bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Big Data Analytics in Manufacturing Agility and Performance: Moderation–Mediation Analysis of Organizational Creativity and of the Involvement of Customers as Data Analysts
Authors: Awan Usama , Bhatti Sabeen Hussain , Shamim Saqib , Khan Zaheer , Akhtar Pervaiz , Balta Maria Elisavet
Published: October 2021

The involvement of customers as data analysts enables firms to gain valuable insights and create value from big data. We provide a theoretical explanation, drawn from the resource‐based view, for the influence of the involvement of customers as data analysts and of the development of big data analytics (BDA) capabilities in business‐to‐business contexts as routes to manufacturing agility and performance. Our study empirically tested a framework in which organizational creativity and the involvement of customers as data analysts may differentially influence the relationship between BDA capabilities and manufacturing agility. We further tested whether the relative impact of manufacturing agility depends on organizational creativity and the involvement of customers as data analysts. To test our proposed framework, we took a partial least‐squares structural modelling approach using data collected through a survey involving 179 engineering manufacturers operating across different industrial sectors in Pakistan. We provide evidence for organizational creativity and customer involvement, presenting a promising opportunity for manufacturers to gain better insights from resources, and for the deployment of BDA capabilities leading to better manufacturing agility and performance.
Leaning towards Cytomegalovirus serological screening in pregnancy to prevent congenital infection: a cost‐effectiveness perspective
Authors: Seror V , Leruez‐Ville M , Ӧzek A , Ville Y
Published: October 2021

Objective

To assess the cost‐effectiveness of prenatal detection of congenital cytomegalovirus (cCMV) following maternal primary infection in the first trimester within standard pregnancy follow‐up or involving population‐based screening (serological testing at 7 and 12 weeks of gestation), with or without secondary prevention (valaciclovir) in maternal CMV primary infection.

Design

Cost‐effectiveness study from the perspective of the French national health insurance system.

Setting

Cost‐effectiveness based on previously published probability estimates and associated plausible ranges hypothetical population of 1,000,000 pregnant women.

Population

Hypothetical population of 1,000,000 pregnant women.

Methods

Cost‐effectiveness of detecting fetal cCMV in terms of the total direct medical costs involved and associated expected outcomes.

Main outcome measures

Detection rates and clinical outcomes at birth.

Results

Moving to a population‐based approach for targeting fetal CMV infections would generate high monetary and organizational costs while increasing detection rates from 15% to 94%. This resource allocation would help implementing horizontal equity according to which individuals with similar medical needs should be treated equally. Secondary prevention with valaciclovir had a significant effect on maternal‐fetal CMV transmission and clinical outcomes in newborns, with a 58% decrease of severely infected newborns for a 3.5% additional total costs. Accounting for women decision‐making (amniocentesis uptake and termination of pregnancy in severe cases) did not impact the cost‐effectiveness results.

Conclusions

These findings could fuel thinking on the opportunity of developing clinical guidelines to rule identification of cCMV infection and administration of in‐utero treatment. These findings could fuel the development of clinical guidelines on the identification of congenital CMV infection and the administration of treatment in utero.

Tweetable abstract

CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy.
Feasibility, utility, and safety of fully incorporating transesophageal echocardiography into emergency medicine practice
Authors: Reardon Robert F. , Chinn Elliott , Plummer Dave , Laudenbach Andrew , Rowland Fisher Andie , Smoot Will , Lee Daniel , Novik Joseph , Wagner Barrett , Kaczmarczyk Chris , Moore Johanna , Thompson Emily , Tschautscher Craig , Dunphy Teresa , Pahl Thomas , Puskarich Michael A. , Miner James R.
Published: October 2021

Introduction

Transthoracic echocardiography (TTE) is a standard procedure for emergency physicians (EPs). Transesophageal echocardiography (TEE) is known to have great utility in patients who are critically ill or in cardiac arrest and has been used by some EPs with specialized ultrasound (US) training, but it is generally considered outside the reach of the majority of EPs. We surmised that all of our EPs could learn to perform focused TEE (F‐TEE), so we trained and credentialed all of the physicians in our group.

Methods

We trained 52 EPs to perform and interpret F‐TEEs using a 4‐h simulator‐based course. We kept a database of all F‐TEE examinations for quality assurance and continuous quality feedback. Data are reported using descriptive statistics.

Results

Emergency physicians attempted 557 total F‐TEE examinations (median = 10, interquartile range = 5–15) during the 42‐month period following training. Clinically relevant images were obtained in 99% of patients. EPs without fellowship or other advanced US training performed the majority of F‐TEEs (417, 74.9%) and 94.3% (95% confidence interval [CI] = 91.4%–96.3%) had interpretable images recorded. When TTE and TEE were both performed (n = 410), image quality of TEE was superior in 378 (93.3%, 95% CI = 89.7%–95%). Indications for F‐TEE included periarrest states (55.7%), cardiac arrest (32.1%), and shock (12.2%). There was one case of endotracheal tube dislodgement during TEE placement, but this was immediately identified and replaced without complication.

