bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and Immunological Assays of F VIII in 133 Haemophiliacs - Characterization of a Subgroup of Patients with Mild Haemophilia A and Discrepancy in 1- and 2-Stage Assays
Authors: Parquet-Gernez Armelle , Mazurier Claudine , Goudemand Maurice 
Published: May 2018

SummaryA systematic study of the levels of FVIII antigen and activity was done in 133 haemophiliacs. No measurable antigen was demonstrated in the 60 severe haemophiliacs, with the exception of 3 patients with levels ranging between 1.5 and 4.5 U/dl, which corresponded to a dramatic FVIII deficiency. The situation was more complex with the 73 moderate and mild haemophiliacs: 39 of them (53.4%) had a partial, concordant deficiency of both the antigen and the procoagulant activity (1- and 2-stage methods), likely corresponding to a decrease in the synthesis of normal FVIII. The conclusion for the other 34 patients, was a qualitative abnormality of FVIII, the levels of antigen in comparison with the procoagulant activity (1-stage method) appearing to be either very reduced (n = 6) or even nil (n = 8), or on the contrary very much higher (n = 20) or normal. For 11 patients in this last category, we found a clear discrepancy between the procoagulant activity levels obtained with the 2 different techniques, the 1-stage levels being higher than the 2-stage levels. This discrepancy which was stable with restudy on multiple occasions and found in different members of the same families was remedied when vWF was absent in one-stage assay. This suggests that we have identified a variant of haemophilia A with an inherited abnormality of FVIII characterized by an in vitro vWF-dependent expression of procoagulant activity.
ADP Plays a Key Role in Thrombogenesis in Rats
Authors: Maffrand J P , Bernat A , Delebassée D , Defreyn G , Cazenave J P , Gordon J L 
Published: May 2018

SummaryThe relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency. Taken together, the results obtained with the drugs and with the fawn-hooded rats support the concept that ADP plays a key role in thrombogenesis in rats.
Congenital Deficiency of Plasminogen and Its Relationship to Venous Thrombosis
Authors: Hach-Wunderle V , Scharrer I , Lottenberg R 
Published: May 2018

SummaryIn a patient with deep venous thrombosis, plasma concentrations of coagulant and inhibitor proteins were normal except for moderate deficiency of plasminogen. Family studies revealed a similar deficiency in the mother and sister of the propositus. Evaluation of purified plasminogen demonstrated that it functioned normally. The patient represents our only example of plasminogen deficiency in 435 German individuals evaluated with a history of thromboembolism.
Estabilización dinámica radiocubital distal para el tratamiento de la rotura del complejo fibrocartílago triangular asociada a fractura de extremidad distal de radio – una nueva técnica quirúrgica
Authors: Pajares Cabanillas Samuel , Catalán Natalia , Crespo Emilio 
Published: May 2018

ResumenLa inestabilidad radiocubital distal (RCD) secundaria a rotura del Complejo fibrocartílago triangular (FCT), producida en fracturas del radio distal es una de las complicaciones más frecuentes y de más difícil manejo en nuestra especialidad. La recuperación funcional precoz de la síntesis del radio, exige movilización temprana y en consecuencia mala cicatrización del FCT. Por otro lado, el correcto tratamiento de esa rotura, independientemente del tratamiento realizado (conservador, reparación abierta o artroscópica), obliga a una inmovilización de la muñeca y codo por un periodo no inferior a 6 semanas. Ese hecho puede comprometer el resultado funcional tanto de la síntesis del radio, como de la pronosupinación. Se describe aquí, la primera técnica quirúrgica en la literatura que permite una correcta cicatrización del FCT, al mismo tiempo que se inicia la movilización a la primera semana del postoperatorio, tanto de la articulación radiocarpiana, como de la RCD. Se trata de una cirugía a realizar inmediatamente después de la síntesis del radio, de técnica sencilla y de escasa morbilidad, que consigue estabilizar la articulación RCD de una forma dinámica, de manera que el sentido del giro donde se reproduce la inestabilidad queda restringido, estabilizando el movimiento de traslación dorsopalmar y la apertura articular.
Reducing Alarm Fatigue in Two Neonatal Intensive Care Units through a Quality Improvement Collaboration
Authors: Hagadorn James , Sink David , Johnson Kendall 
Published: May 2018

