bluuebunny/crossref_metadata_2025 huggingface dataset:
zUMIs - A fast and flexible pipeline to process RNA sequencing data with UMIs
Authors: Parekh Swati , Ziegenhain Christoph , Vieth Beate , Enard Wolfgang , Hellmann Ines
Published: May 2018

Background

Single-cell RNA-sequencing (scRNA-seq) experiments typically analyze hundreds or thousands of cells after amplification of the cDNA. The high throughput is made possible by the early introduction of sample-specific bar codes (BCs), and the amplification bias is alleviated by unique molecular identifiers (UMIs). Thus, the ideal analysis pipeline for scRNA-seq data needs to efficiently tabulate reads according to both BC and UMI.

Findings

zUMIs is a pipeline that can handle both known and random BCs and also efficiently collapse UMIs, either just for exon mapping reads or for both exon and intron mapping reads. If BC annotation is missing, zUMIs can accurately detect intact cells from the distribution of sequencing reads. Another unique feature of zUMIs is the adaptive downsampling function that facilitates dealing with hugely varying library sizes but also allows the user to evaluate whether the library has been sequenced to saturation. To illustrate the utility of zUMIs, we analyzed a single-nucleus RNA-seq dataset and show that more than 35% of all reads map to introns. Also, we show that these intronic reads are informative about expression levels, significantly increasing the number of detected genes and improving the cluster resolution.

Conclusions

zUMIs flexibility makes if possible to accommodate data generated with any of the major scRNA-seq protocols that use BCs and UMIs and is the most feature-rich, fast, and user-friendly pipeline to process such scRNA-seq data.
Error correcting optical mapping data
Authors: Mukherjee Kingshuk , Washimkar Darshan , Muggli Martin D , Salmela Leena , Boucher Christina
Published: May 2018

Optical mapping is a unique system that is capable of producing high-resolution, high-throughput genomic map data that gives information about the structure of a genome . Recently it has been used for scaffolding contigs and for assembly validation for large-scale sequencing projects, including the maize, goat, and Amborella genomes. However, a major impediment in the use of this data is the variety and quantity of errors in the raw optical mapping data, which are called Rmaps. The challenges associated with using Rmap data are analogous to dealing with insertions and deletions in the alignment of long reads. Moreover, they are arguably harder to tackle since the data are numerical and susceptible to inaccuracy. We develop cOMet to error correct Rmap data, which to the best of our knowledge is the only optical mapping error correction method. Our experimental results demonstrate that cOMet has high prevision and corrects 82.49% of insertion errors and 77.38% of deletion errors in Rmap data generated from the Escherichia coli K-12 reference genome. Out of the deletion errors corrected, 98.26% are true errors. Similarly, out of the insertion errors corrected, 82.19% are true errors. It also successfully scales to large genomes, improving the quality of 78% and 99% of the Rmaps in the plum and goat genomes, respectively. Last, we show the utility of error correction by demonstrating how it improves the assembly of Rmap data. Error corrected Rmap data results in an assembly that is more contiguous and covers a larger fraction of the genome.
Constrained global adaptive controller for a plug-flow tubular reactor with partial temperature measurements
Authors: Beniich N , El Bouhtouri A , Dochain D
Published: May 2018

In this work, a global constrained adaptive output feedback is presented for a class of plug-flow tubular reactors models described by non-linear partial differential equations. The output of the system is the measured temperature in a fixed zone of the reactor. It is then used to regulate the temperature throughout the reactor to a ball with radius $\lambda $ (arbitrarily small) centred at the fixed temperature profile.
Bispectrality and Time–Band Limiting: Matrix-valued Polynomials
Authors: Grünbaum F Alberto , Pacharoni Inés , Zurrián Ignacio
Published: May 2018

The subject of time–band limiting, originating in signal processing, is dominated by the miracle that a naturally appearing integral operator admits a commuting differential one allowing for a numerically efficient way to compute its eigenfunctions. Bispectrality is an effort to dig into the reasons behind this miracle and goes back to joint work with H. Duistermaat. This search has revealed unexpected connections with several parts of mathematics, including integrable systems. Here we consider a matrix-valued version of bispectrality and give a general condition under which we can display a constructive and simple way to obtain the commuting differential operator. Furthermore, we build an operator that commutes with both the time-limiting operator and the band-limiting operators.
Vein of Galen Aneurysmal Malformation: Advances in Management and Endovascular treatment
Authors: Berenstein Alejandro , Paramasivam Srinivasan , Sorscher Michelle , Molofsky Walter , Meila Dan , Ghatan Saadi
Published: May 2018

BACKGROUND

Vein of Galen aneurysmal malformation (VGAM) is a rare congenital vascular malformation representing <1% of all arteriovenous malformations. The knowledge and strategies in the management are constantly evolving.

OBJECTIVE

To review our series of postneonatal VGAM patients treated over 11-yr period.

METHODS

Retrospective analysis of 113 VGAM treated between January 2004 and April 2015. After exclusions, 45 patients were included: 33 choroidal and 12 mural types.