Conclusion

After initiating a mandatory group F‐TEE training and credentialing program, we report the largest series to date of EP‐performed resuscitative F‐TEE. The majority of F‐TEE examinations (75%) were performed by EPs without advanced US training beyond residency.
Comparative clinical effectiveness and safety of tobacco cessation pharmacotherapies and electronic cigarettes: a systematic review and network meta‐analysis of randomized controlled trials
Authors: Thomas Kyla H. , Dalili Michael N. , López‐López José A. , Keeney Edna , Phillippo David M. , Munafò Marcus R. , Stevenson Matt , Caldwell Deborah M. , Welton Nicky J.
Published: October 2021

Aim

To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety.

Method

Systematic reviews and Bayesian network meta‐analyses of randomized controlled trials, in any setting, of varenicline, bupropion, NRT and e‐cigarettes (in high, standard and low doses, alone or in combination) in adult smokers and smokeless tobacco users with follow‐up duration of 24 weeks or greater (effectiveness) or any duration (safety). Nine databases were searched until 19 February 2019. Primary outcomes were sustained tobacco abstinence and serious adverse events (SAEs). We estimated odds ratios (ORs) and treatment rankings and conducted meta‐regression to explore covariates.

Results

We identified 363 trials for effectiveness and 355 for safety. Most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence; the most effective of these, estimated with some imprecision, were varenicline standard [OR = 2.83, 95% credible interval (CrI) = 2.34–3.39] and varenicline standard + NRT standard (OR = 5.75, 95% CrI = 2.27–14.88). Estimates were higher in smokers receiving counselling than in those without and in studies with higher baseline nicotine dependence scores than in those with lower scores. Varenicline standard + NRT standard showed a high probability of being ranked best or second‐best. For safety, only bupropion at standard dose increased the odds of experiencing SAEs compared with placebo (OR = 1.27, 95% CrI = 1.04–1.58), and we found no evidence of effect modification.

Conclusions

Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence, with varenicline appearing to be most effective based on current evidence. There does not appear to be strong evidence of associations between most tobacco cessation pharmacotherapies and adverse events; however, the data are limited and there is a need for improved reporting of safety data.
Geographical distribution of 3 allied health professions in South Australia: A summary of access and disadvantage
Authors: Yisma Engida , Gillam Marianne , Versace Vincent L. , Jones Sara , Walsh Sandra , May Esther , Jones Martin
Published: October 2021

Objective

To describe the distribution of 3 allied health professionals—occupational therapists, physiotherapists and podiatrists—in South Australia stratified by the Modified Monash Model and the Index of Relative Socio‐Economic Disadvantage.

Design

A descriptive data linkage cross‐sectional study.

Setting

The state of South Australia, Australia.

Participants and main outcome measures

Distribution of the 3 registered allied health professional groups stratified by Modified Monash Model and Index of Relative Socio‐Economic Disadvantage.

Results

The largest proportion of the 3 allied health professional groups (occupational therapists, physiotherapists and podiatrists) were found in areas classified as Modified Monash 1 and Modified Monash 2 (86.5%). The lowest proportion of allied health professionals were found in Modified Monash 7. The largest number of allied health professionals per 10 000 population was found in areas classified as Modified Monash 1 and Modified Monash 2. The lowest number of allied health professionals per 10 000 population was found in Modified Monash 7 areas. The largest number of allied health professionals per 10 000 population was found in areas with Index of Relative Socio‐Economic Disadvantage quintile 2, while the lowest number of allied health professionals per 10 000 population was found in areas with Index of Relative Socio‐Economic Disadvantage quintile 1.

Conclusions

The distribution of allied health professionals according to geographical remoteness, socio‐economic disadvantage and per 10 000 population varies widely in South Australia. The number of allied health professionals per 10 000 population was lowest in rural and remote/very remote areas, explaining the typically poor access to allied health services for communities in these areas. The number of allied health professionals per 10 000 population according to Index of Relative Socio‐Economic Disadvantage was variable within the context of both urban and rural areas.
Failure to drink, failure to launch? A model of the perceived stigma of nondrinkers in the workplace
Authors: Ghumman Sonia , Park Jin Suk , Kim Sooyeol
Published: October 2021

Although drinking alcohol in the workplace is usually prohibited, certain work‐related activities (e.g., happy hours and office parties) might encourage drinking as part of the work socialization process. Cultures with strong drinking norms may even hold expectations for employees to drink as a means to bond with colleagues and clients, resulting in the perception of the stigma of nondrinkers. However, research has yet to examine the influence of strong workplace drinking cultures on employees with drinking restrictions. In this study, we sample participants from South Korea, a country with high workplace drinking norms, to identify the presence of the perceived stigma of nondrinkers (PSND) among employees. We also examine the identity management of individuals' drinking restrictions at work along with organizational factors related to PSND in workplace settings. We find that strong organizational drinking norms and lack of perceived supervisor support are related to greater PSND. High PSND is related to fear of disclosing one's nondrinking status and a greater likelihood of drinking for work functions among nondrinkers. We also identify negative work outcomes related to PSND (higher turnover, lower organizational commitment) and find that organizational commitment mediates the relationship between PSND and turnover intentions. Implications of our findings are discussed.
Decision tree outcome prediction of acute acetaminophen exposure in the United States: A study of 30,000 cases from the National Poison Data System
Authors: Mehrpour Omid , Saeedi Farhad , Hoyte Christopher
Published: October 2021

