bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectivity of a mHealth intervention for individuals with obesity: a study protocol for a controlled intervention study
Authors: Fritsch Julian , Feil Katharina , Weyland Susanne , Schmidt Detlef , Jekauc Darko
Published: September 2021

Background

Obesity is considered an epidemic problem with an increasing number of individuals affected. The physical and psychological complaints associated with obesity point to the importance of implementing effective interventions. Innovative mHealth applications appear to be promising in helping provide a continuous and flexible support during the intervention. Since research on mHealth interventions is still relatively sparse, the main goal of the current study is to assess the effectiveness of an mHealth obesity intervention in terms of weight reduction, health behaviours as well as health-related quality of life. In addition, the study aims to investigate various psychological explicit and implicit processes associated with physical activity behaviour.

Methods

The study includes quantitative and qualitative methods. Regarding the quantitative methods, the goal is to recruit up to 450 individuals at baseline in different obesity centres across Germany with some of these centres offering an mHealth intervention. All individuals who agree to take part in the mHealth intervention will be assigned to the intervention group, while all other individuals will be assigned to the control group. The mHealth obesity intervention consists of three stays at an obesity centre, with approximately six months between stays during which patients are supported by the digital platform CASPAR. The study includes three measurements with a baseline measurement and two follow-up measurements, one after six months and one after twelve months. To assess the effectiveness of the intervention, body weight, physical activity behaviour, eating behaviour as well as health related quality of life will be assessed. In addition, motivation, intentions, self-efficacy, enjoyment, and habit will be used to assess the psychological processes related with physical activity behaviour. A multivariate analysis of variance with repeated measurement and latent growth curve models will be used to compare the development of the variables within the two groups. In relation to the qualitative methods, interviews with individuals of the intervention group will be conducted to shed light on the applicability, acceptance, and usability of the mHealth intervention.

Discussion

This study may provide a valuable insight into the potential of mHealth obesity interventions and the psychological processes related to physical activity behaviour.

Trial registration The trial has been registered with the German Register of Clinical Studies (DRKS) on June 30, 2021 under the registration number: DRKS00024836.
Hi-C profiling of cancer spheroids identifies 3D-growth-specific chromatin interactions in breast cancer endocrine resistance
Authors: Li Jingwei , Fang Kun , Choppavarapu Lavanya , Yang Ke , Yang Yini , Wang Junbai , Cao Ruifeng , Jatoi Ismail , Jin Victor X.
Published: September 2021

Background

Organoids or spheroids have emerged as a physiologically relevant in vitro preclinical model to study patient-specific diseases. A recent study used spheroids of MCF10 cells to model breast cancer progression and identified targetable alterations more similar to those in vivo. Thus, it is practical and essential to explore and characterize the spheroids of the commonly used human breast cancer (BC) cells.

Methods

In this study, we conducted Hi-C analyses in three-dimensional (3D) spheroids of MCF10A, MCF7 and MCF7TR cells and compared TADs and looping genes with those in 2D monolayers. Furthermore, we performed in silico functional analysis on 3D-growth-specific looping genes and to compare patient outcomes with or without endocrinal therapy. Finally, we performed 3C/RT-qPCR validations in 3D spheroids and 3D-FISH confirmations in organoids of breast cancer patient tissues.

Results

We found that chromatin structures have experienced drastic changes during the 3D culture growth of BC cells although there is not much change in the quantity of chromatin domains. We also observed that the strengths of looping genes were statistically different between 2D monolayers and 3D spheroids. We further identified novel 3D growth-specific looping genes within Hippo relevant pathways, of which two genes showed potential prognostic values in measuring the outcome of the endocrine treatment. We finally confirmed a few selected genes in Hippo relevant pathways with enhanced looping in organoids of breast cancer patient tissues.

Conclusions

Hence, our work has provided significant insights into our understanding of 3D-growth-specific chromatin architecture in tamoxifen-resistant breast cancer. Our analyses suggest that the strengthened looping-mediated Hippo relevant pathways may contribute to endocrine therapy resistance in breast cancer patients.
Salvianolic acid-B improves fat graft survival by promoting proliferation and adipogenesis
Authors: Sun Jia-Ming , Ho Chia-Kang , Gao Ya , Chong Chio-Hou , Zheng Dan-Ning , Zhang Yi-Fan , Yu Li
Published: September 2021

Background

Our previous study proved thatSalvia miltiorrhizacould enhance fat graft survival by promoting adipogenesis. However, the effect of salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound inSalvia miltiorrhiza, on fat graft survival has not yet been investigated.

Objective

This study aims to investigate whether salvianolic acid B could improve fat graft survival and promote preadipocyte differentiation. The underlying mechanism has also been studied.

Methods

In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2 and 4 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the adipogenesis and proliferative activities of salvianolic acid B were analyzed in cultured human adipose-derived stem cells (h-ADSCs) and 3T3-L1 cells to detect the mechanism by which salvianolic acid B affects graft survival.

Results

In vivo, the weights and volumes of the fat grafts in the Sal-B-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity and more viable adipocytes were observed in the Sal-B-treated groups. In vitro, salvianolic acid B showed the ability to promote 3T3-L1 and h-ADSC proliferation and adipogenesis.

