bluuebunny/crossref_metadata_2025 huggingface dataset:
Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting
Authors: Chehadeh Wassim , Albaksami Osama , Al-Shammari Shaikhah
Published: May 2020

Background

With the advent of next generation integrase strand transfer inhibitors, the rates of virologic failure in treated subjects are expected to decrease. In this study, we analyzed the mutation patterns leading to virologic failure before and after starting integrase strand transfer inhibitor-based regimen as first-line or salvage therapy.

Methods

Between 2016 and 2019, blood samples were received from 258 patients with HIV-1 infection. Plasma HIV-1 RNA concentrations, and pol gene sequences were determined at baseline, and 16–48 weeks of treatment with integrase strand transfer inhibitor-based regimen. Only patients who did not achieve viral suppression at 48 weeks of integrase strand transfer inhibitor-based treatment were eligible for the current study.

Results

Virologic failure was observed in seven patients on raltegravir-based regimen. All patients with virologic failure but one were infected with CRF01_AE virus subtype. Raltegravir based-regimen was offered as first-line therapy for four patients, and as salvage therapy for three patients. M184V mutation associated with high level resistance to lamivudine and emtricitabine was detected in six out of seven patients. Primary mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to raltegravir were detected in only three patients. Pre-existing polymorphic integrase mutation (T97A) was detected in two patients. Furthermore, two patients reported low adherence to treatment.

Conclusions

Emergence of primary mutations in the integrase gene can account for virologic failure in less than half of patients on raltegravir-based regimen. Low adherence to treatment, pre-existing accessory mutations, and resistance to reverse transcriptase inhibitors may have some role in virologic outcome.
A novel BMPR2 mutation with widely disparate heritable pulmonary arterial hypertension clinical phenotype
Authors: Oriaku Ifeoma , LeSieur Mallory N. , Nichols William C. , Barrios Roberto , Elliott C. Gregory , Frost Adaani
Published: May 2020

Mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2) have been associated with heritable pulmonary arterial hypertension (HPAH), whereas mutations in the gene encoding eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) are associated with heritable pulmonary veno‐occlusive disease/pulmonary capillary hemangiomatosis (HPVOD/PCH). We describe two unrelated patients found to carry the same hitherto unreported pathogenic BMPR2 mutation; one of whom presented with typical pulmonary arterial hypertension, whereas the second patient presented with aggressive disease and characteristic clinical features of PVOD/PCH. These two clinically divergent cases representative of the same novel pathogenic mutation exemplify the variable phenotype of HPAH and the variable involvement of venules and capillaries in the pathology of the pulmonary vascular bed in pulmonary arterial hypertension.
Transitions between infused and oral prostacyclin pathway agents in pulmonary arterial hypertension: key considerations
Authors: Sargent Therese , Hansen Lillian , Hohsfield Robin
Published: May 2020

Prostacyclin pathway agents are a critical treatment for patients with pulmonary arterial hypertension. Seven prostacyclin pathway agents are available, including agents administered by parenteral infusion, by inhalation, and orally. Pulmonary arterial hypertension patients are now transitioned from one prostacyclin pathway agent to another with increasing frequency. Such transitions require careful downtitration and uptitration to avoid decompensation from rapid withdrawal and to achieve a patient's optimal dose based on efficacy and tolerability. Clinical guidance is especially lacking for transitions involving the newer, oral prostacyclin pathway agents; specifically, selexipag and oral treprostinil. We present three case reports of patients with pulmonary arterial hypertension who underwent one or more transition between parenteral and oral prostacyclin pathway agents, including some transitions that were successful and some that were not. These cases illustrate key considerations, such as titration protocols, patient selection, side effect management, and pharmacokinetics.
Participatory design and evaluation of virtual reality games to promote engagement in physical activity for people living with dementia
Authors: Eisapour Mazhar , Cao Shi , Boger Jennifer
Published: May 2020

Background

Exercise is a key component of physical health and quality of life for people living with dementia; however, challenges related to dementia symptoms and aging can make it difficult for people living with dementia to engage in exercise. While immersive virtual reality is showing increasing promise for exercise and rehabilitation applications, there is a lack of research regarding its use with people living with dementia.

Methods

Through participatory design with exercise therapists, kinesiologists, and people living with dementia, we designed two virtual reality environments (a farm and a gym) that were implemented on head-mounted displays to support five different upper-body exercises. Virtual reality and comparable human-guided exercises were tested with six people living with dementia. Both qualitative and quantitative measures were used, including reaching distance, distance traversed, and speed as well as feelings of enjoyment, engagement, interest, easiness, comfort, and level of effort.

Results

Participants’ subjective responses, motion, and fitness parameters all demonstrated comparable results between virtual reality and human-guided exercises. Therapists’ feedback also supported virtual reality exercise as an appropriate and engaging method for people living with dementia.

