bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Public Housing Affordability for Large Income Diversity Groups in a New-Town Capital City: A Case Study of Abuja, Nigeria
Authors: Jiburum Uloma , Nwachukwu Maxwell Umunna , Mba Harold Chike , Okonkwo Celestine Nnaji , Okeke Donald Chiuba
Published: September 2021

Scholars are polarized on the issue of the best approach for measuring housing affordability. This has generated a lack of consensus on the best method to adopt in measuring the concept. Consequently, this study is set-out to extend the literature on housing affordability by examining the public housing affordability for each income group in Nigeria using Abuja as a case study city. This study is aimed at providing the contextual framework for the redefinition of housing affordability based on the diversity of income. The housing cost approach was used to measure housing affordability, whereas the principal component analysis determined factors that caused the unaffordable housing market. The results showed that public housing was not affordable to low and medium-income earners. The unaffordable housing market for each of the three income groups was influenced by diverse factors. Consequently, public housing provision should consider the affordability of each income group. This is because factors that determine housing affordability are peculiar to each of the three income groups.
A Longitudinal Study on the Effects of Parasocial Relationships and Breakups With Characters of a Health-Related TV Show on Self-Efficacy and Exercise Behavior: The Case of The Biggest Loser
Authors: Siegenthaler Perina , Aegerter Tanja , Fahr Andreas
Published: September 2021

Overweight is one of the major health-related challenges in industrialized countries and mostly preventable through a healthy diet and regular engagement in physical activity. Health communication practitioners and researchers, therefore, started using the media’s persuasive potential by creating entertainment-education (E-E) programs that promote healthy nutrition and exercise. By observing the characters in E-E programs, audience members can learn vicariously and eventually develop personal bonds with them. The current study investigates the effects of parasocial relationships (PSRs) with characters of a health-related E-E show, as well as the impact of parasocial breakups (PSBUs) on health-relevant outcomes. Using the setting of the show The Biggest Loser (TBL), we conducted a quasi-experimental longitudinal field study. Participants ( N = 149) watched shortened episodes of the show once a week for 5 weeks. Results showed that PSRs with the reality TV characters did not increase over time and after repeated exposure. Findings furthermore suggest that PSR did not influence self-efficacy perceptions or exercise behavior over time. Parasocial breakup distress intensity was neither related to self-efficacy nor to exercise behavior. Interpretations of these findings and implications for better understanding the effects of PSRs and PSBUs are discussed.
Early Onset Lyme Myopericarditis With Left Ventricular Dysfunction and Mitral Regurgitation
Authors: Malik Muhammad B. , Baluch Amarah , Adhikari Soumya , Quraeshi Sahir , Rao Suman
Published: September 2021

Lyme carditis is a rare manifestation of early disseminated Lyme disease with an incidence of 0.5% with left ventricular dysfunction and valvular involvement being exceedingly rare. Clinical manifestations typically occur 1 to 2 months after infection and include arrhythmias, conduction abnormalities, myopericarditis, and ventricular dysfunction. If left untreated, Lyme carditis can lead to acute heart failure and sudden cardiac death thus prompt diagnosis and treatment are essential in management. Here, we present a case of Lyme carditis with left ventricular dysfunction and valvular involvement occurring shortly after known tick exposure.
Changes to the Cleft Nose Esthetic After Le Fort I Advancement: A 3-Dimensional Analysis
Authors: Marji Fady P. , Bruce Madeleine K. , Anstadt Erin E. , Ma Irene T. , Lee Jonathan Y. , Chow Ian , Beiriger Justin , Losee Joseph E. , Goldstein Jesse A.
Published: September 2021

Background and Purpose: The study of nasal changes in cleft lip and palate (CLP) orthognathics is limited. This study aimed to determine differences in 3-dimensional (3D) nasal changes for unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) patients after Le Fort I advancement. Methods: This study was a retrospective cohort evaluation of 18 subjects (9 male, 9 female) treated at a single institution over a 5-year period who had class III skeletal and dentoalveolar malocclusion related to non-syndromic cleft lip and/or palate and underwent surgical correction via Le Fort I osteotomy. Patients underwent pre- and postoperative cephalometric measurements and 3D volumetric assessment for comparison to analyze nasal changes. Statistical analysis was performed to determine changes in nasal parameters using student’s t-test and multivariate analysis. Differences were considered significant for P-values ≤.05. Results: All nasal parameters except for nasolabial angle and nasal length changed significantly postoperatively in the entire cohort. Alar base and flare width both increased significantly (2.1 mm, P = .0002, 1.4 mm, P = .0005), while both relative and total tip projection decreased (−3.4 mm, P = .000004, −2.2 mm, P = .0008). An advancement of the entire nasal complex was seen postoperatively (1.0 mm, P = .0005). UCLP patients had a significantly larger decrease in total nasal tip projection following surgery relative to BCLP patients (−3.5 ± 1.2 mm, −0.8 ± 2.1 mm, P = .008). BCLP morphology increases the degree of 3D nasal surface area advancement relative to UCLP (1.2 mm ± 0.3, 0.8 mm ± 0.6, P = .028). Alar cinch stitch decreases nasolabial angle ( P = .024) but increases nasal length ( P = .004). Conclusion: Discrepancies exist in nasal changes after Le Fort I advancement between UCLP and BCLP patients. Increased understanding of outcomes for cleft patients undergoing Le Fort I can help improve the predictability of nasal esthetic changes in this patient population.
Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia
Authors: DeAngelo Daniel J. , Jonas Brian A. , Liesveld Jane L. , Bixby Dale L. , Advani Anjali S. , Marlton Paula , Magnani John L. , Thackray Helen M. , Feldman Eric J. , O’Dwyer Michael E. , Becker Pamela S.
Published: September 2021

