bluuebunny/crossref_metadata_2025 huggingface dataset:
A long‐acting GDF15 analog causes robust, sustained weight loss and reduction of food intake in an obese nonhuman primate model
Authors: Zheng Songmao , Polidori David , Wang Yuanping , Geist Brian , Lin‐Schmidt Xiefan , Furman Jennifer L. , Nelson Serena , Nawrocki Andrea R. , Hinke Simon A.
Published: May 2023

Growth Differentiation Factor‐15 (GDF15) is a circulating polypeptide linked to cellular stress and metabolic adaptation. GDF15's half‐life is ~3 h and activates the glial cell line‐derived neurotrophic factor family receptor alpha‐like (GFRAL) receptor expressed in the area postrema. To characterize sustained GFRAL agonism on food intake (FI) and body weight (BW), we tested a half‐life extended analog of GDF15 (Compound H [CpdH]) suitable for reduced dosing frequency in obese cynomolgus monkeys. Animals were chronically treated once weekly (q.w.) with CpdH or long‐acting GLP‐1 analog dulaglutide. Mechanism‐based longitudinal exposure‐response modeling characterized effects of CpdH and dulaglutide on FI and BW. The novel model accounts for both acute, exposure‐dependent effects reducing FI and compensatory changes in energy expenditure (EE) and FI occurring over time with weight loss. CpdH had linear, dose‐proportional pharmacokinetics (terminal half‐life ~8 days) and treatment caused exposure‐dependent reductions in FI and BW. The 1.6 mg/kg CpdH reduced mean FI by 57.5% at 1 week and sustained FI reductions of 31.5% from weeks 9–12, resulting in peak reduction in BW of 16 ± 5%. Dulaglutide had more modest effects on FI and peak BW loss was 3.8 ± 4.0%. Longitudinal modeling of both the FI and BW profiles suggested reductions in BW observed with both CpdH and dulaglutide were fully explained by exposure‐dependent reductions in FI without increase in EE. Upon verification of the pharmacokinetic/pharmacodynamic relationship established in monkeys and humans for dulaglutide, we predicted that CpdH could reach double digit BW loss in humans. In summary, a long‐acting GDF15 analog led to sustained reductions in FI in overweight monkeys and holds potential for effective clinical obesity pharmacotherapy.
Superficial CD34 fibroblastic tumors and PRDM10‐rearranged soft tissue neoplasm: An evolving diagnosis
Authors: Johnson Cassandra , Parsa Leila , Gibbs Julie , Sligh James
Published: May 2023

Superficial CD34 fibroblastic tumors (SCD34FT) and PRDM10‐rearranged tumors (PRTs) are mesenchymal tumors that have recently received increased scientific attention due to their irrefutable similarities yet debatable relationship. A 74‐year‐old male presented to the dermatology clinic with a violaceous, well‐defined nodule on the left medial knee of 2‐year duration. Shave biopsy demonstrated spindle cells arranged in a vaguely storiform pattern forming fascicles. Immunohistochemical stains were positive for vimentin, CD68, CD10, and CD34 diffusely. ERG, S‐100, HMB45, and SOX‐10 were negative. Molecular studies identified a mediator complex subunit 12 (MED12)‐PR/SET Domain 10 (PRDM10) gene fusion thus favoring confirming the diagnosis of a PRT. Our patient underwent wide local excision with negative margins and had no complications. This case aims to provide context for considering SCD34FT and PRT as intersecting entities and to discuss a diagnostic approach when encountering these tumors.
Experiences of children and adolescents with attention‐deficit/hyperactivity disorder taking methylphenidate
Authors: Jacobs Delphine
Published: May 2023

To improve clinical counselling for adolescents about the use of stimulant medication, it is crucial to understand the experiences of young people diagnosed with attention‐deficit/hyperactivity disorder (ADHD) who are taking such treatment. For this narrative review, five databases were searched for studies investigating the personal experiences of control issues in adolescents diagnosed with ADHD taking methylphenidate. We extracted the data using NVivo 12 and interpretatively synthesized them according to the procedures of thematic analysis. Interviewed youngsters spontaneously put forward self‐experiences about self‐esteem and sense of control, although these issues were rarely explicitly addressed in the research question. The overarching theme in these studies was ‘improving the self’. Two subthemes emerged: (1) medication sometimes delivered on its promise to improve the self, but regularly it did not; and (2) youngsters felt pressurized to conform to behavioural norms and comply with the medication use that adults had decided on. To genuinely involve youngsters diagnosed with ADHD for whom stimulant medication is prescribed in the shared decision‐making process, we recommend to specifically involve them in a dialogue on the medication's potential effects on their self‐experiences. This will allow them to feel at least partly in control of their body and life, and less pressurized to conform to others' norms.
General population screening for paediatric type 1 diabetes—A qualitative study of UK professional stakeholders
Authors: Quinn Lauren M. , Narendran Parth , Randell Matthew J. , Bhavra Kirandeep , Boardman Felicity , Greenfield Sheila M. , Litchfield Ian
Published: May 2023

Aims

Identifying children at risk of type 1 diabetes allows education for symptom recognition and monitoring to reduce the risk of diabetic ketoacidosis at presentation. We aimed to explore stakeholder views towards paediatric general population screening for type 1 diabetes in the United Kingdom (UK).

