bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired Resistance to BET-PROTACs (Proteolysis-Targeting Chimeras) Caused by Genomic Alterations in Core Components of E3 Ligase Complexes
Authors: Zhang Lu , Riley-Gillis Bridget , Vijay Priyanka , Shen Yu 
Published: May 2019

Abstract
Proteolysis-targeting chimeras (PROTAC) are bifunctional molecules that hijack endogenous E3 ubiquitin ligases to induce ubiquitination and subsequent degradation of protein of interest. Recently, it has been shown that PROTACs with robust in vitro and in vivo activities and, in some cases, drug-like pharmaceutical properties can be generated using small-molecule ligands for the E3 ligases VHL and CRBN. These findings stoked tremendous enthusiasm on using PROTACs for therapeutics development. Innate and acquired drug resistance often underlies therapeutic failures, particularly for cancer therapy. With the PROTAC technology progressing rapidly toward therapeutic applications, it would be important to understand whether and how resistance to these novel agents may emerge. Using BET-PROTACs as a model system, we demonstrate that resistance to both VHL- and CRBN-based PROTACs can occur in cancer cells following chronic treatment. However, unlike what was often observed for many targeted therapeutics, resistance to BET-PROTACs did not result from secondary mutations that affect compound binding to the target. In contrast, acquired resistance to both VHL- and CRBN-based BET-PROTACs was primarily caused by genomic alterations that compromise core components of the relevant E3 ligase complexes.
Population Control of Free-Ranging Dogs in Turkey: Never Kill Strategy
Authors: Salgirli Demirbas Yasemin , Saral Begum , Safak C. Etkin , Graça Da Pereira Gonçalo 
Published: May 2019

Abstract
Turkey is one of the developing countries facing a serious free-ranging dog problem. Although the Catch, Neuter, Vaccinate, Return (CNVR) method has been implemented in shelters since 2004, the population of free ranging dogs continues to increase. In this review, Turkey’s control strategy for free-ranging dog population, its effectiveness and other factors affecting free-ranging dog control are discussed.
Linkages between the South and East Asian Monsoon Water Vapor Transport during Boreal Summer
Authors: Liu Yong , Huang Ronghui 
Published: May 2019

AbstractThis study provides a water vapor transport (WVT) perspective on the linkages between the South Asian and East Asian summer monsoons (SASM and EASM) and indicates two robustly coupled modes of the vertical integrated WVT (VIWVT) over the two monsoons that accounts for above 90% of the total squared covariance fraction. The first coupled mode [singular value decomposition mode 1 (SVD1 mode)] depicts a meridional linkage between the meridional dipole VIWVT anomalies over both the SASM and EASM, while the second coupled mode (SVD2 mode) illustrates a zonal connection of an anomalous cyclonic/anticyclonic VIWVT over the SASM and a zonal wavelike VIWVT over the EASM. The SVD1 mode is linked through the anomalous subtropical high over the western North Pacific (WNPSH) and is primarily associated with the transition phase of El Niño/La Niña (ENSO) and simultaneous Indian Ocean basin mode (IOBM) SST warming/cooling. The meridional connection of the VIWVT in the SVD1 mode experienced a clear intensification since the late 1970s that may be attributed to the strengthened impacts of the ENSO/IOBM on the EASM and SASM after the late 1970s. The SVD2 mode is connected by the circumglobal teleconnection (CGT) pattern and related to the developing phase of ENSO and summer North Atlantic tripole (NAT) SST anomalies. The zonal VIWVT connection in SVD2 mode is strongly modulated by the SASM–CGT connections and reveals significant weakening since the late 1970s but reintensifies after the early 1990s. This may be associated with the weakened ENSO–SASM relationship after the late 1970s and interdecadal decreasing of the all Indian summer rainfall since the early 1990s.
Hydroclimate Responses over Global Monsoon Regions Following Volcanic Eruptions at Different Latitudes
Authors: Zuo Meng , Zhou Tianjun , Man Wenmin 
Published: May 2019