Acetaminophen is one of the most commonly used analgesic drugs in the United States. However, the outcomes of acute acetaminophen overdose might be very serious in some cases. Therefore, prediction of the outcomes of acute acetaminophen exposure is crucial. This study is a 6‐year retrospective cohort study using National Poison Data System (NPDS) data. A decision tree algorithm was used to determine the risk predictors of acetaminophen exposure. The decision tree model had an accuracy of 0.839, an accuracy of 0.836, a recall of 0.72, a specificity of 0.86 and an F1_score of 0.76 for the test group and an accuracy of 0.848, a recall of 0.85, a recall of 0.74, a specificity of 0.87 and an F1_score of 0.78 for the training group. Our results showed that elevated serum levels of liver enzymes, other liver function test abnormality, anorexia, acidosis, electrolyte abnormality, increased bilirubin, coagulopathy, abdominal pain, coma, increased anion gap, tachycardia and hypotension were the most important factors in determining the outcome of acute acetaminophen exposure. Therefore, the decision tree model is a reliable approach in determining the prognosis of acetaminophen exposure cases and can be used in an emergency room or during hospitalization.
A small molecule CFTR potentiator restores ATP‐dependent channel gating to the cystic fibrosis mutant G551D‐CFTR
Authors: Liu Jia , Berg Allison P. , Wang Yiting , Jantarajit Walailak , Sutcliffe Katy J. , Stevens Edward B. , Cao Lishuang , Pregel Marko J. , Sheppard David N.
Published: October 2021

Background and Purpose

Cystic fibrosis transmembrane conductance regulator (CFTR) potentiators are small molecules developed to treat the genetic disease cystic fibrosis (CF). They interact directly with CFTR Cl− channels at the plasma membrane to enhance channel gating. Here, we investigate the action of a new CFTR potentiator, CP‐628006 with a distinct chemical structure.

Experimental Approach

Using electrophysiological assays with CFTR‐expressing heterologous cells and CF patient‐derived human bronchial epithelial (hBE) cells, we compared the effects of CP‐628006 with the marketed CFTR potentiator ivacaftor.

Key Results

CP‐628006 efficaciously potentiated CFTR function in epithelia from cultured hBE cells. Its effects on the predominant CFTR variant F508del‐CFTR were larger than those with the gating variant G551D‐CFTR. In excised inside‐out membrane patches, CP‐628006 potentiated wild‐type, F508del‐CFTR, and G551D‐CFTR by increasing the frequency and duration of channel openings. CP‐628006 increased the affinity and efficacy of F508del‐CFTR gating by ATP. In these respects, CP‐628006 behaved like ivacaftor. CP‐628006 also demonstrated notable differences with ivacaftor. Its potency and efficacy were lower than those of ivacaftor. CP‐628006 conferred ATP‐dependent gating on G551D‐CFTR, whereas the action of ivacaftor was ATP‐independent. For G551D‐CFTR, but not F508del‐CFTR, the action of CP‐628006 plus ivacaftor was greater than ivacaftor alone. CP‐628006 delayed, but did not prevent, the deactivation of F508del‐CFTR at the plasma membrane, whereas ivacaftor accentuated F508del‐CFTR deactivation.

Conclusions and Implications

CP‐628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
Effect of barriers to creativity on innovation in small and medium enterprises: Moderating role of institutional networks
Authors: Castillo‐Vergara Mauricio , García‐Pérez‐de‐Lema Domingo , Madrid‐Guijarro Antonia
Published: October 2021

Creativity has been recognized as a critical factor in innovation development companies. Small companies find it more difficult to develop creative activities and achieve innovation, thereby affecting their competitiveness significantly. In this study, we examine the barriers to creativity in a sample of 154 manufacturing small and medium enterprises (SMEs) in Chile. The barriers related to the environment, managers, and employees, which limit the development of creativity, were examined. Besides, the moderating role of institutional networks was studied. Results show that (1) creativity positively affects innovation in SMEs; (2) environmental barriers impact barriers related to on both managers and employees; (3) managers' barriers influence employee barriers; and (4) employee barriers negatively impact creativity, although this negative effect is diminished by the moderating effect of developing activities with institutional networks, such as higher education institutions, research centres or business associations. These results have important implications. Managers should encourage greater cooperation between companies and universities and be mindful of their impact on their employees. Government policies that encourage and support collaboration with SMEs can enable companies to be competitive and develop innovation, directly impacting employment and economic growth in a country.
The determinants of IMF fiscal conditionality: Economics or politics?
Authors: Guimaraes Bernardo , Ladeira Carlos Eduardo
Published: October 2021

