bluuebunny/crossref_metadata_2025 huggingface dataset:
Undifferentiated–dedifferentiated endometrial carcinoma; the reappearance of an old friend with insights into the new data
Authors: Mourtzoukou Despoina , Thomakos Nikolaos , Lazaris Andreas C. , Vlachodimitropoulos Dimitrios , Goutas Nikolaos , Sotiropoulou Maria , Rodolakis Alexandros , Nonni Aphrodite
Published: March 2023

Endometrial carcinoma is a common malignancy in women and shows increasing incidence. Except for its two main pathogenetic types I and II, the continuing evolution on molecular genetics have led to a new classification system (TCGA), that includes four main molecular subtypes: (i) POLE‐mutant (ultramutated), (ii) hypermutated (MSI), (iii) copy‐number low/MSS (p53wt) and (iv) copy‐number high/serous‐like (p53mut). The undifferentiated and dedifferentiated endometrial carcinomas are rare and clinically aggressive variants, comprising about 10% of the high‐grade endometrial carcinomas and 2% of the endometrial carcinomas in general. Until recently, they were under‐recognized and not fully described morphologically and immunohistochemically/molecularly. Their recognition diagnostically is crucial because of their poor prognosis; approximately 40% of patients with these subtypes will die within 0.5–20 months after diagnosis, so additional therapeutic strategies are important for an effective management. Because of their rarity, the responsiveness to other than conventional treatment, such as immunotherapy, has not been sufficiently investigated yet. The aim of this review is to provide an update on the knowledge about these two uncommon subtypes according to the current literature.
Longitudinal assessment of the impact of aging on wastage, productivity and welfare of ewes
Authors: Robertson SM , Friend MA
Published: March 2023

Retention of aging ewes is a strategy producers may use to maintain or increase flock size. Older ewes can have a higher risk of mortality and health issues, but these may be minimised with early intervention and culling. This retrospective study examined the incidence and causes of mortality and culling in a flock of Merino ewes as they aged from 4.5 to 5.5 until 9.5 to 10.5 years. The annual rate of ewe mortality ranged from 6.2% to 9.9%, with lambing complications being the major source of reported loss. Annual culling rates ranged from 1.6% to 42.8%, the larger rates reflecting opportunistic replacement with younger ewes rather than essential culling to maintain welfare and productivity. The major reasons for culling were low condition score, worn or missing teeth or faulty udders. The incidence of other faults was low. Only 18.3% of ewes remained when aged 9.5–10.5 years and these were fertile (89% pregnant) with a high proportion of multiple fetuses (52%) in their final year, although fleece weight had declined. Younger ewes born in 2004/2005 tended to have lower annual mortality rates than the aged ewes, but 8%–12% were still culled annually. It is concluded that an annual inspection pre‐joining of all ewes and preventative culling for health issues is necessary to minimise any increase in mortality and risk to ewe welfare from retaining aging ewes. More frequent inspection will be required as potential health issues develop during the year, as these may not be evident pre‐joining.
Artificial intelligence and the doctor–patient relationship expanding the paradigm of shared decision making
Authors: Lorenzini Giorgia , Arbelaez Ossa Laura , Shaw David Martin , Elger Bernice Simone
Published: March 2023

Artificial intelligence (AI) based clinical decision support systems (CDSS) are becoming ever more widespread in healthcare and could play an important role in diagnostic and treatment processes. For this reason, AI‐based CDSS has an impact on the doctor–patient relationship, shaping their decisions with its suggestions. We may be on the verge of a paradigm shift, where the doctor–patient relationship is no longer a dual relationship, but a triad. This paper analyses the role of AI‐based CDSS for shared decision‐making to better comprehend its promises and associated ethical issues. Moreover, it investigates how certain AI implementations may instead foster the inappropriate paradigm of paternalism. Understanding how AI relates to doctors and influences doctor–patient communication is essential to promote more ethical medical practice. Both doctors' and patients' autonomy need to be considered in the light of AI.
Detecting the Spatial Clustering of Exposure–Response Relationships with Estimation Error: A Novel Spatial Scan Statistic
Authors: Wang Wei , Li Sheng , Zhang Tao , Yin Fei , Ma Yue
Published: March 2023

Detecting the spatial clustering of the exposure–response relationship (ERR) between environmental risk factors and health-related outcomes plays important roles in disease control and prevention, such as identifying highly sensitive regions, exploring the causes of heterogeneous ERRs, and designing region-specific health intervention measures. However, few studies have focused on this issue. A possible reason is that the commonly used cluster-detecting tool, spatial scan statistics, cannot be used for multivariate spatial datasets with estimation error, such as the ERR, which is often defined by a vector with its covariance estimated by a regression model. Such spatial datasets have been produced in abundance in the last decade, which suggests the importance of developing a novel cluster-detecting tool applicable for multivariate datasets with estimation error. In this work, by extending the classic scan statistic, we developed a novel spatial scan statistic called the estimation-error-based scan statistic (EESS), which is applicable for both univariate and multivariate datasets with estimation error. Then, a two-stage analytic process was proposed to detect the spatial clustering of ERRs in practical studies. A published motivating example and a simulation study were used to validate the performance of EESS. The results show that the clusters detected by EESS can efficiently reflect the clustering heterogeneity and yield more accurate ERR estimates by adjusting for such heterogeneity.
Acute chest syndrome in adult patients with sickle cell disease: The relationship with the time to onset after hospital admission
Authors: Cheminet Geoffrey , Brunetti Antoine , Khimoud Djamal , Ranque Brigitte , Michon Adrien , Flamarion Edouard , Pouchot Jacques , Jannot Anne‐Sophie , Arlet Jean‐Benoît
Published: March 2023