Methods

Qualitative interviews were undertaken with 25 stakeholders, including diabetes specialists, policymakers and community stakeholders who could be involved in a future type 1 diabetes screening programme in the UK. A thematic framework analysis was performed using the National Screening Committee's evaluative criteria as the overarching framework.

Results

Diabetic ketoacidosis prevention was felt to be a priority and proposed benefits of screening included education, monitoring and helping the family to better prepare for a future with type 1 diabetes. However, diabetes specialists were cautious about general population screening because of lack of evidence for public acceptability. Concerns were raised about the harms of living with risk, provoking health anxiety and threatening the child's right to an ‘open future’. Support systems that met the clinical and psychological needs of the family living with risk were considered essential. Stakeholders were supportive of research into general population screening and acknowledged this would be a priority if an immunoprevention agent were licensed in the UK.

Conclusions

Although stakeholders suggested the harms of UK paediatric general population screening currently outweigh the benefits, this view would potentially be altered if prevention therapies were licensed. In this case, an evidence‐based screening strategy would need to be formulated and public acceptability explored.
Systematic review of the barriers and facilitators to dietary modification in people living with type 2 diabetes and pre‐diabetes from South Asian ethnic populations
Authors: Rai Amar , Misra Rohan , Khan Hasaan , Shukla Shivani , Patel Dipesh C. , Brown Adrian
Published: May 2023

Aims

Lifestyle and dietary modification are effective in the prevention and management of Type 2 diabetes Mellitus (T2DM). However, South Asian (SA) populations living in Western countries have low adherence rates to healthcare advice and experience poor diabetes control and clinical outcomes compared with the general population. This systematic review aimed to summarise the barriers and facilitators of dietary modification within people from South Asian (SA) ethnicity with T2DM or pre‐diabetes.

Methods

A systematic search of PubMed, Web of Science and Scopus generated 3739 articles, of which seven were included. Qualitative and quantitative data were inputted utilising COVIDENCE. Qualitative data were analysed by thematic analysis.

Results

Thematic analysis identified three facilitators: (1) cultural sensitivity, (2) health education and (3) support networks. Barriers include (1) healthcare inequity, (2) cultural insensitivity, (3) social pressures, (4) misconceptions and (5) time constraints. Good access to health care and motivation were the most common facilitators discussed. Misconceptions on T2DM management and cultural insensitivity contributed to the majority of barriers discussed.

Conclusions

Culturally tailored interventions could improve adherence to diet modification in people with T2DM from SA ethnicity. Interventions involving the application of social media to challenge intergenerational stigmas and misinformation, distributing culturally appropriate resources and providing diets tailored to the SA palate could help.
Non‐lesional treatments for tremor in Parkinson's disease: A systematic review and meta‐analysis
Authors: Pedrosa Anna J. , Waldthaler Josefine , Mügge Felicitas , Timmermann Lars , Pedrosa David J.
Published: May 2023

Introduction

Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non‐lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta‐analysis assessing the efficacy/effectiveness and safety of non‐lesional treatments for tremor in iPD.

Methods

Three electronic databases were searched using a combination of title/abstract keywords complemented by hand‐searching of reference lists. A random‐effects meta‐analysis of standardized mean change scores was conducted where appropriate.

Results

Some 114 studies met inclusion criteria involving 8045 patients. The meta‐analysis revealed an overall reduction of standardized mean change scores by (−0.93 [CI: −1.42; −0.43], p < 0.001) by 14 different dopaminergic and non‐dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non‐pharmacological interventions for tremor, except for electrical stimulation.

Conclusions

The results of this meta‐analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high‐quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non‐lesional treatments in cases with refractory tremor is lacking.
Respiratory symptoms are common in stiff person syndrome spectrum disorders and are associated with number of body regions involved
Authors: Pimentel Maldonado Daniela A. , Balshi Alexandra , Hu Chen , Fitzgerald Kathryn C. , Koshorek Jacqueline , Reyes‐Mantilla Maria I. , Obando Danielle , Wang Yujie , Newsome Scott D.
Published: May 2023

Background and purpose

Stiff person syndrome (SPS) spectrum disorders (SPSSD) cause spasms and rigidity throughout different body regions and can be associated with apnea and acute respiratory failure. There are limited data on the prevalence and predictors of respiratory symptoms with spasms (RSwS) in SPSSD. We sought to characterize the spirometry patterns and the frequency and predictors of RSwS in a large SPSSD cohort.

Methods

Participants were recruited from the Johns Hopkins SPS Center between 1997 and 2021, as part of an ongoing, longitudinal observational study. Medical records were reviewed to assess demographics and clinical characteristics. Data were analyzed using descriptive statistics and multivariable logistic regression models.

Results

One‐hundred ninety‐nine participants (mean age = 53.4 ± 13.6 years, median time to diagnosis = 36 [IQR 66] months, 74.9% women, 69.8% White, 62.8% classic SPS phenotype) were included in final analyses; 35.2% of participants reported RSwS, of whom 24.3% underwent spirometry as part of routine clinical care. Obstructive (23.5%) and restrictive (23.5%) patterns were most commonly observed in those with SPSSD. An increasing number of body regions involved predicted the presence of RSwS (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.50–2.53); those with ≥5 body regions involved (vs. ≤4) had higher odds (OR = 6.19, 95% CI = 2.81–13.62) of experiencing RSwS in adjusted models. Two patients died from SPSSD‐associated respiratory compromise.