AbstractUnderstanding the influence of volcanic eruptions on the hydroclimate over global monsoon regions is of great scientific and social importance. However, the link between the latitude of volcanic eruptions and related hydroclimate changes over global monsoon regions in the last millennium remains inconclusive. Here we show divergent hydroclimate responses after different volcanic eruptions based on large sets of reconstructions, observations, and climate model simulation. Both the proxy and observations show that Northern Hemispheric (Southern Hemispheric) monsoon precipitation is weakened by northern (southern) and tropical eruptions but is enhanced by the southern (northern) eruptions. A similar relationship is found in coupled model simulations driven by volcanic forcing. The model evidence indicates that the dynamic processes related to changes in atmospheric circulation play a dominant role in precipitation responses. The dry conditions over the Northern Hemisphere (Southern Hemisphere) and global monsoon regions following northern (southern) and tropical eruptions are induced through weakened monsoon circulation. The wet conditions over Northern Hemispheric (Southern Hemispheric) monsoon regions after southern (northern) eruptions are caused by the enhanced cross-equator flow. We extend our model simulation analysis from mean state precipitation to extreme precipitation and find that the response of the extreme precipitation is consistent with that of the mean precipitation but is more sensitive over monsoon regions. The response of surface runoff and net primary production is stronger than that of precipitation over some submonsoon regions. Our results imply that it is imperative to consider the potential volcanic eruptions at different hemispheres in the design of near-term decadal climate prediction experiments.
Completion Rates, Adverse Effects, and Costs of a 3-Month and 9-Month Treatment Regimen for Latent Tuberculosis Infection in California Inmates, 2011-2014
Authors: Wheeler Charlotte , Mohle-Boetani Janet 
Published: May 2019

Objectives: In California, about 80% of tuberculosis disease is caused by untreated latent tuberculosis infection (LTBI), and the rate of LTBI is higher among incarcerated persons (16%) than among nonincarcerated persons (6%). We compared 2 regimens to treat LTBI in an adult prison population in California: 9 months of twice-weekly isoniazid (9H; previous standard of care) and 12 once-weekly doses of isoniazid and rifapentine (3HP; introduced in 2011). Methods: We evaluated the rates of completion and discontinuation caused by hepatotoxicity among randomly selected patients with LTBI prescribed the 9H regimen in 2011 and among patients with LTBI prescribed the 3HP regimen who entered California prisons during September 2013–March 2014. We compared the cost per fully treated patient for the 2 regimens. Results: Of 92 patients treated with the 9H regimen, the treatment completion rate was 42% and discontinuation due to hepatotoxicity was 14%. Of 122 patients who accepted the 3HP regimen, the completion rate was 90% and discontinuation due to hepatotoxicity was 2%. The cost per fully treated patient for the 9H regimen was $981 and for 3HP was $652. Conclusions: In an incarcerated population, the 3HP regimen had a higher completion rate, lower hepatotoxicity, and lower cost per fully treated patient than the 9H regimen. If coupled with a high treatment initiation rate, the high rate of LTBI treatment completion with 3HP may contribute to reducing tuberculosis morbidity in California.
Venous Thromboembolism in Neurocritical Care Patients
Authors: Viarasilpa Tanuwong , Panyavachiraporn Nicha , Jordan Jack , Marashi Seyed Mani , van Harn Meredith , Akioyamen Noel O. , Kowalski Robert G. , Mayer Stephan A. 
Published: May 2019

Background: Venous thromboembolism (VTE) is a potentially life-threatening complication among critically ill patients. Neurocritical care patients are presumed to be at high risk for VTE; however, data regarding risk factors in this population are limited. We designed this study to evaluate the frequency, risk factors, and clinical impact of VTE in neurocritical care patients. Methods: We obtained data from the electronic medical record of all adult patients admitted to neurological intensive care unit (NICU) at Henry Ford Hospital between January 2015 and March 2018. Venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both diagnosed by Doppler, chest computed tomography (CT) angiography or ventilation–perfusion scan >24 hours after admission. Patients with ICU length of stay <24 hours or who received therapeutic anticoagulants or were diagnosed with VTE within 24 hours of admission were excluded. Results: Among 2188 consecutive NICU patients, 63 (2.9%) developed VTE. Prophylactic anticoagulant use was similar in patients with and without VTE (95% vs 92%; P = .482). Venous thromboembolism was associated with higher mortality (24% vs 13%, P = .019), and longer ICU (12 [interquartile range, IQR 5-23] vs 3 [IQR 2-8] days, P < .001) and hospital (22 [IQR 15-36] vs 8 [IQR 5-15] days, P < .001) length of stay. In a multivariable analysis, potentially modifiable predictors of VTE included central venous catheterization (odds ratio [OR] 3.01; 95% confidence interval [CI], 1.69-5.38; P < .001) and longer duration of immobilization (Braden activity score <3, OR 1.07 per day; 95% CI, 1.05-1.09; P < .001). Nonmodifiable predictors included higher International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) scores (which accounts for age >60, prior VTE, cancer and thrombophilia; OR 1.66; 95% CI, 1.40-1.97; P < .001) and body mass index (OR 1.05; 95% CI, 1.01-1.08; P = .007). Conclusions: Despite chemoprophylaxis, VTE still occurred in 2.9% of neurocritical care patients. Longer duration of immobilization and central venous catheterization are potentially modifiable risk factors for VTE in critically ill neurological patients.
Use of a simulation-based advanced resuscitation training curriculum: Impact on cardiopulmonary resuscitation quality and patient outcomes
Authors: Young Amanda K , Maniaci Michael J , Simon Leslie V , Lowman Philip E , McKenna Ryan T , Thomas Colleen S , Cochuyt Jordan J , Vadeboncoeur Tyler F 
Published: May 2019