Conclusions

Our in vitro experiments demonstrated that salvianolic acid B can promote the proliferation of adipose stem cells and enhance the differentiation of adipose stem cells. Simultaneously, in vivo experiments showed that salvianolic acid B can improve the survival rate of fat transplantation. Therefore, our research shed light on the potential therapeutic usage of salvianolic acid B in improving the survival rate of fat transplantation.
Geometric-algebra affine projection adaptive filter
Authors: Ren Yuetao , Zhi Yongfeng , Zhang Jun
Published: September 2021

Geometric algebra (GA) is an efficient tool to deal with hypercomplex processes due to its special data structure. In this article, we introduce the affine projection algorithm (APA) in the GA domain to provide fast convergence against hypercomplex colored signals. Following the principle of minimal disturbance and the orthogonal affine subspace theory, we formulate the criterion of designing the GA-APA as a constrained optimization problem, which can be solved by the method of Lagrange Multipliers. Then, the differentiation of the cost function is calculated using geometric calculus (the extension of GA to include differentiation) to get the update formula of the GA-APA. The stability of the algorithm is analyzed based on the mean-square deviation. To avoid ill-posed problems, the regularized GA-APA is also given in the following. The simulation results show that the proposed adaptive filters, in comparison with existing methods, achieve a better convergence performance under the condition of colored input signals.
Seroprevalence of coxsackievirus A16 antibody among people of various age groups: a systematic review and meta-analysis
Authors: Li Peng , Chen Yan , Tang An , Gao Fan , Yan Jian-Bo
Published: September 2021

Background

Coxsackie virus group A type 16 (CoxA16) is the main pathogen and usually an alternative to or joins in prevalence with enterovirus 71 (EV71) causing hand, foot and mouth disease (HFMD). The objective of this study was to estimate the seroprevalence of CoxA16 antibody among people of various age groups by a systematic review and meta-analysis.

Methods

The literature of seroprevalence of CoxA16 antibody among people has been systematically searched through databases from the date of their establishment to Jan. 2021. Estimates of seroprevalence of CoxA16 antibody by gender and age groups have been summarized by using fixed- and random- effect models. All analyses have been conducted in STATA version 12.0 software.

Results

A total of 14 publications with 9 in English and 5 in Chinese containing 9562 samples were finally included in the meta-analysis. The seroprevalence of CoxA16 antibody reported in different studies range from 24.85 to 76.92 %. Meta-analysis has revealed that the seroprevalence of CoxA16 antibody was 56.3 % (95 %CI: 47.7 %~64.9 %) in the overall population and 55.1 % (95 %CI: 44.1 %~66.1 %) in the Chinese population. Subgroup analysis by gender has revealed that the seroprevalence of CoxA16 antibody was 56.1 % (95 %CI: 45.2 %~67.1 %) in males and 60.0 % (95 %CI: 50.0 %~69.9 %) in females. Subgroup analysis by age groups has revealed that the seroprevalence of CoxA16 antibody was 49.1 % (95 %CI: 36.2 %~62.0 %) in the 0 ~ 5 age group and 63.9 % (95 %CI: 53.1 %~74.7 %) in the over 5 age group. Begg’s funnel plots have suggested that there were no publication bias in all groups. Sensitive analysis has suggested that the result of the meta-analysis was stable.

Conclusions

The seroprevalence of CoxA16 antibody was closely related to age. Children under 5 years old were the main susceptible groups for CoxA16 and also the key groups for the prevention and control of HFMD.
Management strategy for hematological malignancy patients with acute respiratory failure
Authors: Jiang Li , Wan Qunfang , Ma Hongbing
Published: September 2021

Acute respiratory failure (ARF) is still the major cause of intensive care unit (ICU) admission for hematological malignancy (HM) patients although the advance in hematology and supportive care has greatly improved the prognosis. Clinicians have to make decisions whether the HM patients with ARF should be sent to ICU and which ventilation support should be administered. Based on the reported investigations related to management of HM patients with ARF, we propose a selection procedure to manage this population and recommend hematological ICU as the optimal setting to recuse these patients, where hematologists and intensivists can collaborate closely and improve the outcomes. Moreover, noninvasive ventilation (NIV) still has its own place for selected HM patients with ARF who have mild hypoxemia and reversible causes. It is also crucial to monitor the efficacy of NIV closely and switch to invasive mechanical ventilation at appropriate timing when NIV shows no apparent improvement. Otherwise, early IMV should be initiated to HM with ARF who have moderate and severe hypoxemia, adult respiratory distress syndrome, multiple organ dysfunction, and unstable hemodynamic. More studies are needed to elucidate the predictors of ICU mortality and ventilatory mode for HM patients with ARF.
The incubation period of COVID-19: a global meta-analysis of 53 studies and a Chinese observation study of 11 545 patients
Authors: Cheng Cheng , Zhang DongDong , Dang Dejian , Geng Juan , Zhu Peiyu , Yuan Mingzhu , Liang Ruonan , Yang Haiyan , Jin Yuefei , Xie Jing , Chen Shuaiyin , Duan Guangcai
Published: September 2021

Background

The incubation period is a crucial index of epidemiology in understanding the spread of the emerging Coronavirus disease 2019 (COVID-19). In this study, we aimed to describe the incubation period of COVID-19 globally and in the mainland of China.

