bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-exome sequencing of individuals from an isolated population implicates rare risk variants in bipolar disorder
Authors: Lescai F , Als T D , Li Q , Nyegaard M , Andorsdottir G , Biskopstø M , Hedemand A , Fiorentino A , O'Brien N , Jarram A , Liang J , Grove J , Pallesen J , Eickhardt E , Mattheisen M , Bolund L , Demontis D , Wang A G , McQuillin A , Mors O , Wang J , Børglum A D 
Published: February 2017

AbstractBipolar disorder affects about 1% of the world’s population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance. Following this approach, we investigated 28 bipolar cases and 214 controls from the Faroe Islands by whole exome sequencing, and the results were followed-up in a British sample of 2025 cases and 1358 controls. Seventeen variants in 16 genes in the single-variant analysis, and 3 genes in the gene-based statistics surpassed exome-wide significance in the discovery phase. The discovery findings were supported by enrichment analysis of common variants from genome-wide association studies (GWAS) data and interrogation of protein–protein interaction networks. The replication in the British sample confirmed the association with NOS1 (missense variant rs79487279) and NCL (gene-based test). A number of variants from the discovery set were not present in the replication sample, including a novel PITPNM2 missense variant, which is located in a highly significant schizophrenia GWAS locus. Likewise, PIK3C2A identified in the gene-based analysis is located in a combined bipolar and schizophrenia GWAS locus. Our results show support both for existing findings in the literature, as well as for new risk genes, and identify rare variants that might provide additional information on the underlying biology of bipolar disorder.
Pulmonary Embolism and Atrial Fibrillation: Two Sides of the Same Coin? A Systematic Review
Authors: Abou Ziki Maen , Lip Gregory , Bikdeli Behnood 
Published: February 2017

AbstractPulmonary embolism (PE) is a common, potentially fatal thrombotic disease. Atrial fibrillation (AF), the most common arrhythmia, may also lead to thromboembolic complications. Although initially appearing as distinct entities, PE and AF may coexist. The direction and extent of this association has not been well characterized. We performed a search of PubMed, Scopus, and the Cochrane Database of Systematic Reviews for publications that reported coexisting AF in patients with PE, or vice versa, to provide a systematic overview of pathophysiological and epidemiological aspects of this association (last search: October 13, 2016). We screened 650 articles following the PubMed search, and 697 through Scopus. PE and AF share many common risk factors, including old age, obesity, heart failure, and inflammatory states. In addition, PE may lead to AF through right-sided pressure overload or inflammatory cytokines. AF, in turn, might lead to right atrial appendage clot formation and thereby PE. Epidemiological studies indicate that AF can be seen as a presenting sign, during the early phase, or later in the course of recovery from PE. Patients with AF are also at increased risk of developing PE, a risk that correlates with the CHA2DS2-VASc score. For the choice of antithrombotic therapy, PE-related factors (provoked or unproved, active cancer, and prior recurrence) and AF-related factors (CHA2DS2-VASc score), risk of bleeding, and patient preferences should be considered. In conclusion, PE and AF may coexist, with an understudied bidirectional association. Prognostication and choice of antithrombotic therapy in patients with both PE and AF might be different compared with those who present with only one of the two and warrants further investigation.
Induced Membrane Technique Combined with a Free Vascularized Fibula Flap for the Management of a Severe Acute Femoral Bone Loss: A Case Report and Literature Review
Authors: Qiu Xu-sheng , Zheng Xin , Shi Hong-fei , Xu Guang-yue , Chen Yi-xin 
Published: February 2017

Background Management of segmental bone defects is a challenge for orthopedic surgeons. The most commonly used methods are the free vascularized bone transfer, bone transport, and induced membrane technique. However, none of these methods is fully suitable for some cases.
Case Report A 41-year-old woman was presented with a Gustilo IIIA left distal femoral fracture (AO 32-C and 33-C) with bone loss. The length of femoral bone loss was 15 cm (12 cm medially and 18 cm laterally). After thorough debridement, the intercondylar fracture was fixed with K-wires, and an external fixator bridged the knee joint. The bone defect was filled with antibiotic cement spacer. After 2 months, the external fixator was removed; the femur was fixed by internal fixation. The induced membrane was opened and the antibiotic cement removed. A free vascularized fibular graft of 18 cm was transferred and the residual bony defect was filled with morcellized cancellous autologous bone graft. At 6 months postoperatively, the graft appeared completely integrated at X-ray and the patient could walk without brace at 11 months postoperatively.
Conclusion The distal femur is a large-caliber bone and is under severe stress during weight bearing. When only the induced membrane technique is used, the autologous bone graft seems not enough for the present case. On the other hand, single free vascularized fibular graft also could not provide sufficient strength to allow weight bearing despite significant hypertrophy. Therefore, the induced membrane technique combined with free vascularized fibular graft used in the present case may be an alternative.
Patellofemoral Osteochondral Allografts: Can We Improve the Matching Process?
Authors: Determann Jason , Fleischli James , D'Alessandro Donald , Piasecki Dana 
Published: February 2017

