bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta-lactam allergy labeling in intensive care units
Authors: Leone Marc , Zunino Claire , Pauly Vanessa , Mathieu Calypso , Antonini François , Orlean Veronica , Cassir Nadim , Pradel Vincent , Bourenne Jérémy , Boussen Salah , Hraiech Sami , Lagier David , Vitte Joana , Wiramus Sandrine , Zieleskiewicz Laurent , Papazian Laurent , Boyer Laurent
Published: July 2021

This retrospective study aimed to describe the association between the “β-lactam allergy” labeling (BLAL) and the outcomes of a cohort of intensive care unit (ICU) patients.

Retrospective cohort study.

Seven ICU of the Aix Marseille University Hospitals from Marseille in France.

We collected the uses of the label “β-lactam allergy” in the electronic medical files of patients aged 18 years or more who required more than 48 hours in the ICU with mechanical ventilation and/or vasopressors admitted to 7 ICUs of a single institution.

We retrospectively compared the patients with this labeling (BLAL group) with those without this labeling (control group).

The primary outcome was the duration of ICU stay. Among the 7146 patients included in the analysis, 440 and 6706 patients were classified in the BLAL group and the control group, respectively. The prevalence of BLAL was 6.2%. In univariate and multivariate analyses, BLAL was weakly or not associated with the duration of ICU and hospital stays (respectively, 6 [3–14] vs 6 [3–14] days, standardized beta −0.09, P = .046; and 18 [10–29] vs 15 [8–28] days, standardized beta −0.09, P = .344). In multivariate analysis, the ICU and 28-day mortality rates were both lower in the BLAL group than in the control group (aOR 0.79 95% CI [0.64–0.98] P = .032 and 0.79 [0.63–0.99] P = .042). Antibiotic use differed between the 2 groups, but the outcomes were similar in the subgroups of septic patients in the BLAL group and the control group.

In our cohort, the labeling of a β-lactam allergy was not associated with prolonged ICU and hospital stays. An association was found between the labeling of a β-lactam allergy and lower ICU and 28-day mortality rates.

Trial registration: Retrospectively registered.
Intrapulmonary lymph node (stations 13 and 14) metastasis in peripheral non-small cell lung cancer
Authors: Bi Lei , Zhang Hong , Ge Mingjian , Lv Zhongzhu , Deng Yiping , Rong Tenghao , Liu Chaolun
Published: July 2021

It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) when resecting peripheral non-small cell lung cancer (NSCLC) is necessary for accurate tumor node metastasis (TNM) staging. This study investigated intrapulmonary lymph node dissection (stations 13 and 14) on the pathological staging of peripheral NSCLC and the metastatic pattern of the lymph nodes.

This retrospective study included patients with primary peripheral NSCLC who underwent radical dissection between January 2013 and December 2015. The clinical data of patients and examination results of intrapulmonary stations 12, 13, and 14 lymph nodes were analyzed.

Of 3019 resected lymph nodes in a total of 234 patients (12.9/patient), 263 (8.7%) had metastasis. Ninety-nine patients had lymph node metastasis (42.3%): 40 (17.1%) were N1, 11 (4.7%) were N2, 48 (20.5%) were both N1 and N2, and 135 (57.7%) had no N1 or N2 metastasis. Sixteen (6.8%) patients had metastasis of stations 13 and/or 14. Metastasis in N1 positive patients of stations 10, 11, 12, 13, and 14 were 2.7%, 10.5%, 9.8%, 10.4%, and 8.5%, respectively. Missed detection without station 13 and 14 dissection was up to 6.8% (16/234).

Dissection of stations 13 and 14 could be helpful for the identification of lymph node metastasis and for the accurate TNM staging of primary NSCLC.
The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit/hyperactivity disorder
Authors: Sugimoto Atsunori , Suzuki Yutaro , Orime Naoki , Hayashi Taketsugu , Yoshinaga Kiyohiro , Egawa Jun , Ono Shin , Sugai Takuro , Inoue Yoshimasa , Someya Toshiyuki
Published: July 2021

Background:

Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy.

Methods:

Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography.

Results:

The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 ± .04 mg/kg [mean ± standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 ± .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 ± 32.3 ng/mL in 7 responders and was significantly higher than 29.5 ± 23.9 ng/mL (P < .01) for the 29 non-responders.

