bluuebunny/crossref_metadata_2025 huggingface dataset:
Heuristic algorithms for best match graph editing
Authors: Schaller David , Geiß Manuela , Hellmuth Marc , Stadler Peter F.
Published: August 2021

Background

Best match graphs (BMGs) are a class of colored digraphs that naturally appear in mathematical phylogenetics as a representation of the pairwise most closely related genes among multiple species. An arc connects a gene x with a gene y from another species (vertex color) Y whenever it is one of the phylogenetically closest relatives of x. BMGs can be approximated with the help of similarity measures between gene sequences, albeit not without errors. Empirical estimates thus will usually violate the theoretical properties of BMGs. The corresponding graph editing problem can be used to guide error correction for best match data. Since the arc set modification problems for BMGs are NP-complete, efficient heuristics are needed if BMGs are to be used for the practical analysis of biological sequence data.

Results

Since BMGs have a characterization in terms of consistency of a certain set of rooted triples (binary trees on three vertices) defined on the set of genes, we consider heuristics that operate on triple sets. As an alternative, we show that there is a close connection to a set partitioning problem that leads to a class of top-down recursive algorithms that are similar to Aho’s supertree algorithm and give rise to BMG editing algorithms that are consistent in the sense that they leave BMGs invariant. Extensive benchmarking shows that community detection algorithms for the partitioning steps perform best for BMG editing.

Conclusion

Noisy BMG data can be corrected with sufficient accuracy and efficiency to make BMGs an attractive alternative to classical phylogenetic methods.
4-Methylumbelliferone suppresses catabolic activation in anterior cruciate ligament-derived cells via a mechanism independent of hyaluronan inhibition
Authors: Idota Masaru , Ishizuka Shinya , Hiraiwa Hideki , Yamashita Satoshi , Oba Hiroki , Kawamura Yusuke , Sakaguchi Takefumi , Haga Takahiro , Mizuno Takafumi , Kawashima Itaru , Kuriyama Kanae , Imagama Shiro
Published: August 2021

Background

The anterior cruciate ligament (ACL) has a key role as a dynamic stabilizer of the knee joints, and ACL dysfunction caused by traumatic or degenerative rupture accelerates osteoarthritis progression. Thus, it is important to prevent the degenerative rupture of the ACL. 4-Methylumbelliferone (4-MU), a pre-approved drug, exerts anti-inflammatory effects in osteoarthritis chondrocytes. It was originally used as an inhibitor of hyaluronan synthesis in chondrocytes.

Methods

In this study, we investigated whether 4-MU affects the expression of catabolic factors, such as matrix metalloproteinase (MMP)-1, MMP-3, and interleukin (IL)-6, in ACL-derived cells and ACL explant cultures using immunohistochemistry, real-time RT-qPCR, and capillary western immunoassay. Furthermore, the hyaluronan concentration was evaluated using a colorimetric assay. Statistical analyses were conducted using analysis of variance for multi-group comparisons, followed by Tukey or Tukey-Kramer post hoc test.

Results

Our results revealed, for the first time, that 4-MU suppressed the IL-β-induced upregulation of pro-catabolic factors, such as MMP-1, MMP-3, and IL-6, in ACL-derived cells. This suppressive effect was also observed in the cultured ligament tissues in ex vivo experiments. 4-MU also reversed an enhanced dependence on glycolysis in IL-1β-activated ACL-derived cells. Furthermore, we found that the suppressive effects of 4-MU were exerted directly and not through the inhibition of hyaluronan synthesis.

Conclusions

We conclude that 4-MU could be an effective and useful treatment for knee osteoarthritis, owing to its anti-inflammatory effect on, not only chondrocytes but also on ligament cells.
Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities
Authors: Liu Yingyue , Zhou Xiangxiang , Wang Xin
Published: August 2021

B-cell lymphoma is a group of hematological malignancies with high clinical and biological heterogeneity. The pathogenesis of B-cell lymphoma involves a complex interaction between tumor cells and the tumor microenvironment (TME), which is composed of stromal cells and extracellular matrix. Although the roles of the TME have not been fully elucidated, accumulating evidence implies that TME is closely relevant to the origination, invasion and metastasis of B-cell lymphoma. Explorations of the TME provide distinctive insights for cancer therapy. Here, we epitomize the recent advances of TME in B-cell lymphoma and discuss its function in tumor progression and immune escape. In addition, the potential clinical value of targeting TME in B-cell lymphoma is highlighted, which is expected to pave the way for novel therapeutic strategies.
Making clinical decisions based on measurable residual disease improves the outcome in multiple myeloma
Authors: Martinez-Lopez Joaquin , Alonso Rafael , Wong Sandy W. , Rios Rafael , Shah Nina , Ruiz-Heredia Yanira , Sanchez-Pina Jose Maria , Sanchez Ricardo , Bahri Natasha , Zamanillo Irene , Poza Maria , Buenache Natalia , Encinas Cristina , Juarez Luis , Miras Fatima , Collado Luis , Barrio Santiago , Martin Thomas , Cedena Maria Teresa , Wolf Jeffrey
Published: August 2021

