bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes
Authors: Hadjadj Jérôme , Aladjidi Nathalie , Fernandes Helder , Leverger Guy , Magérus-Chatinet Aude , Mazerolles Fabienne , Stolzenberg Marie-Claude , Jacques Sidonie , Picard Capucine , Rosain Jérémie , Fourrage Cécile , Hanein Sylvain , Zarhrate Mohammed , Pasquet Marlène , Abou Chahla Wadih , Barlogis Vincent , Bertrand Yves , Pellier Isabelle , Colomb Bottollier Elodie , Fouyssac Fanny , Blouin Pascale , Thomas Caroline , Cheikh Nathalie , Dore Eric , Pondarre Corinne , Plantaz Dominique , Jeziorski Eric , Millot Frédéric , Garcelon Nicolas , Ducassou Stéphane , Perel Yves , Leblanc Thierry , Neven Bénédicte , Fischer Alain , Rieux-Laucat Frédéric
Published: April 2019

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M− group). The M+ group displayed more severe disease than the M− group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.
Leflunomide regulates c-Myc expression in myeloma cells through PIM targeting
Authors: Buettner Ralf , Morales Corey , Caserta Enrico , Troadec Estelle , Gunes Emine G. , Viola Domenico , Khalife Jihane , Li Hongzhi , Keats Jonathan J. , Christofferson Austin , Wu Xiwei , Synold Timothy W. , Palmer Joycelynne , Sanchez James F. , Pozhitkov Alexander , Vaidehi Nagarajan , Marcucci Guido , Krishnan Amrita , Rosenzweig Michael A. , Pichiorri Flavia , Rosen Steven T.
Published: April 2019

Key Points

Teriflunomide, the active metabolite of leflunomide, downregulates c-Myc expression through inhibition of PIM kinases. Leflunomide together with lenalidomide significantly extended survival in an in vivo MM model.
Presenting symptoms in inflammatory bowel disease: descriptive analysis of a community-based inception cohort
Authors: Perler Bryce K. , Ungaro Ryan , Baird Grayson , Mallette Meaghan , Bright Renee , Shah Samir , Shapiro Jason , Sands Bruce E.
Published: April 2019

Background

Few data are currently available on the initial presenting symptoms of patients with inflammatory bowel disease (IBD).

Methods

We evaluated the initial symptom presentation of patients with IBD in the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), a community-based inception cohort that enrolled Rhode Island IBD patients at time of diagnosis with longitudinal follow up. A 41-question symptom inventory was administered at time of enrollment to capture symptoms experienced during the 4 weeks preceding diagnosis of IBD. Frequencies of presenting symptoms were calculated. Principal component analysis (PCA) with promax rotation was used to examine possible symptom profiles among Crohn’s disease (CD) and ulcerative colitis (UC) patients, respectively. Using the Scree plot, the 4-component solution was found to be optimal for both CD and UC.

Results

A total of 233 CD and 150 UC patients were included. The most common presenting symptoms in CD were tiredness/fatigue (80.6%) and abdominal pain (80.4%) while passage of blood with bowel movements (BM) (86.6%) and loose/watery BMs (86.5%) were most common in UC. The 5 symptoms with greatest differences between UC and CD were passage of blood with BM (UC 86.6%/CD 45.3%), urgent BM (UC 82.5%/CD 63.9%), passage of mucus with BM (UC 67.7%/CD 36.9%), passage of blood from the anus (UC 59.7%/CD 32.1%), and anxiety about distance from bathroom (UC 59%/CD 38.7%). The PCA analysis yielded a 4 symptom components solution for CD and UC.

Conclusion

The most common presenting symptoms in CD are fatigue and abdominal pain while in UC bloody BM and diarrhea are most common. Distinct symptom phenotypes are seen with PCA analysis. Our study demonstrates symptomatic similarities and differences between CD and UC and suggests that patients may also be classified by symptom phenotype at time of diagnosis.
Effect of food intake on 92 oncological biomarkers by the Proseek Oncology II panel
Authors: Dencker Magnus , Björgell Ola , Hlebowicz Joanna
Published: April 2019

Objective

To evaluates the effect of food intake on 92 oncological biomarkers to evaluate whether the timing of blood sampling could be relevant. Twenty-two healthy subjects were investigated. A total of 92 biomarkers were measured before a standardised meal as well as 30 and 120 min afterwards with the Proseek Multiplex Oncology II kit.

Results

The levels of 6 biomarkers decreased significantly (P < 0.001) 30 min after food intake, and 4 biomarkers remained decreased (P < 0.001) 120 min after food intake. One biomarker was significantly increased (P < 0.001) at both 30 and 120 min after food intake. Some changes were less than 10%. Those biomarkers that showed a difference of more than 10% include: Granzyme H (13%), Methionine aminopeptidase 2 (14%), Secretory carrier-associated membrane protein 3 (39%), FAS-associated death domain protein (41%), and Pancreatic prohormone (79%). This study shows that food intake has a very modest effect on 92 different oncological biomarkers.