Conclusions

Collaborating with experts and people living with dementia throughout the design process resulted in an intuitive and engaging design. The results suggest that head-mounted virtual reality has promising potential to support physical activity for people living with dementia.
Donor Aid and Private Investment: Their Interplay With Media Development
Authors: Nyarko Jacob , Mensah Eric Opoku , Hamusokwe Basil
Published: May 2020

Media development requires substantial funding, and therefore, donors, foreign governments, nongovernmental organizations (NGOs), and foundations have found a way to play an influential role through their financial support. However, it appears that the donors are also fighting a losing battle considering the rapidly changing political-economic structures of contemporary society spearheaded by the very private sector they enhanced. This study generally presents a systematic review of “foreign aid” to Africa as a base “to explore how donor funders and private investment impact media functions.” The work also sheds light on the extent to which donor support impacted the governance system within the media political economy of Africa. It establishes that donors, who are the very saviors, are also a threat to media freedom because they set the agenda for content, resulting in undue influence on the type of stories that are told. As a result, media development becomes constricted.
Corporate Social Responsibility Programs and Community Perceptions of Societal Progress in Bangladesh: A Multimethod Approach
Authors: Mahmud Appel , Ding Donghong , Kiani Ataullah , Hasan Md. Morshadul
Published: May 2020

Grounded on stakeholder theory and contemporary corporate social responsibility (CSR) literature, this study aims to investigate the broad categories of CSR programs (CSRPs) of scheduled banks and nonbanking financial institutions of Bangladesh Bank (the central bank of Bangladesh). This study also attempts to build the relationship between CSRPs and community perceptions of societal progress. Qualitative and quantitative methods were used to analyze the data collected from primary and secondary sources. The findings of this study show that CSRPs positively influence community perceptions of societal progress. The results of this study will have significant practical implications on societal progress and future research on CSR and community development.
Nondual Awareness and the Whole Person
Authors: Mills Paul J , Barsotti Tiffany J , Blackstone Judith , Chopra Deepak , Josipovic Zoran
Published: May 2020

Integrative Health aims to treat the whole person and to do so within the context of whole systems and practices. We raise questions as to what constitutes the whole person and what must be taken into account to support the creation of optimal well-being. We propose that in order to fully account for the whole person, the transcendent aspects of human awareness, the development of which is the goal of many meditative traditions, must be taken into account. “Nondual awareness” is a term increasingly used in the literature to describe a state of awareness that is characterized by the experience of nonseparation, compassion, and love. Well-being in this state does not depend on anything being experienced per se, but it is rather an innate attribute of living in nonduality. For these reasons, nondual awareness can be considered foundational to the realization of the whole person and achieving the state of optimal well-being.
Reversible Fulminant Hepatitis Secondary to Cocaine in the Setting of β-Blocker Use
Authors: Sharma Rohan , Kapoor Nidhi , Chaudhari Kaustubh Suresh , Scofield Robert Hal
Published: May 2020

Background. Fulminant hepatitis is acute hepatic injury with severe decline in hepatic function manifested by encephalopathy, hypercoagulable state, jaundice, renal failure, hypoglycemia, or a constellation of these symptoms in patients without preexisting liver disease. Etiologies include viral infections, hepatotoxic drugs, autoimmune diseases, vaso-occlusive diseases, sepsis, and malignant infiltration. Case Report. A 56-year-old man presented with acute heart failure in the setting of cocaine use. The patient subsequently developed fulminant hepatic failure manifested by acute hypoglycemia, elevated liver enzyme, and worsening liver function, which resolved over 1 week with supportive care. The patient was on β-blocker, which was stopped during the admission. He was again admitted on several different occasion for cocaine-induced acute heart failure but did not develop hepatic failure as his β-blocker was discontinued. Discussion. Cocaine has been known to cause hepatotoxicity in humans. However, our patient developed fulminant hepatic failure in the setting of concomitant cocaine and β-blocker use likely secondary to unopposed α-adrenergic activity and ischemic hepatopathy. The patient did not develop hepatic failure on subsequent admissions with cocaine use after discontinuation of β-blockers.
Unmet Dental Care Need and Associated Barriers by Race/Ethnicity among US Adults
Authors: Bhoopathi V. , Luo H. , Moss M. , Bhagavatula P.
Published: May 2020

Introduction:

Ability to access needed dental care may vary among population subgroups. We assessed 1) the differences in the proportions of adults who reported unmet dental care needs in the past 12 months and the associated barriers (structural, financial, and cognitive) in 2015 to 2016 versus 2003 to 2004 by race/ethnicity and 2) the subgroups that are more likely to report unmet dental care needs.

Methods:

Data of 10,029 respondents aged ≥19 y from the 2003–2004 and 2015–2016 National Health and Nutrition Examination Surveys were used. Chi-square tests assessed the differences in the proportions of adults who reported not getting the needed dental care between the periods. A multiple logistic regression model was run to identify characteristics that were significantly associated with unmet need after adjusting for other factors.

