bluuebunny/crossref_metadata_2025 huggingface dataset:
Mid-term outcomes of Sapien 3 versus Perimount Magna Ease for treatment of severe aortic stenosis
Authors: Virtanen Marko P. O. , Eskola Markku , Savontaus Mikko , Juvonen Tatu , Niemelä Matti , Laakso Teemu , Husso Annastiina , Jalava Maina P. , Tauriainen Tuomas , Ahvenvaara Tuomas , Maaranen Pasi , Kinnunen Eeva-Maija , Dahlbacka Sebastian , Laine Mika , Mäkikallio Timo , Valtola Antti , Raivio Peter , Rosato Stefano , D’Errigo Paola , Vento Antti , Airaksinen Juhani , Biancari Fausto
Published: June 2020

Background

There is limited information on the longer-term outcome after transcatheter aortic valve replacement (TAVR) with new-generation prostheses compared to surgical aortic valve replacement (SAVR). The aim of this study was to compare the mid-term outcomes after TAVR with Sapien 3 and SAVR with Perimount Magna Ease bioprostheses for severe aortic stenosis.

Methods

In a retrospective study, we included patients who underwent transfemoral TAVR with Sapien 3 or SAVR with Perimount Magna Ease bioprosthesis between January 2008 and October 2017 from the nationwide FinnValve registry. Propensity score matching was performed to adjust for differences in the baseline characteristics. The Kaplan-Meir method was used to estimate late mortality.

Results

A total of 2000 patients were included (689 in the TAVR cohort and 1311 in the SAVR cohort). Propensity score matching resulted in 308 pairs (STS score, TAVR 3.5 ± 2.2% vs. SAVR 3.5 ± 2.8%, p = 0.918). In-hospital mortality was 3.6% after SAVR and 1.3% after TAVR (p = 0.092). Stroke, acute kidney injury, bleeding and atrial fibrillation were significantly more frequent after SAVR, but higher rate of vascular complications was observed after TAVR. The cumulative incidence of permanent pacemaker implantation at 4 years was 13.9% in the TAVR group and 6.9% in the SAVR group (p = 0.0004). At 4-years, all-cause mortality was 20.6% for SAVR and 25.9% for TAVR (p = 0.910). Four-year rates of coronary revascularization, prosthetic valve endocarditis and repeat aortic valve intervention were similar between matched cohorts.

Conclusions

The Sapien 3 bioprosthesis achieves comparable midterm outcomes to a surgical bioprosthesis with proven durability such as the Perimount Magna Ease. However, the Sapien 3 bioprosthesis was associated with better early outcome.

Trial registration

ClinicalTrials.gov Identifier: NCT03385915.
Mechanisms of generation and exudation of Tibetan medicine Shilajit (Zhaxun)
Authors: Ding Rong , Zhao Mingming , Fan Jiuyu , Hu Xiuquan , Wang Meng , Zhong Shihong , Gu Rui
Published: June 2020

Background

Shilajit is a commonly used Tibetan medicine, and its water extract is mainly used for various heat-related syndrome, especially that of stomach, liver and kidney. Shilajit is found to exudate from rocks of cliff at an altitude of 2000–4000 m as a water-soluble mixture of black paste and animal feces of Trodocterus spp. or Ochotona spp. Because it is difficult to reach the exudation points so as to explain the its formation process, the source of Shilajit still remains unclear and controversial, which severely impedes its safety and efficacy in clinical application.

Methods

In this work, a series of investigations as rock flakes identification, porosity determination, rock mineral analysis, scanning electron microscopy (SEM), and energy dispersive spectrometer (EDS) have been carried out to clarify the source of Shilajit, including the storage condition and exudation process of its organic matter, and to investigate the geological structure of the exudation points as well as physical and chemical characteristics of the mother rocks.

Results

The Shilajit exudation points were mainly distributed on the steep cliffs, where there were cavities and sections that could not be eroded by rainwater. The fundamental structure of the exudation points was determined by the rock’s bedding planes, joints, fracture surfaces and faults, and developed into micro-topography later. The exudation points were distributed in the Triassic strata and scattered in the Early Mesozoic granitoids. The lithologic features were mainly slate, carbonaceous slate and sandy slate etc. The background rocks were characterized by intergranular pores, dissolved pore, joint and fracture development. Organic matter was widely distributed in these pores and fissures, which had condition for storage and exudation of organic matter.

Conclusions

Shilajit mainly distributed on sunny steep slopes and cliffs with a slope of 60° or above at altitude of 2000–4000 m. The lithology character of the Shilajit exudation area were mainly various metamorphic rocks of sedimentary rocks that were rich in organic carbon. The organic matter in Shilajit was found to flow out naturally from rocks along pore, structural plane and even accumulate on the surface of rock as a result of storage environment change caused by rock tectonic action.
Non-deletional alpha thalassaemia: a review
Authors: Kalle Kwaifa Ibrahim , Lai Mei I. , Md Noor Sabariah
Published: June 2020

Background

Defective synthesis of the α-globin chain due to mutations in the alpha-globin genes and/or its regulatory elements leads to alpha thalassaemia syndrome. Complete deletion of the 4 alpha-globin genes results in the most severe phenotype known as haemoglobin Bart’s, which leads to intrauterine death. The presence of one functional alpha gene is associated with haemoglobin H disease, characterised by non-transfusion-dependent thalassaemia phenotype, while silent and carrier traits are mostly asymptomatic.

