bluuebunny/crossref_metadata_2025 huggingface dataset:
Market Responses to Private and Public Targets: The Role of Goodwill Valuation*
Authors: Kwon Shin Hyoung , Wang Irene Guannan
Published: September 2022

Investors overprice goodwill value acquired from a private target during a merger and acquisition (M&A) announcement. However, the overpricing of goodwill is corrected in the years following the deal's completion. Our results show that investors predict the decreasing value of goodwill and promptly adjust their pricing regardless of goodwill impairment. The differential market reactions to goodwill between private and public targets are economically significant. The pricing on goodwill obtained from a private target is 47% higher around the announcements and 44% (33%) lower one (two) year(s) after the M&A completion than that from the public target.
Development and internal validation of a model for postoperative morbidity in adults undergoing major elective colorectal surgery: the peri‐operative quality improvement programme (PQIP) colorectal risk model
Authors: Bedford J. , Martin P. , Crowe S. , Wagstaff D. , Santos C. , Singleton G. , Baumber R. , Vindrola‐Padros C. , Vohra R. , Swart M. , Oliver C. M. , Dorey J. , Leeman I. , Moonesinghe S. R. ,   for the peri‐operative quality improvement programme (PQIP) collaborative
Published: September 2022

Over 1.5 million major surgical procedures take place in the UK NHS each year and approximately 25% of patients develop at least one complication. The most widely used risk‐adjustment model for postoperative morbidity in the UK is the physiological and operative severity score for the enumeration of mortality and morbidity. However, this model was derived more than 30 years ago and now overestimates the risk of morbidity. In addition, contemporary definitions of some model predictors are markedly different compared with when the tool was developed. A second model used in clinical practice is the American College of Surgeons National Surgical Quality Improvement Programme risk model; this provides a risk estimate for a range of postoperative complications. This model, widely used in North America, is not open source and therefore cannot be applied to patient populations in other settings. Data from a prospective multicentre clinical dataset of 118 NHS hospitals (the peri‐operative quality improvement programme) were used to develop a bespoke risk‐adjustment model for postoperative morbidity. Patients aged ≥ 18 years who underwent colorectal surgery were eligible for inclusion. Postoperative morbidity was defined using the postoperative morbidity survey at postoperative day 7. Thirty‐one candidate variables were considered for inclusion in the model. Death or morbidity occurred by postoperative day 7 in 3098 out of 11,646 patients (26.6%). Twelve variables were incorporated into the final model, including (among others): Rockwood clinical frailty scale; body mass index; and index of multiple deprivation quintile. The C‐statistic was 0.672 (95%CI 0.660–0.684), with a bootstrap optimism corrected C‐statistic of 0.666 at internal validation. The model demonstrated good calibration across the range of morbidity estimates with a mean slope gradient of predicted risk of 0.959 (95%CI 0.894–1.024) with an index‐corrected intercept of −0.038 (95%CI −0.112–0.036) at internal validation. Our model provides parsimonious case‐mix adjustment to quantify risk of morbidity on postoperative day 7 for a UK population of patients undergoing major colorectal surgery. Despite the C‐statistic of < 0.7, our model outperformed existing risk‐models in widespread use. We therefore recommend application in case‐mix adjustment, where incorporation into a continuous monitoring tool such as the variable life adjusted display or exponentially‐weighted moving average‐chart could support high‐level monitoring and quality improvement of risk‐adjusted outcome at the population level.
Linear and circular stapled gastrojejunal anastomoses in Roux‐en‐Y gastric bypass: stomal diameter at onset and at long‐term follow‐up
Authors: Campanello Magnus , Lindskog Stefan , Zilling Thomas
Published: September 2022

Background

In the laparoscopic Roux‐en‐Y gastric bypass procedure, the gastrojejunal stoma is constructed with either a circular (CSD) or a linear stapling device (LSD). The diameter of the stoma following stapling with the 21 mm CSD is expected to be approximately 12 mm (diameter of the anvil). Measuring the stoma diameter after linear stapling is a little more complex since the remaining opening in the linear anastomosis is closed by hand. The aim of this prospective randomized study was to follow up on changes in the diameter of gastrojejunal stomata after laparoscopic Roux‐en‐Y gastric bypass using either a CSD or an LSD between that at construction and at a long‐term follow‐up of 12–72 months later.

Methods

Twenty patients were randomly assigned to gastrojejunostomy with either a 21 mm CSD or a 45 mm LSD. Directly after completion of the surgery, the diameter of the gastrojejunal stoma was measured using a Fogarty occlusion catheter and again at follow‐up 12–72 months later.

Results

Five patients were lost for follow‐up, and 15 patients remained. The mean diameter of the CSD stomata at construction was 19.3 ± 5.3 mm (mean ± SD) and increased to 26.4 ± 6.6 mm at follow‐up after a mean of 46 months (P = 0.02). The corresponding figures for the LSD stomata were 26.2 ± 4.1 mm, increasing to 32.7 ± 3.0 mm also after a mean follow‐up of 46 months (P = 0.03).

Conclusions

The mean diameter of the circular stapled gastrojejunostomy stomata at construction was 20 mm, that is, considerably larger than the 12 mm expected. After a mean of 5 years, the mean diameter had increased by 37%. The mean diameter of the linear stapled stomata increased by 25%.
Reversal of Hartmann's procedure: timelines, preoperative investigations and early outcomes. A single Australian institution's ten‐year experience
Authors: Suthakaran Reshi , Faragher Ian G. , Yeung Justin M. C.
Published: September 2022

Background

Real‐world data on outcomes following Hartmann's reversal is necessary to help optimize the patient experience. We have explored the timing between the index operation and its reversal; what investigations were carried out prior to this, and the associated short‐term outcomes.