The assessment of measurable residual disease (MRD) in bone marrow has proven of prognostic relevance in patients with multiple myeloma (MM). Nevertheless, and unlike other hematologic malignancies, the use of MRD results to make clinical decisions in MM has been underexplored to date. In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes. As expected, achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity (median PFS 104 vs. 45 months, p < 0.0001). In addition, however, 67 out of 400 patients underwent a clinical decision (treatment discontinuation, intensification or initiation of a new therapy) based on MRD results. Those patients in whom a treatment change was made showed a prolonged PFS in comparison with those 333 patients in which MRD results were not acted upon (respectively, mPFS 104 vs. 62 months, p = 0.005). In patients who achieved MRD negativity during maintenance (n = 186) on at least one occasion, stopping therapy in 24 patients vs. continuing in 162 did not alter PFS (mPFS 120 months vs. 82 months, p = 0.1). Most importantly, however, in patients with a positive MRD during maintenance (n = 214), a clinical decision (either intensification or change of therapy) (n = 43) resulted in better PFS compared to patients in whom no adjustment was made (n = 171) (mPFS NA vs. 39 months, p = 0.02). Interestingly, there were no significant differences when MRD was assessed by flow cytometry or by next-generation sequencing. Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.
Zelen design clinical trials: why, when, and how
Authors: Simon Gregory E. , Shortreed Susan M. , DeBar Lynn L.
Published: August 2021

Background

In 1979, Marvin Zelen proposed a new design for randomized clinical trials intended to facilitate clinicians’ and patients’ participation. The defining innovation of Zelen’s proposal was random assignment of treatment prior to patient or participant consent. Following randomization, a participant would receive information and asked to consent to the assigned treatment.

Methods

This narrative review examined recent examples of Zelen design trials evaluating clinical and public health interventions.

Results

Zelen designs have often been applied to questions regarding real-world treatment or intervention effects under conditions of incomplete adherence. Examples include evaluating outreach or engagement interventions (especially for stigmatized conditions), evaluating treatments for which benefit may vary according to participant motivation, and situations when assignment to a control or usual care condition might prompt a disappointment effect. Specific practical considerations determine whether a Zelen design is scientifically appropriate or practicable. Zelen design trials usually depend on identifying participants automatically from existing records rather than by advertising, referral, or active recruitment. Assessments of baseline or prognostic characteristics usually depend on available records data rather than research-specific assessments. Because investigators must consider how exposure to treatments or interventions might bias ascertainment of outcomes, assessment of outcomes from routinely created records is often necessary. A Zelen design requires a waiver of the usual requirement for informed consent prior to random assignment of treatment. The Revised Common Rule includes specific criteria for such a waiver, and those criteria are most often met for evaluation of a low-risk and potentially beneficial intervention added to usual care. Investigators and Institutional Review Boards must also consider whether the scientific or public health benefit of a Zelen design trial outweighs the autonomy interests of potential participants. Analysis of Zelen trials compares outcomes according to original assignment, regardless of any refusal to accept or participate in the assigned treatment.

Conclusions

A Zelen design trial assesses the real-world consequences of a specific strategy to prompt or promote uptake of a specific treatment. While such trials are poorly suited to address explanatory or efficacy questions, they are often preferred for addressing pragmatic or policy questions.
Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial
Authors: Venhoff Nils , Schmidt Wolfgang A. , Lamprecht Peter , Tony Hans-Peter , App Christine , Sieder Christian , Legeler Carolin , Jentzsch Claudia , Thiel Jens
Published: August 2021

Background

One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA.

Methods

This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied.

Discussion

The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA.

Trial registration

ClinicalTrials.gov NCT03765788. Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.
Discrepancy between PCR based SARS-CoV-2 tests suggests the need to re-evaluate diagnostic assays
Authors: Mushtaq Muhammad Zain , Shakoor Sadia , Kanji Akbar , Shaheen Najma , Nasir Asghar , Ansar Zeeshan , Ahmed Imran , Mahmood Syed Faisal , Hasan Rumina , Hasan Zahra
Published: August 2021

Objective

We investigated the discrepancy between clinical and PCR-based diagnosis of COVID-19. We compared results of ten patients with mild to severe COVID-19. Respiratory samples from all cases were tested on the Roche SARS-CoV-2 (Cobas) assay, Filmarray RP2.1 (bioMereiux) and TaqPath™ COVID19 (Thermofisher) PCR assays.

