bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aromatase Inhibitors Are Associated with Low Sexual Desire Causing Distress and Fecal Incontinence in Women: An Observational Study
Authors: Robinson Penelope J. , Bell Robin J. , Christakis Marie K. , Ivezic Stephanie R. , Davis Susan R. 
Published: October 2017

Abstract

Background
Little is known of the impact of aromatase inhibitor (AI) therapy on sexual and pelvic floor function.

Aim
To document the prevalence of, and factors associated with, low desire, sexually related personal distress, hypoactive sexual desire dysfunction (HSDD), and pelvic floor dysfunction in women 10 years after breast cancer diagnosis.

Methods
This was a prospective, observational, community-based cohort study of Australian women with invasive breast cancer recruited within 12 months of diagnosis. 1,053 of the 1,305 who completed the initial 5 years of study follow-up agreed to be re-contacted, and 992 of these women alive 10 years after diagnosis were sent the study questionnaire.

Outcomes
The main outcome measure was HSDD determined by a score no higher than 5.0 on the desire domain of the Female Sexual Function Index (FSFI) plus a score of at least 11.0 on the Female Sexual Distress Scale–Revised (FSDS-R). Pelvic floor disorders, including urinary incontinence, fecal incontinence, and pelvic organ prolapse, were assessed using validated questionnaires. Multivariable logistic regression was used to assess factors associated with low desire, personal distress, and HSDD.

Results
625 completed questionnaires were returned. The respondents’ median age was 65.1 years (range = 36.4–95.5). Current AI use was reported by 10% and tamoxifen use was reported by 3.4%. 521 of the 608 women (85.7%; 95% CI = 82.9–88.5) who competed the FSFI desire domain had low sexual desire, and 246 of the 563 women (43.7%; 95% CI = 39.6–47.8%) who completed the FSDS-R had sexually related personal distress. 221 of the 559 women (39.5%; 95% CI = 35.5–43.6%) who completed the 2 questionnaires had HSDD. Current AI users were more likely to have HSDD than non-users (55.2% [95% CI = 42.2–68.1] vs 37.8% [95% CI = 33.5–42.0]; P = .01). HSDD was more prevalent in sexually active, current AI users (66.7%; 95% CI = 49.4–83.9) vs current non-users (43.6%; 95% CI = 37.0–50.2; P = .02). In a logistic regression model, HSDD was significantly associated with current AI use and inversely associated with age. Fecal incontinence was more prevalent in AI users than in current non-users (29.8% [95% CI = 17.8–41.8] vs 16.4% [95% CI = 13.2–19.6], respectively; P = .01).

Clinical Implications
It is important to address women’s sexual health even many years after their breast cancer diagnosis.

Strengths and Limitations
Strengths include a representative sample, use of validated questionnaires, and few missing data. Limitations include sexual activity being a 4-week recall.

Conclusions
AI use is associated with HSDD and fecal incontinence in women who are 10 years after breast cancer diagnosis.
Removable Rigid Dressings for Postoperative Management of Transtibial Amputations: A Review of Published Evidence
Authors: Reichmann James P. , Stevens Phillip M. , Rheinstein John , Kreulen Christopher D. 
Published: October 2017

