bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Executive Orders and Proclamations to Create Immigration Policy: Trump in Historical Perspective
Authors: Waslin Michele 
Published: March 2020

Executive Summary This article examines presidential immigration policy making through executive orders (EOs) and proclamations. Donald Trump’s overall volume of EOs has been remarkably similar to that of other presidents, while his number of proclamations has been relatively high. His immigration-related EOs and proclamations, however, diverge from those of his predecessors in several ways. Of the 56 immigration-related EOs and 64 proclamations issued since 1945, Trump has issued 10 and nine, respectively. Overall, about 1 percent of all EOs and proclamations during this period have been immigration related, compared to 8 percent of Trump’s EOs and 2.4 percent of Trump’s proclamations. In a sharp departure from previous presidents, a greater share of his EOs and proclamations have been substantive policy-making documents intended to restrict admissions of legal immigrants and increase enforcement along the border and in the interior of the United States. This article explores Trump’s unorthodox use of executive tools to make immigration policy, circumventing Congress and even members of his own administration. It recommends that: Congress should hold oversight hearings and should consider revoking or modifying EOs and proclamations that have been issued pursuant to the authority provided to the president by Congress, as opposed to those based on the executive’s constitutional authority. Advocacy organizations should continue to challenge the president’s executive actions, the insufficient process and consultation leading to them, their statutory or constitutional justification, and their impact. Congress should take an inventory of the immigration authorities it has delegated, both explicitly and implicitly, to the executive branch and determine when this authority can and should be limited. Congress should pass legislation to update and reform the US immigration system, and thus clarify its intentions regarding US immigration law, policy, and executive authority in this area.
Outcomes Following Ankle Fracture Fixation With or Without Ankle Arthroscopy
Authors: Smith Kenneth S. , Drexelius Katherine , Challa Shanthan , Moon Daniel K. , Metzl Joshua A. , Hunt Kenneth J. 
Published: March 2020

Background: Ankle fractures are one of the most common orthopedic injuries, and although most patients have a satisfactory outcome following operative fixation, there are patients that have persistent pain despite anatomic reduction. Intra-articular injuries have been suggested as one potential cause of these suboptimal outcomes. Our study assesses the clinical impact of performing an ankle arthroscopy during ankle fracture open reduction and internal fixation (ORIF). Methods: This was a retrospective chart review of all patients who underwent operative fixation of a bimalleolar or trimalleolar ankle fracture at our institution from 2014 through 2018. We extracted all demographic data, fracture pattern, operative procedures performed, tourniquet times, arthroscopic findings and any arthroscopic interventions. We then conducted a phone and e-mail survey. Our study included 213 total patients (142 traditional ORIF, 71 ORIF plus arthroscopy) with an average age of 40 years. The average follow-up was 32.4 months with a survey follow-up rate of 50.7% (110/213). Results: The average tourniquet time for the arthroscopy cohort was 10 minutes longer (89 minutes vs 79 minutes). During the arthroscopy, there was a 28% (20/71) rate of full-thickness osteochondral lesions, 33% (24/71) rate of loose bodies, and a 49% (35/71) rate of partial-thickness cartilage injury. The mean Patient Reported Outcome Information System (PROMIS) physical function score among Weber B fibula fractures was 45.8 and 42.3 in the arthroscopy and nonarthroscopy groups, respectively ( P = .012). In addition, the patient satisfaction rate in Weber B fibula fractures was higher in those patients who underwent arthroscopy compared with ORIF alone (93% vs 75%, P = .05). Patients who had a tibiotalar joint dislocation at the time of the ankle fracture had a significantly higher PROMIS physical function score (46.6 vs 40.2, P = .005) when their surgery included arthroscopy. Conclusion: Ankle arthroscopy at the time of ORIF led to statistically significant improvements in patient-reported outcomes for Weber B fibula fractures and ankle dislocations. There was no increase in complication rates and the arthroscopy took 10 minutes longer on average. Level of Evidence: Level III, retrospective cohort study.
Talar Osteonecrosis After Subchondroplasty for Acute Lateral Ligament Injuries: Case Series
Authors: Foran Ian M. , Bohl Daniel D. , Vora Anand M. , Mehraban Nasima , Hamid Kamran S. , Lee Simon 
Published: March 2020