Uproleselan (GMI-1271) is a novel E-selectin antagonist that disrupts cell survival pathways, enhances chemotherapy response, improves survival in mouse xenograft and syngeneic models, and decreases chemotherapy toxicity in vivo. A phase 1/2 study evaluated the safety, tolerability, and antileukemic activity of uproleselan (5-20 mg/kg) with MEC (mitoxantrone, etoposide, and cytarabine) among patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Among the first 19 patients, no dose-limiting toxicities were observed. The recommended phase 2 dose (RP2D) was 10 mg/kg twice daily. An additional 47 patients with R/R AML were treated with uproleselan at the RP2D plus MEC. At the RP2D, the remission rate (complete response [CR]/CR with incomplete count recovery [CRi]) was 41% (CR, 35%), and the median overall survival (OS) was 8.8 months. In a separate cohort, 25 newly diagnosed patients age ≥60 years received uproleselan at the RP2D plus cytarabine and idarubicin (7 + 3). In these frontline patients, the CR/CRi rate was 72% (CR, 52%), and the median OS was 12.6 months. The addition of uproleselan was associated with low rates of oral mucositis. E-selectin ligand expression on leukemic blasts was higher in patients with relapsed vs primary refractory AML and in newly diagnosed older patients with high-risk cytogenetics and secondary AML. In the R/R cohort, E-selectin expression >10% was associated with a higher response rate and improved survival. The addition of uproleselan to chemotherapy was well tolerated, with high remission rates, low induction mortality, and low rates of mucositis, providing a strong rationale for phase 3 randomized confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02306291.
Defining the transcriptional control of pediatric AML highlights RARA as a superenhancer-regulated druggable dependency
Authors: Perez Monika W. , Sias-Garcia Oscar , Daramola Alfred , Wei Helen , Terrell Maci , Rashid Raushan , Park Woojun D. , Duong Kevin , Horton Terzah M. , Li Feng , Cherayil Nikitha , Koren Jost Vrabic , Gant Vincent U. , Junco Jacob J. , Curry Choladda V. , Stevens Alexandra M. , Lin Charles Y. , Yi Joanna S.
Published: September 2021

Somatic mutations are rare in pediatric acute myeloid leukemia (pAML), indicating that alternate strategies are needed to identify targetable dependencies. We performed the first enhancer mapping of pAML in 22 patient samples. Generally, pAML samples were distinct from adult AML samples, and MLL (KMT2A)–rearranged samples were also distinct from non–KMT2A-rearranged samples. Focusing specifically on superenhancers (SEs), we identified SEs associated with many known leukemia regulators. The retinoic acid receptor alpha (RARA) gene was differentially regulated in our cohort, and a RARA-associated SE was detected in 64% of the study cohort across all cytogenetic and molecular subtypes tested. RARA SE+ pAML cell lines and samples exhibited high RARA messenger RNA levels. These samples were specifically sensitive to the synthetic RARA agonist tamibarotene in vitro, with slowed proliferation, apoptosis induction, differentiation, and upregulated retinoid target gene expression, compared with RARA SE− samples. Tamibarotene prolonged survival and suppressed the leukemia burden of an RARA SE+ pAML patient-derived xenograft mouse model compared with a RARA SE− patient-derived xenograft. Our work shows that examining chromatin regulation can identify new, druggable dependencies in pAML and provides a rationale for a pediatric tamibarotene trial in children with RARA-high AML.
Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy
Authors: Kambhampati Swetha , Sheng Ying , Huang Chiung-Yu , Bylsma Sophia , Lo Mimi , Kennedy Vanessa , Natsuhara Kelsey , Martin Thomas , Wolf Jeffrey , Shah Nina , Wong Sandy W.
Published: September 2021

B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy (BCMA CAR-T) is an effective treatment of relapsed refractory multiple myeloma (MM). However, the pattern of infectious complications is not well elucidated. We performed a single-center retrospective analysis of infection outcomes up to 1 year after BCMA CAR-T for MM from 2018 to 2020. Fifty-five patients with MM were treated with BCMA CAR-T. Before lymphodepletion (LD), 35% of patients had severe hypogammaglobulinemia and 18% had severe lymphopenia. Most patients (68%) received bridging chemotherapy (BC) before LD. In the first month after CAR-T, 98% patients had grade 3 to 4 neutropenia. At 1 year after infusion, 76% patients had hypogammaglobulinemia. With a median follow-up of 6.0 months (95% confidence interval, 4.7-7.4), there were a total of 47 infection events in 29 (53%) patients: 40% bacterial, 53% viral, and 6% fungal. Most (92%) were mild-moderate and of the lower/upper respiratory tract system (68%). Half of the infections (53%) occurred in the first 100 days after CAR-T infusion. Although no statistically significant risk factors for infection were identified, prior lines of therapy, use of BC, recent infections, and post–CAR-T lymphopenia were identified as possible risk factors that need to be further explored. This is the largest study to date to assess infectious complications after BCMA CAR-T. Despite multiple risk factors for severe immunosuppression in this cohort, relatively few life-threatening or severe infections occurred. Further larger studies are needed to better characterize the risk factors for and occurrence of infections after BCMA CAR-T.
CGRP antibody therapy in patients with drug resistant migraine and chronic daily headache: a real-world experience
Authors: Scheffler Armin , Schenk Hannah , Wurthmann Sebastian , Nsaka Michael , Kleinschnitz Christoph , Glas Martin , Holle Dagny
Published: September 2021

Background

Calcitonin gene-related peptide (CGRP) (receptor) antibodies (erenumab, fremanezumab and galcanezumab) are increasingly used in prophylactic treatment of migraine. In the approval studies, severely affected patients with migraine and chronic daily headache without any headache free days were excluded. Thus, less is known about the effectiveness of CGRP antibody treatment in this cohort.

