs. Hence, identifying CSCs and targeting epigenetic pathways therein can offer new insights into the treatment of cancer. In the present review, recent studies are addressed in terms of the characteristics of CSCs, the resistance thereof, and the factors influencing the development thereof, with an emphasis on different types of epigenetic changes in genes and main signaling pathways involved therein. Finally, targeted therapy for CSCs by epigenetic drugs is referred to, which is a new approach in overcoming resistance and recurrence of cancer.
Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation
Authors: Wei Sung-Tai , Huang Yen-Chih , Chiang Jung-Ying , Lin Chia-Ching , Lin Yu-Jung , Shyu Woei-Cherng , Chen Hui-Chen , Hsieh Chia-Hung 
Published: July 2021

Abstract
Background
The major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear.

Methods
Gain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA).

Results
CXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs.

Conclusions
CXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.
Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release
Authors: Zhou Lin , Zhang Tong , Shao Wei , Lu Ruohan , Wang Lin , Liu Haisheng , Jiang Bin , Li Shiqin , Zhuo Huiqin , Wang Suheng , Li Qinxi , Huang Caihua , Lin Donghai 
Published: July 2021

AbstractBackgroundCancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia.MethodsThe CT26 and LLC tumor cells were subcutaneously injected into mice to induce colon cancer cachexia and lung cancer cachexia, respectively. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 model and the LLC model were separately characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius.ResultsThe CT26 and LLC cachexia models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue, and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. Both the CT26 and LLC cachexia mice showed increased plasma exosome densities which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis, and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius.ConclusionsAmiloride ameliorates cachectic muscle wasting and alleviates cancer cachexia progression through inhibiting tumor-derived exosome release. Our results are beneficial to understanding the underlying molecular mechanisms, shedding light on the potentials of amiloride in cachexia therapy.
Efficacy of chest X-ray in the diagnosis of COVID-19 pneumonia: comparison with computed tomography through a simplified scoring system designed for triage
Authors: Çinkooğlu Akın , Bayraktaroğlu Selen , Ceylan Naim , Savaş Recep 
Published: July 2021

Abstract
Background
There is no consensus on the imaging modality to be used in the diagnosis and management of Coronavirus disease 2019 (COVID-19) pneumonia. The purpose of this study was to make a comparison between computed tomography (CT) and chest X-ray (CXR) through a scoring system that can be beneficial to the clinicians in making the triage of patients diagnosed with COVID-19 pneumonia at their initial presentation to the hospital.

Results
Patients with a negative CXR (30.1%) had significantly lower computed tomography score (CTS) (p < 0.001). Among the lung zones where the only infiltration pattern was ground glass opacity (GGO) on CT images, the ratio of abnormality seen on CXRs was 21.6%. The cut-off value of X-ray score (XRS) to distinguish the patients who needed intensive care at follow-up (n = 12) was 6 (AUC = 0.933, 95% CI = 0.886–0.979, 100% sensitivity, 81% specificity).

Conclusions
Computed tomography is more effective in the diagnosis of COVID-19 pneumonia at the initial presentation due to the ease detection of GGOs. However, a baseline CXR taken after admission to the hospital can be valuable in predicting patients to be monitored in the intensive care units.
Pulmonary mucormycosis presenting as central bronchopleural fistula—a case report with review of literature
Authors: Padmanaban Elamparidhi , Kannan Preethi , Amirthalingam Umamageswari , Pitchumani Sudhakar , Rekha Padma 
Published: July 2021

Abstract
Background
Bronchopleural fistula (BFF) is a fistulous communication between the trachea or bronchus and the pleural space. Central type of bronchopleural fistula is usually post-surgical. Infective cause for central bronchopleural fistula is rare. This case report encompasses an infective cause of central bronchopleural fistula, mucormycosis. Pulmonary mucormycosis is a rapidly progressive condition with high mortality. A high index of suspicion and timely intervention is required to alleviate fatal outcome. The present case is discussed in detail about the clinical presentation and diagnostic imaging of pulmonary mucormycosis presenting with central bronchopleural fistula.

Case presentation
Thirty-five years old diabetic male, presented with fever, productive cough, mild haemoptysis and chest pain for 10 days duration. The patient was pale on general examination and had decreased breath sound in the right suprascapular and interscapular areas with coarse crackles in the right infrascapular and infra-axillary areas. The laboratory investigations were unremarkable except for anaemia and raised blood glucose level. Sputum examination on potassium hydroxide (KOH) mount showed broad aseptate hyphae. There was a loculated right hydropneumothorax with collapsed lung in chest radiograph. Multi-detector computed tomography of the thorax revealed central type of bronchopleural fistula with the right main bronchus, consolidation of the middle lobe and superior segment of the right lower lobe with multiple internal thick-walled cavities. Right pneumonectomy was performed as the patient did not improve on medical management and showed worsening of symptoms. Histopathological examination was suggestive of mucormycosis.

