bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections
Authors: Maravelia Panagiota , Frelin Lars , Ni Yi , Caro Pérez Noelia , Ahlén Gustaf , Jagya Neetu , Verch Georg , Verhoye Lieven , Pater Lena , Johansson Magnus , Pasetto Anna , Meuleman Philip , Urban Stephan , Sällberg Matti
Published: January 2020

Background

Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry.

Methods

Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes.

Results

The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice.

Conclusions

We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation.
Development and Validation of a Free Carbamazepine Assay on an Automated Chemistry Analyzer
Authors: Zhang Xiaochun , Boyert Nicole , Mitro Matthew , Tang Xiaoying , Bowers Kathleen , McShane Adam J
Published: January 2020

Background

Carbamazepine is an effective drug for treating seizures and trigeminal neuralgia. Therapeutic drug monitoring of free carbamazepine in serum can be useful in situations that drug--protein binding is altered to guide regimen adjustment and to aid in the diagnosis of clinical toxicity.

Methods

Separation of the nonprotein bound carbamazepine was achieved via ultrafiltration through a molecular weight cut-off filter. A method for free carbamazepine measurement was developed on the automated cobas chemistry analyzers (Roche Diagnostics) by modifying the Carbamazepine Gen 4 assay (Roche Diagnostics). Assay performance characteristics were established including precision, accuracy, reportable range, analytical specificity, and stability.

Results

The intra- and inter-assay imprecision was 0%-1.4% and 2.4%-5.1%, respectively. The lower limit of quantitation was 0.3 µg/mL, and the assay was linear up to 10.0 µg/mL. A spike recovery study, using reference standard material, showed recovery was 93.5%--101.3% across the analytical measurement range. Method comparison with a reference laboratory method demonstrated equivalent performance with a slope of 1.01, intercept of 0.09, and correlation coefficient of 0.9948.

Conclusion

This assay provides a simple and accurate method for monitoring free carbamazepine with a fast turnaround time.
Surgical hip dislocation and varus derotation osteotomy for extra-articular cause of femoroacetabular impingement: a single case report
Authors: Cho Su-Hyun , Cho Hyuk-Jin , Cho Young-Jin
Published: January 2020

Femoral retroversion is an extra-articular cause of cam-type femoroacetabular impingement (FAI) via early engagement with anterior rim. Valgus hip also causes extra-articular FAI by decreasing the range of motion. We present a case of valgus hip accompanied by femoral retroversion, which was refractory to prior arthroscopic femoroplasty. As a reasonable strategy, we have performed extra-articular correction via femoral subtrochanteric varus derotation osteotomy as well as intra-articular decompression by surgical hip dislocation. Femoral varus derotation osteotomy with surgical hip dislocation is a rational and appropriate solution in patients with extra-articular FAI, which is refractory to arthroscopic FAI surgery. Extra-articular causes of FAI should be suspected in every refractory case.
Radiomics Response Signature for Identification of Metastatic Colorectal Cancer Sensitive to Therapies Targeting EGFR Pathway
Authors: Dercle Laurent , Lu Lin , Schwartz Lawrence H , Qian Min , Tejpar Sabine , Eggleton Peter , Zhao Binsheng , Piessevaux Hubert
Published: January 2020

Background

The authors sought to forecast survival and enhance treatment decisions for patients with liver metastatic colorectal cancer by using on-treatment radiomics signature to predict tumor sensitiveness to irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) alone (F) or in combination with cetuximab (FC).

Methods

We retrospectively analyzed 667 metastatic colorectal cancer patients treated with F or FC. Computed tomography quality was classified as high (HQ) or standard (SD). Four datasets were created using the nomenclature (treatment) – (quality). Patients were randomly assigned (2:1) to training or validation sets: FCHQ: 78:38, FCSD: 124:62, FHQ: 78:51, FSD: 158:78. Four tumor-imaging biomarkers measured quantitative radiomics changes between standard of care computed tomography scans at baseline and 8 weeks. Using machine learning, the performance of the signature to classify tumors as treatment sensitive or treatment insensitive was trained and validated using receiver operating characteristic (ROC) curves. Hazard ratio and Cox regression models evaluated association with overall survival (OS).

Results

The signature (area under the ROC curve [95% confidence interval (CI)]) used temporal decrease in tumor spatial heterogeneity plus boundary infiltration to successfully predict sensitivity to antiepidermal growth factor receptor therapy (FCHQ: 0.80 [95% CI = 0.69 to 0.94], FCSD: 0.72 [95% CI = 0.59 to 0.83]) but failed with chemotherapy (FHQ: 0.59 [95% CI = 0.44 to 0.72], FSD: 0.55 [95% CI = 0.43 to 0.66]). In cetuximab-containing sets, radiomics signature outperformed existing biomarkers (KRAS-mutational status, and tumor shrinkage by RECIST 1.1) for detection of treatment sensitivity and was strongly associated with OS (two-sided P < .005).