Methods

A retrospective study of all patients who underwent Hartmann's reversal from 2010 to 2020 within a tertiary referral centre in Melbourne, Australia. One hundred from a total of 406 (25%) who underwent an emergency Hartmann's procedure had a subsequent reversal. Complete patient data was available for 83 of these patients.

Results

The average patient age was 60 years, and the median time for reversal was 14.0 (IQR 10–23) months. Seventy‐nine of 83 (95%) reversals had a preoperative endoscopic evaluation of both their rectal stump and a complete colonoscopy. Stoma stenosis (n = 2), patient refusal (n = 1) and emergency reversal (n = 1) were cited reasons for not undergoing preoperative endoscopic evaluation. A third (n = 28, 34%) had a computed tomography prior to reversal; the majority was due to their underlying cancer surveillance (n = 21, 75%). Reversal was associated with a morbidity rate of 47% (n = 39). Surgical site infections (SSIs) (n = 21, 25%) were the most common type of complications encountered, with the majority being superficial (n = 15, 71%). SSIs were associated with steroid use (5/21 versus 4/62, p = 0.03) and greater hospital length of stay (6 versus 10 days, p = 0.03).

Conclusion

Only a quarter of emergency Hartmann's procedures within our institution were reversed. A significant proportion developed postoperative complications. Surgical site infection was the most common morbidity.
Technical insights to multivisceral resections using the da Vinci Xi
Authors: Ngu James Chi‐Yong , Shannon Nicholas Brian , Eu Ernest Wencong , Lee Lip Seng , Tan Siong San , Lim Sey Kiat Terence , Ng Foo Cheong , Chiow Adrian Kah Heng
Published: September 2022

Background

There have been few reports on the feasibility and safety of robotic multivisceral surgeries. The da Vinci Xi boasts significant upgrades that improve its applicability in combined resections. We report our early experience of multivisceral, multi‐quadrant resections with the Xi system.

Methods

Between May 2015 and August 2019, 13 multivisceral resections were performed. Patient demographics, procedural data, and perioperative outcomes were evaluated.

Results

The procedures were completed at a median operative time of 290 (range, 210–535) minutes. The median postoperative length of hospital stay was 3.5 (range, 2–7) days. There was one case of readmission for anastomotic leak, but no positioning injuries, external robot arm collisions or issues arising from trocar position. There were no cases of perioperative mortality.

Conclusion

Multivisceral resections can be safely accomplished using the Xi. Further studies are necessary to ascertain whether there are benefits of the robotic approach over conventional laparoscopy in these complex cases.
Wearable and implantable artificial kidney devices for end‐stage kidney disease treatment: Current status and review
Authors: Groth Thomas , Stegmayr Bernd G. , Ash Stephen R. , Kuchinka Janna , Wieringa Fokko P. , Fissell William H. , Roy Shuvo
Published: September 2022

Background

Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end‐stage kidney disease (ESKD, or CKD stage 5), yet only 5.4 million will receive kidney replacement therapy (KRT) due to economic, social, and political factors. Even for those who are offered KRT by various means of dialysis, the life expectancy remains far too low.

Observation

Researchers from different fields of artificial organs collaborate to overcome the challenges of creating products such as Wearable and/or Implantable Artificial Kidneys capable of providing long‐term effective physiologic kidney functions such as removal of uremic toxins, electrolyte homeostasis, and fluid regulation. A focus should be to develop easily accessible, safe, and inexpensive KRT options that enable a good quality of life and will also be available for patients in less‐developed regions of the world.

Conclusions

Hence, it is required to discuss some of the limits and burdens of transplantation and different techniques of dialysis, including those performed at home. Furthermore, hurdles must be considered and overcome to develop wearable and implantable artificial kidney devices that can help to improve the quality of life and life expectancy of patients with CKD.
Oesophageal secretions reveal local food‐specific antibody responses in eosinophilic oesophagitis
Authors: Pyne Ashley L. , Hazel Mark W. , Uchida Amiko M. , Qeadan Fares , Jordan Kristine C. , Holman Amy , Harward Brinnlie , Gleich Gerald J. , Peterson Kathryn A.
Published: September 2022

Background

Eosinophilic oesophagitis (EoE) is associated with elevated IgG4 in oesophageal tissue and serum. Previously, we showed brush‐collected oesophageal secretions of EoE patients contained food antigen‐specific antibodies IgA and IgG4. It is unknown whether other food‐specific antibodies are present along the surface of the oesophagus in EoE.

Aim

To identify whether immunoglobulins other than IgG4 and food‐specific antibodies are elevated along the oesophageal mucosal surface in oesophageal secretions in EoE patients

Methods

Concentrations of total IgA, IgG1, IgG2, IgG3, IgG4, IgM and IgE were measured in oesophageal secretions from patients with active (n = 19) and inactive EoE (n = 9), and non‐EoE controls (n = 10). Food‐specific antibodies were measured using beads coupled to protein components from dairy, wheat and egg. Total immunoglobulin and cytokine and chemokine concentrations were measured in serum, saliva and oesophageal secretions of four patients with active EoE.