Conclusions:

These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.
Expression and prognostic analyses of HDACs in human gastric cancer based on bioinformatic analysis
Authors: Chen Luting , Fei Yuchang , Zhao Yurong , Chen Quan , Chen Peifeng , Pan Lei
Published: July 2021

Gastric cancer (GC) is a common cancerous tumor, and is the third leading cause of cancer mortality worldwide. Although comprehensive therapies of GC have been widely used in clinical set ups, advanced gastric cancer carries is characterized by poor prognosis, probably due to lack of effective prognostic biomarkers. Mammalian histone deacetylase family, histone deacetylases (HDACs), play significant roles in initiation and progression of tumors. Aberrant expression of HDACs is reported in many cancer types including gastric cancer, and may serve as candidate biomarkers or therapeutic targets for GC patients.

Gene Expression Profiling Interactive Analysis was used to explore mRNA levels of HDACs in GC. Kaplan–Meier plotter was used to determine the prognostic value of HDACs mRNA expression in GC. Genomic profiles including mutations of HDACs were retrieved from cBioPortal webserver. A protein–protein interaction network was constructed using STRING database. GeneMANIA was used to retrieve additional genes or proteins related to HDACs. R software was used for functional enrichment analyses.

Analysis of mRNA levels of HDAC1/2/4/8/9 showed that they were upregulated in GC tissues, whereas HDAC6/10 was downregulated in GC tissues. Aberrant expression of HDAC1/3/4/5/6/7/8/10/11 was all correlated with prognosis in GC. In addition, expression levels of HDACs were correlated with different Lauren classifications, and clinical stages, lymph node status, treatment, and human epidermal growth factor receptor 2 status in GC.

The findings of this study showed that HDAC members are potential biomarkers for diagnosis or prognosis of gastric cancer. However, further studies should be conducted to validate these findings.
Contrast-enhanced CT radiomics features to predict recurrence of locally advanced oesophageal squamous cell cancer within 2 years after trimodal therapy
Authors: Tang Sun , Ou Jing , Wu Yu-Ping , Li Rui , Chen Tian-Wu , Zhang Xiao-Ming
Published: July 2021

Radiomics transforms the medical images into high-dimensional quantitative features and provides potential information about tumor phenotypes and heterogeneity. We conducted a retrospective analysis to explore and validate radiomics model based on contrast-enhanced computed tomography (CECT) to predict recurrence of locally advanced oesophageal squamous cell cancer (SCC) within 2 years after trimodal therapy. This study collected CECT and clinical data of consecutive 220 patients with pathology-confirmed locally advanced oesophageal SCC (154 in the training cohort and 66 in the validation cohort). Univariate statistical test and the least absolute shrinkage and selection operator method were performed to select the optimal radiomics features. Logistic regression was conducted to build radiomics model, clinical model, and combined model of both the radiomics and clinical features. Predictive performance was judged by the area under receiver operating characteristics curve (AUC), accuracy, and F1-score in the training and validation cohorts. Ten optimal radiomics features and/or 7 clinical features were selected to build radiomics model, clinical model, and the combined model. The integrated model of radiomics and clinical features was superior to radiomics model or clinical model in predicting recurrence of locally advanced oesophageal SCC within 2 years in the training (AUC: 0.879 vs 0.815 or 0.763; accuracy: 0.844 vs 0.773 or 0.740; and F1-score: 0.886 vs 0.839 or 0.815, respectively) and validation (AUC: 0.857 vs 0.720 or 0.750; accuracy: 0.788 vs 0.700 or 0.697; and F1-score: 0.851 vs 0.800 or 0.787, respectively) cohorts. The combined model of radiomics and clinical features shows better performance than the radiomics or clinical model to predict the recurrence of locally advanced oesophageal SCC within 2 years after trimodal therapy.
Anterolateral thigh free flaps with T-shaped pedicles and multiple venous anastomosis for extremity reconstruction
Authors: Lee Jun Ho , Choi Hwan Jun , Kwak Si Hyun , Lee Da Woon , Tak Min Sung , Kang Jin Seok
Published: July 2021

The anterolateral thigh free flap is one of the most preferred options for reconstructing soft tissues of the extremities and vascular anastomosis is one of the most important factors for flaps survival. T-anastomosis and double venous anastomosis have been widely used for increasing flap survival. This report shows both application of T-shape pedicle and multiple venous anastomosis to each 43 cases for extremity reconstruction that have not been described so far in the literature and it showed the necessity of multiple anastomosis. The locations of the lesions were 8 upper extremities (4 hands, 3 forearms, and 1 upper arm) and 35 lower extremities (5 forefeet, 6 dorsal feet, 4 plantar feet, 11 ankles, and 9 lower legs). We applied T-shaped arterial pedicle to limited anatomical area that had 2 or more major arterial communication sites to overcome the obstruction by reverse flow from communication vessels when 1 of the 2 anastomosis was obstructed. We classified multiple venous anastomosis according to flow direction and the vascular connections between the superficial and deep veins. In result, 37 cases survived completely but 2 flaps developed severe necrosis (>50%) because of infection and hematoma and 4 flaps developed partial necrosis due to wound infection. In conclusion, T-shaped pedicle and multiple venous anastomosis is a method to improve free flap survival and useful in cases where sacrificing a dominant vessel is inevitable or those in which only 1 vessel remains.
Severe bacterial infection in young infants with pyrexia admitted to the emergency department
Authors: Chen Yin-Ting , Chang Yu-Jun , Liu Bang-Yan , Lee En-Pei , Wu Han-Ping
Published: July 2021

