bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of short, oral treatment regimens for rifampicin resistant tuberculosis
Authors: Sweeney Sedona , Berry Catherine , Kazounis Emil , Motta Ilaria , Vassall Anna , Dodd Matthew , Fielding Katherine , Nyang’wa Bern-Thomas
Published: November 2022

Introduction

Current options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens.

Methods

We used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazimine (BPaLC) compared with the current mix of long and short standard of care (SOC) regimens to treat RR-TB from the provider perspective in India, Georgia, Philippines, and South Africa. We estimated total costs (2019 USD) and disability-adjusted life years (DALYs) over a 20-year time horizon. Costs and DALYs were discounted at 3% in the base case. Parameter uncertainty was tested with univariate and probabilistic sensitivity analysis.

Results

We found that all three regimens would improve health outcomes and reduce costs compared with the current programmatic mix of long and short SOC regimens in all four countries. BPaL was the most cost-saving regimen in all countries, saving $112-$1,173 per person. BPaLM was the preferred regimen at a willingness to pay per DALY of 0.5 GDP per capita in all settings.

Conclusions

Our findings indicate BPaL-based regimens are likely to be cost-saving and more effective than the current standard of care in a range of settings. Countries should consider programmatic uptake of BPaL-based regimens.
Drought effects of annual and long-term temperature and precipitation on mortality risk for 9 common European tree species
Authors: Neumair Matthias , Ankerst Donna P. , Potočić Nenad , Timmermann Volkmar , Ognjenović Mladen , Brandl Susanne , Falk Wolfgang
Published: November 2022

Risk factors for natural tree mortality in managed forests, excluding wind and snow induced breakage, fires and thinning, can be difficult to identify due to correlated confounders of long- and short-term weather patterns with tree age. This study quantified the association of annual and long-term 30-year average temperature and precipitation effects on individual tree death across Europe from 2011 to 2020 for European beech, sessile and pedunculate oak, silver birch, black pine, Austrian oak, Scots pine, European hornbeam, and Norway spruce. For each species, logistic regression approaches for predicting annual mortality evaluated the influence of age, exposition and weather effects on individual tree death, while accounting for multi-collinearity of risk factors. For all species except sessile oak, higher 30-year-temperature averages were associated with higher odds of tree mortality. Effect size of other risk factors varied among species, with similar weather associations between Austrian and sessile oak on the one hand, and Scots pine, Norway spruce and pedunculate oak on the other hand. In particular, warmer winters reduced mortality for silver birch, sessile and Austrian oaks, while having the opposite association for the other species. Sessile oak was most robust against drought effects and could serve as an important tree species under climate change scenarios.
A potential function for the helicase Dbp5 in cytoplasmic quality control
Authors: Querl Luisa , Lu Yen-Yun , Beißel Christian , Krebber Heike
Published: November 2022

Accurate translation requires correct mRNAs with intact open reading frames. Cells eliminate defective transcripts to prevent mistranslation by three cytoplasmic mRNA quality control events termed nonsense-mediated decay (NMD), no-go decay (NGD) and non-stop decay (NSD). Translation termination on correct transcripts requires Dbp5 (human DDX19), which delivers eRF1 to the ribosomes and prevents an early contact of eRF1 with eRF3, precluding the immediate dissociation of both release factors and subsequent termination readthrough. Here, we report evidence for an influence of Dbp5 on NMD, as it delivers eRF1 also to PTC-containing transcripts. In contrast to regular translation termination and NMD, functional NGD and NSD require the eRF1-eRF3-like proteins Dom34-Hbs1. We suggest that Dbp5 delivers Dom34 to NGD and NSD substrates as well. However, in contrast to regular termination, it does not prevent an Hbs1 contact, but allows formation of a ternary Dom34-Hbs1-Dbp5 complex. The Dbp5-mediated delivery of Dom34-Hbs1 in NGD and NSD might rather shield and position the complex to prevent a premature contact of Dom34 and Rli1 to prevent inefficient splitting of the ribosomal subunits. Together, we have gathered evidence suggesting an important role of Dbp5 in cytoplasmic mRNA quality control.
The capital logic of platform economy globalisation and it’s critique and transcendence
Authors: Han Wenlong
Published: November 2022

Purpose

To realise the shared development of the digital economy, people need to transcend the capital logic and advocate the logic of cooperative development, i.e. “co-construction, benefit-sharing and co-governance”. This study aims to discuss the aforementioned statement.

Design/methodology/approach

Platform economy is a new economic form produced by the transformation of the social production patterns in the era of digital capitalism. In the neo-imperialist stage, a new stage of capitalist development, capital logic promotes the global expansion of the platform economy and influences its development process, organisational form, contradictions and dilemmas and internal transcendence. Having the spatiotemporal chain of capital circulation repaired, the globalisation of the platform economy is reshaping how the means of production are combined with labour, affecting the local changes in the general relations of production and “international relations of production”.