Results

Oesophageal secretions have a unique immune profile. Patients with active EoE had elevated IgG2, IgG4 and IgM concentrations in oesophageal secretions compared to those with inactive EoE. Food‐specific IgG1, IgG2, IgG4 and IgM were significantly increased in patients with active EoE compared to inactive EoE and non‐EoE patients. Furthermore, active patients with a known dairy trigger display higher dairy‐specific IgG1, IgG2, IgG4, IgM, IgA and IgE.

Conclusions

There is a distinct localised profile of immunoglobulins and food‐specific antibodies found within oesophageal secretions in EoE. These findings expand our knowledge about the currently identified immune responses in EoE and suggest possible roles for multiple immunoglobulins and food‐specific antibodies in the pathophysiology of EoE.
Validation of the Achalasia Patient‐Reported Outcomes Questionnaire
Authors: Pandolfino John E. , Carlson Dustin A. , McGarva Josie , Kahrilas Peter J. , Vaezi Michael , Katzka David , Taft Tiffany H.
Published: September 2022

Background

Achalasia is a debilitating major motor disorder of the oesophagus. Hypervigilance and symptom‐specific anxiety substantially impact dysphagia symptom reporting, and quality of life is a critical patient outcome. Earlier achalasia symptom scales did not consider these constructs in their psychometric development.

Aim

To develop a new symptom measure, the Achalasia Patient‐Reported Outcomes (APRO) Questionnaire

Methods

Four gastroenterologists with achalasia expertise generated preliminary items. Patients reviewed items via cognitive interviews. Patients undergoing high‐resolution manometry completed the APRO with Oesophageal Hypervigilance and Anxiety Scale, Northwestern Oesophageal Quality of Life Scale, and three measures of reflux and dysphagia. Full APRO psychometric assessment (reliability, validity, factor structure) was done. Cluster analysis evaluated APRO + symptom‐anxiety/hypervigilance patient phenotypes.

Results

We included 961 patients with normal motility and 296 with achalasia. The APRO yielded three subscales: dysphagia, reflux, chest pain with two items for weight change and diet modifications. Reliability and validity were excellent. Twenty‐five percent of achalasia patients may have high levels of anxiety/hypervigilance despite low symptoms, while 8% may report severe symptoms with low anxiety/hypervigilance. The APRO significantly predicted quality of life, but less cognitive‐affective processes.

Conclusions

The APRO is a reliable and valid measure of achalasia symptoms that addresses the limitations of existing questionnaires. Symptom anxiety and hypervigilance moderate the relationship between APRO and quality of life; 33% of patients with achalasia exhibit concerning patterns in symptom severity, anxiety and hypervigilance that may contribute to poorer outcomes.
Concave Likelihood-Based Regression with Finite-Support Response Variables
Authors: Ekvall K.O. , Bottai M.
Published: September 2022

We propose a unified framework for likelihood-based regression modeling when the response variable has finite support. Our work is motivated by the fact that, in practice, observed data are discrete and bounded. The proposed methods assume a model which includes models previously considered for interval-censored variables with log-concave distributions as special cases. The resulting log-likelihood is concave, which we use to establish asymptotic normality of its maximizer as the number of observations n tends to infinity with the number of parameters d fixed, and rates of convergence of L1-regularized estimators when the true parameter vector is sparse and d and n both tend to infinity with . We consider an inexact proximal Newton algorithm for computing estimates and give theoretical guarantees for its convergence. The range of possible applications is wide, including but not limited to survival analysis in discrete time, the modeling of outcomes on scored surveys and questionnaires, and, more generally, interval-censored regression. The applicability and usefulness of the proposed methods are illustrated in simulations and data examples.
Immunomodulation for early‐onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?
Authors: Moise Kenneth J.
Published: September 2022

When cases of severe fetal anaemia due to maternal red‐cell alloimmunization present in the early second trimester, standard treatment with intrauterine transfusion often results in fetal loss. The report by Vlachodimitropoulou et al. offers new insight into the use of maternal intravenous immune globulin to delay the need for intrauterine transfusion. Performing these procedures at a later gestational age increases the likelihood of technical success and subsequent perinatal survival.

Commentary on: Vlachodimitropoulou et al. Intravenous immune globulin in the management of severe early onset of red cell alloimmunization. Br J Haematol 2023; 200:97‐103
BSACIguideline for the set‐up of penicillin allergy de‐labelling services by non‐allergists working in a hospital setting
Authors: Savic Louise , Ardern‐Jones Michael , Avery Anthony , Cook Tim , Denman Sarah , Farooque Sophie , Garcez Tomaz , Gold Rochelle , Jay Nicola , Krishna Mamidipudi Thirumala , Leech Sue , McKibben Shauna , Nasser Shuaib , Premchand Nikhil , Sandoe Jonathan , Sneddon Jacqueline , Warner Amena
Published: September 2022

