bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-reported Outcomes in Arthrogryposis
Authors: Wall Lindley B. , Vuillerman Carley , Miller Patricia E. , Bae Donald S. , Goldfarb Charles A.
Published: February 2020

Background:

Little is known about patient-reported health status in children and adolescents with arthrogryposis. Utilizing the Patient-Reported Outcome Measurement Information System (PROMIS) and Pediatric Outcomes Data Collection Instrument (PODCI) questionnaires, we investigated functional and psychosocial measures in arthrogryposis.

Methods:

A total of 118 patients with arthrogryposis were identified from a prospective longitudinal cohort (the Congenital Upper Limb Difference Registry) from 2014 to 2018. Demographics and patient-reported outcome measures were evaluated, including the PROMIS [upper extremity (UE) function, pain, depression, anxiety, and peer relations] and PODCI questionnaires (UE function, pain, happiness, and global function).

Results:

A total of 29 arthrogrypotic patients had complete PROMIS and PODCI data. This cohort was divided into distal arthrogryposis and amyoplasia groups, with 15 and 14 patients in each group, respectively. There were 8 males in the distal arthrogryposis group with a median age of 9 years and 7 males in the amyoplasia group with a median age of 8 years. For both cohorts, the median UE function PROMIS scores were significantly below population norms, 31 for distal arthrogryposis and 22 for amyoplasia. PODCI UE function was statistically lower for amyoplasia compared with the distal arthrogryposis cohort. PROMIS pain, depression, anxiety, and peer relations were in the normal range for both amyopasia and distal arthrogryposis. Median PODCI pain and happiness ranged from 85 to 88 for all patients with no statistical difference between groups.

Conclusions:

Arthrogryposis patients have lower UE function scores compared with population normals, but they have emotional states that are consistent with populations norms. Amyoplasia patients were functionally worse than distal arthrogryposis patients.

Levels of Evidence:

Level II.
Infections and the development of childhood acute lymphoblastic leukemia: a population-based study
Authors: Hwee Jeremiah , Sutradhar Rinku , Kwong Jeffrey C. , Sung Lillian , Cheng Stephanie , Pole Jason D.
Published: February 2020

An infectious trigger for childhood acute lymphoblastic leukemia is hypothesized and we assessed the association between the rate, type, and critical exposure period for infections and the development of acute lymphoblastic leukemia. We conducted a matched case-control study using administrative databases to evaluate the association between the rate of infections and childhood acute lymphoblastic leukemia diagnosed between the ages of 2–14 years from Ontario, Canada and we used a validated approach to measure infections. In 1600 cases of acute lymphoblastic leukemia, and 16 000 matched cancer-free controls aged 2–14 years, having >2 infections/year increased the odds of childhood acute lymphoblastic leukemia by 43% (odds ratio = 1.43, 95% confidence interval 1.13–1.81) compared to children with ≤0.25 infections/year. Having >2 respiratory infections/year increased odds of acute lymphoblastic leukemia by 28% (odds ratio =1.28, 95% confidence interval 1.05–1.57) compared to children with ≤0.25 respiratory infections/year. Having an invasive infection increased the odds of acute lymphoblastic leukemia by 72% (odds ratio =1.72, 95% confidence interval 1.31–2.26). Having an infection between the age of 1–1.5 years increased the odds of acute lymphoblastic leukemia by 20% (odds ratio = 1.20, 95% confidence interval 1.04–1.39). Having more infections increased the odds of developing childhood acute lymphoblastic leukemia and having an infection between the ages of 1–1.5 years increased the odds of childhood acute lymphoblastic leukemia.
The Firehawk Stent: A Review of a Novel Abluminal Groove-Filled Biodegradable Polymer Sirolimus-Eluting Stent
Authors: Saito Yuichi , Grubman Daniel , Cristea Ecaterina , Lansky Alexandra
Published: February 2020

Despite recent advances in drug-eluting stent (DES) technology, late adverse events remain concerns after percutaneous coronary intervention. The persistence of polymer material on DES has been suggested as a trigger for chronic inflammation. The Firehawk, a novel DES, has a unique design with recessed abluminal grooves, to which sirolimus and biodegradable polymer are applied. The Firehawk stent is designed to minimize polymer volume and antiproliferative drug concentration to reduce inflammation and hypersensitivity reactions. Several recent trials have reported the clinical outcomes of this device. This article provides a review of the current clinical evidence concerning the Firehawk stent.
Pulmonary Artery Denervation as an Innovative Treatment for Pulmonary Hypertension With and Without Heart Failure
Authors: Kim Chan W. , Aronow Wilbert S. , Dutta Tanya , Spevack Daniel M. , Frishman William H.
Published: February 2020