Data on acute chest syndrome (ACS) in adult sickle cell disease patients are scarce. In this study, we describe 105 consecutive ACS episodes in 81 adult patients during a 32‐month period and compare the characteristics as a function of the time to onset after hospital admission for a vaso‐occlusive crisis (VOC), that is early‐onset episodes (time to onset ≤24 h, 42%) versus secondary episodes (>24 h, 58%; median [interquartile range] time to onset: 2 [2–3] days). The median age was 27 [22–34] years, 89% of the patients had an S/S or S/β0‐thalassaemia genotype; 81% of the patients had a history of ACS (median: 3 [2–5] per patient), only 61% were taking a disease‐modifying treatment at the time of the ACS. Fever and chest pain were noted in respectively 54% and 73% of the episodes. Crackles (64%) and bronchial breathing (32%) were the main abnormal auscultatory findings. A positive microbiological test was found for 20% of episodes. Fifty percent of the episodes required a blood transfusion; ICU transfer and mortality rates were respectively 29% and 1%. Secondary and early‐onset forms of ACS did not differ significantly. Disease‐modifying treatments should be revaluated after each ACS episode because the recurrence rate is high.
Pathophysiology of gastrointestinal acute graft‐versus‐host disease and the potential role of glucagon‐like peptide 2
Authors: Zeiser Robert , Chen Yi‐Bin , Youssef Nader N. , Ayuk Francis
Published: March 2023

Acute graft‐versus‐host disease (aGVHD) is a life‐threatening complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being one of the leading causes of morbidity and mortality. Whilst systemic steroids are the standard first‐line treatment for aGVHD, approximately 50% of patients become steroid refractory (SR), which is associated with poor outcomes. Existing options for SR‐GVHD are limited, and there is a significant unmet need for new non‐immunosuppressive treatment approaches in patients with GI aGVHD. Here, we review newer concepts in the pathogenesis of GI aGVHD and present the evidence for the role of glucagon‐like peptide 2 (GLP‐2) in maintaining and protecting GI epithelial cells, including the enterocytes, intestinal stem cells and Paneth cells, which are direct targets of aGVHD. Finally, we discuss the therapeutic rationale for GLP‐2 treatment as a tissue regeneration approach and the potential use of the novel GLP‐2 analogue apraglutide as an adjunctive treatment for GI aGVHD.
Targeting mitochondrial stress with Szeto‐Schiller 31 prevents experimental abdominal aortic aneurysm: Crosstalk with endoplasmic reticulum stress
Authors: Navas‐Madroñal Miquel , Almendra‐Pegueros Rafael , Puertas‐Umbert Lidia , Jiménez‐Altayó Francesc , Julve Josep , Pérez Belén , Consegal‐Pérez Marta , Kassan Modar , Martínez‐González José , Rodriguez Cristina , Galán María
Published: March 2023

Background and Purpose

Mitochondrial dysfunction and inflammation contribute to a myriad of cardiovascular diseases. Deleterious crosstalk of mitochondria and persistent endoplasmic reticulum (ER) stress triggers oxidative stress, which is involved in the development of vascular diseases. This study determined if inhibition of mitochondrial stress reduces aneurysm development in angiotensin II (Ang II)‐infused apolipoprotein‐E‐deficient (ApoE−/−) mice and its effect on ER stress.

Experimental Approach

The mitochondria‐targeted tetrapeptide, Szeto‐Schiller 31 (SS31), ameliorated mitochondrial dysfunction and the enhanced expression of ER stress markers triggered by Ang II in ApoE−/− mice, and limited plasmatic and vascular reactive oxygen species (ROS) levels. Interestingly, SS31 improved survival, reduced the incidence and severity of abdominal aortic aneurysm (AAA), and the Ang II‐induced increase in aortic diameter as evaluated by ultrasonography, resembling the response triggered by the classic ER stress inhibitors tauroursodeoxycholic acid (TUDCA) and 4‐phenylbutyrate (PBA).

Key Results

Disorganization of the extracellular matrix, increased expression of metalloproteinases and pro‐inflammatory markers and infiltration of immune cells induced by Ang II in the abdominal aorta were effectively reduced by SS31 and ER inhibitors. Further, C/EBP homologous protein (CHOP) deficiency in ApoE−/− mice attenuated Ang II‐mediated increase in vascular diameter and incidence of AAA, suggesting its contribution to the favourable response induced by ER stress inhibition.

