bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation
Authors: Penter Livius , Zhang Yi , Savell Alexandra , Huang Teddy , Cieri Nicoletta , Thrash Emily M. , Kim-Schulze Seunghee , Jhaveri Aashna , Fu Jingxin , Ranasinghe Srinika , Li Shuqiang , Zhang Wandi , Hathaway Emma S. , Nazzaro Matthew , Kim Haesook T. , Chen Helen , Thurin Magdalena , Rodig Scott J. , Severgnini Mariano , Cibulskis Carrie , Gabriel Stacey , Livak Kenneth J. , Cutler Corey , Antin Joseph H. , Nikiforow Sarah , Koreth John , Ho Vincent T. , Armand Philippe , Ritz Jerome , Streicher Howard , Neuberg Donna , Hodi F. Stephen , Gnjatic Sacha , Soiffer Robert J. , Liu X. Shirley , Davids Matthew S. , Bachireddy Pavan , Wu Catherine J. 
Published: March 2021

Abstract
Relapsed myeloid disease after allogeneic stem cell transplantation (HSCT) remains largely incurable. We previously demonstrated the potent activity of immune checkpoint blockade in this clinical setting with ipilimumab or nivolumab. To define the molecular and cellular pathways by which CTLA-4 blockade with ipilimumab can reinvigorate an effective graft-versus-leukemia (GVL) response, we integrated transcriptomic analysis of leukemic biopsies with immunophenotypic profiling of matched peripheral blood samples collected from patients treated with ipilimumab following HSCT on the Experimental Therapeutics Clinical Trials Network 9204 trial. Response to ipilimumab was associated with transcriptomic evidence of increased local CD8+ T-cell infiltration and activation. Systemically, ipilimumab decreased naïve and increased memory T-cell populations and increased expression of markers of T-cell activation and costimulation such as PD-1, HLA-DR, and ICOS, irrespective of response. However, responding patients were characterized by higher turnover of T-cell receptor sequences in peripheral blood and showed increased expression of proinflammatory chemokines in plasma that was further amplified by ipilimumab. Altogether, these data highlight the compositional T-cell shifts and inflammatory pathways induced by ipilimumab both locally and systemically that associate with successful GVL outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01822509.
Mitochondrial dynamics and reactive oxygen species initiate thrombopoiesis from mature megakaryocytes
Authors: Poirault-Chassac Sonia , Nivet-Antoine Valérie , Houvert Amandine , Kauskot Alexandre , Lauret Evelyne , Lai-Kuen René , Dusanter-Fourt Isabelle , Baruch Dominique 
Published: March 2021

AbstractBlood platelets are essential for controlling hemostasis. They are released by megakaryocytes (MKs) located in the bone marrow, upon extension of cytoplasmic protrusions into the lumen of bone marrow sinusoids. Their number increases in postpulmonary capillaries, suggesting a role for oxygen gradient in thrombopoiesis (ie, platelet biogenesis). In this study, we show that initiation of thrombopoiesis from human mature MKs was enhanced under hyperoxia or during pro-oxidant treatments, whereas antioxidants dampened it. Quenching mitochondrial reactive oxygen species (mtROS) with MitoTEMPO decreased thrombopoiesis, whereas genetically enhancing mtROS by deacetylation-null sirtuin-3 expression increased it. Blocking cytosolic ROS production by NOX inhibitors had no impact. Classification according to the cell roundness index delineated 3 stages of thrombopoiesis in mature MKs. Early-stage round MKs exhibited the highest index, which correlated with low mtROS levels, a mitochondrial tubular network, and the mitochondrial recruitment of the fission activator Drp1. Intermediate MKs at the onset of thrombopoiesis showed high mtROS levels and small, well-delineated mitochondria. Terminal MKs showed the lowest roundness index and long proplatelet extensions. Inhibiting Drp1-dependent mitochondrial fission of mature MKs by Mdivi-1 favored a tubular mitochondrial network and lowered both mtROS levels and intermediate MKs proportion, whereas enhancing Drp1 activity genetically had opposite effects. Reciprocally, quenching mtROS limited mitochondrial fission in round MKs. These data demonstrate a functional coupling between ROS and mitochondrial fission in MKs, which is crucial for the onset of thrombopoiesis. They provide new molecular cues that control initiation of platelet biogenesis and may help elucidate some unexplained thrombocytopenia.
A change in temporal muscle thickness is correlated with past energy adequacy in bedridden older adults: a prospective cohort study
Authors: Hasegawa Yoko , Yoshida Mikako , Sato Aya , Fujimoto Yumiko , Minematsu Takeo , Sugama Junko , Sanada Hiromi 
Published: March 2021

