bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch activation is pervasive in SMZL and uncommon in DLBCL: implications for Notch signaling in B-cell tumors
Authors: Shanmugam Vignesh , Craig Jeffrey W. , Hilton Laura K. , Nguyen Matthew H. , Rushton Christopher K. , Fahimdanesh Kian , Lovitch Scott , Ferland Ben , Scott David W. , Aster Jon C.
Published: January 2021

Notch receptors participate in a signaling pathway in which ligand-induced proteolysis frees the Notch intracellular domain (NICD), allowing it to translocate to the nucleus, form a transcription complex, and induce target gene expression. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), splenic marginal zone B-cell lymphoma (SMZL), and distinct subsets of diffuse large B-cell lymphoma (DLBCL) are strongly associated with mutations in the 3′ end of NOTCH1 or NOTCH2 that disrupt a proline, glutamic acid, serine, and threonine (PEST) degron domain and stabilize NICD1 and NICD2. By contrast, mutations leading to constitutive Notch activation are rare in primary B-cell neoplasms, suggesting that Notch activation is confined to ligand-rich tumor microenvironments, or that cryptic strong gain-of-function mutations have been missed in prior analyses. To test these ideas, we used immunohistochemical stains to screen a broad range of B-cell tumors for Notch activation. Our analyses reveal that among small B-cell neoplasms, NICD2 is primarily detected in SMZL and is a common feature of both NOTCH2 wild-type and NOTCH2-mutated SMZLs, similar to prior findings with NOTCH1 in CLL/SLL. The greatest NOTCH2 activation was observed in NOTCH2-mutated SMZLs, particularly within splenic marginal zones. By contrast, little evidence of NOTCH2 activation was observed in DLBCL, even in NOTCH2-mutated tumors, suggesting that selective pressure for NOTCH2 activation is mainly confined to low-grade B-cell neoplasms, whereas DLBCLs with NOTCH1 mutations frequently showed evidence of ongoing NOTCH1 activation. These observations have important implications for the pathogenic role of Notch and its therapeutic targeting in B-cell lymphomas.
Pre-HCT mosaicism increases relapse risk and lowers survival in acute lymphoblastic leukemia patients post–unrelated HCT
Authors: Wang Yiwen , Zhou Weiyin , Wang Junke , Karaesmen Ezgi , Tang Hancong , McCarthy Philip L. , Pasquini Marcelo C. , Wang Youjin , McReynolds Lisa J. , Katki Hormuzd A. , Machiela Mitchell J. , Yeager Meredith , Pooler Loreall , Sheng Xin , Haiman Christopher A. , Van Den Berg David , Spellman Stephen R. , Wang Tao , Kuxhausen Michelle , Chanock Stephen J. , Lee Stephanie J. , Clay-Gilmour Alyssa I. , Hahn Theresa E. , Gadalla Shahinaz M. , Sucheston-Campbell Lara E.
Published: January 2021

Key Points

Pre-HCT mosaicism is related to increased relapse risk and lower survival after unrelated HCT, independent of cytogenetics at diagnosis. Pre-HCT mosaicism could be a useful clinical tool to guide risk stratification in acute lymphoblastic leukemia patients.
scReQTL: an approach to correlate SNVs to gene expression from individual scRNA-seq datasets
Authors: Liu Hongyu , Prashant N. M. , Spurr Liam F. , Bousounis Pavlos , Alomran Nawaf , Ibeawuchi Helen , Sein Justin , Słowiński Piotr , Tsaneva-Atanasova Krasimira , Horvath Anelia
Published: January 2021

Background

Recently, pioneering expression quantitative trait loci (eQTL) studies on single cell RNA sequencing (scRNA-seq) data have revealed new and cell-specific regulatory single nucleotide variants (SNVs). Here, we present an alternative QTL-related approach applicable to transcribed SNV loci from scRNA-seq data: scReQTL. ScReQTL uses Variant Allele Fraction (VAFRNA) at expressed biallelic loci, and corelates it to gene expression from the corresponding cell.

Results

Our approach employs the advantage that, when estimated from multiple cells, VAFRNAcan be used to assess effects of SNVs in a single sample or individual. In this setting scReQTL operates in the context of identical genotypes, where it is likely to capture RNA-mediated genetic interactions with cell-specific and transient effects. Applying scReQTL on scRNA-seq data generated on the 10 × Genomics Chromium platform using 26,640 mesenchymal cells derived from adipose tissue obtained from three healthy female donors, we identified 1272 unique scReQTLs. ScReQTLs common between individuals or cell types were consistent in terms of the directionality of the relationship and the effect size. Comparative assessment with eQTLs from bulk sequencing data showed that scReQTL analysis identifies a distinct set of SNV-gene correlations, that are substantially enriched in known gene-gene interactions and significant genome-wide association studies (GWAS) loci.

Conclusion

ScReQTL is relevant to the rapidly growing source of scRNA-seq data and can be applied to outline SNVs potentially contributing to cell type-specific and/or dynamic genetic interactions from an individual scRNA-seq dataset.