Background Despite a continued focus on improved cardiopulmonary resuscitation quality, survival remains low from in-hospital cardiac arrest. Advanced Resuscitation Training has been shown to improve survival to hospital discharge and survival with good neurological outcome following in-hospital cardiac arrest at its home institution. We sought to determine if Advanced Resuscitation Training implementation would improve patient outcomes and cardiopulmonary resuscitation quality at our institution. Methods This was a prospective, before–after study of adult in-hospital cardiac arrest victims who had cardiopulmonary resuscitation performed. During phase 1, standard institution cardiopulmonary resuscitation training was provided. During phase 2, providers received the same quantity of training, but with emphasis on Advanced Resuscitation Training principles. Primary outcomes were return of spontaneous circulation, survival to hospital discharge, and neurologically favorable survival. Secondary outcomes were cardiopulmonary resuscitation quality parameters. Results A total of 156 adult in-hospital cardiac arrests occurred during the study period. Rates of return of spontaneous circulation improved from 58.1 to 86.3% with an adjusted odds ratios of 5.31 (95% CI: 2.23–14.35, P < 0.001). Survival to discharge increased from 26.7 to 41.2%, adjusted odds ratios 2.17 (95% CI: 1.02–4.67, P < 0.05). Survival with a good neurological outcome increased from 24.8 to 35.3%, but was not statistically significant. Target chest compression rate increased from 30.4% of patients in P1 to 65.6% in P2, adjusted odds ratios 4.27 (95% CI: 1.72–11.12, P = 0.002), and target depth increased from 23.2% in P1 to 46.9% in P2, adjusted odds ratios 2.92 (95% CI: 1.16–7.54, P = 0.024). Conclusions After Advanced Resuscitation Training implementation, there were significant improvements in cardiopulmonary resuscitation quality and rates of return of spontaneous circulation and survival to discharge.
Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials
Authors: Liu Jie , Pong Annpey , Gallo Silvina , Darekar Amanda , Terra Steven G. 
Published: May 2019