The objectives of this study were to understand the clinical presentations of febrile young infants with severe bacterial infection (SBI), and to investigate the pathogen variations throughout the vaccine era and after antenatal group B Streptococcus (GBS) screening.

All infants < 90 days old with a body temperature of ≥38.0°C and admitted to the emergency department were retrospectively enrolled in our study. SBI was defined as a positive culture of urine, blood, or cerebrospinal fluid. All clinical variables were analyzed and compared between the SBI group and the non-SBI group, to identify the relevant risk factors for SBI in infants with pyrexia.

A total of 498 infants were studied, 279 of whom (56%) had SBI. The body temperature at triage was higher in the SBI group, and the difference was highly obvious in the neonatal group. White blood cell count and C-reactive protein levels were both significantly higher in the SBI group (P < .05), whereas neutrophil percentage and band percentage demonstrated no significant differences. Escherichia coli was the most common pathogen and plasmid-mediated extended-spectrum lactamases were detected in up to 9.1%. GBS was detected in 16 cases of bacteremia (6 cases with concurrent meningitis).

The body temperature at triage may provide a clue for differentiating sick babies, especially in the neonatal group. Complete serum analysis is required for infection survey, especially white blood cell and C-reactive protein. Escherichia coli is the most common pathogen, and clinician should raise awareness of drug resistance in some patients. The prevalence of GBS infection in the young infant group remains high after routine antenatal GBS screening
Acute interstitial nephritis associated with ingesting a Momordica charantia extract
Authors: Bae Wooram , Kim Seongmin , Choi Jungyoon , Lee Tae Won , Bae Eunjin , Jang Ha Nee , Jung Sehyun , Lee Seunghye , Chang Se-Ho , Park Dong Jun
Published: July 2021

Rationale:

Momordica charantiais often used to treat type 2 diabetes mellitus in Korea. Drug-induced acute interstitial nephritis (AIN) accounts for 60% to 70% of AIN cases. However, only 1 case of AIN associated with ingestingM charantiahas been reported in the English literature. We report an extremely rare case of AIN that occurred after a patient ingested a pureM charantiaextract over 7 months.

Patient concerns:

A 60-year-old Korean woman was admitted to our hospital for a renal biopsy. Her renal function had decreased gradually over the last 9 months without symptoms or signs.

Diagnosis:

Her blood urea nitrogen and serum creatinine levels were 29.7 mg/dL (range: 8.0–20.0 mg/dL) and 1.45 mg/dL (range: 0.51–0.95 mg/dL) on admission. Renal histology indicated AIN; there was immune cell infiltration into the interstitium, tubulitis, and epithelial casts, although the glomeruli were largely intact.

Interventions:

M charantiawas discontinued and prednisolone was prescribed.

Outcomes:

The value of serum creatinine has almost been restored to the baseline level after 3 months.

Conclusion

s: This is the first case report of AIN associated with the ingestion of a pureM charantiaextract. Recognition of the possible adverse effects of these agents by physicians is very important for early diagnosis and appropriate management.
Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals
Authors: Alem Shereen Abdel , Eletreby Rasha , Abdellatif Zeinab , Ramadan Ahmed , Nagy Ahmed , AbdAllah Mohamed , Elsharkawy Aisha , Fouad Rabab , Esmat Gamal , Tantawi Omnia
Published: July 2021

Objective:

Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens.

Methods:

a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed.

Results:

Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time.

Conclusion:

This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.
Comparison of transient elastography and Model for End-Stage Liver Disease-sodium to Model for End-Stage Liver Disease-sodium alone to predict mortality and liver transplantation
Authors: Trivedi Hirsh D. , Danford Christopher J. , Iriana Sentia , Ochoa-Allemant Pedro , Rourke Meredith , Yang Kuen-Cheh , Curry Michael P. , Lai Michelle
Published: July 2021

Objectives

Model for End-Stage Liver Disease (MELD) alone and with sodium (MELD-Na) have decreasing predictive capacity as trends in liver disease evolve. We sought to combine transient elastography (TE) with MELD-Na to improve its predictive ability.