Availability:https://github.com/HorvathLab/NGS/tree/master/scReQTL
Effects of the scope of practice on family physicians: a systematic review
Authors: Zomahoun Hervé Tchala Vignon , Samson Isabelle , Sawadogo Jasmine , Massougbodji José , Gogovor Amédé , Diendéré Ella , Turgeon Frédéric , Légaré France
Published: January 2021

Background

Family medicine is a branch of medicine that manages common and long-term illnesses in children and adults. Family physicians in particular play a major role and their scope of practice is expected to impact patient and population. However, little is known about its impact on physicians. We aimed to assess the effects of scope of practice on family physician outcomes.

Methods

We performed a systematic review that we reported using PRISMA guidelines. For the inclusion criteria, any study exploring an association between the scope of practice and physician outcomes was considered. Three bibliographic databases Medline, Embase, and ERIC were consulted through OVID interface from their respective inceptions to November, 2020. Two reviewers independently selected studies, extracted data and assessed the risk of bias of studies using appropriate tools. We conducted data synthesis using a narrative form. GRADE was used for evaluating quality of cumulative evidence.

Results

In total, we included 12 studies with 38,732 participants from 6927 citations identified. Eleven of them were cross-sectional, and one was a cohort study with acceptable methodological quality. We found that: 1) family physicians with diverse clinical and nonclinical activities significantly improve their job satisfaction (p<0.05); 2) family physicians with a variety of clinical practices significantly improve their competences and health status (p<0.05); 3) family physicians who perform clinical procedures (mainly extended to gynecological procedures) significantly improve their psychosocial outcomes (e.g., job satisfaction) (p<0.05); and 4) some associations are not statistically significant (e.g., relation between variety of practice settings and outcomes). We observed that the evidence available has a very low level.

Conclusions

Our findings suggest that the scope of practice may be favorably associated with some family physician outcomes but with a very low level of evidence available. Based on these findings, healthcare system managers could monitor the scope of practice among family physicians and encourage future research in this field.

Systematic review registration

Our protocol was registered under the number CRD42019121990 in PROSPERO.
Case Report of a pathologically confirmed vascular parkinsonism with early cognitive impairment and Behavioral disturbance
Authors: Zhang Shouzi , Wang Yuanyuan , Liu Lixin , Zhang Li , Ma Li , Wu Haiyan , He Xuelin , Zhu Mingwei , Wang Luning , Mei Fan
Published: January 2021

Background

Vascular Parkinsonism(VaP) is defined as parkinsonism resulting from cerebral vascular disease(CVD), with presence of variable motor and non-motor signs that are corroborated by clinical, anatomic or imaging findings of cerebrovascular disease. Overlapping syndromes with mixed pathologies make VaP difficult to distinguish from primary neurodegenerative parkinsonism.To understand the clinical and pathological features of VaP,we report a case of autopsy confirmed vascular Parkinsonism that was clinical misdiagnosed as idiopathic Parkinson’s disease.Clinical features include early mixed symptoms of dementia,behavioral disturbance and parkinsonism that were similar to Dementia with lewy Body(DLB) and Parkinson disease Dementia(PDD).

Case presentation

A 84-year-old man presented progressive parkinsonism with prominent postural instability, gait impairment, pseudobulbar, early cognitive impairment, irritability, hallucination, urinary symptoms and poor responsiveness to dopaminergic drugs. He was clinically diagnosed as Parkinson disease(PD). In the post-mortem study, we examined Aβ and phospho-tau as pathological biomarker for Alzheimer’s disease(AD), α-synucleing in medulla, pons and midbrain for PD and DLB. Hematoxylin and eosin staining in cerebral cortex, cerebellum and brainstem examines vascular pathological changes and microvascular lesion.Neither Lewy bodies in the substantia nigra ,locus ceruleus and cerebrumnor accumulation of Aβ, neurofibrillary tangles were noted. Instead, there were many cerebral infarctions and widespread arteriosclerosis in the brain. The final brain autopsy supported a diagnosis of VaP not PD.

Conclusions

This case of pathologically confirmed VaP misdiagnosed as idiopathic PD suggested that we must be vigilant about the possibility of VaP for patients with parkinsonisms, cognitive impairments, early behavioral and psychological symptoms,imaging performances of cerebral small vessel disease and other vascular damages.
The microbiologic spectrum of dacryocystitis
Authors: Luo Ban , Li Mu , Xiang Nan , Hu Weikun , Liu Rong , Yan Xiaoqin
Published: January 2021

Background

To investigate the microbiologic spectrum of dacryocystitis in adult and pediatric groups, specifically the microbiologic differences between chronic dacryocystitis with nasolacrimal duct obstruction (NLDO) and acute dacryocystitis in pediatric group.

Methods

This retrospective study was reviewed for demographic and microbiologic profile of dacryocystitis. The culture results were reported.