Trial registration National Library of Medicine trial registration number NCT01027507 (retrospectively registered on December 8, 2009)
70%-Damped Spectral Acceleration as a Ground Motion Intensity Measure for Predicting Highly Nonlinear Response of Structures
Authors: Buyco Kenny , Heaton Thomas H.
Published: April 2019

We investigate 70%-damped spectral acceleration, Sa70%( T), as a ground motion intensity measure for predicting maximum interstory drift ratios of 0.03, 0.06, and 0.1 as well as collapse. We perform incremental dynamic analysis with 50 ground motions on 22 steel moment frame building models with heights of 3, 9, and 20 stories. We find that if T1 ≤ T ≤ 2 T1, Sa70%( T) is efficient and usually sufficient for the considered levels of highly nonlinear response. Sa70%(1.5 T1) is generally an efficient choice. We find that Sa70%( T) is similar to average spectral acceleration, Saavg, in many ways, as both intensity measures emphasize a wide range of periods in a ground motion when compared to Sa5%( T1). Sa70%( T) is equivalent to the peak of a ground motion's low-pass filtered acceleration, and this interpretation may be useful for estimating the potential of a ground motion to elicit a highly nonlinear response.
Comparative Efficacy of Therapeutics for Chronic Cancer Pain: A Bayesian Network Meta-Analysis
Authors: Huang Rongzhong , Jiang Lihong , Cao Yu , Liu Hongli , Ping Minsheng , Li Wei , Xu Yu , Ning Jie , Chen Yuqing , Wang Xiaojing
Published: April 2019

PURPOSE

Opioids are the primary choice for managing chronic cancer pain. However, many nonopioid therapies are currently prescribed for chronic cancer pain with little published evidence comparing their efficacy.

METHODS

Electronic databases were searched for randomized controlled trials (RCTs) comparing any systemic pharmaceutical intervention and/or combination thereof in treating chronic cancer pain. The primary outcome was global efficacy reported as an odds ratio (OR). The secondary outcome was change in pain intensity reported as a standardized mean difference (SMD).

RESULTS

We included 81 RCTs consisting of 10,003 patients investigating 11 medication classes. Most RCTs (80%) displayed low risk of bias. The top-ranking classes for global efficacy were nonopioid analgesics (network OR, 0.30; 95% credibility interval [CrI], 0.13 to 0.67), nonsteroidal anti-inflammatory drugs (network OR, 0.44; 95% CrI, 0.22 to 0.90), and opioids (network OR, 0.49; 95% CrI, 0.27 to 0.86), whereas the top-ranked interventions were lidocaine (network OR, 0.04; 95% CrI, 0.01 to 0.18; surface under the cumulative ranking curve analysis [SUCRA] score, 98.1), codeine plus aspirin (network OR, 0.22; 95% CrI, 0.08 to 0.63; SUCRA score, 81.1), and pregabalin (network OR, 0.29; 95% CrI, 0.08 to 0.92; SUCRA score, 73.8). In terms of reducing pain intensity, we found that no class was superior to placebo, whereas the following top-ranked interventions were superior to placebo: ziconotide (network SMD, −24.98; 95% CrI, −32.62 to −17.35; SUCRA score, 99.8), dezocine (network SMD, −13.56; 95% CrI, −23.37 to −3.69; SUCRA score, 93.5), and diclofenac (network SMD, −11.22; 95% CrI, −15.91 to −5.80; SUCRA score, 92.9).

CONCLUSION

There are significant differences in efficacy among current regimens for chronic cancer pain. Our evidence suggests that certain nonopioid analgesics and nonsteroidal anti-inflammatory drugs can serve as effectively as opioids in managing chronic cancer pain.
Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Tolaney Sara M. , Guo Hao , Pernas Sonia , Barry William T. , Dillon Deborah A. , Ritterhouse Lauren , Schneider Bryan P. , Shen Fei , Fuhrman Kit , Baltay Michele , Dang Chau T. , Yardley Denise A. , Moy Beverly , Marcom P. Kelly , Albain Kathy S. , Rugo Hope S. , Ellis Mathew J. , Shapira Iuliana , Wolff Antonio C. , Carey Lisa A. , Overmoyer Beth , Partridge Ann H. , Hudis Clifford A. , Krop Ian E. , Burstein Harold J. , Winer Eric P.
Published: April 2019

PURPOSE

The Adjuvant Paclitaxel and Trastuzumab trial was designed to address treatment of patients with small human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The primary analysis of the Adjuvant Paclitaxel and Trastuzumab trial demonstrated a 3-year disease-free survival (DFS) of 98.7%. In this planned secondary analysis, we report longer-term outcomes and exploratory results to characterize the biology of small HER2-positive tumors and genetic factors that may predispose to paclitaxel-induced peripheral neuropathy (TIPN).

PATIENTS AND METHODS

In this phase II study, patients with HER2-positive breast cancer with tumors 3 cm or smaller and negative nodes received paclitaxel (80 mg/m2) with trastuzumab for 12 weeks, followed by trastuzumab for 9 months. The primary end point was DFS. Recurrence-free interval (RFI), breast cancer–specific survival, and overall survival (OS) were also analyzed. In an exploratory analysis, intrinsic subtyping by PAM50 (Prosigna) and calculation of the risk of recurrence score were performed on the nCounter analysis system on archival tissue. Genotyping was performed to investigate TIPN.