Objective To reduce nonactionable oximeter alarms by 80% without increasing time infants were hypoxemic (oxygen saturation [SpO2] ≤ 80%) or hyperoxemic (SpO2 > 95% while on supplemental oxygen).
Study Design In 2015, a multidisciplinary team at Connecticut Children's Medical Center initiated a quality improvement project to reduce nonactionable oximeter alarms in two referral neonatal intensive care units (NICUs). Changes made through improvement cycles included reduction of the low oximeter alarm limit for specific populations, increased low alarm delay, development of postmenstrual age-based alarm profiles, and updated bedside visual reminders. Manual alarm tallies and electronic SpO2 data were collected throughout the project.
Results Alarm tallies were collected for 158 patient care hours with SpO2 data available for 138 of those hours. Mean number of total nonactionable alarms per patient per hour decreased from 9 to 2 (78% decrease) and the mean number of nonactionable low alarms per patient per hour decreased from 5 to 1 (80% decrease). No change was noted in the balancing measures of percentage time with SpO2 ≤ 80% (mean 4.3%) or SpO2 > 95% (mean 23.7%).
Conclusion Through small changes in oximeter alarm settings, including revision of alarm limits, alarm delays, and age-specific alarm profiles, our NICUs significantly reduced nonactionable alarms without increasing hypoxemia.
Postoperative Complications and Reoperation Rates Following Open Reduction and Internal Fixation of Ankle Fracture
Authors: Macera Armando , Carulli Christian , Sirleo Luigi , Innocenti Massimo 
Published: May 2018

Purpose The purpose of this study was to determinate the overall postoperative complication and reoperation rates related to open reduction and internal fixation (ORIF) of ankle fractures.
Methods All patients who had undergone an ankle fracture operation at our institution from January 2005 through December 2013 were identified by querying the hospital surgical procedure database for diagnoses codes. Medical records, surgical procedure, and outpatient control reports were reviewed to collect pre-, intra-, and postoperative details. All data obtained were retrospectively analyzed by the authors to evaluate the postoperative complications and the type of further surgical treatment required to treat them.
Results A total of 378 consecutive patients were included in the study. Overall complications rate was 36.0%. Minor complications (4.5%) were represented by superficial infection (1.3%) and impaired wound healing (3.2%). All these patients required advanced wound care and prolonged oral antibiotics. Major complications (31.5%) included: residual pain (17.2%), deep infection (3.4%), malunion (2.4%), posttraumatic ankle osteoarthritis (5.0%), implant breakage (0.3%), complex regional pain syndrome (1.3%), and arthrofibrosis (1.9%). Note that 21.7% of major complications required further surgical procedure. Reoperations included arthroscopic debridement (15.1%), hardware removal and debridement of all necrotic tissue (4.5%), and ankle fusion (2.1%). Surgery was necessary mainly for pain removal and function recovery.
Conclusion Ankle fracture ORIF represents a satisfying surgical treatment. Nevertheless, postoperative complications are not uncommon. Minor complications can be easily managed with medications and repeated outpatient controls. Reoperation is occasionally required to treat major complications. Revision surgery is mandatory to ensure pain relief and function improvement.
Level of Evidence Level II, retrospective cohort study.
Tendon Healing in Bone Tunnel after Human Anterior Cruciate Ligament Reconstruction: A Systematic Review of Histological Results
Authors: Lu Hongbin , Chen Can , Xie Shanshan , Tang Yifu , Qu Jin 
Published: May 2018