Methods

This is a retrospective cohort study comparing the use of TE, MELD-Na, and composite MELD-Na-TE to predict liver transplantation and all-cause mortality, with hepatic decompensation as a secondary outcome. Cox proportional hazards regression was used to measure predictive ability and control for confounders.

Results

Of the 214 patients, the mean age was 53 years with 35% being female and 76% being Caucasian. Hepatitis C (59%) and nonalcoholic fatty liver disease (22%) were the most frequent liver disease etiologies. On univariable analysis, MELD-Na [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06–1.2, P < 0.001], TE (HR 1.04, 95% CI 1.03–1.06, P < 0.001) and composite MELD-Na-TE (HR 1.13, 95% CI 1.08–1.19, P < 0.001) were associated with death or transplant. On multivariable analysis, MELD-Na was no longer significant (HR 1.08, 95% CI 0.95–1.22, P = 0.27) after adjusting for TE (HR 1.05, 95% CI 1.03–1.07, P < 0.001) while composite MELD-Na-TE remained significant (HR 1.16, 95% CI 1.09–1.24, P < 0.001). Composite MELD-Na-TE predicts mortality or liver transplant with the highest C-statistic of 0.81. Age (HR 1.05, 95% CI 1–1.09, P = 0.04), TE (HR 1.04, 95% CI 1.03–1.06, P < 0.001) and composite MELD-Na-TE (HR 1.11, 95% CI 1.06–1.15, P < 0.001) were significantly associated with hepatic decompensation.

Conclusion

Composite MELD-Na-TE better predicts liver transplantation, death, and hepatic decompensation compared to MELD/MELD-Na or TE alone.
Functional gastrointestinal disorders as predictors of suicidal ideation. An observational study
Authors: Deutsch David , Bouchoucha Michel , Devroede Ghislain , Raynaud Jean-Jacques , Sabate Jean-Marc , Benamouzig Robert
Published: July 2021

Background/objectives

Suicidal ideation (SI), a symptom of depression, is known to be associated with irritable bowel syndrome (IBS) but is not known to be associated with other functional gastrointestinal disorders (FGIDs). However, the source of this association is discussed. It could be related to a possible abnormal biochemical pathway implicating neurotransmitters common to both disorders like serotonin or pain and an ill-being associated with a chronic disorder of unknown etiology. The present study aims to search for the FGIDs associated with suicidal ideation.

Design

Observational study.

Methods

A total of 1469 patients with FGIDs (71% of women) were included in the present study. They filled the Rome III questionnaire, Beck depression inventory, and state and trait anxiety questionnaires. Data were analyzed using analysis of variance with Bonferroni correction and logistic regression analysis.

Results

Suicidal ideation was reported by 15% of patients, associated with increased scales of depression (P < 0.001), state (P = 0.006), and trait anxiety (P = 0.021). Clinically, these patients reported a higher prevalence of IBS-diarrhea subtype (P = 0.045), fecal incontinence (P = 0.020), soiling (P = 0.016), and difficult defecation (P = 0.005), and higher perceived severity for constipation, diarrhea, bloating, and abdominal pain (P < 0.001 for all scales).

Conclusions

This study shows that only functional bowel and functional anorectal disorders are associated with suicidal ideation. This result must be taken into account in the management of these patients.
Recent lessons learned for ex-vivo platelet production
Authors: Tang Alice , Mendelson Avital
Published: July 2021

Purpose of review

Platelet transfusion can be life-saving but carries a risk of infection or alloimmunization and is limited by insufficient donor sources and restricted unit shelf life. Generating sufficient platelets in vitro to replace a unit of collected blood remains a challenge. Here, we examine the latest advances in the regulation of megakaryocyte maturation and expansion along with platelet formation and survival. We also discuss alternative therapies investigated to induce platelet production.

Recent findings

Recent studies examined candidate niche cells in the bone marrow microenvironment for promoting platelet formation and developed an explant-based bioreactor to enhance platelet production ex vivo. Chemical inhibitors were examined for their ability to promote megakaryocyte maturation and expansion. Microparticles from megakaryocytes or platelets were found to improve megakaryocyte maturation and platelet formation. Membrane budding was identified as a novel mode of platelet formation. Lastly, a chemical inhibitor to improve cold-stored platelets was identified.

Recent advances in the regulation of megakaryocyte expansion and platelet production provide exciting promise for the development of improved approaches to generate platelets in vitro. These findings bring the field one step closer to achieving the ultimate goal of creating a unit of platelets without the need for donation.
The place of robotic-assisted laparoscopy for BPO surgical management in 2021
Authors: Grobet-Jeandin Elisabeth , Pinar Ugo , Rouprêt Morgan
Published: July 2021

Purpose of review

Robot-assisted laparoscopic simple prostatectomy (RASP) is being used increasingly for the surgical treatment of benign prostatic obstruction (BPO). Our purpose is to review the main outcomes of RASP for the management of BPO.