Methods

The searched studies were published from December 1, 2019 to May 26, 2021 in CNKI, Wanfang, PubMed, and Embase databases. A random-effect model was used to pool the mean incubation period. Meta-regression was used to explore the sources of heterogeneity. Meanwhile, we collected 11 545 patients in the mainland of China outside Hubei from January 19, 2020 to September 21, 2020. The incubation period fitted with the Log-normal model by the coarseDataTools package.

Results

A total of 3235 articles were searched, 53 of which were included in the meta-analysis. The pooled mean incubation period of COVID-19 was 6.0 days (95% confidence interval [CI] 5.6–6.5) globally, 6.5 days (95% CI 6.1–6.9) in the mainland of China, and 4.6 days (95% CI 4.1–5.1) outside the mainland of China (P = 0.006). The incubation period varied with age (P = 0.005). Meanwhile, in 11 545 patients, the mean incubation period was 7.1 days (95% CI 7.0–7.2), which was similar to the finding in our meta-analysis.

Conclusions

For COVID-19, the mean incubation period was 6.0 days globally but near 7.0 days in the mainland of China, which will help identify the time of infection and make disease control decisions. Furthermore, attention should also be paid to the region- or age-specific incubation period.

Graphic Abstract
A recurrent RYR1 mutation associated with early-onset hypotonia and benign disease course
Authors: Biancalana Valérie , Rendu John , Chaussenot Annabelle , Mecili Helen , Bieth Eric , Fradin Mélanie , Mercier Sandra , Michaud Maud , Nougues Marie-Christine , Pasquier Laurent , Sacconi Sabrina , Romero Norma B. , Marcorelles Pascale , Authier François Jérôme , Gelot Bernabe Antoinette , Uro-Coste Emmanuelle , Cances Claude , Isidor Bertrand , Magot Armelle , Minot-Myhie Marie-Christine , Péréon Yann , Perrier-Boeswillwald Julie , Bretaudeau Gilles , Dondaine Nicolas , Bouzenard Alison , Pizzimenti Mégane , Eymard Bruno , Ferreiro Ana , Laporte Jocelyn , Fauré Julien , Böhm Johann
Published: September 2021

The ryanodine receptor RyR1 is the main sarcoplasmic reticulum Ca2+ channel in skeletal muscle and acts as a connecting link between electrical stimulation and Ca2+-dependent muscle contraction. Abnormal RyR1 activity compromises normal muscle function and results in various human disorders including malignant hyperthermia, central core disease, and centronuclear myopathy. However, RYR1 is one of the largest genes of the human genome and accumulates numerous missense variants of uncertain significance (VUS), precluding an efficient molecular diagnosis for many patients and families. Here we describe a recurrent RYR1 mutation previously classified as VUS, and we provide clinical, histological, and genetic data supporting its pathogenicity. The heterozygous c.12083C>T (p.Ser4028Leu) mutation was found in thirteen patients from nine unrelated congenital myopathy families with consistent clinical presentation, and either segregated with the disease in the dominant families or occurred de novo. The affected individuals essentially manifested neonatal or infancy-onset hypotonia, delayed motor milestones, and a benign disease course differing from classical RYR1-related muscle disorders. Muscle biopsies showed unspecific histological and ultrastructural findings, while RYR1-typical cores and internal nuclei were seen only in single patients. In conclusion, our data evidence the causality of the RYR1 c.12083C>T (p.Ser4028Leu) mutation in the development of an atypical congenital myopathy with gradually improving motor function over the first decades of life, and may direct molecular diagnosis for patients with comparable clinical presentation and unspecific histopathological features on the muscle biopsy.
Assessment of cognitive functions in patients with multiple sclerosis
Authors: Al-Falaki Tara A. , Hamdan Farqad B. , Sheaheed Nawfal M.
Published: September 2021

Background

About 40–70% of patients with multiple sclerosis (MS) develop cognitive impairment (CI) throughout their life. We aim to study the influence of MS on cognitive changes. This is a case–control study of fifty patients with MS who met the revised 2017 Mc Donald Criteria and fifty age- and sex-matched healthy subjects. The Expanded Disability Status Scale (EDSS) was used to assess the degree of disability, and the Montreal Cognitive Assessment (MoCA) scoring system was used to assess cognitive function.

Results

MS patients show low total MoCA score than the controls. Total MoCA scores were lower in patients with CI versus those with intact cognition. CI was higher in those with a longer duration of illness and a high EDSS. MoCA was positively correlated with education level but negatively with EDSS and disease duration.

Conclusion

MoCA scale has optimal psychometric properties for routine clinical use in patients with MS, even in those with mild functional disability. The longer the disease duration and the higher the EDSS, the lower the MoCA score and the higher the education level, the higher the MoCA score. As for the profile of cognitive dysfunction in patients with MS, the domains most frequently failed by the patients were memory, attention, visuospatial learning, and language.
Performance and reaction of faba bean genotypes to chocolate spot disease
Authors: Abdalla M. M. F. , Shafik M. M. , Saleh Heba A. M. A. , Khater M. A. , Ghazy N. A.
Published: September 2021

Background

This study aimed to development new faba bean hybrids resistant to chocolate spot disease and using them in breeding programs. Six faba bean genotypes were crossed in a diallel system excluding reciprocals during three growing seasons of 2017/18, 2018/19 and 2019/20 growing seasons.