AbstractForty years of clinical experience and peer‐reviewed research studies support the use of nonweight‐bearing removable rigid dressings (RRDs) as an effective means of postoperative management of transtibial amputations. We reviewed the published medical evidence regarding the use of RRDs as a postoperative management strategy, culminating in an evidence‐based practice recommendation. Published peer‐reviewed literature on the topic was searched and classified by level of evidence based on the research design using the scale recommended by the PM&R (level I through V). The search uncovered a total of 15 articles, including 5 level I randomized controlled trials, 6 level III retrospective matched controlled trials, and 4 level V case reports.A number of benefits associated with the application of RRDs compared with soft dressings were reported across these 15 studies. These included faster healing times, reduced limb edema, preparatory contouring of the residual limb in anticipation of prosthetic use, the prevention of knee flexion contractures, and reduced external trauma to the limb. Also described were an increased probability of successful prosthetic use and pain reduction. The RRDs studied permitted regular inspection of surgical wounds with greater ease and consistency of application than traditional soft dressing approaches. Rigid dressings provide all the same benefits of RRDs except ease of wound inspection, therefore rendering them impractical for the 82% of patients receiving an amputation for ischemic disease that are at high risk of developing wound dehiscence. Weight‐bearing immediate postoperative prostheses are almost exclusively reserved for use on trauma patients who usually do not show evidence of vascular or neurologic impairment. The inherent risks of falls and inconsistent pressure on the surgical wound have further restricted their use in practice to a limited patient type.The benefits of RRDs compared with soft dressings are universally recognized in the published peer‐reviewed medical evidence to be superior to soft dressings. Based on the best‐available current published evidence, nonweight‐bearing removable rigid dressings should be considered the first treatment choice for the postoperative care of transtibial amputees to optimize outcomes with regard to reductions in injury due to falls, knee flexion contractures, edema, healing time, time to prosthetic fitting, and pain.Level of EvidenceII
On the role of the present indicative in variable future-time reference in Hexagonal French
Authors: Gudmestad Aarnes , Edmonds Amanda , Donaldson Bryan , Carmichael Katie 
Published: October 2017

AbstractThis article investigates variable future-time expression among native speakers of Hexagonal French who participated in informal conversations. The quantitative analysis is the first to examine the inflectional future, periphrastic future, and present indicative as separate forms within a single statistical model of French oral production. Results indicate that temporal distance and presence/absence of a temporal expression predict use of these verb forms. The second phase of the analysis focused on the use of the present indicative in future-time contexts. The examination of each instance of the present indicative shows that an immediate lexical temporal indicator is not necessary for this form to convey futurity and that future-time reference is often established at the discourse level and occasionally through apparent shared knowledge between the interlocutors. This investigation suggests the value of including the present indicative in the analysis of future-time reference in Hexagonal French in order to fully capture variation.
In hand and in mind: Effects of gesture production and viewing on second language word learning
Authors: MORETT LAURA M. 
Published: October 2017

ABSTRACTTo date, within the context of second language (L2) word learning, nonspontaneous representational gesture viewing's impact on memory and spontaneous gesture production's impact on communication have been examined separately. Thus, it is unclear whether and how these effects interact, particularly in the same individuals. The present study addresses this question by comparing these effects and by examining their influence on one another. To do so, a dialogic task was employed in which participants learned words from a novel L2 and taught them to other similar participants. The results show that viewing nonspontaneous representational gesture did not affect L2 word recall whereas spontaneous production of different gesture types affected communication and memory of L2 word meanings in varying ways. Furthermore, the results provide evidence that gesture viewing primes production of similar types of gestures, and that the quantity and types of gestures produced differ based on the context of communication. These results indicate that the effects of spontaneous gesture production on communication are stronger than the effects of nonspontaneous gesture viewing on memory, and that these effects influence one another. Together, these results demonstrate that spontaneous gesture production and nonspontaneous gesture viewing play distinct but interrelated roles in L2 acquisition.
Reproducibility of Cognitive Profiles in Psychosis Using Cluster Analysis
Authors: Lewandowski Kathryn E. , Baker Justin T. , McCarthy Julie M. , Norris Lesley A. , Öngür Dost 
Published: October 2017

AbstractObjectives:Cognitive dysfunction is a core symptom dimension that cuts across the psychoses. Recent findings support classification of patients along the cognitive dimension using cluster analysis; however, data-derived groupings may be highly determined by sampling characteristics and the measures used to derive the clusters, and so their interpretability must be established. We examined cognitive clusters in a cross-diagnostic sample of patients with psychosis and associations with clinical and functional outcomes. We then compared our findings to a previous report of cognitive clusters in a separate sample using a different cognitive battery.Methods:Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, and clinical and community functioning assessments. Cluster analyses were performed on cognitive variables, and clusters were compared on demographic, cognitive, and clinical measures. Results were compared to findings from our previous report.Results:A four-cluster solution provided a good fit to the data; profiles included a neuropsychologically normal cluster, a globally impaired cluster, and two clusters of mixed profiles. Cognitive burden was associated with symptom severity and poorer community functioning. The patterns of cognitive performance by cluster were highly consistent with our previous findings.Conclusions:We found evidence of four cognitive subgroups of patients with psychosis, with cognitive profiles that map closely to those produced in our previous work. Clusters were associated with clinical and community variables and a measure of premorbid functioning, suggesting that they reflect meaningful groupings: replicable, and related to clinical presentation and functional outcomes. (JINS, 2018,24, 382–390)
World health by place: the politics of international health system metrics, 1924–c.2010
Authors: Gorsky Martin , Sirrs Christopher 
Published: October 2017

