bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the yield of systematic screening for tuberculosis among three priority groups in Ho Chi Minh City, Viet Nam
Authors: Vo Luan Nguyen Quang , Codlin Andrew James , Forse Rachel Jeanette , Nguyen Nga Thuy , Vu Thanh Nguyen , Le Giang Truong , Van Truong Vinh , Do Giang Chau , Dang Ha Minh , Nguyen Lan Huu , Nguyen Hoa Binh , Nguyen Nhung Viet , Levy Jens , Lonnroth Knut , Squire S. Bertel , Caws Maxine
Published: December 2020

Background

In order to end tuberculosis (TB), it is necessary to expand coverage of TB care services, including systematic screening initiatives. However, more evidence is needed for groups among whom systematic screening is only conditionally recommended by the World Health Organization. This study evaluated concurrent screening in multiple target groups using community health workers (CHW).

Methods

In our two-year intervention study lasting from October 2017 to September 2019, CHWs in six districts of Ho Chi Minh City, Viet Nam verbally screened three urban priority groups: (1) household TB contacts; (2) close TB contacts; and (3) residents of urban priority areas without clear documented exposure to TB including hotspots, boarding homes and urban slums. Eligible persons were referred for further screening with chest radiography and follow-on testing with the Xpert MTB/RIF assay. Symptomatic individuals with normal or without radiography results were tested on smear microscopy. We described the TB care cascade and characteristics for each priority group, and calculated yield and number needed to screen. Subsequently, we fitted a mixed-effect logistic regression to identify the association of these target groups and secondary patient covariates with TB treatment initiation.

Results

We verbally screened 321 020 people including 24 232 household contacts, 3182 social and close contacts and 293 606 residents of urban priority areas. This resulted in 1138 persons treated for TB, of whom 85 were household contacts, 39 were close contacts and 1014 belonged to urban priority area residents. The yield of active TB in these groups was 351, 1226 and 345 per 100 000, respectively, corresponding to numbers needed to screen of 285, 82 and 290. The fitted model showed that close contacts [adjusted odds ratio (aOR) = 2.07; 95% CI: 1.38–3.11; P < 0.001] and urban priority area residents (aOR = 2.18; 95% CI: 1.69–2.79; P < 0.001) had a greater risk of active TB than household contacts.

Conclusions

The study detected a large number of unreached persons with TB, but most of them were not among persons in contact with an index patient. Therefore, while programs should continue to optimize screening in contacts, to close the detection gap in high TB burden settings such as Viet Nam, coverage must be expanded to persons without documented exposure such as residents in hotspots, boarding homes and urban slums.
Psychometric properties of the Chinese version of adjustment disorder new module-20 in breast cancer patients
Authors: Tang Haiyan , Xiong Huihua , Deng Lingchao , Maercker Andreas , Zhang Jun , Meng Heng
Published: December 2020

Background

After the new definition of adjustment disorder (AjD) by the International Classification of Diseases-11(ICD-11), AjD has attracted more and more attention. Adjustment disorder new module-20 (ADNM-20), which is used to diagnose AjD, has been verified in some countries, but it has not been verified in China. As a result, the purpose of this study was to investigate the validity and reliability of the Chinese version of the Adjustment disorder new module-20 (ADNM-20) in female breast cancer patients.

Methods

The ADNM-20 translated into Chinese employed the translation and back translation technique. Three hundred fifty four newly diagnosed (< 1 year) female breast cancer patients were recruited from Tongji Hospital and Hubei Cancer Hospital in Hubei, China. The patients completed the self-report questionnaire including demographic characteristics and the scale ADNM-20. Data on psychometric properties were evaluated in terms of internal consistency, item-total correlations, test-retest reliability, and factorial validity.

Results

ADNM-20 core symptoms included 8 items and two factors, which were extracted by using exploratory factor analysis (EFA). It could explain 61.74% of the total variance. ADNM-20 accessory symptoms including 12 items and four factors, which were extracted by using EFA. It could explain 68.34% of the total variance. Cronbach’s α coefficient for ADNM-20 was 0.93, split-half reliability was 0.87, and the test-retest correlation coefficient was 0.74. The correlation coefficient between each subscale was ranged from 0.53 to 0.71 (P < 0.01), while the correlation coefficient between the subscales and total scale was ranged from 0.79 to 0.89 (P < 0.01).

Conclusions

The study verified the validity and reliability of the Chinese version of ADNM-20. It is applicable to measure the prevalence of adjustment disorder in the breast cancer population.
Self-reported psychological distress during the COVID-19 outbreak in Nepal: findings from an online survey
Authors: Gautam Kamal , Adhikari Ramesh P. , Gupta Aman Sen , Shrestha Rajan Kumar , Koirala Pitambar , Koirala Suraj
Published: December 2020

Background

A lower respiratory tract infection caused by novel coronavirus termed as Corona Virus Disease (COVID-19) was first identified in China and subsequently took the form of pandemic. Studies on disease outbreak in the past and recent COVID-19 outbreak have demonstrated increased psychological distress and adverse impacts on mental health and psychological wellbeing of people. However, the impact of COVID-19 on psychological wellbeing of people in Nepal hasn't been studied adequately. So, this paper aims to report the findings from a social media survey on psychological impacts of COVID-19 in Nepal.