Results:

Overall, 19.4% of the adults reported an unmet dental care need in 2015 to 2016, as compared with 21% in 2003 to 2004. The overall unmet dental care need decreased only in the Hispanic groups (34% to 28%, P = 0.045) between 2003–2004 and 2015–2016. Between the periods, unmet need decreased among Hispanics aged 19 to 64 y (35% to 28%, P = 0.02), Hispanics with some college education or above (33.5% to 21.0%, P = 0.008), and nonpoor Hispanic adults (29.8% to 20.4%, P = 0.048). No significant differences were observed in the proportions of adults reporting structural ( P = 0.09), financial ( P = 0.86), or cognitive ( P = 0.07) barriers between the periods. When compared with their counterparts, nonelderly adults, women, Hispanics, adults with a high school education, those with less than a high school education, and poor adults were significantly more likely to report unmet dental care needs.

Conclusions:

Racial and ethnic disparities in accessing and receiving the needed dental care still exist. Financial barriers to dental care are the most commonly cited reasons for not getting the needed dental care.

Knowledge Transfer Statement:

The results of the study will inform policy makers, public health planners, and dental professionals about subgroups that still face difficulty in receiving the dental care they need. Policy makers should develop new policies to mitigate the financial barriers that are still prevalent. Dental professionals can mitigate the public’s cognitive and financial barriers by educating the community through outreach programs and by providing services to low-income populations at reduced charges or through alternative payment plans.
Does non-conforming urban development mean the failure of zoning? A framework for conformance-based evaluation
Authors: Shen Xiaoqiang , Wang Xiangdong , Zhang Zhou , Fei Luocheng
Published: May 2020

The conformance approach is frequently used to evaluate the effectiveness of spatial plans in containing urban sprawl. However, non-conformances are widely considered inevitable. Prior conformance-based evaluations fail to answer the essential question of whether plans influence non-conforming situations. To address this gap, we built a framework for conformance measurement to reveal how plans affect non-conforming urban development. The multi-indicator framework includes quantitative indicators, the spatial distribution relationship between new non-conforming urban land and zoning maps, and the location and original land use of new non-conforming urban land. When applied to a case study, this framework reveals that most new non-conforming urban land was adjacent to conforming urban land and located in zones without strict restrictions on urban development. Moreover, the type of land use that the zoning map aimed to conserve was rarely converted, suggesting attempts by decision-makers to control the severity of conflicts between non-conforming development and the zoning map. A logistic regression also evidences the significant influence of zoning on non-conforming urban development. These findings, in turn, verify the operability and theoretical value of the proposed framework.
Simultaneous Septal Perforation and Deviation Repair with a Chondromucosal Transposition Flap
Authors: Lu G. Nina , Eytan Danielle F. , Desai Shaun C.
Published: May 2020

Nasal septal perforations can cause issues of epistaxis, whistling, crusting, saddle deformity, and obstruction, which motivate patients to seek surgical repair. Numerous methods of septal perforation repair have been described, with surgical success rates ranging from 52% to 100%, but few studies address situations with concomitant septal deviation. In treating patients with septal perforation and deviation, both issues should be addressed for optimal outcomes. While routine septoplasty involves the removal of septal cartilage, septal perforation repair involves the addition of interposition grafts. The composite chondromucosal septal rotation flap harmoniously combines these seemingly conflicting goals as an effective and efficient technique for septal perforation repair. We present 3 patients successfully treated for their septal perforation and septal deviation concurrently with this technique.
CD86-based analysis enables observation of bona fide hematopoietic responses
Authors: Kanayama Masashi , Izumi Yuta , Yamauchi Yasuharu , Kuroda Shoko , Shin Takaei , Ishikawa Shun , Sato Taku , Kajita Mihoko , Ohteki Toshiaki
Published: May 2020

Hematopoiesis is a system that provides red blood cells (RBCs), leukocytes, and platelets, which are essential for oxygen transport, biodefense, and hemostasis; its balance thus affects the outcome of various disorders. Here, we report that stem cell antigen-1 (Sca-1), a cell surface marker commonly used for the identification of multipotent hematopoietic progenitors (Lin−Sca-1+c-Kit+ cells; LSKs), is not suitable for the analysis of hematopoietic responses under biological stresses with interferon production. Lin−Sca-1−c-Kit+ cells (LKs), downstream progenitors of LSKs, acquire Sca-1 expression upon inflammation, which makes it impossible to distinguish between LSKs and LKs. As an alternative and stable marker even under such stresses, we identified CD86 by screening 180 surface markers. The analysis of infection/inflammation-triggered hematopoiesis on the basis of CD86 expression newly revealed urgent erythropoiesis producing stress-resistant RBCs and intact reconstitution capacity of LSKs, which could not be detected by conventional Sca-1–based analysis.
Influence of time under mechanical ventilation on bronchopulmonary dysplasia severity in extremely preterm infants: a pilot study
Authors: Escobar Victoria , Soares Darllyana S. , Kreling Jane , Ferrari Ligia S. L. , Felcar Josiane M. , Camillo Carlos A. M. , Probst Vanessa S.
Published: May 2020

Background

The relation between mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) - a common disease in extremely premature newborn (PTNB) - is well stabilished, but is unknown, however, how much time under MV influences the severity of the disease.