AbstractThis article examines the development of health system metrics by international organizations, exploring their relationship to the politics of world health. Current historiography treats measurement either as progressive illumination or adopts a critical stance, viewing indicators as instruments of global governance by powerful nations. We draw on diverse statistical publications to provide an empirical overview of change and continuity, beginning with the League of Nations Health Organization, which initiated health system statistics, and concluding with theWorld health report 2000, with its controversial comparative rankings. We then develop analysis and explanation of these trends. Population indicators appeared consistently owing to their protective function and compatibility with development thinking. Others, related to provision, financing, and coverage, appeared more sporadically, owing to changing trends and assumptions in international health. While partly affirming the critical literature, metrics were also used by peripheral or resistant actors to challenge or influence policy at the centre.
Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior
Authors: Bocchi Riccardo , Egervari Kristof , Carol-Perdiguer Laura , Viale Beatrice , Quairiaux Charles , De Roo Mathias , Boitard Michael , Oskouie Suzanne , Salmon Patrick , Kiss Jozsef Z. 
Published: October 2017

AbstractPerturbed neuronal migration and circuit development have been implicated in the pathogenesis of neurodevelopmental diseases; however, the direct steps linking these developmental errors to behavior alterations remain unknown. Here we demonstrate that Wnt/C-Kit signaling is a key regulator of glia-guided radial migration in rat somatosensory cortex. Transient downregulation of Wnt signaling in migrating, callosal projection neurons results in delayed positioning in layer 2/3. Delayed neurons display reduced neuronal activity with impaired afferent connectivity causing permanent deficit in callosal projections. Animals with these defects exhibit altered somatosensory function with reduced social interactions and repetitive movements. Restoring normal migration by overexpressing the Wnt-downstream effector C-Kit or selective chemogenetic activation of callosal projection neurons during a critical postnatal period prevents abnormal interhemispheric connections as well as behavioral alterations. Our findings identify a link between defective canonical Wnt signaling, delayed neuronal migration, deficient interhemispheric connectivity and abnormal social behavior analogous to autistic characteristics in humans.
BCL-XL directly modulates RAS signalling to favour cancer cell stemness
Authors: Carné Trécesson Sophie de , Souazé Frédérique , Basseville Agnès , Bernard Anne-Charlotte , Pécot Jessie , Lopez Jonathan , Bessou Margaux , Sarosiek Kristopher A. , Letai Anthony , Barillé-Nion Sophie , Valo Isabelle , Coqueret Olivier , Guette Catherine , Campone Mario , Gautier Fabien , Juin Philippe Paul 
Published: October 2017

AbstractIn tumours, accumulation of chemoresistant cells that express high levels of anti-apoptotic proteins such as BCL-XL is thought to result from the counter selection of sensitive, low expresser clones during progression and/or initial treatment. We herein show that BCL-XL expression is selectively advantageous to cancer cell populations even in the absence of pro-apoptotic pressure. In transformed human mammary epithelial cells BCL-XL favours full activation of signalling downstream of constitutively active RAS with which it interacts in a BH4-dependent manner. Comparative proteomic analysis and functional assays indicate that this is critical for RAS-induced expression of stemness regulators and maintenance of a cancer initiating cell (CIC) phenotype. Resistant cancer cells thus arise from a positive selection driven by BCL-XL modulation of RAS-induced self-renewal, and during which apoptotic resistance is not necessarily the directly selected trait.
Genomic variation in microbial populations inhabiting the marine subseafloor at deep-sea hydrothermal vents
Authors: Anderson Rika E. , Reveillaud Julie , Reddington Emily , Delmont Tom O. , Eren A. Murat , McDermott Jill M. , Seewald Jeff S. , Huber Julie A. 
Published: October 2017