AbstractMost studies concerning to tendon healing and incorporation into bone are mainly based on animal studies due to the invasive nature of the biopsy procedure. The evidence considering tendon graft healing to bone in humans is limited in several case series or case reports, and therefore, it is difficult to understand the healing process. A computerized search using relevant search terms was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies that investigated tendon graft healing to bone by histologic examination after anterior cruciate ligament (ACL) reconstruction with hamstring. Ten studies were determined to be eligible for this systematic review. Thirty-seven cases were extracted from the included studies. Most studies showed that a fibrovascular interface would form at the tendon–bone interface at the early stage and a fibrous indirect interface with Sharpey-like fibers would be expected at the later stage. Cartilage-like tissue at tendon graft–bone interface was reported in three studies. Tendon graft failed to integrate with the surrounding bone in 10 of the 37 cases. Unexpectedly, suspensory type of fixation was used for the above failure cases. An indirect type of insertion with Sharpey-like fibers at tendon–bone interface could be expected after ACL reconstruction with hamstring. Regional cartilage-like tissue may form at tendon–bone interface occasionally. The underlying tendon-to-bone healing process is far from understood in the human hamstring ACL reconstruction. Further human studies are highly needed to understand tendon graft healing in bone tunnel after hamstring ACL reconstruction.
Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review
Authors: Arican Pinar , Gencpinar Pinar , Cavusoglu Dilek , Olgac Dundar Nihal 
Published: May 2018

AbstractCongenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. CMS due to choline acetyltransferase (CHAT) gene is characterized by episodic apnea. We report a case of a 12-month-old female patient presented with recurrent episodic apnea carrying a mutation in CHAT gene, p.I336T. Furthermore, we describe the genetic and clinical findings in 44 CMS patients due to CHAT mutations in the literature up to date. Episodes of apnea and respiratory insufficiency are the hallmarks of CHAT mutations. Clinical manifestations usually provoked by infections and fever. CMS due to CHAT mutations are rare, but it is important to diagnosis. Early diagnosis and appropriate treatment can improve morbidity and mortality.
Assessment of Likelihood Ratio for Four Contact Dermatitis Symptoms of Vinca Minor
Authors: Nayak Chaturbhuja , Rutten Lex , Koley Munmun , Saha Subhranil , Roy Mousumi , Abbas Sk , Ghosh Simantini , Halder Suman , Wani Ghulam , Mir Anaitulah , Bhat Showket , Bagchi Suman 
Published: May 2018

Background Contact dermatitis (CD) is a frequently occurring medical condition, for which Vinca minor (VM) is one of the recommended homeopathic medicines. However, the symptoms indicating this medicine have not yet been assessed systematically. Likelihood ratio (LR), based on Bayesian statistics, may yield better estimation of a medicine's indication than the existing method of entry of symptoms into materia medica and repertories.
Methods We investigated LRs of four CD symptoms of VM: (1) great sensitiveness of skin, with redness and soreness from slightest rubbing; (2) weeping eczema with foul, thick crusts; (3) itching amelioration in open air; and (4) CD of scalp. An observational, prospective, patient-outcome study was conducted in five different practice settings on 390 CD patients over 18 months using three outcomes—Glasgow Homeopathic Hospital Outcome Scale (GHHOS), Scoring Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI), assessed at baseline, after 3 and 6 months. The LR of each of the four symptoms was estimated as per the patient-rated outcomes on GHHOS.
Results Seventy-four VM and 316 non-VM cases were analyzed. Estimated LRs were as follows: symptom 1, 1.29 (95% confidence interval [CI]: 0.65 to 2.60); symptom 2, 1.48 (95% CI: 0.80 to 2.74); symptom 3, 1.70 (95% CI: 0.94 to 3.07); symptom 4, 1.36 (95% CI: 0.74 to 2.51). There were statistically significant reductions in SCORAD and DLQI scores over 3 and 6 months.
Conclusion There was insufficient evidence to attribute any of the four assessed symptoms clearly to VM. Though non-significant, a high LR was observed for “itching amelioration in open air” (symptom 3). Symptoms in the homeopathic materia medica for VM are perhaps over-represented. More research of this nature is warranted.
Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome
Authors: Depner Christopher M. , Melanson Edward L. , McHill Andrew W. , Wright Kenneth P. 
Published: May 2018