Results

Laboratory records of ten patients with mild to severe COVID-19 were examined. Initially, respiratory samples from the patients were tested as negative on the SARS-CoV-2 Roche® assay. Further investigation using the BIOFIRE® Filmarray RP2.1 assay identified SARS-CoV-2 as the pathogen in all ten cases. To investigate possible discrepancies between PCR assays, additional testing was conducted using the TaqPath™ COVID19 PCR. Eight of ten samples were positive for SARS-CoV-2 on the TaqPath assay. Further, Spike gene target failures (SGTF) were identified in three of these eight cases. Discrepancy between the three PCR assays could be due to variation in PCR efficiencies of the amplification reactions or, variation at primer binding sites. Strains with SGTF indicate the presence of new SARS-CoV-2 variant strains. Regular modification of gene targets in diagnostic assays may be necessary to maintain robustness and accuracy of SARS-CoV-2 diagnostic assays to avoid reduced case detection, under-surveillance, and missed opportunities for control.
Lipoprotein lipase hydrolysis products induce pro-inflammatory cytokine expression in triple-negative breast cancer cells
Authors: Tobin Alexandria J. , Noel Nicholas P. , Christian Sherri L. , Brown Robert J.
Published: August 2021

Objectives

Breast cancer cell growth and proliferation requires lipids for energy production, cell membrane synthesis, or as signaling molecules. Lipids can be delivered to cells by lipoprotein lipase (LPL), an extracellular lipase that hydrolyzes triacylglycerols and phospholipids from lipoproteins, that is expressed by adipose tissue and some breast cancer cell lines. Studies have shown that lipoprotein hydrolysis products induce pro-inflammatory cytokine secretion by endothelial cells. Thus, our objective was to determine if hydrolysis products generated by LPL from total lipoproteins can also promote pro-inflammatory cytokine secretion from breast cancer cells.

Results

Using cytokine arrays, we found that MDA-MB-231 cells increased secretion of seven cytokines in response to treatment with lipoprotein hydrolysis products. In contrast, MCF-7 cells showed decreased secretion of two cytokines. Expanding the analysis to additional cell lines by ELISA, we found increased secretion of TNF-α and IL-6 by MDA-MB-468 cells, and increased secretion of IL-4 by MDA-MB-468 and SKBR3 cells. The changes to cytokine secretion profiles of the breast cancer cell types examined, including the non-cancerous MCF-10a breast cells, were independent of increased cell metabolic activity. These results provide information on how lipoprotein hydrolysis products within the tumor microenvironment might affect breast cancer cell viability and progression.
Combination of white matter hyperintensities and Aβ burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort
Authors: Ortega G. , Espinosa A. , Alegret M. , Monté-Rubio GC. , Sotolongo-Grau O. , Sanabria A. , Tartari JP. , Rodríguez-Gómez O. , Marquié M. , Vivas A. , Gómez-Chiari M. , Alarcón-Martín E. , Pérez-Cordón A. , Roberto N. , Hernández I. , Rosende-Roca M. , Vargas L. , Mauleón A. , Abdelnour C. , Esteban De Antonio E. , López-Cuevas R. , Alonso-Lana S. , Moreno-Grau S. , de Rojas I. , Orellana A. , Montrreal L. , Tárraga L. , Ruiz A. , Boada M. , Valero S. ,   FACEHBI group, Aguilera N. , Alonso-Lana S. , Berthier M. , Buendia M. , Bullich S. , Campos F. , Cañabate P. , Cañada L. , Cuevas C. , Diego S. , Gailhajenet A. , García P. , Giménez J. , Gismondi R. , Guitart M. , Ibarria M. , Lafuente A. , Lomeña F. , Masip E. , Martín E. , Martínez J. , Moreno M. , Niñerola A. , Nogales A. B. , Núñez L. , Páez A. , Pancho A. , Pelejà E. , Pérez-Grijalba V. , Perissinotti A. , Pesini P. , Preckler S. , Roé-Vellvé N. , Romero J. , Ramis M. I. , Sarasa M. , Tejero M. A. , Torres M.
Published: August 2021

Background

To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aβ) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD).

Methods

Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI),18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables.

Results

Adjusted multiple linear regression models showed that FreeSurfer (B − .245; 95% CI − .1.676, − .393,p = .016) and β burden (SUVR) (B − .180; 95% CI − 2.140, − .292;p = .070) were associated with face–name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face–name associative performance indicated that those individuals with either higher WMH load or higher Aβ burden showed the worst performance on the face–name associative memory CCs domain score.

