bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double‐blind, placebo‐controlled, dose‐titration trial
Authors: Wagner Kathryn R. , Kuntz Nancy L. , Koenig Erica , East Lilly , Upadhyay Sameer , Han Baoguang , Shieh Perry B.
Published: June 2021

Introduction/Aims

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene resulting in the absence of dystrophin. Casimersen is a phosphorodiamidate morpholino oligomer designed to bypass frameshift DMD mutations and produce internally truncated, yet functional, dystrophin protein in patients amenable to exon 45 skipping. Our primary study objective was to evaluate safety and tolerability of casimersen; the secondary objective was to characterize the plasma pharmacokinetics.

Methods

This multicenter, phase 1/2 trial enrolled 12 participants (aged 7‐21 years, who had limited ambulation or were nonambulatory) and comprised a 12‐week, double‐blind dose titration, then an open‐label extension for up to 132 weeks. During dose titration, participants were randomized 2:1 to weekly casimersen infusions at escalating doses of 4, 10, 20, and 30 mg/kg (≥2 weeks per dose), or placebo.

Results

Participants received casimersen for a mean 139.6 weeks. Treatment‐emergent adverse events (TEAEs) occurred in all casimersen‐ and placebo‐treated participants and were mostly mild (over 91.4%) and unrelated to casimersen or its dose. There were no deaths, dose reductions, abnormalities in laboratory parameters or vital signs, or casimersen‐related serious AEs. Casimersen plasma concentration increased with dose and declined similarly for all dose levels over 24 hours postinfusion. All pharmacokinetic parameters were similar at weeks 7 and 60.

Discussion

Casimersen was well tolerated in participants with DMD amenable to exon 45 skipping. Most TEAEs were mild, nonserious, and unrelated to casimersen. Plasma exposure was dose proportional with no suggestion of plasma accumulation. These results support further studies of casimersen in this population.
Development of an Effective Cryopreservation Protocol for Blue Catfish Oogonia
Authors: Abualreesh Muyassar , Myers Jaelen N. , Gurbatow Jeremy , Johnson Andrew , Xing De , Wang Jinhai , Li Shangjia , Coogan Michael , Vo Khoi , El Husseini Nour , Creamer David , Dunham Rex A. , Butts Ian A. E.
Published: June 2021

Long-term storage of oogonia and germ-line stem cells provides an alternative to the limitations associated with cryopreserving eggs of important fish species. These cell types are less vulnerable to the stresses of freezing. Cryopreservation has enormous potential for aquaculture advancement, but protocols must be developed for each species and cell type since its success hinges on various input factors. Blue Catfish Ictalurus furcatus were selected as the test species in this study because of the need to improve fry production of Blue Catfish ♂ × Channel Catfish I. punctatus ♀ hybrids, which can be facilitated by storing oogonia in gene banks. Our objective was to develop a freezing protocol for oogonia of this species. We tested different permeating and nonpermeating cryoprotectants, concentrations of these agents, and freezing rates. We proved that all three factors influenced postthaw recovery of oogonia. Of the permeating cryoprotectants, 1.0 M dimethyl sulfoxide resulted in the most live cells with the highest viability percentages, and adding 0.2 M lactose with 10% egg yolk further improved the results. There were also specific interactions in which the effects of concentration and freezing rate varied among the cryoprotectant treatments. The most effective freezing rate was −1.0°C/min, and cell viability was reduced at −2.5°C/min and −5.0°C/min. From these results, we propose adding 1.0 M dimethyl sulfoxide with 0.2 M lactose and 10% egg yolk to cryomedia and freezing it at a rate of −1.0°C/min. By developing a cryopreservation protocol for a commonly cultured catfish, this work may guide the development of protocols for other species of interest.
Ultrasound measurements of abdominal muscle thickness are associated with postmenstrual age at full oral feedings in preterm infants: A preliminary study
Authors: Nagel Emily M. , Hickey Marie , Teigen Levi M. , Kuchnia Adam , Schifsky Holly , Holm Tara , Earthman Carrie P. , Demerath Ellen , Ramel Sara E.
Published: June 2021

Background

A premature infant's discharge from the neonatal intensive care unit (NICU) is dependent on factors such as respiratory stability, adequate growth, and the ability to consume oral feeds. Once infants have achieved respiratory stability, a tool that can better predict age at discharge is desirable. Thus, we conducted a secondary data analysis to assess the association between ultrasound measurements of abdominal muscle thickness and postmenstrual age (PMA) at full oral feedings.

Methods

Forty‐nine (n = 49) healthy, premature infants (mean gestational age = 32 weeks) were recruited from the NICU. Anthropometric measurements and ultrasound measurements of the rectus abdominis were conducted when infants were medically stable. Fat‐free mass (FFM) was obtained using air displacement plethysmography. The relationship between ultrasound measurements of muscle thickness and PMA at full oral feedings was assessed using linear regression analysis. The relationship between FFMz‐scores and PMA at full oral feedings was also assessed for comparison.

Results

When adjusting for gestational age at birth, PMA at measurement, days of positive pressure respiratory support, weight, and length, ultrasound measurements of abdominal muscle thickness were independently, negatively associated with PMA at full oral feedings (β estimate: −0.71,P= .03).