Conditionalities, measures that a borrowing country should adopt to obtain loans from the International Monetary Fund (IMF), are pervasive in IMF programs. Empirical work on the determinants of IMF conditionalities typically employs indicators based on the number of conditions as proxies for program austerity. This paper estimates the effects of political and economic factors on a different measure of stringency of conditionality: the fiscal balance requested in an agreement. The correlation between the number of conditions and the requested fiscal adjustment is close to zero in our sample. The requested adjustment is strongly linked to the country's fiscal deficit but is also affected by politics. For middle‐income and upper‐income countries, political alignment with the US has a significant negative effect on the fiscal effort required by the IMF.
Improved survival of multiple myeloma patients treated with autologous transplantation in the modern era of new medicine
Authors: Shimazu Yutaka , Mizuno Shohei , Fuchida Shin‐ichi , Suzuki Kazuhito , Tsukada Nobuhiro , Hanagaishi Akira , Itagaki Mitsuhiro , Kataoka Keisuke , Kako Shinichi , Sakaida Emiko , Yoshioka Satoshi , Iida Shinsuke , Doki Noriko , Oyake Tatsuo , Ichinohe Tatsuo , Kanda Yoshinobu , Astuta Yoshiko , Takamatsu Hiroyuki ,   the working group of the Japan Society for Transplantation, Cellular Therapy
Published: October 2021

New drugs for multiple myeloma (MM) have dramatically improved patients’ overall survival (OS). Autologous stem cell transplantation (ASCT) remains the mainstay for transplant‐eligible MM patients. To investigate whether the post‐ASCT prognosis of MM patients has been improved by new drugs, we undertook a retrospective observational analysis using the Transplant Registry Unified Management Program database in Japan. We analyzed 7323 patients (4135 men and 3188 women; median age, 59 years; range 16‐77 years) who underwent upfront ASCT between January 2007 and December 2018. We categorized them by when they underwent ASCT according to the drugs’ introduction in Japan: group 1 (2007‐2010), group 2 (2011‐2016), and group 3 (2017‐2018). We compared the groups’ post‐ASCT OS. The 2‐year OS rates (95% confidence interval [CI]) of groups 1, 2, and 3 were 85.8% (84.1%‐87.4%), 89.1% (88.0%‐90.1%), and 92.3% (90.0%‐94.2%) (P < .0001) and the 5‐year OS (95% CI) rates were 64.9% (62.4%‐67.3%), 71.6% (69.7%‐73.3%), and not applicable, respectively (P < .0001). A multivariate analysis showed that the post‐ASCT OS was superior with these factors: age less than 65 years, performance status 0/1, low International Staging System (ISS) stage, receiving SCT for 180 days or less post‐diagnosis, better treatment response pre‐ASCT, later year of ASCT, and receiving SCT twice. A subgroup analysis showed poor prognoses for the patients with unfavorable karyotype and poor treatment response post‐ASCT. The post‐ASCT OS has thus improved over time (group 1 < 2 < 3) with the introduction of new drugs for MM. As the prognosis of high‐risk‐karyotype patients with ISS stage III remains poor, their treatment requires improvement.
Flurbiprofen axetil protects against cerebral ischemia/reperfusion injury via regulating miR‐30c‐5p and SOX9
Authors: Yang Bangkun , Nie Ying , Wang Lesheng , Xiong Wenping
Published: October 2021

The modulatory mechanism of flurbiprofen axetil (FPA) by which it relieves cerebral ischemia/reperfusion (I/R) injury (CIRI) is still obscure. In the present work, adult male Sprague‐Dawley (SD) rats were pre‐treated with FPA before the construction of a rat model of CIRI. Longa's scoring method and dry–wet method were employed to examine the neurological function and brain water content of the rats. MiR‐30c‐5p, SOX9, AQP4, SOX9, NF‐κB, and p‐NF‐κB expression levels in the brain tissues of the rats were examined by qRT‐PCR or Western blot. ELISA was executed to evaluate the IL‐10, IL‐6, and TNF‐α levels in the serum of rat. SOD and MDA levels in rat brain homogenates were also examined to indicate the oxidative stress. Hematoxylin‐eosin (HE) staining was used to examine the pathological changes of the brain tissues. Dual‐luciferase reporter gene experiment was implemented to validate the binding relationship between miR‐30c‐5p and SOX9. In the present work, compared with the rats with CIRI, FPA pre‐treatment attenuated neurological injury, cerebral edema, oxidative stress, inflammatory response, and cerebral pathological changes in the rat model with CIRI. FPA up‐modulated miR‐30c‐5p expression. SOX9 was a downstream target of miR‐30c‐5p. In conclusion, FPA ameliorates CIRI through up‐modulating miR‐30c‐5p expression and reducing SOX9 expression.
Empty pelvis syndrome: a systematic review of reconstruction techniques and their associated complications
Authors: Johnson Yanika L. , West Malcolm A. , Gould Laura E. , Drami Ioanna , Behrenbruch Corina , Burns Elaine M. , Mirnezami Alexander H. , Jenkins John T.
Published: October 2021

Aim

Empty pelvis syndrome is a major contributor to morbidity following pelvic exenteration. Several techniques for filling the pelvis have been proposed; however, there is no consensus on the best approach. We evaluated and compared the complications associated with each reconstruction technique with the aim of determining which is associated with the lowest incidence of complications related to the empty pelvis.

