bluuebunny/crossref_metadata_2025 huggingface dataset:
An interactive qualitative analysis of academics’ views of a competency-based undergraduate qualification in risk management
Authors: Marx Johan , de Swardt Cecilia Jacoba
Published: January 2023

Purpose

The purpose of this research was first to determine the competencies mandatory of risk managers, and second, to consider the implications of such competencies in determining modules appropriate for inclusion in any prospective undergraduate qualification with specialisation in risk management.

Design/methodology/approach

A qualitative research approach was followed, involving academics teaching risk management in a focus group and making use of interactive qualitative analysis (IQA).

Findings

The competencies identified were business management skills, financial knowledge, an understanding of the risk management process, governance and compliance, people management and technical skills. These will be explained in greater detail in the paper.

Research limitations/implications

The implications for teaching are that an undergraduate curriculum in risk management will have to combine majors such as business management, financial management, risk management, industrial psychology and communication. These majors need to be complemented by modules in governance and compliance management, as well as information and communication technology.

Practical implications

The implication for practice is that risk management professionals and members of the Institute of Risk Management of South Africa need to avail themselves to serve on an advisory board of academic departments offering risk management qualifications. Risk management is a developing science and requires inputs about research and the curriculation of qualifications.

Social implications

The implication for public policy is that the South African Qualifications Authority and the Council for Higher Education should reconsider their requirements for designators (specialised qualifications). The implications for research are that IQA provides clarity on the knowledge and skills required to develop a competency-based qualification in risk management. Further research should benchmark qualifications and propose a curriculum for a bachelor’s degree in risk management.

Originality/value

The use of IQA is a novel way of ensuring rigour and objectivity in arriving at a description of the required knowledge, skills, values and attributes of risk managers. This paper will assist in the compilation of a new curriculum for an undergraduate qualification in risk management; thus, ensuring such qualification will provide a competency-based qualification that will meet the needs of the profession.
Mediating role of workplace happiness in enhancing work engagement
Authors: Shelke Ashwini Uttamrao , Shaikh Naim
Published: January 2023

Purpose

This research seeks to explain the mediating function of workplace happiness in enhancing employee engagement through the drivers of employee engagement among the IT sector employees of India.

Design/methodology/approach

Quantitative data were acquired from 104 respondents from the Indian IT industry via an online survey utilizing Google Forms, employing a stratified random sample method. The study hypotheses were tested using PLS-SEM.

Findings

Results indicated that workplace happiness positively mediates employee engagement and drivers of employee engagement.

Research limitations/implications

The current study followed a cross-sectional analysis where establishing causality is difficult; however, there is a scope to do longitudinal study on the same phenomenon. Research data are produced through online surveys. Possible sources of bias may be selective memory, attribution and/or exaggeration. This study covers specific variables of workplace happiness and drivers of employee engagement other variables remain unaddressed, such as COVID-19-related impacts. The nature of the industry and sample size were limited.

Practical implications

This study shows that workplace happiness has a mediating effect on both drivers of employee engagement and employee engagement; as a result, organizations should consider the function of workplace happiness as a mediating factor when implementing drivers of employee engagement and employee engagement.

Social implications

On the social level, this research will help organizations to understand the drivers for employee engagement and linkages between workplace happiness and employee engagement. It hopes to create more happy workplaces and have good social impact.

Originality/value

This is the first study to look into the function of workplace happiness as a mediator between the drivers of work engagement and work engagement.
Long-term robot manipulation task planning with scene graph and semantic knowledge
Authors: Miao Runqing , Jia Qingxuan , Sun Fuchun
Published: January 2023

Purpose

Autonomous robots must be able to understand long-term manipulation tasks described by humans and perform task analysis and planning based on the current environment in a variety of scenes, such as daily manipulation and industrial assembly. However, both classical task and motion planning algorithms and single data-driven learning planning methods have limitations in practicability, generalization and interpretability. The purpose of this work is to overcome the limitations of the above methods and achieve generalized and explicable long-term robot manipulation task planning.

Design/methodology/approach

The authors propose a planning method for long-term manipulation tasks that combines the advantages of existing methods and the prior cognition brought by the knowledge graph. This method integrates visual semantic understanding based on scene graph generation, regression planning based on deep learning and multi-level representation and updating based on a knowledge base.

Findings

The authors evaluated the capability of this method in a kitchen cooking task and tabletop arrangement task in simulation and real-world environments. Experimental results show that the proposed method has a significantly improved success rate compared with the baselines and has excellent generalization performance for new tasks.

Originality/value

The authors demonstrate that their method is scalable to long-term manipulation tasks with varying complexity and visibility. This advantage allows their method to perform better in new manipulation tasks. The planning method proposed in this work is meaningful for the present robot manipulation task and can be intuitive for similar high-level robot planning.
Outreaching to find and engage older people “no-one knows”: a necessary element of work to address social isolation and loneliness
Authors: MacIntyre Helen , Collins Annabel , Stapleton Jo
Published: January 2023

Purpose

The purpose of this paper is to share a model of skilled outreach working to find and engage the hidden group of socially isolated and lonely older people who are reluctant or unable to access community activities, formal services or support. The model can inform the practice of community development, housing or other workers concerned with initiating behaviour change among older people to increase their social connectedness.