Main body

Clinical manifestations of non-deletional in alpha thalassaemia are varied and have more severe phenotype compared to deletional forms of alpha thalassaemia. Literature for the molecular mechanisms of common non-deletional alpha thalassaemia including therapeutic measures that are necessarily needed for the understanding of these disorders is still in demand. This manuscript would contribute to the better knowledge of how defective production of the α-globin chains due to mutations on the alpha-globin genes and/or the regulatory elements leads to alpha thalassaemia syndrome.

Conclusion

Since many molecular markers are associated with the globin gene expression and switching over during the developmental stages, there is a need for increased awareness, new-born and prenatal screening program, especially for countries with high migration impact, and for improving the monitoring of patients with α-thalassaemia.
Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock
Authors: Jiao Yang , Li Weiwei , Wang Wei , Tong Xingyu , Xia Ran , Fan Jie , Du Jianer , Zhang Chengmi , Shi Xueyin
Published: June 2020

Background

Platelets have been demonstrated to be potent activators of neutrophil extracellular trap (NET) formation during sepsis. However, the mediators and molecular pathways involved in human platelet-mediated NET generation remain poorly defined. Circulating plasma exosomes mostly originating from platelets may induce vascular apoptosis and myocardial dysfunction during sepsis; however, their role in NET formation remains unclear. This study aimed to detect whether platelet-derived exosomes could promote NET formation during septic shock and determine the potential mechanisms involved.

Methods

Polymorphonuclear neutrophils (PMNs) were cocultured with exosomes isolated from the plasma of healthy controls and septic shock patients or the supernatant of human platelets stimulated ex vivo with phosphate buffer saline (PBS) or lipopolysaccharide (LPS). A lethal cecal ligation and puncture (CLP) mouse model was used to mimic sepsis in vivo; then, NET formation and molecular pathways were detected.

Results

NET components (dsDNA and MPO-DNA complexes) were significantly increased in response to treatment with septic shock patient-derived exosomes and correlated positively with disease severity and outcome. In the animal CLP model, platelet depletion reduced plasma exosome concentration, NET formation, and lung injury. Mechanistic studies demonstrated that exosomal high-mobility group protein 1 (HMGB1) and/or miR-15b-5p and miR-378a-3p induced NET formation through the Akt/mTOR autophagy pathway. Furthermore, the results suggested that IκB kinase (IKK) controls platelet-derived exosome secretion in septic shock.

Conclusions

Platelet-derived exosomes promote excessive NET formation in sepsis and subsequent organ injury. This finding suggests a previously unidentified role of platelet-derived exosomes in sepsis and may lead to new therapeutic approaches.
Update of the treatment of nosocomial pneumonia in the ICU
Authors: Zaragoza Rafael , Vidal-Cortés Pablo , Aguilar Gerardo , Borges Marcio , Diaz Emili , Ferrer Ricard , Maseda Emilio , Nieto Mercedes , Nuvials Francisco Xavier , Ramirez Paula , Rodriguez Alejandro , Soriano Cruz , Veganzones Javier , Martín-Loeches Ignacio
Published: June 2020

In accordance with the recommendations of, amongst others, the Surviving Sepsis Campaign and the recently published European treatment guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), in the event of a patient with such infections, empirical antibiotic treatment must be appropriate and administered as early as possible. The aim of this manuscript is to update treatment protocols by reviewing recently published studies on the treatment of nosocomial pneumonia in the critically ill patients that require invasive respiratory support and patients with HAP from hospital wards that require invasive mechanical ventilation. An interdisciplinary group of experts, comprising specialists in anaesthesia and resuscitation and in intensive care medicine, updated the epidemiology and antimicrobial resistance and established clinical management priorities based on patients’ risk factors. Implementation of rapid diagnostic microbiological techniques available and the new antibiotics recently added to the therapeutic arsenal has been reviewed and updated. After analysis of the categories outlined, some recommendations were suggested, and an algorithm to update empirical and targeted treatment in critically ill patients has also been designed. These aspects are key to improve VAP outcomes because of the severity of patients and possible acquisition of multidrug-resistant organisms (MDROs).
Brain tight junction protein expression in sepsis in an autopsy series
Authors: Erikson Kristo , Tuominen Hannu , Vakkala Merja , Liisanantti Janne Henrik , Karttunen Tuomo , Syrjälä Hannu , Ala-Kokko Tero Ilmari
Published: June 2020

Background

Neuroinflammation often develops in sepsis along with increasing permeability of the blood-brain barrier (BBB), which leads to septic encephalopathy. The barrier is formed by tight junction structures between the cerebral endothelial cells. We investigated the expression of tight junction proteins related to endothelial permeability in brain autopsy specimens in critically ill patients deceased with sepsis and analyzed the relationship of BBB damage with measures of systemic inflammation and systemic organ dysfunction.