Method

The systematic review protocol was prospectively registered with PROSPERO (CRD42021239307). PRISMA‐P guidelines were used to present the literature. PubMed and MEDLINE were systematically searched up to 1 February 2021. A dataset containing predetermined primary and secondary outcomes was extracted.

Results

Eighteen studies fulfilled our criteria; these included 375 patients with mainly rectal and gynaecological cancer. Only three studies had a follow‐up greater than 2 years. Six surgical interventions were identified. Mesh reconstruction and breast prosthesis were associated with low rates of small bowel obstruction (SBO), entero‐cutaneous fistulas and perineal hernia. Findings for myocutaneous flaps were similar; however, they were associated with high rates of perineal wound complications. Omentoplasty was found to have a high perineal wound infection rate (40%). Obstetric balloons were found to have the highest rates of perineal wound dehiscence and SBO. Silicone expanders effectively kept small bowel out of the pelvis, although rates of pelvic collections remained high (20%).

Conclusion

The morbidity associated with an empty pelvis remains considerable. Given the low quality of the evidence with small patient numbers, strong conclusions in favour of a certain technique and comparison of these interventions remains challenging.
Distribution of cellular remnants of melanocytes in the nail plate: Clue to the diagnosis of subungual melanoma
Authors: Oh Se Jin , Lee Jongeun , Lee Jae Ho , Bae Jaihee , Park Ji‐Hye , Lee Jong Hee , Lee Dongyoun
Published: October 2021

Background

Previous studies reported that cellular remnants in the nail plate could be a diagnostic clue for subungual melanoma (SUM). We sought to characterize the histopathologic features of cellular remnants in the nail plates of SUM patients.

Methods

A retrospective case‐control study was conducted in a single tertiary center from 2012 to 2019. Twenty‐three patients with pathologically diagnosed SUM and eight nail matrix nevi (NMN) patients were recruited. The analysis of the nail plate specimens focused on large cellular remnants of melanocytes (LCRMs). Longitudinal linear density and vertical distribution pattern of the LCRMs were scrutinized for possible features distinguishing SUM from NMN.

Results

The median linear density of the LCRMs was significantly higher in the SUM samples than in the NMN samples. LCRMs in the SUM samples were more dorsally distributed than those in the NMN samples. In invasive SUM, LCRMs were more likely to be found in the dorsal part of the nail plate compared to SUM in situ.

Conclusion

Nail plate specimens should not be overlooked in the histopathological examination of melanonychia. High‐density LCRMs with more dispersion to the dorsal side might be suggestive of SUM.
Evaluation of pharyngeal lidocaine anesthesia for esophagogastroduodenoscopy: Double‐blind randomized control trial
Authors: Martín‐Marcos Irene , Fernández‐Morte Nuria , Balsategui‐Martín María , Ortiz‐Cantero Alexandra , Bermúdez‐Ampudia Cristina , López‐Picado Amanda , Pérez‐Vaquero Pilar , Salvador‐Pérez Marta , Cristóbal‐Domínguez Estíbaliz
Published: October 2021

Objectives

The aim of this study was to assess whether the use of topical pharyngeal anesthesia improves endoscopist‐ and patient‐reported tolerance and satisfaction, the total dose of propofol used and the rate of adverse effects associated with this procedure.

Methods

This double‐blind randomized clinical trial was conducted in patients undergoing elective oesophagogastroduodenoscopy, who met the inclusion criteria. Patients were randomly assigned to receive five squirts of lidocaine 10% spray (50 mg, n = 268) or placebo (n = 271) 3 min before starting the procedure or sedation. The main outcome measures were patient‐ and endoscopist‐reported tolerance, and additionally, satisfaction with the procedure, adverse events and supplementary propofol used.

Results

In the lidocaine group, it was twice (odds ratio [OR] 2.136, 95% confidence interval [CI] 1.228–3.715) or three times (OR 3.311, 95% CI 1.623–6.757) more likely that the endoscopist rated the procedure as well tolerated and easy to intubate than as well tolerated but the patient difficult to intubate or as poorly tolerated, respectively. Further, in these patients, less propofol was used (80 vs. 100 mg, P = 0.001). Controls were more likely to cough during the intubation (OR 2.172, 95% CI 1.378–3.423) and the procedure (OR 1.989, 95% CI 1.325–2.984), as well as more likely to retch (OR 3.582, 95% CI 1.667–7.7).

