bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a dual hybrid AAV vector for endothelial-targeted expression of von Willebrand factor
Authors: Barbon Elena , Kawecki Charlotte , Marmier Solenne , Sakkal Aboud , Collaud Fanny , Charles Severine , Ronzitti Giuseppe , Casari Caterina , Christophe Olivier D. , Denis Cécile V. , Lenting Peter J. , Mingozzi Federico 
Published: January 2021

AbstractVon Willebrand disease (VWD), the most common inherited bleeding disorder in humans, is caused by quantitative or qualitative defects in von Willebrand factor (VWF). VWD represents a potential target for gene therapy applications, as a single treatment could potentially result in a long-term correction of the disease. In recent years, several liver-directed gene therapy approaches have been exploited for VWD, but their efficacy was generally limited by the large size of the VWF transgene and the reduced hemostatic activity of the protein produced from hepatocytes. In this context, we aimed at developing a gene therapy strategy for gene delivery into endothelial cells, the natural site of biosynthesis of VWF. We optimized an endothelial-specific dual hybrid AAV vector, in which the large VWF cDNA was put under the control of an endothelial promoter and correctly reconstituted upon cell transduction by a combination of trans-splicing and homologous recombination mechanisms. In addition, we modified the AAV vector capsid by introducing an endothelial-targeting peptide to improve the efficiency for endothelial-directed gene transfer. This vector platform allowed the reconstitution of full-length VWF transgene both in vitro in human umbilical vein endothelial cells and in vivo in VWD mice, resulting in long-term expression of VWF.
Effectiveness of Dual Medication Therapy (Oral Acetaminophen and Oral Ibuprofen) for the Management of Patent Ductus Arteriosus in Extremely Premature Infants: A Feasibility Trial
Authors: Shah Sanket D. , Makker Kartikeya , Nandula Padma , Smotherman Carmen , Kropf Andrea , Hudak Mark L. 
Published: January 2021

Objective The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA).
Study Design In a prospective case–control cohort study (July 2017–May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The p-values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%.
Results Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], p = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21–0.96, adjusted p-value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10–0.47, adjusted p-value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment.
Conclusion DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile.
Key Points
Isolated and On Guard: Preparing Neonatal Intensive Care Unit Families for Life with Hydrocephalus
Authors: Dorner Rebecca A. , Boss Renee D. , Burton Vera J. , Raja Katherine , Robinson Shenandoah , Lemmon Monica E. 
Published: January 2021

Objective This study was aimed to characterize the parent experience of caring for a child with posthemorrhagic hydrocephalus and to describe parent preferences for counseling in the neonatal period and beyond.
Study Design This was a qualitative interview study. Parents of infants born preterm with posthemorrhagic hydrocephalus completed semistructured interviews. Data were analyzed using a content analysis approach.
Results Thematic saturation was reached on parent communication preferences after 10 interviews. Parent experiences of infant hydrocephalus broadly fell into two time periods, the neonatal intensive care unit (NICU) and after NICU discharge. The themes of uncertainty, isolation, hypervigilance, and the need for advocacy were common to each phase.
Conclusion Parents expressed interest in the development of tiered NICU counseling tools that would provide evidence-based and family-centric information to (1) initiate connections with community and peer resources and (2) combat the isolation and hypervigilance that characterized their family experience of living with hydrocephalus.
Key Points
Antimicrobial Prophylaxis Use in the Neonatal Intensive Care Unit: An Antimicrobial Stewardship Target That Deserves Attention!
Authors: Viel-Thériault Isabelle , Agarwal Amisha , Bariciak Erika , Le Saux Nicole , Thampi Nisha 
Published: January 2021

