bluuebunny/crossref_metadata_2025_split huggingface dataset:
gflow: software for modelling circuit theory‐based connectivity at any scale
Authors: Leonard Paul B. , Duffy Edward B. , Baldwin Robert F. , McRae Brad H. , Shah Viral B. , Mohapatra Tanmay K. 
Published: November 2016

SummaryIncreasing habitat connectivity is important for mitigating the effects of climate change, landscape fragmentation and habitat loss for biodiversity conservation. However, modelling connectivity at the relevant scales over which these threats occur has been limited by computational requirements.Here, we introduce the open‐source softwaregflow, which massively parallelizes the computation of circuit theory‐based connectivity. The software is developed for high‐performance computing, but scales to consumer‐grade desktop computers running modern Linux or MacOSX operating systems.We report high computational efficiency representing a 173× speedup over existing software using high‐performance computing and a 8·4× speedup using a desktop computer while drastically reducing memory requirements.gflowallows large‐extent and high‐resolution connectivity problems to be calculated over many iterations and at multiple scales. We envisiongflowbeing immediately useful for large‐landscape efforts, including climate‐driven animal range shifts, multitaxa connectivity, and for the many developing use‐cases of circuit theory‐based connectivity.
Methamphetamine self‐administration reduces alcohol consumption and preference in alcohol‐preferring P rats
Authors: Winkler Madeline C. , Greager Emilee M. , Stafford Jacob , Bachtell Ryan K. 
Published: November 2016

AbstractSubclinical levels of polysubstance use are a prevalent and understudied phenomenon. Alcohol is a substance commonly co‐used with other substances of other drug classes. These studies sought to determine the consumption effects of combining alcohol drinking and methamphetamine (MA) self‐administration. Male alcohol‐preferring P rats had continuous access to a two‐bottle alcohol drinking procedure in the home cage. Control rats remained alcohol naïve. Rats were also surgically implanted with intra‐jugular catheters and trained to self‐administer saline (control) or MA in daily 2‐hour sessions. We first measured the acquisition and maintenance of MA intake in alcohol‐consuming or control rats. MA intake was initially enhanced by alcohol consumption on a fixed ratio 1 schedule of reinforcement, but this effect did not prevail as the difficulty of the schedule (FR5 and progressive ratio) was increased. We next measured both alcohol consumption and preference before, during and after MA (or saline) self‐administration. MA self‐administration significantly reduced alcohol intake and preference ratios, a robust effect that persisted across several experimental variations. Interestingly, alcohol consumption rebounded following the cessation of MA self‐administration. The effects of MA self‐administration were specific to alcohol intake because it did not alter total fluid consumption or consumption of sucrose. MA self‐administration did not impact blood‐alcohol concentrations or alcohol‐induced loss of righting reflex suggesting no effect of MA intake on the alcohol metabolism or sensitivity. Together, the results suggest that MA intake disrupts alcohol consumption and preferences but not the reverse in alcohol‐preferring P rats.
Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis
Authors: Egeberg A. , Andersen Y. M. F. , Gislason G. H. , Skov L. , Thyssen J. P. 
Published: November 2016

AbstractBackgroundAtopic dermatitis (AD) is a common chronic skin disorder, which may persist into adulthood; however, the prevalence of comorbidities in patients with AD is not well characterized. AD is considered a systemic disorder like psoriasis, which has raised a need for data on the comorbidity profile of patients with AD, to assess the potential risks, benefits, and complications in management of patients with AD. We described the occurrence of medical and psychiatric comorbidities and associated risk factors in adults with AD compared with psoriasis and the general population.MethodsAll Danish individuals aged ≥18 years with a hospital (inpatient or ambulatory) diagnosis of AD or psoriasis during the study period (January 1, 1995–December 31, 2012) were linked in administrative registers.ResultsOverall, prevalence of smoking and alcohol abuse was higher among patients with AD than the general population, but lower than psoriasis patients. Similarly, patients with AD had more risk factors and higher prevalence of comorbidity than the general population, but lower prevalence and reduced risk compared to psoriasis patients, except for use of anxiolytics, which was higher in severe AD. Prevalence of diabetes was lower in AD than psoriasis patients as well as general population controls.ConclusionsDespite an increased risk of various medical and psychiatric comorbidities compared to general population controls, adult patients with AD had markedly lower prevalence of cardiovascular disease than psoriasis patients. However, prevalence of psychiatric comorbidity and tobacco smoking was alarmingly high in severe patients with AD, which might be target for intervention in patient management.
Detection of drug‐responsive B lymphocytes and antidrug IgG in patients with β‐lactam hypersensitivity
Authors: Amali M. O. , Sullivan A. , Jenkins R. E. , Farrell J. , Meng X. , Faulkner L. , Whitaker P. , Peckham D. , Park B. K. , Naisbitt D. J. 
Published: November 2016