Methods

Data were collected through social media from 2082 Nepalese respondents between 23rd April, 2020 and 3rd May, 2020. A total of 2014 respondents who were currently residing in Nepal were included in the analysis.

Results

The study suggested that half of the respondents suffered from at least one symptom of psychological distress whereas 32% suffered from two or more symptoms of psychological distress such as restlessness, fearfulness, anxiety and worry and sadness in the past 2 weeks preceding the survey date. The findings further suggested that respondents having lower family income, residing in rented room, and participants from province 2 were more likely to suffer from both single and multiple symptoms of psychological distress.

Conclusion

The study has shown high prevalence of psychological distress amongst the Nepalese respondents following COVID-19 outbreak. Appropriate mental health and psychosocial support response needs to be instituted to adequately respond to psychological impacts of the epidemic.
Associations of serious physical injuries with posttraumatic stress and depressive symptoms: a cross-sectional survey among university students in 26 countries
Authors: Pengpid Supa , Peltzer Karl
Published: December 2020

Background

Evidence of the relationship between serious physical injury and poor mental health among university students from low- and middle-income countries is limited. The aim of the study is to assess the association between serious physical injury and posttraumatic stress disorder (PTSD) and depressive symptoms in university students from low- and middle-income countries.

Methods

In a cross-sectional survey, 18,382 university students from 26 countries responded to a short screening scale for DSM-IV PTSD, Center for Epidemiologic Studies Depression Scale as well as questions on injury and sociodemographics.

Results

The overall prevalence of past 12-month serious physical injury was 24.7%. In adjusted logistic regression analysis, compared to having no past 12-month serious physical injury, having a past 12-month serious injury was associated with 1.35 (95% CI 1.18, 1.56) times higher odds for PTSD symptoms and 1.49 (95% CI 1.32, 1.67) times higher odds for depressive symptoms in university students.

Conclusion

Compared to students who had not sustained a serious physical injury in the past 12 months, students with an injury had significantly higher PTSD and depressive symptoms. Mental health support of students who sustained physical injuries may prevent PTSD and depressive symptoms.
Exposure therapy for PTSD during pregnancy: a feasibility, acceptability, and case series study of Narrative Exposure Therapy (NET)
Authors: Stevens Natalie R. , Miller Michelle L. , Soibatian Christina , Otwell Caitlin , Rufa Anne K. , Meyer Danie J. , Shalowitz Madeleine U.
Published: December 2020

Background

Prenatal posttraumatic stress disorder (PTSD) is a significant complication of pregnancy linked to increased risk of adverse perinatal outcomes. Although 1 in 5 pregnant trauma-exposed individuals have PTSD, most PTSD treatment trials exclude participants who are pregnant, and none focus on treatment specifically during pregnancy. Moreover, access to mental health treatment is particularly challenging in low-resource settings with high rates of trauma. This study examined implementation of Narrative Exposure Therapy (NET), a short-term evidence-based PTSD treatment, in an urban prenatal care setting. Partial telehealth delivery was used to increase accessibility. Study aims were to examine (a) feasibility, (b) acceptability, and (c) case-based treatment outcomes associated with NET participation.

Method

Eight pregnant participants (median age = 27, median gestational week in pregnancy = 22.5) received up to six sessions of NET with partial telehealth delivery. PTSD and depression symptoms were assessed at pre-treatment intake (T1), at each session (T2), and 1-week post-treatment (T3). A multiple case study approach was used to examine recruitment and engagement, retention, treatment completion, treatment barriers, use of telehealth, participants’ experiences of treatment, and PTSD and depression symptoms.

Results

Nine of the 16 participants (56%) who were invited to participate engaged in treatment, and one dropped out after the first session. Eight participants completed the minimum “dose” of 4 NET sessions (N = 8/9, 89%). Seven participants gave the highest ratings of treatment acceptability. The most frequently reported barriers to treatment were competing priorities of work and caring for other children. Pre-post treatment symptom measures revealed clinically meaningful change in PTSD severity for nearly all participants (7/8, 88%).

Conclusions

Results suggest that a brief exposure therapy PTSD treatment can be successfully implemented during pregnancy, suggesting promising results for conducting a larger-scale investigation.

Trial registration ClinicalTrials.gov, NCT04525469. Registered 20 August 2020–Retrospectively registered, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=View&listmode=Edit&uid=U00058T2&ts=3&sid=S000A59A&cx=-w1vnvn
Longitudinal CITE-Seq profiling of chronic lymphocytic leukemia during ibrutinib treatment: evolution of leukemic and immune cells at relapse
Authors: Cadot Sarah , Valle Carine , Tosolini Marie , Pont Frederic , Largeaud Laetitia , Laurent Camille , Fournie Jean Jacques , Ysebaert Loic , Quillet-Mary Anne
Published: December 2020

Background

Ibrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not to BTK mutations. Patterns of CLL evolution under ibrutinib therapy are well characterized for the leukemic cells but not for their microenvironment.