Aim

To define the duration under MV with greater chance to develop moderate to severe BPD in extremely PTNB and to compare clinical outcomes before and during hospitalization among patients with mild and moderate to severe BPD.

Methods

Fifty-three PTNB were separated into mild and moderate to severe BPD groups and their data were analyzed. Time under MV with a greater chance of developing moderate to severe BPD was estimated by the ROC curve. Perinatal and hospitalization outcomes were compared between groups. A logistic regression was performed to verify the influence of variables associated to moderate to severe BPD development, such as pulmonary hypertension (PH), gender, gestational age (GA) and weight at birth, as well the time under MV found with ROC curve. The result of ROC curve was validated using an independent sample (n = 16) by Chi-square test.

Results

Time under MV related to a greater chance of developing moderate to severe BPD was 36 days. Moderate to severe BPD group had more males (14 vs 5, p = 0,047), longer time under MV (43 vs 19 days, p < 0,001), more individuals with PH (12 vs 3, p = 0,016), worse retinopathy of prematurity (grade 3, 2 vs 11, p = 0,003), longer hospital length of stay (109 vs 81,5 days, p < 0,001), greater PMA (41 vs 38 weeks, p < 0,001) and weight (2620 vs 2031 g, p < 0,001) at discharge and the mild BPD group had more CPAP use prior to MV (12 vs 7, p = 0,043). Among all variables included in logistic regression, only PH and MV < 36 days were significant in the model, explaining 72% of variation in moderate to severe BPD development. In the validation sample, prevalence of preterm infants who needed MV for more than 36 days in the moderate to severe BPD group was 100% (n = 6) and 0% in mild BPD group (p = 0,0001).

Conclusion

Time under MV related to moderate to severe BPD development is 36 days, and worst outcomes are related to disease severity. PH and time under MV for more than 36 days are related to development of moderate to severe BPD.
Correction to: Central line bundle including split-septum device and single-use prefilled flushing syringes to prevent port-associated bloodstream infections: a cost and resource-utilization analysis
Authors: Devrim İlker , Özkul Mustafa Taha , Çağlar İlknur , Oruç Yeliz , Demiray Nevbahar , Tahta Neryal , Vergin Canan
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Assessment of medical intern’s knowledge, awareness and practice of familial hypercholesterolemia at academic institutes in Jeddah, Saudi Arabia
Authors: Alzahrani Sami H. , Bima Abdulhadi , Algethami Mohammed R. , Awan Zuhier
Published: May 2020

Background

Familial Hypercholesterolemia (FH) is a serious under-diagnosed disease characterized by raised low-density lipoprotein cholesterol (LDL-C) and premature coronary artery diseases (CAD). The scarcity of FH reported patients in Saudi Arabia indicates lack of FH awareness among physicians.

Objective

The goal of this research was to assess knowledge, awareness, and practice (KAP) about FH disorder among Saudi medical interns and to identify areas that need educational attention.

Methods

This cross-sectional study involved 170 Saudi medical interns (83 males and 87 females) from academic institutes in Jeddah, Saudi Arabia. The interns were asked to fill an online FH-KAP questionnaire. Total score for each separate domain measured by adding correct answers.

Results

Although, knowledge of FH definition (76.5%) and classical lipid profile (52.4%) were reasonable; knowledge on inheritance (43.5%), prevalence (12.4%) and CAD risks (7.1%) were poor. Knowledge score was significantly higher in female than male (7.5 ± 3 vs. 5.3 ± 2.6, P < 0.001). Regarding awareness, 54.1% were familiar with FH disorder, 50.6% with the presence of lipid clinic but only 16.5% were acquainted with guidelines. Furthermore, in the practice domain 82.9% selected statin as first line treatment and 62.9% chose routinely checking the rest of the family, while 15.3% chose ages 13–18 years to screen for hypercholesterolemia in patients with a positive family history of premature CAD.

Conclusion

Substantial defects in FH-KAP among Saudi medical interns were found, emphasizing the importance of professional training. Extensive and constant medical education programs as early as an internship are required to close the gap in CAD prevention.
Speckle tracking echocardiographically-based analysis of ventricular strain in children: an intervendor comparison
Authors: Ferraro Alessandra M. , Adar Adi , Ghelani Sunil J. , Sleeper Lynn A. , Levy Philip T. , Rathod Rahul H. , Marx Gerald R. , Harrild David M.
Published: May 2020

Background

Strain and synchrony can be calculated from a variety of software packages, but there is a paucity of data with inter-vendor comparisons in children. To test the hypothesis that different packages may affect results, independent of acquisition, we compared values obtained using two commercially available analysis tool (QLAB and TomTec), with several different settings.