Conclusions

Topical lidocaine may improve the procedure as rated by the endoscopist, as well as reduce the requirement for propofol and rate of adverse events such as retching and coughing. No adverse events associated with lidocaine administration were observed. ClinicalTrials registration no. NCT02733471.
Endoscopic management of gastroesophageal reflux disease: Panacea for proton pump inhibitors dependent/refractory patients
Authors: Kalapala Rakesh , Singla Neeraj , Reddy Duvvur Nageshwar
Published: October 2021

Endoscopic therapies in proton pump inhibitors (PPI) dependent/refractory gastroesophageal reflux disease (GERD) are increasingly indicated in patients who are not suitable or willing for chronic medical therapy and surgical fundoplication. Currently available endoluminal anti‐reflux procedures include radiofrequency therapy (Stretta), suturing/plication and mucosal ablation/resection techniques at the gastroesophageal junction. Meticulous work up and patient selection results in a favorable outcome with these endoscopic therapies, especially the quality of life and partially the PPI independence. Stretta can be considered in patients with PPI refractory GERD and might have a role in patients with reflux hypersensitivity and functional heartburn. Endoscopic fundoplication using the Esophyx device and the GERD‐X device have strong evidence (multiple randomized controlled trials) in patients with small hiatus hernia and high volume reflux episodes. Mucosal resection/ablation techniques like anti‐reflux mucosectomy and anti‐reflux mucosal ablation have shown promising results but need long term follow‐up studies to prove their efficacy. The subset of PPI dependent GERD population will benefit from endoscopic therapies and the future of endoscopic management of GERD looks promising.
The effect of bedtime snacks on fasting blood glucose levels in gestational diabetes mellitus
Authors: Henze Meg , Burbidge Hanna , Nathan Elizabeth , Graham Dorothy F.
Published: October 2021

Aim

To investigate the effect of different bedtime snacks (higher carbohydrate versus lower carbohydrate versus no snack) on first morning fasting blood glucose levels (BGLs) in women with diet‐controlled gestational diabetes mellitus (GDM) and borderline fasting glucose levels.

Methods

This prospective randomised crossover trial enrolled women with diet controlled GDM between 24 and 34 weeks gestation who had two or more first morning fasting BGLs between 4.7 and 5.4 mmol/L in the week prior to recruitment. The women were randomly allocated to 6 different orders of 5 days each of a standardised higher carbohydrate bedtime snack, a lower carbohydrate bedtime snack and no bedtime snack. The primary outcome was fasting capillary BGL as measured with a home glucometer, and the secondary outcome was requirement for insulin as assessed by a physician.

Results

A total of 68 women with GDM were enrolled in and completed the study at a median gestation of 30.8 weeks. Compared with no bedtime snack, the higher carbohydrate snack (4.96 vs 4.87 mmol/L, mean difference: 0.09 mmol/L, 95% CI 0.05–0.13,p < 0.001) and the lower carbohydrate snack (5.01 vs 4.87 mmol/L, mean difference: 0.14 mmol/L, 95% CI 0.09–0.18,p < 0.001) were both associated with a slightly higher fasting BGL the following morning.

Conclusions

Taking a bedtime snack was associated with slightly higher fasting BGLs in women with diet‐controlled GDM compared with no bedtime snack (Clinical trial registration: ACTRN12617000659303).
Expression of CD47 in the pancreatic β‐cells of people with recent‐onset type 1 diabetes varies according to disease endotype
Authors: Leslie Kaiyven Afi , Richardson Sarah J. , Russell Mark A. , Morgan Noel G.
Published: October 2021

Aims

We are studying the dialogue between β‐cells and the immune system in type 1 diabetes and have identified a cell surface receptor, signal regulatory protein‐alpha (SIRPα) as an important component in the regulation of β‐cell survival. SIRPα interacts with another protein, CD47, to mediate signalling. In the present work, we have studied the expression and role of CD47 in human islet cells in type 1 diabetes.

Methods

Clonal EndoC‐βH1 cells were employed for functional studies. Cells were exposed to pro‐inflammatory cytokines and their viability monitored by flow cytometry after staining with propidium iodide. Targeted knockdown of CD47 or SIRPα was achieved with small interference RNA molecules and the expression of relevant proteins studied by Western blotting or immunocytochemistry. Human pancreas sections were selected from the Exeter Archival Diabetes Biobank and used to examine the expression of CD47 by immunofluorescence labelling. Image analysis was employed to quantify expression.

Results

CD47 is abundantly expressed in both α and β cells in human pancreas. In type 1 diabetes, the levels of CD47 are increased in α cells across all age groups, whereas the expression in β‐cells varies according to disease endotype. Knockdown of either CD47 or SIRPα in EndoC‐βH1 cells resulted in a loss of viability.

Conclusions

We conclude that the CD47 plays a previously unrecognised role in the regulation of β‐cell viability. This system is dysregulated in type 1 diabetes suggesting that it may be targeted therapeutically to slow disease progression.
Effects of dipeptidyl peptidase‐4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents
Authors: Zullo Andrew R. , Duprey Matthew S. , Smith Robert J. , Gutman Roee , Berry Sarah D. , Munshi Medha N. , Dore David D.
Published: October 2021

Aims

Dipeptidyl peptidase‐4 inhibitors (DPP4Is) may mitigate hypoglycaemia‐mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents.