Pulmonary hypertension (PH) is categorized into 5 groups based on etiology. The 2 most prevalent forms are pulmonary arterial hypertension (PAH) and PH due to left heart disease (PH-LHD). Therapeutic options do exist for PAH to decrease symptoms and improve functional capacity; however, the mortality rate remains high and clinical improvements are limited. PH-LHD is the most common cause of PH; however, no treatment exists and the use of PAH-therapies is discouraged. Pulmonary artery denervation (PADN) is an innovative catheter-based ablation technique targeting the afferent and efferent fibers of a baroreceptor reflex in the main pulmonary artery (PA) trunk and its bifurcation. This reflex is involved in the elevation of the PA pressure seen in PH. Since 2013, both animal trials and human trials have shown the efficacy of PADN in improving PAH, including improved hemodynamic parameters, increased functional capacity, decreased PA remodeling, and much more. PADN has been shown to decrease the rate of rehospitalization, PH-related complications, and death, and is an overall safe procedure. PADN has also been shown to be effective for PH-LHD. Additional therapeutic mechanisms and benefits of PADN are discussed along with new PADN techniques. PADN has shown efficacy and safety as a potential treatment option for PH.
Mitochondrial Translocation of DJ-1 Is Mediated by Grp75: Implication in Cardioprotection of Resveratrol Against Hypoxia/Reoxygenation-Induced Oxidative Stress
Authors: Zhou Ting-Ting , Wang Xue-Ying , Huang Jiao , Deng Yi-Zhang , Qiu Le-Jia , Liu Hao-Yue , Xu Xing-Wang , Ma Zhao-Xia , Tang Lei , Chen He-Ping
Published: February 2020

Resveratrol (Res) was recently reported to ameliorate hypoxia/reoxygenation (H/R)-caused oxidative stress in H9c2 cardiomyocytes through promoting the mitochondrial translocation of DJ-1 protein and subsequently preserving the activity of mitochondrial complex I. However, it is noteworthy that DJ-1 possesses no mitochondria-targeting sequence. Therefore, how Res induces DJ-1 mitochondrial translocation is an important and interesting question for further exploration. Glucose-regulated protein 75 (Grp75), whose N-terminus contains a 51-amino acid long mitochondrial-targeting signal peptide, is a cytoprotective chaperone that partakes in mitochondrial import of several proteins. Here, the contribution of Grp75 to mitochondrial import of DJ-1 by Res was investigated in a cellular model of H/R. Our results showed that Res upregulated the expression of DJ-1 protein, enhanced the interaction of DJ-1 and Grp75, and promoted DJ-1 translocation to mitochondria from cytosol in H9c2 cardiomyocytes undergoing H/R. Importantly, knockdown of Grp75 markedly reduced the interaction of DJ-1 with Grp75 and subsequent DJ-1 mitochondrial translocation induced by Res. Furthermore, Res pretreatment promoted the association of DJ-1 with ND1 and NDUFA4 subunits of complex I, preserved the activity of complex I, decreased mitochondria-derived reactive oxygen species production, and eventually ameliorated H/R-caused oxidative stress damage. Intriguingly, these effects were largely prevented also by small interfering RNA targeting Grp75. Overall, these results suggested that Grp75 interacts with DJ-1 to facilitate its translocation from cytosol to mitochondria, which is required for Res-mediated preservation of mitochondria complex I and cardioprotection from H/R-caused oxidative stress injury.
Invasive Haemophilus influenzae Type b Disease in the Post Hexavalent Era
Authors: Ricci Silvia , Canessa Clementina , Lodi Lorenzo , Giovannini Mattia , Lippi Francesca , Moriondo Maria , Nieddu Francesco , Azzari Chiara
Published: February 2020

Background:

The epidemiologic characteristics of invasive Haemophilus influenzae type b disease (HIBD) have markedly changed since the introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine worldwide. The immunization schedule against Haemophilus influenzae type b differs in Europe.

Methods:

This is a retrospective observational study which evaluates all the data included in the molecular surveillance register for invasive infectious diseases at the Laboratory of Molecular Diagnosis at Meyer Children’s University Hospital from December 2008 to December 2018 with a diagnosis of invasive HIBD in children <5 years of age.

Results:

We identified 4 cases of HIBD: all the cases presented signs or symptoms of invasive infection and the H. influenzae type b was identified in cerebrospinal fluid, or blood or bronchoalveolar lavage by molecular test. The crude incidence for Hib invasive disease in Tuscany is 0.26/100,000 p-y in children younger than 5 years, significantly different from the incidence rate before the introduction of the Hib vaccination. Vaccination effectiveness can be estimated at 97.9% and the impact of hexavalent (2p+1) vaccine at 99.6%.

Conclusions:

This work confirms the high impact of the hexavalent vaccine 2p+1 schedule for HIBD in children <5 years, emphasizing the role of molecular test for HIBD diagnosis and surveillance.
Labor Market Participation Before and After Long-Term Part-Time Sickness Absence in Finland
Authors: Ervasti Jenni , Kausto Johanna , Koskinen Aki , Pentti Jaana , Vahtera Jussi , Joensuu Matti , Turunen Jarno , Oksanen Tuula , Kivimäki Mika
Published: February 2020

Objective:

To examine trends in labor market participation among those with long-term part-time or long-term full-time sickness absence.

Methods:

Finnish population-based cohort study including 3406 individuals with greater than 30-day part-time sickness absence in 2011 and 42,944 individuals with greater than 30-day full-time sickness absence in 2011.

Results:

Compared to previous years, the rates of sickness absence and vocational rehabilitation increased after 2011 in both groups. Sickness absence rate was higher in 2012 in the full-time sickness absence group than in the part-time sickness absence group. An increasing trend in unemployment after 2011 was observed in both groups, but the absolute level of unemployment was higher in the full-time sickness absence group.

