bluuebunny/crossref_metadata_2025 huggingface dataset:
Healing hand ulcers caused by focal spasticity
Authors: Gupta Anupam D. , Addison Samantha
Published: March 2020

Spasticity is a common manifestation of many upper motor neuron lesions such as stroke, traumatic brain injury, and multiple sclerosis. In some cases, spastic fingers in the hand press hard into the palm, resulting in skin breakdown and atypical pressure ulcerations. We treated 10 such patients living in the nursing homes with long‐standing treatment‐resistant hand ulcers in our spasticity clinic first, with Botulinum toxin A (BoNTA) injection into the spastic muscles followed by dressing, splinting, and hand therapy. These ulcers failed to respond to standard treatment, causing significant pain, offensive smell, increased carer burden, and difficulty in maintaining hygiene as hands could barely be opened for dressing and therapy. We noted complete healing of ulcers with significant improvement in the following outcome measures—Modified Ashworth Scale for spasticity, Visual Analog Scale for pain, pressure ulcer grading for the ulcers, Fingertip to Palm distance for hand opening, Carer Burden Scale, and in the Goal Attainment Scale pre, 4 weeks, and 3 months postinjection with P values of .003, .003, .004, .005, .004, and .004, respectively. Reducing spasticity with BoNTA should be the first step in treating hand ulcerations caused by focal spasticity, followed by dressing, splinting, and hand therapy.
Associated factors of hope in cancer patients during treatment: A systematic literature review
Authors: Nierop‐van Baalen Corine , Grypdonck Maria , van Hecke Ann , Verhaeghe Sofie
Published: March 2020

Aim

To identify the associated factors of hope during treatment in cancer patients.

Background

Hope is very important to cancer patients at all stages of the disease process. Hope is seen as an important coping mechanism. Most research about hope in cancer patients considered the end of life or in palliative care. Several and different factors are associated with hope. It is not yet sufficiently clear which factors are associated with hope during the treatment.

Design

A systematic literature review of quantitative empirical studies on hope in cancer patients during treatment.

Data Sources

Search in MEDLINE (PubMed interface), CINAHL (EBSCO interface), Psychinfo and Cochrane (January 2009–December 2018).

Review Methods

Empirical quantitative studies were included regardless of the disease stage, written in English or Dutch, measuring hope from the perspective of cancer patients. Two authors independently screened all the studies and assessed their quality.

Results

Thirty‐three studies were included. Positive relationship has been established between hope and quality of life, social support, spiritual and existential well‐being. Hope appears to be negatively associated with symptom burden, psychological distress and depression. There appears to be no relationship between hope and demographic and clinical variables. The relationship between anxiety and hope remains unclear.

Conclusions

Hope primarily seems to be a process that takes place in a person's inner being rather than being determined from outside.

Impact

Health professionals may want to focus on the meaning of hope for cancer patients in relation to the associated factors. A better understanding of the meaning of hope during treatment can be of great value in supporting cancer patients with regard to treatment decisions, psychosocial support, the experienced quality of life and symptom burden and any wishes they may have with regard to advanced care planning.
Molecular characterization and expressional quantification of lgp2, a modulatory co‐receptor of RLR‐signalling pathway in the Indian major carp Labeo rohita following pathogenic challenges and PAMP stimulations
Authors: Mohanty Arpita , Sadangi Sushmita , Paichha Mahismita , Samanta Mrinal
Published: March 2020

Lgp2 (laboratory of genetics and physiology 2) is a cytosolic viral sensor of the RLR (retinoic acid‐inducible gene 1 like receptor) family member without the caspase recruitment domain, having both inhibitory and stimulatory roles in RLR‐signalling pathway. In India, Labeo rohita (rohu) is one of the leading and economically favoured freshwater fish species. Several immunological sentry proteins have been reported in this fish species, but no information is available on the RLR members. This study was aimed at cloning and characterization of full‐length lgp2‐cDNA (complementary DNA) in rohu and investigation of its expressional modulations following various pathogen‐associated molecular pattern stimulations and bacterial infections. The full‐length lgp2‐cDNA sequence obtained through rapid amplification of cDNA ends‐PCR consisted of 2299 nucleotides with an open reading frame of 2034 bp encoding 677 amino acids. In rohu‐Lgp2, four conserved domains – a DEAD/DEAH box helicase domain, Pfam type‐III restriction enzyme domain, helicase superfamily c‐terminal domain and RIG‐I C‐terminal regulatory domain – have been detected. Within these domains, several important functional motifs, such as ATP‐binding site, ATPase motif, RNA unwinding motif and RNA‐binding sites, have also been identified. In healthy rohu, lgp2 gene was abundantly expressed in gill, liver, kidney, spleen and blood. In response to both in vitro and in vivo treatments using double‐stranded RNA (poly I:C), lgp2 gene expression was significantly (P < 0.05) upregulated in all tested tissues and also in the LRG (Labeo rohita gill) cells. lgp2 gene expression significantly (P < 0.05) increased on stimulation of LRG cells using γ‐d‐glutamyl‐meso‐diaminopimelic acid and muramyl dipeptide. In vivo treatment using lipopolysaccharide and Aeromonas hydrophila‐derived RNA resulted in both up‐ and down‐regulation of lgp2 gene expression. Upon gram‐positive and gram‐negative bacterial infections, the expression of the lgp2 gene increased at different times in almost all the tested tissues. These integrated observations in rohu suggest that Lgp2 is an antiviral and antibacterial cytosolic receptor.