Design/methodology/approach

This practice-focused paper presents a description of key elements of the Ageing Better in Camden (ABC) outreach approach along with a snapshot of operational data and examples from interviews/case studies to indicate impact of the work.

Findings

ABC’s Outreach Team engaged with individuals facing significant barriers to social connection including physical and mental health problems, living alone, bereavement and caring responsibilities. A high proportion of Team engagements were with men (41%) who are typically hard to engage. In total, 23% of people who the Team met took some “Action” towards social connection. Qualitative examples indicated that encounters with the Team could be uplifting and act as a “nudge” towards “Action”. This paper discusses the need to strengthen evidence of the impact of the approach and challenges of doing so.

Originality/value

There are few descriptions in practice or research literature of outreach work with older people and the elements which make it effective. This paper addresses this gap.
Estimation of seismic attenuation for reservoirs mapping and inverse Q‐filtering: An application on land seismic data
Authors: Alshangiti Abdullah , Zhou Hua‐Wei
Published: January 2023

Seismic attenuation values based on inverse Q‐filtering are useful in enhancing seismic data resolution for quantitative interpretation. However, as field attenuation estimations are often contaminated by noise and overburden effects, an inverse Q‐filter may reduce the signal‐to‐noise ratio. To help reservoir mapping with seismic resolution enhancement, we use well logs and surface seismic data to estimate the attenuation of a depth interval composed of several carbonate oil reservoirs onshore the Arabian Peninsula. From applying a prestack Q inversion on τ–p gathers from a large 3D seismic survey, the estimated effective attenuation values show spatially coherent patterns, likely corresponding to changes in the petrophysical and fluid properties. The patterns of the estimated effective attenuation values correlate considerably with the anticline geometry, with higher values on its crest than its flanks. The small percentage of the negative effective attenuation values indicates that the apparent attenuation and overburden effects are insignificant. At well locations, the effective attenuation values show a good correlation with the average porosity of the main reservoir, verifying that they are related to changes in petrophysical properties in the analysis interval. We propose an extended inverse Q‐filter with two additional parameters to make it more robust and flexible and test it with synthetic and field datasets. We estimate a multiple‐scattering attenuation value from well logs and use it in the proposed filter for the field dataset. The compensation for the multiple‐scattering effects suppresses the overprints of the data components unrelated to the target interval, hence benefitting the quantitative data interpretation.
Noninsulin‐based antihyperglycemic medications in patients with diabetes and COVID‐19: A systematic review and meta‐analysis
Authors: Nassar Mahmoud , Abosheaishaa Hazem , Singh Awadhesh Kumar , Misra Anoop , Bloomgarden Zachary
Published: January 2023

Background

Patients with diabetes are more likely to suffer COVID‐19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID‐19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID‐19.

Methods

We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID‐19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non‐English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission.

Results

The use of metformin rather than other glucose‐lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase‐4 inhibitor (DPP‐4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT‐2i users vs nonusers (RR: 0.89, 95% CI: 0.84–0.95, p < .001). Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69–0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).

Conclusions

AGM use was not associated with increased mortality. However, metformin and GLP‐1RA use reduced mortality risk statistically significantly. DPP‐4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.
Retrieval of a Cook Celect inferior vena cava (IVC) filter after prolonged dwell time of 5,117 days: Factors to consider for retrieval of long‐dwell IVC filters
Authors: Goh Gerard S , Ng Nico , Fitzgerald Mark , Mathew Joseph
Published: January 2023

Inferior vena cava (IVC) filters are used in certain patients to help prevent the occurrence of pulmonary embolism (PE). IVC filters are generally recommended to be removed once PE prophylaxis is no longer required. Long‐dwelling IVC filters are associated with higher complication rates (Vasa 2020; 49: 449), being more difficult to retrieve and associated with higher retrieval complications (Cardiovasc Diagn Ther 2016; 6: 632). This report describes the pre‐procedural work‐up and removal of an IVC filter with a prolonged dwell time of 5,117 days (14 years, 3 days) using the loop snare advanced retrieval technique. As far as the authors are aware this case is the longest‐described successful retrieval of a Cook Celect IVC filter at 5,117 days.
Preoperative prescriptions and polypharmacy in elective total hip and knee arthroplasty from 2010 to 2017, a descriptive cohort study
Authors: Rasmussen Nina Brendborg , Kehlet Henrik , Knudsen Troels Bygum , Printzlau Pernille , Jørgensen Christoffer Calov
Published: January 2023

Background

Evaluation of regular medication is an essential part of the preanesthetic consultation. However, even in elective surgical patients, such as those scheduled for total hip (THA) and knee arthroplasty (TKA), this task may be increasingly complex due to increasing age and number of pharmacologically treated comorbidities. Nevertheless, data on prescribed drugs and polypharmacy in elective surgical patients is sparse.