AbstractLittle is known about evolutionary drivers of microbial populations in the warm subseafloor of deep-sea hydrothermal vents. Here we reconstruct 73 metagenome-assembled genomes (MAGs) from two geochemically distinct vent fields in the Mid-Cayman Rise to investigate patterns of genomic variation within subseafloor populations. Low-abundance populations with high intra-population diversity coexist alongside high-abundance populations with low genomic diversity, with taxonomic differences in patterns of genomic variation between the mafic Piccard and ultramafic Von Damm vent fields. Populations from Piccard are significantly enriched in nonsynonymous mutations, suggesting stronger purifying selection in Von Damm relative to Piccard. Comparison of nine Sulfurovum MAGs reveals two high-coverage, low-diversity MAGs from Piccard enriched in unique genes related to the cellular membrane, suggesting these populations were subject to distinct evolutionary pressures that may correlate with genes related to nutrient uptake, biofilm formation, or viral invasion. These results are consistent with distinct evolutionary histories between geochemically different vent fields, with implications for understanding evolutionary processes in subseafloor microbial populations.
Sliding of coherent twin boundaries
Authors: Wang Zhang-Jie , Li Qing-Jie , Li Yao , Huang Long-Chao , Lu Lei , Dao Ming , Li Ju , Ma Evan , Suresh Subra , Shan Zhi-Wei 
Published: October 2017

AbstractCoherent twin boundaries (CTBs) are internal interfaces that can play a key role in markedly enhancing the strength of metallic materials while preserving their ductility. They are known to accommodate plastic deformation primarily through their migration, while experimental evidence documenting large-scale sliding of CTBs to facilitate deformation has thus far not been reported. We show here that CTB sliding is possible whenever the loading orientation enables the Schmid factors of leading and trailing partial dislocations to be comparable to each other. This theoretical prediction is confirmed by real-time transmission electron microscope experimental observations during uniaxial deformation of copper pillars with different orientations and is further validated at the atomic scale by recourse to molecular dynamics simulations. Our findings provide mechanistic insights into the evolution of plasticity in heavily twinned face-centered cubic metals, with the potential for optimizing mechanical properties with nanoscale CTBs in material design.
A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation
Authors: Zhou Haibin , Lu Jianfeng , Liu Liu , Bernard Denzil , Yang Chao-Yie , Fernandez-Salas Ester , Chinnaswamy Krishnapriya , Layton Stephanie , Stuckey Jeanne , Yu Qing , Zhou Weihua , Pan Zhenqiang , Sun Yi , Wang Shaomeng 
Published: October 2017

AbstractThe Cullin-RING E3 ubiquitin ligases (CRLs) regulate homeostasis of ~20% of cellular proteins and their activation require neddylation of their cullin subunit. Cullin neddylation is modulated by a scaffolding DCN protein through interactions with both the cullin protein and an E2 enzyme such as UBC12. Here we report the development of DI-591 as a high-affinity, cell-permeable small-molecule inhibitor of the DCN1–UBC12 interaction. DI-591 binds to purified recombinant human DCN1 and DCN2 proteins with Ki values of 10–12 nM, and disrupts the DCN1–UBC12 interaction in cells. Treatment with DI-591 selectively converts cellular cullin 3 into an un-neddylated inactive form with no or minimum effect on other cullin members. Our data firmly establish a previously unrecognized specific role of the DCN1–UBC12 interaction for cellular neddylation of cullin 3. DI-591 is an excellent probe compound to investigate the role of the cullin 3 CRL ligase in biological processes and human diseases.
Harnessing a catalytic lysine residue for the one-step preparation of homogeneous antibody-drug conjugates
Authors: Nanna Alex R. , Li Xiuling , Walseng Even , Pedzisa Lee , Goydel Rebecca S. , Hymel David , Burke Terrence R. , Roush William R. , Rader Christoph 
Published: October 2017