Methods

Clinical routine data of 32 patients with migraine and daily headache were analysed after three months of treatment with a CGRP antibody (16 erenumab, 7 galcanezumab, 9 fremanezumab), including changes of monthly headache days (MHD) monthly migraine days (MMD) and monthly acute medication intake (AMD) as well as migraine characteristics. Statistical analysis was performed with the Wilcoxon-Test. Migraine characteristics were analysed descriptively.

Results

The number of MHD was significantly reduced (mean reduction (standard error), p-value): (-4.2 (1.3), p = 0.009) as well as MMD (-4.3 (1.6), p = 0.033). Four patients (13 %) reached a 50 % reduction regarding MHD and 8 patients (25 %) regarding MMD, migraine duration and intensity improved under therapy.

Conclusions

Despite the low responder rate, CGRP antibodies can be effective at least in a few cases of severely affected patients with drug resistant migraine and chronic daily headache.

Trial registration

Retrospective registered.
Plasmon-Enhanced Light Absorption in (p-i-n) Junction GaAs Nanowire Solar Cells: An FDTD Simulation Method Study
Authors: Dawi E. A. , Karar A. A. , Mustafa E. , Nur O.
Published: September 2021

A finite-difference time-domain method is developed for studying the plasmon enhancement of light absorption from vertically aligned GaAs nanowire arrays decorated with Au nanoparticles. Vertically aligned GaAs nanowires with a length of 1 µm, a diameter of 100 nm and a periodicity of 165–500 nm are functionalized with Au nanoparticles with a diameter between 30 and 60 nm decorated in the sidewall of the nanowires. The results show that the metal nanoparticles can improve the absorption efficiency through their plasmonic resonances, most significantly within the near-bandgap edge of GaAs. By optimizing the nanoparticle parameters, an absorption enhancement of almost 35% at 800 nm wavelength is achieved. The latter increases the chance of generating more electron–hole pairs, which leads to an increase in the overall efficiency of the solar cell. The proposed structure emerges as a promising material combination for high-efficiency solar cells.
Effects of co-adsorption on interfacial charge transfer in a quantum dot@dye composite
Authors: Cui Peng , Xue Yuan
Published: September 2021

The sensitive electronic environment at the quantum dot (QD)–dye interface becomes a roadblock to enhancing the energy conversion efficiency of dye-functionalized quantum dots (QDs). Energy alignments and electronic couplings are the critical factors governing the directions and rates of different charge transfer pathways at the interface, which are tunable by changing the specific linkage groups that connect a dye to the QD surface. The variation of specific anchors changes the binding configurations of a dye on the QD surface. In addition, the presence of a co-adsorbent changes the dipole–dipole and electronic interactions between a QD and a dye, resulting in different electronic environments at the interface. In the present work, we performed density functional theory (DFT)-based calculations to study the different binding configurations of N719 dye on the surface of a Cd33Se33 QD with a co-adsorbent D131 dye. The results revealed that the electronic couplings for electron transfer were greater than for hole transfer when the structure involved isocyanate groups as anchors. Such strong electronic couplings significantly stabilize the occupied states of the dye, pushing them deep inside the valence band of the QD and making hole transfer in these structures thermodynamically unfavourable. When carboxylates were involved as anchors, the electronic couplings for hole transfer were comparable to electron transfer, implying efficient charge separation at the QD–dye interface and reduced electron–hole recombination within the QD. We also found that the electronic couplings for electron transfer were larger than those for back electron transfer, suggesting efficient charge separation in photoexcited QDs. Overall, the current computational study reveals some fundamental aspects of the relationship between the interfacial charge transfer for QD@dye composites and their morphologies which benefit the design of QD-based nanomaterials for photovoltaic applications.
Biogenic Synthesis, Characterization and Antibacterial Potential Evaluation of Copper Oxide Nanoparticles Against Escherichia coli
Authors: Ali Mohsin , Ijaz Muhammad , Ikram Muhammad , Ul-Hamid Anwar , Avais Muhammad , Anjum Aftab Ahmad
Published: September 2021

The development of resistance against antibiotics used to treat bacterial infections along with the prevalence of medication residues presents significant public health problems globally. Antibiotic-resistant germs result in infections that are difficult or impossible to treat. Decreasing antibiotic effectiveness calls for rapid development of alternative antimicrobials. In this respect, nanoparticles (NPs) of copper oxide (CuO) manifest a latent and flexible inorganic nanostructure with noteworthy antimicrobial impact. Green synthesis of CuO NPs was performed in the current study, which was then doped with varying amounts of ginger (Zingiber officinale, ZO) and garlic (Allium sativum, AS) extracts. In low and high doses, the synthesized compound was used to measure the antimicrobial effectiveness against pathogenic Escherichia coli. The present research successfully demonstrated a renewable, eco-friendly synthesis technique with natural materials that is equally applicable to other green metal oxide NPs.
Evaluating post-operative venous thromboembolism risk in urology patients using a validated risk assessment model
Authors: Padayachee Winston Paul René , Haffejee Mohamed , Nel Marietha
Published: September 2021

Background

Venous thromboembolism (VTE) is an important cause of post-surgical morbidity and mortality. This study aimed to apply a validated risk assessment model to evaluate the risk of post-operative VTE in urology patients.

