bluuebunny/crossref_metadata_2025 huggingface dataset:
Lagovirus europeus GI.2 (rabbit hemorrhagic disease virus 2) infection in captive mountain hares (Lepus timidus) in Germany
Authors: Buehler Melanie , Jesse Sonja T. , Kueck Heike , Lange Bastian , Koenig Patricia , Jo Wendy K. , Osterhaus Albert , Beineke Andreas
Published: May 2020

Background

Rabbit hemorrhagic disease virus (RHDV, Lagovirus europeus GI.1) induces a contagious and highly lethal hemorrhagic disease in rabbits. In 2010 a new genotype of lagovirus (GI.2), emerged in Europe, infecting wild and domestic population of rabbits and hares.

Case presentation

We describe the infection with a GI.2 strain, “Bremerhaven-17”, in captive mountain hares (Lepus timidus) in a zoo facility in Germany. Postmortem examination revealed RHD-like lesions including necrotizing hepatitis. RT-qPCR and AG-ELISA confirmed presence of GI.2. Recombination and phylogenetic analysis grouped the identified strain with other GI.2 strains, sharing nucleotide identity of 91–99%.

Conclusion

Our findings confirm that mountain hares are susceptible to GI.2 infection, due to a past recombination event facilitating virus spillover from sympatric rabbits.
Utility of Plasmodium falciparum DNA from rapid diagnostic test kits for molecular analysis and whole genome amplification
Authors: Srisutham Suttipat , Suwannasin Kanokon , Mathema Vivek Bhakta , Sriprawat Kanlaya , Smithuis Frank M. , Nosten Francois , White Nicholas J. , Dondorp Arjen M. , Imwong Mallika
Published: May 2020

Background

Rapid diagnostic tests (RDTs) have become the most common diagnostic tool for detection of Plasmodium falciparum malaria, in particular in remote areas. RDT blood spots provide a source of parasite DNA for molecular analysis. In this study, the utility of RDTs for molecular analysis and the performance of different methods for whole genome amplification were investigated.

Methods

Positive P. falciparum RDTs were collected from Kayin, Myanmar from August 2014 to January 2016. The RDT samples were stored for 6 months, 9 months, 20 months, 21 months, and 32 months before DNA extraction and subsequent molecular analysis of P. falciparum kelch 13 (pfkelch13) mutations, P. falciparum multidrug resistance 1 (pfmdr1), and P. falciparum plasmepsin 2 (pfplasmepsin2) gene amplification. In addition, performance of four whole genome amplification (WGA) kits were compared, including REPLI-g®, MALBACTM, PicoPLEX®, and GenomePlex®, for which DNA quantity and quality were compared between original DNA and post-WGA products.

Results

The proportion of successful amplification of the different molecular markers was similar between blood spots analysed from RDTs stored for 6, 9, 20, 21, or 32 months. Successful amplification was dependent on the molecular markers fragment length (p value < 0.05): 18% for a 1245 bp fragment of pfkelch13, 71% for 364 bp of pfkelch13, 81% for 87 bp of pfmdr1, 81% for 108 bp of pfplasmepsin2. Comparison of the four WGA assay kits showed that REPLI-g®, MALBACTM, and PicoPLEX® increased the quantity of DNA 60 to 750-fold, whereas the ratio of parasite DNA amplification over human DNA was most favourable for MALBAC®. Sequencing results of pfkelch13, P. falciparum chloroquine resistance transporter (pfcrt), P. falciparum dihydrofolate reductase (pfdhfr) and six microsatellite markers assessed from the post-WGA product was the same as from the original DNA.

Conclusions

Blood spots from RDTs are a good source for molecular analysis of P. falciparum, even after storage up to 32 months. WGA of RDT-derived parasite DNA reliably increase DNA quantity with sufficient quality for molecular analysis of resistance markers.
“Everyone can take photos.” Feasibility and relative validity of phone photography-based assessment of children’s diets – a mixed methods study
Authors: Norman Åsa , Kjellenberg Karin , Torres Aréchiga Diana , Löf Marie , Patterson Emma
Published: May 2020

Background

Dietary assessment methods that are user-friendly, simple, yet valid are of interest to both researchers and participants, particularly for use in disadvantaged settings, where language barriers and low levels of education are often present. We tested if parents taking photos of what children ate, using mobile phones, would be a feasible, acceptable method that could still provide information with adequate relative validity.