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and a committee of experts and key stakeholders have developed this guideline for the evaluation and testing of patients with an unsubstantiated label of penicillin allergy. The guideline is intended for UK clinicians who are not trained in allergy or immunology, but who wish to develop a penicillin allergy de‐labelling service for their patients. It is intended to supplement the BSACI 2015 guideline “Management of allergy to penicillin and other beta‐lactams” and therefore does not detail the epidemiology or aetiology of penicillin allergy, as this is covered extensively in the 2015 guideline (1). The guideline is intended for use only in patients with a label of penicillin allergy and does not apply to other beta‐lactam allergies. The recommendations include a checklist to identify patients at low risk of allergy and a framework for the conduct of drug provocation testing by non‐allergists. There are separate sections for adults and paediatrics within the guideline, in recognition of the common differences in reported allergy history and likelihood of true allergy.
Response to school‐based interventions for overweight and obesity: A systematic scoping review
Authors: Arlinghaus Katherine R. , Cepni Aliye B. , Helbing Rachel R. , Goodman Lenora P. , Ledoux Tracey A. , Johnston Craig A.
Published: September 2022

Heterogeneity of response to paediatric obesity interventions is one of the greatest challenges to obesity care. While evaluating school‐based interventions by mean changes compared to control is important, it does not provide an understanding of the individual variability in response to intervention. The objective of this study was to comprehensively review school‐based interventions that reported study results in terms of response and identify definitions of response used. A scoping review was conducted using a systematic search of five scientific databases from 2009 to 2021. Inclusion criteria included randomized controlled trial design, school‐based setting, weight‐based outcomes (e.g., BMI, BMI z‐score), weight‐based outcomes analysed among youth with overweight/obesity, a study conducted in a developed country and publication in English. A total of 26 reports representing 25 unique studies were included. Overall, 19% (5/26) of articles reported response. Response was defined in three ways: maintenance/decrease in BMI z‐score, decrease in BMI z‐score ≥0.10, and decrease in BMI z‐score ≥0.20. Few school‐based interventions identified an a priori intervention goal or identified the proportion of participants who responded to the intervention. Without such evaluation participants who do not benefit are likely to be overlooked.
Leveraging patient‐centric sampling for clinical drug development and decentralized clinical trials: Promise to reality
Authors: Maass Katie F. , Barfield Matthew D. , Ito Mototsugu , James Christopher A. , Kavetska Olga , Kozinn Marc , Kumar Parag , Lepak Maureen , Leuthold Luc Alexis , Li Wenkui , Mikhailov Dmitri , Patel Shefali , Perez Nisha L. , Jackson Rudd Deanne , Vakkalagadda Blisse , Williams Tracy M. , Zha Jiuhong , Zhang Xin , Anderson Melanie D.
Published: September 2022

Advances in the technologies to enable patient‐centric sampling (PCS) have the potential to improve blood sample collection by enabling clinical trial participants to collect samples via self‐collection or with the help of a caregiver in their home. Typically, blood samples to assess pharmacokinetics and pharmacodynamics of a drug during clinical development are collected at a clinical site via venous blood draw. In this position paper by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the potential value PCS can bring to patients, to the clinical datasets generated, and to clinical trial sponsors is discussed, along with considerations for program decision making, bioanalytical feasibility, operations, and regulatory implications. With an understanding of the value of PCS and considerations when implementing during clinical drug development, we can bring the promise of PCS closer to reality and enable decentralized clinical trials.
中国儿童遗传性痉挛性截瘫的临床与遗传特点
Authors: 王 佳平 , 方 方 , 丁 昌红 , 李 久伟 , 伍 妘 , 张 炜华 , 包 新华 , 吕 俊兰 , 王 晓慧 , 任 晓暾 ,   小儿科神经病学研究小组
Published: September 2022

[摘要]

目的

探讨中国儿童遗传性痉挛性截瘫的临床和遗传特点。

方法

这项回顾性研究于2014年1月至2021年10月在临床诊断为单纯HSP (pHSP)或复杂HSP (cHSP)的儿童中进行。

结果

我们调查了45例儿童(男32例，女13例;出现症状时的平均年龄为4岁[SD=7个月]。35例得到基因确诊，常染色体显性HSP患者多为pHSP(16/18)，而常染色体隐性HSP患者多为cHSP(14/16)。SPG11是最常见的常染色体隐性亚型，其次是FA2H/SPG35，而SPAST/SPG4是最常见的常染色体显性亚型。2例CPT1C突变患者表现为复杂型。同时，在10例患者中发现了6个HSP相关基因的可能致病变异/临床意义不明变异。

结论 SPG11和SPG4分别是中国儿童常染色体隐性HSP和常染色体显性HSP最常见的亚型。然而，SPG4的患病率远低于成人，这可能是由于该疾病发病较晚的原因。另一方面，FA2H/SPG35在我们的队列中很常见，但在成人病例中只占很小的比例，这可能是由于其进展迅速，一些患者早期死亡。我们还扩展了SPG73的遗传和临床谱。
Did cryptocurrencies exhibit log‐periodic power law signature during the second wave of COVID‐19?
Authors: Ghosh Bikramaditya , Papathanasiou Spyros , Pergeris Georgios
Published: September 2022

Many studies have associated cryptocurrencies with bubbles, especially during stressed market conditions such as the recent outbreak of the second wave of COVID‐19. Although the majority of studies have focused on Bitcoin, we investigate the predictability of bubble formation in the cryptocurrency market by using the log‐periodic power law and we uncover some important stylized facts of this market. Our sample consists of data for a selection of 15 cryptocurrencies for the period between 1 January 2021 and 1 September 2021 which coincides with the second wave of COVID‐19. We analyse 86 speculative bubbles, and we find that the cryptocurrency market has three times higher drawdown over equities during stressed market conditions.
Life‐stage‐related desiccation and starvation resistance in the biological control agent Neolema abbreviata
Authors: Mulaudzi Lugisani , Mutamiswa Reyard , Zachariades Costas , Chidawanyika Frank
Published: September 2022