Results

Sixty-four adults and one hundred and five pediatrics with dacryocystitis were included in this study. Of all adults, only chronic dacryocystitis with NLDO was observed. Of all pediatric patients, 89 had chronic dacryocystitis with NLDO and 16 had acute dacryocystitis. Gram positive and negative isolates were numerically equal in adult group (both 36(48.65%)), while gram positive isolates were the major organism in pediatric group (71(58.68%)).Streptococcus pneumoniawas the most common isolate in both adult (11(14.86%)) and pediatric (30(24.79%)) dacryocystitis. For both pediatric subgroups, gram positive isolates were the major organism (59(57.84%) for chronic dacryocystitis with NLDO and 12 (63.16%) for acute dacryocystitis). However, the leading isolates in those two subgroups were distinct, withStreptococcus pneumonia(29(28.43%)) being most common in chronic dacryocystitis with NLDO andStaphylococcus aureus(8(42.11%)) being most common in acute dacryocystitis.

Conclusions

In adult group, gram negative isolates were more common in dacryocystitis than before. In pediatric group, gram positive isolates were still the major infection pathogen. Moreover, the more virulent organisms were more common in acute dacryocystitis than chronic dacryocystitis with NLDO.
Retrospective and prospective measures of post-traumatic growth reflect different processes: longitudinal evidence of greater decline than growth following a hematopoietic stem-cell transplantation
Authors: Corman Maya , Rubio Marie-Thérèse , Cabrespine Aurélie , Brindel Isabelle , Bay Jacques-Olivier , De La Tour Régis Peffault , Dambrun Michaël
Published: January 2021

Background

This prospective longitudinal study examined and compared two measures (prospective and retrospective ones) of post-traumatic growth (PTG) following Hematopoietic Stem-Cell Transplantation (HSCT) and their respective relationships with mental health and psychological disposition. We also tested the hypothesis that unwillingness to be in contact with distressing thoughts and feelings—i.e. experiential avoidance—would moderate the relationship between Post-Traumatic Stress Disorder (PTSD) and growth.

Methods

This study was carried out with 187 patients. Patients completed the Post-Traumatic Growth Inventory (PTGI) 5 months after HSCT and scales tapping into the five domains of PTGI during hospitalisation and 5 months after HSCT. Mental health and psychological disposition were also assessed prior to hospitalisation. A PTSD scale was administered at the five-month follow-up.

Results

Prospective and retrospective measures of PTG were weakly correlated. Bayesian pre/post-HSCT comparisons in the prospective measure of PTG revealed substantial to very strong decline in four of the five dimensions assessed. Overall, RCI indicated a reliable increase for 5.6% of patients and a reliable decrease for 40.8% of patients. Confirming that retrospective and prospective measures of PTG reflect different processes, they were not related to the same mental health and psychological disposition variables. Moreover, the hypothesis that acquiring positive outcomes from a potentially traumatic experience, such as HSCT, requires direct confrontation with the source of distress was supported in the case of the retrospective measure of growth but not in the case of the prospective measure growth.

Conclusions

Retrospective measures such as the PTGI do not appear to assess actual pre- to post-HSCT change. HSCT seems more linked to psychological decline than to growth.
Qualitative, longitudinal exploration of coping strategies and factors facilitating infant and young child feeding practices among mothers in rural Rwanda
Authors: Ahishakiye Jeanine , Vaandrager Lenneke , Brouwer Inge D. , Koelen Maria
Published: January 2021

Background

Mothers in low-income countries face many challenges to appropriately feed their children in the first year such as poverty, food insecurity and high workloads. However, even in the lowest income families there are mothers who succeed to feed their children according to the recommendations. In this paper, we explored the coping strategies that facilitate appropriate breastfeeding and complementary feeding practices among rural Rwandan mothers from birth to one year of a child’s life.

Methods

This qualitative longitudinal study recruited a purposive sample of 17 mothers who followed the infant and young child feeding recommendations (IYCF). They were selected from a larger study of 36 mothers. In-depth interviews were conducted with mothers of the total group (36 mothers) within the first week, at 4th, 6th, 9th and 12th months postpartum. Interviews were audio-recorded, transcribed verbatim and analyzed thematically.

Results

Coping strategies included improving mothers’ own diet for adequate breastmilk production, prioritizing child feeding over livelihood chores, livelihood diversification and mothers’ anticipatory behaviors such as preparing child’s food in advance. Some of those coping strategies were shifting overtime depending on the development of the children. Personal factors such as breastfeeding self-efficacy, religious beliefs and perceived benefits of breastfeeding were among the facilitating factors. Additionally, social support that mothers received from family members, other mothers in the community, Community Health Workers (CHWs) and health professionals played an important role.

Conclusion

In challenging contextual conditions, mothers manage to follow the recommended breastfeeding and complementary feeding practices through the interplay of active coping strategies, feeling to be in control and social support. Nutrition promotion interventions that aim to improve IYCF should consider strengthening mothers’ capability in gaining greater control of their IYCF practices and the factors facilitating their appropriate IYCF practices.
Perceptions of medical students towards the practice of professionalism at the Arabian Gulf University
Authors: Al Gahtani Haifa Mohammed Saleh , Jahrami Haitham Ali , Silverman Henry J.
Published: January 2021

Background

To enhance the development of a curriculum in professionalism for medical students, the aim of this research was to evaluate medical students’ responses regarding professionalism teaching and behaviors in their clinical experience at the Arabian Gulf University (AGU).