Methods

We used a mixed-methods design, with parents of 21 5- to 7-year-olds from disadvantaged areas in Sweden. Parents reported all dietary intake, during non-school hours, on three days (two weekdays) using a photo method (PM). The PM consisted of simple instructions and a fiduciary card, but no training, equipment or software. Text messages could be sent if necessary. As a reference method, parents completed three 24-h recalls (24HRs) with an interviewer each following day. The next week, parents completed a 9-item semi-FFQ regarding the preceding week. The outcomes were intakes (in dl) of 9 food groups, categorised as fruits and vegetables, energy-dense sweet/salty foods, and sweet drinks. Agreement with the reference 24HRs was assessed using correlations, median differences and Bland-Altman plots. Parents completed an open-ended questionnaire on barriers and facilitators. Data collectors provided complementary information. Qualitative data was analysed using qualitative manifest analysis.

Results

Nineteen parents (90%) provided complete data. The majority (n = 13) spoke Swedish as a second language, few (n = 4) were proficient. Compared to 24HRs, intakes measured by PM correlated well for all categories (Spearman’s rho = 0.609–0.845). However, intakes were underreported, significantly so for fruits and vegetables; Bland-Altman plots indicated that the underestimation was fairly constant across intake levels. When the FFQ was compared to the 24HRs, parameters of agreement were generally inferior than for the PM. Parents found the PM a positive experience, primarily facilitated by its simplicity and familiarity. Barriers, mainly related to time and logistics, can inform further methodological refinements.

Conclusions

The PM was an acceptable and feasible way to measure children’s diet outside of school hours in this population of parents from disadvantaged areas. While the absolute validity should be evaluated further, this relatively simple method has potential for assessing intakes of well-defined foods at group level.
Trends in the dietary patterns of Mexican adults by sociodemographic characteristics
Authors: Pérez-Tepayo Sandra , Rodríguez-Ramírez Sonia , Unar-Munguía Mishel , Shamah-Levy Teresa
Published: May 2020

Background

Sociodemographic characteristics are associated with the dietary patterns of populations. However, the direction of the association is not consistent among countries: it is contingent on the nutritional transition phase, level of economic development, cultural contexts and both the social and health policies prevailing in each country. The objective of this study was to identify the trends in dietary patterns observed in 2006, 2012 and 2016 among Mexican adults by sociodemographic characteristic.

Methods

To determine and compare dietary patterns, we performed a secondary analysis of dietary and sociodemographic data for adults 20–59 years old. Data were drawn from the 2006 and 2012 National Health and Nutrition Surveys (ENSANUTs) together with the 2016 Half-Way National Health and Nutrition Survey (ENSANUTMC). To estimate the dietary patterns, we used an adapted version of the Healthy Eating Index-2015 (HEI-2015) and a quantile-based regression model to compare the HEI medians by sociodemographic characteristic.

Results

From 2006 to 2016, the quality of the diet of Mexican adults scored under 50 points on a scale of 0 to 100, markedly below the maximum scores for the majority of HEI-2015 components. Diet quality varied according to age, sex, socioeconomic status (SES), area (urban/rural) and region of residence, with the highest quality observed among older individuals (within the 40–59 age group), women, people of lower SES and residents of rural areas, particularly in southern Mexico. Although this trend remained constant overall throughout 2006, 2012 and 2016, specific HEI-2015 components showed an opposite trend by sociodemographic strata.

Conclusion

The diet quality of Mexican adults was suboptimal from 2006 to 2016, with notorious disparities persisting over time among sociodemographic strata. Our results can serve as a basis for formulating recommendations on ways to improve the population diet, where those components diverging the most from adequate scores could be highlighted in public-health messages.
Acoustic analysis and detection of pharyngeal fricative in cleft palate speech using correlation of signals in independent frequency bands and octave spectrum prominent peak
Authors: He Fei , Wang Xiyue , Yin Heng , Zhang Han , Yang Gang , He Ling
Published: May 2020

Background

Pharyngeal fricative is one typical compensatory articulation error of cleft palate speech. It passively influences daily communication for people who suffer from it. The automatic detection of pharyngeal fricatives in cleft palate speech can provide information for clinical doctors and speech-language pathologists to aid in diagnosis.

Results

This paper proposes two features (CSIFs: correlation of signals in independent frequency bands; OSPP: octave spectrum prominent peak) to detect pharyngeal fricative speech. CSIFs feature is proposed to detect the distribution characteristics of frequency components in pharyngeal fricative speech caused by the changed place of articulation and movement of articulators. While OSPP is presented to reflect the concentration degree of prominent peak which is closely related to the place of articulation in pharyngeal fricative, both features are investigated to relate to the altered production process of pharyngeal fricative. To evaluate the capability of these two features to detect pharyngeal fricative, we collected a speech database covering all the types of initial consonants in which pharyngeal fricatives occur. In this detection task, the classifier used to discriminate pharyngeal fricative speech and normal speech is based on ensemble learning.