Abstract
Background
Energy inadequacy has a great impact on health outcomes in older adult patients; however, it is difficult to evaluate energy adequacy in these patients, especially in home-care settings. We recently reported that temporal muscle thickness can be an indicator of nutritional status. The present study aims to examine whether a change in temporal muscle thickness is directly correlated with energy adequacy and, if so, to determine the cutoff value of a change in temporal muscle thickness to detect energy inadequacy.

Methods
A prospective cohort study was conducted from September 2015 to June 2016 in two hospitals in Japan, and included bedridden older adult patients aged ≥65 years. Temporal muscle thickness was measured using ultrasonography. Energy intake was estimated by photographic diet records. Total energy expenditure (TEE) was estimated by multiplying basal energy expenditure calculated using the Harris– Benedict equation by activity and stress factors. Energy adequacy was then calculated by dividing TEE by energy intake. Pearson’s correlation coefficient was used to examine the relationship between percentage change in temporal muscle thickness and energy adequacy. Multiple logistic regression analysis was conducted to determine the direct relationship between percentage change in temporal muscle thickness and moderate energy inadequacy (energy adequacy< 75%). Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point for percentage change in temporal muscle thickness to detect moderate energy inadequacy.

Results
Forty-eight patients were analyzed (mean age 84.4 ± 7.8 years; 54.2% were women). The percentage change in muscle thickness was significantly correlated with energy adequacy (r = 0.733, p < 0.001). ROC analysis identified a percentage change in temporal muscle thickness of − 3.6% as the optimal cutoff point for detecting moderate energy inadequacy. Percentage change in muscle thickness was independently correlated with energy inadequacy after adjusting for age, sex, and masticatory status (AOR 0.281, 95% CI 0.125–0.635).

Conclusions
Changes in temporal muscle thickness are directly correlated with energy adequacy and can indicate moderate energy inadequacy in bedridden older adults. These results suggest the assessment of changes in temporal muscle thickness could be useful for guiding nutritional care in older adult patients in home-care settings.
Pregnancy-related anxiety and its associated factors during COVID-19 pandemic in Iranian pregnant women: a web-based cross-sectional study
Authors: Hamzehgardeshi Zeinab , Omidvar Shabnam , Amoli Arman Asadi , Firouzbakht Mojgan 
Published: March 2021

Abstract
Background
Pregnancy is a risk factor for coronavirus disease 2019 (COVID-19). Pregnant women suffer from varying levels of pregnancy-related anxiety (PRA) which can negatively affect pregnancy outcomes. The aim of this study was to assess PRA and its associated factors during the COVID-19 pandemic.

Methods
This web-based cross-sectional study was conducted in 2020 on 318 pregnant women purposively recruited from primary healthcare centers in Sari and Amol, Iran. Data were collected using questionnaires (PRAQ, Edinburg, KAP of COVID-19, CDA-Q and Demographic questionnaire), which were provided to participants through the social media or were completed for them over telephone. Data were analyzed with the linear regression and the logistic regression analysis, at the significance level of 0.05 using the SPSS software (v. 21).

Results
Around 21% of participants had PRA, 42.1% had depression, and 4.4% had COVID-19 anxiety. The significant predictors of PRA were number of pregnancies (P = 0.008), practice regarding COVID-19 (P < 0.001), COVID-19 anxiety (P < 0.001), depression (P < 0.001), and social support (P = 0.025) which explained 19% of the total variance. Depression and COVID-19 anxiety increased the odds of PRA by respectively four times and 13%, while good practice regarding COVID-19 decreased the odds by 62%.