AbstractAn important consideration for the successful use of fresh osteochondral allografts for the patellofemoral joint is selection of appropriately sized donor allografts. This is particularly challenging for matching grafts to the patella because of the substantial variability in articular contour that exists. At present, selection of donor patellae is based only on the width of the proximal tibia, with no established means of quantifying basic patellar size, facet configuration, or articular contour. We hypothesized that using a combination of standard radiographic measurements to generate an accurate profile of the recipients native patella would result in a more accurate donor graft. We radiographically measured seven dimensions of 30 fresh frozen cadaveric patellar specimens, and then, following dissection, accurate ex vivo measurements of patellar morphology were taken. Measurements obtained on the merchant view included total width, width of the medial and lateral facets, central ridge height (CRH) and location, as well as the patellar angle. The lateral view was obtained to measure the articular length. Ex vivo measurements were subsequently taken using a standard ruler, caliper, and goniometer following removal of all soft tissue attachments. To simulate a larger population of knees, we then used bootstrapping methods with simple random selection and replacement to generate a sample of measurements from 4,500 knees. In the bootstrapping process, measurements from one random specimen are added to the “population” at each iteration until the target sample size is reached. Data from this bootstrapped population were subsequently used to calculate statistically significant radiographic predictors of each ex vivo measurement, using a multivariate regression model with backward elimination. These predictors were then used to compare the calculated values to the actual ex vivo measurements for each dimension in our original 30 specimens' sample. Overall, these formulas were very successful in predicting ex vivo measurements. While further validation is warranted, we propose that these formulas can be utilized to select a more accurate donor.
Essential role of immobilized chemokine CXCL12 in the regulation of the humoral immune response
Authors: Barinov Aleksandr , Luo Lingjie , Gasse Pamela , Meas-Yedid Vannary , Donnadieu Emmanuel , Arenzana-Seisdedos Fernando , Vieira Paulo 
Published: February 2017

Significance
High-affinity antibodies confer protective immunity against external antigens and are generated during germinal center (GC) reactions when B-lymphocytes, migrating between the dark zone (DZ) and light zone (LZ) of the GC, accumulate mutations in their immunoglobulin genes and are selected for high affinity to antigen. B cells move between DZ and LZ, guided by gradients of CXCL12 and CXCL13 chemokines. We show that immobilized CXCL12 is essential for the correct positioning of B-lymphocytes during the GC reaction and for the production of high-affinity antibodies. Our results provide fundamental insights into the role of surface-immobilized chemokines, molecules that regulate the migration of many cell types, thus controlling homeostasis in multiple tissues.
Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody
Authors: Frescas David , Roux Christelle M. , Aygun-Sunar Semra , Gleiberman Anatoli S. , Krasnov Peter , Kurnasov Oleg V. , Strom Evguenia , Virtuoso Lauren P. , Wrobel Michelle , Osterman Andrei L. , Antoch Marina P. , Mett Vadim , Chernova Olga B. , Gudkov Andrei V. 
Published: February 2017

SignificanceUnderstanding the mechanisms underlying the development of senescence and the consequences related to the accumulation of senescent cells is a major focus of ongoing research. Our report shows that senescent cells express a form of oxidized vimentin on their cell surface and that oxidized vimentin is secreted into the blood of senescence-prone senescence-accelerated mouse prone 8 mice. Given the growing evidence that oxidized proteins are involved in the development of human diseases, the detection and monitoring of secreted proteins like malondialdehyde-modified vimentin is certain to become a vital and noninvasive biomarker for studying senescence and monitoring age-related illnesses.
Investigations of human myosin VI targeting using optogenetically controlled cargo loading
Authors: French Alexander R. , Sosnick Tobin R. , Rock Ronald S. 
Published: February 2017

Significance
Myosins are a broad class of motor proteins that generate force on actin filaments and fulfill contractile, transport, and anchoring roles. Myosin VI, the only myosin to walk toward the pointed end of actin filaments, is implicated in cancer metastasis and deafness. Intriguingly, myosin VI may play both transport and anchoring roles, depending on where it is activated in the cell. Here we develop an optogenetic tool for studying myosin VI activation with high spatial and temporal resolution. Our approach photoactivates unmodified myosin VI through its native cargo pathway, enabling investigation of motor function and activation partners with minimal perturbation. This approach allows us to detect how and where myosin VI integrates multiple protein and second messenger signals to activate.
Periodic assembly of nanoparticle arrays in disclinations of cholesteric liquid crystals
Authors: Li Yunfeng , Prince Elisabeth , Cho Sangho , Salari Alinaghi , Mosaddeghian Golestani Youssef , Lavrentovich Oleg D. , Kumacheva Eugenia 
Published: February 2017