Materials and Methods

This new‐user cohort study included long‐stay NH residents aged ≥65 years from the 2007‐2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6‐point MDS Cognitive Performance Scale, functional decline from the validated 28‐point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180‐day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models.

Results

The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180‐day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31‐1.19], altered mental status events (HR = 0.71, 95% CI 0.39‐1.27), and functional decline (HR = 0.89, 95% CI 0.51‐1.56), but estimates were imprecise.

Conclusions

Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.
Two Epichloë festucae var. lolii endophytes in Lolium perenne reduce larval populations of the wheat sheath miner, Cerodontha australis
Authors: Jensen Joanne G. , Miller Taryn A. , Cave Vanessa M. , Johnson Richard D. , Scott Barry , Popay Alison J.
Published: October 2021

The wheat sheath miner, Cerodontha australis Malloch (Diptera: Agromyzidae), is a small leaf‐ and stem‐mining fly that is native to New Zealand and eastern Australia where it feeds on grasses and cereals. Although not considered to be a major insect pest of pastures in New Zealand, it can be abundant during spring and summer in Waikato, New Zealand, and infests tillers of the introduced pasture plant, perennial ryegrass, Lolium perenne L. (Poaceae). Cerodontha australis is not deterred from feeding on L. perenne infected with commercially available strains of the fungal endophyte Epichloë festucae var. lolii, which have been shown to provide protection from a range of other insect pests. In this study, three‐pot trials and periodic examination over 18 months of field‐collected L. perenne tillers showed that two Epichloë endophyte strains, AR47 and AR48, reduced the survival and feeding damage by C. australis larvae, but there was no evidence of an effect on adult female feeding or oviposition. Compared to other strains of E. festucae var. lolii endophytes tested, plants infected with AR47 and AR48 had fewer and smaller larvae and less larval mining. The number of tillers with mining was reduced in AR47 relative to endophyte‐free (Nil) by 57.1% (ranging from 25.0 to 92.5% across trials) and in AR48 by 67.1% (26.3–100%). Larvae in AR47 and AR48 were found further from the base of the tiller where they were less likely to damage the meristem and cause tiller death. The number of larvae and pupae in pseudostems was reduced in AR47 and AR48 compared with Nil by 78.4 and 82.0%, respectively, in the field trial. Very few larvae survived to pupation in AR47 and AR48 plants, with a reduction compared to Nil of over 81.5% in AR47 and over 97% in AR48 in each of the four trials presented here.
Feeding strategies and diet variation in livebearing fishes of the genusLimia(Cyprinodontiformes: Poeciliidae) in the Greater Antilles
Authors: Rodriguez‐Silva Rodet , Spikes Montrai , Iturriaga Manuel , Bennett Kerri‐Ann , Josaphat James , Torres‐Pineda Patricia , Bräger Stefan , Schlupp Ingo
Published: October 2021

Feeding specialisations are known to play an important role in the ecology and evolution of many organisms. In this study, we performed a comparative analysis based on the data of the gut content of eight species of the genusLimia(family Poeciliidae) to explore the potential role of feeding ecology in the radiation of this genus in the Caribbean. We analysed the feeding strategies using the modified Costello's graphical method. In addition, we estimated the contribution of each food item to the diet by calculating the alimentary index of six different functional categories that summarised the variation in main type of consumed items. We also compared the niche breadth for all analysed species and the niche breadth variation between wet and dry seasons in four species we were able to sample in both periods of the year. Most of the analysed species showed preference for detritus and algae. Species that exhibited a more omnivorous diet such asL. versicolorandL. perugiaerevealed moderate levels of consumption of terrestrial and aquatic invertebrates. Nonetheless, some species such asL. yaguajaliandL. nigrofasciatashowed specialisations towards detritus as the dominant food item found in the gut content analysis. In general, niche breadth values were higher in the wet season than in the dry period. Our study showed that the majority of species analysed tend to be feeding generalists, but some degree of specialisation occurs in some species from Hispaniola where the diversity of the genusLimiais remarkably higher compared to the rest of the Greater Antilles.
Non‐invasive brain stimulation in modulation of mental rotation ability: A systematic review and meta‐analysis
Authors: Veldema Jitka , Gharabaghi Alireza , Jansen Petra
Published: October 2021