Methods

The case series included all (385) adult patients deceased due to sepsis in the years 2007–2015 with available brain specimens taken at autopsy. Specimens were categorized according to anatomical location (cerebrum, cerebellum). The immunohistochemical stainings were performed for occludin, ZO-1, and claudin. Patients were categorized as having BBB damage if there was no expression of occludin in the endothelium of cerebral microvessels.

Results

Brain tissue samples were available in 47 autopsies, of which 38% (18/47) had no expression of occludin in the endothelium of cerebral microvessels, 34% (16/47) developed multiple organ failure before death, and 74.5% (35/47) had septic shock.

The deceased with BBB damage had higher maximum SOFA scores (16 vs. 14, p = 0.04) and more often had procalcitonin levels above 10 μg/L (56% vs. 28%, p = 0.045) during their ICU stay. BBB damage in the cerebellum was more common in cases with C-reactive protein (CRP) above 100 mg/L as compared with CRP less than 100 (69% vs. 25%, p = 0.025).

Conclusions

In fatal sepsis, damaged BBB defined as a loss of cerebral endothelial expression of occludin is related with severe organ dysfunction and systemic inflammation.
T-tube drainage versus choledochojejunostomy in hepatolithiasis patients with sphincter of Oddi laxity: study protocol for a randomized controlled trial
Authors: Chen Jiang-ming , Yan Xi-yang , Zhu Tao , Chen Zi-xiang , Zhao Yi-jun , Xie Kun , Liu Fu-bao , Geng Xiao-ping
Published: June 2020

Background

Residual and recurrent stones remain one of the most important challenges of hepatolithiasis and are reported in 20 to 50% of patients treated for this condition. To date, the two most common surgical procedures performed for hepatolithiasis are choledochojejunostomy and T-tube drainage for biliary drainage. The goal of the present study was to evaluate the therapeutic safety and perioperative and long-term outcomes of choledochojejunostomy versus T-tube drainage for hepatolithiasis patients with sphincter of Oddi laxity (SOL).

Methods/design

In total, 210 patients who met the following eligibility criteria were included and were randomized to the choledochojejunostomy arm or T-tube drainage arm in a 1:1 ratio: (1) diagnosed with hepatolithiasis with SOL during surgery; (2) underwent foci removal, stone extraction and stricture correction during the operation; (3) provided written informed consent; (4) was willing to complete a 3-year follow-up; and (5) aged between 18 and 70 years. The primary efficacy endpoint of the trial will be the incidence of biliary complications (stone recurrence, biliary stricture, cholangitis) during the 3 years after surgery. The secondary outcomes will be the surgical, perioperative and long-term follow-up outcomes.

Discussion

This is a prospective, single-centre and randomized controlled two-group parallel trial designed to demonstrate which drainage method (Roux-en-Y hepaticojejunostomy or T-tube drainage) can better reduce biliary complications (stone recurrence, biliary stricture, cholangitis) in hepatolithiasis patients with SOL.

Trial registration

Clinical Trials.gov: NCT04218669. Registered on 6 January 2020.
Cutaneous wound healing: canine allogeneic ASC therapy
Authors: Enciso Nathaly , Avedillo Luis , Fermín María Luisa , Fragío Cristina , Tejero Concepción
Published: June 2020

Background

Wound healing is a complex biological process comprised of a series of sequential events aiming to repair injured tissue. Adult mesenchymal stem cells (MSCs) have been used in cellular therapy in preclinical animal studies; a promising source of MSCs is adipose tissue (AT). In this paper, we evaluated the clinical value and safety of the application of cultured allogenic MSCs from AT for acute and chronic skin wound healing in a canine model.

Methods

Twenty-four dogs of different breeds between 1 and 10 years of age with acute and chronic wounds were studied. Morphology of the wounded skin was monitored for changes over time via serial photographs and histopathological studies.

Results

The percentage of the wounds that exhibited contraction and re-epithelialization were significantly different between wounds treated with adipose mesenchymal stem cells (ASCs) and control wounds; this effect was observed in both acute and chronic conditions. At 90 days, re-epithelization of acute and chronic wounds reached more than 97%. Histopathological study revealed a reduction in inflammatory infiltrate and the presence of multiple hair follicles on day 7 after treatment with ASCs, promoting epidermal and dermal regeneration. To guarantee the safety of our treatment, we determined the serum levels of cytokine markers in our patients. ASC treatment upregulated granulocyte-macrophage colony stimulating factor (GM-CSF) at the gene level, which may contribute to the recruitment of cells that participate in skin repair to the site of injury.