Results

Results scored high variability among genotypes (parents and their crosses) in most studied characters. All characters were affected by inbreeding and most crosses recorded high significant in all characters especially the positive significance of resistance to chocolate spot disease (gain) was 5 for all studied resistance characters.

Conclusions

All studied plant growth and yield characters were affected negatively by chocolate spot disease. Moreover, it can be concluded that the commercial cost of producing hybrid seed can be reduced by growing F1 or directly.
The pharmacological treatment of epilepsy: recent advances and future perspectives
Authors: Perucca Emilio
Published: September 2021

The pharmacological armamentarium against epilepsy has expanded considerably over the last three decades, and currently includes over 30 different antiseizure medications. Despite this large armamentarium, about one third of people with epilepsy fail to achieve sustained seizure freedom with currently available medications. This sobering fact, however, is mitigated by evidence that clinical outcomes for many people with epilepsy have improved over the years. In particular, physicians now have unprecedented opportunities to tailor treatment choices to the characteristics of the individual, in order to maximize efficacy and tolerability. The present article discusses advances in the drug treatment of epilepsy in the last 5 years, focusing in particular on comparative effectiveness trials of second-generation drugs, the introduction of new pharmaceutical formulations for emergency use, and the results achieved with the newest medications. The article also includes a discussion of potential future developments, including those derived from advances in information technology, the development of novel precision treatments, the introduction of disease modifying agents, and the discovery of biomarkers to facilitate conduction of clinical trials as well as routine clinical management.
Analytic and numeric analysis for deformation of non-prismatic beams resting on elastic foundations
Authors: Elshabrawy Mohamed , Abdeen Mostafa Ahmed , Beshir Salah
Published: September 2021

Background

The buckling load as well as the natural frequency under axial load for non-prismatic beam is a changeling problem. Determination of buckling load, natural frequency, and elastic deflection is very important in civil applications. The current paper used both perturbation method (PM), analytic method, and differential quadrature method (DQM), numerical method, to find buckling load and natural frequency with different end supports. The deflection of the beam resting on an elastic foundation under transverse distributed and axial loads is also obtained. Both PM and DQM are used for non-prismatic beams with rectangular and circular cross sections in the vibration analysis. The comparisons of results obtained from both PM and DQM showed perfect agreement with analytical solution for uniform beams with different end supports. The PM and DQM succeeded powerfully for investigating the buckling load as well as the natural frequency for non-prismatic beam.

Results

The percentage of relative error between DQM and PM doesn’t exceed than 5% if the gradient of rectangular section height and the gradient of circular section radius are less than 0.6. As the gradient of height and radius increase, the maximum deflection decreases and the location of maximum deflection displaced toward the smaller moment of inertia.

Conclusions

The PM has not been used for solving the problem of non-prismatic beams resting on elastic foundations subjected to transverse distributed and axial loads. The current research proved the good ability of PM as an analytical solution for a complicated problem and defined its range of accuracy as compared to DQM. Also, it introduced accurate empirical formulae to find both natural frequency and buckling load of non-prismatic beams. These empirical formulae represent a good achievement in vibration analysis of non-prismatic beams.
Impact of COVID-19 on vocal cord mobility: a case series study
Authors: Zamzam Sameh M. , Hanafy Rania Gamal
Published: September 2021

Background

The World Health Organization (WHO) has declared the pandemic of COVID-19 infection in March 2020, most of cases presented with mild symptoms, and a significant number of cases showed variable neurological pictures. Vocal cord paralysis with no clear cause is termed as idiopathic vocal cord paralysis and supposed to be caused by viral infection. This is a case series study; data were collected prospectively from patients presented to the ENT clinic of Kasr Alainy (Cairo university) and Railway hospitals. Patients presented with defective vocal cord movement with concurrently or recently passed COVID-19 infection were reported from March 2020 to April 2021.

Results

Authors have reported 6 cases of vocal cord paralysis mainly unilateral due to COVID-19 infection as an only clear cause within 14 months. Age ranges from 39 to 69 years, 2 males and 4 females. Patients presented with different clinical scenarios. Follow-up of the cases showed spontaneous recovery in 5 cases and one case underwent cord medialization.

Conclusion

Viral infection could be an underlying cause of idiopathic laryngeal cord paralysis; in the new era of the COVID-19 pandemic, physicians all over the world noticed variable neurological pictures; in this study, we presented 6 cases of vocal cord paralysis mainly unilateral supposed to be due to COVID-19 infection; all cases showed spontaneous recovery apart from one case that needed medialization of the cord.
Patient, family and provider views of measurement-based care in an early-psychosis intervention programme
Authors: Cuperfain Ari B. , Hui Katrina , Berkhout Suze G. , Foussias George , Gratzer David , Kidd Sean A. , Kozloff Nicole , Kurdyak Paul , Linaksita Brandon , Miranda Dielle , Soklaridis Sophie , Voineskos Aristotle N. , Zaheer Juveria
Published: September 2021

Background

Measurement-based care (MBC) in mental health improves patient outcomes and is a component of many national guidelines for mental healthcare delivery. Nevertheless, MBC is not routinely integrated into clinical practice. Several known reasons for the lack of integration exist but one lesser explored variable is the subjective perspectives of providers and patients about MBC. Such perspectives are critical to understand facilitators and barriers to improve the integration of MBC into routine clinical practice.