Significance Statement

Lgp2, a cytosolic viral sensor of retinoic acid‐inducible gene 1 like receptor family member, has been cloned in Labeo rohita.

The complete sequence of rohu lgp2‐complementary DNA consisted of 2299 nucleotides with an open reading frame of 2034 bp encoding 677 amino acids.

It consisted of a DExDc, RES‐III, HELICc, Pfam RIG‐I_C‐RD, ATP‐binding site, ATPase motif, RNA unwinding motif and RNA‐binding site.

Upon bacterial infection, double‐stranded RNA and various pathogen‐associated molecular pattern stimulations, lgp2 gene expression significantly increased, indicating its role as an antiviral and antibacterial cytosolic receptor.
Application of ultra‐high voltage electron microscope tomography to 3D imaging of microtubules in neurites of cultured PC12 cells
Authors: NISHIDA T. , YOSHIMURA R. , NISHI R. , IMOTO Y. , ENDO Y.
Published: March 2020

Electron tomography methods using the conventional transmission electron microscope have been widely used to investigate the three‐dimensional distribution patterns of various cellular structures including microtubules in neurites. Because the penetrating power of electrons depends on the section thickness and accelerating voltage, conventional TEM, having acceleration voltages up to 200 kV, is limited to sample thicknesses of 0.2 µm or less. In this paper, we show that the ultra‐high voltage electron microscope (UHVEM), employing acceleration voltages of higher than 1000 kV (1 MV), allowed distinct reconstruction of the three‐dimensional array of microtubules in a 0.7‐µm‐thick neurite section. The detailed structure of microtubules was more clearly reconstructed from a 0.7‐µm‐thick section at an accelerating voltage of 1 MV compared with a 1.0 µm section at 2 MV. Furthermore, the entire distribution of each microtubule in a neurite could be reconstructed from serial‐section UHVEM tomography. Application of optimised UHVEM tomography will provide new insights, bridging the gap between the structure and function of widely‐distributed cellular organelles such as microtubules for neurite outgrowth.

Lay Description

An optimal 3D visualisation of microtubule cytoskeleton using ultra‐high voltage electron microscopy tomography

The ultra‐high voltage electron microscope (UHVEM) is able to visualise a micrometre‐thick specimen at nanoscale spatial resolution because of the high‐energy electron beam penetrating such a specimen. In this study, we determined the optimal conditions necessary for microtubule cytoskeleton imaging within 0.7‐µm‐thick section using a combination with UHVEM and electron tomography method. Our approach provides excellent 3D information about the complex arrangement of the individual microtubule filaments that make up the microtubule network.
Untangling the Integration–Performance Link: Levels of Integration and Functional Integration Strategies in Post‐Acquisition Integration
Authors: Wei Tian , Clegg Jeremy
Published: March 2020

The integration–performance link created during post‐acquisition integration has defied satisfactory theoretical explanation. To address this gap, we conduct a functional analysis to explore the intermediating mechanisms between the level of integration – which represents the extent of the target firm’s integration with the acquirer – and acquisition performance. We use six in‐depth acquisition case studies in the medical technology industry to develop an integrated model with which to untangle the integration–performance link. First, our model connects the level of integration to specific functional integration strategies, which refer to the approaches acquirers employ to manage functional resources. Second, we identify value creation and value leakage as the two routes through which functional integration strategies impact acquisition performance. Finally, we propose two qualitative measures of acquisition performance: value gap and time delay. Our study suggests that a functional analysis of the integration–performance link may help resolve long‐standing conflicts within the literature.
Role of electrolyte abnormalities and unmeasured anions in the metabolic acid‐base abnormalities in dogs with parvoviral enteritis
Authors: Burchell Richard K. , Gal Arnon , Friedlein Ryan , Leisewitz Andrew L.
Published: March 2020

Background

The strong ion model (SIM) is an alternative paradigm in the characterization of acid‐base disturbances particularly in complex disorders.

Hypothesis/Objectives

To compare the acid‐base changes in dogs with parvoviral enteritis (PE) using the Henderson‐Hasselbalch (HH) approach, with 2 strong ion approaches.

Animals

Forty‐four dogs with PE, and 16 age‐matched control dogs.

Methods

Prospective controlled observational study. Acid‐base status was evaluated using the HH model, Fencl‐Stewart (FS) approach and a validated strong ion model (VDM). The acid‐base changes according to each model were classified and compared. Statistical correlations between pH, CO2, and various SIM variables were performed, as well as between the sum of effects (SOE) of the SIM and the individual variables comprising the SOE.

Results

The HH model identified acid‐base disorders in 31/44 cases of which 16/31 were mixed with metabolic acidosis and concurrent respiratory alkalosis the most common (10/31). Using the FS approach, metabolic changes were present 36/42 cases, with changes in free water (FW), chloride, and unmeasured anions (UA) being the most prevalent. Both FW and UA correlated well with pH; however, UA were most consistently abnormal in severe acidemia. Similarly to the HH, the VDM detected acid‐base disturbances in 28/44 cases. Major contributors to the acid‐base changes were hyponatremia, hypochloremia, and Atotacidosis because of elevated globulins and increased UA.