Conclusions

RSwS are common in SPSSD and may be predicted by an increasing number of body regions involved by SPSSD. Close clinical monitoring and having a low threshold to obtain spirometry should be considered in people with SPSSD.
Etiologic distribution of isolated abducens nerve palsy: Analysis of 807 patients and literature review
Authors: Kim Hyun‐Jae , Kim Hyo‐Jung , Choi Jeong‐Yoon , Yang Hee Kyung , Hwang Jeong‐Min , Kim Ji‐Soo
Published: May 2023

Background and Purpose

The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated abducens nerve palsy by recruiting patients from all departments in a referral‐based university hospital.

Methods

We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies.

Results

The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes.

Conclusions

The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.
Antibody response elicited by the SARS‐CoV‐2 vaccine booster in patients with multiple sclerosis: Who gains from it?
Authors: Schiavetti Irene , Inglese Matilde , Frau Jessica , Signoriello Elisabetta , Caleri Francesca , Stromillo Maria Laura , Ferrò Maria Teresa , Rilla Maria Teresa , Gandoglia Ilaria , Gazzola Paola , Brichetto Giampaolo , Pasquali Livia , Grimaldi Luigi , Ulivelli Monica , Marinelli Fabiana , Cordera Susanna , Clerico Marinella , Conte Antonella , Salvetti Marco , Battaglia Mario Alberto , Franciotta Diego , Uccelli Antonio , Sormani Maria Pia ,   CovaXiMS Study Group
Published: May 2023

Background and purpose

Although two doses of COVID‐19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease‐modifying therapies (DMTs) showed less efficient responses.

Methods

This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS.

Results

Four hundred seventy‐three pwMS were analyzed. Compared to untreated patients, there was a 50‐fold decrease (95% confidence interval [CI] = 14.3–100.0, p < 0.001) in serum SARS‐CoV‐2 antibody levels in those on rituximab, a 20‐fold decrease (95% CI = 8.3–50.0, p < 0.001) in those on ocrelizumab, and a 2.3‐fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti‐CD20 drugs rituximab and ocrelizumab showed a 2.3‐fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7‐fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs.

Conclusions

All pwMS increased their serum SARS‐CoV‐2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff.
Decreasing incidence of stroke, ischaemic heart disease and dementia in Norway, 1990–2019, a Global Burden of Disease study: an opportunity
Authors: Avan Abolfazl , Aamodt Anne Hege , Selbæk Geir , Bovim Gunnar , Bassetti Claudio L. A. , Boon Paul , Grisold Wolfgang , Hachinski Vladimir
Published: May 2023

Background and purpose

The declining incidence of stroke, ischaemic heart disease (IHD) and dementia (the ‘triple threat’) in Norway encourages further investigation. The risks and trends of the three conditions were analysed using data from the Global Burden of Disease study.

Methods

Global Burden of Disease 2019 estimations were used for age‐, sex‐ and risk‐factor‐specific incidence and prevalence of the ‘triple threat’, their risk‐factor‐attributed deaths and disability combined, their age‐standardized rates per 100,000 population in 2019 and their changes during 1990–2019. Data are presented as means and 95% uncertainty intervals.

Results

In 2019, 71.1 thousand Norwegians were living with dementia, 157.2 thousand with IHD and 95.2 thousand with stroke. In 2019, there were 9.9 thousand (8.5 to 11.3) new cases of dementia (35.0% increase since 1990), 17.0 thousand (14.6 to 19.6) with IHD (3.6% decrease) and 8.0 thousand (7.0 to 9.1) with stroke (12.9% decrease) in Norway. During 1990–2019, their age‐standardized incidence rates decreased significantly—dementia by −5.4% (−8.4% to −3.2%), IHD by −30.0% (−31.4% to −28.6%) and stroke by −35.3% (−38.3% to −32.2%). There were significant declines in the attributable risks to both environmental and behavioural factors in Norway, but contradictory trends for metabolic risk factors during 1990–2019.

Conclusions

The risk of the ‘triple threat’ conditions is declining in Norway, despite the increased prevalence. This offers the opportunity to find out why and how and to accelerate their joint prevention through new approaches and the promotion of the National Brain Health Strategy.
University research by the numbers: Epistemic methods of using digitized performance measures and their implications for research practices
Authors: Mauro Sara Giovanna , Cinquini Lino , Malmmose Margit , Nørreklit Hanne
Published: May 2023

