bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Personalized Intervention for Alzheimer’s Disease
Authors: Peng Xing , Xing Peiqi , Li Xiuhui , Qian Ying , Song Fuhai , Bai Zhouxian , Han Guangchun , Lei Hongxing 
Published: October 2016

Abstract
Alzheimer’s disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells (iPSCs). Comprehensive information collection, better understanding of the disease mechanisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.
Which types of mental work demands may be associated with reduced risk of dementia?
Authors: Then Francisca S. , Luck Tobias , Heser Kathrin , Ernst Annette , Posselt Tina , Wiese Birgitt , Mamone Silke , Brettschneider Christian , König Hans‐Helmut , Weyerer Siegfried , Werle Jochen , Mösch Edelgard , Bickel Horst , Fuchs Angela , Pentzek Michael , Maier Wolfgang , Scherer Martin , Wagner Michael , Riedel‐Heller Steffi G. , Abholz Heinz‐Harald , Brettschneider Christian , Bachmann Cadja , Bickel Horst , Blank Wolfgang , van den Bussche Hendrik , Eifflaender‐Gorfer Sandra , Eisele Marion , Ernst Annette , Fuchs Angela , Heser Kathrin , Jessen Frank , Kaduszkiewicz Hanna , Kaufeler Teresa , Köhler Mirjam , König Hans‐Helmut , Koppara Alexander , Lange Carolin , Lubisch Diana , Luck Tobias , Luppa Melanie , Maier Wolfgang , Mayer Manfred , Mösch Edelgard , Pentzek Michael , Posselt Tina , Prokein Jana , Riedel‐Heller Steffi , Röhr Susanne , Scherer Martin , Schumacher Anna , Stein Janine , Steinmann Susanne , Tebarth Franziska , Wagner Michael , Weckbecker Klaus , Weeg Dagmar , Werle Jochen , Weyerer Siegfried , Wiese Birgitt , Wolfsgruber Steffen , Zimmermann Thomas , van den Bussche Hendrik , Maier Wolfgang , Scherer Martin 
Published: October 2016

IntroductionPrevious studies have demonstrated that an overall high level of mental work demands decreased dementia risk. In our study, we investigated whether this effect is driven by specific mental work demands and whether it is exposure dependent.MethodsPatients aged 75+ years were recruited from general practitioners and participated in up to seven assessment waves (every 1.5 years) of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work demands on dementia risk were carried out via multivariate regression modeling (n = 2315).ResultsWe observed a significantly lower dementia risk in individuals with a higher level of “information processing” (HR, 0.888), “pattern detection” (HR, 0.878), “mathematics” (HR, 0.878), and “creativity” (HR, 0.878). Yet, exposure‐dependent effects were only significant for “information processing” and “pattern detection.”DiscussionOur longitudinal observations suggest that dementia risk may be reduced by some but not all types of mental work demands.
The financial burden and health care utilization patterns associated with amnestic mild cognitive impairment
Authors: Ton Thanh G.N. , DeLeire Thomas , May Suepattra G. , Hou Ningqi , Tebeka Mahlet G. , Chen Er , Chodosh Joshua 
Published: October 2016

AbstractIntroductionIndividuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia.MethodsWith data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross‐sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns.ResultsPatients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < .001) and were also significantly less likely to have been hospitalized (P = .04) and admitted to nursing home (P < .001). Compared to individuals with normal cognition, patients with aMCI had significantly less household income (P = .018).DiscussionPatients with aMCI had lower medical expenditures than patients with AD dementia. Poor cognitive status was linearly associated with lower household income, higher medical expenditures, higher likelihood of nursing and home care services, and lower likelihood of outpatient visits.
Longitudinal brain structural changes in preclinical Alzheimer's disease
Authors: Pegueroles Jordi , Vilaplana Eduard , Montal Victor , Sampedro Frederic , Alcolea Daniel , Carmona‐Iragui Maria , Clarimon Jordi , Blesa Rafael , Lleó Alberto , Fortea Juan ,   Alzheimer's Disease Neuroimaging Initiative
Published: October 2016

AbstractIntroductionBrain structural changes in preclinical Alzheimer's disease (AD) are poorly understood.MethodsWe compared the changes in cortical thickness in the ADNI cohort during a 2‐year follow‐up between the NIA‐AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates.ResultsAt follow‐up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ1–42 levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ1–42 levels.DiscussionOur longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy.
mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease
Authors: Norambuena Andrés , Wallrabe Horst , McMahon Lloyd , Silva Antonia , Swanson Eric , Khan Shahzad S. , Baerthlein Daniel , Kodis Erin , Oddo Salvatore , Mandell James W. , Bloom George S. 
Published: October 2016