Conclusion

The detection accuracy obtained with CSIFs and OSPP features ranges from 83.5 to 84.5% and from 85 to 87%, respectively. When these two features are combined, the detection accuracy for pharyngeal fricative speech ranges from 88 to 89%, with an AUC (area under the receiver operating characteristic curve) value of 93%.
Peritoneal spillage is not an issue in patients undergoing minimally invasive surgery for colorectal cancer
Authors: Ambe Peter C. , Kankam Joseph , Zarras Konstantinos
Published: May 2020

Background

Surgery for colorectal cancer (CRC) is increasingly being performed via the minimally invasive route. However, reports of postoperative wound and port site seeding as well as peritoneal spillage have been worrisome. We investigated the risk of peritoneal spillage in patients undergoing laparoscopic surgery for CRC.

Methods

Cytology specimens were gained from the retrieval bag following intracorporeal resection and specimen retrieval using an endoscopic retrieval bag. Histopathologic examination of the cytology specimens was performed for the presence of malignant cells.

Results

Cytology specimens of 73 (34 female and 39 male) consecutive patients with a median age of 71 years were included for analysis. Advanced CRC in stages III and IV was present in 41% of the study population. Malignant cells were not found in any specimen.

Conclusion

Laparoscopic oncologic resection of colorectal cancer is not a risk factor for peritoneal spillage. Minimally invasive oncologic colorectal resection is safe without the increased risk of peritoneal carcinomatosis.
How is increased selectivity of medical school admissions associated with physicians’ career choice? A Japanese experience
Authors: Takaku Reo
Published: May 2020

Background

During the long-lasting economic stagnation, the popularity of medical school has dramatically increased among pre-medical students in Japan. This is primarily due to the belief that medicine is generally a recession-proof career. As a result, pre-medical students today who want to enter medical school have to pass a more rigorous entrance examination than that in the 1980s. This paper explores the association between the selectivity of medical school admissions and graduates’ later career choices.

Methods

A unique continuous measure of the selectivity of medical school admissions from 1980 to 2017, which is defined as the deviation value of medical schools, was merged with cross-sectional data of 122 990 physicians aged 35 to 55 years. The association between the deviation value of medical schools and various measures of physicians’ career choices was explored by logistic and ordinary least square regression models. Graduates from medical schools in which the deviation value was less than 55 were compared with those from more competitive medical schools, after controlling for fixed effects for the medical school attended by binary variables.

Results

From 1980 to 2017, the average deviation value increased from 58.3 to 66.3, indicating a large increase in admission selectivity. Empirical results suggest that increasing selectivity of a medical school is associated with graduates having a higher probability of choosing a career in an acute hospital as well as having a lower probability of opening their own clinic and choosing a career in primary health care. Graduating from a highly competitive medical school (i.e., deviation value of more than 65) significantly increases the probability of working at typical acute hospitals such as so-called 7:1 hospitals (OR 1.665 2, 95%CI 1.444 0–1.920 4) and decreases the probability of working at primary care facilities (OR 0.602 6, 95%CI 0.441 2–0.823 0). It is also associated with graduates having a higher probability of becoming medical board certified (OR 1.294 6, 95%CI 1.108 8–1.511 4).

Conclusion

Overall, this paper concludes that increased selectivity of medical school admissions predicts a higher quality of physicians in their own specialty, but at the same time, it is associated with a lower supply of physicians who go into primary care.
CAMKK2-CAMK4 signaling regulates transferrin trafficking, turnover, and iron homeostasis
Authors: Sabbir Mohammad Golam
Published: May 2020

Background

Circulatory iron is a hazardous biometal. Therefore, iron is transported in a redox-safe state by a serum glycoprotein - transferrin (TF). Different organs acquire iron from the systemic circulation through a tightly regulated mechanism at the blood-tissue interface which involves receptor-mediated internalization of TF. Thus, abnormal TF trafficking may lead to iron dyshomeostasis associated with several diseases including neurodegeneration. Iron -induced toxicity can cause neuronal damage to iron-sensitive brain regions. Recently, it was discovered that CAMKK2, a calcium (Ca2+)/calmodulin-activated kinase, controls receptor-mediated TF trafficking in mouse tissues, specifically in the brain. The biological function of CAMKK2 is mediated through multiple downstream effectors. Both CAMKK2 and one of its downstream kinase, CAMK4, exhibit overlapping expression in mouse brain. The role of CAMK4 in vesicular transport has been reported and loss of CAMKK2 or CAMK4 leads to cognitive defects in mouse. Therefore, it was hypothesized that CAMKK2-CAMK4 signaling regulates receptor-mediated TF trafficking and iron homeostasis which may be responsible for the neuronal malfunction observed in CAMKK2- or CAMK4-deficient mice.