This paper explores the way by which universities create meaning of digitized performance measures on research quality and their effects on university scholars’ actions. Drawing on pragmatic constructivism, we scrutinize the epistemic methods by which the digitized performance measures of research quality are handled and used in the governance of research activities in two disciplinary fields in two university settings (Denmark and Italy) and their implications for constructing scholarly research practices. The analysis elucidates exemplars of two epistemic methods of building meaning of and using digitized performance measures: one reflective and interactive, and one authoritative and mechanical. The latter constrains the researchers’ scholarly reasoning and communication and, hence, infringes upon the scholarly fundamentals of university practices. The paper concludes that if the issues of misconceptions of research quality related to the transitions from analog to digital language are neglected, the digital transformation results in dysfunctional human and social practices.
Influence of diabetes mellitus and effectiveness of metformin on hepatocellular carcinoma
Authors: Ono Masafumi , Fujita Koji , Kobayashi Kiyoyuki , Masaki Tsutomu
Published: May 2023

Hepatocellular carcinoma (HCC) is one of the most common cancers, and it is important to elucidate the carcinogenic factors and improve the recurrence and prognosis of HCC patients. Diabetes mellitus (DM) has been reported to be a risk factor for the carcinogenesis of many cancers including HCC, and the mechanism of DM for carcinogenesis is gradually being elucidated. Metformin, a drug for DM, has been reported to have anticancer effects on many cancers, including HCC. Metformin not only suppresses carcinogenesis but also improves the prognosis of recurrence after treatment, and there are many reports on the mechanism of these effects. In this review, we describe the mechanism of action of hyperglycemia and hyperinsulinemia on carcinogenesis by DM against HCC. The carcinogenic effects of DM on hepatitis B, hepatitis C, and nonalcoholic fatty liver disease by etiology are also described. In addition, the carcinogenic effect of metformin on HCC and its mechanism of action are reviewed. We also discuss the effects of metformin on recurrence after hepatectomy and radiofrequency therapy and the effects of metformin in combination with anticancer medicine, focusing on the inhibition of HCC development.
Pocket closure in stage III–IV grade C periodontitis: A multilevel analysis following non‐surgical periodontal therapy
Authors: Citterio Filippo , Kanmaz Burcu , Baima Giacomo , Romano Federica , Buduneli Nurcan , Aimetti Mario
Published: May 2023

Background

Risk of disease progression and tooth loss is higher in cases where deep probing pocket depths (PPDs) and bleeding on probing (BOP) persist after active periodontal treatment. This study aimed to investigate the efficacy of non‐surgical periodontal therapy on pocket closure (PC), defined as PPD ≤4 mm without BOP (PC1) or PPD ≤4 mm solely (PC2) 3 months after non‐surgical periodontal treatment and to compare PC between smokers and non‐smokers.

Methods

This cohort study is a secondary analysis from a controlled clinical trial consisting of systemically healthy patients with stage III or IV grade C periodontitis. All the sites with baseline PPD ≥5 mm are included as diseased sites and PC at 3 months after completion of non‐surgical periodontal treatment was calculated. PC was compared between smokers and non‐smokers at site and patient levels. Multilevel analysis is used to investigate factors at patient, tooth and site levels affecting PPD changes and the probability of PC.

Results

A total of 1998 diseased sites in 27 patients were included in the analysis. The rates of PC1 and PC2 were 58.4% and 70.2% and were significantly correlated to smoking habits at site level (r (1) = 7.03, p = 0.008; r (1) = 36.17, p < 0.001). Tooth type, mobility, clinical attachment level (CAL) and PPD at baseline significantly affected PC.

Conclusions

The present findings indicate that non‐surgical periodontal treatment is effective in PC, but its performance is influenced by baseline PPD and CAL and residual pockets may remain.
Von Willebrand factor testing ratios in the diagnosis and subtyping of von Willebrand disease
Authors: Smock Kristi J.
Published: May 2023

Von Willebrand disease (VWD) is a common bleeding disorder of platelet adhesion with six currently recognized subtypes. Laboratory diagnosis consists of an initial test panel including antigen, activity and factor VIII measurements, sometimes followed by further specialized testing. VWF activity/antigen testing ratios help to differentiate type 1 and type 2 disease, which is important for selection of proper therapy. Recommended ratio cutoffs differ by guideline, ranging from 0.5 to 0.7, with 0.7 commonly recommended. The ratio cutoff used affects the sensitivity and specificity for type 2 diagnosis. Variability in VWD due to underlying mutations and patient factors, as well as variability in VWF tests, impact the accuracy of ratios for VWD subtyping. This review discusses the use of activity/antigen ratios in the diagnosis and subtyping of VWD with a focus on technical aspects of the tests.
Suicidality and mood disorders in psychiatric emergency patients: Results from SBQ‐R
Authors: Brousseau‐Paradis Camille , Lesage Alain , Larue Caroline , Labelle Réal , Giguère Charles‐Édouard , Rassy Jessica ,   with the collaboration of the Signature Consortium
Published: May 2023