Conclusion:

Long-term part-time sickness absence seems to mark a decline in labor market participation, but the decline is smaller than that in employees with full-time sickness absence.
Reasons for Staying With Your Employer
Authors: Steiner Sarah , Cropley Mark , Simonds Laura , Heron Richard
Published: February 2020

Objective:

Drawing upon the social exchange theory, this study developed and tested a theoretical model to identify factors predicting intentions to stay within a global energy business.

Methods:

Structural equation modeling was applied to an annual employee survey (N = 30,094).

Results:

The most significant factors predicting intention to stay were organizational engagement (when employees are seen to role model company values and behaviors) and relationship with supervisor (when “my manager treats me fairly”). Perceived supervisor support (when employees believe that the company “really cares about my health and well-being”) and communication significantly predicted both work engagement and organizational commitment.

Conclusion:

When employees believe that their supervisor is concerned about their well-being, recognizes their contributions, and role-models the organization's values, they reported more engagement and a stronger commitment to remain with the organization.
A Case of Medial Tibial Crest Friction Syndrome: A Rare Cause of Medial Knee Pain
Authors: Johnson Wade O. , Johnson Adam C. , Payne Jeffrey M.
Published: February 2020

Knee pain is among the most common problems in active patients, with common causes of medial knee pain including meniscal injury, osteoarthritis, medial collateral ligament (MCL) injury, and pes anserine bursopathy/distal hamstring tendinopathy. Some cases of medial knee pain are refractory to standard treatment options and may be caused by rare pathology. We present a case of medial knee pain secondary to medial tibial crest friction syndrome (MTCFS) in a 22-year-old male training for a sprint triathlon after rapidly increasing his training program. Magnetic resonance imaging revealed bone marrow and soft-tissue edema about the MTC deep to the MCL consistent with MTCFS. The patient failed a period of relative rest and activity modification, but improved with corticosteroid injection deep to the MCL in the location of his symptoms. This case highlights a potential management option for MTCFS, a disorder previously described only in radiologic literature.
The Functional Impact of the Absence of a Bulbocavernosus Reflex in the Postoperative Period After a Motor-Complete Traumatic Spinal Cord Injury
Authors: Greciet Nicolas , Mac-Thiong Jean-Marc , Nguyen Bich-Han , Richard-Denis Andréane
Published: February 2020

Objective

The aim of the study was to investigate the impact of the absence of a bulbocavernosus reflex in the postoperative period on the neurological and functional recovery 6–12 mos after a motor-complete traumatic spinal cord injury.

Design

A retrospective review of a prospective database was completed among 66 patients. The functional and neurological statuses between individuals with and without a bulbocavernosus reflex were compared. A general linear model was used to investigate the association between the postoperative bulbocavernosus reflex status and the functional outcome, using the Spinal Cord Independence Measure.

Results

Forty percent of the cohort had no bulbocavernosus reflex 5 days after trauma. Individuals with a bulbocavernosus reflex showed a higher rate of American Spinal Injury Association Impairment Scale grade conversion, improvement of the level of injury, and higher functional scores; however, it did not reach a significant level. The bulbocavernosus reflex status in the postoperative period was not significantly associated with the functional status 6–12 mos after injury.

Conclusions

Late recovery of the bulbocavernosus reflex in the postoperative period may be associated with poorer neurological and functional outcome for individuals sustaining a motor-complete traumatic spinal cord injury, for which the prognosis estimation is limited. A prospective study including a larger number of patients is necessary to confirm results of this study.
Patients’ Perspective on Carpal Tunnel Release with WALANT or Intravenous Regional Anesthesia
Authors: Ayhan Egemen , Akaslan Filiz
Published: February 2020

Background:

The authors conducted a prospective study to compare patients’ intraoperative experience of open carpal tunnel release under “wide awake, local anesthesia, no tourniquet” (WALANT) on the one hand and intravenous regional anesthesia on the other. The authors hypothesized that WALANT would offer a better intraoperative experience than intravenous regional anesthesia.

Methods:

Twenty-four patients with bilateral carpal tunnel syndrome had one hand operated on using WALANT and the contralateral hand with the intravenous regional anesthesia method. At the postoperative second hour, patients completed a questionnaire to quantify their pain levels on a numerical rating scale and compare the operation with dental procedures. They were also asked about their expectations and feelings about reoperation with the anesthesia methods. The results were compared for the two anesthesia methods.

Results:

There were no significant differences between numerical rating scale pain values during anesthetic administration or for surgical site pain on the WALANT and intravenous regional anesthesia sides. Patients reported moderate tourniquet pain for intravenous regional anesthesia sides. For WALANT sides, a significantly higher number of patients reported carpal tunnel release to be an easier procedure than dental procedures (91.6 percent WALANT and 37.5 percent intravenous regional anesthesia). For WALANT sides, a significantly higher number of patients reported carpal tunnel release to be an easier procedure than they expected (91.6 percent WALANT and 50 percent intravenous regional anesthesia). For the reoperation, 83.3 percent of patients preferred WALANT, 8.3 percent preferred intravenous regional anesthesia, and 8.3 percent reported no preference.

