bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Related Differences in Psychosocial Function of Children with Craniofacial Anomalies
Authors: Volpicelli Elizabeth J. , Pfaff Miles J. , Hakimi Kevin , Bradley James P. , Solem R. Christian , Lee Justine C.
Published: September 2017

Background:

Age is a frequent consideration for surgical timing in pediatric craniofacial surgery for optimal psychosocial development. However, systematic evaluations of the effects of age in children under active treatment have not been thoroughly evaluated.

Methods:

Ninety-nine patients (age, 8 to 17 years; 46.5 percent male) from the University of California, Los Angeles, Craniofacial Clinic were prospectively evaluated using the Pediatric Patient-Reported Outcomes Measurement Information System to assess anger, anxiety, depression, and quality of peer relationships. Patients were stratified into three age groups by years: group A, 8 to 10 years, n = 30; group B, 11 to 13 years, n = 41; and group C, 14 to 17 years, n = 28. Analyses of variance and logistic regression analyses were performed.

Results:

Significant differences in anxiety (F
2,96 = 5.1; p = 0.008), depression (F
2,96 = 9.7; p < 0.001), peer relationships (F
2,96 = 3.5; p = 0.03), and anger (F
2,96 = 4.9; p = 0.009) were found among the age groups. Group A demonstrated the highest anxiety, highest depression, and lowest peer relationship scores overall. Although there were no differences in anger between groups A and C, group B had the lowest anger scores. Children with poor scores of higher severity, defined as greater than 1 SD worse than the national mean, were compared. Group A contributed the highest percentages of more severely affected children in all categories. A logistic regression analysis demonstrated that group A was a statistically significant predictor for scores of higher severity in both anxiety (OR, 3.8; 95 percent CI, 1.3 to 11.5; p = 0.02) and peer relationships (OR, 3.4; 95 percent CI, 1.3 to 9.3; p = 0.02).

Conclusions:

Children between 8 and 10 years of age with craniofacial anomalies constitute a high-risk subset for psychosocial dysfunction. The authors’ work suggests that tight surveillance with family and school awareness may be necessary for this age group.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
The Horizontal Myocutaneous Infrahyoid Island Flap for Soft-Tissue Head and Oral Reconstruction: Step-by-Step Video Description
Authors: Verbruggen Charlie , Majoufre Claire , Derosamel Laure , Dubreuil Pierre-Antoine , Vallade Gabrielle , Mage Caroline , Sessiecq Quentin , Bondaz Mathieu
Published: September 2017

A clinical case is presented of a 70-year-old woman suffering from a right hemilingual epidermoid carcinoma. A step-by-step video description of the regional infrahyoid island flap is presented and narrated. Long-term results at 2 months in terms of aesthetics and function at the recipient and donor sites are excellent.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Rhinoplasty Refinements: The Role of the Open Approach
Authors: Rohrich Rod J. , Afrooz Paul N.
Published: September 2017

The open rhinoplasty technique facilitates accurate visualization of deformities and aesthetic disharmonies in addition to visualization for precise correction. Through a series of videos, this case represents the evolution of the open rhinoplasty technique, demonstrating a wide range in complexity of maneuvers to achieve the desired correction in rhinoplasty. The video demonstrates reduction of the nasal dorsum by way of a component dorsal reduction, reconstitution of the cartilaginous midvault, and suture techniques for reshaping the nasal tip. Nasal tip deprojection and placement of alar contour grafts are also demonstrated in this case. The aim is to provide the rhinoplasty surgeon with examples of basic and sophisticated techniques and also to demonstrate the minutia and nuance of open rhinoplasty.
Brief Report: Context Matters: PrEP Adherence is Associated With Sexual Behavior Among HIV Serodiscordant Couples in East Africa
Authors: Haberer Jessica E. , Ngure Kenneth , Muwonge Timothy , Mugo Nelly , Katabira Elly , Heffron Renee , Musinguzi Nicholas , Bangsberg David R. , Celum Connie , Baeten Jared M. ,   on behalf of the Partners Mobile Adherence to PrEP (PMAP) Team
Published: September 2017

Background:

Short message service (SMS) surveys are a promising tool for understanding whether preexposure prophylaxis (PrEP) adherence aligns with risk for HIV acquisition—a concept known as prevention-effective adherence.

Methods:

The Partners Demonstration Project was an open-label study of integrated PrEP and antiretroviral therapy (ART) delivery among high-risk HIV serodiscordant couples in East Africa. HIV-uninfected partners were offered PrEP until their HIV-infected partner had taken ART for ≥6 months. At 2 study sites, HIV-uninfected partners were offered enrollment into the Partners Mobile Adherence to PrEP (PMAP) substudy based on ongoing PrEP use, personal cell phone ownership, and ability to use SMS. SMS surveys asked about PrEP adherence and sexual activity in the previous 24 hours; these surveys were sent daily for the 7 days before and 7 days after routine study visits in the Partners Demonstration Project.

Results:

The PMAP substudy enrolled 373 HIV-uninfected partners; 69% were men and mean age was 31 years. Participants completed 17,030 of 23,056 SMS surveys sent (74%) with a mean of 47 surveys per participant over 9.8 months of follow-up. While HIV-infected partner use of ART was <6 months, mean reported PrEP adherence was 92% on surveys concurrently reporting sex within the serodiscordant partnership, and 84% on surveys reporting no sex (P < 0.001).

