bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Covid-19 Pandemic on Prostate Cancer Investigation and Diagnosis in the Brazilian Public Health System (SUS)
Authors: Kieling Lucas , Estacia da Silveira Izadora Bouzeid , Seixas de Sá Beltramo Luiza , Hass Lopes Yasmin Ricarte , Lech Gabriele Eckerdt , Marques da Silva Laura Tibola , Mateus Danna Gomes
Published: May 2022

PURPOSE

Prostate cancer was the second most deadly type of cancer in males in Brazil in 2019. Therefore, early diagnosis is fundamental to reduce its morbimortality. Diagnosis is essentially confirmed by prostate biopsy. The overload on health systems caused by the coronavirus pandemic has strongly affected the investigation process in Brazilian public healthcare (SUS). Under these circumstances, we aim to expose the effects of COVID-19 in the screening and diagnosis of prostate cancer performed by SUS.

METHODS

A cross-sectional design of data collected from DATASUS's Hospital Information System. The study analyzes absolute numbers of prostate biopsies and diagnosis of prostate cancer registered between January and July in 10 years (2011-2020) which were comparatively evaluated. Statistical analysis was performed to assess the number of procedures compared over the years.

RESULTS

The number of prostate biopsies in Brazil, through the Public Health System (SUS), between January 2011 and December 2019, was 393,678 with a yearly average of 43,742 procedures. In 2020, there was a 27.23% decrease, meaning only 31,829 procedures. In agreement with that, a decrease of 49.71%, 33.73%, 37.25% and 40.76% on prostate cancer diagnosis was reported in the months of April, May, June and July, respectively, when comparing 2019 and 2020. The total number of prostate cancer diagnoses also suffered a decrease of 27.32% between the years of 2019 and 2020, going from 41,981 procedures to only 30,511.

CONCLUSION

The reduction on the number of prostate cancer diagnosis is evident and is going to affect the morbimortality of the patients who haven't had access to the health system during the covid 19 pandemic. It is fundamental to know the amount of damming on those diagnoses to propose measures to prevent the worst outcomes, reducing avoidable deaths.
Coverage and Socio-Economic Inequalities in Breast Cancer Screening in Low- and Middle-Income Countries: Analysis of Demographic and Health Surveys Between 2010 and 2019
Authors: Abila Derrick Bary , Kangoma Grace , Kisuza Ruth Ketty , Wasukira Sulaiman Bugosera , Ainembabazi Provia , Wabinga Henry
Published: May 2022

PURPOSE

The World Health Organisation (WHO) launched the Global Breast Cancer Initiative (GBCI) in 2020 intending to reduce global breast cancer mortality by 2.5% per year until 2040, thereby averting an estimated 2.5 million deaths. In this study, we aimed to determine the coverage and socio-economic inequalities in the screening for breast cancer over one decade before the establishment of the GBCI.

METHODS

For each country, using STATA 16 software and sampling weights, we analyzed the datasets of Demographic and Health Surveys (DHS) that included questions on breast cancer screening and were conducted between 2010 and 2019 in low- and middle-income countries. We included women aged 15-49 years and considered screening using breast self-examination (BSE), clinical breast examination (CBE), and mammography. Absolute and relative inequalities were determined using the Slope Index of Inequality (SII) and Concentration Index (CIX) respectively.

RESULTS

A total of 18 surveys from 13 countries were included in this study. Only six surveys from five countries measured the rates of screening by mammography which ranged from 5.58% to 12.96%. Considering screening using any method, the proportion that had ever screened for breast cancer ranged from 2.53% to 60.21%. Higher rates of screening were seen in upper-middle-income countries compared to low-income countries. For the CIX for screening using any method, the inequalities were pro-rich in all the countries except the Philippines where it was pro-poor with a CIX of –2.84 ( P value .015). For the CIX and SII for screening using mammography, the inequalities were pro-rich in all the countries.

CONCLUSION

There exist socio-economic disparities in the coverage of breast cancer using mammography, clinical breast examination, and breast self-exam. There is a need to address these disparities to achieve the targets of breast cancer control by the GBCI.
Accelerating Learning Health Systems Using Alicanto Collaboration Platforms
Authors: Quintana Yuri , Einstein David , Joyce Robin , Lyu Andrew , El Sayed Nuha , Andrews Carolyn , Rebbeck Tim
Published: May 2022

PURPOSE

Global health challenges require systematic approaches that bring together a wide range of stakeholders and experts unevenly distributed worldwide. We saw an even greater need to find novel ways to collaborate during the pandemic due to limited in-person meetings and travel restrictions. The purpose of this project is to accelerate collaborations in learning health systems with online technologies to improve communication, education, and knowledge management.

METHODS

We developed Alicanto Cloud, an online collaboration platform for healthcare professionals to support learning health systems. Alicanto aims to help groups communicate, share educational resources, discuss complex clinical cases across institutions and countries. Alicanto provides multiple ways for users to create synchronous and asynchronous discussions. Alicanto was developed by the BIDMC Division of Clinical Informatics in collaboration with local and international colleagues with a specific focus on global health and capacity building.

RESULTS

Alicanto is being used worldwide for cancer, pediatrics, and diabetes collaborations. Online communities use Alicanto to standardize care guidelines, disseminate clinical care best practices, provide online training, conduct virtual tumor boards, and improve knowledge management. Beth Israel Deaconess Medical Center has used Alicanto to connect 13 hospitals and has completed over 600 virtual tumor board case discussions. Dana-Farber Cancer Institute uses Alicanto as an online cancer training network for sub-Saharan Africa. Doctors from Joslin Clinic have used Alicanto to create a global diabetes education network. We will discuss lessons learned in implementing these networks and best practices for accelerating the process of evidence synthesis to dissemination and capacity building.