Findings

In the accumulation of digital capitalism, the social contradictions and fundamental contradictions in the capitalist world have been further intensified, making exploitation, income distribution gap, monopoly and other problems increasingly severe. The imbalance and inequality in the global development of the digital economy are increasingly prominent.

Originality/value

Regarding the global governance of the digital economy, China, as a major responsible country, will strive to encourage all countries to co-build a community with a shared future in cyberspace. In the new international development pattern of digital economy globalisation, China must take effective measures to actively safeguard its national security and development interests to meet specific challenges.
The impact of the number of participants and platform transparency on prosumers’ creative performance
Authors: Zeng Fue , Song Yining , Song Yiping Amy , Zuo Siqing , Yu Jinjun
Published: November 2022

Purpose

Prosumers’ creative performance in a co-creation activity is greatly affected by the disclosure of activity information. Extant research has separately examined the impact of participant numbers and the impact of platform transparency, but there is a lack of research on the interaction between the two. However, testing the joint effect of the two sources of information can provide a more comprehensive understanding of individuals’ co-creation behaviour. This paper aims to fill the gap and further reveal the psychological mechanism behind the behaviour.

Design/methodology/approach

Three experimental studies were conducted to test the hypotheses.

Findings

The results show that a large number of participants will stimulate and inhibit creative performances on untransparent and transparent co-creation platforms, respectively. Moreover, this study found that the effect of the number of participants on creative performance is mediated by arousal on untransparent platforms and by the constraint on idea expression on transparent platforms.

Research limitations/implications

This study advances knowledge of how the number of participants in an activity and platform transparency jointly influence prosumers’ creative performance and the corresponding mechanism. However, the main limitation of the study is that the findings are from scenario-based experiments.

Practical implications

This study provides a more comprehensive understanding of prosumers’ creative performance under the influence of the number of activity participants and platform transparency. The findings can help co-creation sponsoring companies and co-creation platforms improve activity performance by designing better information disclosure strategies, thereby enhancing platform value.

Originality/value

The findings enrich the literature on platform ecosystem and co-creation by integrating previously separate knowledge on the effects of participant numbers and platform transparency. In addition, the findings deepen the overall understanding of prosumers’ behaviour.
From local to the whole: understanding construction projects as multiteam systems
Authors: Jia Jianyao , Li Yang , Gan Xueqing , Ma Guofeng
Published: November 2022

Purpose

In today's digital and post-pandemic era, construction teams can span their boundary to obtain important resources and support in computer-mediated ways. However, the benefits of computer-mediated team boundary spanning (TBS) are mostly assumed. Empirical evidence for these benefits is in lack. Thus, this study attempts to investigate the influence of computer-mediated (instant messaging in this study) TBS on construction project performance and the underlying mechanism.

Design/methodology/approach

From the multiteam system (MTS) perspective, this study employs the input-process-outcome (IPO) framework and coordination theory to explore the influence of instant messaging-based team boundary spanning (IMTBS) on construction project coordination processes and project performance. A theoretical model is built and validated with a survey involving 206 construction projects.

Findings

Results show that IMTBS positively affects knowledge integration and project coordination, but negatively affects project commitment. The positive link between IMTBS and project performance is attributable to knowledge integration and project coordination. Further, project commitment is also found to negatively mediate the relationship between IMTBS and construction project performance.

Originality/value

To the best of the authors’ knowledge, this study is the first to empirically investigate the influence of TBS on construction project performance. As such, this study contributes to the literature on TBS in the construction field. In addition, the findings of this study unveil the double-edged characteristic of IMTBS, which should attract managers' attention. This also indicates that the form of TBS is a significant determinant of its effectiveness, which should attract scholars' attention in the future.
Quantitative thermography: a powerful but simple tool to assess the fatigue strength of metals in a one-specimen test–capabilities and limitations in the test setup
Authors: Rauber Jonas , Motz Christian , Schaefer Florian
Published: November 2022

Purpose

The aim of the study is the question, that is, which evaluation method for the measured temperature profile is more suitable and feasible for quantitative thermometry (QT): A simple measurement setup based on 3-point temperature sensing by means of semiconductor sensors (NTCs) or thermographic methods which offer 2-dimensional (2D) temperature measurements of the sample with good spatial resolution but an inferior temperature sensitivity. What experimental effort is required to adjust the test setup to satisfy the boundary conditions of the underlying thermodynamic equations?

Design/methodology/approach

In this paper results of both methods are contrasted and the error of QT measurement is assessed by finite element analysis (FEA) in this follow-up.