Discussion:

SMS surveys provided daily assessment of concurrent PrEP adherence and sexual behavior. Higher PrEP adherence was temporally associated with increased risk for HIV acquisition.
Intraoral Excision of a Huge Cheek Lipoma
Authors: Coelho Rodrigo Carvalho Pinto , Oliveira Eduardo Morato , Silva Guilherme Costa Carvalho , Aguiar Evandro Guimarães , Moreira Allyson Nogueira , Souza Leandro Napier
Published: September 2017

Lipomas are benign tumors of mature adipocytes unusual in the oral and maxillofacial region. The average size of cheek lipomas in the literature ranges from 1.5 to 2.5 cm, with the maximum size of 5 cm. Their etiology remains unclear. Lipomas present, clinically, as well circumscribed, slow growing, painless masses, usually treated by complete excision. The aim of this paper is to present a 78-year-old Caucasian male patient with a huge cheek lipoma compromising facial esthetics and treated through an intraoral excision. Postoperative period was uneventful with no signs of recurrence. Concluding, the intraoral approach is a relatively simple technique that should be taken into account when considering the surgical removal of cheek lipomas.
Posterior Iliac Crest Bone Graft: How Much Is Enough?
Authors: Boucree Thaddeus , McLaughlin Dylan , Akrawe Silvy , Darian Vigen , Siddiqui Aamir
Published: September 2017

Autogenous bone grafting is the gold standard for reconstructing craniofacial defects. Mandibular defects are reliably reconstructed with free nonvascularized bone, such as from the posterior iliac crest (PIC). In light of improved imaging, including 3-dimensional computed tomography scanning, a more accurate defect estimation is possible. A strong understanding of bone graft available is necessary. The purpose of this study was an updated review of the dissection and quantification of the amount of bone that can be safely harvested. Bilateral bicortical osteotomy was performed on 55 cadavers to obtain 110 PIC bone grafts. Demographic factors and bicortical osteotomy measurements were recorded. Average osteotomy lengths, widths, and depths were 7.4, 5.5, and 1 cm, respectively. The average bicortical osteotomy volume was 40.6 cm3. During the dissection, the authors identified 2 anatomical variants with respect to muscle insertion into the PIC. In variation 1, which occurred in 62% of dissections, the latissimus dorsi and thoracolumbar fascia did not originate from the PIC. When this occurred, the quadratus lumborum attached to the PIC. In variation 2, which occurred in 38% of dissections, the latissimus dorsi and thoracolumbar fascia originate from the PIC. By identifying the maximal bone volume obtainable from a PIC graft and noting 2 anatomical variants, this study allows for more accurate surgical planning and management.
Propranolol Treatment of Vascular Anomalies Other Than Infantile Hemangioma
Authors: Goss Jeremy A. , Konczyk Dennis J. , Alomari Mohammed H. , Maclellan Reid A. , Greene Arin K.
Published: September 2017

Background:

Oral propranolol has become first-line intervention for problematic infantile hemangioma (IH) that is not amenable to topical or intralesional therapies. Consensus data supporting its efficacy for other vascular anomalies does not exist. The purpose of this study was to determine the frequency and causes of propranolol use for vascular lesions other than IH.

Methods:

Referrals to our Vascular Anomalies Center between 2008 and 2017 were reviewed for patients treated with propranolol at an outside institution. Patient history, photographs, imaging studies, and/or histopathology were evaluated by an interdisciplinary team to diagnose the vascular anomaly. Our center's diagnosis was compared to the referral diagnosis to categorize patients into 3 groups: Group 1 (patients were appropriately labeled with an IH); Group 2 (individuals were erroneously diagnosed with IH); and Group 3 (subjects were diagnosed with a vascular anomaly other than IH).

Results:

Two hundred thirty-six patients met inclusion criteria. Group 1 (39%; n = 91) had an IH and were treated appropriately. Group 2 (20%; n = 49) was misdiagnosed with IH and incorrectly received propranolol. Group 3 (41%; n = 96) was given propranolol to treat another vascular anomaly. Propranolol did not have efficacy for vascular anomalies other than IH.

Conclusions:

Propranolol commonly is used to treat lesions other than IH; misdiagnosis of a lesion as IH is a common cause. Propranolol should be used with caution to treat other types of vascular anomalies because patients are subjected to the risks of the drug without data supporting its efficacy.
Three-Dimensional Reconstruction of the Distribution of Neurons Contributing to Ophthalmic, Maxillary, and Mandibular Nerves in the Trigeminal Ganglion of Experimental Model
Authors: Wei Wenbin , Han Zixiang , Chen Minjie , Zhang Weijie , Chai Ying , Wang Yiwen , Zhang Wenhao
Published: September 2017