Patients with mood disorders are at high risk of suicidality, and emergency departments (ED) are essential in the management of this risk. This study aims to (1) describe the suicidal thoughts and behaviours of patients with mood disorders who come to ED; (2) assess the psychometric properties of the Suicidal Behaviours Questionnaire‐Revised (SBQ‐R) in a psychiatric ED; and (3) determine the best predictors of suicidality for these patients. A total of 300 participants with mood disorders recruited for the Signature Bank of the Institut universitaire en santé mentale de Montréal (IUSMM) were retained. Suicidality was assessed using the SBQ‐R. Other clinical and demographic details were recorded. Bivariate analyses, correlations and multivariate regression analyses were conducted. SBQ‐R's internal consistency, construct and convergent validities were also tested. In the Patient Health Questionnaire‐9 (PHQ‐9), 53.3% of the sample stated they had suicidal or self‐harm thoughts in the last 2 weeks. The mean score obtained at the SBQ‐R was 8.3. Multivariate analysis found that SBQ‐R scores were associated with depressive symptoms and substance use, especially alcohol, accounting for 44.3% of the model variance. Cronbach's alpha was 0.81 [0.78, 0.84] and factor loadings for items 1–4 were 0.68, 0.88, 0.54, and 0.85, respectively. The confirmatory factor analysis indicated that the model fit the data well. The SBQ‐R is a brief and valid instrument that can easily be used in busy emergency departments to assess suicide risk. Depressive symptoms and alcohol use shall also be assessed, as they are determinants of increased risk of suicidality.
Psychological outcomes of local heritage engagement: Participation in community archeological excavations increases well‐being, self‐efficacy, and perceived community support
Authors: Brizi Ambra , Rabinovich Anna , Lewis Carenza
Published: May 2023

There is evidence that engagement with tangible heritage is linked to improvements in well‐being. However, experimental tests of this association, as well as theoretical accounts explaining this relationship, are lacking. The present study aims to compensate for this gap by developing a theoretical framework based on the social identity approach that explains the effect of community‐based heritage engagement on well‐being, and testing this effect in a quasi‐experimental field study in the context of community test pit archeological excavations. In line with the predictions, the results demonstrate that excavation participants (but not participants in the control condition) report improvements on a number of psychological outcomes after (as compared to before) participation in a 2‐day excavation program (including well‐being, self‐efficacy, and perceived community support). The findings offer implications for community‐based approaches to enhancing well‐being, as well as the practice of conducting community‐based archeological excavations.
Apoptotic effect and cell arrest of deoxyshikonin in human osteosarcoma cells through the p38 pathway
Authors: Hsieh Ming‐Chang , Hsieh Yi‐Hsien , Chou Chia‐Hsuan , Yang Jia‐Sin , Lu Peace Wun‐Ang , Huang Tzu‐Yu , Yang Shun‐Fa , Lu Ko‐Hsiu
Published: May 2023

Osteosarcoma is the most common primary bone cancer that affects adolescents with early metastatic potential and drastically reduces their long‐term survival rate if pulmonary metastases are detected at diagnosis. The natural naphthoquinol compound deoxyshikonin exhibits anticancer properties, so we hypothesized that it has an apoptotic effect on osteosarcoma U2OS and HOS cells and studied its mechanisms. After deoxyshikonin treatment, dose‐dependent decreases in cell viability, induction of cell apoptosis and arrest in the sub‐G1 phase of U2OS and HOS cells were observed. The increases in cleaved caspase 3 expression and the decreases in X‐chromosome‐linked IAP (XIAP) and cellular inhibitors of apoptosis 1 (cIAP‐1) expressions after deoxyshikonin treatment in the human apoptosis array were identified in HOS cells, and dose‐dependent expression changes of IAPs and cleaved caspase 3, 8 and 9 were verified by Western blotting in U2OS and HOS cells. Phosphorylation of extracellular signal‐regulated protein kinases (ERK)1/2, c‐Jun N‐terminal kinases (JNK)1/2 and p38 expressions in U2OS and HOS cells was also increased by deoxyshikonin in a dose‐dependent manner. Subsequently, cotreatment with inhibitors of ERK (U0126), JNK (JNK‐IN‐8) and p38 (SB203580) was performed to show that p38 signalling is responsible for deoxyshikonin‐induced apoptosis in U2OS and HOS cells, but not via the ERK and JNK pathways. These discoveries demonstrate that deoxyshikonin may be a possible chemotherapeutic candidate to induce cell arrest and apoptosis by activating extrinsic and intrinsic pathways through p38 for human osteosarcoma.
Numerical and experimental investigation of flow and heat transfer in a fixed bed of non‐spherical grains using the DEM‐CFD method
Authors: Liu Wenlei , Chen Guixiang , Zheng Deqian , Ge Mengmeng , Liu Chaosai
Published: May 2023

Fixed‐bed drying of grains is a widely used method for determining temperature and humidity changes and pressure drop characteristics during aeration. In this study, an accurate particle‐resolved computational fluid dynamics (CFD) numerical model was developed to investigate the flow and heat transfer in fixed beds of soybean, wheat, and maize grains. A randomly filled non‐spherical grain fixed bed structure was generated using the discrete element method (DEM), and the contact areas between the packed particles are automated. The distribution of grain particles near the wall surface was approximately circular, and the circle became more regular with increase grain sphericity. Compared with the fixed beds of soybean and maize, there was no significant stratification in the fixed beds of wheat, and the difference between the peaks and troughs of porosity oscillations was smaller. Detailed particle‐resolved CFD simulations of the flow and heat transfer in fixed beds with different grains were performed. The results showed that the pressure drop results of the DEM–CFD simulation of different grain shapes were in good agreement with the Nemec–Levec equation and experimental results. The velocity and temperature distribution in the fixed bed have obvious non‐uniform distribution characteristics, which are more visible in the maize pile. Regions with high porosity have a higher average velocity, and the temperature near the wall is higher than that at the center when the heat transfer is unbalanced. The DEM‐CFD model includes the heat conduction process between the fluid and solid phases, which is consistent with the experimental temperature results.