Conclusion
Central bronchopleural fistula due to an infective aetiology is uncommon. However, mucormycosis should be considered as a differential diagnosis in cases of central bronchopleural fistula with the destroyed lung, especially in diabetic individuals. Hence, a high index of suspicion is necessary for early diagnosis and management as mucormycosis is a rapidly progressive disease with delay in treatment leading to high mortality.
COVID-19 Pandemic and Its Gendered Impact on Indian Physicians
Authors: Jiwnani Sabita , Ranganathan Priya , Tiwari Virendra , Ashok Apurva , Niyogi Devayani , Karimundackal George , Pramesh C. S. 
Published: July 2021

PURPOSE The 2018 WHO health workforce report analyzing gender equity in 104 countries reported that although women constituted 70% of the workers, they were less likely to be employed full-time and faced a 28% gender pay gap. The ongoing COVID-19 pandemic has affected professional as well as personal lives of physicians. We conducted a survey among Indian physicians to understand this impact. METHODS A 31-point anonymized survey to evaluate the impact of the COVID-19 pandemic and resultant lockdown on physicians' domestic responsibilities was disseminated via e-mail and text messaging applications. Our aim was to evaluate whether the impact was gender-based and to look for differences in aspects of domestic work, childcare, and professional commitments. RESULTS We obtained 1,041 responses, of which 643 identified themselves as men and 393 as women. An increase in the domestic responsibilities during the lockdown was confirmed by 90% of the women compared with 82% men. More women than men were solely responsible for domestic chores (38.7% v 23.7%), managed their children's education (74% v 31%), and felt an adverse impact of the pandemic on their professional work (60.8% v 42.6%). Fewer women's spouses (57/359) than men's (174/594, P = .00001) were forced to take leave or work reduced hours, and double the proportion of women (3.5% v 1.5%) had to quit their jobs to manage responsibilities at home. CONCLUSION As the COVID-19 pandemic and the lockdown measures threw newer challenges, more women physicians than men (81% v 63%) shouldered the burden of increased domestic work and childcare. This survey highlights the need to re-examine the specific challenges faced by women physicians and identify means to support and empower them.
Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001
Authors: Vrooman Lynda M. , Blonquist Traci M. , Stevenson Kristen E. , Supko Jeffrey G. , Hunt Sarah K. , Cronholm Sarah M. , Koch Victoria , Kay-Green Samantha , Athale Uma H. , Clavell Luis A. , Cole Peter D. , Harris Marian H. , Kelly Kara M. , Laverdiere Caroline , Leclerc Jean-Marie , Michon Bruno , Place Andrew E. , Schorin Marshall A. , Welch Jennifer J. G. , Neuberg Donna S. , Sallan Stephen E. , Silverman Lewis B. 
Published: July 2021

PURPOSE Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase. METHODS Patients age 1 to ≤ 21 years with newly diagnosed ALL or lymphoblastic lymphoma were randomly assigned to intravenous pegaspargase or calaspargase, 2,500 IU/m2/dose. Patients received one induction dose. Beginning week 7, pegaspargase was administered every 2 week for 15 doses and calaspargase every 3 week for 10 doses (30 weeks). Serum asparaginase activity (SAA) (≥ 0.1 IU/mL considered therapeutic) was assessed 4, 11, 18, and 25 days after the induction dose and before each postinduction dose. RESULTS Between 2012 and 2015, 239 eligible patients enrolled (230 ALL, nine lymphoblastic lymphoma); 120 were assigned to pegaspargase and 119 to calaspargase. After the induction dose, SAA was ≥ 0.1 IU/mL in ≥ 95% of patients on both arms 18 days after dosing. At day 25, more patients had SAA ≥ 0.1 IU/mL with calaspargase (88% v 17%; P ˂ .001). Postinduction, median nadir SAAs were similar (≥ 1.0 IU/mL) for both arms. Of 230 evaluable patients, 99% of pegaspargase and 95% of calaspargase patients achieved complete remission ( P = .12), with no difference in frequency of high end-induction minimal residual disease among evaluable patients with B acute lymphoblastic leukemia (B-ALL). There were no differences in frequencies of asparaginase allergy, pancreatitis, thrombosis, or hyperbilirubinemia. With 5.3 years median follow-up, 5-year event-free survival for pegaspargase was 84.9% (SE ± 3.4%) and 88.1% (± SE 3.0%) for calaspargase ( P = .65). CONCLUSION Every 3-week calaspargase had similar nadir SAA, toxicity, and survival outcomes compared with every 2-week pegaspargase. The high nadir SAA observed for both preparations suggest dosing strategies can be further optimized.
Technological Progress and Health Convergence: The Case of Penicillin in Postwar Italy
Authors: Alsan Marcella , Atella Vincenzo , Bhattacharya Jay , Conti Valentina , Mejía-Guevara Iván , Miller Grant 
Published: July 2021

AbstractThroughout history, technological progress has transformed population health, but the distributional effects of these gains are unclear. New substitutes for older, more expensive health technologies can produce convergence in population health outcomes but may also be prone to elite capture and thus divergence. We study the case of penicillin using detailed historical mortality statistics and exploiting its abruptly timed introduction in Italy after WWII. We find that penicillin reduced both the mean and standard deviation of infectious disease mortality, leading to substantial convergence across disparate regions of Italy. Our results do not appear to be driven by competing risks or confounded by mortality patterns associated with WWII.
A polarized nucleus-cytoskeleton-ECM connection in migrating cardioblasts controls heart tube formation in Drosophila
Authors: Dondi Cristiana , Bertin Benjamin , Da Ponte Jean-Philippe , Wojtowicz Inga , Jagla Krzysztof , Junion Guillaume 
Published: July 2021