Methods

Here, we addressed this question at the single cell level of both transcriptome and immune-phenotype. The PBMCs from a CLL patient were monitored during ibrutinib treatment using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq) technology.

Results

This unveiled that the short clinical relapse of this patient driven by BTK mutation is associated with intraclonal heterogeneity in B leukemic cells and up-regulation of common signaling pathways induced by ibrutinib in both B leukemic cells and immune cells. This approach also pinpointed a subset of leukemic cells present before treatment and highly enriched during progression under ibrutinib. These latter exhibit an original gene signature including up-regulated BCR, MYC-activated, and other targetable pathways. Meanwhile, although ibrutinib differentially affected the exhaustion of T lymphocytes, this treatment enhanced the T cell cytotoxicity even during disease progression.

Conclusions

These results could open new alternative of therapeutic strategies for ibrutinib-refractory CLL patients, based on immunotherapy or targeting B leukemic cells themselves.
A new method for quantitative and qualitative representation of the noises type in Allan (and related) variances
Authors: Maciuk Kamil , Kudrys Jacek , Bagherbandi Mohammad , Bezmenov Igor V.
Published: December 2020

Allan variances and its related methods are commonly used to analyse a sequence of data in the time domain to measure frequency stability of oscillators. It allows for a determination of noise type as a function of the averaging time. This method is one of the most popular for identifying different noise types in the sensors data, and it is usually used for a wide range of studies on the stability of oscillators or atomic clocks. In this paper, the authors propose their own algorithm for a qualitative and quantitative expression of noise type using Allan and related variation. The methods currently used allow for the determination of the noise type graphically only, without quantifying the type and percentages for each of the integration steps. Our study allows for a numerical interpretation of the Allan (and related) variances data. A numerical example of the described method is based on GPS satellite clock corrections for 1825–2086 GPS Week (5 years) based on daily 30-s sampling interval products.
Kidney dosimetry in 777 patients during 177Lu-DOTATATE therapy: aspects on extrapolations and measurement time points
Authors: Sandström Mattias , Freedman Nanette , Fröss-Baron Katarzyna , Kahn Tanweera , Sundin Anders
Published: December 2020

Purpose

Fractionated peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is increasingly applied as an effective treatment for patients with disseminated neuroendocrine tumors. In parallel to dose planning before external beam radiation therapy, dosimetry is also needed to optimize PRRT to the individual patient. Accordingly, absorbed doses to organs at risk need to be calculated during PRRT, based on serial measurements of radioactivity distribution utilizing SPECT/CT. The dosimetry should be based on as few measurements as possible, while still retaining reliable results. The main aim of the present work was to calculate the fractional contribution of the extrapolations of the curve fits for the absorbed dose calculations to the kidneys. The secondary aim was to study agreement between absorbed dose (AD) and the effective half-life (teff) for the kidneys, estimated by means of measurements at one or two time points, in comparison to our current method employing three time points.

Methods

In 777 patients with disseminated neuroendocrine tumors undergoing PRRT, SPECT/CT over the abdomen was acquired at 1, 4, and 7 days after 177Lu-DOTATATE infusion. The absorbed dose to the kidneys was calculated from SPECT/CT radioactivity distribution data, and the teff and fractional contributions of the extrapolations were estimated, utilizing data from one, two, and three time points, respectively.

Results

The fractional contributions from extrapolations before day 1 measurement and after day 7 measurement were approximately 26% and 11%, respectively. The mean differences in absorbed dose, based on one, two, and three time points were small, but with high method dependence for individual patients. The differences in estimated teff were small when it was based on measurements at days 1 and 7, but high for days 1 and 4 time points.

Conclusion

When assessing simplifications of methods for calculation of the absorbed dose to the kidneys, it was of the uttermost importance to incorporate the fractional contribution for the extrapolations included in the reference method. Measurements at an early and a late time point were found most important. An intermediate measurement contributes with an idea of the goodness of the fit.
RETRACTED ARTICLE: Prevalence and associated factors of early initiation of breastfeeding among women delivered via Cesarean section in South Gondar zone hospitals Ethiopia, 2020
Authors: Getnet Bekalu , Degu Alemu , Yenealem Fantahun
Published: December 2020

Background

Early initiation of breastfeeding is putting the newborn to breast within one hour after birth. This study was aimed to assess prevalence of early initiation of breastfeeding and its associated factors among mothers who delivered by cesarean section in South Gondar Zone hospitals Northwest Ethiopia, 2020.

Methods

An institutional based cross-sectional study was employed in South Gondar Zone hospitals from June 12 to July 03, 2020. A total of 356 cesarean delivered mothers were included. Data were collected using interviewer administered questionnaire and entered in to Epi Data version 4.2 and then exported to SPSS version 23.0. Logistic regression statistical analyses were used to identify factors associated with the outcome variables.