Conclusions

The development of an allogenic ASC therapy to improve wound healing in a canine model could have a clinical impact in human treatment.
Deep-learned faces: a survey
Authors: K. Wickrama Arachchilage Samadhi P. , Izquierdo Ebroul
Published: June 2020

Deep learning technology has enabled successful modeling of complex facial features when high-quality images are available. Nonetheless, accurate modeling and recognition of human faces in real-world scenarios “on the wild” or under adverse conditions remains an open problem. Consequently, a plethora of novel deep network architectures addressing issues related to low-quality images, varying pose, illumination changes, emotional expressions, etc., have been proposed and studied over the last few years.This survey presents a comprehensive analysis of the latest developments in the field. A conventional deep face recognition system entails several main components: deep network, optimization loss function, classification algorithm, and train data collection. Aiming at providing a complete and comprehensive study of such complex frameworks, this paper first discusses the evolution of related network architectures. Next, a comparative analysis of loss functions, classification algorithms, and face datasets is given. Then, a comparative study of state-of-the-art face recognition systems is presented. Here, the performance of the systems is discussed using three benchmarking datasets with increasing degrees of complexity. Furthermore, an experimental study was conducted to compare several openly accessible face recognition frameworks in terms of recognition accuracy and speed.
Effects of free-air CO2 enrichment (FACE) and nitrogen (N) supply on N uptake and utilization of indica and japonica cultivars (Oryza sativa L.)
Authors: Jiang Qian , Zhang Jishuang , Xu Xi , Liu Gang , Zhu Jianguo
Published: June 2020

Background

Increasing atmospheric [CO2] can increase photosynthesis and promote plant growth, consequently influencing nitrogen (N) cycling. Yet, there is no systematic information on the N response among different organs of japonica and indica rice genotypes to elevated [CO2] as affected by N application. To investigate the impacts of elevated [CO2] and N fertilization on N uptake and utilization of different genotypic rice (Oryza sativa L.) during grain filling, a free-air CO2 enrichment (FACE) experiment with indica cv. Liangyou 084 (IIY084) and japonica cv. Wuyunjing 23 (WYJ23) was conducted in Eastern China. Crops were exposed to ambient [CO2] and elevated [CO2] (200 μmol mol−1 above ambient) at two levels of N: control (0N) and 22.5 g N m−2 (normal N, NN), and they were sampled at 82 days after transplanting (DAT), 99 DAT, and maturity, respectively.

Results

Under FACE, significant declines of N concentration in all tissues and the whole plants were observed with the greater decrease in leaves and stems at three stages. Positive responses of N use efficiency (NUE) to elevated [CO2] were recorded over the study period. The total N accumulation remained unchanged, while a large amount of N was partitioned to panicles at the expense of leaves and stems. As compared to WYJ23, greater N transportation from roots to aboveground, especially the panicles, was observed on IIY084 accompanied by higher panicle biomass (82 DAT and 99 DAT), N concentrations (maturity), and greater NUE for leaves through the study season. Across all [CO2] and cultivars, N fertilization increased N partitioning to leaves and stems while decreasing that to panicles. Additionally, N supply decreased NUE while stimulating N concentrations and N amounts of rice plants. Among all treatments, IIY084 had the highest N accumulation and allocation in panicles under elevated [CO2] in combination with N fertilizer at maturity.

Conclusion

Data from this study were helpful for understanding the temporal N uptake and utilization of different rice genotypes as affected by N availability and suggest that IIY084 promises a considerable prospect for its grain yield and quality under future elevated atmospheric [CO2].
How do state Medicaid programs determine what substance use disorder treatment medications need prior authorization? An overview for clinicians
Authors: Bachhuber Marcus A.
Published: June 2020

The process by which state Medicaid programs develop their preferred drug lists, and determine which medications require prior authorization, is opaque to many clinicians. This process is a synthesis of cost and clinical information. For cost, the federal Medicaid Drug Rebate Program establishes mandatory rebates that pharmaceutical manufacturers must pay state Medicaid programs. In addition, state Medicaid programs may also negotiate supplemental rebates whereby, in exchange for a preferred position on the preferred drug list, manufacturers pay an additional rebate. These supplemental rebates are most important in therapeutic classes with multiple brand competitors (e.g., medication treatments for opioid use disorder). For clinical information, state Medicaid programs convene pharmaceutical and therapeutics committees, drug utilization review boards, or both, composed of a variety of stakeholders such as practicing clinicians. Cost factors such as federal rebate calculations and supplemental rebate negotiations may lead to counterintuitive preferred drug lists, for example, a state Medicaid program requiring prior authorization for a generic medication but not for its brand equivalent (e.g., buprenorphine/naloxone products). Because of states’ reliance on rebates, mandates to remove prior authorization may have the unintended consequence of increasing costs significantly through the loss of rebate negotiating power. In the face of high and rising medication costs, state Medicaid programs are also implementing innovative policy approaches to maintain access and control costs, such as targeted rebate negotiation and value-based pricing. Through participation in state Medicaid program clinical advisory committees, individual clinicians can have a powerful voice. Interested clinicians should consider joining to inform policy and help ensure their patients’ needs are met.
The impact of antimicrobial stewardship program implementation at four tertiary private hospitals: results of a five-years pre-post analysis
Authors: Al-Omari Awad , Al Mutair Abbas , Alhumaid Saad , Salih Samer , Alanazi Ahmed , Albarsan Hesham , Abourayan Maha , Al Subaie Maha
Published: June 2020