Conclusions and Implications

Our data demonstrate that inhibition of mitochondrial stress by SS31 limits AAA formation and increases survival through a reduction of vascular remodelling, inflammation and ROS, and support that attenuation of ER stress contributes to the favourable response elicited by SS31.
Developing technological capabilities for Industry 4.0 adoption: An analysis of the role of inbound open innovation in small and medium‐sized enterprises
Authors: Lepore Dominique , Vecciolini Claudia , Micozzi Alessandra , Spigarelli Francesca
Published: March 2023

To keep up with rapid technological change, firms are pushed to acquire new competencies and resources, often leveraging the external networks in which they are involved. The paper examines how firms' engagement in inbound open innovation (OI) enables the adoption of Industry 4.0 (I4.0) technologies in small and medium‐sized enterprises (SMEs) through the deployment of technological capabilities. We combine the OI and dynamic capabilities frameworks to assess how the absorption of knowledge from different actors impacts the necessary technological capabilities for adopting I4.0 technologies. The capabilities are categorized in technological sensing, seizing and reconfiguring. The study is based on in‐depth case studies of two selected SMEs from the footwear industry. The cases show that engaging in external collaborations, particularly with universities, pushes SMEs to renew the bundle of competencies underlying their technological capabilities. However, this effect is influenced by the OI modalities adopted by both companies. While in Company A OI takes place through a broader array of formal and informal linkages that contribute to the exploration of distant knowledge bases and the experimentation of more diverse technologies, such as the Internet of Things, Company B relies on informal networking concentrated in its own field of specialization for the adoption of manufacturing‐specific I4.0 solutions, such as automated robots and 3D printing.
Educational attainment and employment of young adults ageing out of care: A registry study based on the Finnish birth cohort 1987
Authors: Pasanen Tytti P. , Keski‐Säntti Markus , Hilli Petri , Ristikari Tiina , Ståhl Timo
Published: March 2023

Adolescents growing up outside their birth homes are at major risk for multiple adversities in early adulthood, including low education and unemployment. The transition from out‐of‐home placement to independent living overlaps with the transition from school to work and higher education. However, the support during this critical phase is often inadequate. Adolescents ageing out of care are also more likely to have faced adversities in their birth families. Yet, the interplay between different risk factors and having aged out of care has gained little attention. This study aimed to assess known risk factors for low education and unstable employment and their interaction with ageing out of care, controlling for birth‐home‐related adversities. We assessed this topic using logistic and linear regression modelling based on the Finnish birth cohort 1987 (n = 59 476) registry. Our analysis showed that obtaining upper secondary and higher education was much less likely among those ageing out of care, and they had spent 52–80 fewer days annually in employment after graduation. Few interactions with other risk factors were, however, found. Efforts are needed to prevent inequalities in education and employment for those ageing out of care in the transition phase from school to work.
Exploring the mechanisms explaining the quality of sibling relationships when children are taken into care: A qualitative study of Norwegian children
Authors: Hovland Wenche , Hean Sarah
Published: March 2023

Sibling relationships are potentially central in children's and young people's lives. Research has shown that the quality of sibling relationships changes in a variety of ways when a sibling(s) moves into care. There is limited understanding of the mechanisms that cause these changes. This study addresses this gap by reanalysing a dataset of 25 semistructured interviews with young people (16 to 23 years) drawn from a municipality in Southern Norway. The original study explored the changes in sibling relationships when the young person moved into care. This reanalysis of the data set explores specifically, using a template analysis, the mechanisms that children describe when exploring why these changes occur. Findings show the intricacies of the young person's social identification with the biological and/or foster family and how sharing a common identity may be key to the development of the sibling relationship when the young person(s) is taken into care. Our findings also show how key adults, such as foster parents and social workers, influence the relationship. The paper concludes with recommendations for social workers on how they may strengthen sibling relationships in families where children have been taken into care.
Acetylated α‐tubulin alleviates injury to the dendritic spines after ischemic stroke in mice
Authors: Yang Chuanyan , Chen Xuezhu , Zhang Chenxu , Lei Xuejiao , Lu Yongling , Wang Yuhai , Feng Hua , Chen Tunan , Yang Yang
Published: March 2023

Background and Aim

Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs) serve a crucial role in regulating dendritic spine formation and plasticity. However, the mechanisms that are involved are poorly understood. This study is designed to understand whether the upregulation of acetylated α‐tubulin (α‐Ac‐Tub, a marker for stable, and polymerized MTs) could alleviate injury to the dendritic spines in the penumbra area and motor dysfunction after ischemic stroke.

Methods

Ischemic stroke was mimicked both in an in vivo and in vitro setup using middle cerebral artery occlusion and oxygen–glucose deprivation models. Thy1‐YFP mice were utilized to observe the morphology of the dendritic spines in the penumbra area. MEC17 is the specific acetyltransferase of α‐tubulin. Thy1 CreERT2‐eYFP and MEC17fl/fl mice were mated to produce mice with decreased expression of α‐Ac‐Tub in dendritic spines of pyramidal neurons in the cerebral cortex. Moreover, AAV‐PHP.B‐DIO‐MEC17 virus and tubastatin A (TBA) were injected into Thy1 CreERT2‐eYFP and Thy1‐YFP mice to increase α‐Ac‐Tub expression. Single‐pellet retrieval, irregular ladder walking, rotarod, and cylinder tests were performed to test the motor function after the ischemic stroke.