Conclusions and Clinical Importance

Acid‐base changes are common and complex in dogs with PE, and were easier to understand using a SIM paradigm. Increases in UA have not been documented in PE in dogs.
Comparison of the pharmacokinetics of tilmicosin in plasma and lung tissue in healthy chickens and chickens experimentally infected with Mycoplasma gallisepticum
Authors: Zhang Nan , Liu Zhenxian , Wei Yanzhe , Zhang Chuanzhen , Mao Chunxiao , Cai Qinren , Shen Xiangguang , Ding Huanzhong
Published: March 2020

The objectives of this study were to compare the plasma and lung tissue pharmacokinetics of tilmicosin in healthy and Mycoplasma gallisepticum‐infected chickens. Tilmicosin was orally administered at 4, 7.5 and 10 mg/kg body weight (b.w) for the infected and 7.5 mg/kg b.w for the uninfected control group. We found no significant differences in plasma tilmicosin pharmacokinetics between diseased and healthy control chickens. In contrast, the lung tissues in M. gallisepticum‐infected chickens displayed a t1/2 (elimination half‐life) 1.76 times longer than for healthy chickens. The Cmax (the maximum concentration of drug in samples) of tilmicosin in M. gallisepticum‐infected chickens was lower than for controls at 7.5 mg/kg b.w (p < .05), and the AUCinf (the area under the concentration–time curve from time 0 extrapolated to infinity) in infected chickens was higher than for the healthy chickens (p < .05). The mean residence time of tilmicosin in infected chickens was also higher than the healthy chickens. These results indicated that the lungs of healthy chickens had greater absorption of tilmicosin than the infected chickens, and the rate of elimination of tilmicosin from infected lungs was slower.
The legal protection of breeder's rights for new plant varieties in Thailand: The need for law reform considering the International Convention for the Protection of New Varieties of Plants 1991
Authors: Supasiripongchai Noppanun
Published: March 2020

This article examines the possible changes to the provisions on the protection of new plant varieties under the Plant Variety Protection Act B.E. 2542 (A.D. 1999), or the Thai PVPA 1999, if Thailand chooses to ratify the 1991 International Convention for the Protection of New Varieties of Plants, or the UPOV Convention 1991. It confirms the need to develop the Thai PVPA 1999, given that several ASEAN countries have already ratified the UPOV Convention 1991, making it the new standard for new plant variety protection in the Southeast Asian region. It argues that although the current provisions of the Thai PVPA 1999 appear to meet the minimum standards of protection under the Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPS Agreement), they still fall short compared with the UPOV Convention 1991 provisions. This article asserts that to make the provisions of the Thai PVPA 1999 consistent with those of the UPOV Convention 1991, several provisions of the former—such as the scope of breeder's rights, exceptions, and the duration of protection—must be further developed.
The Economic Consequences of Accidents at Work
Authors: Mazzolini Gabriele
Published: March 2020

This paper investigates the economic consequences of workplace accidents in the British labour market. For the empirical analysis, I use data on employment and earnings from the British Household Panel Survey and exploit fixed effects estimators to control for time‐invariant unobserved workers’ characteristics. I provide evidence that accidents at work negatively affect both job opportunities and workers’ earnings. First, employment probabilities following a state of injury are significantly lower. This effect persists over time and is stronger in those regions where unemployment rate is higher. Second, a serious workplace accident also results in significant delayed wage penalties, which increase with the accident's seriousness.
The feasibility of leadless pacemaker implantation for superelderly patients
Authors: Tachibana Motomi , Banba Kimikazu , Matsumoto Kensuke , Ohara Minako
Published: March 2020

Background

The safety and efficacy of the leadless pacemaker (LP) have been confirmed in previous reports, yet studies on LPs in superelderly patients are limited.

Methods and Results

A total of 62 patients aged over 85 years old were implanted with single‐chamber pacemakers due to symptomatic bradyarrhythmia at Sakakibara Heart Institute from May 2014 through July 2019. We divided them into two groups, a transvenous (TV) single‐chamber pacemaker group (35 patients) and an LP group (27 patients), and compared the groups. Mean participant age was 90.3 ± 3.8 y.o., 41.9% were male, and mean participant body mass index (BMI) was 21.3 kg/m2. The LP group contained a significantly larger proportion of patients with dementia than the TV group did (63% vs. 37.1%, P = .04). The complication‐free rate tended to be lower in the LP group in spite of the higher frequency of dementia (88.6% vs. 92.6%, P = .68). At implantation, the pacing threshold was significantly higher in the LP group than in the TV group (1.30 ± 0.91 V vs. 0.71 ± 0.23 V, P < .01), but over the first 3 months after the operation the pacing threshold in the LP group gradually improved (0.82 ± 0.2 V vs. 1.05 ± 1.02 V, P = .16). The procedure time and time from operation to discharge were also shorter in the LP group.

Conclusions

LP implantation appears to be safe and is accordingly becoming the cornerstone for Japanese superelderly patients indicated for single‐chamber pacemakers, even for those with small bodies and dementia. However, careful procedures and long follow‐ups are needed until a greater volume of data is reported.
Hypervolemic hyponatremia and transplant‐free survival in children with cirrhosis due to biliary atresia
Authors: Silva Duarte dos Santos Renata , Kieling Carlos Oscar , Adami Marina Rossato , Guedes Renata Rostirola , Vieira Sandra Maria Gonçalves
Published: March 2020

Background

Biliary atresia is the number one cause of cirrhosis and liver transplantation in children. Hyponatremia is the most important electrolytic disturbance observed in decompensated cirrhosis. Studies of hyponatremia in cirrhotic children are scarce and those that exist have defined hyponatremia as serum sodium < 130 mEq/L lasting for at least 7 days.