Conclusions

Our results suggest that increased WMH load and increased Aβ are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.
Investigating the sex-dependent effects of prefrontal cortex stimulation on response execution and inhibition
Authors: Fehring Daniel J. , Samandra Ranshikha , Haque Zakia Z. , Jaberzadeh Shapour , Rosa Marcello , Mansouri Farshad A.
Published: August 2021

Context-dependent execution or inhibition of a response is an important aspect of executive control, which is impaired in neuropsychological and addiction disorders. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been considered a remedial approach to address deficits in response control; however, considerable variability has been observed in tDCS effects. These variabilities might be related to contextual differences such as background visual-auditory stimuli or subjects' sex. In this study, we examined the interaction of two contextual factors, participants' sex and background acoustic stimuli, in modulating the effects of tDCS on response inhibition and execution. In a sham-controlled and cross-over (repeated-measure) design, 73 participants (37 females) performed a Stop-Signal Task in different background acoustic conditions before and after tDCS (anodal or sham) was applied over the DLPFC. Participants had to execute a speeded response in Go trials but inhibit their response in Stop trials. Participants' sex was fully counterbalanced across all experimental conditions (acoustic and tDCS). We found significant practice-related learning that appeared as changes in indices of response inhibition (stop-signal reaction time and percentage of successful inhibition) and action execution (response time and percentage correct). The tDCS and acoustic stimuli interactively influenced practice-related changes in response inhibition and these effects were uniformly seen in both males and females. However, the effects of tDCS on response execution (percentage of correct responses) were sex-dependent in that practice-related changes diminished in females but heightened in males. Our findings indicate that participants' sex influenced the effects of tDCS on the execution, but not inhibition, of responses.
A detailed analysis of innate and adaptive immune responsiveness upon infection with Salmonella enterica serotype Enteritidis in young broiler chickens
Authors: Meijerink Nathalie , van den Biggelaar Robin H. G. A. , van Haarlem Daphne A. , Stegeman J. Arjan , Rutten Victor P. M. G. , Jansen Christine A.
Published: August 2021

Salmonella entericaserotype Enteritidis (SE) is a zoonotic pathogen which causes foodborne diseases in humans as well as severe disease symptoms in young chickens. More insight in innate and adaptive immune responses of chickens to SE infection is needed to understand elimination of SE. Seven-day-old broiler chickens were experimentally challenged with SE and numbers and responsiveness of innate and adaptive immune cells as well as antibody titers were assessed. SE was observed in the ileum and spleen of SE-infected chickens at 7 days post-infection (dpi). At 1 dpi numbers of intraepithelial cytotoxic CD8+T cells were significantly increased alongside numerically increased intraepithelial IL-2Rα+ and 20E5+ natural killer (NK) cells at 1 and 3 dpi. At both time points, activation of intraepithelial and splenic NK cells was significantly enhanced. At 7 dpi in the spleen, presence of macrophages and expression of activation markers on dendritic cells were significantly increased. At 21 dpi, SE-induced proliferation of splenic CD4+and CD8+T cells was observed and SE-specific antibodies were detected in sera of all SE-infected chickens. In conclusion, SE results in enhanced numbers and activation of innate cells and we hypothesized that in concert with subsequent specific T cell and antibody responses, reduction of SE is achieved. A better understanding of innate and adaptive immune responses important in the elimination of SE will aid in developing immune-modulation strategies, which may increase resistance to SE in young broiler chickens.
Distributed energy-efficient and secure offloading in air-to-ground MEC networks
Authors: Liu Wanning , Xu Yitao , Wu Ducheng , Wang Haichao , Zheng Xueqiang , Chen Xueqiang
Published: August 2021

This paper mainly investigates the energy-efficient and secure offloading problem in air-to-ground Mobile Edge Computing (MEC) networks. The proposed efficient offloading mechanism is as per the requirements of the heterogeneous tasks of ground users. Further, the optimizing offloading rate, offloading object, and channel access jointly formulate system energy consumption and eavesdropping rate minimization. A distributed two-stage offloading scheme is proposed for achieving the sub-optimal solution for the Mixed-integer Nonlinear Programming (MINLP) problem. Finally, simulation results demonstrate that the proposed scheme is superior to several benchmark schemes.
The boundedness of variation associated with the commutators of approximate identities
Authors: Wen Yongming , Hou Xianming
Published: August 2021

In this paper, we establish$L^{p}$Lp-boundedness and endpoint estimates for variation associated with the commutators of approximate identities, which are new for variation operators. As corollaries, we obtain the corresponding boundedness results for variation associated with the commutators of heat semigroups and Poisson semigroups.
Characterization and stability analysis of advanced multi-quadratic functional equations
Authors: Bodaghi Abasalt , Moshtagh Hossein , Dutta Hemen
Published: August 2021