RESULTS

Presenting symptom in the order of frequency: enlarged head circumference, antenatal diagnosis, mild CHF, and PHT at birth. Older patients were diagnosed following trauma, headache, cognitive decline, and incidentally during workup for other diseases. Hydrocephalus due to hydrodynamic disorder was present in 70% of choroidal and 58% of mural types. Only a quarter needed cerebrospinal fluid diversion procedure. Radiological cure was achieved in 82%; the outcome graded on a 5-point scale: 0 (death) to 4 (normal). A total of 66.6% are neurologically and developmentally intact with outcome score 4, 20% had outcome score of 3, and 8.9% had outcome score of 2. There was 4.4% mortality. Dural feeders to VGAM were found either in the initial or during the treatment in 22.2% in the current series. Angiogenesis from pial vessels developed after partial embolization in 17.7% that resolved completely following complete obliteration of VGAM.

CONCLUSION

Technical and technological advancements in endovascular embolization along with better understanding of clinical, anatomic, and pathophysiological aspects have resulted in significantly improved outcome and prognosis in VGAM. Most patients with proper treatment can now survive and most develop normally following appropriately timed treatment.
Interstitial Stereotactic Laser Anterior Corpus Callosotomy: A Report of 2 Cases with Operative Technique and Effectiveness
Authors: Tao James X , Issa Naoum P , Wu Shasha , Rose Sandra , Collins John , Warnke Peter C
Published: May 2018

BACKGROUND AND IMPORTANCE

Corpus callosotomy is an effective palliative treatment for medically intractable Lennox–Gastaut syndrome (LGS) that disrupts the interhemispheric synchronization of epileptiform discharges. However, traditional open corpus callosotomy carries a significant risk of surgical complications associated with craniotomy and a parafalcine approach to the corpus callosum. Here, we report 2 cases of anterior corpus callosotomy using MRI-guided stereotactic laser interstitial thermal therapy (LITT) as a minimally invasive technique for mitigating the risks of craniotomy while achieving favorable outcomes.

CLINICAL PRESENTATION

Two patients with medically intractable LGS underwent stereotactic laser anterior corpus callosotomy using a 2 laser-fiber approach. Ablation of 70%-80% of the corpus callosum was confirmed by postoperative MRI diffusion tensor imaging and volumetric analysis. Marked reduction of epileptiform activity was observed in both patients during postoperative video-EEG studies as compared to preoperative video-EEG studies. Freedom from disabling seizures including drop attacks was achieved in 1 patient for 18 mo, and more than a 90% reduction of disabling seizures was achieved in the other patient for 7 mo with cognitive improvement and without surgical complications.

CONCLUSION

These early data demonstrate the technical feasibility, safety, and favorable outcomes of MRI-guided stereotactic laser anterior corpus callosotomy in patients with LGS, making it a potentially safe and effective alternative to traditional open corpus callosotomy and other stereotactic methods including radiofrequency ablation and radiosurgery due to the ability to monitor the ablation in real time with MRI.
Protecting only white children: the impact of child restraint legislation in Brazil
Authors: Nazif-Muñoz José Ignacio , Nandi Arijit , Ruiz-Casares Mónica
Published: May 2018

Background

In 2010, Brazil introduced child restraint legislation (CRL). We assessed the effectiveness of CRL in reducing child (aged 0–8 years) injuries and fatalities by race. We performed an evaluation study with an interrupted time–series design.

Methods

We measured the effect of CRL on two outcomes—number of child deaths and number of child injured in traffic collisions per child population, stratified by race, from 2008 to 2014. We controlled for time, unemployment rate and oil consumption (barrels/day in thousands).

Results

The CRL was associated with a 3% reduction in the rate of child injuries among whites (incidence rate ratio (IRR): 0.97; 95% CI: 0.96–0.99), but no reduction in child injuries among non-whites (IRR: 0.99; 95% CI: 0.99–1.00). In the first month after the implementation of Brazil’s CRL we observed a 39% reduction in all child fatalities (IRR: 0.61; 95% CI: 0.44–0.84), including a 52% reduction among whites (IRR: 0.48; 95% CI: 0.33–0.68), but no reduction in non-white fatalities (IRR: 0.87; 95% CI: 0.55–1.37).

Conclusions

Our results support the hypothesis that socially advantaged populations were more likely to consistently adopt and employ restraint devices following the reform. Countries should also consider complementary policies that facilitate an equitable distribution of safety devices that reach vulnerable populations.
The 70th anniversary of glucocorticoids in rheumatic diseases: the second youth of an old friend
Authors: Palmowski Yannick , Buttgereit Thomas , Buttgereit Frank
Published: May 2018

Seventy years ago, the first administration of cortisone in a patient with RA marked a milestone in the treatment of inflammatory diseases. However, the initial enthusiasm rapidly vanished as the administration of high doses for lengthy periods revealed worrisome adverse effects. It has taken several decades to overcome the (sometimes excessive) mistrust and to achieve a more differentiated evaluation of the benefit–risk profile and the adequate usage of glucocorticoids (GCs). Today, GCs remain indispensable for the treatment of many inflammatory conditions and their usefulness in RA as a disease-modifying low-dose co-medication is widely acknowledged. Recent studies show promising results concerning both traditional GCs and new formulations. Still, decades of relatively little scientific attention have resulted in a continuing lack of detailed evidence. Hence there is an ongoing need for further research regarding mechanisms of GC actions, the further optimization of treatment parameters for traditional GCs and new formulations.
The effect of zilpaterol hydrochloride on beef producer and processor revenue of calf-fed Holstein steers
Authors: McEvers Trent J , May Nathan D , Reed Jacob A , Walter Lee-Anne J , Hutcheson John P , Lawrence Ty E
Published: May 2018