Results

α‐Ac‐Tub was colocalized with postsynaptic density 95. Although knockout of MEC17 in the pyramidal neurons did not affect the density of the dendritic spines, it significantly aggravated the injury to them in the penumbra area and motor dysfunction after stroke. However, MEC17 upregulation in the pyramidal neurons and TBA treatment could maintain mature dendritic spine density and alleviate motor dysfunction after stroke.

Conclusion

Our study demonstrated that α‐Ac‐Tub plays a crucial role in the maintenance of the structure and functions of mature dendritic spines. Moreover, α‐Ac‐Tub protected the dendritic spines in the penumbra area and alleviated motor dysfunction after stroke.
Inhibition of hippocampal cyclin‐dependent kinase 5 activity ameliorates learning and memory dysfunction in a mouse model of bronchopulmonary dysplasia
Authors: Tao Fang‐Fei , Wang Zi‐Yu , Wang Ying , Lv Qian‐Ru , Cai Peng‐Peng , Min Hai‐Wen , Ge Jian‐Wei , Yin Chun‐Yu , Cheng Rui
Published: March 2023

Aims

Oxygen therapy plays a vital role in the development of bronchopulmonary dysplasia (BPD), which is the independent risk factor for neurodevelopment deficits in premature infants. However, the effect of hippocampal cyclin‐dependent kinase 5 (CDK5) on BPD‐associated neurodevelopment deficits is not fully understood.

Methods

Mice were placed in a hyperoxia chamber from postnatal Day 1 to Day 7. Hematoxylin and eosin staining was used to evaluate the lung histomorphological characteristics. Learning and memory functions of mice were detected by Morris water maze. TUNEL staining was applied to measure the number of apoptotic cells. The expression of CDK5, apoptosis‐related protein, and neuroplasticity‐related proteins were analyzed by Western blot. Golgi staining was used to assess the structure of dendritic spines.

Results

Hyperoxia‐induced BPD mice showed a long‐term learning and memory dysfunction, more severe neuronal apoptosis, and a decline of synaptic plasticity. Inhibition of CDK5 overactivation ameliorated cognitive deficits, neuronal apoptosis, and synaptic plasticity disorders in BPD mice.

Conclusions

This study first found a vital role of CDK5 in BPD‐associated neurodevelopmental disorders. Inhibition of CDK5 overexpression could effectively improve cognitive dysfunctions in BPD mice, which indicated that hippocampal CDK5 may be a new target for prevention and treatment in learning and memory dysfunction of BPD.
“Happy to close?” The relationship between surgical experience and incisional hernia rates following abdominal wall closure in colorectal surgery
Authors: Smith Laurie , Coxon‐Meggy Alexandra , Shinkwin Michael , Cornish Julie , Watkins Alan , Fegan Greg , Torkington Jared ,   HART Trial Collaborators
Published: March 2023

Aim

Incisional hernia (IH) is a common complication of colorectal surgery, affecting up to 30% of patients at 2 years. Given the associated morbidity and high recurrence rates after attempted repair of IH, emphasis should be placed on prevention. There is an association between surgeon volume and outcomes in hernia surgery, yet there is little evidence regarding impact of the seniority of the surgeon performing abdominal wall closure on IH rate. The aim of our study was to assess the rates of IH at 1 year following abdominal wall closure between junior and senior surgeons in patients undergoing elective colorectal surgery.

Methods

This was an exploratory analysis of patients who underwent elective surgery for colorectal cancer between 2014–2018 as part of the Hughes Abdominal Repair Trial (HART), a prospective, multicentre randomised control trial comparing abdominal wall closure methods. Grade of surgeon performing abdominal closure was categorised into “trainee” and “consultant” and compared to IH rate at one year.

Results

A total of 663 patients were included in this retrospective analysis of patients in the HART trial. The rate of IH in patients closed by trainees was 20%, compared to 12% in those closed by consultants (p = <0.001). When comparing closure methods, IH rates were significantly higher in the Hughes closure arm between trainees and consultants (20% vs. 12%, p = 0.032), but not high enough in the mass closure arm to reach statistical significance (21% vs. 13%, p = 0.058). On multivariate analysis, age (p = 0.036, OR: 1.02, 95% CI: 1.00–1.04), Male sex (p = 0.049, OR: 1.61, 95% CI: 1.00–2.59) and closure by a trainee (p = 0.006, OR: 1.85, 95% CI: 1.20–2.85) were identified as risk factors for developing IH.

Conclusion

Patients who undergo abdominal wall closure by a surgeon in training have an increased risk of developing IH when compared to those closed by a consultant. Further work is needed to determine the impact of supervised and unsupervised trainees on IH rates, but abdominal wall closure should be regarded as a training opportunity in its own right.
External validation of the Codman score in colorectal surgery: a pragmatic tool to drive quality improvement
Authors: Spence Richard T. , Guidolin Keegan , Quereshy Fayez A. , Chadi Sami A. , Chang David C. , Hutter Matthew M.
Published: March 2023

Aim

The simple six‐variable Codman score is a tool designed to reduce the complexity of contemporary risk‐adjusted postoperative mortality rate predictions. We sought to externally validate the Codman score in colorectal surgery.