Methods

A retrospective cross-sectional, questionnaire-based study involving Year 5 medical students at the AGU. We used a “climate of professionalism” survey that consisted of two parts. The first part asked students to rate their perceptions of the frequency of professionalism practices of their peers (medical students), residents, and faculty. The response choices included: “mostly”, “sometimes”, and “rarely”. The second part asked the students to assess their perceptions of the professionalism teaching and behaviors of the faculty. The response choices included: “mostly”, “sometimes”, and “rarely”. We calculated an overall score for the responses in both parts of the questionnaire by assigning 3, 2, and 1 points to the response choices, respectively. We also calculated subscale scores reflecting different professionalism constructs. We used descriptive statistics and a one-way Analysis of Variance (ANOVA) followed by multiple testing comparisons with Bonferroni correction to examine pairwise comparisons. Ap < 0.05 was considered statistically significant.

Results

The mean total scores of participants’ ratings of professional behaviors of medical students, residents, and faculty for each academic year were approximately 60% of the total maximum score. The mean total scores of participants’ rating of faculty’s teaching and modeling behaviors concerning professionalism were approximately 58% of the maximum score. Compared with similar studies performed in the Arab Region, ratings regarding professional teaching and modeling of professionalism were lower.

Conclusion

We recommend the further evaluation of professionalism teaching and behaviors at the AGU and further discussions regarding curriculum reform.
Acting between guidelines and reality- an interview study exploring the strategies of first line managers in patient safety work
Authors: Hedsköld Mats , Sachs Magna Andreen , Rosander Torleif , von Knorring Mia , Pukk Härenstam Karin
Published: January 2021

Background

Safety culture can be described and understood through its manifestations in the organization as artefacts, espoused values and basic underlying assumptions and is strongly related to leadership-yet it remains elusive as a concept. Even if the literature points to leadership as an important factor for creating and sustaining a mature safety culture, little is known about how the safety work of first line managers’ is done and how they balance the different and often conflicting organizational goals in everyday practice. The purpose of this study was to explore how health care first line managers perceive their role and how they promote patient safety and patient safety culture in their units.

Methods

Interview study with first line managers in intensive care units in eight different hospitals located in the middle of Sweden. An inductive qualitative content analysis approach was used, this was then followed by a deductive analysis of the strategies informed by constructs from High reliability organizations.

Results

We present how first line managers view their role in patient safety and exemplify concrete strategies by which managers promote patient safety in everyday work.

Conclusions

Our study shows the central role of front-line managers in organizing for safe care and creating a culture for patient safety. Although promoted widely in Swedish healthcare at the time for the interviews, the HSOPSC was not mentioned by the managers as a central source of information on the unit’s safety culture.
Novel susceptibility loci identified in a genome-wide association study of type 2 diabetes complications in population of Latvia
Authors: Ustinova Monta , Peculis Raitis , Rescenko Raimonds , Rovite Vita , Zaharenko Linda , Elbere Ilze , Silamikele Laila , Konrade Ilze , Sokolovska Jelizaveta , Pirags Valdis , Klovins Janis
Published: January 2021

Background

Type 2 diabetes complications cause a serious emotional and economical burden to patients and healthcare systems globally. Management of both acute and chronic complications of diabetes, which dramatically impair the quality of patients' life, is still an unsolved issue in diabetes care, suggesting a need for early identification of individuals with high risk for developing diabetes complications.

Methods

We performed a genome-wide association study in 601 type 2 diabetes patients after stratifying them according to the presence or absence of four types of diabetes complications: diabetic neuropathy, diabetic nephropathy, macrovascular complications, and ophthalmic complications.

Results

The analysis revealed ten novel associations showing genome-wide significance, including rs1132787 (GYPA, OR = 2.71; 95% CI = 2.02–3.64) and diabetic neuropathy, rs2477088 (PDE4DIP, OR = 2.50; 95% CI = 1.87–3.34), rs4852954 (NAT8, OR = 2.27; 95% CI = 2.71–3.01), rs6032 (F5, OR = 2.12; 95% CI = 1.63–2.77), rs6935464 (RPS6KA2, OR = 2.25; 95% CI = 6.69–3.01) and macrovascular complications, rs3095447 (CCDC146, OR = 2.18; 95% CI = 1.66–2.87) and ophthalmic complications. By applying the targeted approach of previously reported susceptibility loci we managed to replicate three associations: MAPK14 (rs3761980, rs80028505) and diabetic neuropathy, APOL1 (rs136161) and diabetic nephropathy.

Conclusions

Together these results provide further evidence for the implication of genetic factors in the development of type 2 diabetes complications and highlight several potential key loci, able to modify the risk of developing these conditions. Moreover, the candidate variant approach proves a strong and consistent effect for multiple variants across different populations.
Identifying novel amino acid substitutions of hemagglutinin involved in virulence enhancement in H7N9 virus strains
Authors: Zhang Ting , Du Haiwei , Guo Li , Liu Feng , Su Haoxiang , Yang Fan
Published: January 2021

Background

To identify site-specific features of amino acid substitutions that confer enhanced H7N9 virulence in humans, we independently generated mammalian-adapted variants of A/Anhui/1/2013 (AH-H7N9) and A/Shanghai/2/2013 (SH-H7N9) by serial passaging in Madin-Darby canine kidney (MDCK) cells.