Climate variability in the tropics is partly associated with reduced and erratic precipitation, heat waves, and cold snaps thereby exerting abiotic environmental stressors to various arthropod species. For herbivorous insects, such extreme weather events may affect host plant quality and availability resulting in additional stressors such as desiccation and starvation. Neolema abbreviata Larcordaire (Coleoptera: Chrysomelidae) is a key biocontrol agent of Tradescantia fluminensis Vell. (Commelinaceae) and has recently been introduced in South Africa for management of its invasive host plant. However, it remains unknown how environmental stressors may influence its performance under anthropogenic climate change. Here, we investigated the effects of desiccation and starvation on performance of N. abbreviata larvae and adults and implications on biological control. Specifically, we measured desiccation and starvation resistance and critical thermal minima (CTmin) and maxima (CTmax) following stress. Desiccation and starvation pre‐treatment reduced both low (CTmin) and high (CTmax) temperature tolerance in both life stages albeit larvae were less cold tolerant and more heat tolerant than adults. In addition, resistance decreased with duration of exposure with desiccation resistance being higher in larvae than in adults, whereas the converse was true for starvation resistance. This indicates the challenges N. abbreviata may encounter when it faces environmental stressors in nature. Therefore, with projected climate change, this may potentially impact on its field establishment, spread, and effectiveness, thereby negatively influencing future classical biocontrol programs. Overall, the results provide valuable information in modelling potential distribution of N. abbreviata and developing sustainable management options of T. fluminensis under rapidly changing environments.
Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers
Authors: Lin Chunxiu , Liu Peng , Shi Chaowen , Qiu Lipeng , Shang Dongsheng , Lu Ziwen , Tu Zhigang , Liu Hanqing
Published: September 2022

The susceptibility of cells to DNA damage and their DNA repair ability are crucial for cancer therapy. Homologous recombination is one of the major repairing mechanisms for DNA double‐strand breaks. Approximately half of ovarian cancer (OvCa) cells harbor homologous recombination deficiency (HRD). Considering that HRD is a major hallmark of OvCas, scholars proposed HRD scoring to evaluate the HRD degree and guide the choice of therapeutic strategies for OvCas. In the last decade, synthetic lethal strategy by targeting poly (ADP‐ribose) polymerase (PARP) in HR‐deficient OvCas has attracted considerable attention in view of its favorable clinical effort. We therefore suggested that the uses of other DNA damage/repair‐targeted drugs in HR‐deficient OvCas might also offer better clinical outcome. Here, we reviewed the current small molecule compounds that targeted DNA damage/repair pathways and discussed the HRD scoring system to guide their clinical uses.
Mechanistic insights into allosteric regulation of methylated DNA and histone H3 recognition by SRA and SET domains of SUVH5 and the basis for di‐methylation of lysine residue
Authors: Abhishek Suman , Deeksha Waghela , Rajakumara Eerappa
Published: September 2022

Su‐(var)3–9 homologue 5 (SUVH5), a member of SUVH family of histone lysine methyltransferase (HKMT) in Arabidopsis, is involved in epigenetic regulation of chromatin by recognizing 5‐methyl‐cytosine (5mC), in both CpG and non‐CpG DNA context, through SRA domain and simultaneously performing the di‐methylation of lysine 9 of histone H3 (H3K9) through SET domain. Here, we establish that the SET domain of SUVH5 allosterically restricts the SRA domain to the 5mC containing strand(s) of fully methylated CpG, hemi‐methylated CpG and methylated CpHpH DNA. In addition, SET domain enhances the binding affinity of the SRA‐SET dual domains to fully‐mCpG but not to hemi‐mCpG. Also, the recognition of methylated DNA by the SRA positively influences the recognition of H3K9 by the SET domain. Our further studies revealed that the SET domain recognizes the “A(R/K)KST” motif present in H3K9 and in other histone H2A variants. Further, computational analyses and quantum mechanics/molecular mechanics calculations explain the bases for robust mono‐MTase but weak di‐MTase activities of SUVH5. Given that the majority of eukaryotic proteins, including those involved in epigenetic gene regulation, contain more than one domain, our study suggests that understanding the allosteric regulation among multiple domains of proteins is relevant for unravelling biological outcomes.
Non‐small cell lung carcinomas with diffuse coexpression of TTF1 and p40: clinicopathological and genomic features of 14 rare biphenotypic tumours
Authors: Savari Omid , Febres‐Aldana Christopher , Chang Jason C. , Fanaroff Rachel E. , Ventura Katia , Bodd Francis , Paik Paul , Vundavalli Murty , Saqi Anjali , Askin Frederic B. , Travis William D. , Rekhtman Natasha
Published: September 2022