Methods

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant user file and colectomy targeted dataset of 2020 were merged. A Codman score (composed of six variables: age, American Society of Anesthesiologists score, emergency status, degree of sepsis, functional status and preoperative blood transfusion) was assigned to every patient. The primary outcome was in‐hospital mortality and secondary outcome was morbidity at 30 days. Logistic regression analyses were performed using the Codman score and the ACS NSQIP mortality and morbidity algorithms as independent variables for the primary and secondary outcomes. The predictive performance of discrimination area under receiver operating curve (AUC) and calibration of the Codman score and these algorithms were compared.

Results

A total of 40 589 patients were included and a Codman score was generated for 40 557 (99.02%) patients. The median Codman score was 3 (interquartile range 1–4). To predict mortality, the Codman score had an AUC of 0.92 (95% CI 0.91–0.93) compared to the NSQIP mortality score 0.93 (95% CI 0.92–0.94). To predict morbidity, the Codman score had an AUC of 0.68 (95% CI 0.66–0.68) compared to the NSQIP morbidity score 0.72 (95% CI 0.71–0.73). When body mass index and surgical approach was added to the Codman score, the performance was no different to the NSQIP morbidity score. The calibration of observed versus expected predictions was almost perfect for both the morbidity and mortality NSQIP predictions, and only well fitted for Codman scores of less than 4 and greater than 7.

Conclusion

We propose that the six‐variable Codman score is an efficient and actionable method for generating validated risk‐adjusted outcome predictions and comparative benchmarks to drive quality improvement in colorectal surgery.
The association with organ procurement techniques and early cardiac transplant outcomes using cardiac MRI
Authors: Coniglio Amanda C. , Kim Han W. , Alenezi Fawaz , Schroder Jacob N. , Bryner Benjamin S. , Agarwal Richa , Patel Chetan B. , DeVore Adam D.
Published: March 2023

Background

Heart transplantation (HT) has historically been limited by organ availability. Use of donation after circulatory death (DCD) donors addresses this limitation by utilizing previously unused hearts through use of the Organ Care System (OCS).

Objectives

This study aimed to determine the impact of procurement and transportation method on allograft structure and function using early post‐transplant cardiac magnetic resonance imaging (MRI).

Methods

Patients who underwent HT at our institution from February 1, 2020, through April 30, 2021 who underwent cardiac MRI imaging <60 days from transplant were included. Recipient and donor characteristics, clinical outcomes, and MRI findings were compared between those who underwent DCD transplantation using the OCS device (DCD‐OCS), brain dead donation (DBD) using the OCS device (DBD‐OCS), and DBD transported via cold storage (DBD‐cold storage) using one‐way analysis of variance.

Results

A total of 85 patients underwent HT with a cardiac MRI during the study period. Thirty‐one (36%) patients received a DCD organ, 16 (19%) received a DBD‐OCS organ and 38 (45%) received a DBD‐cold storage organ. Rates of primary graft dysfunction (PGD) were significantly higher in DCD transplants (19.5% DCD vs. .0% DBD‐OCS and 5.3% DBD‐cold storage; p < .050 across three groups), but with no differences in mortality or rejection. There were no differences in cardiac MRI findings between the three transplant types, including presence of gadolinium hyperenhancement after transplant (all p > .050).

Conclusions

We observed no differences in early cardiac MRI findings between patients that received DCD and DBD‐OCS heart transplants compared with those receiving DBD‐cold storage transplants.
Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation
Authors: Picard Benjamin , Sigaut Stéphanie , Roux Olivier , Abback Paër‐Selim , Choinier Pierre‐Marie , Hachouf Marina , Giabicani Mikhael , Kavafyan Juliette , Francoz Claire , Dondero Federica , Lesurtel Mickaël , Durand François , Cauchy François , Paugam‐Burtz Catherine , Dahmani Souhayl , Weiss Emmanuel
Published: March 2023

Purpose

Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit‐balance of intraparenchymal pressure catheter monitoring is controversial during ALF.

Aims

Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation.

Material and methods

Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2.

Results

Among 106 patients with ALF, forty‐seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1–2) days after LT.

Conclusion

TCD may be a useful non‐invasive tool for ICH detection and management, then guide sedation withdrawal.
Guidelines and principles for the care of the cardiothoracic transplant patient in the intensive care unit
Authors: Nurok Michael , Nunnally Mark E. , O'Connor Michael , Pierson Richard N. , Baran David A. , Harper Michael D. , Malinoski Darren , El Banayosy Aly , Orija Abiodun , Hall Shelley , Edelman Jeffrey D. , Sundt Thoralf M. , Levine Deborah , Kobashigawa Jon , Nelson David
Published: March 2023

Heart and lung transplant recipients require care provided by clinicians from multiple different specialties, each contributing unique expertise and perspective. The period the patient spends in the intensive care unit is one of the most critical times in the perioperative trajectory. Various organizational models of intensive care exist, including those led by intensivists, surgeons, transplant cardiologists, and pulmonologists. Coordinating timely efficient intensive care is an essential and logistically difficult goal. The present work product of the American Society of Transplantation's Thoracic and Critical Care Community of Practice, Critical Care Task Force outlines operational guidelines and principles that may be applied in different organizational models to optimize the delivery of intensive care for the cardiothoracic organ recipient.
Hidden problems in a case of atrial fibrillation
Authors: Espejel‐Guzman Adrian , Cabello‐Ganem Aldo , Armendariz‐Ferrari Jose C. , Serrano‐Roman Javier , Aparicio‐Ortiz Alexis D. , Espinola‐Zavaleta Nilda
Published: March 2023