ABSTRACT
The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here, we have identified CAP and MSP300 as novel actors involved during CB migration. They both exhibit highly similar temporal and spatial expression patterns in Drosophila migrating cardiac cells, and are necessary for the correct number and alignment of CBs, a prerequisite for the coordination of their collective migration. Our data suggest that CAP and MSP300 are part of a protein complex linking focal adhesion sites to nuclei via the actin cytoskeleton that maintains post-mitotic state and correct alignment of CBs.
Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells
Authors: Jarysta Amandine , Tarchini Basile 
Published: July 2021

ABSTRACT
Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here, we report a role for multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis in mouse. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprint proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.
The evolution of autophagy proteins – diversification in eukaryotes and potential ancestors in prokaryotes
Authors: Zhang Sidi , Hama Yutaro , Mizushima Noboru 
Published: July 2021

ABSTRACT
Autophagy is a degradative pathway for cytoplasmic constituents, and is conserved across eukaryotes. Autophagy-related (ATG) genes have undergone extensive multiplications and losses in different eukaryotic lineages, resulting in functional diversification and specialization. Notably, even though bacteria and archaea do not possess an autophagy pathway, they do harbor some remote homologs of Atg proteins, suggesting that preexisting proteins were recruited when the autophagy pathway developed during eukaryogenesis. In this Review, we summarize our current knowledge on the distribution of Atg proteins within eukaryotes and outline the major multiplication and loss events within the eukaryotic tree. We also discuss the potential prokaryotic homologs of Atg proteins identified to date, emphasizing the evolutionary relationships and functional differences between prokaryotic and eukaryotic proteins.
Protein phosphatase 2A – structure, function and role in neurodevelopmental disorders
Authors: Sandal Priyanka , Jong Chian Ju , Merrill Ronald A. , Song Jianing , Strack Stefan 
Published: July 2021

ABSTRACTNeurodevelopmental disorders (NDDs), including intellectual disability (ID), autism and schizophrenia, have high socioeconomic impact, yet poorly understood etiologies. A recent surge of large-scale genome or exome sequencing studies has identified a multitude of mostly de novo mutations in subunits of the protein phosphatase 2A (PP2A) holoenzyme that are strongly associated with NDDs. PP2A is responsible for at least 50% of total Ser/Thr dephosphorylation in most cell types and is predominantly found as trimeric holoenzymes composed of catalytic (C), scaffolding (A) and variable regulatory (B) subunits. PP2A can exist in nearly 100 different subunit combinations in mammalian cells, dictating distinct localizations, substrates and regulatory mechanisms. PP2A is well established as a regulator of cell division, growth, and differentiation, and the roles of PP2A in cancer and various neurodegenerative disorders, such as Alzheimer's disease, have been reviewed in detail. This Review summarizes and discusses recent reports on NDDs associated with mutations of PP2A subunits and PP2A-associated proteins. We also discuss the potential impact of these mutations on the structure and function of the PP2A holoenzymes and the etiology of NDDs.
Total energy expenditure of bottlenose dolphins (Tursiops truncatus) of different ages
Authors: Rimbach Rebecca , Amireh Ahmad , Allen Austin , Hare Brian , Guarino Emily , Kaufman Chana , Salomons Hannah , Pontzer Herman 
Published: July 2021

ABSTRACTMarine mammals are thought to have an energetically expensive lifestyle because endothermy is costly in marine environments. However, measurements of total energy expenditure (TEE; kcal day−1) are available only for a limited number of marine mammals, because large body size and inaccessible habitats make TEE measurements expensive and difficult to obtain for many taxa. We measured TEE in 10 adult common bottlenose dolphins (Tursiops truncatus) living in natural seawater lagoons at two facilities (Dolphin Research Center and Dolphin Quest) using the doubly labeled water method. We assessed the relative effects of body mass, age and physical activity on TEE. We also examined whether TEE of bottlenose dolphins, and more generally of marine mammals, differs from that expected for their body mass compared with other eutherian mammals, using phylogenetic least squares (PGLS) regressions. There were no differences in body mass or TEE (unadjusted TEE and TEE adjusted for fat-free mass) between dolphins from the two facilities. Our results show that adjusted TEE decreased and fat mass increased with age. Different measures of activity were not related to age, body fat or adjusted TEE. Both PGLS and the non-phylogenetic linear regression indicate that marine mammals have an elevated TEE compared with that of terrestrial mammals. However, bottlenose dolphins expended 17.1% less energy than other marine mammals of similar body mass. The two oldest dolphins (&gt;40 years) showed a lower TEE, similar to the decline in TEE seen in older humans. To our knowledge, this is the first study to show an age-related metabolic decline in a large non-human mammal.