CONCLUSION

Communities of practice can accelerate their communications and collaborations with the appropriate tools and platforms tailored to their network needs. Further research is needed to understand the optimal ways to create sustained growth and support of communities of practice in learning health systems.
Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of FAM19A4/miR124-2 DNA Methylation (CONCERVE Study)
Authors: Kremer Wieke W. , Dick Stèfanie , Heideman Daniëlle A.M. , Steenbergen Renske D.M. , Bleeker Maaike C.G. , Verhoeve Harold R. , van Baal W. Marchien , van Trommel Nienke , Kenter Gemma G. , Meijer Chris J.L.M. , Berkhof Johannes
Published: May 2022

PURPOSE

Cervical screening can prevent cancer by detection and treatment of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Screening also results in considerable overtreatment because many CIN2/3 lesions show spontaneous regression when left untreated. In this multicenter longitudinal cohort study of women with untreated CIN2/3, the prognostic value of FAM19A4/miR124-2 methylation was evaluated for clinical regression.

PATIENTS AND METHODS

Women with CIN2/3 were prospectively followed for 24 months. Surgical excision was replaced by a wait-and-see policy. FAM19A4/miR124-2 methylation was evaluated on all clinician-collected samples and self-collected samples collected at baseline. Every 6 months, human papillomavirus (HPV) testing and cytology were conducted on a clinician-collected sample, and a colposcopic examination was performed by a gynecologist to exclude progression. At the final study visit, two biopsies were taken. Clinical regression was defined as histologically confirmed absence of CIN2+ or an HPV-negative clinician-collected sample with normal cytology. Regression incidences were estimated using the Kaplan-Meier method.

RESULTS

One hundred fourteen women (median age, 30 years; range, 20-53 years) were included, 80 of whom were diagnosed with CIN2 and 34 with CIN3. During the study, 65.8% of women (75/114) did not receive surgical treatment. Women with a negative FAM19A4/miR124-2 result on the baseline clinician-collected sample showed more clinical regression (74.7%) than women with a positive methylation result (51.4%, P = .013). Regression in women with a negative FAM19A4/miR124-2 methylation test was highest when cytology was atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (88.4%) or HPV16 was negative (85.1%).

CONCLUSION

Most women with untreated CIN2/3 and a negative baseline FAM19A4/miR124-2 methylation test showed clinical regression. Methylation, in combination with cytology or HPV genotyping, can be used to support a wait-and-see policy in women with CIN2/3.
Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial
Authors: Yoshino Takayuki , Oki Eiji , Misumi Toshihiro , Kotaka Masahito , Manaka Dai , Eto Tetsuya , Hasegawa Junichi , Takagane Akinori , Nakamura Masato , Kato Takeshi , Munemoto Yoshinori , Nakamura Fumitaka , Bando Hiroyuki , Taniguchi Hiroki , Sakamoto Yasuhiro , Shiozawa Manabu , Nishi Masayasu , Horiuchi Tetsuya , Yamagishi Hisakazu , Sakamoto Junichi , Mizushima Tsunekazu , Ohtsu Atsushi , Mori Masaki
Published: May 2022

PURPOSE

The phase III ACHIEVE trial conducted in Japan was one of six prospective studies included in the International Duration Evaluation of Adjuvant Therapy collaboration, which explored whether 3 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) therapy would be noninferior to 6 months of treatment in patients with curatively resected stage III colon cancer. We report the final analyses of survival and long-term safety.

PATIENTS AND METHODS

Eligible patients were randomly assigned (1:1) to either 3 or 6 months of adjuvant chemotherapy (modified [m]FOLFOX6 or CAPOX, as selected by the treating physician). Random assignment was stratified according to number of involved lymph nodes, center, regimen, primary site, and age. The primary end point was disease-free survival, assessed in the modified intention-to-treat population. Overall survival (OS) was a secondary end point.

RESULTS

The modified intention-to-treat population comprised 1,291 patients: 641 in the 6-month treatment group and 650 in the 3-month treatment group. Median follow-up for this analysis was 74.7 months. Five-year OS rates were comparable: 87.0% in the 3-month treatment group and 86.4% in the 6-month treatment group (hazard ratio, 0.91; 95% CI, 0.69 to 1.20; P = .51). Subgroup analysis of OS did not reveal a significant interaction between baseline characteristics and treatment duration. Peripheral sensory neuropathy lasting longer than 5 years was more common in the 6- compared with 3-month treatment group (16% v 8%, respectively), and in those receiving mFOLFOX6 compared with CAPOX (14% v 11%, respectively).

CONCLUSION

In Asian patients, shortening adjuvant therapy duration from 6 to 3 months did not compromise efficacy and reduced the rate of long-lasting peripheral sensory neuropathy. In this setting, 3 months of CAPOX therapy is an appropriate adjuvant treatment option.
Serum PFAS and Urinary Phthalate Biomarker Concentrations and Bone Mineral Density in 12-19 Year Olds: 2011-2016 NHANES
Authors: Carwile Jenny L , Seshasayee Shravanthi M , Ahrens Katherine A , Hauser Russ , Driban Jeffrey B , Rosen Clifford J , Gordon Catherine M , Fleisch Abby F
Published: May 2022

Context

Per- and polyfluoroalkyl substances (PFAS) and phthalates are 2 families of environmental endocrine disruptors that may be associated with areal lower bone mineral density (aBMD).

Objective

To examine associations between serum PFAS and urinary phthalate biomarker concentrations and their mixtures with aBMD Z-scores in adolescents.