Atrial fibrillation (AF) is the most common cardiac arrhythmia. However, the relation between congenital heart defects and the predisposition to AF is not fully understood. A 65‐year‐old male was admitted into the emergency department due to progressive dyspnea, orthopnea, palpitations, and edema. Transthoracic echocardiogram showed bi‐atrial enlargement and dysplasia of the mitral leaflets with severe mitral regurgitation. Also, a membrane was noted in the LA, dividing the chamber into two parts, suggestive of cor triatriatum sinister. Coronary computed tomography angiography demonstrated a soft tissue septum in the left atrium. Multimodal evaluation is of vital importance for a complete approach, since, detected in time, it has an excellent prognosis.
Rebooting disruptive science: Exploring the challenges and potential solutions
Authors: Rust Ruslan
Published: March 2023

There has been a decline in the number of disruptive scientific discoveries and breakthroughs. Here, reasons for the decline of disruptive science are explored including declining funding for basic research, increasing risk‐aversion among scientists, pressure to publish quickly and increasing administrative workload. Solutions are proposed to reverse the trend and encourage disruptive research especially for young scientists.
The definition of long COVID used in interventional studies
Authors: Haslam Alyson , Olivier Timothée , Prasad Vinay
Published: March 2023

Introduction

There has been little consensus for a specific definition of long COVID, though several organizations have created varying ones. We sought to examine the definition of long COVID used in ongoing clinical trials.

Methods

We searched ‘long COVID’ and related terms on both PubMed and clinicaltrials.gov for randomized studies that either included patients with long COVID or had a persistent or long‐term COVID‐related outcome and abstracted long COVID definition components.

Results

Of the 92 studies, a laboratory‐only confirmed diagnosis of COVID‐19 was stipulated in 54.3% (n = 50) studies. We found eight different time durations specified for how long symptoms needed to have occurred, ranging from 4 to 52 weeks, with 12 weeks being the most common (34.8%; n = 32). 35.9% (n = 33) did not specify a time duration. There were 57 different symptoms specified in total, with a median of one symptom identified per study (range 0–32). 8.7% of trials adhered to NICE or WHO definitions.

Conclusion

Standardized definitions of long COVID should be applied in studies assessing this condition to unify and harmonize research on this topic.
Identifying important prognostic factors and outcomes for autotransplantation of developing teeth: Clinicians' perspectives
Authors: Barber Sophy K. , Kenny Kate , Czochrowska Ewa , Plakwicz Pawel , Houghton Nadine Y. , Day Peter F.
Published: March 2023

Background/Aim

Variability in the outcome measures used to assess the success of tooth autotransplantation presents challenges for combining data to examine the success of the technique. Reaching agreement on the most important outcomes will enable routine procedural and follow‐up data to be collected in a standardised way. In turn this will promote greater data synthesis to evaluate outcomes and examine which procedural techniques influence outcome. The aim of this study was to identify which prognostic factors and outcomes are most important to clinicians with experience in autotransplantation of developing teeth.

Methods

The Delphi method was used to build consensus on the most important prognostic factors and outcomes. Item identification involved a systematic literature review and review of current clinical datasets in use. A two‐round Delphi questionnaire was undertaken with clinicians providing tooth autotransplantation, followed by a consensus meeting to finalise the most important items.

Results

Outcomes and prognostic factors were identified from the systematic review (82 studies and eight reviews), one guideline and three existing clinical datasets. Patient interviews and a clinician survey added a number of items that would not have been identified from the literature only. A total of 56 outcomes and 93 prognostic factors were included for rating in the Delphi questionnaire. The Delphi questionnaire was completed by 15 respondents in round one and 13 respondents in round two. The consensus meeting was attended by nine participants. The final items that were judged to be most important included 29 outcomes (25 clinical, three patient‐reported and one service delivery) and 49 prognostic factors (18 patient characteristics, four presurgical, 17 surgical and 10 postsurgical). Clinical outcomes were consistently rated higher than patient‐reported outcomes.

Conclusions

The clinical outcomes rated as the most important were transplant survival and reason for failure, outcomes relating to pulp health, different types of resorption and evidence of infection (suppuration). Important patient‐reported outcomes were satisfaction with overall treatment experience, and outcome and quality of life related to function of the transplanted tooth. Procedural information rated as being the most important related to the donor tooth: stage of root development, method for surgical removal and storage and condition of the donor tooth root surface following removal.
A word on habitat complexity
Authors: Madin Joshua S. , Asbury Mollie , Schiettekatte Nina , Dornelas Maria , Pizarro Oscar , Reichert Jessica , Torres‐Pulliza Damaris
Published: March 2023

In their recent synopsis, Loke and Chisholm (Ecology Letters, 25, 2269–2288, 2022) present an overview of habitat complexity metrics for ecologists. They provide a review and some sound advice. However, we found several of their analyses and opinions misleading. This technical note provides a different perspective on the complexity metrics assessed.
Investigating the eco‐evolutionary response of microbiomes to environmental change
Authors: Martiny Jennifer B. H. , Martiny Adam C. , Brodie Eoin , Chase Alexander B. , Rodríguez‐Verdugo Alejandra , Treseder Kathleen K. , Allison Steven D.
Published: March 2023