Methods

Virus was respectively extracted from cell culture supernatant and cells, and was absolutely quantified by using real-time polymerase chain reaction. Viral RNAs were extracted and subjected to sequencing for identifying mutations. Then, site-specific mutations introduced by viral passaging were selected for further constructing HA7 or NA9 mutant plasmids, which were used to generate recombinant viruses. The interaction between the recombinant HA and receptors, H7N9-pseudotyped viruses and receptors were detected.

Results

Both subtypes displayed high variability in replicative capability and virulence during serial passaging. Analysis of viral genomes revealed multiple amino acid mutations in the hemagglutinin 7 (HA7) (A135T [AH-H7N9], T71I [SH-H7N9], T157I [SH-H7N9], T71I-V223I [SH-H7N9], T71I-T157I-V223I [SH-H7N9], and T71I-T157I-V223I-T40I [SH-H7N9]), and NA9 (N171S [AH-H7N9] and G335S [AH-H7N9]) proteins in various strains of the corresponding subtypes. Notably, quite a few amino acid substitutions indeed collectively strengthened the interactions between H7N9 strains and sialic acid receptors. Moreover, some of the amino acid substitutions identified were highly and specifically cytopathogenic to MDCK cells.

Conclusions

This study demonstrated that AH-H7N9 and SH-H7N9 subtypes can acquire enhanced receptor affinity for sialic receptors through novel amino acid substitutions. Such changes in affinitive interactions are conferred by site-specific mutations of HA7 proteins that affect the virulence and pathology of the virus strain, and/or limited compatibility between the host and the virus strain.
Mesenchymal stem cells genetically engineered to express platelet-derived growth factor and heme oxygenase-1 ameliorate osteoarthritis in a canine model
Authors: Oh Jiwon , Son Yeon Sung , Kim Wan Hee , Kwon Oh-Kyeong , Kang Byung-Jae
Published: January 2021

Background

Mesenchymal stem cells (MSCs) are used for the treatment of osteoarthritis (OA), and MSC genetic engineering is expected to enhance cartilage repair. Here, we aimed to investigate the effect of MSCs overexpressing platelet-derived growth factor (PDGF) or heme oxygenase-1 (HO-1) in chondrocytes and synovial cells with an OA phenotype and assess the in vivo efficacy of intra-articular injections of these MSCs in canine OA models.

Methods

Canine adipose-derived MSCs were transfected with canine PDGF (PDGF-MSCs) or HO-1 (HO-1-MSCs) using lentiviral vectors. Canine chondrocytes or synovial cells were stimulated with lipopolysaccharide (LPS) to mimic the inflammatory OA model and then co-cultured with MSCs, PDGF-MSCs, or HO-1-MSCs for 24 h and 72 h. The mRNA levels of pro-inflammatory, extracellular matrix-degradative/synthetic, or pain-related factors were measured after co-culture by real-time PCR. Furthermore, a surgery-induced canine OA model was established and the dogs were randomized into four groups: normal saline (n = 4), MSCs (n = 4), PDGF-MSCs (n = 4), and HO-1-MSCs (n = 4). The OA symptoms, radiographic OA severity, and serum matrix metallopeptidase (MMP)-13 levels were assessed before and 10 weeks after treatment, to evaluate the safety and efficacy of the modified MSCs.

Results

PDGF or HO-1 overexpression significantly reduced the expression of pro-inflammatory factors, MMP-13, and nerve growth factor elicited by LPS and increased that of aggrecan and collagen type 2 in chondrocytes (P < 0.05). In addition, the expression of aggrecanases was significantly downregulated in synovial cells, whereas that of tissue inhibitor of metalloproteinases was upregulated (P < 0.05). Furthermore, the co-cultured MSCs highly expressed genes that contributed to the maintenance of joint homeostasis (P < 0.05). In vivo studies showed that OA symptoms improved after administration of all MSCs. Also, PDGF-MSCs significantly improved limb function and reduced pain (P < 0.05). The results of the radiographic assessment and serum MMP-13 levels did not vary significantly compared to those of the control.

Conclusions

Genetically modifying PDGF and HO-1 in MSCs is an effective strategy for treating OA, suggesting that PDGF-MSCs can be novel therapeutic agents for improving OA symptoms.
A 9 mRNAs-based diagnostic signature for rheumatoid arthritis by integrating bioinformatic analysis and machine-learning
Authors: Liu Jianyong , Chen Ningjie
Published: January 2021

Background

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease that carries a substantial burden for both patients and society. Early diagnosis of RA is essential to prevent disease progression and select an optimal therapeutic strategy. However, RA diagnosis is challenging, partly due to a lack of reliable biomarkers. Here, we aimed to explore the diagnostic signature and establish a predictive model of RA.

Methods

The mRNA expression profiling data of GSE17755, containing blood samples of 112 RA patients and 53 healthy control patients, were obtained from the Gene Expression Omnibus (GEO) database, followed by differential expression, GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. A PPI network was constructed to select candidate hub genes, then logistic regression and random forest models were established based on the identified genes.