Conclusions

Radiomics response signature can serve as an intermediate surrogate marker of OS. The signature outperformed known biomarkers in providing an early prediction of treatment sensitivity and could be used to guide cetuximab treatment continuation decisions.
Mapping a double flower phenotype-associated gene DcAP2L in Dianthus chinensis
Authors: Wang Qijian , Zhang Xiaoni , Lin Shengnan , Yang Shaozong , Yan Xiuli , Bendahmane Mohammed , Bao Manzhu , Fu Xiaopeng
Published: January 2020

The double flower is a highly important breeding trait that affects the ornamental value in many flowering plants. To get a better understanding of the genetic mechanism of double flower formation in Dianthus chinensis, we have constructed a high-density genetic map using 140 F2 progenies derived from a cross between a single flower genotype and a double flower genotype. The linkage map was constructed using double-digest restriction site-associated DNA sequencing (ddRAD-seq) with 2353 single nucleotide polymorphisms (SNPs). Quantitative trait locus (QTL) mapping analysis was conducted for 12 horticultural traits, and major QTLs were identified for nine of the 12 traits. Among them, two major QTLs accounted for 20.7% and 78.1% of the total petal number variation, respectively. Bulked segregant RNA-seq (BSR-seq) was performed to search accurately for candidate genes associated with the double flower trait. Integrative analysis of QTL mapping and BSR-seq analysis using the reference genome of Dianthus caryophyllus suggested that an SNP mutation in the miR172 cleavage site of the A-class flower organ identity gene APETALA2 (DcAP2L) is responsible for double flower formation in Dianthus through regulating the expression of DcAG genes.
Cusp-to-core transition in low-mass dwarf galaxies induced by dynamical heating of cold dark matter by primordial black holes
Authors: Boldrini Pierre , Miki Yohei , Wagner Alexander Y , Mohayaee Roya , Silk Joseph , Arbey Alexandre
Published: January 2020

We performed a series of high-resolution N-body simulations to examine whether dark matter candidates in the form of primordial black holes (PBHs) can solve the cusp–core problem in low-mass dwarf galaxies. If some fraction of the dark matter in low-mass dwarf galaxies consists of PBHs and the rest is cold dark matter, dynamical heating of the cold dark matter by the PBHs induces a cusp-to-core transition in the total dark matter profile. The mechanism works for PBHs in the 25–100 M⊙ mass window, consistent with the Laser Interferometer Gravitational-Wave Observatory (LIGO) detections, but requires a lower limit on the PBH mass fraction of 1 ${{\rm per\ cent}}$ of the total dwarf galaxy dark matter content. The cusp-to-core transition time-scale is between 1 and 8 Gyr. This time-scale is also a constant multiple of the relaxation time between cold dark matter particles and PBHs, which depends on the mass, the mass fraction, and the scale radius of the initial density profile of PBHs. We conclude that dark matter cores occur naturally in haloes composed of cold dark matter and PBHs, without the need to invoke baryonic processes.
A turbulent-entropic instability and the fragmentation of star-forming clouds
Authors: Keto Eric , Field George B , Blackman Eric G
Published: January 2020

The kinetic energy of supersonic turbulence within interstellar clouds is subject to cooling by dissipation in shocks and subsequent line radiation. The clouds are therefore susceptible to a condensation process controlled by the specific entropy. In a form analogous to the thermodynamic entropy, the entropy for supersonic turbulence is proportional to the log of the product of the mean turbulent velocity and the size scale. We derive a dispersion relation for the growth of entropic instabilities in a spherical self-gravitating cloud and find that there is a critical maximum dissipation time-scale, about equal to the crossing time, that allows for fragmentation and subsequent star formation. However, the time-scale for the loss of turbulent energy may be shorter or longer, for example, with rapid thermal cooling or the injection of mechanical energy. Differences in the time-scale for energy loss in different star-forming regions may result in differences in the outcome, for example, in the initial mass function.
Classification of Individual Finger Movements Using Intracortical Recordings in Human Motor Cortex
Authors: Jorge Ahmed , Royston Dylan A , Tyler-Kabara Elizabeth C , Boninger Michael L , Collinger Jennifer L
Published: January 2020

BACKGROUND

Intracortical microelectrode arrays have enabled people with tetraplegia to use a brain–computer interface for reaching and grasping. In order to restore dexterous movements, it will be necessary to control individual fingers.

OBJECTIVE

To predict which finger a participant with hand paralysis was attempting to move using intracortical data recorded from the motor cortex.

METHODS

A 31-yr-old man with a C5/6 ASIA B spinal cord injury was implanted with 2 88-channel microelectrode arrays in left motor cortex. Across 3 d, the participant observed a virtual hand flex in each finger while neural firing rates were recorded. A 6-class linear discriminant analysis (LDA) classifier, with 10 × 10-fold cross-validation, was used to predict which finger movement was being performed (flexion/extension of all 5 digits and adduction/abduction of the thumb).