Conclusions:

WALANT offered a better intraoperative experience. Tourniquet pain, preoperative preparation basics, and the extended anesthesia duration are likely the major drawbacks of the intravenous regional anesthesia method.
Neurodevelopment of HIV-Exposed Uninfected Infants Born to Women With Perinatally Acquired HIV in the United States
Authors: Jao Jennifer , Kacanek Deborah , Yu Wendy , Williams Paige L. , Patel Kunjal , Burchett Sandra , Scott Gwendolyn , Abrams Elaine J. , Sperling Rhoda S. , Van Dyke Russell B. , Smith Renee , Malee Kathleen ,   for the Pediatric HIV/AIDS Cohort Study
Published: February 2020

Background:

Lifelong HIV and antiretroviral therapy may confer neurodevelopmental risk on the children of women with perinatally acquired HIV infection (PHIV).

Setting:

We analyzed data from HIV-exposed uninfected (HEU) infants born to women with PHIV vs. non–perinatally acquired HIV (NPHIV) enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities (SMARTT) study.

Methods:

Using the Bayley Scales of Infant and Toddler Development, third Ed. (Bayley-III), we compared neurodevelopmental outcomes at the age of 1 year in HEU infants born to women with PHIV vs. NPHIV. Those with valid Bayley-III data at the age of 1 year and a mother born after 1982 were included. Cognitive, language, and motor domains were assessed as continuous composite scores. Linear mixed effects models were fit to estimate the mean difference in Bayley-III scores between groups, adjusting for confounders.

Results:

Five hundred fifty women with HIV gave birth to 678 HEU children (125 and 553 born to women with PHIV and NPHIV, respectively). Mean scores for each of the Bayley-III domains were not significantly different between infants born to women with PHIV vs. NPHIV in unadjusted models. After adjustment, infants of women with PHIV had lower language (91.9 vs. 94.8, P = 0.05) and motor (93.7 vs. 96.8, P = 0.03) composite scores, but no differences in cognitive composite scores.

Conclusions:

Cognitive domain outcomes of infants born to women with PHIV vs. NPHIV are reassuring. Differences in early language and motor functioning, while of modest clinical significance, highlight the importance of long-term monitoring of neurodevelopment in children of women with PHIV.
Preprocedural Imaging Evaluation of Pulmonary Valve Replacement After Repair of Tetralogy of Fallot
Authors: Flors Lucia , Bueno Juliana , Gish David , White Shelby , Norton Patrick T. , Hagspiel Klaus D. , Leiva-Salinas Carlos
Published: February 2020

Tetrallogy of Fallot (TOF) is the most frequent form of cyanotic congenital heart disease. Despite advances in surgical and medical treatment, mortality remains high. Residual dysfunction of the pulmonary valve (PV) after correction of right ventricular outflow tract obstruction is an important cause of morbidity, leading to irreversible right ventricular dysfunction, arrhythmias, heart failure and occasionally, death. The strategies for PVR have evolved over the last decades, and the timing of the intervention remains the foundation of the decision-making process. Symptoms of heart failure are unreliable indicators for optimal timing of repair. Imaging plays an essential role in the assessment of PV integrity and dysfunction. The identification of the best timing for PVR requires a multimodality approach. Transthoracic echocardiography is the most commonly used imaging modality for the initial assessment and follow-up of TOF patients, although its utility has technical limitations, especially in adults. Cardiac computed tomography and magnetic resonance imaging are now routinely used for preoperative and postoperative evaluation of these patients, and provide highly valuable information about the anatomy and pathophysiology. Imaging evidence of disease progression is now part of the major guidelines to define the best timing for reintervention. The purpose of this article is to review the pathophysiology after TOF repair, identify the main imaging anatomic and physiologic features, describe the indications for PVR and recognize the role of imaging in the assessment of these patients to define the appropriate timing of PVR.
Laparoscopic Single Anastomosis Sleeve Ileal (SASI) Bypass for Patients With Morbid Obesity: Technical Description and Short-term Outcomes
Authors: Madyan Amr , Emile Sameh H. , Abdel-Razik Mohamed A. , Ellithy Ramadan , Elbanna Hosam G. , Elshobaky Ayman
Published: February 2020

Background:

Morbid obesity has been recognized as a public health crisis, particularly in developed countries. Single anastomosis sleeve ileal (SASI) bypass has been introduced as a novel bariatric and metabolic procedure. The present study aimed to describe the technical steps and assess the short-term outcomes of SASI bypass in patients with super morbid obesity.

Patients and Methods:

Adult patients of both sexes with body mass index (BMI) ≥50 kg/m2 underwent SASI bypass and were followed for 12 months postoperatively. Changes in BMI, excess weight loss (EWL), and improvement in comorbidities were recorded on follow-up.

Results:

Twenty patients (17 female) of the mean age of 35.4 years were included in the study. The mean preoperative BMI (53.7±5.9) showed a significant decrease at 6 months (39.9±5.2) and then at 12 months (33.6±6) postoperatively. The mean %EWL was 44.3±7.8 at 6 months and 65.2±12.6 at 12 months. All patients with diabetes mellitus, osteoarthritis, and reflux esophagitis showed resolution at 12 months after the SASI bypass. Complications were recorded in 2 patients and no mortality was reported.