Conclusion
Around 21% of pregnant women suffer from PRA during the COVID-19 pandemic and the significant predictors of PRA during the pandemic include number of pregnancies, practice regarding COVID-19, COVID-19 anxiety, depression, and social support. These findings can be used to develop appropriate strategies for the management of mental health problems during pregnancy in the COVID-19 pandemic.
The characteristics of circRNA as competing endogenous RNA in pathogenesis of acute myeloid leukemia
Authors: Zhang Siyuan 
Published: March 2021

Abstract
Background
As one of the novel molecules, circRNA has been identified closely involved in the pathogenesis of many diseases. However, the function of circRNA in acute myeloid leukemia (AML) still remains unknown.

Methods
In the current study, the RNA expression profiles were obtained from Gene Expression Omnibus (GEO) datasets. The differentially expressed RNAs were identified using R software and the competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed to identify the candidate circRNA-mediated aberrant signaling pathways. The hub genes were identified by MCODE and CytoHubba plugins of Cytoscape, and then a subnetwork regulatory module was established.

Results
A total of 27 circRNA-miRNA pairs and 208 miRNA-mRNA pairs, including 12 circRNAs, 24 miRNAs and 112 mRNAs were included in the ceRNA network. Subsequently, a subnetwork, including 4 circRNAs, 5 miRNAs and 6 mRNAs, was established based on related circRNA-miRNA-mRNA regulatory modules.

Conclusions
In summary, this work analyzes the characteristics of circRNA as competing endogenous RNA in AML pathogenesis, which would provide hints for developing novel prognostic, diagnostic and therapeutic strategy for AML.
A place-based analysis of COVID-19 risk factors in Bangladesh urban slums: a secondary analysis of World Bank microdata
Authors: Hasan Shaikh Mehdi , Das Susmita , Hanifi Syed Manzoor Ahmed , Shafique Sohana , Rasheed Sabrina , Reidpath Daniel D. 
Published: March 2021

AbstractBackgroundThere is a lack of research investigating the confluence of risk factors in urban slums that may make them accelerators for respiratory, droplet infections like COVID-19. Our working hypothesis was that, even within slums, an inverse relationship existed between living density and access to shared or private WASH facilities.MethodsIn an exploratory, secondary analysis of World Bank, cross-sectional microdata from slums in Bangladesh we investigated the relationship between intra-household population density (crowding) and access to private or shared water sources and toilet facilities.ResultsThe analysis showed that most households were single-room dwellings (80.4%). Median crowding ranged from 0.55 m2per person up to 67.7 m2per person. The majority of the dwellings (83.3%), shared both toilet facilities and the source of water, and there was a significant positive relationship between crowding and the use of shared facilities.ConclusionThe findings highlight the practical constraints on implementing, in slums, the conventional COVID19 management approaches of social distancing, regular hand washing, and not sharing spaces. It has implications for the management of future respiratory epidemics.
NO2 exposure increases eczema outpatient visits in Guangzhou, China: an indication for hospital management
Authors: Zhang Luwen , Jing Dian , Lu Qiaochu , Shen Shuqun 
Published: March 2021

Abstract
Background
Ambient nitrogen dioxide (NO2) is a common air pollutant in developing countries and causes skin conditions, but its effect on eczema in subtropical areas is not clear in China.

Object
To measure the effect of short-term exposure of NO2 on the incidence of eczema and the change of outpatient visits.

Methods
Data of daily temperature, air pollutants, and outpatient visits from 2013 to 2018 were collected in a row. The generalized additive model (GAM) and Poisson distribution were used to assess the association between short-term exposure of NO2 and the outpatient visits of patients with eczema. The cumulative exposure effect of lag 0–3 days and the displacement effect of NO2 and other pollutants were considered as well. A single pollutant model was used to examine the independent association, and a two-pollutant model was adopted to control the confounding effect.