Aims

This study aimed to uncover the perspectives of various stakeholders towards MBC within a single treatment centre.

Method

Researchers conducted qualitative semi-structured interviews with patients (n = 15), family members (n = 7), case managers (n = 8) and psychiatrists (n = 6) engaged in an early-psychosis intervention programme. Data were analysed using thematic analysis, informed by critical realist theory.

Results

Analysis converged on several themes. These include (a) implicit negative assumptions; (b) relevance and utility to practice; (c) equity versus flexibility; and (d) shared decision-making. Providers assumed patients’ perspectives of MBC were negative. Patients’ perspectives of MBC were actually favourable, particularly if MBC was used as an instrument to engage patients in shared decision-making and communication rather than as a dogmatic and rigid clinical decision tool.

Conclusions

This qualitative study presents the views of various stakeholders towards MBC, providing an in-depth examination of the barriers and facilitators to MBC through qualitative investigation. The findings from this study should be used to address the challenges organisations have experienced in implementing MBC.
Knockout of Nephron ATP6AP2 Impairs Proximal Tubule Function and Prevents High-Fat Diet-Induced Obesity in Male Mice
Authors: Culver Silas A , Akhtar Safia , Rountree-Jablin Callie , Keller Susanna R , Cathro Helen P , Gildea John J , Siragy Helmy M
Published: September 2021

ATP6AP2 expression is increased in the nephron during high-fat diet (HFD) and its knockout (ATP6AP2 KO) reduces body weight (WT) in mice. We evaluated the contribution of ATP6AP2 to urinary glucose (UG) and albumin (Ualb) handling during HFD. We hypothesized that nephron ATP6AP2 KO increases UG and Ualb and minimizes HFD-induced obesity. Eight-week-old male C57BL/6J mice with inducible nephron-specific ATP6AP2 KO and noninduced controls were fed either normal diet (ND, 12% kcal fat) or HFD (45% kcal fat) for 6 months. ATP6AP2 KO mice on ND had 20% (P < 0.01) lower WT compared with controls. HFD-fed mice had 41% (P < 0.05) greater WT than ND-fed control mice. In contrast, ATP6AP2 KO abrogated the increase in WT induced by HFD by 40% (P < 0.05). Mice on HFD had less caloric intake compared with ND controls (P < 0.01). There were no significant differences in metabolic rate between all groups. UG and Ualb was significantly increased in ATP6AP2 KO mice on both ND and HFD. ATP6AP2 KO showed greater levels of proximal tubule apoptosis and histologic evidence of proximal tubule injury. In conclusion, our results demonstrate that nephron-specific ATP6AP2 KO is associated with glucosuria and albuminuria, most likely secondary to renal proximal tubule injury and/or dysfunction. Urinary loss of nutrients may have contributed to the reduced WT of knockout mice on ND and lack of WT gain in response to HFD. Future investigation should elucidate the mechanisms by which loss of renal ATP6AP2 causes proximal tubule injury and dysfunction.
Atmospheres of Violence
Authors: Stanley Eric A.
Published: September 2021

Advances in LGBTQ rights in the recent past—marriage equality, the repeal of Don't Ask, Don't Tell, and the expansion of hate crimes legislation—have been accompanied by a rise in attacks against trans, queer and/or gender-nonconforming people of color. In Atmospheres of Violence, theorist and organizer Eric A. Stanley shows how this seeming contradiction reveals the central role of racialized and gendered violence in the United States. Rather than suggesting that such violence is evidence of individual phobias, Stanley shows how it is a structuring antagonism in our social world. Drawing on an archive of suicide notes, AIDS activist histories, surveillance tapes, and prison interviews, they offer a theory of anti-trans/queer violence in which inclusion and recognition are forms of harm rather than remedies to it. In calling for trans/queer organizing and worldmaking beyond these forms, Stanley points to abolitionist ways of life that might offer livable futures.
RASSF8-mediated transport of Echinoid via the exocyst promotesDrosophilawing elongation and epithelial ordering
Authors: Chan Eunice H. Y. , Zhou Yanxiang , Aerne Birgit L. , Holder Maxine V. , Weston Anne , Barry David J. , Collinson Lucy , Tapon Nicolas
Published: September 2021

Cell-cell junctions are dynamic structures that maintain cell cohesion and shape in epithelial tissues. During development, junctions undergo extensive rearrangements to drive the epithelial remodelling required for morphogenesis. This is particularly evident during axis elongation, where neighbour exchanges, cell-cell rearrangements and oriented cell divisions lead to large-scale alterations in tissue shape. Polarised vesicle trafficking of junctional components by the exocyst complex has been proposed to promote junctional rearrangements during epithelial remodelling, but the receptors that allow exocyst docking to the target membranes remain poorly understood. Here, we show that the adherens junction component Ras Association domain family 8 (RASSF8) is required for the epithelial re-ordering that occurs during Drosophila pupal wing proximo-distal elongation. We identify the exocyst component Sec15 as a RASSF8 interactor. Loss of RASSF8 elicits cytoplasmic accumulation of Sec15 and Rab11-containing vesicles. These vesicles also contain the nectin-like homophilic adhesion molecule Echinoid, the depletion of which phenocopies the wing elongation and epithelial packing defects observed in RASSF8 mutants. Thus, our results suggest that RASSF8 promotes exocyst-dependent docking of Echinoid-containing vesicles during morphogenesis.
CREB regulates the expression of type 1 inositol 1,4,5-trisphosphate receptors
Authors: Arige Vikas , Terry Lara E. , Malik Sundeep , Knebel Taylor R. , Wagner II Larry E. , Yule David I.
Published: September 2021