Recent findings

A computerised bibliographic search of Medline was performed for articles that included detailed results of RASP, published over the past 2 years. Although RASP seems to be associated with better perioperative and functional outcomes, this procedure remains expensive when compared to open or endoscopic surgery. However, considering the enhanced safety of RASP compared to open simple prostatectomy and its favourable learning-curve when compared to endoscopic laser enucleation, RASP seems to be a good and effective option in centres with extended robotic expertise. Single-port robotic surgery appeared to be safe and effective in two preliminary studies. Other studies reported interesting and improved results for the preservation of ejaculatory function.

Many RASP techniques have been developed, with the common goal of improving the quality of life of patients. Although the cost of RASP is higher than open surgery, the perioperative benefits of the robotic approach make RASP a favourable option in centres with extended robotic expertise.
Laser endoscopic procedures on the prostate: it is the small details that count
Authors: Taratkin Mark , Azilgareeva Camilla , Taratkina Daria , Goryacheva Evgenia , Rapoport Leonid , Enikeev Dmitry
Published: July 2021

Purpose of review

This review aims to highlight the pros and cons of each laser device and to consider additional possible milestones for the development of laser technologies in the surgical treatment of benign prostate hyperplasia.

Recent findings

Over the last three decades, lasers’ role in endourology has gone from strength to strength. Specifically, the primary techniques where laser surgery for BPO relief is concerned are vaporization and enucleation. The idea behind vaporization is that lasers are able to vaporize substantial amounts of tissue due to deep ablation depth and increased power. The most efficient devices for vaporization are those affecting hemoglobin as primary chromophore and/or using a continuous firing mode (KTP/LBO:YAG, diode lasers, Tm:YAG). As for enucleation, multiple devices have been suggested for the adequate anatomical enucleation of the prostate (EEP). As it is a skill-dependent technique, the EEP is effective irrespective of which device the surgeon uses. However, some devices have shown significant advances where enucleation is concerned.

The choice of device should be based primarily on the technique the surgeon prefers. Although the most suitable lasers for vaporization are hemoglobin-targeting and/or continuous wave devices, the EEP may be done with any enough powered laser, yet some provides specific effects which you should be aware before the surgery.
Use of Lacrimal Symptoms Questionnaire After Punctoplasty Surgery: Retrospective Data of Technical Strategy
Authors: Meduri Alessandro , Tumminello Giuseppe , Oliverio Giovanni William , Inferrera Leandro , Delia Gabriele , Aragona Pasquale , Cicciù Marco
Published: July 2021

The goal of this study is to evaluate postpunctoplasty symptoms with lacrimal symptoms questionnaire (Lac-Q). A retrospective study was conducted on 31 patients (14 men and 17 woman) with a diagnosis of canalicular stenosis: 26 patients with unilateral occlusion and 5 patients with bilateral occlusion. The Lac-Q was administered preoperative and at 1, at 3, and at 6 months following the surgery. Moreover, the Lac-Q questionnaire was administered by an independent observer (SI). The mono-lateral and bilateral postoperative Lac-Q score showed a significant improvement of symptoms at 1, 3, and 6 months than the preoperative results. The Lac-Q questionnaire is a way to evaluate the quality of outcomes after punctoplasty surgery. In this study, all patients showed a significant improvement of symptoms after surgery.
What is behavior? No seriously, what is it?
Authors: Calhoun Adam , Hady Ahmed El
Published: July 2021

Studying ‘behavior’ lies at the heart of many disciplines. Nevertheless, academics rarely provide an explicit definition of what ‘behavior’ actually is. What range of definitions do people use, and how does that vary across disciplines? To answer these questions we have developed a survey to probe what constitutes ‘behavior’. We find that academics adopt different definitions of behavior according to their academic discipline, animal model that they work with, and level of academic seniority. Using hierarchical clustering, we identify at least six distinct types of ‘behavior’ which are used in seven distinct operational archetypes of ‘behavior’. Individual respondents have clear consistent definitions of behavior, but these definitions are not consistent across the population. Our study is a call for academics to clarify what they mean by ‘behavior’ wherever they study it, with the hope that this will foster interdisciplinary studies that will improve our understanding of behavioral phenomena.
Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis
Authors: Zeraatkar Dena , Cusano Ellen , Martinez Juan Pablo Díaz , Qasim Anila , Mangala Sophia O. , Kum Elena , Bartoszko Jessica J. , Devji Tahira , Agoritsas Thomas , Lamontagne Francois , Rochwerg Bram , Vandvik Per O , Brignardello-Petersen Romina , Siemieniuk Reed
Published: July 2021

Objective

To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19.