Methods

The study population included 108 children; patients were divided into three groups: (1) normal cardiac structure and conduction; (2) ventricular paced rhythm; and (3) flattened ventricular septum (reflecting right ventricular pressure or volume load lesions). We analyzed the same image acquired from the apical 4-chamber (AP4) and short-axis at the mid-papillary level (SAXM) views in both QLAB (versions 10.5 and 10.8) and TomTec (version 1.2). In QLAB version 10.8, low, medium, and high quantification smoothness settings were employed. In TomTec, images were analyzed with both low and high frame rates. Tracking quality for each package was graded. AP4 and SAXM strain and synchrony values were recorded. A mixed-effects linear regression model was used, with main effect considered significant if the p-value was < 0.05.

Results

Tracking scores were high for all packages except QLAB 10.5 in the SAXM view. AP4 and SAXM strain values varied significantly between QLAB 10.5 and the other packages. Synchrony values varied widely for all strain values (p < 0.001 for both) in all packages. Quantification smoothness changes in QLAB 10.8 did not impact strain significantly in any patient group; temporal resolution changes in TomTec resulted in strain differences in children with flat ventricular septums, but not those with normal or ventricular paced hearts.

Conclusion

Synchrony values varied substantially among all packages in children. Strain values varied widely between QLAB 10.5 and all other software packages, recommending avoidance of QLAB 10.5 for future studies. Quantification smoothness settings in QLAB 10.8 resulted in minimal strain differences. In TomTec, low and high frame rate strain values differed only in a subset of patients (flattened septum). These data suggest that reliable comparisons between strain values derived from QLAB and TomTec is possible in certain cases, but that caution should be used especially in different hemodynamics conditions.
Postoperative outcomes of gastric carcinoma with lymphoid stroma
Authors: Iwasaki Kenichi , Suda Takeshi , Takano Yuki , Ohno Yuki , Yamada Erika , Okazaki Naoto , Takahashi Kosuke , Watanabe Takafumi , Makuuchi Yosuke , Ota Yoshihiro , Osaka Yoshiaki , Seshimo Akiyoshi , Katsumata Kenji , Tsuchida Akihiko
Published: May 2020

Background

Gastric carcinoma with lymphoid stroma (GCLS) is a rare subtype of gastric cancer. There have been several reports demonstrating the favorable prognosis of early GCLS without lymph node metastasis (LNM) compared with gastric adenocarcinomas. However, it remains unknown whether advanced GCLS (AGCLS) with LNM has a similar prognosis and clinicopathological features. This study aimed to assess the clinicopathological features of GCLS of all stages.

Methods

We retrospectively assessed 375 patients who were pathologically diagnosed with gastric cancer and underwent curative surgical resection at Tokyo Medical University, Japan, between September 2013 and October 2019. Of these patients, 357 (95.2%) patients were pathologically diagnosed with gastric adenocarcinomas, and 18 (4.8%) patients were diagnosed with GCLS. The GCLS patients (n = 18) were compared with the gastric adenocarcinoma patients (non-GCLS patients, control) (n = 357) in terms of their clinicopathological features and clinical outcome.

Results

The GCLS patients showed significantly predominant upper gastric locations (P = 0.003), lower number of LNM (P = 0.01), and better overall survival rate than the non-GCLS patients (P = 0.029). The predominant upper gastric locations (P = 0.0002), lower number of LNM (P = 0.003), and better overall survival rate (P = 0.04) were significantly correlated in the AGCLS with LNM patients compared with the advanced non-GCLS with LNM patients. For survival analyses, surgical procedure, tumor location, and numbers of positive LNM were adjusted by 1:1 propensity score matching. After adjustment, the overall survival rate was significantly higher in the AGCLS group than in the advanced non-GCLS group (P = 0.03).

Conclusion

AGCLS has distinct clinicopathological features and clinical behavior that are similar to those of early GCLS. AGCLS with LNM patients showed a significantly lower number of LNM and a better survival rate than advanced non-GCLS with LNM patients. To our knowledge, this study is the first report to describe the clinicopathological features of AGCLS.
The lethal sex gap: COVID-19
Authors: Márquez Eladio J. , Trowbridge Jennifer , Kuchel George A. , Banchereau Jacques , Ucar Duygu
Published: May 2020

While Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is disrupting lives across the globe for everyone, it has a more devastating impact on the health of older adults, especially that of older men. This pandemic has highlighted the crucial importance of considering an individual’s age and biological sex in the clinic in addition to other confounding diseases (Kuchel, G.A, J Am Geriatr Soc, 67, 203, 2019, Tannenbaum, C., Nature, 575 451-458, 2009) As an interdisciplinary team of scientists in immunology, hematology, genomics, bioinformatics, and geriatrics, we have been studying how age and sex shape the human immune system. Herein we reflect on how our recent findings on the alterations of the immune system in aging might contribute to our current understanding of COVID-19 infection rate and disease risk.
Trends, Patterns, and Treatment Outcomes of Cancer Among Older Patients in Jordan: A Retrospective Analysis of National Cancer Registry and Institutional Outcome Data
Authors: Abdel-Razeq Hikmat , Mansour Asem , Bater Rayan
Published: May 2020

PURPOSE

Cancer is a leading cause of morbidity and the second leading cause of mortality in Jordan and worldwide. Because of their age and comorbidities, older patients may receive suboptimal cancer therapy. This article addresses trends in cancer incidence and reports key treatment outcomes in this age group.