Methods

CAMK4−/−mouse was used to study tissue-specific turnover of TF, TF-receptor (TFRC) and iron. CRISPR/Cas9-based CAMKK2 and/or CAMK4 deleted human embryonic kidney-derived HEK293 cell clones were used to study the molecular defects in receptor-mediated TF trafficking. Further, a “zero functional G protein” condition in HEK293 cell was exploited to study CAMKK2-CAMK4 signaling-mediated regulation of intracellular Ca2+homeostasis which was linked to calcium signaling during TF trafficking.

Results

Loss of CAMK4 leads to abnormal post-translational modifications (PTMs) and turnover of TF in mouse cerebellum and liver which was associated with iron dyshomeostasis in these tissues. The HEK293 cell-based study revealed that the absence of CAMKK2-CAMK4 signaling altered intracellular Ca2+homeostasis and lead to abnormal calcium signaling during TF trafficking. Also, CAMKK2-CAMK4 signaling deficiency affected the molecular interaction of TF and TF-receptor-associated protein complexes which indicated a potential failure in the recruitment of interacting proteins due to differential PTMs in TF.

Conclusion

Overall, this study established a novel mechanistic link between intracellular Ca2+ level, receptor-mediated TF trafficking, and iron homeostasis, all regulated by CAMKK2-CAMK4 signaling.

Graphical abstract
Views among Malawian women about joining HIV prevention clinical trials when pregnant
Authors: Sullivan Kristen , Mtande Tiwonge , Jaffe Elana , Rosenberg Nora , Zimba Chifundo , Hoffman Irving , Little Maggie , Faden Ruth , Lyerly Anne Drapkin
Published: May 2020

Background

The pressing need to expand the biomedical HIV prevention evidence base during pregnancy is now increasingly recognized. Women’s views regarding participation in such trials and initiating PrEP while pregnant are critical to inform evolving policy and best practices aimed at responsibly expanding evidence-based access for this population.

Methods

We conducted 35 semi-structured interviews with reproductive-aged women in Malawi in the local language, Chichewa. Participants were HIV-negative and purposively sampled to capture a range of experience with research during pregnancy. Women’s perspectives on enrolling in three hypothetical HIV prevention trial vignettes while pregnant were explored, testing: (1) oral PrEP (Truvada) (2) a vaginal ring (dapivirine), and (3) a randomized trial comparing the two. The vignettes were read aloud to participants and a simple visual was provided. Interviews were audio-recorded, transcribed, translated, and coded using NVivo 11. Thematic analysis informed the analytic approach.

Results

A majority of women accepted participation in all trials. Women’s views on research participation varied largely based on their assessment of whether participation or nonparticipation would best protect their own health and that of their offspring. Women interested in participating described power dynamics with their partner as fueling their HIV exposure concerns and highlighted health benefits of participation—principally, HIV protection and access to testing/treatment and ancillary care, and perceived potential risks of the vignettes as low. Women who were uninterested in participating highlighted potential maternal and fetal health risks of the trial, challenges of justifying prevention use to their partner, and raised some modality-specific concerns. Women also described ways their social networks, sense of altruism and adherence requirements would influence participation decisions.

Conclusions

The majority of participants conveyed strong interest in participating in biomedical HIV prevention research during pregnancy, largely motivated by a desire to protect themselves and their offspring. Our results are consistent with other studies that found high acceptance of HIV prevention products during pregnancy, and support the current direction of HIV research policies and practices that are increasingly aimed at protecting the health of pregnant women and their offspring through responsible research, rather than defaulting to their exclusion.
Resveratrol ameliorates atherosclerosis induced by high-fat diet and LPS in ApoE−/− mice and inhibits the activation of CD4+ T cells
Authors: Zhou Liyu , Long Jun , Sun Yuting , Chen Weikai , Qiu Runze , Yuan Dongping
Published: May 2020

Background

Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE−/−mice and investigate the underlying mechanism.

Methods

ApoE−/−mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4+T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4+T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4+T cells were measured.

Results

In vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4+T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4+T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4+T cells.

Conclusion

These results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE−/−mice, inhibited the proliferation and activation of CD4+T cells and regulated the expression of Dnmt1 and Dnmt3b.
Occurrence of mood disorders among educationally active older adults in Bialystok, Poland: a cross-sectional study
Authors: Cybulski Mateusz , Cybulski Lukasz , Krajewska-Kulak Elzbieta , Orzechowska Magda , Cwalina Urszula , Kowalewska Beata
Published: May 2020

Background

Mood disorders in older people are an increasingly serious health and social problem, and their prevalence increases with age. The most common mood disorders are bipolar disorder, which is the occurrence of mania and hypomania, and depressive disorders. The aim of this study was to determine the prevalence of mood disorders in a group of educationally active elderly people living in Bialystok, Poland.