Talar osteonecrosis is a well-described phenomenon following talar neck fracture, but is a rarely described complication after procedures about the foot and ankle. Here we describe the clinical course of 5 cases of talar osteonecrosis following injection of calcium phosphate into the talus (subchondroplasty) with or without acute lateral ligament repair after acute lateral ankle ligament injuries performed at an outside institution. Practitioners should be aware of this potentially devastating complication. Future research is indicated to determine the safety and efficacy of subchondroplasty for the talus. Level of Evidence: Level V, case series.
Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models
Authors: Tarantelli Chiara , Lange Martin , Gaudio Eugenio , Cascione Luciano , Spriano Filippo , Kwee Ivo , Arribas Alberto J. , Rinaldi Andrea , Jourdan Thibaud , Berthold Melanie , Sturz Andrea , Sperl Carolyn , Margheriti Francesco , Scalise Lorenzo , Gritti Giuseppe , Rossi Davide , Stathis Anastasios , Liu Ningshu , Zucca Emanuele , Politz Oliver , Bertoni Francesco 
Published: March 2020

Abstract
Copanlisib is a pan–class I phosphoinositide 3-kinase (PI3K) inhibitor with preferred activity toward PI3Kα and PI3Kδ. Despite the clear overall clinical benefit, the number of patients achieving complete remissions with the single agent is relatively low, a problem shared by the vast majority of targeted agents. Here, we searched for novel copanlisib-based combinations. Copanlisib was tested as a single agent, in combination with an additional 17 drugs in 26 cell lines derived from mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and T-cell lymphomas. In vivo experiments, transcriptome analyses, and immunoblotting experiments were also performed. Copanlisib as a single agent showed in vitro dose-dependent antitumor activity in the vast majority of the models. Combination screening identified several compounds that synergized with copanlisib. The strongest combination was with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. The benefit of the combination over single agents was also validated in an MZL xenograft model and in MCL primary cells, and was due to increased induction of apoptosis, an effect likely sustained by the reduction of the antiapoptotic proteins myeloid cell leukemia 1 (MCL1) and BCL-XL, observed in MCL and MZL cell lines, respectively. These data supported the rationale for the design of the Swiss Group for Clinical Cancer Research (SAKK) 66/18 phase 1 study currently exploring the combination of copanlisib and venetoclax in relapsed/refractory lymphomas.
Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status
Authors: Shrestha Raksha , Sakata-Yanagimoto Mamiko , Maie Koichiro , Oshima Motohiko , Ishihara Masatomo , Suehara Yasuhito , Fukumoto Kota , Nakajima-Takagi Yaeko , Matsui Hirotaka , Kato Takayasu , Muto Hideharu , Sakamoto Tatsuhiro , Kusakabe Manabu , Nannya Yasuhito , Makishima Hideki , Ueno Hiroo , Saiki Ryunosuke , Ogawa Seishi , Chiba Kenichi , Shiraishi Yuichi , Miyano Satoru , Mouly Enguerran , Bernard Olivier A. , Inaba Toshiya , Koseki Haruhiko , Iwama Atsushi , Chiba Shigeru 
Published: March 2020

AbstractLoss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events in acute myeloid leukemia (AML) as well as in preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 mutations are infrequent in AML, but the level of TET3 expression in HSCs has been found to decline with age. We examined the impact of gradual decrease of TET function in AML development by generating mice with Tet deficiency at various degrees. Tet2f/f and Tet3f/f mice were crossed with mice expressing Mx1-Cre to generate Tet2f/wtTet3f/fMx-Cre+ (T2ΔT3), Tet2f/fTet3f/wtMx-Cre+ (ΔT2T3), and Tet2f/fTet3f/fMx-Cre+ (ΔT2ΔT3) mice. All ΔT2ΔT3 mice died of aggressive AML at a median survival of 10.7 weeks. By comparison, T2ΔT3 and ΔT2T3 mice developed AML at longer latencies, with a median survival of ∼27 weeks. Remarkably, all 9 T2ΔT3 and 8 ΔT2T3 mice with AML showed inactivation of the remaining nontargeted Tet2 or Tet3 allele, respectively, owing to exonic loss in either gene or stop-gain mutations in Tet3. Recurrent mutations other than Tet3 were not noted in any mice by whole-exome sequencing. Spontaneous inactivation of residual Tet2 or Tet3 alleles is a recurrent genetic event during the development of AML with Tet insufficiency.
Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma
Authors: Merryman Reid W. , Edwin Natasha , Redd Robert , Bsat Jad , Chase Matthew , LaCasce Ann , Freedman Arnold , Jacobson Caron , Fisher David , Ng Samuel , Crombie Jennifer , Kim Austin , Odejide Oreofe , Davids Matthew S. , Brown Jennifer R. , Jacene Heather , Cashen Amanda , Bartlett Nancy L. , Mehta-Shah Neha , Ghobadi Armin , Kahl Brad , Joyce Robin , Armand Philippe , Jacobsen Eric 
Published: March 2020