Findings

The low-cost NTC method allows a straightforward determination of a lower estimate of the fatigue strength with only a very small measurement error. Even asymmetries in the thermal boundary conditions of the test setup are broadly tolerated, as well as a lack of thermal isolation.

Practical implications

The method is restricted to metallic materials without phase transitions during fatigue in the fatigue strength regime.

Originality/value

QT is not a new method. The assessment of the methods proposed in the literature regarding their practicability in terms of accuracy is innovative focus of this work. Nevertheless, highly accurate thermometric measurements can be performed by using simple commercial sensors in combination with a standard digital multimeter.
Political connection, family ownership and corporate philanthropy: empirical evidence from Jordan
Authors: Ananzeh Husam , Alshirah Malek Hamed , Alshira'h Ahmad Farhan , Al-Hazaima Huthaifa
Published: November 2022

Purpose

A key goal of this research is to examine empirically whether politically connected board members are likely to impact corporate philanthropy. A further goal of this study is to contribute to the existing literature by examining the moderating role of political connections on the relationship between family ownership and corporate donations.

Design/methodology/approach

Based on the content analysis approach, the authors determined the level of cash and in-kind donations made by a group of 94 non-financial Jordanian companies listed on the Amman Stock Exchange. This study examined 658 annual reports spanning over seven years from 2010 to 2016. Ordinary least squares regression (OLS) is used to test the study hypotheses. In addition, this study used the probit regression to validate those results reported by the OLS regression.

Findings

Compared to unconnected companies, politically connected companies in Jordan are more likely to donate to philanthropic causes. Moreover, the results revealed that the presence of significant family ownership shareholding in a firm can weaken the firm tendency to donate. Despite this, the regression analysis results indicate that family-controlled firms with political connections are more likely to engage in charitable giving activities compared to those without political nexuses.

Research limitations/implications

The study contributes to the conversation surrounding corporate giving and sheds light on the role political connections and ownership structure (particularly family-owned firms) play in affecting donations by firms.

Practical implications

Managers of Jordanian firms listed on the stock exchange can use the study's findings to make better decisions about their donations and other philanthropic activities.

Originality/value

This study is the first to examine the relationship between firm donations and political connections in Jordan, and how political nexuses can moderate the relationship between family ownership and corporate donations. Hence, it extends prior research significantly.
Consumer purchase intention of social enterprise products: mediating role of emotional value
Authors: Ravi Nima , Subramoniam Suresh , VR Hareendrakumar , Chinta Ravi
Published: November 2022

Purpose

Social enterprises are organizations striving to address social issues. These enterprises sell products to be self-sustainable. Social entrepreneurial success depends on the intention of consumers to purchase social enterprise products. This study aims to assess and understand the consumer intention to buy social enterprise products.

Design/methodology/approach

This descriptive study integrates consumers’ emotional values with the theory of planned behaviour as a framework. The intention is to investigate the role of customer emotion in mediating the relationship between predictor and predicted variables. A mixed sampling technique is adopted to select sample units from the consumers with a consideration for regional balance. Data from 336 respondents were collected using a survey instrument administered online.

Findings

Structural equation modelling shows that among the three predictor variables, only attitude has a direct impact on consumer’s purchase intention, while subjective norms have an indirect impact through the mediating variable (emotional value). Behavioural control showed no effect on consumer’s purchase intention of products sold by social enterprises.

Originality/value

The results of this study have theoretical as well as practical implications. The success of social enterprises depends on the acceptance of their products by consumers. The social enterprise can strategize its marketing communications to strengthen the emotional values, attitudes and subjective norms of the consumers so that the market acceptance for these products can be increased.
Authorship, Image‐Making, and Excess: William Hunter's Anatomia uteri humani gravidi tabulis illustrata (1774)
Authors: Hughes Alicia
Published: November 2022

In 1774, the physician‐anatomist William Hunter (1718–1783) published Anatomia uteri humani gravidi tabulis illustrata/The Anatomy of the Human Gravid Uterus, Exhibited in Figures (1774). Issued as an elephant folio, the book is the culmination of twenty‐four years of work and includes thirty‐four plates with life‐size hyper‐naturalistic engravings by artists such as Robert Strange after drawings by Jan Van Rymsdyk. Anticipating potential critique of the book's stylistic choices, Hunter took pains in his preface to assure readers that although the book was lavishly illustrated, it was not excessively so, stating that he had ‘actually kept back several drawings which had been made, and two plates which had been engraved’. The decision to exclude these extra images was based on a desire ‘that the work not be overcharged’. On the eve of the 250th anniversary of the publication of Anatomia, this article takes Hunter's claim of authorial restraint as a departure point from which to examine the anatomist's construction of authorship within the illustrated book. Analysing the paratextual features of the book alongside previously unstudied contemporary reviews reveals how Hunter exerted rhetorical control over the production and reception of the book and its complex visual language. Through examination of the yet unstudied material remnants of the book's production, the drawings and prints Hunter excluded from the book are identified and examined to determine the extent to which Hunter's authorial control manifested in the material conditions of the book's production. Through the close analysis of Hunter's authorship within the context of eighteenth‐century anxieties about excess, this article offers a new understanding of the production and reception of the Anatomia as well as the collaborative process of scientific image‐making practices and book production in the eighteenth century.
Mishel's uncertainty in illness theory: Informing nursing diagnoses and care planning
Authors: Reinken Desiree N. , Reed Sean M.
Published: November 2022