Conclusions:

SASI bypass is an effective and safe bariatric procedure that confers significant loss of weight and improvement in medical comorbidities. As compared with previous studies on patients with lower BMI, patients with super morbid obesity attained lower %EWL but similar resolution of diabetes mellitus at 12 months after SASI bypass.
Novel neuroprotection using antioxidant nanoparticles in a mouse model of head trauma
Authors: Takahashi Toshihide , Marushima Aiki , Nagasaki Yukio , Hirayama Aki , Muroi Ai , Puentes Sandra , Mujagic Arnela , Ishikawa Eiichi , Matsumura Akira
Published: February 2020

INTRODUCTION

Free radicals and reactive oxygen species are related to deteriorating pathological conditions after head trauma because of their secondary effects. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) scavenges free radicals; however, this molecule is also toxic. Here, we have evaluated the neuroprotective effect of antioxidant nanoparticles, which consisted of a novel core-shell type nanoparticle containing 4-amino-TEMPO, that is, redox-active nitroxide radical–containing nanoparticles (RNPs).

METHODS

Institute of Cancer Research mice were subjected to a head-impact procedure, randomly divided into four groups and intravenously (3 mg/kg) administered phosphate-buffered saline, TEMPO, micelle (a self-assembling block copolymer micelle without a TEMPO moiety), or RNP through the tail vein immediately thereafter and intraperitoneally at days 1, 3, and 5 after traumatic brain injury (TBI). The RNP distribution was detected by rhodamine labeling. Cognitive behavior was assessed using the neurological severity score and a rotarod test at days 1, 3, and 7 following TBI, and contusion volume was measured at day 7 after TBI. Free radical-scavenging capacity was analyzed by electron paramagnetic resonance on day 1 after TBI, and immunostaining was used to observe mobilization of microglia (Iba-1) and rescued neuronal cells (NeuN).

RESULTS

Redox-active nitroxide radical–containing nanoparticle was detected in the microvessels around the injured area in the brain. Cognitive behavior assessment was significantly better, and contusion volume was significantly smaller in the RNP group compared with the other groups. Superoxide anion scavenging capacity was significantly higher in the RNP group, and neuronal loss was significantly suppressed around the injured area at day 7 after TBI. Furthermore, in the RNP group, neurodegenerative microglia production was suppressed at days 3 and 7 after TBI, whereas neuroprotective microglia production was higher at day 7 after TBI.

CONCLUSION

The RNP administration after TBI improved cognitive behavior and reduced contusion volume by improving reactive oxygen species scavenging capacity. Therefore, RNP may have a neuroprotective effect after TBI.

LEVEL OF EVIDENCE

Therapeutic test.
MicroRNA-338-5p alleviates cerebral ischemia/reperfusion injury by targeting connective tissue growth factor through the adenosine 5′-monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway
Authors: Yi Xiaojing , Fang Qi , Li Lejun
Published: February 2020

Cerebral ischemia/reperfusion (CIR) injury could lead to the function of brain cell disorder and cerebral infarction. MicroRNAs (miRNAs) have been reported to participate in the progression and protection of CIR injury. Thus, our study aimed to investigate the functional effects of microRNA-338-5p (miR-338-5p) on proliferation, apoptosis, and inflammatory response of CIR injury. According to the results, miR-338-5p was downregulated in the brain of the mice caused by CIR injury, and overexpression of miR-338-5p reduced the neurological deficit and infarct volume of the brain in the mice caused by CIR injury. Meanwhile, miR-338-5p overexpression promoted the proliferation, while suppressed the apoptosis and the inflammatory response of Neuro-2a cells exposed to hypoxia/reoxygenation (H/R). Interestingly, miR-338-5p directly targeted connective tissue growth factor (CTGF) and overexpression of CTGF reversed the functional effects of miR-338-5p on proliferation, apoptosis, and inflammatory response in Neuro-2a cells caused by H/R. More importantly, miR-338-5p affected the adenosine 5¢-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway by regulating CTGF expression in Neuro-2a cells exposed to H/R. Taken together, we concluded that MiR-338-5p promoted the proliferation, while suppressed the apoptosis and the inflammatory response of cells exposed to H/R by targeting CTGF through the AMPK/mTOR signaling pathway.
Hedgehog Signalling Modulates Glial Proteostasis and Lifespan
Authors: Rallis Andrew , Navarro Juan A. , Rass Mathias , Hu Amélie , Birman Serge , Schneuwly Stephan , Thérond Pascal P.
Published: February 2020

The conserved Hedgehog (Hh) signaling pathway has a well-established role in animal development, however its function during adulthood remains largely unknown. Here, we investigated whether the Hh signaling pathway is active during adult life inDrosophila melanogasterand uncovered a protective function for Hh signaling in coordinating correct proteostasis in glial cells. Adult-specific depletion of Hh reduces lifespan, locomotor activity and dopaminergic neuron integrity. Conversely, increased expression of Hh extends lifespan and improves fitness. Moreover, Hh pathway activation in glia rescues the lifespan and age-associated defects ofhedgehog(hh) mutants. At the molecular level, the Hh pathway regulates downstream chaperones, principallyhsp40andhsp68, whose overexpression in glial cells rescues the shortened lifespan and proteostasis defects ofhhmutants. Finally, we demonstrate the protective ability of Hh signalling in aDrosophilaAlzheimer’s disease model expressing human Amyloid Beta (Aβ1-42) in the glia. Overall, we propose that Hh signalling is requisite for lifespan determination and correct proteostasis in glial cells and may have potential in ameliorating a wide range of degenerative diseases.
Large-scale RNAi screening uncovers new therapeutic targets in the human parasiteSchistosoma mansoni
Authors: Wang Jipeng , Paz Carlos , Padalino Gilda , Coghlan Avril , Lu Zhigang , Gradinaru Irina , Collins Julie N.R. , Berriman Matthew , Hoffman Karl F , Collins James
Published: February 2020