RESULTS

The mean overall classification accuracy was 67% (range: 65%-76%, chance: 17%), which occurred at an average of 560 ms (range: 420-780 ms) after movement onset. Individually, thumb flexion and thumb adduction were classified with the highest accuracies at 92% and 93%, respectively. The index, middle, ring, and little achieved an accuracy of 65%, 59%, 43%, and 56%, respectively, and, when incorrectly classified, were typically marked as an adjacent finger. The classification accuracies were reflected in a low-dimensional projection of the neural data into LDA space, where the thumb-related movements were most separable from the finger movements.

CONCLUSION

Classification of intention to move individual fingers was accurately predicted by intracortical recordings from a human participant with the thumb being particularly independent.
Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy
Authors: Borha Alin , Chagnot Audrey , Goulay Romain , Emery Evelyne , Vivien Denis , Gaberel Thomas
Published: January 2020

Background

Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis.

Objective

To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux.

Methods

Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area.

Results

Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP.

Conclusion

The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.
Tailored Communicating Bypass for the Management of Complex Anterior Communicating Artery Aneurysms: “Flow-Counteraction” In Situ Bypass and Interposition Bypass Using Contralateral A2 Orifice as Donor Site
Authors: Wang Xuan , Tong Xiaoguang , Liu Jie , Shi Minggang , Shang Yanguo , Wang Hu
Published: January 2020

BACKGROUND

The use of bypass surgery for anterior communicating artery (ACOM) aneurysms is technically challenging. Communicating bypass (COMB), such as pericallosal artery side-to-side anastomosis, is the most frequently used and anatomically directed reconstruction option. However, in many complex cases, this technique may not afford a sufficient blood supply or necessitate sacrificing the ACOM and the eloquent perforators arising from it.

OBJECTIVE

To evaluate tailored COMB and propose a practical algorithm for the management of complex ACOM aneurysms.

METHODS

For 1 patient with an aneurysm incorporating the entire ACOM, conventional in Situ A3-A3 bypass was performed as the sole treatment in order to create competing flow for aneurysm obliteration, sparing the sacrifice of eloquent perforators. In situations in which A2s were asymmetric in the other case, the contralateral A2 orifice was selected as the donor site to provide adequate blood flow by employing a short segment of the interposition graft.

RESULTS

The aneurysm was not visualized in patients with in Situ A3-A3 bypass because of the “flow-counteraction” strategy. The second patient, who underwent implementation of the contralateral A2 orifice for ipsilateral A3 interposition bypass, demonstrated sufficient bypass patency and complete obliteration of the aneurysm.

CONCLUSION

The feasibility of conventional COMB combined with complete trapping may only be constrained to selected ideal cases for the treatment of complex ACOM aneurysms. Innovative modifications should be designed in order to create individualized strategies for each patient because of the complexity of hemodynamics and the vascular architecture. Flow-counteraction in Situ bypass and interposition bypass using the contralateral A2 orifice as the donor site are 2 novel modalities for optimizing the advantages and broadening the applications of COMB for the treatment of complex ACOM aneurysms.
Left Parietal Craniotomy for Resection of Grade IV Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: January 2020

Parieto-occipital arteriovenous malformations (AVMs) are the second most common site for cranial AVMs. These lesions are defined as eloquent when the nidus involves either the postcentral gyrus or the occipital pole. If located on the dominant hemisphere, these lesions can also involve the arcuate fasciculus ventrally. This patient had a large unruptured Spetzler-Martin grade IV AVM within the parieto-occipital region extending deeply to the ventricle, following presentation with a seizure. The digital subtraction angiography demonstrated feeding vessels from both the middle cerebral artery and posterior cerebral artery distributions. Despite the high Spetzler-Martin grade, the lesion demonstrated favorable features such as a compact nidus, convexity presence, and lack of involvement of the precentral and postcentral gyrus. Preoperative embolization was utilized. The AVM was successfully resected both superficially and deeply to the level of the atrium of the lateral ventricle. Postoperative angiography demonstrated complete removal of the AVM, and the patient made a complete recovery from the procedure. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Implantation of Sacral Nerve Stimulator Without Rhizotomy for Neurogenic Bladder in Patient With Spinal Cord Injury: 2-Dimensional Operative Video
Authors: Ehsanian Reza , Creasey Graham , Elliott Christopher S , Abu-Eid Cherine A , Ali Arshad , Prutton Michael , Singh Harminder
Published: January 2020