Purpose

Patients with glioblastoma multiforme (GBM) face uncertainty during the illness trajectory that decreases their quality of life. Uncertainty manifests as an altered state of mind in patients with GBM and increases the burden of managing their diagnosis. The uncertainty in illness theory (UIT) can be used to guide nursing practice and create care plans to decrease this uncertainty.

Data sources

The UIT and conceptual model were used to pair diagnoses from NANDA‐I Nursing Diagnoses to form care plans for patients with GBM.

Methods

In a stepwise approach, concepts from the UIT were organized and cross‐walked into an integrated theory‐driven practice framework to enhance care planning.

Conclusions

The UIT helps define and identify circumstances of uncertainty in patients experiencing illness, and Nursing Diagnoses provide engagement and outcomes for those uncertainty‐based diagnoses. Some examples of the UIT guiding Nursing Diagnoses includes a patient's cognitive level guiding a Nursing Diagnosis care plan of Risk for Acute Confusion. Social Support can guide the care plan of Risk for Loneliness, and appraisal of uncertainty can guide a care plan for Ineffective Individual Coping. Using the UIT to guide theory‐driven practice links interventions and outcomes in patients with GBM.

Implications for practice

The UIT can guide NANDA‐I Nursing Diagnoses to assist nurses in creating a nursing care plan for nursing engagement to decrease uncertainty and increase the quality of life in patients with GBM. Theory‐driven research defines the application of the UIT in GBM and provides foundational knowledge for theory‐driven practice to occur.
Phenological growth stages and growing degree days of peach [Prunus persica (L.) Batsch] in sub‐temperate climatic zone of North‐Western Himalayan region using BBCH scale
Authors: Verma Pramod , Singh Jagveer , Sharma Shivani , Thakur Hrithik
Published: November 2022

In this study, the phenological stages of peach have been described for the first time according to the BBCH scale (Biologische Bundesanstalt, Bundessortenamt and Chemische Industrie) and Baggiolini codes for five cultivars (Pratap, Tropic Snow, Tropic Beauty, Redhaven and July Elberta) in sub‐temperate region of India, which markedly differentiates vegetative and reproductive stages occurring in peach. The growing degree days (GDD) are the best indicators for monitoring the different phenological growth stages and were determined from dormancy breaking to fruit harvest when the cultivars reached maturity. Pratap, Tropic Snow and Tropic Beauty were identified as early‐season maturing with 814 ± 5.10, 996 ± 8.13 and 1004 ± 8.72 GDD, respectively. While, Redhaven was mid‐season cultivar with 1502 ± 16.17 GDD, and July Elberta was the late‐season cultivar with 1894 ± 6.00 GDD. Mid‐season cultivar Redhaven performed better in India's sub‐temperate region, accounting for higher yield (54.87 kg per tree), fruit length: diameter (1.11), TSS (12.26%) and total sugars content (10.26%). The description presented in the paper will act as a tool to provide a consensual unified approach for standardisation of phenological stages in peach and also for various cultural inputs and timely planning of harvesting. Moreover, the BBCH scale will act as a tool to assess the impact of climate change on crop phenology and to evaluate the adaptation of particular peach cultivars to different conditions.
The prognostic value of elevated neutrophil–lymphocyte ratio for cardiac surgery‐associated acute kidney injury: A systematic review and meta‐analysis
Authors: Wheatley Joseph , Liu Zhengyang , Loth Joel , Plummer Mark P. , Penny‐Dimri Jahan C. , Segal Reny , Smith Julian , Perry Luke A.
Published: November 2022

Background

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil–lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.

Methods

We conducted a systematic review and meta‐analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta‐analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta‐regression to explore inter‐study statistical heterogeneity.

Results

Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18–1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50–3.72). Postoperative NLR measurements were not of prognostic significance.

Conclusions

Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.
Mood stabilizers and risk of all‐cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study
Authors: Chen Pao‐Huan , Tsai Shang‐Ying , Chen Po‐Yu , Pan Chun‐Hung , Su Sheng‐Siang , Chen Chiao‐Chicy , Kuo Chian‐Jue
Published: November 2022

Objectives

People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all‐cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder.