Schistosomes kill 250,000 people every year and are responsible for serious morbidity in 240 million of the world's poorest people. Despite their profound global impact, only a single drug (praziquantel) is available to treat schistosomiasis, highlighting the need to better understand schistosome biology to drive the development of a new generation of therapeutics. A major barrier to this goal is the paucity of large-scale datasets exploring schistosome gene function. Here, we describe the first large-scale RNA interference screen in adult Schistosoma mansoni examining the function of over 2000 genes representing approximately 20 percent of the protein coding genome. More than 250 genes were found to have phenotypes affecting neuromuscular function, tissue integrity, stem cell maintenance, and parasite survival. Leveraging these data, we bioinformatically prioritized several compounds with in vitro activity against parasites and validated p97, a component of the ubiquitin proteasome system, as a drug target in the worm. We further reveal a potentially druggable protein kinase-signaling module involving the TAO and STK25 kinases that are essential for maintaining the transcription of muscle-specific mRNAs. Importantly, loss of either of these kinases results in paralysis and death of schistosomes following surgical transplantation into a mammalian host. We anticipate this work will invigorate studies into the biology of these poorly studied organisms and expedite the development of new therapeutics to treat an important neglected tropical disease.
A robust mean and variance test with application to high-dimensional phenotypes
Authors: Staley James R , Windmeijer Frank , Suderman Matthew , Lyon Matthew S , Smith George Davey , Tilling Kate
Published: February 2020

Most studies of high-dimensional phenotypes focus on assessing differences in mean levels (location) of the phenotype by exposure, e.g. epigenome-wide association studies of DNA methylation at CpG sites. However, identifying effects on the variability (scale) of these outcomes, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. Here, we review variability tests, specifically an extended (for continuous exposures) version of the Brown-Forsythe test, and develop a novel joint location-and-scale score test for both categorical and continuous exposures (JLSsc). The Brown-Forsythe test and JLSsc performed well in comparison to alternative approaches in simulations. These approaches identified >7500 CpG sites that were associated with either mean or variability with gender or gestational age in cord blood methylation in ARIES (Accessible Resource for Integrated Studies). The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect.
Ascorbate maintains a low plasma low oxygen level
Authors: Injarabian Louise , Scherlinger Marc , Devin Anne , Ransac Stéphane , Lykkesfeldt Jens , Marteyn Benoit S
Published: February 2020

In human blood, oxygen is mainly transported by red blood cells. Accordingly, the oxygen level in plasma is expected to be limited, although it has not been quantified yet. Here, by developing dedicated methods and tools, we determined that human plasma pO2= 8.4 mmHg (1.2% O2). Oxygen solubility in plasma was believed to be similar to water. Here we reveal that plasma has an additional ascorbate-dependent oxygen-reduction activity. Plasma oxygenation oxidizes ascorbate (49.5 μM in fresh plasma vs <2 μM in oxidized plasma) and abolishes this capacity, which is restored by ascorbate supplementation. We confirmed these resultsin vivo, showing that the plasma pO2is significantly higher in ascorbate-deficient guinea pigs (plasma ascorbate < 2μM), compared to control (plasma ascorbate > 15μM). Plasma low oxygen level preserves the integrity of oxidation-sensitive components such as ubiquinol. Circulating leucocytes are well adapted to these conditions, since the abundance of their mitochondrial network is limited.

These results shed a new light on the importance of oxygen exposure on leucocyte biological study, in regards with the reducing conditions they encounterin vivo; but also on the manipulation of blood products to improve their integrity and potentially improve transfusions’ efficacy.

Key points
Epstein Barr virus epitope/MHC interaction combined with convergent recombination drive selection of diverse T cell receptor α and β repertoires
Authors: Gil Anna , Kamga Larisa , Chirravuri-Venkata Ramakanth , Aslan Nuray , Clark Fransenio , Ghersi Dario , Luzuriaga Katherine , Selin Liisa K.
Published: February 2020

Recognition modes of individual T cell receptors (TCR) are well studied, but factors driving the selection of TCR repertoires from primary through persistent human virus infections are less well understood. Using deep sequencing, we demonstrate a high degree of diversity of EBV-specific clonotypes in acute infectious mononucleosis. Only 9% of unique clonotypes detected in AIM persisted into convalescence; the majority (91%) of unique clonotypes detected in AIM were not detected in convalescence and were seeming replaced by equally diverse “de-novo” clonotypes. The persistent clonotypes had a greater probability of being generated than non-persistent due to convergence recombination of multiple nucleotide sequences to encode the same amino acid sequence, as well as the use of shorter CDR3 regions with fewer nucleotide additions (i.e. sequences closer to germline). Moreover, the two most immunodominant HLA-A2-restricted EBV epitopes, BRLF1109and BMLF1280, show highly distinct antigen-specific public (i.e. shared between individuals) features. In fact, TCRα CDR3 motifs played a dominant role, while TCRβ played a minimal role, in the selection of TCR repertoire to an immunodominant EBV epitope, BRLF1. This contrasts with the majority of previously reported repertoires, which appear to be selected either on TCRβ CDR3 interactions with peptide/MHC or in combination with TCRα CDR3. Understanding of how TCR/peptide/MHC complex interactions drive repertoire selection can be used to develop optimal strategies for vaccine design or generation of appropriate adoptive immunotherapies for viral infections in transplant settings or for cancer.