Conclusion

Preliminary results suggest infants with greater abdominal muscle thickness may reach full oral feedings at an earlier PMA (nearly 1 week per millimeter). Thus, ultrasound measurements of abdominal muscle thickness may be helpful in assessing readiness for discharge in healthy preterm infants. Further research is needed for development and validation of a prediction equation.
Phase II Study of 5-Fluorouracil, Oxaliplatin plus Dasatinib (FOLFOX-D) in First-Line Metastatic Pancreatic Adenocarcinoma
Authors: George Thomas J. , Ali Azka , Wang Yu , Lee Ji-Hyun , Ivey Alison M. , DeRemer David , Daily Karen C. , Allegra Carmen J. , Hughes Steven J. , Fan Z. Hugh , Cameron Miles E. , Judge Andrew R. , Trevino Jose G.
Published: June 2021

Lessons Learned

Preclinical studies have demonstrated that Src inhibition through dasatinib synergistically enhances the antitumor effects of oxaliplatin. In this phase II, single-arm study, FOLFOX with dasatinib in previously untreated patients with mPC only showed only modest clinical activity, with a progressive-free survival of 4 months and overall survival of 10.6 months. Continued investigation is ongoing to better understand the role of Src inhibition with concurrent 5-fluorouracil and oxaliplatin in a subset of exceptional responders.

Background

Src tyrosine kinase activity is overexpressed in many human cancers, including metastatic pancreatic cancer (mPC). Dasatinib is a potent inhibitor of Src family of tyrosine kinases. This study was designed to investigate whether dasatinib can synergistically enhance antitumor effects of FOLFOX regimen (FOLFOX-D).

Methods

In this single-arm, phase II study, previously untreated patients received dasatinib 150 mg oral daily on days 1–14, oxaliplatin 85 mg/m2 intravenous (IV) on day 1 every 14 days, leucovorin (LV) 400 mg/m2 IV on day 1 every 14 days, 5-fluorouracil (5-FU) bolus 400 mg/m2 on day 1 every 14 days, and 5-FU continuous infusion 2,400 mg/m2 on day 1 every 14 days. Primary endpoint was progression-free survival (PFS) with preplanned comparison to historical controls.

Results

Forty-four patients enrolled with an estimated median PFS of 4.0 (95% confidence interval [CI], 2.3–8.5) months and overall survival (OS) of 10.6 (95% CI, 6.9–12.7) months. Overall response rate (ORR) was 22.7% (n = 10): one patient (2.3%) with complete response (CR) and nine patients (20.5%) with partial response (PR). Fifteen patients (34.1%) had stable disease (SD). Nausea was the most common adverse event (AE) seen in 35 patients (79.5%).

Conclusion

The addition of dasatinib did not appear to add incremental clinical benefit to FOLFOX in untreated patients with mPC.
It Takes Two to Tango: Patients’ and Providers’ Perspectives in Tobacco Cessation and Head/Neck Cancer
Authors: Khodadadi Alexandra B. , Carroll William , Lee Erica L. , Hansen Barbara , Scarinci Isabel C.
Published: June 2021

Background

Tobacco cessation among patients with head/neck cancer continues to be challenging despite evidence that cessation improves treatment outcomes. The purpose of this study was to understand barriers/facilitators to tobacco cessation among patients with head/neck cancer and health care providers and to obtain perspectives toward the development of a patient-centered tobacco cessation intervention.

Materials and Methods

In-depth qualitative interviews with 10 health care providers and 21 patients with head/neck cancer (12 inpatients and 9 outpatients) who were current or former smokers.

Results

Health was a common motivator to quit among patients. Although most patients indicated that their health care provider asked and advised them to quit, they were unaware of cessation resources. Suggestions for a tobacco cessation program included involvement of former smokers, health care provider involvement/counseling, supporting written materials, and incorporating follow-up and family support. Health care providers identified patients’ anger/frustration associated with the disease, social/demographic issues, and poor quality of life as the three most frequent challenges in treating patients. Although all providers reported asking about tobacco use, 70% emphasized a lack of formal training in tobacco cessation and lack of time. Their suggestions for a cessation program included having a “quarterback” responsible for this component with support from the entire health care team and continuity between outpatient and inpatient services to promote cessation, prevent relapse, and highlight the importance of follow-up and social support.

Conclusion

There is great interest and need, both from patients and providers, for tobacco cessation services in the oncology setting tailored for patients with head/neck cancer in the context of cancer care.

Implications for Practice

Although the combination of pharmacotherapy and cognitive-behavioral intervention is the standard evidence-based treatment for tobacco dependence, it must be adapted to meet the needs and wants of patients and providers to be effective. This study provides an in-depth examination of such needs among patients with head and neck cancer and providers in the context of cancer care. Providers and patients emphasized the need of having a trained health care provider dedicated to providing tobacco cessation through seamless integration between outpatient and inpatient services as well as follow-up with an emphasis on family involvement throughout the process.
Budget deficit and current account deficit in case of South Africa
Authors: Banday Umer Jeelanie , Aneja Ranjan
Published: June 2021

This article investigates the relationship between budget deficit and current account deficit using ARDL bound testing approach for the developing country South Africa over the period of 1990–2018 featured with liquidity constraints and decreasing consumption. The results of the study confirm the long‐run and short‐run cointegrating relationship between the two deficits and accept Keynesian preposition and do not find any evidence in favor of Ricardian equivalence hypothesis based on these data. The other control variables used in this model found to have both long‐run and short‐run relationship with BD. The results of Granger causality reveal bidirectional causality between budget deficit and current account deficit and unidirectional causality from INT, REER, and INF to budget deficit and current account deficit. From the policy point of view, economic integration and macroeconomic stability are viewed as supportive in accomplishing an ideal growth with both external and internal stability.
Chitosan‐functionalized Fe3O4 nanoparticles as an excellent biocompatible nanocarrier for silymarin delivery
Authors: Zare Mahboobeh , Sarkati Malihe Norouzi
Published: June 2021

