bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel variant of DHH in a familial case of 46,XY disorder of sex development: Insights from molecular dynamics simulations
Authors: Paris Francoise , Flatters Delphine , Caburet Sandrine , Legois Bérangère , Servant Nadège , Lefebvre Hervé , Sultan Charles , Veitia Reiner A. 
Published: July 2017

SummaryObjectiveDisorders of sex development (DSD) are a heterogeneous group of conditions affecting the differentiation and development of the internal and external genitalia. Here, we aimed at identifying the genetic cause of DSD in two 46,XY sisters from a consanguineous family.DesignWe performed a whole‐exome sequencing of two 46,XY female individuals. Sanger sequencing was used to validate the most likely candidate variant, affecting the desert hedgehog (DHH) gene. Molecular dynamics simulations were performed to get insights into the impact of the variant on protein structure and on its interaction with the protein partner BOC (brother of CDO/cell adhesion molecule, downregulated by oncogenes).PatientsThe index patient presented with a female phenotype, primary amenorrhoea (low oestradiol and testosterone and high FSH and LH). She also had an apparent absence of intra‐abdominal gonads and uterus, facial dysmorphy, psychomotor retardation and neuropathy. Her sister displayed a similar gonadal and endocrinological picture, without dysmorphy or psychomotor retardation.ResultsWhole‐exome sequencing revealed a homozygous variant in DHH leading to the p.Trp173Cys substitution. The relevant Trp residue is conserved, and its alteration was predicted to be deleterious. Molecular dynamics simulations showed that the mutation increases the conformational flexibility of the protein and potentially alters its interaction with BOC, a positive regulator of Hedgehog signalling. We do not exclude an interference of the mutation with DHH‐intein‐mediated auto‐processing.ConclusionsThis report increases the number of described homozygous DHH variants and highlights the importance of advanced bioinformatic tools to better understand the pathogenicity of human variants.
Conversion from calcineurin inhibitors to mTOR inhibitors as primary immunosuppressive drugs in pediatric heart transplantation
Authors: Asante‐Korang Alfred , Carapellucci Jennifer , Krasnopero Diane , Doyle Abigail , Brown Brian , Amankwah Ernest 
Published: July 2017

AbstractThere are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections, and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995 to 2015. Nineteen patients were switched from tacrolimus (n=15) or cyclosporin (n=4) to everolimus (n=4) or sirolimus (n=15) due to nephrotoxicity (n=5), malignancy (n=8), EBV viremia/reactive plasmacytic changes (n=5), and immune hemolytic anemia (n=1). We monitored for rejection, infection, BUN, creatinine, hyperlipidemia, EBV and CMV copies, CBC, cardiac allograft vasculopathy (CAV), and death. Target trough levels of sirolimus and everolimus were 4‐10. Four treatment failures included debilitating rash, bone marrow suppression, recurrent rejection, and renal transplantation. There were no deaths. One patient had recurrent rejection episodes, and tacrolimus was reinitiated. One patient with preexisting CAV underwent heart retransplantation. One patient, who was treated for PTLD, transformed to CD30+ Hodgkins disease, and was treated with brentuximab. There were three acute rejection episodes. Median creatinine preswitch was higher 0.82 than postswitch 0.78 (P=.016). Median eGFR was lower preswitch, 75.6, than postswitch, 91.2 (P=.0004). These results indicate that conversion to mTORI as primary immunosuppression may be safely accomplished in some pediatric heart transplant patients.
CD13 is a marker for onychofibroblasts within nail matrix onychodermis: Comparison of its expression patterns in the nail unit and in the hair follicle
Authors: Park Ji‐Hye , Lee Dong‐Youn , Jang Kee‐Taek , Ha Sang‐Yun , Kwon Ghee Young , Lee Kyung‐Hoon , Shim Jong Sup , Kwon Eun Ji 
Published: July 2017