Methods

This prospective descriptive observational study used the Caprini risk assessment model to evaluate VTE risk in patients planned for elective urology surgery at a tertiary Johannesburg hospital from January to June 2020.

Results

Two hundred and twenty-six patients with a mean age of 52 years were evaluated for post-operative VTE risk. The population was generally overweight, with a mean BMI of 26.3 kg/m2. The mean Caprini score was 4.42, reflecting a population at high risk for post-operative VTE. There was no statistically significant difference between males and females in this regard. On average, participants had three risk factors for post-operative VTE. Fifteen per cent of all patients were at low risk for VTE, while 40.3% of participants were categorised as moderate risk. The category with the highest percentage of participants (44.7%) was the high-risk category (Caprini score ≥ 5). High-risk patients undergoing oncology surgery comprised 16.8% of the population, and these patients may require extended duration pharmacological thromboprophylaxis to prevent VTE. The most clinically significant risk factors for post-operative VTE included age, obesity, malignancy and HIV infection.

Conclusion

Venous thromboembolism may be difficult to diagnose, and clinicians may underestimate the risk for it to develop. Risk assessment models, such as the Caprini score, are objective and a practical tool to guide the application of thromboprophylaxis. The application of the Caprini RAM in the elective urological surgery population at Chris Hani Baragwanath Academic Hospital yields similar results to studies performed elsewhere on similar surgical populations. Further research is required to evaluate whether the actual incidence of VTE correlates with the risk assessment in this population. Clinician compliance with the use of RAMs as well as the corresponding recommendations for prophylaxis may need to be evaluated. A validated risk assessment model which accounts for procedure-specific risks in urology may be useful.
Reverse engineering gene regulatory network based on complex-valued ordinary differential equation model
Authors: Yang Bin , Bao Wenzheng , Zhang Wei , Wang Haifeng , Song Chuandong , Chen Yuehui , Jiang Xiuying
Published: September 2021

Background

The growing researches of molecular biology reveal that complex life phenomena have the ability to demonstrating various types of interactions in the level of genomics. To establish the interactions between genes or proteins and understand the intrinsic mechanisms of biological systems have become an urgent need and study hotspot.

Results

In order to forecast gene expression data and identify more accurate gene regulatory network, complex-valued version of ordinary differential equation (CVODE) is proposed in this paper. In order to optimize CVODE model, a complex-valued hybrid evolutionary method based on Grammar-guided genetic programming and complex-valued firefly algorithm is presented.

Conclusions

When tested on three real gene expression datasets fromE.coliand Human Cell, the experiment results suggest that CVODE model could improve 20–50% prediction accuracy of gene expression data, which could also infer more true-positive regulatory relationships and less false-positive regulations than ordinary differential equation.
Genome-wide identification and expression profile under abiotic stress of the barley non-specific lipid transfer protein gene family and its Qingke Orthologues
Authors: Duo Jiecuo , Xiong Huiyan , Wu Xiongxiong , Li Yuan , Si Jianping , Zhang Chao , Duan Ruijun
Published: September 2021

Background

Plant non-specific lipid transfer proteins (nsLTPs), a group of small, basic ubiquitous proteins to participate in lipid transfer, cuticle formation and stress response, are involved in the regulation of plant growth and development. To date, although the nsLTP gene family of barley (Hordeum vulgare L.) has been preliminarily identified, it is still unclear in the recently completed genome database of barley and Qingke, and its transcriptional profiling under abiotic stress has not been elucidated as well.

Results

We identified 40 barley nsLTP (HvLTP) genes through a strict screening strategy based on the latest barley genome and 35 Qingke nsLTP (HtLTP) orthologues using blastp, and these LTP genes were divided into four types (1, 2, D and G). At the same time, a comprehensive analysis of the physical and chemical characteristics, homology alignment, conserved motifs, gene structure and evolution of HvLTPs and HtLTPs further supported their similar nsLTP characteristics and classification. The genomic location of HvLTPs and HtLTPs showed that these genes were unevenly distributed, and obvious HvLTP and HtLTP gene clusters were found on the 7 chromosomes including six pairs of tandem repeats and one pair of segment repeats in the barley genome, indicating that these genes may be co-evolutionary and co-regulated. A spatial expression analysis showed that most HvLTPs and HtLTPs had different tissue-specific expression patterns. Moreover, the upstream cis-element analysis of HvLTPs and HtLTPs showed that there were many different stress-related transcriptional regulatory elements, and the expression pattern of HvLTPs and HtLTPs under abiotic stress also indicated that numerous HvLTP and HtLTP genes were related to the abiotic stress response. Taken together, these results may be due to the differences in promoters rather than by genes themselves resulting in different expression patterns under abiotic stress.