Design, Patients, and Measures

We examined serial cross-sectional data from male (n = 453) and female (n = 395) 12- to 19-year-old participants in the 2011 through 2016 National Health and Nutrition Examination Survey with measures of serum PFAS, urinary phthalate metabolites, and dual-energy X-ray absorptiometry aBMD Z-scores (total body less head). In sex-specific models, we used linear regression to examine associations of individual PFAS and phthalate biomarkers with aBMD Z-scores, and Bayesian kernel machine regression to examine the association of the overall PFAS/phthalate biomarker mixture with aBMD Z-scores. We replicated the analysis, stratifying by race/ethnicity.

Results

Participants were (mean ± SD) 15 ± 2.1 years of age. In males, each doubling of serum perfluorooctanoate (PFOA), perfluorooctane sulfonate, urinary mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate, and the overall PFAS/phthalate mixture was associated with a lower aBMD Z-score (eg, for PFOA: -0.24; 95% CI, -0.41 to -0.06). Serum PFOA and urinary MiBP were associated with higher aBMD Z-scores in females (eg, for PFOA: 0.09; 95% CI, -0.07 to 0.25). Findings did not differ by race/ethnicity.

Conclusions

Certain PFAS and phthalates may be associated with reduced bone mineral density in adolescent males. Bone mineral density tracks across the life course, so if replicated in longitudinal cohorts, this finding may have implications for lifelong skeletal health.
Approach to the Patient: Hyponatremia and the Syndrome of Inappropriate Antidiuresis (SIAD)
Authors: Martin-Grace Julie , Tomkins Maria , O’Reilly Michael W , Thompson Chris J , Sherlock Mark
Published: May 2022

Hyponatremia is the most common electrolyte disturbance seen in clinical practice, affecting up to 30% of acute hospital admissions, and is associated with significant adverse clinical outcomes. Acute or severe symptomatic hyponatremia carries a high risk of neurological morbidity and mortality. In contrast, chronic hyponatremia is associated with significant morbidity including increased risk of falls, osteoporosis, fractures, gait instability, and cognitive decline; prolonged hospital admissions; and etiology-specific increase in mortality. In this Approach to the Patient, we review and compare the current recommendations, guidelines, and literature for diagnosis and treatment options for both acute and chronic hyponatremia, illustrated by 2 case studies. Particular focus is concentrated on the diagnosis and management of the syndrome of inappropriate antidiuresis. An understanding of the pathophysiology of hyponatremia, along with a synthesis of the duration of hyponatremia, biochemical severity, symptomatology, and blood volume status, forms the structure to guide the appropriate and timely management of hyponatremia. We present 2 illustrative cases that represent common presentations with hyponatremia and discuss the approach to management of these and other causes of hyponatremia.
The Impact of Endogenous Estrogen Exposure Duration on Fracture Incidence: a Longitudinal Cohort Study
Authors: Farahmand Maryam , Rahmati Maryam , Azizi Fereidoun , Behboudi Gandevani Samira , Ramezani Tehrani Fahimeh
Published: May 2022

Context

Although it is well documented that estrogen hormone is positively associated with bone mineral density and lower risk of fracture, there are limited studies on the association between duration of endogenous estrogen exposure (EEE) and fracture, especially by longitudinal design.

Objective

This study aimed to investigate the relationship between EEE with fracture incidence by longitudinal design in a community-based study.

Methods

A total of 5269 eligible postmenarcheal women, including 2411 premenopausal and 2858 menopausal women, were recruited from among the Tehran Lipid and Glucose Study. Cox proportional hazards regression model with adjustment of potential confounders was performed to assess the relationship between duration of EEE and incident of any hospitalized fractures.

Results

A total of 26.7% (1409/5269) women were menopausal at the baseline, and 2858 of the remaining participants reached menopause at the end of follow-up. Results of the unadjusted model demonstrated that the EEE z-score was negatively associated with fracture incidence [unadjusted hazard ratio (HR) 0.81, 95% CI 0.68-0.96] in postmenarchal women, indicating that per 1-SD increase of EEE z-score, the hazard of fracture reduced by 19%. Results remained statistically unchanged after adjustment for potential confounders (adjusted HR 0.70, 95% CI 0.58-0.86).

Conclusion

The findings of this cohort study suggest that a longer duration of EEE has a protective effect on fracture incidence; a point that needs to be considered in fracture risk assessment.
Increased Adipose Tissue Indices of Androgen Catabolism and Aromatization in Women With Metabolic Dysfunction
Authors: Ostinelli Giada , Laforest Sofia , Denham Scott G , Gauthier Marie-Frederique , Drolet-Labelle Virginie , Scott Emma , Hould Frédéric-Simon , Marceau Simon , Homer Natalie Z M , Bégin Catherine , Andrew Ruth , Tchernof André
Published: May 2022

Context

Body fat distribution is a risk factor for obesity-associated comorbidities, and adipose tissue dysfunction plays a role in this association. In humans, there is a sex difference in body fat distribution, and steroid hormones are known to regulate several cellular processes within adipose tissue.

Objective

Our aim was to investigate if intra-adipose steroid concentration and expression or activity of steroidogenic enzymes were associated with features of adipose tissue dysfunction in individuals with severe obesity.

Methods

Samples from 40 bariatric candidates (31 women, 9 men) were included in the study. Visceral (VAT) and subcutaneous adipose tissue (SAT) were collected during surgery. Adipose tissue morphology was measured by a combination of histological staining and semi-automated quantification. Following extraction, intra-adipose and plasma steroid concentrations were determined by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Aromatase activity was estimated using product over substrate ratio, while AKR1C2 activity was measured directly by fluorogenic probe. Gene expression was measured by quantitative PCR.