Abstract
The addition of high-dose cytarabine to rituximab/bendamustine (RB) induction could improve outcomes for transplant-eligible patients with mantle cell lymphoma (MCL). We conducted a pooled analysis of 2 phase 2 trials and an off-trial cohort each testing 3 cycles of RB and 3 cycles of rituximab/high-dose cytarabine (RC) followed by autologous stem cell transplantation (ASCT) among untreated, transplant-eligible patients with MCL. Dana-Farber Cancer Institute (DFCI) and Washington University in St. Louis (WUSTL) led separate phase 2 trials testing sequential and alternating cycles of RB/RC, respectively. Patients treated at DFCI with sequential RB/RC off trial were retrospectively identified. Minimal residual disease (MRD) was assessed in the DFCI trial. A total of 88 patients (23 DFCI trial, 18 WUSTL trial, and 47 off trial) received RB/RC; 92% of patients completed induction, and 84% underwent planned consolidative ASCT. Grade 3 or 4 adverse events among trial patients included lymphopenia (88%), thrombocytopenia (85%), neutropenia (83%), and febrile neutropenia (15%). There were no treatment-related deaths during induction and 2 following ASCT. Among 87 response-evaluable patients, the end-of-induction overall and complete response rates were 97% and 90%, respectively. After a median follow-up of 33 months, 3-year progression-free survival and overall survival were 83% and 92%, respectively. Patients undergoing MRD testing experienced prolonged MRD negativity after ASCT with emergence of MRD occurring in only 1 patient who subsequently relapsed. RB/RC followed by ASCT achieves high rates of durable remissions in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT01661881 (DFCI trial) and #NCT02728531 (WUSTL trial).
The influence of blood on the human gut microbiome
Authors: Chénard Thierry , Malick Mandy , Dubé Jean , Massé Eric 
Published: March 2020

Abstract
Background
Colorectal cancer (CRC) is one of the prevailing causes of cancer mortality in the world. A common screening test for CRC is based on the human hemoglobin immunochemical based fecal occult blood test (iFOBT), which consists in the detection of blood in the patient’s stool. In addition to iFOBT, recent studies support the use of the gut microbiome as a biomarker for CRC prediction. However, these studies did not take into account the effect of blood itself on the microbiome composition, independently of CRC. Therefore, we investigated the microbiome of patients undergoing the iFOBT screening in order to determine the effect of blood alone. Our cohort consisted of patients who had no blood in their stools (n = 265) or did have blood but no underlying precancerous or cancerous lesions (n = 235). We also identified bacterial taxa specifically associated with the presence of blood in stools.

Results
We observed significant differences in the intestinal bacterial composition that could be solely caused by the presence of blood in stools. More precisely, we identified 12 bacterial species showing significant differences in abundance between both our study groups. These species, Bacteroides uniformis, Collinsella aerofaciens, Eggerthella lenta and Clostridium symbiosum demonstrated increased abundance in the presence of blood. In contrast, the species Prevotella copri, Coprococcus eutactus and catus, Faecalibacterium prausnitzii, Roseburia faecis, Blautia obeum, Gemmiger formicilis and Clostridium celatum showed decreased abundance in patients with blood in their stools. Notably, we found multiple taxa that were reported in previous studies linking microbiome composition and diseases.