Methods

In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time‐dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome.

Results

The SMRs of all‐cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all‐cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5‐year follow‐up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all‐cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001).

Conclusion

In addition to having protective effects against suicide and all‐cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality.
Within‐person associations of escalated electronic nicotine delivery systems use with cigarette, alcohol, marijuana and drug use behaviors among US young adults
Authors: Han Dae‐Hee , Elam Kit K. , Quinn Patrick D. , Huang Chunfeng , Seo Dong‐Chul
Published: November 2022

Aims

Most extant evidence has addressed between‐person differences, short‐term or cross‐sectional associations of electronic nicotine delivery systems (ENDS) use with other substance use, the majority focusing on current rather than escalated use. The present study aimed to examine within‐person changes in escalated ENDS use and their associations with individual and combined substance use over a 6‐year period.

Design, Setting and Participants

This study used a longitudinal cohort design with US young adults. A generalized linear mixed‐model approach was employed to fit a series of weighted logistic regression models. Data were drawn from waves 1–5 of the Population Assessment of Tobacco and Health (PATH) study in the United States. Of the 9110 young adults at baseline, aged 18–24 years, a total of 5042 individuals had matched data across all five waves of assessments.

Measurements

Escalated ENDS use was computed by subtracting the number of days of ENDS use within the past 30 days at wave
from that at wave
and coded as 1 = escalated, if the value was greater than zero (otherwise, coded as 0 = not escalated).

Findings

Escalated ENDS use gradually decreased over time, with the lowest prevalence at wave 4 (4.0%) but sharply increasing at wave 5 (8.4%). Escalated ENDS use was associated with increased odds of using each substance (binge drinking, marijuana use, marijuana vaping, prescription and illicit drugs) and different combinations of polysubstance use between cigarette smoking, binge drinking and marijuana use (Ps < 0.05). In addition, sweet/fruit flavor use (versus menthol/mint) was associated with increased likelihood of reporting co‐use of cigarettes and marijuana.

Conclusions

In the United States, the prevalence of young adults using electronic nicotine delivery systems appears to have increased steadily between 2013 and 2019, although the rate of increase may have started to accelerate in recent years. Escalated electronic nicotine delivery systems use and time‐lagged established electronic nicotine delivery systems use appear to be prospectively associated with individual and combined substance use, particularly between cigarettes, alcohol and marijuana. Among established electronic nicotine delivery systems users, sweet/fruit flavor appears to be associated with increased risk of co‐using cigarettes and marijuana.
Wardens of Civilisation: The Political Ecology of Australian Far‐Right Civilisationism
Authors: McFadden Alexandra
Published: November 2022

The notion of a superior “civilisation” has been a hallmark of the politics of Western institutions and fringe white supremacists alike. Known ideologically as “civilisationism”, it has occupied a prominent position in the ideology of the Australian far‐right. Paying tribute to their settler‐colonial origins, the far‐right has consistently promoted “white civilisation”, even inspiring terrorist attacks. Despite this propensity for violence, far‐right civilisationism remains largely unexplored. Through investigating a dataset of Australian far‐right content, this paper reveals civilisationism as a significant part of their ideology, an ideology which relies on the idealisation of European technologies and environments to render Indigenous land and people uncivilised. A critical narrative analysis of the data illustrates the ways that these ecological factors are drawn into narrative to articulate Australian far‐right civilisationism, an ideology inseparable from the political ecology of European history and colonialism, that today represents a particularly virulent version of its legacy.
Interspecies normalization of dose‐response relationship for adeno‐associated virus‐mediated haemophilia gene therapy—Application to human dose prediction
Authors: Zou Peng
Published: November 2022

Aims

The aim of this study is to develop an approach to predict human dose–response relationship and first‐in‐human (FIH) dose for adeno‐associated virus (AAV)‐mediated haemophilia gene therapy.

Methods

Preclinical dose–response relationships of 7 AAV vectors were normalized to a species‐invariant scale using an exponent of 0.25, and the normalized dose–response relationship was then used for FIH dose prediction. The performance of this dose–response normalization approach for FIH dose prediction was compared to that of direct body weight‐based dose (vg/kg) conversion and allometric scaling approaches.

Results

A power regression analysis of normalized factor VIII (FVIII) or factor IX (FIX) showed a moderate‐to‐strong correlation between FVIII or FIX and vector dose across 3 species (R2 ranged 0.59 to 0.89), indicating it was feasible to normalize dose–response in multiple species to a species‐invariant scale. When the mean values of normalized FVIII or FIX at each dose level were used for regression, the R2 values of the 7 vectors were improved to be >0.84. The FIH doses predicted by the 3 approaches were ranked as allometric scaling > dose–response normalization > direct vg/kg conversion for all vectors except for rAAV2‐hAAT‐FIX and scAAV2/8‐LP1‐hFIXco. Among the 7 vectors, dose–response normalization, direct vg/kg conversion and allometric scaling generated accurate FIH dose predictions for 2, 2 and 3 vectors, respectively.