AbstractA major obstacle to presymptomatic diagnosis and disease‐modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid‐β oligomers (AβOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AβO‐induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1‐dependent tau phosphorylation, and that CCR can be prevented by insulin‐stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death.
Usefulness of early colonoscopy in the diagnosis and treatment of moderate or severe lower gastrointestinal bleeding
Authors: Correa Paulo , Teixeira Carolina , Zago Rodrigo R. , Rossini Giulio , Paccos Jose Luiz , Popoutchi Pedro , Loureiro Jarbas F. , Borges Jose Luiz , Averbach Marcelo 
Published: October 2016

AbstractA total of 38,686 colonoscopies were performed between January 1985 and December 2012 at Hospital Sírio-Libanês, in São Paulo, Brazil. Two hundred thirty-four patients (0.6%) had acute lower gastrointestinal bleeding of moderate or severe intensity. A definitive diagnosis was possible in 151 cases, 64.5% of these patients.This study was approved by the Institutional Review Board. Medical charts were reviewed.All examinations were done under sedation by the same medical team.The predominant sources of bleeding were colonic diverticula (73 patients; 31%), ischemic or infectious colitis (18 patients; 7.7%) and radiation proctitis (18 patients; 7.7%).A specific therapeutic intervention was performed on 61 of the 151 patients who had the diagnosis confirmed (40.4%), according to the source of bleeding. Most patients with postpolypectomy bleeding were treated with injection of epinephrine (40%) and clipping (40%). Patients with angiodysplasia were treated predominantly with argon plasma coagulation (42%).Injection of epinephrine was the most frequent treatment, regardless of the source of bleeding (34.4%), followed by argon plasma coagulation (31.1%).Control of active hemorrhage was achieved endoscopically in 98.8% of the patients.Our data shows that early colonoscopy in the management of patients with suspected acute lower gastrointestinal bleeding is a useful tool for diagnosis and treatment.
TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women with Vulvar and Vaginal Atrophy: The REJOICE Trial
Authors: Kingsberg Sheryl A. , Derogatis Leonard , Simon James A. , Constantine Ginger D. , Graham Shelli , Bernick Brian , Gasper Gina , Mirkin Sebastian 
Published: October 2016

ABSTRACTIntroductionTX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17β-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA).AimTo evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA.MethodsThe REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 μg) with placebo in postmenopausal women (40–75 years old) with VVA and a most bothersome symptom of moderate to severe dyspareunia. Changes in the percentage of superficial and parabasal cells, vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual dysfunction was evaluated as a secondary end point using the Female Sexual Function Index (FSFI) patient self-report inventory.Main Outcome MeasuresChanges from baseline to week 12 in total and individual domain FSFI scores for each TX-004HR dose were compared with those for placebo.ResultsAll three TX-004HR doses increased the baseline total FSFI score after 12 weeks, with 10 μg (P &lt; .05) and 25 μg (P = .0019) having a significantly greater effect than placebo. A similar trend was observed for the individual FSFI domains, with 10 and 25 μg significantly improving baselines scores for pain and lubrication at 12 weeks (P ≤ .015 for all vs placebo). Changes from baseline to week 12 in arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for TX-004HR 25 μg vs placebo. All three TX-004HR doses were comparable to placebo in their effect on desire and orgasm.ConclusionTX-004HR improved FSFI scores in a dose-dependent manner. The observed improvements in sexual function suggest that TX-004HR is a promising treatment option for postmenopausal VVA with a potential added beneficial effect on female sexual dysfunction.
Role of Body Esteem in the Sexual Excitation and Inhibition Responses of Women with and Without a History of Childhood Sexual Abuse
Authors: Kilimnik Chelsea D. , Meston Cindy M. 
Published: October 2016