BackgroundWe previously demonstrated the presence of onychodermis, a specialized mesenchymal cell population beneath the nail matrix and proximal nail bed demonstrating CD10 expression. We hypothesize that the onychodermis could be the nail analog of the follicular dermal papilla, which is known to express CD13. We compare CD13 expression patterns between specialized mesenchymes of nail and hair, and compare these findings with CD10 expression patterns.Methods
CD10 and CD13 immunohistochemistry was performed on polydactyly and adult cadaveric nail units, and on hair follicles in scalp nevus sebaceus excision specimens.Results
CD10 and CD13 were expressed in the mesenchyme below the nail matrix and nail bed. Stronger CD13 expression was observed in the mesenchyme containing onychofibroblasts below the nail matrix compared with that below the nail bed. CD10 was expressed in the dermal sheath of terminal hair follicles, but it was expressed in the dermal sheath and follicular dermal papilla of primitive hair follicles within nevus sebaceus lesions. CD13 was expressed in the dermal sheath and dermal papilla of terminal and primitive hair follicles.Conclusion
CD13 may be a marker for onychofibroblasts within nail matrix onychodermis. We demonstrate CD13 expression in the specialized mesenchymes of both nail and hair.
Effect of optogenetic manipulation of accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine‐induced behavioral sensitization
Authors: Kang Byeong Jun , Song Shelly Sooyun , Wen Lei , Hong Ki‐Pyo , Augustine George J. , Baik Ja‐Hyun 
Published: July 2017

AbstractRepetitive exposure to addictive drugs causes synaptic modification in the mesocorticolimbic dopamine (DA) system. Dopamine D1 receptors (D1R) or D2 receptors (D2R) expressed in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) play critical roles in the control of addictive behaviors. Optogenetic activation of D2R‐expressing MSNs (D2R‐MSNs) in the NAc previously demonstrated that these neurons play a key role in withdrawal‐induced plasticity. Here, we examined the effect of optogenetic inhibition of D2R‐MSNs in the NAc on cocaine‐induced behavioral sensitization. Adeno‐associated viral vectors encoding archaerhodopsin (ArchT) were delivered into the NAc of D2‐Cre transgenic mice. Activation of ArchT produced photoinhibition of D2R‐MSNs and caused disinhibition of neighboring MSNs in the NAc. However, such optogenetic silencing of D2R‐MSNs in the NAc in vivo affected neither the initiation nor the expression of cocaine‐induced behavioral sensitization. Similarly, photoinhibition of NAc D2R‐MSNs in the NAc during the drug withdrawal period did not affect the expression of cocaine‐induced behavioral sensitization. More detailed analysis of the effects of optogenetic activation of D2R‐MSNs suggests that D2R‐MSNs in the NAc exert important modulatory effects on neighboring MSN neurons, which may control the balanced output of NAc MSNs to control addictive behaviors.
Utility of digital subtraction angiography‐based collateral evaluation in medically treated acute symptomatic basilar artery stenosis
Authors: Lee W.‐J. , Jung K.‐H. , Ryu Y. J. , Kim J.‐M. , Lee S.‐T. , Chu K. , Kim M. , Lee S. K. , Roh J.‐K. 
Published: July 2017