Conclusion

This study first demonstrated that it is feasible to normalize dose–response relationship of AAV‐mediated haemophilia gene therapy in multiple species to a species‐invariant scale. The normalized dose‐response relationship from preclinical species was successfully extrapolated to patients for FIH dose prediction.
Exploring Silence in Psychoanalytic Theory and Clinical Work
Authors: Acheson Rachel , Avdi Evrinomy
Published: November 2022

Silence, as an element of the therapeutic encounter has been of interest in psychoanalytic theory from the early stages of its development. Theoretical views on the functions of silence have broadened considerably since the phenomenon was first examined, in line with developments of theory and technique. This literature review aims to explore silence in psychoanalytic theoretical literature and proposes three broad categories of silence in psychoanalytic psychotherapy, namely: silence as defence; silence as connection; and silence as withdrawal. From this review it appears that silences in psychoanalytic therapy may often be multidetermined in nature; it is suggested that there are limits to the extent to which these can, and possibly should, be understood. The implications of the theoretical understanding of silence for clinical practice are then explored, and the importance of each therapist finding their own way to incorporate silence into their work with each patient is acknowledged. Debate within the literature as well as research in this area are important to further understanding of this phenomenon.
Temporary sutures using reopenable clips and barbed threads
Authors: Kato Hiroki , Kobayashi Makoto , Yano Motoyoshi
Published: November 2022

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Evaluation of the Mayo Additive Staging System in patients with newly diagnosed multiple myeloma: A real‐world analysis
Authors: Chen Haimin , Shi Haotian , Zhou Nian , Yu Wenjun , Wu Lixia , Peng Rong , Wei Wei , Wang Dongjiao , Zhou Fan
Published: November 2022

Objectives

Recently, the Mayo Clinic introduced a new staging system (the Mayo Additive Staging System [MASS]) for patients with newly diagnosed multiple myeloma (NDMM) based on the number of high‐risk (HR) abnormalities, including HR IgH translocations, 1q gain/amplification, chromosome 17 abnormalities, International Staging System (ISS)‐III, and elevated lactate dehydrogenase. Patients with 0, 1, or ≥2 HR abnormalities were defined as stage I, II, or III, respectively. We aimed to validate the real‐world prognostic value of the MASS.

Methods

We retrospectively analyzed the cytogenetic and laboratory results of 544 patients with NDMM at a single center.

Results

Ninety (16.5%) patients had no HR factors (MASS I), 193 (35.5%) had 1 HR factor (MASS II), and 261 (48%) had ≥2 HR factors (MASS III). The median progression‐free survival (PFS) and overall survival (OS) times were 48, 28, and 20 months and 137, 73, and 39 months in the three groups, respectively (p < .001). In the subgroup analysis, patients had different OS outcomes based on the MASS when grouped by age, renal function, or therapeutic regimens. The MASS identified patients with the worst outcomes among those rated revised ISS II.

Conclusion

The MASS system is a reliable risk stratification tool for patients with NDMM in real‐world clinical practice.
Functional disorders as a common motor manifestation of COVID‐19 infection or vaccination
Authors: Fung Wilson K. W. , Sa'di Qais , Katzberg Hans , Chen Robert , Lang Anthony E. , Cheung Angela M. , Fasano Alfonso
Published: November 2022

Background and purpose

There have been over 500 million confirmed cases of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), also known as coronavirus disease 2019 (COVID‐19), across the globe. To date, a broad spectrum of neurological manifestations following acute infections as well as COVID‐19 vaccines have been reported. The aim of this study was to describe the spectrum of neurological manifestations seen in the ‘COVID‐19 clinic’ established in a tertiary Movement Disorders clinic.

Methods

In this consecutive case‐series study over the period March 2020–January 2022, clinical information regarding demographic data, clinical history and examination findings, investigation results and video recordings of outpatients with motor manifestations associated with COVID‐19 infection or vaccination were reviewed.

Results

Twenty‐one adult patients were reviewed in this ad hoc clinic at Toronto Western Hospital. The majority of the patients were female (76%) and the mean (range) age was 50.7 ± 17.2 (21–80) years. Nine patients (43%) presented with motor manifestations following COVID‐19 infection. Twelve patients (57%) developed neurological symptoms following at least one dose of the mRNA or viral vector‐based COVID‐19 vaccine. The most common manifestation observed was a functional movement disorder (43%). The vaccine group demonstrated a higher number of functional disorders compared to the infection group (58% vs. 22%; p = 0.08).