RESULTS

A total of 410 patients were enrolled from October 2007 to September 2010. After a median follow-up of 6.5 years, there were 23 DFS events. The 7-year DFS was 93% (95% CI, 90.4 to 96.2) with four (1.0%) distant recurrences, 7-year OS was 95% (95% CI, 92.4 to 97.7), and 7-year RFI was 97.5% (95% CI, 95.9 to 99.1). PAM50 analyses (n = 278) showed that most tumors were HER2-enriched (66%), followed by luminal B (14%), luminal A (13%), and basal-like (8%). Genotyping (n = 230) identified one single-nucleotide polymorphism, rs3012437, associated with an increased risk of TIPN in patients with grade 2 or greater TIPN (10.4%).

CONCLUSION

With longer follow-up, adjuvant paclitaxel and trastuzumab is associated with excellent long-term outcomes. Distribution of PAM50 intrinsic subtypes in small HER2-positive tumors is similar to that previously reported for larger tumors.
Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide
Authors: Fonseca Vivian A , Capehorn Matthew S , Garg Satish K , Jódar Gimeno Esteban , Hansen Oluf H , Holst Anders G , Nayak Gurudutt , Seufert Jochen
Published: April 2019

Context

Semaglutide, a once-weekly glucagon-like peptide-1 analog approved for use in patients with type 2 diabetes (T2D), demonstrated superior body weight (BW) reductions and decreased insulin resistance (IR) vs comparators across the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) 1–3 clinical trials.

Objective

To investigate the relationship between IR and BW across the SUSTAIN 1–3 trials.

Design

Post hoc analysis of the SUSTAIN 1–3 trials.

Setting

Three hundred and eleven sites in 30 countries.

Patients or other participants

2432 subjects with T2D.

Interventions

Semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg).

Main Outcome Measure

To assess the extent of the effect on IR that is mediated (indirect effect) and not mediated (direct effect) by the effect on BW.

Results

Across SUSTAIN 1–3, mean BW was significantly reduced with semaglutide 0.5 mg (3.7 kg to 4.3 kg; P < 0.0001) and semaglutide 1.0 mg (4.5 kg to 6.1 kg; P < 0.0001) vs comparators (1.0 kg to 1.9 kg). There were greater reductions in IR with semaglutide 0.5 mg (27% to 36%) and semaglutide 1.0 mg (32% to 46%) vs comparators (17% to 28%). Greater reductions in BW were generally associated with greater decreases in IR. The effect on IR was primarily mediated by weight loss (70% to 80% and 34% to 94%, for semaglutide 0.5 mg and 1.0 mg, respectively, vs comparator).

Conclusions

Semaglutide consistently reduced BW and IR in subjects with T2D in SUSTAIN 1–3. In this analysis, IR improvement was positively associated with, and primarily mediated by, the effect of semaglutide on BW.
Role of Cdx factors in early mesodermal fate decisions
Authors: Foley Tanya E. , Hess Bradley , Savory Joanne G. A. , Ringuette Randy , Lohnes David
Published: April 2019

Murine cardiac and hematopoietic progenitors are derived from Mesp1+ mesoderm. Cdx function impacts both yolk sac hematopoiesis and cardiogenesis in zebrafish, suggesting that Cdx family members regulate early mesoderm cell fate decisions. We found that Cdx2 occupies a number of transcription factor loci during embryogenesis, including key regulators of both cardiac and blood development, and that Cdx function is required for normal expression of the cardiogenic transcription factors Nkx2-5 and Tbx5. Furthermore, Cdx and Brg1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, co-occupy a number of loci, suggesting that Cdx family members regulate target gene expression through alterations in chromatin architecture. Consistent with this, we demonstrate loss of Brg1 occupancy and altered chromatin structure at several cardiogenic genes in Cdx-null mutants. Finally, we provide evidence for an onset of Cdx2 expression at E6.5 coinciding with egression of cardiac progenitors from the primitive streak. Together, these findings suggest that Cdx functions in multi-potential mesoderm to direct early cell fate decisions through transcriptional regulation of several novel target genes, and provide further insight into a potential epigenetic mechanism by which Cdx influences target gene expression.
Transient activity of the florigen complex during the floral transition in Arabidopsis thaliana
Authors: Abe Mitsutomo , Kosaka Shingo , Shibuta Mio , Nagata Kenji , Uemura Tomohiro , Nakano Akihiko , Kaya Hidetaka
Published: April 2019

FLOWERING LOCUS T (FT) is an essential component of florigen in Arabidopsis thaliana. Transcription of FT is induced in leaves, and the resulting FT protein is transported to the shoot apex, in which it initiates floral development. Previous analyses suggest that, together with the b-ZIP transcription factor FD, FT regulates the transcription of downstream targets such as APETALA1 (AP1) in floral anlagen. However, conclusive in vivo evidence that FT is transported to the shoot apex to form an FT–FD complex is lacking. Here, using an innovative in vivo imaging technique, we show that the FT–FD complex and AP1 colocalise in floral anlagen. In addition, the FT–FD complex disappears soon after the floral transition owing to a reduction in FD transcripts in the shoot apex. We further show that misinduction of FD activity after the transition leads to defective reproductive development. Taken together, our results indicate that the FT–FD complex functions as a transient stimulus and imply that a regulatory mechanism exists during the floral transition that reduces FT–FD complex levels via modulation of FD expression.
Capital Flows and Foreign Exchange Intervention
Authors: Cavallino Paolo
Published: April 2019