Results

VAT aromatase activity was positively associated with VAT adipocyte hypertrophy (P valueadj < 0.01) and negatively with plasma high-density lipoprotein (HDL)-cholesterol (P valueadj < 0.01), while SAT aromatase activity predicted dyslipidemia in women even after adjustment for waist circumference, age, and hormonal contraceptive use. We additionally compared women with high and low visceral adiposity index (VAI) and found that VAT excess is characterized by adipose tissue dysfunction, increased androgen catabolism mirrored by increased AKR1C2 activity, and higher aromatase expression and activity indices.

Conclusion

In women, increased androgen catabolism or aromatization is associated with visceral adiposity and adipose tissue dysfunction.
Denosumab and Risk of Community-acquired Pneumonia: A Population-based Cohort Study
Authors: Lyu Houchen , Zhao Sizheng , Li Jiatian , Li Xiaoxiao , Wang Yilun , Xie Dongxing , Zeng Chao , Lei Guanghua , Wei Jie , Li Hui
Published: May 2022

Context

Recent meta-analyses of randomized controlled trials have raised concerns that denosumab might increase the risk of infection. However, data of denosumab on the risk of community-acquired pneumonia are sparse.

Objective

This work aimed to examine the risk of community-acquired pneumonia in individuals receiving denosumab compared to those receiving alendronate.

Methods

We conducted a propensity score-matched cohort study with a UK primary care database (IQVIA Medical Research Database). We examined the relation of denosumab to community-acquired pneumonia using a Cox proportional hazard model. The study participants were osteoporotic patients older than 45 years who were initiators of denosumab or alendronate from August 1, 2010, to September 17, 2020. The outcome measure was community-acquired pneumonia.

Results

Patients treated with denosumab (n = 933) were compared with those treated with alendronate (n = 4652). In the matched population, the mean (SD) age was 77 (11) years, 89% were women, and about half of the study population had a history of major osteoporotic fracture. Over 5 years of follow-up, the incidence of community-acquired pneumonia per 1000 person-years was 72.0 (95% CI, 60.1-85.7) in the denosumab group and 75.1 (95% CI, 69.4-81.2) in the alendronate group. The hazard of community-acquired pneumonia was similar between denosumab and alendronate users (hazard ratio [HR] 0.96; 95% CI, 0.79-1.16). The results remained consistent in a series of sensitivity analyses, with HR ranging from 0.82 (95% CI, 0.65-1.04) to 0.99 (95% CI, 0.81-1.21).

Conclusion

Denosumab does not significantly increase the susceptibility of community-acquired pneumonia and could possibly be safely used for the management of osteoporosis.
Influence of Maternal Exercise on Glucose and Lipid Metabolism in Offspring Stem Cells: ENHANCED by Mom
Authors: Chaves Alec , Weyrauch Luke A , Zheng Donghai , Biagioni Ericka M , Krassovskaia Polina M , Davidson Breanna L , Broskey Nicholas T , Boyle Kristen E , May Linda E , Houmard Joseph A
Published: May 2022

Context

Recent preclinical data suggest exercise during pregnancy can improve the metabolic phenotype not only of the mother, but of the developing offspring as well. However, investigations in human offspring are lacking.

Objective

To characterize the effect of maternal aerobic exercise on the metabolic phenotype of the offspring’s mesenchymal stem cells (MSCs).

Design

Randomized controlled trial.

Setting

Clinical research facility.

Patients

Healthy female adults between 18 and 35 years of age and ≤ 16 weeks’ gestation.

Intervention

Mothers were randomized into 1 of 2 groups: aerobic exercise (AE, n = 10) or nonexercise control (CTRL, n = 10). The AE group completed 150 minutes of weekly moderate-intensity exercise, according to American College of Sports Medicine guidelines, during pregnancy, whereas controls attended stretching sessions.

Main Outcome Measures

Following delivery, MSCs were isolated from the umbilical cord of the offspring and metabolic tracer and immunoblotting experiments were completed in the undifferentiated (D0) or myogenically differentiated (D21) state.

Results

AE-MSCs at D0 had an elevated fold-change over basal in insulin-stimulated glycogen synthesis and reduced nonoxidized glucose metabolite (NOGM) production (P ≤ 0.05). At D21, AE-MSCs had a significant elevation in glucose partitioning toward oxidation (oxidation/NOGM ratio) compared with CTRL (P ≤ 0.05). Immunoblot analysis revealed elevated complex I expression in the AE-MSCs at D21 (P ≤ 0.05). Basal and palmitate-stimulated lipid metabolism was similar between groups at D0 and D21.

Conclusions

These data provide evidence of a programmed metabolic phenotype in human offspring with maternal AE during pregnancy.
Sex and Gender Differences in Anticancer Treatment Toxicity: A Call for Revisiting Drug Dosing in Oncology
Authors: Özdemir Berna C , Gerard Camille L , Espinosa da Silva Cristina
Published: May 2022

The practice of oncology has dramatically changed in the last decade with the introduction of molecular tumor profiling into routine tumor diagnostics and the extraordinary progress in immunotherapies. However, there remains an unmet need to explore personalized dosing strategies that take into account the patient’s sex and gender to optimize the balance between efficacy and toxicity for each individual patient. In this mini-review, we summarize the evidence on sex and gender differences in toxicity of anticancer therapies and present data on dose reduction and dose discontinuation rates for selected chemotherapies and targeted therapies. Finally, we propose the investigation of body composition (specifically fat-free muscle mass) as a viable approach for personalized treatment dosage.
Catastrophic Art
Authors: Moradi Fazil
Published: May 2022