Methods

We evaluated transplant‐free survival (Kaplan‐Meier) of children with cirrhosis due to biliary atresia and serum sodium < 130 mEq/L persisting for 1, 2‐6, and ≥7 days. This was a single‐center, historical cohort that included all patients aged ≤ 18 years on a liver transplantation waiting list.

Results

We studied 128 patients. The overall frequency of hyponatremia was 30.5% (39/128). Thirteen patients (10.2%) had hyponatremia when put on the list, and 20.3% developed it during follow‐up. The Kaplan‐Meier overall transplant‐free survival rate was 83.3%. Patients with persistent hyponatremia for at least two days had the lowest transplant‐free survival. Glomerular filtration rate (P = .00, RR = 0.96, IC 95% = 0.94‐0.99), BMI/age Z‐score (P = .02, RR = 0.59, IC 95% = 0.39‐0.91), INR (P = .00, RR = 1.43, IC 95% = 1.17‐1.74), and serum sodium (P = .04, RR = 0.91, IC 95% = 0.84‐0.99) were independently associated with transplant‐free survival. We did not observe any difference in mortality prediction after adding sodium to the original PELD score.

Conclusions

We conclude that persistent hyponatremia lasting at least two days may herald poor prognosis for children with cirrhosis due to biliary atresia.
The moderating role of flexible goal adjustment in the link between pain and depressive symptoms: findings based on a nationally representative sample of older adults
Authors: Hajek André , König Hans‐Helmut
Published: March 2020

Background

Pain is a frequent phenomenon in old age. It has been shown that increases in pain are longitudinally associated with depressive symptoms. This strong link can be attenuated by coping strategies like resilience. However, to date, there is a lack of longitudinal studies, based on nationally representative samples that have examined whether flexible goal adjustment moderates the relation between pain and depressive symptoms. Thus, the purpose of this study was to identify whether there is a longitudinal association between pain and depressive symptoms, and to examine whether flexible goal adjustment moderates this link.

Methods

Longitudinal data (wave 3 and wave 4; 5582 observations) were taken from a sample (German Ageing Survey) which is nationally representative for middle‐aged and older adults (40 years and over). A widely used pain measurement (single‐item measure) served as the key independent variable. An instrument created by Brandstaedter and Renner was used to quantify flexible goal adjustment. The 15‐item version of the Centre for Epidemiologic Studies Depression Scale was used to measure depressive symptoms.

Results

Linear fixed effects regressions demonstrated that an increase in pain was associated with an increase in depressive symptoms (β = 0.42, P < 0.001). Moreover, flexible goal adjustment significantly moderated this association (β = −0.39, P < 0.01). With regard to potential confounders, an increase in depressive symptoms was associated with increasing age and worsening self‐rated health.

Conclusion

The study findings showed that increasing pain leads to more depressive symptoms using a longitudinal approach. In addition, flexible goal adjustment moderated this link. Therefore, programs aiming at improving flexible goal adjustment may assist in avoiding an increase in depressive symptoms alongside pain increases among older adults.
Multiple-Systems Analysis for the Quantification of Modern Slavery: Classical and Bayesian Approaches
Authors: Silverman Bernard W.
Published: March 2020

Multiple-systems estimation is a key approach for quantifying hidden populations such as the number of victims of modern slavery. The UK Government published an estimate of 10000–13000 victims, constructed by the present author, as part of the strategy leading to the Modern Slavery Act 2015. This estimate was obtained by a stepwise multiple-systems method based on six lists. Further investigation shows that a small proportion of the possible models give rather different answers, and that other model fitting approaches may choose one of these. Three data sets collected in the field of modern slavery, together with a data set about the death toll in the Kosovo conflict, are used to investigate the stability and robustness of various multiple-systems-estimate methods. The crucial aspect is the way that interactions between lists are modelled, because these can substantially affect the results. Model selection and Bayesian approaches are considered in detail, in particular to assess their stability and robustness when applied to real modern slavery data. A new Markov chain Monte Carlo Bayesian approach is developed; overall, this gives robust and stable results at least for the examples considered. The software and data sets are freely and publicly available to facilitate wider implementation and further research.
Injustice in the Spaces between Concepts
Authors: Fairbairn Fran
Published: March 2020

I argue that epistemic injustice manifests not only in the content of our concepts, but in the spaces between them. Others have shown that epistemic injustice arises in the form of “testimonial injustice,” where an agent is harmed because her credibility is undervalued, and “hermeneutical injustice,” where an agent is harmed because some community lacks the conceptual resources that would allow her to render her experience intelligible. I think that epistemic injustice also arises as a result of prejudiced and harmful defects in the inferential architecture of both scientific practice and everyday thinking. Drawing on lessons from the philosophy of science, I argue that the inferential architecture of our epistemic practices can be prejudiced and wrongful, leading to a variety of epistemic injustice that I am calling “inferential injustice.” This type of injustice is fully structural; it inheres in our epistemic practices themselves rather than as a direct result of an individual's action. For this reason, cases of inferential injustice are importantly different from extant cases of epistemic injustice and are especially hard to track. We need a better understanding of inferential injustice so that we can avoid and ameliorate cases such as the ones I present here.
The Sense and Sensibility of Equality
Authors: Lebron Chris
Published: March 2020