AbstractBackgroundDelayed‐type β‐lactam hypersensitivity develops in subset of patients. The cellular immunological processes that underlie the drug‐specific response have been described; however, little is known about involvement of the humoral immune system. Thus, the aim of this study was to utilize piperacillin hypersensitivity as an exemplar to (i) develop cell culture methods for the detection of drug‐specific B‐cell responses, (ii) characterize drug‐specific IgG subtypes and (iii) assess reactivity of IgG antibodies against proteins modified to different levels with piperacillin haptens.MethodsIgG secretion and CD19+CD27+ expression on B cells were measured using ELISPOT and flow cytometry, respectively. A piperacillin–BSA adduct was used as an antigen in ELISA antibody binding studies. Adducts generated using different ratios of drug to protein were used to determine the degree of conjugation required to detect IgG binding.ResultsB cells from hypersensitive patients, but not controls, were stimulated to secrete IgG and increase CD27 expression when cultured with soluble piperacillin. A piperacillin–BSA adduct with cyclized and hydrolysed forms of the hapten bound to eight lysine residues was used to detect hapten‐specific IgG 1‐4 subclasses in patient plasma. Hapten inhibition and the use of structurally unrelated hapten–BSA adducts confirmed antigen specificity. Antibody binding was detected with antigens generated at piperacillin/BSA ratios of 10:1 and above, which corresponded to a minimum epitope density of 1 for antibody binding.ConclusionThese data show that antigen‐specific B lymphocytes and T lymphocytes are activated in piperacillin‐hypersensitive patients. Further work is needed to define the role different IgG subtypes play in regulating the iatrogenic disease.
The Subject of Suffering
Authors: Pollock Susan 
Published: November 2016

ABSTRACTAs the German philosopher Theodor W. Adorno argued, suffering is one of the most fundamental of human experiences. In archaeological narratives, however, suffering seldom appears. Instead, current trends in archaeology, including the focus on the relevance of things, the dissolution of boundaries between subjects and objects, and the foregrounding of agency, shift attention away from the subject of suffering. I discuss an archaeology that takes suffering as a central issue, drawing on archaeological work at sites of the Nazi period in Berlin. Rather than promoting positive identifications with the past, I argue that we need archaeologies that work toward respect and responsibility by acknowledging suffering, both past and present. [suffering, experience, archaeology of Nazi times, Berlin]
The Contingency of Humanitarianism: Moral Authority in an African HIV Clinic
Authors: Brada Betsey Behr 
Published: November 2016

ABSTRACTOne consequence of the recent expansion of anthropological interest in humanitarianism is the seeming obviousness and conceptual stability of “humanitarianism” itself. In this article, I argue that, rather than being a stable concept and easily recognizable phenomenon, humanitarianism only becomes apparent in relation to other categories. In short, humanitarianism is contingent: it depends on circumstance and varies from one context to another. Furthermore, its perceptibility rests on individuals’ capacity to mobilize categorical similarities and distinctions. One cannot call a thing or person “humanitarian” without denying the humanitarian character of someone or something else. Drawing on research conducted in clinical spaces where Botswana's national HIV treatment program and private US institutions overlapped, I examine the processes by which individuals claimed people, spaces, and practices as humanitarian, the contrasts they drew to make these claims, and the moral positions they attempted to occupy in the process. More than questions of mere terminology, these processes of categorization and contradistinction serve as crucibles for the larger struggles over sovereignty, inequality, and the legacies of colonialism that haunt US‐driven global health interventions. [humanitarianism, global health, expertise, semiotics, Botswana, HIV/AIDS]
Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen
Authors: Hadad Ronza , Marks Ellen , Kalbina Irina , Schön Karin , Unemo Magnus , Lycke Nils , Strid Åke , Andersson Sören 
Published: November 2016