Methods

The study included a total of 162 people—residents of Bialystok—aged 60 or older; 135 women (83.33%) and 27 men (16.67%). The study used five standardized psychometric scales: The Mood Disorder Questionnaire (MDQ), Hypomania Check List (HCL-32), Geriatric Depression Scale (GDS) and The Zung Self-Rating Depression Scale (Zung SDS).

Results

Nearly 90.00% of the respondents obtained GDS scores indicating the presence of mild depressive symptoms; however, on the Zung SDS, which also evaluates depression symptom levels, the result obtained in almost the same number of respondents showed an absence of these symptoms. A similar percentage of respondents also obtained values on the MDQ that allow to determine a lack of bipolar disorder characteristics in the studied population. Over half of the respondents (58.02%) did not show symptoms of hypomania using the HCL-32. There was a significant correlation between the results of the GDS and Zung SDS, the HCL-32 and MDQ, as well as the HCL-32 and Zung SDS in the total studied group.

Conclusions

Mood disorders, particularly depression, constitute a significant social and health problem in the group of educationally active older adults living in Bialystok. In light of the obtained research results, it is recommended to conduct and improve already realized health education programs for the elderly on the subject of mood disorder prevention and their impact on quality of life. There is a need for further research on mood disorders in the elderly to determine their prevalence on a national scale.
Preliminary result of carbon-ion radiotherapy using the spot scanning method for prostate cancer
Authors: Takakusagi Yosuke , Katoh Hiroyuki , Kano Kio , Anno Wataru , Tsuchida Keisuke , Mizoguchi Nobutaka , Serizawa Itsuko , Yoshida Daisaku , Kamada Tadashi
Published: May 2020

Background

Carbon-ion radiotherapy (CIRT) for prostate cancer was initiated at Kanagawa Cancer Center in 2015. The present study analyzed the preliminary clinical outcomes of CIRT for prostate cancer.

Methods

The clinical outcomes of 253 patients with prostate cancer who were treated with CIRT delivered using the spot scanning method between December 2015 and December 2017 were retrospectively analyzed. The irradiation dose was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. Biochemical relapse was defined using the Phoenix definition. Toxicities were assessed according to CTCAE version 4.0. Results: The median patient age was 70 (47–86) years. The median follow-up duration was 35.3 (4.1–52.9) months. According to the D’Amico classification system, 8, 88, and 157 patients were classified as having low, intermediate, and high risks, respectively. Androgen deprivation therapy was administered in 244 patients. The biochemical relapse-free rate in the low-, intermediate-, and high-risk groups at 3 years was 87.5, 88.0, and 97.5%, respectively (P = 0.036). Grade 2 acute urinary toxicity was observed in 12 (4.7%) patients. Grade 2 acute rectal toxicity was not observed. Grade 2 late urinary toxicity and grade 2 late rectal toxicity were observed in 17 (6.7%) and 3 patients (1.2%), respectively. Previous transurethral resection of the prostate was significantly associated with late grade 2 toxicity in univariate analysis. The predictive factor for late rectal toxicity was not detected.

Conclusion

The present study demonstrated that CIRT using the spot scanning method for prostate cancer produces favorable outcomes.
Durability of bioprosthetic aortic valves in patients under the age of 60 years – rationale and design of the international INDURE registry
Authors: Meuris Bart , Borger Michael A. , Bourguignon Thierry , Siepe Matthias , Grabenwöger Martin , Laufer Günther , Binder Konrad , Polvani Gianluca , Stefano Pierluigi , Coscioni Enrico , van Leeuwen Wouter , Demers Philippe , Dagenais Francois , Canovas Sergio , Theron Alexis , Langanay Thierry , Roussel Jean-Christian , Wendler Olaf , Mariscalco Giovanni , Pessotto Renzo , Botta Beate , Bramlage Peter , de Paulis Ruggero
Published: May 2020

Background

There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR.

Methods

The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20–22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery.

The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life.

Discussion

INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years.

Trial registration

ClinicalTrials.gov identifier: NCT03666741 (registration received September, 12th, 2018).
Diversity of hydrolase-producing halophilic bacteria and evaluation of their enzymatic activities in submerged cultures
Authors: Drissi Kaitouni Leila Batsoule , Anissi Jaouad , Sendide Khalid , El Hassouni Mohammed
Published: May 2020

Purpose

In this work, we assessed the diversity of culturable halophilic bacteria that produce hydrolytic enzymes from both natural and artificial hypersaline regions in the pre-Rif region of Morocco.

Methods

Bacteria were isolated from three hypersaline sites, in solid medium supplemented with various salt concentrations ranging from 0 to 330 g/L. Physical and chemical characteristics of samples from the isolation site were determined to suggest eventual correlations with the occurrence of the halophilic bacteria. Assays on enzymatic activities were performed in submerged cultures in the presence of various salt concentrations and appropriate substrates.