A serial harvest was conducted every 28 d from 254 to 534 days on feed (DOF) to quantify changes in growth and composition of calf-fed Holstein steers (n = 110, initial BW = 449.2 ± 19.9 kg). One-half were supplemented the β-2 adrenergic agonist zilpaterol hydrochloride (ZH; 8.33 mg/kg 100% DM basis), and the remainder fed a control (CON) ration during the final 20 d followed by a 3 d withdrawal prior to harvest. Cattle were randomly allocated to dietary treatment and harvest endpoint (254, 282, 310, 338, 366, 394, 422, 450, 478, 506, and 534 DOF) using a 2 × 11 factorial treatment structure and a completely randomized experimental design structure. The objective of this ad-hoc investigation was to quantify changes in value across multiple harvest endpoints and marketing strategies for cattle supplemented with ZH. Cattle-fed ZH had increased (P < 0.01) value when sold on a dressed basis (+$82.64) or on a value-based formula (+$75.59) compared with CON cattle. No differences (P ≥ 0.14) were detected between ZH and CON carcasses for premiums and discounts related to HCW, yield grade, or quality grade. Moreover, no differences (P = 0.98) were detected for overall adjusted carcass value between ZH and CON carcasses. Fabrication values revealed that ZH carcasses had greater (P < 0.01) revenue than CON carcasses for primal round (+$36.23), loin (+$38.16), flank (+$8.95), rib (+$16.33), and chuck (+$27.49) regardless of DOF. Increased primal values ultimately led to greater (P < 0.01) processor revenue (+$138.94) and carcass value per 45.4 kg (+$6.45) for cattle-fed ZH compared with CON cattle. Overall, increased carcass weight and improved fabrication yield led to greater revenue at all harvest endpoints for cattle-fed ZH. Linear increases in live and dressed values indicated the daily change in live value was $3.48, which is less than an increase of $3.77 daily for dressed carcass value. Greater beef processor margin and profitability are expected when this growth technology is used.
Conserved forage-based systems for backgrounding weaned beef calves1
Authors: Forte Erin M , Mullenix Mary Kimberly , Tucker Jennifer J , Elmore Joshua B , Bergen Werner G
Published: May 2018

A 45-d backgrounding study was conducted to compare animal performance, forage nutritive value, digestion dynamics, and diet costs of conserved forage systems for weaned beef calves. One hundred and eight weaned Angus × Simmental beef calves (initial BW 279 ± 34 kg) were randomly assigned to one of three diets (n = 3 pens/treatment): 1) free-choice annual ryegrass (RB; cv. ‘Marshall’) baleage and 4 kg of a 50/50 mixture of pelleted soybean hulls and corn gluten feed, 2) free-choice Tifton 85 bermudagrass (BH) and 3 kg of a 50/50 mixture of pelleted soybean hulls and corn gluten feed, or 3) free-choice corn silage (CS; cv. Pioneer P1662YHR) and 2 kg of a 85% cracked corn and 15% cottonseed meal mixture. Diets were formulated to achieve a target gain of 0.9 kg/d based on the NRC (2000) requirement for a 270 kg growing calf. Animal performance (initial BW, final BW, and ADG) was measured on days 0 and 45 of the study. Forage nutritive value and an in vitro digestion trial were conducted to evaluate supplementation effects on forage diet digestion dynamics. Data were analyzed using PROC Mixed in SAS 9.4 as a completely randomized design. Pen was the experimental unit. Mean initial and final BW of the animals did not differ (P = 0.50 and P = 0.99, respectively) across treatments. Calf ADG for RB, BH, and CS diets were 0.61, 0.72, and 0.72 kg/d, respectively, and did not differ across treatments (P = 0.57). Based on these results, these forage options supported a similar level of gain when used for backgrounding beef calves. Forage in vitro DM digestibility differed 48 h after digestion, and BH + 50:50 had greater 48-h digestibility than when unsupplemented, which may be related to complementary forage-supplement interactions. In diets containing RB and CS, digestibility was greater with no supplementation at the 48-h time point. These data support the observation that supplementation type and level influence conserved forage diet digestibility compared with forage alone. The cost of feeding a baleage-based diet in this system was higher ($1.37/d) than CS or BH diets ($1.02 and $0.95/d, respectively). Results suggest that RB baleage-based diets may support a similar level of gain to BH or CS diets in growing beef calves, but supplement type, level, and ration costs should be evaluated when determining cost-effective backgrounding options in the Southeastern United States.
Development and the Labor Share
Authors: Maarek Paul , Orgiazzi Elsa
Published: May 2018

A U-shaped relationship between development and the labor share of income is brought to light. To do so, a panel dataset on the labor share in the manufacturing sector of developing countries is exploited. This dataset has greater coverage than the ones of previous studies focusing on developing countries. These data are also available at the disaggregated level for 28 manufacturing subsectors. This allows us to show that the U-shaped pattern of the labor share is also observed at the subsector level, suggesting that it does not correspond to reallocation forces across manufacturing subsectors during the development process. Standard theories of development economics that feature duality in the labor market easily generate such a pattern.
Negative Illness Perceptions are Associated With a Pronociceptive Modulation Profile and Augmented Pelvic Pain
Authors: Grinberg Keren , Granot Michal , Lowenstein Lior , Abramov Liora , Weissman-Fogel Irit
Published: May 2018

Objectives:

A patient’s personal interpretations of a health threat or “illness perceptions” (IPs) are associated with their clinical outcomes. This study explored whether IPs are associated with pain severity and ability to modulate pain in women with chronic pelvic pain syndrome (CPPS), as well as the predictive value of IPs on myofascial manual therapy (MMT) success.