Significance
Circadian misalignment (i.e., behavioral processes such as food intake or sleep occurring at inappropriate endogenous circadian times) commonly occurs during shift work and is associated with health problems. Identifying mechanisms underlying health problems associated with circadian misalignment will help develop precision medicine countermeasures. Thus, we investigated the impact of circadian misalignment on the human plasma proteome using a simulated nightshift protocol in healthy volunteers. We demonstrate that circadian and/or behavioral wake–sleep/food intake–fasting cycles regulate 24-h time-of-day patterns of the human plasma proteome. Further, we show that proteins altered during circadian misalignment are associated with biological pathways involved in immune function, metabolism, and cancer and with altered glucose and energy metabolism, identifying potential mechanisms contributing to metabolic dysregulation.
Biological species in the viral world
Authors: Bobay Louis-Marie , Ochman Howard 
Published: May 2018

Significance
The biological species concept (BSC) has served as the basis for defining species for over 75 years. Members of a biological species are defined by their ability to exchange genetic material, and it was originally thought that asexual lineages were not amenable to species-level classification based on the BSC since clonal individuals are reproductively isolated from one another. In this study, we demonstrate that the rates and patterns of gene exchange in acellular organisms (viruses and bacteriophages) allow the assignment of true biological species, an essential step to organizing the tree of life. Our results show that a universal species definition, based on the BSC, can be used to define biological species in all major lifeforms.
Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems
Authors: Sherlock Madeline E. , Sudarsan Narasimhan , Breaker Ronald R. 
Published: May 2018

Significance
Bacteria and other organisms make extensive use of signaling molecules that are derived from ribonucleotides or their derivatives. Previously, five riboswitch classes had been discovered that sense the four RNA-derived signaling molecules: c-di-GMP, c-di-AMP, c-AMP-GMP, and ZTP. We now report the discovery and biochemical validation of bacterial riboswitches for the widespread alarmone guanosine tetraphosphate (ppGpp), which signals metabolic and physiological adaptations to starvation. These findings expand the number of natural partnerships between riboswitches and ribonucleotide-like signaling molecules, and provide RNA-based sensors for detecting ppGpp production in cells.
Xenoprotein engineering via synthetic libraries
Authors: Gates Zachary P. , Vinogradov Alexander A. , Quartararo Anthony J. , Bandyopadhyay Anupam , Choo Zi-Ning , Evans Ethan D. , Halloran Kathryn H. , Mijalis Alexander J. , Mong Surin K. , Simon Mark D. , Standley Eric A. , Styduhar Evan D. , Tasker Sarah Z. , Touti Faycal , Weber Jessica M. , Wilson Jessica L. , Jamison Timothy F. , Pentelute Bradley L. 
Published: May 2018

Significance
Combinatorial protein libraries—prepared via molecular biology-based approaches—are invaluable tools for protein engineering. The inclusion of noncanonical amino acids in such libraries is of considerable interest. However, at present no approach competes with chemical synthesis in terms of the variety and number of noncanonical amino acids that can be simultaneously incorporated into a protein molecule. Here, we describe selection from synthetic libraries as a strategy for protein engineering. The approach enables identification of small (∼30 aa), functional protein variants comprising a virtually unlimited variety of noncanonical amino acids. Increasing the throughput of synthetic library screening, which was achieved through this effort, is anticipated to improve the utility of synthetic libraries for identifying polypeptide-based ligands with de novo function.
Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy
Authors: Kaushik Mahesh K. , Aritake Kosuke , Imanishi Aya , Kanbayashi Takashi , Ichikawa Tadashi , Shimizu Tetsuo , Urade Yoshihiro , Yanagisawa Masashi 
Published: May 2018