Silymarin (SIL) contains a various flavonolignans extracted from Silybum marianum and has an anti‐cancer properties against a variety of cancers. In this study, two types of improved nanocarriers based on iron oxide magnetic nanoparticles (MNPs) including chitosan anchored onto silica coated and uncoated Fe3O4 MNPs (Cs‐f‐SiO2@Fe3O4 MNPs and Cs‐f‐Fe3O4 MNPs) were successfully fabricated and characterized. Next, silymarin was loaded into the nanocarriers (SIL‐Cs‐f‐SiO2@Fe3O4 MNPs and SIL‐Cs‐f‐Fe3O4 MNPs). These systems were characterized and silymarin content, antioxidant activity and intrinsic cytotoxicity were assessed. The functionalization degree of silymarin was assessed by the Folin–Ciocalteu method, finding 120 mg of SIL/g of Cs‐f‐SiO2@Fe3O4 MNPs and 99 mg of SIL/g of Cs‐MNPs. The antioxidant activity of the silymarin after loading into Cs‐f‐SiO2@Fe3O4 MNPs and Cs‐f‐Fe3O4 MNPs was proved by DPPH method. These compounds have high antioxidant effect and their radical scavenging activity increased with increasing these concentrations. SIL‐Cs‐f‐SiO2@Fe3O4 MNPs showed higher antioxidant activity than the SIL‐Cs‐f‐Fe3O4 MNPs in same concentrations. The cytotoxicity of Cs‐f‐SiO2@Fe3O4 MNPs and SIL‐Cs‐f‐SiO2@Fe3O4 MNPs against MCF‐7 was investigated by MTT assay and IC50 values were 110.03 and 73.56 μgml−1 respectively. In conclusion, SIL‐loaded MNPs can be used as drug delivery system on target in the treatment of cancer cells.
Design of thermosensitive polymer‐coated magnetic mesoporous silica nanocomposites with a core‐shell‐shell structure as a magnetic/temperature dual‐responsive drug delivery vehicle
Authors: Asgari Mahsa , Soleymani Meysam , Miri Taghi , Barati Aboulfazl
Published: June 2021

A stimuli‐responsive nanocomposite with a core‐shell‐shell structure consisting of iron oxide (Fe3O4) nanoparticles as core, mesoporous silica as middle shell, and poly(N‐isopropyl acrylamide‐co‐acrylic acid) (P[NIPAAm‐co‐AAc]) as an exterior shell with thermo‐responsivity properties was synthesized to be used as a magnetic/temperature responsive drug delivery system. The structure, morphology, and size of P(NIPAAm‐co‐AAc)‐coated mesoporous silica embedded magnetite nanoparticles (P(NIPAAm‐co‐AAc)@mSiO2@Fe3O4) were characterized by XRD, FTIR, and TEM analyses. Also, the heating ability of mesoporous silica‐coated Fe3O4 nanoparticles, and P(NIPAAm‐co‐AAc)@mSiO2@Fe3O4 nanocomposites was investigated under the exposure of an alternating magnetic field (AMF). The results indicated that the prepared nanocomposites could generate enough heat for hyperthermia applications. Moreover, the magnetic/temperature‐responsive drug release behavior of P(NIPAAm‐co‐AAc)@mSiO2@Fe3O4 nanocomposites loaded with fluorouracil (5‐FU) was studied under the exposure of the AMF (frequency = 120 kHz, and amplitude = 22 kA m−1), as well as two different temperatures (37°C and 45°C). The results showed that only 7.8% of the drug could be released after 20 h at 37°C (below the LCST of the copolymer). In contrast, by increasing the temperature of release medium up to 45°C (above the LCST of the copolymer), the amount of released drug was increased up to 47%. Moreover, by exposing the prepared nanocomposite to a safe AMF, a burst release of drug was observed, indicating the excellent responsivity of the carrier to an external magnetic field. These results proved that the obtained nanocomposite has a great performance to be used as a magnetic/temperature‐sensitive drug carrier for advanced drug delivery applications.
Novel antifouling nanofiltration PES membranes incorporating with C‐KIT‐6 for heavy metal ions removal
Authors: Moradi Golshan , Rahimi Masoud , Zinadini Sirus
Published: June 2021