AbstractBackgroundThe efficacy of ertugliflozin, a sodium–glucose cotransporter 2 inhibitor, for glycemic and blood pressure (BP) control has been demonstrated in phase 3 studies. To further evaluate the effects of ertugliflozin on BP and other hemodynamic parameters, an analysis was conducted on the pooled patient populations from these studies.MethodsThis was a post hoc analysis of data from three phase 3 studies (NCT01958671, NCT02033889, and NCT02036515) of adults with type 2 diabetes mellitus who received placebo, ertugliflozin 5 mg, or ertugliflozin 15 mg. Outcomes at 26 weeks were analyzed for the pooled population and according to relevant baseline factors, including BP.ResultsOf the 1544 patients included (placebo, n = 515; ertugliflozin 5 mg, n = 519; ertugliflozin 15 mg, n = 510), most (67.4–69.0%) had hypertension at baseline. Mean baseline BP was similar across treatment groups (placebo, 129.7/78.0 mmHg; ertugliflozin 5 mg, 131.0/78.4 mmHg; ertugliflozin 15 mg, 130.5/78.4 mmHg). At Week 26, placebo-adjusted least squares (LS) mean changes (95% confidence intervals [CI]) from baseline in systolic BP (SBP) were − 3.7 mmHg (− 5.1, − 2.3) for both ertugliflozin doses. Reductions were consistent across all baseline subgroups. At Week 26, more patients with a baseline SBP ≥ 130 mmHg had a SBP < 130 mmHg with ertugliflozin (38.7% both doses) than with placebo (24.0%), and more patients with a baseline SBP ≥ 140 mmHg attained a SBP < 140 mmHg with ertugliflozin (59.5% [5 mg] and 66.7% [15 mg]) than with placebo (43.8%). Placebo-adjusted LS mean changes (95% CI) in diastolic BP (DBP) with ertugliflozin 5 mg and 15 mg were − 1.8 mmHg (− 2.7, − 0.9) and − 1.6 mmHg (− 2.5, −  0.7), respectively, and in pulse rate were − 1.3 beats per minute (bpm) (− 2.2, − 0.3) and − 1.5 bpm (− 2.5, − 0.6), respectively. Greater reductions in pulse pressure, mean arterial pressure, and double product were observed with ertugliflozin than with placebo. Incidence of adverse event-related osmotic diuresis was low, but greater with ertugliflozin (2.9% [5 mg], 2.4% [15 mg]) than placebo (1.0%).ConclusionErtugliflozin treatment led to reductions in SBP, DBP, and pulse rate relative to placebo. Reductions in SBP were generally consistent across the subgroups evaluated.Trial registrationNCT01958671; NCT02033889; NCT02036515
miRNA Profiles in Extracellular Vesicles From Serum Early in Pregnancies Complicated by Gestational Diabetes Mellitus
Authors: Gillet Virginie , Ouellet Annie , Stepanov Yulia , Rodosthenous Rodosthenis S , Croft Erika Kathe , Brennan Kasey , Abdelouahab Nadia , Baccarelli Andrea , Takser Larissa 
Published: May 2019

Abstract

Context
Underlying mechanisms leading to gestational diabetes mellitus (GDM) are still under investigation, and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating miRNAs are involved in placental development and function and are encapsulated in extracellular vesicles (EVs).

Objective
To compare differential expression of miRNAs in circulating EVs in pregnancies complicated by GDM vs controls.

Methods
This was a case-control study nested in a prospective pregnancy cohort including 23 women with GDM and 46 matched controls. The presence of serum EVs in early pregnancy was validated by transmission electron microscopy. Placental dimensions were assessed at 11 to 13 weeks of gestation. Differential expression of 17 miRNAs encapsulated in EVs (miR‒122-5p, miR‒132-3p, miR-1323, miR‒182-3p, miR‒210-3p, miR‒29a-3p, miR‒29b-3p, miR‒342-3p, miR‒517-5p, miR‒517a-3p, miR‒518b, miR-520h, miR‒525-5p, miR‒136-5p, miR‒342-3p, miR‒376c-5p, and miR‒494-3p) was assessed using quantitative reverse transcription PCR.

Results
EVs were present in the early phase of placentation (6 to 15 weeks of gestation) in both cases and controls. No differences were observed for placental dimensions and estimated placental volume between GDM and control groups. Ten miRNAs (miR‒122-5p; miR‒132-3p; miR‒1323; miR‒136-5p; miR‒182-3p; miR‒210-3p; miR‒29a-3p; miR‒29b-3p; miR‒342-3p, and miR-520h) showed significantly higher levels in GDM cases than in controls (P ≤ 0.05). Bioinformatics analysis showed that these miRNAs are involved in trophoblast proliferation/differentiation as well as in insulin secretion/regulation and glucose transport in pregnant women.

Conclusion
The miRNA content of blood EVs may be a promising avenue for studying the early effect of impaired glucose metabolism on placental development.
Haptic Tactic
Authors: Delgado Huitrón Cynthia Citlallin 
Published: May 2019

Abstract
In 2017, Mexican transfeminist artist and activist Lia García (La Novia Sirena) made weekly visits to dorm 10Bis of the prison Reclusorio Norte, engaging in performative actions with a group of cis-male prisoners. Sprouting from images of Proyecto 10Bis (2017), this article argues that, within conditions of increasing violence and impunity, Lia transgenders touch in ways that, by (re)producing hypertenderness, serve as a balm for a hyperviolent state. Unpacking the haptics in the mechanics of production, and considering the Derridian impossibility of tact and of the law, the author argues that by placing herself—cuerpo y corazón—between the state and the body, Lia engenders a haptic tactic that, through a transgendered hypertender touch, activates transaffective resistances that contend with the law and the state.
Living on All Fours
Authors: Hernández Bernadine 
Published: May 2019