ABSTRACTIntroductionWomen's sexuality is influenced by their perceptions of their bodies. Negative body appraisals have been implicated in the development and maintenance of sexual concerns in women with a history of childhood sexual abuse (CSA). The sexuality of these women is often expressed in extremes of approach and avoidant sexual tendencies, which have been related to the sexual inhibition and sexual excitation pathways of the dual control model.AimTo test the influence of body esteem on the sexual excitation and inhibition responses of women with and without a history of CSA.MethodsOne hundred thirty-nine women with CSA and 83 non-abused women reported on their abuse history, depressive symptomology, sexual response, and affective appraisals of their body.Main Outcome MeasuresValidated self-report measurements of sexual excitation and inhibition responses (Sexual Excitation/Sexual Inhibition Inventory for Women) and body esteem (Body Esteem Scale) were administered.ResultsBody esteem was significantly associated with sexual inhibition responses of women regardless of CSA history status but was significantly related only to the sexual excitation responses of women with a CSA history. Perceived sexual attractiveness was a unique predictor of sexual excitation in women with a history of CSA.ConclusionWomen with a history of CSA have lower body esteem than non-abused women, particularly in self-perceived sexual attractiveness, and these perceptions appear to influence their sexual responses by acting on the sexual excitation and inhibition response pathways.
Psychosexual Outcome Among Iranian Individuals with 5α-Reductase Deficiency Type 2 and Its Relationship with Parental Sexism
Authors: Khorashad Behzad S. , Aghili Zahra , Kreukels Baudewijntje P.C. , Hiradfar Mehran , Roshan Ghasem M. , Afkhamizadeh Mozhgan , Abbaszadegan Mohammad Reza , Ghaemi Nosrat , Khazai Behnaz , Cohen-Kettenis P.T. 
Published: October 2016

ABSTRACTIntroductionFew studies exist on the psychosexual outcome of homogeneous groups of individuals with 5α-reductase deficiency type 2 (5α-RD-2) and the relation between gender changes and parental hostile and benevolent sexism, which are two components of ambivalent sexism that assume a stereotypical approach toward women in an overtly negative way or a chivalrous, seemingly positive way.AimTo report on the psychosexual outcome of individuals with 5α-RD-2 and to investigate its relation to the level of parental sexism in a relatively large sample of Iranians with 5α-RD-2.MethodsTwenty participants (mean age = 19.5 years, SD = 6.345) with a molecularly confirmed diagnosis of 5α-RD-2 who were assigned the female gender at birth and raised as female were included in the study. Participants and their parents were interviewed and their medical records were assessed. Parents also completed the Ambivalent Sexism Inventory (ASI), which includes hostile and benevolent sexism subscales.Main Outcome MeasuresPsychosexual outcome and parental hostile and benevolent sexism measurements.ResultsTwelve of 20 participants (60%) were diagnosed with gender identity disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision). Ten of these transitioned to the male gender. The other 10 participants (50%), including the two diagnosed with gender identity disorder not otherwise specified, continued living in a female gender role. When comparing the ASI subscale scores between families of participants who changed their gender and those who did not, no significant difference was found for ASI total and hostile sexism scores, but there was a difference for benevolent sexism (P = .049): those whose daughters had changed their gender had higher benevolent sexism scores.ConclusionThe high prevalence of gender change and gender dysphoria reported in the literature was confirmed in this relatively large and homogeneous sample of Iranians with 5-α-RD-2 raised as female. Prenatal exposure to testosterone is hypothesized to play a role in the development of gender identity and sexual orientation, but parental attitudes also might be important. Although gender change in individuals with 5-α-RD-2 is often attributed to high levels of hostile sexism in some cultures, our findings show this to be associated with benevolent sexism.
Differential Effects of Cyproterone Acetate vs Spironolactone on Serum High-Density Lipoprotein and Prolactin Concentrations in the Hormonal Treatment of Transgender Women
Authors: Fung Raymond , Hellstern-Layefsky Miriam , Tastenhoye Camille , Lega Iliana , Steele Leah 
Published: October 2016