MATERIALS AND METHODS

This is a retrospective study using data obtained from the national Jordan Cancer Registry (JCR) and our institutional cancer registry. The first data set reports only on demographics, whereas the second data set reports also on treatment outcomes. Older patients were defined as those age 65 years or older at time of diagnosis.

RESULTS

Between 2001 and 2015, a total of 19,397 older patients were diagnosed with cancer, representing 29.8% of the total 65,050 patients with cancer diagnosed during this time. More men than women developed cancer, and colorectal, breast, lung, prostate, and bladder cancers were the most commonly reported cancers. Among this age group over the 15-year study period, cancer diagnoses increased by a rate of 77%, much higher than the 55% increment among all ages during the same study period. The 5-year survival rate for all of the 3,821 older patients diagnosed, treated, and followed up at our institution was 33% but varied by stage (63% for stage I disease and 14% for stage IV disease).

CONCLUSION

Cancer diagnoses among older patients are increasing at a rate higher than that of all ages and much higher than the witnessed increase in Jordanian population in same age group, which highlights the importance of looking for factors other than just aging to explain this increase. Strategies to offer better care for this rapidly expanding group are highly needed.
Intragenic Deletions of GNAS in Pseudohypoparathyroidism Type 1A Identify a New Region Affecting Methylation of Exon A/B
Authors: Li Dong , Bupp Caleb , March Michael E , Hakonarson Hakon , Levine Michael A
Published: May 2020

Context

Pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are caused by inactivating mutations in the exons of GNAS that encode the alpha-subunit of the stimulatory G protein (Gsα). In some cases abnormal methylation of exon A/B of GNAS, a hallmark of PHP1B, has been reported.

Objective

To identify the underlying genetic basis for PHP1A/PPHP in patients in whom molecular defects were not detected by GNAS sequencing and microarray-based analysis of copy number variations.

Methods

Whole genome sequencing (WGS) and pyrosequencing of differentially methylated regions (DMRs) of GNAS using genomic deoxyribonucleic acid from affected patients.

Results

We identified 2 novel heterozygous GNAS deletions: a 6.4 kb deletion that includes exon 2 of GNAS in the first proband that was associated with normal methylation (57%) of exon A/B DMR, and a 1438 bp deletion in a second PHP1A patient that encompasses the promoter region and 5′ untranslated region of Gsα transcripts, which was inherited from his mother with PPHP. This deletion was associated with reduced methylation (32%) of exon A/B DMR.

Conclusions

WGS can detect exonic and intronic mutations, including deletions that are too small to be identified by microarray analysis, and therefore is more sensitive than other techniques for molecular analysis of PHP1A/PPHP. One of the deletions we identified led to reduced methylation of exon A/B DMR, further refining a region needed for normal imprinting of this DMR. We propose that deletion of this region can explain why some PHP1A patients have reduced of methylation of the exon A/B DMR.
The Peripubertal Decline in Makorin Ring Finger Protein 3 Expression is Independent of Leptin Action
Authors: Roberts Stephanie A , Abreu Ana Paula , Navarro Victor M , Liang Joy N , Maguire Caroline A , Kim Han Kyeol , Carroll Rona S , Kaiser Ursula B
Published: May 2020

A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of Makorin Ring Finger Protein 3 (MKRN3), in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic Mkrn3 mRNA levels observed in mice during pubertal development. We first used a leptin-deficient (ob/ob) mouse model. Mkrn3 mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in ob/ob mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on Mkrn3 expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in Mkrn3 expression levels in either the MBH or POA. In summary, regulation of Mkrn3 expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in Mkrn3 at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.
Borders Be Damned!
Authors: Hobson Geary
Published: May 2020

This article provides a summary of Canadian First Nations writing and publishing within the context of Native American literature, with references to the entire area of Western Hemisphere Native writing. Admittedly, some readers and scholars will notice the omission of certain writers and their works, but it is maintained that this is somewhat the essence of the article: Native writing in the Western Hemisphere is still in the process of being identified, read, and recognized as such. Thus this article underpins the notion that the work of recognizing and categorizing such work is a continuing, necessary, and wonderful endeavor.
Restitution of Human Remains and Landscape Resignification
Authors: Curtoni Rafael Pedro , Heider Guillermo , Chaparro María Gabriela , Tuninetti Ángel T.
Published: May 2020

The restitution of human remains is a process wherein diverse agencies and meanings emerge. In Argentina there has been a significant increase of these processes, as well as claims of human bodies, during the early twenty-first century, allowing the appearance of new actors, the reconfiguration of public policies, and varied academic approaches. This article deals with a seldom-studied phenomenon—resignification of the territory as a consequence of a restitution—focusing on a recent example that involved the Rankülche Nation, an Indigenous nation in central Argentina, and its relationship with the government of La Pampa province, with scientists, and with members of the local community.
Indigenous-Inspired Authorial Figures and Networks of Rural-Urban Migrants inThe Fox from Up Above and the Fox from Down Below(1971), by José María Arguedas
Authors: Muñoz-Diaz Javier Alonso
Published: May 2020