Objective Previous analyses of neonatal intensive care units (NICU) antimicrobial stewardship programs have identified key contributors to overall antibiotic use, including prolonged empiric therapy >48 hours for early-onset sepsis (EOS). However, most were performed in mixed NICU settings with onsite birthing units, resulting in a high proportion of inborn patient admissions. The study aimed to describe and analyze the most common reasons for antimicrobial use in an outborn tertiary care NICU.
Study Design This was a 10-month review of all antimicrobial doses prescribed in a 20-bed level III NICU. The primary outcome was the total days of therapy (DOT) and length of therapy (LOT) for each clinical indication. Secondary outcomes included total DOT for each antimicrobial and appropriateness of antimicrobial courses.
Results Of 235 antibiotic courses and 1,899 DOT (519 DOT/1,000 patient days) prescribed in 173 infants during the study period, the most common indications were suspected EOS, followed by prophylaxis. Among the 85 DOT/1,000 patient days (PD; 38 courses) prescribed for prophylaxis, 52.5 DOT/1,000 PD (25 courses; 62%) were for surgical prophylaxis. Of 17 postoperative antibiotic courses, 15 (88.2%) were deemed to be inappropriate mostly due to a duration greater than 24 hours postoperatively (n = 13; median LOT = 3 days).
Conclusion Surgical prophylaxis is a common reason for antimicrobial misuse in outborn NICU. NICU-based prospective audit and feedback between neonatologists and antimicrobial stewardship teams alone may not be impactful in this setting. Partnerships with neonatologists and surgeons will be key to achieving the target of less than 24 hours of postoperative antimicrobials.
Key Points
Effect of Hypothermia on Serum Myelin Basic Protein and Tumor Necrosis Factor–α in Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Wang Qiuli , Lv Hongyan , Wu Sujing , Song Junxia , Li Junqin , Huo Haihua , Ren Pengshun , Li Lianxiang 
Published: January 2021

Objective Multiple randomized controlled trials have shown that hypothermia is a safe and effective treatment for neonatal moderate or severe hypoxic-ischemic encephalopathy (HIE). The neuroprotective mechanisms of hypothermia need further study. The aim of this study was to investigate the effect of hypothermia on the serum levels of myelin basic protein (MBP) and tumor necrosis factor-α (TNF-α) as well as neurodevelopmental outcomes in neonatal HIE.
Study Design Eighty-five neonates with moderate-to-severe HIE were divided into a hypothermia group (n = 49) and a control group (n = 36). Serum levels of MBP and TNF-α within 6 hours after birth and after 3 days of treatment were determined by enzyme-linked immunosorbent assay, and neurodevelopmental outcome at the age of 12 to 15 months was assessed by using the Gesell development scale.
Results After 3 days of treatment, serum levels of MBP and TNF-α in the control group were not significantly different from levels before treatment (p > 0.05), and serum levels of MBP and TNF-α in the hypothermia group were significantly lower than levels before treatment (p < 0.05). Serum levels of MBP and TNF-α were significantly negatively correlated with developmental quotient (DQ; r =  − 0.7945, p = 0.0000; r =  − 0.7035, p = 0.0000, respectively). Serum levels of MBP and TNF-α in neurodevelopmentally impaired infants were significantly higher than those in infants with suspected neurodevelopmental impairment and those in neurodevelopmentally normal infants (both p < 0.01). The rate of reduction of neurodevelopmental impairment was higher among infants in the hypothermia group than among those in the control group (χ2 = 16.3900, p < 0.05).
Conclusion Hypothermia can reduce serum levels of MBP and TNF-α in neonates with HIE. Inhibiting the release of TNF-α may be one of the mechanisms by which hypothermia protects the myelin sheath.
Key Points
Attitudes of Argentinean Neonatologists toward Resuscitation of Infants with Trisomies 21, 18, and 13: A Multicenter Survey
Authors: Silberberg Agustín , Etchegaray Adolfo , Juárez Peñalva Sofía , Villar Marcelo J. , Musante Gabriel 
Published: January 2021