AbstractCurrent strategies to produce homogeneous antibody-drug conjugates (ADCs) rely on mutations or inefficient conjugation chemistries. Here we present a strategy to produce site-specific ADCs using a highly reactive natural buried lysine embedded in a dual variable domain (DVD) format. This approach is mutation free and drug conjugation proceeds rapidly at neutral pH in a single step without removing any charges. The conjugation chemistry is highly robust, enabling the use of crude DVD for ADC preparation. In addition, this strategy affords the ability to precisely monitor the efficiency of drug conjugation with a catalytic assay. ADCs targeting HER2 were prepared and demonstrated to be highly potent and specific in vitro and in vivo. Furthermore, the modular DVD platform was used to prepare potent and specific ADCs targeting CD138 and CD79B, two clinically established targets overexpressed in multiple myeloma and non-Hodgkin lymphoma, respectively.
Generalist species drive microbial dispersion and evolution
Authors: Sriswasdi Sira , Yang Ching-chia , Iwasaki Wataru 
Published: October 2017

AbstractMicrobes form fundamental bases of every Earth ecosystem. As their key survival strategies, some microbes adapt to broad ranges of environments, while others specialize to certain habitats. While ecological roles and properties of such “generalists” and “specialists” had been examined in individual ecosystems, general principles that govern their distribution patterns and evolutionary processes have not been characterized. Here, we thoroughly identified microbial generalists and specialists across 61 environments via meta-analysis of community sequencing data sets and reconstructed their evolutionary histories across diverse microbial groups. This revealed that generalist lineages possess 19-fold higher speciation rates and significant persistence advantage over specialists. Yet, we also detected three-fold more frequent generalist-to-specialist transformations than the reverse transformations. These results support a model of microbial evolution in which generalists play key roles in introducing new species and maintaining taxonomic diversity.
HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells
Authors: Lin Yuan , Fang Zhe-Ping , Liu Hong-Juan , Wang Li-Jing , Cheng Zhiqiang , Tang Na , Li Tingting , Liu Tengfei , Han Hai-Xiong , Cao Guangwen , Liang Li , Ding Yan-Qing , Zhou Wei-Jie 
Published: October 2017

AbstractInduction of endogenous adult stem cells by administering soluble molecules provides an advantageous approach for tissue damage repair, which could be a clinically applicable and cost-effective alternative to transplantation of embryonic or pluripotent stem cell-derived tissues for the treatment of acute organ failures. Here, we show that HGF/Rspo1 induce liver stem cells and rescue liver dysfunction. Carbon tetrachloride treatment promotes both fibrosis and Lgr5+ liver stem cell proliferation, whereas Lgr5 knockdown worsens fibrosis. Injection of HGF in combination with Rspo1 increases the number of Lgr5+ liver stem cells and improves liver function by attenuating fibrosis. We observe Lgr5+ liver stem cells in human liver fibrosis tissues, and once they are isolated, these cells are able to form organoids, and treatment with HGF/Rspo1 promotes their expansion. We suggest that Lgr5+ liver stem cells represent a valuable target for liver damage treatment, and that HGF/Rspo1 can be used to promote liver stem cell expansion.
Human microbiome signatures of differential colorectal cancer drug metabolism
Authors: Guthrie Leah , Gupta Sanchit , Daily Johanna , Kelly Libusha 
Published: October 2017

AbstractIt is well appreciated that microbial metabolism of drugs can influence treatment efficacy. Microbial β-glucuronidases in the gut can reactivate the excreted, inactive metabolite of irinotecan, a first-line chemotherapeutic for metastatic colorectal cancer. Reactivation causes adverse drug responses, including severe diarrhea. However, a direct connection between irinotecan metabolism and the composition of an individual’s gut microbiota has not previously been made. Here, we report quantitative evidence of inter-individual variability in microbiome metabolism of the inactive metabolite of irinotecan to its active form. We identify a high turnover microbiota metabotype with potentially elevated risk for irinotecan-dependent adverse drug responses. We link the high turnover metabotype to unreported microbial β-glucuronidases; inhibiting these enzymes may decrease irinotecan-dependent adverse drug responses in targeted subsets of patients. In total, this study reveals metagenomic mining of the microbiome, combined with metabolomics, as a non-invasive approach to develop biomarkers for colorectal cancer treatment outcomes.