Practical Applications

In this work, an accurate particle‐resolved computational fluid dynamics numerical model was developed to investigate the flow and heat transfer in fixed beds of soybean, wheat, and maize grains. The randomly filled non‐spherical grain fixed bed structure is generated by the discrete element method (DEM), and the contact areas between the packed particles are automated treated. The pressure drop and heat transfer processes of different grains were measured using the fixed bed drying experimental platform. The results show that the pressure drop results of DEM–CFD simulation of different grain shapes are in good agreement with Nemec–Levec equation results and experimental results. The DEM‐CFD model includes the heat conduction process between fluid and solid phases, which is in close agreement with the experimental temperature results.
A straight‐forward seed production technology system for foxtail millet (Setaria italica)
Authors: Zhang Wei , Qi Xiantao , Zhi Hui , Ren Yushuang , Zhang Linlin , Gao Yuanzhu , Sui Yi , Zhang Haoshan , Tang Sha , Jia Guanqing , Xie Chuanxiao , Wu Chuanyin , Diao Xianmin
Published: May 2023

For autogamous crops, a precondition for using heterosis is to produce sufficient pure male‐sterile female parents that can be used to produce hybrid seeds. To date, cytoplasmic male sterility (CMS) and environment‐sensitive genic male sterility (EGMS) have been used commercially to exploit heterosis for autogamous species. However, neither CMS nor EGMS has been established for foxtail millet (Setaria italica). Here, we report on the establishment and application of a seed production technology (SPT) system for this crop. First, we established a DsRed‐based SPT system, but found that it was unsuitable because it required the use of a fluorescent device for seed sorting. Instead, we constructed an SPT system with de novo betalain biosynthesis as the selection marker. This allowed us to distinguish transgenic seeds with the naked eye, thereby facilitating the identification of SPT maintainer line seeds. In this system, a seed sorter was not required to obtain sufficient seeds. The key point of the strategy is that the seed pool of the SPT maintainer line is propagated by artificial identification and harvesting of male‐fertile individuals in the field, and the male‐sterile line seed pool for hybrid production is produced and propagated by free pollination of male‐sterile plants with the SPT maintainer line. In a field experiment, we obtained 423.96 kg male‐sterile line seeds per acre, which is sufficient to plant 700.18 acres of farmland for hybrid seed production or male‐sterile line reproduction. Our study therefore describes a powerful tool for hybrid seed production in foxtail millet, and demonstrates how the SPT system can be used for a small‐grained crop with high reproduction efficiency.
Thickness measurement of cell walls of closed‐cell foams in micro‐CT images
Authors: Zhu Xiaochun , Cheng Zhengkun , Chen Youming
Published: May 2023

Characterising the microstructure of foams is an important task for improving foam manufacturing processes and building foam numerical models. This study proposed a method for measuring the thickness of individual cell walls of closed‐cell foams in micro‐CT images. It comprises a distance transform on CT images to obtain thickness information of cell walls, a watershed transform on the distance matrix to locate the midlines of cell walls, identifying the intersections of midlines of cell walls by examining how many regions each pixel on the midlines of cell walls connects with, disconnecting and numbering the midlines of cell walls, extracting the distance values of the pixels on the midlines (or midplanes) of cell walls, and calculating the thickness of individual cell walls by multiplying the extracted distance values by two. Using this method, the thickness of cell walls of a polymeric closed‐cell foam was measured. It was found that cell wall thickness measured in 2D images shows larger average values (around 1.5 times) and dispersion compared to that measured in volumetric images.
Collaborative practice among general ward staff on escalating care in clinical deterioration: A systematic review
Authors: Hong Jordan Qi Yang , Chua Wei Ling , Smith Duncan , Huang Chi Ming , Goh Qin Ling Pearlyn , Liaw Sok Ying
Published: May 2023

Aim

To understand the issues surrounding collaborative practice and collaboration experiences among general ward staff in the escalation of care for clinically deteriorating patients.

Design

A systematic synthesis without meta‐analysis.

Review Methods

Seven electronic databases (CINAHL, Cochrane, Embase, PsycINFO, PubMed, Scopus and ProQuest Theses and Dissertations) were searched from their inception to 30 April 2022. Two reviewers independently screened titles, abstracts and full text for eligibility. The critical appraisal skill programme, Joanna Briggs Institute checklist for analytical cross‐sectional studies and mixed methods appraisal tool were used to appraise the quality of the included studies. Both quantitative and qualitative research data were extracted, analysed and then synthesised using the data‐based convergent qualitative synthesis approach. This review adhered to the Synthesis without meta‐analysis (SWiM) reporting guidelines.

Results

A total of 17 studies were included. Two themes and six sub‐themes were generated: (1) intraprofessional factors—inadequate handover, workload and mutual support, raising and acting on concerns, and seeking help from seniors and (2) interprofessional factors—differences in communication styles, and hierarchical approach versus interpersonal relationships.