Conclusion

Functional motor manifestations can be associated with COVID‐19 and are likely to be under‐reported. In view of the co‐existence of functional symptoms, movement disorders and mental health conditions observed in this study, we would advocate the use of dedicated COVID‐19 Neurology clinics with full access to an experienced multidisciplinary team.
Identification of reversed portal flow on 4DCT and of factors contributing to reversed portal flow in patients with liver cirrhosis and portosystemic shunt before interventional radiology procedures
Authors: Kageyama Ken , Yamamoto Akira , Jogo Atsushi , Sohgawa Etsuji , Izuta Shinichiro , Himoto Daisuke , Kakimi Akihiko , Kita Ryuichi , Miki Yukio
Published: November 2022

Aim

Patients with liver cirrhosis and portosystemic shunt occasionally develop reversed portal flow in the portal venous system. The factors contributing to reversed portal flow in these patients remain unclear. The aim of this study was to identify factors contributing to reversed portal flow in patients with portosystemic shunts based on four‐dimensional computed tomography (4DCT), which visualized flow dynamics in the portal venous system.

Methods

Data from 34 consecutive patients with portosystemic shunts who had undergone 4DCT before interventional radiology procedures were retrospectively investigated in this study. Uni‐ and multivariate analyses were performed to identify factors contributing to reversed portal flow.

Results

Flow dynamics could be visualized on 4DCT in 32 of the 34 patients. Fifteen patients had forward portal flow; 17 had reversed portal flow. The main portal, splenic, and superior mesenteric veins displayed reversed portal flow in five, 12, and five vessels, respectively. Portosystemic shunt originating from splenic and superior mesenteric veins, worse albumin‐bilirubin score, and small main portal vein diameter were significant factors contributing to reversed portal flow in both univariate (p = 0.049, p = 0.027, and p = 0.002) and multivariate (odds ratio [OR] 6.345, p = 0.012; OR 4.279, p = 0.039; and OR 5.516, p = 0.019) analyses.

Conclusions

The reversed portal flow was visualized on 4DCT. Portosystemic shunt originating distant to the liver, worse albumin‐bilirubin score, and small diameter of the main portal vein were factors contributing to reversed flow in the portal venous system.
Epidemiology, comorbidities at diagnosis and outcomes associated with HIV late diagnosis from 2010 to 2019 in a Belgian reference centre: A retrospective study
Authors: Severin Simon , Delforge Marc , De Wit Stéphane
Published: November 2022

Objectives

Our objective was to investigate the demographic factors, comorbidities, and outcomes of patients with a late diagnosis (LD) of HIV in a Belgian HIV reference centre.

Methods

All patients with HIV who presented for care between 2010 and 2019 were included. They were excluded if time between diagnosis and presentation or first CD4 count exceeded 6 months or if they had previously received antiretroviral therapy (ART). LD was defined as a CD4 cell count ≤350/mm3or an AIDS‐defining event at diagnosis. Data were retrospectively collected and included data on demographic variables, cardiovascular risk factors, comorbidities at diagnosis, first prescribed ART, and outcomes. Logistic regression was used to determine factors associated with LD.

Results

Of 1078 patients, 427 (39.6%) were LD. In multivariable analysis, the following factors were associated with LD: non‐homosexual transmission route, being born in Sub‐Saharan Africa (SSA), and age ≥35 years. Prevalence at diagnosis of malignancies, diabetes, and cardiovascular diseases did not differ between non‐LD and LD, whereas renal impairment was more frequent in LD. In univariable analysis, high‐density lipoprotein (HDL) cholesterol <40 mg/dL and estimated glomerular filtration rate <60 ml/min were associated with LD; in multivariable analysis, only HDL cholesterol <40 mg/dL was associated. Patients with LD experienced more adverse events leading to a switch in ART, virological failure, and death during follow‐up.

Conclusion

LD remains common in our centre, especially in non‐homosexual patients and those born in SSA. Although not associated with an important burden of comorbidities at diagnosis, it still results in poorer outcomes, emphasizing the need to expand coverage and access to HIV testing.
The adverse impact of ecotropic viral integration site‐1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes
Authors: Liu Xin‐xin , Pan Xin‐an , Gao Meng‐ge , Kong Jun , Jiang Hao , Chang Ying‐jun , Zhang Xiao‐hui , Wang Yu , Liu Kai‐yan , Chen Zhong , Zhao Xiao‐su , Huang Xiao‐jun
Published: November 2022

Introduction

AML patients with KMT2A‐MLLT3 and other 11q23 abnormalities belong to the intermediate and high‐risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site‐1 (EVI1) overexpression suits either the subtypes of KMT2A‐MLLT3 or Non‐KMT2A‐MLLT3 AML patients (intermediate and high risk group) needs to be further investigated.