Thyroid transcription factor 1 (TTF1) and p40 are widely‐utilized diagnostic markers of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), respectively. Diffuse coexpression of TTF1 and p40 has been described in only rare case reports. In a multi‐institutional study, we collected the largest cohort of these unusual tumours to‐date (n = 14), with the goal of elucidating their clinicopathological and genomic characteristics. Lung tumours with diffuse coexpression (labelling 50–100% tumour cells) of TTF1 clone 8G7G3/1 and p40 clone BC28 were identified. Detailed clinicopathological and immunohistochemical parameters were analyzed. Eight tumours were analyzed by next‐generation sequencing (NGS) and the results were compared to those in > 9 K LUAD and > 1 K LUSC. All tumours with diffuse TTF1/p40 coexpression were poorly differentiated non‐small cell lung carcinomas (NSCLC), 42% of which had basaloid features. Some tumours exhibited focal keratinization (14%), napsin A and/or mucicarmine labelling (46%) or both squamous and glandular features (7%). NGS revealed a uniquely high rate of FGFR1 amplifications (70%) compared to either LUAD (0.7%, P < 0.0001) or LUSC (11%, P = 0.001). LUAD‐type targetable driver alterations were identified in 38% of cases (one EGFR, two KRAS G12C). The tumours were clinically aggressive, exhibiting metastatic disease in most patients. Lung carcinomas with diffuse TTF1/p40 coexpression represent poorly differentiated NSCLCs with frequent basaloid features, but some show evidence of focal squamous, glandular or dual differentiation with a distinctly high rate of FGFR1 amplifications. The presence of targetable LUAD‐type alterations (EGFR, KRAS G12C) emphasizes the importance of molecular testing in these tumours.
The UK National Health Service's migration infrastructure in times of Brexit and COVID‐19: Disjunctures, continuities and innovations
Authors: Ciupijus Zinovijus , Forde Chris , Giralt Rosa Mas , Shi Jiachen , Sun Li
Published: September 2022

The COVID‐19 pandemic and Brexit were separate yet inter‐related developments which affected the British National Health Service (NHS). The UK's state‐funded health sector had historically relied on migrant labour and depended on a migration infrastructure designed to solve its nursing labour shortages. The analysis of primary qualitative and secondary quantitative data shows that the NHS migration infrastructure increased its orientation towards Asia to compensate for the effects of Brexit. The paper reveals how the persistent use of temporary visas along with conditional contractual arrangements has led to various exclusions for migrant nurses and midwives. These data also demonstrate how international travel restrictions associated with COVID‐19 created temporary obstacles for nurses' inflows. Alongside Brexit, this has also resulted in an increase in outflows amongst EU health workers. The article identifies the development of migrant support infrastructure amongst Filipino and Indian nurses as a major COVID‐19 linked innovation.
People with intellectual disability and employment sustainability: A qualitative interview study
Authors: Helena Taubner , Magnus Tideman , Carin Staland‐Nyman
Published: September 2022

Background

Swedish employment rates are disproportionately low among people with intellectual disability and research on employment sustainability in this group is scarce. This study investigated employment sustainability among people with intellectual disability, with a focus on identifying facilitators.

Method

Fifteen persons with intellectual disability who were gainfully employed and had been so for at least 1 year during the last 3 years, and 10 representatives from their employers, were interviewed.

Results

Five facilitators were identified: (1) having tried various types of work, (2) liking to be at work, (3) balance concerning expectations and adaptations, (4) mutual engagement and flexibility, and (5) wage subsidies.

Conclusion

Employment sustainability needs to be understood at individual as well as environmental and societal levels. In addition, both duration and progress should be considered regarding employment sustainability in this population.
Evolution of immune function in response to dietary macronutrients in male and female decorated crickets
Authors: Letendre Corinne , Rios‐Villamil Alejandro , Williams Alexandria , Rapkin James , Sakaluk Scott K. , House Clarissa M. , Hunt John
Published: September 2022

Although dietary macronutrients are known to regulate insect immunity, few studies have examined their evolutionary effects. Here, we evaluate this relationship in the cricket Gryllodes sigillatus by maintaining replicate populations on four diets differing in protein (P) to carbohydrate (C) ratio (P‐ or C‐biased) and nutritional content (low‐ or high‐nutrition) for >37 generations. We split each population into two; one maintained on their evolution diet and the other switched to their ancestral diet. We also maintained populations exclusively on the ancestral diet (baseline). After three generations, we measured three immune parameters in males and females from each population. Immunity was higher on P‐biased than C‐biased diets and on low‐ versus high‐nutrition diets, although the latter was most likely driven by compensatory feeding. These patterns persisted in populations switched to their ancestral diet, indicating genetic divergence. Crickets evolving on C‐biased diets had lower immunity than the baseline, whereas their P‐biased counterparts had similar or higher immunity than the baseline, indicating that populations evolved with dietary manipulation. Although females exhibited superior immunity for all assays, the sexes showed similar immune changes across diets. Our work highlights the important role that macronutrient intake plays in the evolution of immunity in the sexes.
Obstructive sleep apnea pathophysiology: A key to understanding obstructive sleep apnea's impact on older adults
Authors: Miner Brienne , Zinchuk Andrey
Published: September 2022

This Editorial comments on the article by Sabil et al. in this issue.
Development of the Basel Version of the Awareness of Social Inference Test – Theory of Mind (BASIT‐ToM) in healthy adults
Authors: Jarsch Marianne , Piguet Olivier , Berres Manfred , Sluka Constantin , Semenkova Anna , Kressig Reto W. , Monsch Andreas U. , McDonald Skye , Sollberger Marc
Published: September 2022