The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell‐mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon‐γ and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.
Perineal alveolar soft part sarcoma treated by laparoscopy‐assisted total pelvic exenteration combined with pubic resection
Authors: Aiba Toshisada , Uehara Keisuke , Tsukushi Satoshi , Yoshino Yasushi , Ebata Tomoki , Yokoyama Yukihiro , Igami Tsuyoshi , Sugawara Gen , Nagino Masato 
Published: November 2016

AbstractA 20‐year‐old woman with a perineal alveolar soft part sarcoma was referred to our hospital. MRI showed that an irregular oval tumor occupied the perineum. The tumor was contiguous to the vagina, rectum, levator muscle, and pubis and was diagnosed as alveolar soft part sarcoma by transvaginal biopsy. Laparoscopy‐assisted total pelvic exenteration combined with a pubic resection was performed, and an R0 resection with a wide margin was achieved. It is well known that only R0 resection improves the outcome of patients with localized alveolar soft part sarcoma. In this case, the perineal manipulation was difficult because the tumor was huge and had a rich blood flow. Massive bleeding occurred during the perineal manipulation. However, we kept the operative field dry thanks to minimal intraoperative blood loss during the laparoscopic phase. The laparoscopic approach might be advantageous for such a demanding surgical procedure for tumors in the distal pelvis and perineum.
Pro‐survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia
Authors: Chen Yixiang , Germano Sandra , Clements Chris , Samuel Jesvin , Shelmani Ghalia , Jayne Sandrine , Dyer Martin J. S. , Macip Salvador 
Published: November 2016

SummaryDinaciclib is a cyclin‐dependent kinase inhibitor with clinical potential in different cancers, including chronic lymphocytic leukaemia (CLL). In order to better understand its cytotoxic action, we characterized its effects on signalling pathways important for the survival of CLL cells. We found that dinaciclib induced apoptosis through the activation of caspases 8 and 9, which was independent of the presence of cytokines to mimic the environment of proliferation centres or IGVH mutation status. Moreover, treatment with dinaciclib led to the inhibition of oncogenic pathways normally activated in stimulated CLL cells, such as STAT3, NF‐κB, p38, PI3K/AKT and RAF/MEK/ERK. Dinaciclib was also able to block the expression of anti‐apoptotic proteins of the BCL2 family such as MCL1 and BCL‐xL (also termed BCL2L1). Finally, we showed that low concentrations of dinaciclib enhanced cell sensitivity to ibrutinib and the BCL2 inhibitor ABT‐199, two drugs with known effects on CLL. Taken together, our data show that dinaciclib targets multiple pro‐survival signalling pathways in CLL, which provides a mechanistic explanation for its potent induction of apoptosis. They also support a therapeutic application of cyclin‐dependent kinase inhibitors in CLL in combination with other relevant targeted therapies.
Management of central nervous system involvement in chronic lymphocytic leukaemia: a retrospective cohort of 30 patients
Authors: Wanquet Anne , Birsen Rudy , Bonnet Charlotte , Boubaya Marouane , Choquet Sylvain , Dupuis Jehan , Lepretre Stephane , Re Daniel , Fahri Jonathan , Michallet Anne‐Sophie , Ysebaert Loïc , Lemal Richard , Lamy Thierry , Delarue Richard , Troussard Xavier , Cymbalista Florence , Levy Vincent , Dietrich Pierre‐Yves , Leblond Veronique , Aurran‐Schleinitz Therese 
Published: November 2016