ABSTRACTIntroductionSpironolactone and cyproterone acetate (CPA) are the two main antiandrogen medications used in feminizing hormone therapy in transgender women. Previous studies have suggested that these two agents might have opposite effects on high-density lipoprotein (HDL) level when used in this context, and limited data have suggested CPA increases prolactin more than spironolactone.AimTo compare the effects of spironolactone and CPA on HDL and prolactin serum concentrations in transgender women.MethodsA retrospective chart review was conducted at three clinical sites in Toronto, Ontario, Canada. Patients were selected if they (i) identified as a transgender woman, (ii) had newly started spironolactone or CPA with estrogen or restarted spironolactone or CPA after a washout period of at least 6 months, and (iii) had not used other antiandrogens within the previous 6 months.Main Outcome MeasuresHDL and prolactin concentrations between the two treatment groups at baseline and at 12 months.ResultsEighty-two patients were included in the spironolactone group and 31 patients were included in the CPA group. Baseline HDL and prolactin levels were not significantly different between the two groups. At 12 months, HDL increased by 0.10 mmol/L (SD = 0.24) in the spironolactone group but decreased by 0.07 mmol/L (SD = 0.21) in the CPA group (P = .002). The difference remained significant after adjusting for baseline HDL, use of lipid-lowering drugs, and age. The change in prolactin was +3.10 μg/L (SD = 5.70) in the spironolactone group and +11.8 μg/L (SD = 8.63) in the CPA group (P &lt; 0.001). This difference also remained significant after adjusting for baseline prolactin level.ConclusionThese data suggest that spironolactone use in transgender women increases HDL levels and that CPA has the opposite effect. CPA also is associated with a larger increase in prolactin. These factors should be considered when choosing between these two antiandrogen agents.
Surgical Outcomes of Erectile Implants After Phalloplasty: Retrospective Analysis of 95 Procedures
Authors: Neuville Paul , Morel-Journel Nicolas , Maucourt-Boulch Delphine , Ruffion Alain , Paparel Philippe , Terrier Jean-Etienne 
Published: October 2016

ABSTRACTIntroductionThe creation of a neophallus is a complex surgery that must meet functional and esthetic requirements. It is a long and demanding surgical process whose final stage consists of the implantation of a rigid or inflatable material that can be used to reproduce an erection. Data in the literature are scarce, with only the pioneering series present, which includes the use of the first devices and techniques.AimTo report the outcome of patients with phalloplasty after implantation of erectile implants using standardized surgical techniques and the use of recent prosthesis types with or without a vascular graft.MethodsThis is a retrospective hospital-based analysis of all patients with phalloplasty who underwent implantation of an erectile prosthesis from March 2007 to May 2015. Factors associated with complications were investigated by multivariate logistic regression analysis.Main Outcome MeasuresEarly-onset (during the first month after surgery) and late-onset complications, including erosion, infections, malpositioning, and dysfunction.ResultsSixty-nine patients were included in the study and 95 procedures were analyzed. After a median follow-up of 4 years (minimum = 169 days, maximum = 6.1 years), the original prosthesis was still in place in 43 patients (62.3%). Patients underwent phalloplasty after female-to-male transsexualism (n = 62, 89.9%), malformation (n = 4, 5.8%), or trauma (n = 3, 4.3%). The proportions for the different types of phalloplasty were 58% for forearm free flap phalloplasty (n = 40), 33.3% for suprapubic phalloplasty (n = 23), and 7% for other (n = 6). The erectile prostheses used were the two-piece AMS Ambicor (n = 71, 74.7%), the Ambicor with a vascular graft (n = 19, 20.0%), and the AMS 700CXR, AMS 700CX, or AMS600-650 (n = 5, 5.2%). There were no early-onset complications in 89 procedures (93.7%) and, when present, they were always related to infection (n = 4, 4.2%). Late-onset complications were erosion (n = 4, 4.2%), infection (n = 4, 4.2%), dysfunction (n = 10, 10.5%), and malpositioning (n = 12, 12.6%). No significant difference was observed for malpositioning (12.7% vs 10.5%, P = .87) and dysfunction (7.0% vs 10.5%, P = .78) between the AMS Ambicor prosthesis and the Ambicor prosthesis with a vascular graft.ConclusionThis study provides updated data on complications after the implantation of erectile implants. Multicenter studies, including the evaluation of patient satisfaction, are needed to increase our understanding of factors associated with the outcomes.
VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase‐mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal
Authors: Bastola Prabhakar , Neums Lisa , Schoenen Frank J. , Chien Jeremy 
Published: October 2016

AbstractValosin‐containing protein (VCP) or p97, a member of AAA‐ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum‐associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline‐based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap‐dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis. Mechanistic studies point to the unresolved unfolded protein response (UPR) as a mechanism by which VCP inhibitors contribute to cytotoxicity. These results support an emerging concept that UPR and endoplasmic reticulum (ER) stress pathways may be targeted in ovarian cancer as a source of vulnerability. Since prolonged ER stress may result in CHOP‐mediated cell death, we tested the hypothesis that VCP inhibitors act synergistically with compounds that enhance CHOP expression. Here, we show that VCP inhibitors act synergistically with Salubrinal, an inhibitor of eIF2α dephosphorylation, by enhancing CHOP expression in ovarian cancer cell lines. Our results provide a proof‐of‐concept that VCP inhibitors can be used as a single agent and can be synergized with compounds that enhance CHOP expression to induce cell death in ovarian cancer cells.