Results

The prevalence of early initiation of breastfeeding among mothers who delivered by cesarean section was 51.9%. Mothers who had intended pregnancy [AOR = 2.69, 95% CI (1.34–5.38)], had professional guidance [AOR = 2.68, 95% CI (1.18–6.10)], had breastfeeding experience [AOR = 2.25, 95% CI (1.35–3.75)], and had four and above antenatal care visits [AOR = 2.20, 95% CI (1.24–3.91)] were positively associated with early initiation of breastfeeding among mothers who delivered by cesarean section.

Conclusion

Type of pregnancy, professional guidance, had four or more antenatal care and breastfeeding experience were significantly associated with early initiation of breast feeding among mothers who delivered by cesarean section. Community based breastfeeding education and counseling to pregnant mothers and encouraging all mothers to follow recommended ANC visit is should be recommended.
Transdermal delivery of FITC-Dextrans with different molecular weights using radiofrequency microporation
Authors: Ahn Guk Young , Eo Hae-Seok , Kim Dongwon , Choi Sung-Wook
Published: December 2020

Background

Transdermal delivery is of great importance for the effective delivery of bioactive or therapeutic agents into a body. The microporation device based on radiofrequency can be used to enhance delivery efficiency by removing the epidermis layer.

Methods

The micropores were developed on pig skin and human cadaver skin with dermal and epidermal layers by the microporation device. The regeneration of micropores in the human cadaver skin caused by microporation was confirmed using an optical microscope and haematoxylin/eosin (H&E) staining. The permeability of fluorescein isothiocyanate-dextrans (FITC-dextrans) with different molecular weights through the pig and human cadaver skins were measured using Franz diffusion cell.

Results

The optical image and histological analysis confirmed that the micropores on the skin were recovered over time. The enhanced permeability through micropores was confirmed by Franz diffusion cell. The lower molecular weight of FITC-dextran permeated more on both human and pig skin. In addition, the permeation rate was higher in pig skin than in human skin.

Conclusions

We believe that the microporation device can be used as a potential technique for effective transdermal drug delivery.
Non-inferiority study of the efficacy of two hyaluronic acid products in post-extraction sockets of impacted third molars
Authors: Yang Hyunwoo , Kim Junghun , Kim Jihong , Kim Dongwook , Kim Hyung Jun
Published: December 2020

Background

Hyaluronic acid (HA) is well known to exert an anti-inflammatory effect during oral wound healing and is commonly applied after tooth extraction. However, no double-blind randomized controlled study comparing two hyaluronate mouthwash products has been conducted so far. The aim of this study was to comparatively analyze the efficacy of Mucobarrier® and Aloclair® in terms of clinical symptoms.

Results

A total of 112 patients were randomly assigned to assess the degree of discomfort, pain reduction, redness, burning sensation, and swelling between two groups on the day of surgery and 7 days later in a double blind test, with a total 56 Aloclair patients and 56 Mucobarrier patients. There was no statistically significant difference in the overall discomfort, degree of pain reduction, redness, burning sensation, and swelling between the Mucobarrier and Aloclair groups.

Conclusion

The local application of hyaluronic acid mouth wash after wisdom tooth extraction is beneficial in reducing overall discomfort and pain reduction, and the clinical utility of Mucobarrier® is no different from Aloclair®.

Trial registration

Institutional Review Board of Yonsei University College of Dentistry, 2-2018-0036. Registered 10 September 2018—prospectively registered, https://eirb.yuhs.ac/
Why crowdsourcing fails
Authors: Dahlander Linus , Piezunka Henning
Published: December 2020

Crowdsourcing—asking an undefined group of external contributors to work on tasks—allows organizations to tap into the expertise of people around the world. Crowdsourcing is known to increase innovation and loyalty to brands, but many organizations struggle to leverage its potential, as our research shows. Most often this is because organizations fail to properly plan for all the different stages of crowd engagement. In this paper, we use several examples to explain these challenges and offer advice for how organizations can overcome them.
Association of culprit lesion plaque characteristics with flow restoration post-fibrinolysis in ST-segment elevation myocardial infarction: an intravascular ultrasound-virtual histology study
Authors: Rao K Raghavendra , Reddy Sreenivas , Kashyap Jeet Ram , Ramalingam Vadivelu , Dash Debabrata , Kadiyala Vikas , Kumar Suraj , Reddy Hithesh , Kaur Jaspreet , Kumar Ashok , Kaur Naindeep , Gupta Anish
Published: December 2020

Background

Not every patient achieves normal coronary flow following fibrinolysis in STEMI (ST-segment elevation myocardial infarction). The culprit lesion plaque characteristics play a prominent role in the coronary flow before and during percutaneous coronary intervention. The main purpose was to determine the culprit lesion plaque features by virtual histology-intravascular ultrasound (VH-IVUS) in patients with STEMI following fibrinolysis in relation to baseline coronary angiogram TIMI (thrombolysis in myocardial infarction) flow. Pre-intervention IVUS was undertaken in 61 patients with STEMI after successful fibrinolysis. After the coronary angiogram, they were separated into the TIMI1–2 flow group (n = 31) and TIMI 3 flow group (n = 30). Culprit lesion plaque composition was evaluated by VH-IVUS.