I consider a small open economy model where international financial markets are imperfect and the exchange rate is determined by capital flows. I use this framework to study the effects of portfolio flow shocks, derive the optimal foreign exchange intervention policy, and characterize its interaction with monetary policy. I derive the optimal intervention rule in closed form as a function of three implicit targets. Finally, using Swiss data, I estimate the model to quantify the inefficiencies generated by capital flow shocks and the optimal size of the intervention. (JEL E44, E52, E63, F31, F32, F33, F41)
Changes in Between-Group Inequality: Computers, Occupations, and International Trade
Authors: Burstein Ariel , Morales Eduardo , Vogel Jonathan
Published: April 2019

We provide a unifying framework to quantify the impact of several determinants of changes in US between-group inequality. We use an assignment framework with many labor groups, equipment types, and occupations in which changes in inequality are driven by changes in workforce composition, occupation demand, computerization, and labor productivity. We parameterize the model using direct measures of computer usage within labor group-occupation pairs and quantify the impact of each shock for various dimensions of between-group inequality between 1984 and 2003. We find, for example, that computerization and shifts in occupation demand jointly account for roughly 80 percent of the rise in the skill premium, with computerization alone accounting for roughly 60 percent. In an open-economy extension of the model, we show how computerization and changes in occupation demand can be caused by changes in the extent of international trade and perform counterfactual exercises to quantify these effects. (JEL D63, J16, J22, J23, J24, J31)
Housing Constraints and Spatial Misallocation
Authors: Hsieh Chang-Tai , Moretti Enrico
Published: April 2019

We quantify the amount of spatial misallocation of labor across US cities and its aggregate costs. Misallocation arises because high productivity cities like New York and the San Francisco Bay Area have adopted stringent restrictions to new housing supply, effectively limiting the number of workers who have access to such high productivity. Using a spatial equilibrium model and data from 220 metropolitan areas we find that these constraints lowered aggregate US growth by 36 percent from 1964 to 2009. (JEL E23, J24, J31, R23, R31)
Stock Market Responses to Unethical Behavior in Organizations: An Organizational Context Model
Authors: Baker Bradford , Derfler-Rozin Rellie , Pitesa Marko , Johnson Michael
Published: April 2019

We develop and test a model that extends the understanding of how people react to news of organizational unethical behavior and how such reactions impact stock performance. We do so by taking into account the interplay between the features of specific unethical acts and the features of the organizational context within which unethical acts occur. We propose a two-stage model in which the first stage predicts that unethical acts that benefit the organization are judged less harshly than are unethical acts that benefit the actor, when the organization is seen as pursuing a moral goal (e.g., producing inexpensive medicine rather than tobacco products). In such cases, the motives behind the unethical act are construed as an individual’s intentions to pursue a moral end. The second stage of our model connects moral judgment to action against the organization as a whole. We propose that moral judgments of an unethical act are more likely to translate into negative economic consequences for the organization when the unethical act is seen as benefiting the organization, because in such cases the organization is construed as an accomplice. Study 1 is an event study of stock market reactions to organizational unethical behavior in which the features of organizational unethical behavior were operationalized by coding media coverage of unethical acts. Study 2 is an experiment that used news stories to manipulate features of unethical behavior and measured participants’ estimates of stock performance, while incentivizing participants for accuracy. Both studies found support for our model.

The online appendix is available at https://doi.org/10.1287/orsc.2018.1244 .
Blurred Lines: How the Collectivism Norm Operates Through Perceived Group Diversity to Boost or Harm Group Performance in Himalayan Mountain Climbing
Authors: Chatman Jennifer A. , Greer Lindred L. , Sherman Eliot , Doerr Bernadette
Published: April 2019

We develop a theory explaining how collectivism causes people to “blur” demographic differences, that is, to see less diversity than actually exists in a group, and reconciling contradictions in how collectivistic norms influence group performance. We draw on the perceived diversity literature, hypothesizing that collectivistic norms cause group members to blur demographic differences, resulting in perceptions that group members are more similar than they actually are. Whether this benefits or harms group performance depends on the group’s objective diversity and the relevance of the perceived diversity attribute for accomplishing the task. For conjunctive tasks, the group’s performance is determined by its weakest member, demanding high levels of cohesion. Our theory suggests that collectivism benefits group conjunctive performance when objective national diversity is high by blurring divisive relational differences but has no effect in groups with low objective national diversity. In contrast, for disjunctive tasks, the group’s performance is determined by its best member. We predict that collectivism harms group disjunctive performance when objective expertness diversity is high by blurring differences in task-relevant expertness but has no effect in low objective expertness diversity groups. We find support for our theory in two studies, an archival study of 5,214 Himalayan climbing expeditions and a laboratory experiment assessing 366 groups. Our results show that collectivism has benefits and detriments for diverse groups and that these contradictory effects can be understood by identifying how the collectivistic blurring of perceived group diversity helps or hurts groups based on the type of tasks on which they are working.
Colonialism, Postcolonialism, Globalization, and Arab Culture
Authors: Mir Salam
Published: April 2019