The authors introduce a new method to build a three-dimensional (3D) model of the 3 branches of the trigeminal nerve in the trigeminal ganglion of rabbit with 3 different kinds of fluorescence. Ten adult New Zealand rabbits of both sexes weighing between 2.0 and 3.0 kg were used in the experiment. Then through an operation under general anesthesia, the maxillary and mandibular nerves were exposed, and red and gold fluorescence were applied to investigate the neurons of the maxillary and mandibular nerves. Subsequently, DiI was used as a marker for the ophthalmic neuron for the other side of the same rabbit. After receiving images of the 3 branches under a fluorescence microscope, a 3D model of the 3 branches of the trigeminal nerve could be built. The authors obtained an image of the 3 branches of neurons in the trigeminal ganglion, and a 3D model of the 3 branches of the trigeminal nerve in the trigeminal ganglion was reconstructed. In the trigeminal ganglion, ophthalmic neurons were concentrated in the anteromedial section, the maxillary division in the middle, and the mandibular division posterolaterally. Overlap was observed between the ophthalmic and maxillary neurons, and also for the maxillary and mandible neurons.
The Directive Growth Approach for Nonsyndromic, Unicoronal Craniosynostosis: Patient and Clinical Outcomes
Authors: Mann Robert J. , Fahrenkopf Matthew P. , Burton Michael , Girotto John , Polley John
Published: September 2017

Deformities of the cranium in patients with nonsyndromic single-suture synostosis occur because of growth restriction at fused sutures and growth over compensation at normal sutures. Traditional surgery includes ostectomies of the synostotic suture to release these restricted areas and osteotomies to enable immediate cranial remodeling. In the process of reshaping the cranium, traditional approaches usually involve obliteration of both the normal functioning suture and the pathologic suture. The directive growth approach (DGA) is a new, simpler, more natural way to repair deformities caused by single-suture cranial synostosis. The DGA works by reversing the original deforming forces by temporarily restricting growth in areas of over compensation and forcing growth in areas of previous synostotic restriction. Most importantly, it preserves a normal functioning suture to allow for improved future cranial growth. Eighteen consecutive nonsyndromic patients with unilateral coronal synostosis were used to illustrate the efficacy of the DGA. Ten patients who underwent DGA treatment were compared with a control group of 8 patients treated with traditional frontal orbital advancement. Postoperative three-dimensional computed tomography (CT) comparison measurements were taken, including bilateral vertical and transverse orbital dimensions, lateral orbital rim to external auditory canal, and forehead measurements from the superior aspect of the orbital rim to the pituitary fossa. The traditional treatment group showed absence of the coronal sutures bilaterally on long-term CT scans. The DGA group showed normal coronal sutures on the unaffected sides. Postoperative CT measurements showed no statistical difference between the 2 techniques (P < 0.05).
Xiphoid Surface Temperature Predicts Mortality in a Murine Model of Septic Shock
Authors: Laitano Orlando , Van Steenbergen David , Mattingly Alex J. , Garcia Christian K. , Robinson Gerard P. , Murray Kevin O. , Clanton Thomas L. , Nunamaker Elizabeth A.
Published: September 2017

Sepsis continues to be a major challenge for modern medicine. Several preclinical models were developed to study sepsis and each has strengths and weaknesses. The cecal slurry (CS) method is a practical alternative because it does not require surgery, and the infection can be dosed. However, one disadvantage is that the dosage must be determined for each CS preparation using survival studies. Our aim was to refine a survival protocol for the CS model by determining a premonitory humane endpoint that would reduce animal suffering. Mice become hypothermic in sepsis; therefore, we tested whether reductions in surface temperature (Ts), measured by noninvasive infrared thermometry, could predict eventual death. We injected 154 C57BL/6J mice with CS (0.9–1.8 mg/g) and periodically monitored Ts at the xiphoid process over 5 days. We used, as predictors, combinations of temperature thresholds (29°C –31°C) and times, postinjection (18–36 h). A receiver-operator curve, sensitivity, and specificity were determined. A Distress Index value was calculated for the threshold conditions. The optimum detection threshold (highest Youden index) was found at Ts ≤ 30.5°C at 24 h (90% specific, 84% sensitive). This threshold condition reduced animal suffering by 41% while providing an accurate survival rate estimate. Using this threshold, only 13 of 154 mice would have died from sepsis; 67 would have been euthanized at 24 h, and only 7 of 154 would have been euthanized unnecessarily. In conclusion, using a humane endpoint of Ts ≤ 30.5°C at 24 h accurately predicts mortality and can effectively reduce animal suffering during CS survival protocols.
Unexpected CRISPR off-target mutation patternin vivoare not typically germline-like
Authors: Wei Zhiting , He Funan , Chuai Guohui , Ma Hanhui , Su Zhixi , Liu Qi
Published: September 2017

To the Editor

Schaefer et al.1(referred to asStudy_1) recently presented the provocative conclusion that CRISPR-Cas9 nuclease can induce many unexpected off-target mutations across the genome that arise from the sites with poor homology to the gRNA. As Wilson et al.2pointed out, however, the selection of a co-housed mouse as the control is insufficient to attribute the observed mutation differences between the CRISPR-treated mice and control mice. Therefore, the causes of these mutations need to be further investigated. In 2015, Iyer et al.3(referred to asStudy_2) used Cas9 and a pair of sgRNAs to mutate the Ar gene invivoand off-target mutations were investigated by comparison the control mice and the offspring of the modified mice. After analyzing the whole genome sequencing (WGS) of the offspring and the control mice, they claimed that off-target mutations are rare from CRISPR-Cas9 engineering. Notably, their study only focused on indel off-target mutations. We re-analyzed the WGS data of these two studies and detected both single nucleotide variants (SNVs) and indel mutations.
A cross-cultural study of sex-typicality and averageness: Correlation between frontal and lateral measures of human faces
Authors: Danel Dariusz P. , Varella Valentova Jaroslava , Sánchez Oscar R. , Leongómez Juan D. , Varella Marco A. C. , Kleisner Karel
Published: September 2017

Objectives

Facial averageness and sexual dimorphism are extensively studied attractiveness markers, which are viewed as possible indicators of biological quality. Both are complex morphological traits and both can be easily assessed from frontal and lateral projection of a human face. Interestingly, examination of mutual relations between the frontal and lateral dimensions of these markers has so far received little attention in published research.