In this paper, we introduce a new quadratic functional equation and, motivated by this equation, we investigaten-variables mappings which are quadratic in each variable. We show that such mappings can be unified as an equation, namely, multi-quadratic functional equation. We also apply a fixed point technique to study the stability for the multi-quadratic functional equations. Furthermore, we present an example and a few corollaries corresponding to the stability and hyperstability outcomes.
Organic and conventional sweetpotato production in the Southeastern of United States: a comparative analysis
Authors: Nwosisi Sochinwechi , Illukpitiya Prabodh , Nandwani Dilip , Arebi Ismail Tubosun , Nwosisi Obinna
Published: August 2021

Background

There has been a piqued interest in alternative agricultural production systems that are environmentally friendly due to concerns on how sustainable it is to grow conventionally. However, in the producer’s point of view, economic returns are an important issue in decision-making in adaptation. The purpose of this study is to assess the economic risk of conventional and organic sweetpotato production in the Southeastern US. The primary and secondary data were used for the analysis. We identified risk variables in stochastic profit function and performed Monte Carlo simulation in analyzing profitability and economic risk of conventional and organic production systems.

Results

Findings from the meta-analysis suggest lower sweetpotato yields and higher selling prices, are to be expected in the organic sweetpotato production systems compared with the conventional. A higher probability of having positive net return from organically grown sweetpotato compared to conventional production systems was observed.

Conclusions

Increase in unit cost leads to a decrease in net profit in both conventional and organic production systems. Sweetpotato price has more effect on net return compared to its yield in conventional production systems. The higher selling price, lower yield and lower unit costs provide a higher net profit return for the organic sweetpotato production systems. Unit cost in conventional production was noted to be higher in general, inferring conventional sweetpotato production could potentially experience a higher variability in net farm income. Despite the high production cost, however, farmers are encouraged to go into sweetpotato production as it appears to be profitable. Further studies should be conducted on conventional treatments without synthetic pesticides and fertilizers as these systems perhaps, may display lower external input costs that might make them more profitable similar to organic systems.
Mental health and quality of life burden in Buruli ulcer disease patients in Ghana
Authors: Amoako Yaw Ampem , Ackam Nancy , Omuojine John-Paul , Oppong Michael Ntiamoah , Owusu-Ansah Abena Gyawu , Boateng Harriet , Abass Mohammed Kabiru , Amofa George , Ofori Elizabeth , Okyere Portia Boakye , Frimpong Michael , Bailey Freddie , Molyneux David Hurst , Phillips Richard Odame
Published: August 2021

Background

Buruli ulcer disease (BUD) is a necrotic skin neglected tropical disease (NTD) that has both a mental and physical health impact on affected individuals. Although there is increasing evidence suggesting a strong association between neglected tropical diseases (NTDs) and mental illness, there is a relative lack of information on BUD’s impact on the mental health and quality of life (QoL) of affected individuals in Ghana. This study is to assess the impact of BUD on mental health and quality of life of patients with active and past BUD infection, and their caregivers.

Methods

We conducted a case control study in 3 BUD endemic districts in Ghana between August and November 2019. Face-to-face structured questionnaire-based interviews were conducted on BUD patients with active and past infection, as well as caregivers of BUD patients using WHO Quality of Life scale, WHO Disability Assessment Schedule, Self-Reporting Questionnaire, Buruli Ulcer Functional Limitation Score and Hospital Anxiety and Depression Scale data tools. Descriptive statistics were used to summarize the characteristics of the study participants. Participant groups were compared using student t test and chi-square (χ2) or Fisher’s exact tests. Mean quality of life scores are reported with their respective 95% confidence intervals. Data was analysed using STATA statistical software.

Results

Our results show that BUD patients with active and past infection, along with their caregivers, face significant levels of distress and mental health sequelae compared to controls. Depression (P = 0.003) was more common in participants with active (27%) and past BU infection (17%), compared to controls (0%). Anxiety was found in 42% (11/26) and 20% (6/29) of participants with active and past BUD infection compared to 14% (5/36) of controls. Quality of life was also significantly diminished in active BUD infection, compared to controls. In the physical health domain, mean QoL scores were 54 ± 11.1 and 56 ± 11.0 (95% CI: 49.5‒58.5 and 52.2‒59.7) respectively for participants with active infection and controls. Similarly in the psychological domain, scores were lower for active infection than controls [57.1 ± 15.2 (95% CI: 50.9‒63.2) vs 64.7 ± 11.6 (95% CI: 60.8‒68.6)]. Participants with past infection had high QoL scores in both physical [61.3 ± 13.5 (95% CI: 56.1‒66.5)] and psychological health domains [68.4 ± 14.6 (95% CI: 62.7‒74.0)].