Materials and Methods:

Illness Perceptions Questionnaire-Revised (IPQ-R), mechanical and heat pain thresholds, mechanical temporal summation, and conditioned pain modulation (CPM) were evaluated in CPPS patients (n=39) before, and 3 months after MMT. CPPS severity was obtained by the Brief Pain Inventory (BPI).

Results:

Stronger perceptions of illness chronicity were correlated with less efficient CPM (r=0.488, P=0.002) and increased mechanical pain intensity (r=0.405, P=0.02). Lower perceptions of control over illness were associated with enhanced mechanical temporal summation (r=0.399, P=0.01). Higher BPI scores were correlated with emotional representations (negative emotional representations) and severe consequences due to CPPS. Regression analyses revealed that negative IPs predict less efficient MMT.

Discussion:

Cognitive representations play a unique role in CPPS expression and MMT outcomes. The interplay between negative IPs and a pronociceptive modulation profile, mediated by enhanced facilitatory and reduced inhibitory processes, may be involved in the manifestation of CPPS.
Spinopelvic Alignment in Subjects With Down Syndrome
Authors: Assi Ayman , Bakouny Ziad , Mansour Elie , Yaacoub Jean-Jacques , Yared Fares , Ghanem Ismat
Published: May 2018

Study Design:

This was a cross-sectional study.

Objective:

The aim of this study was to describe the spinopelvic alignment of subjects with Down syndrome (DS).

Summary of Background Data:

Subjects with DS are known to suffer from a large prevalence of scoliosis. While scoliosis is known to significantly affect postural alignment, there are currently no studies on the spinopelvic alignment of subjects with DS.

Materials and Methods:

In total, 41 subjects (28 female subjects and 13 male subjects) with DS, age and sex-matched to 41 asymptomatic subjects, underwent biplanar x-rays with 3-dimensional reconstructions of their spines and pelvises, followed by measurement of commonly used spinopelvic sagittal and coronal alignment parameters. Subjects were then classified into one of Roussouly’s 4 types of sagittal alignment. Alignment parameters and prevalence of alignment patterns were compared between the 2 groups.

Results:

Subjects with DS were found to be relatively hypokyphotic (T4–T12=−29.0 vs. −37.5 degrees; P<0.001) and hyperlordotic (L1–L5=53.8 vs. 44.3 degrees; P<0.001) with larger pelvic incidence (53.2 vs. 45.1 degrees; P<0.001), sacral slope (47.7 vs. 36.8 degrees; P<0.001), Cobb angle (10.2 vs. 8.0 degrees; P=0.005), and axial rotation of the apical vertebra (6.6 vs. 3.7 degrees; P<0.001) but had smaller pelvic tilt (4.9 vs. 8.1 degrees; P<0.001) compared with control subjects. Roussouly’s type 4 was found to be the most frequent pattern in DS subjects (68.3% vs. 14.6%; P<0.001).

Conclusions:

Subjects with DS were found to have a peculiar pattern of hypokyphosis, hyperlordosis, large pelvic incidence, and small pelvic tilt. The altered spinopelvic alignment found in DS could predispose these subjects to hip instability and osteoarthritis.

Level of Evidence:

Level III.
The Outcomes of Posterior Arthrodesis for Atlantoaxial Subluxation in Down Syndrome Patients
Authors: Scollan Joseph P. , Alhammoud Abduljabbar , Tretiakov Mikhail , Hollern Douglas A. , Bloom Lee R. , Shah Neil V. , Naziri Qais , Diebo Bassel G. , Yoshihara Hiroyuki , Scott Claude B. , Hesham Khalid , Paulino Carl B.
Published: May 2018

Study Design:

This is a meta-analysis.

Objective:

To establish rates of (1) neurological complications, (2) bony-related complications, (3) complications delaying recovery, (4) reoperation, and (5) fatalities following posterior cervical arthrodesis in Down syndrome (DS) patients with atlantoaxial subluxation. To determine if presenting symptoms had any relationship to postoperative complications.

Summary of Background Data:

Posterior arthrodesis is commonly utilized to correct cervical instability secondary to atlantoaxial instability in DS patients. However, there has never been a global evaluation of postoperative complications associated with posterior cervical spinal arthrodesis in DS patients.

Methods:

A comprehensive search of Medline/PubMed, EMBASE, and Ovid databases between January 1980 and July 2017 was utilized to identify DS patients with atlantoaxial subluxation who underwent posterior cervical arthrodesis. Data were sorted by neurological complications, complications delaying recovery, bony-related complications, reoperations, and fatalities. Patients were sorted into 2 groups based on presentation with or without neurological deficits.

Results:

Twelve studies met inclusion criteria, including 128 DS patients. Mean age was 13.8 years (range: 6.7–32.7 y; 47.8% male). Mean follow-up was 31.7 months (range: 14.9–77 mo). All patients underwent primary posterior cervical arthrodesis with an average of 2.5 vertebrae fused. A total of 39.6% of patients had bony-related complications [95% confidence interval (CI), 31.4%–48.5%], 23.3% had neurological deficits (95% CI, 16.6%–31.6%), and 26.4% experienced complications delaying recovery (95% CI, 19.4%–34.9%). The reoperation rate was 34.9% (95% CI, 25.5%–45.6%). The mortality rate was 3.9% (95% CI, 1.5%–9.7%). Neurological complications were 4-fold (P<0.05) and reoperation was 5.5-fold (P<0.05) more likely in patients presenting with neurological deficits compared with those without.