The removal of Pb2+, Ni2+, and Zn2+ from contaminated water was investigated using the curcumin functionalized KIT‐6 (C‐KIT‐6) incorporated polyethersulfone (PES) nanofiltration (NF) membranes. The prepared C‐KIT‐6 was characterized by scanning electron microscope (SEM), X‐ray powder diffraction (XRD), zeta potential, Energy dispersive X‐Ray (EDX), and Fourier‐transform infrared spectroscopy (FTIR). EDX mapping, SEM, and FTIR were used to show that C‐KIT‐6 mixed in the membrane. Zeta potential, mechanical properties, pore radius, pore radius distribution, and overall porosity were also studied to further characterize the prepared membranes. The hydrophilicity of the membranes was determined by the water contact angle and pure water flux study, and it was increased with respect to increasing C‐KIT‐6 loading. Atomic force microscopy (AFM) images of the C‐KIT‐6 incorporated membranes represented favorable alterations in surface roughness resulting in the amelioration of antifouling behavior. The maximum flux recovery ratio (FRR) and minimum irreversible permeability decay rate (DRir) were attained to be 95.2 and 4.8%, respectively, for the membrane with 0.3 wt% C‐KIT‐6 (M2‐C‐KIT‐6). The rejection of all testing heavy metal ions was maximum (Pb2+ = 91.4%, Ni2+ = 93.1% and Zn2+ = 98.0%) for M2‐C‐KIT‐6. Moreover, M2‐C‐KIT‐6 showed good long‐term reusability performance. The obtained results prove the antifouling C‐KIT‐6 incorporated PES NF membranes are potential candidates for heavy metal ion removal.
SNAP: Supportive noninvasive ventilation for acute chest syndrome prevention in children with sickle cell disease
Authors: Guenther Cara S. , Pae Victoria J. , Neri Caitlin M. , Barry Karan , Duggan Molly A. , Cohen Robyn T.
Published: June 2021

Background

Acute chest syndrome (ACS) is a leading cause of morbidity and mortality among children with sickle cell disease (SCD). Preventing hypoxemia by optimizing lung aeration during sleep remains a challenge.

Objectives

To explore safety, feasibility, and tolerability of noninvasive, bi‐level positive airway pressure ventilation (BiPAP) as preventative, supportive care for hospitalized, medically stable children with SCD on a general pediatric inpatient unit.

Methods

Retrospective chart review of patients ≤22 years of age with SCD admitted to the general pediatric inpatient unit from February 1, 2017 to March 1, 2020 for whom BiPAP was recommended as supportive care. Hospitalizations were excluded if patients were admitted to the pediatric intensive care unit (PICU), required BiPAP for respiratory failure, or used BiPAP at home for obstructive sleep apnea.

Results

Twenty‐three patients had 53 hospitalizations in which BiPAP was recommended. Fifty‐two (98%) hospitalizations included acute SCD pain. Indications for BiPAP included prior ACS (94%), chest or back pain (79%), and/or oxygen desaturation (66%). On 17 occasions, patients already had mild to moderate ACS but were stable when BiPAP was recommended. BiPAP was used successfully during 75% of hospitalizations for a median of two nights. There were no adverse effects associated with BiPAP. PICU transfer for respiratory support occurred during three hospitalizations. In 26 hospitalizations of children at risk for ACS who tolerated BiPAP, 23 (88%) did not develop ACS.

Conclusions

BiPAP is safe, feasible, and well tolerated as supportive care for hospitalized children with SCD. Next steps include an intervention trial to further assess the efficacy of BiPAP on ACS prevention.
Can recombinant technology address asparaginase Erwinia chrysanthemi shortages?
Authors: Maese Luke , Rizzari Carmelo , Coleman Russell , Power Austin , van der Sluis Inge , Rau Rachel E.
Published: June 2021

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Bacterial L‐asparaginase has played an important role in ALL treatment for several decades; however, hypersensitivity reactions to Escherichia coli‐derived asparaginases often preclude their use. Inability to receive asparaginase due to hypersensitivities is associated with poor patient outcomes. Erwinia chrysanthemi‐derived asparaginase (ERW) is an effective, non‐cross‐reactive treatment option, but is limited in supply. Consequently, alternative asparaginase preparations are needed to ensure asparaginase availability for patients with hypersensitivities. Recombinant technology can potentially address this unmet need by programming cells to produce recombinant asparaginase. JZP‐458, a recombinant Erwinia asparaginase derived from a novel Pseudomonas fluorescens expression platform with no immunologic cross‐reactivity to E. coli‐derived asparaginases, has the same primary amino acid sequence as ERW, with comparable activity based on in vitro measurements. The efficient manufacturing of JZP‐458 would provide an additional asparaginase preparation for patients with hypersensitivities.
Vertical transmission of SARS‐CoV2 during pregnancy: A high‐risk cohort
Authors: Maeda Mariane de Fátima Yukie , Brizot Maria de Lourdes , Gibelli Maria Augusta Bento Cicaroni , Ibidi Silvia Maria , Carvalho Werther Brunow de , Hoshida Mara Sandra , Machado Clarisse Martins , Sabino Ester Cerdeira , Oliveira da Silva Lea Campos de , Jaenisch Thomas , Mendes‐Correa Maria Cássia Jacintho , Mayaud Philippe , Francisco Rossana Pulcinelli Vieira ,   HC‐FMUSP‐Obstetric COVID19 Study Group
Published: June 2021

Objective

Identify the potential for and risk factors of SARS‐CoV‐2 vertical transmission.

Methods

Symptomatic pregnant women with COVID‐19 diagnosis in whom PCR for SARS‐CoV‐2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS‐CoV‐2 positivity in AF and/or CB on neonatal outcomes were investigated.

Results

Overall 73.4% (80/109) were admitted in hospital due to COVID‐19, 22.9% needed intensive care and there were four maternal deaths. Positive RT‐PCR for SARS‐CoV‐2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID‐19 symptoms and delivery was inversely associated with SARS‐CoV‐2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS‐CoV‐2 in AF and/or CB (p = 0.001). SARS‐CoV‐2 positivity in the compartments was not associated with neonatal outcomes.