This article discusses the representation of Indigenous-inspired authorial figures in The Fox from Up Above and the Fox from Down Below, by José María Arguedas. In the context of the 1960s Latin American Boom, Arguedas’s novel includes a reflection on the professionalization of literary writing, as well as the impact of commodification on Indigenous migrants in Chimbote. This article draws parallels between the diarist Arguedas (who defines himself as a nonprofessional writer attached to Indigenous cultures), the fishing entrepreneur Braschi (a mythical figure and the begetter of Chimbote’s industrialization), and the networks of rural-urban migrants (which assimilate the “gringo” Maxwell, performer of Andean folklore). As a model for Indigenous-inspired authorial figures, this article suggests the importance of Arguedas’s articles about the mestizo retablista Joaquín Lopez Antay, who defended the artistic integrity of his craftwork against economic demands. On that note, the networks of rural-urban migrants negotiate their standing in the modernizing process with a strong and flexible Indigenous identity.
The atypical histone variant H3.15 promotes callus formation in Arabidopsis thaliana
Authors: Yan An , Borg Michael , Berger Frédéric , Chen Zhong
Published: May 2020

Plants are capable of regenerating new organs after mechanical injury. The regeneration process involves genome-wide reprogramming of transcription, which usually requires dynamic changes in the chromatin landscape. We show that the histone 3 variant HISTONE THREE RELATED 15 (H3.15) plays an important role in cell fate reprogramming during plant regeneration in Arabidopsis. H3.15 expression is rapidly induced upon wounding. Ectopic overexpression of H3.15 promotes cell proliferation to form a larger callus at the wound site, whereas htr15 mutation compromises callus formation. H3.15 is distinguished from other Arabidopsis histones by the absence of the lysine residue 27 that is trimethylated by the POLYCOMB REPRESSIVE COMPLEX 2 (PRC2) in constitutively expressed H3 variants. Overexpression of H3.15 promotes the removal of the transcriptional repressive mark H3K27me3 from chromatin, which results in transcriptional de-repression of downstream genes, such as WUSCHEL RELATED HOMEOBOX 11 (WOX11). Our results reveal a new mechanism for a release from PRC2-mediated gene repression through H3.15 deposition into chromatin, which is involved in reprogramming cell fate to produce pluripotent callus cells.
Minimizing contrast media dose in CT pulmonary angiography with high-pitch technique
Authors: Alobeidi Hanan , Alshamari Muhammed , Widell Jonas , Eriksson Tomas , Lidén Mats
Published: May 2020

Objectives:

To perform CT pulmonary angiography (CTPA) using a minimal amount of iodinated contrast media.

Methods:

47 patients (25 females) with mean age 69 years (range 41–82 years) referred for contrast-enhanced chest CT were prospectively included in this Phase IV clinical drug trial. All participants underwent a study specific CTPA in addition to the chest CT. The participants received 80 mg I/kg body weight Iohexol contrast media using a preparatory saline bolus, a dual flow contrast/saline bolus and a saline flush, and a scanner protocol with 80 kVp dual source high-pitch mode. Three readers independently assessed the image quality on the 3-point scale non-diagnostic, adequate or good-excellent image quality. Additionally, the pulmonary arterial contrast opacification was measured.

Results:

On average, the patients received 16.8 ml Iohexol 350 mg I/mL (range 12–20 ml). Mean patient weight was 71 kg (range 50–85 kg). Identically for all readers, pulmonary embolism (PE) was detected in 1/47 participants. The median number of examinations visually scored concerning pulmonary embolism as good–excellent was 47/47 (range 44–47); adequate 0/47 (0–3) and non-diagnostic 0/47 (range 0–0). The proportion adequate or better examinations was for all readers 47/47, 100% [95% confidence interval 92–100%]. The mean attenuation ± standard deviation in the pulmonary trunk was 325 ± 72 Hounsfield unit (range 165–531 Hounsfield unit).

Conclusions:

Diagnostic CTPA with 17 ml contrast media is possible in non-obese patients using low kVp, high pitch and carefully designed contrast media administration.

Advances in knowledge:

By combining several procedures in a CTPA protocol, the contrast media dose can be minimized.
The impact of restricted length of treatment field and anthropometric factors on selection of head and neck cancer patients for treatment on the MR-Linac
Authors: Ng-Cheng-Hin Brian , Nutting Christopher , Newbold Kate , Bhide Shreerang , McQuaid Dualta , Dunlop Alex , Harrington Kevin , Wong Kee Howe
Published: May 2020

Objective:

This study investigates the impact of a restricted craniocaudal (CC) field length of <20 cm on the selection of head and neck cancer (HNC) patients who can be treated on the MR-Linac using a single isocentre technique. We also assess the effects of anthropometric factors and the neck position on the CC field length.