Conclusions

BUD is associated with significant mental health distress and reduced quality of life in affected persons and their caregivers in Ghana. There is a need for integration of psychosocial interventions in the management of the disease.

Graphic abstract
How and why does the disease progress? A qualitative investigation of the transition into long-standing anorexia nervosa
Authors: Broomfield Catherine , Rhodes Paul , Touyz Stephen
Published: August 2021

Objective

Despite an increased interest in understanding characteristics of long-standing anorexia nervosa (AN), there is a lack of knowledge into the processes that occur with the development and maintenance of the disease. This has impeded the development of novel treatment approaches that may prove more effective than traditional medical models of therapy. To improve the prognosis of these long-standing presentations, an understanding as to how and why the AN disease progresses is required. It was therefore the aim of the current study to investigate the transition of AN from earlier to later stages.

Method

The study adopted a narrative inquiry approach and a total of 11 women with long-standing AN participated in an interview. The newly developed photovoice method assisted in data collection with typologies of chronic illness facilitating the emergence of salient themes.

Results

The qualitative analysis resulted in the identification of five themes: (a) transition, (b) trauma, (c) functionality, (d) identity, and (e) failure of current models of treatment.

Conclusions

Together with identifying key themes, the study provides insight into some possible reasons why current treatment models are failing to promote recovery. Future research examining the effectiveness of treatment that targets underlying causes and maintaining factors of the illness are suggested. Additional education for health professionals is also recommended in order to reduce the trauma that is currently being experienced by some patients with a long-standing illness.
Attenuations of bacterial spot disease Xanthomonas euvesicatoria on tomato plants treated with biostimulants
Authors: da Silva Aminthia Pombo Sudré , Olivares Fábio Lopes , Sudré Cláudia Pombo , Peres Lázaro Eustáquio Pereira , Canellas Natália Aguiar , da Silva Rakiely Martins , Cozzolino Vicenza , Canellas Luciano Pasqualoto
Published: August 2021

Background

The bacterial-spot disease caused by different Xanthomonas species is one of the major tomato diseases that reduce crop production and quality. Pesticides indiscriminate usage has resulted in an increase in resistant bacterial strains as well as contamination of farmers, consumers and the environment. Plant growth-promoting bacteria and humic acids can act as elicitors of plant defence mechanism causing extensive transcriptional and metabolic reprogramming which, in turn, produce a range of plant chemical defences. The purpose of this study was to study how humic acids and plant growth-promoting bacteria, when applied to the substrate, affected the severity of bacterial spot symptoms in tomato leaves.

Materials and methods

One-month-old Micro-Tom tomato (Solanum lycopersicum L.) were transferred to 3 L pots filled with a sterile mixture of sand and vermiculite (2:1, v:v) and treated or not (control) with 250 mL of 4.5 mmol C. L−1 of humic acids, Herbaspirillum seropedicae (108 CFU. mL−1) and the combination of humic acids plus H. seropedicae. One day after substrate treatment, the leaves were inoculated (or not) with X. euvesicatoria (Xe). The area below the disease progression curve based on severity scores and the number of symptomatic leaflets was used to assess phytopathogen virulence. The concentration of oxalic, citric and succinic acids in leaf extracts were determined using HPLC analysis.

Results

Sole or combined H. seropedicae (BAC) and humic acids (HA) application promoted shoot and root growth related to control when plants were challenged with Xe pathogen. For plants inoculated with Xe, more significant plant-growth promotion results were obtained for HA + BAC treatment. The first visible symptoms were observed 16 days after inoculation with 2 × 104 CFU. g−1 of Xe cells in leaves of control plants. HA and BAC applied alone or combined reduced disease severity. Only plants treated with HA were able to reduce disease incidence (number of the leaflets with symptoms). Organic acids, such as oxalic, citric and succinic acids, rose in Xe-inoculated leaves. The reduced amount of organic acids in diseased leaves treated with HA + BAC may be linked to a decrease in disease progression.

Conclusion

Humic acids and H. seropedicae increased growth by modulating the content of organic acids in leaf tissue, attenuating the symptoms of the bacterial spot disease.