Methods

In our cross-cultural study, we used geometric morphometric data from male and female faces from Brazil, Cameroon, Colombia, and the Czech Republic, and analysed correlations between frontal and lateral measurements of averageness and degree of maleness/femaleness, i.e. individual variation in features that characterize sexual dimorphism. We also analysed whether the association between frontal and lateral measurements differs in men and women.

Results

In general, our results showed a moderate correlation in sexually dimorphic features between lateral and frontal facial configuration in both sexes, while frontal and lateral facial averageness was moderately correlated only in women. This pattern was less consistent when individual populations were analysed separately.

Conclusions

Referring to the multiple signalling theory, we propose that especially in women, lateral/frontal correlations support a hypothesis of redundancy of information provided by the frontal and lateral dimension of a given facial attractiveness marker. The absence of a significant correlation in male facial averageness suggests that frontal and lateral averageness may convey different information about an individual.
Characterization of the Novel Mitochondrial Genome Replication Factor MiRF172 inTrypanosoma brucei
Authors: Amodeo Simona , Jakob Martin , Ochsenreiter Torsten
Published: September 2017

The unicellular parasiteTrypanosoma bruceiharbors one individual mitochondrial organelle with a singular genome the kinetoplast DNA or kDNA. The kDNA largely consists of concatenated minicircles and a few maxicircles that are also interlocked into the kDNA disc. More than 30 proteins involved in kDNA replication have been described, however several mechanistic questions are only poorly understood. Here, we describe and characterize MiRF172, a novel mitochondrial genome replication factor, which is essential for proper cell growth and kDNA maintenance. Using super-resolution microscopy, we localize MiRF172 to the antipodal sites of the kDNA. We demonstrate that depletion of MiRF172 leads to continuous loss of mini- and maxicircles during the cell division cycle. Detailed analysis suggests that MiRF172 is likely involved in the reattachment of replicated minicircles to the kDNA disc. Furthermore, we provide evidence that the localization of the replication factor MiRF172 not only depends on the kDNA itself, but also on the mitochondrial genome segregation machinery suggesting a tight interaction between the two essential entities.

Summary Statement

MiRF172 is a novel protein involved in the reattachment of replicated minicircles inTrypanosoma brucei, which requires the mitochondrial segregation machinery for proper localization.
Method for identification of condition-associated public antigen receptor sequences
Authors: Pogorelyy M.V. , Minervina A.A. , Chudakov D.M. , Mamedov I.Z. , Lebedev Y.B. , Mora T. , Walczak A.M.
Published: September 2017

Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform repertoire-wide disease association studies of antigen receptor sequences. We developed a statistical framework for associating receptors to disease from only a small cohort of patients, with no need for a control cohort. Our method successfully identifies previously validated Cytomegalovirus and type 1 diabetes responsive receptors.
A screen for combination therapies inBRAF/NRASwild type melanoma identifies nilotinib plus MEK inhibitor as a synergistic combination
Authors: Ranzani Marco , Kemper Kristel , Michaut Magali , Krijgsman Oscar , Aben Nanne , Iyer Vivek , Wong Kim , Roumeliotis Theodoros I. , Velasco-Herrera Martin Del Castillo , Nsengimana Jérémie , Turner Gemma , Thompson Nicola , Shahrabi Aida , Sjoberg Marcela , Rashid Mamunur , Speak Anneliese O. , Grinkevich Vera , Behan Fiona , Tamborero David , Iorio Francesco , van Dongen Stijn , Bignell Graham R. , Alsinet Clara , Chen Sofia , Supper Emmanuelle , Dutton-Regester Ken , Pritchard Antonia , Wong Chi , Enright Anton , Newton-Bishop Julia , McDermott Ultan , Hayward Nicholas K. , Choudhary Jyoti S. , Yusa Kosuke , Wessels Lodewyk , Garnett Mathew J. , Peeper Daniel , Adams David J.
Published: September 2017

Despite recent therapeutic advances in the management ofBRAFV600-mutant melanoma, there is still a compelling need for more effective treatments for patients who developedBRAF/NRASwild type disease. Since the activity of single targeted agents is limited by innate and acquired resistance, we performed a high-throughput drug screen using 180 drug combinations to generate over 18,000 viability curves, with the aim of identifying agents that synergise to killBRAF/NRASwild type melanoma cells. From this screen we observed strong synergy between the tyrosine kinase inhibitor nilotinib and MEK inhibitors and validated this combination in an independent cell line collection. We found that AXL expression was associated with synergy to the nilotinib/MEK inhibitor combination, and that both drugs work in concert to suppress pERK. This finding was supported by genome-wide CRISPR screening which revealed that resistance mechanisms converge on regulators of the MAPK pathway. Finally, we validated the synergy of nilotinib/trametinib combinationin vivousing patient-derived xenografts. Our results indicate that a nilotinib/MEK inhibitor combination may represent an effective therapy inBRAF/NRASwild type melanoma patients.
Global Land Use Implications of Dietary Trends: A Tragedy of the Commons
Authors: Rizvi Sarah , Pagnutti Chris , Bauch Chris T. , Anand Madhur
Published: September 2017