Results

Significantly, we identified 52 differentially expressed genes (DEGs), including 16 upregulated genes and 36 downregulated genes in RA samples compared with control samples. GO and KEGG analysis showed that several immune-related cellular processes were particularly enriched. We identified nine hub genes in the PPI network, including CFL1, COTL1, ACTG1, PFN1, LCP1, LCK, HLA-E, FYN, and HLA-DRA. The logistic regression and random forest models based on the nine identified genes reliably distinguished the RA samples from the healthy samples with substantially high AUC.

Conclusion

The diagnostic logistic regression and random forest models based on nine hub genes reliably predicted the occurrence of RA. Our findings could provide new insights into RA diagnostics.
Dynamics of non-communicable disease prevention, diagnosis and control in Lebanon, a fragile setting
Authors: Zablith Nadine , Diaconu Karin , Naja Farah , El Koussa Maria , Loffreda Giulia , Bou-Orm Ibrahim , Saleh Shadi
Published: January 2021

Background

Non-communicable diseases (NCD) present an increasing global health challenge, particularly for settings affected by fragility where access to care may be disrupted, and where high-quality continuous care delivery is difficult to achieve. This study documents the complex dynamics of NCD prevention and management in the fragile setting of rural Beqaa, Lebanon.

Methods

Participatory system dynamics methods were used, including 30 semi-structured interviews and three Group Model Building (GMB) workshops. Participants included health care providers offering NCD care, and Lebanese host- and Syrian refugees community members affected by NCDs.

Results

Participants across all groups articulated a shared complex understanding of both the structural and direct determinants behind NCD onset. Lebanese and Syrian community members further identified several barriers to health seeking, including restrictions in health coverage, limited availability of services in the Beqaa and perceptions of poor-quality care. Health providers and community members described a health system overtly focused on disease control and overwhelmed by delivery of care to people living with NCD across both communities.

Conclusion

Participants across all groups agreed on the need for health promotion and primary prevention activities and identified priority interventions in these areas.
Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs
Authors: Wang Chen , Lin Haifan
Published: January 2021

PIWI proteins, a subfamily of PAZ/PIWI Domain family RNA-binding proteins, are best known for their function in silencing transposons and germline development by partnering with small noncoding RNAs called PIWI-interacting RNAs (piRNAs). However, recent studies have revealed multifaceted roles of the PIWI-piRNA pathway in regulating the expression of other major classes of RNAs in germ cells. In this review, we summarize how PIWI proteins and piRNAs regulate the expression of many disparate RNAs, describing a highly complex global genomic regulatory relationship at the RNA level through which piRNAs functionally connect all major constituents of the genome in the germline.
eRegCom—Quality Improvement Dashboard for healthcare providers and Targeted Client Communication to pregnant women using data from an electronic health registry to improve attendance and quality of antenatal care: study protocol for a multi-arm cluster randomized trial
Authors: Mørkrid Kjersti , Bogale Binyam , Abbas Eatimad , Abu Khader Khadija , Abu Ward Itimad , Attalh Amjad , Awwad Tamara , Baniode Mohammad , Frost Kimberly Suzanne , Frost Michael James , Ghanem Buthaina , Hijaz Taghreed , Isbeih Mervett , Issawi Sally , Nazzal Zaher A. S. , O’Donnell Brian , Qaddomi Sharif E. , Rabah Yousef , Venkateswaran Mahima , Frøen J. Frederik
Published: January 2021

Background

This trial evaluates interventions that utilize data entered at point-of-care in the Palestinian maternal and child eRegistry to generate Quality Improvement Dashboards (QID) for healthcare providers and Targeted Client Communication (TCC) via short message service (SMS) to clients. The aim is to assess the effectiveness of the automated communication strategies from the eRegistry on improving attendance and quality of care for pregnant women.

Methods

This four-arm cluster randomized controlled trial will be conducted in the West Bank and the Gaza Strip, Palestine, and includes 138 clusters (primary healthcare clinics) enrolling from 45 to 3000 pregnancies per year. The intervention tools are the QID and the TCC via SMS, automated from the eRegistry built on the District Health Information Software 2 (DHIS2) Tracker. The primary outcomes are appropriate screening and management of anemia, hypertension, and diabetes during pregnancy and timely attendance to antenatal care. Primary analysis, at the individual level taking the design effect of the clustering into account, will be done as intention-to-treat.

Discussion

This trial, embedded in the implementation of the eRegistry in Palestine, will inform the use of digital health interventions as a health systems strengthening approach.

Trial registration

ISRCTN Registry, ISRCTN10520687. Registered on 18 October 2018
Navigate: a study protocol for a randomised controlled trial of an online treatment decision aid for men with low-risk prostate cancer and their partners
Authors: Schofield Penelope , Gough Karla , Hyatt Amelia , White Alan , Frydenberg Mark , Chambers Suzanne , Gordon Louisa G. , Gardiner Robert , Murphy Declan G. , Cavedon Lawrence , Richards Natalie , Murphy Barbara , Quinn Stephen , Juraskova Ilona
Published: January 2021

Background

Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol.

Methods

Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outcome measures before randomisation and 1, 3 and 6 months after study consent.