Conclusion

Vertical transmission is possible in pregnant women with COVID‐19 and a shorter interval between maternal symptoms and delivery is an influencing factor.
Research on viscoelastic behavior of semi‐crystalline polymers using instrumented indentation
Authors: Liu Erqiang , Wu Jianguo , Li Huaying , Liu Haitao , Xiao Gesheng , Shen Qiang , Kong Lingyu , Lin Jinbao
Published: June 2021

In this study, the viscoelastic behavior of a polyamide 12 (PA12) polymer was evaluated using instrumented indentation technology based on a rheological model. The creep compliance and retardation spectra were obtained to analyze the viscoelastic response during the holding stage according to the rheological model under different preloading conditions. The results showed that the viscoelastic responses were independent of the indentation depth or load under step loading conditions. However, the creep compliance increases, and the peak intensity of the retardation spectrum decreases with a decrease in the preloading rate owing to the structural relaxation observed during the preloading stage under ramp loading conditions. Furthermore, softening dispersion can be completed during the loading stage under continuous stiffness measurement (CSM) conditions. As the preloading strain rate changes, the peak of the retardation spectrum gradually decreases until it disappears completely. Moreover, studies on indentation creep using the CSM method are challenging because of the complicated viscoelastic response observed during the preloading stage.
Pediatric long‐COVID: An overlooked phenomenon?
Authors: Brackel Caroline L. H. , Lap Coen R. , Buddingh Emilie P. , van Houten Marlies A. , van der Sande Linda J. T. M. , Langereis Eveline J. , Bannier Michiel A. G. E. , Pijnenburg Marielle W. H. , Hashimoto Simone , Terheggen‐Lagro Suzanne W. J.
Published: June 2021

Background

Long‐COVID is a well‐documented multisystem disease in adults. Far less is known about long‐term sequelae of COVID in children. Here, we report on the occurrence of long‐COVID in Dutch children.

Patients and Methods

We conducted a national survey asking Dutch pediatricians to share their experiences on long‐COVID in children. We furthermore describe a case series of six children with long‐COVID to explore the clinical features in greater detail.

Results

With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2–18 years, suspected of long‐COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post‐COVID complaints.

Conclusion

Our study shows that long‐COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management.
Target volume‐guarantee in high‐frequency oscillatory ventilation for preterm respiratory distress syndrome: Low volumes and high frequencies lead to adequate ventilation
Authors: Solís‐García Gonzalo , González‐Pacheco Noelia , Ramos‐Navarro Cristina , Rodríguez Sánchez de la Blanca Ana , Sánchez‐Luna Manuel
Published: June 2021

Background and Objectives

Respiratory distress syndrome (RDS) and ventilation‐induced lung injury lead to significant morbidity in preterm infants. High‐frequency oscillatory ventilation with volume‐guarantee (HFOV‐VG) has been used as a rescue therapy and might lead to lower rates of death and bronchopulmonary dysplasia, especially when using low tidal volumes and high frequencies. The aim of the study was to define HFOV‐VG parameters leading to adequate ventilation in the first 72 h of preterm RDS using a low volume and high‐frequency strategy.

Design and Methods

Retrospective cohort study in a tertiary‐level neonatology unit. Infants <32 weeks with severe respiratory insufficiency needing HFOV‐VG were included. Patients were ventilated following a standard mechanical ventilation aiming for low tidal volumes and high frequencies. Clinical data, perinatal characteristics and high‐frequency parameters corresponding with adequate ventilation were recorded.

Results

116 patients were included. Median gestational age was 25 weeks (interquartile range [IQR] = 24–27), median birth weight 724 g (IQR = 600–900 g). HFOV‐VG was started at 2 h, median high‐frequency tidal volume was 1.63 ml/kg (IQR = 1.44–1.84) and median frequency was 16 Hz (IQR = 15–18). Weight‐adjusted tidal volumes did not depend on gestational age, antenatal corticosteroids nor chorioamnionitis, and were inversely correlated with frequencies (R
2 = −0.10, p = .001).

Conclusion

HFOV‐VG can reach adequate ventilation at high frequencies when using adequate volumes, providing a feasible ventilation strategy that might be of help in preterm infants with RDS.
Experimental Investigation of the Thermal Decomposition Pathways and Kinetics of TATB by Isotopic Substitution
Authors: Koroglu Batikan , Crowhurst Jonathan C. , Kahl Evan M. , Moore Jason S. , Racoveanu Ana , Mason Harris E. , Weisz David G. , Reynolds John G. , Burnham Alan K.
Published: June 2021

Real‐time measurements of the product gases arising from the thermal decomposition of triamino‐trinitro benzene (TATB), its deuterated analogue, and plastically bonded TATB (LX‐17) are presented in this study. Gas‐phase decomposition products are identified by IR absorption spectroscopy. The frequency shifts in rovibrational spectra due to isotopic substitution and the change in rate of formation of decomposition products due to the kinetic‐isotope‐effect (KIE) help elucidate the decomposition pathways. The formation of H2O precedes other molecules (e. g., HCN, HNCO) during decomposition. After the concentrations of HCN and HNCO molecules reach a peak, their amounts gradually decrease. The concentrations of the other decomposition products (e. g., NH3 and CO2) rapidly rise after an induction period, which is attributed to the presence of autocatalytic reactions. The trends of chemical evolution are similar for all the samples, but their kinetic behaviors are different. This indicates the rates of consistent pathways are changed during thermal decomposition. The kinetics of deuterated TATB decomposition is slower than that of unsubstituted TATB due to the KIE (kH/kD∼1.41). The rate of LX‐17 decomposition is slightly lower than unsubstituted TATB (kTATB/kLX‐17∼1.15). The KIE is more pronounced during the early stage of decomposition, which is attributed to the first steps of TATB decomposition involving water formation (i. e., H vs D transfer). The KIE slows down the formation of all gases, including those lacking hydrogen (e. g., CO2). These results suggest the TATB thermal decomposition mechanism might involve a series of pathways rather than a set of independent and parallel reactions.
Design of acid‐activated cell‐penetrating peptides with nuclear localization capacity for anticancer drug delivery
Authors: Huang Sujie , Zhu Zhongwen , Jia Bo , Zhang Wei , Song Jingjing
Published: June 2021