Global food security and agricultural land management represent two urgent and intimately related challenges that humans must face in the coming decades. Here, we quantify the changes in the global agricultural land footprint if the world were to adhere to the dietary guidelines put forth by the United States Department of Agriculture (USDA), while accounting for the land use change incurred by import/export required to meet those guidelines. We analyze data at country, continent, and global levels. USDA guidelines are viewed as an improvement on the current land-intensive diet of the average American, but despite this our results show that global adherence to USDA guidelines would require up to 1 gigahectare of additional agricultural land--roughly the size of Canada. The results also show a strong divide between Eastern and Western hemispheres. Because countries increasingly import most of their food, meeting USDA guidelines could cause a Tragedy of the Commons, where self-interested actors race to over-exploit the shared resource of global agricultural lands. National dietary guidelines and practices thus need to be coordinated internationally in order to spare our remaining natural lands, in much the same way that countries are coordinating greenhouse gas emissions.
The cytoskeleton as a smart composite material: A unified pathway linking microtubules, myosin-II filaments and integrin adhesions
Authors: Rafiq Nisha Bte Mohd , Nishimura Yukako , Plotnikov Sergey V. , Thiagarajan Visalatchi , Zhang Zhen , Natarajan Meenubharathi , Shi Shidong , Viasnoff Virgile , Jones Gareth E. , Kanchanawong Pakorn , Bershadsky Alexander D.
Published: September 2017

The interrelationship between microtubules and the actin cytoskeleton in mechanoregulation of integrin-mediated adhesions is poorly understood. Here, we show that the effects of microtubules on two major types of cell-matrix adhesions, focal adhesions and podosomes, are mediated by KANK family proteins connecting the adhesion protein talin with microtubule tips. Both total microtubule disruption and microtubule uncoupling from adhesions by manipulations with KANKs trigger a massive assembly of myosin-IIA filaments. Myosin-IIA filaments, augmenting the focal adhesions and disrupting the podosomes, are indispensable effectors in the microtubule-dependent regulation of integrin-mediated adhesions. Myosin-IIA filament assembly depends on Rho activation by the RhoGEF, GEF-H1, which is trapped by microtubules when they are connected with integrin-mediated adhesions via KANK proteins but released after their disconnection. Thus, microtubule capturing by integrin-mediated adhesions modulates the GEF-H1-dependent effect of microtubules on the myosin-IIA filaments. Subsequent actomyosin reorganization then remodels the focal adhesions and podosomes, closing the regulatory loop.
Gradual progression from sensory to task-related processing in cerebral cortex
Authors: Brincat Scott L. , Siegel Markus , von Nicolai Constantin , Miller Earl K.
Published: September 2017

Somewhere along the cortical hierarchy, behaviorally relevant information is distilled from raw sensory inputs. We examined how this transformation progresses along multiple levels of the hierarchy by comparing neural representations in visual, temporal, parietal, and frontal cortices in monkeys categorizing across three visual domains (shape, motion direction, color). Representations in visual areas MT and V4 were tightly linked to external sensory inputs. In contrast, lateral prefrontal cortex (PFC) largely represented the abstracted behavioral relevance of stimuli (task rule, motion category, color category). Intermediate-level areas—posterior inferotemporal (PIT), lateral intraparietal (LIP), and frontal eye fields (FEF)—exhibited mixed representations. While the distribution of sensory information across areas aligned well with classical functional divisions—MT carried stronger motion information, V4 and PIT carried stronger color and shape information—categorical abstraction did not, suggesting these areas may participate in different networks for stimulus-driven and cognitive functions. Paralleling these representational differences, the dimensionality of neural population activity decreased progressively from sensory to intermediate to frontal cortex. This shows how raw sensory representations are transformed into behaviorally relevant abstractions and suggests that the dimensionality of neural activity in higher cortical regions may be specific to their current task.

Significance statement

The earliest stages of processing in cerebral cortex reflect a relatively faithful copy of sensory inputs, but intelligent behavior requires abstracting behaviorally relevant concepts and categories. We examined how this transformation progresses through multiple levels of the cortical hierarchy by comparing neural representations in six cortical areas in monkeys categorizing across three visual domains. We found that categorical abstraction occurred in a gradual fashion across the cortical hierarchy and reached an apex in prefrontal cortex. Categorical coding did not respect classical models of large-scale cortical organization. The dimensionality of neural population activity was reduced in parallel with these representational changes. Our results shed light on how raw sensory inputs are transformed into behaviorally relevant abstractions.
Zwitterionic hydrogels modulate the foreign body response in a modulus-dependent manner
Authors: Jansen LE , Amer LD , Chen E Y-T , Nguyen TV , Saleh LS , Emrick TS , Liu WF , Bryant SJ , Peyton SR
Published: September 2017

Reducing the foreign body response (FBR) to implanted biomaterials will enhance theirin vivoperformance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost and ease of use. PEG hydrogels can elicit chronic inflammation upon implantation, but recent evidence has suggested that extremely hydrophilic, zwitterionic hydrogels can reduce the FBR to particles and gels. To expand on this approach, we synthesized hydrogels of co-monomers PEG and the zwitterion phosphorylcholine (PC) to quantify the combinatorial effects of modulus and hydrophilicity on the FBR. Surprisingly, hydrogels with the highest amount of zwitterionic co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% to 0 wt%), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment to these hydrogels. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.