There are approximately 12 000 new individuals with spinal cord injury (SCI) each year, and close to 200 000 individuals live with a SCI-related disability in the United States. The majority of patients with SCI have bladder dysfunction as a result of their injury, with over 75% unable to void volitionally following their injury. In patients with traumatic SCI, intermittent catheterization is commonly recommended, but a lack of adherence to clean intermittent catheterization (CIC) has been observed, with up to 50% discontinuing CIC within 5 yr of injury. The Finetech Brindley Bladder System (FBBS) is an implantable sacral nerve stimulator for improving bladder function in patients with SCI, avoiding the need for CIC. The FDA-approved implantation (Humanitarian Device Exemption H980008) of the FBBS is combined with a posterior rhizotomy to reduce reflex contraction of the bladder, improving continence. However, the posterior rhizotomy is irreversible and has unwanted effects; therefore, the current FDA-approved implantation is being studied without rhizotomy as part of a clinical trial (Investigational Device Exemption G150201) (ClinicalTrials.gov Identifier: NCT02978638). In this video, we present a case of a 66-yr-old female who presented 40-yr status post-T12 SCI, resulting in complete paraplegia and neurogenic bladder not satisfactorily controlled with CIC. We demonstrate the operative steps to complete the implantation of the device without rhizotomy in the first patient enrolled as part of the clinical trial Electrical Stimulation for Continence After SCI (NCT02978638). Appropriate IRB and patient consent were obtained.
Double-Nerve Transfer to the Axillary Nerve in Traumatic Upper Trunk Brachial Plexus Injuries Using an Axillary Approach: Anatomical Description and Preliminary Case Series
Authors: Lafosse Thibault , Gerosa Thibault , Serane Julien , Bouyer Michael , Masmejean Emmanuel H , Le Hanneur Malo
Published: January 2020

BACKGROUND

Restoration of shoulder external rotation remains challenging in patients with C5/C6 brachial plexus injuries (BPI).

OBJECTIVE

To describe a double-nerve transfer to the axillary nerve (AN), targeting both its anterior and posterior motor branches, through an axillary route.

METHODS

A total of 10 fresh-frozen cadaveric brachial plexuses were dissected. Using an axillary approach, the infraclavicular brachial plexus terminal branches were exposed, including the axillary, ulnar, and radial nerves. Under microscopic magnification, the triceps long head motor branch (TLHMB), anteromedial fascicles of the ulnar nerve (UF), the anterior motor branch of the axillary nerve (AAMB), and the teres minor motor branch (TMMB) were dissected and transected to simulate 2 nerve transfers, THLMB-AAMB and UF-TMMB. Several anatomical criteria were assessed, including the overlaps between fascicles when placed side-by-side. Six patients with C5/C6 BPI were then operated on using this technique.

RESULTS

TLHMB-AAMB and UF-TMMB transfers could be simulated in all specimens, with mean overlaps of 37.1 mm and 6.5 mm, respectively. After a mean follow-up of 23 mo, all patients had recovered grade-3 strength or more in the deltoid and teres minor muscles. Mean active shoulder flexion, abduction, and external rotation with the arm 90° abducted were of 128°, 117°, and 51°, respectively. No postoperative motor deficit was found in the UF territory.

CONCLUSION

A double-nerve transfer, based on radial and ulnar fascicles, appears to be an adequate option to reanimate both motor branches of the AN, providing satisfactory shoulder active elevations and external rotation in C5/C6 BPI patients.
Successes and Problems with Measuring Water Consumption in Beef Systems
Authors: Bruce Mieghan , Bellet Camille , Rushton Jonathan
Published: January 2020

Beef production is considered to have a large water footprint, with values ranging from 3.3 to 75,000 L H20/kg. The water consumption in beef production is primarily associated with feed, estimated to be about 98%, with other requirements representing less than 1%. However, beef production is a complex system where cattle are often raised in different areas using a range of resources over their lifetime. This complexity is demonstrated using three countries with very different environments and production systems, namely Australia, Brazil, and Kenya. To achieve efficient water use in beef systems, and food systems more generally, a classification system that reflects how animals are managed, slaughtered, and processed is required. Methods for assessing water use in livestock systems, from production to consumption, need to be standardized, whilst also including the alternative uses, multiple uses, and benefits of a certain resource in a specific location.
The Feminization of Agriculture
Authors: Slavchevska Vanya , Kaaria Susan , Taivalmaa Sanna Liisa
Published: January 2020

Male outmigration from rural, primary agricultural areas and the globalization of agri-food systems have both been linked to a significant increase in women’s work and responsibilities in agriculture, a phenomenon referred to as the ‘feminization of agriculture’. While the term has been broadly used to bring attention to the increasing number of women, relative to men, in agricultural employment, little attention has been paid to what the ‘feminization of agriculture’ means for women’s empowerment and their roles in agriculture more generally. Similarly, there is no clear understanding of how this will impact the agricultural sector and what the consequences for food and water security are. This chapter reviews the global evidence surrounding the “feminization of agriculture” and provides a critical discussion of the implications for women’s empowerment and for food and water security.
Cape Town’s Contested Hierarchy of Demand for Agricultural and Municipal Water in a Rainfed Economy 2017–2018
Authors: Colman Anthony
Published: January 2020

The article provides an analysis of the stakeholders involved in policy decision making on water utilization, especially during the Water Crisis of 2017–2018. It looks at this through the prism of the meetings and key informants of the South African Parliament Portfolio Committee on Water and Sanitation, the City of Cape Town Council and the farmers of the Western Cape. It also considers the effects of the prioritization of the use of water for drinking water and sanitation over agriculture. The South Africa water policy principles set by its Constitution and the Acts of 1996–1997 provide a comparator.
Lab-Grown Meat
Authors: Keulertz Martin
Published: January 2020