Results

On gray-scale IVUS, the lesion external elastic membrane cross-sectional area (EEM CSA) was significantly higher in the TIMI 1–2 groups as compared to the TIMI 3 group (15.71 ± 3.73 mm2 vs 13.91 ± 2.94 mm2, p = 0.041) with no significant difference in plaque burden (82.42% vs. 81.65%, p = 0.306) and plaque volume (108.3 mm3 vs. 94.3 mm3, p = 0.194). On VH-IVUS, at the minimal luminal area site (MLS), the fibrous area (5.83 mm2 vs. 4.37 mm2, p = 0.024), necrotic core (NC) area (0.95 mm2 vs. 0.59 mm2, p < 0.001), and NC percentage (11% vs. 7.1%, p = 0.024) were higher in the TIMI 1–2 groups in contrast to the TIMI 3 group. The absolute necrotic core (NC) volume (8.3 mm3 vs. 3.65 mm3, p < 0.001) and NC percentage (9.3% vs. 6.0%, p = 0.007) were significantly higher in the TIMI 1–2 groups as compared to the TIMI 3 group. Absolute dense calcium (DC) volume was higher in TIMI 1–2 groups with a trend towards significance (1.0 mm3 vs.0.75 mm3, p = 0.051). In multivariate analysis, absolute NC volume was the only independent predictor of TIMI 1–2 flow (odds ratio = 1.561; 95% CI 1.202–2.026, p = 0.001). Receiver operating characteristic curves showed absolute NC volume has best diagnostic accuracy (AUC = 0.816, p < 0.001) to predict TIMI 1–2 flow with an optimal cutoff value of 4.5 mm3 with sensitivity and specificity of 79% and 61%, respectively.

Conclusions

This study exemplifies that the necrotic core component of the culprit lesion plaque in STEMI is associated with the coronary flow after fibrinolysis. The absolute necrotic core volume is a key determinant of flow restoration post-fibrinolysis and aids in prognostication of less than TIMI 3 flow.
A review on phytoconstituents of marine brown algae
Authors: Hakim Masuma M. , Patel Illa C.
Published: December 2020

Background

From the last few years, the development and discovery of bioactive compounds and their potential properties from marine algae have been enhanced significantly. The coastal area is a huge storehouse for propitious algae. It has been the genuine reality that the consequence of marine algae as a source of different compounds is increasing.

Main body

Numerous advanced research devices are available for the discovery of synthetic compounds but still many researchers are working on natural bioactive compounds to discover their biological properties, which are useful to society. Marine algae are taking the preponderance of consideration from investigators owing to its phenomenon of biological activity like anti-cancer, anti-viral, cholesterol-reducing, and many more. A variety of compounds are collected from algae with specific purposes as they remain in an extremely ambitious and hard state; this condition is responsible for the synthesis of very particularly effective bioactive compounds. The present article is concentrating on the brown algae of the Gujarat coast, phlorotannins, polyphenol, phytosterol from brown algae, and their various applications. The main importance has been given to the secondary metabolites and various applications of marine brown algae.

Conclusion

From this review, it can be concluded that the prominent bioactive compounds from brown algae can cure many serious diseases. Besides, the potential biological activities of a special bioactive compound may represent the interest in the industry of pharmaceuticals, cosmeceutical, and functional foods.
Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma
Authors: Richardson Paul G. , Oriol Albert , Larocca Alessandra , Bladé Joan , Cavo Michele , Rodriguez-Otero Paula , Leleu Xavier , Nadeem Omar , Hiemenz John W. , Hassoun Hani , Touzeau Cyrille , Alegre Adrián , Paner Agne , Maisel Christopher , Mazumder Amitabha , Raptis Anastasios , Moreb Jan S. , Anderson Kenneth C. , Laubach Jacob P. , Thuresson Sara , Thuresson Marcus , Byrne Catriona , Harmenberg Johan , Bakker Nicolaas A. , Mateos María-Victoria ,   on behalf of the HORIZON (OP-106) Investigators
Published: December 2020

PURPOSE

Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need.

PATIENTS AND METHODS

Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing.

RESULTS

Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4.

CONCLUSION

Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.
Genome-Wide Estrogen Receptor Activity in Breast Cancer
Authors: Farcas Anca M , Nagarajan Sankari , Cosulich Sabina , Carroll Jason S
Published: December 2020

The largest subtype of breast cancer is characterized by the expression and activity of the estrogen receptor alpha (ERalpha/ER). Although several effective therapies have significantly improved survival, the adaptability of cancer cells means that patients frequently stop responding or develop resistance to endocrine treatment. ER does not function in isolation and multiple associating factors have been reported to play a role in regulating the estrogen-driven transcriptional program. This review focuses on the dynamic interplay between some of these factors which co-occupy ER-bound regulatory elements, their contribution to estrogen signaling, and their possible therapeutic applications. Furthermore, the review illustrates how some ER association partners can influence and reprogram the genomic distribution of the estrogen receptor. As this dynamic ER activity enables cancer cell adaptability and impacts the clinical outcome, defining how this plasticity is determined is fundamental to our understanding of the mechanisms of disease progression.
A Positive Feedback Loop Between TGFβ and Androgen Receptor Supports Triple-negative Breast Cancer Anoikis Resistance
Authors: Rosas Emmanuel , Roberts Justin T , O’Neill Kathleen I , Christenson Jessica L , Williams Michelle M , Hanamura Toru , Spoelstra Nicole S , Vahrenkamp Jeffery M , Gertz Jason , Richer Jennifer K
Published: December 2020