Objective This study was aimed to explore the attitude of Argentinean neonatologists in the delivery room on resuscitating infants with trisomies.
Study Design An anonymous questionnaire was completed by neonatologists staffing level-III neonatal intensive care units (NICUs) on resuscitation of children with trisomies 21, 18, and 13. Potential sociocultural factors influencing the decision to resuscitate were included.
Results Overall, 314 neonatologists in 34 units in the Buenos Aires region participated (response rate of 54%). The position of neonatologists regarding the resuscitation in the delivery room was that 98% would resuscitate newborns with trisomy 21, and 47% with trisomy 18 or trisomy 13. Resuscitation of newborns with trisomy 18 or trisomy 13 by neonatologists was significantly associated with working in the public sector, religious beliefs, and legal framework.
Conclusion With improvement in the management and treatment of infants with trisomies 18 and 13, Argentinean neonatologists showed a favorable attitude toward resuscitating them in the delivery room.
Key Points
Association between Low Cord Serum Cortisol Level and Transient Tachypnea of the Newborn in Late Preterm and Term Neonates Delivered by Elective Cesarean Section
Authors: Umran Raid M.R. , Khalil Roaa M. 
Published: January 2021

Objective Transient tachypnea of the newborn (TTN), a common neonatal respiratory morbidity, is associated with failure of adequate clearance of fetal lung fluid. Glucocorticoids have an important role in lung maturity and the mechanisms of lung fluid clearance. The aim of this study is to assess the association between umbilical cord cortisol levels and transient TTN in late preterm and term neonates delivered by elective cesarean section (CS).
Study Design A case-control study of 37 newborns diagnosed with TTN (cases) was compared with 40 healthy newborns (controls). All infants were delivered by elective CS without labor. Umbilical cord cortisol levels were measured using enzyme-linked immunosorbent assay.
Results Mean cord cortisol levels were significantly lower in cases than controls (131.36 vs. 233.32 nmol/L, p = 0.0001; odds ratio [OR] = 3.7; 95% confidence interval [CI]: 1.40–9.53), respectively. Cord serum cortisol correlated inversely with the duration of tachypnea and the respiratory rate (r =  − 0.678 and −0.535, respectively).
Conclusion Umbilical cord cortisol levels are significantly lower in newborns with transient TTN, and lower cortisol levels are associated with an increased respiratory rate and longer duration of admission. Antenatal glucocorticoids can be recommended for late preterm delivered by CS.
Key Points
Cardiopulmonary Function Abnormalities in Cohort of Adults following Bronchopulmonary Dysplasia as Preterm Infants
Authors: Lasry Ariane , Kavabushi Patrick , Canakis Anne-Marie , Luu Thuy M. , Nuyt Anne-Monique , Perreault Thérèse , Simoneau Jessica , Landry Jennifer , Altit Gabriel 
Published: January 2021

Objective This study was aimed to describe the cardiopulmonary profiles of adult patients with bronchopulmonary dysplasia (BPD), comparing them to normative adult values.
Study Design This study presents a retrospective chart review of all BPD patients followed in the adult BPD clinic, identified from institutional and archive databases, born preterm at ≤33 weeks of estimated gestational age (EGA) between January 1980 and December 2000.
Results Forty-four patients with BPD (26.4 ± 2.7 weeks of EGA) were included. Average age at follow-up was 19 years. Majority (61.4%) of the patients had a diagnosis of asthma. Mean spirometry values were: first second of forced expiration (FEV1) 74.1%, forced vital capacity (FVC) 80.7%, and FEV1/FVC 82.5%. Echocardiography (ECHO) images were reviewed, left ventricular (LV) structure and performance did not differ between obstructive and nonobstructive pulmonary function test (PFT) groups, but values of LV longitudinal strain were 4.8% lower than expected normal for adults. Patients with obstructive PFT had additional decreased right ventricular (RV) function by ECHO.
Conclusion BPD patients in this study were found to have a burden of cardiorespiratory alterations that persisted into adulthood, with RV performance abnormalities found among patients with obstructive PFT.
Key Points
Thiol-Disulfide Homeostasis in Neonatal Patients with Urinary Tract Infection
Authors: Öktem Ahmet , Zenciroğlu Ayşegül , Dilli Dilek , Bidev Duygu , Özyazıcı Ahmet , Özçelik Emine , Erel Özcan 
Published: January 2021