Design

Systematic review and network meta-analysis

Data sources

WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses

Study selection

Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care.

Results

We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach.

We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty).

Conclusion

IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.

Systematic review registration

NA

What is already known on this topic?

IL-6 receptor blockers have immunosuppressive effects that may be important in COVID-19 patients with immune system dysfunction and inflammation

Corticosteroids reduce the risk of death in patients with severe or critical COVID-19

What this study adds

Our systematic review and network meta-analysis provides a comprehensive review of the evidence addressing the effects of IL-6 receptor blockers, alone or in combination with corticosteroids, in COVID-19

IL-6 receptor blockers when added to a standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality.

Tocilizumab and sarilumab in combination with corticosteroids may have similar effectiveness for reducing mortality.
Impairment of a cyanobacterial glycosyltransferase that modifies a pilin results in biofilm development
Authors: Suban Shiran , Sendersky Eleonora , Golden Susan S , Schwarz Rakefet
Published: July 2021

A biofilm inhibiting mechanism operates in the cyanobacteriumSynechococcus elongatus. Here, we demonstrate that the glycosyltransferase homolog, Ogt, participates in the inhibitory process – inactivation ofogtresults in robust biofilm formation. Furthermore, a mutational approach shows requirement of the glycosyltransferase activity for biofilm inhibition. This enzyme is necessary for glycosylation of the pilus subunit and for adequate pilus formation. In contrast to wild-type culture in which most cells exhibit several pili, only 25% of the mutant cells are piliated, half of which possess a single pilus. In spite of this poor piliation, natural DNA competence was similar to that of wild-type, therefore, we propose that the unglycosylated pili facilitate DNA transformation. Additionally, conditioned medium from wild-type culture, which contains a biofilm inhibiting substance(s), only partially blocks biofilm development by theogt-mutant. Thus, we suggest that inactivation ofogtaffects multiple processes including production or secretion of the inhibitor as well as the ability to sense or respond to it.

Originality-Significance Statement

The molecular mechanisms that underlie biofilm development in cyanobacteria are just emerging. Using the cyanobacteriumS. elongatusas a model, we demonstrate that glycosylation of the pilus subunit is crucial for the biofilm self-suppression mechanism, however, it is dispensable for DNA competence.
Proteolytic Activation of Human-specific Olduvai Domains by the Furin Protease
Authors: Pacheco Ashley , Issaian Aaron , Davis Jonathan , Anderson Nathan , Nemkov Travis , Vögeli Beat , Hansen Kirk , Sikela James M.
Published: July 2021

Olduvai protein domains (formerly DUF1220) show the greatest human-specific increase in copy number of any coding region in the genome and are highly correlated with human brain evolution and cognitive disease. The majority of human copies are found within four NBPF genes organized in a variable number of a tandemly arranged three-domain blocks called Olduvai triplets. Here we show that these human-specific Olduvai domains are posttranslationally processed by the furin protease, with a cleavage site occurring once at each triplet. These findings suggest that all expanded human-specific NBPF genes encode proproteins consisting of many independent Olduvai triplet proteins which are activated by furin processing. The exceptional correlation of Olduvai copy number and brain size taken together with our new furin data, indicates the ultimate target of selection was a rapid increase in dosage of autonomously functioning Olduvai triplet proteins, and that these proteins are the primary active agent underlying Olduvai’s role in human brain expansion.
Ca2+-dependent liquid-liquid phase separation underlies intracellular Ca2+ stores
Authors: Mayfield Joshua E. , Pollak Adam J. , Worby Carolyn A. , Xu Joy C. , Tandon Vasudha , Newton Alexandra C. , Dixon Jack E.
Published: July 2021

Endoplasmic/sarcoplasmic reticulum Ca2+ stores are essential to myriad cellular processes, however, the structure of these stores is largely unknown and existing models neither explain observations made in vivo nor sufficiently account for physiological data. We investigate CASQ1 - the major Ca2+ binding protein of skeletal muscle – and discover Ca2+-dependent liquid-liquid phase separation activity. The intrinsic disorder of CASQ1 underlies this activity and is regulated via phosphorylation by the secretory pathway kinase FAM20C. This novel divalent cation driven condensation demonstrates liquid-liquid phase separation occurs within the endoplasmic/sarcoplasmic reticulum, mechanistically explains efficient Ca2+ buffering and storage, and represents a largely unexplored mechanism of divalent-cation driven protein association.
Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition
Authors: Chen Rou-An , Wu Wei-Kai , Panyod Suraphan , Liu Po-Yu , Chuang Hsiao-Li , Chen Yi-Hsun , Lyu Qiang , Hsu Hsiu-Ching , Lin Tzu-Lung , Shen Ting-Chin David , Yang Yu-Tang , Zou Hsin-Bai , Huang Huai-Syuan , Lin Yu-En , Chen Chieh-Chang , Ho Chi-Tang , Lai Hsin-Chih , Wu Ming-Shiang , Hsu Cheng-Chih , Sheen Lee-Yan
Published: July 2021

Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have implicated that exposure to these antibiotic residues in food may be associated to childhood obesity. Herein, the effect of exposure to residual dose of tylosin—an antibiotic growth promoter—on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat diet-induced obesity, induce insulin resistance, and perturb the composition of gut microbiota in mice. The obesity-related phenotypes were transferrable to germ-free recipient mice, indicating that the effects of TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, which is the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low dose of antibiotic residues, whether continuously or in early life, can exert long-lasting effects on host metabolism by altering gut microbiota and its metabolites.

Importance

Evidence has indicated that chronic exposure to antibiotic residues in food could contribute to obesity. However, few studies have investigated the effect of chronic exposure to very low-dose antibiotic residue in food (~1000-fold lower than the therapeutic dose) on gut microbiota and host metabolism. Our study demonstrates that even with limited exposure in early life, a residual dose of tylosin causes lasting metabolic disturbances through altering gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.
BAM15 treats mouse sepsis and sepsis-AKI, linking circulating mitochondrial DNA and tubule reactive oxygen species
Authors: Tsuji Naoko , Tsuji Takayuki , Yamashita Tetsushi , Hu Xuzhen , Yuen Peter S.T. , Star Robert A.
Published: July 2021

The pathogenesis of sepsis is complex and heterogeneous; hence, a precision medicine strategy may be required. Acute kidney injury (AKI) following sepsis portends higher mortality. Overproduction of mitochondrial reactive oxygen species (mtROS) is a potential mediator of sepsis and sepsis-induced AKI. BAM15 is a chemical uncoupler that dissipates the mitochondrial proton gradient without generating mtROS, and improves experimental renal ischemic injury. We injected BAM15 into mice at 0 or 6 hours after cecal ligation and puncture (CLP) treated with fluids and antibiotics. BAM15 reduced mortality, even when started at 6 hours, when mice were ill, and reduced kidney damage but did not affect other organs. Serial plasma and urinary levels of mitochondrial DNA (mtDNA) were increased following CLP, and decreased after BAM15 (at 0 and at 6 hours).In vitroBAM15 prevented mtROS overproduction and mtDNA release from septic kidney tubule cells; mtROS generation correlated with mtDNA release. BAM15 also promotes mitochondrial biogenesis signaling. We conclude that BAM15 is an effective preventive and therapeutic candidate in experimental sepsis, and that BAM15 and mtDNA are mechanistically linked via mtROS, which may form a drug-companion diagnostic pair to improve precision medicine approaches to diagnosing and treating clinical sepsis.
Development of employees’ resilience in technologically turbulent environments: probing the mechanisms of consonance–dissonance and crisis leadership
Authors: Senbeto Dagnachew L. , Hon Alice H.Y.
Published: July 2021

Purpose

This study aims to examine the impact of technological turbulence on employee resilience based on cognitive dissonance theory and through a process of consonance and dissonance. First, the study investigates employee openness to represent cognitive consonance and then resistance to change to represent cognitive dissonance processes. Such processes mediate the relationship between technological turbulence and employee resilience. Second, this study proposes that the above associations will be moderated by crisis leadership efficacy.

Design/methodology/approach

The study uses multi-source data from service employees and their immediate superiors in hospitality, including a two-phase data collection process. Moreover, the study conducts a two-step structural equation modeling.

Findings

This study finds that employee openness and resistance to change mediate the association between technological turbulence and employee resilience. Furthermore, results reveal that crisis leadership efficacy strengthens the relationships (direct and indirect, through openness and resistance to change) between technological turbulence and employee resilience. The study discusses the implications for theory and practice for tourism scholars and practitioners.

Research limitations/implications

This study provides empirical evidence showing the importance of employee resilience and the underlying mechanisms in responding to technological turbulence in the hospitality industry.

Originality/value

Resilience research in the hospitality and service context is timely and necessary to cope up with the changing market and turbulences. This study extends the extant literature that mainly examined the crisis and dynamic conditions. The study contributes to crisis management, marketing and leadership literature concerning technological turbulence and employee resilience in the hospitality context.
Augmented reality (AR)-based sharia financial literacy system (AR-SFLS): a new approach to virtual sharia financial socialization for young learners
Authors: Candra Sari Ratna , Rika Fatimah P.L. , Ilyana Sariyatul , Dwi Hermawan Hardika
Published: July 2021

Purpose

This study aims to examine financial socialization based on augmented reality (AR) technology for elementary school students, which it is hoped will improve their sharia financial knowledge.