SignificanceLinear defects-disclinations in thermotropic liquid crystals are known to serve as templates for self-assembly of nanoparticles and molecules into continuous thread-like structures. Here, we show that disclinations in lyotropic cholesteric liquid crystals can act as templates for nanoparticle dispersions, producing both continuous and discontinuous morphologies, with discrete beads of the dispersion periodically organized along the disclination axis. The beading effect is rooted in the anisotropic properties of the cholesteric phase. The observed mode of assembly expands the design spectrum of architectures of soft materials. The lyotropic nature of the liquid crystal formed by an aqueous suspension of cellulose nanocrystals broadens the range of materials used for the self-assembly of periodical structures.
Safety in unpredictable complex systems – a framework for the analysis of safety derived from the nuclear power industry
Authors: Webster Craig S. 
Published: February 2017

Abstract
The increasing complexity and power of our technologies compels us to find new ways in which to conceptualise, understand and maintain their safety in the long term. Some complex technological industries have performed better than others in terms of applying sustained and systematic approaches to the maintenance of safety. The United States nuclear power industry can be seen as an ideal test-bed for the development of safety initiatives, being responsible for the control of potentially unpredictable technology that involves extraordinary forces and costs. This paper describes and formalises a framework for better understanding the safety of complex socio-technological systems, based on key events in the development of safety in the United States nuclear power industry. The framework comprises two components: (1) a state-space approach for better conceptualising system failures, the benefits of incident reporting and remedial safety initiatives; and (2) a set of milestones that can be used to assess the development of safety in socio-technological industries. Healthcare and the United States nuclear power industry both represent complex socio-technological systems with similar technical characteristics. However, safety strategies in healthcare have not kept pace with the increasing complexity of clinical practice, and there have been international calls for improvements in patient safety. The framework is applied to the analysis of safety in healthcare, demonstrating its utility as an alternative safety analogy in healthcare. Use of the framework indicates substantial scope for improvements in healthcare safety through major evidence-based system redesign. By lowering the threshold for the reporting of incident data to include accident precursors, it is possible to identify problem areas before patient harm occurs.
Multiple Perspectives of Symptoms and Suffering at End of Life in the NICU
Authors: Shultz Emily L. , Switala Mary , Winning Adrien M. , Keim Madelaine C. , Baughcum Amy E. , Gerhardt Cynthia A. , Fortney Christine A. 
Published: February 2017

Background:
Despite technological advances in the neonatal intensive care unit, not all infants survive. Limited research has focused on infants' symptoms and suffering at end of life (EOL) from multiple perspectives.

Purpose:
To compare retrospective parent report and electronic medical record (EMR) documentation of symptoms and to examine associations with parent perceptions of infants suffering at EOL.

Methods/Search Strategy:
Bereaved parents of 40 infants (40 mothers and 27 fathers) retrospectively reported on their perceptions of infant symptoms and suffering during the last week of life. EMRs were also reviewed.

Findings/Results:
Parents were asked about their observations of 23 symptoms. Within the 27 parental dyads, mothers reported 6.15 symptoms (standard deviation = 3.75), which was not significantly different from fathers' report of 5.67 symptoms (standard deviation = 5.11). Respiratory distress, agitation, and pain were most common according to mothers and EMR, whereas respiratory distress, agitation, and lethargy were most common according to fathers. Few differences were found between mothers, fathers, and EMRs. However, missing data (range: 0%-20%) indicated that some parents had challenges assessing symptoms. Parents reported that the worst symptom was respiratory distress. In addition, parents reported moderate infant suffering, which was correlated with the total number of symptoms.

Implications for Practice:
Parents demonstrate awareness of their infant's symptoms at EOL, and these observations should be valued as they closely parallel EMR documentation. However, some parents did have difficulty reporting symptoms, highlighting the importance of education.