Results
The daily outpatient visits of eczema increased from 75.26 to 190.85 from 2013 to 2018 (P < 0.001). The combined influence of NO2 and the related pollutant exerted a stronger influence on the incidence of eczema. The maximum effect of NO2 appeared on the exposed day.
(lag 0) and disappeared on day 4 (lag 3). The children and seniors were more vulnerable to NO2 exposure.

Conclusion
Exposure to NO2 is tightly associated with eczema incidence and outpatient visits. The hospitals should react to the visit fluctuations and adjust physician duty shifts to improve outpatient service efficiency.
Association between plasma interleukin-33 level and acute exacerbation of chronic obstructive pulmonary disease
Authors: Joo Hyonsoo , Park Seoung Ju , Min Kyung Hoon , Rhee Chin Kook 
Published: March 2021

Abstract
Background
The role of interleukin (IL)-33 in patients with chronic obstructive pulmonary disease (COPD) has not been well elucidated. The aim of this study is to analyze the association between plasma IL-33 level and acute exacerbation of COPD.

Methods
Plasma IL-33 was measured in 62 COPD patients during their stable state. Patients were prospectively followed up for 1 year. The expression of IL-33 was measured in lung tissue obtained from 38 patients who underwent surgery.

Results
The number of exacerbations was significantly higher in the high plasma IL-33 group compared with the low plasma IL-33 group. On Poisson regression analysis, high plasma IL-33 was associated with increased risk of exacerbation (incidence rate ratio = 2.166, P = 0.043). The expression of IL-33 in the lung was higher in COPD patients than in controls. The expression of IL-33 was significantly correlated with smoking pack years (R = 0.45, P < 0.01) and Forced expiratory volume in 1 s (%) (R = − 0.58, P < 0.01).

Conclusion
The plasma level of IL-33 in patients with COPD was significantly associated with the risk of exacerbation in prospective follow up. The expression of IL-33 in the lung was positively correlated with smoking and negatively correlated with lung function.
Muscle volume imbalance may be associated with static posterior humeral head subluxation
Authors: Mitterer Marian , Matis Nicholas , Steiner Gernot , Vasvary Imre , Ortmaier Reinhold 
Published: March 2021

Abstract
Background
The transverse force couple (TFC) of the rotator cuff (subscapularis vs. infraspinatus and teres minor muscle) is an important dynamic stabilizer of the shoulder joint in the anterior-posterior direction. In patients with posterior static subluxation of the humeral head (PSSH), decentration of the humeral head posteriorly occurs, which is associated with premature arthritis. We hypothesize that not only pathologic glenoid retroversion but also chronic muscle volume imbalance in the transverse force couple leads to PSSH.

Methods
A retrospective analysis of the TFC muscle volumes of 9 patients with symptomatic, atraumatic PSSH, within 8 were treated with glenoid correction osteotomy, was conducted. The imaging data (CT) of 9 patients/10 shoulders of the full scapula and shoulder were analyzed, and the muscle volumes of the subscapularis (SSC), infraspinatus (ISP) and teres minor muscles (TMM) were measured by manually marking the muscle contours on transverse slices and calculating the volume from software. Furthermore, the glenoid retroversion and glenohumeral distance were measured.

Results
The mean glenoid retroversion was − 16° (− 7° to − 31°). The observed mean glenohumeral distance was 4.0 mm (0 to 6.8 mm). Our study population showed a significant muscle volume imbalance between the subscapularis muscle and the infraspinatus and teres minor muscles (192 vs. 170 ml; p = 0.005). There was no significant correlation between the subscapularis muscle volume and the glenohumeral distance (r = 0.068), (p = 0.872).

Conclusion
The muscle volume of the SSC in patients with PSSH was significantly higher than the muscle volume of the posterior force couple (ISP and TMM). This novel finding, albeit in a small series of patients, may support the theory that transverse force couple imbalance is associated with PSSH.