Conclusions:

This study detailed global complication rates of posterior arthrodesis for DS patients, identifying bony-related complications and reoperations among the most common. Patients presenting with neurological symptoms and cervical instability have increased postoperative rates of neurological complications and reoperations than patients with instability alone. Further investigation into how postoperative complications effect patient independence is warranted.
A Comparative Study Between 2 Intracarpal Partial Shortening Osteotomy Techniques for Type II Lunate Kienbock Disease
Authors: Naeem Atyyia Ahmed , Diab Ramy A. , Nabil Amr
Published: May 2018

Partial capitate shortening is a decompression procedure for the treatment of positive or neutral ulnar variance Kienbock disease. In 45% to 73% of population, the lunate has a separate hamate facet which is also known as a type II lunate. We hypothesized that capitate shortening alone may not ensure adequate decompression of type II lunate, therefore, an added hamate shortening was performed aiming at a better distal unloading in these situations. Thirty Kienbock patients, stage II, type II lunate, and ulna positive or neutral variance, were recruited in this study, Half of which underwent an isolated partial capitate osteotomy, while the other half underwent a combined partial capitate-hamate osteotomy. The 2 groups were matched making the osteotomy type the only variable in the study. Postoperative changes in visual analogue score, the quick Disability of the Arm Shoulder and Hand questionnaire, Stahl index, and radioscaphoid angle in lateral view radiograph were recorded. Flexion and extension range of motion using a goniometer, and grip strength using dynamometer were recorded as percentage of the contralateral normal wrist. All the patients were followed up for 18 months. The 2 groups were comparable preoperatively as regards to the clinical and radiologic parameters. Postoperatively, there was no clinical nor radiologic, statistically significant differences between the 2 groups. We conclude that either isolated capitate shortening osteotomy or combined capitate/hamate osteotomy techniques can achieve very comparable results, both with good outcomes.
Gynecological sarcomas: what's new in 2018, a brief review of published literature
Authors: Gantzer Justine , Ray-Coquard Isabelle
Published: May 2018

Purpose of review

In this article, we focus on recent published data (2017) on the management of gynecologic sarcomas.

Recent findings

The most significant data published in 2017 develop definition of a new molecular subtype of high grade endometrial stromal sarcoma (ESS) using molecular technics added to histological analysis. The identification of a new translocation on presumed uterine leiomyosarcoma (LMS) points to refinement of nosological classification, with fragmentation of even rare tumors into distinct molecular entities: gynecologic sarcomas are now distinguished into distinct entities from a heterogeneous group of tumors. Other articles have discussed the real incidence of unsuspected sarcomas after fibroid mini-invasive surgery and evaluate the risk of relapse and dissemination after morcellation. Among several criteria, preoperative imagery could become a useful tool. For systemic treatment, no clinical trials changing practices were published, only one positive nonrandomized phase II with carboplatin and pegylated liposomal doxorubicin (PLD) in the treatment of uterine sarcomas after the conventional first line, especially in LMSs and ESSs.

Many articles were published on this confidential domain in oncology demonstrating interests on rare sarcomas. All specialties were represented in the literature, even though we are still waiting for urgent improvements in early diagnosis and therapeutic strategies to transform the poor prognostic of these tumors.
Bioprosthetic Versus Synthetic Mesh: Analysis of Tissue Adherence and Revascularization in an Experimental Animal Model
Authors: Adelman David M. , Cornwell Kevin G.
Published: May 2018

Background:

Both synthetic and bioprosthetic meshes play important roles in surgical procedures such as ventral hernia repair. Although sometimes used interchangeably, these devices have inherently different properties. We therefore sought to better understand how these materials interact with the host environment to optimize surgical techniques and to improve outcomes.

Methods:

Synthetic mesh (polypropylene, Prolene) or bioprosthetic mesh (acellular fetal/neonatal bovine dermis, SurgiMend) was implanted intraperitoneally into rats lateral to a ventral incision in a novel intra-abdominal implant model. Two variables were modified with each material: (1) tight or loose tissue apposition, altered by modifying suture placement; and (2) abdominal wall injury, altered by selective abrasion of the peritoneal lining. After 5 weeks, the meshes and abdominal wall were evaluated grossly and histologically. The analysis focused on the degree of inflammatory response, neovascularization, and mesh adherence to the surrounding tissues.

Results:

Synthetic mesh adhered to the abdominal wall and visceral organs, regardless of the degree of apposition or tissue injury, due to a foreign body–mediated inflammatory reaction. In areas of noninjured peritoneal lining, SurgiMend was adherent peri-suture. Neovascularization entered the mesh from these apposition points and spread outward. In areas of denuded peritoneal lining, the adherent and vascularized areas were significantly greater and not merely coincident with suture placement.