Results

Out of a collection of 227 halophilic bacteria, four halophilic groups were established as slightly halophilic, moderately halophilic, halotolerant, or extremely halophilic, with a predominance of halophilic bacteria in the natural hypersaline sites compared to the artificial one. Within this collection, 189 strains showed important hydrolytic activities in submerged cultures with enzymatic activities up to 76 U/mg. Strain characterization and identification was based on phenotypic and molecular traits and allowed the identification of at least 26 genera including Bacillus, Chthonibacter, Mariniabilia, Halobacillus, Salinococcus, Cerasicoccus, Ulvibacter, Halorubrum, Jeatgalicoccus, Brevibacterium, Sanguibacter, Shewanella, Exiguobacterium, Gemella, and Planomicrobium.

Conclusion

Data from this study give insights about the origin and the occurrence of halophilic bacteria in natural hypersaline environments compared to artificial hypersaline sites. The occurrence of halophilic hydrolase enzymes from halophilic bacteria gives insights to different applications in biotechnology, thanks to their ability to produce adaptive enzymes and survival strategies to overcome harsh conditions.
A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
Authors: Shoma Suresh K. , Bhat Samatha , Guru Bharath Raja , Muttigi Manjunatha S. , Seetharam Raviraja N.
Published: May 2020

Background

Mesenchymal stromal cell conditioned medium (MSC-CM) contains a cocktail of bioactive factors that act synergistically to induce therapeutic effects. This has been clearly demonstrated by in vivo applications of MSC-CM, but the establishment of controlled delivery systems is an unmet requirement for clinical translation.

Methods

We developed a nanocomposite-hydrogel (NP-H) comprised of poly-L-lactide nanoparticles (NPs) embedded in gelatin/hyaluronic acid (Gel/HA) hydrogel as a delivery vehicle for MSC-CM. First, we optimized the culture conditions for bone marrow-derived MSCs using serum-containing medium (SCM) and serum-free medium (SFM) and characterized the corresponding CM (serum-containing conditioned medium (ScCM) and serum-free conditioned medium (SfCM), respectively) for its potency and xeno markers. Then we prepared a composite matrix followed by physiochemical characterization and functional assays were performed.

Results

Nanocomposite hydrogel displayed an even distribution of NPs along with high porosity (> 60%) and swelling ratios > 1500%, while its protein release pattern corresponded to a mix of degradation and diffusion kinetics. Functional evaluation of the composites was determined using MSCs and human fibroblasts (HFFs). The cells seeded directly onto the composites displayed increasing metabolic activities over time, with ScCM-NP-H groups having maximum activity. The cells treated in vitro with 5% and 10% extracts of ScCM-NP-H and SfCM-NP-H exhibited a dose- and duration-dependent response. Cell activities reduced considerably for all groups, except 10% ScCM-NP-H, which displayed a significant increase over time.

Conclusion

We observed that sustained release of MSC-CM is required to prevent dose-dependent cytotoxicity. The proposed nanocomposite hydrogel for MSC-CM delivery can open up a new array for its clinical application.
Evaluation of oxidant/antioxidant status, metabolic profile and milk production in cows with metritis
Authors: Mikulková Karolína , Kadek Romana , Filípek Jaroslav , Illek Josef
Published: May 2020

Background

The aim of the study was to evaluate oxidant/antioxidant status in 21 Holstein dairy cows with metritis compared to 8 healthy controls. Blood samples were taken during the first 21 days postpartum. Malondialdehyde (MDA), a marker of oxidative stress, total antioxidant status (TAS) and antioxidant parameters such as glutathione peroxidase (GPx), selenium (Se), vitamins A and E and beta-carotene were determined from all cows. The differences in beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), calcium, bilirubin concentrations and aspartate aminotransferase (AST) activity were also monitored, as were milk production and milk composition. Metritis was defined by an unpleasant discharge of varying color (milky-grey/brown/sanguineous) and consistency (muco-purulent/purulent/watery) and by the presence of increased temperature (> 38.5 °C) in cows within 21 days postpartum. Rectal examination revealed increased uterine size, thickened uterine wall and increased uterine tone. The affected cows had significantly reduced daily milk production. Additionally, hematological parameters and haptoglobin concentration were also measured in metritic cows.

Results

Higher MDA concentration (P <  0.001) was recorded in cows with metritis, while vitamin A and vitamin E concentrations were lower (P <  0.01) compared to healthy cows. Higher BHB (P <  0.05), NEFA (P <  0.05), AST (P <  0.05) and bilirubin (P <  0.001) concentrations was recorded in cows with metritis as compared to the control group. Significant differences in beta-carotene concentration, GPx activity, and Se, TAS and Ca concentrations in cows with metritis compared to control group were not observed in the present study (P >  0.05). Milk production was decreased in the cows with metritis (P <  0.001) and alterations in milk composition were also observed in metritic cows as compared to healthy cows.