Objective Urinary tract infection (UTI) is a disease that can cause significant complications in the neonatal period. The thiol-disulfide homeostasis is one of the important antioxidant defense mechanisms. The purpose of this study is to show the relationship between UTI and thiol-disulfide homeostasis in newborns.
Study Design In this prospective study, 40 newborns with UTI and 40 healthy controls were included. Thiol-disulfide tests (disulfide, native thiol, and total thiol levels) and septic screening tests were performed before and after antibiotherapy in UTI group. The control group was selected from healthy newborns who applied to the outpatient clinic.
Results The C-reactive protein and interleukin-6 levels were higher, while native thiol and native thiol/total thiol ratio were significantly lower in pretreatment group compared with posttreatment and control group. Also, the levels of disulfide, ischemia modified albumin, disulfide/native thiol ratio, and disulfide/total thiol ratio were higher in pretreatment group compared with posttreatment group.
Conclusion The thiol-disulfide homeostasis is an important indicator of oxidative stress during infections. It is valuable to be detected with small amounts of serum in newborns. These molecules can be used to support the diagnosis of UTI in the newborn. Further studies are needed to define the role of thiol-disulfide homeostasis in the UTI of newborn.
Key Points
Clinical Study of 107 Hospitalized Patients with Peritonsillar Abscess
Authors: Wakisaka Risa , Kumai Takumi , Kishibe Kan , Takahara Miki , Katada Akihiro , Hayashi Tatsuya , Harabuchi Yasuaki 
Published: January 2021

AbstractWe conducted a retrospective analysis of the data of 107 cases of peritonsillar abscess treated at our hospital between January 2014 and December 2018. Data on age, sex, affected site, duration of hospitalization, method of drainage, presence/absence of laryngeal edema, antibacterial drugs used, and isolated bacteria were analyzed. Of the 107 patients, 71 were males and 36 were females; the median age was 44 years (range: 18–88 years).The left side was affected in 55 patients, the right side in 50 patients, and both sides in two patients. The abscess was localized in the superior pole in 71 patients, and in the inferior pole in 36 patients. Thirty-five patients had laryngeal edema, of which three underwent tracheotomy. Recurrence of the abscess was observed in 15 cases, with the recurrence developing within 3 months in 7 cases, and over a period of 3 years in 4 cases. As for the sensitivity of the causative bacteria to antibacterial drugs, 17% of the causative bacteria showed resistance to clindamycin, while none showed resistance to ampicillin/sulbactam (ABPC/SBT). We concluded that ABPC/SBT might be suitable for the initial treatment of peritonsillar abscess, and that we need to bear in mind the possibility of long-term recurrence.
Political corporate social responsibility in authoritarian contexts
Authors: Maier Anna-Lena 
Published: January 2021

AbstractPolitical CSR emphasizes the need for the democratic governance of business conduct through public deliberation, and expects multinational enterprises (MNEs) to contribute to self-regulation and public goods provision to fill the gaps left by unwilling or unable governments. In the under-researched context of autocracies, however, political pluralism and participation are severely limited, which confronts MNEs with limited governance spaces for such activities. In this article, Ideconstructthe assumptions on political–institutional context prevalent in political CSR and IB research on political and CSR activities of MNEs. Drawing on political science literature on state power and authoritarianism, Ireconstructpolitical CSR in the political–institutional context of authoritarianism, using different autocracies across the globe as illustrative examples. I elucidate the boundaries and room for responsible business policies in autocracies drawing on a framework I developed that distinguishes between high- and low-capacity autocracies. My framework implies that MNEs face constraints in autocracies with regard to public deliberation and self-regulation, while there is considerable room for public goods provision. Finally, I explain why the normative desirability for the former two is high, whereas the normative desirability of public goods provision through MNEs in authoritarian contexts is lower given its implications for stabilization of autocratic rule.
Normative Reference Values, Reliability, and Item-Level Symptom Endorsement for the PROMIS® v2.0 Cognitive Function-Short Forms 4a, 6a and 8a
Authors: Iverson Grant L , Marsh Jacqueline M , Connors Eric J , Terry Douglas P 
Published: January 2021