Background and purposeAlthough a stroke from atherosclerosis in the basilar artery (BA) often presents with mild initial stroke severity, it has heterogeneous clinical courses. We investigated the efficacy of digital subtraction angiography (DSA)‐based collateral perfusion evaluation in association with long‐term outcomes of medically treated symptomatic basilar artery stenosis.MethodsFrom a registry database of all consecutive patients with stroke, we included 98 medically treated patients (due to mild initial stroke severity) [National Institute of Health Stroke Scale (NIHSS) scores ≤ 4; symptomatic basilar artery stenosis, 70–99%] with available initial diagnostic DSA. Basilar collateral scoring was performed via the DSA, using a modified version of the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system in both the superior cerebellar artery and anterior/posterior‐inferior cerebellar artery territories (score 0–8). The outcomes were designated as the 90‐day modified Rankin Scale (mRS90) score (poor, 3–6). Student's t‐test, chi‐square test and logistic regression analyses were used to identify factors associated with a poor outcome.ResultsThe median initial NIHSS score was 2 [interquartile range (IQR), 0–3], median posterior circulation Alberta Stroke Program Early CT Score was 8 (IQR, 7–10), median collateral score was 7 (IQR, 7–8) and 20 (20.4%) had poor mRS90 scores. In multivariate analysis, poorer collateral scores (P = 0.003), higher NIHSS scores (P = 0.005) and lower posterior circulation Alberta Stroke Program Early CT Score (P = 0.017) were independently associated with a poor mRS90 score.ConclusionsThe DSA‐based collateral scoring of the BA large branches might predict long‐term outcome in medically treated symptomatic basilar artery stenosis with mild initial severity. Evaluation of BA collateral perfusion status might be useful to determine appropriate treatment strategies.
The ecology of fish in the surf zones of ocean beaches: A global review
Authors: Olds Andrew D. , Vargas‐Fonseca Elena , Connolly Rod M. , Gilby Ben L. , Huijbers Chantal M. , Hyndes Glenn A. , Layman Craig A. , Whitfield Alan K. , Schlacher Thomas A. 
Published: July 2017

AbstractThe surf zones of ocean beaches provide habitat for a diversity of fishes and are prime sites for recreational angling and commercial net fisheries. Here, we review the global literature (152 studies) on surf fish ecology to better inform fisheries management and coastal conservation planning. These studies suggest that surf zones support diverse fish assemblages, which are characterized by high numerical dominance (10 species typically comprise 95% of catches), but also show that few families are especially common. The composition of assemblages is highly variable, changing with fluctuations in water temperature, wave climate and the biomass of drifting algae or seagrass. Fish use surf zones as feeding habitats and transit routes, but these areas might not be widely used as spawning sites or juvenile nurseries. These systems are under escalating human pressures, most notably from coastal urbanization and recreational angling. Despite the recognized ecological and economic importance of surf‐zone fishes, few studies have tested for impacts of urbanization or fishing. The benefits of marine reserves for fish in surf zones are also rarely measured. We suggest that progress will be made by moving from largely descriptive studies to hypothesis‐driven research, which is guided by contemporary ecological theory and adapts modern techniques from research in other ecosystems. A key challenge is to obtain empirical data that are needed to improve the effectiveness of fisheries management and underpin conservation planning for coastal waters.
Survive the droughts, I wish you well: Principles and cases of liquidity risk management
Authors: Tuckman Bruce 
Published: July 2017

AbstractShort‐term, liquid assets are highly valued by lenders, but pose liquidity risk management challenges to borrowers. Basic principles to meet those challenges are to conduct liquidity stress scenario analysis; to form business plans for each stress scenario; to hold enough capital to sustain the planned, post‐shock balance sheet; and to hold a large enough liquidity reserve to survive the transition from the pre‐ to the post‐shock balance sheet. Historical failures, like Northern Rock, Bear Stearns, and MF Global have a lot to teach about implementing these principles. While regulatory frameworks constrain liquidity positions, they are no substitute for firm‐specific liquidity risk management.
“Do you dive?”: Methodological considerations for engaging with “volume”
Authors: Squire Rachael 
Published: July 2017

AbstractThe idea that we inhabit three dimensions is clearly not new, yet the explicit articulation of “volume” in recent literature has proved to be an extremely useful means through which to produce novel insights into the conduct and practice of geopolitics. Although the value of engaging with “volume” has been well established and taken discussions in new directions, yet the practicalities of doing this research are yet to be considered in great detail. How methodologically do we approach the three‐dimensional within political geography? Although this paper does not seek to outline a methodological framework, it draws on my own research to prompt discussion about the role of “immersive” methodologies in generating different perspectives within political geography. The paper ends by suggesting that a stronger interface between political geography and methodologies utilised in other geographical subdisciplines might be useful in producing novel insights into the earth's geopolitical volumes.
Prediction of geriatric rehabilitation outcomes: Comparison between three cognitive screening tools
Authors: Heyman Noemi , Tsirulnicov Tatyana , Ben Natan Merav 
Published: July 2017