Microorganisms are the primary engines of biogeochemical processes and foundational to the provisioning of ecosystem services to human society. Free‐living microbial communities (microbiomes) and their functioning are now known to be highly sensitive to environmental change. Given microorganisms' capacity for rapid evolution, evolutionary processes could play a role in this response. Currently, however, few models of biogeochemical processes explicitly consider how microbial evolution will affect biogeochemical responses to environmental change. Here, we propose a conceptual framework for explicitly integrating evolution into microbiome–functioning relationships. We consider how microbiomes respond simultaneously to environmental change via four interrelated processes that affect overall microbiome functioning (physiological acclimation, demography, dispersal and evolution). Recent evidence in both the laboratory and the field suggests that ecological and evolutionary dynamics occur simultaneously within microbiomes; however, the implications for biogeochemistry under environmental change will depend on the timescales over which these processes contribute to a microbiome's response. Over the long term, evolution may play an increasingly important role for microbially driven biogeochemical responses to environmental change, particularly to conditions without recent historical precedent.
Licking their wounds: Social response to trauma by free‐ranging bison (Bison bison)
Authors: Jung Thomas S. , Thacker Caeley , Lewis Christopher J.
Published: March 2023

The epidermis of wild mammals is occasionally lacerated or punctured and wound care behaviours evolved to keep animals healthy in nature. Communal wound licking may promote healing of affected sites, relieve stress after a traumatic experience, and reinforce social bonds among individuals. Yet, there are few reported cases of communal wound licking in free‐ranging mammals. We report observations of communal wound licking in a social ungulate—free‐ranging bison (Bison bison). Two adult female bison presented with minor open puncture wounds after we chemically immobilized each of them with a dart fired from a rifle. The day after being darted, we observed three different adult bison lick the wounds of the two wounded bison. Both bison were <3 m of each other during this time and all of the observed wound licking occurred in <10 min. Our observation provides an additional example of communal wound licking in free‐ranging mammals and extends it to a social ungulate. Benefits to bison of communal wound licking are perhaps largely social. However, targeted research is needed to better understand both the frequency and cost and benefits of communal wound licking.
Behaviour in a novel environment provides clues to the success of an invasive species
Authors: Vázquez María G. , Bas Claudia C.
Published: March 2023

Behavioural traits play an important role in invasion success, yet little is known about how species behave when they arrive in a new environment. In this study we examined the behaviour of the invasive shrimp Palaemon macrodactylus after entering in a novel place with a single refuge during a 24 h solitary phase, and after the introduction of a conspecific or heterospecific (the native goby Gobiosoma parri), in the next 24 h (competition phase), comparing their responses as residents and as intruders. Time spent swimming, using the shelter and the frequency of interactions (withdrawing touches) were quantified. Shrimps entering to a new empty environment, swam most of the time in the first hours, while the use of shelter increased steadily. The use of shelter in shrimps was affected by sex and residency status. Females won the shelter to males, while residents won the shelter to intruders. In the interspecific competition, refuge was always won by gobies and shrimps showed no resistance. Obtaining shelter was not generated through aggressive behaviours, but rather a hierarchy established through some other type of interactions. We propose that both prolonged swimming, which could indicate exploratory behaviour, and a social organization without aggressive confrontations could be key to the initiation of an invasion in this species.
The influence of cultural tightness–looseness, religiosity, and the institutional environment on tax evasion behaviour: A cross‐country study
Authors: Ben Othman Hakim , Hussainey Khaled , Moumen Nejia
Published: March 2023

We examine whether the strength of norms and tolerance for deviations play a role in explaining cross‐country differences in tax evasion (TEVA). We also investigate the effects of religiosity, legal enforcement, voice and accountability, and the stability of political systems on TEVA across 48 countries over the period 1997–2018. Results show that the higher the voice and accountability and the lower the degree of cultural tightness–looseness, the rule of law, and political stability, the higher the degree of TEVA across nations. The results are important for policymakers to assess the likelihood of TEVA from a holistic perspective.
Intraspecific diversity in the mechanisms underlying abamectin resistance in a cosmopolitan pest
Authors: Villacis‐Perez Ernesto , Xue Wenxin , Vandenhole Marilou , De Beer Berdien , Dermauw Wannes , Van Leeuwen Thomas
Published: March 2023

Pesticide resistance relies on a myriad of mechanisms, ranging from single mutations to a complex and polygenic architecture, and it involves mechanisms such as target‐site insensitivity, metabolic detoxification, or a combination of these, with either additive or synergistic effects. Several resistance mechanisms against abamectin, a macrocyclic lactone widely used in crop protection, have been reported in the cosmopolitan pest Tetranychus urticae. However, it has been shown that a single mechanism cannot account for the high levels of abamectin resistance found across different mite populations. Here, we used experimental evolution combined with bulked segregant analyses to map quantitative trait loci (QTL) associated with abamectin resistance in two genetically unrelated populations of T. urticae. In these two independent QTL mapping experiments, three and four QTLs were identified, of which three were shared between experiments. Shared QTLs contained genes encoding subunits of the glutamate‐gated chloride channel (GluCl) and harboured previously reported mutations, including G314D in GluCl1 and G326E in GluCl3, but also novel resistance candidate loci, including DNA helicases and chemosensory receptors. Surprisingly, the fourth QTL, present only in only one of the experiments and thus unique for one resistant parental line, revealed a non‐functional variant of GluCl2, suggesting gene knock‐out as resistance mechanism. Our study uncovers the complex basis of abamectin resistance, and it highlights the intraspecific diversity of genetic mechanisms underlying resistance in a cosmopolitan pest.
Climatic oscillation promoted diversification of spinous assassin bugs during Pleistocene glaciation
Authors: Du Zhenyong , Zhao Qian , Wang Xuan , Sota Teiji , Tian Li , Song Fan , Cai Wanzhi , Zhao Ping , Li Hu
Published: March 2023