Graphic abstract
Management of superficial venous thrombosis based on individual risk profiles: protocol for the development and validation of three prognostic prediction models in large primary care cohorts
Authors: van Royen F. S. , van Smeden M. , Moons K. G. M. , Rutten F. H. , Geersing G. J.
Published: August 2021

Background

Superficial venous thrombosis (SVT) is considered a benign thrombotic condition in most patients. However, it also can cause serious complications, such as clot progression to deep venous thrombosis (DVT) and pulmonary embolism (PE). Although most SVT patients are encountered in primary healthcare, studies on SVT nearly all were focused on patients seen in the hospital setting. This paper describes the protocol of the development and external validation of three prognostic prediction models for relevant clinical outcomes in SVT patients seen in primary care: (i) prolonged (painful) symptoms within 14 days since SVT diagnosis, (ii) for clot progression to DVT or PE within 45 days and (iii) for clot recurrence within 12 months.

Methods

Data will be used from four primary care routine healthcare registries from both the Netherlands and the UK; one UK registry will be used for the development of the prediction models and the remaining three will be used as external validation cohorts. The study population will consist of patients ≥18 years with a diagnosis of SVT. Selection of SVT cases will be based on a combination of ICPC/READ/Snowmed coding and free text clinical symptoms. Predictors considered are sex, age, body mass index, clinical SVT characteristics, and co-morbidities including (history of any) cardiovascular disease, diabetes, autoimmune disease, malignancy, thrombophilia, pregnancy or puerperium and presence of varicose veins. The prediction models will be developed using multivariable logistic regression analysis techniques for models i and ii, and for model iii, a Cox proportional hazards model will be used. They will be validated by internal-external cross-validation as well as external validation.

Discussion

There are currently no prediction models available for predicting the risk of serious complications for SVT patients presenting in primary care settings. We aim to develop and validate new prediction models that should help identify patients at highest risk for complications and to support clinical decision making for this understudied thrombo-embolic disorder. Challenges that we anticipate to encounter are mostly related to performing research in large, routine healthcare databases, such as patient selection, endpoint classification, data harmonisation, missing data and avoiding (predictor) measurement heterogeneity.
Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: together we grow
Authors: Jabeen Shumyla , Arbind Arpana , Kumar Dinesh , Singh Pardeep Kumar , Saini Jitender , Sadashiva Nishanth , Krishna Uday , Arimappamagan Arivazhagan , Santosh Vani , Nagaraj Chandana
Published: August 2021

Purpose

The aim of this study is to compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in identifying recurrence in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition.

Methods

A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax, and SUVmean from the PET images; rCBV from perfusion; and ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0, 1, and 2 representing discordance, < 50% and > 50% concordance respectively.

Results

There were 35 cases of recurrence and 13 cases of post-treatment changes without recurrence. The highest area under curve (AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases.

Conclusion

Amino acid PET had the highest diagnostic accuracy in identifying recurrence in post-treatment gliomas. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.
The Malay’s traditional sweet, dodol: a review of the Malaysia’s heritage delicacy alongside with the rendition of neighbouring countries
Authors: Ismail Norsyahidah , Ab. Karim Muhammad Shahrim , Che Ishak Farah Adibah , Arsyad Mohd Mursyid , Karnjamapratum Supatra , Sirison Jiraporn
Published: August 2021

The Malaysia’s cultural heritage is authentic, unique and colourful with various local cuisines of different races and cultures. It is mainly originated from the Malay culture being the largest ethnic group in the country. The Malays themselves have contributed to many local cuisines ranging from appetiser, soup, main course and dessert. However, some Malay heritage foods have almost been forgotten and jeopardized in quality. This is especially happening to the Malay sweets or desserts which have gradually become less appealing to the younger generations. They are not even familiar with Malay foods, let alone consuming them. Among the popular Malay heritage foods in Malaysia are lemang, ketupat, rendang, wajik and dodol. Dodol specifically has been listed as one of the endangered heritage foods in Malaysia. Preserving the Malay cuisines is part of sustaining the Malay culture and this should begin with a great amount of knowledge and understanding about any elements within the culture itself. This article highlights a nostalgic and evergreen Malay’s traditional sweet, known by the locals as dodol by discussing its history, different types and names of dodol, as well as the recipes, preparation, cooking methods and packaging. Furthermore, this article hopes to aid the readers, especially among the younger generations in the Malay community to have greater understanding and appreciation about their own beautiful culture.
Relaxation behavior in low-frequency complex conductivity of sands caused by bacterial growth and biofilm formation by Shewanella oneidensis under a high-salinity condition
Authors: Joo Hyun-Woo , Kwon Tae-Hyuk , Lee Seung-Rae , Wu Yuxin
Published: August 2021