Background

Antimicrobial stewardship (AMS) programs have shown to reduce the emergence of antimicrobial resistance (AMR) and health-care-associated infections (HAIs), and save health-care costs associated with an inappropriate antimicrobial use. The primary objective of this study was to compare the consumption and cost of antimicrobial agents using defined daily dose (DDD) and direct cost of antibiotics before and after the AMS program implementation. Secondary objective was to determine the rate of HAIs [Clostridium difficile(C. difficile), ventilator-associated pneumonia (VAP), and central line-associated bloodstream infection (CLABSI) before and after the AMS program implementation.

Methods

This is a pre-post quasi-experimental study. Adult inpatients were enrolled in a prospective fashion under the active AMS arm and compared with historical inpatients who were admitted to the same units before the AMS implementation. Study was conducted at four tertiary private hospitals located in two cities in Saudi Arabia. Adult inpatients were enrolled under the pre- AMS arm and post- AMS arm if they were on any of the ten selected restricted broad-spectrum antibiotics (imipenem/cilastatin, piperacillin/tazobactam, colistin, tigecycline, cefepime, meropenem, ciprofloxacin, moxifloxacin, teicoplanin and linezolid).

Results

A total of 409,403 subjects were recruited, 79,369 in the pre- AMS control and 330,034 in the post- AMS arm. Average DDDs consumption of all targeted broad-spectrum antimicrobials from January 2016 to June 2019 post- AMS launch was lower than the DDDs use of these agents pre- AMS (233 vs 320 DDDs per 1000 patient-days,p = 0.689). Antimicrobial expenditures decreased by 28.45% in the first year of the program and remained relatively stable in subsequent years, with overall cumulative cost savings estimated at S.R. 6,286,929 and negligible expenses of S.R. 505,115 (p = 0.648). Rates of healthcare associated infections involvingC. difficile, VAP, and CLABSI all decreased significantly after AMS implementation (incidence of HAIs in 2015 compared to 2019: forC. difficile, 94 vs 13,p = 0.024; for VAP, 24 vs 6,p = 0.001; for CLABSI, 17 vs 1,p = 0.000; respectively).

Conclusion

Implementation of AMS program at HMG healthcare facilities resulted in reduced antimicrobials use and cost, and lowered incidence of healthcare associated infections.
The effects of aqueous extract of Maca on energy metabolism and immunoregulation
Authors: Fei Wenting , Hou Yan , Yue Na , Zhou Xue , Wang Yujie , Wang Linyuan , Li Aimin , Zhang Jianjun
Published: June 2020

Background

In the present work, we investigated the effects of aqueous extract of Maca (AEM) on energy metabolism and immunoregulation in spleen-deficient mice.

Method

We established a cyclophosphamide-induced spleen-deficiency model with ginseng, a herb that strengthens splenic function, as a control. Sixty male Kunming mice were randomly divided among 5 groups: normal, model, ginseng control (1.5 g/kg), AEM high dose (1.5 g/kg), and AEM low dose (0.75 g/kg). All animals, except those in the normal group, were injected with cyclophosphamide to induce spleen deficiency. Furthermore, we investigated differences in the thermotropic behaviors of mice using the Animal Thermotropism Behavior Surveillance System to detect energy metabolism-related assays and immune regulation assays.

Results

Mice given AEM exhibited tropism in response to hot plate exposure. AEM inhibited loss of body weight and immune organ atrophy caused by cyclophosphamide, increased the cAMP/cGMP ratio in blood, and enhanced the activities of Na+–K+-ATPase, Ca2+–Mg2+-ATPase, lactate dehydrogenase, and hepatic glycogen. AEM significantly reversed declining white blood cells and platelet counts, and increased the hemoglobin content within peripheral blood cells. AEM improved the protein levels of IFN-γ, TNF-β, IL-2, and IL-4 in the spleen.

Conclusions

Maca possesses the Traditional Chinese Medicine (TCM) property of warm and appears to strengthen spleen function.
A critical assessment of marine predator isoscapes within the southern Indian Ocean
Authors: Carpenter-Kling Tegan , Pistorius Pierre , Reisinger Ryan , Cherel Yves , Connan Maëlle
Published: June 2020

Background

Precise and accurate retrospective geolocation of marine predators via their tissues’ isotopic composition relies on quality reference maps of relevant isotopic gradients (“isoscapes”). Additionally, a good working knowledge of any discrimination factors that may offset a marine predator’s isotopic composition from baseline isotopic values, as well as tissue specific retention rates, are imperative. We provide a critical assessment of inter-specific differences among marine predator-level isoscapes within the Indian Sector of the Southern Ocean.

Methods

We combined fine-scale GPS tracking data and concurrent blood plasma δ13C and δ15N values of eight seabird species (three albatross, two giant petrel and three penguin species) breeding at Marion Island to produce species- and guild-specific isoscapes.