Design/methodology/approach

The experimental method with pre- and post-test and control groups was used to test the improvement in the young learners’ sharia financial knowledge. This study used AR for sharia financial socialization on elementary school students and focused on sharia’s basic concepts, which include earning money, balanced spending, borrowing, saving, investment, payment methods, financial technology and the concept of protection.

Findings

This study finds empirical evidence that the treatment group, who received sharia financial socialization via the AR media, increased their sharia financial knowledge to a greater extent than the control group did.

Research limitations/implications

This study provides encouraging evidence about the potential of sharia financial education for elementary school students using the appropriate learning strategies and media. The weakness in this study is that it was only carried out in one elementary school, with the children of middle- to upper-income parents. Further research should be undertaken at several schools with the children of parents with different income levels.

Practical implications

A shift in learning styles from verbal or visual to virtual encourages the use of AR-based learning media. Financial concepts can be abstract ones, and AR-based learning media is able to present intangible virtual elements so they become more concrete and tangible.

Social implications

The global COVID-19 pandemic has affected all aspects. One of the most severe and likely to be multiyear ahead is the financial aspect. Therefore, this research is expected to be a preparation for the younger generation as early as possible to strengthen social benefits in order to improve sharia financial literacy.

Originality/value

Research into the financial literacy, especially sharia financial literacy aimed at elementary school students, is still very limited. The teaching of financial literacy will be more effective if educators use the appropriate strategies and media. This study used financial socialization strategies and AR learning media that are aligned with the learning styles of young learners.
Enhancing the organisational commitment of public sector accounting staff through the pursuit of CSR objectives
Authors: McCarthy Dermot , Alexander Phyllis , Jung Young
Published: July 2021

Purpose

This study aims to examine the interrelationship between the employee public service motivations (PSM), organisational corporate social responsibility (CSR) objectives and employee organisational commitment amongst accounts department staff in public service organisations.

Design/methodology/approach

Survey data is taken from tax accountants and accounts administration staff (n = 285) across seven South Korean state-owned enterprises involved in the provision of various public services (utilities, infrastructure, energy and housing). Structural equation modeling techniques are used to conduct mediation and moderated-mediation analysis.

Findings

Results show that both employee PSM and organisational CSR are significant in determining organisational commitment, especially where they result in value congruence. The authors also find that perceived levels of internal and external CSR are significant in moderating the impact of different dimensions of PSM.

Practical implications

As accounting in public service organisations faces growing professional and commercial demands to address stakeholder needs, the need for organisations to retain accounts staff with the necessary motivations is vital. The findings highlight the importance of value congruence in achieving long-term employee organisational commitment and the need for the CSR objectives of organisations to take account of both external and internal stakeholders.

Originality/value

Little research has examined the relationship between PSM and organisational commitment amongst accounting staff in the quasi-public/private state-owned enterprise sector. This despite the level of organisational (e.g. introduction of new public management approach) and professional change (e.g. regulatory changes) experienced over the past two decades and the importance of the sector in public service provision.
Methods for eliciting user experience insights in workplace studies: spatial walkthroughs, experience curve mapping and card sorting
Authors: Babapour Chafi Maral , Cobaleda-Cordero Antonio
Published: July 2021

Purpose

Drawing on a user-centred design perspective, the purpose of this paper is to (i) provide an overview of three contextual user research methods, namely, spatial walkthroughs, experience curve mapping and card sorting, (ii) exemplify their applications in different case studies and (iii) compare the methods according to their contributions for the study of users’ workplace experiences. Previous workplace studies with qualitative approaches mainly rely on methods such as interviews and observations. Although these methods provide rich data, the understanding of office users, their use situations and finding more fitting workplace designs can benefit from deeper user experience insights.

Design/methodology/approach

Three methods and their variants were tested in studies of user experience in flexible offices: spatial walkthroughs, experience curve mapping and card sorting. The methods were tested during workshops and interviews in four case studies with a total of 114 participants.

Findings

Spatial walkthroughs were more immersive and provided the most insights on the actual context with respect to spatial design qualities, while experience curve mapping enabled understanding the temporal aspects of the user experience and card sorting enabled exploring user experiences with respect to predetermined spatial qualities and contextual aspects.

Originality/value

Spatial walkthroughs, experience curve mapping and card sorting methods have not previously been applied in workplace studies. They facilitate dialogue, participation and user involvement and provide insights for making evidence-based recommendations for designing or redesigning office environments that fit users’ needs and preferences.