SummaryCentral nervous system involvement (CNSi) is a rare and poorly reported complication of chronic lymphocytic leukaemia (CLL). Establishing cause and effect between the CLL and the neurological symptoms remains challenging. We have analysed a retrospective cohort of 30 CLL patients with CNSi, documented by lymphocytic infiltration either by flow cytometry of the cerebrospinal fluid (CSF; n = 29) or CNS biopsy (n = 1). Neurological symptoms were heterogeneous. At the time of CNSi, less than half of the patients had a progressive CLL and 20 had never been treated for CLL. Initial treatment with fludarabine‐based immuno‐chemotherapy, with or without intra‐CSF therapy, led to durable response in eight out of nine untreated patients. In contrast, 50% patients receiving various prior treatments needed additional therapy within a median of 4 months (1–16). Ibrutinib led to complete response in 4/4 heavily pre‐treated patients. From CNSi, 5‐year overall survival was 72% and 48% for treatment‐naïve and previously treated patients respectively (P = 0·06); 5‐year progression‐free survival (PFS) was 43% and 0% (P = 0·125). 17p deletion was significantly associated with poor PFS (P = 0·006). CNSi may be the only sign of progression of CLL and should be considered an initiation criterion of systemic treatment. Prognosis seemed to be related to CLL characteristics rather than to CNSi itself.
Introduction of robot‐assisted radical cystectomy within an established enhanced recovery programme
Authors: Miller Catherine , Campain Nicholas J. , Dbeis Rachel , Daugherty Mark , Batchelor Nicholas , Waine Elizabeth , McGrath John S. 
Published: November 2016

ObjectivesTo describe the implementation phase of a robot‐assisted radical cystectomy (RARC) programme including side‐effect profiles and impact on length of stay (LOS).Patients and MethodsIn all, 114 consecutive patients (82% male) underwent RARC and urinary diversion between April 2013 and December 2015 [ileal conduit (97 patients) and orthotopic neobladder (17)]. Surgery was performed by two surgeons within a designated regional cancer centre. No exclusion criteria were applied. All patients were managed on the Exeter Enhanced Recovery Pathway (ERP) in a unit where embedded enhanced recovery practice was already established. Data were collected prospectively on the national cystectomy registry – the British Association of Urological Surgeons (BAUS) Complex Operations Dataset.ResultsRARC was technically feasible in all but one case. The mean operating time was 3–5 h with an overall transfusion rate of 8.8%. There were higher‐grade complications (Clavien–Dindo grade III–IV) in 18.4% of patients, with a 30‐day mortality rate of 0.9%. The median (range) LOS after RARC was 7 (3–68) days, with a re‐admission rate of 18.4%.ConclusionsThe present series shows that RARC can be safely implemented in a unit experienced in robot‐assisted surgery (RAS). Case‐selection in this setting is not deemed necessary. There are benefits in terms of lower transfusion rates and reduced LOS. The side‐effect profile appears to differ from that of open RC, and despite the fact that complication rate is equivalent; ‘technical’ complications are over‐represented in the RAS group. As such, they should improve with experience, recognition, and modification of surgical technique. ERPs can be safely applied to all patients undergoing RARC to maximise the benefits of minimally invasive surgery.
Telomeric repeat‐containing RNA (TERRA) related to polycystic ovary syndrome (PCOS)
Authors: Wang Caiqin , Shen Fengxian , Zhu Yuning , Fang Yuying , Lu Shiming 
Published: November 2016

SummaryContextTelomeric repeat‐containing RNA (TERRA) participates in the regulation of telomere length, and leucocyte telomere length (LTL) plays an important role in the pathophysiology of polycystic ovary syndrome (PCOS), but little is known about the role of TERRA in PCOS.ObjectiveTo evaluate the role of TERRA and peripheral blood LTL in PCOS.Design and participantsForty women with PCOS and 35 healthy women without PCOS were recruited. A prospective case–control study was performed.MeasurementsRNA fluorescence in situ hybridization (FISH) was used to detect TERRA expression in peripheral blood leucocyte. Quantitative PCR was used to measure TERRA expression and the mean LTL in the PCOS and control groups. We analysed the association between related clinical parameters and the age‐adjusted ratio of the telomere repeat length (T/S ratio) or TERRA.ResultsTelomeric repeat‐containing RNA was expressed in human peripheral blood leucocytes, and the signal was abolished after culture with RNase A. The age‐adjusted LTLs were significantly longer in the PCOS group than in the control group (P < 0·01). The age‐adjusted TERRA level was significantly lower in the PCOS group than in the control group (P < 0·01). Testosterone (TTE) was related positively to LTL and negatively to TERRA in the PCOS group (r = 0·532, P = 0·002; r = −0·477, P = 0·017).ConclusionWe found TERRA expression in human peripheral blood leucocytes, and LTLs were positively associated with PCOS. TERRA and testosterone play an important role in the LTL regulation in PCOS.
Contact sensitization in Dutch children and adolescents with and without atopic dermatitis – a retrospective analysis
Authors: Lubbes Stefanie , Rustemeyer Thomas , Sillevis Smitt Johannes H. , Schuttelaar Marie Louise , Middelkamp‐Hup Maritza A. 
Published: November 2016