Conclusion

Due to a stringent screening and comprehensive analysis of the nsLTP gene family in barley and Qingke and its expression profile under abiotic stress, this study can be considered a useful source for the future studies of nsLTP genes in either barley or Qingke or for comparisons of different plant species.
Genome-wide identification and analysis of WRKY gene family in maize provide insights into regulatory network in response to abiotic stresses
Authors: Hu Wenjing , Ren Qiaoyu , Chen Yali , Xu Guoliang , Qian Yexiong
Published: September 2021

Background

The WRKY transcription factor family plays significant roles in biotic and abiotic stress responses, which has been associated with various biological processes in higher plants. However, very little is known regarding the structure and function of WRKY genes in maize.

Results

In this study, a total of 140 ZmWRKY proteins encoded by 125 ZmWRKY genes were eventually identified in maize. On the basis of features of molecular structure and a comparison of phylogenetic relationships of WRKY transcription factor families from Arabidopsis, rice and maize, all 140 ZmWRKY proteins in maize were divided into three main groups (Groups I, II and III) and the Group II was further classified into five subgroups. The characteristics of exon-intron structure of these putative ZmWRKY genes and conserved protein motifs of their encoded ZmWRKY proteins were also presented respectively, which was in accordance with the group classification results. Promoter analysis suggested that ZmWRKY genes shared many abiotic stress-related elements and hormone-related elements. Gene duplication analysis revealed that the segmental duplication and purifying selection might play a significant role during the evolution of the WRKY gene family in maize. Using RNA-seq data, transcriptome analysis indicated that most of ZmWRKY genes displayed differential expression patterns at different developmental stages of maize. Further, by quantitative real-time PCR analysis, twenty-one ZmWRKY genes were confirmed to respond to two different abiotic stress treatments, suggesting their potential roles in various abiotic stress responses. In addition, RNA-seq dataset was used to conduct weighted gene co-expression network analysis (WGCNA) in order to recognize gene subsets possessing similar expression patterns and highly correlated with each other within different metabolic networks. Further, subcellular localization prediction, functional annotation and interaction analysis of ZmWRKY proteins were also performed to predict their interactions and associations involved in potential regulatory network.

Conclusions

Taken together, the present study will serve to present an important theoretical basis for further exploring function and regulatory mechanism of ZmWRKY genes in the growth, development, and adaptation to abiotic stresses in maize.
IgG4-related disease as a rare cause of gastric outlet obstruction: a case report and literature review
Authors: Chen Lina , Almudaires Abdulaziz , Alzahrani May , Qumosani Karim , Chakrabarti Subrata
Published: September 2021

Background

IgG4-related disease involvement of the digestive tract is very rare. In few reported cases of isolated gastric/duodenal IgG4-related disease, none of which resulted in luminal obstruction.

Case presentation

A 59 years old female presented with longstanding gastrointestinal symptoms. CT showed mural thickening of the proximal duodenum. Gastroscopy showed antral ulcer extending into the duodenum with outlet obstruction and biopsy showed acute on chronic duodenitis. Whipple’s procedure was performed and IgG4-related disease was diagnosed on final pathology. Symptoms were revolved on mycophenolate mofetil and prednisone with no recurrence.

Conclusions

Our case is the only reported case with gastric outlet obstruction secondary to gastroduodenal IgG4-related disease. The diagnosis should be considered in the differential diagnosis of unexplained duodenal stricture, gastric outlet obstruction or gastrointestinal ulceration. IgG4-related disease usually responds to steroids but long-term response rates to steroid-sparing agents, especially in the subset of patients with luminal IgG4-related disease remains to be determined.
Diversity of cancer-related identities in long-term prostate cancer survivors after radical prostatectomy
Authors: Jahnen Matthias , Mynzak Eike , Meissner Valentin H. , Schiele Stefan , Schulwitz Helga , Ankerst Donna P. , Gschwend Jürgen E. , Herkommer Kathleen , Dinkel Andreas
Published: September 2021

Background

Individuals affected by cancer need to integrate this experience into their personal biography as their life continues after primary therapy, leading to substantial changes in self-perception. This study identified factors uniquely associated with 5 different cancer-related identities in order to improve the understanding of how self-perception in men affected by prostate cancer is associated with certain clinical and psychosocial characteristics.

Methods

In this cross-sectional study, long-term prostate cancer survivors after radical prostatectomy were asked to choose one of 5 cancer-related identities that described them best. Associations with sociodemographic, clinical, and psychological variables were investigated using multivariable logistic regression.

Results

Three thousand three hundred forty-seven men (mean age 78.1 years) surveyed on average 15.6 years after prostatectomy were included. Most men favored the terms “someone who has had cancer” (43.9%) which was associated with a mild disease course, and “patient” (26.3%) which was associated with ongoing therapy and biochemical disease recurrence. The self-descriptions “cancer survivor” (16.8%), “cancer conqueror” (10.9%) and “victim” (2.1%) were less common. “Cancer survivor” was associated with high perceived disease severity (OR: 1.86 [1.44–2.40]). “Cancer survivor” and “cancer conqueror” were related to high benefit finding (OR: 1.89 [1.48–2.40], OR: 1.46 [1.12–1.89] respectively), and only “cancer conqueror” was associated with high well-being (OR: 1.84 [1.35–2.50]). Identification as “victim” was associated with a positive depression screening and low well-being (OR: 2.22 [1.15–4.31], OR: 0.38 [0.20–0.72] respectively) (allp < 0.05).