Discussion

The Navigate online decision aid has the potential to increase the choice of AS in LRPC, avoiding or delaying unnecessary radical treatments and associated side effects. In addition, Navigate is likely to reduce patients’ and partners’ confusion and distress in management decision-making and increase their quality of life.

Trial registration

Australian and New Zealand Clinical Trial Registry ACTRN12616001665426. Registered on 2 December 2016. All items from the WHO Trial Registration Data set can be found in this manuscript.
Effective treatment of osmotic demyelination syndrome with plasmapheresis: a case report and review of the literature
Authors: Wijayabandara Maheshi , Appuhamy Shenal , Weerathunga Praveen , Chang Thashi
Published: January 2021

Background

Treatment options for chronic osmotic demyelination syndrome are limited to case reports and only a very few show complete recovery. We report a case of complete recovery of chronic osmotic demyelination syndrome with plasmapheresis.

Case presentation

A 43-year-old Sri Lankan man presented with fever, repeated vomiting, unsteady gait, increased tonicity of his right upper limb and paucity of speech for three days. He was treated in the local hospital with antibiotics and antivirals as per central nervous system infection. He had hyponatraemia, which was rapidly corrected with hypertonic saline from 97 to 119 mmol/L. He was transferred to our hospital because of progressive reduction of consciousness, rapidly worsening rigidity and bradykinesia of all four limbs and worsening dysarthria and bradyphrenia. Magnetic resonance imaging of the brain was compatible with osmotic demyelination syndrome. He was commenced on plasmapheresis twenty-two days after rapid correction of sodium. He regained independent mobility with complete resolution of rigidity, bradykinesia and speech dysfunction after five cycles of alternate day plasmapheresis.

Conclusion

Plasmapheresis can be considered as an effective treatment modality in chronic osmotic demyelination syndrome.
Substructure-based neural machine translation for retrosynthetic prediction
Authors: Ucak Umit V. , Kang Taek , Ko Junsu , Lee Juyong
Published: January 2021

With the rapid improvement of machine translation approaches, neural machine translation has started to play an important role in retrosynthesis planning, which finds reasonable synthetic pathways for a target molecule. Previous studies showed that utilizing the sequence-to-sequence frameworks of neural machine translation is a promising approach to tackle the retrosynthetic planning problem. In this work, we recast the retrosynthetic planning problem as a language translation problem using a template-free sequence-to-sequence model. The model is trained in an end-to-end and a fully data-driven fashion. Unlike previous models translating the SMILES strings of reactants and products, we introduced a new way of representing a chemical reaction based on molecular fragments. It is demonstrated that the new approach yields better prediction results than current state-of-the-art computational methods. The new approach resolves the major drawbacks of existing retrosynthetic methods such as generating invalid SMILES strings. Specifically, our approach predicts highly similar reactant molecules with an accuracy of 57.7%. In addition, our method yields more robust predictions than existing methods.
Development of Chinese chestnut whiskey: yeast strains isolation, fermentation system optimization, and scale-up fermentation
Authors: Li Wanzhen , Shi Cuie , Guang Jiaquan , Ge Fei , Yan Shoubao
Published: January 2021

In this study, we used Chinese chestnut as the main raw material to develop a novel type of whiskey. First, 16 yeasts were isolated and identified for producing aroma using olfactory plate assay. Of these, we screened nine yeast strains based on their fermentation capacity, aroma profile, and sensory evaluation. The results demonstrated the combination of strains HN006 (Saccharomyces cerevisiae) and HN010 (Wickerhamomyces anomalus) provided satisfactory wine fermentation with an interesting flavor profile, as strain HN010 was highly aromatic and had elevated sensory scores with comparatively low ethanol yield, while strain HN006 had a poor flavor profile but produced the largest amount of ethanol. Subsequently, we co-cultured strains HN006 and HN010 to optimize the fermentation system. The results revealed the following optimum parameters: a mixed inoculum of 6% (v/v) at an HN006/HN010 ratio of 1:2 (v/v), a raw material ratio of 5:3:2 (chestnut: malt: glutinous rice), and yeast extract concentration of 6 g/L. Additionally, this fermentation system was successfully scaled-up to a 1000 L pilot-scale system. The results of this study showed that strains HN006 and HN010 could be used as alternatives for whiskey fermentation, as well as provided a generalized experimental scheme to assess other microorganisms.
Theories of change for e-health interventions targeting HIV/STIs and sexual risk, substance use and mental ill health amongst men who have sex with men: systematic review and synthesis
Authors: Meiksin Rebecca , Melendez-Torres G. J. , Falconer Jane , Witzel T. Charles , Weatherburn Peter , Bonell Chris
Published: January 2021

Background

Sexual risk, substance use, and mental ill health constitute a syndemic of co-occurring, mutually reinforcing epidemics amongst men who have sex with men (MSM). Developed since 1995, e-health interventions offer accessible, anonymous support and can be effective in addressing these outcomes, suggesting the potential value of developing e-health interventions that address these simultaneously amongst MSM. We conducted a systematic review of e-health interventions addressing one or more of these outcomes amongst MSM and in this paper describe the theories of change underpinning relevant interventions, what these offer and how they might complement each other.