Highlights

Modulus and zwitterion content independently modulate the foreign body response to soft hydrogels

Soft PEG hydrogels synthesized with the zwitterionic PC co-monomer are pro-inflammatory as modulus is increased

The chemical and physical properties of hydrogels influence the foreign body response via macrophage recruitment and protein adsorption
MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?
Authors: Abbas Hussein H.K. , Alhamoudi Kheloud M.H. , Evans Mark D. , Jones George D.D. , Foster Steven S.
Published: September 2017

Background

Targeted therapies are based on exploiting cancer-cell-specific genetic features or phenotypic traits to selectively kill cancer cells while leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype. Given that free nucleotide pools are particularly vulnerable to oxidation, the nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential in cancer cells. However, findings from previous MTH1 studies have been contradictory, meaning the relevance of MTH1 in cancer is still to be determined. Here we ascertained the role of MTH1 specifically in lung cancer cell maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy to improve lung cancer treatments.

Method

Using siRNA-mediated knockdown or small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1 deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non-small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We also assessed if MTH1 inhibition augments current therapies.

Results

MTH1 knockdown increased levels of oxidatively damaged DNA and DNA damage signaling alterations in all lung cancer cell lines but not normal fibroblasts, despite no detectable differences in reactive oxygen species levels between any cell lines. Furthermore, MTH1 knockdown reduced H23 cell proliferation. However, unexpectedly, it did not induce apoptosis in any cell line or enhance the effects of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly, TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only increased oxidative DNA damage levels in H23, indicating that they kill cells independently of DNA oxidation and seemingly via MTH1-distinct mechanisms.

Conclusions

MTH1 has a NSCLC-specific p53-independent role for suppressing DNA oxidation and genomic instability, though surprisingly the basis of this may not be reactive-oxygen-species-associated oxidative stress. Despite this, overall our cell viability data indicates that targeting MTH1 will likely not be an across-the-board effective NSCLC therapeutic strategy; rather it induces non-cytotoxic DNA damage that could promote cancer heterogeneity and evolution.
Non-order–disorder allotwinning of the rhenium pincer complexcis-Re[(PNPCH2-iPr)(CO)2Cl]
Authors: Glatz Mathias , Stöger Berthold , Kirchner Karl
Published: September 2017

Crystals ofcis-Re[(PNPCH2-iPr)(CO)2Cl] (1) are made up of two geometrically non-equivalent polytypes with respective symmetries ofP21/candI2/a. The structures were determined in a concurrent refinement, taking into account overlap of diffraction spots. The polytypes are composed of layers withpx121/c1 symmetry and are of the non-order–disorder (OD) type (the layer interfaces are non-equivalent). Whereas the molecules of (1) differ in both polytypes, the Re atoms are located at nearly identical positions.
Using invariom modelling to distinguish correct and incorrect central atoms in `duplicate structures' with neighbouring 3delements
Authors: Wandtke Claudia M. , Weil Matthias , Simpson Jim , Dittrich Birger
Published: September 2017

Modelling coordination compounds has been shown to be feasible using the invariom method; for the best fit to a given set of diffraction data, additional steps other than using lookup tables of scattering factors need to be carried out. Here such procedures are applied to a number of `duplicate structures', where structures of two or more supposedly different coordination complexes with identical ligand environments, but with different 3dmetal ions, were published. However, only one metal atom can be plausibly correct in these structures, and other spectroscopic data are unavailable. Using aspherical scattering factors, a structure can be identified as correct from the deposited Bragg intensities alone and modelling only the ligand environment often suffices to make this distinction. This is not possible in classical refinements using the independent atom model. Quantum-chemical computations of the better model obtained after aspherical-atom refinement further confirm the assignment of the element in the respective figures of merit.
Multidimensional structural variation in the cyanotrichite family of merotypes: camerolaite-3b-F\bar 1
Authors: Mills Stuart J. , Christy Andrew G. , Favreau Georges , Galea-Clolus Valérie
Published: September 2017

A new superstructure of the mineral camerolaite, Cu6Al3(OH)18(H2O)2[Sb(OH)6](SO4), has been refined in space group P\bar 1 with unit-cell parameters aP
= 7.7660 (16), bP
= 8.759 (4), cP
= 11.306 (2) Å, α
P
= 108.67 (4), β
P
= 83.41 (3), γ
P
= 126.64 (2)°, V = 581.6 (3) Å3 and Z = 1, with R
1 = 0.0951 (all data). This is the first refined example of a cyanotrichite-group mineral in which long-range order of interlayer anions produces a superstructure along b, although diffuse scattering has previously been reported that corresponds to short-range order. Though the structure shares with other members of the cyanotrichite group a structural unit in which ribbons of edge-sharing Cu and Al octahedra form layers || (001), the superstructure arises from regular alternation of [SO4] and [Sb(OH)6] polyhedra along rods that lie between the layers, and phase coupling between rods that maximizes the distance between [SO4] groups of adjacent rods along a and c directions. This arrangement suggests an alternative nearly orthogonal choice of unit cell in F\bar 1 with parameters aF
= 12.473 (26), bF
= 8.759 (4), cF
= 21.476 (7) Å, α
F
= 85.94 (4), β
F
= 95.91 (5), γ
F
= 92.34 (9)°, which is recommended for comparing this structural variety of camerolaite with other members of the group.
Empirical Lewis acid strengths for 135 cations bonded to oxygen
Authors: Gagné Olivier Charles , Hawthorne Frank Christopher
Published: September 2017