Methods

Descriptive study in elective unilateral fast‐track THA and TKA between 2010 and 2017 based on data from the Centre for fast‐track Hip and Knee Replacement Database. Nationwide information on dispensed prescriptions up to 3 months preoperatively was acquired from the Danish National Database of Reimbursed Prescriptions. Drugs were divided into individual subgroups according to the fourth Anatomical Therapeutic Chemical level (ATC4). Primary outcome was changes in the median number of prescribed drugs/year. Secondarily, we investigated the fraction of patients with polypharmacy (≥5 individual ATC4‐subgroups), severe polypharmacy (≥10) and specific drugs of relevance at the preanesthetic evaluation.

Results

Of 36,934 procedures in 32,515 patients with a median age of 69 years, we found a median of 3 ATC4‐subgroups with no time‐related changes regardless of year of surgery but increasing in patients ≥65 years (median: 3 [IQR: 2–4]) versus < 65 years (2 [IQR 1–3]; p < .001). In total, 35.1% and 4.2% had polypharmacy or severe polypharmacy. There was a significant declining trend in severe polypharmacy from 2010 to 2017 (p = .003). Drugs of anesthetic relevance were used by 41.1% of all patients, most often ANG‐II or ACE inhibitors and betablockers, which were used by 28.0% and 15.7%. Oral antihyperglycemics was used by 7.8% and 2.0% used insulin. Only 4.0% and 2.1% of patients used vitamin‐K antagonists and direct oral anticoagulants, respectively. MAO‐inhibitors/Lithium salts were used by 0.3%. The combination of ANG‐II/ACE inhibitors, a diuretic and NSAID (“triple whammy”) was present in 4.3% of all patients.

Conclusion

Patients scheduled for elective THA and TKA used a median of 3 prescribed drugs. However, 1/3 of patients qualified as having polypharmacy and 41% used drugs requiring anesthetic consideration when planning for surgery.
Taming the wild: Attracting capital through populist mobilization in the urban landscapes of Istanbul
Authors: Kurt Firat
Published: January 2023

Urban transformation in Turkey, ranging in scale from gigantic infrastructural investments to small property‐redevelopment ventures, has posed one of the most puzzling questions for scholars and activists: Why do the urban poor, despite being the most vulnerable to such projects, continue to partake in the populist mobilization around the ruling Justice and Development Party (AKP)? Grounded in an analysis of how neoliberal assemblages are entangled with urban land markets at the margins of Istanbul, I argue that neoliberal policies are not necessarily implicated in the prevalence of depoliticized individuals, conceptually framed as homo oeconomicus, but can also serve to create a fertile environment for populist mobilization. The partisans and sympathizers of the AKP find that their social and political activities, from neighborhood organizations to single‐party hegemony in the parliament, are inherently inseparable from economic values. At this nexus between populist politics and economic forces, global capital emerges as a salient interlocutor that interfaces with political developments and social characteristics, having various predispositions and predilections—an actor whose miraculous powers can be unleashed and destructive tendencies controlled only through collective political mobilization.
Distributed humanitarianism
Authors: Cullen Dunn Elizabeth , Kaliszewska Iwona
Published: January 2023

When Russia invaded Ukraine in 2022, the world's largest humanitarian aid agencies were largely nowhere to be seen. In their absence, tens of thousands of volunteers from Ukraine, Poland, and further abroad helped the more than 16 million displaced and war‐affected Ukrainians. This massive volunteer response represents a case of “distributed humanitarianism,” a post‐Fordist form of humanitarian aid that disrupts the Fordist international aid industry that has existed since the end of World War II. Because it uses donated money, labor, and goods; avoids bureaucratic accountability measures; and relies on person‐to‐person aid chains, distributed humanitarianism is faster, more cost‐efficient, and more resilient than large‐scale institutionalized aid.
The association between episiotomy or OASIS at vacuum extraction in nulliparous women and subsequent prelabor cesarean delivery: A nationwide observational study
Authors: Brismar Wendel Sophia , Liu Can , Stephansson Olof
Published: January 2023

Introduction

Severe perineal injuries at childbirth affect women's postnatal health, including future childbirths. First births with vacuum extraction carry an increased risk of obstetric anal sphincter injuries (OASIS). Lateral or mediolateral episiotomy at vacuum extraction may decrease the risk of OASIS. Our aim was to assess whether lateral or mediolateral episiotomy, or OASIS, at vacuum extraction in nulliparous women is associated with prelabor cesarean delivery in the subsequent childbirth.

Material and methods

This is a nationwide observational study using data from the Swedish Medical Birth Register, including women having a first birth with vacuum extraction and a second birth in 2000–2014. Both births were live, single, cephalic, ≥34 gestational weeks without malformations. The association between episiotomy or OASIS in the first birth and prelabor cesarean delivery in the second birth was examined using univariate and multivariate logistic regression with inverse probability of treatment weighting, and interaction analysis. Main outcome measure was prelabor cesarean delivery in the second birth.

Results

In total, 44 656 women with vacuum extraction at their first birth were included. The rate of prelabor cesarean delivery in the second birth was 5.9% (824 of 13 950) in women with episiotomy, compared with 6.0% (1830 of 30 706) in women without episiotomy. Thus, women with episiotomy did not have an increased risk of prelabor cesarean delivery (adjusted odds ratio [aOR] 1.00, 95% confidence interval [95% CI] 0.83–1.20) compared with women without episiotomy. For comparison, the rate of prelabor cesarean delivery in the second birth was 20.6% (1275 of 6176) in women with OASIS, compared with 3.6% (1379 of 38 480) in women without OASIS (aOR 6.57, 95% CI 5.97–7.23). There was no interaction between episiotomy and OASIS.