The alternative protein industry has attracted much media attention. It has become increasingly clear that current meat production systems are unsustainable except in grass-fed low-volume production systems. The new alternative meat industry seeks to introduce new technologies that produce ‘meat’ sustainably. By using IT-terms such as 1.0 to 4.0, this analysis classifies traditional herding and grazing systems as 1.0, feedlot production as meat 2.0, plant-based meat alternatives as meat 3.0, and cultured meat alternatives as meat 4.0. An overview of current developments in the meat 3.0 and 4.0 industries highlights the recent technological advances. The environmental and health benefits of meat 3.0 and 4.0 are discussed and the cultural and business implications. Finally, the consequences of meat 4.0 for a sustainable planet and its social foundations are revealed, identifying the billion livelihoods that depend on meat 1.0 and 2.0 production. The alternative protein industry could have disruptive effects as well as benefits to the planet and society.
Musical Disorders
Authors: Royal Isabelle , Paquette Sébastien , Tranchant Pauline
Published: January 2020

Nearly everyone is exposed to music on a daily basis and the human brain is equipped with the necessary neural architecture to naturally acquire musical abilities during early development. Despite the universality of music, a minority of individuals present with very specific musical deficits that cannot be attributed to a general auditory dysfunction, intellectual disability, or a lack of musical exposure. These musical deficiencies can either be present from birth (congenital amusia, beat finding disorder) or acquired following a neurological event (acquired amusia). The purpose of the present chapter is to provide an overview of these intriguing musical disorders, highlight their common and different underlying features, and to demonstrate how they represent a unique opportunity to study brain function and to isolate brain areas that play a specific role in musical processing.
New Horizons for Brain Research in Music
Authors: Thaut Michael H. , Hodges Donald A.
Published: January 2020

This final chapter of The Oxford Handbook of Music and Neuroscience tries to appraise potential new horizons for future brain-based research in music, including new trajectories in the neuroscience of music perception and production, clinical applications, music learning, musician health, and intersections of biology, culture, and aesthetics. The study of music as a science and an object of scientific inquiry has actually a long and rich history in human culture and the more prevalent belief that music should, as one of its primary functions, express and induce emotions, is a relatively recent one—firmly implanted only since the early nineteenth-century Romantic period (Berlyne, 1971). The evidence presented in the previous chapters has provided a comprehensive basis to shape a future architecture of basic and applied neuroscience research in music, whose outlines are sketched out here. Therefore, as a draft for future possibilities, this chapter contains few new references. The references for this chapter are the previous chapters.
Neural Basis of Music Perception: Melody, Harmony, and Timbre
Authors: Koelsch Stefan
Published: January 2020

During listening, acoustic features of sounds are extracted in the auditory system (in the auditory brainstem, thalamus, and auditory cortex). To establish auditory percepts of melodies and rhythms (i.e., to establish auditory “Gestalten” and auditory objects), sound information is buffered and processed in the auditory sensory memory. Musical structure is then processed based on acoustical similarities and rhythmical organization. In addition, musical structure is processed according to (implicit) knowledge about musical regularities underlying scales, melodic and harmonic progressions, and so on. These structures are based on both local and (hierarchically organized) nonlocal dependencies. This chapter reviews neural correlates of these processes, with regard to both brain-electric responses to sounds, and the neuroanatomical architecture of music perception.
Modifiable Factors Associated With Poststroke Physical Activity at Discharge From Rehabilitation: Prospective Cohort Study
Authors: Thilarajah Shamala , Bower Kelly J , Pua Yong-Hao , Tan Dawn , Williams Gavin , Larik Ashfaq , Bok Chek-Wai , Koh Gerald , Clark Ross A
Published: January 2020

Background

People with stroke are not meeting recommended levels of physical activity. The modifiable factors associated with poststroke physical activity levels need to be identified to develop targeted interventions.

Objective

The objective of this study was to investigate the factors at discharge from inpatient rehabilitation that are associated with physical activity levels at 3 months following discharge.

Design

This was a prospective cohort study.

Methods

Sixty-four people with stroke completed baseline assessments at discharge from inpatient rehabilitation and 55 completed the follow-up 3 months later. The candidate factors (ie, gait speed, balance, strength, cognition, mood, and motivation) were measured at discharge. The primary outcome measure at follow-up was walking-related activity (measured by wrist-worn accelerometer). Secondary outcome measures were physical activity participation (Activity Card Sort) and intensity of physical activity (International Physical Activity Questionnaire–Short 7 days). Adjusted separate multivariable linear regression models or proportional odds regression models were used to evaluate the associations between candidate factors and physical activity.

Results

Gait speed and balance were associated with all aspects of physical activity. Higher level of intrinsic motivation was also associated with higher physical activity participation. Anxiety demonstrated a significant nonlinear relationship with physical activity participation.

Limitations

Inclusion of fatigue and individual muscle strength could have provided further insights into associations with steps per day.