Conclusions

Although long-term survival is common among men affected by PCa, they display a large diversity in cancer-related identities, which are associated with unique clinical and psychological characteristics. These cancer-related identities and their distinctive properties are associated with psychological well-being even after a long follow-up.
Imaging mass cytometry for high-dimensional tissue profiling in the eye
Authors: Schlecht Anja , Boneva Stefaniya , Salie Henrike , Killmer Saskia , Wolf Julian , Hajdu Rozina Ida , Auw-Haedrich Claudia , Agostini Hansjürgen , Reinhard Thomas , Schlunck Günther , Bengsch Bertram , Lange Clemens AK
Published: September 2021

Background

Imaging mass cytometry (IMC) combines the principles of flow cytometry and mass spectrometry (MS) with laser scanning spatial resolution and offers unique advantages for the analysis of tissue samples in unprecedented detail. In contrast to conventional immunohistochemistry, which is limited in its application by the number of possible fluorochrome combinations, IMC uses isoptope-coupled antibodies that allow multiplex analysis of up to 40 markers in the same tissue section simultaneously.

Methods

In this report we use IMC to analyze formalin-fixed, paraffin-embedded conjunctival tissue. We performed a 18-biomarkers IMC analysis of conjunctival tissue to determine and summarize the possibilities, relevance and limitations of IMC for deciphering the biology and pathology of ocular diseases.

Results

Without modifying the manufacturer’s protocol, we observed positive and plausible staining for 12 of 18 biomarkers. Subsequent bioinformatical single-cell analysis and phenograph clustering identified 24 different cellular clusters with distinct expression profiles with respect to the markers used.

Conclusions

IMC enables highly multiplexed imaging of ocular samples at subcellular resolution. IMC is an innovative and feasible method, providing new insights into ocular disease pathogenesis that will be valuable for basic research, drug discovery and clinical diagnostics.
Local government responses for COVID-19 management in the Philippines
Authors: S. Talabis Dylan Antonio , Babierra Ariel L. , H. Buhat Christian Alvin , Lutero Destiny S. , Quindala Kemuel M. , Rabajante Jomar F.
Published: September 2021

Background

Responses of subnational government units are crucial in the containment of the spread of pathogens in a country. To mitigate the impact of the COVID-19 pandemic, the Philippine national government through its Inter-Agency Task Force on Emerging Infectious Diseases outlined different quarantine measures wherein each level has a corresponding degree of rigidity from keeping only the essential businesses open to allowing all establishments to operate at a certain capacity. Other measures also involve prohibiting individuals at a certain age bracket from going outside of their homes. The local government units (LGUs)–municipalities and provinces–can adopt any of these measures depending on the extent of the pandemic in their locality. The purpose is to keep the number of infections and mortality at bay while minimizing the economic impact of the pandemic. Some LGUs have demonstrated a remarkable response to the COVID-19 pandemic. The purpose of this study is to identify notable non-pharmaceutical interventions of these outlying LGUs in the country using quantitative methods.

Methods

Data were taken from public databases such as Philippine Department of Health, Philippine Statistics Authority Census, and Google Community Mobility Reports. These are normalized using Z-transform. For each locality, infection and mortality data (dataset Y) were compared to the economic, health, and demographic data (dataset X) using Euclidean metric d=(x−y)2, where x∈X and y∈Y. If a data pair (x,y) exceeds, by two standard deviations, the mean of the Euclidean metric values between the sets X and Y, the pair is assumed to be a ‘good’ outlier.

Results

Our results showed that cluster of cities and provinces in Central Luzon (Region III), CALABARZON (Region IV-A), the National Capital Region (NCR), and Central Visayas (Region VII) are the ‘good’ outliers with respect to factors such as working population, population density, ICU beds, doctors on quarantine, number of frontliners and gross regional domestic product. Among metropolitan cities, Davao was a ‘good’ outlier with respect to demographic factors.

Conclusions

Strict border control, early implementation of lockdowns, establishment of quarantine facilities, effective communication to the public, and monitoring efforts were the defining factors that helped these LGUs curtail the harm that was brought by the pandemic. If these policies are to be standardized, it would help any country’s preparedness for future health emergencies.
Late-onset hypophysitis after discontinuation of nivolumab treatment for advanced skin melanoma: a case report
Authors: Antoniou Sofia , Bazazo Georgios , Röckl Ludwig , Papadakis Marios , Berg Christian
Published: September 2021

Background

Nivolumab is an anti-programmed cell death protein 1 antibody, typically used as cancer immunotherapy agent. Despite multiple clinical benefits it might cause autoimmune-related side-effects, often involving the endocrine system. To our knowledge, this is the first case of nivolumab-induced hypophysitis manifesting several months after treatment discontinuation.

Case presentation

We, herein, report a 53-year-old patient with hypophysitis and isolated adrenocorticotropic hormone deficiency, who presented with recurring syncopal episodes and persistent mild hyponatremia. The performed challenged tests were consistent with secondary adrenal insufficiency, while responses of other anterior pituitary hormones were preserved. Magnetic resonance imaging revealed thickened pituitary stalk, consistent with hypophysitis. The patient’s condition gradually improved after administration of hydrocortisone, with normalization of sodium and glucose-levels. The related literature is discussed.