This article will address two major related issues regarding Arab culture as an integral part of the globalization ethos. In order to expand the conceptual parameters of globalization and cultural studies, the exclusivity of political and economic globalization will be interrogated in favor of a more diverse, humanitarian definition of the term. At the heart of this argument, inflected by interdisciplinarity and the literature and theory of postcolonial studies, is tolerance, respect, and recognition of difference and for the marginalized voices of the “other.” The theoretical framework challenges the stereotyping, homogenization, and misrepresentation of Arabs, colonialist ideas that have been carried over into the practice of globalism and the marginalization of Arab history and culture within world heritage. It is my hope to correct the negative perceptions about the Arab people, mainstream misperceptions of politicians, the media, and public discourse. The article will underscore the diversity and complexity of the identity and history of people in the Middle East and North Africa. Although in the West Arabs are usually synonymous with Muslims, a discussion of Islam and/or Islamophobia will not be addressed in this article. The first part will elaborate on the historical context of the creation of the modern Arab world. Next, various definitions of the main domains of globalism and their correlation to the contemporary Arab world will be summarized. Integrated into both sections are two major issues: the creative resistance that has accompanied the founding of the modern Arab world and the impact of globalization on Arab society, concepts that have played out in the containment of this region.
The Palestinian Refugee Camps in Lebanon Post 1990: Dilemmas of Survival and Return to Palestine
Authors: Siklawi Rami
Published: April 2019

This article addresses the issue of the Palestinian refugees in Lebanon, their camps, their resistance, and the challenges they have been facing “as refugees” to survive in the deeply divided state of Lebanon and to return to Palestine. Currently there are about 450,000 Palestinian refugees scattered among 12 official and recognized Palestinian refugee camps in Lebanon as well as many refugee gatherings; this number is part of the 6 million Palestinian refugees who are scattered in the world as a result of the establishment of the Zionist entity in 1948. However, on December 11, 1948, the United Nations General Assembly issued the UN resolution 194, during its third session, which stipulated that Palestinians have the right of return to their homes in Palestine. The Palestinian right of return is a Right and therefore it is not negotiable and cannot be compromised under any condition and/or circumstance. There have been continual attempts and proposals to terminate this Palestinian right of return to historic Palestine. To stop these toxic proposals from reaching their goals and to achieve their strategic goal, the Palestinian resistance has the legitimate right to use any means necessary, including armed struggle against the occupiers. The Palestinians in Lebanon are part of this process and they have been struggling on all levels to achieve their civil and human rights in order to improve their social and economic conditions in their refugee camps. Furthermore, the Palestinians have the legitimate right to continue their national struggle against Israel, which is the only way for the Palestinians to achieve their national goal for total liberation. However, there have been additional challenges affecting the Palestinians and their refugee camps in Lebanon post 1990; by the end of the Lebanese Civil War, the Palestinian refugee camps witnessed the emergence and growth of takfiri groups. Consequently, the Palestinian refugees have been sandwiched between oppressive Lebanese rules and the rise of the takfiris inside the camps. The article attempts to answer the following questions: What are the challenges affecting the Palestinian refugees in Lebanon? How can the Palestinians protect their identity from erasure and achieve their right of return to Palestine? Which internal and external groups currently control the camps? In what ways has takfiri ideology impacted the Palestinian identity? How can the Palestinian refugees and their camps survive under such conditions?
Politicizing Disability/Disablement: A Case of Hunger-Strike/Death-Fast by a Kurdish Political Prisoner in Turkey
Authors: Kazemi Sona , Sarikaya Berivan
Published: April 2019

Over the past several years, we have been engaged in human-rights/disability-rights activism and organizing with disabled and/or traumatized survivors who have been victims of the state violence (e.g., war, incarceration, forced migration). As we interviewed them, documented their narratives, and/or read their prison memoirs, we re-lived our own past experiences with state violence as two racialized Middle Eastern women who have experienced incarceration in Turkey and Iran. Given our experiences, and being Disability Studies (DS) scholars and feminists, we have developed a new model to approach disability and disablement in the global southern/“third world” contexts. Herein, we narrate a real-life story of incarceration, torture, and hunger strike that has resulted in permanent disability. Following that we introduce our Transnational Disability theory to set the foundation for a historical and dialectical materialist understanding (DHM) of disablement. Finally, we apply the new model to our interviewee's narrative and analyze it through a DS lens. We end the paper by offering future directions for DS and Ethnic Studies scholars, prison abolitionists, and/or disability-rights activists who are enthusiastic about using the transnational disability approach in theory and political praxis.
Balanço hídrico em sistema hidrogeológico cárstico, região de Lagoa Santa, Minas Gerais
Authors: Paula Rodrigo Sergio , Velásquez Leila Nunes Menegasse
Published: April 2019