Methods

We retrospectively analyzed the clinical characteristics of 166 KMT2A‐r and KMT2A‐PTD AML patients.

Results

For the Non‐KMT2A‐MLLT3 group, patients in the EVI1‐high subgroup had shorter OS and DFS and higher CIR than those in the EVI1‐low subgroup (p = .027, p = .018, and p = .020, respectively). Additionally, both KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo‐HSCT) regardless of their EVI1 expression level (all p < .001). For transplanted patients with KMT2A‐MLLT3 or Non‐KMT2A‐MLLT3 rearrangement, the EVI1‐high subgroup had worse prognosis than the EVI1‐low subgroup (all p < .05). The 2‐year CIR of the KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2‐year CIR of transplanted patients with KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 was relatively low.

Conclusions

Our study showed that for the Non‐KMT2A‐MLLT3 group, the EVI1‐high group had shorter OS and DFS than the EVI1‐low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1‐high patients with non‐KMT2A‐MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration.
Effects of neutrophil‐to‐lymphocyte ratio, serum calcium, and serum albumin on prognosis in patients with diabetic foot
Authors: Xu Su , Wang Yijia , Hu Zhensheng , Ma Ling , Zhang Fan , Liu Pei
Published: November 2022

The purpose of this study is to investigate the predictive value of neutrophil‐to‐lymphocyte ratio (NLR), serum calcium, and serum albumin on the prognosis of patients with diabetic foot. A total of 156 patients who were treated in the Department of Burn and Plastic Surgery of Qilu Hospital of Shandong University from 1 January 2014 to 1 August 2020 were selected. All the patients were randomly divided into a healing group, minor amputation group, major amputation group, and death group according to their treatment outcomes. The levels of NLR, serum calcium and serum albumin in each group were examined and compared. The correlations between NLR, serum calcium, and serum albumin with the prognosis of diabetic foot were analysed to investigate their predictive effects on the prognosis of diabetic foot. The results of one‐way ANOVA showed that among the 4 groups of patients, the difference in NLR values between the healing group and the minor amputation group was slightly smaller, but they were significantly different from the major amputation group and the death group, respectively. There was no significant difference in serum calcium levels between the healing group and the minor amputation group, but the serum calcium levels of the major amputation group and the death group gradually decreased. The levels of NLR in the 4 groups gradually increased, while the albumin levels gradually decreased. Spearman's rank correlation test indicated that NLR was significantly related to the prognosis of patients with diabetic foot. The group with higher NLR had a worse prognosis in diabetic foot patients. Serum calcium and serum albumin were strongly correlated with the prognosis of patients with diabetic foot. The group with lower serum calcium and serum albumin values had a worse prognosis in diabetic foot patients. The areas under the receiver operator characteristic curve of NLR, serum calcium and serum albumin were 0.901, 0.803, and 0.816, respectively. NLR, serum calcium and serum albumin can be used as reliable indicators to predict the prognosis of diabetic foot. Preoperative diabetic foot patients with higher NLR values or lower serum calcium and serum albumin have a poorer prognosis.
Selection on sperm size in response to promiscuity and variation in female sperm storage organs
Authors: Cramer Emily R. A. , Yilma Zelealem B. , Lifjeld Jan T.
Published: November 2022

Sperm cells are exceptionally morphologically diverse across taxa. However, morphology can be quite uniform within species, particularly for species where females copulate with many males per reproductive bout. Strong sexual selection in these promiscuous species is widely hypothesized to reduce intraspecific sperm variation. Conversely, we hypothesize that intraspecific sperm size variation may be maintained by high among‐female variation in the size of sperm storage organs, assuming that paternity success improves when sperm are compatible in size with the sperm storage organ. We use individual‐based simulations and an analytical model to evaluate how selection on sperm size depends on promiscuity level and variation in sperm storage organ size (hereafter, female preference variation). Simulations of high promiscuity (10 mates per female) showed stabilizing selection on sperm when female preference variation was low, and disruptive selection when female preference variation was high, consistent with the analytical model results. With low promiscuity (2–3 mates per female), selection on sperm was stabilizing for all levels of female preference variation in the simulations, contrasting with the analytical model. Promiscuity level, or mate sampling, thus has a strong impact on the selection resulting from female preferences. Furthermore, when promiscuity is low, disruptive selection on male traits will occur under much more limited circumstances (i.e. only with higher among‐female variation) than many previous models suggest. Variation in female sperm storage organs likely has strong implications for intraspecific sperm variation in highly promiscuous species, but likely does not explain differences in intraspecific sperm variation for less promiscuous taxa.