Insect speciation is among the most fascinating topics in evolutionary biology; however, its underlying mechanisms remain unclear. Allopatric speciation represents one of the major types of speciation and is believed to have frequently occurred during glaciation periods, when climatic oscillation may have caused suitable habitats to be fragmented repeatedly, creating geographical isolation among populations. However, supporting evidence for allopatric speciation of insects in East Asia during the Pleistocene glaciation remains lacking. We aim to investigate the effect of climatic oscillation during the Pleistocene glaciation on the diversification pattern and evolutionary history of hemipteran insects and to test the hypothesis of Pleistocene species stability using spinous assassin bugs Sclomina (Hemiptera: Reduviidae), a small genus widely distributed in southern China but was later found to have cryptic species diversity. Here, using the whole mitochondrial genome (mitogenome) and nuclear ribosomal RNA genes, we investigated both interspecific and intraspecific diversification patterns of spinous assassin bugs. Approximate Bayesian computation, ecological niche modeling, and demographic history analyses were also applied to understand the diversification process and driven factors. Our data suggest that the five species of Sclomina are highly diverged, despite three of them currently being cryptic. Speciation occurred during the Pleistocene when suitable distribution areas were possibly fragmented. Six phylogeographic groups in the type species S. erinacea were identified, among which two groups underwent expansion during the early Last Glacial Period and after Last Glacier Maximum. Our analyses suggest that this genus may have experienced climate‐driven habitat fragmentation and postglacial expansion in the Pleistocene, promoting allopatric speciation and intraspecific diversification. Our results reveal underestimated species diversity in a small insect group and illustrate a remarkable example of allopatric speciation of insects in East Asia promoted by Pleistocene climatic oscillations. These findings provide important insights into the speciation processes and aid the conservation of insect species diversity.
Parameter identification of elastoplastic model for CuCrZr alloy by the neural network‐aided Bayesian inference
Authors: Chen Zhiwei , Jin Ping , Li Ruizhi , Qi Yaqun , Cai Guobiao
Published: March 2023

The constitutive model serves as the foundation for executing structure analysis to obtain the deformation and stress/strain. In this paper, a neural network‐assisted Bayesian parameter identification framework is presented to calibrate parameters of the constitutive model while considering the unavoidable uncertainties. The low‐cycle fatigue test of the CuCrZr alloy at 700 K is first performed to provide realistic data. The posterior distributions are obtained by applying the transitional Markov Chain Monte Carlo method. To accelerate the identification, the neural network is adopted to directly predict the likelihood function value given material parameters. The effect of prior distributions on the identification parameters is also studied. The characteristic parameters of the normal distribution have almost no effect on the identification results. In the absence of prior information, uniform prior distributions can be used to perform Bayesian identification of material parameters, and satisfactory identification parameters can also be acquired.
Bcat1 is controlled by Tsc2/mTORC1 pathway at expression levels and its deficiency together with Bcat2 inactivation suppresses the growth of a Tsc2−/− tumor cell line
Authors: Nishikawa Keiko , Mezawa Yoshihiro , Kobayashi Toshiyuki
Published: March 2023

The tuberous sclerosis complex (TSC) gene products (TSC1/TSC2) negatively regulate mTORC1. Although mTORC1 inhibitors are used for the treatment of TSC, incomplete tumor elimination and the adverse effects from long‐term administration are problems that need to be solved. Branched‐chain amino acid (BCAA) metabolism is involved in the growth of many tumor cells via the mTORC1 pathway. However, it remains unclear how BCAA metabolism affects the growth of mTORC1‐dysregulated tumors. We show here that the expression of branched‐chain amino transferase1 (Bcat1) was suppressed in Tsc2‐deficient murine renal tumor cells either by treatment with rapamycin or restoration of Tsc2 expression suggesting that Bcat1 is located downstream of Tsc2‐mTORC1 pathway. We also found that gabapentin, a Bcat1 inhibitor suppressed the growth of Tsc2‐deficient tumor cells and increased efficacy when combined with rapamycin. We investigate the functional importance of Bcat1 and the mitochondrial isoform Bcat2 by inhibiting each enzyme separately or both together by genome editing and shRNA in Tsc2‐deficient cells. We found that deficiency of both enzymes, but not either alone, inhibited cell growth, indicating that BCAA‐metabolic reactions support Tsc2‐deficient cell proliferation. Our results indicate that inhibition of Bcat1 and Bcat2 by specific drugs should be a useful method for TSC treatment.