A área estudada, APA Carste de Lagoa Santa e seus entornos, localiza-se a 35 km norte de Belo Horizonte abrange cerca de 505 km². A região tem sido alvo de vários empreendimentos que prever um aumento pela demanda de água, diante deste crescimento e da fragilidade do sistema carste é imprescindível o conhecimento do sistema hidrológico, tal como a compreensão balanço hídrico. Geologicamente, a região é representada por metacalcárias e metapelíticas neoproterozoicas do Grupo Bambuí, com rica densidade de feições de dissolução cársticas que favorecem a recarga e a condução rápida da água. As drenagens da região são afluentes pela margem esquerda do rio das Velhas que funciona como nível de base. O objetivo do trabalho foi realizar o balanço hídrico, com ênfase na recarga aquífera, atentando para a complexa rede de drenagem subterrânea com entradas e saídas do sistema. Informações disponíveis sobre conexões hídricas auxiliaram no modelo de circulação adotado para equacionamento do balanço hídrico. Foram instaladas 6 estações fluviométricas em 6 bacias, monitoradas no ano hidrológico 2016/2017, cujos dados foram empregados no cálculo da recarga aplicando a metodologia de Rutledge e Daniel (1994). O escoamento de base médio das bacias de 91% do total confirma a importância da água subterrânea para o sistema hidrológico e a recarga de 12% da precipitação anual (1010 mm) pode ser adotada como valor mínimo por haver ainda outras saídas hídricas não contempladas no trabalho.
PERFIL DO REGISTRO SANITÁRIO DE DISPOSITIVOS INTERSOMÁTICOS NA AGÊNCIA NACIONAL DE VIGILÂNCIA SANITÁRIA (ANVISA)
Authors: Colli Luciana Ferreira Mattos , Martins Anna Luisa Dantas , Cabral Lucio Mendes
Published: April 2019

Produtos para saúde são dispositivos de uso médico utilizados em variados procedimentos e estão sujeitos à vigilância sanitária. A comercialização, no Brasil, requer o registro na Agência Nacional de Vigilância Sanitária (Anvisa), que avalia o grau de risco dos mesmos e o impacto na Saúde Pública. O objetivo do presente trabalho foi avaliar o perfil do registro sanitário de dispositivos intersomáticos ou cages. Atualmente existem 103 cages listados na Anvisa, perfazendo 74 registros válidos, 4 registros cancelados e 25 registros vencidos. Estes registros pertencem a empresas fabricantes nacionais e internacionais e sua composição prevalente é o peek ou titânio. Dessa forma, a análise dos registros apontou que o perfil das empresas detentoras do registro varia em nacionalidade, localização no país e na seleção da matéria prima utilizada na fabricação dos dispositivos.
ANÁLISE DA ADEQUAÇÃO DE EMBALAGENS, BULAS E PEÇAS PUBLICITÁRIAS DE MEDICAMENTOS FITOTERÁPICOS
Authors: Júnior Wanderley do Nascimento , Do Nascimento Wanderson Lima , Costa Debora de Alencar Franco
Published: April 2019

Medicamentos fitoterápicos são produtos obtidos pelo emprego exclusivo de matéria-prima ativa vegetal, cuja eficácia e segurança são validadas por meio de levantamentos etnofarmacológicos, documentações tecnocientíficas em bibliografia ou publicações indexadas ou por estudos farmacológicos e toxicológicos pré-clínicos e clínicos. Sua qualidade não está vinculada somente a sua segurança e eficácia, mas sim a diversos quesitos que englobam desde os aspectos envolvidos na pesquisa até a sua utilização pelo usuário final. Dentre eles, a embalagem possui um papel preponderante, pois além de fazer parte do produto, serve para prover determinada apresentação, proteção, identificação, informação, aceitabilidade e comodidade do produto durante as fases de desenvolvimento, produção, armazenamento, transporte, exposição e uso. Assim, a embalagem representa um objeto de contato direto entre o produto e o usuário, por isso, suas funções técnicas, estéticas e informativas, devem obedecer à legislação vigente e aos conceitos éticos e morais. Este trabalho teve como objetivo avaliar a aplicação da legislação brasileira quanto a embalagem e rotulagem de medicamentos fitoterápicos do mercado nacional e de peças publicitárias relacionadas à venda de fitoterápicos, comparando os resultados obtidos com os de estudos anteriores. Trata-se de uma pesquisa de campo, tendo-se como objeto de avaliação 10 medicamentos fitoterápicos oriundos de diferentes drogarias da cidade de Teresina, PI e 20 peças publicitárias para a realização da análise. As regras passaram a ser mais exercidas em comparação aos resultados obtidos em estudos anteriores.
Konsultacje ludowe. Kilka uwag na tle rozwiązań szwajcarskich
Authors: Aleksandrowicz Maciej
Published: April 2019

Konsultacje ludowe są jedną ze współcześnie spotykanych form partycypacji obywateli w procesach podejmowania rozstrzygnięć spraw ogólnospołecznych, w tym w procesach prawotwórczych. W czasie nasilonych dyskusji w polskiej sferze publicznej na temat kształtu modelu demokratycznego warto przedstawić, jak tego typu rozwiązanie uregulowane jest w państwie o ugruntowanej demokracji, to jest w Szwajcarii oraz jakie są konsekwencje praktyczne takich unormowań. Wnioski płynące z porównania obu systemów są następujące: choć regulacje polskie można, z pewnymi zastrzeżeniami, ocenić pozytywnie, jako potencjalnie umożliwiające współudział jednostek w procesach decyzyjnych, to realizacja tych założeń normatywnych, na tle praktyki szwajcarskiej nie wygląda okazale.
Lithologic heterogeneity of lacustrine shale and its geological significance for shale hydrocarbon-a case study of Zhangjiatan Shale
Authors: Fan Bojiang , Shi Liang , Li Yating , Zhang Tianjing , Lv Lei , Shikai Tong
Published: April 2019