Importance

Several lines of evidence suggest that TCRα and β repertoires play a role in disease outcomes and treatment strategies during viral infections in transplant patients, and in cancer and autoimmune disease therapy. Our data suggests that it is essential that we understand the basic principles of how to drive optimum repertoires for both TCR chains, α and β. We address this important issue by characterizing the CD8 TCR repertoire to a common persistent human viral infection (EBV), which is controlled by appropriate CD8 T cell responses. The ultimate goal would be to determine if the individuals who are infected asymptomatically develop a different TCR repertoire than those that develop the immunopathology of AIM. Here, we begin by doing an in depth characterization of both CD8 T cell TCRα and β repertoires to two immunodominant EBV epitopes over the course of AIM identifying potential factors that may be driving their selection.
Phase transition and structures of the twinned low-temperature phases of (Et4N)[ReS4]
Authors: Bernhardt Eduard , Herbst-Irmer Regine
Published: February 2020

The title compound, tetraethylammonium tetrathiorhenate, [(C2H5)4N][ReS4], has, at room temperature, a disordered structure in the space groupP63mc(Z = 2, α-phase). A phase transition to the monoclinic space groupP21(Z = 2, γ-phase) at 285 K leads to a pseudo-merohedral twin. The high deviation from the hexagonal metric causes split reflections. However, the different orientations could not be separated, but were integrated using a large integration box. Rapid cooling to 110–170 K produces a metastable β-phase (P63,Z = 18) in addition to the γ-phase. All crystals of the β-phase are contaminated with the γ-phase. Additionally, the crystals of the β-phase are merohedrally twinned. In contrast to the α-phase, the β- and γ-phases do not show disorder.
Effect of carbides on sensitivity of pitting corrosion in Inconel 718 alloy
Authors: Wei Xianping , Zheng Wen Jie
Published: February 2020

Purpose

This paper aims to expand the application area of Inconel 718 alloy in marine environment, the sensitivity of pitting corrosion should be analyzed and discussed, especially the effect of block carbides.

Design/methodology/approach

Effect of carbides on the sensitivity of pitting corrosion for Inconel 718 alloy was carried out at 30°C in 3.5% NaCl solution using dynamic electrochemical impedance spectroscopy and anodic polarization techniques. In addition, the initiation of pitting corrosion was investigated by immersion test in 0.05 M HCl + 6% FeCl3 solution.

Findings

As a result, the precipitation of carbides, as the initiation of pitting corrosion, increased pitting corrosion susceptibility, especially the block carbides could lead to deep-spalling. Within that process, temperature and potential acted as the main controlling factors, and the effect of the latter was more distinct.

Originality/value

The initiation of pitting corrosion was revealed by the immersion test. The mechanism of pitting corrosion was analyzed and discussed.
Staged implementation of inclusionary zoning as a mechanism to improve housing affordability in Auckland, New Zealand
Authors: Fernandez Mario A. , Martin Shane L.
Published: February 2020

Purpose

The purpose of this paper is to analyse how the staged implementation of inclusionary zoning (IZ) performs relative to conventional IZ programmes in terms of increasing the number of low- and moderate-income households become homeowners.

Design/methodology/approach

The paper applies a matching model implemented through a mixed-integer programme model taking Auckland (New Zealand) housing market as a case study. The IZ is simulated by two features: a target price (below which affordable houses are defined) and the income threshold (below which any household gains access to the programme). The staging of IZ consists of first directing affordable houses to low-income households, where those houses that are not sold are cascaded to subsequent population groups with higher incomes.

Findings

The staged implementation of IZ does not necessarily imply that the number of sales will increase both for affordable and market-rate houses. However, a hybrid approach defined by two target prices results in a greater number of sales relative to a conventional IZ and a baseline affordable market while achieving market efficiency and equity.

Research limitations/implications

The paper is limited to the marginal impact of new affordable houses entering the market. It does not address further market rounds for houses left empty for tractability purposes. Also, the analysis is circumscribed to current renters and not owners, if owners were included they would outbid renters and distort the intended impact of IZ as an affordable housing policy.

Originality/value

The paper has relevance for policymakers because it provides evidence about the dimensions of IZ to have a lasting effect on housing affordability. The model is applied to a single housing market but is suitable to be generalized and adapted to a different urban environment.
Housing prices and expectations: a study of Auckland
Authors: Yang Yang , Zhou Mingquan , Rehm Michael
Published: February 2020

Purpose

The purpose of this paper is twofold. First, the study aims to test whether expectations are adaptive in the Auckland housing market. The second purpose is to examine the interplay between expectations and Auckland housing prices.

Design/methodology/approach

In this study, two vector error correction models (VECM) are built: one VECM includes survey-based expectations and another one encompasses model-based expectations with the assumption that property investors’ expectations are adaptive. The paper goes on by comparing and examining the results of Granger causality tests and impulse response analyses.