The idea of equality in political thought is often approached from a distributive perspective that entails a rethinking of institutional arrangements. In this paper I present an approach to conceived as a complement to the common institutional approach in liberal theory. The foundational claim is that blacks do not come into view for a wide range of people as worthy of full human recognition, that is, persons in possession of human vulnerabilities that require responses and in possession of warrants to rights that demand respect. The central argument is that this problem of diminished social value can be addressed by imagination and that imagination is crucially important to bridge the experiential divide between white and black Americans. I deploy two ideas I claim are essential for leveraging imagination: attentiveness and skill. When we are attentive we provide the imagination range to sense the more difficult aspects of others’ lives under inequality; when we are skilled we deploy a finer sensibility in taking the proper ethical stance towards others’ experiential difficulties under a regime of racial inequality. To achieve this, I provide a schematic of three pairs of concepts that provide a foundation though not full accounting of the necessary skills in response to ethical challenges: narrative/receptivity, reasons/responsibility, affect/compassion.
Phylogenetic comparison of 5′ splice site determination in central spliceosomal proteins of the U1‐70K gene family, in response to developmental cues and stress conditions
Authors: Chen Mo‐Xian , Zhang Kai‐Lu , Gao Bei , Yang Jing‐Fang , Tian Yuan , Das Debatosh , Fan Tao , Dai Lei , Hao Ge‐Fei , Yang Guang‐Fu , Zhang Jianhua , Zhu Fu‐Yuan , Fang Yan‐Ming
Published: March 2020

Intron‐containing genes have the ability to generate multiple transcript isoforms by splicing, thereby greatly expanding the eukaryotic transcriptome and proteome. In eukaryotic cells, precursor mRNA (pre‐mRNA) splicing is performed by a mega‐macromolecular complex defined as a spliceosome. Among its splicing components, U1 small nuclear ribonucleoprotein (U1 snRNP) is the smallest subcomplex involved in early spliceosome assembly and 5′‐splice site recognition. Its central component, named U1‐70K, has been extensively characterized in animals and yeast. Very few investigations on U1‐70K genes have been conducted in plants, however. To this end, we performed a comprehensive study to systematically identify 115 U1‐70K genes from 67 plant species, ranging from algae to angiosperms. Phylogenetic analysis suggested that the expansion of the plant U1‐70K gene family was likely to have been driven by whole‐genome duplications. Subsequent comparisons of gene structures, protein domains, promoter regions and conserved splicing patterns indicated that plant U1‐70Ks are likely to preserve their conserved molecular function across plant lineages and play an important functional role in response to environmental stresses. Furthermore, genetic analysis using T‐DNA insertion mutants suggested that Arabidopsis U1‐70K may be involved in response to osmotic stress. Our results provide a general overview of this gene family in Viridiplantae and will act as a reference source for future mechanistic studies on this U1 snRNP‐specific splicing factor.
The value of transfusion of phenotyped blood units for thalassemia and sickle cell anemia patients at an academic center
Authors: Hindawi Salwa , Badawi Maha , Elfayoumi Refaat , Elgemmezi Tarek , Al Hassani Abrar , Raml Mohamed , Alamoudi Seraj , Gholam Kholoud
Published: March 2020

BACKGROUND

Blood transfusion is the first‐line treatment for patients with thalassemia and many sickle cell patients. However, cases of unregulated blood transfusion are shown to carry a high risk of alloimmunization to red blood cells (RBCs), which can lead to a hemolytic transfusion reaction and be fatal to patients. Screening and identification of alloantibodies are, therefore, essential practice in blood transfusion services. Transfusion of phenotyped blood can minimize these risks to patients.

STUDY DESIGN AND METHODS

A prospective study was carried out on 1015 donors, and a prospective and retrospective study was carried out on 208 multiple transfused patients with β‐thalassemia and sickle cell anemia. Donor and patient samples were subjected to Rh & K typing, and patient samples were also subjected to screening & identification of RBC antibodies. We aimed to determine the prevalence of RBC antigens in thalassemia and sickle cell patients, as well as blood donors, at King Abdulaziz University Hospital and the frequency of alloimmunization in the selected patients.

RESULTS

The most commonly detected Rh‐phenotype in donors was R1r (32.02%), followed by R1R1 (23.25%). Only 9.16% of donors were positive for the K antigen. The prevalence of Rh and K blood group antigens was also reported: the highest detected Rh‐phenotype was R1r (40.86%) followed by R1R2 (24.04%) with only (6.25%) positive patients for K antigen. The rate of alloimmunization among sickle cell anemia and thalassemia patients was 39.42% and 35.57%, respectively. The highest specificity rates of the alloantibodies were recorded for anti‐E and anti‐K in both patient groups.