Conclusion

The results demonstrated that better physical function at discharge from inpatient rehabilitation was associated with future increased levels of physical activity. Additionally, higher levels of motivation impacted on increased physical activity participation. The influence of anxiety on physical activity participation requires further exploration. Mixed-method study designs can be utilized to further understand the factors associated with poststroke physical activity.
Comparative study of the effects of gold and silver nanoparticles on the metabolism of human dermal fibroblasts
Authors: Huang Yan , Lü Xiaoying , Chen Rong , Chen Ye
Published: January 2020

The purpose of this article was to explore the effects of gold nanoparticles (GNPs) and silver nanoparticles (SNPs) with different cytotoxicities on human dermal fibroblasts (HDFs) at the metabolic level. First, ∼20 nm of GNPs and SNPs were prepared, and their effects on the proliferation of HDFs were evaluated. Then, a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4, 8 and 24 h of treatment. Furthermore, the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments. The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h, while the cytotoxicity of the SNPs reached grade 1 after 72 h. By using metabolomics analysis, 29, 30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment, while SNPs induced the differential expression of 13, 33 and 22 metabolites after 4, 8 and 24 h of treatment, respectively. Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis, respectively. The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway (the key metabolite of which was glutathione) and the citrate cycle pathway (the key metabolite of which was malic acid). Based on the experiments used to verify the key metabolites and key metabolic pathways, it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity. After exposure to SNPs, the citric acid content was increased, mainly through the citrate cycle pathway, thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.
Candida albicans aspects of binary titanium alloys for biomedical applications
Authors: Chen Shuyang , Tsoi James K H , Tsang Peter C S , Park Yeong-Joon , Song Ho-Jun , Matinlinna Jukka P
Published: January 2020

Titanium and its alloys are widely used in biomedical devices, e.g. implants, due to its biocompatibility and osseointegration ability. In fact, fungal (Candida spp.) infection has been identified as one of the key reasons causing the failure of the device that is inevitable and impactful to the society. Thus, this study evaluated the surface morphology, surface chemical composition and Candida albicans adhesion on specimens of 16 binary Ti-alloys (∼5 wt% of any one of the alloy elements: Ag, Al, Au, Co, Cr, Cu, Fe, In, Mn, Mo, Nb, Pd, Pt, Sn, V and Zr) compared with cp-Ti, targeting to seek for the binary Ti-alloys which has the lowest C. albicans infection. Candida albicans cultures were grown on the specimens for 48 h, and colony forming units (CFUs) and real-time polymerase chain reaction (RT-PCR) were used to evaluate the biofilm formation ability. Scanning electron microscopy and confocal laser scanning microscopy confirmed the formation of C. albicans biofilm on all specimens’ surfaces, such that CFU results showed Ti-Mo, Ti-Zr, Ti-Al and Ti-V have less C. albicans formed on the surfaces than cp-Ti. RT-PCR showed Ti-Zr and Ti-Cu have significantly higher C. albicans DNA concentrations than Ti-Al and Ti-V (P < 0.05), whereas Ti-Cu has even showed a statistically higher concentration than Ti-Au, Ti-Co, Ti-In and Ti-Pt (P < 0.05). This study confirmed that Ti-Mo, Ti-Zr, Ti-Al and Ti-V have lower the occurrence of C. albicans which might be clinically advantageous for medical devices, but Ti-Cu should be used in caution.
The observed difference of macrophage phenotype on different surface roughness of mineralized collagen
Authors: Li Jun , Zhang Yu-Jue , Lv Zhao-Yong , Liu Kun , Meng Chun-Xiu , Zou Bo , Li Ke-Yi , Liu Feng-Zhen , Zhang Bin
Published: January 2020

Biomaterials regulate macrophages and promote regeneration function, which is a new hot pot in tissue engineering and regenerative medicine. The research based on macrophage materials biology has appeared happy future, but related research on regulating macrophages and promoting tissue regeneration is still in its infancy. The surface roughness of biomaterials is one of the important factors affecting macrophage behavior. Previous study also found that the surface roughness of many biomaterials regulating macrophage polarization, but not including mineralized collagen (MC). In this study, we designed and fabricated MC with different roughness and investigated the influence of MC with different roughness on macrophages. In the study, we found that on the rough surface of MC, macrophages exhibited M1 phenotype-amoeboid morphology and high-level secretory of inflammatory factor (tumor necrosis factor-α and interleukin-6), while smoother surface exhibited M2 phenotype. These data will be beneficial to understand the mechanism deeply and enrich biomaterials tissue regeneration theory, provide a new train of thought biomaterials inducing tissue regeneration and repair and guide the optimum design of new biomaterials, development and reasonable applications.
Innovation system formation in international development cooperation: The role of intermediaries in urban sanitation
Authors: van Welie Mara J , Boon Wouter P C , Truffer Bernhard
Published: January 2020