The Zhangjiatan shale of the Southeastern Ordos Basin, which deposits in deep lake facies, has strong lithologic heterogeneity; it represents as shale, sandy laminae shale and thin sandstone. Shale with mm- to cm-scale sandy laminae is defined as Sandy Laminae Shale (SLS). However, the relationship between lithologic heterogeneity and hydrocarbon accumulation has never been studied. This study shows that lithologic heterogeneity, especially the occurrence of SLS will influence the accumulation of hydrocarbons within the shale system. SLS commonly has a larger pore size, higher porosity and better connectivity than thick and homogeneous shale. SLS commonly contains fewer residual hydrocarbons than homogeneous thick shale, indicating comparative ease in hydrocarbon expulsion. SLS commonly generates more bedding fractures. More fractures can be incurred when fracture extending into SLS. The occurrence of SLS can provide more storage spaces for fluids and gases, including oil, water, adsorbed gas, dissolved gas and free gas. SLS has been the pilot exploration and development target for shale hydrocarbon in the southeastern Ordos Basin. Homogeneous and thick shales, which have a large content of residual hydrocarbons, would be the targets for future exploration.
A comparative sorption study of Cr3+ and Cr6+ using mango peels: kinetic, equilibrium and thermodynamic
Authors: Haq Atta ul , Saeed Muhammad , Usman Muhammad , Yameen Muhammad , Muneer Majid , Tubbsum Saiqa
Published: April 2019

The present study investigates a comparative study of the sorption of Cr3+and Cr6+from water using an agricultural by-product; mango peels in batch system under the effect of initial metal ion concentrations, solution pH, temperature, sorbent dose and contact time. Characterization of the mango peels was done before and after sorption of Cr3+and Cr6+using scanning electron microscopy, surface area pore size analyzer and FTIR spectroscopy. The pH study revealed that that maximum removal of Cr3+and Cr6+was obtained at pH 5.0 and 7.0 respectively. Among various kinetic models, pseudo-2ndorder well explained the data owing to the higher values of R2and the nearness between the values of experimental and calculated sorption capacities. The isotherms study revealed that Freundlich is the suitable isotherm for explanation of the equilibrium data due to higher R2values. The monolayer sorption capacity of mango peels was found to be 98.039 mg g-1for Cr3+and 66.666 mg g-1for Cr6+. The spontaneity and exothermic nature of the sorption process of Cr3+and Cr6+using mango peels was reflected from thermodynamic study.
Adolescent characteristics and parenting style as the determinant factors of bullying in Indonesia: a cross-sectional study
Authors: Krisnana Ilya , Rachmawati Praba Diyan , Arief Yuni Sufyanti , Kurnia Iqlima Dwi , Nastiti Aria Aulia , Safitri Indah Febriana Nila , Putri Ayu Tria Kartika
Published: April 2019

Background

The incidence of adolescents bullying in Indonesia has increased. The purpose of this study was to analyze the correlation of demographic characteristics, parental interactions and parenting style as the potential determinants of bullying behavior in adolescents.

Method

The research design used was cross-sectional. The study population consisted of adolescents in Indonesia who accessed the Google form, and adolescents who study at a junior high school and a vocational high school in Surabaya. The study sample totaled 705 adolescents based on consecutive sampling with a study period of 3 months. The independent variables were demographic characteristics, parental interactions and parenting style, while the dependent variable was bullying behavior. The data collection method used was a questionnaire filled in by the adolescents through a Google form and a questionnaire sheet. The statistical analysis used the chi-square test for the adolescent’s characteristics and Spearman’s rank correlation with α = 0.05.

Results

The results showed that the characteristics of the adolescents, namely age and place of residence, were related to bullying behavior. A permissive and authoritarian parenting style had a positive correlation with being a bullying perpetrator, while only permissive parenting style had a positive correlation with being a bullying victim.

Conclusion

Adolescents experience bullying behavior as both the perpetrators and victims. Adolescents living in rural areas are more likely to commit bullying as the perpetrators. A parenting style that is either too rigid or too free has a high risk of being a bullying behavior factor as the perpetrator. Parents are expected to apply an authoritative parenting style in order to prevent the risk of bullying in adolescents.
Communities That Care: integrierte Gewaltprävention in der Kommune
Authors: Groeger-Roth Frederick
Published: April 2019

In dem Beitrag wird die kommunale Präventionsstrategie „Communities That Care (CTC)“ beschrieben. CTC ist ein settingübergreifender Ansatz, mit dessen Hilfe Kommunen integrierte Strategien zur Gewaltprävention und Gesundheitsförderung (weiter-)entwickeln können. Kommunen können mit CTC ihre Präventionsangebote stärker auf die bedeutsamsten Risikofaktoren und Schutzfaktoren für Kinder und Jugendliche fokussieren und evaluierte Präventionsprogramme nachhaltig in den Regeleinrichtungen verankern.
Treatments for child and adolescent victims of sexual violence: are they effective?
Authors: Averdijk Margit
Published: April 2019