CONCLUSION

The rate of alloimmunization in transfused patients was high and particularly observed against the Rh and K antigens. This study emphasizes the clinical need for typing patient RBCs prior to transfusion so as to provide phenotyped matched blood units and minimize the risks and associated morbidities of alloimmunization. Keeping a database of phenotyped blood donors is essential for the clinically effective and safe management of transfusion patients.
Supplemental findings of the 2017 National Blood Collection and Utilization Survey
Authors: Sapiano Mathew R. P. , Jones Jefferson M. , Savinkina Alexandra A. , Haass Kathryn A. , Berger James J. , Basavaraju Sridhar V.
Published: March 2020

INTRODUCTION

This report provides supplemental results from the 2017 National Blood Collection and Utilization Survey on characteristics of the donor population, autologous and directed donations and transfusions, platelets, plasma and granulocyte transfusions, pediatric transfusions, severe donor‐related adverse events, cost of blood units, hospitals policies and practices, and inventory, dosing, and supply.

METHODS

Weighting and imputation were used to generate national estimates including number of donors, donations, donor deferrals, autologous and directed donations and transfusions, severe donor‐related adverse events, platelet and plasma collections and transfusions, number of cross‐match procedures, irradiation and leukoreduction, and pediatric transfusions.

RESULTS

Between 2015 and 2017, successful donations decreased slightly by 2.1% with a 10.3% decrease in donations by persons aged 16‐18 years and a 14.4% increase in donations by donors aged >65 years. The median price paid for blood components by hospitals decreased from $211 to $207 for leukoreduced red blood cell units, from $523 to $517 for leukoreduced apheresis platelet units, and from $54 to $51 for fresh frozen plasma units. Plasma transfusions decreased 13.6%, but group AB plasma units transfused increased 24.7%.

CONCLUSION

Between 2015 and 2017, blood donations declined slightly because of decreases in donations from younger donors, but the number of donations from older donors increased. The price hospitals pay for blood has continued to decrease. Plasma transfusions have decreased, but the proportion of plasma transfusions involving group AB plasma have increased.
Successful prevention of severe allergic transfusion reactions with omalizumab
Authors: Shi Sensen , Han Jingjing , Yao Yao , Xu Yang , Wu Depei , Wang Ying
Published: March 2020

BACKGROUND

Allergic transfusion reactions (ATRs) are a common adverse reaction to transfusion therapy and can be potentially fatal. Washing blood products is the most effective strategy for preventing ATRs; however, washed products, especially platelets, are not available at many blood centers.

STUDY DESIGN AND METHODS

A 29‐year‐old female patient with an advanced myelodysplastic/myeloproliferative neoplasm, unclassifiable, developed severe ATRs after four platelet transfusions in a week. She showed no response to premedication with histamines and steroids and still had severe ATRs with the next three platelet transfusions. A laboratory workup revealed that her IgA level was slightly decreased, while her haptoglobin level was normal. Anti‐IgA testing was not available. The patient decided to undergo allogeneic peripheral blood stem cell (PBSC) transplantation. As the onset of symptoms ATR, which were similar to Type 1 hypersensitivity reactions mediated by IgE antibodies, occurred immediately after transfusion and omalizumab is a humanized monoclonal anti‐IgE, we elected to offer off‐label use of omalizumab before administering the conditioning regimen.

RESULTS

Omalizumab was injected subcutaneously at a dose of 150 mg. Surprisingly, transfusion reactions fully resolved within 24 hours. No serious side effects were noticed. Another 150 mg of omalizumab was administered 1 day before PBSC infusion. The patient remained asymptomatic without any signs of ATRs throughout the whole period of transplantation. Seven months after transplantation, the patient was in complete remission without overt complications.

CONCLUSION

This case suggests that omalizumab is a promising new alternative treatment for the prevention of severe ATRs.
The development of an indirect computed tomography lymphography protocol for sentinel lymph node detection in head and neck cancer and comparison to other sentinel lymph node mapping techniques
Authors: Randall Elissa K. , Jones Matthew D. , Kraft Susan L. , Worley Deanna R.
Published: March 2020

Identification of metastatic disease critically impacts the care and prognosis of patients with neoplasia. Multiple techniques exist for identifying the sentinel or first lymph node(s) that receive draining tumour lymph. Identification of the sentinel lymph node enables accurate tissue sampling for determination of lymphatic metastasis. The aims of this study were to develop a computed tomography (CT) protocol for identifying the sentinel lymph node in dogs with tumours of the head and neck. In addition, indirect CT lymphography was compared to lymphoscintigraphy and vital dye injection to determine which technique more reliably identified the sentinel lymph node. CT indirect lymphography using intratumoral injection of iodinated contrast identified draining lymphatic vessels in eight of 18 dogs and identified the sentinel lymph node in five of 18 dogs. CT indirect lymphography employing four‐quadrant peritumoral injection of iodinated contrast identified draining lymphatic vessels in 18 of 20 dogs and identified the sentinel lymph node in 11 of 20 dogs. Vital dye injection and lymphoscintigraphy identified the sentinel lymph node in 17 of 18 and 20 of 20 dogs, respectively. Identified sentinel lymph nodes were either ipsilateral or bilateral to the primary tumour. Both CT techniques were found to be safe and simple. Peritumoral injection has the greatest promise for the detection of sentinel lymph nodes in various head and neck cancers using CT, while lymphoscintigraphy had the greatest success of the compared techniques.
A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics
Authors: Huon Jean‐François , Gaborit Benjamin , Caillon Jocelyne , Boutoille David , Navas Dominique
Published: March 2020

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL‐17A compared to control mice that resulted in an IL‐17/IFN‐γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL‐10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL‐10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL‐10/IFN‐γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.
The effects of hypoxia and fatigue on skeletal muscle electromechanical delay
Authors: Jacunski Mark , Rafferty Gerrard F.
Published: March 2020

New Findings

What is the central question of this study?