Triple-negative breast cancer (TNBC) is an aggressive subtype with peak recurrence as metastatic disease within the first few years of diagnosis. Androgen receptor (AR) expression is increased in anchorage-independent cells in TNBC preclinical models. Both AR knockdown and inhibition lead to reduced TNBC invasion in vitro, reduced tumorigenicity, and less recurrence in vivo in preclinical models. Transforming growth factor β (TGFβ) pathway gene signatures also increased during anchorage-independent survival both in vitro and in vivo in preclinical models and in circulating tumor cells (CTCs) from patients during emergence of chemo resistant disease. We hypothesized that a positive loop between AR and TGFβ signaling facilitates TNBC anchorage-independent survival. We find that multiple components of the TGFβ pathway, including TGFβ1 and 3, as well as pathway activity measured by nuclear localization and transcriptional activity of phosphorylated Smad3, are enhanced in anchorage-independent conditions. Further, exogenous TGFβ increased AR protein while TGFβ inhibition decreased AR and TNBC viability, particularly under anchorage-independent culture conditions. ChIP-seq experiments revealed AR binding to TGFB1 and SMAD3 regulatory regions in MDA-MB-453 cells. In clinical datasets, TGFB3 and AR positively correlate and high expression of both genes together corresponded to significantly worse recurrence-free and overall survival in both ER-negative and basal-like breast cancer. Finally, inhibiting both AR and TGFβ decreased cell survival, particularly under anchorage-independent conditions. These findings warrant further investigations into whether combined inhibition of AR and TGFβ pathways might decrease metastatic recurrence rates and mortality from TNBC.
Genres of Valuation: Marginalist Economics and American Literary Realism
Authors: Wonham Henry B.
Published: December 2020

This essay argues that late nineteenth-century American fiction, as exemplified by William Dean Howells’s The Rise of Silas Lapham (1885) and Theodore Dreiser’s Sister Carrie (1900), is entangled in the period’s embrace of a new understanding of economic conditions, one premised on the significance of consumer data as the raw material of economic interpretation and fixated on mathematical analysis as a source of knowledge about value. Marginalism in economic theory and realism in American literary practice were contemporaneous efforts to mediate value at a moment of decisive transition in America, as a model of commodity-centered competitive capitalism yielded to the regime of corporate finance. The young academic economists of the period and their literary counterparts explained the economic landscape in much the same way and to many of the same ends. Both began with the daunting question of how to reimagine value in a world characterized by fictitious goods and increasingly abstract financial instruments, a world in which the labor theory of value seemed hopelessly outdated. Both responded to this challenge by proposing novel intellectual procedures for making values appear stable again by focusing on the subjective experiences of consumers. Finally, both marginalists and realists sought to provide a quasi-scientific bedrock for fixing values in consumer society not only by appealing nostalgically to an economy of actual goods and honest work but more importantly by accommodating readers, policy makers, and stakeholders of all kinds to the new realities of finance capitalism.
Establishment of Etv5 gene knockout mice as a recipient model for spermatogonial stem cell transplantation
Authors: Zhang Xianyu , Zhao Xin , Li Guoling , Zhang Mao , Xing Pingping , Li Zicong , Chen Bin , Yang Huaqiang , Wu Zhenfang
Published: December 2020

Transplantation of spermatogonial stem cells (SSCs) is an alternative reproductive method to achieve conservation and production of elite animals in livestock production. Creating a recipient animal without endogenous germ cells is important for effective SSC transplantation. However, natural mutants with depletion of SSCs are difficult to obtain, and drug ablation of endogenous germ cells is arduous to perform for practical use. In this study, we used mouse models to study the preparation of recipients with congenital germ cell ablation. We knocked out (KO) Ets-variant gene 5 (Etv5) in mice using the CRISPR/Cas9 system. The testicular weight of Etv5-/- mice was significantly lower than that of wild-type (WT) mice. The germ cell layer of the seminiferous tubules gradually receded with age in Etv5-/- mice. At 12 weeks of age, the tubules of Etv5-/- mice lacked germ cells (Sertoli cell-only syndrome), and sperm were completely absent in the epididymis. We subsequently transplanted allogeneic SSCs with enhanced green fluorescent protein (EGFP) into 3- (immature) or 7-week-old (mature) Etv5-/- mice. Restoration of germ cell layers in the seminiferous tubules and spermatogenesis was observed in all immature testes but not in mature adult testes at 2 months post-transplantation. The presence of heterologous genes Etv5 and EGFP in recipient testicular tissue and epididymal sperm by PCR indicated that sperm originated from the transplanted donor cells. Our study demonstrates that, although Etv5-/- mice could accommodate and support foreign germ cell transplantation, this process occurs in a quite low efficiency to support a full spermatogenesis of transplanted SSCs. However, using Etv5-/- mice as a recipient model for SSC transplantation is feasible, and still needs further investigation to establish an optimized transplantation process.
The long noncoding RNA Meg3 regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition
Authors: Dill Tiffany L. , Carroll Alina , Pinheiro Amanda , Gao Jiachen , Naya Francisco J.
Published: December 2020