Conclusions

Lateral or mediolateral episiotomy at vacuum extraction in nulliparous women did not increase the risk of prelabor cesarean delivery in the subsequent childbirth. OASIS increased the odds of prelabor cesarean delivery more than sixfold.
Microaxial circulatory support for percutaneous coronary intervention: A systematic review and meta‐analysis
Authors: Leon Sophie A. , Rosen Jake L. , Ahmad Danial , Austin Melissa A. , Vishnevsky Alec , Rajapreyar Indranee N. , Ruggiero Nicholas J. , Rame J. Eduardo , Entwistle John W. , Massey Howard T. , Tchantchaleishvili Vakhtang
Published: January 2023

Background

Microaxial circulatory support devices have been used to support patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction complicated by cardiogenic shock (AMICS). The purpose of this systematic review and meta‐analysis was to pool and analyze the existing evidence on the baseline characteristics, periprocedural data, and outcomes of microaxial support before and after PCI in AMICS.

Methods

An electronic database search was performed to identify all cohort studies on Impella and PCI for cardiogenic shock in the English language. A total of five articles comprising 543 patients were included. These patients received microaxial support either before (pre‐PCI) or after (post‐PCI) undergoing PCI. Comparative analyses were done between both groups.

Results

The mean patient age was 66 years [95% Confidence Interval (58–74)], and 22% (89/396) of patients were female. ST‐elevation myocardial infarctions (MI) comprised 64% (44–80) of MIs and 50% (44–56) of MIs involved the left anterior descending artery. The mean number of diseased vessels was 2.21 (1.62–2.80). The mean left ventricular ejection fraction was 31% (23.4–38.6). The mean arterial pressure was 66.3 mm Hg (54.1–78.5). Mean serum lactate [6.1 mmol/L (3.3–8.9)] and serum creatinine [1.4 mg/dl (1.0–1.7)] were similar between groups. 30‐day mortality was lower in the pre‐PCI group [41% (34%–49%)] compared to the post‐PCI group [61% (42%–77%), p < 0.01]. Pooled Kaplan–Meier analysis showed better early survival in the pre‐PCI group (p < 0.001).

Conclusion

Patients presenting with AMICS were similar at baseline in both pre‐PCI and post‐PCI groups. Nevertheless, pre‐PCI group showed better early survival compared to post‐PCI group.
Review article: controversies surrounding the use of carvedilol and other beta blockers in the management of portal hypertension and cirrhosis
Authors: Gillespie Sarah‐Louise , Hanrahan Timothy P. , Rockey Don C. , Majumdar Avik , Hayes Peter C.
Published: January 2023

Background

Advanced chronic liver disease is an increasing cause of premature morbidity and mortality in the UK. Portal hypertension is the primary driver of decompensation, including the development of ascites, hepatic encephalopathy and variceal haemorrhage. Non‐selective beta blockers (NSBB) reduce portal pressure and are well established in the prevention of variceal haemorrhage. Carvedilol, a newer NSBB, is more effective at reducing portal pressure due to additional α‐adrenergic blockade and has additional anti‐oxidant, anti‐inflammatory and anti‐fibrotic effects.

Aim

To summarise the available evidence on the use of beta blockers, specifically carvedilol, in cirrhosis, focussing on when and why to start

Methods

We performed a comprehensive literature search of PubMed for relevant publications.

Results

International guidelines advise the use of NSBB in primary prophylaxis against variceal haemorrhage in those with high‐risk varices, with substantial evidence of efficacy comparable with endoscopic band ligation (EBL). NSBB are also well established in secondary prophylaxis, in combination with EBL. More controversial is their use in patients without large varices, but with clinically significant portal hypertension. However, there is gathering evidence that NSBB, particularly carvedilol, reduce the risk of decompensation and improve survival. While caution is advised in patients with advanced cirrhosis and refractory ascites, recent evidence suggests that NSBB can continue to be used safely, and that premature discontinuation may be detrimental.

Conclusions

With increasing evidence of benefit independent of variceal bleeding, namely retardation of decompensation and improvement in survival, it is time to consider whether carvedilol should be offered to all patients with advanced chronic liver disease.
Comparison of the efficacy and safety of standard‐ and high‐dose daptomycin: A systematic review and meta‐analysis
Authors: Samura Masaru , Takada Keisuke , Hirose Naoki , Kurata Takenori , Nagumo Fumio , Uchida Masaki , Inoue Junki , Tanikawa Koji , Enoki Yuki , Taguchi Kazuaki , Matsumoto Kazuaki , Ueda Takashi , Fujimura Shigeru , Mikamo Hiroshige , Takesue Yoshio , Mitsutake Kotaro
Published: January 2023

Aims

Standard doses of daptomycin at 4 and 6 mg/kg were used for the treatment of skin and soft tissue for infections and bacteraemia, respectively. However, increased doses of daptomycin are recommended for complicated infections by Gram‐positive organisms.