Conclusions:

The inflammatory and wound healing responses with bioprosthetic mesh seem fundamentally different from synthetic mesh. Understanding these differences may lead to varied outcomes in adherence and vascularization of the materials, and ultimately the efficacy of hernia repair. Additionally, these differences highlight the need for further basic research to optimize mesh selection for surgical technique.
The Utility of Silk-elastin Hydrogel as a New Material for Wound Healing
Authors: Kawabata Shingo , Kanda Norikazu , Hirasawa Yasushi , Noda Kazuo , Matsuura Yoshitaka , Suzuki Shigehiko , Kawai Katsuya
Published: May 2018

Cutaneous ulcers are treated with dressing materials and/or ointments to keep the wound in an appropriately moist environment. However, chronic cutaneous ulcers commonly have bacterial colonization that can cause local infection in such an environment. Therefore, the dressing materials and/or ointments should have antibacterial potency to treat chronic ulcers. Acute cutaneous wounds, by contrast, heal rapidly without local infection. The aim of treating acute cutaneous wounds is therefore not only wound closure but also preventing scar contracture after wound healing. However, no dressing materials or ointments available at present are simultaneously effective for preventing infection in chronic ulcers and reducing wound contracture in acute ulcers. Silk-elastin is a recombinant protein polymer with repeating units of silk-like and elastin-like blocks. Silk-elastin solution can self-assemble from a liquid to a hydrogel. We preliminarily reported that silk-elastin hydrogels have the potential to accelerate wound healing in decubitus ulcers of diabetic mice, which are animal models of severe, intractable cutaneous ulcers. In the present study, we examined the effects of silk-elastin hydrogels in chronic and acute ulcer models in comparison with conventional products (carboxymethyl cellulose gel). Silk-elastin hydrogels resulted in significantly higher epithelialization rates than conventional hydrogels in both the chronic and acute ulcer models and significantly larger areas of granulation tissue in acute ulcer models. These results show that silk-elastin hydrogel is a promising material for promoting the healing of cutaneous wounds, including decubitus ulcers, chronic ulcers, and acute ulcers.
Managing Complications of Submental Artery Involvement after Hyaluronic Acid Filler Injection in Chin Region
Authors: Fang Martha , Rahman Eqram , Kapoor Krishan Mohan
Published: May 2018

Hyaluronic acid dermal fillers are becoming popular all over the world, but due to the presence of many blood vessels in the face, there is always a small possibility of vascular complications. We present a case with the ischemic involvement of chin and neck skin after accidental submental artery involvement after hyaluronic acid filler injection for chin region. Impending skin necrosis on the chin and upper neck on the right side was diagnosed quickly by observing the skin changes in the immediate postfiller phase. Pain in the mandible and in the muscles during swallowing due to possible ischemia of muscles supplied by submental artery was another crucial diagnostic feature. All parts of the affected zone were treated with high-dose pulsed hyaluronidase protocol using 4 pulses of hyaluronidase injection in first 24 hours after filler injection. Complete resolution of cutaneous ischemic changes and painful swallowing was achieved within days after treatment. Knowledge of presenting features of postfiller vascular complications and the extent of vascular territory of the involved artery is quite helpful in quickly instituting treatment leading to the near-complete recovery with minimal sequelae.
Brincidofovir (CMX001) Toxicity Associated With Epithelial Apoptosis and Crypt Drop Out in a Hematopoietic Cell Transplant Patient: Challenges in Distinguishing Drug Toxicity From GVHD
Authors: Detweiler Claire J. , Mueller Sarah B. , Sung Anthony D. , Saullo Jennifer L. , Prasad Vinod K. , Cardona Diana M.
Published: May 2018

Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.
Biliary tract external drainage improves inflammatory mediators and pathomorphology of the intestine, liver, and lung in septic rats
Authors: Liu Yong-Jun , Sun Qing , Chen Juan , Chen Min-Ying , Ouyang Bin , Sun Hua-Dong , Nie Yao , Wang Ping-Ping , Ma Jie , Guan Xiang-Dong
Published: May 2018

BACKGROUND

To investigate the effect of biliary tract external drainage (BTED) on inflammatory mediators and pathomorphism of intestine, liver, and lung in septic rats.

METHOD

48 SD rats (n = 8 per group) were randomized into six groups: control, sepsis, sepsis plus BTED, normal bile (obtained from eight healthy rats), and septic bile infusion for 6 hours respectively to test the effects of BTED bile infusion on cytokines’ expression and tissue injury in the intestine, liver, and lung of septic/normal rats. Co-cultivation of intestinal epithelial cells (IEC-6) with bile for 12 hours was performed to evaluate the potential cytotoxicity of septic bile. Survival rate for sepsis plus BTED rats was detected compared with sepsis without BTED group (n = 20 per group) at 24, 48, and 72 hours, respectively.

RESULTS

BTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1β (allp< 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1β in the intestine was increased after 6 hours’ septic bile infusion compared with normal bile infusion group (allp< 0.05). TNF-α concentration in septic bile was significantly higher than that in the control group (p< 0.001). Tissue injury was significantly attenuated after 6 hours’ BTED.

CONCLUSIONS

BTED can significantly restrain the mRNA expression of TNF-α and IL-1β in the intestine, liver, and lung and attenuate histological damage in septic rats.
Outcomes following trauma laparotomy for hypotensive trauma patients: A UK military and civilian perspective
Authors: Marsden Max , Carden Rich , Navaratne Lalin , Smith Iain M. , Penn-Barwell Jowan G. , Kraven Luke M. , Brohi Karim , Tai Nigel R.M. , Bowley Douglas M.
Published: May 2018

BACKGROUND

The management of trauma patients has changed radically in the last decade, and studies have shown overall improvements in survival. However, reduction in mortality for the many may obscure a lack of progress in some high-risk patients. We sought to examine the outcomes for hypotensive patients requiring laparotomy in UK military and civilian cohorts.