Conclusions

This systematic review highlights the need to address the intra‐ and interprofessional issues surrounding collaborative practice in escalation of care among general ward staff.

Implications for the Profession

Findings from this review will inform healthcare leaders and educators on the development of relevant strategies and multi‐disciplinary training to foster effective teamwork among nurses and doctors, with the goal of improving the escalation of care for patients with clinical deterioration.

No Patient or Public Contribution

This systematic review did not directly involve patient or public contribution to the manuscript.
Serum endocan levels in patients with habitual abortion
Authors: Yoruk Nurcan , Bulut Erdem Ebru , Aksoy Ayse Nur , Sebin Engin , Aras Gökhan
Published: May 2023

Aim

The aim of this study was to investigate whether there is a new factor in the etiology of recurrent loss of pregnancy. For this purpose, serum malondialdehyde (MDA) and nitric oxide (NO) levels as indicators of oxidative stress, and endocan levels, a marker of vascular dysfunction, were investigated in patients diagnosed with habitual abortion.

Materials and Methods

The research was conducted as a prospective case–control study. Patients aged 18–40 years with two or more consecutive pregnancy losses revealed by ultrasonographic or histopathological examination, and with no pathology capable of causing habitual abortion were included in the study group. Patients with no history of abortion, with at least one healthy pregnancy, who were planning pregnancies, and who presented to the outpatient clinic for routine prepregnancy tests were selected as the control group. Two groups were established—habitual abortion (n = 30) and control (n = 29). At the end of the menstrual cycle, blood samples were collected and centrifuged. Serum NO, MDA, and endocan levels were studied.

Results

Serum endocan, NO, and MDA levels were higher in women with habitual abortion compared to healthy controls. Pearson's correlation analysis revealed a positive correlation between serum endocan levels and NO and MDA levels. A positive correlation was also observed between serum MDA and NO levels. Multiple regression was run to predict serum endocan levels from MDA and NO levels. These variables emerged as statistically significant predictors of endocan.

Conclusion

These findings suggest the presence of vascular endothelial dysfunction in patients with habitual abortion.
A step toward a biofloc system with no‐carbon addition: Increasing dietary lipid level enhances the water quality and body chemical composition without affecting tilapia health status
Authors: Suloma Ashraf , Mabroke Rania S. , Khattab Marwa S. , Salaah Sally M. , El‐Husseiny Osama M. , Eid Ali
Published: May 2023

A 70‐day experiment was carried out to evaluate biofloc system operation with no carbon addition by manipulating dietary protein and lipid levels for Nile tilapia (Oreochromis niloticus) cultivation. Three treatments were conducted; Control treatment (C; fed on a 30% crude protein [CP] diet supplemented with 3% vegetable oil [VO] + addition of external carbon source [ECS] in rearing tank), low protein–low lipid treatment (LPLL; fed on 23% CP diet supplemented with 3% (VO) + no addition of ECS) and low protein–high lipid treatment (LPHL; fed on 23% CP diet supplemented with 9% VO + no addition of ECS). The C treatment recorded the highest values (p < 0.05) in terms of final body weight (FBW), specific growth rate, floc volume, total suspended solids, and ammonia nitrogen. No significant differences were observed between C and LPHL treatments regarding FBW and protein efficiency ratio. The liver sections of LPHL treatment showed better values for histological alteration index compared to the control. It could be concluded that applying a biofloc system with no carbon addition using LPHL diets may afford better water quality conditions, limit the environmental impact and decrease dietary costs with limited effect on fish performance.
Physician empathy in patient empowerment … and patient empowerment in physician empathy
Authors: Rawal Surabhi
Published: May 2023

Rawal argues for the importance of physician empathy in fostering patient engagement and empowerment, being mindful of tools that may facilitate patient empowerment but pose risks of physician burnout and loss of empathy.
Duodenal–jejunal bypass liners are superior to optimal medical management in ameliorating metabolic dysfunction: A systematic review and meta‐analysis
Authors: McLennan Steffane , Verhoeff Kevin , Purich Kieran , Dang Jerry , Kung Janice Y. , Mocanu Valentin
Published: May 2023

This systematic review and meta‐analysis evaluates metabolic and anthropometric outcomes of duodenal–jejunal bypass liners (DJBLs) compared to optimal medical management for the treatment of obesity and its associated metabolic complications. A systematic search of MEDLINE, Embase, Scopus, and Web of Science databases was conducted. Studies were reviewed and data were extracted following the PRISMA guidelines. The primary outcome was glycated hemoglobin (HbA1c) change at device explant with secondary outcomes including body mass index (BMI), weight, fasting plasma glucose (FPG), and adverse events. Twenty‐eight studies met inclusion criteria evaluating a total of 1229 patients undergoing DJBL treatment. When compared to medical management, DJBLs provided superior reductions in HbA1c (mean difference, MD −0.96%; 95% CI −1.43, −0.49; p < 0.0001), FPG (MD −1.76 mmol/L; 95% CI −2.80, −0.72; p = 0.0009), BMI (MD −2.80 kg/m2; 95% CI −4.18, −1.41; p < 0.0001), and weight (MD −5.45 kg; 95% CI −9.80, −1.09, p = 0.01). Post‐explant data reveals a gradual return to baseline status. Incidence of early device explant was 20.2%. Complications were resolved conservatively or with device explant without long‐term morbidity or mortality. We conclude that DJBLs provide significant metabolic and anthropometric improvements for patients with obesity. Uncertainty about the extent to which improvements are maintained after device removal may limit the use of DJBLs as a standalone treatment for obesity and associated metabolic complications.
Molecular‐based phenotype variations in amelogenesis imperfecta
Authors: Dong Jing , Ruan Wenyan , Duan Xiaohong
Published: May 2023

