***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : Bronchopulmonary dysplasia ( BPD ) is the focus of many intervention trials , yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians . Thus , we wished to define BPD by a st and ardized oxygen saturation monitoring at 36 weeks corrected age , and compare this physiologic definition with the st and ard clinical definition of BPD based solely on oxygen administration . METHODOLOGY : A total of 199 consecutive very low birthweight infants ( VLBW , 501 to 1500 g birthweight ) were assessed prospect ively at 36±1 weeks corrected age . Neonates on positive pressure support or receiving > 30 % supplemental oxygen were assigned the outcome BPD . Those receiving ≤30 % oxygen underwent a stepwise 2 % reduction in supplemental oxygen to room air while under continuous observation and oxygen saturation monitoring . Outcomes of the test were “ no BPD ” ( saturations ≥88 % for 60 minutes ) or “ BPD ” ( saturation < 88 % ) . At the conclusion of the test , all infants were returned to their baseline oxygen . Safety ( apnea , bradycardia , increased oxygen use ) , inter-rater reliability , test – retest reliability , and validity of the physiologic definition vs the clinical definition were assessed . RESULTS : A total of 199 VLBW were assessed , of whom 45 ( 36 % ) were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks corrected age . The physiologic definition identified 15 infants treated with oxygen who successfully passed the saturation monitoring test in room air . The physiologic definition diagnosed BPD in 30 ( 24 % ) of the cohort . All infants were safely studied . The test was highly reliable ( inter-rater reliability , κ=1.0 ; test – retest reliability , κ=0.83 ) and highly correlated with discharge home in oxygen , length of hospital stay , and hospital readmissions in the first year of life . CONCLUSIONS : The physiologic definition of BPD is safe , feasible , reliable , and valid and improves the precision of the diagnosis of BPD . This may be of benefit in future multicenter clinical trials OBJECTIVES This is a preliminary , single-center , prospect i ve study in the field of autologous cord blood transplant . We investigated the feasibility , safety , and tolerability of autologous whole cord blood transplant in extremely premature infants as a potential therapeutic modality to prevent developing complications related to prematurity . MATERIAL S AND METHODS This preliminary prospect i ve study ( Clinical Trials.gov identifier NCT02050971 ) included preterm infants born at less than 32 weeks of gestational age who developed anemia because of prematurity . Infants were assigned to 2 groups : ( 1 ) those receiving an autologous cord blood transfusion within 5 days postpartum ( n = 5 ) and ( 2 ) those who obtained only an allogeneic red blood cell transfusion when necessary ( n = 9 ; control group ) . Vital measurements were performed during and after transfusion , and peripheral blood pH , hematocrit , glucose , and calcium and potassium ion levels were measured over the next 4 days . RESULTS Oxygen saturation was significantly increased throughout the cord blood transfusion and in the subsequent 48 hours . No significant differences were found in vital measurements , such as arterial blood pressure ( mean , systolic , and diastolic ) or heart rate over the first 48 hours posttransfusion . Similarly , no significant differences were found in biochemical analyses of blood with the exception of pH level . We found initial pH level to be significantly augmented in the cord blood recipient group by the first day after transplant , which remained significantly higher for next 24 hours compared with that shown in the control group . CONCLUSIONS Collection , preparation , and short-term storage of unfrozen cord blood are feasible for clinical use . Our results showed general safety and tolerability of the procedure of whole autologous cord blood transplant in recruited preterm newborns . However , because our study group was small , these results need to be confirmed in further investigations with a larger patient cohort In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Background Mesenchymal stem cells ( MSC ) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia ( BPD ) . Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC . Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown . Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males . Objective To determine whether intra-tracheal ( IT ) administration of female MSC to neonatal rats with experimental BPD has more beneficial reparative effects as compared to IT male MSC . Methods Newborn Sprague-Dawley rats exposed to normoxia ( RA ) or hyperoxia ( 85 % O2 ) from postnatal day ( P ) 2- P21 were r and omly assigned to receive male or female IT bone marrow (BM)-derived green fluorescent protein ( GFP+ ) MSC ( 1 x 106 cells/50 μl ) , or Placebo on P7 . Pulmonary hypertension ( PH ) , vascular remodeling , alveolarization , and angiogenesis were assessed at P21 . PH was determined by measuring right ventricular systolic pressure ( RVSP ) and pulmonary vascular remodeling was evaluated by quantifying the percentage of muscularized peripheral pulmonary vessels . Alveolarization was evaluated by measuring mean linear intercept ( MLI ) and radial alveolar count ( RAC ) . Angiogenesis was determined by measuring vascular density . Data are expressed as mean ± SD , and analyzed by ANOVA . Results There were no significant differences in the RA groups . Exposure to hyperoxia result ed in a decrease in vascular density and RAC , with a significant increase in MLI , RVSP , and the percentage of partially and fully muscularized pulmonary arterioles . Administration of both male and female MSC significantly