METHODS

We undertook a review of two prospectively maintained trauma databases: the UK Joint Theatre Trauma Registry for the military cohort (February 4, 2003, to September 21, 2014) and the trauma registry of the Royal London Hospital major trauma center (January 1, 2012, to January 1, 2017) for civilian patients. Adults undergoing trauma laparotomy within 90 minutes of arrival at the emergency department (ED) were included.

RESULTS

Hypotension was present on arrival at the ED in 155 (20.4%) of 761 military patients. Mortality was higher in hypotensive casualties (25.8% vs. 9.7% in normotensive casualties; p < 0.001). Hypotension was present on arrival at the ED in 63 (35.7%) of 176 civilian patients. Mortality was higher in hypotensive patients (47.6% vs. 12.4% in normotensive patients; p < 0.001). In both cohorts of hypotensive patients, neither the average injury severity, the prehospital time, the ED arrival systolic blood pressure, nor mortality rate changed significantly during the study period.

CONCLUSIONS

Despite improvements in survival after trauma for patients overall, the mortality for patients undergoing laparotomy who arrive at the ED with hypotension has not changed and appears stubbornly resistant to all efforts. Specific enquiry and research should continue to be directed at this high-risk group of patients.

LEVEL OF EVIDENCE

Prognostic/Epidemiologic, level IV.
Time to stroke: A Western Trauma Association multicenter study of blunt cerebrovascular injuries
Authors: Burlew Clay Cothren , Sumislawski Joshua J. , Behnfield Charles D. , McNutt Michelle K. , McCarthy James , Sharpe John P. , Croce Martin A. , Bala Miklosh , Kashuk Jeffry , Spalding M. Chance , Beery Paul R. , John Scott , Hunt Darren J. , Harmon Laura , Stein Deborah M. , Callcut Rachael , Wybourn Chris , Sperry Jason , Anto Vincent , Dunn Julie , Veith Jacob P. , Brown Carlos V. R. , Celii Amanda , Zander Tyler L. , Coimbra Raul , Berndtson Allison E. , Moss Tovah Z. , Malhotra Ajai K. , Hazelton Joshua P. , Linden Kimberly , West Michaela , Alam Hasan B. , Williams Aaron M. , Kim Jennie , Inaba Kenji , Moulton Steve , Choi Young Mee , Warren Harry L. , Collier Bryan , Ball Chad G. , Savage Stephanie , Hartwell Jennifer L. , Cullinane Daniel C. , Zielinski Martin D. , Ray-Zack Mohamed D. , Morse Bryan C. , Rhee Peter , Rutherford Edmund J. , Udekwu Pascal , Reynolds Cassandra , Toschlog Eric , Gondek Steve , Ju Tammy , Haan James M. , Lightwine Kelly L. , Kulvatunyou Narong , Coates Brian , Khouqeer Ahmed F. , Todd S. Rob , Zarzaur Ben , Waller Christine J. , Kallies Kara J. , Neideen Todd , Eddine Savo Bou Zein , Peck Kimberly A. , Dunne Casey E. , Kramer Kristina , Bokhari Faran , Dhillon Tejveer S. , Galante Joseph M. , Cohen Mitchell J.
Published: May 2018

BACKGROUND

Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients. The purpose of this study was to determine the time to stroke in patients with a BCVI-related stroke. We hypothesized that the majority of patients suffer stroke between 24 hours and 72 hours after injury.

METHODS

Patients with a BCVI-related stroke from January 2007 to January 2017 from 37 trauma centers were reviewed.

RESULTS

During the 10-year study, 492 patients had a BCVI-related stroke; the majority were men (61%), with a median age of 39 years and ISS of 29. Stroke was present at admission in 182 patients (37%) and occurred during an Interventional Radiology procedure in six patients. In the remaining 304 patients, stroke was identified a median of 48 hours after admission: 53 hours in the 144 patients identified by neurologic symptoms and 42 hours in the 160 patients without a neurologic examination and an incidental stroke identified on imaging. Of those patients with neurologic symptoms, 88 (61%) had a stroke within 72 hours, whereas 56 had a stroke after 72 hours; there was a sequential decline in stroke occurrence over the first week. Of the 304 patients who had a stroke after admission, 64 patients (22%) were being treated with antithrombotics when the stroke occurred.

CONCLUSIONS

The majority of patients suffer BCVI-related stroke in the first 72 hours after injury. Time to stroke can help inform clinicians about initiation of treatment in the multiply injured patient.