Impairments of Theory of Mind (ToM) abilities occur in a wide range of brain disorders. Therefore, reliable and ecologically valid examination of these abilities is a crucial part of any comprehensive neuropsychological assessment. An established and ecologically valid, English‐language test identifying deficits in ToM abilities is “The Awareness of Social Inference Test – Social Inference Minimal (TASIT‐SIM)”. However, no comparable German‐language ToM test currently exists. In this study, we aimed to develop the first German‐language adaption of TASIT‐SIM in healthy adults. We selected 13 scenes [four scenes per message type (i.e., honesty, simple sarcasm, paradoxical sarcasm) and one practice scene] out of the 30 TASIT‐SIM scenes. In collaboration with a film institute, we filmed each scene at three different intensities. These intensity version scenes were then administered to 240 healthy adults, equally distributed in sex and age, ranging from 35 to 92 years. By applying Rasch analysis, we selected intensity versions that showed neither floor nor ceiling effects in the majority of ToM questions in participants whose ToM abilities were in the medium range. In conclusion, we have developed the first German‐language adaption of TASIT‐SIM, i.e., the “Basel Version of the Awareness of Social Inference Test – Theory of Mind (BASIT‐ToM)”. The BASIT‐ToM incorporates the strengths of TASIT‐SIM, while overcoming its limitations such as inconsistencies in cinematic realization and ceiling effects in healthy participants. Next, the BASIT‐ToM needs to be validated in healthy people and clinical populations.
Psychological pain in depressive disorder: A concept analysis
Authors: Chen Shuyan , Cheng Yin , Zhao Weiwei , Zhang Yanhong
Published: September 2022

Aim and objectives

The purpose of this paper is to identify a precise definition of the concept of psychological pain in the field of depressive disorder.

Background

Psychological pain is widespread in patients with depressive disorder and plays a central role in the suicide process. However, psychological pain is currently complex and broadly defined and does not reflect the unique nature of psychological pain in depressed patients.

Design

A concept analysis.

Methods

Rodgers' evolutionary approach was used to analyse the concept of psychological pain in depressive disorders. PubMed, CINAHL, Embase, PsycINFO, Sinomed, CNKI, and Wanfang were searched and 49 articles met the inclusion criteria.

Results

The key attributes of psychological pain were identified as negative affective perception, passive cognition and ineffective response, extreme behavioural tendency, and both state and trait characteristics. Antecedents included stressful life events, frustrated psychological needs, disease factors, physical factors, and negative cognitive biases. Consequences were the promotion of personal growth, enhanced meaning in life, low quality of life, barriers to treatment, high rates of psychiatric morbidity, self‐harm, and suicide.

Conclusion

Psychological pain is a subjectively widespread, intense, and complex affective experience centered on feelings of suffering resulting from negative self‐perceptions and ineffective coping based on personality traits. In addition, psychological pain has two traits: an immediate affective reflection arising from experiencing stressful life events and a persistent and stable emotional trait, respectively.

Relevance to clinical practice

This study provides a conceptual framework to help clinical staff expand their knowledge of psychological pain and distinguish it from related terms. Interventions should address both the antecedents and the consequences and so this study suggests that future interventions could be developed in terms of positive emotions.

No patient or public contribution

This study did not recruit participants, therefore details of participants will not be involved.
No Beer No Friends: Quantifying the Effect of the Beer Boycott*
Authors: Kim In Kyung , Kim Kyoo il
Published: September 2022

We study the impact of the boycott on Japanese products, initiated in July, 2019, in the Korean beer market. First, sales of japanese beer decreased by more than 70 percent during the 14‐month boycott period in the data. Second, the decrease in Japanese beer sales mostly reflected an increase in domestic beer sales. Lastly, the intensity of the boycott's effect has remained strong and stable despite a substantial decrease in traditional media coverage since the outbreak of the boycott movement. Our empirical findings suggest that political tensions can change market outcomes and negatively affect international trade for an extended period.
The phonetics and phonology of Uspanteko (Mayan)
Authors: Bennett Ryan , Harvey Meg , Henderson Robert , Méndez López Tomás Alberto
Published: September 2022

Uspanteko is an endangered Mayan language spoken by up to 6000 people in the Guatemalan highlands. We provide an overview of the phonetics and phonology of Uspanteko, focussing on phenomena which are common in Mayan languages and/or typologically interesting. These include glottalised consonants (ejectives, implosives, and glottal stop), uvular consonants, vowel length contrasts, syllable structure, stress, and lexical tone. Tone is unusual among Mayan languages, especially in Guatemala, and the phonetic description here complements the small handful of existing descriptions of tone in Uspanteko and within the Mayan family.
Linking pathogen–microbiome–host interactions to explain amphibian population dynamics
Authors: Torres‐Sánchez María , Longo Ana V.
Published: September 2022

Symbiotic interactions can determine the evolutionary trajectories of host species, influencing genetic variation through selection and changes in demography. In the context of strong selective pressures such as those imposed by infectious diseases, symbionts providing defences could contribute to increase host fitness upon pathogen emergence. Here, we generated genome‐wide data of an amphibian species to find evidence of evolutionary pressures driven by two skin symbionts: a batrachochytrid fungal pathogen and an antifungal bacterium. Using demographic modelling, we found evidence of decreased effective population size, probably due to pathogen infections. Additionally, we investigated host genetic associations with infection status, antifungal bacterium abundance and overall microbiome diversity using structural equation models. We uncovered relatively lower nucleotide diversity in infected frogs and potential heterozygote advantage to recruit the candidate beneficial symbiont and fight infections. Our models indicate that environmental conditions have indirect effects on symbiont abundance through both host body traits and microbiome diversity. Likewise, we uncovered a potential offsetting effect among host heterozygosity–fitness correlations, plausibly pointing to different ecological and evolutionary processes among the three species due to dynamic interactions. Our findings revealed that evolutionary pressures not only arise from the pathogen but also from the candidate beneficial symbiont, and both interactions shape the genetics of the host. Our results advance knowledge about multipartite symbiotic relationships and provide a framework to model ecological and evolutionary dynamics in wild populations. Finally, our study approach can be applied to inform conservation actions such as bioaugmentation strategies for other imperilled amphibians affected by infectious diseases.
Pedicled Double‐Barrel Fibular Transplantation Versus Bone Transport in the Treatment of Upper Tibial Osteomyelitis with Bone Defects: A Retrospective Study
Authors: Huang Qiang , Lu Yao , Ma Teng , Wang Qian , Wang ChaoFeng , Li Zhong , Zhang Kun , Ren Cheng
Published: September 2022