Sexual violence among children and adolescents can have detrimental consequences. This article presents a brief overview of the current international knowledge base on the effectiveness of treatment programs for child and adolescent victims of sexual violence. Overall, treatment programs show moderate to large beneficial effects on victims’ well-being. Treatments that have a longer duration and shorter sessions are more effective than other treatments. Some of the challenges include that few victims receive treatment and that a considerable number of prior studies does not meet the standards for thorough effectiveness research.
Elevated resting-state connectivity in the medial temporal lobe and the prefrontal cortex among patients with Cushing’s syndrome in remission
Authors: Stomby Andreas , Salami Alireza , Dahlqvist Per , Evang Johan Arild , Ryberg Mats , Bollerslev Jens , Olsson Tommy , Johannsson Gudmundur , Ragnarsson Oskar
Published: April 2019

Objective

Cushing’s syndrome is associated with long-term cognitive deficits and affective symptoms such as depression and anxiety. The alterations in brain function underlying these deficits after Cushing’s syndrome are unclear and therefore we aimed to explore alterations in resting-state functional connectivity in patients with Cushing’s syndrome in remission.

Design

Cross-sectional case–control study.

Methods

Nineteen women with Cushing’s syndrome in remission for a median time of 7 years (IQR: 6–10) and a mean age of 45 years were included at three university clinics. These patients and 38 age-matched female controls underwent brain imaging at a single center. The main outcome measure was functional connectivity at rest, measured with functional magnetic resonance imaging.

Results

The medial temporal lobe (MTL) and prefrontal cortex networks, exhibited elevated functional connectivity among patients compared to controls. The degree of elevated functional connectivity in the MTL was negatively associated with time in remission.

Conclusions

Resting-state functional connectivity within glucocorticoid receptor-rich regions, particularly the MTL and medial prefrontal cortex, was increased in patients. These differences in connectivity may provide a neural basis for the cognitive deficits and affective symptoms commonly experienced by patients with Cushing’s syndrome in remission.
Effects of novel somatostatin-dopamine chimeric drugs in 2D and 3D cell culture models of neuroendocrine tumors
Authors: Herrera-Martínez Aura D , van den Dungen Rosanna , Dogan-Oruc Fadime , van Koetsveld Peter M , Culler Michael D , de Herder Wouter W , Luque Raúl M , Feelders Richard A , Hofland Leo J
Published: April 2019

Control of symptoms related to hormonal hypersecretion by functioning neuroendocrine tumors (NETs) is challenging. New therapeutic options are required. Since novel in vitro tumor models seem to better mimic the tumor in vivo conditions, we aimed to study the effect of somatostatin and dopamine receptor agonists (octreotide and cabergoline, respectively) and novel somatostatin-dopamine chimeric multi-receptor drugs (BIM-065, BIM-23A760) using 2D (monolayer) and 3D (spheroids) cultures. Dose–response studies in 2D and 3D human pancreatic NET cell cultures (BON-1 and QGP-1) were performed under serum-containing and serum-deprived conditions. Cell proliferation, somatostatin and dopamine receptor expression (SSTs and D2R), apoptosis, lactate dehydrogenase, as well as serotonin and chromogranin A (CgA) release were assessed. The following results were obtained. 3D cultures of BON-1/QGP-1 allowed better cell survival than 2D cultures in serum-deprived conditions. SSTs and D2R mRNA levels were higher in the 3D model vs 2D model. Octreotide/cabergoline/BIM-065/BIM-23A760 treatment did not affect cell growth or spheroid size. In BON-1 2D-cultures, only BIM-23A760 significantly inhibited CgA release –this effect being more pronounced in 3D cultures. In BON-1 2D cultures, cabergoline/BIM-065/BIM-23A760 treatment decreased serotonin release (maximal effect up to 40%), being this effect again more potent in 3D cultures (up to 67% inhibition; with BIM-23A760 having the most potent effects). In QGP-1, cabergoline/BIM-065 treatment decreased serotonin release only in the 3D model. In conclusion, cultures of NET 3D spheroids represent a promising method for evaluating cell proliferation and secretion in NET cell-line models. Compared to 2D models, 3D models grow relatively serum independent. In 3D model, SST-D2R multi-receptor targeting drugs inhibit CgA and serotonin secretion, but not NET cell growth.
Regulation of long non-coding RNAs and circular RNAs in spermatogonial stem cells
Authors: Zhou Fan , Chen Wei , Jiang Yiqun , He Zuping
Published: April 2019

Spermatogonial stem cells (SSCs) are one of the most significant stem cells with the potentials of self-renewal, differentiation, transdifferentiation and dedifferentiation, and thus, they have important applications in reproductive and regenerative medicine. They can transmit the genetic and epigenetic information across generations, which highlights the importance of the correct establishment and maintenance of epigenetic marks. Accurate transcriptional and post-transcriptional regulation is required to support the highly coordinated expression of specific genes for each step of spermatogenesis. Increasing evidence indicates that non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play essential roles in controlling gene expression and fate determination of male germ cells. These ncRNA molecules have distinct characteristics and biological functions, and they independently or cooperatively modulate the proliferation, apoptosis and differentiation of SSCs. In this review, we summarized the features, biological function and fate of mouse and human SSCs, and we compared the characteristics of lncRNAs and circRNAs. We also addressed the roles and mechanisms of lncRNAs and circRNAs in regulating mouse and human SSCs, which would add novel insights into the epigenetic mechanisms underlying mammalian spermatogenesis and provide new approaches to treat male infertility.