Methods

We identified eligible reports via expert requests, reference-checking and database and Google searches. Results were screened for reports published in 1995 or later; focused on MSM; reporting on e-health interventions providing ongoing support to prevent HIV/STIs, sexual risk behaviour, substance use, anxiety or depression; and describing intervention theories of change. Reviewers assessed report quality, extracted intervention and theory of change data, and developed a novel method of synthesis using diagrammatic representations of theories of change.

Results

Thirty-three reports on 22 intervention theories of change were included, largely of low/medium-quality. Inductively grouping these theories according to their core constructs, we identified three distinct groupings of theorised pathways. In the largest, the ‘cognitive/skills’ grouping, interventions provide information and activities which are theorised to influence behaviour via motivation/intention and self-efficacy/perceived control. In the ‘self-monitoring’ grouping, interventions are theorised to trigger reflection, self-reward/critique and self-regulation. In the ‘cognitive therapy’ grouping, the theory of change is rooted in cognitive therapy techniques, aiming to reframe negative emotions to improve mental health.

Conclusions

The synthesised theories of change provide a framework for developing e-health interventions that might holistically address syndemic health problems amongst MSM. Improving reporting on theories of change in primary studies of e-health interventions would enable a better understanding of how they are intended to work and the evidence supporting this. The novel diagrammatic method of theory of change synthesis used here could be used for future reviews where interventions are driven by existing well-defined behaviour and behaviour change theories.

Systematic review registration

PROSPERO CRD42018110317
Structural stigma and its impact on healthcare for consumers with borderline personality disorder: protocol for a scoping review
Authors: Klein Pauline , Fairweather Alicia Kate , Lawn Sharon , Stallman Helen Margaret , Cammell Paul
Published: January 2021

Background

Structural stigma in health systems experienced by consumers diagnosed with Borderline Personality Disorder (BPD) is a widespread phenomenon that causes major health inequities and harm for this population. Structural stigma in this context relates to institutional policies, cultural norms, and organizational practices that limit consumers’ access to health services, quality of care, and capacity to achieve optimal health and well-being. BPD is a serious mental illness with high morbidity and mortality, characterized by instability in interpersonal relationships, self-image, and emotional and behavioral deregulation, which stem from significant traumatic childhood/life events, and/or biological etiologies. The objectives of this scoping review are to explore the international literature on structural stigma in healthcare systems specific to BPD, and to provide an overview of the impact of structural stigma on health services for BPD consumers and their carers/families.

Methods

This scoping review will follow the Joanna Briggs Institute (JBI) scoping review guidelines. We will search the following electronic databases (from inception onwards): MEDLINE, CINAHL, PsycINFO, Scopus, Cochrane Library, and JBI-Evidence databases. Grey literature will be identified through the Google search engine. We will include all types of literature in English, published and unpublished, including any study design, reviews, clinical practice guidelines, policy reports, and other documents. No restrictions on publication date of sources of evidence will be applied. International literature should examine structural stigma associated with BPD in any healthcare setting such as, outpatients, inpatients, primary health care, or community-based facilities. Two reviewers will independently screen all titles, abstracts, and full-text citations. Quality appraisal of the included sources of evidence will be assessed using the Mixed Methods Appraisal Tool (MMAT) 2018 version. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., thematic analysis) methods.

Discussion

This review is anticipated to enhance both identification and understanding of those structures in health systems (i.e., institutional policies, cultural norms, and practices) that manifest and perpetuate stigma experienced by consumers with BPD and their carers/families. The findings can be used to inform future research, policy, and practice relating to stigma reduction strategies that can be adopted to improve the provision of BPD-responsive services and care for this population.

Systematic review registration

Open Science Framework (https://osf.io/bhpg4).
Riemann–Liouville fractional stochastic evolution equations driven by both Wiener process and fractional Brownian motion
Authors: Yang Min , Gu Haibo
Published: January 2021

This article is devoted to the study of the existence and uniqueness of mild solution to a class of Riemann–Liouville fractional stochastic evolution equations driven by both Wiener process and fractional Brownian motion. Our results are obtained by using fractional calculus, stochastic analysis, and the fixed-point technique. Moreover, an example is provided to illustrate the application of the obtained abstract results.
An efficient numerical scheme based on Lucas polynomials for the study of multidimensional Burgers-type equations
Authors: Ali Ihteram , Haq Sirajul , Nisar Kottakkaran Sooppy , Baleanu Dumitru
Published: January 2021

We propose a polynomial-based numerical scheme for solving some important nonlinear partial differential equations (PDEs). In the proposed technique, the temporal part is discretized by finite difference method together withθ-weighted scheme. Then, for the approximation of spatial part of unknown function and its spatial derivatives, we use a mixed approach based on Lucas and Fibonacci polynomials. With the help of these approximations, we transform the nonlinear partial differential equation to a system of algebraic equations, which can be easily handled. We test the performance of the method on the generalized Burgers–Huxley and Burgers–Fisher equations, and one- and two-dimensional coupled Burgers equations. To compare the efficiency and accuracy of the proposed scheme, we computed$L_{\infty }$L∞,$L_{2}$L2, and root mean square (RMS) error norms. Computations validate that the proposed method produces better results than other numerical methods. We also discussed and confirmed the stability of the technique.