Level of evidence
Level 4 – Case series with no comparison group.
Evaluation of metabolic equivalents of task (METs) in the preoperative assessment in aortic repair
Authors: Zientara Alicja , Schwegler Igor , Dzemali Omer , Bruijnen Hans , Bernheim Alain , Dick Florian , Attigah Nicolas 
Published: March 2021

Abstract
Background
Reliable prediction of the preoperative risk is of crucial importance for patients undergoing aortic repair. In this retrospective cohort study, we evaluated the metabolic equivalent of task (MET) in the preoperative risk assessment with clinical outcome in a cohort of consecutive patients.

Methods
Retrospective analysis of prospectively collected data in a single center unit of 296 patients undergoing open or endovascular aortic repair from 2009 to 2016. The patients were divided into four anatomic main groups (infrarenal (endo: n = 94; open: n = 88), juxta- and para-renal (open n = 84), thoraco-abdominal (open n = 13) and thoracic (endo: n = 11; open: n = 6). Out of these, 276 patients had a preoperative statement of their functional capacity in metabolic units and were evaluated concerning their postoperative outcome including survival, in-hospital mortality, postoperative complications, myocardial infarction and stroke, and the need of later cardiovascular interventions.

Results
The median follow-up of the cohort was 10.8 months. Patients with < 4MET had a higher incidence of diabetes mellitus (p = 0.0002), peripheral arterial disease (p < 0.0001), history of smoking (p = 0.003), obesity (p = 0.03) and chronic obstructive pulmonary disease (p = 0.05). Overall in-hospital mortality was 4.4% (13 patients). There was no significant difference in the survival between patients with a functional capacity of more than 4 MET (220 patients, mean survival: 74.5 months) and patients with less than 4 MET (56 patients, mean survival: 65.4 months) (p = 0.64). The mean survival of the infrarenal cohort (n = 169) was 74.3 months with no significant differences between both MET groups (> 4 MET: 131 patients, mean survival 75.5 months; < 4 MET: 38 patients, mean survival 63.6 months. p = 0.35). The subgroup after open surgical technique with less than 4 MET had the lowest mean survival of 38.8 months. In 46 patients with > 4MET (20.9%) perioperative complications occurred compared to the group with < 4MET with 18 patients (32.1%) (p = 0.075). There were no significant differences in both groups in the late cardiovascular interventions (p = 0.91) and major events including stroke and myocardial infarction (p = 0.4) monitored during the follow up period. The risk to miss a potential need for cardiac optimization in patients > 4MET was 7%.

Conclusion
The functional preoperative evaluation by MET in patients undergoing aortic surgery is a useful surrogate marker of perioperative performance but cannot be seen as a substitute for preoperative cardiopulmonary testing in selected individuals. Trial registration clinicaltrials.gov, registration number NCT03617601 (retrospectively registered).
Genome-scale model reconstruction of the methylotrophic yeast Ogataea polymorpha
Authors: Liebal Ulf W , Fabry Brigida A , Ravikrishnan Aarthi , Schedel Constantin VL , Schmitz Simone , Blank Lars M , Ebert Birgitta E 
Published: March 2021

Abstract
Background
Ogataea polymorpha is a thermotolerant, methylotrophic yeast with significant industrial applications. While previously mainly used for protein synthesis, it also holds promise for producing platform chemicals. O. polymorpha has the distinct advantage of using methanol as a substrate, which could be potentially derived from carbon capture and utilization streams. Full development of the organism into a production strain and estimation of the metabolic capabilities require additional strain design, guided by metabolic modeling with a genome-scale metabolic model. However, to date, no genome-scale metabolic model is available for O. polymorpha.

Results
To overcome this limitation, we used a published reconstruction of the closely related yeast Komagataella phaffii as a reference and corrected reactions based on KEGG and MGOB annotation. Additionally, we conducted phenotype microarray experiments to test the suitability of 190 substrates as carbon sources. Over three-quarter of the substrate use was correctly reproduced by the model and 27 new substrates were added, that were not present in the K. phaffii reference model.

Conclusion
The developed genome-scale metabolic model of O. polymorpha will support the engineering of synthetic metabolic capabilities and enable the optimization of production processes, thereby supporting a sustainable future methanol economy.