The transformation of urban basic service sectors towards more sustainability is one of the ‘grand challenges’ for public policy, globally. A particular urgent problem is the provision of sanitation in cities in low-income countries. The globally dominant centralised sewerage approach has proven incapable to reach many of the urban poor. Recently, an increasing number of actors in international development cooperation has started to develop alternative safely managed non-grid approaches. We approach their efforts as an emerging ‘global innovation system’ and investigate how its development can be supported by systemic intermediaries. We analyse the activities of the ‘Sustainable Sanitation Alliance’, an international network that coordinates activities in the sanitation sector and thereby supports this innovation system. The findings show how demand ing it is to fulfil an intermediary role in a global innovation system, because of the need to consider system processes at different scales, in each phase of system building.
Efficacy of Bronchoalveolar Lavage as Adjunct Therapy in the Treatment of Neonatal Severe Pneumonia: A Prospective Case–Control Study
Authors: Liu Jing , Zhao Hui-Rong , Wei Hua-Li , Chen Chen , Qiu Ru-Xin , Ren Xiao-Ling , Zhang Li , Gao Yue-Qiao
Published: January 2020

Objective

The aim of this study was to investigate the efficacy and safety of bronchoalveolar lavage (BAL) in the treatment of neonatal severe pneumonia (NSP).

Methods

One hundred patients with severe pneumonia were randomly divided into two groups, the BAL and control groups, with 50 patients in each group. In the BAL group, normal saline was instilled into the endotracheal tube for BAL. Before and after lavage, lung ultrasound (LUS) monitoring was performed to observe the lung pathological changes. Conventional treatment was administered in the control group. The need for and duration of invasive mechanical ventilation, the complication rate, the duration and cost of hospitalization and the mortality rate were compared between the two groups.

Results

The results of this study showed that there were 35 (70%) patients who meet the indications of the invasive mechanical ventilation (IMV) at admission in the BAL group, while there were only 15 (30%) patients still requiring IMV after BAL therapy. The duration of IMV was 41.7 ± 7.5 vs. 97.7 ± 12.9 h in BAL and controls, the incidence rate of complications was 8.0% vs. 20.0% in both groups, the length of hospital stay was 9.2 ± 1.9 vs. 14.1 ± 2.1 days in both groups, and the expense of hospital cost was 12 557 ± 832 vs. 19 121 ± 929 Chinese Yuan in both groups. All patients had stable vital signs during lavage, and no significant adverse side effects were observed.

Conclusion

BAL was significantly beneficial for NSP with no significant adverse side effects; LUS is a useful tool for the timely detection of BAL effects.
Foreign body aspiration in a child with cardiac arrest
Authors: George Tim R.
Published: January 2020

Foreign body aspiration is a true medical emergency and is the fifth most common cause of mortality due to unintentional injury in the United States. Children who have aspirated a foreign body may present with a variety of symptoms, from mild irritation and cough to respiratory failure. Treatment is removal of the foreign body, often via rigid bronchoscopy. Clinicians must have a high degree of suspicion to ensure a foreign body aspiration is not missed on initial presentation.
Antiretroviral therapy in older people with HIV
Authors: Richterman Aaron , Sax Paul E.
Published: January 2020

Purpose of review

The age of people with HIV) continues to rise, and yet older people have tended to be under-represented or excluded from premarketing studies of antiretroviral therapy (ART). In this review, we highlight special considerations for the use of ART in older people with HIV, with a focus on toxicities associated with specific antiretroviral agents or drug classes as well as key research questions moving forward.

Recent findings

Like all people with HIV, older people with HIV should be started on ART as soon as possible, regardless of CD4 count, and with a regimen that includes an integrase strand transfer inhibitor (INSTI) and two nucleoside reverse transcriptase inhibitors. Important toxicities to consider when choosing an ART regimen include bone and renal effects related to tenofovir, weight gain related to INSTIs and tenofovir alafenamide, neurocognitive and neuropsychiatric toxicities related to efavirenz, and increased cardiovascular risk associated with abacavir and boosted protease inhibitors. With the ongoing importance of INSTIs as a component of preferred ART regimens, further characterization of INSTI-related weight gain is a critical current research priority in understanding ART toxicity.

There are multiple potential toxicities of ART to consider when selecting a regimen for older people. Specific agents or drug classes have been implicated in adverse bone or renal effects, weight gain, neuropsychiatric and neurocognitive effects, and cardiovascular risk.
3D-Reconstruction of the Human Conventional Outflow System by Ribbon Scanning Confocal Microscopy
Authors: Loewen Ralitsa T. , Waxman Susannah , Wang Chao , Atta Sarah , Chen Si , Watkins Simon C. , Watson Alan M. , Loewen Nils A.
Published: January 2020

Purpose

Risk for glaucoma is driven by the microanatomy and function of the anterior segment. We performed a computation-intense, high-resolution, full-thickness ribbon-scanning confocal microscopy (RSCM) of the outflow tract of two human eyes. We hypothesized this would reveal important species differences when compared to existing data of porcine eyes, an animal that does not spontaneously develop glaucoma.

Methods

After perfusing two human octogenarian eyes with lectin-fluorophore conjugate and optical clearance with benzyl alcohol benzyl benzoate (BABB), anterior segments were scanned by RSCM and reconstructed in 3D for whole-specimen rendering. Morphometric analyses of the outflow tract were performed for the trabecular meshwork (TM), limbal, and perilimbal outflow structures and compared to existing porcine data.