Mental rotation, the ability to manipulate mental images, is an important function in human cognition. This systematic review and meta‐analysis investigates the potential of non‐invasive brain stimulation in modulation of this component of visuo‐spatial perception. The PubMed database was reviewed prior to 31 September 2020 on randomized controlled trials investigating the effects of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) on the mental rotation ability in healthy persons. A total of 17 studies (including 485 subjects) matched our inclusion criteria. Within their scope, overall, 46 sham‐controlled experiments were performed. Methodology and results of each experiment are presented in a meta‐analysis. The data show a large variety of methods and effects. The influence of (1) stimulation‐technique (tDCS, tACS, and rTMS), (2) stimulation protocol (anodal, cathodal, bilateral tDCS, tACS, high‐frequency rTMS, low‐frequency rTMS, paired pulse rTMS, and theta burst stimulation), (3) stimulation timing (preconditioning and simultaneous), (4) stimulation location (left, right hemisphere, frontal, and parietal area), and (5) stimulus type (bodily and non‐bodily) is discussed. The data indicate a beneficial effect of anodal tDCS and of tACS and no effect of cathodal tDCS on the mental rotation ability. Bilateral tDCS protocols both improved and worsened the parameters assessed. The small effect sizes obtained in mostly rTMS experiments require cautious interpretation.
A genetically based ecological trade‐off contributes to setting a geographic range limit
Authors: Mauro Alexander A. , Torres‐Dowdall Julián , Marshall Craig A. , Ghalambor Cameron K.
Published: October 2021

Understanding the ecological factors that shape geographic range limits and the evolutionary constraints that prevent populations from adaptively evolving beyond these limits is an unresolved question. Here, we investigated why the euryhaline fish, Poecila reticulata, is confined to freshwater within its native range, despite being tolerant of brackish water. We hypothesised that competitive interactions with a close relative, Poecilia picta, in brackish water prevents P. reticulata from colonising brackish water. Using a combination of field transplant, common garden breeding, and laboratory behaviour experiments, we find support for this hypothesis, as P. reticulata are behaviourally subordinate and have lower survival in brackish water with P. picta. We also found a negative genetic correlation between P. reticulata growth in brackish water versus freshwater in the presence of P. picta, suggesting a genetically based trade‐off between salinity tolerance and competitive ability could constrain adaptive evolution at the range limit.
The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage
Authors: van der Harst J. Joep , Luijckx Gert‐Jan R. , Elting Jan Willem J. , Lammers Thijs , Bokkers Reinoud P. H. , van den Bergh Walter M. , Eshghi Omid S. , Metzemaekers Jan D. M. , Groen Rob J. M. , Mazuri Aryan , Veeger Nic J. G. M. , van Dijk J. Marc C. , Uyttenboogaart Maarten
Published: October 2021

Background and purpose

Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage.

Methods

The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI‐DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut‐off scores. Inter‐rater reliability was evaluated by Cohen's kappa coefficient.

Results

This study included 59 patients. CI‐DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI‐)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI‐DCI 0.89 (95% confidence interval [CI] 0.79–0.99), DCI 0.68 (95% CI 0.50–0.87) and functional outcome 0.74 (95% CI 0.57–0.91). Cohen's kappa between the two raters was moderate to substantial (0.57–0.63).

Conclusions

This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI‐)DCI and unfavorable outcome.
Ocrelizumab treatment in multiple sclerosis: A Danish population‐based cohort study
Authors: Pontieri Luigi , Blinkenberg Morten , Bramow Stephan , Papp Viktoria , Rasmussen Peter V. , Kant Matthias , Schäfer Jakob , Mathiesen Henrik K. , Jensen Michael B. , Sirakov Georgi , Berg Jonas M. , Kopp Tine I. , Joensen Hanna , Sellebjerg Finn , Magyari Melinda
Published: October 2021

Background and purpose

Real‐world evidence regarding the effectiveness and safety of ocrelizumab for the treatment of multiple sclerosis (MS) is limited. The aim was to evaluate the effectiveness and safety of ocrelizumab treatment for MS in a real‐world setting.

Methods

A nationwide population‐based cohort study was conducted where clinical and magnetic resonance imaging data of MS patients enrolled prospectively in the Danish Multiple Sclerosis Registry who initiated ocrelizumab treatment between January 2018 and November 2020 were analyzed.

Results

A total of 1104 patients (85.7% relapsing–remitting MS [RRMS], 8.8% secondary progressive MS [SPMS], 5.5% primary progressive MS [PPMS]) were included, with a median follow‐up period of 1.3 years. At baseline, the mean age was 41.4 years in the RRMS group, 44.5 years in the PPMS group and 50.3 years in the SPMS group. Median Expanded Disability Status Scale score was 2.5, 3.5 and 5.5, respectively. Most RRMS and SPMS patients had received previous disease‐modifying therapies (87.5% and 91.8%, respectively), whereas PPMS patients were mostly treatment naïve (78.7%). After ocrelizumab initiation, 9.3% of the patients experienced a relapse and 8.7% a 24 weeks confirmed disability worsening. Conversely, 16.7% showed a 24 weeks confirmed disability improvement. After ~1 year of treatment, most patients (94.5%) were free of magnetic resonance imaging activity. Ocrelizumab was generally well tolerated, as side effects were only reported for 10% of patients, mostly consisting of infusion‐related reactions and infections.

Conclusions

It is shown that most MS patients treated with ocrelizumab are clinically stabilized and with an adverse event profile consistent with the experience from the pivotal clinical trials.