Conclusions

The results of the study showed that cows with metritis in early postpartum are exposed to a higher degree of oxidative stress and that the incidence of metritis can negatively affect milk production in dairy cows.
The compensatory phenomenon of the functional connectome related to pathological biomarkers in individuals with subjective cognitive decline
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Chen Haifeng , Sheng Xiaoning , Luo Caimei , Qin Ruomeng , Ye Qing , Zhao Hui , Xu Yun , Bai Feng
Published: May 2020

Background

Subjective cognitive decline (SCD) is a preclinical stage along the Alzheimer’s disease (AD) continuum. However, little is known about the aberrant patterns of connectivity and topological alterations of the brain functional connectome and their diagnostic value in SCD.

Methods

Resting-state functional magnetic resonance imaging and graph theory analyses were used to investigate the alterations of the functional connectome in 66 SCD individuals and 64 healthy controls (HC). Pearson correlation analysis was computed to assess the relationships among network metrics, neuropsychological performance and pathological biomarkers. Finally, we used the multiple kernel learning-support vector machine (MKL-SVM) to differentiate the SCD and HC individuals.

Results

SCD individuals showed higher nodal topological properties (including nodal strength, nodal global efficiency and nodal local efficiency) associated with amyloid-β levels and memory function than the HC, and these regions were mainly located in the default mode network (DMN). Moreover, increased local and medium-range connectivity mainly between the bilateral parahippocampal gyrus (PHG) and other DMN-related regions was found in SCD individuals compared with HC individuals. These aberrant functional network measures exhibited good classification performance in the differentiation of SCD individuals from HC individuals at an accuracy up to 79.23%.

Conclusion

The findings of this study provide insight into the compensatory mechanism of the functional connectome underlying SCD. The proposed classification method highlights the potential of connectome-based metrics for the identification of the preclinical stage of AD.
A systematic review on spatial crime forecasting
Authors: Kounadi Ourania , Ristea Alina , Araujo Adelson , Leitner Michael
Published: May 2020

Background

Predictive policing and crime analytics with a spatiotemporal focus get increasing attention among a variety of scientific communities and are already being implemented as effective policing tools. The goal of this paper is to provide an overview and evaluation of the state of the art in spatial crime forecasting focusing on study design and technical aspects.

Methods

We follow the PRISMA guidelines for reporting this systematic literature review and we analyse 32 papers from 2000 to 2018 that were selected from 786 papers that entered the screening phase and a total of 193 papers that went through the eligibility phase. The eligibility phase included several criteria that were grouped into: (a) the publication type, (b) relevance to research scope, and (c) study characteristics.

Results

The most predominant type of forecasting inference is the hotspots (i.e. binary classification) method. Traditional machine learning methods were mostly used, but also kernel density estimation based approaches, and less frequently point process and deep learning approaches. The top measures of evaluation performance are the Prediction Accuracy, followed by the Prediction Accuracy Index, and the F1-Score. Finally, the most common validation approach was the train-test split while other approaches include the cross-validation, the leave one out, and the rolling horizon.

Limitations

Current studies often lack a clear reporting of study experiments, feature engineering procedures, and are using inconsistent terminology to address similar problems.

Conclusions

There is a remarkable growth in spatial crime forecasting studies as a result of interdisciplinary technical work done by scholars of various backgrounds. These studies address the societal need to understand and combat crime as well as the law enforcement interest in almost real-time prediction.

Implications

Although we identified several opportunities and strengths there are also some weaknesses and threats for which we provide suggestions. Future studies should not neglect the juxtaposition of (existing) algorithms, of which the number is constantly increasing (we enlisted 66). To allow comparison and reproducibility of studies we outline the need for a protocol or standardization of spatial forecasting approaches and suggest the reporting of a study’s key data items.
Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non–Small-Cell Lung Cancer
Authors: Reck Martin , Wehler Thomas , Orlandi Francisco , Nogami Naoyuki , Barone Carlo , Moro-Sibilot Denis , Shtivelband Mikhail , González Larriba Jose Luis , Rothenstein Jeffrey , Früh Martin , Yu Wei , Deng Yu , Coleman Shelley , Shankar Geetha , Patel Hina , Kelsch Claudia , Lee Anthony , Piault Elisabeth , Socinski Mark A.
Published: May 2020

PURPOSE

Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non–small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC.

METHODS

Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13.

RESULTS

Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly.

CONCLUSION

ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.
Multiple Myeloma Cost of Care Under the Oncology Care Model: The Influence of High-Cost Therapies
Authors: Theroux Haley , Williams Alaysia , Liu Mark , Dahl Alyssa , Dreyer Theresa , Horvath Keith , Isola Luis
Published: May 2020

PURPOSE:

As expenditures for cancer care continue to grow substantially, value-based payment models are being tested to control costs. The Oncology Care Model (OCM) is the largest value-based payment program in oncology. The primary objective of this analysis was to determine the impact of high-cost novel agents on total cost of care for multiple myeloma (MM) episodes of care in the OCM.