This article is a transdisciplinary inquiry into catastrophic art—artworks whose worlds the empires destroyed and brutally deported to the imperial metropoles. At issue is the impossibility of seeing and speaking of catastrophic art, without at the same time speaking of both systems of knowledge and life forms and of the colonial inheritance and epistemicide. The article follows various historical events, such as Léopold Sédar Senghor's encounter with African art in Paris after World War I and the British colonial destruction of the Kingdom of Benin in 1897; turns to a conference held at the Ethnological Museum in Berlin in 2018; and disturbs Emmanuel Macron's 2017 speech at the University of Ouagadougou and the 2018 French presidential report on restitution. It shows how provenance exhibits epistemicide as it restitutes “looted” art to colonial beneficiaries, and how the incalculability of catastrophic art is to be found in hospitality.
Post-grid Imaginaries
Authors: Nucho Joanne Randa
Published: May 2022

This essay describes an emerging “post-grid imaginary” that is informing visions of future collapse, growing scarcity, and deepening infrastructural fragmentation. By examining electrical grid failures in Lebanon and California, we can move beyond developmentalist assumptions about the supposedly different trajectories of the so-called Global North and South. The post-grid imaginary is at the center of a present and future struggle that is continuous with a global process that looks a lot like structural adjustment in the “Global South” and rampant privatization and austerity in the “Global North.” As states turn away from promises of endless expansion and universal access, the post-grid imaginary is one way in which states, private utilities, and individuals respond to the urgent need to transform the existing energy system. While a post-grid imaginary is not inevitable, it is an increasingly visible approach that can lead to geographical disconnection, uneven access, and infrastructural abandonment.
Green Magic
Authors: Sims Christo
Published: May 2022

Apple's corporate headquarters in Silicon Valley has become an object of public fascination for its technical marvels and green magnificence. However, architectural critics and urbanists have widely critiqued the campus for being socially retrograde and ecologically injurious. This essay queries this divergence in public responses to Apple's headquarters by examining how the campus has been designed to counter a growing disenchantment with neoliberalism, its technologies, and its environmental defilements. In doing so, the essay argues for the analytical potential of adapting anthropological theories of enchantment and magic to the study of contemporary uses of the built environment for branding and public relations purposes.
Transitions in development – an interview with Aissam Ikmi
Authors: Zenner Helen L.
Published: May 2022

Aissam Ikmi is a group leader at the European Molecular Biology Laboratory in Heidelberg, Germany. Aissam uses the sea anemone Nematostella vectensi to interrogate how genetic and environmental factors combine to influence development. Aissam shared with us his thoughts on the ups and downs of scientific careers, and the importance of surrounding yourself with the ‘right’ people.
The retromer complex regulates C. elegans development and mammalian ciliogenesis
Authors: Xie Shuwei , Dierlam Carter , Smith Ellie , Duran Ramon , Williams Allana , Davis Angelina , Mathew Danita , Naslavsky Naava , Iyer Jyoti , Caplan Steve
Published: May 2022

The mammalian retromer consists of subunits VPS26 (either VPS26A or VPS26B), VPS29 and VPS35, and a loosely associated sorting nexin (SNX) heterodimer or a variety of other SNX proteins. Despite involvement in yeast and mammalian cell trafficking, the role of retromer in development is poorly understood, and its impact on primary ciliogenesis remains unknown. Using CRISPR/Cas9 editing, we demonstrate that vps-26-knockout worms have reduced brood sizes, impaired vulval development and decreased body length, all of which have been linked to ciliogenesis defects. Although preliminary studies did not identify worm ciliary defects, and impaired development limited additional ciliogenesis studies, we turned to mammalian cells to investigate the role of retromer in ciliogenesis. VPS35 localized to the primary cilium of mammalian cells, and depletion of VPS26, VPS35, VPS29, SNX1, SNX2, SNX5 or SNX27 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the centriolar protein, CP110 (also known as CCP110), and was required for its removal from the mother centriole. Herein, we characterize new roles for retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, suggesting a novel role for retromer in CP110 removal from the mother centriole.
Model-driven adaptation of Function-as-a-Service applications
Authors: Τσαγκαρόπουλος Ανδρέας
Published: May 2022