Methods

A systematic review was conducted using 4 databases. We compared treatment success between standard‐dose (SD, 4–6 mg/kg) and high‐dose (HD, >6 mg/kg) daptomycin in patients with all‐cause bacteraemia, complicated bacteraemia, infective endocarditis, osteomyelitis and foreign body/prosthetic infection as the primary outcome. We also compared the success between SD and HD2 (≥8 mg/kg) daptomycin treatments in patients with these diseases as the secondary outcome. The incidence of creatine phosphokinase (CPK) elevation was evaluated as safety.

Results

In patients with complicated bacteraemia and infective endocarditis, the treatment success was significantly lower in the SD group than in the HD group (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30–0.76 and OR 0.50, 95% CI 0.30–0.82) and HD2 group (OR 0.38, 95% CI 0.21–0.69 and OR 0.30, 95% CI 0.15–0.60), respectively. A significant difference was demonstrated only in the HD2 group in patients with bacteraemia, including simple infection. SD did not decrease the success rate for the treatment of osteomyelitis and foreign body/prosthetic infection. The incidence of elevated CPK was significantly lower in SD group than in HD group.

Conclusion

SD daptomycin was associated with significantly lower treatment success than HD in patients with complicated bacteraemia/infective endocarditis. The CPK elevation should be considered in patients treated with high daptomycin doses.
Bile duct ligation increased dopamine levels in the cerebral cortex of rats partly due to induction of tyrosine hydroxylase
Authors: Kong Weimin , Sun Xueying , Yu Siyu , Liu Peihua , Zheng Xiaoke , Zhang Jiaxin , Zhu Liang , Jiang Tianxin , Jin Mengmeng , Gao Jinghui , Fan Xiaomin , Liu Xiaodong , Liu Li
Published: January 2023

Background and Purpose

Liver failure is associated with psychiatric alterations, partly resulting from the increased brain dopamine levels. We investigated the relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and the mechanism by which liver failure increased dopamine levels in SH‐SY5Y cells.

Behavioural tests were carried out on day 13 and 27 following BDL, along with measurements of dopamine and metabolites, expressions of enzymes and transporters related to dopamine metabolism, and its transport into the cortex and the hippocampus. SH‐SY5Y cells were used to investigate whether NH4Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase or not. Tyrosine hydroxylase (TH) expression in SH‐SY5Y cells co‐incubated with bilirubin and signal pathway inhibitors was measured.

Key Results

Open‐field test results demonstrated BDL rats showed anxiety‐like behaviour, accompanied by increased dopamine levels and expression of TH protein in the cortex. Membrane bound long form (MB)‐COMT, slightly but significantly decreased. SH‐SY5Y cells indicated that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF‐κB pathway BAY 11‐7082 and silencing NF‐κB p65 reversed bilirubin‐induced upregulation of TH protein. NF‐κB activator TNF‐α increased expression of TH protein. Roles of bilirubin in increases of TH protein expressions and dopamine levels were measured using hyperbilirubinemia rats. Anxiety‐like behaviour, was associated with increased dopamine levels and TH protein expressions in hyperbilirubinemia rats.

Conclusion and Implications

BDL significantly increased dopamine levels in rat cortex partly due to bilirubin‐mediated TH induction. Increased bilirubin induced TH expression via activating NF‐κB signalling pathway.
Crizotinib‐based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation
Authors: Chen Jin‐Jiao , Jin Jin‐Mei , Gu Wen‐Jie , Zhao Zeng , Yuan Hu , Zhou Yu‐Dong , Nagle Dale G. , Xi Qiu‐Lei , Zhang Xue‐Mei , Sun Qing‐Yan , Wu Ye , Zhang Wei‐Dong , Luan Xin
Published: January 2023

As one of the common malignant cancer types, gastric cancer (GC) is known for late‐stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the “occupancy‐driven” model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET‐targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO‐6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET‐positive GC cells. In the MKN‐45 xenograft model, PRO‐6 E showed pronounced antitumor efficacy with a well‐tolerated dosage regimen. These results validated PRO‐6 E as the first oral PROTAC for MET‐dependent GC.
Conversations about violence, risk and responsibility with divorced and support‐seeking fathers in Sweden
Authors: Bruno Linnéa , Eriksson Maria
Published: January 2023

The aim of this paper is to analyse approaches to issues of risk, responsibility and representations of violence in women social workers' conversations with alleged or confirmed violent fathers. The study adds to a growing body of research on agencies' handling of intimate partner violence (IPV) in the context of separation. Empirically, the study draws from 12 structured, audio recorded and transcribed interviews with support‐seeking and divorced fathers, from five municipalities in Sweden, conducted as part of a cooperation project in which a risk‐detection method (Family Law Detection Of Overall Risk Screen [FL‐DOORS]) was also tested. The results suggest a tension between different professional tasks. To validate information on IPV, detect risk and enhance a child perspective competes with other professional projects, most obviously with promoting cooperation between parents. The study confirms previous research, which demonstrates unique challenges facing women social workers and counsellors when working with men as perpetrators. In conclusion, the paper concurs with the call for a focus on responsibility and on safe parenting in professional conversations with allegedly or confirmed abusive fathers.
Implant prosthodontic design as a predisposing or precipitating factor for peri‐implant disease: A review
Authors: Hamilton Adam , Putra Armand , Nakapaksin Pranai , Kamolroongwarakul Pongrapee , Gallucci German O.
Published: January 2023