LEVEL OF EVIDENCE

Prognostic/Epidemiologic, level III.
Tandem duplications lead to loss of fitness effects in CRISPR-Cas9 data
Authors: Gonçalves Emanuel , Behan Fiona M , Louzada Sandra , Arnol Damien , Stronach Euan , Yang Fengtang , Yusa Kosuke , Stegle Oliver , Iorio Francesco , Garnett Mathew J
Published: May 2018

CRISPR-Cas9 gene-editing is widely used to study gene function and is being advanced for therapeutic applications. Structural rearrangements are a ubiquitous feature of cancers and their impact on CRISPR-Cas9 gene-editing has not yet been systematically assessed. Utilising CRISPR-Cas9 knockout screens for 163 cancer cell lines, we demonstrate that targeting tandem amplified regions is highly detrimental to cellular fitness, in contrast to amplifications caused by chromosomal duplications which have little to no effect. Genomically clustered Cas9 double-strand DNA breaks are associated with a strong gene-independent decrease in cell fitness. We systematically identified collateral vulnerabilities in 25% of cancer cells, introduced by tandem amplifications of tissue non-expressed genes. Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing technology, and how resulting collateral vulnerabilities are a generalisable strategy to target cancer cells.
Nucleus- and plastid-targeted annexin 5 promotes reproductive development in Arabidopsis and is essential for pollen and embryo formation
Authors: Lichocka Malgorzata , Rymaszewski Wojciech , Morgiewicz Karolina , Barymow-Filoniuk Izabela , Chlebowski Aleksander , Sobczak Miroslaw , Samuel Marcus A. , Schmelzer Elmon , Krzymowska Magdalena , Hennig Jacek
Published: May 2018

Background

Pollen development is a strictly controlled post-meiotic process during which microspores differentiate into microgametophytes and profound structural and functional changes occur in organelles. Annexin 5 is a calcium- and lipid-binding protein that is highly expressed in pollen grains and regulates pollen development and physiology. To gain further insights into the role of ANN5 in Arabidopsis development, we performed detailed phenotypic characterization of Arabidopsis plants with modified ANN5 levels. In addition, interaction partners and subcellular localization of ANN5 were analyzed to investigate potential functions of ANN5 at cellular level.

Results

Here, we report that RNAi-mediated suppression of ANN5 results in formation of smaller pollen grains, enhanced pollen lethality, and delayed pollen tube growth. ANN5 RNAi knockdown plants also displayed aberrant development during the transition from the vegetative to generative phase and during embryogenesis, reflected by delayed bolting time and reduced embryo size, respectively. At the subcellular level, ANN5 was delivered to the nucleus, nucleolus, and cytoplasm, and was frequently localized in plastid nucleoids, suggesting a likely role in interorganellar communication. Furthermore, ANN5-YFP co-immunoprecipitated with RABE1b, a putative GTPase, and interaction in planta was confirmed in plastidial nucleoids using FLIM-FRET analysis.

Conclusions

Our findings let us to propose that ANN5 influences basal cell homeostasis via modulation of plastid activity during pollen maturation. We hypothesize that the role of ANN5 is to orchestrate the plastidial and nuclear genome activities via protein-protein interactions however not only in maturing pollen but also during the transition from the vegetative to the generative growth and embryo development.
Eradication ofENO1-deleted Glioblastoma through Collateral Lethality
Authors: Lin Yu-Hsi , Satani Nikunj , Hammoudi Naima , Ackroyd Jeffrey J. , Khadka Sunada , Yan Victoria C. , Georgiou Dimitra K. , Sun Yuting , Zielinski Rafal , Tran Theresa , Pando Susana Castro , Wang Xiaobo , Maxwell David , Peng Zhenghong , Pisaneschi Federica , Mandal Pijus , Leonard Paul G. , Xu Quanyu , Wu Qi , Jiang Yongying , Czako Barbara , Kang Zhijun , Asara John M. , Priebe Waldemar , Bornmann William , Marszalek Joseph R. , DePinho Ronald A. , Muller Florian L.
Published: May 2018

Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We recently demonstrated that SF2312, a natural product phosphonate antibiotic, is a potent inhibitor of the glycolytic enzyme Enolase with potential utility for the collateral lethality-based treatment of Enolase-deficient glioblastoma (GBM). However, phosphonates are anionic at physiological pH, limiting cell and tissue permeability. Here, we show that addition of pivaloyloxymethyl (POM) groups to SF2312 (POMSF) dramatically increases potency, leading to inhibition of glycolysis and killing ofENO1-deleted glioma cells in the low nM range. But the utility of POMSFin vivois dose-limited by severe hemolytic anemia. A derivative, POMHEX, shows equipotency to POMSF without inducing hemolytic anemia. POMHEX can eradicate intracranial orthotopicENO1-deleted tumors, despite sub-optimal pharmacokinetic properties. Taken together, our data providein vivoproof-of-principal for collateral lethality in precision oncology and showcase POMHEX as a useful molecule for the study of glycolysis in cancer metabolism.
Establishing a cell-freeVibrio natriegensexpression system
Authors: Wiegand Daniel J. , Lee Henry H. , Ostrov Nili , Church George M.
Published: May 2018

The fast growing bacteriumVibrio natriegensis an emerging microbial host for biotechnology. Harnessing its productive cellular components may offer a compelling platform for rapid protein production and prototyping of metabolic pathways or genetic circuits. Here, we report the development of aV. natriegenscell-free expression system. We devised a simplified crude extract preparation protocol and achieved >260 μg/mL of super-folder GFP in a small-scale batch reaction after three hours. Culturing conditions, including growth media and cell density, significantly affect translation kinetics and protein yield of extracts. We observed maximal protein yield at incubation temperatures of 26°C or 30°C, and show improved yield by tuning ions crucial for ribosomal stability. This work establishes an initialV. natriegenscell-free expression system, enables probing ofV. natriegensbiology, and will serve as a platform to accelerate metabolic engineering and synthetic biology applications.