Conclusions

We conclude that even after discontinuation of nivolumab, isolated adrenal insufficiency can occur. Therefore, in case of administration of such agents, clinical assessment, and routine monitoring of blood pressure, sodium-, glucose-levels, pituitary hormones as well as magnetic resonance imaging are needed to identify such conditions and prevent an adrenal crisis.
Predicting the risk of mortality during hospitalization in sick severely malnourished children using daily evaluation of key clinical warning signs
Authors: Wen Bijun , Brals Daniella , Bourdon Celine , Erdman Lauren , Ngari Moses , Chimwezi Emmanuel , Potani Isabel , Thitiri Johnstone , Mwalekwa Laura , Berkley James A. , Bandsma Robert H. J. , Voskuijl Wieger
Published: September 2021

Background

Despite adherence to WHO guidelines, inpatient mortality among sick children admitted to hospital with complicated severe acute malnutrition (SAM) remains unacceptably high. Several studies have examined risk factors present at admission for mortality. However, risks may evolve during admission with medical and nutritional treatment or deterioration. Currently, no specific guidance exists for assessing daily treatment response. This study aimed to determine the prognostic value of monitoring clinical signs on a daily basis for assessing mortality risk during hospitalization in children with SAM.

Methods

This is a secondary analysis of data from a randomized trial (NCT02246296) among 843 hospitalized children with SAM. Daily clinical signs were prospectively collected during ward rounds. Multivariable extended Cox regression using backward feature selection was performed to identify daily clinical warning signs (CWS) associated with time to death within the first 21 days of hospitalization. Predictive models were subsequently developed, and their prognostic performance evaluated using Harrell’s concordance index (C-index) and time-dependent area under the curve (tAUC).

Results

Inpatient case fatality ratio was 16.3% (n=127). The presence of the following CWS during daily assessment were found to be independent predictors of inpatient mortality: symptomatic hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever. Daily risk scores computed using these 7 CWS together with MUAC<10.5cm at admission as additional CWS predict survival outcome of children with SAM with a C-index of 0.81 (95% CI 0.77–0.86). Moreover, counting signs among the top 5 CWS (reduced consciousness, symptomatic hypoglycemia, chest indrawing, not able to complete foods, and MUAC<10.5cm) provided a simpler tool with similar prognostic performance (C-index of 0.79; 95% CI 0.74–0.84). Having 1 or 2 of these CWS on any day during hospitalization was associated with a 3 or 11-fold increased mortality risk compared with no signs, respectively.

Conclusions

This study provides evidence for structured monitoring of daily CWS as recommended clinical practice as it improves prediction of inpatient mortality among sick children with complicated SAM. We propose a simple counting-tool to guide healthcare workers to assess treatment response for these children.

Trial registration

NCT02246296
The plasma exosomal miR-1180-3p serves as a novel potential diagnostic marker for cutaneous melanoma
Authors: Guo Yeye , Zhang Xu , Wang Linconghua , Li Min , Shen Minxue , Zhou Zhe , Zhu Susi , Li Keke , Fang Zhiqin , Yan Bei , Zhao Shuang , Su Juan , Chen Xiang , Peng Cong
Published: September 2021

Background

Exosomes are a promising tool in disease detection because they are noninvasive, cost-effective, sensitive and stable in body fluids. MicroRNAs (miRNAs) are the main exosomal component and participate in tumor development. However, the exosomal miRNA profile among Asian melanoma patients remains unclear.

Methods

Exosomal miRNAs from the plasma of melanoma patients (n = 20) and healthy individuals (n = 20) were isolated and subjected to small RNA sequencing. Real-time PCR was performed to identify the differential miRNAs and to determine the diagnostic efficiency. Proliferation, scratch and Transwell assays were performed to detect the biological behavior of melanoma cells.

Results

Exosomal miRNA profiling revealed decreased miR-1180-3p expression as a potential diagnostic marker of melanoma. The validation group of melanoma patients (n = 28) and controls (n = 28) confirmed the diagnostic efficiency of miR-1180-3p. The level of miR-1180-3p in melanoma cells was lower than that in melanocytes. Accordingly, the level of miR-1180-3p was negatively associated with the proliferation, migration and invasion of melanoma cells. Functional analysis and target gene prediction found that ST3GAL4 was a potential target and highly expressed in melanoma tissues and was negatively regulated by miR-1180-3p. Knockdown of ST3GAL4 hindered the malignant phenotype of melanoma cells.

Conclusions

This study indicates that reduced exosomal miR-1180-3p in melanoma patient plasma is a promising diagnostic marker and provides novel insight into melanoma development.
Mechanistic study of lncRNA UCA1 promoting growth and cisplatin resistance in lung adenocarcinoma
Authors: Fu Jiali , Pan Jingjing , Yang Xiang , Zhang Yan , Shao Fanggui , Chen Jie , Huang Kate , Wang Yumin
Published: September 2021

Aim

This study aimed to explore the mechanism of LncRNA urothelial carcinoma-associated 1 (UCA1) promoting cisplatin resistance in lung adenocarcinoma (LUAD).

Method

The UCA1 expression level in LUAD cell lines was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We overexpressed UCA1 in A549 cells and downregulated UCA1 in A549/DDP cells by the lentivirus‑mediated technique. Subsequently, in vitro, and in vivo functional experiments were performed to investigate the functional roles of UCA1 in the growth and metastasis of LUAD cell lines. Furthermore, RNA pulldown, mass spectrometry, and RNA immunoprecipitation technique were performed to analyze various downstream target factors regulated by UCA1.