Camptothecin (CPT), a DNA‐toxin drug, exerts anticancer activity by inhibiting topoisomerase I. Targeted delivery of CPT into the cancer cell nucleus is important for enhancing its therapeutic efficiency. In this study, a new type of acid‐activated cell‐penetrating peptide (CPP) with nuclear localization capacity was constructed by conjugating six histidine residues and a hydrophobic peptide sequence, PFVYLI, to the nuclear localization sequence (NLS). Our results indicated that HNLS‐3 displayed significant pH‐dependent cellular uptake efficiency, endosomal escape ability, and nuclear localization activity. More importantly, the HNLS‐3–CPT conjugate showed obviously enhanced cytotoxicity and selectivity compared with CPT. Taken together, our findings provide an effective approach to develop efficient CPPs with both cancer‐ and nucleus‐targeting properties.
Robotic system for magnetic resonance guided focused ultrasound ablation of abdominal cancer
Authors: Antoniou Anastasia , Giannakou Marinos , Evripidou Nikolas , Evripidou Georgios , Spanoudes Kyriakos , Menikou Georgios , Damianou Christakis
Published: June 2021

Background

A prototype robotic system that uses magnetic resonance guided focused ultrasound (MRgFUS) technology is presented. It features three degrees of freedom (DOF) and is intended for thermal ablation of abdominal cancer.

Methods

The device is equipped with three identical transducers being offset between them, thus focussing at different depths in tissue. The efficacy and safety of the system in ablating rabbit liver and kidney was assessed, both in laboratory and magnetic resonance imaging (MRI) conditions.

Results

Despite these organs' challenging location, in situ coagulative necrosis of a tissue area was achieved. Heating of abdominal organs in rabbit was successfully monitored with MR thermometry.

Conclusions

The MRgFUS system was proven successful in creating lesions in the abdominal area of rabbits. The outcomes of the study are promising for future translation of the technology to the clinic.
The in situ treatment of Basic Violet 16 synthetic dye in groundwater
Authors: McGregor Rick , Maziarz Anastasia
Published: June 2021

Synthetic dyes have been shown to be micropollutants in various aquatic and groundwater systems, often occurring at milligram per liter (mg/L) concentrations. Synthetic dyes are typically introduced into the environment either as a continuous stream from wastewater or as episodic events related to the disposal of residues or spills generated during the manufacturing process. Various studies for the treatment of synthetic dyes have been undertaken for wastewater but studies for the in situ treatment of synthetic dyes in groundwater are limited. A pilot‐scale test was conducted to determine if the use of colloidal activated carbon (CAC) could effectively reduce dissolved concentrations of the synthetic dye Basic Violet (BV16) in groundwater using in situ methods. The pilot test was carried out downgradient of a textile manufacturing facility where historic disposal practices resulted in the release of various chemicals of concern including BV16 to an unconfined silty sand aquifer. A 10‐weight percent CAC solution was injected into a series of temporary direct push injection points to target the synthetic dye that was present at concentrations of up to 1,640 micrograms per liter (μg/L) during the 738‐day study. The results from the pilot test indicated that the CAC was effectively delivered to the target injection zone resulting in a three order of magnitude increase in total organic carbon (TOC) concentrations compared to preinjection TOC concentrations within the aquifer. Distribution of the CAC within the targeted injection zone indicated that heterogeneity affected the distribution with a zone of higher horizontal hydraulic conductivity (KH) having an average TOC concentration approximately 100 percent greater than the mean TOC concentration within the surrounding aquifer targeted by the CAC injection. Analyses of the groundwater chemistry before and postinjection indicated that the CAC had no detrimental impact on the groundwater quality while reducing the concentration of dissolved BV16 within the plume to below the method detection limits within 62 days of injection. The concentration of BV16 remained below the method detection limit of 10 µg/L for the 738‐day duration of the study apart from one detection of 180 µg/L at Day 183 within groundwater sampled from one monitoring well suggesting that the CAC was effective in attenuating the BV16 over the short and moderate term.
Managing National Food Security in the Global North: Is collaborative governance a possible route forward?
Authors: Larsson Oscar L. , Sjöqvist Sara
Published: June 2021

Many countries in the “Global North” that have enjoyed relative food security for a number of decades now face challenges that may lead to disturbances in food supplies. Global markets and global flows are not as self‐evident as they were a few years ago and new modes of governance for managing national food security during crisis are required. Recent events such as the COVID‐19 pandemic have further showed that global production systems and communications are fragile to a range of different disturbances. This article examines the possibility of managing national food security through collaborative arrangements between public authorities and private food companies through a case study of the Swedish approach to food security. The analysis is based on a theoretical framework that highlights the importance of motivation, leadership, shared understanding, and trust as four dimensions that evaluate collaborative governance in precrisis situations. We conclude that although a broader understnding of the importance of food security has emerged, collaborative governance arrangements run the risk of creating only an illusion of readiness, due to unclear mandates and clear leadership not able to advance trust, legal structures, or concrete agreements for ensuring national food security.
IGF‐I and NGFβ enhance in vitro progressive motility and vitality of human spermatozoa
Authors: Asimakopoulos Byron , Tiptiri‐Kourpeti Aggeliki , Metallinou Chrysa
Published: June 2021

Purpose

Progressive motility (PM) and vitality are positively associated with fertilization ability of spermatozoa. Here, the effects of IGF‐I and NGFβ on PM and vitality of human spermatozoa were investigated.