Implications for Research:
Future larger sample research should prospectively examine parent perceptions of infant symptom burden, suffering, and associations with other infant and parent outcomes (eg, decision making and grief).
Low-Grade Neuroendocrine Carcinoma of the Skin (Primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review
Authors: Goto Keisuke , Anan Takashi , Nakatsuka Takashi , Kaku Yo , Sakurai Takaki , Fukumoto Takaya , Kimura Tetsunori , Shibata Arihiro 
Published: February 2017

Abstract:There is scarcity of information on primary cutaneous low-grade neoplasms commonly known as carcinoid tumors, owing to their rarity. The authors present 3 cases that were named “low-grade neuroendocrine carcinoma of the skin” (LGNECS). These occurred in the dermis and subcutis of the anterior chest or the inguinal region in the elderly. Histologically, the tumors showed infiltrating proliferation of nests of various sizes, with low-grade neuroendocrine cytologic features but without mucin production. All cases exhibited varying degrees of intraductal tumor components. On immunohistochemical examination, these tumors expressed estrogen receptor alpha, progesterone receptor, androgen receptor, gross cystic disease fluid protein 15, mammaglobin, and GATA3 as well as neuroendocrine markers. Although a literature review revealed 8 additional possible cases with no evidence of other diseases, it was difficult to determine if these were true cases of LGNECS, because of the limited information available. Based on its characteristic histologic features and immunoprofile, it can be proposed designating LGNECS as a distinct entity among cutaneous neuroendocrine tumors. Otherwise, such tumors could be misdiagnosed as mammary carcinomas (particularly when involving the skin of the breast) or as metastatic visceral neuroendocrine tumors of the skin.
Lipophagic Panniculitis of Childhood: A Case Report and Comprehensive Review of the Literature
Authors: Levy Jack , Burnett Mark E. , Magro Cynthia M. 
Published: February 2017

Abstract:
Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis.
Cutaneous Apocrine Carcinoma With an In Situ Component and Histiocytoid and Signet-Ring Cells
Authors: Berdugo Jérémie , Dumont-Mackay Vincent , Brissy-Lachery Sophie , Leclerc Yves E. , Doyon Josée , Mitchell Andrew , Petrella Tony , Désy Delphine 
Published: February 2017

Abstract:
We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation.
Factitious Dermatitis Due to Thermal Burn With Histologic Features Simulating Fixed Drug Eruption
Authors: Persad Leah , Salim Sadia , Motaparthi Kiran 
Published: February 2017

Abstract:
Factitious dermatitis (FD) (dermatitis artefacta) is rare and often difficult to diagnose because of conflicting history and nonspecific clinical and histologic findings. It can present with varied clinical features including geometric ulcers, erosions, and less commonly bullae secondary to external trauma from chemicals, electric burns, heat, and suction. Herein, we describe a case of bullous FD due to thermal burn with histologic features demonstrating overlap with fixed drug eruption. Histopathology demonstrated a subepidermal blister with epidermal necrosis along with pigment incontinence and dermal eosinophils and neutrophils. Although these features, and the clinician's impression, were suggestive of fixed drug eruption, several morphologic findings allowed accurate diagnosis of FD: sharp demarcation of necrotic keratinocytes from adjacent uninvolved epidermis, elongated keratinocytes reminiscent of thermal or electrical artifact, and multinucleated keratinocytes. Although FD is often considered a diagnosis of exclusion, these clues may help dermatopathologists distinguish this entity from inflammatory dermatoses.
Liguzinediol Enhances the Inotropic Effect of Rat Hearts via Inhibition of Protein Phosphatase (PP1 and PP2A) Activities
Authors: Li Sha , Huang Huili , Zhang Mengdan , Wang Wei , Xue Shuyin , Gao Ying , Xie Ming , Chen Kesu , Liu Fuming , Chen Long 
Published: February 2017

Abstract:
It has been demonstrated that liguzinediol (2,5-dihydroxymethyl-3,6-dimethylpyrazine, LZDO), a derivative of ligustrazine from Ligusticum wallichii Franch, exerts positive inotropy in isolated rat heart mediated by the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). Here, we further explore the underlying mechanism of the positive inotropic effect of LZDO in rat hearts. In vivo and ex vivo rat heart experiments, biochemistry, and Western blot techniques were used to analyze the rat heart contractility, and SERCA2a activity, phospholamban (PLB) phosphorylation, and protein phosphatase (PP1 and PP2A) activities in rat left ventricular myocytes, respectively. LZDO (20 mg/kg) significantly increased the inotropy of rat heart in vivo. In isolated rat heart experiments, LZDO (100 μM) restored the decreased inotropy induced by caffeine (0.5 mM); however, calyculin A (4 nM), an inhibitor of PP1 and PP2A, eliminated the inotropic effect of LZDO (100 μM). Moreover, LZDO (1, 10, and 100 μM) significantly enhanced SERCA2a activity and increased the levels of phosphorylated PLB on both serine-16 (Ser-16) and threonine-17 (Thr-17). In addition, LZDO (100 μM) significantly inhibited the activities of PP1 and PP2A. The positive inotropic effects of LZDO on in vivo and ex vivo rat hearts seem to be mediated through inhibition of PP1/PP2A, which may suppress dephosphorylated PLB and enhance SERCA2a activity. LZDO may prove effective in treating heart failure in clinical settings based on its unique biological mechanism.