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) play a central role in regulating intracellular Ca2+ signals in response to a variety of internal and external cues. Dysregulation of IP3R signaling is the underlying cause for numerous pathological conditions. It is well established that the activities of IP3Rs are governed by several post-translational modifications, including phosphorylation by protein kinase A (PKA). However, the long-term effects of PKA activation on expression of IP3R subtypes remains largely unexplored. In this report, we investigate the effects of chronic stimulation and tonic activity of PKA on the expression of IP3R subtypes. We demonstrate that expression of the type 1 IP3R (IP3R1) is augmented upon prolonged activation of PKA or upon ectopic overexpression of cyclic AMP-response element-binding protein (CREB) without altering IP3R2 and IP3R3 abundance. By contrast, inhibition of PKA or blocking CREB diminished IP3R1 expression. We also demonstrate that agonist-induced Ca2+-release mediated by IP3R1 is significantly attenuated upon blocking of CREB. Moreover, CREB – by regulating the expression of KRAS-induced actin-interacting protein (KRAP) – ensures correct localization and licensing of IP3R1. Overall, we report a crucial role for CREB in governing both the expression and correct localization of IP3R1.

This article has an associated First Person interview with the first author of the paper.
The evolutionary and physiological significance of the Hif pathway in teleost fishes
Authors: Mandic Milica , Joyce William , Perry Steve F.
Published: September 2021

The hypoxia-inducible factor (HIF) pathway is a key regulator of cellular O2 homeostasis and an important orchestrator of the physiological responses to hypoxia (low O2) in vertebrates. Fish can be exposed to significant and frequent changes in environmental O2, and increases in Hif-α (the hypoxia-sensitive subunit of the transcription factor Hif) have been documented in a number of species as a result of a decrease in O2. Here, we discuss the impact of the Hif pathway on the hypoxic response and the contribution to hypoxia tolerance, particularly in fishes of the cyprinid lineage, which includes the zebrafish (Danio rerio). The cyprinids are of specific interest because, unlike in most other fishes, duplicated paralogs of the Hif-α isoforms arising from a teleost-specific genome duplication event have been retained. Positive selection has acted on the duplicated paralogs of the Hif-α isoforms in some cyprinid sub-families, pointing to adaptive evolutionary change in the paralogs. Thus, cyprinids are valuable models for exploring the evolutionary significance and physiological impact of the Hif pathway on the hypoxic response. Knockout in zebrafish of either paralog of Hif-1α greatly reduces hypoxia tolerance, indicating the importance of both paralogs to the hypoxic response. Here, with an emphasis on the cardiorespiratory system, we focus on the role of Hif-1α in the hypoxic ventilatory response and the regulation of cardiac function. We explore the effects of the duration of the hypoxic exposure (acute, sustained or intermittent) on the impact of Hif-1α on cardiorespiratory function and compare relevant data with those from mammalian systems.
DDX3X and DDX3Y are redundant in protein synthesis
Authors: Venkataramanan Srivats , Gadek Margaret , Calviello Lorenzo , Wilkins Kevin , Floor Stephen N.
Published: September 2021

DDX3 is a DEAD-box RNA helicase that regulates translation and is encoded by the X- and Y-linked paralogsDDX3XandDDX3Y. While DDX3X is ubiquitously expressed in human tissues and essential for viability, DDX3Y is male-specific and shows lower and more variable expression than DDX3X in somatic tissues. Heterozygous genetic lesions inDDX3Xmediate a class of developmental disorders called DDX3X syndrome, while loss ofDDX3Yis implicated in male infertility. One possible explanation for female-bias in DDX3X syndrome is thatDDX3Yencodes a polypeptide with different biochemical activity. In this study, we use ribosome profiling and in vitro translation to demonstrate that the X- and Y-linked paralogs of DDX3 play functionally redundant roles in translation. We find that transcripts that are sensitive to DDX3X depletion or mutation are rescued by complementation with DDX3Y. Our data indicate that DDX3X and DDX3Y proteins can functionally complement each other in the context of mRNA translation in human cells. DDX3Y is not expressed in a large fraction of the central nervous system. These findings suggest that expression differences, not differences in paralog-dependent protein synthesis, underlie the sex-bias of DDX3X-associated diseases.
Salivary biomarkers associated with the progression of disease in people living with HIV: A scoping review protocol
Authors: Prasad Priyanka , D’Souza Viola , Mithra Prasanna , Radhakrishnan Raghu
Published: September 2021

Background: Biomarkers are measurable indicators of normal biological processes, which provide an objective assessment of the physiologic state of living systems. Saliva contains several biomarkers that serve as a diagnostic tool in health and disease. Evaluation of a multitude of salivary components could potentially predict the clinical outcome. This is especially critical in a chronic, potentially life-threatening condition like human immunodeficiency virus (HIV) infection. Scrupulous evaluation of relevant biomarkers could facilitate the early detection of HIV, determine the stage of infection and monitor the disease progression. Currently, there is a paucity of validated biomarkers in saliva predicting the disease progression in people living with HIV. In this scoping review, we aim to provide an overview of the available evidence on salivary markers associated with the progression of disease in people living with HIV.