Methods

Forty‐three volunteers gave semen samples after 2‐3 days of sexual abstinence. Each sample was processed with density gradient centrifugation and sperm washing. The pellet was divided into 3 aliquots. An aliquot containing one million of progressively motile spermatozoa was incubated for an hour (37°C) in standard culture medium (control group), and two aliquots with the same number of progressively motile spermatozoa were incubated in medium supplemented with IGF‐I or NGFβ. Two concentrations of IGF‐I (100 ng/ml and 1000 ng/ml) and NGFβ (0,5 ng/ml and 5 ng/ml) were tested.

Results

Both growth factors significantly increased PM and vitality in comparison with control either at the low or the high concentration. IGF‐I seemed to be more effective than NGFβ. The effects did not seem to be dose dependent with the exception of the effect of IGF‐I on vitality.

Conclusions

The enhancement of PM and vitality of human spermatozoa by IGF‐I and NGFβ opens new ways for the improvement of sperm processing. Further research is needed to determine the most effective concentrations.
ASSURED‐compliant point‐of‐care diagnostics for the detection of human viral infections
Authors: Naseri Mahdi , Ziora Zyta M , Simon George P , Batchelor Warren
Published: June 2021

Viral disease outbreaks have been always a threat to global public health making affordable, rapid and accurate diagnostics highly important tools to slow down the spread of viruses and decrease the mortality rate. Point‐of‐care (POC) diagnostics have emerged as a strong tool for the diagnosis of viral infections, especially in countries where health‐care systems are inadequate to provide proper services to all citizens. According to the World Health Organization, an ideal POC diagnostic must be Affordable, Sensitive, Specific, User‐friendly, Rapid/Robust, Equipment‐free and Deliverable (ASSURED). This review surveys carefully each ASSURED criterion and identifies where existing viral POC diagnostics fail to meet these criteria. Given the widespread concern with plastic pollution, we also propose the addition of 'disposability' to the existing ASSURED criteria and consider the letter “D” as the representative of both Deliverable and Disposable. Next, the POC tests used for the diagnosis of several common human viral infections which met all the ASSURED criteria (ASSURED‐compliant) are described in detail. Finally, the future of ASSURED‐compliant POC diagnostics, capable of generating comparable results to the viral diagnostic gold standards, is discussed.
Carbon dioxide flush as a soil health indicator related to soil properties and crop yields
Authors: Sainju Upendra M. , Liptzin Daniel , Dangi Sadikshya M.
Published: June 2021

Carbon dioxide flush after rewetting of dried soils has been recommended as a promising soil health indicator, but it has not been related to most soil properties and crop yields. We evaluated the effect of cropping systems and N fertilization on CO2 flushes at 1‐ (1dC) and 4‐d incubations (4dC) after rewetting of dried soils and related to 54 soil physical, chemical, and biological properties and annualized crop yields in two long‐term experimental sites in eastern Montana (USA). Treatments included till and no‐till spring wheat (Triticum aestiveum L.), pea (Pisum sativum L.), and fallow rotations with and without N fertilization. Carbon dioxide flushes were lower in till crop–fallow than in no‐till continuous cropping systems at both sites. The 1dC was correlated to 5 soil physical, 7 chemical, and 12 biological properties, and 4dC was correlated to 9 physical, 8 chemical, and 11 biological properties in Froid. In Sidney, 1dC was correlated to 10 physical, 13 chemical, and 9 biological properties, and 4dC was correlated to 7 physical, 11 chemical, and 2 biological properties (1–8 moderately, 18–21 strongly, and 1–3 very strongly related). Carbon dioxide flushes were also related to mean annualized crop yields in both sites, except for the relationship between 4dC and crop yield in Sidney. Because of its stronger relationship with soil properties and crop yields, 1dC after rewetting of dried soils determined by using the infrared gas analyzer can be used as a simple, rapid, reliable, and inexpensive indicator of measuring soil health in dryland cropping systems.
Skin Cancers in Skin Types IV–VI: Does the Fitzpatrick Scale Give a False Sense of Security?
Authors: Goon P. , Banfield C. , Bello O. , Levell N. J.
Published: June 2021

The Fitzpatrick scale has been in use for skin colour typing according to the tanning potential of skin since its inception in 1975–1976. Thomas Fitzpatrick developed the scale to classify persons with ‘white skin’ in order to select the correct amount of UVA in Joules/cm2 for PUVA treatment for psoriasis. Since then, it has been widely used in Dermatology to gauge the skin's reaction to UV exposure, tanning potential, assessment of sunburn risk and amount of sun protection required for individual patients. However, the use of this scale has been of limited utility because of different self-perception in different areas of the world, particularly among those with skin of colour. Skin cancer risk is loosely inversely correlated with the initial genetic/inherent amount of melanin (most research has focused on eumelanin) present in the skin, although the pattern of exposure and amount of UV radiation required causing DNA damage varies widely according to different cancers. In this review, we have shown that the Fitzpatrick scale is neither correct nor adequate to reflect sunburn and tanning risk for skin of colour. Therefore, it may give both patients and physicians a false sense of security that there is little risk that people of colour can develop skin cancers. We have reviewed the small but not insignificant risk of skin of colour developing skin cancers and emphasise that there remains much research that needs to be done in this field.
Detection of AFP by Electrochemical Immunosensor Based on Ag/Fe3O4/g‐C3N4
Authors: Zhang Mengmeng , Cao Kaihang , Mei Lisha , Wang Xiao , Liao Xiaochen , Qiao Xiuwen , Hong Chenglin
Published: June 2021