Abstract
En Cuatro Patas, part of the Pacific Standard Time Festival: Live Art LA/LA and translated as On All Fours, redefines the boundaries of the human through the animalistic, arthropod, subhuman, and transhuman. It is curated by Nao Bustamante and Xandra Ibarra, known as La Chica Boom, two artists who utilize ironic avant-garde, spectacle-driven kitsch performance aesthetics in their own right. Bustamante and Ibarra very specifically curated the performances to explore and embody the limits of the human in relation to the Latinx body, which interestingly pushes against and beyond queerness by evoking the prefix trans as Latinx transhuman.
Oliverio Rodriguez's The Last Seduction/La Seducción Fatal (2015–)
Authors: Adeyemi Kemi 
Published: May 2019

Abstract
This review of Oliverio Rodriguez's ongoing series The Last Seduction/La Seducción Fatal examines how his images press against European and South American “masters” of painting through explicitly queer and kinky optics. As Rodriguez uses collage techniques to activate the obvious, he creates a suite that theorizes the queerer grounds on which alternate modes of imaging might reflect the broader, more nuanced and quotidian practices of inhabiting bodies marked as other.
Risk factors of knee osteoarthritis: A case-control study
Authors: Moghimi Nasrin , Rahmani Khaled , Delpisheh Ali , Saidi Afshin , Azadi Namam Ali , Afkhamzadeh Abdorrahim 
Published: May 2019

Background and Objective: Knee osteoarthritis is one of the most common rheumatologic problems. To investigate risk factors related to the knee osteoarthritis a case-control study was performed using cases diagnosed in the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) study, stage I.
Methods: Using data from the 2012 COPCORD study, stage-I that was conducted in Sanandaj, northwestern of Iran, we runned a case-control study in 2014-2015. Cases were 700 knee osteoarthritis using American College of Rheumatology (ACR) criteria, frequency matched with 700 healthy controls that were randomly selected from the general population.
Results: In multivariate analysis, statistical significant relation was observed between knee OA and some studied factors such as body mass index (P <0.001), lodging (living in highland vs. plain) (P <0.001), type of used toilet (regular vs. toilet) (P <0.001), history of using high-heeled shoes (>3 cm) (P = 0.005), history of knee Injury (P = 0.04), history of lower limb fracture (P = 0.02), Number of pregnancies (P <0.001) and history of pain and swelling (lasting for one months) (P = 0.04).
Conclusions: Living in highland area, using regular toilet, having knee injury and lower limb fracture in the past were most significant associated factors with occurrence of knee osteoarthritis.
doi: https://doi.org/10.12669/pjms.35.3.277
How to cite this:Moghimi N, Rahmani K, Delpisheh A, Saidi A, Azadi NA, Afkhamzadeh A. Risk factors of knee osteoarthritis: A case-control study. Pak J Med Sci. 2019;35(3):636-640. doi: https://doi.org/10.12669/pjms.35.3.277
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Medical Education in Iraq: The cradle of Civilisation
Authors: Zaidi Shabih H , Abutiheen Ali 
Published: May 2019

Medical education is in a state of flux in Iraq. What used to be the best physicians and surgeons in the Arab world have fallen down to much lower status due to deliberate neglect and punishment of the intellectuals and professionals by the previous authorities. Once again medical educators and health professional are gaining momentum, gathering national and international support, to enter the contemporary world of medical education employing an integrated curriculum, PBL and Problem Solving Methods, Skill labs, simulation and structuring etc. Much needs to be done to return to formal glory but Iraqis are a dynamic nation of determined, dedicated and committed people. It is up to the international community to join hands with the Medics International to expedite the process. One such effort was the medical education conference held on 15-16 September 2018 with large input from medical educationists from Pakistan.
doi: https://doi.org/10.12669/pjms.35.3.972
How to cite this:Zaidi SH, Abutiheen A. Medical Education in Iraq: The cradle of Civilisation. Pak J Med Sci. 2019;35(3):868-872. doi: https://doi.org/10.12669/pjms.35.3.972
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.