New and updated Lewis acid strengths are listed for 135 cations bonded to oxygen for use with published Lewis base strengths. A strong correlation between Lewis acid strength and ionization energy is shown, and correlation with electronegativity is confirmed.
Non-covalent interactions in the multicomponent crystal of 1-aminocyclopentane carboxylic acid, oxalic acid and water: a crystallographic and a theoretical approach
Authors: Mora Asiloé J. , Belandria Lusbely M. , Delgado Gerzon E. , Seijas Luis E. , Lunar Angel , Almeida Rafael
Published: September 2017

Single-crystal X-ray diffraction and quantum mechanical theories were used to examine in detail the subtle nature of non-covalent interactions in the [2:1:1] multicomponent crystal of 1,1-aminocyclopentanecarboxylic acid:oxalic acid:water. The crystal, which is a hydrate salt of the amino acid with the hydrogen-oxalate ion, also contains the zwitterion of the amino acid in equal proportions. It was found that a dimeric cation [Acc5(Z)...Acc5(C)]+bonded by an O—H...O hydrogen bond exists due to a charge transfer between acid and carboxylate groups. The three-dimensional crystal is built by blocks stacked along the [101] direction by dispersion interactions, with each block growing along two directions: a hydrogen oxalate HOX−...HOX−catameric supramolecular structure along the [010] direction; and double ...HOX−—W—[Acc5(Z)... Acc5(C)]+... chains related by inversion centers along the [1 0 {\bar 1}] direction. A PBE-DFT optimization, under periodic boundary conditions, was carried out. The fully optimized structure obtained was used to extract the coordinates to calculate the stabilization energy between the dimers under the crystal field, employing the M062X/aug-cc-pVTZ level of theory. The non-covalent index isosurfaces employed here allow the visualization of where the hydrogen bond and dispersion interactions contribute within the crystal. The crystal atomic arrangements are analyzed by employing the Atoms in Molecules and electron localization function theories. Within this context, the presence of density bond critical points is employed as a criterion for proving the existence of the hydrogen bond and it was found that these results agree with those rendered by the crystallographic geometrical analysis, with only three exceptions, for which bond critical points were not found.
Predicting displacements of octahedral cations in ferroelectric perovskites using machine learning
Authors: Balachandran Prasanna V. , Shearman Toby , Theiler James , Lookman Turab
Published: September 2017

In ferroelectric perovskites, displacements of cations from the high-symmetry lattice positions in the paraelectric phase break the spatial inversion symmetry. Furthermore, the relative magnitude of ionic displacements correlate strongly with ferroelectric properties such as the Curie temperature. As a result, there is interest in predicting the relative displacements of cations prior to experiments. Here, machine learning is used to predict the average displacement of octahedral cations from its high-symmetry position in ferroelectric perovskites. Published octahedral cation displacements data from density functional theory (DFT) calculations are used to train machine learning models, where each cation is represented by features such as Pauling electronegativity, Martynov–Batsanov electronegativity and the ratio of valence electron number to nominal charge. Average displacements for ten new octahedral cations for which DFT data do not exist are predicted. Predictions are validated by comparing them with new DFT calculations and existing experimental data. The outcome of this work has implications in the design and discovery of novel ferroelectric perovskites.
Crystal structure offac-tricarbonylchloridobis(4-hydroxypyridine)rhenium(I)–pyridin-4(1H)-one (1/1)
Authors: Argibay-Otero Saray , Carballo Rosa , Vázquez-López Ezequiel M.
Published: September 2017

The asymmetric unit of the title compound, [ReCl(C5H5NO)2(CO)3]·C5H5NO, contains one molecule of the complexfac-[ReCl(4-pyOH)2(CO)3] (where 4-pyOH represents 4-hydroxypyridine) and one molecule of pyridin-4(1H)-one (4-HpyO). In the molecule of the complex, the Re atom is coordinated to two N atoms of the two 4-pyOH ligands, three carbonyl C atoms, in a facial configuration, and the Cl atom. The resulting geometry is slightly distorted octahedral. In the crystal structure, both fragments are associated by hydrogen bonds; two 4-HpyO molecules bridge between two molecules of the complex using the O=C group as acceptor for two different HO– groups of coordinated 4-pyOH from two neighbouring metal complexes. The resulting square arrangements are extented into infinite chains by hydrogen bonds involving the N—H groups of the 4-HpyO molecule and the chloride ligands. The chains are further stabilized by π-stacking interactions.
(Acetonitrile-κN)aqua[N,N′-bis(pyridin-2-ylmethyl)ethane-1,2-diamine-κ4N,N′,N′′,N′′′]zinc(II) perchlorate
Authors: Okeke Ugochukwu , Gultneh Yilma , Butcher Ray J.
Published: September 2017