Methods: The authors shall develop a tailored search strategy for each database using relevant keywords. We will search for eligible studies indexed in the following databases: MEDLINE, EMBASE, and the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and gray literature. We will restrict the search to studies published in the English language. Following deduplication, all search results will be exported to the EPPI reviewer web, where two independent reviewers using a data extraction tool developed and pretested by the review authors will screen eligible studies. The result of this review will be reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist and reporting guidelines.

Discussion: The proposed scoping review protocol will enable the identification and assessment of salivary biomarkers, which can predict disease progression in patients with HIV infection. The synthesis of evidence from this review will assist in improving our current understanding of biomarkers used to evaluate the progression of HIV infection.
Case Report: Diabetic nephropathy aggravates the progression and prognosis of COVID-19-associated acute limb ischemia
Authors: Hertanto Decsa M. , Sutanto Henry , Adi Soebagijo
Published: September 2021

Hypercoagulation is a hallmark of both the novel coronavirus disease (COVID-19) and type 2 diabetes mellitus (T2DM). It increases the risk for vascular thrombosis, including peripheral artery diseases. Among others, acute limb ischemia (ALI) is one of most common complications that requires immediate and prompt treatments to reduce morbidity and mortality. However, the complex interplay between COVID-19, T2DM and its complications (e.g., diabetic nephropathy), and ALI creates a great challenge in the management of the disease. Here, we present a case of a 59-year-old diabetic female with progressive pain in her left leg in the last five years, which was significantly intensified following COVID-19 diagnosis. Bluish coloration, numbness and functional impairments were observed during examinations with no palpable pulsation on left posterior tibial and dorsalis pedis arteries. The patient also had diabetic nephropathy (stage III), hypoalbuminemia, anemia and a urinary tract infection that complicated the management of the disease. Due to the excruciating pain and the worsening of the limb conditions, right leg revascularization and left leg amputation were performed at day 14 after admission. Following the surgeries, no more pain was observed and patient was discharged for further follow-up at the outpatient clinic.
The impact of testing and treatment on the dynamics of Hepatitis B virus
Authors: Oludoun Olajumoke , Adebimpe Olukayode , Ndako James , Adeniyi Michael , Abiodun Oluwakemi , Gbadamosi Babatunde
Published: September 2021

Despite the intervention of WHO on vaccination for reducing the spread of Hepatitis B Virus (HBV), there are records of the high prevalence of HBV in some regions. In this paper, a mathematical model was formulated to analyze the acquisition and transmission process of the virus with the view of identifying the possible way of reducing the menace and mitigating the risk of the virus. The models' positivity and boundedness were demonstrated using well-known theorems. Equating the differential equations to zero demonstrates the equilibria of the solutions i.e., the disease-free and endemic equilibrium. The next Generation Matrix method was used to compute the basic reproduction number for the models. Local and global stabilities of the models were shown via linearization and Lyapunov function methods respectively. The importance of testing and treatment on the dynamics of HBV were fully discussed in this paper. It was discovered that testing at the acute stage of the virus and chronic unaware state helps in better management of the virus.
A hybrid recommender system based on data enrichment on the ontology modelling
Authors: Chew Lit-Jie , Haw Su-Cheng , Subramaniam Samini
Published: September 2021

Background: A recommender system captures the user preferences and behaviour to provide a relevant recommendation to the user. In a hybrid model-based recommender system, it requires a pre-trained data model to generate recommendations for a user. Ontology helps to represent the semantic information and relationships to model the expressivity and linkage among the data.

Methods: We enhanced the matrix factorization model accuracy by utilizing ontology to enrich the information of the user-item matrix by integrating the item-based and user-based collaborative filtering techniques. In particular, the combination of enriched data, which consists of semantic similarity together with rating pattern, will help to reduce the cold start problem in the model-based recommender system. When the new user or item first coming into the system, we have the user demographic or item profile that linked to our ontology. Thus, semantic similarity can be calculated during the item-based and user-based collaborating filtering process. The item-based and user-based filtering process are used to predict the unknown rating of the original matrix.

Results: Experimental evaluations have been carried out on the MovieLens 100k dataset to demonstrate the accuracy rate of our proposed approach as compared to the baseline method using (i) Singular Value Decomposition (SVD) and (ii) combination of item-based collaborative filtering technique with SVD. Experimental results demonstrated that our proposed method has reduced the data sparsity from 0.9542% to 0.8435%. In addition, it also indicated that our proposed method has achieved better accuracy with Root Mean Square Error (RMSE) of 0.9298, as compared to the baseline method (RMSE: 0.9642) and the existing method (RMSE: 0.9492).