Results

Overall, our study revealed latitudinal spatial gradients in both δ13C and δ15N for far-ranging seabirds (albatrosses and giant petrels) as well as inshore-offshore gradients for near-ranging seabirds (penguins). However, at the species level, latitudinal spatial gradients were not reflected in the δ13C and δ15N isoscapes of two and three, respectively, of the five far-ranging species studied. It is therefore important when possible to estimate and apply species-specific isoscapes or have a good understanding of any factors and pathways affecting marine predators’ isotopic composition when estimating the foraging distribution of marine predators via their tissues’ stable isotope compositions.

Conclusions

Using a multi-species approach, we provide evidence of large and regional scale systematic spatial variability of δ13C and δ15N at the base of the marine food web that propagates through trophic levels and is reflected in the isotopic composition of top predators’ tissues.
A guide for studying among-individual behavioral variation from movement data in the wild
Authors: Hertel Anne G. , Niemelä Petri T. , Dingemanse Niels J. , Mueller Thomas
Published: June 2020

Animal tracking and biologging devices record large amounts of data on individual movement behaviors in natural environments. In these data, movement ecologists often view unexplained variation around the mean as “noise” when studying patterns at the population level. In the field of behavioral ecology, however, focus has shifted from population means to the biological underpinnings of variation around means. Specifically, behavioral ecologists use repeated measures of individual behavior to partition behavioral variability into intrinsic among-individual variation and reversible behavioral plasticity and to quantify: a) individual variation in behavioral types (i.e. different average behavioral expression), b) individual variation in behavioral plasticity (i.e. different responsiveness of individuals to environmental gradients), c) individual variation in behavioral predictability (i.e. different residual within-individual variability of behavior around the mean), and d) correlations among these components and correlations in suites of behaviors, called ‘behavioral syndromes’. We here suggest that partitioning behavioral variability in animal movements will further the integration of movement ecology with other fields of behavioral ecology. We provide a literature review illustrating that individual differences in movement behaviors are insightful for wildlife and conservation studies and give recommendations regarding the data required for addressing such questions. In the accompanying R tutorial we provide a guide to the statistical approaches quantifying the different aspects of among-individual variation. We use movement data from 35 African elephants and show that elephants differ in a) their average behavior for three common movement behaviors, b) the rate at which they adjusted movement over a temporal gradient, and c) their behavioral predictability (ranging from more to less predictable individuals). Finally, two of the three movement behaviors were correlated into a behavioral syndrome (d), with farther moving individuals having shorter mean residence times. Though not explicitly tested here, individual differences in movement and predictability can affect an individual’s risk to be hunted or poached and could therefore open new avenues for conservation biologists to assess population viability. We hope that this review, tutorial, and worked example will encourage movement ecologists to examine the biology of individual variation in animal movements hidden behind the population mean.
A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy
Authors: Baderna Valentina , Schultz Joshua , Kearns Lisa S. , Fahey Michael , Thompson Bryony A. , Ruddle Jonathan B. , Huq Aamira , Maltecca Francesca
Published: June 2020

Autosomal dominant optic atrophy (ADOA) is a neuro-ophthalmic condition characterized by bilateral degeneration of the optic nerves. Although heterozygous mutations in OPA1 represent the most common genetic cause of ADOA, a significant number of cases remain undiagnosed.

Here, we describe a family with a strong ADOA history with most family members spanning three generation having childhood onset of visual symptoms. The proband, in addition to optic atrophy, had neurological symptoms consistent with relapsing remitting multiple sclerosis. Clinical exome analysis detected a novel mutation in the AFG3L2 gene (NM_006796.2:c.1010G > A; p.G337E), which segregated with optic atrophy in family members. AFG3L2 is a metalloprotease of the AAA subfamily which exerts quality control in the inner mitochondrial membrane. Interestingly, the identified mutation localizes close to the AAA domain of AFG3L2, while those localized in the proteolytic domain cause dominant spinocerebellar ataxia type 28 (SCA28) or recessive spastic ataxia with epilepsy (SPAX5). Functional studies in patient fibroblasts demonstrate that the p.G337E AFG3L2 mutation strongly destabilizes the long isoforms of OPA1 via OMA hyper-activation and leads to mitochondrial fragmentation, thus explaining the family phenotype. This study widens the clinical spectrum of neurodegenerative diseases caused by AFG3L2 mutations, which shall be considered as genetic cause of ADOA.
Living donor liver transplantation for congenital absence of portal vein in portal venous reconstruction with a great saphenous vein graft
Authors: Li Peilin , Hidaka Masaaki , Hamada Takashi , Ikeda Satoshi , Ono Shinichiro , Maruya Yasuhiro , Kugiyama Tota , Hara Takanobu , Yoshimoto Tomoko , Adachi Tomohiko , Tanaka Takayuki , Miyoshi Takayuki , Murakami Shunsuke , Huang Yu , Kanetaka Kengo , Eguchi Susumu
Published: June 2020

Background

Congenital absence of portal vein (CAPV) is a rare structural anomaly in which the portal vein (PV) blood that normally flow into the liver directly drains into the systemic venous system through other collateral circulation. Congenital portal vein shunts (CPSs) is classified into types I and II according to the absence or presence of the intrahepatic portal vein, respectively. The CPS type I is also known as CAPV. The liver transplantation may be the only treatment option for CAPV. The key point of liver transplantation for CAPV is the reconstruction of the PV.