Results

The results revealed a higher UCA1 expression level in A549/DDP cells and LUAD tissues than in A549 cells and adjacent cancer tissues. UCA1 expression was significantly associated with distant metastasis, clinical stage, and survival time of patients with LUAD. UCA1 overexpression significantly increased the proliferation, invasion, clone formation, and cisplatin resistance ability and enhanced the expression levels of proliferating cell nuclear antigen and excision repair cross-complementing gene 1 in A549 cells. However, these trends were mostly reversed after the knockdown of UCA1 in A549/DDP cells. Tumorigenic assays in nude mice showed that UCA1 knockdown significantly inhibited tumor growth and reduced cisplatin resistance. Enolase 1 was the RNA-binding protein (RBP) of UCA1.

Conclusion

Based on the results, we concluded that UCA1 promoted LUAD progression and cisplatin resistance and hence could be a potential diagnostic marker and therapeutic target in patients with LUAD.
The clinical–epidemiological profile of malaria patients from Southern Venezuela, a critical hotspot in Latin America
Authors: Forero-Peña David A. , Carrión-Nessi Fhabián S. , Chavero Melynar , Gamardo Ángel , Figuera Luisamy , Camejo-Ávila Natasha A. , Marcano María V. , Hidalgo Mariana , Arenas-Leal Cariagne J. , Villegas Leopoldo , Grillet María E. , Pacheco M. Andreína , Mora Marisol Sandoval-de , Escalante Ananías A.
Published: September 2021

Background

Venezuela accounted for 55% of the cases and 73% of the malaria deaths in the Americas in 2019. Bolivar state, in the southeast, contributes > 60% of the country's Plasmodium vivax and Plasmodium falciparum cases every year. This study describes the clinical–epidemiological characteristics of clinical malaria patients in this high-transmission area.

Methods

A prospective study was conducted on patients seeking medical attention in three medical centres in the state capital, Ciudad Bolivar, between June and October 2018. Malaria diagnosis was carried out using microscopy following national standards. Malaria-positive patients were examined for clinical symptoms, and haematological tests were performed at the time of diagnosis. Patients were followed up by telephone to evaluate malaria recurrences.

Results

Out of 287 patients, 200 (69.7%) were positive for P. vivax, 69 (24%) for P. falciparum, and 18 (6.3%) had mixed (P. vivax/P. falciparum) infections. Patients' median age was 33 years (IQR 20), 168 (69%) were men, and 40% practiced gold mining as the main occupation. Fever (96.5%), chills (91.3%), and headaches (90.6%) were the most frequent symptoms. At least one symptom associated with severe malaria was observed in 69 out of 161 patients with complete clinical evaluation (42.9%). Plasmodium vivax infections were found in 42 out of 69 (60.9%) severe cases; by contrast, P. falciparum and mixed malaria caused 34.8% (24/69) and 4.4% (3/69) of infections, respectively. Two patients died of cerebral malaria. Mean hemoglobin was lower in the patients infected with P. falciparum than those infected with P. vivax. Regardless of the parasite causing the infection, patients presented high levels of total bilirubin, aminotransferases (AST, ALT), and lactate dehydrogenase (LDH). Out of the 142 patients followed up by phone for three months (49.5% of the 287 patients), 35 (24.7%) reported recurrences.

Conclusions

The high malaria prevalence among young male adults practicing gold mining suggests that this occupation is a significant risk factor. The unexpected high prevalence of P. vivax patients with at least one criteria of severe clinical disease is a matter of concern. Whether it is the result of a lack of timely diagnosis and effective treatment should be explored.
Validation of multiple equations for estimating low-density lipoprotein cholesterol levels in Korean adults
Authors: Choi Rihwa , Park Mi-Jung , Oh Youngju , Kim Sung Ho , Lee Sang Gon , Lee Eun Hee
Published: September 2021

Background

Limited data are available for validation of low-density lipoprotein cholesterol (LDL) calculation (LDLcal) in the adult Korean population. The aim of this study was to develop and validate a new equation for LDLcal and to compare it with previous such equations in a Korean population.

Methods

A new equation for LDLcal was developed (LDLChoi). LDLChoi and 11 other previously published equations were applied and compared with directly measured LDL concentration (LDLdirect) in a development cohort (population 1), an independent validation cohort in the same laboratory (population 2), and the Korea National Health and Nutrition Examination Survey 2017 cohort (population 3).

Results

Among the 12 equations, the newly-developed equation (LDLChoi = total cholesterol – 0.87 x high-density lipoprotein cholesterol – 0.13 x triglycerides) had the highest intraclass correlation coefficient (ICC) and the lowest mean systemic difference and median absolute percentage error in populations 1 and 2 but not in population 3. Subgroup analysis showed good agreement between LDLChoi and LDLdirect (ICC > 0.75) in population 2, whose LDLdirect < 70 mg/dL. For samples with high triglycerides (> 400 mg/dL), equation accuracy varied. Categorization concordance according to the National Cholesterol Education Program Adult Treatment Panel III criteria with the other 11 equations were less than 80%; that of LDLChoi was 87.6 and 87.4% in populations 1 and 2, respectively.

Conclusions

Accuracy of 12 equations for LDLcal varied by cohort and subgroup based on LDLdirect and triglycerides. A laboratory-specific equation for LDLcal and/or LDLdirect may be needed for accurate evaluation of LDL status.