Significance
Narcolepsy is a chronic neurological disorder that severely affects the day-to-day life and general well-being of the affected individuals. Unfortunately, treatments available to date are symptomatic therapies with an array of adverse effects. Animal studies showed that orexin peptide can be a mechanistic therapy to treat narcolepsy. However, nonpermeability of orexin to brain–blood barrier limits its use in humans. Here we showed that orexin delivered via intrathecal route at the lumbar level significantly inhibited narcoleptic symptoms in mice without altering sleep/wake profile. Although the outcome of intrathecal treatment may be different in clinical studies, our data indicate the possibility that orexin can be delivered intrathecally in humans, using an implantable, refillable, and programmable miniature pump to treat narcolepsy.
Structure of xyloglucan xylosyltransferase 1 reveals simple steric rules that define biological patterns of xyloglucan polymers
Authors: Culbertson Alan T. , Ehrlich Jacqueline J. , Choe Jun-Yong , Honzatko Richard B. , Zabotina Olga A. 
Published: May 2018

Significance
The recalcitrant nature of the plant cell wall presents a significant challenge in the industrial processing of biomass. Poor understanding of plant polysaccharide biosynthesis impedes efforts to engineer cell walls susceptible to efficient and unnatural pathways of degradation. Despite numerous genetic and in vitro studies of the xyloglucan xylosyltransferases (XXT1, XXT2, and XXT5), the specific roles of each in the xylosylation of the xyloglucan backbone is unclear. On the basis of steric constraints imposed by the active-site cleft of structures presented here, we propose a multienzyme complex capable of producing the xylosylation patterns of native xyloglucans. This model significantly extends our limited understanding of branched polysaccharide biosynthesis.
Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin
Authors: Tao Wucheng , Díaz-Alonso Javier , Sheng Nengyin , Nicoll Roger A. 
Published: May 2018

Significance
The delta glutamate receptors (GluD1 and GluD2) shared high homology with ionotropic glutamate receptors but, surprisingly, are not gated by glutamate, or any other known ligand. GluD2 is only expressed in cerebellar Purkinje cells, where it forms a scaffolding complex with Cbln1 and presynaptic neurexin 1β (+S4). Might other synapses in the brain use a similar mechanism? We have found that GluD1, a long-neglected receptor subtype, powerfully and specifically regulates synapses in the hippocampus. We show that Cbln2 interacts with GluD1 and presynaptic neurexin 1β (+S4). This tripartite complex plays critical roles in both synaptogenesis and maintenance. Finally, we provide evidence that our results likely apply to synapses throughout the forebrain where GluD1 is widely expressed.
Uncovering universal rules governing the selectivity of the archetypal DNA glycosylase TDG
Authors: Dodd Thomas , Yan Chunli , Kossmann Bradley R. , Martin Kurt , Ivanov Ivaylo 
Published: May 2018

Significance
The most prominent epigenetic modification in mammalian genomes is cytosine methylation at position 5 on the pyrimidine ring. Thymine DNA glycosylase (TDG) plays a central role in the pathways for 5-methyl cytosine removal and thus influences gene silencing, stem cell differentiation, and alterations in normal development. Additionally, methylation abnormalities in DNA are often observed in diseases, specifically cancer. Here we examine the mechanisms by which TDG detects, extrudes, and excises modified bases in DNA. Using path-sampling methodologies, we compute minimum free energy paths for TDG base extrusion. The computed paths reveal a unique mechanism underpinning TDG selectivity for DNA lesions or modified bases, which involves DNA sculpting, global protein dynamics, conformational gating, and specific protein–nucleic acid interactions.
Consistent and powerful non-Euclidean graph-based change-point test with applications to segmenting random interfered video data
Authors: Shi Xiaoping , Wu Yuehua , Rao Calyampudi Radhakrishna 
Published: May 2018

Significance
A webcam collects tons of short video clips for home security, fire inspection, and animal’s behavior study, etc. For efficiency, effectiveness, and economy of the variety of purposes of the use of the video data, we need to remove informationless data. To solve this problem, we propose two non-Euclidean graph-based change-point tests: SHP* and MST*. The proposed test SHP* is not only distribution-free but also, consistent. As shown in the real data example of a bee’s flower visitation, it has successfully detected both landing and departure times of a bee from the video data with random interference.