H διδακτορική διατριβή τοποθετείται στην περιοχή της προσαρμογής και διαχείρισης υπολογιστικών τοπολογιών νέφους, της ειδικής κατηγορίας εφαρμογών FaaS. Προτείνει μια μεθοδολογία με την οποία μπορεί να γίνει ο ορισμός της τοπολογίας με βάση το TOSCA standard συμπεριλαμβάνοντας και πόρους στο άκρο του δικτύου. Επίσης, η μεθοδολογία συμπεριλαμβάνει μια καινοτόμα προσέγγιση για τη δυναμική ανανέωση της επεξεργαστικής τοπολογίας βάσει κριτηρίων που θέτει ο διαχειριστής της εφαρμογής.Σχετικά με το καθορισμό της περιγραφής των εφαρμογών, έγινε βιβλιογραφική επισκόπηση των σημαντικότερων προτάσεων που έχουν προταθεί, και βασίζονται σε σύγχρονες γενικές γλώσσες περιγραφής εφαρμογών. Επίσης συνοψίστηκε η εκφραστικότητα της κάθε γλώσσας περιγραφής σε σχέση με την αναλυόμενη περιοχή και πραγματοποιήθηκε σύγκριση με μία από τις σημαντικότερες και πιο ευρέως χρησιμοποιούμενες γλώσσες περιγραφής (Terraform).Ως προς το ζήτημα της αναπροσαρμογής των εφαρμογών, πραγματοποιήθηκε έρευνα των υπαρχόντων τρόπων αναπροσαρμογής, και προτάθηκε μία νέα μεθοδολογία που βασίζεται σε κανόνες και αξιολογεί τη ‘Σοβαρότητα’ μιας κατάστασης (Severity) προκειμένου να προτείνει αντίστοιχες ενέργειες αναπροσαρμογής. Οι τιμές της ‘Σοβαρότητας’ προκυπτουν λαμβάνοντας υπόψιν όλες τις δυναμικές τιμές των μετρικών που σχετίζονται με τον εκάστοτε κανόνα. Η αξιοποίηση των τιμών της σοβαρότητας με διαφορετικές τεχνικές επιτρέπει διαφορετικούς τρόπους αντιμετώπισης των υπολογιστικών φορτίων.Πλαισιώνοντας τη παραπάνω έρευνα, δημιουργήθηκαν τέσσερα αυτοτελή υπολογιστικά συστήματα εκ των οποίων τα δύο αποτελούν λογισμικό ανοικτού κώδικα. Το πρώτο από αυτά σχετίζεται με την δημιουργία περιγραφών τοπολογίας εφαρμογών, ενσωματώνοντας τις νέες επεκτάσεις για τη γλώσσα TOSCA. Τα υπόλοιπα τρία αφορούν την πραγματοποίηση αναπροσαρμογής τοπολογιών αξιοποιώντας τεχνικές που βασίζονται πρώτιστα στην έννοια της Σοβαρότητας, ενώ σε δύο από τα συστήματα υποστηρίχθηκαν και άλλοι αλγόριθμοι οι οποίοι χρησιμοποιούνται ευρέως στη παραγωγή σήμερα. Ένα από τα παραπάνω συστήματα επιτρέπει τη διεξαγωγή προσομοιώσεων.Η νέα μεθοδολογία αναπροσαρμογής δείχτηκε ότι επιτρέπει τον ορισμό τεχνικών που οδηγούν σε καλύτερα αποτελέσματα σε αρκετές περιπτώσεις φορτίων μέσα από αντικειμενική συνάρτηση. Τα πειράματα που πραγματοποιήθηκαν σε επίπεδο προσομοιώσεων αλλά και πραγματικής τοπολογίας αποκαλύπτουν την ανάγκη επιλογής διαφορετικών τεχνικών ανάλογα με το υπολογιστικό φορτίο. Η πειραματική εφαρμογή της μεθοδολογίας αναπροσαρμογής που έγινε αξιοποιώντας μια δημοφιλή, πραγματική πλατφόρμα (OpenFaas) καταδεικνύει το εφικτό της προσέγγισης.
Low temperature deposition of functional polycrystalline TiO2 thin films by RF magnetron sputtering
Authors: Βρακατσέλη Βασιλική-Ελευθερία
Published: May 2022

Tα λεπτά υμένια διοξειδίου του τιτανίου (TiO2) αποτελούν αντικείμενο ευρείας έρευνας τις τελευταίες δεκαετίες, τόσο λόγω των μοναδικών τους ιδιοτήτων (φωτοκατάλυση, φωτοεπαγόμεη υπερυδροφιλία, βιοσυμβατότητα κ.α.), όσο και λόγω της λειτουργικότητάς τους σε εφαρμογές παραγωγής ενέργειας (φωτοβολταΐκές διατάξεις 3ης γενιάς), στην οπτοηλεκτρονική και σε περιβαλλοντικές εφαρμογές. Η απόδοσή τους εξαρτάται σημαντικά από την κρυσταλλική τους δομή και την μορφολογία της επιφάνειας. Επίσης έχει διαπιστωθεί ότι η φάση του ανατάση και τα υμένια μικτής φάσης ανατάση/ρουτίλη αποτελούν καλύτερους φωτοτακαλύτες συγκριτικά με τη φάση του ρουτίλη. Ωστόσο, για την εναπόθεση πολυκρυσταλλικών υμενίων TiO2, συνήθως απαιτείται υψηλή θερμοκρασία υποστρώματος (>300οC) ή ανόπτησή τους. Για αυτό τον λόγο, η εναπόθεση κρυσταλλικών υμενίων TiO2 σε πολυμερικά υποστρώματα χαμηλού κόστους δεν είναι πάντοτε δυνατή. Η παρούσα διατριβή ερευνά τις δυνατότητες εναπόθεσης πολυκρυσταλλικών υμενίων ΤiO2 σε χαμηλή θερμοκρασία μέσω της τεχνικής RF magnetron sputtering. Στοχεύοντας στην εναπόθεση υμενίων ΤiO2, με την επιθυμητή κρυσταλλική φάση και μορφολογία. πραγματοποιήθηκαν εναποθέσεις υπό διαφορετικές παραμέτρους και σε δύο διαφορετικές γεωμετρίες του συστήματος: με το υπόστρωμα σε έκκεντρη θέση σε σχέση με την πηγή sputtering και με το υπόστρωμα υπό κλίση σε σχέση με την πηγή. Επετεύχθη η εναπόθεση υμενίων ρουτίλη, ανατάση και μικτής φάσης σε μη θερμαινόμενα υποστρώματα και με υψηλό ρυθμό εναπόθεσης. Η επίδραση των παραμέτρων στις δομικές, μορφολογικές και οπτικές ιδιότητες των υμενίων αξιολογήθηκε εφαρμόζοντας διάφορες τεχνικές χαρακτηρισμού. Διαπιστώθηκε ότι η γωνία κλίσης του υποστρώματος καθώς και η πίεση του συστήματος επιδρούν σημαντικά στην δομή και την μορφολογία των υμενίων. Η μεταβολή της κρυσταλλικής φάσης και της τραχύτητας των υμενίων με την μεταβολή του γινομένου πίεση x γωνία κλίσης υποστρώματος, αναδεικνύεται για πρώτη φορά στη βιβλιογραφία. Επίσης αξιολογήθηκαν οι ιδιότητες διαβρεξιμότητας των υμενίων και αποδόθηκαν στην συνεργιστική δράση της κρυσταλλικής φάσης και της μορφολογίας τους. Τέλος, μέσω ανάλυσης του ρυθμού εναπόθεσης σε δυο συστατικά ειδών υψηλής και χαμηλής ενέργειας και επιπρόσθετης μέλετης της δόμησης των υμενίων κατά την εναπόθεση με μικροσκοπία ΤΕΜ, προτάθηκε ο μηχανισμός δόμησης ανατάση και ρουτίλη σε χαμηλή θερμοκρασία μέσω RF magnetron sputtering.
Messdaten der Keramikanalysen
Authors: Gottardi Corina
Published: May 2022