Abstract

Objective
Reliable, valid, and precise measures of perceived cognitive functioning are useful in clinical practice and research. We present normative data, internal consistency statistics, item-level symptom endorsement, and the base rates of symptoms endorsed for the PROMIS® v2.0 Cognitive Function-Short Forms.

Method
The four-, six -, and eight-item short form of the PROMIS® v2.0 Cognitive Function scale assess subjective cognitive functioning. We stratified the normative sample from the U.S. general population (n = 1,009; 51.1% women) by gender, education, health status, self-reported history of a depression or anxiety diagnosis, and recent mental health symptoms (i.e., feeling anxious or depressed in the past week) and examined cognitive symptom reporting.

Results
Internal consistency was measured using Cronbach’s alpha and ranged from .85 to .95 for all three forms, across all groups. Mann–Whitney U test comparisons showed that individuals with past or present mental health difficulties scored significantly lower (i.e., worse perceived cognitive functioning) on the self-report questionnaires, particularly the eight-item form (history of depression, men: p &lt; .001, Cohen’s d = 1.07; women: p &lt; .001, d = .99; history of anxiety, men: p &lt; .001, d = 1.06; women: p &lt; .001, d = .98; and current mental health symptoms, men: p &lt; .001, d = 1.38; women: p &lt; .001, d = 1.19).

Conclusions
All three short forms of the PROMIS® v2.0 Cognitive Function scale had strong internal consistency reliability, supporting its use as a reliable measure of subjective cognitive functioning. The subgroup differences in perceived cognitive functioning supported the relationship between emotional and cognitive well-being. This study is the first to present normative values and base rates for several community-dwelling subgroups, allowing for precise interpretation of these measures in clinical practice and research.
Comparative performances of nomograms and conditional survival after resection of adrenocortical cancer
Authors: de Jong M C , Khan S , Christakis I , Weaver A , Mihai R 
Published: January 2021

Abstract

Background
Adrenocortical carcinomas (ACCs) carry a poor prognosis. This study assessed the comparative performance of existing nomograms in estimating the likelihood of survival, along with the value of conditional survival estimation for patients who had already survived for a given length of time after surgery.

Methods
This was an observational study based on a prospectively developed departmental database that recorded details of patients operated for ACC in a UK tertiary referral centre.

Results
Of 74 patients with ACC managed between 2001 and 2020, data were analysed for 62 patients (32 women and 30 men, mean(s.d.) age 51(17) years) who had primary surgical treatment in this unit. Laparoscopic (9) or open adrenalectomies (53) were performed alone or in association with a multivisceral resection (27). Most of the tumours were left-sided (40) and 18 were cortisol-secreting.
Overall median survival was 33 months, with 1-, 3- and 5-year survival rates of 79, 49, and 41 per cent respectively. Age over 55 years, higher European Network for Study of Adrenal Tumours stage, and cortisol secretion were associated with poorer survival in univariable analyses. Four published nomograms suggested widely variable outcomes that did not correlate with observed overall survival at 1, 3 or 5 years after operation. The 3-year conditional survival at 2 years (probability of surviving to postoperative year 5) was 65 per cent, compared with a 5-year actuarial survival rate of 41 per cent calculated from the time of surgery.

Conclusion
Survival of patients with ACC correlates with clinical parameters but not with published nomograms. Conditional survival might provide a more accurate estimate of survival for patients who have already survived for a certain amount of time after resection.