What are the mechanisms underlying impaired muscular endurance and accelerated fatigue during acute hypoxia?

What is the main finding and its importance?

Hypoxia had no effect on the electrochemical latency associated with muscle contraction elicited by supramaximal electrical motor nerve stimulation in vivo. This provides greater insight into the effects of hypoxia and fatigue on the mechanisms of muscle contraction in vivo.

Acute hypoxia impairs muscle endurance and accelerates fatigue, but the underlying mechanisms, including any effects on muscle electrical activation, are incompletely understood. Electromyographic, mechanomyographic and force signals, elicited by common fibular nerve stimulation, were used to determine electromechanical delay (EMDTOT) of the tibialis anterior muscle in normoxia and hypoxia ( 0.125) at rest and following fatiguing ankle dorsiflexor exercise (60% maximum voluntary contraction, 5 s on, 3 s off) in 12 healthy participants (mean (SD) age 27.4 (9.0) years). EMDTOT was determined from electromyographic to force signal onset, electrical activation latency from electromyographic to mechanomyographic (EMDE‐M) and mechanical latency from mechanomyographic to force (EMDM‐F). Twitch force fell significantly following fatiguing exercise in normoxia (46.8 (14.7) vs. 20.6 (14.3) N, P = 0.0002) and hypoxia (52.9 (15.4) vs. 28.8 (15.2) N, P = 0.0006). No effect of hypoxia on twitch force at rest was observed. Fatiguing exercise resulted in significant increases in mean (SD) EMDTOT in normoxia (Δ 4.7 (4.57) ms P = 0.0152) and hypoxia (Δ 3.7 (4.06) ms P = 0.0384) resulting from increased mean (SD) EMDM‐F only (normoxia Δ 4.1 (4.1) ms P = 0.0391, hypoxia Δ 3.4 (3.6) ms P = 0.0303). Mean (SD) EMDE‐M remained unchanged during normoxic (Δ 0.6 (1.08) ms) and hypoxic (Δ 0.25 (0.75) ms) fatiguing exercise. No differences in percentage change from baseline for twitch force, EMDTOT, EMDE‐M and EMDM‐F between normoxic and hypoxic fatigue conditions were observed. Hypoxia in isolation or in combination with fatigue had no effect on the electrochemical latency associated with electrically evoked muscle contraction.
Protease‐dependent excitation of nodose ganglion neurons by commensal gut bacteria
Authors: Pradhananga Sabindra , Tashtush Ayssar A. , Allen‐Vercoe Emma , Petrof Elaine O. , Lomax Alan E.
Published: March 2020

Key points

The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory products of commensal gut bacteria can modulate the excitability of vagal afferent neurons with cell bodies in nodose ganglia.

Cysteine proteases from commensal bacteria increased the excitability of vagal afferent neurons via activation of protease‐activated receptor 2 and modulation of the voltage dependence of Na+ conductance activation.

Lipopolysaccharide, a component of the cell wall of gram‐negative bacteria, increased the excitability of nodose ganglia neurons via TLR4‐dependent activation of nuclear factor kappa B.

Our study identified potential mechanisms by which gut microbiota influences the activity of vagal afferent pathways, which may in turn impact on autonomic reflexes and behaviour.

Behavioural studies have implicated vagal afferent neurons as an important component of the microbiota‐gut‐brain axis. However, the mechanisms underlying the ability of the gut microbiota to affect vagal afferent pathways are unclear. We examined the effect of supernatant from a community of 33 commensal gastrointestinal bacterial derived from a healthy human donor (microbial ecosystem therapeutics; MET‐1) on the excitability of mouse vagal afferent neurons. Perforated patch clamp electrophysiology was used to measure the excitability of dissociated nodose ganglion (NG) neurons. NG neuronal excitability was assayed by measuring the amount of current required to elicit an action potential, the rheobase. MET‐1 supernatant increased the excitability of NG neurons by hyperpolarizing the voltage dependence of activation of Na+ conductance. The increase in excitability elicited by MET‐1 supernatant was blocked by the cysteine protease inhibitor E‐64 (30 nm). The protease activated receptor‐2 (PAR2) antagonist (GB 83, 10 μm) also blocked the effect of MET‐1 supernatant on NG neurons. Supernatant from Lactobacillus paracasei 6MRS, a component of MET‐1, recapitulated the effect of MET‐1 supernatant on NG neurons. Lastly, we compared the effects of MET‐1 supernatant and lipopolysaccharide (LPS) from Escherichia coli 05:B5 on NG neuron excitability. LPS increased the excitability of NG neurons in a toll‐like receptor 4 (TLR4)‐dependent and PAR2‐independent manner, whereas the excitatory effects of MET‐1 supernatant were independent of TLR4 activation. Together, our findings suggest that cysteine proteases from commensal bacteria increase the excitability of vagal afferent neurons by the activation of PAR2.
Predictive power of cepstral coefficients and spectral moments in the classification of Azerbaijani fricatives
Authors: Ghaffarvand Mokari Payam , Mahdinezhad Sardhaei Nasim
Published: March 2020