Results

RSCM provided high-resolution data for IMARIS-based surface reconstruction of outflow tract structures in 3D. Different from porcine eyes with an abundance of highly interconnected, narrow, and short collector channels (CCs), human eyes demonstrated fewer CCs which had a 1.5x greater cross-sectional area (CSA) and 2.6x greater length. Proximal CC openings at the level of Schlemm’s canal (SC) had a 1.3x larger CSA than distal openings into the scleral vascular plexus (SVP). CCs were 10.2x smaller in volume than the receiving SVP vessels. Axenfeld loops, projections of the long ciliary nerve, were also visualized.

Conclusion

In this high-resolution, volumetric RSCM analysis, human eyes had far fewer outflow tract vessels than porcine eyes. Human CCs spanned several clock-hours and were larger than in porcine eyes. These species differences may point to factors downstream of the TM that increase our vulnerability to glaucoma.

Grant information

National Eye Institute K08EY022737 (NAL); Initiative to Cure Glaucoma of the Eye and Ear Foundation of Pittsburgh (NAL); Wiegand Fellowship of the Eye and Ear Foundation of Pittsburgh (YD); P30-EY08098 (NAL); Department grant by Research to Prevent Blindness (NAL); an unrestricted fellowship grant from the Xiangya Hospital of Central South University (SC).
A mosaic renal myeloid subtype with T-cell inhibitory and protumoral features is linked to immune escape and survival in clear cell renal cell cancer
Authors: Brech Dorothee , Straub Tobias , Kokolakis Evangelos , Irmler Martin , Beckers Johannes , Buettner Florian , Schaeffeler Elke , Winter Stefan , Schwab Matthias , Nelson Peter J. , Noessner Elfriede
Published: January 2020

Mononuclear phagocytes moderate tissue repair, immune activation and tolerance. In the renal tubulo-interstitium specialized dendritic cells help maintain homeostasis and protect tubuli from immune injury. Human renal cell carcinoma (RCC) is immunogenic; yet immunotherapies that target T-cell dysfunction show limited clinical efficacy suggesting additional mechanisms of immunoinhibiton. We previously described “enriched-in-renal cell carcinoma” (erc)DCs that are often found in tight contact with T cells which are dysfunctional. Here we describe that ercDCs exhibit a distinct polarization state imparted by tissue-specific signals characteristic for RCC and renal tissue homeostasis. The resulting mosaic transcript signature includes features associated with host defense activity, angiogenesis/invasion and T-cell inhibition. An ercDC-specific profile was predictive for patient survival and suggests potential therapeutic targets for improved immunotherapy.

Significance

Immunotherapies, which re-invigorate T-cell activity, achieve clinical responses in subsets of patients only revealing additional layers of T-cell inhibition. Mononuclear phagocytes can be immunoinhibitory. But, they are highly plastic and repolarization may be possible if key programming molecules can be identified, potentially enabling antitumor responses in tumors refractory to checkpoint blockade. We describe a myeloid cell type with mosaic feature including tumor-promotion and immunoinhibition in human clear cell renal cell carcinoma. Observed tight contacts with T cells may translate into T-cell dysfunction. A high ercDC score in tumor tissue correlates with poor patient survival suggesting ercDCs as targets for therapeutic intervention. Targeting molecules that are identified in the ercDC profile may expand the range of patients effectively treated by immunotherapy.

Highlights

Bullet points:

Renal cell carcinoma (ccRCC) harbors polarized mosaic myeloid cells (ercDCs)

ercDCs are found in contact with dysfunctional T cells in ccRCC

ercDCs express novel immunoinhibitory proteins

High ercDC z-score in ccRCC tissue correlates with poor patient survival
High-quality human preimplantation embryos stimulate endometrial stromal cell migration via secretion of microRNA hsa-miR-320a
Authors: Berkhout Robbert P. , Keijser Remco , Repping Sjoerd , Lambalk Cornelis B. , Afink Gijs B. , Mastenbroek Sebastiaan , Hamer Geert
Published: January 2020

Implantation failure is one of the major success limiting factors in human reproduction. Despite, the mechanisms that determine successful human embryo implantation remain largely unknown. We here show that high-quality human preimplantation embryos secrete soluble signaling factors, including micro RNA (miRNA) hsa-miR-320a, that promote migration of human endometrial stromal cells (hESCs). By using miRNA mimics and inhibitors, we demonstrate that hsa-miR-320a alone can stimulate migration of decidualized hESCs, accurately resembling the response typically triggered only by high-quality embryos. Transcriptome analysis further demonstrated that this effect is very likely mediated via altered expression of genes involved in cell adhesion and cytoskeleton organization. In conclusion, by secreting hsa-miR-320a, high-quality human preimplantation embryos directly influence endometrial stromal cells, most likely to prime the endometrium at the implantation site for successful implantation. Together, our results indicate that hsa-miR-320a may be a promising target to further increase success rates in assisted reproduction.