Amelogenesis imperfecta (AI) is one of the typical dental genetic diseases in human. It can occur isolatedly or as part of a syndrome. Previous reports have mainly clarified the types and mechanisms of nonsyndromic AI. This review aimed to compare the phenotypic differences among the hereditary enamel defects with or without syndromes and their underlying pathogenic genes. We searched the articles in PubMed with different strategies or keywords including but not limited to amelogenesis imperfecta, enamel defects, hypoplastic/hypomaturation/hypocalcified, syndrome, or specific syndrome name. The articles with detailed clinical information about the enamel and other phenotypes and clear genetic background were used for the analysis. We totally summarized and compared enamel phenotypes of 18 nonsyndromic AI with 17 causative genes and 19 syndromic AI with 26 causative genes. According to the clinical features, radiographic or ultrastructural changes in enamel, the enamel defects were basically divided into hypoplastic and hypomineralized (hypomaturated and hypocalcified) and presented a higher heterogeneity which were closely related to the involved pathogenic genes, types of mutation, hereditary pattern, X chromosome inactivation, incomplete penetrance, and other mechanisms.The gene‐specific enamel phenotypes could be an important indicator for diagnosing nonsyndromic and syndromic AI.
RUNX2 mutation inhibits the cellular senescence of dental follicle cells via ERK signalling pathway
Authors: Ji LingLi , Li Jie , Liu Dandan , Qiao Yanchun , Zhao Weiwei , Liu Yang , Zheng Shuguo
Published: May 2023

Objective

The aim of this study was to explore the regulatory effect of RUNX2 mutation on dental follicle cells (DFCs) senescence and clarify the underlying mechanism. This study aimed to explore the basis for a novel mechanism of delayed permanent tooth eruption in cleidocranial dysplasia (CCD) patients.

Materials and Methods

Dental follicles were collected from a CCD patient and healthy controls. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining, Ki67 staining, cell cycle assays, and senescence‐related gene and protein expression assays were performed to assess DFCs senescence. Western blotting was performed to detect the activation of mitogen‐activated protein kinase (MAPK) signalling pathways, and the molecular mechanism underlying RUNX2 regulating in DFCs senescence was explored.

Results

RUNX2 mutation inhibited the cellular senescence of DFCs from the CCD patient compared with healthy controls. Ki67 staining showed that mutant RUNX2 promoted DFCs proliferation, and cell cycle assays revealed that the healthy control‐derived DFCs arrested at G1 phase. RUNX2 mutation significantly downregulated senescence‐associated gene and protein expression. RUNX2 mutation suppressed ERK signalling pathway activation, an ERK inhibitor decreased healthy control‐derived DFCs senescence, and an ERK activator promoted CCD patient‐derived DFCs senescence.

Conclusions

RUNX2 mutation delayed DFCs senescence through the ERK signalling pathway, which may be responsible for delayed permanent tooth eruption in CCD patients.
Beyond Magnification and Illumination: Ergonomics with a 3D Exoscope in Lumbar Spine Microsurgery to Reduce Musculoskeletal Injuries
Authors: Lin Hailin , Chen Fenyong , Lin Taotao , Mo Jiadong , Chen Zhi , Wang Zhenyu , Liu Wenge
Published: May 2023

Objective

The risk of musculoskeletal injuries (MSIs) increases over years of practice which may lead to career‐ending among surgeons. Exoscopes represent a new generation of imaging systems that help surgeons operate in a more comfortable posture. This article aimed to assess advantages and limitations, especially ergonomics with a 3D exoscope in lumbar spine microsurgery versus an operating microscope (OM) to reduce MSIs.

Methods

From March 2018 to May 2020, 90 patients with lumbar disc herniation undergoing a single‐level minimally invasive transforaminal lumbar interbody fusion (MIS‐TLIF) procedure were included. Forty‐seven patients were operated with the assistance of the exoscope and 43 patients were operated with the assistance of the OM. Clinical data, magnification, and illumination were evaluated. In particular, the ergonomics of surgeons was evaluated by a questionnaire (subjective) and a rapid entire body assessment (REBA; objective).

Results

The postoperative outcomes were reasonably well balanced between the two groups. The handling of the exoscope was comparable to that of the OM. The depth perception, image quality, and illumination of the exoscope were inferior to those of the OM in MIS‐TLIF with long and deep approaches. The educational and training function of the exoscope was superior to that of the OM. Importantly, surgeons rated the ergonomics of the exoscope as very high on the questionnaire and the REBA to the OM (P = 0.017).

Conclusions

This study showed that the exoscope was a safe and effective alternative to the OM for assisting the MIS‐TLIF procedure with the unique advantage of ergonomics to reduce musculoskeletal injuries.