Conclusions
We show that, in the absence of disease, blood in the stools has a major influence on the composition of the microbiome. Our data suggest that blood itself should be taken into consideration when investigating the microbiome signatures of intestinal diseases.
Cardiac surgical outcome prediction by blood pressure variability indices Poincaré plot and coefficient of variation: a retrospective study
Authors: Packiasabapathy Senthil , Prasad Varesh , Rangasamy Valluvan , Popok David , Xu Xinling , Novack Victor , Subramaniam Balachundhar 
Published: March 2020

Abstract
Background
Recent literature suggests a significant association between blood pressure variability (BPV) and postoperative outcomes after cardiac surgery. However, its outcome prediction ability remains unclear. Current prediction models use static preoperative patient factors. We explored the ability of Poincaré plots and coefficient of variation (CV) by measuring intraoperative BPV in predicting adverse outcomes.

Methods
In this retrospective, observational, cohort study, 3687 adult patients (> 18 years) undergoing cardiac surgery requiring cardio-pulmonary bypass from 2008 to 2014 were included. Blood pressure variability was computed by Poincare plots and CV. Standard descriptors (SD) SD1, SD2 were measured with Poincare plots by ellipse fitting technique. The outcomes analyzed were the 30-day mortality and postoperative renal failure. Logistic regression models adjusted for preoperative and surgical factors were constructed to evaluate the association between BPV parameters and outcomes. C-statistics were used to analyse the predictive ability.

Results
Analysis found that, 99 (2.7%) patients died within 30 days and 105 (2.8%) patients suffered from in-hospital renal failure. Logistic regression models including BPV parameters (standard descriptors from Poincare plots and CV) performed poorly in predicting postoperative 30-day mortality and renal failure [Concordance(C)-Statistic around 0.5]. They did not add any significant value to the standard STS risk score [C-statistic: STS alone 0.7, STS + BPV parmeters 0.7].

Conclusions
In conclusion, BP variability computed from Poincare plots and CV were not predictive of mortality and renal failure in cardiac surgical patients. Patient comorbid conditions and other preoperative factors are still the gold standard for outcome prediction. Future directions include analysis of dynamic parameters such as complexity of physiological signals in identifying high risk patients and tailoring management accordingly.
Bone complications in patients with multiple myeloma in five European countries: a retrospective patient chart review
Authors: Mateos María-Victoria , Fink Leah , Koneswaran Niranchana , Intorcia Michele , Giannopoulou Christina , Niepel Daniela , Cavo Michele 
Published: March 2020

AbstractBackgroundBone complications (pathologic fracture, spinal cord compression, surgery to bone and radiation to bone) are a common problem in patients with multiple myeloma (MM). We set out to provide insights into the real-world burden of bone complications in patients with newly diagnosed MM (NDMM).MethodsWe conducted a retrospective review of medical charts of patients with NDMM whose disease had progressed following first-line treatment in the 3 months before data collection in 2016 in five European countries (France, Germany, Italy, Spain and the United Kingdom).ResultsThe aggregated study population included 813 patients. Bone pain commonly led to MM diagnosis (63%) and 74% of all patients had two or more bone lesions at initiation of first-line treatment. Furthermore, 26% of patients experienced a new bone complication between MM diagnosis and disease progression following first-line treatment, despite 75% of individuals receiving bisphosphonates. Most bone complications (52%) occurred in the period before initiation of first-line treatment (mean duration: 2.3 months) and more than half of patients (56%) who experienced a new bone complication were hospitalised. Analgesics were used more frequently in patients with bone complications than in those without them (76% vs 50%, respectively). Furthermore, 51% of patients had renal impairment by the time first-line treatment was started. Overall, 25% of patients did not receive bisphosphonates for prevention of bone complications and one in four of those with renal impairment at initiation of first-line treatment did not receive bisphosphonates.ConclusionsBone complications are common in patients with NDMM. They are frequently associated with hospitalization and analgesic use. Data from this study, conducted in the era of novel anti-myeloma therapies and before the approval of denosumab for use in patients with MM, suggest that although most patients (75%) received bisphosphonates, use of anti-resorptive therapy for prevention of bone complications may be suboptimal in patients with NDMM, irrespective of renal function.
Physical function in patients newly diagnosed with multiple myeloma; a Danish cohort study
Authors: Larsen Rikke Faebo , Jarden Mary , Minet Lisbeth Rosenbek , Frølund Ulf Christian , Möller Sören , Abildgaard Niels 
Published: March 2020