Over the past decade, emerging evidence indicates a strong relationship between prosthetic design and peri‐implant tissue health. The objective of this narrative review was to evaluate the evidence for the corresponding implant prosthodontic design factors on the risk to peri‐implant tissue health. One of the most important factors to achieve an acceptable implant restorative design is the ideal implant position. Malpositioned implants often result in a restorative emergence profile at the implant‐abutment junction that can restrict the access for patients to perform adequate oral hygiene. Inadequate cleansability and poor oral hygiene has been reported as a precipitating factors to induce the peri‐implant mucositis and peri‐implantitis and are influenced by restorative contours. The implant–abutment connection, restorative material selection and restoration design are also reported in the literature as having the potential to influence peri‐implant sort tissue health.
Strontium‐modified titanium substrate promotes osteogenic differentiation of MSCs and implant osseointegration via upregulating CDH2
Authors: Zhou Chuan , Ge Ziyu , Song Lu , Yan Jiahui , Lang Xinrui , Zhang Yanzhen , He Fuming
Published: January 2023

Objectives

Our previous studies showed that strontium (Sr)‐modified sand‐blasted, large grit, acid etched titanium surface (Sr‐SLA) is beneficial for osseointegration; however, the supporting mechanisms have not been explored in detail.

Materials and Methods

Whole‐transcriptome RNA sequencing of peri‐implant bone tissue was performed, and CDH2 was selected as a key mediator of Sr‐SLA‐mediated osseointegration. To test this hypothesis, a lentivirus‐mediated vector targeting the silencing of the CDH2 gene was used in mesenchymal stem cells (MSCs) prior to seeding on Ti substrates. The effects of CDH2 interference on MSCs vitality, differentiation, and β‐catenin signaling activity were evaluated. In vivo, a recombinant adeno‐associated virus 9 vector carrying an artificial siRNA that target CDH2 (AAV9‐CDH2i) was intravenously injected in mice, followed by tibial surgery with implant placement. Osseointegration were monitored using micro‐CT analysis.

Results

CDH2 expression in MSCs on Sr‐SLA was higher than the control group, which was in parallel with the enhanced cell migration, adhesion, and upregulation of early osteogenic markers. Knocking down CDH2 in MSCs resulted in decreased cell viability and osteogenic differentiation, and the elevated biocompatibility and osteoinductive effect of Sr‐SLA were greatly diminished. Surprisingly, Sr‐SLA‐induced upregulation of CDH2 was not followed by restriction of β‐catenin signaling because Sr‐SLA also promoted the expression and nuclear translocation of β‐catenin. Systemic administration of AAV9‐CDH2i effectively knocked down CDH2 expression in bone marrow cells, and in turn, inhibited bone formation induced by Sr‐SLA.

Conclusions

The results indicated that CDH2 is required for Sr‐SLA‐mediated bone regeneration, which reveals a new mechanism to explain the osteoinductive effect of Sr‐SLA. Thus, biomaterial modifications targeting CDH2 may help improve early osseointegration and bone healing.
Prosthodontic outcomes of mandibular overdenture treatment with one or two implants: 4‐year results of a randomized clinical trial
Authors: de Resende Gabriela Pereira , de Menezes Eunice Ellen Gontijo , Maniewicz Sabrina , Srinivasan Murali , Leles Cláudio Rodrigues
Published: January 2023

Objective

To assess the incidence of prosthodontic maintenance events and complications during 4 years of follow‐up after mandibular overdenture treatment with one or two implants.

Methods

Participants received one or two implants inserted in the midline (1‐IOD group) or the lateral incisor‐canine area bilaterally (2‐IOD group). Implants were loaded with an early loading protocol after 3 weeks. Programmed recall visits were scheduled at the 6‐, 12‐, 36‐, and 48‐month follow‐ups and nonprogrammed visits in case of prosthodontic complaints. The type of maintenance was registered, and the final treatment outcome was classified as successful, surviving, unknown, dead, repair, or retreatment.

Results

Forty‐seven participants, mean age 65.4 ± 8.6, 74.5% female, were included (1‐IOD = 23; 2‐IOD = 24) and 44 completed the 4‐year follow‐up. A total of 159 prosthodontic maintenance events occurred and 89 in unscheduled visits. The most common event was the need for minor modifications of the denture base due to sore spots in the oral mucosa (n = 56 in 31 patients), matrix activation (n = 54 in 34 patients), and overdenture fracture (n = 25 in 18 patients). A “successful” or “surviving” outcome could be attributed to 57.5% of cases, whereas 38.3% needed repair. No significant differences in the incidence of prosthodontic events or treatment outcomes were found between the two groups.