Objective

This study aimed to compare the clinical effects of using pedicled double‐barrel fibular transplantation (PDBFT) and bone transport (BT) for the treatment of upper tibial osteomyelitis with bone defects.

Methods

A total of 83 patients with upper tibial osteomyelitis and bone defects were selected and retrospectively studied in Xi'an Hong Hui Hospital from January 2009 to January 2019. There were 52 males and 31 females, aged 19–72 years. The tibial defect range was 5–12 cm. Patients were divided into two groups, including the PDBFT (40 cases) and the BT group (43 cases). All patients were classified according to Cierny–Mader classification, including 48 cases of type III and 35 cases of type IV. Operation time, blood loss and cure time were compared. Ennecking score was used to evaluate limb functions, including pain, activity function, self‐perception, brace use, walking ability, and gait change, while self‐rating anxiety scale (SAS) was used for postoperative mental and psychological status. In addition, complications were recorded. All patients were followed for at least 2 years. SPSS 23.0 software was used to process data.

Results

There was no significant difference in demographic data between the two groups (p > 0.05). Operation time was 182.5 ± 22.7 min in PDBFT group vs, 124.2 ± 15.6 min in BT group, respectively (p < 0.05); intra‐operative blood loss was 286 ± 34 ml vs 45 ± 18 ml (p < 0.05); cure time was 7.3 ± 1.8 months vs 11.6 ± 3.7 months (p < 0.05); and Ennecking score was 87.3% and 76.0%, respectively (p < 0.05). So, the PDBFT group showed longer operation time, more blood loss, shorter cure time, and better Ennecking score than the BT group. Importantly, limb functions of the PDBFT group were better than that of the BT group. Moreover, the PDBFT group presented better postoperative mental status and fewer complications than that in BT group (p < 0.05).

Conclusions

Patients were successfully cured by both the PDBFT and BT techniques. Compared with the BT group, the PDBFT group brought better clinical effects and fewer complications which could be the first operative choice for the treatment of upper tibial osteomyelitis with bone defects.
The Comparison between Mini‐Subvastus Approach and Medial Parapatellar Approach in TKA: A Prospective Double‐Blinded Randomized Controlled Trial
Authors: Geng Lei , Fu Jun , Xu Chi , Ren Peng , Wang Yi‐ming , Ji Quan‐bo , Xin Peng , Zheng Qing‐yuan , Ni Ming , Zhang Guo‐qiang
Published: September 2022

Objective

Minimal invasive approach has been increasingly used in total knee arthroplasty (TKA) and more is expected of early rehabilitation in terms of pain release and recovery of knee function. The approach type is one of the major factors that determines the early rehabilitation after TKA. The purpose of this study is to determine whether mini‐subvastus approach (MSVA) is superior to the traditional medial parapatellar approach (MPA) in TKA.

Methods

From 2018 to 2019, a randomized double‐blinded prospective study was conducted on 58 patients who underwent simultaneous bilateral TKA. The subjects included eight men and 50 women, with an average age of 65 years. One side was randomized using MSVA and the other side using MPA. Visual analog scale (VAS), operative duration, recovery time to straight leg raising (SLR), range of motion (ROM), HSS score, release rate of lateral retinaculum, satisfaction rate were recorded and compared. Paired‐samples T test were used for quantitative data and chi‐square test for qualitative data.

Results

There was no statistical difference in the ratio of left and right sides, preoperative ROM, VAS, HSS score, muscular strength of lower limbs, KL grade, operative order, and operative duration between the two groups. The average ROM (118.91 ± 8.21 vs. 107.60 ± 7.99, t = 14.320, p = 0.0000) and HSS score (72.03 ± 4.55 vs. 61.22 ± 4.36, t = 13.095, p = 0.0000) on POD 3, VAS in rest and motion on POD 1 and 3, the recovery time to SLR (1.17 ± 0.38 vs. 3.09 ± 0.76, t = 19.902, p = 0.0000), and the satisfaction rate on POD 1 (96.55% vs. 74.14%, χ2 = 9.9251, p = 0.0016) were superior in the MSVA group over MPA group. ROM in rest and motion and HSS score on POD 30 had no difference. The release rate of lateral retinaculum was less in the MSVA group than in the MPA group. The mean value of HKA, FFC, and FTC and the proportion of outliers did not differ significantly between the two groups.

Conclusions

Compared with MPA, MSVA can make ROM of knee and SLR recover earlier, reduce postoperative pain after TKA, improve the early postoperative satisfaction and reduce the lateral release rate. MSVA can be used as a favorable measure in the concept of enhanced recovery after surgery (ERAS).