AbstractAimComparison between the predictions of functional rehabilitation outcomes at a department of geriatric rehabilitation using three cognitive screening tools – Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).MethodsThis study is a prospective study. The study participants were 212 patients aged 65 and older admitted to rehabilitation departments at a geriatric facility in central Israel, from April 2016 to October 2016. The cognitive functioning of each patient was assessed using the MMSE, MoCA, and IQCODE. Upon discharge, rehabilitation outcomes were examined using the Functional Independence Measure (FIM), cognitive FIM, delta FIM (Δ FIM), and ADL.ResultsCognitive impairment was found to interfere with the rehabilitation process. The MMSE was the best predictor of functional rehabilitation outcomes at discharge, compared to the IQCODE, while the MoCA did not predict these measures. In addition, when distinguishing between patients by ethnicity (Jewish versus Arab), the MMSE and the IQCODE predicted FIM upon discharge among Jewish patients, while only the IQCODE predicted FIM upon discharge among Arab patients.ConclusionsThe research findings show that cognitive assessment upon admission for rehabilitation – MMSE among Jewish patients and IQCODE among Arab patients – can help predict functional rehabilitation outcomes and make the appropriate adaptations in the rehabilitation program. Geriatr Gerontol Int 2017; 17: 2507–2513.
New insights into sinusoidal obstruction syndrome
Authors: Piccin Andrea , Sartori Maria T. , Bisogno Gianni , Van Schilfgaarde Muriel , Saggiorato Graziella , Pierro Angela M. D. , Corvetta Daisy , Marcheselli Luigi , Mega Andrea , Gastl Günther , Cesaro Simone 
Published: July 2017

AbstractBackgroundEntry criteria included patients who developed sinusoidal obstruction syndrome (SOS) at a single centre from January 2000 to December 2011. Patients who underwent haemopoietic stem cell transplantation or actinomicyn‐based chemotherapy for nephroblastoma were selected. The study group comprised five patients with SOS who were compared with a control group of seven patients without SOS.AimTo study the relationships between endothelial extracellular vesicles (EV) and plasminogen‐activator inhibitor type 1(PAI‐1) to assess their modification in the early phase of SOS.MethodsConsecutive blood samples were tested for cell‐derived EV, PAI‐1 and coagulation parameters. Any statistically significant correlation between all datasets was searched.ResultsAntithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI‐1:Ag and PAI‐1:act showed an inverse relationship with platelet counts (coef. −0.034, SE = 0.016; P = 0.041 and −0.052, SE = 0.019; P = 0.011 respectively). During follow up, PAI‐1:Ag was inversely related to EV CD144+ (coef. −0.261, SE = 0.094; P = 0.007) and antithrombin (coef −0.509, SE = 0.175; P = 0.005). PAI‐1:act showed an inverse association with EV CD144+ (coef.−0.251, SE = 0.121; P = 0.043), EV CD31+/CD41+ (coef. −0.004, SE = 0.002; P = 0.026) and antithrombin (coef. −0.470, SE = 0.220; P = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and also showed a change over time.ConclusionThis study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI‐1, as a new biomarker for SOS.
Predict disease progression from T‐cell phenotypes in northern pig‐tailed macaques (Macaca leonina) during SIVmac239 infection
Authors: Zhang Ming‐Xu , Zheng Hong‐Yi , Jiang Jin , Song Jia‐Hao , Chen Min , Xiao Yu , Lian Xiao‐Dong , Song Tian‐Zhang , Tian Ren‐Rong , Pang Wei , Zheng Yong‐Tang 
Published: July 2017