SummaryBackgroundAllergic contact dermatitis is known to occur in children with and without atopic dermatitis, but more data are needed on contact sensitization profiles in these two groups.ObjectivesTo identify frequent allergens in children with and without atopic dermatitis suspected of having allergic contact dermatitis.MethodsA retrospective analysis of children aged 0–17 years patch tested between 1996 and 2013 was performed.ResultsOf all 1012 children tested because of suspected contact dermatitis, 46% developed one or more positive reactions, the proportions for children with (n = 526) and without (n = 395) atopic dermatitis being 48% and 47%, respectively. Children with atopic dermatitis reacted more often to lanolin alcohol (30% pet., p = 0.030), Amerchol L‐101 (p = 0.030), and fragrances [fragrance mix I (p = 0.048) and Myroxylon pereirae (p = 0.005)]. Allergens outside the European baseline series that frequently gave positive reactions in these groups included cocamidopropyl betaine and Amerchol L‐101. Reactivity to these allergens was significantly more common in atopic dermatitis children.ConclusionSensitization prevalences in children with and without atopic dermatitis were similar, but children with atopic dermatitis reacted significantly more often to lanolin alcohol and fragrances. Testing with additional series besides the European baseline series may be necessary, as reactions to, for example, cocamidopropyl betaine and Amerchol L‐101 may otherwise be missed.
Depressive symptoms and early mortality following lung transplantation: A pilot study
Authors: Smith Patrick J. , Blumenthal James A. , Snyder Laurie D. , Mathew Joseph P. , Durheim Michael T. , Hoffman Benson M. , Rivelli Sarah K. , Palmer Scott M. 
Published: November 2016

AbstractBackgroundImpaired psychological function is common among lung transplant candidates and may affect clinical outcomes following transplantation. Although numerous studies have examined the relationship between pretransplant depression, quality of life (QoL), and post‐transplant outcomes, few have examined the relationship between depression and QoL shortly following transplantation and subsequent clinical outcomes. We therefore examined the association between depression, QoL, and short‐term mortality in a consecutive series of lung transplant recipients.MethodsDepression (Patient Health Questionnaire‐9; Hospital Anxiety and Depression Scale; Centers for Epidemiologic Studies Depression Scale) and QoL (UCSD Shortness of Breath Questionnaire; Pulmonary Quality of Life Scale) were assessed prior to transplantation (median 0.9 months [IQR=1.6]) and again approximately 2 weeks following transplantation (median=0.5 months [IQR=0.5]), in a series of 66 patients transplanted between March 2013 and April 2014. The association between psychiatric diagnoses from participants’ comprehensive pretransplant assessment and mortality also was examined. Cox proportional hazards models were used to examine the association between depression, QoL, and mortality.ResultsDuring a median follow‐up of 2.8 years (range 0.4‐3.3), 21 patients died (32%). Greater depressive symptoms assessed shortly after transplant were associated with subsequent mortality (HR=2.17 [1.01, 4.67], P=.048), and this relationship persisted after controlling for primary graft dysfunction, duration of transplant hospitalization, and gender. In contrast, neither pretransplant depression, history of depression, nor QoL was associated with mortality.ConclusionsGreater post‐transplant depressive symptoms are independently associated with mortality among lung transplant recipients.