Conclusions: Our proposed method enhanced the dataset information by integrating user-based and item-based collaborative filtering techniques. The experiment results shows that our system has reduced the data sparsity and has better accuracy as compared to baseline method and existing method.
Johann Peter Ernst von Scheffler (1739–1810). Medyk i mineralog między Gdańskiem a Warszawą
Authors: Banditt Marc
Published: September 2021

Johann Peter Ernst von Scheffler (1739–1810) był jedną z najwybitniejszych osobowości gdańskich XVIII wieku. Ten lekarz o szerokim wachlarzu zainteresowań i rozległej sieci kontaktów doświadczył awansu do najwyższych kręgów uczonych w swoim mieście rodzinnym, zanim wyjechał do Warszawy w 1780 roku. Tam działał w otoczeniu króla, był łącznikiem komunikacyjnym między Warszawą i Gdańskiem oraz podróżował po Polsce jako mineralog.
Polscy uczeni w służbie dyplomacji. Konferencja pokojowa w Paryżu w 1919 roku: ludzie, zadania, dylematy
Authors: Szymczak Damian
Published: September 2021

Polska dyplomacja formowała się jeszcze przed odzyskaniem niepodległości, w okresie I wojny światowej. Jej zaczątki tworzyła powołana do życia w Warszawie w 1917 roku Rada Regencyjna. Jednym z zadań powstającego aparatu władzy były przygotowania na nadchodzącą konferencję pokojową. W tym celu starano się o pozyskanie kompetentnego grona uczonych, którzy weszli przede wszystkim w skład Biura Prac Kongresowych, działającego od 26 listopada 1918 do 1 lipca 1919 roku. Uczeni odegrali istotną rolę w pracach polskiej delegacji podczas konferencji pokojowej w Paryżu, choć nie tak wielką, jak oczekiwali.
Combined Global and Local Search for Optimization with Gaussian Process Models
Authors: Meng Qun , Wang Songhao , Ng Szu Hui
Published: September 2021

Gaussian process (GP) model based optimization is widely applied in simulation and machine learning. In general, it first estimates a GP model based on a few observations from the true response and then uses this model to guide the search, aiming to quickly locate the global optimum. Despite its successful applications, it has several limitations that may hinder its broader use. First, building an accurate GP model can be difficult and computationally expensive, especially when the response function is multimodal or varies significantly over the design space. Second, even with an appropriate model, the search process can be trapped in suboptimal regions before moving to the global optimum because of the excessive effort spent around the current best solution. In this work, we adopt the additive global and local GP (AGLGP) model in the optimization framework. The model is rooted in the inducing points based GP sparse approximations and is combined with independent local models in different regions. With these properties, the AGLGP model is suitable for multimodal responses with relatively large data sizes. Based on this AGLGP model, we propose a combined global and local search for optimization (CGLO) algorithm. It first divides the whole design space into disjoint local regions and identifies a promising region with the global model. Next, a local model in the selected region is fit to guide detailed search within this region. The algorithm then switches back to the global step when a good local solution is found. The global and local natures of CGLO enable it to enjoy the benefits of both global and local search to efficiently locate the global optimum.

Summary of Contribution: This work proposes a new Gaussian process based algorithm for stochastic simulation optimization, which is an important area in operations research. This type of algorithm is also regarded as one of the state-of-the-art optimization algorithms for black-box functions in computer science. The aim of this work is to provide a computationally efficient optimization algorithm when the baseline functions are highly nonstationary (the function values change dramatically across the design space). Such nonstationary surfaces are very common in reality, such as the case in the maritime traffic safety problem considered here. In this problem, agent-based simulation is used to simulate the probability of collision of one vessel with the others on a given trajectory, and the decision maker needs to choose the trajectory with the minimum probability of collision quickly. Typically, in a high-congestion region, a small turn of the vessel can result in a very different conflict environment, and thus the response is highly nonstationary. Through our study, we find that the proposed algorithm can provide safer choices within a limited time compared with other methods. We believe the proposed algorithm is very computationally efficient and has large potential in such operational problems.
FairPlay: Detecting and Deterring Online Customer Misbehavior
Authors: Wu Ji , Zheng Zhiqiang (Eric) , Zhao J. Leon
Published: September 2021

This study examines how firms can detect and manage customer misbehavior in online brand communities. We first develop a data science approach to detect customer misbehavior on social media and devise intervention strategies to deter it. Our design science approach achieves superior performance, improving detection by 7%–9% compared with traditional methods. We then implement two types of intervention policies based on injunctive (i.e., a punishment policy) and descriptive norms (i.e., a common identity policy) to restrain customer misbehavior. The results of field experiments indicate that punishment considerably reduces customer misbehavior in the short term, but this effect decays over time, whereas common identity has a smaller but more persistent effect on misbehavior reduction. In addition, punishing dysfunctional customers decreases their purchase frequency, whereas imposing a common identity increases it. Our results also show that combining the two policies effectively alleviates the detrimental effect of punishment, especially in the long run.
Ovarian abscessation and oophoritis in a first lactation dairy cow: a case report
Authors: Charles David , Wyse Victoria , Waine Katie , Wessels Mark
Published: September 2021

A 28-month-old first lactation dairy cow presented as ‘oestrus not observed’ and transrectal ultrasound showed a hyperechoic mass on the right ovary. The mass continued to grow despite treatment, and 8 weeks later a right-sided ovariectomy was performed. A single, large, cavitated mass was found on gross pathological examination with histopathology confirming ovarian abscessation and oophoritis, a rare condition in cattle.