Formation of skeletal muscle is among the most striking examples of cellular plasticity in animal tissue development, where muscle progenitor cells are reprogrammed by epithelial-mesenchymal transition (EMT) to produce multinucleated myofibers. The regulation of EMT in muscle formation remains poorly understood. Here, we demonstrate that the long noncoding RNA (lncRNA) Meg3 regulates EMT in myoblast differentiation and skeletal muscle regeneration. Chronic inhibition of Meg3 in C2C12 myoblasts induced EMT, and suppressed cell state transitions required for differentiation. Furthermore, adenoviral Meg3 knockdown compromised muscle regeneration, which was accompanied by abnormal mesenchymal gene expression and interstitial cell proliferation. Transcriptomic and pathway analyses of Meg3-depleted C2C12 myoblasts and injured skeletal muscle revealed a significant dysregulation of EMT-related genes, and identified TGFβ as a key upstream regulator. Importantly, inhibition of TGFβR1 and its downstream effectors, and the EMT transcription factor Snai2, restored many aspects of myogenic differentiation in Meg3-depleted myoblasts in vitro. We further demonstrate that reduction of Meg3-dependent Ezh2 activity results in epigenetic alterations associated with TGFβ activation. Thus, Meg3 regulates myoblast identity to maintain proper cell state for progression into differentiation.
A csf1rbmutation uncouples two waves of microglia development in zebrafish
Authors: Ferrero Giuliano , Miserocchi Magali , Di Ruggiero Elodie , Wittamer Valérie
Published: December 2020

In vertebrates, the ontogeny of microglia, the resident macrophages of the central nervous system, initiates early during development from primitive macrophages. While murine embryonic microglia then persist through life, in zebrafish these cells are transient, as they are fully replaced by an adult population originating from larval hematopoietic stem cell (HSC)-derived progenitors. Colony-stimulating factor receptor 1 (csf1r) is a fundamental regulator of microglia ontogeny in vertebrates, including zebrafish which possess two paralogous genes: csf1ra and csf1rb. While previous work showed mutation in both genes completely abrogates microglia development, the specific contribution of each paralog remains largely unknown. Here, using a fate-mapping strategy to discriminate between the two microglial waves, we uncover non-overlapping roles for csf1ra and csf1rb in hematopoiesis, and identified csf1rb as an essential regulator of adult microglia development. Notably, we demonstrate that csf1rb positively regulates HSC-derived myelopoiesis, resulting in macrophage deficiency, including microglia, in adult mutant animals. Overall, this study contributes to new insights into evolutionary aspects of Csf1r signaling and provides an unprecedented framework for the functional dissection of embryonic versus adult microglia in vivo.
Catalytic Enantioselective Allylic C–F Bond Functionalization
Authors: Wang Minyan , Shi Zhaungzhi
Published: December 2020

Catalytic enantioselective defluorinative functionalization of easily accessible allylic fluorines is well recognized as one of the most attractive strategies for creating allylic stereogenic centers with high enantioselectivity. This highlight review precisely aims to summarize the recent developments of this area mainly from the following six aspects: enantioselective defluoroarylation, enantioselective defluoroalkylation, enantioselective defluoroborylation, enantioselective defluorosilylation, enantioselective defluorohydrolation, and desymmetrization of difluoromethylene groups. Primarily, these reactions occur through two pathways, including β-fluorine elimination and C–F oxidative addition. Despite this, the mechanisms and limitations of these strategies have been a focus, and it is hoped that this review will provide a comprehensive overview to evaluate the prospects of this rapidly emerging field.
The Parable of the Auctioneer: Complexity in Paul R. Milgrom’sDiscovering Prices
Authors: Kominers Scott Duke , Teytelboym Alexander
Published: December 2020

Designing marketplaces in complex settings requires both novel economic theory and real-world engineering, often drawing upon ideas from fields such as computer science and operations research. In Discovering Prices: Auction Design in Markets with Complex Constraints, Milgrom (2017) explains the theory and design of the United States’ “incentive auction” that reallocated wireless spectrum licenses from television broadcasters to telecoms. Milgrom’s account teaches us how economic designers can grapple with complexity both in theory and in practice. Along the way, we come to understand several different types of complexity that can arise in marketplace design. (JEL D43, D44, D47, L96, L98)
How Well Do Automated Linking Methods Perform? Lessons from US Historical Data
Authors: Bailey Martha J. , Cole Connor , Henderson Morgan , Massey Catherine
Published: December 2020