Case presentation

A 29-year-old man was diagnosed with CAPV with splenomegaly and gastroesophageal varix when being treated for pancytopenia and liver dysfunction. A living donor liver transplantation was performed for him using the right lobe which had been donated by his mother. The PV was reconstructed using his own great saphenous vein (GSV) as a graft vein. The end of the GSV graft was anastomosed to the inferior mesenteric vein while the other end was anastomosed to the vein graft of the right hepatic vein from the explanted liver.

Conclusion

Using the patient’s own GSV for PV reconstruction during living donor transplantation in the patient with CAPV seems to be an effective method.
4-Hexylresorcinol induced angiogenesis potential in human endothelial cells
Authors: Kim Min-Keun , Kim Seong-Gon , Lee Suk Keun
Published: June 2020

Background

4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified.

Methods

As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera.

Results

Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization.

Conclusion

Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.
Correlation between operating parameters and removal efficiency for chemically enhanced primary treatment system of wastewater
Authors: Al Bazedi Ghada A. , Abdel-Fatah Mona A.
Published: June 2020

Background

“Chemically enhanced primary treatment” (CEPT) is an approach to wastewater treatment. It can be utilized as a specially designed step in “biological” secondary treatment processes. The aim of this study is to create an empirical model of separation efficiency for wastewater chemically enhanced primary treatment.

Methods

The empirical model is undertaken using the simulation of the data obtained from pilot plant experimental studies using different types of coagulant (FeCl3, alum, lime, and Magna-floc155).

The empirical modeling techniques used multivariate regression model. Different values of BOD5, COD, TSS, as well as separation efficiencies for COD and TSS were investigated in accordance to achieve final effluent results that would meet the Egyptian standards limit.

Results

Multiple regression analysis showed that removal efficiencies of COD and TSS can be predicted to be (R2 = 0.973 and 0.978, respectively).

Conclusion

The present work provides an approach for using chemically enhanced primary treatment of wastewater. The obtained results showed that the empirical model can predict removal efficiencies with R2 = 0.973, and 0.978 for COD and TSS. The advantage of this model is that it would allow better process control and treatment efficiency. The results show that chemically enhanced primary treatment method can be used as an efficient method in conventional municipal wastewater treatment plants to reduce the organic load of biological treatment and enhance nutrients removal.
Repetitive transcranial magnetic stimulation of the prefrontal cortex for fibromyalgia syndrome: a randomised controlled trial with 6-months follow up
Authors: Tanwar Suman , Mattoo Bhawna , Kumar Uma , Bhatia Renu
Published: June 2020

Objectives

Fibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS.

Methods

Ninety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months).

Results

In Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed.

Conclusion

Right DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation .

Trial registration: Ref No: CTRI/2013/12/004228.
Statistical Assessment of Depth Normalization for Small RNA Sequencing
Authors: Qin Li-Xuan , Zou Jian , Shi Jiejun , Lee Ann , Mihailovic Aleksandra , Farazi Thalia A. , Tuschl Thomas , Singer Samuel
Published: June 2020

PURPOSE

Methods for depth normalization have been assessed primarily with simulated data or cell-line–mixture data. There is a pressing need for benchmark data enabling a more realistic and objective assessment, especially in the context of small RNA sequencing.

METHODS

We collected a unique pair of microRNA sequencing data sets for the same set of tumor samples; one data set was collected with and the other without uniform handling and balanced design. The former provided a benchmark for evaluating evidence of differential expression and the latter served as a test bed for normalization. Next, we developed a data perturbation algorithm to simulate additional data set pairs. Last, we assembled a set of computational tools to visualize and quantify the assessment.

RESULTS

We validated the quality of the benchmark data and showed the need for normalization of the test data. For illustration, we applied the data and tools to assess the performance of 9 existing normalization methods. Among them, trimmed mean of M-values was a better scaling method, whereas the median and the upper quartiles were consistently the worst performers; one variation of remove unwanted variation had the best chance of capturing true positives but at the cost of increased false positives. In general, these methods were, at best, moderately helpful when the level of differential expression was extensive and asymmetric.