Die Messdaten der Keramikanalysen zum Artikel «Methodisches Vorgehen bei der geochemischen Analyse der Keramik von Basel-Gasfabrik» von Corina Gottardi sind hier als PDF-Download erhältlich oder bei der Archäologischen Bodenforschung Basel-Stadt (www.archaeologie.bs.ch) als Excel-Datei zu beziehen.
An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol
Authors: Krolewiecki Alejandro , Enbiale Wendemagegn , Gandasegui Javier , van Lieshout Lisette , Kepha Stella , Messa Junior Augusto , Bengtson Michel , Gelaye Woyneshet , Escola Valdemiro , Martinez-Valladares María , Cambra-Pellejà María , Algorta Jaime , Martí-Soler Helena , Fleitas Pedro , Ballester Maria Rosa , Doyle Stephen R. , Williams Nana Aba , Legarda Almudena , Mandomando Inacio , Mwandawiro Charles , Muñoz José
Published: May 2022

Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH.

Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance.

Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH.

ClinicalTrials.gov registration: NCT05124691 (18/11/2021).
An Algorithm for the Separation-Preserving Transition of Clusterings
Authors: Borgwardt Steffen , Happach Felix , Zirkelbach Stetson
Published: May 2022

The separability of clusters is one of the most desired properties in clustering. There is a wide range of settings in which different clusterings of the same data set appear. We are interested in applications for which there is a need for an explicit, gradual transition of one separable clustering into another one. This transition should be a sequence of simple, natural steps that upholds separability of the clusters throughout. We design an algorithm for such a transition. We exploit the intimate connection of separability and linear programming over bounded-shape partition and transportation polytopes: separable clusterings lie on the boundary of partition polytopes and form a subset of the vertices of the corresponding transportation polytopes, and circuits of both polytopes are readily interpreted as sequential or cyclical exchanges of items between clusters. This allows for a natural approach to achieve the desired transition through a combination of two walks: an edge walk between two so-called radial clusterings in a transportation polytope, computed through an adaptation of classical tools of sensitivity analysis and parametric programming, and a walk from a separable clustering to a corresponding radial clustering, computed through a tailored, iterative routine updating cluster sizes and reoptimizing the cluster assignment of items.

Funding: Borgwardt gratefully acknowledges support of this work through National Science Foundation [Grant 2006183] Circuit Walks in Optimization, Algorithmic Foundations, Division of Computing and Communication Foundations; through Air Force Office of Scientific Research [Grant FA9550-21-1-0233] The Hirsch Conjecture for Totally-Unimodular Polyhedra; and through Simons Collaboration [Grant 524210] Polyhedral Theory in Data Analytics. Happach has been supported by the Alexander von Humboldt Foundation with funds from the German Federal Ministry of Education and Research.
Histogram Distortion Bias in Consumer Choices
Authors: Lu Tao , Yuan May , Wang Chong (Alex) , Zhang Xiaoquan (Michael)
Published: May 2022

Existing research on word-of-mouth considers various descriptive statistics of rating distributions, such as the mean, variance, skewness, kurtosis, and even entropy and the Herfindahl-Hirschman index. But real-world consumer decisions are often derived from visual assessment of displayed rating distributions in the form of histograms. In this study, we argue that such distribution charts may inadvertently lead to a consumer-choice bias that we call the histogram distortion bias (HDB). We propose that salient features of distributions in visual decision making may mislead consumers and result in inferior decision making. In an illustrative model, we derive a measure of the HDB. We show that with the HDB, consumers may make choices that violate well-accepted decision rules. In a series of experiments, subjects are observed to prefer products with a higher HDB despite a lower average rating. They could also violate widely accepted modeling assumptions, such as branch independence and first-order stochastic dominance.

This paper was accepted by Chris Forman, information systems.

Funding: This work was supported by the National Natural Science Foundation of China [Grants 72131001 and 92146003] and the Research Grants Council, University Grants Committee [GRF 14500521, GRF 14501320, GRF 14503818, and TRS:T31-604/18-N].