SummaryMacaca leonina (northern pig‐tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analysed, for the first time, the correlations between T‐cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T‐cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T‐cell count and CD4 : CD8 ratio, and lower plasma viral load than NPs. CD4+ T‐cell count and CD4 : CD8 ratio decreased more sharply in NPs than in SPs. Furthermore, T cells in NPs were more highly differentiated, at least in acute infection, than in SPs. These results indicated that T‐cell phenotypes were correlated with disease progression in SIVmac239‐infected NPMs and these correlations may provide valuable guidance for the improvement of therapeutic strategies tested in NPMs.
Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome
Authors: Guo Qing‐Hua , Wang Cheng‐Zhi , Wu Zhi‐Qiang , Qin Yan , Han Bai‐Yu , Wang An‐Ping , Wang Bao‐An , Dou Jing‐Tao , Wu Xiao‐Sheng , Mu Yi‐Ming 
Published: July 2017

AbstractPituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole‐exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.
Safer and more appropriate opioid prescribing: a large healthcare system's comprehensive approach
Authors: Losby Jan L. , Hyatt Joel D. , Kanter Michael H. , Baldwin Grant , Matsuoka Denis 
Published: July 2017

AbstractRationale, aims, and objectivesThe United States is in the midst of a public health epidemic with more than 40 people dying each day from prescription opioid overdoses. Health care systems are taking steps to address the opioid overdose epidemic by implementing policy and practice interventions to mitigate the risks of long‐term opioid therapy. Kaiser Permanente Southern California launched a comprehensive initiative to transform the way that chronic pain is viewed and treated. Kaiser Permanente Southern California created prescribing and dispensing policies, monitoring and follow‐up processes, and clinical coordination through electronic health record integration. The purpose of this paper is to describe the implementation of these interventions and assess the impact of this set of interventions on opioid prescribing.MethodThe study used a retrospective pre‐post evaluation design to track outcomes before and after the intervention. Kaiser Permanente Southern California members age 18 and older excluding cancer, hospice, and palliative care patients and this sub‐population of 3 203 880 was approximately 75% of all Kaiser Permanente Southern California members. All data are from Kaiser Permanente's pharmacy data systems and electronic health record collected on a rolling basis as interventions were implemented from January 2010 to December 2015.ResultsThere were reductions in all tracked outcomes: a 30% reduction in prescribing opioids at high doses; a 98% reduction in the number of prescriptions with quantities greater than 200 pills; a 90% decrease in the combination of an opioid prescription with benzodiazepines and carisoprodol; a 72% reduction in the prescribing of Long Acting/Extended Release opioids; and a 95% reduction in prescriptions of brand name opioid‐acetaminophen products. In addition, methadone prescribing did not increase during this period.ConclusionsThis study adds promising results that a comprehensive system‐level strategy has the ability to positively affect opioid prescribing. The basic components of the intervention are generalizable and applicable to other health care settings.
A Minchinia mercenariae‐like parasite infects cockles Cerastoderma edule in Galicia (NW Spain)
Authors: Ramilo A , Abollo E , Villalba A , Carballal M J 
Published: July 2017

AbstractThe cockle Cerastoderma edule fishery has traditionally been the most important shellfish species in terms of biomass in Galicia (NW Spain). In the course of a survey of the histopathological conditions affecting this species in the Ria of Arousa, a haplosporidan parasite that had not been observed in Galicia was detected in one of the most productive cockle beds of Galicia. Uni‐ and binucleate cells and multinucleate plasmodia were observed in the connective tissue mainly in the digestive area, gills and gonad. The parasite showed low prevalence, and it was not associated with abnormal cockle mortality. Molecular identification showed that this parasite was closely related to the haplosporidan Minchinia mercenariae that had been reported infecting hard clams Mercenaria mercenaria from the Atlantic coast of the United States. The molecular characterization of its SSU rDNA region allowed obtaining a fragment of 1,796 bp showing 98% homology with M. mercenariae parasite. Phylogenetic analysis supported this identification as this parasite was clustered in the same clade as M. mercenariae from the United States and other M. mercenariae‐like sequences from the UK, with bootstrap value of 99%. The occurrence of M. mercenariae‐like parasites infecting molluscs outside the United States is confirmed.