Findings

The findings reveal that Auckland property buyers’ expectations are adaptive. In addition, this study provides some evidence of a feedback cycle between Auckland housing prices and expectations.

Research limitations/implications

This study posits that Auckland property buyers’ expectations in the next 12 months are based on three-year price movements with more emphasis being placed on recent price history. This assumption may not be an accurate reflection of true expectations.

Practical implications

This paper helps policymakers to deepen their understanding of Auckland property buyers by showing that their expectations form through the extrapolation of the past price trend.

Originality/value

The study possibly marks the first attempt to test and compare the relationship between housing prices and two forms of expectations: survey-based and model-based. Additionally, this study is probably the first one that empirically examines whether there is a feedback cycle between expectations and property prices in the Auckland housing market.
Smooth adaptive hybrid impedance control for robotic contact force tracking in dynamic environments
Authors: Cao Hongli , He Ye , Chen Xiaoan , Zhao Xue
Published: February 2020

Purpose

The purpose of this paper is to take transient contact force response, overshoots and steady-state force tracking error problems into account to form an excellent force controller.

Design/methodology/approach

The basic impedance function with a pre-PID tuner is designed to improve the force response. A dynamic adaptive adjustment function that combines the advantages of hybrid impedance and adaptive hybrid impedance control is presented to achieve both force overshoots suppressing and tracking ability.

Findings

The introduced pre-PID tuner impedance function can achieve more than the pure impedance function in aspects of converging to the desired value and reducing the force overshoots. The performance of force overshoots suppression and force tracking error are maintained by introducing the dynamic adaptive sigma adjustment function. The simulation and experimental results both show the achieved control performance by comparing with the previous control methods.

Practical implications

The implementation of the controller is easy and convenient in practical manufacture scenes that require force control using industrial robots.

Originality/value

A superior robot controller adapting to a variety of complex tasks owing to the following characteristics: maintenance of high-accuracy position tracking capability in free-space (basic capabilities of modern industrial robots); maintenance of high speed, stability and smooth contact performance in collision stage; and presentation of high-precision force tracking capability in steady contact.
Equity crowdfunding and regulation: implications for the real estate sector in Italy
Authors: Battisti Enrico , Creta Fabio , Miglietta Nicola
Published: February 2020

Purpose

This paper gathers initial evidence about the nature and features of the equity crowdfunding model in Italy, especially in terms of regulations. The purpose of this study is to examine how equity crowdfunding might support the real estate sector in Italy.

Design/methodology/approach

To explore the recent initiatives in the development of FinTech in Italy, especially referring to equity crowdfunding’s instrument, a qualitative perspective is used. In particular, this paper relies on primary data from regulations and secondary data from the public domain, which are examined in relation to the current literature.

Findings

The results of this study show that equity crowdfunding represents a funding method that is rapidly increasing in Italy, despite rather rigid regulation. Among the various sectors involved, the real estate sector could benefit from the crowdfunding models and, specifically, from the equity one. The development of new real estate equity crowdfunding portals that allow diversification of investment (by reducing the typical entry barriers for real estate investment) could guarantee greater investment transparency and simplicity.

Practical implications

Real estate crowdfunding can be a simple way to invest in the real estate industry. Thanks to the use of technology, specifically internet-based platforms, this type of crowdfunding allows for small investors, as well as professional investors, to access an asset class otherwise not open to small investment tickets and improve the diversification of investments.

Originality/value

Although recent literature has examined the concept of crowdfunding and highlighted different models, aspects and campaigns, no prior studies, to the authors’ knowledge, have explicitly and jointly investigated, also based on the state of art of regulation, the equity crowdfunding model and the real estate sector in Italy.
Drivers of physicians’ satisfaction and continuance intention toward the cloud-based hospital information system
Authors: Cheng Yung-Ming
Published: February 2020

Purpose

The purpose of this study is to propose an integrated model based on expectation-confirmation model (ECM) and technology acceptance model (TAM) to examine whether environmental, human, organizational and technology factors as the antecedents to physicians’ beliefs can affect their satisfaction and continuance intention of the cloud-based hospital information system (HIS).

Design/methodology/approach

Sample data for this study were collected from physicians at six hospitals in Taiwan. A total of 600 questionnaires were distributed, and 471 (78.5 per cent) usable questionnaires were analyzed using structural equation modeling in this study.

Findings

This study proposes a solid research model that is based on ECM and TAM, four types of factors, environmental factor, human factor, organizational factors and technology factors, as antecedents to physicians’ continuance intention of the cloud-based HIS have been examined. This study’s results strongly support the research model with all hypothesized links being significant, and control variables have no confounding effects on physicians’ continuance intention of the cloud-based HIS.

Originality/value

This study contributes to physicians’ continuance intention toward the cloud-based HIS based on ECM, TAM, technology-organization-environment framework and human-organization-technology fit framework, and reveals deep insights into the evaluation of determinants in the field of physicians’ continuance intention of the cloud-based HIS. Accordingly, it is particularly worth mentioning that IS and non-IS determinants are simultaneously evaluated and taken into consideration in this study’s theoretical development of physicians’ continuance intention of the cloud-based HIS to acquire a more comprehensive and robust analysis.