METHODS:

This was a retrospective analysis using Medicare claims data for 258 MM OCM episodes initiated between July 1, 2016, and July 1, 2017. Patients were organized into 3 cohorts: those who received pomalidomide (cohort A), those who received lenalidomide (cohort B), and those who did not receive either drug but had received another chemotherapy agent (cohort C). We compared the actual episode expenditures and the Centers for Medicare and Medicaid target price to create an observed versus expected (O/E) ratio.

RESULTS:

The average O/E for cohort A (n = 73) was 1.73, compared with 1.31 for cohort B (n = 84) and 1.01 for cohort C (n = 101). The difference the in O/E ratio among the groups was statistically significant ( P < .001). The average episode target price for cohorts A, B, and C was $66,149, $63,483, and $63,937, respectively. Despite the high cost of pomalidomide and lenalidomide, there was no significant difference in the average episode target prices of the cohorts.

CONCLUSION:

The O/E ratio and target prices of the cohorts demonstrate a lack of adequate adjustment to the OCM target price for episodes in which pomalidomide and lenalidomide were used to treat patients with MM.
Corticosterone, Adrenal, and the Pituitary-Gonadal Axis in Neonatal Rats: Effect of Maternal Separation and Hypoxia
Authors: Gehrand Ashley L , Phillips Jonathan , Malott Kevin , Raff Hershel
Published: May 2020

Hypoxia, a common stressor in prematurity, leads to sexually dimorphic, short- and long-term effects on the adult hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. We hypothesized that these effects are due to stress-induced increases in testosterone during early postnatal life. We evaluated this phenomenon by systematically assessing the short-term effects of normoxic or hypoxic separation on male and female pups at birth, postnatal hours (H) 2, 4, and 8, and postnatal days (PD) 2 to 7. Our findings were (a) hypoxic separation led to a large increase in plasma corticosterone from 4H-PD4, (b) neither normoxic nor hypoxic separation affected critical adrenal steroidogenic pathway genes; however, a significant decrease in baseline Cyp11a1, Mc2r, Mrap, and Star adrenal expression during the first week of neonatal life confirmed the start of the adrenal stress hyporesponsive period, (c) a luteinizing hormone/follicle-stimulating hormone–independent increase in plasma testosterone occurred in normoxic and hypoxic separated male pups at birth, (d) testicular Cyp11a1, Lhcgr, and Star expression was high at birth and decreased thereafter suggesting a hyporesponsive period in the testes, and (e) elevated estrogen in the early neonatal period occurred independently of gonadotropin stimulation. We conclude that a large corticosterone response to hypoxia during the first 5 days of life occurs as an adaptation to neonatal stress, that the testosterone surge during the first hours after birth occurs independently of gonadotropins but is associated with upregulation of the steroidogenic pathway genes in the testes, and that high postnatal estrogen production also occurs independently of gonadotropins.
Postcritical Howells: American Realism and Liberal Guilt
Authors: Wonham Henry B.
Published: May 2020

This essay explores the concept of liberal guilt in William Dean Howells’s fiction, focusing especially on his 1888 novel Annie Kilburn. Genealogies of liberal guilt rarely mention Howells, and yet no American writer has more painstakingly elaborated the embarrassing predicament of middle-class complicity in social arrangements that entail the widespread suffering of others. I provide a summary of theoretical positions on liberal guilt as a structure of feeling that entails what Richard Rorty calls “doubt about [one’s] own sensitivity to the pain and humiliation of others, doubt that present institutional arrangements are adequate to deal with this pain and humiliation.” Howells felt these doubts profoundly, and yet he understood liberal guilt as a productive emotional and intellectual predicament. Put simply, Howells viewed liberal guilt, like realism itself, as an attitude of resigned acceptance of persistent social injustices but an attitude capable of animating, rather than dissipating, liberal commitments and public agendas.
Readerly Revisions: Letters to the Editor in the Crisis
Authors: Quinn William Reed
Published: May 2020

This essay examines how the editorial staff of the Crisis positioned readers as collaborators and literary activists. Looking at letters to the editor, I argue that readers helped reevaluate representations of blackness in American literary taste. These letters bridge past, present, and future issues of the magazine and, therefore, evoke a temporality that exceeds the critical capacities of close reading. To address how editors, readers, and authors responded to each other over time, I combine close reading with topic modeling, a method of computational text analysis. This mixed methodology shows how readers participated in the magazine’s cultural campaign against racism by calling for socially progressive depictions of blackness.