Supplemental Material: Data and the online appendices are available at https://doi.org/10.1287/mnsc.2022.4306 .
Examples of Pathological Dynamics of the Subgradient Method for Lipschitz Path-Differentiable Functions
Authors: Ríos-Zertuche Rodolfo
Published: May 2022

We show that the vanishing step size subgradient method—widely adopted for machine learning applications—can display rather messy behavior even in the presence of favorable assumptions. We establish that convergence of bounded subgradient sequences may fail even with a Whitney stratifiable objective function satisfying the Kurdyka-Łojasiewicz inequality. Moreover, when the objective function is path-differentiable, we show that various properties all may fail to occur: criticality of the limit points, convergence of the sequence, convergence in values, codimension one of the accumulation set, equality of the accumulation and essential accumulation sets, connectedness of the essential accumulation set, spontaneous slowdown, oscillation compensation, and oscillation perpendicularity to the accumulation set.
Clot In Transit in a Patient with Protein S Deficiency
Authors: Kashfi Simon , Farhan Nasser Mohamed , Soleiman Aron , Sharma Sapna , Sandeep Koripalli Venkata , Sharma Shorabh
Published: May 2022

Clot in transit (CIT) is a rare condition in which a venous thromboembolism becomes lodged in the right heart. It is seen in up to 18% of patients with massive pulmonary embolism, and if left untreated, mortality rates are between 80% and 100%. The identification and management of CIT are crucial. However, there are no current guidelines for the treatment of CIT. We present the case of a 44-year-old woman who was found to have CIT that was ultimately treated with medical management.
Compact Cauliflower-Shaped Antenna for Ultra-Wideband Applications
Authors: Guenad Boumediene , Chaabane Abdelhalim , Aissaoui Djelloul , Bouacha Abdelhafid , Denidni Tayeb A.
Published: May 2022

A compact coplanar waveguide (CPW) fed cauliflower-shaped antenna is presented and discussed in this paper. To extend the impedance bandwidth and to improve the impedance matching, fractal geometry having a cauliflower shape is introduced along the edges of the radiator. To validate the simulated results by experimental ones, a prototype of the designed antenna was fabricated on the RO-4350B substrate having a compact size of 0.3623λ0 × 0.41λ0 × 0.01524λ0 at 3 GHz. An Agilent 8722ES vector network was used for the reflection coefficient measurement revealing that the –10 dB bandwidth of the fabricated antenna offers an impedance bandwidth of 113% extending from 3.05 to 10.96 GHz. Besides, the antenna’s radiation patterns are measured in an anechoic chamber showing consistent radiation patterns characteristic over the entire working band. Furthermore, the proposed antenna has a peak gain of around 6 dBi and an average radiation efficiency almost over 90% across the entire operating band. Thus, the proposed antenna could be useful in many modern ultra-wideband (UWB) communication systems.
Continuous current-injected waveforms shaping for suppressing relaxation oscillations of direct modulation based on equivalent circuit model
Authors: Ding Qingan , Wang Xiaojuan , Cheng Xudong , Liu Huixin , Du Liuge , Liang Anhui , Zheng Li , Yang Qunying
Published: May 2022

An improved technique of continuous shaping current-injected waveforms based on the single-mode rate equations is proposed to suppress relaxation oscillations (ROs) from direct modulation of distributed feedback laser (DFB). The signal expression of shaping current is deduced theoretically from the dependence of DFB desired output waveforms in detail, and the specific parameters derivation of the different polynomial degree is also discussed necessarily. Furthermore, a polynomial p-function with inverse operation is adopted to construct the Fourier series corresponding to injection current waveform signal. The equivalent circuit model with DFB phenomenological description is injected into shaping current signal to verity the proposed validity by evaluating the static and dynamic characteristics. The simulation results of the optimized shaping signal show the good agreement with the desired output pulse including rising and falling edge and suppress the ROs amplitude dramatically at the two jump edges.
Light transfer transitions beyond higher-order exceptional points in parity-time and anti-parity-time symmetric waveguide arrays
Authors: Du Chuanxun , Wang Gang , Zhang Yan , Wu Jin-Hui
Published: May 2022

We propose two non-Hermitian arrays consisting of N = 2l + 1 waveguides and exhibiting parity-time (

P
T

) or anti-

P
T

symmetry for investigating light transfer dynamics based on Nth-order exceptional points (EPs). The

P
T

-symmetric array supports two Nth-order EPs separating an unbroken and a broken phase with real and imaginary eignvalues, respectively. Light transfer dynamics in this array exhibits radically different behaviors, i.e. a unidirectional oscillation behavior in the unbroken phase, an edge-towards localization behavior in the broken phase, and a center-towards localization behavior just at Nth-order EPs. The anti-

P
T

-symmetric array supports also two Nth-order EPs separating an unbroken and a broken phase, which refer however to imaginary and real eigenvalues, respectively. Accordingly, light transfer dynamics in this array exhibits a center-towards localization behavior in the unbroken phase and an origin-centered oscillation behavior in the broken phase. These nontrivial light transfer behaviors and their controlled transitions are not viable for otherwise split lower-order EPs and depend on the underlying SU(2) symmetry of spin-l matrices.
Magnetically tunable and enhanced spin Hall effect of reflected light in a multilayer structure containing anisotropic graphene
Authors: Yin Keqiang , Zhang Chi , Wang Shenping , Jiang Jie , Jiang Leyong
Published: May 2022

In this paper, the magnetically tunable and enhanced photonic spin Hall effect (PSHE) of reflected light beam at terahertz frequencies is achieved by using a multilayer structure where anisotropic graphene is inserted. This enhanced PSHE phenomenon results from the excitation of surface plasmon polariton (SPP) at the interface between two dielectric materials. By considering the 4×4 transfer matrix method and the quantum response of graphene, the PSHE of the reflected light can be enhanced by harnessing the anisotropic conductivity of graphene. Besides, the PSHE can be tuned through the external magnetic field and structural parameters. This enhanced and tunable PSHE approach is promising for fabricating anisotropic graphene-based terahertz spin devices and other applications in nanophotonics.