improved vascular density , alveolarization , RVSP , percent of muscularized vessels and alveolarization . Interestingly , the improvement in PH and vascular remodeling was more robust in the hyperoxic rodents who received MSC from female donors . In keeping with our hypothesis , male animals receiving female MSC , had a greater improvement in vascular remodeling . This was accompanied by a more significant decrease in lung pro-inflammatory markers and a larger increase in anti-inflammatory and pro-angiogenic markers in male rodents that received female MSC . There were no significant differences in MSC engraftment among groups . Conclusions Female BM-derived MSC have greater therapeutic efficacy than male MSC in reducing neonatal hyperoxia-induced lung inflammation and vascular remodeling . Furthermore , the beneficial effects of female MSC were more pronounced in male animals . Together , these findings suggest that female MSC maybe the most potent BM-derived MSC population for lung repair in severe BPD complicated by PH Bone marrow ( BM ) and subcutaneous adipose tissue ( Ad ) are both considered being prospect i ve sources of MSC for therapeutic applications . However , functional properties and therapeutic efficacy of MSC derived from different tissues of the same patient are still poorly investigated . In our study , BM-MSC and F-MSC cultures from 43 adult donors were evaluated in successive passages for immunophenotype , secretion of VEGF , SDF1 , MCP1 , IL6 and TGFβ1 , frequency of colony-forming units ( CFU-F ) , frequency of adipo- and osteo-progenitors ( CFU-Ad , CFU-Ost ) , and for onset of in vitro replicative senescence . We have demonstrated that at early passages ( P2-P4 or up to 14 - 15 in vitro population doublings ) BM- and Ad- derived MSC cultures are comparable in such important characteristics as proliferation rate ( population doubling time : 3,4±0,2 % in BM-MSC , 3±0,3 % in F-MSC ) , clonogenity ( CFU-F frequency : 32±5 % in BM-MSC , 31±5 % in F-MSC ) , differentiation potential ( CFU-Ad frequency : 10,4±2 % in BM-MSC , 13±3 % in F-MSC ; CFU-Ost frequency : 18,5±5,5 % in BM-MSC , 18±5 % in F-MSC ) , but differ significantly in abundance of CD146 + fraction within the sample ( 25±5 % in BM-MSC , 7±3 % in F-MSC ) and in a level of VEGF , SDF-1 , MCP1 and TGFβ1 secretion . We have also demonstrated that BM-MSC enter senescence after P3 - 4 while most of F-MSC did not show senescence features up to P6 - 8 . Together , these data demonstrate that specific properties of MSC from different sources should be always taken into account , when developing and optimizing the specific protocol s for MSC expansion and evaluation for each particular clinical application OBJECTIVE To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell ( MSC ) transplantation in preterm infants . STUDY DESIGN In a phase I dose-escalation trial , we assessed the safety and feasibility of a single , intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia ( BPD ) . The first 3 patients were given a low dose ( 1 × 10(7 ) cells/kg ) of cells , and the next 6 patients were given a high dose ( 2 × 10(7 ) cells/kg ) . We compared their adverse outcomes , including BPD severity , with those of historical case-matched comparison group . RESULTS Intratracheal MSC transplantation was performed in 9 preterm infants , with a mean gestational age of 25.3 ± 0.9 weeks and a mean birth weight of 793 ± 127 g , at a mean of 10.4 ± 2.6 days after birth . The treatments were well tolerated , without serious adverse effects or dose-limiting toxicity attributable to the transplantation . Levels of interleukin-6 , interleukin-8 , matrix metalloproteinase-9 , tumor necrosis factor α , and transforming growth factor β1 in tracheal aspirates at day 7 were significantly reduced compared with those at baseline or at day 3 posttransplantation . BPD severity was lower in the transplant recipients , and rates of other adverse outcomes did not differ between the comparison group and transplant recipients . CONCLUSION Intratracheal transplantation of allogeneic hUCB-derived MSCs in preterm infants is safe and feasible , and warrants a larger and controlled phase II study IMPORTANCE Bronchopulmonary dysplasia ( BPD ) remains a serious morbidity in very low-birth-weight ( VLBW ) infants ( < 1500 g ) . Deregionalization of neonatal care has result ed in an increasing number of VLBW infants treated in community hospitals with unknown impact on the development of BPD . OBJECTIVE To identify individual risk factors for BPD development and hospital variation of BPD rates across all levels of neonatal intensive care units ( NICUs ) within the California Perinatal Quality Care Collaborative . DESIGN , SETTING , AND PARTICIPANTS Retrospective cohort study ( January 2007 to December 2011 ) from the California Perinatal Quality Care Collaborative including more than 90 % of California 's NICUs . Eligible VLBW infants born between 22 to 29 weeks ' gestational age . EXPOSURES Varying levels of intensive care . MAIN OUTCOMES AND MEASURES Bronchopulmonary dysplasia was defined as continuous supplemental oxygen use at 36 weeks ' postmenstrual age . A combined outcome of BPD or mortality prior to 36 weeks was used . Multivariable logistic regression accounting for hospital as a r and om effect and gestational age as a risk factor was used to assess individual risk factors for BPD . This model was applied to determine risk-adjusted rates of BPD across hospitals and assess associations between levels of care and BPD rates . RESULTS The study cohort included 15,779 infants , of which 1534 infants died prior to 
    Output:
    
There is insufficient evidence to determine the safety and efficacy of MSCs  in the treatment or prevention of BPD in premature infants .