Methods:

110 HNC patients who underwent radical primary or adjuvant radiotherapy were retrospectively analysed. We assessed the proportion of treatment fields with a CC length of <20 cm and the effects of gender, height, hyo-sternal neck length (distance from superior surface of hyoid to sternal notch measured on the coronal reconstruction of the planning CT) and neck position on CC length.

Results:

95% of HNC patients had a CC field length <20 cm. Female patients showed a significantly shorter median CC length than male patients in both extended (p = 0.0003) and neutral (p = 0.008) neck positions. Neck position influenced the median CC length with neutral neck being significantly shorter than extended neck (p = 0.0119). Patient height and hyo-sternal neck length showed positive correlation with the CC length, with neck length in neutral position having the strongest correlation (r = 0.65, p = 0.0001 and r = 0.63, p < 0.0001, respectively for extended neck; r = 0.55, p = 0.0070 and r = 0.80, p < 0.0001, respectively for neutral neck). A hyo-sternal neck length of <14.6 cm predicted a CC length of <20 cm in neutral neck position.

Conclusion:

The majority of patients with HNC at the Royal Marsden Hospital have anthropometric features compatible with their being treated on the MR-Linac using a single isocentre technique. The absolute CC field size may vary according to primary tumour site, patient factors and neck position. A hyo-sternal neck length cut-off of 14.6 cm in the neutral neck position can be used as a surrogate marker for suitability of treatment on MR-Linac.

Advances in knowledge:

This paper highlights the potential impact of a restricted CC field in HNC patient selection for the MR-Linac treatment. This is the first report to suggest the use of neck length as a surrogate marker for suitability of treatment on the MR-Linac.
Lizbona – miasto zawłaszczone
Authors: Golemo Karolina
Published: May 2020

Lisbon – A City Taken Over. Who Does the Portuguese Capital Belong to?

Dynamic development of tourism is a force transforming many of today’s cities. Changes caused by growing tourism mobility are visible at different levels: economic (imbalance of housing market, increasing prices), socio-cultural (gentrification and its consequences: change of inhabitants’ profiles, new neighborhood relations, new styles of consumption) and aesthetic-symbolic (intervention in urban landscapes through modernization and reorganization of traditional spaces). As an answer to these processes different forms of social protest appear against the uncontrolled development of mass tourism. The aim of this paper is to show the dynamics between the inhabitants of historical zones of Lisbon and visitors, as well as to explain the consequences of touristification on social relations in urban space.
Identyfikacja społeczno-kulturowa oraz samoocena kompetencji ogólnych do komunikacji międzykulturowej wśród studentów obcokrajowców
Authors: Majcher-Legawiec Urszula
Published: May 2020

Socio-cultural Identification and Self-Appraisal of General Competence in Multicultural Communication in Foreign Students

The article presents the results of research on socio-cultural identification and self-assessment of general competences for intercultural communication carried out among foreign students preparing for studies in Polish under the socalled zero year. The behaviors of participants in the communication process, including intercultural communication, are conditioned by situational factors that are based on the socio-cultural context. Interaction participants set the situation in a known cultural context, which in the case of intercultural communication can lead to misunderstanding and frustration. Therefore, negotiating the meanings in the interaction of multicultural partners faces many conditions. Among those conditions, knowledge of the language (or lack thereof ) is just one of many elements. The remaining elements are general, cognitive and cultural competences as well as a set of competences including knowledge, practical skills and mindsets relating to social and communication behavior. The research was conducted among MCK PK students and it pertained to competences for multicultural communication. To reach this goal, slightly modified research tools prepared by a research team from the University of Bialystok were used. The collected data has been subjected to statistical analysis and interpretation.
Tożsamość narodowa Szkotów w Zjednoczonym Królestwie Wielkiej Brytanii i Irlandii Północnej
Authors: Radowicz Joanna Aleksandra
Published: May 2020

Scottish National Identity in the United Kingdom of Great Britain and Northern Ireland Scotland became part of the United Kingdom in 1707, when the Act of Union was signed by both the Scottish and English Parliaments. Even though Scots were then largely subordinated to the decisions taken by Westminster, they maintained a sense of independence. One of the most important elements of building Scottish national identity is their history, mainly based on Scottish- English relations and traditions that have been thought to be “invented” by intellectual elites in the eighteenth and nineteenth centuries. The aim of the article is to present Scottish national identity in comparison to historical conditions, with particular emphasis on Scottish-English relations.
Pozycja ustrojowa Prezydenta RP w systemie konstytucyjnym Rzeczpospolitej Polskiej w kontekście członkostwa w Unii Europejskiej
Authors: Budzanowska Anna
Published: May 2020

The Constitutional Role of the President of the Republic of Poland in the Context of Membership of the European Union

The article presents a synthetic analysis of issues related to the constitutional position of the President of the Republic of Poland in constitutional and institutional order in the context of Poland’s membership in the structures of the European Union. The text mentions the basics of not only legal but also functional elements of the constitutional system. The purpose of this article is also to indicate how much the constitutional model of the executive bodies is sufficient to resolving problematic political issues when there is a particular kind of relationship between the head of state and the government administration.