Abstract
Background
Multiple myeloma is a cancer in the bone marrow causing bone destruction. Patients experience various symptoms related to the disease and/or treatment, such as pain and fatigue, leading to poorer quality of life. The symptom burden might affect physical function and physical activity levels, posing a risk of physical deterioration. The aim was to investigate whether physical function in newly diagnosed patients with multiple myeloma differs from the reference values of the normal population and other cancer patients.

Methods
The study is a cross sectional descriptive analysis of a prospective cohort of 100 patients newly diagnosed with multiple myeloma. Four physical function tests were carried out; Six-Minute-Walk-Test, Sit-to-Stand-Test, grip strength and knee extension strength. Age and gender specific results of physical function from the multiple myeloma population were compared to normative data and to data from other cancer populations.

Results
Of the 100 patients included, 73% had bone disease and 55% received pain relieving medicine. Mean age was 67.7 years (SD 10.3). Patients with multiple myeloma had significantly poorer physical function compared to normative data, both regarding aerobic capacity and muscle strength, although not grip strength. No differences in physical function were found between patients with multiple myeloma and other cancer populations.

Conclusions
Physical function in newly diagnosed Danish patients with multiple myeloma is lower than in the normal population. Exercise intervention studies are warranted to explore the value of physical exercise on physical function.

Trial registration
ClinicalTrials.gov, ID NCT02439112, registered 8 May 2015.
A girl with protein-losing enteropathy during a ketogenic diet: a case report
Authors: Wang Juan , Jiang Li , Cheng Min 
Published: March 2020

Abstract
Background
A ketogenic diet (KD) is an effective treatment for intractable epilepsy in children. Protein–losing enteropathy (PLE) is a rarely reported but serious complication of KDs.

Case presentation
A 3-month-old female patient presented with PLE while following a KD as treatment for intractable epilepsy. She also had genovariation of the STXBP1 gene. The patient suffered from general edema and hypoalbuminemia but no diarrhea. Esophagogastroduodenoscopy (EDG) revealed lymphatic ectasia in the lamina propria. We diagnosed her with intestinal lymphangiectasia, and after decreasing the KD ratio from 4:1 to 1.05:1, we successfully controlled her edema and hypoalbuminemia. As of now, the convulsions and hypsarrhythmia have disappeared, and the seizure-free state has lasted for 20 months.

Conclusions
PLE may be managed by decreasing the ketogenic ratio rather than discontinuing a KD since for some patients, a KD is the only effective therapy available at present.
Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and –independent apoptosis via Smad or Akt signaling pathways in HOS cells
Authors: Huang Cheng , Lu Hsu-Feng , Chen Yu-Hsuan , Chen Jui-Chieh , Chou Wen-Hsiang , Huang Hsiu-Chen 
Published: March 2020

Abstract
Background
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity. However, both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown.

Methods
To evaluate the growth inhibitory effects of CUR, DMC and BDMC on osteosarcoma (HOS and U2OS), breast (MDA-MB-231), and melanoma (A2058) cancer cells, we employed the MTT assay, annexin V-FITC /7-AAD staining, and clonogenic assay.

Results
CUR,DMC, and BDMC all decreased the viability of HOS, U2OS, MDA-MB-231, and A2058 cancer cells. Additionally, CUR,DMC, and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway. Furthermore, the combination of CUR,DMC, and BDMC synergistically reduced cell viability, colony formation and increased apoptosis than either two or a single agent in HOS cells.

Conclusions
The combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.
Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS
Authors: Liu Yibin , Cheng Jingfei , Siejka-Zielińska Paulina , Weldon Carika , Roberts Hannah , Lopopolo Maria , Magri Andrea , D’Arienzo Valentina , Harris James M. , McKeating Jane A. , Song Chun-Xiao 
Published: March 2020

AbstractWe present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.