CONCLUSION

Our study (1) provides the much-needed benchmark data and computational tools for assessing depth normalization, (2) shows the dependence of normalization performance on the underlying pattern of differential expression, and (3) calls for continued research efforts to develop more effective normalization methods.
Chasing ctDNA in Patients With Sarcoma
Authors: Coombs Catherine C. , Dickherber Tony , Crompton Brian D.
Published: June 2020

Liquid biopsies are new technologies that allow cancer profiling of tumor fragments found in body fluids, such as peripheral blood, collected noninvasively from patients with malignancies. These assays are increasingly valuable in clinical oncology practice as prognostic biomarkers, as guides for therapy selection, for treatment monitoring, and for early detection of disease progression and relapse. However, application of these assays to rare cancers, such as pediatric and adult sarcomas, have lagged. In this article, we review the technical challenges of applying liquid biopsy technologies to sarcomas, provide an update on progress in the field, describe common pitfalls in interpreting liquid biopsy data, and discuss the intersection of sarcoma clinical care and commercial assays emerging on the horizon.
Newborn Screening TSH Values Less Than 15 mIU/L Are Not Associated With Long-term Hypothyroidism or Cognitive Impairment
Authors: West Rachel , Hong Joyce , Derraik José G B , Webster Dianne , Heather Natasha L , Hofman Paul L
Published: June 2020

Background

It is unclear whether newborns with mild thyrotropin elevation (mTSHe) are at risk of neurocognitive impairment. We assessed whether mTSHe at birth persists during childhood and compared neurocognitive functioning to siblings.

Methods

This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition.

Results

Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P = .040), they were not associated with the magnitude of the IQ difference within sibling pairs (P = .56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P = .36), with a minor isolated difference in motor coordination scores.

Conclusions

Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long-term benefit for those detected.
Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome
Authors: Vaduva Patricia , Bonnet Fideline , Bertherat Jérôme
Published: June 2020

This review reports the main molecular alterations leading to development of benign cortisol- and/or aldosterone-secreting adrenal tumors. Causes of adrenal Cushing syndrome can be divided in 2 groups: multiple bilateral tumors or adenomas secreting cortisol. Bilateral causes are mainly primary pigmented nodular adrenocortical disease, most of the time due to PRKAR1A germline-inactivating mutations, and primary bilateral macronodular adrenal hyperplasia that can be caused in some rare syndromic cases by germline-inactivating mutations of MEN1, APC, and FH and of ARMC5 in isolated forms. PRKACA somatic-activating mutations are the main alterations in unilateral cortisol-producing adenomas. In primary hyperaldosteronism (PA), familial forms were identified in 1% to 5% of cases: familial hyperaldosteronism type I (FH-I) due to a chimeric CYP11B1/CYP11B2 hybrid gene, FH-II due to CLCN-2 germline mutations, FH-III due to KCNJ5 germline mutations, FH-IV due to CACNA1H germline mutations and PA, and seizures and neurological abnormalities syndrome due to CACNA1D germline mutations. Several somatic mutations have been found in aldosterone-producing adenomas in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 genes.

In addition to these genetic alterations, genome-wide approaches identified several new alterations in transcriptome, methylome, and miRnome studies, highlighting new pathways involved in steroid dysregulation.
The Narco Uncanny
Authors: Muehlmann Shaylih
Published: June 2020

This article analyzes the unease created in northern Mexico by the prevalence of “narco-accusations,” which single out individuals suspected of being drug traffickers. The official discourse to justify the Mexican government’s unwillingness to investigate the majority of the 235,000 murders created by the “war on drugs” since 2006 is that the deaths consist of “narcos killing each other off.” However, as a result of the profound interlocking of legal and illegal sectors, most forms of livelihood in the borderlands are potentially implicated in the drug economy. Therefore, the way that deaths are dismissed when labeled as those of “narcos” produces a particular discomfort among people working at the blurry edges of the narco-economy. By analyzing these experiences through the lens of “the uncanny” this article argues that the subject position of the narco is not just derivative of a set of political discourses but a powerful way that people attempt to distance themselves, and their loved ones, from violence.
Susanne K. Langer, Philosophy in a New Key (1942)
Authors: Isaac Joel
Published: June 2020

Susanne Langer’s Philosophy in a New Key (1942) is the most famous book you’ve never heard of. It has had a remarkable career: a big seller on the mass paperback market of the post–World War II decades; a key text in musicology, aesthetics, religious studies, and anthropology; a founding work of Langer’s decades-long attempt to reinvent philosophy. And yet, precisely because the book possessed such remarkable crossover appeal for generations of nonspecialist readers, it has become a neglected Undead text. This article recovers its purpose and reception.
Simone de Beauvoir, The Second Sex (1949; trans. 1953)
Authors: Marcus Sharon
Published: June 2020

Undead texts are works that help to found fields only to find themselves eventually rejected by specialists and embraced by novices. Simone de Beauvoir’s The Second Sex is an exemplary Undead text: hailed as a classic when it was first published in 1949, dismissed by many scholars of gender and sexuality studies by the 1980s, yet still in print and still inspiring to undergraduates today. This article explores the work’s other Undead characteristics, including its combination of erudition and generalism, its memorable turns of phrase, and its invention of the very criteria by which it would later be found wanting (e.g., anti-essentialism). The article then turns to the original reception of the first English-language translation (published in 1953) to understand why the text initially had such a strong impact, and ends by speculating about why it continues to inspire today’s undergraduates.