This study compares the classification of Azerbaijani fricatives based on two sets of features: (a) spectral moments, spectral peak, amplitude, duration, and (b) cepstral coefficients employing Hidden Markov Models to divide each fricative into three regions such that the variances of the measures within each region are minimized. The cepstral coefficients were found to be more reliable predictors in the classification of all nine Azerbaijani fricatives and the cepstral measures yielded highly successful classification rates (91.21% across both genders) in the identification of the full set of fricatives of Azerbaijani.
The role of third windows on human sound transmission of forward and reverse stimulations: A lumped-parameter approach
Authors: Xue Lin , Liu Houguang , Wang Wenbo , Yang Jianhua , Zhao Yu , Huang Xinsheng
Published: March 2020

The vestibular and cochlear aqueducts serve as additional sound transmission paths and produce different degrees of volume velocity shunt flow in cochlear sound transmission. To investigate its effect on forward and reverse stimulations, a lumped-parameter model of the human ear, which incorporates the third windows, was developed. The model combines a transmission-line ear-canal model, a middle-ear model, and an inner-ear model, which were developed previously by different investigators. The model is verified by comparison with experiments. The intracochlear differential-pressure transfer functions, which reflect the input force to the organ of Corti, were calculated. The results show that middle-ear gain for forward sound transmission is greater than the gain for reverse sound transmission. Changes in the cochlear aqueduct impedance have little effect on forward and reverse stimulations. The vestibular aqueduct has little effect on forward stimulation, but increasing its impedance causes deterioration on reverse stimulation below 300 Hz. Decreasing its impedance increases the excitation effect during reverse stimulation over the entire frequency, especially below 1000 Hz. Moreover, compared with the case without the third windows, the presence of the third windows has little effect on forward stimulation. Whereas, it boosts the reverse stimulation's performance below 300 Hz.
Mapping the structure and biological functions within mesenchymal bodies using microfluidics
Authors: Sart Sébastien , Tomasi Raphaël F.-X. , Barizien Antoine , Amselem Gabriel , Cumano Ana , Baroud Charles N.
Published: March 2020

MSC spheroids self-organize in a hierarchical manner, resulting in a spatial patterning of the function of individual cells.
Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes
Authors: Reis Aramys S. , Barboza Renato , Murillo Oscar , Barateiro André , Peixoto Erika P. M. , Lima Flávia A. , Gomes Vinícius M. , Dombrowski Jamille G. , Leal Vinícius N. C. , Araujo Franciele , Bandeira Carla L. , Araujo Rosana B. D. , Neres Rita , Souza Rodrigo M. , Costa Fabio T. M. , Pontillo Alessandra , Bevilacqua Estela , Wrenger Carsten , Wunderlich Gerhard , Palmisano Giuseppe , Labriola Leticia , Bortoluci Karina R. , Penha-Gonçalves Carlos , Gonçalves Lígia A. , Epiphanio Sabrina , Marinho Claudio R. F.
Published: March 2020

IL-1 axis activation during placental malaria induces poor pregnancy outcomes that are obliterated after treatment with Anakinra.
Human transport of thirdhand tobacco smoke: A prominent source of hazardous air pollutants into indoor nonsmoking environments
Authors: Sheu Roger , Stönner Christof , Ditto Jenna C. , Klüpfel Thomas , Williams Jonathan , Gentner Drew R.
Published: March 2020

Tobacco smoke off-gassing from prior exposure releases contaminants that are equivalent to several cigarettes of secondhand smoke.
Polycomb regulation is coupled to cell cycle transition in pluripotent stem cells
Authors: Asenjo Helena G. , Gallardo Amador , López-Onieva Lourdes , Tejada Irene , Martorell-Marugán Jordi , Carmona-Sáez Pedro , Landeira David
Published: March 2020

Epigenetic regulation by the chromatin modifier Polycomb is modulated across cell cycle in stem cells.
Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration
Authors: Yao Bin , Wang Rui , Wang Yihui , Zhang Yijie , Hu Tian , Song Wei , Li Zhao , Huang Sha , Fu Xiaobing
Published: March 2020

3D-bioprinted microenvironment directs MSC differentiation and promotes SG regeneration.
Frank Press (1924–2020)
Authors: McNutt Marcia
Published: March 2020

Policy adviser and National Academy of Sciences president
Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection
Authors: Leyre Louise , Kroon Eugène , Vandergeeten Claire , Sacdalan Carlo , Colby Donn J. , Buranapraditkun Supranee , Schuetz Alexandra , Chomchey Nitiya , de Souza Mark , Bakeman Wendy , Fromentin Rémi , Pinyakorn Suteeraporn , Akapirat Siriwat , Trichavaroj Rapee , Chottanapund Suthat , Manasnayakorn Sopark , Rerknimitr Rungsun , Wattanaboonyoungcharoen Phandee , Kim Jerome H. , Tovanabutra Sodsai , Schacker Timothy W. , O’Connell Robert , Valcour Victor G. , Phanuphak Praphan , Robb Merlin L. , Michael Nelson , Trautmann Lydie , Phanuphak Nittaya , Ananworanich Jintanat , Chomont Nicolas ,   on behalf of the RV254/SEARCH010, RV304/SEARCH013, SEARCH011 study groups
Published: March 2020

Although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation.