bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Associated Coagulopathy: Thrombosis, Hemorrhage and Mortality Rates with an Escalated-Thromboprophylaxis Strategy
Authors: Daughety Molly , Ortel Thomas L. , Frost Erin , Morgan Andrew , Kao Chester , Hwang Joyce , Patel Bhavik , Welsby Ian J
Published: February 2021

Introduction: Early studies identified a prothrombotic state associated with novel coronavirus disease 2019 (COVID-19) as well as a survival benefit observed with heparin use in severely ill COVID-19 patients. There is a need to clarify the incidence of thromboembolic events (TEs), as well as major hemorrhage in COVID-19 patients in the context of an escalated-dose thromboprophylaxis strategy.

Methods: We conducted a single center, retrospective study of 192 consecutive patients with COVID-19 admitted to the hospital between March 26th and May 8th 2020. Our study aimed to investigate the rates of thromboembolic events (TEs), hemorrhage and mortality of in the context of an escalated-dose thromboprophylaxis strategy implemented early in our experience with hospitalized patients with COVID-19.

Results: The incidence of radiographically-confirmed venous thromboembolism (VTE) was 7.3% (n=14), and the rate of combined TEs was 12% (n=23). The rate of major hemorrhage was 6.3% (n=12), including one fatal CNS bleed. The overall mortality rate was 27.6% (n=53).

Conclusion: The rate of VTE and overall TE was much lower than was reported in early studies, and the majority of VTEs occurred in ambulatory patients. Our data suggest that an escalated-dose thromboprophylaxis strategy may help reduce the incidence of inpatient VTEs, and that ambulatory COVID-19 patients may benefit from primary thromboprophylaxis. However, the risk of bleeding was not negligible, and must therefore be assessed on an individual and continual basis when using a more aggressive thromboprophylaxis strategy.

Disclosures

No relevant conflicts of interest to declare.
Clinical Utility of Flow Cytometry Immunophenotyping in Acute Lymphoblastic Leukemia
Authors: Silva Alessandra Suelen Jardim , Oliveira Gustavo Henrique de Medeiros , Júnior Lenilton Silva DA Silva , Ferreira Hugo Henrique de Freitas , Araujo Maria das Graças Pereira , Soares Victor lima , Freitas Rodrigo Villar , Bahia Frank , Oliveira Taissa Moura , Silva Dany GKC , Sales Valéria SF , Soares Rodolfo DA , Paiva Hugo Diogenes De Oliveira , Paiva Aldair Sousa , Cavalcanti Geraldo Barroso
Published: February 2021

The acute lymphoblastic leukemia (ALL) is a malignant disease of the immune system and hematologic characterized by accumulation of neoplastic B lymphoid precursors or T (lymphoblasts) in the bone marrow and / or peripheral blood. The diagnosis of these leukemias occurs by morphological classification of French-American-British (L1, L2 or L3) associated with features of immunological profile T or B cell malignancies, based on the expression profile of monoclonal antibodies (MoAb) directed against the antigens of cell differentiation by flow cytometry (FC). Several studies have shown that blast cell immunophenotypes of cases of acute lymphoblastic leukemia does not always exhibit characteristics of lymphoid differentiation normal but exhibit aberrant immunophenotypes. Thus, blasts some cases of acute lymphoblastic leukemia of B lineage may show myeloid or T antigens. Also blasts of cases of acute lymphoblastic leukemia T cell determinants may possess B or myeloid cells.Objective:To determine the immunophenotypic profile by FC in 88 patients with ALL (B or T lineage) diagnosed in the Laboratory of Flow Cytometry Blood Center of Dalton Cunha - HEMONORTE, from State of Rio Grande do Norte, Brazil.Methods:All samples from peripheral blood and / or bone marrow were subjected to FC immunophenotyping using a panel of MoAb specific for diagnosis of acute leukemia (AL) directly conjugated to fluorochromes as fluorescein isothiocyanate (FITC), phycoerythrin (PE), peridinin-chlorophyll protein (PerCP) and allophycocyanin (APC).Results:The patients' age range was between 1 month and 84 years old, with an average of 20.3 years, with 62.5% of the patients being male. The most frequently observed strain was B and the most evident subtype was the Common Pre-B ALL. Among the cell markers evaluated, the most expressed in lineage B were CD19, CD10, HLADR and cCD79a and the antigens most frequently expressed in lineage T were cytoplasmic CD3 (cCD3) and membrane (mCD3), CD7, CD5 and CD2. A small percentage (6.8%) were doubly positive T cells.Conclusion:It is concluded that individuals with ALL in this study have demographic, clinical and immunophenotypic characteristics similar to those observed in other studies, demonstrating that CF immunophenotyping is an essential methodology in the diagnosis of follow-up of these leukemias.

Disclosures

No relevant conflicts of interest to declare.
Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma
Authors: Strati Paolo , Ahmed Sairah , Furqan Fateeha , Fayad Luis E. , Lee Hun J. , Iyer Swaminathan P. , Nair Ranjit , Nastoupil Loretta J. , Parmar Simrit , Rodriguez Maria A. , Samaniego Felipe , Steiner Raphael E. , Wang Michael , Pinnix Chelsea C. , Horowitz Sandra B. , Feng Lei , Sun Ryan , Claussen Catherine M. , Hawkins Misha C. , Johnson Nicole A. , Singh Prachee , Mistry Haleigh , Johncy Swapna , Adkins Sherry , Kebriaei Partow , Shpall Elizabeth J. , Green Michael R. , Flowers Christopher R. , Westin Jason , Neelapu Sattva S.
Published: February 2021

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities.
NGlyAlign: an automated library building tool to align highly divergent HIV envelope sequences
Authors: Akand Elma H. , Murray John M.
Published: February 2021

Background

The high variability in envelope regions of some viruses such as HIV allow the virus to establish infection and to escape subsequent immune surveillance. This variability, as well as increasing incorporation of N-linked glycosylation sites, is fundamental to this evasion. It also creates difficulties for multiple sequence alignment methods (MSA) that provide the first step in their analysis. Existing MSA tools often fail to properly align highly variable HIV envelope sequences requiring extensive manual editing that is impractical with even a moderate number of these variable sequences.

Results

We developed an automated library building tool NGlyAlign, that organizes similar N-linked glycosylation sites as block constraints and statistically conserved global sites as single site constraints to automatically enforce partial columns in consistency-based MSA methods such as Dialign. This combined method accurately aligns variable HIV-1 envelope sequences. We tested the method on two datasets: a set of 156 founder and chronic gp160 HIV-1 subtype B sequences as well as a set of reference sequences of gp120 in the highly variable region 1. On measures such as entropy scores, sum of pair scores, column score, and similarity heat maps, NGlyAlign+Dialign proved superior against methods such as T-Coffee, ClustalOmega, ClustalW, Praline, HIValign and Muscle. The method is scalable to large sequence sets producing accurate alignments without requiring manual editing. As well as this application to HIV, our method can be used for other highly variable glycoproteins such as hepatitis C virus envelope.

Conclusions

NGlyAlign is an automated tool for mapping and building glycosylation motif libraries to accurately align highly variable regions in HIV sequences. It can provide the basis for many studies reliant on single robust alignments. NGlyAlign has been developed as an open-source tool and is freely available at https://github.com/UNSW-Mathematical-Biology/NGlyAlign_v1.0 .
IUPACpal: efficient identification of inverted repeats in IUPAC-encoded DNA sequences
Authors: Alamro Hayam , Alzamel Mai , Iliopoulos Costas S. , Pissis Solon P. , Watts Steven
Published: February 2021

Background

An inverted repeat is a DNA sequence followed downstream by its reverse complement, potentially with a gap in the centre. Inverted repeats are found in both prokaryotic and eukaryotic genomes and they have been linked with countless possible functions. Many international consortia provide a comprehensive description of common genetic variation making alternative sequence representations, such as IUPAC encoding, necessary for leveraging the full potential of such broad variation datasets.

Results

We presentIUPACpal, an exact tool for efficient identification of inverted repeats in IUPAC-encoded DNA sequences allowing also for potential mismatches and gaps in the inverted repeats.

Conclusion

Within the parameters that were tested, our experimental results show thatIUPACpalcompares favourably to a similar application packaged withEMBOSS. We show thatIUPACpalidentifies many previously unidentified inverted repeats when compared withEMBOSS, and that this is also performed with orders of magnitude improved speed.
In silico drug repositioning based on the integration of chemical, genomic and pharmacological spaces
Authors: Chen Hailin , Zhang Zuping , Zhang Jingpu
Published: February 2021

Background

Drug repositioning refers to the identification of new indications for existing drugs. Drug-based inference methods for drug repositioning apply some unique features of drugs for new indication prediction. Complementary information is provided by these different features. It is therefore necessary to integrate these features for more accurate in silico drug repositioning.

Results

In this study, we collect 3 different types of drug features (i.e., chemical, genomic and pharmacological spaces) from public databases. Similarities between drugs are separately calculated based on each of the features. We further develop a fusion method to combine the 3 similarity measurements. We test the inference abilities of the 4 similarity datasets in drug repositioning under the guilt-by-association principle. Leave-one-out cross-validations show the integrated similarity measurement IntegratedSim receives the best prediction performance, with the highest AUC value of 0.8451 and the highest AUPR value of 0.2201. Case studies demonstrate IntegratedSim produces the largest numbers of confirmed predictions in most cases. Moreover, we compare our integration method with 3 other similarity-fusion methods using the datasets in our study. Cross-validation results suggest our method improves the prediction accuracy in terms of AUC and AUPR values.

Conclusions

Our study suggests that the 3 drug features used in our manuscript are valuable information for drug repositioning. The comparative results indicate that integration of the 3 drug features would improve drug-disease association prediction. Our study provides a strategy for the fusion of different drug features for in silico drug repositioning.
Impact of PNPase on the transcriptome of Rhodobacter sphaeroides and its cooperation with RNase III and RNase E
Authors: Spanka Daniel-Timon , Reuscher Carina Maria , Klug Gabriele
Published: February 2021

Background

The polynucleotide phosphorylase (PNPase) is conserved among both Gram-positive and Gram-negative bacteria. As a core part of the Escherichia coli degradosome, PNPase is involved in maintaining proper RNA levels within the bacterial cell. It plays a major role in RNA homeostasis and decay by acting as a 3′-to-5′ exoribonuclease. Furthermore, PNPase can catalyze the reverse reaction by elongating RNA molecules in 5′-to-3′ end direction which has a destabilizing effect on the prolonged RNA molecule. RNA degradation is often initiated by an endonucleolytic cleavage, followed by exoribonucleolytic decay from the new 3′ end.

Results

The PNPase mutant from the facultative phototrophic Rhodobacter sphaeroides exhibits several phenotypical characteristics, including diminished adaption to low temperature, reduced resistance to organic peroxide induced stress and altered growth behavior. The transcriptome composition differs in the pnp mutant strain, resulting in a decreased abundance of most tRNAs and rRNAs. In addition, PNPase has a major influence on the half-lives of several regulatory sRNAs and can have both a stabilizing or a destabilizing effect. Moreover, we globally identified and compared differential RNA 3′ ends in RNA NGS sequencing data obtained from PNPase, RNase E and RNase III mutants for the first time in a Gram-negative organism. The genome wide RNA 3′ end analysis revealed that 885 3′ ends are degraded by PNPase. A fair percentage of these RNA 3′ ends was also identified at the same genomic position in RNase E or RNase III mutant strains.

Conclusion

The PNPase has a major influence on RNA processing and maturation and thus modulates the transcriptome of R. sphaeroides. This includes sRNAs, emphasizing the role of PNPase in cellular homeostasis and its importance in regulatory networks. The global 3′ end analysis indicates a sequential RNA processing: 5.9% of all RNase E-dependent and 9.7% of all RNase III-dependent RNA 3′ ends are subsequently degraded by PNPase. Moreover, we provide a modular pipeline which greatly facilitates the identification of RNA 5′/3′ ends. It is publicly available on GitHub and is distributed under ICS license.
Correction to: miR168 targets Argonaute1A mediated miRNAs regulation pathways in response to potassium deficiency stress in tomato
Authors: Liu Xin , Tan Chunchang , Cheng Xin , Zhao Xiaoming , Li Tianlai , Jiang Jing
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
The effects of a preoperative multidisciplinary conference on outcomes for high-risk patients with challenging surgical treatment options: a retrospective study
Authors: Koike Masayoshi , Yoshimura Mie , Mio Yasushi , Uezono Shoichi
Published: February 2021

Background

Surgical options for patients vary with age and comorbidities, advances in medical technology and patients’ wishes. This complexity can make it difficult for surgeons to determine appropriate treatment plans independently. At our institution, final decisions regarding treatment for patients are made at multidisciplinary meetings, termed High-Risk Conferences, led by the Patient Safety Committee.

Methods

In this retrospective study, we assessed the reasons for convening High-Risk Conferences, the final decisions made and treatment outcomes using conference records and patient medical records for conferences conducted at our institution from April 2010 to March 2018.

Results

A total of 410 High-Risk Conferences were conducted for 406 patients during the study period. The department with the most conferences was cardiovascular surgery (24%), and the reasons for convening conferences included the presence of severe comorbidities (51%), highly difficult surgeries (41%) and nonmedical/personal issues (8%). Treatment changes were made for 49 patients (12%), including surgical modifications for 20 patients and surgery cancellation for 29. The most common surgical modification was procedure reduction (16 patients); 4 deaths were reported. Follow-up was available for 21 patients for whom surgery was cancelled, with 11 deaths reported.

Conclusions

Given that some change to the treatment plan was made for 12% of the patients discussed at the High-Risk Conferences, we conclude that participants of these conferences did not always agree with the original surgical plan and that the multidisciplinary decision-making process of the conferences served to allow for modifications. Many of the modifications involved reductions in procedures to reflect a more conservative approach, which might have decreased perioperative mortality and the incidence of complications as well as unnecessary surgeries. High-risk patients have complex issues, and it is difficult to verify statistically whether outcomes are associated with changes in course of treatment. Nevertheless, these conferences might be useful from a patient safety perspective and minimize the potential for legal disputes.
Correlation of the severity of coronary artery disease with patients' metabolic profile- rationale, design and baseline patient characteristics of the CorLipid trial
Authors: Karagiannidis Efstratios , Sofidis Georgios , Papazoglou Andreas S. , Deda Olga , Panteris Eleftherios , Moysidis Dimitrios V. , Stalikas Nikolaos , Kartas Anastasios , Papadopoulos Anastasios , Stefanopoulos Leandros , Karvounis Haralambos , Gika Helen , Theodoridis Georgios , Sianos Georgios
Published: February 2021

Background

Coronary artery disease (CAD) remains one of the leading causes of mortality and morbidity worldwide. As oxygen and nutrient supply to the myocardium significantly decrease during ischemic periods, important changes occur regarding myocardial intermediary energy metabolism. Metabolomics is an emerging field in systems biology, which quantifies metabolic changes in response to disease progression. This study aims to evaluate the diagnostic utility of plasma metabolomics-based biomarkers for determining the complexity and severity of CAD, as it is assessed via the SYNTAX score.

Methods

Corlipid is a prospective, non-interventional cohort trial empowered to enroll 1065 patients with no previous coronary intervention history, who undergo coronary angiography in University Hospital AHEPA, Thessaloniki. Venous blood samples are collected before coronary angiography. State-of the-art analytical methods are performed to calculate the serum levels of novel biomarkers: ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and the ratio of apolipoprotein B/apolipoprotein A1. Furthermore, all patients will be categorized based on the indication for coronary angiography (acute coronary syndrome, chronic coronary syndrome, preoperative coronary angiography) and on the severity of CAD using the SYNTAX score. Follow-up of 12 months after enrollment will be performed to record the occurrence of major adverse cardiovascular events. A risk prediction algorithm will be developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD based on their metabolite signatures. The first patient was enrolled in July 2019 and completion of enrollment is expected until May 2021.

Discussion

CorLipid is an ongoing trial aiming to investigate the correlation between metabolic profile and complexity of coronary artery disease in a cohort of patients undergoing coronary angiography with the potential to suggest a decision-making tool with high discriminative power for patients with CAD. To our knowledge, Corlipid is the first study aspiring to create an integrative metabolomic biomarkers-based algorithm by combining metabolites from multiple classes, involved in a wide range of pathways with well-established biochemical markers.

Trial registration CorLipid trial registration: ClinicalTrials.gov number: NCT04580173. Registered 8 October 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04580173.
Circulating level of microRNA-142-5p is a potential biomarker for predicting in-stent restenosis: a case–control study
Authors: Pan Chun-Hsu , Chien Shu-Chen , Chen Chang-Jui , Shih Chun-Ming , Hsieh Ming-Hsiung , Huang Chun-Yao , Bi Wei-Fung , Chan Chao-Shun , Kao Yung-Ta , Hsiao Cheng-Yi , Chiang Shuo-Ju , Chiang Kuang-Hsing , Huang Jen-Hung , Liu Yun-Ru , Luo Ji-Dung , Huang Hui-Yu , Wu Chieh-Hsi
Published: February 2021

Background

Patients who receive percutaneous coronary intervention (PCI) have different chances of developing in-stent restenosis (ISR). To date, no predictable biomarker can be applied in the clinic. MicroRNAs (miRNAs or miRs) play critical roles in transcription regulation, and their circulating levels were reported to have potential as clinical biomarkers.

Methods

In total, 93 coronary stent-implanted patients without pregnancy, liver or renal dysfunction, malignancy, hemophilia, or autoimmune diseases were recruited in this clinical study. All recruited participants were divided into an ISR group (n = 45) and a non-ISR group (n = 48) based on their restenotic status as confirmed by cardiologists at the first follow-up visit (6 months after surgery). Blood samples of all participants were harvested to measure circulating levels of miRNA candidates (miR-132, miR-142-5p, miR-15b, miR-24-2, and miR-424) to evaluate whether these circulating miRNAs can be applied as predictive biomarkers of ISR.

Results

Our data indicated that circulating levels of miR-142-5p were significantly higher in the ISR population, and results from the receiver operating characteristic (ROC) curve analysis also demonstrated superior discriminatory ability of miR-142-5p in predicting patients’ restenotic status. In addition, circulating levels of miR-15b, miR-24-2, and miR-424 had differential expressions in participants with diabetes, hyperlipidemia, and hypertension, respectively.

Conclusions

The current study revealed that the circulating level of miR-142-5p has potential application as a clinical biomarker for predicting the development of ISR in stent-implanted patients.
Reliability and validity of an adapted hip abductor strength measure as a potential new fall risk assessment for older persons: a study protocol
Authors: Gafner Simone Chantal , Bastiaenen Caroline Henrice Germaine , Biver Emmanuel , Ferrari Serge , Allet Lara
Published: February 2021

Background

Persons aged ≥ 65 years are currently the world’s fastest growing age group. An important complication of age is the increasing risk of falls. Falls have multifactorial etiology and modifiable risk factors open for interventions in prevention and rehabilitation, are of high interest. In this context, strong hip abductors seem to be important to prevent falls. A newly adapted measurement device to measure hip abductor strength (HAS) in a closed chain position was developed. We aim to assess feasibility, intra- and inter-tester reliability and construct and criterion validity of the new measure.

Methods

In two subsequent parts a feasibility, reliability and validity study with an adapted measurement instrument for the assessment of HAS (index test) in a closed chain position in persons aged ≥ 65 years will be conducted. Part I investigates feasibility of the measure in clinical settings as well as reliability of the new HAS test (n = 26). Part II evaluates construct and criterion validity (n = 169). Construct validity will be assessed cross-sectional, criterion validity by comparison with prospectively followed up fall history for 12 months (external criterion) and other functional fall risk assessments (Short Physical Performance Battery, Timed Up and Go test, usual gait speed and hand grip strength).

Discussion

Results of feasibility, will give insight in its applicability in daily clinical life and clinimetric properties will show if measurements of HAS in a closed chain position should be encouraged to include in fall risk assessments in older adults.
Prosthetic hip joint infection by Bacillus Calmette-Guerin therapy following intravesical instillation for bladder cancer identified using whole-genome sequencing: a case report
Authors: Riste Michael , Davda Pretin , Smith E. Grace , Wyllie David H. , Dedicoat Martin , Jog Simantini , Laird Steven , Langman Gerald , Jenkins Neil , Stevenson Jonathan , O’Shea Matthew K.
Published: February 2021

Background

Joint replacement is an effective intervention and prosthetic joint infection (PJI) is one of the most serious complications of such surgery. Diagnosis of PJI is often complex and requires multiple modalities of investigation. We describe a rare cause of PJI which highlights these challenges and the role of whole-genome sequencing to achieve a rapid microbiological diagnosis to facilitate prompt and appropriate management.

Case presentation

A 79-year-old man developed chronic hip pain associated with a soft-tissue mass, fluid collection and sinus adjacent to his eight-year-old hip prosthesis. His symptoms started after intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer. Synovasure™ and 16S polymerase chain reaction (PCR) tests were negative, but culture of the periarticular mass and genome sequencing diagnosed BCG infection. He underwent a two-stage joint revision and a prolonged duration of antibiotic therapy which was curative.

Conclusions

BCG PJI after therapeutic exposure can have serious consequences, and awareness of this potential complication, identified from patient history, is essential. In addition, requesting appropriate testing is required, together with recognition that traditional diagnostics may be negative in non-pyogenic PJI. Advanced molecular techniques have a role to enhance the timely management of these infections.
Effect of postpartum depression on exclusive breast-feeding practices in sub-Saharan Africa countries: a systematic review and meta-analysis
Authors: Woldeyohannes Demelash , Tekalegn Yohannes , Sahiledengle Biniyam , Ermias Dejene , Ejajo Tekele , Mwanri Lillian
Published: February 2021

Background

Postpartum depression (PPD) is a serious mood disorder that affects behavioural, physical and mental health of women and newborn after childbirth. Although a wide range of research have been conducted on maternal and infant health outcomes, the effect of postpartum depression on exclusive breastfeeding practices remains ambiguous, and needs addressing. The aim of this study was to assess the effect of postpartum depression on exclusive breast feeding practices in sub-Saharan African countries.

Methods

PubMed, Google Scholar, Science Direct and Cochrane Library were systematically searched for relevant articles published between 2001 and 2020. STATA version 14 was used to calculate the pooled odd ratio with 95% confidence intervals (95% CI). The DerSimonian and Laird random effects meta-analysis was used to measure the effect of postpartum depression on exclusive breast feeding practices. The heterogeneity and publication bias were assessed by using I2test statistics and Egger’s test, respectively. This review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Result

A total of 1482 published articles and gray literatures were retrieved from different databases. Additional articles were identified from the reference list of identified reports and articles. After assessment of obtained articles, studies not meeting the inclusion criteria were excluded. Twenty six studies involving 30,021 population met the inclusion criteria were included in this review. In sub Saharan Africa the overall estimated level of postpartum depression was 18.6% (95% CI: 13.8, 23.4). This review found that postpartum depression had no significant effect on exclusive breast feeding practices (OR = 0.46, 95% CI: 0.18, 1.14).

Conclusion

In Sub Saharan Africa, the prevalence of postpartum depression was lower than the report of World Health Organization for developing Country in 2020. This review reveled that maternal postpartum depression has no significant effect on exclusive breast feeding practices. Thus, the investigators strongly recommend the researchers to conduct primary studies using strong study design in sub-Saharan Africa.
Diallyl thiosulfinate enhanced the anti-cancer activity of dexamethasone in the side population cells of multiple myeloma by promoting miR-127-3p and deactivating the PI3K/AKT signaling pathway
Authors: He Wenfeng , Fu Yonghui , Zheng Yongliang , Wang Xiaoping , Liu Bin , Zeng Junquan
Published: February 2021

Background

Side population (SP) cells, which have similar features to those of cancer stem cells, show resistance to dexamethasone (Dex) treatment. Thus, new drugs that can be used in combination with Dex to reduce the population of SP cells in multiple myeloma (MM) are required. Diallyl thiosulfinate (DATS, allicin), a natural organosulfur compound derived from garlic, has been shown to inhibit the proliferation of SP cells in MM cell lines. Therefore, we investigated the effect of a combination of DATS and Dex (DAT + Dex) on MM SP cells.

Methods

SP cells were sorted from MM RPMI-8226 and NCI-H929 cell lines using Hoechst 33342-labeled fluorescence-activated cell sorting. The growth of SP cells was evaluated using the cell counting kit-8 assay. Cell cycle and apoptosis assays were conducted using a BD Calibur flow cytometer. miRNA expression was measured using quantitative reverse transcription-polymerase chain reaction. Phosphoinositide 3-kinase (PI3K), phosphorylated AKT (p-AKT), AKT, p-mechanistic target of rapamycin (mTOR), and mTOR levels were measured using western blot analysis.

Results

Our results showed that the combination of DATS+Dex inhibited sphere formation, colony formation, and proliferation of MM SP cells by inducing apoptosis and cell cycle arrest in the G1/S phase. In addition, the combination of DATS+Dex promoted miR-127-3p expression and inhibited PI3K, p-AKT, and p-mTOR expression in SP cells. Knockdown of miR-127-3p expression weakened the effect of DATS+Dex on cell proliferation, colony formation, apoptosis, and cell cycle of MM SP cells. Additionally, knockdown of miR-127-3p activated the PI3K/AKT/mTOR signaling pathway in MM SP cells cotreated with DATS+Dex.

Conclusion

We demonstrated that cotreatment with DATS+Dex reduced cell proliferation, promoted apoptosis, and caused cell cycle arrest of MM SP cells by promoting miR-127-3p expression and deactivating the PI3K/AKT/mTOR signaling pathway.
Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma
Authors: Shen Rui , Liu Bo , Li Xuesen , Yu Tengbo , Xu Kuishuai , Ma Jinfeng
Published: February 2021

Background

Sarcomas is a group of heterogeneous malignant tumors originated from mesenchymal tissue and different types of sarcomas have disparate outcomes. The present study aims to identify the prognostic value of immune-related genes (IRGs) in sarcoma and establish a prognostic signature based on IRGs.

Methods

We collected the expression profile and clinical information of 255 soft tissue sarcoma samples from The Cancer Genome Atlas (TCGA) database and 2498 IRGs from the ImmPort database. The LASSO algorithm and Cox regression analysis were used to identify the best candidate genes and construct a signature. The prognostic ability of the signature was evaluated by ROC curves and Kaplan-Meier survival curves and validated in an independent cohort. Besides, a nomogram based on the IRGs and independent prognostic clinical variables was developed.

Results

A total of 19 IRGs were incorporated into the signature. In the training cohort, the AUC values of signature at 1-, 2-, and 3-years were 0.938, 0.937 and 0.935, respectively. The Kaplan-Meier survival curve indicated that high-risk patients were significantly worse prognosis (P < 0.001). In the validation cohort, the AUC values of signature at 1-, 2-, and 3-years were 0.730, 0.717 and 0.647, respectively. The Kaplan-Meier survival curve also showed significant distinct survival outcome between two risk groups. Furthermore, a nomogram based on the signature and four prognostic variables showed great accuracy in whole sarcoma patients and subgroup analyses. More importantly, the results of the TF regulatory network and immune infiltration analysis revealed the potential molecular mechanism of IRGs.

Conclusions

In general, we identified and validated an IRG-based signature, which can be used as an independent prognostic signature in evaluating the prognosis of sarcoma patients and provide potential novel immunotherapy targets.
Paliperidone induced neutropenia in first episode psychosis: a case report
Authors: Martos Natalie , Hall William , Marhefka Alicia , Sedlak Thomas W. , Nucifora Frederick C.
Published: February 2021

Background

Neutropenia, a decrease in total number of neutrophils below 1500/mm3 and particularly severe neutropenia, defined as neutrophils less than 500/mm3, is a potential adverse effect of antipsychotic medications that can lead to increased risk of infections and death. However, much of the attention on the potential adverse effect is centered exclusively on clozapine, which remains the only antipsychotic medication in the United States requiring standardized monitoring of blood work. We demonstrate here that paliperidone can also cause neutropenia and therefore clinicians should be aware of this possibility especially during initiation of treatment.

Case presentation

The following report presents the case of a 23-year-old African American male with first episode psychosis who developed neutropenia after initiation of paliperidone. Neutropenia resolved after discontinuation of paliperidone and initiation of an alternative antipsychotic, haloperidol.

Conclusions

This case report demonstrates an example of paliperidone induced neutropenia which resolved with a switch to haloperidol. We conclude that when initiating paliperidone, clinicians should be more aware of the risk of neutropenia. Moreover, neutropenia may be a more common and overlooked issue in patients on antipsychotic medications other than clozapine and increased awareness of comparative risk across antipsychotics could help direct treatment.
Factors associated with suicide attempts among Australian transgender adults
Authors: Zwickl Sav , Wong Alex Fang Qi , Dowers Eden , Leemaqz Shalem Yiner-Lee , Bretherton Ingrid , Cook Teddy , Zajac Jeffrey D. , Yip Paul S. F. , Cheung Ada S.
Published: February 2021

Background

Transgender, including gender diverse and non-binary people, henceforth referred to collectively as trans people, are a highly marginalised population with alarming rates of suicidal ideation, attempted suicide and self-harm. We aimed to understand the risk and protective factors of a lifetime history of attempted suicide in a community sample of Australian trans adults to guide better mental health support and suicide prevention strategies.

Methods

Using a non-probability snowball sampling approach, a total of 928 trans adults completed a cross-sectional online survey between September 2017 and January 2018. The survey assessed demographic data, mental health morbidity, a lifetime history of intentional self-harm and attempted suicide, experiences of discrimination, experiences of assault, access to gender affirming healthcare and access to trans peer support groups. Logistic regression was used to examine the risk or protective effect of participant characteristics on the odds of suicide.

Results

Of 928 participants, 73% self-reported a lifetime diagnosis of depression, 63% reported previous self-harm, and 43% had attempted suicide. Higher odds of reporting a lifetime history of suicide attempts were found in people who were; unemployed (adjusted odds ratio (aOR) 1.54 (1.04, 2.28), p = 0.03), had a diagnosis of depression (aOR 3.43 (2.16, 5.46), p < 0.001), desired gender affirming surgery in the future (aOR 1.71 (1.134, 2.59), p = 0.01), had experienced physical assault (aOR 2.00 (1.37, 2.93), p < 0.001) or experienced institutional discrimination related to their trans status (aOR 1.59 (1.14, 2.22), p = 0.007).

Conclusion

Suicidality is associated with desiring gender affirming surgery in the future, gender based victimisation and institutionalised cissexism. Interventions to increase social inclusion, reduce transphobia and enable access to gender affirming care, particularly surgical interventions, are potential areas of intervention.
Physical multimorbidity and lifetime suicidal ideation and plans among rural older adults: the mediating role of psychological distress
Authors: Jing Zhengyue , Li Jie , Fu Pei Pei , Wang Yi , Yuan Yemin , Zhao Dan , Hao Wenting , Yu Caiting , Zhou Chengchao
Published: February 2021

Background

Previous studies have revealed that single physical chronic condition was associated with suicidal ideation/plans, but few studies have examined the relationship between multimorbidity and suicidal ideation/plans, and no studies have explored the underlying potential mechanism on this relationship in China. This study aimed to explore association between physical multimorbidity and suicidal ideation as well as plans, and further examine the mediating role of psychological distress (PD) on this relationship.

Methods

This study was based on the data from a survey about the health service of rural elderly household in Shandong, China. A total of 3242 adults aged 60 years and older were included in this study. PD was measured by Kessler Psychological Distress Scale (K10). Ordinal and binary logistic regression analyses were employed to explore the association between physical multimorbidity, PD and suicide ideation/plans. Bootstrapping analysis was further used to examine the mediation effect of PD on the association of multimorbidity and suicidal ideations/plans.

Results

The prevalence of multimorbidity, lifetime suicidal ideation, and suicidal plan in rural older adults was 35.2, 10.6 and 2.2%, respectively. Older adults living in rural areas with two or more chronic physical conditions experienced significantly higher risk of suicidal ideation and suicidal plans. The association between multimorbidity and suicidal ideations/plans was partially mediated by PD, of which, the mediating effect of PD accounted for 31.7 and 25.5% of the total effect, respectively.

Conclusion

This study demonstrated the associations between physical multimorbidity and suicidal ideation/plans, and the mediating role of PD on this relationship among Chinese rural elderly. Healthcare providers in rural community should provide regular surveillance for the mental health status among the rural elderly with multimorbidity, and carry out various effective intervention measures to improve the mental health status, so as to reduce the risk of suicide.
Prevalence and risk factors for seclusion and restraint in old-age psychiatry inpatient units
Authors: Chieze Marie , Kaiser Stefan , Courvoisier Delphine , Hurst Samia , Sentissi Othman , Fredouille Jérôme , Wullschleger Alexandre
Published: February 2021

Background and objectives

Coercion in psychiatry is legally tolerated as a last resort. The reduction of the use of coercion is a shared goal of hospital administrators, medical and nursing staff and representatives of patients and families but requires the identification of risk factors for coercion. These risk factors in geriatric psychiatric inpatient settings are not well known, especially regarding seclusion. Through examining the prevalence of coercion and patients’ characteristics, this study aims to identify risk factors for coercion in elderly people.

Methods

The use of coercion in the geriatric psychiatry division of Geneva University Hospital in 2017 was retrospectively analyzed. The incidence rate ratios were estimated with multivariable Poisson regressions to assess risk factors for coercion.

Results

Eighty-one of 494 patients (16.4%) experienced at least one coercive measure during their stay (mainly seclusion). The risk factors for coercion were younger age, male gender, being divorced or married, cognitive disorders, high item 1 of the Health of the Nation Outcome Scales (HoNOS) score (overactive, aggressive, disruptive or agitated behavior) at admission, previous psychiatric hospitalizations and involuntary referrals from the emergency department. Other disorders and global HoNOS scores were not associated with the use of coercion.

Conclusion

Higher risks of coercion were outlined in men with cognitive disorders, agitated behaviors, and previous psychiatric hospitalizations. They differed from those observed in younger adults in terms of age, civil status, disorders, global HoNOS scores and referrals. Therefore, geriatric psychiatric populations should be specifically investigated for the development of interventions aiming coercion reduction.
The role of aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and medication use: results of a pooled-analysis from seven European countries
Authors: Baudin Clémence , Lefèvre Marie , Babisch Wolfgang , Cadum Ennio , Champelovier Patricia , Dimakopoulou Konstantina , Houthuijs Danny , Lambert Jacques , Laumon Bernard , Pershagen Göran , Stansfeld Stephen , Velonaki Venetia , Hansell Anna L. , Evrard Anne-Sophie
Published: February 2021

Background

Few studies have considered aircraft noise annoyance and noise sensitivity in analyses of the health effects of aircraft noise, especially in relation to medication use. This study aims to investigate the moderating and mediating role of these two factors in the relationship between aircraft noise levels and medication use among 5860 residents of ten European airports included in the HYENA and DEBATS studies.

Methods

Information on aircraft noise annoyance, noise sensitivity, medication use, and demographic, socio-economic and lifestyle factors was collected during a face-to-face interview at home. Medication was coded according to the Anatomical Therapeutic Chemical (ATC) classification. Outdoor aircraft noise exposure was estimated by linking the participant’s home address to noise contours using Geographical Information Systems (GIS) methods. Logistic regressions with adjustment for potential confounding factors were used. In addition, Baron and Kenny’s recommendations were followed to investigate the moderating and mediating effects of aircraft noise annoyance and noise sensitivity.

Results

A significant association was found between aircraft noise levels at night and antihypertensive medication only in the UK (OR = 1.43, 95%CI 1.19–1.73 for a 10 dB(A)-increase in Lnight). No association was found with other medications. Aircraft noise annoyance was significantly associated with the use of antihypertensive medication (OR = 1.33, 95%CI 1.14–1.56), anxiolytics (OR = 1.48, 95%CI 1.08–2.05), hypnotics and sedatives (OR = 1.60, 95%CI 1.07–2.39), and antasthmatics (OR = 1.44, 95%CI 1.07–1.96), with no difference between countries. Noise sensitivity was significantly associated with almost all medications, with the exception of the use of antasthmatics, showing an increase in ORs with the level of noise sensitivity, with differences in ORs among countries only for the use of antihypertensive medication. The results also suggested a mediating role of aircraft noise annoyance and a modifying role of both aircraft noise annoyance and noise sensitivity in the association between aircraft noise levels and medication use.

Conclusions

The present study is consistent with the results of the small number of studies available to date suggesting that both aircraft noise annoyance and noise sensitivity should be taken into account in analyses of the health effects of exposure to aircraft noise.
“It’s a secret between us”: a qualitative study on children and care-giver experiences of HIV disclosure in Kinshasa, Democratic Republic of Congo
Authors: Sumbi Elysée Manziasi , Venables Emilie , Harrison Rebecca , Garcia Mariana , Iakovidi Kleio , van Cutsem Gilles , Chalachala Jean Lambert
Published: February 2021

Background

It is estimated that 64,000 children under 15 years of age are living with HIV in the Democratic Republic of Congo (DRC). Non-disclosure – in which the child is not informed about their HIV status - is likely to be associated with poor outcomes during adolescence including increased risk of poor adherence and retention, and treatment failure. Disclosing a child’s HIV status to them can be a difficult process for care-givers and children, and in this qualitative study we explored child and care-giver experiences of the process of disclosing, including reasons for delay.

Methods

A total of 22 in-depth interviews with care-givers and 11 in-depth interviews with HIV positive children whom they were caring for were conducted in one health-care facility in the capital city of Kinshasa. Care-givers were purposively sampled to include those who had disclosed to their children and those who had not. Care-givers included biological parents, grandmothers, siblings and community members and 86% of them were female. Interviews were conducted in French and Lingala. All interviews were translated and/or transcribed into French before being manually coded. Thematic analysis was conducted. Verbal informed consent/assent was taken from all interviewees.

Results

At the time of interview, the mean age of children and care-givers was 17 (15–19) and 47 (21–70) years old, respectively. Many care-givers had lost family members due to HIV and several were HIV positive themselves. Reasons for non-disclosure included fear of stigmatisation; wanting to protect the child and not having enough knowledge about HIV or the status of the child to disclose. Several children had multiple care-givers, which also delayed disclosure, as responsibility for the child was shared. In addition, some care-givers were struggling to accept their own HIV status and did not want their child to blame them for their own positive status by disclosing to them.

Conclusions

Child disclosure is a complex process for care-givers, health-care workers and the children themselves. Care-givers may require additional psycho-social support to manage disclosure. Involving multiple care-givers in the care of HIV positive children could offer additional support for disclosure.
Is there a health inequality in gambling related harms? A systematic review
Authors: Raybould Jodie N. , Larkin Michael , Tunney Richard J.
Published: February 2021

Background

Here we present a systematic review of the existing research into gambling harms, in order to determine whether there are differences in the presentation of these across demographic groups such as age, gender, culture, and socioeconomic status, or gambling behaviour categories such as risk severity and participation frequency.

Primary and secondary outcome measures

Inclusion criteria were: 1) focus on gambling harms; 2) focus on harms to the gambler rather than affected others; 3) discussion of specific listed harms and not just harms in general terms. Exclusion criteria were: 1) research of non-human subjects; 2) not written in English; 3) not an empirical study; 4) not available as a full article.

Methods

We conducted a systematic search using the Web of Science and Scopus databases in August 2020. Assessment of quality took place using Standard Quality Assessment Criteria.

Results

A total of 59 studies published between 1994 and 2020 met the inclusion criteria. These were categorised into thematic groups for comparison and discussion. There were replicated differences found in groups defined by age, socioeconomic status, education level, ethnicity and culture, risk severity, and gambling behaviours.

Conclusion

Harms appear to be dependent on specific social, demographic and environmental conditions that suggests there is a health inequality in gambling related harms. Further investigation is required to develop standardised measurement tools and to understand confounding variables and co-morbidities. With a robust understanding of harms distribution in the population, Primary Care Workers will be better equipped to identify those who are at risk, or who are showing signs of Gambling Disorder, and to target prevention and intervention programmes appropriately.