Conclusions

Findings show that 1‐IODs perform similar to 2‐IODs when considering the incidence of fractures and the need for prosthodontic maintenance, including adjustments of the overdenture and the attachment system.
Outcomes of DCD kidneys with CIT‐induced delayed graft function
Authors: Zaphiros Nikolas H. , Nie Jing , Alchaer Michael W. , Kayler Liise K.
Published: January 2023

Donation after circulatory death (DCD) kidneys are exposed to warm ischemia, which, coupled with cold ischemia time (CIT) exacerbates delayed graft function (DGF) and is possibly associated with worse graft survival. To analyze the risk of CIT‐induced DGF on DCD kidney outcomes, we evaluated national data between 2008 and 2018 of adult kidney‐only recipients of paired DCD kidneys where one kidney recipient experienced DGF and the other did not. Of 5602 paired DCD kidney recipients, multivariate analysis between recipients with higher CIT relative to lower CIT showed that increasing CIT differences had a significant dose‐dependent effect on overall graft survival. The graft survival risk was minimal with CIT differences of ≥1‐h (adjusted hazard ratio [aHR] 1.07, 95% CI .95– 1.20, n = 5602) and ≥5‐h (aHR 1.09, 95% CI .93–1.29, n = 2710) and became significant at CIT differences of ≥10‐h (aHR 1.37, 95% CI 1.05–1.78, n = 1086) and ≥15‐h (aHR 1.78, 95% CI 1.15–2.77, n = 1086). Between each of the four delta‐CIT levels of shorter and longer CIT, there were no statistically significant differences in the proportion of acute rejection. These results suggest that in the setting of DCD kidney transplantation (KTX), DGF, specifically mediated by prolonged CIT, impacts long‐term graft outcomes.
State‐of‐the‐art therapy for Down syndrome
Authors: Lorenzon Nicola , Musoles‐Lleó Juanluis , Turrisi Federica , Gomis‐González Maria , De La Torre Rafael , Dierssen Mara
Published: January 2023

In the last decade, an important effort was made in the field of Down syndrome to find new interventions that improve cognition. These therapies have added to the traditional symptomatic treatments and to the drugs for treating Alzheimer disease in the general population repurposed for Down syndrome. Defining next‐generation therapeutics will involve biomarker‐based therapeutic decision‐making, and preventive and multimodal interventions. However, translation of specific findings into effective therapeutic strategies has been disappointingly slow and has failed in many cases at the clinical level, leading to reduced credibility of mouse studies. This is aggravated by a tendency to favour large‐magnitude effects and highly significant findings, leading to high expectations but also to a biased view of the complex pathophysiology of Down syndrome. Here, we review some of the most recent and promising strategies for ameliorating the cognitive state of individuals with Down syndrome. We studied the landscape of preclinical and clinical studies and conducted a thorough literature search on PubMed and ClinicalTrials.gov for articles published between June 2012 and August 2022 on therapies for ameliorating cognitive function in individuals with Down syndrome. We critically assess current therapeutic approaches, why therapies fail in clinical trials in Down syndrome, and what could be the path forward. We discuss some intrinsic difficulties for translational research, and the need for a framework that improves the detection of drug efficacy to avoid discarding compounds too early from the companies’ pipelines.
Therapeutic inertia related to the injectable glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care
Authors: von Arx Lill‐Brith , Rachman Jonathan , Webb Joanne , Casey Caroline , Patel Amisha , Diomatari Christina , Wood Robert , Idris Iskandar
Published: January 2023

Aims

To determine the extent of therapeutic inertia related to the weekly injectable glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes (T2D) in the United Kingdom.

Materials and methods

Adults with T2D who received their first primary care prescription of dulaglutide or semaglutide between January and July 2019 were identified from the UK Clinical Practice Research Datalink GOLD primary care database. Doses prescribed, glycated haemoglobin (HbA1c), body mass index (BMI) and concomitant T2D medications were assessed at first prescription and at 3, 6 and 9 months.

Results

Of the patients prescribed dulaglutide (N = 748; mean [SD] age 59.0 [11.2] years) and semaglutide (N = 437; mean [SD] age 58.4 [10.6] years), 93.0% and 89.0%, respectively, had an HbA1c level ≥7.5% (≥58.46 mmol/mol), and 56.4% and 54.9%, respectively, had an HbA1c level ≥9.0% (≥74.86 mmol/mol), at first prescription. At 6 to 9 months, 75.0% of those on dulaglutide 0.75 mg and 57.6% of those on semaglutide 0.25 mg or 0.5 mg had an HbA1c level ≥7.5% (≥58.46 mmol/mol). At 9 months, 21.9% of the dulaglutide cohort were on the suboptimal dose of 0.75 mg, and 46.1% of the semaglutide cohort were on the suboptimal doses of 0.25 mg or 0.5 mg.

Conclusions

Multiple examples of therapeutic inertia were identified, including first prescription at HbA1c levels considerably above target and failure to escalate to optimal doses even with evidence of suboptimal metabolic control. A substantial proportion of patients therefore did not achieve optimal HbA1c targets.
Estimates of COVID‐19 deaths in Mainland China after abandoning zero COVID policy
Authors: Ioannidis John P. A. , Zonta Francesco , Levitt Michael
Published: January 2023

Background

China witnessed a surge of Omicron infections after abandoning ‘zero COVID’ strategies on 7 December 2022. The authorities report very sparse deaths based on very restricted criteria, but massive deaths are speculated.