Complex electrical conductivity is increasingly used to monitor subsurface processes associated with microbial activities because microbial cells mostly have surface charges and thus electrical double layers. Although highly saline environments are frequently encountered in coastal and marine sediments, there are limited data available on the complex conductivity associated with microbial activities under a high-salinity condition. Therefore, we have developed the spectral responses of complex conductivity of sand associated with bacterial growth and biofilm formation under a highly saline condition of approximately 1% salinity and approximately 2 S/m pore water conductivity with an emphasis on relaxation behavior. A column test is performed, in which the model bacteria Shewanella oneidensis MR-1 are stimulated for cell growth and biofilm formation in a sand pack, whereas the complex conductivity is monitored from 0.01 Hz to 10 kHz. The test results indicate that the real conductivity increases in the early stage due to the microbial metabolites and the increased surface conduction with cell growth but soon begin to decrease because of the reduction of charge passages due to bioclogging. However, the imaginary conductivity significantly increases with time, and clear bell-shaped relaxation behaviors are observed with the peak frequency of 0.1–1 Hz, associated with the double-layer polarization of cells and electrically conductive pili and biofilms. The Cole-Cole relaxation model appears to capture such relaxation behaviors well, and the modeling results indicate gradual increases in normalized chargeability and decreases in relaxation time during bacterial growth and biofilm formation in the highly saline condition. Comparison with previous literature confirms that the high-salinity condition further increases the normalized chargeability, whereas it suppresses the phase shift and thus the imaginary conductivity. Our results suggest that the complex conductivity can effectively capture microbial biomass formation in sands under a highly saline condition.
Numerical modeling of seismic responses from fractured reservoirs in 4D monitoring — Part 1: Seismic responses from fractured reservoirs in carbonate and shale formations
Authors: Leviant Vladimir , Marmalevsky Naum , Kvasov Igor , Stognii Polina , Petrov Igor
Published: August 2021

One of the most urgent problems of oil and gas reservoir monitoring is the assessment of fractured reservoir infill type — with fluid-filled, gas-filled, or closed (no-reservoir situation) fractures, which is of significant value for time-lapse seismic technology. We used the grid-characteristic method for numerical modeling of seismic responses from fractured periodic elastoacoustic structures. We consider every single fracture individually (without using the effective medium approach), and we set explicit boundary conditions on fracture surfaces. We assume realistic height-to-thickness ratios — fracture opening (aperture) — equaling three to five orders of magnitude. These techniques make our models as close to real fractured reservoirs as possible. Analyzing the simulated seismic responses, we solve the problem of assessing the fractured reservoir infill type. As a result, previously unknown properties of seismic responses from fractured reservoirs were revealed. We use amplitude variation with offset (AVO) as the main tool for the analysis of the fracture infill type effect on the seismic response in three frequency ranges. Three out of four models exhibit a stable positive AVO gradient regardless of the rock type and frequency range. The analysis of linearized Zoeppritz equations confirms such AVO behavior. We have developed quantitative criteria (indicators) for recognition of a fracture infill type. Amplitude-frequency analysis is shown to expand the capabilities of the infill type recognition. Thus, a method for determining the fractured reservoir infill type is established for carbonate and shale formations, which could become the basis for a new direction in time-lapse technology.
Joint microseismic moment-tensor inversion and location using P- and S-wave diffraction stacking
Authors: Xu Jincheng , Zhang Wei , Liang Xing , Rong Jiaojun , Li Junlun
Published: August 2021

Microseismic location methods based on diffraction stacking, which does not require arrival picking, can yield accurate and reliable source locations for data with a low signal-to-noise ratio. However, due to the complex radiation pattern from a rupturing source, variation in the waveform polarities brings challenges to diffraction stacking-based methods. The current implementations of joint source mechanism inversion and location methods that only use compressional wave (P-wave) amplitudes have limitations in noise resistance and location accuracy. To mitigate those issues, we have developed a new method for joint microseismic moment-tensor inversion and event location using diffraction stacking with P- and S-waves amplitudes, both of which are used to invert for the moment tensor of a microseismic event; then, the inverted moment tensor is used to correct the waveform polarity changes before stacking. In addition, to expedite the large amount of calculations required for moment-tensor inversion at each potential source position and origin time, we develop an optimized grid search scheme and implement the algorithm with GPUs. Our location method does not require manual picking of the first arrivals, and it can automatically detect and locate microseismic events from continuous data. We first validated the method with two synthetic examples, and then we apply it to a surface monitoring data set for hydraulic fracturing at a shale gas well pad in the southern Sichuan Basin, China, where billions of cubic meters of shale gas are being produced annually. The locations of the microseismic events are nicely correlated with the fracturing stages, and the determined source mechanisms are also consistent with the expected fracture growth. Our method is feasible for microseismic surface monitoring with dense nodal arrays and can provide important information for fracture growth and regional stress characterization.