The structure of the title compound, [Zn(C14H18N4)(C2H3N)(H2O)](ClO4)2, contains a six-coordinate cation consisting of the tetradentate bispicen ligand, coordinated water, and coordinated acetonitrile, with the latter two ligands adopting acisconfiguration. There are two formula units in the asymmetric unit. Both cations show almost identical structural features with the bispicen ligand adopting the more commoncis-β conformation. One of the four perchlorate anions is disordered over two positions, with occupancies of 0.9090 (15) and 0.0910 (15). There is extensive inter-ionic hydrogen bonding between the perchlorate anions and O—H and N—H groups in the cations, including a bifurcated hydrogen bond between an N—H group and two O atoms of one perchlorate anion. As a result of this extended hydrogen-bond network, the ions are linked into a complex three-dimensional array.
Supramolecular patterns and Hirshfeld surface analysis in the crystal structure of bis(2-amino-4-methoxy-6-methylpyrimidinium) isophthalate
Authors: Jeevaraj Muthaiah , Sivajeyanthi Palaniyappan , Edison Bellarmin , Thanigaimani Kaliyaperumal , Balasubramani Kasthuri , Razak Ibrahim Abdul
Published: September 2017

In the title molecular salt, 2C6H10N3O+·C8H4O42−, the N atom of each of the two 2-amino-4-methoxy-6-methylpyrimidine molecules lying between the amine and methyl groups has been protonated. The dihedral angles between the pyrimidine rings of the cations and the benzene ring of the succinate dianion are 5.04 (8) and 7.95 (8)°. Each of the cations is linked to the anion through a pair of N—H...O(carboxylate) hydrogen bonds, forming cyclicR22(8) ring motifs which are then linked through inversion-related N—H...O hydrogen bonds, giving a centralR24(8) motif. Peripheral amine N—H...O hydrogen-bonding interactions on either side of the succinate anion, also through centrosymmetricR22(8) extensions, form one-dimensional ribbons extending along [211]. The crystal structure also features π–π stacking interactions between the aromatic rings of the pyrimidine cations [minimum ring centroid separation = 3.6337 (9) Å]. The intermolecular interactions were also investigated using Hirshfeld surface studies and two-dimensional fingerprint images.
Towards a compact and precise sample holder for macromolecular crystallography
Authors: Papp Gergely , Rossi Christopher , Janocha Robert , Sorez Clement , Lopez-Marrero Marcos , Astruc Anthony , McCarthy Andrew , Belrhali Hassan , Bowler Matthew W. , Cipriani Florent
Published: September 2017

Most of the sample holders currently used in macromolecular crystallography offer limited storage density and poor initial crystal-positioning precision upon mounting on a goniometer. This has now become a limiting factor at high-throughput beamlines, where data collection can be performed in a matter of seconds. Furthermore, this lack of precision limits the potential benefits emerging from automated harvesting systems that could provide crystal-position information which would further enhance alignment at beamlines. This situation provided the motivation for the development of a compact and precise sample holder with corresponding pucks, handling tools and robotic transfer protocols. The development process included four main phases: design, prototype manufacture, testing with a robotic sample changer and validation under real conditions on a beamline. Two sample-holder designs are proposed: NewPin and miniSPINE. They share the same robot gripper and allow the storage of 36 sample holders in uni-puck footprint-style pucks, which represents 252 samples in a dry-shipping dewar commonly used in the field. The pucks are identified with human- and machine-readable codes, as well as with radio-frequency identification (RFID) tags. NewPin offers a crystal-repositioning precision of up to 10 µm but requires a specific goniometer socket. The storage density could reach 64 samples using a special puck designed for fully robotic handling. miniSPINE is less precise but uses a goniometer mount compatible with the current SPINE standard. miniSPINE is proposed for the first implementation of the new standard, since it is easier to integrate at beamlines. An upgraded version of the SPINE sample holder with a corresponding puck named SPINEplus is also proposed in order to offer a homogenous and interoperable system. The project involved several European synchrotrons and industrial companies in the fields of consumables and sample-changer robotics. Manual handling of miniSPINE was tested at different institutes using evaluation kits, and pilot beamlines are being equipped with compatible robotics for large-scale evaluation. A companion paper describes a new sample changer FlexED8 (Pappet al., 2017,Acta Cryst., D73, 841–851).
2-[Tris(pyridin-2-yl)methyl]pyridiniumtrans-bis(acetonitrile)tetrachloridoruthenate(III) acetonitrile monosolvate
Authors: Matsumoto Kouzou , Kannami Masaki , Oda Masaji
Published: September 2017

The asymmetric unit of the title compound, [(C5H4N)3C(C5H5N)][RuCl4(CH3CN)2]·CH3CN, contains one 2-[tris(pyridin-2-yl)methyl]pyridinium cation, onetrans-bis(acetonitrile)tetrachloridoruthenate(III) anion and one acetonitrile solvent molecule. The RuIIIion is coordinated by four Cl−anions in the equatorial plane and by two acetonitrile ligands in the axial positions, forming a distorted octahedral geometry. The cation, the monoprotonated species of tetrakis(pyridin-2-yl)methane, forms an intramolecular N—H...N hydrogen bond between the pyridinium ring and one of the pyridine rings. The complex anions are linked to each otherviaC—H...Cl hydrogen bonds, forming an undulating sheet parallel to theacplane. A C—H...N hydrogen bond between the cation and the anion is also observed. The solvate acetonitrile molecule forms C—H...N and C—H...Cl hydrogen bonds, respectively, with the cation and the anion.