Herein, a novel electrochemical immunosensor was prepared to detect cancer alpha‐fetoprotein (AFP). An iron oxide/graphite‐phase carbon nitride/silver (Fe3O4−g‐C3N4−Ag) composite was used as the carrier. Metal‐free graphitic carbon nitrides (g‐C3N4) have been recently recognized as high‐performance photocatalysts; however, their large‐scale applications are limited because of their poor electronic properties and low dispersion. Fe3O4 particles were incorporated in the composite to improve the conductivity and dispersibility of g‐C3N4. Silver nanoparticles were prepared through UV irradiation and did not involve the use of reducing agents. A signal probe was prepared from Fe3O4−g‐C3N4−Ag and acetylene black. Cyclic voltammetry was conducted to detect AFP. Under optimized conditions, the proposed immunosensor exhibited excellent analytical abilities. The dynamic response range of the AFP concentration was 0.0001–80 ng ⋅ mL−1. The detection limit was relatively low at 0.078 pg ⋅ mL−1 (S/N=3). The immunosensor also exhibited high specificity and good reproducibility. The results showed that the proposed immunosensor can be successfully used to detect AFP in human serum samples.
A Practical Electrochemical Nanotool for Facile Quantification of Amino Acids in Single Cell
Authors: Xu Yi‐Tong , Ruan Yi‐Fan , Wang Hai‐Yan , Yu Si‐Yuan , Yu Xiao‐Dong , Zhao Wei‐Wei , Chen Hong‐Yuan , Xu Jing‐Juan
Published: June 2021

Though significant advances are made in the arena of single‐cell electroanalysis, quantification of intracellular amino acids of human cells remains unsolved. Exemplified by l‐histidine (l‐His), this issue is addressed by a practical electrochemical nanotool synergizing the highly accessible nanopipette with commercially available synthetic DNAzyme. The fabricated nanotools are screened before operation of a single‐use manner, and the l‐His‐provoked cleavage of the DNA molecules can be sensibly transduced by the ionic current rectification response, the intrinsic property of nanopipette governed by its interior surface charges. Regional distribution of cytosolic l‐His level in human cells is electrochemically quantified for the first time, and time‐dependent drug treatment effects are further revealed. This work unveils the possibility of electrochemistry for quantification of cytosolic amino acids of a spatial‐ and time‐based manner and ultimately enables a better understanding of amino acid‐involved events in living cells.
Outlier robust model averaging based on Sp criterion
Authors: Guo Yunfei , Li Zhonghua
Published: June 2021

In this paper, we consider the problem of obtaining appropriate weights for model averaging in the face of model uncertainty and outliers. Most of the current model averaging methods are based on ordinary least squares (OLS) estimators, which are very sensitive to outliers or departures from the normality assumption on the error distribution. To overcome this problem, we propose an outlier robust Sp‐type model averaging (SMA) procedure whenever data contain outliers. The proposed method combines the advantages of model averaging and robust model selection. Therefore, it performs better than other classical model averaging and robust model section methods, especially in the outlier data case, and nearly the same as Mallows's model averaging (MMA) even in the clean data case. Moreover, the proposed criterion is quadratic in the weights, so it is operationally simple to implement. The performance of the proposed method is illustrated through some extensive simulation studies as well as real data examples.
Starch Modified by Natural Fermentation in Orange‐Fleshed Sweet Potato
Authors: Paixão e Silva Giselle de Lima , Bento Juliana Aparecida Correia , Lião Luciano Morais , Soares Júnior Manoel Soares , Caliari Márcio
Published: June 2021

This study aims to modify starch via the spontaneous fermentation of orange‐fleshed sweet potato for a period of 0, 4, 8, 12, 16, and 20 days and evaluates the effects of this process in this starch. In Brazil, this flour which is naturally fermented from manioc is described as “puba.” Thus, the results of “puba” from the orange‐fleshed sweet potato ferment for 12 days show increases in the amylose content, luminosity, gelatinization enthalpy from Differential Scanning Calorimeter (DSC), final paste viscosity from Rapid Viscous Analyzer (RVA), and gel hardness but the water solubility and absorption (WSI and WAI) indexes are reduced. Using Scanning Electron Microscopy (SEM), the consumption of non‐starchy materials and depressions on the surface of the granules resulting from the fermentation could be seen. The Fourier Transform Infrared (FT‐IR) Spectroscopy, X‐Ray Diffraction, and Nuclear Magnetic Resonance (NMR) Spectroscopy analyses show that no new functional groups are formed, and there are no changes in the crystallinity pattern (showing the same native CA‐ pattern) or molecular arrangement, respectively. Therefore, the sweet potato “puba” flour shows production viability due to the advantageous changes in its technological characteristics, as well as the potential to be studied for further food applications.