Methods

We aimed to estimate the COVID‐19 fatalities in Mainland China until summer 2023 using the experiences of Hong Kong and of South Korea in 2022 as prototypes. Both these locations experienced massive Omicron waves after having had very few SARS‐CoV‐2 infections during 2020–2021. We estimated age‐stratified infection fatality rates (IFRs) in Hong Kong and South Korea during 2022 and extrapolated to the population age structure of Mainland China. We also accounted separately for deaths of residents in long‐term care facilities in both Hong Kong and South Korea.

Results

Infection fatality rate estimates in non‐elderly strata were modestly higher in Hong Kong than South Korea and projected 987,455 and 619,549 maximal COVID‐19 deaths respectively, if the entire China population were infected. Expected COVID‐19 deaths in Mainland China until summer 2023 ranged from 49,962 to 691,219 assuming 25–70% of the non‐elderly population being infected and variable protection of elderly (from none to three‐quarter reduction in fatalities). The main analysis (45% of non‐elderly population infected and fatality impact among elderly reduced by half) estimated 152,886–249,094 COVID‐19 deaths until summer 2023. Large uncertainties exist regarding potential changes in dominant variant, health system strain and impact on non‐COVID‐19 deaths.

Conclusions

The most critical factor that can affect total COVID‐19 fatalities in China is the extent to which the elderly can be protected.
Global, regional and national burden of alopecia areata and its associated diseases, 1990–2019: A systematic analysis of the Global Burden of Disease Study 2019
Authors: Jang Hyeokjoo , Park Seoyeon , Kim Min Seo , Yon Dong Keon , Lee Seung Won , Koyanagi Ai , Kostev Karel , Shin Jae Il , Smith Lee
Published: January 2023

Background

No study to date has concomitantly reported the global burden of alopecia areata (AA) and its associated diseases.

Methods

The crude and age‐standardized rates of prevalence (ASPR), incidence (ASIR) and years lived with disability (YLDs) of AA were extracted from the global burden of disease, injuries and risk factors study (GBD) database between 1990 and 2019 for 204 countries and territories. We stratified the analysis by global region, nation, sex, age and sociodemographic index (SDI) to dissect the epidemiology of AA and its associated diseases.

Results

Alopecia areata was responsible for 0.024% of the total DALYs. Age‐standardized DALYs rate of AA was 7.51 [4.73–11.14] per 100,000. Overall ASPR, ASIR and age‐standardized YLDs rates were stable from 1990 to 2019 globally. All three rates were about two times higher in females compared to males and had a bimodal distribution with peaks at age 30–34 years and 60–64 years. AA burden was positively correlated with SDI (r = .375, p < .001) and was most prevalent in high‐income countries, especially North America. Countries with a high AA incidence were more likely to have high incidences of autoimmune diseases and low incidences of ischaemic heart disease and ischaemic stroke.

Conclusions

The burden of AA was prominent in females, young adults, high sociodemographic countries and North Americans. The study corroborates sex‐ and region‐specific implications and public health measures for AA and its associated burdens. These epidemiological data on AA burden can guide future research efforts, prevention strategies and allocation of resources.
Global and local drivers of the relative importance of allochthonous and autochthonous energy sources to freshwater food webs
Authors: Leal Juliana S. , González Angélica L. , Soares Bruno E. , Casa Nova Clarice , Marino Nicholas A. C. , Farjalla Vinicius F.
Published: January 2023

Resource quantity (i.e. organic matter; OM) is a main driver of the prevailing energy pathway in freshwater food webs. The OM pool is mainly composed of allochthonous material, a primary resource for freshwater consumers. Contrastingly, small amounts of autochthonous OM (i.e. algae) can subsidize aquatic communities due to its higher nutritional quality. To date, there is no consensus about the relative importance of allochthonous and autochthonous OM for freshwater food webs or the environmental factors driving their relative importance. We fill this gap by evaluating the relative importance of allochthonous and autochthonous OM sources for freshwater food webs on a global scale through a meta‐analytical approach. We gathered the outcome of stable isotope mixing models of 2789 cases from 58 published studies and calculated a response ratio between the mean contributions of allochthonous and autochthonous OM for freshwater consumers. Using mixed‐effect models and a multimodel inference approach, we tested the influence of latitude, habitat type, ecosystem size, climate and terrestrial productivity over the response ratio. The relative contribution of autochthonous OM was higher in lotic systems. In lentic systems, increasing terrestrial productivity increased the relative contribution of autochthonous OM, while increasing precipitation and temperature seasonality reduced this relative contribution. We suggested that factors increasing terrestrial productivity might also boost autochthonous OM in these systems, while precipitation increases the transport of allochthonous OM to freshwater habitats. We did not find any relationship between environmental factors and the relative contribution of autochthonous OM for lotic systems. We concluded that the relative contribution of allochthonous and autochthonous energy sources to freshwater food webs differs between lotic and lentic ecosystems and it is dependent on multiple environmental factors.