This paper reviews the literature in historical record linkage in the United States and examines the performance of widely used record-linking algorithms and common variations in their assumptions. We use two high-quality, hand-linked data sets and one synthetic ground truth to examine the direct effects of linking algorithms on data quality. We find that (i) no algorithm (including hand linking) consistently produces representative samples; (ii) 15 to 37 percent of links chosen by widely used algorithms are classified as errors by trained human reviewers; and (iii) false links are systematically related to baseline sample characteristics, showing that some algorithms may introduce systematic measurement error into analyses. A case study shows that the combined effects of (i)–(iii) attenuate estimates of the intergenerational income elasticity by up to 29 percent, and common variations in algorithm assumptions result in greater attenuation. As current practice moves to automate linking and increase link rates, these results highlight the important potential consequences of linking errors on inferences with linked data. We conclude with constructive suggestions for reducing linking errors and directions for future research. (JEL C45, C81, J62, N31, N32)
A CT-based radiomics nomogram for predicting prognosis of coronavirus disease 2019 (COVID-19) radiomics nomogram predicting COVID-19
Authors: Chen Hang , Zeng Ming , Wang Xinglan , Su Liping , Xia Yuwei , Yang Quan , Liu Dan
Published: December 2020

Objectives:

To identify the value of radiomics method derived from CT images to predict prognosis in patients with COVID-19.

Methods:

A total of 40 patients with COVID-19 were enrolled in the study. Baseline clinical data, CT images, and laboratory testing results were collected from all patients. We defined that ROIs in the absorption group decreased in the density and scope in GGO, and ROIs in the progress group progressed to consolidation. A total of 180 ROIs from absorption group (n = 118) and consolidation group (n = 62) were randomly divided into a training set (n = 145) and a validation set (n = 35) (8:2). Radiomics features were extracted from CT images, and the radiomics-based models were built with three classifiers. A radiomics score (Rad-score) was calculated by a linear combination of selected features. The Rad-score and clinical factors were incorporated into the radiomics nomogram construction. The prediction performance of the clinical factors model and the radiomics nomogram for prognosis was estimated.

Results:

A total of 15 radiomics features with respective coefficients were calculated. The AUC values of radiomics models (kNN, SVM, and LR) were 0.88, 0.88, and 0.84, respectively, showing a good performance. The C-index of the clinical factors model was 0.82 [95% CI (0.75–0.88)] in the training set and 0.77 [95% CI (0.59–0.90)] in the validation set. The radiomics nomogram showed optimal prediction performance. In the training set, the C-index was 0.91 [95% CI (0.85–0.95)], and in the validation set, the C-index was 0.85 [95% CI (0.69–0.95)]. For the training set, the C-index of the radiomics nomogram was significantly higher than the clinical factors model (p = 0.0021). Decision curve analysis showed that radiomics nomogram outperformed the clinical model in terms of clinical usefulness.

Conclusions:

The radiomics nomogram based on CT images showed favorable prediction performance in the prognosis of COVID-19. The radiomics nomogram could be used as a potential biomarker for more accurate categorization of patients into different stages for clinical decision-making process.

Advances in knowledge:

Radiomics features based on chest CT images help clinicians to categorize the patients of COVID-19 into different stages. Radiomics nomogram based on CT images has favorable predictive performance in the prognosis of COVID-19. Radiomics act as a potential modality to supplement conventional medical examinations.
Πρόσφυγες από την Ελλάδα και τα Δωδεκάνησα στην Τουρκία κατά τη διάρκεια του Δεύτερου Παγκόσμιου Πολέμου (1941-1944)
Authors: Λάμπρου Αλέξανδρος
Published: December 2020

Το θέμα της παρούσας έρευνας είναι οι προσφυγικές ροές από την κατεχόμενη Ελλάδα και τα Δωδεκάνησα προς την Τουρκία μεταξύ των ετών 1941 και 1944. H έρευνα βασίζεται σε αρχειακή και βιβλιογραφική έρευνα στην Ελλάδα και την Τουρκία, εμπνέεται από τη διεθνή βιβλιογραφία για τις προσφυγικές μετακινήσεις και εντάσσεται στις ιστορικές μελέτες των πληθυσμιακών μετακινήσεων κατά τη διάρκεια του Δεύτερου Παγκόσμιου Πολέμου, αλλά και κατά τη μεταπολεμική περίοδο, στην Ευρώπη. Με πρωταρχικό σκοπό να καλύψει ένα υφιστάμενο κενό στην ιστοριογραφία της περιόδου, η έρευνα προσφέρει μια περιεκτική παρουσίαση των προσφυγικών μετακινήσεων προς την Τουρκία, μέσα από την ποσοτική και την ποιοτική ανάλυση του φαινομένου, καθώς και των κρατικών πολιτικών διαχείρισης των προσφύγων από τα δύο κράτη. Η μελέτη των πολιτικών αυτών λαμβάνει υπόψη τους ιδεολογικούς, οικονομικούς, στρατιωτικούς και διπλωματικούς περιορισμούς και τις ανησυχίες των δύο κρατών, καθώς και τις πρακτικές διακρίσεων τις οποίες επιφύλασσαν έναντι των προσφύγων με βάση τις διαφορές κοινωνικού φύλου, κοινωνικών και εθνοτικών ταυτοτήτων, καθώς και πολιτικών προτιμήσεων ανάμεσα στους πρόσφυγες.